A highly enhanced thrombopoietic activity by monomethoxy polyethylene glycol-modified recombinant human interleukin-6.
Interleukin-6 (IL-6) is a novel cytokine with activities that can affect hematopoietic cells including those of the megakaryocytic lineage. We have examined the effects of monomethoxy polyethylene glycol-modified recombinant human interleukin-6 (Peg-IL-6) on thrombopoiesis in vivo. To compare the thrombopoietic activity between Peg-IL-6 and unmodified IL-6, each was administered subcutaneously to mice every 24 hours at various doses. A dose-response experiment showed that Peg-IL-6 and IL-6 increased platelet counts in a dose-dependent fashion at a plateau stimulation level of 0.5 micrograms/day and 10 micrograms/day, respectively. This dose of Peg-IL-6 and IL-6 induced the elevated platelet counts by approximately 140% to 160% and 50% to 60%, respectively. Peg-IL-6 treatment (0.5 micrograms/day) for x-ray (6.0 Gy) irradiated mice induced an increase in the rate of platelet recovery, and a higher dosage (5 micrograms/day) completely blocked the induction of thrombocytopenia in this model. In contrast, IL-6 (10 micrograms/day) could not protect the animals from platelet nadir but reduced the period of thrombocytopenia after x-ray irradiation. Furthermore, when administered to 5-fluorouracil-treated mice, 5 micrograms/day of Peg-IL-6 diminished the platelet nadir and increased platelet counts on individual days during the recovery phase. The potent thrombopoietic activity of Peg-IL-6 were due to prolongation of circulating IL-6 levels that were reverted from Peg-IL-6 in vivo. These findings indicate that reduction of total body clearance of IL-6 induces potent thrombopoiesis and that Peg-IL-6 may be a useful thrombopoietic agent.


Impact of cold ischemia time on the outcomes of kidneys with Kidney Donor Profile Index ≥85%: mate kidney analysis - a retrospective study.
The new kidney allocation system recommends local and regional sharing of deceased donor kidneys (DDK) with 86-100% Kidney Donor Profile Index (KDPI) to minimize discard. Regional sharing can increase cold ischemia time (CIT) which may negatively impact transplant outcomes. Using a same donor mate kidney model, we aimed to define a CIT that should be targeted to optimize outcomes. Using Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified recipients of DDK from 2000 to 2013 with ≥85% KDPI. From this cohort, three groups of mate kidney recipients were identified based on CIT: group 1 (≥24 vs. ≥12 to <24 h), group 2 (≥24 vs. <12 h), and group 3 (≥12 to <24 vs. <12 h). Adjusted delayed graft function (DGF), and graft and patient survivals were compared for mate kidneys. DGF risk was significantly lower for patients with CIT <12 vs. ≥24 h in group 2 (adjusted OR: 0.25, 95% CI: 0.12-0.57, P < 0.001) while trending lower for CIT ≥12 to <24 vs. ≥24 h in group 1 (adjusted OR: 0.78, 95% CI: 0.59-1.03, P = 0.08) and CIT <12 vs. ≥12 to <24 h in group 3 (adjusted OR: 0.74, 95% CI: 0.55-1.0, P = 0.05). Adjusted graft and patient survivals were similar between mate kidneys in all groups. Minimizing CIT improves outcomes with regional sharing of marginal kidneys.


Production of gamma-aminobutyric acid from alcohol distillery lees by Lactobacillus brevis IFO-12005.
Lactobacillus brevis IFO-12005 showed good growth in rice shochu distillery lees (kome shochu kasu). Almost all of the free glutamic acid (10.50 mM) in shochu kasu was converted to gamma-amino-butyric acid (GABA) within 2 d of stationary culture at 30 degrees C. The amount of GABA in the kome shochu kasu medium finally reached 10.18 mM. After centrifugation of the broth culture, the supernatant fraction was treated with a flocculation agent to form a clear solution, then passed through a column containing a synthetic adsorbents, SP-207 to remove the yellow pigment and flavors which are unnecessary from a sensory perspective. An economical and simple production process for GABA was established.


The management of alcoholic hepatitis: a prospective comparison of scoring systems.
The assessment of alcoholic hepatitis remains controversial. Several scores have been developed or used for this purpose. To study the use of the Glasgow Alcoholic Hepatitis Score (GAHS), the Discriminant Function (DF), Model for End-Stage Liver Disease (MELD) and the ABIC (age, bilirubin, INR and creatinine) scores as well as scores to assess corticosteroid response in the management of alcoholic hepatitis. A total of 182 patients were studied prospectively. The GAHS, MELD, ABIC and DF scores were recorded on admission and serially over the first week of hospital management. Treatment with corticosteroids or pentoxifylline was considered if the GAHS was ≥9. There were no differences in outcome between favourable scores as per recommended cut-off points. Patients with a GAHS<9 had similar outcome whether their MELD, DF or ABIC scores were favourable or unfavourable. Treated patients with a GAHS≥9 had a significantly better 90-day outcome than those who did not: 58% and 30% respectively, P = 0.01; HR 0.33 (0.14, 0.78). Patients treated with corticosteroids who had a fall in bilirubin of 25% after a week of treatment had an improved survival: 82% compared with 44% [P = 0.0005: HR 3.70 (1.77, 7.73)]. The Lille Score or a 25% fall in bilirubin had greater sensitivities than an early change in bilirubin level (95% and 90% compared with 58%) to assess treatment response. In this single-centre study, a GAHS ≥9 identified patients who may benefit from treatment of alcoholic hepatitis. Intention-to-treat randomised-controlled trials using a GAHS ≥9 as the threshold for treatment are needed to validate these findings. Response to corticosteroids can be assessed using the Lille Score or by a 25% fall in bilirubin.


Web-Based Tool to Facilitate Shared Decision Making With Regard to Neoadjuvant Chemotherapy Use in Muscle-Invasive Bladder Cancer.
Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) for the treatment of muscle-invasive bladder cancer (MIBC), but observational data demonstrate that this approach is underused. A barrier to shared decision making is difficulty in predicting and communicating survival estimates after cystectomy with or without NAC. We included patients with MIBC from the National Cancer Database treated with cystectomy. A state-transition model was constructed for calculating 5-year death risk using baseline patient-, tumor-, and facility-level variables. Internal-external cross-validation by geographic region was performed. The effect of NAC was integrated using a literature-derived hazard ratio. Bladder cancer-specific and other-cause mortality was estimated from all-cause mortality rates from US life tables. From the state-transition model, a Web-based tool was developed and pilot usability testing performed. A total of 9,824 patients with MIBC who underwent cystectomy were eligible for inclusion. Median overall survival was 39.6 months (95% CI, 37.4 to 42.4 months). Increasing age, higher clinical T stage, higher comorbidity index, and black race were associated with shorter survival. Private insurance, higher income, and cystectomy at a high-volume facility were associated with longer survival. The prediction model was well calibrated across geographic regions, with observed-to-predicted 5-year death risks ranging from 0.85 to 1.17. Absolute risk reductions with NAC varied from 8.6% to 10.1%. The Web-based tool allowed input of the predictor variables and a user-defined hazard ratio associated with the effect of NAC to generate individualized survival estimates. The tool demonstrated good usability with clinicians. A Web-based tool was developed to individualize outcome prediction and communication in patients with MIBC treated with cystectomy with or without NAC to facilitate shared decision making.


The clinical features that contribute to poor bone health in young Australians living with cystic fibrosis: A recommendation for BMD screening.
For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Z score and potential risk factors was conducted using DXA and historical data. The main predictor of future BMD was the previous BMD Z score (p < .001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1 ), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1 , and number of hospital admissions. Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.


In ovo injection with glycerol and insulin-like growth factor (IGF-I): hatchability, intestinal morphometry, performance, and carcass characteristics of broilers.
The objective of this study was to evaluate the effects of in ovo injection with glycerol (GLY) and insulin-like growth factor (IGF-I) on hatchability, biochemical parameters, intestinal morphometry, performance, and carcass characteristics of broiler chickens. A total of 400 fertilised eggs were distributed into five experimental groups. The treatments were arranged as non-injected (control), saline solution injected (0.9% NaCl solution), GLY solution injected (10 nmol/ml), IGF-I solution injected (100 ng/ml), and GLY + IGF-I solution injected. At 17.5 d of incubation, 0.5 ml of each solution was injected into the amniotic fluid of each egg of the injected groups. The injection of different solutions did not influence the hatchability and incubation time of the eggs. Compared to intact eggs, IGF-I and IGF-I+ GLY increased (p < 0.01) the blood IGF-I at hatching. Higher hepatic glycogen was observed (p < 0.05) with GLY or IGF-I. The tested substances decreased (p = 0.02) the fructose 1,6-biphosfate phosphatase activity but did not affect glycaemia. No difference in performance was observed in the first week. Higher feed intake and weight gain with lower feed conversion ratio was obtained ( p < 0.05) with IGF-I at 14 d. At 21 d, higher weight gain was obtained (p = 0.05) with IGF-I, GLY, IGF-I, and GLY + IGF-I, resulting (p < 0.01) in birds with greater weight gain at 35 and 42 d of age. GLY provided higher villus height in the ileum at hatching and at 7 d of age. The tested solutions increased the relative weight of the liver at hatching. At 42 d of age, no carcass characteristics were influenced. It is concluded that GLY and IGF-I, together or separately, can be used in the in ovo feeding to improve the post-hatch performance of broilers, without affecting hatchability and carcass composition.


Variant endothelial cells. Fibronectin as a transducer of signals for migration and neovascularisation.
A morphologic and growth control variant of bovine aortal endothelial cells has been isolated and shown to synthesise factor VIII antigen (McAuslan and Reilly '79). The variant also possesses the endothelial surface markers angiotensin converting enzyme and alpha 2-microglobulin. The normal cell synthesises fibronectin and deposits it underneath the cells; the variant also synthesises fibronectin. At least three times more fibronectin is distributed over the upper cell surface of variants. This correlates with the three-fold increased binding of the replication inhibitor Con A and suggests a role of fibronectin in endothelial cell growth control. When stimulated to migrate by CuII ions, the variant leaves deposits of fibronectin in its trail; in contrast, migrating normal cells do not, but they do redistribute their surface fibronectin. As revealed by scanning electron microscopy, variant cells are unusual in that they grow over or under cultured normal endothelial cells. It is proposed that during the process of neovascularisation, variant cells have a special function as lead cells that lay down fibronectin on which an endothelium can become established.


The incidence of spina bifida occulta in a historic and a modern London population.
The incidence of spina bifida occulta was assessed in two London populations, one historic and the other contemporaneous. No significant differences were found between the two groups with regard to either overall frequency or frequency at specific sites within the lumbosacral column. This finding was compared to other studies reporting secular increases in the frequency of spina bifida occulta in areas outside the United Kingdom.


Cardiac, renal and vascular complications in the diabetic patient.
Type 2 diabetes has long been known to be associated with an increased risk of cardiovascular disease. Patients with type 2 diabetes have also been shown to benefit more from antihypertensive therapy than do non-diabetics with hypertension. The benefits of aggressive antihypertensive therapy are reflected in the recent reduction of blood pressure (BP) targets in international guidelines. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) have well-documented efficacy, and results from large-scale trials with highly selective angiotensin II (Ang II) receptor blockers (ARBs), such as valsartan, are awaited. The VALUE trial will provide the largest body of information yet on the comparative benefits of using an ARB or calcium channel blocker in hypertensive patients with diabetes.


A surgical procedure and tethering system for chronic blood sampling, infusion, and temperature monitoring in caged nonhuman primates.
A jacket and tethering system was used to maintain chronic catheters in monkeys, which provided catheter access and manipulability without further restraint. Surgical placement of catheters and a temperature probe allowed for a common cutaneous exit and interface with the jacket and tether. Monkeys were fitted in a sterile leather or denim jacket which was attached to a sterilized flexible stainless steel cable. Through this conduit, an indwelling temperature probe, as well as catheters from the internal jugular and femoral veins, were attached to a swivel unit located on the upper portion of the cage. The internal jugular catheter was used for the continuous infusion of support solution. The catheter from the femoral vein was maintained with a heparin lock and used for serial blood sampling. Using this system, it was possible to obtain frequent blood samples and body temperature readings, and to administer a continuous intravenous infusion without chemical or excessive physical restraint. To date, 367 monkeys, 322 cynomolgus (Macaca fasicularis), 16 rhesus (Macaca mulatta), and 21 African green (Cercopithecus aethiops) have been studied using this procedure.


Possible psychosomatic hazards to the therapist: patients as self-objects.
This speculative paper concerns certain fundamentals of healing and psychotherapy which we mistakenly tend to take for granted. I discuss our need for the feeling of harmony, wholeness, and oneness. I call this archetypal need our 'normal autistic expectation'. When met, we experience well-being and 'healing'. If not sufficiently and reliably met, this expectation becomes an omnipotent demand ('autistic demand'). Frustration then brings about angry destructiveness, either outwardly directed or inwardly directed, with bodily changes which must be processed if bodily damage is to be minimized. Bereavement, the loss of a person necessary for one's feeling of wholeness (a 'self-object'), is an extreme and well-researched example of such damage. Our selfobjects are 'healing' when they help us to complete our sense of self. Our patients-, our profession, our colleagues, our place of work and our financial security are normally all part of our self-object structure. I give examples where patients' own needs for survival or intactness mean that they have to externalize their own hurt and anger for long periods of their therapy. This often means that the therapist's own wholeness and health are under attack, and even damaged permanently, or at least until the damage can be processed. The nature of 'processing' in this sense is therefore in need of energetic research.


Genetics of the immune response to gluten in coeliac disease.
Accumulating evidence indicates that coeliac disease (CD) is a multifactorial disorder where several heritable factors in conjunction with environmental factors are involved in the disease development. Gluten proteins are a critical environmental factor as the presence of disease in affected individuals is strictly dependent on dietary gluten exposure. Most likely coeliac patients have genetically shaped immune responses to gluten proteins that cause intestinal pathology. Many of the CD genes thus supposedly encode variants of proteins with immune functions. HLA has been identified as a major genetic factor, but yet no further genes have been identified. There probably exist several predisposing non-HLA genes, but available data indicate that the heritable contribution by each of them can be small. Combined genetic and functional studies will hopefully identify additional predisposing genes in the future.


Innovative Use of Interventional Hardware in Surgical Embolectomy in Small Infants.
Surgical embolectomy for thrombosis and ischemia following femoral arterial cannulation in small infants is rare. The nonavailability of embolectomy balloons in small sizes and the small size of the native vessels pose a challenge in repair. We describe the use of a coronary angioplasty balloon for the purpose of embolectomy in a 2.5-kg infant with femoral arterial occlusion and limb ischemia.


Assessment of occupational exposure to radiofrequency fields and radiation.
The use of personal monitors for the assessment of exposure to radiofrequency fields and radiation in potential future epidemiological studies of occupationally exposed populations has been investigated. Data loggers have been developed for use with a commercially available personal monitor and these allowed personal exposure records consisting of time-tagged measurements of electric and magnetic field strength to be accrued over extended periods of the working day. The instrumentation was worn by workers carrying out tasks representative of some of their typical daily activities at a variety of radio sites. The results indicated significant differences in the exposures of workers in various RF environments. A number of measures of exposure have been examined with a view to assessing possible exposure metrics for epidemiological studies. There was generally a good correlation between a given measure of electric field strength and the same measure of magnetic field strength.


Production of Water-Soluble Carbohydrates from Aspen Wood Flour with Hydrogen Chloride Gas.
The aim of this study was to optimize the reaction conditions for concentrated acid hydrolysis of aspen wood flour by employing anhydrous hydrogen chloride gas to produce fermentable sugars. Gas hydrolysis with HCl was conducted both with and without temperature control during hydrolysis under a relatively low pressure of 0.1 MPa. Process parameters for HCl gas hydrolysis included the moisture content of aspen wood flour (0.7-50%) and reaction time under pressure (30 min to 24 h). In addition, liquid-phase hydrolysis with concentrated hydrochloric acid was conducted in concentrations of 32-42% and 15 min to 24 h reaction times for comparison with the gas-phase process. The highest yields (>90%) for water-soluble carbohydrates from aspen wood flour were achieved with temperature-controlled gas hydrolysis using 50% moisture content and 2 h total reaction time, which is in line with the previous research and comparable to hydrolysis with concentrated (42%) hydrochloric acid.


The remission rate, metabolic changes, and quality of life assessment among patients with type 2 diabetes post-bariatric surgery in Riyadh, Saudi Arabia: A cross-sectional study.
To assess the remission rate, metabolic changes, and quality of life after bariatric surgery among Saudi patients with type 2 diabetes (T2DM). This cross-sectional study was conducted in 2 main centers in the Riyadh, Saudi Arabia. The study included patients with T2DM who underwent either laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass (RYGB) surgery from 2014 to 2018. The remission rate was defined based on the American Diabetes Association (ADA) and the International Diabetes Federation (IDF) criteria. Quality of life was assessed using the World Health Organization Quality of Life (WHOQOL)-BREF. A total of 232 patients were included with a mean age of 44.3 ± 10.3 years. 93.4% of the patients had LSG, while only 6.6% had RYGB surgery. Among patients who underwent either LSG or RYGB surgery, there was a significant improvement in metabolic and glycemic markers compared to the baseline. According to the ADA criteria, 48.5% of the patients had complete remission, while 18.9% had partial remission. Overall, 7% of the patients met the IDF optimization criteria, while 5.7% met the IDF improvement criteria. The mean score for all the QOL domains exceeded 63 ± 13, with the environmental and physical health domains having the highest scores. Among Saudi patients, bariatric surgery was associated with high remission rates and a better quality of life.


[Long-term treatment using antidepressants. Tianeptine: methodology of a long-term study and preliminary results].
Numerous authors insist on the need for prolonged prescription of antidepressant drugs. Legislation develops and now requires long-term controls for psychotropic drugs. In order to assess long-term efficacy and safety of tianeptine, a clinical trial was undertaken with the objective of 100 patients completing one year of treatment. This multicentered study involves 157 psychiatrists all over France, under the responsibility of a national coordinator and 19 regional coordinators. The methodology is explained, as well as the various means that have been planned to set up the protocol, to follow the case reports and to analyse the results. The use of a central computer assisted monitoring and the organization of national and regional meetings with the investigators seem to take an important part in the management of the study. Preliminary results after 6 months of treatment for 478 patients are discussed. They confirm the prolonged efficacy and the safety of tianeptine. The effective contribution made by the logistic support should allow the study to reach its objectives. When completed, it should be a pilot study for further long-term studies with antidepressants.


The Role of Tea Tree Oil in Alleviating Palmitic Acid-Induced Lipid Accumulation in Bovine Hepatocytes.
Tea tree oil (TTO) plays an important role in lipid metabolism, alleviating the inflammatory responses. Fatty liver is associated with lipid accumulation in hepatocytes, leading to inflammation. However, there is very limited information on the effects of TTO on lipid accumulation, and inflammation in bovine hepatocytes. This study aimed to evaluate whether TTO alleviates palmitic acid (PA)-induced lipid accumulation in bovine hepatocytes. Hepatocytes isolated from mid-lactating Holstein cows were pretreated with 100 μM PA for 72 h. Cells were either pretreated with PA alone (PA group) or with PA followed by 0.00625% TTO treatment for 12 h (PT group). Expression of fatty acid oxidant genes increased (P < 0.05) while fatty acid synthesis genes decreased (P < 0.05) in the PT group compared with the PA group. PA treatment resulted in increased (P < 0.05) expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but these increases were less in the PT group (P < 0.05). Compared to the PA group, expression of phosphorylated (p)-p65 and p-inhibitor κBα (p-IκBα) was suppressed (P < 0.05) by TTO treatment. TTO treatment limited (P < 0.05) the increase in intracellular reactive oxygen species (ROS) and prevented (P < 0.05) a reduction in mitochondrial membrane potential observed in response to PA treatment. Expression of endoplasmic reticulum (ER) stress genes was reduced (P < 0.05) in the PT group compared with the PA group. Our results suggest that TTO treatment attenuates the effects of PA in hepatocytes, leading to fatty acid oxidation, decreased fatty acid synthesis, suppressed inflammatory response, and reduced ER stress. Taken together, the results of this study suggest that TTO treatment may be a promising therapeutic approach to imbalanced lipid homeostasis, inflammation and ER stress in dairy cows shortly before and after calving.


The relational core of nursing practice as partnership.
Consideration of the relational core of nursing has gained significance in today's health systems, where the work of nurses is dominated by technologically-driven, prescriptive, and outcome-oriented approaches. This has led to disregard for individual experiences of living life with diverse health conditions. The aim of this paper is to articulate the relational core of nursing practice as partnership. The relational core of nursing practice is explicated as a process of professional partnership, focusing on the evolving dialogue between nurse and patient. In partnership, the dialogue is open, caring, mutually responsive and non-directive. The nurse attends to that which is of concern to patients in relation to their health predicaments and the meaning in the health experience unfolds. Nurse and patient reach insight that represents more useful ways of comprehending and acting on their health predicaments. Partnership represents theoretically-driven practice that invites nurses to meet patients where they are in understanding their health predicaments and what can be done about them. As such, partnership strengthens the resolve of nurses to resist the pressures of contemporary health service delivery to provide a technical form of practice and it protects the relational core of a fully professional practice.


Deposition of dust with active substances in pesticides from treated seeds in adjacent fields during drilling: disentangling the effects of various factors using an 8-year field experiment.
The side effects from the use of plant protection products and their potential effects on non-target arthropods (NTAs) such as honey bees, other insects within the vegetation layer and epigeic arthropods nowadays receive more attention. However, uncertainties about the factors driving the deposition of active substances (a.s.) into off-crop areas persist, in particular during sowing of treated seeds. Analysing a highly standardised 8-year field experiment, we assessed the importance of various factors potentially affecting dust drift and deposition of a.s., emitted during the sowing process of treated seeds and deposited on fields adjacent to the drilling field, i.e. on the ground, on flowers, and on nonflowering plant parts. Regarding a.s. deposition, the Heubach a.s. value has a predictive capability, which is independent from all other factors taken into account in this study, and can thus be considered as a scenario-independent measure of potential dust deposition. Petri dish samplers, an established standard method for measuring a.s. deposition, were representative of the results from the plant samplers for a given combination of drilling technique and adjacent crop type. Adjacent crop type is likely to impact on a.s. deposition. The present work will enable a more field-realistic exposure assessment for bees and other NTAs.


Unilateral megalencephaly in association with Dandy-Walker complex.
Unilateral megalencephaly is a rare congenital anomaly. The authors report a case of unilateral megalencephaly associated with Dandy-Walker complex. The embryonic pathogenesis of both entities is discussed. In the absence of magnetic resonance imaging, computed tomography can be used to document these abnormalities.


Identification of the New Covalent Allosteric Binding Site of Fructose-1,6-bisphosphatase with Disulfiram Derivatives toward Glucose Reduction.
Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric site distinct from the original C128 site in APO FBPase. Further identification of the allosteric inhibition mechanism reveals that the covalent binding of a fragment of 214 will result in the movement of C128 and the dissociation of helix H4 (123-128), which in turn allows S123 to more easily form new hydrogen bonds with K71 and D74 in helix H3 (69-72), thereby inhibiting FBPase activity. Notably, both disulfiram and 212 might moderately reduce blood glucose output in vivo. Therefore, our current findings not only identify a new covalent allosteric site of FBPase but also establish a structural foundation and provide a promising way for the design of covalent allosteric drugs for glucose reduction.


Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients.
Mutations in hepatitis B virus (HBV) surface promoter II (SPII) have not been well studied in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. We aimed to investigate SPII mutations in such patients and their biological and clinical impacts. Direct sequencing was used to detect SPII mutations in 106 HBeAg-positive treatment-naïve CHB patients with genotype C (82.1% (87/106) was C2) HBV infection. Results showed that mutation frequency in transcription factor (TF) unbinding region was significantly higher than that in TF binding region of SPII (C1: 3.4% vs. 1.3%; C2: 2.6% vs. 1.3%; p < 0.0001). Luciferase assay revealed distinct promoter activities among SPII mutants; especially SPII of G120A mutant had a 15-fold higher activity than that of wild-type (p < 0.001). In vitro experiments in HepG2 cells showed that G82A, A115C and G120A mutants increased the hepatitis B surface antigen (HBsAg) levels, while C18T had an opposite effect. G82A, A115C and G120A mutants boosted the intracellular HBV total RNA level. G120A mutation resulted in an increased HBV DNA level in vitro, consistent with the serological results in patients. Thus, novel SPII mutations would affect promoter activity, HBsAg, HBV DNA and HBV total RNA levels, suggesting their potential biological and clinical significances.


Use of the covariance matrix in directly fitting kinetic parameters: application to GABAA receptors.
A new method of analysis is described that begins to explore the relationship between the phases of ion channel desensitization and the underlying states of the channel. The method, referred to as covariance fitting (CVF), couples Q-matrix calculations with a maximum likelihood algorithm to fit macroscopic desensitization data directly to kinetic models. Unlike conventional sum-of-squares minimization, CVF fits both the magnitude of the recorded current and the strength of the correlations between different time points. When applied to simulated data generated using various kinetic models with up to 11 free parameters, CVF leads to reasonable parameter estimates. Coupled with the likelihood ratio test, it accurately discriminates between models with different numbers of states, discriminates between most models with the same number but a different arrangement of states, and extracts meaningful information on the relationship between the desensitized states and the phases of macroscopic desensitization. When applied to GABA(A) receptor traces (outside out patches, alpha 1 beta 2 gamma 2S, 1 mM GABA, >2.5 s), a model with two open states and three desensitized states is favored. When applied to simulated data generated using a consensus model, CVF leads to reasonable parameter estimates and accurately discriminates between this and other models.


[Diastolic opening of the pulmonary valve in a case of cardiomyopathy with restrictive dysfunction. Case report and review of the literature].
In a case of cardiomyopathy with restrictive ventricular dysfunction a complete diastolic opening of the pulmonary valve immediately following the atrial contraction could be visualized by echocardiography and at the same time a forward blood flow into the pulmonary artery could be shown by conventional and color Doppler. The velocity of this flow (0.37 m/s) was as high as the maximal velocity of the systolic outflow. As an expression of the unpaired compliance of the right ventricle and a compensatory hyperkinetic right atrium the heart catheterization revealed a high a-wave of 18 mm Hg, which was transmitted into the right ventricle and the pulmonary artery. This produced a short diastolic pressure drop between the right ventricle and pulmonary artery causing an opening of the pulmonary valve which could be shown by echocardiography. In connection with similar cases in the literature the pathophysiology of this phenomenon is discussed.


Genome-Wide Association Studies Associated with Backfat Thickness in Landrace and Yorkshire Pigs.
Although pork quality traits are important commercially, genome-wide association studies (GWASs) have not well considered Landrace and Yorkshire pigs worldwide. Landrace and Yorkshire pigs are important pork-providing breeds. Although quantitative trait loci of pigs are well-developed, significant genes in GWASs of pigs in Korea must be studied. Through a GWAS using the PLINK program, study of the significant genes in Korean pigs was performed. We conducted a GWAS and surveyed the gene ontology (GO) terms associated with the backfat thickness (BF) trait of these pigs. We included the breed information (Yorkshire and Landrace pigs) as a covariate. The significant genes after false discovery rate (<0.01) correction were AFG1L, SCAI, RIMS1, and SPDEF. The major GO terms for the top 5% of genes were related to neuronal genes, cell morphogenesis and actin cytoskeleton organization. The neuronal genes were previously reported as being associated with backfat thickness. However, the genes in our results were novel, and they included ZNF280D, BAIAP2, LRTM2, GABRA5, PCDH15, HERC1, DTNBP1, SLIT2, TRAPPC9, NGFR, APBB2, RBPJ, and ABL2. These novel genes might have roles in important cellular and physiological functions related to BF accumulation. The genes related to cell morphogenesis were NOX4, MKLN1, ZNF280D, BAIAP2, DNAAF1, LRTM2, PCDH15, NGFR, RBPJ, MYH9, APBB2, DTNBP1, TRIM62, and SLIT2. The genes that belonged to actin cytoskeleton organization were MKLN1, BAIAP2, PCDH15, BCAS3, MYH9, DTNBP1, ABL2, ADD2, and SLIT2.


Plant odor and sex pheromone are integral elements of specific mate recognition in an insect herbivore.
Specific mate recognition relies on the chemical senses in most animals, and especially in nocturnal insects. Two signal types mediate premating olfactory communication in terrestrial habitats: sex pheromones, which blend into an atmosphere of plant odorants. We show that host plant volatiles affect the perception of sex pheromone in males of the African cotton leafworm Spodoptera littoralis and that pheromone and plant volatiles are not perceived as independent messages. In clean air, S. littoralis males are attracted to single synthetic pheromone components or even the pheromone of a sibling species, oriental cotton leafworm S. litura. Presence of host plant volatiles, however, reduces the male response to deficient or heterospecific pheromone signals. That plant cues enhance discrimination of sex pheromone quality confirms the idea that specific mate recognition in noctuid moths has evolved in concert with adaptation to host plants. Shifts in either female host preference or sex pheromone biosynthesis give rise to new communication channels that have the potential to initiate or contribute to reproductive isolation.


Is the G-quadruplex an effective nanoconductor for ions?
We use a stepwise pulling protocol in molecular dynamics simulations to identify how a G-quadruplex selects and conducts Na(+), K(+), and NH4(+) ions. By estimating the minimum free-energy changes of the ions along the central channel via Jarzynski's equality, we find that the G-quadruplex selectively binds the ionic species in the following order: K(+) > Na(+) > NH4(+). This order implies that K(+) optimally fits the channel. However, the features of the free-energy profiles indicate that the channel conducts Na(+) best. These findings are in fair agreement with experiments on G-quadruplexes and reveal a profoundly different behavior from the prototype potassium-ion channel KcsA, which selects and conducts the same ionic species. We further show that the channel can also conduct a single file of water molecules and deform to leak water molecules. We propose a range for the conductance of the G-quadruplex.


Wallifoliol, a taxol congener with a novel carbon skeleton, from Himalayan Taxus wallichiana.
A new taxoid, wallifoliol [3], has been isolated, along with five known taxoids (taxol, cephalomannine, 10-deacetylbaccatin III, brevifoliol, 2-acetoxy brevifoliol = taxchinin A) from extracts of the needles of Himalayan Taxus wallichiana. The structure of wallifoliol has been assigned primarily from nmr studies. Wallifoliol [3] is assigned a structure in which rings A and B of the taxane system have undergone putative rearrangements producing a novel skeleton. Wallifoliol is the first diterpene to be found in nature with this particular 5/6/6/6/4 ring system.


Constitutive properties of hypertrophied myocardium: cellular contribution to changes in myocardial stiffness.
Recent studies have suggested that pressure overload hypertrophy (POH) alters the viscoelastic properties of individual cardiocytes when studied in isolation. However, whether these changes in cardiocyte properties contribute causally to changes in the material properties of the cardiac muscle as a whole is unknown. Accordingly, a selective, isolated, acute change in cardiocyte constitutive properties was imposed in an in vitro system capable of measuring the resultant effect on the material properties of the composite cardiac muscle. POH caused an increase in both myocardial elastic stiffness, from 20.5 +/- 1.3 to 28.4 +/- 1.8, and viscous damping, from 15.2 +/- 1.1 to 19.8 +/- 1.5 s (normal vs. POH, P < 0.05), respectively. Recent studies have shown that cardiocyte constitutive properties could be acutely altered by depolymerizing the microtubules with colchicine. Colchicine caused a significant decrease in the viscous damping in POH muscles (19.8 +/- 1.5 s at baseline vs. 14.7 +/- 1.3 s after colchicine, P < 0.05). Therefore, myocardial material properties can be altered by selectively changing the constitutive properties of one element within this muscle tissue, the cardiocyte. Changes in the constitutive properties of the cardiocytes themselves contribute to the abnormalities in myocardial stiffness and viscosity that develop during POH.


Signaling events during initiation of arbuscular mycorrhizal symbiosis.
Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal (AM) fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intracellular association with plant roots where they transfer phosphate and nitrogen to the plant in exchange for carbon. They are obligate fungi, relying on their host as their only carbon source. Much has been discovered in the last decade concerning the signaling events during initiation of the AM symbiosis, including the identification of signaling molecules generated by both partners. This signaling occurs through symbiosis-specific gene products in the host plant, which are indispensable for normal AM development. At the same time, plants have adapted complex mechanisms for avoiding infection by pathogenic fungi, including an innate immune response to general microbial molecules, such as chitin present in fungal cell walls. How it is that AM fungal colonization is maintained without eliciting a defensive response from the host is still uncertain. In this review, we present a summary of the molecular signals and their elicited responses during initiation of the AM symbiosis, including plant immune responses and their suppression.


Tetraphenylphosphonium-selective electrode as a tool for evaluating mitochondrial permeability transition pore function in isolated rat hepatocytes.
The changes in mitochondrial membrane potential (Deltapsi(m)) were used as an indicator for evaluating the mitochondrial permeability transition pore (MPTP) function. We found that in situ mitochondria in digitonin-permeabilized hepatocytes were coupled and responded to the addition of substrates, inhibitors and uncouplers. Ca(2+)-induced Deltapsi(m) dissipation was caused by MPTP opening because this process was inhibited by cyclosporin A. MPTP opening was enhanced by the pro-oxidant tert-butyl hydroperoxide.


Mechanism analysis for excitatory interneurons dominating poly-spike wave and optimization of electrical stimulation.
In addition to inhibitory interneurons, there exist excitatory interneurons (EINs) in the cortex, which mainly have excitatory projections to pyramidal neurons. In this study, we improve a thalamocortical model by introducing EIN, investigate the dominant role of EIN in generating spike and slow wave discharges (SWDs), and consider a non-rectangular pulse to control absence seizures. First, we display here that the improved model can reproduce typical SWDs of absence seizures. Moreover, we focus on the function of EIN by means of bifurcation analysis and find that EIN can induce transition behaviors under Hopf-type and fold limit cycle bifurcations. Specifically, the system has three stable solutions composing a tri-stable region. In this region, there are three attraction basins, which hints that external stimulation can drive the system trajectory from one basin to another, thereby eliminating abnormal oscillations. Furthermore, we compare the increasing ramp with rectangular pulse and optimize stimulation waveforms from the perspective of electrical charges input. The controlling role of the single increasing ramp to absence seizures is remarkable and the optimal stimulus parameters have been found theoretically. This work provides a computational model containing EIN and a theoretical basis for future physiological experiments and clinical research studies.


Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the putative pore-forming region of TRPM6.
Hypomagnesemia with secondary hypocalcemia is an autosomal recessive disorder caused by mutations in the TRPM6 gene. Current experimental evidence suggests that TRPM6 may function in a specific association with TRPM7 by means of heterooligomeric channel complex formation. Here, we report the identification and functional characterization of a new hypomagnesemia with secondary hypocalcemia missense mutation in TRPM6. The affected subject presented with profound hypomagnesemia and hypocalcemia caused by compound heterozygous mutation in the TRPM6 gene: 1208(-1)G > A affecting the acceptor splice site preceding exon 11, and 3050C > G resulting in the amino acid change (P1017R) in the putative pore-forming region of TRPM6. To assess the functional consequences of the P1017R mutation, TRPM6(P1017R) and wild-type TRPM6 were co-expressed with TRPM7 in Xenopus oocytes and HEK 293 cells, and currents were assessed by two-electrode voltage clamp and whole cell patch clamp measurements, respectively. Co-expression of wild-type TRPM6 and TRPM7 resulted in a significant increase in the amplitude of TRPM7-like currents. In contrast, TRPM6(P1017R) suppressed TRPM7 channel activity. In line with these observations, TRPM7, containing the corresponding mutation P1040R, displayed a dominant-negative effect upon co-expression with wild-type TRPM7. Confocal microscopy and fluorescence resonance energy transfer recordings demonstrated that the P1017R mutation neither affects assembly of TRPM6 with TRPM7, nor co-trafficking of heteromultimeric channel complexes to the cell surface. We conclude that a functional defect in the putative pore of TRPM6/7 channel complexes is sufficient to impair body magnesium homeostasis.


α-Asarone Attenuates Osteoclastogenesis and Prevents Against Oestrogen-Deficiency Induced Osteoporosis.
Osteoporosis (OP) is defined as low bone mineral density which features over activated osteoclasts (OCs) and bone resorption. Targeting excessive OCs activity is thought to be an effective therapeutic approach for OP treatment. α-asarone (ASA), a compound from the traditional Chinese medicinal herb Acorus tatarinowii, has been widely used as a therapeutic agent against several diseases such as epilepsy, cough, bronchitis and asthma for many years. Recently, it was reported that ASA-derived lignins which were purified from Acorus tatarinowii root tissues effectively suppressed both RANKL-induced osteoclastogenesis and bone resorption. Besides, a classic Chinese formulation Bajitianwan (BJTW) which consisted of root and rhizome of Acorus tatarinowii Schott also showed positive effects on age-related bone loss. In the present study, we aimed to study the effects of ASA on osteoclastogenesis in vitro and in vivo. As illustrated by TRAP staining, ASA was capable of inhibiting RANKL-induced osteoclastogenesis in a dose-dependent manner, not only at an early-stage, but also in the late-stage. Besides, it also effectively suppressed bone resorption of mature OCs in a pit resorption assay. The formation of F-actin ring during osteoclastogenesis, which was important in OCs bone-resorption, was impaired as well. Subsequent mechanism experiments exposed that ASA inhibited osteoclastogenesis related genes in a time-dependent manner through AKT, p38 and NF-κB, followed by NFATc1/c-fos signaling pathway. Notably, our in vivo study uncovered that ASA was capable of improving the bone microstructure in oestrogen-deficiency induced OP models. Thus, our current work highlighted the important role of an old drug ASA in bone metabolism especially in OCs differentiation. ASA may find its potential as a lead compound to treat excessive OCs activity-induced bone loss diseases and more structure optimization is further needed.


Gazing left, gazing right: exploring a spatial bias in social attention.
Faces oriented rightwards are sometimes perceived as more dominant than faces oriented leftwards. In this study, we explored whether faces oriented rightwards can also elicit increased attentional orienting. Participants completed a discrimination task in which they were asked to discriminate, by means of a keypress, a peripheral target. At the same time, a task-irrelevant face oriented leftwards or rightwards appeared at the centre of the screen. The results showed that, while for faces oriented rightwards targets appearing on the right were responded to faster as compared to targets appearing on the left, for faces oriented leftwards no differences emerged between left and right targets. Furthermore, we also found a negative correlation between the magnitude of the orienting response elicited by the faces oriented leftwards and the level of conservatism of the participants. Overall, these findings provide evidence for the existence of a spatial bias reflected in social orienting.


How the cornea heals: cornea-specific repair mechanisms affecting surgical outcomes.
In mammals, penetrating injuries typically heal by deposition of fibrotic "repair tissue" that fills and seals wounds but does not restore normal function. Excessive deposition of fibrotic repair tissue can lead to pathologies involving excessive scarring and contracture. In the cornea, fibrotic repair presents special challenges affecting both clarity and shape of the cornea. With the increasing popularity of surgical techniques that alter corneal refractive errors, understanding of cornea repair mechanisms has acquired new significance. The cornea has unique anatomic, cellular, molecular, and functional features that lead to important mechanistic differences in the process of repair in comparison with what occurs in skin and other organs. Moreover, corneal function calls for special outcomes. This review addresses these features from the viewpoint of the authors' research on factors of importance to understanding and improving surgical outcomes.


Mesenchymal stem cells and their potential as cardiac therapeutics.
Mesenchymal stem cells (MSCs) represent a stem cell population present in adult tissues that can be isolated, expanded in culture, and characterized in vitro and in vivo. MSCs differentiate readily into chondrocytes, adipocytes, osteocytes, and they can support hematopoietic stem cells or embryonic stem cells in culture. Evidence suggests MSCs can also express phenotypic characteristics of endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte cells. When introduced into the infarcted heart, MSCs prevent deleterious remodeling and improve recovery, although further understanding of MSC differentiation in the cardiac scar tissue is still needed. MSCs have been injected directly into the infarct, or they have been administered intravenously and seen to home to the site of injury. Examination of the interaction of allogeneic MSCs with cells of the immune system indicates little rejection by T cells. Persistence of allogeneic MSCs in vivo suggests their potential "off the shelf" therapeutic use for multiple recipients. Clinical use of cultured human MSCs (hMSCs) has begun for cancer patients, and recipients have received autologous or allogeneic MSCs. Research continues to support the desirable traits of MSCs for development of cellular therapeutics for many tissues, including the cardiovascular system. In summary, hMSCs isolated from adult bone marrow provide an excellent model for development of stem cell therapeutics, and their potential use in the cardiovascular system is currently under investigation in the laboratory and clinical settings.


Cladribine underdosing in hairy-cell leukemia: a cause for apparent response failure.
While chemotherapy overdose is often readily discovered, underdosing errors are seldom appreciated. We report two patients with hairy-cell leukemia who apparently failed to respond to cladribine administered by continuous portable pump infusion. It was determined that both patients received one-seventh of the prescribed dose, although the orders were written correctly. The errors resulted in the administration of 1 day's dose over 1 week. The use of 7-day portable pump infusion therapy for cladribine can be associated with misdosing, and is an occult cause of apparent failure to respond in hairy-cell leukemia.


The AmpC phenotype in Norwegian clinical isolates of Escherichia coli is associated with an acquired ISEcp1-like ampC element or hyperproduction of the endogenous AmpC.
The aim of the study was to examine resistance mechanisms associated with an AmpC phenotype in Norwegian clinical isolates of Escherichia coli. Clinical E. coli isolates (n = 106) with reduced susceptibility to third-generation cephalosporins without clavulanic acid synergy were collected from 12 Norwegian laboratories from 2003 to 2005. Twenty-two isolates with an AmpC phenotype were selected for further characterization by PFGE, isoelectric focusing, different PCR-based techniques, DNA sequencing, AmpC qRT-PCR, transfer studies and plasmid analyses. The 22 isolates were not clonally related by the PFGE analysis. All isolates expressed a beta-lactamase with a pI of 9.0-9.2. Ten isolates contained a bla(CMY) gene, which was linked to an ISEcp1-like element in all cases. Twelve isolates had mutations or insertions in the promoter or the attenuator regions, leading to increased expression of the chromosomal ampC gene. One of these isolates had an ISEc10 element inserted upstream of the chromosomal ampC gene. This is the first molecular study of Norwegian clinical E. coli isolates with an AmpC phenotype. Resistance was mediated either by expression of bla(CMY) from acquired ISEcp1-like-bla(CMY) elements, or by mutations or insertions in the chromosomal ampC gene control region leading to hyperproduction of the endogenous AmpC enzyme. There was no correlation between the level of ampC mRNA and the MICs of cephalosporins.


Abnormal ankle brachial index and the presence of significant coronary artery disease.
To determine the association between an abnormal ankle brachial index (ABI) and the presence of significant coronary artery disease (CAD) on coronary angiography. Cross-sectional, observational study. The study was carried out at Sheikh Zayed Hospital, Lahore, from July to October 2007. A series of 41 patients undergoing coronary angiography in Sheikh Zayed Hospital were selected and their ABI were calculated before the diagnostic coronary angiography. ABI calculations and coronary angiography reporting were done by separate individuals and data was analysed using SPSS 12.0. All patients undergoing diagnostic coronary angiography were included in the study except for those having peripheral arterial disease documented by lower extremity revascularization, lower extremity ulceration and lower extremity amputation. Proportion were compared using chi-square test with significance at p < 0.05. Out of the 41 patients 31 male (76%) and 10 female (24%), 3 patients (7.31%) had ABI < 0.9 and all 3 had triple vessel disease. Ten patients (24%) had ABI 0.91-0.99 and 2 (20%) of them had single vessel disease. Two (20%) had double vessel disease and 6 (60%) had triple vessel disease. Twenty four patients (58%) had ABI of 1.00-1.28 and 8 (33%) of these had single vessel disease, 3 (12%) had double vessel disease and 13 (55%) had triple vessel disease, while 4 patients had normal coronaries. A total of 22 patients were found to have triple vessel disease and only 3 (13.6%) of these 22 patients had an ABI < 0.9 which is statistically not significant (p=0.07). This study was not able to establish a direct association between ABI and significant CAD as only 3 patients out of 22 with triple vessel disease had an ABI < 0.9. However, an approximately log linear relationship was noted between ABI and CAD risk which means that not only the average CAD risk increased exponentially at values < 1.0 but also that the CAD risk continued to decline as ABI values increased above 1.0.


Spontaneous perilymphatic fistula in children.
Treatment of fistulae in children should be targeted at four different problem areas. The surgical intervention of these fistulae is most efficacious in controlling recurrent meningitis, which has not been discussed in this paper, and in the controlling of vestibular symptoms. Whether or not it will stop the progression of hearing loss or restore hearing is not known in a group of patients. It has been documented in this and other reports that the closure of the fistula will in specific cases appear to be associated in time with a stopping of the progression of the hearing loss and is associated also in time with the restoration of hearing function. Various factors must be considered in developing criteria for intervention. A decision to explore the ear should be based on history, audiometric change, vestibular testing including a fistula test, and malformation of bony labyrinth.


Methylthiosulfonate-Based Cysteine Modifiers as Alternative Inhibitors of Mercurial-Sensitive Aquaporins.
(1) Background: Several members of the ubiquitous aquaporin family, AQP, of water and neutral solute channels carry a cysteine residue in the selectivity filter region. Traditionally, toxic mercury-containing compounds are used to bind to the cysteine as covalent AQP inhibitors for physiological studies or analysis of structure-function relationships. (2) Methods: We tested thiol-reactive methylthiosulfonate reagents, MTS, as alternative Cys modifiers for AQP inhibition. Three MTS reagents transferring S-alkyl moieties of increasing size, i.e., S-methyl, S-n-propyl, and S-benzyl, were used with yeast-expressed water-selective AQP1 and the aquaglyceroporin AQP9. Respective Cys-to-Ala variants and mouse erythrocytes that naturally express AQP1 and AQP9 served as controls. (3) Results: Both wildtype AQP isoforms were inhibited by the Cys modifiers in a size-dependent manner, whereas the Cys-to-Ala-variants exhibited resistance. Sub-millimolar concentrations and incubation times in the minute range were sufficient. The modifications were reversible by treatment with the thiol reagents acetylcysteine, ACC, and dithiothreitol, DTT. (4) Conclusions: MTS reagents represent a valid alternative of low toxicity for the inhibition of mercurial-sensitive AQPs.


Fabrication of Polymeric Micelles with Aggregation-Induced Emission and Forster Resonance Energy Transfer for Anticancer Drug Delivery.
With the aim of obtaining effective cancer therapy with simultaneous cellular imaging, dynamic drug-release monitoring, and chemotherapeutic treatment, a polymeric micelle with aggregation-induced emission (AIE) imaging and a Forster resonance energy transfer (FRET) effect was fabricated as the drug carrier. An amphiphilic conjugate of 1H-pyrrole-1-propanoicacid (MAL)-poly(ethylene glycol) (PEG)-Tripp-bearing AIE molecules were synthesized and self-assembled into micelles to load the anticancer drug doxorubicin (DOX). Spherical DOX-loaded micelles with the mean size of 106 nm were obtained with good physiological stability (CMC, 12.5 μg/mL), high drug-loading capacity (10.4%), and encapsulation efficiency (86%). The cellular uptake behavior of DOX-loaded MAL-PEG-Tripp micelles was visible for high-quality intracellular imaging due to the AIE property. The delivery of DOX from the drug-loaded micelles was dynamic monitored by the FRET effect between the DOX and MAL-PEG-Tripp. Both in vitro (IC50, 2.36 μg/mL) and in vivo anticancer activity tests revealed that the DOX-loaded MAL-PEG-Tripp micelles exhibited promising therapeutic efficacy to cancer with low systematic toxicity. In summary, this micelle provided an effective way to fabricate novel nanoplatform for intracellular imaging, drug-delivery tracing, and chemotherapy.


Mixed β-γ-Cyclodextrin Branched Polymer with Multiple Photo-Chemotherapeutic Cargos.
The achievement of biocompatible platforms for multimodal therapies is one of the major challenges in the burgeoning field of nanomedicine. Here, we report on a mixed β- and γ-cyclodextrin-based branched polymeric material (βγCD-NOPD) covalently integrating a nitric oxide (NO) photodonor (NOPD) within its macromolecular scaffold, and its supramolecular ensemble with a singlet oxygen (1O2) photosensitizer (PS) Zn(II) phthalocyanine (ZnPc) and the chemodrug Lenvatinib (LVB). This polymer is highly water-soluble and generates NO under visible blue light stimuli with an efficiency of more than 1 order of magnitude higher than that of the single NOPD. The PS, which in an aqueous solution is aggregated and non-photoresponsive, can be entangled in the polymeric network as a photoresponsive monomeric species. In addition, the poorly water-soluble LVB can be co-encapsulated within the polymeric host, which increases the drug solubility by more than 30-fold compared to the free drug and more than 2-fold compared with a similar branched polymer containing only βCD units. The supramolecular nanoensemble, ca. 15 nm in diameter, retains well the photochemical properties of both the NOPD and PS, which can operate in parallel under light stimuli of different energies. Irradiation with blue and red light results in the photogeneration of NO and 1O2 associated with red fluorescence emission, without inducing any photodegradation of LVB. This result is not trivial and is due to the absence of significant, mutual interactions between the NOPD, the PS and LVB both in the ground and excited states, despite these components are confined in the same host. The proposed polymeric nanoplatform may represent a potential trimodal nanomedicine for biomedical research studies, since it combines the double photodynamic action of NO and 1O2, two species that do not suffer multidrug resistance, with the therapeutic activity of a conventional chemodrug.


Bringing research findings to the clinic and back: Commentary on the special issue on mentalization in borderline personality disorder.
The articles assembled in this special issue demonstrate the broadening acceptance that a failure of "mentalization" is central in borderline personality disorder (BPD). This idea has emerged from a number of places, from astute clinicians who recognized that individuals with BPD were often limited in their ability to recognize and describe their own emotions to empirical work on emotion recognition in BPD. These articles provide a compelling argument that mentalization, with its relatively distinct and testable cognitive components, is a fertile ground for translational research. They also suggest a pathway by which empirical studies can illuminate clinical understanding. To highlight this point, it is now the routine to explain the laboratory evidence for deficits in emotional interoception to patients with BPD. This has been useful in helping to explain the internal and nuanced nature of patients' difficulties (apparent in laboratory testing but not obvious in casual encounters. This translational discussion with patients maps very closely onto an approach the editors argue for in this special issue.


Could lateral tilt mattresses be the answer to pressure ulcer prevention and management?
Pressure ulcers have been part of illness for thousands of years and are not reducing in number. Traditionally, since the Crimean War, patients have been ritually repositioned every 2 hours, regardless of the individual need. Pressure ulcers occur mainly on bony prominences, and so it makes sense to reposition into the 30 degree tilt, off of bony prominences. Nevertheless, this still takes time in order to reposition on a regular basis. It is time to look at automatic repositioning, reducing nursing time, increasing patient comfort and releasing carers to provide more social support to the patients.


Perceptions of Participants in a Group, Community, Exercise Programme for People with Multiple Sclerosis.
Purpose. The purpose of this study was to explore the perceptions of people with multiple sclerosis of a community based, group exercise programme. Method. A pragmatic programme evaluation approach using qualitative research design was adopted. Focus groups were used to gather data from 14 participants who had taken part in a RCT of community based exercise interventions for PwMS who used at most a stick to walk outdoors. Data were transcribed verbatim and thematic analysis was used to first identify categories and then to group them into themes. Results. Three themes emerged, psychological benefits, physical benefits, and knowledge gained. The psychological benefits included the role of the group as a social and motivational factor, empowerment, confidence, hope, sense of achievement, and pride. Physical benefits were improved energy and reduced fatigue and improved ability and participation. Knowledge gained caused a shift from thoughts that exercise might do harm, to sufficient knowledge that would give participants confidence to exercise themselves. The role of the group was a key element in the positive outcomes. Conclusions. The qualitative analysis supports the findings of the main trial confirming positive effects of community exercise interventions by reducing the impact of MS and fatigue and improving participation.


Multicore myopathy, microcephaly, aganglionosis, and short stature.
Multicore myopathy, classified with the benign congenital myopathies, is manifest clinically as proximal muscle weakness, hypotonia, and delayed motor development. We report an unusual case of multicore myopathy with an expanded clinical syndrome involving the central nervous system, as well as additional congenital malformations. Clinical manifestations included microcephaly, mental retardation, spasticity with hyperreflexia, cerebellar dysfunction, short stature, Hirschsprung's disease, pharyngeal web, and facial dysmorphism.


Optimizing the composition of gelatin methacryloyl and hyaluronic acid methacryloyl hydrogels to maximize mechanical and transport properties using response surface methodology.
Hydrogel materials are promising candidates in cartilage tissue engineering as they provide a 3D porous environment for cell proliferation and the development of new cartilage tissue. Both the mechanical and transport properties of hydrogel scaffolds influence the ability of encapsulated cells to produce neocartilage. In photocrosslinkable hydrogels, both of these material properties can be tuned by changing the crosslinking density. However, the interdependent nature of the structural, physical and biological properties of photocrosslinkable hydrogels means that optimizing composition is typically a complicated process, involving sequential and/or iterative steps of physiochemical and biological characterization. The combinational nature of the variables indicates that an exhaustive analysis of all reasonable concentration ranges would be impractical. Herein, response surface methodology (RSM) was used to efficiently optimize the composition of a hybrid of gelatin-methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) with respect to both mechanical and transport properties. RSM was employed to investigate the effect of GelMA, HAMA, and photoinitiator concentration on the shear modulus and diffusion coefficient of the hydrogel membrane. Two mathematical models were fitted to the experimental data and used to predict the optimum hydrogel composition. Finally, the optimal composition was tested and compared with the predicted values.


Enhanced ion anisotropy by nonconventional coordination geometry: single-chain magnet behavior for a [{Fe(II)L}2{Nb(IV)(CN)8}] helical chain compound designed with heptacoordinate Fe(II).
Nonconventional heptacoordination in combination with efficient magnetic exchange coupling is shown to yield a 1-D heteronuclear {Fe(II)Nb(IV)} compound with remarkable magnetic features when compared to other Fe(II)-based single chain magnets (SCM). Cyano-bridged heterometallic {3d-4d} and {3d-5d} chains are formed upon assembling Fe(II) bearing a pentadentate macrocycle as the blocking ligand with octacyano metallates, [M(CN)(8)](4-) (M = Nb(IV), Mo(IV), W(IV)). X-ray diffraction (single-crystal and powder) measurements reveal that the [{(H(2)O)Fe(L(1))}{M(CN)(8)}{Fe(L(1))}](infinity) architectures consist of isomorphous 1-D polymeric structures based on the alternation of {Fe(L(1))}(2+) and {M(CN)(8)}(4-) units (L(1) stands for the pentadentate macrocycle). Analysis of the magnetic susceptibility behavior revealed cyano-bridged {Fe-Nb} exchange interaction to be antiferromagnetic with J = -20 cm(-1) deduced from fitting an Ising model taking into account the noncollinear spin arrangement. For this ferrimagnetic chain a slow relaxation of its magnetization is observed at low temperature revealing a SCM behavior with Delta/k(B) = 74 K and tau(0) = 4.6 x 10(-11) s. The M versus H behavior exhibits a hysteresis loop with a coercive field of 4 kOe at 1 K and reveals at 380 mK magnetic avalanche processes, i.e., abrupt reversals in magnetization as H is varied. The origin of these characteristics is attributed to the combination of efficient {Fe-Nb} exchange interaction and significant anisotropy of the {Fe(L(1))} unit. High field EPR and magnetization experiments have revealed for the parent compound [Fe(L(1))(H(2)O)(2)]Cl(2) a negative zero field splitting parameter of D approximately = -17 cm(-1). The crystal structure, magnetic behavior, and Mossbauer data for [Fe(L(1))(H(2)O)(2)]Cl(2) are also reported.


Aggressive behavior of children exposed to intimate partner violence: an examination of maternal mental health, maternal warmth and child maltreatment.
Over 4.5 million children each year are exposed to intimate partner violence (IPV). Furthermore, IPV rarely occurs without other forms of violence and aggression in the home. IPV is associated with mental health and parenting problems in mothers, and children experience a wide variety of short-term social adjustment and emotional difficulties, including behavioral problems. The current study investigated the influence of IPV exposure on children's aggressive behavior, and tested if this relation was mediated by poor maternal mental health, and, in turn, by maternal warmth and child maltreatment, and moderated by children's age and gender. Study findings highlight the indirect consequences of IPV in the home on children's aggressive behavior. Secondary data analysis using structural equation modeling (SEM) was conducted with the National Survey of Child and Adolescent Well-Being (NSCAW). Children were between the ages of 3-8 (n = 1,161). Mothers reported past year frequency of phsycial assualt by their partner, frequency of child psychological and physical abuse, maternal mental health, and children's aggressive behavior problems. Maternal warmth was measured by observation. IPV was significantly related to poor maternal mental health. Poor maternal mental health was associated with more child aggressive behavior, lower maternal warmth, and more frequent child physical and psychological abuse. Psychological abuse and low maternal warmth were directly related to more aggressive behavior while IPV exposure and physical abuse were not directly associated with aggressive behavior. Neither age nor gender moderated the modeled paths. Expanding knowledge about child outcomes is especially critical for children who were involved in investigations of child maltreatment by child protective services (CPS) in order to identify relevant risk factors that can lead to interventions. The results identified maternal mental health as an important variable in mediating the relationship between IPV exposure and aggressive behavior. One implication is for multicomponent family interventions that could be tailored toward helping the mother cope with such mental health issues while also addressing deficits in children's social behavior development.


[Coffee hulls and pulp. XII. Effect of storage of coffee pulp on its nutritive value for calves].
Coffee pulp, dehydrated and stored for 7, 13 and 17 months or ensiled for 4, 10 and 14 months, was studied in calves with a rapid growing rate. Storage of dehydrated coffee pulp did not affect its chemical composition, but ensiling reduced crude fiber and increased its nitrogen free extract content after 10 and 14 months. Three growth trials were carried out with Holstein calves averaging 95 kg in the first and second trials, and 130 kg in the third. Eighteen calves were used in the first trial and 24 in each of the other two. In each trial the animals were divided into three equal groups and randomly assigned to one of the following treatments: control, which contained 48% cottonseed hulls, and the other two, with 30% dehydrated coffee pulp or 30% ensiled coffee pulp. Basically, the difference between trials consisted in the time of storage or ensiling of coffee pulp. In all trials, weight gains of calves fed coffee pulp (1.00, 0.90 and 0.98 kg/day, and 1.06, 0.94 and 1.08 kg/day, respectively) were significantly lower (P less than 0.05) than the weight gains induced by the control ration (1.21, 1.08 and 1.19 kg/day). Feed intake was also lower, but feed conversion ratio was higher for those rations containing coffee pulp. Calf performance was better with ensiled than with deydrated coffee pulp, particularly in the third trial, where the differences in weight gains were significantly higher (P less than 0.05). It is concluded that storage time does not change nutritive value of coffee pulp; and the ensiling is an adequate process for storing pulp during coffee harvesting, and, possibly also, for improving its nutritive value.


Improving the yield of GaAs nanowires on silicon by Ga pre-deposition.
GaAs nanowire (NW) arrays were grown by molecular beam epitaxy using the self-assisted vapor-liquid-solid method with Ga droplets as seed particles. A Ga pre-deposition step is examined to control NW yield and diameter. The NW yield can be increased with suitable duration of a Ga pre-deposition step but is highly dependent on oxide hole diameter and surface conditions. The NW diameter was determined by vapor-solid growth on the NW sidewalls, rather than Ga pre-deposition. The maximum NW yield with a Ga pre-deposition step was very close to 100%, established at shorter Ga deposition durations and for larger holes. This trend was explained within a model where maximum yield is obtained when the Ga droplet volume approximately equals the hole volume.


Simplified photometric copper-soap method for rapid assay of serum lipase activity.
We modified the method of Yang and Biggs [Clin. Chem. 17, 512 (1971)] for greater speed and simplicity. Serum is incubated with an emulsified olive oil substrate, the fatty acids extracted, the copper soap formed, and phases separated, all in a single tube. An aliquot of the organic phase is removed for color development. One analysis can be completed in 35 min, 20 in less than 2 h. The method is accurate and precise. Results correlate well with the unmodified colorimetric method, and with the classical titrimetric lipase procedure. The reference interval (normal range) is 20 to 180 U/liter.


Using grounded theory to examine people's attitudes toward how animals are used.
This study uses qualitative methodology to examine why people have different attitudes toward different types of nonhuman animal use. Seventeen participants took part in a semi-structured interview. The study used Grounded Theory to analyze the interviews and developed a model that consists of 4 major themes: (a) "attitudes toward animals," (b) "knowledge of animal use procedures," (c) "perceptions of choice," and (d) "cost-benefit analysis." The findings illustrate that cognitive processing, characteristics of the species of animal being used, and the type of animal use can all influence attitudes toward animal use. Because previous research has focused on participant variables such as age and gender to explain variance in attitudes toward animal use (Furnham & Pinder, 1990; Kellert & Berry, 1981) and measured attitudes toward animal use in general (rather than distinguishing between different types of use) (Armstrong & Hutchins, 1996), these findings can add to knowledge of people's views on animal use. This paper discusses how such views may be justified and maintained.


Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data.
To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low.


Clean Synthesis of an Economical 3D Nanochain Network of PdCu Alloy with Enhanced Electrocatalytic Performance towards Ethanol Oxidation.
A one-pot method for the fast synthesis of a 3D nanochain network (NNC) of PdCu alloy without any surfactants is described. The composition of the as-prepared PdCu alloy catalysts can be precisely controlled by changing the precursor ratio of Pd to Cu. First, the Cu content changes the electronic structure of Pd in the 3D NNC of PdCu alloy. Second, the 3D network structure offers large open pores, high surface areas, and self-supported properties. Third, the surfactant-free strategy results in a relatively clean surface. These factors all contribute to better electrocatalytic activity and durability towards ethanol oxidation. Moreover, the use of copper in the alloy lowers the price of the catalyst by replacing the noble metal palladium with non-noble metal copper. The composition-optimized Pd80 Cu20 alloy in the 3D NNC catalyst shows an increased electrochemically active surface area (80.95 m(2) g(-1) ) and a 3.62-fold enhancement of mass activity (6.16 A mg(-1) ) over a commercial Pd/C catalyst.


Stability of rare gas structure H clathrate hydrates.
Molecular dynamics simulations are used to study the stability of structure H (sH) clathrate hydrates with the rare gases Ne, Ar, Kr, and Xe. Simulations on a 3 x 3 x 3 sH unit cell replica are performed at ambient pressure at 40 and 100 K temperatures. The small and medium (s+m) cages of the sH unit cell are assigned rare gas guest occupancies of 1 and for large (l) cages guest occupancies of 1-6 are considered. Radial distribution functions for guest pairs with occupancies in the l-l, l-(s+m), and (s+m)-(s+m) cages are presented. The unit cell volumes and configurational energies are studied as a function of large cage occupancy for the rare gases. Free energy calculations are carried out to determine the stability of clathrates for large cage occupancies at 100 K and 1 bar and 20 kbar pressures. These studies show that the most stable argon clathrate has five guests in the large cages. For krypton and xenon the most stable configurations have three and two guests in the large cages, respectively.


Effectiveness and Safety of Hypodermoclysis Patients With Cancer: A Single-Center Experience From Saudi Arabia.
Decreased intake of food or fluid causes dehydration in hospitalized adult patients. This has led to a negative impact on patients and increased the morbidity and mortality rate at the Princess Noorah Oncology Center, where patients with advanced cancer who suffer from dehydration have been treated with parenteral fluids until the date of discharge from the hospital. The objective of this pilot study is to assess the effectiveness and safety of hypodermoclysis (HDC) to close the gap of treatment for home-based palliative patients with cancer. During home visits, the home health care (HHC) nurse assessed these patients through history and physical examination for dehydration. Our team also incorporated the Edmonton Symptom Assessment System revised (ESAS-r) Scale in the assessment of these patients' symptoms. Informed consent has been obtained from the patient and the caregiver. The trained nurses initiated the subcutaneous infusion. The caregivers monitored it and disconnected it when completed. The study population consists of palliative patients with advanced cancer under the services of palliative care. Effectiveness and safety have been assessed using the ESAS-r scale. A total of 25 (92.6%) HDC treatments were successfully completed for nine patients (seven males and two females). One female patient had only one session because her health had deteriorated for reasons other than dehydration and was transferred to the hospital. No serious side effects were observed. One (3.6%) patient developed redness at the site of cannula insertion. The mean duration of the infusions was 8.44 hours. The median age was 70 years. This study has concluded that HDC is effective, safe, and can enhance the patient's comfort level without the need for hospitalization. The fact that HDC can be administered at home with minimum equipment and technical support makes it an ideal option in several countries with varied income settings.


Role of genetic heterogeneity and epistasis in bladder cancer susceptibility and outcome: a learning classifier system approach.
Detecting complex patterns of association between genetic or environmental risk factors and disease risk has become an important target for epidemiological research. In particular, strategies that provide multifactor interactions or heterogeneous patterns of association can offer new insights into association studies for which traditional analytic tools have had limited success. To concurrently examine these phenomena, previous work has successfully considered the application of learning classifier systems (LCSs), a flexible class of evolutionary algorithms that distributes learned associations over a population of rules. Subsequent work dealt with the inherent problems of knowledge discovery and interpretation within these algorithms, allowing for the characterization of heterogeneous patterns of association. Whereas these previous advancements were evaluated using complex simulation studies, this study applied these collective works to a 'real-world' genetic epidemiology study of bladder cancer susceptibility. We replicated the identification of previously characterized factors that modify bladder cancer risk--namely, single nucleotide polymorphisms from a DNA repair gene, and smoking. Furthermore, we identified potentially heterogeneous groups of subjects characterized by distinct patterns of association. Cox proportional hazard models comparing clinical outcome variables between the cases of the two largest groups yielded a significant, meaningful difference in survival time in years (survivorship). A marginally significant difference in recurrence time was also noted. These results support the hypothesis that an LCS approach can offer greater insight into complex patterns of association. This methodology appears to be well suited to the dissection of disease heterogeneity, a key component in the advancement of personalized medicine.


Ecologically different earthworm species are the driving force of microbial hotspots influencing Pb uptake by the leafy vegetable Brassica campestris.
Food chain contamination by soil lead (Pb), beginning with Pb uptake by leafy vegetables, is a threat to food safety and poses a potential risk to human health. This study highlights the importance of two ecologically different earthworm species (the anecic species Amynthas aspergillum and the epigeic species Eisenia fetida) as the driving force of microbial hotspots to enhance Pb accumulation in the leafy vegetable Brassica campestris at different Pb contamination levels (0, 100, 500, and 1,000 mg·kg-1). The fingerprints of phospholipid fatty acids (PLFAs) were employed to reveal the microbial mechanism of Pb accumulation involving earthworm-plant interaction, as PLFAs provide a general profile of soil microbial biomass and community structure. The results showed that Gram-positive (G+) bacteria dominated the microbial community. At 0 mg·kg-1 Pb, the presence of earthworms significantly reduced the total PLFAs. The maximum total of PLFAs was found at 100 mg·kg-1 Pb with E. fetida inoculation. A significant shift in the bacterial community was observed in the treatments with E. fetida inoculation at 500 and 1,000 mg·kg-1 Pb, where the G+/G- bacteria ratio was significantly decreased compared to no earthworm inoculation. Principal component analysis (PCA) showed that E. fetida had a greater effect on soil microbial hotspots than A. aspergillum, thus having a greater effect on the Pb uptake by B. campestris. Redundancy analysis (RDA) showed that soil microbial biomass and structure explained 43.0% (R2 = 0.53) of the total variation in Pb uptake by B. campestris, compared to 9.51% of microbial activity. G- bacteria explained 23.2% of the total variation in the Pb uptake by B. campestris, significantly higher than the other microbes. The Mantel test showed that microbial properties significantly influenced Pb uptake by B. campestris under the driving force of earthworms. E. fetida inoculation was favorable for the G- bacterial community, whereas A. aspergillum inoculation was favorable for the fungal community. Both microbial communities facilitated the entry of Pb into the vegetable food chain system. This study delivers novel evidence and meaningful insights into how earthworms prime the microbial mechanism of Pb uptake by leafy vegetables by influencing soil microbial biomass and community composition. Comprehensive metagenomics analysis can be employed in future studies to identify the microbial strains promoting Pb migration and develop effective strategies to mitigate Pb contamination in food chains.


Comparing different methods for fast screening of microbiological quality of beach sand aimed at rapid-response remediation.
There is scientific evidence that beach sands are a significant contributor to the pathogen load to which visitors are exposed. To develop beach quality guidelines all beach zones must be included in microbiological evaluations, but monitoring methods for beach sand quality are relatively longstanding, expensive, laborious and require moderate laboratory infrastructure. This paper aimed to evaluate the microorganism activity in different beach zones applying and comparing a classical method of membrane filtration (MF) with two colorimetric screening methods based on fluorescein (FDA) and tetrazolium (TTC) salt biotransformation to evaluate a new rapid and low-cost method for beach sand microbiological contamination assessments. The colorimetric results can help beach managers to evaluate rapidly and at low cost the microbiological quality of different beach zones in order to decide whether remedial actions need to be adopted to prevent exposure of the public to microbes due to beach sand and/or water contamination.


Seasonal and tissue distribution of Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, in retail freshwater fish in Hong Kong.
Laribacter hongkongensis, a recently discovered bacterium associated with community-acquired gastroenteritis, has been found in the intestines of freshwater fish. To better understand the epidemiology and ecology of the bacterium, we carried out a surveillance study to investigate possible seasonal variation in the recovery of L. hongkongensis and its distribution in various organs in retail freshwater fish in Hong Kong. Forty whole freshwater fish of two species (20 grass carps and 20 bighead carps), and intestines from 120 grass carps were sampled during a one-year period. L. hongkongensis was isolated from 11 (55%) of the 20 grass carps and 6 (30%) of the 20 bighead carps; and the intestines of 49 (41%) of 120 grass carps. Seasonal variation in the recovery of L. hongkongensis from both whole fish and intestines was observed, with higher isolation rates in spring and summer than in fall and winter. There was also positive correlation between temperature and the isolation rates. When L. hongkongensis was cultured in vitro at different temperatures, shorter lag time and higher growth rate were observed at higher temperatures, with 37 degrees C being optimal among the tested temperatures. L. hongkongensis was commonly found in the gills, stomachs and intestines in both grass carps and bighead carps, and on the skin surface of one fish, but not in other organs. Proper handling of freshwater fish for cooking, especially the gills and gut, is recommended to prevent acquisition of L. hongkongensis, and other freshwater fish related infections.


Characterizing the roles of alpha and theta oscillations in multisensory attention.
Cortical alpha oscillations (8-13Hz) appear to play a role in suppressing distractions when just one sensory modality is being attended, but do they also contribute when attention is distributed over multiple sensory modalities? For an answer, we examined cortical oscillations in human subjects who were dividing attention between auditory and visual sequences. In Experiment 1, subjects performed an oddball task with auditory, visual, or simultaneous audiovisual sequences in separate blocks, while the electroencephalogram was recorded using high-density scalp electrodes. Alpha oscillations were present continuously over posterior regions while subjects were attending to auditory sequences. This supports the idea that the brain suppresses processing of visual input in order to advantage auditory processing. During a divided-attention audiovisual condition, an oddball (a rare, unusual stimulus) occurred in either the auditory or the visual domain, requiring that attention be divided between the two modalities. Fronto-central theta band (4-7Hz) activity was strongest in this audiovisual condition, when subjects monitored auditory and visual sequences simultaneously. Theta oscillations have been associated with both attention and with short-term memory. Experiment 2 sought to distinguish these possible roles of fronto-central theta activity during multisensory divided attention. Using a modified version of the oddball task from Experiment 1, Experiment 2 showed that differences in theta power among conditions were independent of short-term memory load. Ruling out theta's association with short-term memory, we conclude that fronto-central theta activity is likely a marker of multisensory divided attention.


The Geoglobus acetivorans genome: Fe(III) reduction, acetate utilization, autotrophic growth, and degradation of aromatic compounds in a hyperthermophilic archaeon.
Geoglobus acetivorans is a hyperthermophilic anaerobic euryarchaeon of the order Archaeoglobales isolated from deep-sea hydrothermal vents. A unique physiological feature of the members of the genus Geoglobus is their obligate dependence on Fe(III) reduction, which plays an important role in the geochemistry of hydrothermal systems. The features of this organism and its complete 1,860,815-bp genome sequence are described in this report. Genome analysis revealed pathways enabling oxidation of molecular hydrogen, proteinaceous substrates, fatty acids, aromatic compounds, n-alkanes, and organic acids, including acetate, through anaerobic respiration linked to Fe(III) reduction. Consistent with the inability of G. acetivorans to grow on carbohydrates, the modified Embden-Meyerhof pathway encoded by the genome is incomplete. Autotrophic CO2 fixation is enabled by the Wood-Ljungdahl pathway. Reduction of insoluble poorly crystalline Fe(III) oxide depends on the transfer of electrons from the quinone pool to multiheme c-type cytochromes exposed on the cell surface. Direct contact of the cells and Fe(III) oxide particles could be facilitated by pilus-like appendages. Genome analysis indicated the presence of metabolic pathways for anaerobic degradation of aromatic compounds and n-alkanes, although an ability of G. acetivorans to grow on these substrates was not observed in laboratory experiments. Overall, our results suggest that Geoglobus species could play an important role in microbial communities of deep-sea hydrothermal vents as lithoautotrophic producers. An additional role as decomposers would close the biogeochemical cycle of carbon through complete mineralization of various organic compounds via Fe(III) respiration.


Anatomy and biomechanical properties of the plantar aponeurosis: a cadaveric study.
To explore the anatomy of the plantar aponeurosis (PA) and its biomechanical effects on the first metatarsophalangeal (MTP) joint and foot arch. Anatomic parameters (length, width and thickness of each central PA bundle and the main body of the central part) were measured in 8 cadaveric specimens. The ratios of the length and width of each bundle to the length and width of the central part were used to describe these bundles. Six cadaveric specimens were used to measure the range of motion of the first MTP joint before and after releasing the first bundle of the PA. Another 6 specimens were used to evaluate simulated static weight-bearing. Changes in foot arch height and plantar pressure were measured before and after dividing the first bundle. The average width and thickness of the origin of the central part at the calcaneal tubercle were 15.45 mm and 2.79 mm respectively. The ratio of the length of each bundle to the length of the central part was (from medial to lateral) 0.29, 0.30, 0.28, 0.25, and 0.27, respectively. Similarly, the ratio of the widths was 0.26, 0.25, 0.23, 0.19 and 0.17. The thickness of each bundle at the bifurcation of the PA into bundles was (from medial to lateral) 1.26 mm, 1.04 mm, 0.91 mm, 0.84 mm and 0.72 mm. The average dorsiflexion of the first MTP joint increased 10.16° after the first bundle was divided. Marked acute changes in the foot arch height and the plantar pressure were not observed after division. The first PA bundle was not the longest, widest, or the thickest bundle. Releasing the first bundle increased the range of motion of the first MTP joint, but did not acutely change foot arch height or plantar pressure during static load testing.


What Explains Divorced Women's Poorer Health?: The Mediating Role of Health Insurance and Access to Health Care in a Rural Iowan Sample*
The economic restructuring in rural areas in recent decades has been accompanied by rising marital instability. To examine the implications of the increase in divorce for the health of rural women, we examine how marital status predicts adequacy of health insurance coverage and health care access, and whether these factors help to account for the documented association between divorce and later illness. Analyzing longitudinal data from a cohort of over 400 married and recently divorced rural Iowan women, we decompose the total effect of divorce on physical illness a decade later using structural equation modeling. Divorced women are less likely to report adequate health insurance in the years following divorce, inhibiting their access to medical care and threatening their physical health. Full-time employment acts as a buffer against insurance loss for divorced women. The growth of marital instability in rural areas has had significant ramifications for women's health; the decline of adequate health insurance coverage following divorce explains a component of the association between divorced status and poorer long-term health outcomes.


Serial and parallel attentive visual searches: evidence from cumulative distribution functions of response times.
Participants searched a visual display for a target among distractors. Each of 3 experiments tested a condition proposed to require attention and for which certain models propose a serial search. Serial versus parallel processing was tested by examining effects on response time means and cumulative distribution functions. In 2 conditions, the results suggested parallel rather than serial processing, even though the tasks produced significant set-size effects. Serial processing was produced only in a condition with a difficult discrimination and a very large set-size effect. The results support C. Bundesen's (1990) claim that an extreme set-size effect leads to serial processing. Implications for parallel models of visual selection are discussed.


Fatal aluminium phosphide poisoning.
Aluminium phosphide (AlP) is a cheap solid fumigant and a highly toxic pesticide which is commonly used for grain preservation. AlP has currently aroused interest with a rising number of cases in the past four decades due to increased use for agricultural and non-agricultural purposes. Its easy availability in the markets has increased also its misuse for committing suicide. Phosphine inhibits cellular oxygen utilization and can induce lipid peroxidation. Poisoning with AlP has often occurred in attempts to commit suicide, and that more often in adults than in teenagers. This is a case of suicidal consumption of aluminium phosphide by a 32-year-old young medical anesthetist. Toxicological analyses detected aluminium phosphide. We believe that free access of celphos tablets in grain markets should be prohibited by law.