Effects of control strategies on gait in robot-assisted post-stroke lower limb rehabilitation: a systematic review.
Stroke related motor function deficits affect patients' likelihood of returning to professional activities, limit their participation in society and functionality in daily living. Hence, robot-aided gait rehabilitation needs to be fruitful and effective from a motor learning perspective. For this reason, optimal human-robot interaction strategies are necessary to foster neuroplastic shaping during therapy. Therefore, we performed a systematic search on the effects of different control algorithms on quantitative objective gait parameters of post-acute stroke patients. We conducted a systematic search on four electronic databases using the Population Intervention Comparison and Outcome format. The heterogeneity of performance assessment, study designs and patients' numerosity prevented the possibility to conduct a rigorous meta-analysis, thus, the results were presented through narrative synthesis. A total of 31 studies (out of 1036) met the inclusion criteria, without applying any temporal constraints. No controller preference with respect to gait parameters improvements was found. However, preferred solutions were encountered in the implementation of force control strategies mostly on rigid devices in therapeutic scenarios. Conversely, soft devices, which were all position-controlled, were found to be more commonly used in assistive scenarios. The effect of different controllers on gait could not be evaluated since conspicuous heterogeneity was found for both performance metrics and study designs. Overall, due to the impossibility of performing a meta-analysis, this systematic review calls for an outcome standardisation in the evaluation of robot-aided gait rehabilitation. This could allow for the comparison of adaptive and human-dependent controllers with conventional ones, identifying the most suitable control strategies for specific pathologic gait patterns. This latter aspect could bolster individualized and personalized choices of control strategies during the therapeutic or assistive path.


Computer-Aided Design and Production of RNA Origami as Protein Scaffolds and Biosensors.
RNA nanotechnology is able to take advantage of the modularity of RNA to build a wide variety of structures and functional devices from a common set of structural modules. The RNA origami architecture harnesses the property of RNA to fold as it is being enzymatically synthesized by the RNA polymerase and enables the design of single-stranded devices that integrate multiple structural and functional RNA motifs. Here, we provide detailed procedures on how to design and characterize RNA origami structures. The process is illustrated by two examples: one that forms lattices and another example that acts as biosensors.


Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.
Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 +/- 0.8 sec. However, arterial partial-volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus-tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations.


Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016.


The indigenization of neurasthenia in Hong Kong.
Despite its origin in Western psychiatry, neurasthenia has become a popular concept in Chinese folk medicine, referring to a variety of somatic and psychological symptoms. Review of Chinese medicinal materials and patent medicines shows that neurasthenia is associated more often with somatic symptoms in tonic type medicine and with psychological and psychosomatic symptoms in sedative and tranquilizer type medicine. Popular Chinese books on neurasthenia suggest that causes might be attributed to lifestyle, psychological factors, and health problems. Recommendations on treatment emphasize self-help approaches through changing lifestyle, examining attitudes, tonic care, and relaxation. As a broad term used loosely by professionals and the lay public in Hong Kong, neurasthenia serves the important function of destigmatizing psychiatric disorders. Psychosexual problems may also be conveyed discreetly through somatic presentation. The indigenization of neurasthenia exemplifies how an originally Western concept acquires cultural meaning. Implications of illness conceptualization and the medical paradigm are discussed.


Black soybean anthocyanins attenuate inflammatory responses by suppressing reactive oxygen species production and mitogen activated protein kinases signaling in lipopolysaccharide-stimulated macrophages.
Oxidative stress is closely related with inflammation and development of many diseases. Black soybean seed coat contains high amount of anthocyanins, which are well-known for free radical scavenging activities. This study investigated inflammatory response and action mechanism of black soybean anthocyanins with regard to antioxidant activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RAW 264.7 cells were treated with anthocyanins extracted from black soybean seed coats in a concentration range of 12.5 to 100 µg/mL. The production of reactive oxygen species (ROS), secretion of pro-inflammatory mediators and cytokines, and the signaling in the mitogen activated protein kinases (MAPKs) pathway were examined. Black soybean anthocyanins significantly decreased LPS-stimulated production of ROS, inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and pro-inflammatory cytokines, including tumor necrosis factor α and interleukin-6, in a dose-dependent manner without cytotoxicity (P < 0.001). Black soybean anthocyanins downregulated the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells (P < 0.001). Moreover, black soybean anthocyanins inhibited LPS-induced phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 (P < 0.001). These results suggest that black soybean anthocyanins exert anti-inflammatory activity by inhibiting ROS generation and subsequent MAPKs signaling, thereby inhibiting inflammatory responses.


Amygdala response to smoking-cessation messages mediates the effects of serotonin transporter gene variation on quitting.
The amygdala is critically involved in detecting emotionally salient stimuli and in enhancing memory for emotional information. Growing evidence also suggests that the amygdala plays a crucial role in addiction, perhaps by strengthening associations between emotionally-charged drug cues and drug-seeking behavior. In the current study, by integrating functional MRI (fMRI), genetics, and outcome data from a large group of smokers who completed a smoking-cessation intervention and attempted to quit, we show that the amygdala also plays a role in quitting. Specifically, we demonstrate that the amygdala response to smoking-cessation messages in smokers trying to quit is a predictor of their post-intervention quitting outcome. We further show that the amygdala response is modulated by genetic variation in the serotonin transporter and mediates the impact of this genetic variation on quitting. These results point to a gene-brain-behavior pathway relevant to smoking cessation, and add to our understanding of the role of the amygdala in nicotine addiction.


Memory Lapses-Winning the Slow Race.
Pre-existing humoral immunity can impact immune responses to heterologous infections. In this issue of Immunity, Wong et al. reveal that memory B cells, while failing to re-enter the germinal center, create an affinity-restricted, diversified B cell repertoire for rapid plasma blast responses. Their findings have important implications to vaccine design.


Near-total gastrectomy for gastric cancer.
Fifty-nine consecutive patients (95 percent) with gastric cancer of the distal portion of the stomach were operated on with 95 percent subtotal gastrectomy between 1975 and 1980. The operations were for cure in all cases. Twenty-five patients were alive after 5 years, for a crude 5 year survival rate of 42 percent. The operative mortality rate was 5 percent (three patients). Twenty-four patients (41 percent) had complications, which consisted of postoperative respiratory infection in 11 patients (19 percent), postoperative ileus in 4 patients (7 percent), and subphrenic abscess in 2 patients (3.4 percent). In addition, there was one wound dehiscence and one liver rupture (with fatal outcome), one deep venous thrombosis, one urinary infection, and one wound infection. Only one patient (1.7 percent) had an anastomotic leak at the gastrojejunostomy site. Seven relaparotomies (12 percent) had to be performed for complications. We have concluded that, in patients with distal gastric cancer, 95 percent subtotal gastrectomy can result in a 5 year survival rate that is comparable to that reported in the literature for total gastrectomy, and it has the advantage of a very low rate of anastomotic leakage between the minute gastric remnant and the jejunum. Therefore, 95 percent subtotal gastrectomy is recommended over total gastrectomy in the treatment of distal gastric cancer.


Does IV Iron Induce Plasma Oxidative Stress in Critically Ill Patients? A Comparison With Healthy Volunteers.
To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers. Multicenter, interventional study. Two ICUs and one clinical research center. Anemic critically ill patients treated with IV iron and healthy volunteers. IV infusion of 100 mg of iron sucrose. Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7-9.2]) (men, 25 [66%]; aged 68 yr [48-77]; Simplified Acute Physiology Score II, 48.5 [39-59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29-50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation-8α-isoprostanes, protein oxidation-advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5-12.9] vs 4.6 pmol/L [3.5-5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes. In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.


Dynamic not isometric training blunts osteo-renal disease and improves the sclerostin/FGF23/Klotho axis in maintenance hemodialysis patients: a randomized clinical trial.
This study compared the effectiveness of dynamic resistance training (DRT) versus isometric RT (IRT) on osteogenesis and hormonal mechanisms involved in maintenance hemodialysis (MHD) patients. One hundred and ninety-three MHD patients were randomized into three groups: control (CTL) (n = 60), DRT (n = 66), and IRT (n = 67). A first visit was required for an anamnesis to evaluate the number of medications, biochemical, and anthropometric measurements (dialysis adequacy, creatinine, urea, body mass, height, and body mass index). Grip strength, bone mineral density (BMD), and renal-bone markers were assessed pre- and postprotocol. The DRT and IRT training was 6 mo with a frequency of three times per week, on alternate days. Each training session consisted of three sets of 8 to 12 repetitions at lower and moderate intensities. Both training sessions were prescribed approximately 1 h prior to dialysis. Statistical significances were adopted with P < 0.05. There was a greater dropout in the IRT group (24%) as compared with the DRT group (14%), which in turn had less adverse clinical effects (67%, 24%, and 61% for CTL, DRT, and IRT, respectively). DRT promoted gains in BMD in different body locations, in addition to increasing pro-osteogenic factors (Klotho and calcitriol) and reducing those related to bone loss, such as sclerostin, FGF23, and PTH. There was an improvement in Ca × PO43 for DRT, whereas these benefits did not occur in the IRT group (P < 0.05). These novel findings suggest that the DRT generates biopositive adaptations in bone tissue in MHD and can be used as a nonpharmacological strategy to improve BMD.NEW & NOTEWORTHY This study shows, for the first time, the effect of dynamic and isometric resistance training on bone mineral density in hemodialysis patients, providing a new understanding of the possible participation of the sclerostin/FGF23/Klotho axis, vitD, PTH, and calcium × phosphate product in this process. However, isometric resistance training may not be sufficient to induce these benefits. Therefore, this study supports the potential therapeutic role of dynamic resistance training counteracting chronic kidney disease-mineral and bone disorder.


Improved mineral balance in very low birth weight infants fed fortified human milk.
Enhanced calcium and phosphorus retention was achieved in 16 very low birth weight infants (birth weight 1117 +/- 42 g, gestation 29 +/- 0.2 weeks) fed a preparation of fortified human milk augmented with calcium lactate and monobasic and dibasic phosphate salts. Measurements of growth and macronutrient utilization were similar to those obtained in a previous study of infants fed a preparation of fortified human milk that contained lower levels of calcium and phosphorus. However, unlike the relative hypophosphatemia, hypophosphaturia, and hypercalciuria noted in the infants in our earlier study, normal serum and urine phosphorus and urine calcium values were observed in this study. Postnatal calcium and phosphorus retentions correlated significantly with respective intakes, the absorption of fat, and the retention of nitrogen. The relationships among calcium and phosphorus intake and retention predict that 160 mg/kg/d and 94 mg/kg/d, respectively, must be fed to achieve retention equivalent to intrauterine estimates. Although postnatal retention of calcium and phosphorus may be increased to levels accumulated by the fetus, technical considerations for the preparation of a formula with sufficiently high levels of calcium and phosphorus must be resolved.


Protective effect of isoflavone derivative against photocarcinogenesis in a mouse model.
Plant-derived isoflavones are currently receiving much attention because of their phyto-estrogenic and antioxidant activities. In this study, we describe novel photoprotective effects of one isoflavone derivative from red clover (NV07), following its application topically in Skh:HR-1 hairless mice. We found that in mice irradiated in the short-term (3 days) with minimally erythemal solar simulated UV radiation, topical lotions containing NV07 dose-responsively reduced the erythema-associated oedema, the induction of ornithine decarboxylase, and the suppression of contact hypersensitivity. In mice irradiated chronically (50 days), daily application of topical NV07-lotion reduced photocarcinogenesis significantly, and appeared to be actively protective during both the initiation phase and the later promotion phase of tumour induction.


Improving outcomes in pediatric procedural sedation.
In Fall 2003, Chris Evert Children's Hospital (CECH; Fort Lauderdale, Florida) exclusively used chloral hydrate for moderate sedation. As procedures became longer and more complex, pentobarbital became the primary sedative used. Yet children receiving pentobarbital were awakening during the procedure from paradoxical drug reactions or insufficient sedation. In 2003, the failed sedation rate was 12.29%--more than six times the national benchmark of 2%. The pediatric sedation team created a pediatric sedation protocol, which reflected the designation of an a2-adrenergic agonist, dexmedetomidine (dex), as the drug of choice and spearheaded a variety of performance improvement changes, including creation of a stand-alone eight-bed sedation unit to accommodate the registration process and pre-assessment and postprocedure monitoring and to include the parent in the treatment continuum. Following the implementation of the new protocol in 2003, the failed sedation rate for children undergoing various diagnostic and therapeutic procedures decreased from 12.29% to 1.63% in 2004, 0.19% in 2005, and 0.28% in 2006; in 2007 the rate was 0.72%--reflecting an average 98% reduction in the failed sedation rate. The continued improvement and success in pediatric sedation over time indicates that the protocol has sustained benefits and lasting value.


Accumulation of 3,4-dihydroxyphenylglycolaldehyde, the neurotoxic monoamine oxidase A metabolite of norepinephrine, in locus ceruleus cell bodies in Alzheimer's disease: mechanism of neuron death.
3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the neurotoxic monoamine oxidase A (MAO-A) metabolite of norepinephrine (NE). NE neurons in the locus ceruleus (LC) die in Alzheimer's disease (AD). To determine if DOPEGAL could contribute to NE neuron death in AD we measured levels of DOPEGAL, NE and their synthesizing enzymes in LC from AD and matched controls. We found 2.8- and 3.6-fold increases in DOPEGAL and MAO-A in AD LC neuronal cell bodies compared to controls. NE and dopamine beta-hydroxylase were increased by 3.8- and 10.7-fold, respectively. Implications for the mechanism of neuron death in AD are discussed.


Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies.
In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.


Conditions controlling tumor cytotoxicity of rat liver macrophages mediated by liposomal muramyl dipeptide.
Activation of rat liver macrophages with free and liposome-encapsulated muramyl dipeptide (MDP) to a tumorcytotoxic state was characterized by employing various experimental conditions. Macrophage-mediated tumor cytotoxicity was determined using two standard assay systems: a [methyl-3H]thymidine release assay to measure the extent of tumor cell lysis and a [methyl-3H]thymidine incorporation assay to measure the combined effects of tumor cell lysis and stasis. The extent of cell lysis was not affected by the ratio of macrophages to tumor cells within the ratio range of 30:1 to 5:1, provided that the macrophages form a confluent monolayer. Tumor cell lysis, however, was significantly influenced by macrophage density; a low macrophage density for example resulted in a low percentage of tumor cell lysis. Tumor target cells used in this study, i.e., C26 adenocarcinoma, B16 melanoma and P815 mastocytoma, differed in their susceptibility towards macrophage-mediated cell lysis, whereas no differences were observed with respect to tumor cell stasis. Non-tumorigenic cell lines such as human fibroblastic cells and LLC monkey kidney cells were not lysed by activated macrophages, although proliferation of these cells was markedly inhibited. Additionally, the effects of liposomal lipid composition on macrophage activation were studied. With a basic composition of phospholipid/cholesterol/dicetylphosphate, we used either egg-yolk, dipalmitoyl-, distearoyl- or dihexadecylphosphatidylcholine as the bulk phospholipid constituent. Although these liposomes display a widely different susceptibility to lysosomal phospholipase activities, we could not detect any significant difference in either the extent or the duration of the tumoricidal activity induced by MDP encapsulated in these different types of liposomes.


The potential role of sestrin 2 in liver regeneration.
Liver regeneration is a remarkably complex phenomenon conserved across all vertebrates, enabling the restoration of lost liver mass in a matter of days. Unfortunately, extensive damage to the liver may compromise this process, often leading to the death of affected individuals. Ischemia/reperfusion injury (IRI) is a common source of damage preceding regeneration, often present during liver transplantation, resection, trauma, or hemorrhagic shock. Increased oxidative stress and mitochondrial dysfunction are key hallmarks of IRI, which can jeopardize the liver's ability to regenerate. Therefore, a better understanding of both liver regeneration and IRI is of important clinical significance. In the current review, we discuss the potential role of sestrin 2 (SESN2), a novel anti-aging protein, in liver regeneration and ischemia/reperfusion preceding regeneration. We highlight its beneficial role in protecting cells from mitochondrial dysfunction and oxidative stress as key aspects of its involvement in liver regeneration. Additionally, we describe how its ability to promote the expression of Nrf2 bears significant importance in this context. Finally, we focus on a potential novel link between SESN2, mitohormesis and ischemic preconditioning, which could explain some of the protective effects of preconditioning.


Surgical treatment of pancreas divisum causing pancreatitis in children.
Although controversial, pancreas divisum has been implicated as a cause of acute pancreatitis when there is stenosis of the accessory papilla that drains the duct of Santorini. Over the past 5 years, four children with pancreas divisum and recurrent pancreatitis were successfully treated surgically. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) in each case. Surgical treatment included sphincteroplasty to the accessory papilla to improve drainage of the duct of Santorini, opening the ampulla of Vater to expose the ostium of the duct of Wirsung to enlarge it, and cholecystectomy.


TREK-1 Null Impairs Neuronal Excitability, Synaptic Plasticity, and Cognitive Function.
TREK-1, a two-pore-domain K+ channel, is highly expressed in the central nervous system. Although aberrant expression of TREK-1 is implicated in cognitive impairment, the cellular and functional mechanism underlying this channelopathy is poorly understood. Here we examined TREK-1 contribution to neuronal morphology, excitability, synaptic plasticity, and cognitive function in mice deficient in TREK-1 expression. TREK-1 immunostaining signal mainly appeared in hippocampal pyramidal neurons, but not in astrocytes. TREK-1 gene knockout (TREK-1 KO) increases dendritic sprouting and the number of immature spines in hippocampal CA1 pyramidal neurons. Functionally, TREK-1 KO increases neuronal excitability and enhances excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). The increased EPSCs appear to be attributed to an increased release probability of presynaptic glutamate and functional expression of postsynaptic AMPA receptors. TREK-1 KO decreased the paired-pulse ratio and severely occluded the long-term potentiation (LTP) in the CA1 region. These altered synaptic transmission and plasticity are associated with recognition memory deficit in TREK-1 KO mice. Although astrocytic expression of TREK-1 has been reported in previous studies, TREK-1 KO does not alter astrocyte membrane K+ conductance or the syncytial network function in terms of syncytial isopotentiality. Altogether, TREK-1 KO profoundly affects the cellular structure and function of hippocampal pyramidal neurons. Thus, the impaired cognitive function in diseases associated with aberrant expression of TREK-1 should be attributed to the failure of this K+ channel in regulating neuronal morphology, excitability, synaptic transmission, and plasticity.


[Tentative classification of the nematodes Trichostrongyloidea (author's transl)].
Taking into consideration the evolution of different characters, and mainly the evolutionary pattern of the "synlophe", we propose to divide the Trichostrongyloidea into 8 families: Ollulanidae, Dictyocaulidae, Strongylacanthidae, Amidostomatidae, Molineidae, Heligmosomidae, Heligmonellidae and Trichostrongylidae.


Evaluating sediment stability at sites with historic contamination.
The stability of cohesive sediment deposits during a rare storm is a critical component in the evaluation of remedial options at a contaminated sediment site. Estimating scour depths during a rare storm, and the resulting contaminant concentrations in the surficial layer of the bed, is necessary for comparing the efficacy of various remedial alternatives. Evaluation of sediment stability is accomplished using sediment transport analyses that employ quantitative procedures. Qualitative analyses or conceptual models can be useful for developing and validating quantitative analysis tools; however, qualitative techniques alone generally are insufficient for conducting defensible remedial alternative evaluations. The level of analysis used for a specific site depends on data availability, required level of accuracy, and time and budget constraints. A tier 1 analysis involves the use of approximate equations to produce order-of-magnitude estimates of scour depths during a rare storm. The second tier of this analysis scheme employs the development and application of a sediment transport model to evaluate bed stability. State-of-the-science sediment transport models have been effectively used as management tools for evaluating remedial options at several contaminated sediment sites. It should not be presumed that rare storm events cause catastrophic impacts at the site under review. Two case studies demonstrate that a rare storm is not necessarily catastrophic; significant increases in surficial bed concentrations caused by reexposure of elevated concentrations buried at depth in the bed will not necessarily occur during a rare storm. However, it is important to note that sediment stability is site-specific.


Laser induced thermal lens spectrometry for cobalt determination after cloud point extraction.
A new approach, employing cloud point extraction (CPE) in combination with thermal lens spectrometry (TLS), has been developed for the determination of cobalt. The CPE and TLS methods have good matching conditions for combination because TLS is suitable for low volume samples obtained after CPE and for organic solvents, which are used for dissolving the remaining analyte phase. 1-(2-Pyridylazo)-2-naphthol (PAN) was used as a complexing agent and octylphenoxypolyethoxyethanol (Triton X-114) was added as a surfactant; then the pH of solution was adjusted. After phase separation at 50 degrees C based on the cloud point extraction of the mixture, the surfactant-rich phase was dried and the remaining phase was dissolved using 20 microL of carbon tetrachloride. The obtained solution was introduced into the quartz micro cell and the analyte was determined by thermal lens spectrometry. The He-Ne laser (632.8 nm) was used as both the probe and the excite source. Under optimum conditions, the analytical curve was linear for the concentration range of 0.2-40 ng mL(-1) and the detection limit was 0.03 ng mL(-1). The enhancement factor of 470 was achieved for a 10 mL sample. Relative standard deviations were lower than 5%. The method was successfully applied to the extraction and determination of cobalt in tap, river and sea water.


Upper abdominal shape as a risk factor of extended operation time and severe postoperative complications in HCC hepatectomy through subcostal incision.
Subcostal incision is the most widely used approach in open surgery for patients with hepatocellular carcinoma (HCC). Body shape is recognised to be a factor influencing the difficulty of surgery; however, the exact impact of the increased difficulty on the patients' operation as well as the outcome has not been analysed. In this study, we retrospectively studied the possible influence of patients' body shape, tumour burden and varied surgical methods on the operation procedure and postoperative complications. From January 2009 to December 2013, 651 patients with HCC were included in the study. We studied the patients' sex, age, body mass index, upper abdominal body shape described by the depth-to-width ratio for the trunk at the celiac axis on CT/MRI, Child-Pugh classification, tumour burden and a different liver dissection method before the surgery and used a regression model for analysis. Prolonged operation time is associated with advanced tumour stage, large CA ratio, previous abdominal surgery, selective hepatic vascular occlusion and dissecting with Cavitron ultrasonic surgical aspirator rather than clamp crushing. Surgical blood loss is associated with operation time, liver function and a different liver dissection method. The incidence of severe postoperative complication was 17.5% (114/651) and was associated with larger CA ratio, Child-Pugh stage B liver function and greater blood loss. Large upper abdominal shape is a risk factor of both prolonged operation time and severe postoperative complication. CA ratio combined with liver function and surgical blood loss has an acceptable power to predict severe postoperative complications.


The steady-state Michaelis-Menten analysis of P-glycoprotein mediated transport through a confluent cell monolayer cannot predict the correct Michaelis constant Km.
Typically, the kinetics of membrane transport is analyzed using the steady-state Michaelis-Menten (or Eadie-Hofstee or Hanes) equations. This approach has been successful when the substrate is picked up from the aqueous phase, like a water-soluble enzyme, for which the Michaelis-Menten steady-state analysis was developed. For membrane transporters whose substrate resides in the lipid bilayer of the plasma membrane, like P-glycoprotein (P-gp), there has been no validation of the accuracy of the steady-state analysis because the elementary rate constants for transport were not known. Recently, we fitted the mass action elementary kinetic rate constants of P-gp transport of three different drugs through a confluent monolayer of MDCKII-hMDR1 cells. With these elementary rate constants in hand, we use computer simulations to assess the accuracy of the steady-state Michaelis-Menten parameters. This limits the simulation to parameter ranges known to be physiologically relevant. Using over 2,300 different vectors of initial elementary parameters spanning the space bounded by the three drugs, which defines 2,300 "virtual substrates", the concentrations of substrate transported were calculated and fitted to Eadie-Hofstee plots. Acceptable plots were obtained for 1,338 cases. The fitted steady-state Vmax values from the analysis correlated to within a factor of 2-3 with the values predicted from the elementary parameters. However, the fitted Km value could be generated by a wide range of underlying "molecular" Km values. This is because of the convolution of the drug passive permeability kinetics into the fitted Km. This implies that Km values measured in simpler systems, e.g., microsomes or proteoliposomes, even if accurate, would not predict the Km values for the confluent monolayer system or, by logical extension, in vivo. Reliable in vitro-in vivo extrapolation seems to require using the elementary rate constants rather than the Michaelis-Menten steady-state parameters.


Lung function improvement in asthma with a cysteinyl-leukotriene receptor antagonist.
In a double-blind study ten asthmatic patients with impaired lung function received the cysteinyl-leukotriene receptor antagonist ICI 204,219 (40 mg by mouth) and placebo in random order on 2 days at least 1 week apart. The increase in forced expiratory volume in 1 s (FEV1) above baseline was significantly greater after ICI 204,219 than after placebo. This effect persisted after nebulised salbutamol. These findings suggest that cysteinyl-leukotrienes are one of the causes of persistent bronchoconstriction in chronic asthma.


Differential anatomical and cellular patterns of connexin43 expression during postnatal development of rat brain.
We have shown previously that connexin43 in the adult rat central nervous system (CNS) is predominantly localized at astrocytic gap junctions. Here we document immunohistochemically the emergence of connexin43-immunoreactive (connexin43-IR) structures and the regional patterns of connexin43 expression during postnatal maturation of the rat brain. On Western blots, connexin43 was detected in brain samples at postnatal day (P) 5, the earliest age studied. Immunohistochemically, most brain regions displayed a characteristic sequence of transient immunoreactive profiles that ultimately gave rise to the uneven distribution of the protein seen in adults. Generally, brains at P1-P5 exhibited long, fibrous connexin43-IR elements which were identified as radial glial cells. This fibrous immunostaining was considerably diminished at P5 and was replaced by short immunoreactive processes which predominated up to P10. These processes had a stellate appearance, emanated from partially stained astrocytic cell bodies and were heterogeneously distributed throughout the developing brain. By P15, there occurred only punctate immunolabelling similar to that seen in adult brain. Some brain regions including the amygdaloid complex, septohypothalamic nucleus, preoptic hypothalamus, zona incerta, ependyma and subfornical organ were exceptional in that they displayed adult immunostaining patterns at early postnatal ages suggesting a precocious maturation of gap junctions in these areas. We conclude that the highly heterogeneous distribution of connexin43-immunoreactivity among defined nuclear structures in adult brain does not reflect an antecedent requirement for connexin43 in early brain morphogenesis, but rather is related to the development of neuronal activity, the establishment of functional circuitry and the contribution of astrocytic gap junctions to glial metabolic coupling and potassium spatial buffering in the mature CNS.


Real-time, in vivo determination of dynamic changes in lung and heart tissue oxygenation using EPR oximetry.
The use of electron paramagnetic resonance (EPR) oximetry for oxygen measurements in deep tissues (>1 cm) is challenging due to the limited penetration depth of the microwave energy. To overcome this limitation, implantable resonators, having a small (0.5 mm diameter) sensory loop containing the oxygen-sensing paramagnetic material connected by a pair of twisted copper wire to a coupling loop (8-10 mm diameter), have been developed, which enable repeated measurements of deep-tissue oxygen levels (pO2, partial pressure of oxygen) in the brain and tumors of rodents. In this study, we have demonstrated the feasibility of measuring dynamic changes in pO2 in the heart and lung of rats using deep-tissue implantable oxygen sensors. The sensory loop of the resonator contained lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) crystals embedded in polydimethylsiloxane (PDMS) polymer and was implanted in the myocardial tissue or lung pleura. The external coupling loop was secured subcutaneously above chest. The rats were exposed to different breathing gas mixtures while undergoing EPR measurements. The results demonstrated that implantable oxygen sensors provide reliable measurements of pO2 in deep tissues such as heart and lung under adverse conditions of cardiac and respiratory motions.


Characteristic features of abdominal organ injuries associated with gastric rupture in blunt abdominal trauma.
Previous studies have investigated the mechanisms of gastric rupture based only on the findings in gastric rupture and excluding gastric lacerations. We investigated 14 cases of gastric injury (five with rupture and nine with laceration) from blunt abdominal trauma with or without thoracic trauma. Gastric injuries were caused by a traffic accident in 12 and by a fall in two patients. All of the patients with gastric rupture had had a full stomach at the time of impact. The patients had associated injuries of adjacent solid organs, the thoracic cage, and extremities. The frequency of injury of the hepatoduodenal or gastrohepatic ligament was higher in patients with gastric laceration than in patients with gastric rupture. Eight of nine patients with a gastric laceration had hepatic or pancreatic injury, whereas none of the patients with gastric rupture had such injury. The results of our study showed that the distended stomach tends to rupture by absorbing the impact from blunt abdominal trauma (i.e., it works like an airbag to protecting adjacent organs such as the liver and pancreas).


Using causal loop analysis to explore pathways for zoonosis control in low-income setting: The case of dog rabies vaccination in Burkina Faso.
Dog vaccination is an effective pathway to control rabies if a minimum of 70% dog vaccination coverage is achieved. For more than six decades, dog vaccination has been adopted as part of the rabies control measures in Burkina Faso. However, the required vaccination coverage in canine population remains challenging and rabies endemic. This study describes the use of systems thinking to explore the dynamics arising from dog vaccination complexity and explain the possibles causes of low vaccination coverage in the dog population. In-depth interviews were conducted in three administrative regions and included various stakeholders. A thematic analysis was performed to analyze the obtained narratives. Subsequently, causal loop diagrams (CLDs) were developed, depicting the causes of low dog vaccination coverage. The CLDs were composed of reinforcing loops and balancing loops, visualizing how different variables including social, economic, technical, political and organizational factors that affect the implementation of rabies vaccination in the country are causally interrelated. Overall, the results revealed the importance of community awareness raising, strengthening the vaccination workforce, enhanced governance and leadership in the dynamics of dog vaccination. The study calls for wide consideration of all drivers and factors that may affect dog vaccination coverage, for the development of any rabies control strategy or vaccination program. Beyond the dog vaccination problem, the methods and findings from this study could be applied to other critical rabies-related questions such as postexposure prophylaxis, epidemiological surveillance, dog population management, laboratory diagnosis, and the One Health collaboration issues, to understand and improve rabies control.


[Effectiveness of endovascular prostheses as initial treatment for superior vena cava syndrome of malignant cause].
Superior vena cava syndrome (SVCS) is caused by venous return obstruction often originated by an invading mediastinal tumour. Our objective was to evaluate the usefulness of stents as initial treatment for SVCS of malignant origin. From December 1996 to August 2010, 120 patients with SVCS were referred for percutaneous treatment. Seventy-six were under oncological follow-up cases and in 44 cases the tumour was unknown. A non-concurrent prospective study was made of 113 patients without prior chemotherapy or radiotherapy, who opted for endovascular treatment as first option. One hundred and two men and 11 women were treated, mean age 61.18 years old (range 45-85). SVCS causes included lung cancer (100), lung metastases (6), compression by enlarged lymph nodes (6), and an embryonic tumour. One hundred and fifty-five prostheses were implanted. One stent was enough in 75 patients, 2 stents in 34, and 3 in 4. Technical success rate was 98.2%. Symptoms disappeared completely in 97 patients and partially in 13. Complications were stent migration (5), epistaxis (1), and post-procedure groin hematoma (1). Seventy-three asymptomatic patients had a mean survival of 210 days (75% primary permeability and 52.9% secondary permeability). The use of stents in malignant SVCS is a safe and effective procedure for venous obstruction, leading to the immediate disappearance of symptoms, allowing the underlying tumour staging, facilitating the establishment of the best treatment and improving life quality.


Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes.
Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes. Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and < 0.01, respectively). Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes. Not Applicable.


Delayed perfusion evaluation in extremity trauma.
After severe trauma to an extremity, it is essential to achieve a stable and non-infected wound in order to facilitate the best outcome following reconstruction. That said, timely, meticulous and adequate debridement is very important. To facilitate the best possible debridement of the wound, it is important to understand the tissue circulation. One available method to evaluate tissue circulation following extremity trauma is indocyanine green (ICG) angiography. Though playing an important role in flap surgeries, ICG may also provide information regarding the perfusion at the zone of injury while circulation quality diminishes. We present a case where ICG angiography initially showed good circulation in a mangled extremity, but later used in alternative way to display lack of flow in the same area of interest.


Diallyl disulfide alleviates hypercholesterolemia induced by a western diet by suppressing endoplasmic reticulum stress in apolipoprotein E-deficient mice.
The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular metabolic homeostasis. ER stress refers to the accumulation of misfolded proteins, which can trigger an unfolded protein response for survival or death in the cells. Diallyl disulfide (DADS), a major active compound in garlic, has many health benefits for patients with metabolic diseases, especially cardiovascular or fatty liver diseases. However, its role in attenuating hypercholesterolemia by suppressing ER stress remains unknown. Therefore, in this study, we determined whether DADS supplementation could reduce ER stress in apolipoprotein E-deficient (ApoE-/-) mice fed a Western-type diet (WD). ApoE-/- mice were fed either a WD alone or a WD supplemented with 0.1% DADS for 12 weeks (n = 10). Levels of plasma total cholesterol, triglyceride, leptin, and insulin were determined. Western blotting was performed to measure protein levels involved in ER stress markers. Histology and Immunostaining were performed on aortic root sections to confirm the effect of DADS on histology and expression of ER chaperone protein GRP78. The metabolic parameters showed that increases in fat weight, leptin resistance, and hypercholesterolemia were reversed in DADS-supplemented mice (p < 0.05). In addition, DADS ameliorated not only the protein of ER stress markers, phospho-eukaryotic initiation factor 2 subunit alpha and C/EBP homologous protein in the liver (p < 0.05) but also glucose-related protein 78 localization in the aorta. This indicates that DADS inhibits diet-induced hypercholesterolemia, at least in parts by regulating ER stress markers. DADS may be a good candidate for treating individuals with diet-induced hypercholesterolemia.


Bringing birth-related paternal depression to the fore.
Maternal postpartum depression is a prevalent health disorder with important consequences to the family and child development. Research evidence demonstrates that fathers can also suffer from psychological distress in the postpartum period and that paternal depression has a detrimental effect on the child's behavioral and emotional development. This study aims to review the current literature available about birth-related paternal depression. A literature search from 1980 to 2007 was conducted through Medline electronic database, using the following Mesh terms: postpartum, postnatal, depression, fathers and paternal. Studies on maternal postpartum depression that examined issues related to paternal depression were also selected. Understanding about paternal depressive disorders during the postnatal period has advanced considerably in the last decade. Various studies demonstrate that birth-related paternal depression is a significant problem and closely associated with maternal depressive symptoms. Children of depressive fathers are also at risk for emotional and behavioral problems. Men may suffer from psychological distress after childbirth and birth-related paternal depression is not a rare phenomenon. Since this disorder, also called 'paternal postpartum depression', presents potential deleterious effects for the child, an increased level of public health awareness and scientific interest is warranted. In addition, a more detailed assessment of fathers during the postnatal period is recommended, especially when their partners are also depressed, so that the condition will be promptly recognized and treated.


Measurements of mobile and bound water by nuclear magnetic resonance correlate with mechanical properties of bone.
Since clinical measures of bone mineral density do not necessarily predict whether a person will fracture a bone without an intervention, there is a need to find supplementary tools for assessing bone quality. Presently, we hypothesized that measures of mobile and bound water by a Nuclear Magnetic Resonance (NMR) technique are correlated with bone strength and toughness, respectively. To test this, bending specimens from the mid-diaphysis of 18 human femurs were collected from 18 male donors and divided into middle aged and elderly groups. After NMR measurements of each hydrated specimen, an inversion technique was used to convert the free induction decay data into a distribution of spin-spin (T2) relaxation rates. Then, the distribution resolved into three distinct components that likely represent solid hydrogen, water bound to bone tissue, and mobile water that occupy microscopic pores within the bone specimen. The integrated signal intensities of the bound and mobile components were normalized by the wet mass of the specimen. Following NMR measurements, three point bending tests were conducted to determine the modulus of elasticity, flexure strength, and work to fracture of each specimen. Next, the porosity, mineral-to-collagen ratio, and pentosidine concentration were measured. In this sample of human cortical bone, there was no age-related difference in the amount of mobile water, but the decrease in the amount of bound water with increasing age was statistically significant. Moreover, bound water was associated with both strength and work to fracture of bone, while mobile water was correlated with modulus of elasticity and appeared to quantify the level of microscopic pores within bone. On the other hand, bound water was correlated with the concentration of non-enzymatic collagen cross-links. The results of this study indicate that quantifying mobile and bound water with magnetic resonance techniques could potentially serve as indicators of bone quality.


Critical reading of medical articles and formation of communities of inquiry
This method emphasizes the interrelation between the pedagogical mode of intervention and the resulting development in the student's way of reasoning. This is reminiscent of Heisenberg's principle of indeterminacy, according to which "there is no way to observe a particle without altering it." Our knowledge of things can only be knowledge of how they act as a result of our observation and experimentation with them. The development of the student's scientific medical thinking is defined according to how he acts when subjected to the tests and stimuli of the forms of pedagogical intervention. Therefore, if the student's medical thinking develops as a result of various pedagogical interventions, then teaching and mental development are inseparable from each other, as we see daily by being dazzled by the ability of our students to understand, learn, incorporate and act. Furthermore, if the student's cognitive performance is a function of the teacher's pedagogical performance, then we must find ways to expand the teacher's ability to challenge the student to respond. I propose here a clear defense of a curricular program that goes far beyond the power of construction attributed to the typical professor; a curricular program that constitutes a discipline dedicated to stimulating the mind and engaging it to understand what it otherwise willingly assumes.


The ameliorative effects of various fish protein hydrolysates in poultry by-product meal based diets on muscle quality, serum biochemistry and immunity in juvenile barramundi, Lates calcarifer.
In an effort to reduce the use of fishmeal (FM), the effect of using protein from poultry by product meal (PBM) along with the supplementation of three different fish protein hydrolysate (FPH) including yellowtail kingfish, carp and tuna hydrolysate (designated as KH, CH and TH, respectively) were evaluated in juvenile barramundi for growth performance, fillet quality, mucosal immunity, serum biochemistry, immune response and infection against Vibrio harveyi. Fish were fed a FM based control diet + three isonitrogenous and isolipidic diets containing 90% of PBM protein supplemented with different types of hydrolysates: 90% PBM +10% KH (90PBM + KH), 90% PBM + 10% CH (90PBM + CH) and 90% PBM + 10% TH (90PBM + TH). Growth performance and indices were unaffected by the hydrolysate supplemented diets when compared to the control. FPH supplemented PBM diets resulted in improved muscle quality by improving poly unsaturated fatty acids (PUFA), ∑n-3, ∑n-6 and ∑n-9, and health related lipid indexes were not affected. The internal architecture of spleen and kidney were not altered by test diets whilst FPH supplemented PBM modulated acidic mucins in intestine and skin of fish. Improved infection rate in response to two weeks post infection with V. harveyi in the FPH supplemented diets was further associated with an increased serum immune response and a concomitant regulation of proinflammatory and inflammatory cytokines in the head kidney. Serum biochemistry including alanine transaminase (ALT), glutamate dehydrogenase (GLDH) and total bilirubin (TB) showed a decreasing trend both in pre-challenge and post-challenge barramundi fed FPH supplemented diets whereas cholesterol level decreased significantly in post-challenge groups fed 90PBM + KH and 90PBM + TH than pre-challenge barramundi. This study signifies that supplementation of 10% with different three FPH, hydrolysed by an alcalase® enzyme in PBM-based diets for barramundi could be good strategies to overcome the negative consequences triggered by animal by-product ingredients.


Effects of contaminated surface water and groundwater from a rare earth mining area on the biology and the physiology of Sprague-Dawley rats.
Previous studies have shown that an effective damage detection method for model rats from macro individual to micro cellular, was applied to assess the groundwater quality from rare earth metals tailings seepage. To determine whether it is universal method for measuring the toxicological damage caused by contaminated water around other mining areas to organisms at the organ-tissue-cell-chromosome-gene level. In this study, a rare earth mining area in North China was used as research base. Firstly, the core pollution factors in surface water and groundwater from five different sites were analyzed. Then, the degree of toxicological damage to Sprague-Dawley (SD) rats caused by contaminated water were systematically assessed using biological methods. Finally, the possible molecular mechanism of toxicological damage was further discussed. The synthesis results showed that the main pollution factors were some metal elements (Mn, Zn, Co, Ni) and rare earth elements (Sc, Nb, La, Ce, Pr, Dy and Y), which might cause significant DNA genetic damage to SD rats. Further, differential gene expression profile showed that DNA damage-inducible genes (Gadd45g and Ddit4), immunity-related genes (Mpo, Slpi and Elane) and two cancer-related genes (Mmp8 and Ltf) were used as a new prognostic and predictive biomarker for biosafety assessment. Therefore, this study provides a possible molecular mechanism for the toxicological damage, and also it provides a universal method to scientifically and effectively evaluate the water pollution risk for other mining areas.


Screen-Printing Technology for Scale Manufacturing of Perovskite Solar Cells.
As a key contender in the field of photovoltaics, third-generation thin-film perovskite solar cells (PSCs) have gained significant research and investment interest due to their superior power conversion efficiency (PCE) and great potential for large-scale production. For commercialization consideration, low-cost and scalable fabrication is of primary importance for PSCs, and the development of the applicable film-forming techniques that meet the above requirements plays a key role. Currently, large-area perovskite films are mainly produced by printing techniques, such as slot-die coating, inkjet printing, blade coating, and screen-printing. Among these techniques, screen printing offers a high degree of functional layer compatibility, pattern design flexibility, and large-scale ability, showing great promise. In this work, the advanced progress on applying screen-printing technology in fabricating PSCs from technique fundamentals to practical applications is presented. The fundamentals of screen-printing technique are introduced and the state-of-the-art studies on screen-printing different functional layers in PSCs and the control strategies to realize fully screen-printed PSCs are summarized. Moreover, the current challenges and opportunities faced by screen-printed perovskite devices are discussed. This work highlights the critical significance of high throughput screen-printing technology in accelerating the commercialization course of PSCs products.


The effects of preanesthetic oral clonidine on total requirement of propofol for general anesthesia.
To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. Randomized double-blinded study. Operating room ASA physical status I and II room and recovery room of the cancer center. 80 breast cancer patients scheduled for surgery. Patients were randomized to one of four treatment groups (placebo, clonidine 75 micrograms, or 150 micrograms of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O2): nitrous oxide (N2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. Preanesthetic oral clonidine (150 micrograms) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 micrograms, clonidine 150 micrograms, and 10 mg of diazepam groups were 841 +/- 70 (9.0 +/- 0.3), 720 +/- 63 (7.1 +/- 0.4), 491 +/- 39 (5.6 +/- 0.2), and 829 +/- 77 mg (7.9 +/- 0.4 mg/kg/h), respectively. The cost of propofol in these groups was $51.0 +/- 3.8, $45.5 +/- 3.2, $33.5 +/- 2.3, and $50.5 +/- 4.4, respectively. Preanesthetic oral clonidine (150 micrograms) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 micrograms of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.


A rating scale for housing-based health hazards.
This study investigated the validity and responsiveness of a rating scale designed to assess the housing-based hazards and their relationships to burden of disease symptoms in the building occupants. A population-based cross-sectional survey. Random-digit dialing with computer-assisted phone interviews was conducted to obtain information from 642 households in the City of Saginaw, Michigan about 71 housing-based hazards, symptoms of 43 diseases often associated with environmental exposures and demographic characteristics. The housing-based hazard index (HHI) was calculated from scores of hazards across the following eight dimensions: structural scale (18 items); moisture/mold scale (8 items), electrical scale (7 items), ventilation and combustion appliances scale (6 items); pest scale (6 items); pets scale (4 items), fire scale (6 items) and lifestyle-associated factors scale (12 items). Each item was assigned a relative score based on the likelihood that the housing occupants would be exposed to the hazard, the potential for serious health impacts, and the reported strength of its association with childhood lead poisoning and respiratory diseases. The psychometric properties of HHI and individual domains (scales) were assessed along with the associations between these indicators and the inventory of disease symptoms. The reliability of HHI was demonstrated by assessments of its dimensionality and internal consistency. Analysis of the predictive validity and responsiveness indicates that HHI and scores for most of the individual scales can discriminate between households in relation to the burden of reported disease symptoms. The HHI represents a valid, reasonably reliable, and parsimonious measure of hazards that are congruent with the burden of symptoms generally associated with housing-related diseases.


Efficient gene transfer of HIV-1-specific short hairpin RNA into human lymphocytic cells using recombinant adeno-associated virus vectors.
The cellular introduction of short, interfering RNA leads to sequence-specific degradation of homologous mRNA, a process termed RNA interference (RNAi). Here, we report that recombinant adeno-associated virus 2 (rAAV-2) can be used to transfer short hairpin (sh) RNA expression cassettes genetically into human cells. HIV-1 replication was suppressed by >95% in H9 cells and primary human lymphocytes that expressed shRNA targeting the first exon of the viral transactivator protein tat compared to control cells. rAAV-2 integrated stably into the host genome, leading to long-term expression of tat shRNA. Our findings demonstrate the utility of rAAV-2 for the genetic transfer of shRNA expression cassettes into human cells, providing an alternative to using retroviral vectors as RNAi delivery systems.


Growth factor deposition in anterior subcapsular cataract.
To characterize immunohistochemically the distribution of growth factors and extracellular matrix (ECM) components in an anterior subcapsular cataract (ASC) and to determine the role of growth factors in the development of ASC. Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. During cataract surgery in 22 patients, anterior capsules with an ASC were obtained. Sections of each specimen were immunostained with a panel of antibodies against ECM components, growth factors, cytoskeletal components, and signal transduction-related molecules. Collagen types I, V, and VI; fibronectin; fibrillin-1; and latent transforming growth factor beta binding protein-1 (LTBP-1) were localized to the ECM in ASC tissues. Collagen IV was localized to the ECM and the capsule. Lens epithelial cells (LECs) were positive for alpha-smooth muscle actin (alphaSMA). Lens epithelial cells and ECM stained for transforming growth factor beta2 (TGFbeta2) and TGFbeta3 in all samples, but TGFbeta1 latency-associated peptide (TGFbeta1-LAP) were detected in some samples. Fibroblast growth factor-2 (FGF-2) and hepatocyte growth factor-alpha (HGF-alpha) were localized to the ECM. Lens epithelial cells with nuclear staining for Erk-1, the mitogen-activated protein kinase (MAP kinase) cascade-related molecule, and Smad3, 1 of the Smad family members involving TGFbeta signaling, were detected. Matrix components (ie, collagen types, fibronectin, fibrillin-1), as well as growth factors such as TGFbeta1-LAP, TGFbeta2, TGFbeta3, FGF-2, and HGF-alpha, were detected in ASC. Fibrillin-1 might serve as a repository for TGFbetas. These growth factors may modulate the phenotypic alteration and behavior of LECs. The MAP kinase cascade and TGFbeta signaling are both activated in LECs in ASC.


The micronucleus assay as a test for the detection of aneugenic activity.
The aim of this work was to determine the usefulness of the micronucleus assay for the detection of aneugenic potential. Chemicals affecting microtubule assembly, i.e., colchicine, vinblastine sulfate and tubulazole, and chemicals affecting targets other than microtubuli, i.e., mitomycin C, cyclophosphamide and miconazole, and the clastogens azathioprine and procarbazine were administered once orally or intraperitoneally to male and female mice. Bone marrow preparations were made at 24, 48 and 72 h after dosing. All the clastogens and aneugens, except miconazole, yielded positive results in the micronucleus test. Measurements of the area of the micronuclei and their distribution clearly showed that the chemicals affecting microtubule assembly produced larger micronuclei than did the clastogens. The pattern of area distribution of the micronuclei found with cyclophosphamide and mitomycin C was between those found for the tubulin inhibitors and the clastogens. These findings indicate that the micronucleus test not only detects chemicals affecting microtubule assembly, but also can discriminate them from clastogens by measurements of the area of the micronuclei.


Laparoscopic enucleation of giant liver hemangioma.
The cavernous hemangioma is the most common benign tumor of the liver. It usually becomes symptomatic as it reaches a certain size. A 49-year-old man was admitted with a 1-year history of epigastric pain, which was not relieved by regular analgesic intake, and nausea. The results of physical examination, routine laboratory tests, and upper gastrointestinal tract endoscopy were normal. Ultrasonography showed a 10-cm mass in the left hepatic lobe. Magnetic resonance imaging (MRI) showed a 90-mm hemangioma at left hepatic lobe. Selective celiac arteriogram was performed, and polyvinyl alcohol particles were used as an embolizing agent. After the embolization, the patient underwent laparoscopic enucleation of the liver hemangioma. No blood transfusion was needed during the operation. The operative time was 75 min. The patient was allowed to take a clear liquid diet on the postoperative day 1. The postoperative course of the patient was uneventful, and he was discharged on the postoperative day 2. Enucleation is the best surgical technique for the management of symptomatic giant hemangiomas. It can be performed with no mortality or morbidity, with preservation of all normal liver parenchyma. Enucleation also has been associated with significantly fewer intraabdominal complications than anatomic resection. The laparoscopic approach for enucleation requires patience and careful dissection to prevent bleeding. In conclusion, laparoscopic enucleation of hemangiomas is safe and easy to perform in selected cases.


Parameter estimation techniques for interaction and redistribution models: a predator-prey example.
The use of parameter estimation techniques for partial differential equations is illustrated using a predatorprey model. Whereas ecologists have often estimated parameters in models, they have not previously been able to do so for models that describe interactions in heterogeneous environments. The techniques we describe for partial differential equations will be generally useful for models of interacting species in spatially complex environments and for models that include the movement of organisms. We demonstrate our methods using field data from a ladybird beetle (Coccinella septempunctata) and aphid (Uroleucon nigrotuberculatum) interaction. Our parameter estimation algorithms can be employed to identify models that explain better than 80% of the observed variance in aphid and ladybird densities. Such parameter estimation techniques can bridge the gap between detail-rich experimental studies and abstract mathematical models. By relating the particular bestfit models identified from our experimental data to other information on Coccinella behavior, we conclude that a term describing local taxis of ladybirds towards prey (aphids in this case) is needed in the model.


Anatomical pancreatic variants in intraductal papillary mucinous neoplasm patients: a cross-sectional study.
No previous studies have examined the possible relationship between intraductal papillary mucinous neoplasm (IPMN) and the developmental ductal variations of the pancreas, such as an ansa pancreatica and a meandering main pancreatic duct (MMPD). This retrospective cross-sectional study enrolled 214 patients, 108 with IPMN disease and 106 subjects from a community at the tertiary care unit. The main pancreatic duct (MPD) was evaluated in the head of the pancreas by its course, which were non-MMPD: descending, vertical, and sigmoid, or MMPD including loop types, reverse-Z subtypes, and an N-shape, which was identified for the first time in this study. IPMN patients were also evaluated for worrisome features (WF) or high-risk stigmata (HRS), and the extent of IPMN cysts. Among IPMN patients, 18.4% had MMPD, which we observed in only 3.0% of the control group (P < 0.001). Patients with MMPD were more likely to belong to the IPMN group compared with non-MMPD patients [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2-24.9]. Compared with a descending shape MPD, IPMN patients with an N-shaped MPD were more likely to have a cystic mural nodule (OR 5.9, 95% CI 1.02-36.0). The presence of ansa pancreatica associated with more extent IPMN disease (OR 12.8, 95% CI 2.6-127.7). IPMN patients exhibited an MMPD more often than control patients. Ansa pancreatica associated with multiple cysts. Furthermore, an N-shape in IPMN patients associated with cystic mural nodules, suggesting that this shape serves as a risk factor for more severe IPMN.


Inhibition of Atherosclerosis Progression, Intimal Hyperplasia, and Oxidative Stress by Simvastatin and Ivabradine May Reduce Thoracic Aorta's Stiffness in Hypercholesterolemic Rabbits.
This study aims to evaluate atherosclerosis, oxidative stress, and arterial stiffness attenuation by simvastatin and ivabradine in hyperlipidemic rabbits. Forty rabbits were randomly divided into 4 groups: atherogenic diet (group C), atherogenic diet plus simvastatin (group S), atherogenic diet plus ivabradine (group I), and atherogenic diet plus simvastatin and ivabradine (group S + I). After 9 weeks, rabbits were euthanized and descending aortas excised for mechanical testing. Atherogenic diet induced the development of significant atherosclerotic lesions in group C animals but in none of groups S, I, and S + I. RAM-11 and HHF-35-positive cells were significantly reduced in groups S, I, and S + I compared with group C (P < .001). A significant neointimal hyperplasia and intima-media ratio reduction was demonstrated in groups S (P = .015 and P < .001), I (P = .021 and P < .001), and S + I (P = .019 and P < .001) compared with group C. Protein nitrotyrosine levels were significantly decreased in group S compared with group C (P = .009), and reactive oxygen species levels were decreased in group I compared with group C (P = .011). Aortic stiffness was significantly reduced in groups S, I, and S + I compared with group C (P = .003, P = .011, and P = .029). Simvastatin and ivabradine significantly inhibited intimal hyperplasia and oxidative stress contributing to aortic stiffness reduction in hyperlipidemic rabbits.


Significance of plasma C-peptide in obese African American adolescents.
C-peptide blood levels can indicate whether or not a person is producing insulin and roughly how much. C-peptide is secreted as a byproduct of the biosynthesis of insulin from proinsulin. C-peptide has proposed biological activity and a well-established diagnostic value. The significance of C-peptide concentration in the plasma and urine in the pediatric population needs further delineation. To determine the significance of plasma C-peptide in obese African American adolescents with mild insulin resistance but no evidence of diabetes. This study included 19 African American adolescents with body mass index (BMI) in at least the 85th percentile evaluated with anthropometric measurements, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) score, and oral glucose tolerance test (OGTT), and 24-hour urine collections. The study also included an age-matched control group of 15 healthy African American adolescent controls and were not subjected for OGTT. The correlation among BMI, fasting plasma C-peptide concentrations, and 24-hour-urine C-peptide concentrations was calculated. T Tests were conducted to compare plasma C-peptide and 24-hour-urine C-peptide concentrations for the test group and controls. Mean HOMA score (3.96 +/- 1.84) signified mild insulin resistance among the adolescent test group. The test subjects exhibited adequate glucose tolerance (glucose range, 89.4-122.5 mg/dL) during the OGTT. A significant positive relationship was observed between BMI and fasting plasma C-peptide concentration in the control group (r = 0.537) but not the test group (r = 0.335). An insignificant positive relationship was exhibited between BMI and 24-hour-urine C-peptide concentration in the test group (r = 0.150) and controls (r = 0.254). The positive relationship among BMI, plasma C-peptide, and urine C-peptide is worth further evaluation in studies conducting multiple rounds of OGTT with a larger sample of pediatric subjects. The potential diagnostic value of C-peptide may facilitate early detection of insulin resistance in the pediatric population.


Retrograde intubation of the trachea.
Retrograde tracheal intubation may be of particular use in situations in which orotracheal intubation is technically impossible or contraindicated. The technique can be performed despite the presence of blood or secretions in the upper airway. It is an alternative to cricothyroidotomy in patients with short, obese, or anatomically distorted necks.


Differential effect of cadmium on GSH-peroxidase activity in the Leydig and the Sertoli cells of rat testis. Suppression by selenium and the possible relationship to heme concentration.
In the testes of rats treated with cadmium acetate (7 or 20 mumoles/kg, 24 hr, s.c.), the activity of glutathione (GSH)-peroxidase was increased. At the same time, the activity of glutathione disulfide (GSSG)-reductase and the cellular GSH concentration were decreased significantly. The basal activity of peroxidase in the Leydig and the Sertoli cell populations was comparable. However, the magnitude of increases in the activities markedly differed in the two cell populations, with that of the Sertoli cells increasing to nearly 450% of the control value in response to treatment with 20 mumoles/kg Cd2+. In the Leydig cells, the enzyme activity in response to the same treatment increased to only about 170% of the control value. Cd2+ treatment increased the concentration of heme in the microsomal and the smooth and rough endoplasmic reticulum fractions of the whole testis, as well as in the microsomal fractions of the Leydig and the Sertoli cells. As with the peroxidase activity, the two cell populations vastly differed in their susceptibilities to Cd2+ treatment, with the Sertoli cells being more severely affected by the metal. In the Sertoli cells the microsomal heme concentration was increased by approximately 11-fold, whereas only a 2-fold increase in the Leydig cells was noted. The increase in GSH-peroxidase activity was not due to the peroxidase activity of GSH-S-transferases, insofar as an increase in transferase activity was not observed in the Leydig and the Sertoli cells. Treatment of rats with sodium selenite (10 mumoles/kg, s.c.) 30 min before Cd2+ treatment (20 mumoles/kg) fully suppressed the above-described spectrum of effects of Cd2+ in the testis. Also, sodium selenite at a lower dose of 5 mumoles/kg prevented an increase in GSH-peroxidase activity. It is hypothesized that increased GSH-peroxidase activity in the Leydig and the Sertoli cells constitutes an adaptive response to increased cellular levels of heme and to the free radicals generated by the heme molecule. Selenium prevents the increase in GSH-peroxidase activity by circumventing the increase in cellular heme concentration. The protection is believed to be related, at least in part, to increased production of cellular GSH.


[Oxidation of sulfur-containing substrates by aboriginal and experimentally designed microbial communities].
Aboriginal and experimental (constructed of pure microbial cultures) communities of acidophilic chemolithotrophs have been studied. The oxidation of elemental sulfur, sodium thiosulfate, and potassium tetrathionate as sole sources of energy has been monitored. The oxidation rate of the experimental community is higher as compared to the aboriginal community isolated from a flotation concentrate of pyrrhotine-containing pyrite-arsenopyrite gold-arsenic sulfide ore. The degree of oxidation of the mentioned S substrates amounts to 17.91, 68.30, and 93.94% for the experimental microbial community and to 10.71, 56.03, and 79.50% for the aboriginal community, respectively. The degree of oxidation of sulfur sulfide forms in the ore flotation concentrate is 59.15% by the aboriginal microbial community and 49.40% by the experimental microbial community. Despite a higher rate of oxidation of S substrates as a sole source of energy by the experimental microbial community, the aboriginal community oxidizes S substrates at a higher rate in the flotation concentrate of pyrrhotine-containing pyrite-arsenopyrite gold-arsenic sulfide ore, from which it was isolated. Bacterial-chemical oxidation of the flotation concentrate by the aboriginal microbial community allows for the extraction of an additional 32.3% of gold from sulfide minerals, which is by 5.7% larger compared to the yield obtained by the experimental microbial community.


Variations of the median nerve in the carpal canal.
Eight hundred twenty-one median nerves were retrospectively and prospectively reviewed for variations during operations to treat carpal tunnel syndrome. Ninety-two cadaver median nerves were also dissected to document the incidence of variations within the carpal canal. The combined incidence of anomalies at operation (Lanz groups 1 to 4) was 9.8% and in the cadaver series 18%. The discrepancy reported by Poisel, 54% in the Lanz group 1 series, versus ours of 1.42% cannot be explained.


Synthesis and self-assembly of dynamic covalent block copolymers: towards a general route to pore-functionalized membranes.
A diblock copolymer is designed to have incompatible blocks, unsymmetrical block lengths, and a reversible linkage. This copolymer self-assembles into nanostructured cylindrical morphology in thin films. Removal of the nanosized cylinders by breaking the reversible linkage then affords nanoporous membranes featuring a chemically reactive functionality in the pores.


The sensitivity of flow cytometry compared with conventional cytology in the detection of superficial bladder carcinoma.
Three groups of patients with superficial bladder carcinoma were studied: 110 patients had carcinoma in situ (TIS), 54 had noninvasive papillary transitional cell carcinoma (TA), and 64 had transitional cell carcinoma infiltrating the lamina propria (T1). One to six conventional cytologic examinations per patient (mean 2.8) were obtained during the 24 hour period before biopsy. For all tumor categories combined, the sensitivity was 49%, 54%, 62%, and 66% for one, two, three, and four cytologic examinations per patient, respectively. Cytologic sensitivity varied according to tumor category; it was greater in the TIS and T1 categories than in the TA category. To compare with the cytologic results, a subset of 103 patients had bladder irrigation performed immediately before the biopsy which was subsequently analyzed by flow cytometry. The sensitivity of a single flow cytometric examination for all tumor categories combined was 78%. As with the cytologic examinations, the sensitivity of flow cytometry varied with tumor category; it was greater in TIS and T1 categories than in the TA category. The sensitivity of one flow cytometric examination was superior (binomial test, P less than or equal to 0.05) to that of one or two cytologic examinations for TA tumors and to that of one, two, or three cytologic examinations for TIS, T1, and all tumor categories combined. Only three of 103 patients had their cancers detected by cytologic examination and not by flow cytometry.


Aminoprocalcitonin protects against hippocampal neuronal death via preserving oxidative phosphorylation in refractory status epilepticus.
Refractory status epilepticus (RSE) is a neurological emergency where sustaining seizure causes severe neuronal death. Currently, there is no available neuroprotectant effective in RSE. Aminoprocalcitonin (NPCT) is a conserved peptide cleaved from procalcitonin, but its distribution and function in the brain remain enigmatic. Survival of neurons relies on sufficient energy supply. Recently, we found that NPCT was extensively distributed in the brain and had potent modulations on neuronal oxidative phosphorylation (OXPHOS), suggesting that NPCT might be involved in neuronal death by regulating energy status. In the present study, combining biochemical and histological methods, high-throughput RNA-sequence, Seahorse XFe analyser, an array of mitochondria function assays, and behavior-electroencephalogram (EEG) monitoring, we investigated the roles and translational values of NPCT in neuronal death after RSE. We found that NPCT was extensively distributed throughout gray matters in rat brain while RSE triggered NPCT overexpression in hippocampal CA3 pyramidal neurons. High-throughput RNA-sequence demonstrated that the influences of NPCT on primary hippocampal neurons were enriched in OXPHOS. Further function assays verified that NPCT facilitated ATP production, enhanced the activities of mitochondrial respiratory chain complexes I, IV, V, and increased neuronal maximal respiration capacity. NPCT exerted multiple neurotrophic effects including facilitating synaptogenesis, neuritogenesis, spinogenesis, and suppression of caspase-3. A polyclonal NPCT immunoneutralization antibody was developed to antagonize NPCT. In the in vitro 0-Mg2+ seizure model, immunoneutralization of NPCT caused more neuronal death, while exogenous NPCT supplementation, though did not reverse death outcomes, preserved mitochondrial membrane potential. In rat RSE model, both peripheral and intracerebroventricular immunoneutralization of NPCT exacerbated hippocampal neuronal death and peripheral immunoneutralization increased mortality. Intracerebroventricular immunoneutralization of NPCT further led to more serious hippocampal ATP depletion, and significant EEG power exhaustion. We conclude that NPCT is a neuropeptide regulating neuronal OXPHOS. During RSE, NPCT was overexpressed to protect hippocampal neuronal survival via facilitating energy supply.


Effect of balanced phacoemulsification tip on the outcomes of torsional phacoemulsification using an active-fluidics system.
To compare the outcomes of torsional phacoemulsification with a new balanced tip (Intrepid) and a conventional tip (Kelman) using a single active-fluidics torsional phacoemulsification machine (Centurion). Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. Prospective comparative case-control study. Patients with senile cataract had torsional phacoemulsification with the Kelman conventional tip or the new Intrepid balanced tip using the active-fluidics torsional machine. Intraoperative parameters, such as cumulative dissipated energy (CDE), total ultrasound (US) time, torsion use time, torsion amplitude, aspiration time, and fluid use, were noted and compared. Endothelial cell loss and central corneal thickness (CCT) changes were evaluated at 1 month. The new tip showed significantly less CDE, total US time, torsion amplitude, aspiration time, and fluid use (8.55 ± 6.9 [SD], 33.59 ± 28.12 seconds, 37.8 ± 13.42, 173.19 ± 47.26 seconds, and 66.59 ± 20.44 mL, respectively) than the conventional tip (13.47 ± 10.65, 42.8 ± 33.46 seconds, 42.58 ± 16.38, 202.25 ± 71.28 seconds, and 97.14 ± 36.86 mL, respectively) (P < .01), especially in higher grades of cataract. Anterior capsulorhexis margin tear occurred in 2 patients with the new tip. There were no corneal burns in either group. The mean endothelial cell loss and the percentage change in CCT were not significantly different at 1 month. The new balanced tip performed phacoemulsification more efficiently, especially in hard cataracts requiring higher energy and prolonged phacoemulsification time.


High degree of circular polarization in WS2 spiral nanostructures induced by broken symmetry.
We present helicity resolved photoluminescence (PL) measurements of WS2 spiral (SPI) nanostructures. We show that very high degree of circular polarization (DCP) (~94 ± 4%) is obtained from multilayer SPI samples at room temperature upon excitation with a circularly polarized laser at a wavelength near-resonant with the A-exciton (633 nm). TEM analysis showed that these SPI nanostructures have AB stacking in which the inversion symmetry is broken, and hence this leads to very high DCP. Comparison with PL from monolayer and bi-layer WS2 samples, along with polarization resolved PL studies provide evidence for suppression of interlayer/intravalley scattering in the multilayer SPI samples.


Influence of sunscreen formulation on the transfer of mineral and organic ultraviolet filters from skin to seawater in simulated ocean bathing tests.
Significant research and regulatory attention have been focussed on the potential for some ultraviolet filters (UVFs) to rinse off from beachgoers' skin into seawater leading to exposure to sea life, especially coral reefs. The amount of UVFs potentially rinsed from skin during recreational beach activities has not been well studied, leading to uncertainty about the potential magnitude of aquatic UVF exposure due to changes in sunscreen use patterns. This study quantifies rinse-off of UVFs in sunscreen from skin into synthetic seawater and identifies differences in rinse-off quantity due to formulation type with a goal of informing future modelling efforts aimed at estimating UVF exposure to sea life associated with recreational activities at the beach. UVF rinse-off from skin during recreation in seawater was simulated by applying eight different sunscreen products to porcine skin samples followed by three periods of shaking in synthetic seawater totalling 40 min. The rinsed mass of six UVFs - zinc oxide, titanium dioxide, avobenzone, homosalate, octisalate, and octocrylene - was determined analytically in synthetic seawater and in extractant rinsate from glassware for organic UVFs and compared among formulas. Among the 22 UVF-formulation combinations tested, 19 resulted in less than 10% of the applied UVF rinsed from skin. All formulation-UVF combinations where the formula types were water-in-oil (reverse phase) emulsions or anhydrous resulted in 5% or less of the applied UVF rinsed to synthetic seawater. Sunscreens formulated as oil-in-water emulsions yielded higher rinse-off percentages for all UVFs tested, with a maximum of 20% rinse-off of avobenzone in one lotion. The potential for sunscreen UVF rinse-off is significantly influenced by formulation and is generally well below the prior assumed rinse-off levels used to estimate risk. Formulation consideration is therefore essential for accurate exposure models used in environmental risk assessment. Anhydrous and reverse phase (water-in-oil) sunscreen formulations tested resulted in lower UVF transfer from skin to synthetic seawater in simulated ocean bathing tests and as a result, are expected to yield lower UVF exposures to sea life. This approach can be used in predictive environmental exposure models to support ecologically safe sunscreen formulation design.


High-performance liquid chromatographic determination for aristolochic acid in medicinal plants and slimming products.
A HPLC procedure with a silica gel RP-18 reversed-phase column for the determination of aristolochic acids I, II in medicinal plants and slimming products was developed. The mobile system 0.3% ammonium carbonate solution-acetonitrile (75:25, v/v) with pH 7.5 was the optimal buffer to clearly separate aristolochic acids I, II within 20 min. The recovery of aristolochic acids I, II in medicinal plants and slimming products was better than 90% by extracting with methanol and purifying through a PHP-LH-20 column. The major component was aristolochic acid I in Aristolochia fangchi and the level ranged from 437 to 668 ppm. Aristolochic acid II was the major component for Aristolochia contorta and its range was <1-115 ppm. Twelve out of 16 samples of slimming pills and powders contained aristolochic acids I and/or II. The major component in most slimming products was aristolochic acid II and the level ranged from <1 to 148 ppm. It may indicate that slimming products were not mainly made of A. fangchi.


The effects of intraoperative blood salvage and induced hypotension on transfusion requirements during spinal surgical procedures.
Spinal surgical procedures, such as placement of Harrington rods for correction of scoliosis, are associated with considerable perioperative blood loss and, hence, with the risks associated with homologous blood transfusions. To test the hypothesis that intraoperative autologous blood transfusions could decrease the amount of homologous blood needed in such operations, we conducted a two-part study: (1) a retrospective review of 142 patients in whom blood salvage was not used and (2) a prospective review of 28 patients who received autologous transfusions. Intraoperative autologous transfusion reduced the amount of homologous blood required by more than 50% (5.1 versus 2.0 units; P less than 0.001). The total amount of homologous blood required during the hospital stay was also significantly reduced by intraoperative autologous transfusion (6.0 versus 3.4 units; P less than 0.001). Induced hypotension in 81 of the 142 patients who did not receive autologous transfusions did not decrease the homologous blood transfusion requirements from those needed by the normotensive patients. We conclude that intraoperative autologous transfusion significantly reduces the need for homologous blood products in patients who undergo spinal surgical procedures. Induced hypotension, which did not affect transfusion requirements in our study, should be further evaluated in a blinded, prospective study.


Enzymatic acetylation of 10-deacetylbaccatin III to baccatin III by C-10 deacetylase from Nocardioides luteus SC 13913.
Baccatin III is a polycyclic diterpene which can be used for the semi-synthesis of paclitaxel and analogs. An enzymatic process was developed for the conversion of 10-deacetylbaccatin III (10-DAB) to baccatin III without requiring protection of the 7-hydroxyl group. A C-10 deacetylase from Nocardioides luteus SC 13912 was immobilized on diethylaminoethyl cellulose (DEAE-Cellulose) and the immobilized enzyme was used in the biotransformation process. The reaction was catalyzed using vinyl acetate as acyl donor at ambient temperature and at pH 7. A reaction yield of 51% was obtained.


Network and systems biology: essential steps in virtualising drug discovery and development.
The biological processes that keep us healthy or cause disease, as well as the mechanisms of action of possible drugs are inherently complex. In the face of this complexity, attempts at discovering new drugs to treat diseases have alternated between trial-and-error (typically on experimental systems) and grand simplification, usually based on much too little information. We now have the chance to combine these strategies through establishment of 'virtual patient' models, centred on a detailed molecular characterisation of thousands or even, in the future, millions of patients. In doing so, we lay the foundations for truly personalised therapy, as well as a far-reaching virtualisation of drug discovery and development in oncology and other areas of medicine.


Lung carcinoids with high proliferative activity: Further support for the identification of a new tumor category in the classification of lung neuroendocrine neoplasms.
Highly proliferative lung carcinoids (HPLC) have been recently reported but information about this subset remains scarce. Clinical and pathological data of 630 patients with lung carcinoids (LC) referred to Gustave Roussy Institute (GR) and European Institute of Oncology (IEO) were retrospectively reviewed to select HPLC and analyze their frequency, behavior and compare their outcome to conventional LC with Ki-67 ≤ 20 % and mitotic count (MC)≤10/2 mm2. Selection criteria were: diagnosis of LC confirmed by local pathologist, and available clinical and follow-up data. Patients with Ki-67 > 20 % and/or MC > 10/ 2 mm2 in primary or metastatic specimens were identified as HPLC. 30/514 patients (6%) met the selection criteria of HPLC. Based on primary tumor evaluation, 22/25 (88 %) were classified as atypical carcinoids (AC). Median MC was 4.5/2 mm2 (1-11) 6/2 mm2 (3-15) in primary tumors and metastasis, respectively. Median Ki-67 was respectively 23 % (15-65) and 25 % (8-60). Recurrence rate was 66 % (12/18) in HPLC and 9 % (33/352) in conventional LC. Median RFS was 24 (10-NR) months in HPLC, 288 (141-NR) months in LC with Ki-67 index≤5 % and NR (148-NR) months in LC with Ki-67 6-20% (p < 001). Median OS was 203 (83-NR) months in LC with Ki-67 index≤5%, 101 (79-NR) months in LC with Ki-67 index 6-20 % and 53 (39-NR) months in HPLC (p = 002). Among 20 metastatic patients with HPLC, median PFS under platinum-based chemotherapy, everolimus, alkylating-based chemotherapy, FOLFOX and PRRT was 5.1 (95 % CI 0.7-9.4), 12.1(95 %CI 0.3-24), 6.8 (95 % CI 0-14.9), 10.2 (95 % CI 0.4-19.9) and 14.2 months (95 % CI 0-30) respectively. Best response was stable disease (SD) under platinum-based chemotherapy and partial response (PR) under alkylating-based chemotherapy and FOLFOX. This study confirms the existence and rarity of HPLC. Their characteristics and clinical behavior are more similar to LC rather than neuroendocrine carcinomas (NECs), suggesting that this entity could be managed accordingly.


Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapse.
Weakening of pelvic supportive tissues is thought to be a contributing etiology in female pelvic floor disorders such as stress urinary incontinence and/or pelvic organ prolapse (SUI/POP). Since elastin modulates the mechanical properties of supportive tissues, we examined elastase activity in vaginal tissue from women with pelvic floor dysfunction compared to asymptomatic controls, by comparing overall elastase activity, human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin (a serine protease inhibitor) mRNA and protein levels. Full-thickness peri-urethral vaginal wall tissues were collected from age and menstrual-phase matched SUI/POP and control women at the time of pelvic surgery. Elastolytic activity in the homogenized tissue was determined by the generation of amino groups from succinylated elastin. To quantify mRNA levels of each protein, quantitative competitive-PCR and confirmatory Western blot analyses were performed on the samples for human neutrophil elastase, cathepsin K, and alpha-1 antitrypsin. The mean elastolytic activity in vaginal tissues from the SUI/POP group was similar to that in the control group. With respect to the proteolytic enzymes, neither human neutrophil elastase nor cathepsin K differed between the two groups. However, alpha-1 antitrypsin mRNA and protein levels were significantly decreased in tissues from affected women. A significant decrease in alpha-1 antitrypsin expression was seen in tissues from women with SUI/POP compared to controls. This data suggest that altered elastin metabolism may contribute to the connective tissue alterations observed in pelvic floor dysfunction. Future investigations are warranted to help define the role of elastin turnover in pelvic floor dysfunction.