Echocardiographic study of cardiac tamponade.
We studied 14 patients with cardiac tamponade and pulsus paradoxus; 11 were studied after relief of tamponade by pericardiocentesis. Right ventricle diastolic diameter increased during inspiration in each of 12 patients; left ventricle diastolic diameter decreased during inspiration in each of 13. Mitral valve DE amplitude decreased with inspiration in 13 of 14 patients. Mitral valve E-F slope could be measured in eight patients, and was rounded and not measurable in six. Six of the eight showed inspiratory decrease in mitral E-F slope. Similar changes were observed in two other patients with pulsus paradoxus who had chronic obstructive airway disease. Twenty patients with large pericardial effusions and no tamponade did not show these changes. These results suggest inspiratory augmentation of right ventricular filling and inspiratory diminution of left ventricular filling, not only in cardiac tamponade, but in obstructive airway disease associated with pulsus paradoxus.


Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings.
A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium.


Defining NAD(P)(H) Catabolism.
Dietary vitamin B3 components, such as nicotinamide and nicotinic acid, are precursors to the ubiquitous redox cofactor nicotinamide adenine dinucleotide (NAD+). NAD+ levels are thought to decline with age and disease. While the drivers of this decline remain under intense investigation, strategies have emerged seeking to functionally maintain NAD+ levels through supplementation with NAD+ biosynthetic intermediates. These include marketed products, such as nicotinamide riboside (NR) and its phosphorylated form (NMN). More recent developments have shown that NRH (the reduced form of NR) and its phosphorylated form NMNH also increases NAD+ levels upon administration, although they initially generate NADH (the reduced form of NAD+). Other means to increase the combined levels of NAD+ and NADH, NAD(H), include the inhibition of NAD+-consuming enzymes or activation of biosynthetic pathways. Multiple studies have shown that supplementation with an NAD(H) precursor changes the profile of NAD(H) catabolism. Yet, the pharmacological significance of NAD(H) catabolites is rarely considered although the distribution and abundance of these catabolites differ depending on the NAD(H) precursor used, the species in which the study is conducted, and the tissues used for the quantification. Significantly, some of these metabolites have emerged as biomarkers in physiological disorders and might not be innocuous. Herein, we review the known and emerging catabolites of the NAD(H) metabolome and highlight their biochemical and physiological function as well as key chemical and biochemical reactions leading to their formation. Furthermore, we emphasize the need for analytical methods that inform on the full NAD(H) metabolome since the relative abundance of NAD(H) catabolites informs how NAD(H) precursors are used, recycled, and eliminated.


Hollow Bulb One Piece Maxillary Definitive Obturator - A Simplified Approach.
In maxillary defects, role of a prosthodontist is to rehabilitate the intra- and extra-oral structures and to endow with the normal function of mastication, speech, deglutition, and esthetics. Malignancies are common in the oral region and are treated usually through surgical intervention. Surgical intervention creates anatomical defects creating communication between oral and nasal cavity. Patients pose difficulties while performing normal functions such as swallowing and speaking, due to this communication. To overcome the problems encountered by the patient, obturators are fabricated. The main problem with rehabilitation of large defect is the weight of prosthesis; the prosthesis becomes very bulky and nonretentive due to its weight. Hollow obturators are fabricated to conquer this tribulation by different techniques. This case report describes a simplified method of fabrication of a definitive hollow bulb obturator for rehabilitation of a maxillary defect (Aramany's class I) by insertion of balloon.


Design and rationale of the high-sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial.
Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events.


Satisfaction of undergraduate students at University of Jordan after root canal treatment of posterior teeth using rotary or hand preparation.
The aim of this study was to report the satisfaction of fifth year undergraduate students on the clinical use of rotary endodontic preparation compared with stainless steel standard technique and to evaluate the impact of rotary nickel-titanium instruments on undergraduate teaching. This study was carried out by the fifth year undergraduate students attending peer review sessions as a part of their training program using a questionnaire to assess their satisfaction with these two techniques. The overall results indicated a statistically significant satisfaction of the undergraduate students with the use of the nickel-titanium system (P < 0.001) compared to stainless steel standard technique. Under the conditions of this study, the results showed a positive acceptance and consensus among novice dental students regarding the use of ProTaper rotary files and the need for undergraduate teaching of rotary nickel-titanium systems in Jordan.


Bone marrow perfusion in healthy subjects assessed by scintigraphy after application of a tourniquet.
By means of a gamma camera technique involving a bolus injection of autologous 99mTc-labeled erythrocytes, we found that despite a tourniquet on the limb, the erythrocytes entered the bone marrow, and caused oozing in both lower (10 subjects) and upper limbs (14 subjects). The 24 healthy volunteers, 18 men, had a mean age of 50 (range 20-86) years. The activity reached the distal femur in a median of 365 (quartile 278-560) seconds and the distal humerus in a median of 280 (quartile 208-370) seconds. The median velocity for movement of erythrocytes in the femur was 3.7 (quartile 2.74.4) cm/min and in the humerus, it was 4.0 (quartile 3.1-5.3) cm/min. In 21 subjects, this activity reached the periarticular soft tissue. After 15 min with the tourniquet inflated, the activity in the distal femur of the tourniquet limb was 9 (quartile 5-18)% of that in the limb without a tourniquet. This study shows that although a tourniquet effectively occludes the extra-osseous blood supply, some intra-osseous blood supply is retained, which makes it difficult to obtain a bloodless field in some patients, despite the use of a tourniquet.


Effect of Bacillus subtilis DSM 32315 on the intestinal structural integrity and growth performance of broiler chickens under necrotic enteritis challenge.
The effect of dietary inclusion of Bacillus subtilis DSM 32315 on the intestinal health and growth performance of Cobb 500 male broilers subjected to a Clostridium perfringens-induced necrotic enteritis (NE) challenge was determined in 2 experiments. In experiment 1, chicks were randomly assigned to 4 treatments of 10 replicate/treatment. In experiment 2, chicks were randomly assigned to 4 treatments of 12 replicates/treatment. The experimental treatments were non-infected, non-supplemented control, infected, non-supplemented control (IC), infected + Bacillus subtilis DSM 32315 (B. subtilis DSM 32315), infected + bacitracin methylene disalicylate (BMD). In both experiments, NE was induced by oral inoculation of toxin producing C. perfringens on 3 consecutive days between 17 and 20 D of age, following exposure of birds to pre-disposing conditions. At day 28 (experiment 1), broilers fed diets with B. subtilis DSM 32315 exhibited a significantly higher body weight, lower mortality, and intestinal NE lesion score, compared to the IC treatment. At day 42 (experiment 2), B. subtilis DSM 32315 supplementation significantly improved BW, feed conversion ratio, production efficiency factor, NE lesion score, and mortality, compared to IC treatment. The effect of B. subtilis DSM 32315 on intestinal integrity of NE challenged chickens was evaluated with histomorphometry. A significantly shallower crypt depth and higher villus height to crypt depth ratio were observed in the mid-intestine of birds belonging to the B. subtilis DSM 32315 group, compared to the IC group. Furthermore, B. subtilis DSM 32315 supplementation significantly reduced the enteritis index associated with NE. In both experiments, the effect of B. subtilis DSM 32315 on the phenotypic measurements of NE and performance was comparable to the effect observed with BMD supplementation. In conclusion, supplementation of the direct fed microbial strain B. subtilis DSM 32315 can ameliorate the pathology and performance detriments associated with NE.


Presenilins in the developing, adult, and aging cerebral cortex.
Mutations in presenilins are the major cause of familial Alzheimer disease. The involvement of presenilins in the pathogenesis of Alzheimer disease, therefore, has been the subject of intense investigation during the past decade. Genetic analysis of phenotypes associated with presenilin mutations in invertebrate and vertebrate systems has greatly advanced our understanding of the in vivo functions of presenilins. In this review, the authors will summarize the current understanding of presenilin function, with an emphasis on the mammalian cerebral cortex. During development, presenilins play crucial roles in the maintenance of neural progenitor cell proliferation, the temporal control of neuronal differentiation, the survival of Cajal-Retzius neurons, and proper neuronal migration in the developing cerebral cortex. Analysis of presenilin function in the adult cerebral cortex has revealed essential roles for presenilins in synaptic plasticity, long-term memory, and neuronal survival. The authors will also discuss the molecular mechanisms through which presenilins may mediate these functions, including the Notch, CREB, and NMDA receptor-mediated signaling pathways. These diverse functions of presenilins in cortical development and function and neuronal survival have important implications for the pathogenesis of neurodegenerative dementia.


Nutrigenomic approaches to study the effects of n-3 PUFA diet in the central nervous system.
Deficiencies in essential, mainly omega-3 and omega-6 (n-3, n-6) long chain polyunsaturated fatty acids (LC-PUFA) result in visual and cognitive impairment and disturbances in mental functions in animals and could be the main reason for the increasing incidence of different mental disorders in humans. Traditional approaches cannot give us a detailed picture on how dietary lipids exert their effects, because they focus on only a few genes or biomarkers. Dietary lipids not only influence the biophysical state of the cell membranes but, via direct and indirect routes, they also act on multiple pathways including signalling and gene and protein activities. Therefore, to understand the molecular basis of the effects and roles of n-3 PUFA in the central nervous system global screening techniques such as DNA- or protein microarrays were used to assess the changes, in a global way, at the transcriptome and at the proteome level. With DNA microarrays we found that cholesterol and fish oil (high in PUFA) diets altered the expression of several genes involved in raft formation and membrane protrusions. By using protein microarrays we detected a decreased concentration of protein kinase C beta, gamma, phospholipase C gamma and other changes in the expression level of proteins involved in the signal transduction pathway in the brain in response to high cholesterol diet. Besides the known cellular effects of lipid nutritions (changing eicosanoid make up, effects on membrane fluidity and raft stability) it is now evident that dietary lipids influence gene and protein activity levels, protein modifications and probably play important role in modulating protein aggregation.


Model of Decision Making Support for a Doctor in the Treatment of an Oncosurgical Patient in a Hospital.
At the present moment, there is no uniform approach to the decision to conduct a planned surgical intervention in case of oncosurgical pathology, with appropriate recommendations in different sources. Consequently, in modern medicine, there is a particular problem of an objective assessment of the patient's physical condition and a risk assessment of an upcoming surgical intervention for developing an individualized tactic of preparation for surgical treatment for each particular patient. The need for introduction of new approaches and technologies, as well as treatment regimens, that allow us to take a fresh look at the possibilities of solving the problems of predicting critical outcomes of planned operations, determined the purpose of our study. The result of our study was the design of a decision rule in the form of the Microsoft Access software, which allows to rank patients with oncological diseases by the probability of lethal outcome in surgery.


Fibrogenic actions of acetaldehyde are β-catenin dependent but Wingless independent: a critical role of nucleoredoxin and reactive oxygen species in human hepatic stellate cells.
We investigated whether the fibrogenic actions of acetaldehyde, the immediate oxidation product of ethanol, are mediated via Wingless (WNT) and/or β-catenin pathways in human hepatic stellate cells (HSC). First, we show that both β-catenin small inhibitory RNA and a dominant negative-MYC expression vector markedly down-regulated the expressions of fibrogenic genes in freshly isolated HSC. We further show that acetaldehyde up-regulated platelet-derived growth factor receptor beta mRNA and protein expressions ranging from 4.0- to 7.2-fold (P<0.001). Acetaldehyde induced MYC and collagen type-1 alpha-2 mRNA and protein expressions were WNT independent because DKK1, an antagonist of the canonical WNT/β-catenin pathway, completely failed to block these inductions. Acetaldehyde increased phospho-glycogen synthase kinase-3 beta (GSK3B) protein by 31% (P<0.01), whereas phospho-β-catenin protein decreased by 50% (P ≤ 0.01). Significantly, in contrast to 43% (P<0.01) inhibition of β-catenin nuclear translocation in nucleoredoxin (NXN)-overexpressed HSC, acetaldehyde profoundly stimulated β-catenin nuclear translocation by 51%, (P<0.01). Acetaldehyde also increased the cellular reactive oxygen species level 2-fold (P<0.001) with a concomitant 2-fold (P<0.001) increase in 4-hydroxynonenal adducts. Conversely, there was a 44% decrease (P<0.001) in glutathione levels with a concomitant 76% (P<0.001) decrease in the level of NXN/ disheveled (DVL) complex. Based on these findings, we conclude that actions of acetaldehyde are mediated by a mechanism that inactivates NXN by releasing DVL, leading to the inactivation of GSK3B, and thereby blocks β-catenin phosphorylation and degradation. Thus, the stabilized β-catenin translocates to the nucleus where it up-regulates the fibrogenic pathway genes. This novel mechanism of action of acetaldehyde has the potential for therapeutic interventions in liver fibrosis induced by alcohol.


The myelodysplastic syndromes.
The myelodysplastic syndromes (MDSs) are a group of haematological disorders found predominantly in the elderly, and are defined by morphological abnormalities of the three cell lines. None of the abnormalities is specific for MDS but, when combined with active or hyperactive haemopoiesis and refractory cytopenia in an elderly person, they suggest the diagnosis. The French-American-British co-operative group divided MDSs into five types: refractory anaemia; refractory anaemia with ring sideroblasts; refractory anaemia with excess of blasts; refractory anaemia with excess of blasts in transformation; and chronic myelomonocytic leukaemia. The classification was based on the number of blasts in the bone marrow, dysplastic features in one or more cell lines, ringed sideroblasts, blasts in the peripheral blood, Auer rods in the granulocyte precursors and absolute monocytosis. MDS can be a primary condition and of unknown aetiology or develop secondary to the action of a known agent such as an alkylating agent, chemical or recombinant human granulocyte colony-stimulating factor. The pathogenesis of MDS is thought to be a multi-step process which begins with a somatic mutation in the pluripotential stem cell, is irreversibly altered and acquires a survival advantage. The abnormal clone expands at the expense of normal haemopoiesis and undergoes further genetic change to give a progressively more malignant phenotype. Present theories of the development of MDS are speculative but further research could cast light on the development of other haematological disorders.


Mixed Self-Assembled Aptamer and Newly Designed Zwitterionic Peptide as Antifouling Biosensing Interface for Electrochemical Detection of alpha-Fetoprotein.
A sensitive and low-fouling aptasensor for alpha-fetoprotein (AFP) was developed based on mixed self-assembled aptamers and newly designed zwitterionic peptides, where densely immobilized peptides formed an antifouling layer to resist nonspecific protein adsorption, and sparsely attached aptamers acted as the recognizing layer to achieve target binding. The obtained biosensing interface responded to the target AFP with a strikingly selective and sensitive manner, exhibited excellent protein-resistant performance even in complex human serum solution, and showed promising feasibility for the quantitative analysis of AFP in real human serum samples.


Response of hand dermatitis to a new skin barrier-protectant cream.
Twenty-five patients with hand dermatitis participated in a pilot study utilizing a new skin barrier cream containing white petrolatum. Each patient received treatment with SBR-Lipocream, which was applied three to four times daily for a period ranging from one to four weeks. All patients completed pre- and postsurvey questionnaires and were evaluated by a staff physician prior to, and upon completion of, the study. All patients completed the evaluation. Results of the survey indicated a general dissatisfaction with currently utilized moisturizers and a positive response to the skin barrier cream: 96 percent believed that this cream helped their condition. Based on this response, further evaluation of this cream's ability to manage this often-chronic condition and prevent exacerbation and flares appears warranted.


Identification and characterization of Acidithiobacillus ferrooxidans YY2 and its application in the biodesulfurization of coal.
The acidophilic Fe-oxidizing and S-oxidizing bacterium YY2 was isolated from the acid drainage of a coalmine. Based on morphological and physiological characteristics and phylogenetic analysis, it was identified as Acidithiobacillus ferrooxidans. Significant differences were observed in the oxidation efficiency and cell morphology when YY2 was cultured in 9K medium with ferrous ion (Fe(2+)), elemental sulfur (S(0)), and pyrite as the sole energy source. YY2 exhibited marked Fe(2+) oxidation activity; 44.2 g · L(-1) FeSO4 · 7H2O was completely oxidized in 30 h, but the rates of S(0) and pyrite oxidization were slower. After 20 days, the efficiencies of oxidizing 10 g · L(-1) S(0) and 10 g · L(-1) pyrite were approximately 9.6% and 20%, respectively. Cells cultured in pyrite as substrate secreted more extracellular polymeric substances than they did when cultured in Fe(2+) or S(0). Additionally, 75% total sulfur removal and 86% pyritic sulfur removal was achieved in a sequencing batch reactor of biodesulfurization of coal.


A phage weaponizes a satellite recombinase to subvert viral restriction.
Bacteria can acquire mobile genetic elements (MGEs) to combat infection by viruses (phages). Satellite viruses, including the PLEs (phage-inducible chromosomal island-like elements) in epidemic Vibrio cholerae, are MGEs that restrict phage replication to the benefit of their host bacterium. PLEs parasitize the lytic phage ICP1, unleashing multiple mechanisms to restrict phage replication and promote their own spread. In the arms race against PLE, ICP1 uses nucleases, including CRISPR-Cas, to destroy PLE's genome during infection. However, through an unknown CRISPR-independent mechanism, specific ICP1 isolates subvert restriction by PLE. Here, we discover ICP1-encoded Adi that counteracts PLE by exploiting the PLE's large serine recombinase (LSR), which normally mobilizes PLE in response to ICP1 infection. Unlike previously characterized ICP1-encoded anti-PLE mechanisms, Adi is not a nuclease itself but instead appears to modulate the activity of the LSR to promote destructive nuclease activity at the LSR's specific attachment site, attP. The PLE LSR, its catalytic activity, and attP are additionally sufficient to sensitize a PLE encoding a resistant variant of the recombination module to Adi activity. This work highlights a unique type of adaptation arising from inter-genome conflicts, in which the intended activity of a protein can be weaponized to overcome the antagonizing genome.


Hierarchical image classification in the bioscience literature.
Our previous work has shown that images appearing in bioscience articles can be classified into five types: Gel-Image, Image-of-Thing, Graph, Model, and Mix. For this paper, we explored and analyzed features strongly associated with each image type and developed a hierarchical image classification approach for classifying an image into one of the five types. First, we applied texture features to separate images into two groups: 1) a texture group comprising Gel Image, Image-of-Thing, and Mix, and 2) a non-texture group comprising Graph and Model. We then applied entropy, skewness, and uniformity for the first group, and edge difference, uniformity, and smoothness for the second group to classify images into specific types. Our results show that hierarchical image classification accurately divided images into the two groups during the initial classification and that the overall accuracy of the image classification was higher than that of our previous approach. In particular, the recall of hierarchical image classification was greatly improved due to the high accuracy of the initial classification.


The impact of cranial irradiation on GH responsiveness to GHRH plus GH-releasing peptide-6.
Patients treated with cranial radiation are at risk of GH deficiency (GHD). We evaluated somatotroph responsiveness to maximal provocative tests exploring the GH releasable pool in relation to the impact of radiation damage to the hypothalamic-pituitary unit. The GH-releasing effect of GHRH plus GH secretagogue [GH-releasing peptide (GHRP)-6] (GHRH+GHRP-6) was studied in 22 adult patients (age, 23.2 +/- 1.4 yr; 8 female and 14 male; mean body mass index, 22.6 +/- 0.7 kg/m(2)) who received cranial radiation for primary brain tumor distant from hypothalamic-pituitary region 7.6 +/- 0.7 yr before GH testing. Two stimulatory tests for GH secretion were employed: insulin tolerance test (ITT, 0.15 IU/kg regular insulin i.v. bolus); and GHRH+GHRP-6 test: GHRH (Geref Serono, Madrid, Spain; l microg/kg) plus GHRP-6 (CLINALFA, Laufelingen, Switzerland; 1 microg/kg) as i.v. bolus. Serum GH was measured (Delphia; Perkin Elmer, Wallac, Turku, Finland) at -30, -15, 0, 15, 30, 45, 60, 90, and 120 min. Anterior pituitary function was normal in all except in 1 female with hyperprolactinemia. Twelve out of 22 irradiated patients were GH-deficient (GHD) with both tests. Eleven out of 22 (50%) irradiated patients were severely GHD, according to the ITT (GH < 3 microg/liter; mean GH peak, 1.5 +/- 0.5 microg/liter). In 9 irradiated patients, in whom ITT was performed as well, mean peak GH after the GHRH+GHRP-6 test was 6.2 +/- 0.8 microg/liter, which is considered as severe GHD, according to our own cut-off for the test (peak GH < 10 microg/liter). GH responses to both tests were highly concordant, but the differential in the GH peak concentrations between GHD and non-GHD irradiated patients was significantly larger for the GHRH+GHRP-6 test than that for the ITT. The 2 discordant responses, i.e. poor response to the ITT and good response to the GHRH+GHRP-6 test, were found in 1 hyperprolactinemic female patient and in 1 other female. One irradiated patient was diagnosed as GHD only with the combined test, because ITT was contraindicated because of epilepsy. PRL and cortisol responses to ITT were normal in all irradiated patients and did not depend on the GH status. IGF-I levels were not informative or discriminative between the GHD and non-GHD irradiated adult patients. In conclusion, the use of GH secretagogues plus GHRH is an easy, reliable and accurate way of assessing GH secretion in cranially irradiated patients. Impairment of the GH releasable pool in the irradiated patients, with a maximal provocative test, reflects alterations in the hypothalamic-pituitary unit caused by radiotherapy.


Trans-carotid access for TAVR allows safe and rapid exchange for bailout valve-in-valve procedures.
Trans-carotid access for trans-catheter aortic valve replacement is a valid alternative in patients with aortic valve dysfunction, severe peripheral vascular disease, and high-risk for surgery. However, in the event of the need for a bailout valve-in-valve procedure, the safety of this access site is uncertain. We report a patient with aortic regurgitation, previous coronary surgery, peripheral vascular disease, and impaired ventricular function who underwent a CoreValve Evolut-R (Medtronic Inc, Minneapolis, MN) implantation through the left carotid artery followed by a successful valve-in-valve procedure with a 26-mm Edwards Sapien3 valve (Edwards Lifesciences, Irvine, CA) through the same carotid access site.


[The dopamine system in rat brain areas in the early period following irradiation with superhigh doses].
In studying the main indices that characterize the neurochemical system of biosynthesis and degradation of a dopamine neuromediator, tyrosine hydroxylase-dopamine-monoamine oxidase, in different brain regions 5-6 min, 1 and 18 h after whole-body irradiation with high energy electrons (100 Gy) the authors have revealed a 25-40% inhibition of tyrosine hydroxylase and monoamine oxidase activity, and a 40% increase in the dopamine content of basal ganglia of the brain that control behavioural reactions of the organism. The neurochemical disturbances revealed are involved in the mechanisms of early transient incapacity after irradiation with superhigh doses.


Tropical fishes vanished after the operation of a nuclear power plant was suspended in the Sea of Japan.
Thermal discharge from a nuclear power plant (NPP) provides an opportunity to foresee changes in faunal communities that may be induced by ocean warming. I assessed these changes by identifying characteristics of the fish community near the thermal discharge from a NPP and by recording temporal changes that occurred after the suspension of the NPP. Underwater visual censuses were conducted near Takahama NPP in the Sea of Japan, and fish assemblages were compared to those in two other sites: a site with discharge from a coal-fired power plant and a control site. During the surveyed period (8 years) when the NPP was in operation, the sea water temperature at the site near the NPP was warmer, had a significantly higher fish abundance, and a higher species richness, including tropical fishes, than the other two sites. However, once the NPP was suspended, tropical fishes dramatically decreased near the NPP. This abrupt change in fish assemblage may be due to the lowest lethal temperatures of tropical fishes being only slightly higher than the winter temperature in this area. Relatively poor ecosystem structure in the local warming area may also have contributed to low resilience of tropical fish species to this temperature change.


Comprehensive Large-Scale Integrative Analysis of Omics Data To Accelerate Specialized Metabolite Discovery.
Microbial specialized metabolites are key mediators in host-microbiome interactions. Most of the chemical space produced by the microbiome currently remains unexplored and uncharacterized. This situation calls for new and improved methods to exploit the growing publicly available genomic and metabolomic data sets and connect the outcomes to structural and functional knowledge inferred from transcriptomics and proteomics experiments. Here, we first describe currently available approaches that support the comprehensive mining of metabolomics and genomics data. Next, we provide our vision on how to move forward toward the automated linking of omics data of specialized metabolites to their structures, biosynthesis pathways, producers, and functions.


A brief review of survival prediction of advanced cancer patients.
Survival prediction of advanced cancer patients remains an important task for palliative clinicians. It has transformed from an art form into a more scientific branch of the discipline with the evolution of palliative medicine and use of statistical estimates of survival. Both clinician predicted survival and actuarial estimation of survival have their uses and drawbacks. This article gives a practical and quick summary of the pros and cons of clinician survival prediction and actuarial-based prognostic tools used at the bedside.


An EVH1/WH1 domain as a key actor in TGFbeta signalling.
EVH1 (enabled VASP (vasodilator-stimulated protein) homology 1)/WH1 (WASP (Wiskott-Aldrich syndrome protein) homology 1) domains, present in Ena VASP and WASP, are protein interaction modules specialised in binding proline-rich ligands. An EVH1/WH1 domain is here identified in the recently cloned SMIF protein, a key protein in transforming growth factor-beta (TGFbeta) signalling which was not yet related to defined domains. The SMIF EVH1/WH1 domain interacts with the proline-rich Smad4 activation domain, leading to translocation of so-formed complex to the nucleus where SMIF possesses strong intrinsic TGFbeta-inducible transcriptional activity. This finding highlights the pivotal role that the EVH1/WH1 family of domains play in multiple eukaryotic signal transduction pathways.


[Expression of FasL and apoptosis in pulmonary tissue of rats exposed to silica at different time].
To investigate the change of the expression of the FasL receptor and apoptosis in the pathology of silicosis of the rats exposed to silica and their roles. Ninety-six wistar rats were randomizedly divided into the control group and the experimental group. The silicotic animal model was established by the direct tracheal instillation of silica into rat lungs surgically. The control rats underwent directly tracheal instillation of saline into lungs surgically. Eight rats from each group were sacrificed at different days. The expression of FasL receptor in the tissue of the model rats was detected by tissuechip microarray and immunohistochemistry and the cell apoptosis induced by silica was determined by TdT-mediated dUTP nick end-labeling method. The integral optical density of positive cells were quantitatively analyzed using Image-Pro Plus Version 4.5 for windows. The expression of FasL in the lung tissue of the model rats on the 7th, the 14th, the 21st, and the 28th day was significantly higher than that in the control group (P < 0.05), and peaked at the 14th day after exposure to silica. Apoptotic cells in the lung tissue of the model rats on the 1st, the 3rd, the 7th, the 14th, the 21st, and the 28th day were significantly more than those in the control group, and peaked at the 7th and the 14th day after exposure to silica. Silica can lead to apoptosis in lung tissues. FasL is expressed in all kinds of cells in the pulmonary tissues of the rats exposed to silica and leads to apoptosis. From the 7th day to 14th day, inflammatory cells dominate in apoptotic cells.


Fungal infections in AIDS. Histoplasmosis and coccidioidomycosis.
Histoplasma capsulatum and Coccidioides immitis are two fungi that are regional in occurrence and cause opportunistic fungal infections in patients with AIDS. Many cases of histoplasmosis have been reported in patients months or years after they have been in an endemic area. These are obviously cases of reactivation of latent infections. With coccidioidomycosis, the cases have been reported from endemic areas, but some also appear to be reactivation infections, and we should anticipate such cases in nonendemic areas just as with histoplasmosis. The clinical presentations may be atypical, even mimicking acute bacterial sepsis. The diagnosis should be sought in any HIV-infected patient with an unexplained infection and residence or travel in an endemic area even in the remote past. Studies should include bone marrow examinations for histoplasmosis as well as skin biopsies with special strains and cultures for fungi for both infections. Sputum or bronchoscopy specimens have often been the source of a diagnosis in coccidioidomycosis. Serologic tests for antibody in both diseases yield inconsistently positive results in AIDS patients. Treatment of the acute infection should be with amphotericin B followed by maintenance suppressive therapy with ketoconazole or Amphotericin B.


The complete chloroplast genome of Salix matsudana f. tortuosa.
In this study, the complete chloroplast genome of Salix matsudana f. tortuosa was sequenced and analyzed. The genome of Salix matsudana f. tortuosa was 155,673 bp in length and was quadripartite in structure, containing a large single-copy region with a length of 84,447 bp, a small single-copy region with a length of 16,320 bp, and two inverted repeats of 27,453 bp in length. The chloroplast genome contains 130 genes, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The GC content is 36.64%. The phylogenetic tree shows that Salix matsudana f. tortuosa, Salix matsudana, and Salix babylonica are closely related and located on the same branch. The chloroplast genome of Salix matsudana f. tortuosa will provide important data for further systematic study of Salicaceae and the genus Salix.


Clinical Usefulness of a Cell-based Assay for Detecting Myelin Oligodendrocyte Glycoprotein Antibodies in Central Nervous System Inflammatory Disorders.
The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients' clinical characteristics. We established the CBA using HEK 293 cells transiently overexpressing full-length human MOG, tested it against 166 samples from a multicenter registry of central nervous system (CNS) inflammatory disorders, and compared the results with those of the Oxford MOG-Ab-based CBA and a commercial MOG-Ab CBA kit. We recruited additional patients with MOG-Abs and compared the clinical characteristics of MOG-Ab-associated disease (MOGAD) with those of neuromyelitis optica spectrum disorder (NMOSD). Of 166 samples tested, 10 tested positive for MOG-Abs, with optic neuritis (ON) being the most common manifestation (4/15, 26.7%). The in-house and Oxford MOG-Ab CBAs agreed for 164/166 (98.8%) samples (κ=0.883, P<0.001); two patients (2/166, 1.2%) were only positive in our in-house CBA, and the CBA scores of the two laboratories correlated well (r=0.663, P<0.001). The commercial MOG-Ab CBA kit showed one false-negative and three false-positive results. The clinical presentation at disease onset differed between MOGAD and NMOSD; ON was the most frequent manifestation in MOGAD, and transverse myelitis was most frequent in NMOSD. The in-house CBA for MOG-Abs demonstrated reliable results and can potentially be used to evaluate CNS inflammatory disorders. A comprehensive, long-term study with a large patient population would clarify the clinical significance of MOG-Abs.


Pseudomelanoma after laser therapy.
An 18-year-old man had a melanocytic nevus on the chin that had been treated with three different lasers at a private clinic for 2.5 years. This lesion was excised and sent to a pathologist. The initial histological diagnosis was reported as compound nevus coexistent with changes suspicious of malignant melanoma. The reevaluation of histology together with the clinical information that the lesion had been pretreated with laser resulted in a revised diagnosis of pseudomelanoma. It is important to be aware of this benign pseudomelanoma, which can arise as a complication of laser therapy, to avoid subjecting patients to unnecessary surgical procedures or other forms of adjuvant treatment.


Simultaneous urethro-cystometry with a new technique.
A new technique for studying simultaneous intravesical-intraurethral pressure is described. The basic principle of our technique is pressure recordings with the aid of micro-transducers. These micro-transducers have excellent frequency response, are easy to calibrate and to sterilize and are free from artefacts induced by motion. They permit a more accurate study of the pressures within the bladder and the urethra than catheter-transducer systems described earlier. Using electronical subtraction the closure pressure can easily be measured under static and dynamic conditions. Typical pressure diagrammes obtained with this catheter system are presented.


Genome sequencing of strains of the most prevalent clonal group of O1:K1:H7 Escherichia coli that causes neonatal meningitis in France.
To describe the temporal dynamics, molecular characterization, clinical and ex vivo virulence of emerging O1:K1 neonatal meningitis Escherichia coli (NMEC) strains of Sequence Type complex (STc) 95 in France. The national reference center collected NMEC strains and performed whole genome sequencing (WGS) of O1:K1 STc95 NMEC strains for phylogenetic and virulence genes content analysis. Data on the clinical and biological features of patients were also collected. Ex vivo virulence was assessed using the Dictyostelium discoideum amoeba model. Among 250 NMEC strains collected between 1998 and 2015, 38 belonged to O1:K1 STc95. This clonal complex was the most frequently collected after 2004, representing up to 25% of NMEC strains in France. Phylogenetic analysis demonstrated that most (74%) belonged to a cluster designated D-1, characterized by the adhesin FimH30. There is no clinical data to suggest that this cluster is more pathogenic than its counterparts, although it is highly predominant and harbors a large repertoire of extraintestinal virulence factors, including a pS88-like plasmid. Ex vivo virulence model showed that this cluster was generally less virulent than STc95 reference strains of O45S88:H7 and O18:H7 serotypes. However, the model showed differences between several subclones, although they harbor the same known virulence determinants. The emerging clonal group O1:K1 STc95 of NMEC strains is mainly composed of a cluster with many virulence factors but of only moderate virulence. Whether its emergence is due to its ability to colonize the gut thanks to FimH30 or pS88-like plasmid remains to be determined.


Proteomic analysis of human bile from malignant biliary stenosis induced by pancreatic cancer.
Stenosis of the common bile duct may be either due to benign (chronic pancreatitis) or malignant (cholangiocarcinoma, pancreatic adenocarcinoma) conditions. The benign nature of the stricture should be first confirmed in order to ensure appropriate therapy. Therefore, the identification of markers allowing discrimination between malignant and benign biliary stenosis would be very valuable in clinical practice. To this intent, we performed a proteomic analysis of bile samples from patients having a biliary stenosis caused by pancreatic adenocarcinoma. Bile samples were collected during endoscopic retrograde cholangiopancreatography and purified using different methods. The extracted proteins were then analyzed by SDS-PAGE and LC-MS/MS. A total of 127 proteins were identified, 34 of which have not been previously detected in proteomic studies of bile. Among them, several proteins have been described as potential biomarkers of pancreatic cancer. We extended our investigation by studying the expression of some of these pancreatic cancer markers in bile samples collected from patients with various etiologies of biliary stenosis including pancreatic cancer, cholangiocarcinoma, chronic pancreatitis, as well as gallstone-induced stenosis. Our data showed a conspicuous overexpression of CEACAM6 and MUC1 (CA19-9) in pancreatic cancer and cholangiocarcinoma samples, according to the hypothesis that bile fluid collects cancer-associated protein leaking from the tumor microenvironment. These results underline the interest of using bile as a source of biomarkers for the diagnosis of malignant biliary stenosis.


Optic Disk Detection in Fundus Image Based on Structured Learning.
Automated optic disk (OD) detection plays an important role in developing a computer aided system for eye diseases. In this paper, we propose an algorithm for the OD detection based on structured learning. A classifier model is trained based on structured learning. Then, we use the model to achieve the edge map of OD. Thresholding is performed on the edge map, thus a binary image of the OD is obtained. Finally, circle Hough transform is carried out to approximate the boundary of OD by a circle. The proposed algorithm has been evaluated on three public datasets and obtained promising results. The results (an area overlap and Dices coefficients of 0.8605 and 0.9181, respectively, an accuracy of 0.9777, and a true positive and false positive fraction of 0.9183 and 0.0102) show that the proposed method is very competitive with the state-of-the-art methods and is a reliable tool for the segmentation of OD.


[Congenital pseudoarthrosis of the tibia treated with the free microvascular fibula].
Congenital pseudoarthrosis (CPT) of the lower leg is still a considerable therapeutic problem. There are many surgical and other procedures to manage pseudoarthrosis, but the results are not always satisfactory, unfortunately, and are accompanied by a big number of complications, even limb amputation in some cases. The most complicated surgical procedure is transplantation of the autogenous free microvascular fibula coil which has had the best results momentarily. We are showing a case of a 2.5-year old patient with congenital pseudoarthrosis of the lower leg previously treated unsuccessfully by a conventional surgical method. This is at the same time the first case of such operative treatment of CPT in the territory of Serbia and Montenegro as well as former Yugoslavia. The patient was operated in October 1992.


Birmingham Hip Resurfacing vs Total Hip Arthroplasty: A Matched-Pair Comparison of Clinical Outcomes.
Birmingham hip resurfacing (BHR) has proven to be a good alternative for younger patients with osteoarthritis. Some have asserted that BHR may yield outcomes which are superior to total hip arthroplasty (THA), and that some studies which failed to show a difference were plagued by ceiling effects and lack of sensitivity of outcome measures. The purpose of this study is to compare outcomes of BHR and THA using the "Forgotten Joint" Score-12 (FJS), a more sensitive score with lesser vulnerability to the ceiling effect. Patients who underwent BHR were matched to patients who underwent posterior THA by computing a propensity score using 5 covariates: age, body mass index, gender, worker's compensation claims, and previous hip surgery. Surgical outcomes were assessed using 6 patient-reported outcome measures, including the FJS, the visual analog scale for pain, and patient satisfaction. There were 42 patients in the BHR group and 18 patients in the THA group. The FJS was 78.0 for the BHR group and 76.0 for the THA group. The Veterans RAND 12-Item Health Survey Mental Component Summary and Short Form 12 Mental Component Summary were significantly higher in the BHR group. No differences were seen between all other patient-reported outcomes. BHR offers excellent results in young patients that are comparable to THA. As no clinical difference could be shown between BHR and THA, even with the use of the FJS, the choice between BHR and THA should not be based solely on any expectation that either yields superior clinical outcomes compared to the other at short-term follow-up.


The relationship of abdominal fat mass assessed by helical or conventional computed tomography to serum leptin concentration.
In the present study, we focused on the relationship of intra-abdominal visceral fat (VF) or subcutaneous fat (SF) mass to serum leptin levels, and also on the relationship of leptin to serum lipid and lipoprotein concentration. Subjects with obesity (26 men, 26 women) were recruited for this study. We obtained helical CT scans with a tube current of 150 mA, voltage of 120 kV and 2:1 pitch (table speed in relation to slice thickness), starting at the upper edge of the liver and continuing to the pelvis. The intra-abdominal visceral fat (VF) volume was measured by drawing a line within the muscle wall surrounding the abdominal cavity. The abdominal SF volume was calculated by subtracting the VF volume from the total abdominal fat volume. By comparison, the abdominal VF and SF areas were determined at the umbilical level by the established slice-by-slice CT scanning technique. We found: 1) abdominal SF mass, either as volume or area, was a more important determinant of serum leptin than was VF mass; 2) among TC, TG, HDL-C and LDL-C, only TG had a positive correlation to serum leptin levels in men, whereas in women no lipid parameters had any relationship with leptin; and 3) VF mass had a positive correlation to serum TC and TG in men, whereas SF did not. The present study provides considerable evidence on the relationship between abdominal fat mass and serum leptin, and shows that the relationships between serum leptin and serum lipids and lipoproteins are not straightforward. We also suggest that fat area measured by conventional CT is a better indicator than its corresponding volume assessed by helical CT, based on the present results showing its closer association to serum lipids.


Antiandrogenic effects of cyproterone acetate and chloromadinone acetate on the rat hypothalamus as revealed by electroencephalographic responses.
Bipolar stainless steel electrodes were implanted stereotaxically into given hypothalamic and cortical regions of the brain of 48 rats. The animals were divided into two groups of equal numbers and the electrical activity of the given regions was recorded electroencephalographically (EEG). The effect of the acute and chronic administration of cyproterone acetate (CPA) or chloromadinone acetate (CHA), in doses inducing sterility, on EEG activity were observed. Apart from slight inhibition in the preoptic region, no appreciable EEG changes were found after CPA, while CHA reduced the discharge frequency in both the preoptic and the posterior hypothalamus. These findings can be attributed to the presence of two different types of androgen receptors in the hypothalamus.


Beta3-adrenoceptors in human detrusor muscle.
The detrusor muscle contains beta-adrenoceptors (beta-AR), and 2 subtypes-beta1-AR and beta2-AR-have been identified in most species. Although beta2-AR has an important role in muscle relaxation via activation of adenylate cyclase, evidence suggests that a third subtype, beta3-AR, which is implicated in metabolic functions of endogenous catecholamines, mediates relaxation of human detrusor muscle. There is a predominant expression of beta3-AR messenger RNA (mRNA) in human bladder tissue, with 97% of total beta-AR mRNA being represented by the beta3-AR subtype and only 1.5% and 1.4% by the beta1-AR and beta2-AR subtypes, respectively. Functionally, selective beta3-AR agonists relax human isolated detrusor, whereas selective beta1-AR/beta2-AR agonists do not. Isoproterenol-induced relaxation is inhibited by selective beta3-AR antagonists but not by selective beta1-AR or beta2-AR antagonists. In animal models, beta3-AR agonists increase bladder capacity and have only weak cardiovascular side effects. Although this evidence points toward the clinical utility of beta3-AR agonists as therapy for overactive bladder, clinical trials of beta3-AR agonists identified in animal models as antiobesity agents indicate side effects of tremor and tachycardia. Development of compounds with high selectivity for the human beta3-AR, identified by screening techniques using cell lines transfected with the human beta1-AR, beta2-AR, and beta3-AR genes, may mitigate such problems. Together with the preliminary finding that 49% (21 of 43) of patients with idiopathic detrusor instability have a tryptophan 64 arginine mutation of the beta3-AR gene, which may be a useful genetic marker, evidence points toward beta3-AR being a therapeutic target for treatment of overactive bladder disorder.


A Hierarchy of Medical Countermeasures Against Biological Threats.
Emerging biological threats represent a serious challenge for force health protection (FHP). Against a novel biological threat, medical countermeasures are the first line of defense. However, as exposed by global pandemic conditions, there are significant complications when administering medical countermeasures against novel threats. One such limitation involved the lack of any guiding structure to discuss and deliberate upon the relative value of employing different countermeasures either alone or in tandem. For example, both personal protective equipment and prophylactic medication can provide some protection, but how are individual protections weighed against operational capabilities and FHP initiatives? The goal of this review is to provide a hierarchical organizing structure to the different medical countermeasures available in response to emerging biological threats. This review used no explicit inclusion or exclusion criteria for its literature review. References are provided for illustrative purposes to represent different components of the medical hierarchy. The hierarchy presented here is organized around a resource-durability structure that functions as a push-pull mechanism. Specifically, lower levels of the hierarchy require more resources to sustain FHP conditions while also providing less durable protection. These countermeasures require continual reapplication, and so resources become conceived as much in time and effort to apply as in exhaustible supplies. Higher-order countermeasures require less resources investment as a single application can provide weeks, months, or years of protection. Moreover, higher-order protections are less likely to interfere with military operational capabilities, which further support their classification as superior countermeasures to sustain FHP. The five levels of the hierarchy are presented here as follows, organized from lowest to highest value as a medical countermeasure: (1) Sanitization, (2) personal protective equipment, (3) prophylaxis, (4) vaccines, and (5) optimized immune system. Rationale and descriptions identify how each higher-order countermeasure is superior to its lower-order counterparts while noting that optimizing FHP will likely require employing multiple countermeasures at different levels. The discussion concludes with an overview as to how different countermeasures were employed to various degrees during a novel global pandemic. Identifying medical countermeasures is important to optimizing FHP. Different countermeasures have different advantages, and the hierarchy distinguishes between inferior and superior countermeasures through the push-pull style mechanism of resource-durability assessment. Future deployment and development should focus on superior countermeasures to maximize medical protections and operational readiness while understanding the relative value and complications inherent with different countermeasures.


[Cardiooncology: Current Aspects of Prevention of Anthracycline Toxicity].
Anthracyclines including doxorubicin, epirubicin, daunorubicin, aclarubicin are extensively used as chemotherapeutic agents for treatment of hematological and other malignancies. In cancer therapy anthracyclines are often used in combinations with other chemotherapeutic drugs and agents for molecularly targeted therapy. Anthracyclines are effective and powerful antineoplastic drugs with wide spectrum of application but active use of preparations of this group is limited because of such side effects as cardiotoxicity, myelotoxicity, thromboembolism, alopecia, etc. Cardiotoxicity is the most severe side effect of anthracycline administration. Clinical studies have shown that it is progressive and irreversible. Therefore, early detection and prevention of anthracycline cardiotoxicity has become an important trend in cardiology.


Serum from pregnant women with gestational diabetes mellitus increases the expression of FABP4 mRNA in primary subcutaneous human pre-adipocytes.
Gestational diabetes mellitus (GDM) is defined as glucose intolerance first detected during pregnancy. It can result in pregnancy complications such as birth injury, stillbirth. Fatty acid-binding protein 4 (FABP4), found in adipose tissue, is associated with insulin resistance, and type 2 diabetes. The aim of this study was to investigate whether FABP4 in the placenta and decidua of pregnant women with GDM is higher than that in normal pregnant women, and whether serum from pregnant women with GDM may cause adipocytes to secrete more FABP4 than does serum from a normal pregnant group. We obtained placentas, deciduas, and serum from 12 pregnant women with GDM and 12 normal pregnant women and performed enzyme-linked immunosorbent assay, real time quantitative-polymerase chain reaction. We cultured human pre-adipocytes for 17 days with GDM and non-GDM serum and performed western blot, real time quantitative-polymerase chain reaction, and oil red O staining. Expression of FABP4 in serum, placenta and decidua of pregnant women with GDM was significantly higher than that in normal pregnant women. Serum from pregnant women with GDM increased the expression of FABP4 mRNA and decreased the expression of adiponectin mRNA in human pre-adipocytes significantly. Adipocyte cultured in GDM serum showed significantly greater lipid accumulation than those cultured in normal serum. Our results suggest that FABP4 is higher in placenta and decidua from pregnant women with GDM. Increased circulating FABP4 in maternal serum from pregnant women with GDM may originate from adipocytes and the placenta. Circulating FABP4 can induce increased insulin resistance and decreased insulin sensitivity.


[Primary pulmonary lymphoma: analysis of 18 cases].
To study the clinical characteristics, pathology, diagnosis and treatment of primary pulmonary lymphoma. Eighteen cases of primary pulmonary lymphoma diagnosed from Jan 1989 to Feb 2007 were retrospectively analyzed. There were 6 males and 12 females, with a median age of 47.5 years (17-71 years). Fifteen cases were diagnosed by surgical lung biopsy; 1 by percutaneous needle lung biopsy (1/6), 1 by percutaneous needle lung biopsy and bronchoscopic examination at the same time, the other 1 by bronchoscopic examination (1/10). Histological diagnosis showed that 2 cases were Hodgkin lymphoma, 9 mucosa-associated lymphoid tissue lymphoma, 1 follicular lymphoma, 2 diffuse large B cell lymphoma 2 anaplastic large cell lymphoma, 2 non-Hodgkin lymphoma whichcould not be classified because the slides were from other hospitals. The most common symptoms were cough (9/18) and fever (6/18). ESR elevation was common (10/12). CT features included solitary or multiple nodules (14/18), patchy opacities (11/18), consolidations (5/18), pleural effusions (5/18), atelectasis (5/18), and cavities (1/18). Misdiagnosis was found in 11 patients. Treatment modalities included surgical resection, radiotherapy and chemotherapy. Median follow-up time was 11 months (10 d to 205 mon). Thirteen patients were still alive, 4 patients were lost, and 1 patient died. The prognosis was associated with the level of [25.1 x 10(9)/L(18.1 - 39. -1) x 10(9)/L in poor prognosis group, 6.7 x 10(9)/L (5.48 - 8.41) x 10(9)/L in good prognosis group, u = 0.000, P <0.05] leukocytosis (3/3 vs 1/10, P <0.05). The clinical manifestations of primary pulmonary lymphoma are nonspecific. Misdiagnosis is common. Surgical lung biopsy is necessary for early diagnosis.


Abnormalities of liver regeneration: a review.
Structural and functional changes during liver regeneration have been studied extensively in experimental animals following partial hepatectomy or hepatic injury induced by noxious substances. These observations have been extended to evaluate abnormalities of liver regeneration which contribute to chronic hepatitis, cirrhosis and/or liver cancer in man. This is facilitated by the simultaneous perfusion of flash frozen percutaneous biopsies or explanted liver in an acrylic chamber with tritiated thymidine and proline to evaluate DNA and collagen synthesis, respectively. Such investigations indicate that chronic liver damage is associated with replication of mesenchymal, ductular and parenchymal cells, accompanied by increased fibrogenesis. The regenerative response of the liver after noxious injury in experimental animals and man is associated with the release of cytokines, increase of growth response genes and change in telomerase activity. The ability to monitor morphological, genetic and biochemical parameters provides new information on the kinetics of the reparative process in hepatobiliary disease. Abnormal liver regeneration and its untoward effects including tumorigenesis may be modified by altering nutrients, blocking antigens or receptors, and inhibiting metabolites which regulate cell replication and collagen deposition.


The tumour suppressor p53 regulates the expression of amyloid precursor protein (APP).
The expression of the APP (amyloid precursor protein), which plays a key role in the development of AD (Alzheimer's disease), is regulated by a variety of cellular mediators in a cell-dependent manner. In this study, we present evidence that p53 regulates the expression of the APP gene in neuroblastoma cells. Transient expression of ectopic p53, activation of endogenous p53 by the DNA-damaging drug camptothecin or Mdm2 (murine double minute 2) depletion decreases the intracellular levels of APP in murine N2abeta neuroblastoma cells. This effect was also observed in primary cultures of rat neurons as well as in SH-SY5Y cells, a human neuroblastoma cell line. Transient transfection studies using plasmids that contain progressive deletions of the 5' region of the gene demonstrate that p53 represses APP promoter activity through a mechanism that is mediated by DNA sequences located downstream of the transcription start site (+55/+101). Accordingly, expression of a dominant-negative p53 mutant significantly increases the transcriptional activity of the APP promoter. In addition, results obtained in gel mobility-shift assays show that p53 does not bind to the +55/+101 APP region, although it reduces binding of the transcription factor Sp1 (stimulating protein 1). Reduction of Sp1 binding after activation of p53 with camptothecin was also observed in chromatin immunoprecipitation assays. Altogether, our results strongly suggest a mechanism by which p53 precludes binding of Sp1 to DNA, and therefore the stimulation of the APP promoter by this transcription factor.


Enhanced Wound Healing- and Inflammasome-Associated Gene Expression in TNFAIP3-Interacting Protein 1- (TNIP1-) Deficient HaCaT Keratinocytes Parallels Reduced Reepithelialization.
TNIP1 protein is a widely expressed, cytoplasmic inhibitor of inflammatory signaling initiated by membrane receptors such as TLRs which recognize pathogen-associated and damage-associated molecular patterns (PAMPs and DAMPs). Keratinocyte TNIP1 deficiency sensitizes cells to PAMPs and DAMPs promoting hyperresponsive expression and secretion of cytokine markers (e.g., IL-8 and IL-6) relevant to cases of chronic inflammation, like psoriasis, where TNIP1 deficiency has been reported. Here, we examined the impact of TNIP1 deficiency on gene expression and cellular responses (migration and viability) relevant to acute inflammation as typically occurs in wound healing. Using siRNA-mediated TNIP1 expression knockdown in cultured HaCaT keratinocytes, we investigated TNIP1 deficiency effects on signaling downstream of TLR3 agonism with low-concentration poly (I:C), a representative PAMP/DAMP. The combination of TNIP1 knockdown and PAMP/DAMP signaling disrupted expression of specific keratinocyte differentiation markers (e.g., transglutaminase 1 and involucrin). These same conditions promoted synergistically increased expression of wound-associated markers (e.g., S100A8, TGFβ, and CCN2) suggesting potential benefit of increased inflammatory response from reduced TNIP1 protein. Unexpectedly, poly (I:C) challenge of TNIP1-deficient cells restricted reepithelialization and reduced cell viability. In these cells, there was not only increased expression for genes associated with inflammasome assembly (e.g., ASC, procaspase 1) but also for A20, a TNIP1 partner protein that represses cell-death signaling. Despite this possibly compensatory increase in A20 mRNA, there was a decrease in phospho-A20 protein, the form necessary for quenching inflammation. Hyperresponsiveness to poly (I:C) in TNIP1-deficient keratinocytes was in part mediated through p38 and JNK pathways. Taken together, we conclude that TNIP1 deficiency promotes enhanced expression of factors associated with promoting wound healing. However, the coupled, increased potential priming of the inflammasome and reduced compensatory activity of A20 has a net negative effect on overall cell recovery potential manifested by poor reepithelialization and viability. These findings suggest a previously unrecognized role for TNIP1 protein in limiting inflammation during successful progression through early wound healing stages.


Effect of Alcaligenes faecalis on nitrous oxide emission and nitrogen removal in three phase fluidized bed process.
Nitrous oxide (N2O), one of the greenhouse effect gases, has not been known that how much N2O is produced from municipal wastewater treatment and what its management should be. In this study, for controlling nitrous oxide emission and removing nitrogen from municipal wastewater, we experimented the three phase fluidized bed process equipped with draft tube along with immobilized Alcaligenes faecalis, a typical heterotrophic nitrifer and a predominant genus. Also we evaluated the optimum treatment condition of the three phase fluidized bed process for emitting nitrous oxide. The results of this study showed that the three phase fluidized bed process was more effective than the activated sludge process for controlling nitrous oxide emission and removing nitrogen. Increasing amount of A. faecalis in reactor should be encouraged for controlling nitrous oxide emission and removing nitrogen. In addition, the activated sludge process using immobilized A. faecalis as a carrier had more nitrogen removal efficiency than conventional activated sludge process. The accumulation of NO2-N, NO3-N resulted in high N2O emission. Therefore, we suggested that it is necessary to reduce NO2-N and NO3-N for both reducing N2O emission and improving nitrogen removal.


Elevated serum levels of pancreatic polypeptide are related to impaired glucose handling in inflammatory states.
Glucose handling and insulin secretion were studied in patients with inflammatory connective tissue diseases and correlated to circulating levels of immunoreactive pancreatic polypeptide (PP). The patients had normal fasting serum levels of insulin and normal insulin response to intravenous glucose loading. Ten of 16 patients had an impaired glucose tolerance, defined as a K rate of less than one. The basal PP levels, which were elevated in half of the patients, were inversely correlated to the K values but showed no relationship to basal or maximum insulin levels. The degree of the impaired glucose handling in the patients was related to the degree of the inflammatory activity as defined by acute-phase reactants. Elevated PP levels may be partly responsible for impaired glucose tolerance in inflammatory states either as an inhibitor of peripheral insulin activity or as an inhibitor of hypersecretion of insulin, needed to overcome decreased tissue sensitivity for insulin.


LncRNAs: From Basic Research to Medical Application.
This review aimed to summarize the current research contents about long noncoding RNAs (lncRNAs) and some related lncRNAs as molecular biomarkers or therapy strategies in human cancer and cardiovascular diseases. Following the development of various kinds of sequencing technologies, lncRNAs have become one of the most unknown areas that need to be explored. First, the definition and classification of lncRNAs were constantly amended and supplemented because of their complexity and diversity. Second, several methods and strategies have been developed to study the characteristic of lncRNAs, including new species identifications, subcellular localization, gain or loss of function, molecular interaction, and bioinformatics analysis. Third, based on the present results from basic researches, the working mechanisms of lncRNAs were proved to be different forms of interactions involving DNAs, RNAs, and proteins. Fourth, lncRNA can play different important roles during the embryogenesis and organ differentiations. Finally, because of the tissue-specific expression of lncRNAs, they could be used as biomarkers or therapy targets and effectively applied in different kinds of diseases, such as human cancer and cardiovascular diseases.


Role of the hydrophobic face of amphipathic alpha-helical peptides in synthetic pulmonary surfactants.
The sequence requirements for the peptide component of a totally synthetic lung surfactant mixture were examined. A series of model amphipathic alpha-helical peptides (MAP) with six to 18 residues were synthesized by solid phase techniques, mixed with dipalmitoylphosphatidylcholine (DPPC) and tested for efficacy in an in vitro adult rat lung model. The most effective peptide in these mixtures contained 10 residues. Peptides containing eight and 14 residues were also highly active when mixed with DPPC in buffer, but a six-residue peptide was inactive. Longer peptides were active only when mixed with DPPC in trifluoroethanol before swelling in buffer; no other lipids were required to elicit high activity. Biologically effective peptides, when combined with DPPC, formed translucent mixtures that were significantly less turbid than ineffective mixtures, dramatically decreased the enthalpy of the main phase transition of DPPC and reduced the gamma min in the pulsating bubble surfactometer. Turbidity and minimal surface tensions were significantly correlated with activity in this series of peptides. These data show that effective synthetic lung surfactants may be prepared with mixtures of DPPC and idealized amphipathic alpha-helical peptides containing as few as eight to 10 residues. They lend further support to the hypothesis that amphipathic alpha-helical peptides with hydrophobic surface areas greater than approximately 6.5 nm2 in simple mixtures with DPPC are biologically active.


Trends in risk and protective factors for child bullying perpetration in the United States.
This study examines trends in prevalence and factors associated with bullying perpetration among children 10-17 years old, using the 2003 and 2007 National Survey of Children's Health. A parent-reported bullying measure and NSCH-designed questions were used to measure factors associated with bullying. The 2003 (n = 48,639) and 2007 (n = 44,152) samples were 51 % male, with mean age of 13.5 (standard deviation 2.3). 23 % of children bullied at least sometimes in 2003 and 15 % bullied in 2007. Parental anger with their child, a child emotional/developmental/behavioral problem, and suboptimal maternal mental health were associated with higher bullying odds in 2003 and 2007, whereas parents talking with their child very/somewhat well, and meeting their child's friends were associated with lower odds. Between 2003 and 2007, parental anger with their child was associated with increasing bullying odds and parents' meeting their child's friends was associated with decreasing odds. Targeting these persistent factors may result in effective bullying-prevention interventions.


The cerebellum in drug craving.
Craving has been considered one of the core features of addiction. It can be defined as the urge or conscious desire to use a drug elicited by the drug itself, drug-associated cues or stressors. Craving plays a major role in relapse, even after prolonged periods of abstinence, as well as in the maintenance of drug seeking in non-abstinent addicts. The circuitry of craving includes medial parts of the prefrontal cortex, ventral striatal zones, ventral tegmental area, ventral pallidum, and limbic regions. Interestingly, the cerebellum shows reciprocal loops with many of these areas. The cerebellum has been linked traditionally to motor functions but increasing evidence indicates that this part of the brain is also involved in functions related to cognition, prediction, learning, and memory. Moreover, the functional neuroimaging studies that have addressed the study of craving in humans repeatedly demonstrate cerebellar activation when craving is elicited by the presentation of drug-related cues. However, the role of cerebellar activity in these craving episodes remains unknown. Therefore, the main goal of this review is to provide a brief update on craving studies and the traditional neural basis of this phenomenon, and then discuss and propose a hypothesis for the function of the cerebellum in craving episodes.


Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle.
Interaction of nanoparticles with proteins is the basis of nanoparticle bio-reactivity. This interaction gives rise to the formation of a dynamic nanoparticle-protein corona. The protein corona may influence cellular uptake, inflammation, accumulation, degradation and clearance of the nanoparticles. Furthermore, the nanoparticle surface can induce conformational changes in adsorbed protein molecules which may affect the overall bio-reactivity of the nanoparticle. In depth understanding of such interactions can be directed towards generating bio-compatible nanomaterials with controlled surface characteristics in a biological environment. The main aim of this review is to summarise current knowledge on factors that influence nanoparticle-protein interactions and their implications on cellular uptake.


Benign fibrous histiocytoma of the hand: a case report and literature review.
Benign fibrous histiocytoma (BFH) of the bone is a rare benign lesion characterised by the presence of fibroblasts and histiocytes. Fibrohistocytic lesions involving bone with identical histological appearances are common during childhood such as fibrous cortical defect. However, BFH is very rare and can only be differentially diagnosed with its presentation, localisation and radiologic features. Here we describe a 33-year-old man with BFH in a rare location, a phalanx. To our knowledge this is the second reported case of a BFH involving the proximal phalanx of the thumb in an adult. We report clinical, radiologic and histological findings of the case and briefly review the literature on the subject.


Pilonidal sinus disease can be treated with crystallized phenol using a simple three-step technique.
Pilonidal sinus disease can be treated with various surgical techniques. However, invasive surgical techniques harbor the risk of wound infection and require a long postoperative wound healing period. The treatment of pilonidal sinus disease with crystallized phenol is minimally invasive with a short postoperative recovery period. This article explains how to treat pilonidal sinus disease with crystallized phenol using a quick and easy three-step technique. Between August 2014 and January 2016, 43 male and 7 female patients with pilonidal sinus disease were treated with crystallized phenol. Hair was gently removed from the sinus openings with a mosquito clamp. Afterwards, the pilonidal sinus openings were gently filled with crystallized phenol. The closure of pilonidal sinus openings without any leakage after a single application of crystallized phenol was accepted as healing. The treatment failed in two of the female patients, who had had prior pilonidal sinus surgery, and in four of the male patients, who had a recurrence after wound site infection. The overall cure rate was 88%. Treatment of pilonidal sinus disease with crystallized phenol using the three-step technique is simple, fast, and comfortable. Therefore, crystallized phenol should be preferentially considered in the treatment of pilonidal sinus disease.


Is total parenteral nutrition immunosuppressive?
Total parenteral nutrition (TPN) has been a major advance in patient therapeutics, particularly for critically ill patients. Incorrect administration of TPN, however, primarily through excessive use of energy, either as dextrose or lipid, is an underappreciated risk factor that leads to serious complications in nutritional support. Even a modest degree of uncontrolled hyperglycemia induced by TPN appears to increase the risk of infection, usually to a level that can nullify any potential benefit of feeding. Rapid and/or excessive lipid administration can interfere with the reticuloendothelial system function, which may also predispose the patient to serious infection. The goals of nutritional support in the critically ill are to provide ample protein at 1.5 to 2.0 g/kg body weight/day, while limiting calories to approximately the patient's resting energy expenditure, which optimally supports the metabolic response to injury. Repleting the critically ill, malnourished patient with calories in excess of the patient's energy expenditure is not effective, but rather increases the likelihood of an adverse outcome.


Patient-specific modeling of the heart: estimation of ventricular fiber orientations.
Patient-specific simulations of heart (dys)function aimed at personalizing cardiac therapy are hampered by the absence of in vivo imaging technology for clinically acquiring myocardial fiber orientations. The objective of this project was to develop a methodology to estimate cardiac fiber orientations from in vivo images of patient heart geometries. An accurate representation of ventricular geometry and fiber orientations was reconstructed, respectively, from high-resolution ex vivo structural magnetic resonance (MR) and diffusion tensor (DT) MR images of a normal human heart, referred to as the atlas. Ventricular geometry of a patient heart was extracted, via semiautomatic segmentation, from an in vivo computed tomography (CT) image. Using image transformation algorithms, the atlas ventricular geometry was deformed to match that of the patient. Finally, the deformation field was applied to the atlas fiber orientations to obtain an estimate of patient fiber orientations. The accuracy of the fiber estimates was assessed using six normal and three failing canine hearts. The mean absolute difference between inclination angles of acquired and estimated fiber orientations was 15.4 °. Computational simulations of ventricular activation maps and pseudo-ECGs in sinus rhythm and ventricular tachycardia indicated that there are no significant differences between estimated and acquired fiber orientations at a clinically observable level.The new insights obtained from the project will pave the way for the development of patient-specific models of the heart that can aid physicians in personalized diagnosis and decisions regarding electrophysiological interventions.


Health-related quality of life variation by socioeconomic status: Evidence from an Iranian population-based study.
Health-Related Quality of Life (HRQoL) values based on the accurate and reliable European Quality of Life Five Dimension (EQ-5D) questionnaire gives health-state utilities as a helpful data set for studying socio-demographic and socio-economic inequalities in health status in the general population. We aimed to do a population-based study to see how HRQoL varies by socio-demographics and socioeconomic status (SES). The study was a cross-sectional population-based study in Shiraz, Iran's southwest. Data was gathered utilizing a personal digital assistant (PDA). A trained interviewer administered the EQ-5D questionnaire to a representative sample of 1036 inhabitants. Principal component analysis (PCA) was used to create SES indices. Because of the skewed distribution, quantile regression was utilized to model the quartiles of HRQoL values. STATA 12.0 was used to perform all statistical analyses. P <0.05 was considered statistically significant. In 1036 study respondents, women had a mean HRQoL of 0.67 ± 0.28, whereas men had a mean HRQoL of 0.78 ± 0.25. Gender and age remained significant in all quartiles of HRQoL value. Participants with insurance showed 0.14 and 0.08 higher HRQoL values in the first and second HRQoL quartiles than those without coverage, respectively. Education [95% CI: 0.034, 0.111)], economy [95% CI: 0.013, 0.077], and assets [95% CI: 0.003, 0.069] all had an impact on HRQoL value in the lowest quintile. In all quartiles of HRQoL value, women had lower reported HRQoL than men. Insurance programs aimed at more disadvantaged groups with poorer HRQoL may help to minimize inequity. Education, economics, and assets all had an impact on the lower quartiles of HRQoL value, emphasizing the importance of general policies in determining public health status.


Vasopressin in plasma and cerebrospinal fluid of hydrated and dehydrated steers.
Levels of arginine-vasopressin (AVP), the antidiuretic hormone, have been concurrently measured by radioimmunoassay (RIA) in plasma (p) and cerebrospinal fluid (CSF) from conscious, unrestrained steers. During 4 days of dehydration, plasma osmolarity (posm) rose progressively from control hydrated levels of 301.3 +/- 0.632 mosm/1(mean +/- SE) to 338.5 +/- 3.090 mosm/1(p less than 0.001). Packed cell volume also rose from 39.9 +/- 0.64% to 44.7 +/- 1.24% (p less than 0.001). Associated with these changes was a progressive increase in pAVP from control levels of 1.3 +/- 0.19 microU/ml to 16.9 +/- 1.88 microU/ml(p less than 0.001) after 4 days without water. Log pAVP was linearly related to posm (r = 0.82, p less than 0.001). Mean level of CSF-AVP in control animals was 5.4 +/- 0.97 microU/ml. During dehydration, CSF-AVP levels also rose, becoming significantly greater than control levels (p less than 0.01) after 3 days without water and further increasing to reach 15.2 +/- 1.83 microU/ml after 4 days without water (p less than 0.001). Log CSF-AVP could also be linearly related to posm (r = 0.62, p less than 0.01). Termination of dehydration by restoration of ad libitum water supply was accompanied by return of pAVP and CSF-AVP to pre-dehydration levels. Regression analysis of concurrent levels of pAVP an CSF-AVP indicates that CSF-AVP levels are linearly correlated to pAVP levels in hydrated and dehydrated animals (r = 0.70, p less than 0.001). These experiments suggest that neurosecretory neurons secreting AVP at sites accessible to CSF respond to similar stimuli during dehydration as those neurons secreting AVP into blood.


Treatment With Multi-Species Probiotics Changes the Functions, Not the Composition of Gut Microbiota in Postmenopausal Women With Obesity: A Randomized, Double-Blind, Placebo-Controlled Study.
Probiotics are known to regulate host metabolism. In randomized controlled trial we aimed to assess whether interventions with probiotic containing following strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58 affect gut microbiota to promote metabolic effects. By 16S rRNA sequencing we analyzed the fecal microbiota of 56 obese, postmenopausal women randomized into three groups: (1) probiotic dose 2.5 × 109 CFU/day (n = 18), (2) 1 × 1010 CFU/day (n = 18), or (3) placebo (n = 20). In the set of linear mixed-effects models, the interaction between pre- or post-treatment bacterial abundance and time on cardiometabolic parameters was significantly (FDR-adjusted) modified by type of intervention (26 and 19 three-way interactions for the pre-treatment and post-treatment abundance, respectively), indicating the modification of the bio-physiological role of microbiota by probiotics. For example, the unfavorable effects of Erysipelotrichi, Erysipelotrichales, and Erysipelotrichaceae on BMI might be reversed, but the beneficial effect of Betaproteobacteria on BMI was diminished by probiotic treatment. Proinflammatory effect of Bacteroidaceae was alleviated by probiotic administration. However, probiotics did not affect the microbiota composition, and none of the baseline microbiota-related features could predict therapeutic response as defined by cluster analysis. Conclusions: Probiotic intervention alters the influence of microbiota on biochemical, physiological and immunological parameters, but it does not affect diversity and taxonomic composition. Baseline microbiota is not a predictor of therapeutic response to a multispecies probiotic. Further multi-omic and mechanistic studies performed on the bigger cohort of patients are needed to elucidate the cardiometabolic effect of investigated probiotics in postmenopausal obesity.


Amended final report on the safety assessment of ethyl methacrylate.
Ethyl Methacrylate is a methacrylate ester used as a chemical additive in artificial fingernail enhancement products. These products may be applied by trained professionals or be provided directly to consumers with instructions for use. Ethyl Methacrylate readily polymerizes and rapidly reacts with multifunction methacrylates to form a highly cross-linked polymer. The oral LD(50) of Ethyl Methacrylate for rats ranged from 12.7 to 18.14 g/kg. In acute studies with rats, hemoglobinuria and respiratory tract lesions were observed. Animal studies indicate that Ethyl Methacrylate is a skin irritant and sensitizer. In some cases the results were dependent on the vehicle. Evidence of embryotoxicity and teratogenicity were observed in rats injected intraperitoneally with 0.1223 to 0.4076 ml/kg Ethyl Methacrylate. Positive evidence of mutagenicity was observed in the L5178Y mouse lymphoma cell assay, but not in two Ames tests. Case reports cite examples of individuals suffering allergic contact dermatitis from exposure to Ethyl Methacrylate and related methacrylates, and some degree of cross-reactivity appears to exist between widely used acrylates and methacrylates. Information from several clinical registries of sensitization reactions to various agents reported that Ethyl Methacrylate is a sensitizer, but not a potent one. Because Ethyl Methacrylate monomer is short-lived in the normal course of using artificial fingernail-enhancement products, the primary hazard is expected to be inadvertant skin contact. In order to avoid sensitization, it is necessary to avoid skin contact. It is recommended that fingernail-enhancement products containing Ethyl Methacrylate include directions to avoid skin contact because of the sensitizing potential. Based on the available data on the formulation of nail products containing this ingredient, it is concluded that Ethyl Methacrylate is safe as used, when application is accompanied by directions for use as above.


Keratitis in relapsing polychondritis.
An 11-year-old girl developed peripheral corneal thinning and superficial pannus formation with no other ocular or systemic signs. During the subsequent two years she developed inflammation of both ears, progressive collapse of the nasal cartilage, and polyarthritis. A clinical diagnosis of relapsing polychondritis was made. A spontaneous perforation of her right eye secondary to progression of peripheral ulcerative keratitis was successfully repaired. Treatment with dapsone, a nonsteroidal anti-inflammatory agent resulted in remission of her ocular and systemic disease.


Machine perfusion preservation with hemoglobin based oxygen vesicles alleviate ultrastructural damages in porcine liver donated after cardiac death.
Midthermic machine perfusion (MMP) of post-circulatory arrest donor liver grafts has the advantage of preserving the functional ultrastructure of hepatocytes in donor grafts. It was reported that oxygenation during MMP reduces portal venous resistance and increases bile production. The MMP with hemoglobin-based oxygen vesicles (HbV) keeps the lower aspartate aminotransferase level (an indicator of liver injury) and maintains the functional ultrastructure of mitochondria in the hepatocytes. To evaluated differences of ultrastructural damages in donor livers between the MMP with and without HbV, porcine liver grafts after 60 min of warm ischemia were perfused at 22°C for 4 h with or without HbV, and a part of liver grafts were analyzed by transmission electron microscopy (TEM) and osmium-maceration scanning electron microscopy (OM-SEM). The remaining grafts were perfused with autologous blood at 38°C for 2 h in an isolated liver reperfusion model (IRM) that mimics the inside of the body after transplantation, and then analyzed by TEM and OM-SEM. Hepatocytes after MMP had small round mitochondria with rod-shaped cristae and reticulovesicular rough endoplasmic reticulum (rER) in both HbV(+) and HbV(-) livers. After IRM of HbV(+) livers, the well-developed lamellar rER was often found in hepatocytes. Liver sinusoidal endothelial cells (LSECs) after MMP contained some large vacuolar structures containing amorphous garbage in the cytoplasm, and their size along with appearance frequency were smaller and lower, respectively, in HbV(+) livers than HbV(-). Oxygenation during the MMP by using HbV suppressed the ultrastructural damages in donor livers, in particular for the LSECs. RESEARCH HIGHLIGHTS: Liver sinusoidal endothelial cells after midthermic machine perfusion had large vacuolar organelles with amorphous garbage. Oxygenation during the perfusion made them less and smaller, ultrastructurally supporting its utility.


Saponin-enriched sea cucumber extracts exhibit an antiobesity effect through inhibition of pancreatic lipase activity and upregulation of LXR-β signaling.
Sea cucumbers have been consumed as tonic, food, and nutrition supplements for many years. The objective of this study is to investigate the antiobesity and lipid-lowering effects of sea cucumber extracts in in vitro and in vivo models and elucidate the mechanism of action of the extracts on obesity and dyslipidemia. The 60% ethanol extracts from the body walls of 10 different sea cucumbers were investigated for the inhibition of pancreatic lipase (PL) activity in vitro. The optimal active extract (SC-3) was further chemically analyzed by LC-MS and UV. And 0.1% and 0.2% of SC-3 was mixed with a high-fat diet to treat C57/BL6 mice for 6 weeks or 2 weeks as preventive and therapeutic study. The body weight, serum, and liver lipid profile in the mice were investigated. The crude extract of Pearsonothuria graeffei Semper (Holothuriidae) inhibited the PL activity by 36.44% of control at 0.5 μg/mL. SC-3 and echinoside A inhibited PL with an IC50 value at 2.86 μg/mL and 0.76 μM. 0.1% of SC-3 reduced the body weight (23.0 ± 0.62 versus 26.3 ± 0.76 g), the serum TC (2.46 ± 0.04 versus 2.83 ± 0.12 mmol/L), TG (0.19 ± 0.08 versus 0.40 ± 0.03 mmo/L), and LDL-c (0.48 ± 0.02 versus 0.51 ± 0.02 mmol/L), and liver TC (1.19 ± 0.17 versus 1.85 ± 0.13 mmol/mg) and TG (6.18 ± 0.92 versus 10.87 ± 0.97 mmol/mg) contents of the obese C57BL/six mice on a high-fat diet. Sea cucumber may be used for developing antiobesity and antihyperlipidemia drugs.


[Risk assessment of drugs during breastfeeding].
Medication intake during the postpartum period is common with discontinuation of breastfeeding sometimes unnecessarily recommended for fear of adverse effects in the breastfed infant, while exposure through human milk is generally low. The assessment of risks associated with medication intake during breastfeeding is based, among other things, on the little clinical evidence available in specialized sources of information, and on pharmacokinetic principles. A decision-making support is presented to facilitate communication with mothers, foster medication adherence and prevent unnecessary interruption of breastfeeding.


Repeated growth-etching-regrowth for large-area defect-free single-crystal graphene by chemical vapor deposition.
Reducing nucleation density and healing structural defects are two challenges for fabricating large-area high-quality single-crystal graphene, which is essential for its electronic and optoelectronic applications. We have developed a method involving chemical vapor deposition (CVD) growth followed by repeated etching-regrowth, to solve both problems at once. Using this method, we can obtain single-crystal graphene domains with a size much larger than that allowed by the nucleation density in the initial growth and efficiently heal structural defects similar to graphitization but at a much lower temperature, both of which are impossible to realize by conventional CVD. Using this method with Pt as a growth substrate, we have grown ∼3 mm defect-free single-crystal graphene domains with a carrier mobility up to 13,000 cm2 V(-1) s(-1) under ambient conditions.


Undulating Seal Whiskers Evolved Optimal Wavelength-to-Diameter Ratio for Efficient Reduction in Vortex-Induced Vibrations.
Seals are well-known for their remarkable hydrodynamic trail-following capabilities made possible by undulating flow-sensing whiskers that enable the seals to detect fish swimming as far as 180 m away. In this work, the form-function relationship in the undulating whiskers of two different phocid seal species, viz. harbor and gray seals, is studied. The geometry and material properties of excised harbor and grey seal whiskers are systematically characterized using blue light 3D scanning, optical and scanning electron microscopy, and nanoindentation. The effect of the undulating geometry on the whiskers' vibration in uniform water flow is studied using both experimental (piezoelectric MEMS and 3D-printed piezoresistive sensors developed in-house) and numerical (finite element method) techniques. The results indicate that the dimensionless ratio of undulation wavelength to mean whisker diameter (λ/Dm ) in phocid seals may have evolved to be in the optimal range of 4.4-4.6, enabling an order-of-magnitude reduction in vortex-induced vibrations (compared to a similarly-shaped circular cylinder) and, consequently, an enhanced flow sensing capability with minimal self-induced noise. The results highlight the importance of the dimensionless λ/Dm ratio in the biomimetic design of seal whisker-inspired vibration-resistant structures, such as marine risers and wake detection sensors for submarines.


Metabolic inactivation: a mechanism of human tumor resistance to bleomycin.
The mechanism of human tumor resistance to the antineoplastic drug bleomycin (BLM) is not known. We now provide evidence implicating metabolic inactivation in the resistance of human Burkitt's (Daudi) lymphoma to BLM. Daudi lymphoma and human head and neck squamous cell carcinoma (A-253) cells grown (s.c.) in nude mice were found to be resistant and sensitive to BLM treatment, respectively. Within 1 h of s.c. injection of [3H]BLM A2, Daudi xenografts accumulated less BLM and metabolized this drug to a much greater extent than did A-253 xenografts. The BLM-resistant Daudi xenografts metabolized BLM A2 to at least 6 metabolites and only a small proportion of the drug remained as unmetabolized BLM A2. In the BLM-sensitive A-253 xenografts, however, BLM A2 remained the major component. Incubation of BLM A2 with Daudi cytosolic fractions resulted in a complex mixture of metabolites similar to that formed by Daudi xenografts in nude mice. This BLM metabolite mixture was biologically inactive in plasmid DNA degradation assays. Treatment of mice bearing Daudi xenografts with an inhibitor of BLM hydrolase, L-trans-epoxysuccinyl-leucylamido-(4-guanidino)butane (E-64), prior to [3H]BLM A2 treatment did not affect the amount of BLM accumulated but inhibited BLM A2 metabolism in the xenografts. Furthermore, although E-64 alone did not inhibit the growth of Daudi xenografts, it potentiated the antitumor activity of BLM. These results indicate that Daudi tumors resist BLM by metabolically inactivating it and that inhibition of BLM metabolism in vivo enhances the antitumor activity of BLM and hence overcomes resistance.


Dibenzosiloles and 12H-indololo[3,2-d]naphtho[1,2-b][1]siloles: exploration of organic chromophores exhibiting efficient solid-state fluorescence.
The construction of a diorganosilylene bridge over a biaryl moiety at the 2,2'-positions is a versatile strategy for fine-tuning its HOMO-LUMO energy gap, which is closely linked to the electronic and optical properties of the compounds. Therefore, there is growing interest in the use of silicon-bridged biaryl motifs as key cores of various types of advanced functional materials, such as light-emitting, semiconducting, photovoltaic, and sensing materials. To accelerate the advances of materials based on silicon-bridged biaryls, it is essential to create new classes of biaryls and explore their functions and properties. This Personal Account describes recent research on the development of organic chromophores based on functionalized dibenzosiloles and 12H-indololo[3,2-d]naphtho[1,2-b][1]siloles as solid-state emitters.


Analysis of binding interaction between the natural apocarotenoid bixin and human serum albumin by circular dichroism and fluorescence spectroscopy.
Bixin is an important, pharmacologically active dietary cis-carotenoid, but its interaction with potential macromolecular targets is completely unexplored. This work was aimed to study the binding of bixin to human serum albumin (HSA), the most abundant protein in blood plasma. Circular dichroism (CD) spectroscopy in combination with UV/VIS absorption spectroscopy and fluorescence quenching techniques were applied. Appearance of induced CD bands in the UV- and VIS-absorption spectral regions indicated the formation of non-covalent carotenoid-albumin complexes. Shape and spectral position of the extrinsic Cotton effects suggested the binding of a single bixin molecule to HSA in chiral conformation. Scatchard and non-linear regression analyses of CD titration data resulted in similar values for the association constant (Ka = 6.6 and 4.6x10(5) M(-1), resp.) and for the number of binding sites (n = 1). The binding interaction was independently confirmed by fluorescence-quenching experiment from which the binding parameters were also calculated. CD Displacement measurements performed with marker ligands established that the main drug binding sites of HSA are not involved in binding of bixin. Palmitic acid decreased the amplitude of the induced CD bands suggesting a common albumin binding site for bixin and long-chain fatty acids. The above data indicate that HSA plays a significant role in the plasma transportation of bixin and related dietary carboxylic acid carotenoids.


Discounted drug prices for hospitals: result in prescriptions for expensive drugs in the community.
Hospital prescribing has a major influence on community prescribing. In France, pharmaceutical companies can sell drugs to hospitals at dramatically reduced prices in the expectation of increasing sales in community pharmacies.