Global motion evoked potentials in autistic and dyslexic children: A cross-syndrome approach.
Atypicalities in psychophysical thresholds for global motion processing have been reported in many neurodevelopmental conditions, including autism and dyslexia. Cross-syndrome comparisons of neural dynamics may help determine whether altered motion processing is a general marker of atypical development or condition-specific. Here, we assessed group differences in N2 peak amplitude (previously proposed as a marker of motion-specific processing) in typically developing (n = 57), autistic (n = 29) and dyslexic children (n = 44) aged 6-14 years, in two global motion tasks. High-density EEG data were collected while children judged the direction of global motion stimuli as quickly and accurately as possible, following a period of random motion. Using a data-driven component decomposition technique, we identified a reliable component that was maximal over occipital electrodes and had an N2-like peak at ~160 msec. We found no group differences in N2 peak amplitude, in either task. However, for both autistic and dyslexic children, there was evidence of atypicalities in later stages of processing that require follow up in future research. Our results suggest that early sensory encoding of motion information is unimpaired in dyslexic and autistic children. Group differences in later processing stages could reflect sustained global motion responses, decision-making, metacognitive processes and/or response generation, which may also distinguish between autistic and dyslexic individuals.


Role of Climate Change in Urologic Health: Kidney Stone Disease.
Kidney stones are rising in incidence and prevalence worldwide. Given the temperature dependence of kidney stone presentations, climate change is projected to further increase the burden of disease for individuals and society. PATIENT SUMMARY: This mini-review reports current knowledge on climate change in relation to kidney stone disease. Kidney stones are more common in patients living in parts of the world that are hotter and more humid. Kidney stone problems are also more common after periods of high heat, which have a greater impact on men than on women. As temperatures rise with climate change, it is likely that the occurrence of kidney stones and the costs associated with their diagnosis and treatment will increase as well.


Expression of two alternative sigma factors of Synechococcus sp. strain PCC 7002 is modulated by carbon and nitrogen stress.
The sigB and sigC genes, encoding two alternative sigma factors of the unicellular marine cyanobacterium Synechococcus sp. PCC 7002, were cloned and characterized. Strains in which the sigB and sigC genes were insertionally inactivated were viable under standard laboratory conditions, indicating that SigB and SigC are group 2 sigma factors. Starvation for either nitrogen or carbon caused an increase in sigB mRNA levels. Transcripts for the sigC gene initially increased but then decreased during nitrogen and carbon starvation. The SigC protein could not be identified in cyanobacterial extracts using antisera to Synechococcus sp. PCC 7002 SigA or RpoD from Bacillus subtilis. The ratio of the principal vegetative sigma factor, SigA, to SigB decreased during either nitrogen starvation or carbon starvation, and the levels of SigB also increased in the sigC mutant strain. These results imply that SigB and SigC play roles in modifying transcription in response to changes in carbon and nitrogen availability in this cyanobacterium.


Evaluating Changes in Ocular Redness Using a Novel Automated Method.
To evaluate interobserver concordance in measured ocular redness among a group of raters using an objective computer-assisted method (ocular redness index [ORI]) and a group of clinicians using an ordinal comparative scale. We conducted a prospective study to evaluate ocular redness in clinical photographs of 12 patients undergoing pterygium surgery. Photographs were acquired preoperatively, and at 1 week and 1 month postoperatively. One group of clinicians graded conjunctival redness in the photographs using an image-based comparative scale. A second group applied the ORI to measure redness in the same photographs. We evaluated redness change between time points, level of agreement among raters, and assessed redness score differences among observers within each group. Interobserver agreement using the image-based redness scale was 0.458 (P < 0.001). Interobserver agreement with the ORI was 0.997 (P < 0.001). We observed statistically significant differences among clinicians' measurements obtained with the image-based redness scale (P < 0.001). There were no significant differences among measurements obtained with the ORI (P = 0.27). We observed a significant change in redness between baseline and follow-up visits with all scoring methods. Detailed analysis of redness change was performed only in the ORI group due to availability of continuous scores. Our findings suggest that the ORI scores provide higher consistency among raters than ordinal scales, and can discriminate redness changes that clinical observers often can miss. The ORI may be a reliable alternative to measure ocular redness objectively in the clinic and in clinical trials.


Immunohistochemical study of p53 overexpression in radiation-induced colon cancers.
The expressions of p53 and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically from paraffin sections of 7 cases (9 lesions) of radiation-induced colon cancer and 42 cases of spontaneous colon cancer. Age distribution of radiation-induced and spontaneous colon cancer were 68.1 years (range, 56 to 77 years) and 67.4 years (range, 31 to 85 years), respectively. Among the radiation-induced colon cancers, there were 3 lesions of mucinous carcinoma (33%), a much higher than found for spontaneous mucinous cancer. Immunohistochemically, p53 protein expression was detected in 7/9 (78%) of radiation-induced cancers and in 23/42 (55%) of spontaneous colon cancers. chi 2 analysis found no significant differences between radiation-induced and spontaneous colon cancers in age distribution or p53-positive staining for frequency, histopathology, or Dukes' classification. In radiation colitis around the cancers including aberrant crypts, spotted p53 staining and abnormal and scattered PCNA-positive staining were observed. In histologically normal cells, p53 staining was almost absent and PCNA-positive staining was regularly observed in the lower half of the crypt. In radiation colitis including aberrant glands, cellular proliferation increased and spotted p53 expression was observed. This study suggests that radiation colitis and aberrant glands might possess malignant potential and deeply associate with carcinogenesis of radiation-induced colon cancer.


Efficiency, costs and benefits of AOPs for removal of pharmaceuticals from the water cycle.
Different advanced oxidation processes (AOP) were developed for the treatment of highly loaded wastewater streams. Optimisation of removal and improvement of efficiency were carried out on a laboratory, semiworks and pilot plant scale. The persistent cytostatic drug cyclophosphamide was selected as a reference substance regarding elimination and evaluation of the various oxidation processes because of its low degradability rate. The investigated processes are cost-efficient and suitable regarding the treatment of wastewater streams since they lead to efficient elimination of antibiotics and antineoplastics. A total reduction of toxicity was proven by means of the umuC-test. However, in order to reduce pharmaceuticals from the water cycle, it must be considered that the input of more than 80 % of the pharmaceuticals entering wastewater treatment systems results from private households. Therefore, advanced technologies should also be installed at wastewater treatment plants.


Short communication: Comparative proteomic analysis of the lactating and nonlactating bovine mammary gland.
The objective of this study was to determine how bovine mammary protein profiles vary during lactation and the dry period. Three lactating and 3 nonlactating cows were selected for mammary gland tissue sampling. Compared with the mammary proteins in nonlactating cows, a total of 60 differentially expressed proteins (DEP, including 57 upregulated and 3 downregulated) were identified in lactating cows using 2-dimensional difference gel electrophoresis combined with mass spectrometry. These DEP included enzymes and proteins associated with various macromolecular metabolic processes, and appeared to promote the increased metabolic activity associated with milk synthesis and secretion. The increased DEP were primarily related to initiation, maintenance, and involution of lactation, and included proteins involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, the pentose phosphate pathway, oxidative phosphorylation, aminoacyl-transfer RNA biosynthesis, and fatty acid biosynthesis. Identified DEP were further validated by real-time, reverse-transcription PCR and Western blot. Five new DEP associated with lactation were uniquely identified. This work provided some protein-associated insights to facilitate further investigation of the mechanisms underlying lactation in dairy cows.


Ethical issues experienced during palliative care provision in nursing homes.
Palliative care is acknowledged as an appropriate approach to support older people in nursing homes. Ethical issues arise from many aspects of palliative care provision in nursing homes; however, they have not been investigated in this context. To explore the ethical issues associated with palliative care in nursing homes in the United Kingdom. Exploratory, sequential, mixed-methods design. Semi-structured interviews with 13 registered nurses and 10 healthcare assistants (HCAs) working in 13 nursing homes in the United Kingdom were used to explore ethical issues in palliative care. The 'Ethical Issues in Palliative Care for Nursing Homes' instrument was used to measure the frequency and level of distress arising from ethical issues through a cross-sectional survey with 69 registered nurses and 129 healthcare assistants. Data collection occurred between December 2014 and November 2015. Ethical approval was granted by Queen's University's School of Nursing and Midwifery Research Ethics Committee and governance sought from each nursing home's manager. The interviews revealed three themes: ethical issues in practice; relational issues; and organisational issues. No significant differences between registered nurses and healthcare assistants were evident, confirming the patterns emerging from the interviews. Relational issues, primarily issues with residents and families, occurred most frequently and caused greater distress. The shared environment is key in the experience of ethical issues; therefore, multidisciplinary education is needed for ethical decision making in palliative care. Addressing staff knowledge and service organisation may reduce ethical issues locally and provide a benchmark for global change.


Bayesian metamodeling of complex biological systems across varying representations.
Comprehensive modeling of a whole cell requires an integration of vast amounts of information on various aspects of the cell and its parts. To divide and conquer this task, we introduce Bayesian metamodeling, a general approach to modeling complex systems by integrating a collection of heterogeneous input models. Each input model can in principle be based on any type of data and can describe a different aspect of the modeled system using any mathematical representation, scale, and level of granularity. These input models are 1) converted to a standardized statistical representation relying on probabilistic graphical models, 2) coupled by modeling their mutual relations with the physical world, and 3) finally harmonized with respect to each other. To illustrate Bayesian metamodeling, we provide a proof-of-principle metamodel of glucose-stimulated insulin secretion by human pancreatic β-cells. The input models include a coarse-grained spatiotemporal simulation of insulin vesicle trafficking, docking, and exocytosis; a molecular network model of glucose-stimulated insulin secretion signaling; a network model of insulin metabolism; a structural model of glucagon-like peptide-1 receptor activation; a linear model of a pancreatic cell population; and ordinary differential equations for systemic postprandial insulin response. Metamodeling benefits from decentralized computing, while often producing a more accurate, precise, and complete model that contextualizes input models as well as resolves conflicting information. We anticipate Bayesian metamodeling will facilitate collaborative science by providing a framework for sharing expertise, resources, data, and models, as exemplified by the Pancreatic β-Cell Consortium.


To die or not to die? Lessons from lesion mimic mutants.
Programmed cell death (PCD) is a ubiquitous genetically regulated process consisting in an activation of finely controlled signaling pathways that lead to cellular suicide. Although some aspects of PCD control appear evolutionary conserved between plants, animals and fungi, the extent of conservation remains controversial. Over the last decades, identification and characterization of several lesion mimic mutants (LMM) has been a powerful tool in the quest to unravel PCD pathways in plants. Thanks to progress in molecular genetics, mutations causing the phenotype of a large number of LMM and their related suppressors were mapped, and the identification of the mutated genes shed light on major pathways in the onset of plant PCD such as (i) the involvements of chloroplasts and light energy, (ii) the roles of sphingolipids and fatty acids, (iii) a signal perception at the plasma membrane that requires efficient membrane trafficking, (iv) secondary messengers such as ion fluxes and ROS and (v) the control of gene expression as the last integrator of the signaling pathways.


In vitro inhibitory activity of sertraline against clinical isolates of Sporothrix schenckii.
Sertraline (SRT) is an antidepressant that has proven its activity in vitro against Cryptococcus, Coccidioides, Trichosporon and other fungi. Disseminated sporotrichosis, although rare, has a high mortality and its treatment is difficult and prolonged, often relying in combining two or more antifungals. In our study we evaluate the antifungal activity of SRT, alone and in combination with itraconazole (ITC), voriconazole (VRC) and amphotericin B (AMB), against 15 clinical isolates of Sporothrix schenckii. We used the broth microdilution method as described by the CLSI to test the susceptibility to antifungals, and the checkerboard microdilution method to evaluate drug interactions. The minimum inhibitory concentration (MIC) with SRT was in the range of 4-8μg/ml, while for AMB, VRC and ITC were 0.5-4μg/ml, 0.5-8μg/ml and 0.125-2μg/ml, respectively. In addition, SRT showed synergy with ITC in one strain, mainly additivity with VRC, and indifference with AMB in others. The MIC values with SRT for the isolates studied show the potential role of this drug as an adjuvant in the treatment of sporotrichosis, especially in disseminated or complicated cases.


Morphological and behavioural differences facilitate tropical butterfly persistence in variable environments.
The thermal biology of ectotherms largely determines their abundance and distributions. In general, tropical species inhabiting warm and stable thermal environments tend to have low tolerance to cold and variable environments, which may restrict their expansion into temperate climates. However, the distribution of some tropical species does extend into cooler areas such as tropical borders and high elevation tropical mountains. Behavioural and morphological differences may therefore play important roles in facilitating tropical species to cope with cold and variable climates at tropical edges. We used field-validated biophysical models to estimate body temperatures of butterflies across elevational gradients at three sites in southern China and assessed the contribution of behavioural and morphological differences in facilitating their persistence in tropical and temperate climates. We investigated the effects of temperature on the activity of 4,844 individuals of 144 butterfly species along thermal gradients and tested whether species of different climatic affinities-tropical and widespread (distributed in both temperate and tropical regions)-differed in their thermoregulatory strategies (i.e. basking). In addition, we tested whether thermally related morphology or the strength of solar radiation (when butterflies were recorded) was related to such differences. We found that activities of tropical species were restricted (low abundance) at low air temperatures compared to widespread species. Active tropical species were also more likely to bask at cooler body temperatures than widespread species. Heat gain from behavioural thermoregulation was higher for tropical species (when accounting for species abundance), and heat gain correlated with larger thorax widths but not with measured solar radiation. Our results indicate that physiological intolerance to cold temperatures in tropical species may be compensated through behavioural and morphological responses in thermoregulation in variable subtropical environments. Increasing climatic variability with climate change may render tropical species more vulnerable to cold weather extremes compared to widespread species that are more physiologically suited to variable environments.


Endovascular treatment of infra-popliteal arteries in patients with critical limb ischemia.
Currently, critical limb ischemia occurs in an ageing population with more and more diabetic patients and infra-popliteal lesions. In order to be as little invasive as possible, endovascular techniques have been proposed as one of the best options for these patients. In the following review, we present the specificities and assess the clinical effectiveness of endovascular treatment for infra-popliteal lesions in critical limb ischemia. We undertook a literature review based on publications dealing with critical limb ischemia and infra-popliteal endovascular treatment and published during the last decade. All relevant studies were systematically reviewed. The recorded outcomes were: immediate technical success, peri-operative complications, 30-day mortality, primary and secondary patency, limb salvage, and patient survival. Thirty-one studies including a total of 3164 patients (range: 13 to 993) were included in this review. Technical success rates ranged between 72% and 100%. Peri-operative complications rates ranged between 0% and 16%, most complications being considered as minor. 30-day mortality rates ranged between 0% and 5%. Primary, secondary patency and limb salvage rates were respectively about 60%, 65%, and 85%. One-year survival was about 80%. In conclusion, endovascular treatment can be considered as a good option for the treatment of infra-popliteal lesions in critical limb ischemia. Despite the non entirely satisfactory patency rates, endovascular treatment may provide wound healing and limb salvage.


Nicotine reinforcement is reduced by cannabinoid CB1 receptor blockade in the ventral tegmental area.
Cannabinoid type 1 (CB1) receptors control the motivational properties and reinforcing effects of nicotine. Indeed, peripheral administration of a CB1 receptor antagonist dramatically decreases both nicotine taking and seeking. However, the neural substrates through which the cannabinoid CB1 receptors regulate the voluntary intake of nicotine remain to be elucidated. In the present study, we sought to determine whether central injections of a CB1 receptor antagonist delivered either into the ventral tegmental area (VTA) or the nucleus accumbens (NAC) may alter nicotine intravenous self-administration (IVSA). Rats were first trained to self-administer nicotine (30 μg/kg/0.1 ml). The effect of central infusions of the CB1 antagonist AM 251 (0, 1 and 10 μg/0.5 μl/side) on nicotine-taking behavior was then tested. Intra-VTA infusions of AM 251 dose dependently reduced IVSA with a significant decrease for the dose 10 μg/0.5 μl/side. Moreover, operant responding for water was unaltered by intra-VTA AM 251 at the same dose. Surprisingly, intra-NAC delivery of AM 251 did not alter nicotine behavior at all. These data suggest that in rats chronically exposed to nicotine IVSA, the cannabinoid CB1 receptors located in the VTA rather than in the NAC specifically control nicotine reinforcement and, subsequently, nicotine-taking behavior.


Antibiotic binding to polytetrafluoroethylene via glucosaminoglycan-keratin luminal coating.
Vascular prosthetic graft infection is one of the most catastrophic problems complicating vascular surgery. The purpose of the present study was to determine the efficacy of binding an antibiotic to a vascular prosthesis via a glucosaminoglycan-keratin luminal coating (GKLC). Ten adult mongrel dogs had polytetrafluoroethylene (PTFE) grafts inserted into the right common carotid artery and PTFE grafts with GKLC bonded with cefoxitin inserted into the left common carotid artery. Before the neck incision was closed, an infusion of 1 X 10(8) Staphylococcus aureus was administered intravenously during a 15-minute period to each dog. Grafts were harvested at 10 different time periods (1, 2, 3, 5, 7, 10, 14, 18, 21, and 28 days). At the time of harvesting, cultures were taken of the lumen of each graft. Washout of antibiotic from the graft lumen was determined by measuring zones of inhibition of disks excised from the antibiotic grafts that were placed on S. aureus plates. Results demonstrated that only 1 of the 10 GKLC-cefoxitin grafts was infected compared with 10 of 10 regular PTFE grafts (p less than 0.003). Regression analysis showed antibiotic elution to occur in an exponential fashion (r = 0.9654) with no detectable antibiotic present after 10 days. GKLC with cefoxitin significantly protects the PTFE graft lumen from infection during bacteremia compared with regular PTFE. The role of antibiotic-bound grafts in relation to the use of intravenous antibiotics will need to be determined by further studies.


Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome.
Glycogen storage disease type III (GSDIII) is a rare disorder of glycogenolysis due to AGL gene mutations, causing glycogen debranching enzyme deficiency and storage of limited dextrin. Patients with GSDIIIa show involvement of liver and cardiac/skeletal muscle, whereas GSDIIIb patients display only liver symptoms and signs. The International Study on Glycogen Storage Disease (ISGSDIII) is a descriptive retrospective, international, multi-centre cohort study of diagnosis, genotype, management, clinical course and outcome of 175 patients from 147 families (86 % GSDIIIa; 14 % GSDIIIb), with follow-up into adulthood in 91 patients. In total 58 AGL mutations (non-missense mutations were overrepresented and 21 novel mutations were observed) were identified in 76 families. GSDIII patients first presented before the age of 1.5 years, hepatomegaly was the most common presenting clinical sign. Dietary management was very diverse and included frequent meals, uncooked cornstarch and continuous gastric drip feeding. Chronic complications involved the liver (hepatic cirrhosis, adenoma(s), and/or hepatocellular carcinoma in 11 %), heart (cardiac involvement and cardiomyopathy, in 58 % and 15 %, respectively, generally presenting in early childhood), and muscle (pain in 34 %). Type 2 diabetes mellitus was diagnosed in eight out of 91 adult patients (9 %). In adult patients no significant correlation was detected between (non-) missense AGL genotypes and hepatic, cardiac or muscular complications. This study demonstrates heterogeneity in a large cohort of ageing GSDIII patients. An international GSD patient registry is warranted to prospectively define the clinical course, heterogeneity and the effect of different dietary interventions in patients with GSDIII.


A Simple and Efficient Synthesis of 4-Arylacridinediones and 6-Aryldiindeno[1,2-b:2,1-e]pyridinediones using CuI Nanoparticles as Catalyst under Solvent-Free Conditions.
The importance of acridine core structure and other heterocycles containing its framework is well known, as they are found in numerous compounds with a variety of biological effects. Pyridine is also an important solvent and heterocyclic nucleus for the design and synthesis of novel molecules with biological properties. It occurs in several natural compounds which are used as a precursor in agrochemicals and pharmaceuticals. The utility of nanostructured metal salts because of their small size and high surface area as catalysts in organic synthesis has drawn special attention due to their better properties such as slower reaction rate, reusability of the catalyst, and higher yields of products compared to the bulk size. Nanosized copper iodide is one reusable Lewis acid catalyst which has revealed several catalytic activities for the synthesis of organic compounds and others. As part of our recent study to develop heterocyclic syntheses using nanostructured catalysts, we now report an efficient and clean synthetic route to 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridinediones via a condensation reaction catalyzed by CuI nanoparticles under solvent-free conditions. The present work deals with the condensation reaction of aromatic aldehydes, ammonium acetate and active methylene compounds comprising dimedone or 1,3- indanedione in the presence of a catalytic amount of the synthesized CuI nanoparticles could be applied for the solvent-free preparation of 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1- e]pyridinediones at 70 °C within 60 min. A series of 9-aryl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridine-5,7-diones were synthesized in high to excellent yields via a simple one-pot three-component coupling reaction using the synthesized CuI nanoparticles as an efficient and recyclable catalyst. All synthesized compounds were well characterized by their satisfactory elemental analyses, IR, 1H and 13C NMR spectroscopy. The synthesized catalyst was fully characterized by XRD, TEM and SEM techniques. A solvent-free condensation between aromatic aldehydes, ammonium acetate and active methylene compounds comprising dimedone or 1,3-indanedione, in the presence of CuI nanoparticles as an efficient and recyclable catalyst leads to the formation of 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridinediones. This novel and practical approach has a number of advantages for instance, the condensation itself is solvent-free, the total amount of solvent used in the whole process is significantly decreased, the yields of pure products are high to excellent without any by-products, the catalyst is reusable, and the work-up is very simple.


Tat-SF1 protein associates with RAP30 and human SPT5 proteins.
The potent transactivator Tat recognizes the transactivation response RNA element (TAR) of human immunodeficiency virus type 1 and stimulates the processivity of elongation of RNA polymerase (Pol) II complexes. The cellular proteins Tat-SF1 and human SPT5 (hSPT5) are required for Tat activation as shown by immunodepletion with specific sera and complementation with recombinant proteins. In nuclear extracts, small fractions of both hSPT5 and Pol II are associated with Tat-SF1 protein. Surprisingly, the RAP30 protein of the heterodimeric transcription TFIIF factor is associated with Tat-SF1, while the RAP74 subunit of TFIIF is not coimmunoprecipitated with Tat-SF1. Overexpression of Tat-SF1 and hSPT5 specifically stimulates the transcriptional activity of Tat in vivo. These results suggest that Tat-SF1 and hSPT5 are indispensable cellular factors supporting Tat-specific transcription activation and that they may interact with RAP30 in controlling elongation.


The use of near-infrared light for safe and effective visualization of subsurface blood vessels to facilitate blood withdrawal in children.
Obtaining access to blood vessels can be difficult, especially in children. Visualization of subsurface blood vessels might be a solution. Ultrasound and visible light have been used to this purpose, but have some drawbacks. Near-infrared light might be a better option since subsurface blood vessels can be visualized in high contrast due to less absorption and scattering in tissue as compared to visible light. Our findings with a multispectral imaging system support this theory. A device, the VascuLuminator, was developed, based on transillumination of the puncture site with near-infrared light. The VascuLuminator was designed to meet the requirements of compact and safe use. A phantom study showed that the maximum depth of visibility (5.5mm for a 3.6mm blood vessel) is sufficient to visualize blood vessels in typical locations for peripheral venous and arterial access. A quantitative comparison of the VascuLuminator and to two other vessel imaging devices, using reflection of near-infrared light instead of transillumination, was conducted. The VascuLuminator is able to decrease failure at first attempt in blood withdrawal in pediatric patients from 10/80 (13%) to 1/45 (2%; P=.05).


Identification of cis-acting promoter elements in cold- and dehydration-induced transcriptional pathways in Arabidopsis, rice, and soybean.
The genomes of three plants, Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and soybean (Glycine max), have been sequenced, and their many genes and promoters have been predicted. In Arabidopsis, cis-acting promoter elements involved in cold- and dehydration-responsive gene expression have been extensively analysed; however, the characteristics of such cis-acting promoter sequences in cold- and dehydration-inducible genes of rice and soybean remain to be clarified. In this study, we performed microarray analyses using the three species, and compared characteristics of identified cold- and dehydration-inducible genes. Transcription profiles of the cold- and dehydration-responsive genes were similar among these three species, showing representative upregulated (dehydrin/LEA) and downregulated (photosynthesis-related) genes. All (4(6) = 4096) hexamer sequences in the promoters of the three species were investigated, revealing the frequency of conserved sequences in cold- and dehydration-inducible promoters. A core sequence of the abscisic acid-responsive element (ABRE) was the most conserved in dehydration-inducible promoters of all three species, suggesting that transcriptional regulation for dehydration-inducible genes is similar among these three species, with the ABRE-dependent transcriptional pathway. In contrast, for cold-inducible promoters, the conserved hexamer sequences were diversified among these three species, suggesting the existence of diverse transcriptional regulatory pathways for cold-inducible genes among the species.


Classification of breast lesions in ultrasound images using deep convolutional neural networks: transfer learning versus automatic architecture design.
Deep convolutional neural networks (DCNNs) have demonstrated promising performance in classifying breast lesions in 2D ultrasound (US) images. Exiting approaches typically use pre-trained models based on architectures designed for natural images with transfer learning. Fewer attempts have been made to design customized architectures specifically for this purpose. This paper presents a comprehensive evaluation on transfer learning based solutions and automatically designed networks, analyzing the accuracy and robustness of different recognition models in three folds. First, we develop six different DCNN models (BNet, GNet, SqNet, DsNet, RsNet, IncReNet) based on transfer learning. Second, we adapt the Bayesian optimization method to optimize a CNN network (BONet) for classifying breast lesions. A retrospective dataset of 3034 US images collected from various hospitals is then used for evaluation. Extensive tests show that the BONet outperforms other models, exhibiting higher accuracy (83.33%), lower generalization gap (1.85%), shorter training time (66 min), and less model complexity (approximately 0.5 million weight parameters). We also compare the diagnostic performance of all models against that by three experienced radiologists. Finally, we explore the use of saliency maps to explain the classification decisions made by different models. Our investigation shows that saliency maps can assist in comprehending the classification decisions.


Multimedia: enhancing instruction for students with learning disabilities.
This article includes an introduction to the terminology and different types of formats of current multimedia technologies. Integration opportunities and challenges for using multimedia for students with learning disabilities are discussed in the framework of learning environments. Multimedia used as a demonstration station, learning research station, and creation station offers teachers and students possibilities for enhancing the teaching-learning environment.


Molecular epidemiology of hepatitis C virus in Iran as reflected by phylogenetic analysis of the NS5B region.
Hepatitis C virus (HCV) subtypes were determined in 125 Iranian patients by phylogenetic analysis within the NS5B or 5'-UTR/core regions. Subtypes 1a and 3a were predominant accounting for 47 and 36%, whereas 1b and 4 accounted for 8 and 7%. This subtype distribution differs from that of Turkey and Pakistan, where subtypes 1b and 3a dominate and also from neighbouring Arabic countries where subtype 4 is the prevalent genotype. The Iranian 1a and 3a strains formed subclusters in the dendrogram indicating that these subtypes are indigenous to Iran. In contrast, the 1b strains intermixed with strains derived worldwide. Subtype 1a was frequent in South Iran (70%), while 3a was more prevalent in North-West Iran (83%), a region with a high proportion of Turkish inhabitants. Patients infected by blood products had more frequently subtype 1a (57%), while younger drug users had more frequently subtype 3a (54%). Genotype 4 was over-represented among haemodialysis patients in Tehran. One strain, most similar to genotype 5, was highly divergent in the NS5B region and further analysis is needed to assess the systematic status of this strain. In half of the patients with unknown source of infection only the 5'-UTR could be amplified, most of which were from North-West Iran and from patients younger than those with unknown source of infection with typable strains, mean age 29 versus 43 years. In conclusion, the NS5B sequence data revealed population based subtype patterns in Iran, the further study of which may help to understand the molecular epidemiology of HCV in a low-endemic area.


Increased fibrosis progression rates in hepatitis C patients carrying the prothrombin G20210A mutation.
To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutations suffer from increased rates of liver fibrosis. We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fibrosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. Fifty two of the patients were categorized as "fast fibrosers" and 116 as "slow fibrosers"; 13% of the "fast fibrosers" carried the PT20210 mutation as compared with 5.5% of the "slow fibrosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fibrosis. Carriage of the PT20210 mutation is related to an increased rate of liver fibrosis in HCV patients.


Synthesis of sulfonamide conjugates of Cu(II), Ga(III), In(III), Re(V) and Zn(II) complexes: carbonic anhydrase inhibition studies and cellular imaging investigations.
Carbonic anhydrase IX (CA IX) is currently generating great interest as a marker of tumour hypoxia and a potential chemotherapeutic target. In order to test the principle that a CA IX inhibitor could be used for targeting PET or SPECT metallic radioisotopes to tumours we have prepared a number of conjugates involving aryl-sulfonamides or an acetazolamide derivative linked to a range of copper, indium, rhenium, 99m-technetium and zinc complexes. Radiolabelled (64)Cu and (99m)Tc analogues of the 'cold' Cu and some of the Re complexes were prepared in good radiochemical incorporation. Inhibition of various human carbonic anhydrase isoforms (I, II, IX and XII) was tested with the 'cold', non-radiolabelled complexes, and compared with an acetazolamide standard (AZA). The molecular structure of a new, tri-sulfonated porphyrin-labeled sulfonamide was determined using synchrotron X-ray crystallography.


Interposition flaps in transabdominal vesicovaginal fistula repairs: are they really necessary?
Objectives. To evaluate the use of interposition flaps in repairing vesicovaginal fistulas (VVFs) of benign and malignant etiologies. Interposition flaps are not routinely used in the repair of VVFs when the surrounding tissues appear healthy and well-vascularized, such as in a benign etiology.Methods. We retrospectively reviewed the charts of 37 women (mean age 49.1 years) at our institution who underwent transabdominal repair of their VVF by urologic surgeons between August 1978 and June 1999. The preoperative and postoperative medical records were reviewed.Results. Of the 37 VVFs repaired transabdominally, 29 had a benign etiology (25 related to gynecologic procedures) and 8 a malignant etiology (all related to gynecologic neoplasia). Of the 29 benign VVFs, an interposition flap was used in 10 repairs with all 10 successful (100%). The remaining 19 benign VVF repairs were performed without using a flap, with 12 successful (63%). Of the 8 malignant fistulas, an interposition flap was used in 2 repairs with both successful (100%). The remaining 6 malignant VVF repairs were performed without a flap, with 4 successful (67%).Conclusions. The results of our study indicate a higher success rate for transabdominal VVF repairs performed with an interposition flap (100% success rate at our institution). This observation holds true regardless of the appearance of healthy surrounding tissue or, more importantly, a benign or malignant etiology. We recommend interposition flaps in transabdominal repairs of VVFs, even in the cases of benign fistulas with well-preserved surrounding tissue.


The role of frontostriatal impairment in freezing of gait in Parkinson's disease.
Freezing of gait (FOG) is a disabling symptom of advanced Parkinson's disease (PD) that leads to an increased risk of falls and nursing home placement. Interestingly, multiple lines of evidence suggest that the manifestation of FOG is related to specific deficits in cognition, such as set shifting and the ability to process conflict-related signals. These findings are consistent with the specific patterns of abnormal cortical processing seen during functional neuroimaging experiments of FOG, implicating increased neural activation within cortical structures underlying cognition, such as the Cognitive Control Network. In addition, these studies show that freezing episodes are associated with abnormalities in the BOLD response within key structures of the basal ganglia, such as the striatum and the subthalamic nucleus. In this article, we discuss the implications of these findings on current models of freezing behavior and propose an updated model of basal ganglia impairment during FOG episodes that integrates the neural substrates of freezing from the cortex and the basal ganglia to the cognitive dysfunctions inherent in the condition.


Spectral and Energy Efficiencies of Millimeter Wave MIMO With Configurable Hybrid Precoding.
Hybrid precoding architectures are widely studied for millimeter wave (mmWave) massive MIMO systems. A major challenge in designing hybrid precoders is the practical constraints on the number of RF chains, which can have a direct impact on the spectral and energy efficiencies of the communication systems. In this paper, we investigate tradeoff between the two performance metrics in both static and mobile communication scenarios via closed-form expressions, when the number of active RF chains can be selected. Based on these expressions, the computational complexity to configure the hybrid precoder is reduced, which can be used to adaptively activate required RF chains for the given MIMO system and channel condition. Numerical results indicate that a certain number of RF chains should be activated in order to maximize energy efficiency at high SNRs, which is generally different from the optimal configuration to maximize spectral efficiency. Further-more, for low SNRs, we have shown that a simple analog beamforming, which uses only a single RF chain, is optimal for both spectral and energy efficiencies. In addition, the proposed mobility-aware hybrid precoding is shown to be capable of effectively achieving beamforming gain between high-speed mobile devices.


Retrospective evaluation of clinical signs, clinical course, and prognosis between dogs with left atrial rupture secondary to myxomatous mitral valve disease and those with neoplastic cardiac tamponade (2015-2019): 70 cases.
To describe the clinical signs, clinical course, and prognosis of suspected left atrial rupture (LAR) secondary to myxomatous mitral valve disease (MMVD) in dogs and to compare them with dogs with suspected neoplastic cardiac tamponade (NCT). Retrospective study from November 2015 to October 2019 SETTING: An out-of-hours Emergency Animal Hospital. Twenty-three dogs with LAR secondary to MMVD (LAR group) and 47 dogs with NCT (NCT group). None. The following were the characteristics of the study population (LAR group vs NCT groups) with P < 0.05 as the significance threshold: male sex, 83% vs 66%; median age, 11.9 vs 12.5 years; and median weight, 3.8 vs 6.4 kg (P < 0.001). Chihuahuas and Miniature Dachshunds were overrepresented in the LAR and NCT groups, respectively. Statistically different clinical findings between the 2 groups were as follows (LAR vs NCT): pulmonary edema, 43% vs 0%; pericardial thrombus, 70% vs 6% (P < 0.001); ineffectiveness of pericardiocentesis (whether aspiration of pericardial fluid was successful or not), 58% vs 2% (P < 0.001); mortality rate within 48 hours of visiting hospital, 35% vs 9% (P < 0.01). No significant difference was observed in survival time after discharge between the 2 groups. The proportion of dogs with a diagnosis of LAR secondary to MMVD in dogs with cardiac tamponade was higher than the previously reported rate. Furthermore, the frequency of pulmonary edema, ineffectiveness of pericardiocentesis, and short-term mortality rate was higher in the LAR group than in the NCT group.


Tumor Expression of Cyclin-Dependent Kinase 5 (Cdk5) Is a Prognostic Biomarker and Predicts Outcome of Oxaliplatin-Treated Metastatic Colorectal Cancer Patients.
In recent years, an increasing number of studies have shown that elevated expression of cyclin dependent kinase (Cdk5) contributes to the oncogenic initiation and progression of many types of cancers. In this study, we investigated the expression pattern of Cdk5 in colorectal cancer (CRC) cell lines and in a large number of tumor samples in order to evaluate its relevance in this pathogenesis and possible use as a prognostic marker. We found that Cdk5 is highly expressed and activated in CRC cell lines and that silencing of the kinase decreases their migration ability. In tumor tissues, Cdk5 is overexpressed compared to normal tissues due to a copy number gain. In patients with localized disease, we found that high Cdk5 levels correlate with poor prognosis, while in the metastatic setting, this was only the case for patients receiving an oxaliplatin-based treatment. When exploring the Cdk5 levels in the consensus molecular subtypes (CMS), we found the lowest levels in subtype 1, where high Cdk5 again was associated with a poorer prognosis. In conclusion, we confirm that Cdk5 is involved in CRC and disease progression and that it could serve as a prognostic and predictive biomarker in this disease.


Advanced glycation in health and disease: role of the modern environment.
It is believed that intracellular and extracellular advanced glycation (AGEs) or lipoxidation end products (ALEs), together with dysregulated glucose and lipid metabolism, are important contributors to oxidant or carbonyl stress, enhanced cellular redox-sensitive transcription factor activity, and impaired innate immune defense, causing over time inappropriate inflammatory responses. However, neither the magnitude nor the persistent nature of this increased prooxidant state are completely understood. A significant correlation has been found between ingested and circulating AGEs in humans in recent years. Based on animal studies, the injurious impact of diet-derived AGEs to vascular and kidney tissues is estimated to rival or even exceed that caused by hyperglycemia or hyperlipidemia. Consistent with this view, dietary AGE restriction has been associated with suppression of several immune defects, insulin resistance, and diabetic complications, whether genetically or diet induced, despite persistent diabetes. These findings are in support of clinical evidence from subjects with diabetes or vascular or kidney disease. Most recently, evidence from animal studies points to AGE restriction as an effective means for extending median life span, similar to that previously shown by marked caloric restriction. We conclude that excessive AGE consumption, in the current dietary/social structure, represents an independent factor for inappropriate oxidant stress responses, which may promote the premature expression of complex diseases associated with adult life, such as diabetes and cardiovascular disease.


Removal of Trace Organic Contaminants by Parallel Operation of Reverse Osmosis and Granular Activated Carbon for Drinking Water Treatment.
In response to increasingly stringent restrictions for drinking water quality, a parallel operation of two common technologies, low-pressure reverse osmosis (LPRO) and activated carbon filtration (ACF), was investigated in a comprehensive five-month pilot study for the removal of 32 typical trace organic contaminants (TrOCs) from Rhine bank filtrates employing a semi- technical plant. TrOCs have been divided into three groups: polyfluorinated aliphatic compounds; pharmaceuticals, pesticides and metabolites; in addition to volatiles, nitrosamines and aminopolycarboxylic acids, which were also examined. The net pressure behavior, normalized salt passage and rejection of TrOCs by LPRO were investigated and compared with ACF operation. In addition, autopsies from the leading and last membrane modules were performed using adenosine triphosphate (ATP), total organic carbon (TOC), ICP-OES and SEM-EDX techniques. Generally, rather stable LPRO membrane performance with limited membrane fouling was observed. TrOCs with a molecular weight of ≥ 150 Da were completely retained by LPRO, while the rejection of di- and trichloro compounds improved as the filtration progressed. ACF also showed significant removal for most of the TrOCs, but without desalination. Accordingly, the ACF and LPRO can be operated in parallel such that the LPRO permeate and the ACF-treated bypass can be mixed to produce drinking water with adjustable hardness and significantly reduced TrOCs.


Mealtime rituals: power and resistance in the construction of mealtime rules.
This paper discusses how child resistance is lived on a daily basis through the construction and operation of mealtime rules in four Australian families with young children. It focuses on the sociologically neglected situation of everyday parent-child conflict and resistance and posits young children as actively engaged in contestation and negotiation of power relationships within the family. Analysis of domestic dialogue and conflict episodes demonstrates how mealtime rituals function as techniques of discipline through which young children are normalized. Although resistance and contestation occurred in all families, the construction and operation of mealtime rules were also a regulatory mechanism for constituting boys and girls in different ways. Girls were constructed as helping to prepare, serve and clean after meals, which boys were the recipients of this service from their mothers and sisters.


Combined 2-D Vector Velocity Imaging and Tracking Doppler for Improved Vascular Blood Velocity Quantification.
Measurement of the maximum blood flow velocity is the primary means for determining the degree of carotid stenosis using ultrasound. The current standard for estimating the maximum velocity is pulsed-wave Doppler with manual angle correction, which is prone to error and interobserver variability. In addition, spectral broadening in the velocity spectra leads to overestimation of maximal velocities. In this paper, we propose to combine two velocity estimation methods to reduce the bias and variability in maximum velocity measurements. First, the direction of the blood flow is estimated using an aliasing-resistant least squares vector Doppler technique. Then, tracking Doppler is performed on the same data, using the direction of the vector Doppler estimate as the tracking direction. Simulations show that the method can estimate a maximum velocity of 2 m/s with accuracy 5% for beam-to-flow angles between 20° and 75°, and that the primary source of error is inaccuracy in the flow direction estimate from vector Doppler. Simulations of complex flow in a carotid bifurcation demonstrated that the combined technique provided spectral velocity profiles corresponding well with the true maximum velocity trace, and that the bias originating from the directional estimate was within 5% for all spatial points. A healthy volunteer and a volunteer with carotid artery stenosis were imaged, showing in vivo feasibility of the method, for high velocities and with beam-to-flow angles varying throughout the cardiac cycle.


Assessing the relationship between early maladaptive schemas and interpersonal problems using interpersonal scenarios depicting rejection.
Early maladaptive schemas (EMSs) have been theorised to contribute to reoccurring interpersonal problems. This study developed a novel experimental paradigm that aimed to assess if EMSs moderate the impact of interpersonal situations on interpersonal responses by manipulating the degree of rejection in a series of interpersonal vignettes depicting acceptance, ambiguous rejection and rejection. In a sample of 158 first-year psychology students (27.2% male; 72.2% female; 0.6% other) participant responses to interpersonal scenarios were measured including degree of perceived rejection, emotional distress, conviction in varying cognitive appraisals consistent with attribution theory and behavioural responses to scenarios. Qualitative data was analysed using inductive content analysis and statistical analyses were conducted using multi-level mixed effect linear and logistic regression models using the software Jamovi. People reporting higher EMSs reported increased emotional distress (F(1, 156) = 24.85, p < .001), perceptions of rejection (F(1, 156) = 34.33, p < .001), self-blame (F(1, 156) = 53.25, p < .001), other-blame (F(1, 156) = 13.16, p < .001) and more intentional (F(1, 156) = 9.24, p = .003), stable (F(1, 156) = 25.22, p < .001) and global (F(1, 156) = 19.55, p < .001) attributions but no differences in reported behavioural responses. The results also supported that EMSs moderate the relationship between interpersonal rejection and perceptions of rejection (F(2, 1252) = 18.43, p < .001), emotional distress (F(2, 1252) = 12.64, p < .001) and self-blame (F(2, 1252) = 14.00, p < .001). Together these findings suggest that people with EMSs experience increased distress and select negative cognitions in situations where there are higher levels of rejection but that distress and negative cognitions are generally higher in people with EMSs irrespective of the situation.


Recent developments in matrix solid-phase dispersion extraction.
Matrix solid-phase dispersion is a sample preparation strategy widely applied to solid, semisolid or viscous samples, including animal tissues and foods with a high lipidic content. The process consists in blending the matrix onto a solid support, allowing the matrix cell disruption and the subsequent extraction of target analytes by means of a suitable elution solvent. First introduced in 1989, MSPD employment and developments are still growing because of the feasibility and versatility of the process, as evidenced by the several reviews that have been published since nineties. Therefore, the aim of the present review is to provide a general overview and an update of the last developments of MSPD.


Gender differences in the mu rhythm of the human mirror-neuron system.
Psychologically, females are usually thought to be superior in interpersonal sensitivity than males. The human mirror-neuron system is considered to provide the basic mechanism for social cognition. However, whether the human mirror-neuron system exhibits gender differences is not yet clear. We measured the electroencephalographic mu rhythm, as a reliable indicator of the human mirror-neuron system activity, when female (N = 20) and male (N = 20) participants watched either hand actions or a moving dot. The display of the hand actions included androgynous, male, and female characteristics. The results demonstrate that females displayed significantly stronger mu suppression than males when watching hand actions. Instead, mu suppression was similar across genders when participants observed the moving dot and between the perceived sex differences (same-sex vs. opposite-sex). In addition, the mu suppressions during the observation of hand actions positively correlated with the personal distress subscale of the interpersonal reactivity index and negatively correlated with the systemizing quotient. The present findings indirectly lend support to the extreme male brain theory put forward by Baron-Cohen (2005), and may cast some light on the mirror-neuron dysfunction in autism spectrum disorders. The mu rhythm in the human mirror-neuron system can be a potential biomarker of empathic mimicry.


Peer support for families of children with complex needs: Development and dissemination of a best practice toolkit.
Benefits of peer support interventions for families of children with disabilities and complex medical needs have been described in the literature. An opportunity to create an evidence-informed resource to synthesize best practices in peer support for program providers was identified. The objective of this paper is to describe the key activities used to develop and disseminate the Peer Support Best Practice Toolkit. This project was led by a team of knowledge translation experts at a large pediatric rehabilitation hospital using a knowledge exchange framework. An integrated knowledge translation approach was used to engage stakeholders in the development process through focus groups and a working group. To capture best practices in peer support, a rapid evidence review and review of related resources were completed. Case studies were also included to showcase practice-based evidence. The toolkit is freely available online for download and is structured into four sections: (a) background and models of peer support, (b) case studies of programs, (c) resources, and (d) rapid evidence review. A communications plan was developed to disseminate the resource and generate awareness through presentations, social media, and champion engagement. Eight months postlaunch, the peer support website received more than 2,400 webpage hits. Early indicators suggest high relevance of this resource among stakeholders. The toolkit format was valuable to synthesize and share best practices in peer support. Strengths of the work include the integrated approach used to develop the toolkit and the inclusion of both the published research literature and experiential evidence.


Self-rated health and mortality: does the relationship extend to a low income setting?
Although a relationship between poor self-reported health status and excess mortality risk has been well-established for industrialized countries, almost no research considers developing countries. We use data from Indonesia to show that in a low-income setting, as in more advantaged parts of the world, individuals who perceive their health to be poor are significantly more likely to die in subsequent follow-up periods than their counterparts who view their health as good. This result characterizes both men and women, holds for multiple time periods, and remains after inclusion of measures of nutritional status, physical functioning, symptoms of poor physical health and depression, and hypertension. We also consider the correlates of self-rated health. Symptoms and physical functioning are strong predictors of reporting poor rather than good health, but neither these indicators nor other covariates we consider distinguish between reports of excellent rather than good health.


Inkjet-printed barcodes for a rapid and multiplexed paper-based assay compatible with mobile devices.
This study reports a simple, rapid, low-cost, robust, and multiplexed barcoded paper-based assay (BPA) compatible with mobile devices. An inkjet printer and an XYZ dispensing platform were used to realize mass-manufacturing of barcoded paper-based analytical devices (BPADs) with high precision and efficiency. We designed a new group of barcodes and developed an application (APP) for the reading of the new code. The new barcodes possess a 16 times higher coding capacity than the standard Codabar code in our experiment on drug residue detection. The BPA system allows applications in the assays of blood-transmitted infections, drug residues in milk and multiplex nucleic acids. The whole detection process and the readout of the results can be completed within 10 minutes. The limit of detection for enrofloxacin (ENR) (8 ng mL-1) satisfies the requirements of drug residue monitoring. Its high rapidity, simplicity, efficiency and selectivity make the BPA system extremely suitable to be applied in rapid and on-site detection.


Efficacy of naturopathy and yoga in bronchial asthma--a self controlled matched scientific study.
Asthma is one of the common psychosomatic illness influenced by many factors. Bronchodilators give temporary relief and have side effects. The present study is aimed at finding the efficacy of a non-pharmacological approach of naturopathy and Yoga in bronchial asthma. A total no of 37 patients (19 men, 18 women) with mean age 35.06 yrs (men), 40.74 yrs (women) admitted to INYS, Bangalore, for the period of 21 days. The treatment included 1. Diet therapy 2. Nature cure treatment and 3. Yoga therapy. The various parameters including lung function test were measured on admission and once a week. Results showed the significant improvement in PEFR, VC, FVC, FEV1, FEV/FEC %, MVV, ESR and absolute eosinophil count. The patients reported a feeling of well being, freshness and comfortable breathing. Naturopathy and yoga helps in inducing positive health, alleviating the symptoms of disease by acting at physical and mental levels.


Allergic shock caused by ingestion of cooked jellyfish: A case report.
Although anaphylaxis caused by jellyfish stings is common in coastal areas, an allergic shock caused by cooked jellyfish ingestion has never been reported in China. In this paper, we report a case of allergic shock being caused by ingestion of cooked salt-preserved jellyfish shortly after being stung by a live jellyfish. A 26-year-old Chinese man presented with dizziness, pruritus, dyspnea, hypotension, and tachycardia after eating cooked salted jellyfish. The patient had been stung twice by jellyfish half a year ago. Allergic shock caused by ingestion of cooked jellyfish. The patient was treated with phenergan (25 mg, intramuscular injection), 250 mL normal saline (NS) and 10 mg dexamethasone (intravenous drip), 500 mL NS and 0.4 g cimetidine (intravenous drip), and 500 mL NS for rapid fluid infusion (intravenous drip). After the treatment, the main clinical symptoms of the patient improved quickly. Five days later, the patient's urticaria had dissipated. A history of jellyfish contact or sting might be an important allergic factor for individuals who consume any kind of jellyfish.


Chk1 Inhibition Potently Blocks STAT3 Tyrosine705 Phosphorylation, DNA-Binding Activity, and Activation of Downstream Targets in Human Multiple Myeloma Cells.
The relationship between the checkpoint kinase Chk1 and the STAT3 pathway was examined in multiple myeloma cells. Gene expression profiling of U266 cells exposed to low (nmol/L) Chk1 inhibitor [PF-477736 (PF)] concentrations revealed STAT3 pathway-related gene downregulation (e.g., BCL-XL, MCL-1, c-Myc), findings confirmed by RT-PCR. This was associated with marked inhibition of STAT3 Tyr705 (but not Ser727) phosphorylation, dimerization, nuclear localization, DNA binding, STAT3 promoter activity by chromatin immunoprecipitation assay, and downregulation of STAT-3-dependent proteins. Similar findings were obtained in other multiple myeloma cells and with alternative Chk1 inhibitors (e.g., prexasertib, CEP3891). While PF did not reduce GP130 expression or modify SOCS or PRL-3 phosphorylation, the phosphatase inhibitor pervanadate antagonized PF-mediated Tyr705 dephosphorylation. Significantly, PF attenuated Chk1-mediated STAT3 phosphorylation in in vitro assays. Surface plasmon resonance analysis suggested Chk1/STAT3 interactions and PF reduced Chk1/STAT3 co-immunoprecipitation. Chk1 CRISPR knockout or short hairpin RNA knockdown cells also displayed STAT3 inactivation and STAT3-dependent protein downregulation. Constitutively active STAT3 diminished PF-mediated STAT3 inactivation and downregulate STAT3-dependent proteins while significantly reducing PF-induced DNA damage (γH2A.X formation) and apoptosis. Exposure of cells with low basal phospho-STAT3 expression to IL6 or human stromal cell conditioned medium activated STAT3, an event attenuated by Chk1 inhibitors. PF also inactivated STAT3 in primary human CD138+ multiple myeloma cells and tumors extracted from an NSG multiple myeloma xenograft model while inhibiting tumor growth. These findings identify a heretofore unrecognized link between the Chk1 and STAT3 pathways and suggest that Chk1 pathway inhibitors warrant attention as novel and potent candidate STAT3 antagonists in myeloma.


When heparin causes thrombosis: significance, recognition, and management of heparin-induced thrombocytopenia in dialysis patients.
Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia and paradoxical hypercoagulability. HIT occurs when an antibody ("HIT antibody") produced against the complex of heparin and platelet factor 4 (PF4) causes systemic platelet consumption and activation. Nephrologists encounter HIT in the care of end-stage renal disease (ESRD) patients because heparin is a routine anticoagulant in hemodialysis. The incidence of HIT in ESRD appears to be lower than in other clinical settings. However, HIT is equally life threatening in ESRD patients and therefore demands the same prompt recognition and aggressive treatment. Diagnosing HIT requires the detection of HIT antibodies. A functional assay (e.g., [(14)C] serotonin release assay) relies on the patient's HIT antibodies to activate donor platelets at pharmacologic heparin concentrations. The more common antigen assay (e.g., enzyme-linked immunosorbent assay [ELISA]) detects the binding of the patient's HIT antibodies to antigens (e.g., heparin-PF4 complex) in a microtiter well and does not involve platelets. The moment HIT is suspected, heparin should be stopped and an alternative anticoagulant initiated immediately, even before the result of a serologic test becomes available. The advent of several new anticoagulants in the last decade, especially argatroban and bivalirudin, has expanded treatment options for HIT in dialysis patients. This review discusses the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of HIT, with special emphasis on concepts relevant to the care of dialysis patients.


Tonsillotomy versus tonsillectomy--a randomized trial regarding dentofacial morphology and post-operative growth in children with tonsillar hypertrophy.
The primary aim of this study was to analyse two different methods of tonsil surgery, tonsillectomy (TE) and tonsillotomy (TT), regarding post-operative dentofacial growth in children with tonsillar hypertrophy. A secondary aim was to analyse these results in relation to cephalometric standards. The study group consisted of 64 subjects (39 boys and 25 girls), mean age 4.8 years ± 4 months. They were randomized to a complete removal of the pharyngeal tonsil, TE, (n = 31) or a partial removal, TT, (n = 33). Pre-operative and 2 years post-operative study material were obtained and analysed. The results were compared with cephalometric standards. Pre-operative, children with hypertrophic tonsils displayed an increased vertical relation (P < 0.05) compared with cephalometric standards. Post-operative, no significant difference could be detected between the two surgical procedures regarding dentofacial growth. Mandibular growth with an anterior inclination was significant (P < 0.001/TE, P < 0.01/TT) for both groups. An increased upper and lower incisor inclination was noted (P < 0.01/TE,TT). The vertical relation decreased (P < 0.001/TE, P < 0.05/TT) as well as the mandibular angle (P < 0.01/TE, P < 0.001/TT). Reduction was also significant for the sagittal intermaxillar (P < 0.001/TE,TT) relation. These post-operative results, together with a more prognatic mandible (P < 0.05/TE,TT) and chin (P < 0.001/TE, P < 0.01/TT), might indicate a more horizontal direction of mandibular growth. TE and TT yielded equal post-operative dentofacial growth in children treated for hypertrophic tonsils. This result should be considered when deciding upon surgical technique.


Long-term increase in serum uric acid and its predictors over a 25 year follow-up: Results of the PAMELA study.
Hyperuricemia (HU) has been shown to be associated with an adverse impact on cardiovascular and metabolic risk. Scanty data are available in the general population on the longitudinal changes in serum uric acid (SUA), the occurrence of HU and their potential predictors. We examined during a 25-year follow-up the SUA changes and the factors associated with HU development in the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study. We analyzed data collected in 561 subjects of the PAMELA study evaluated during an average follow-up time amounting to 25.4 ± 1.0 years (mean ± SD). HU was defined by the Uric Acid Right for Heart Health (URRAh) cutoff (5.1 for females and 5.6 mg/dl for males). Mean SUA values during follow-up increased from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dl (P<0.001), the average SUA elevation amounting to of 0.3 ± 1.1 mg/dl 26.7 % of the subjects displayed HU at the follow-up. This was associated at the multivariable analysis with female gender, office, home and 24-h blood pressure, diuretic treatment, serum triglycerides and baseline SUA, as well as the increase in waist circumference and the reduction in renal function. The present study provides longitudinal evidence that in the general population during a 25 year follow-up there is a progressive increase in SUA and HU development. Baseline SUA represents the most important factor associated with these modifications. Gender, renal dysfunction, triglycerides, obesity, diuretic treatment and blood pressure represent other variables capable to predict future occurrence of HU.


Scheduling multiprocessor job with resource and timing constraints using neural networks.
The Hopfield neural network is extensively applied to obtaining an optimal/feasible solution in many different applications such as the traveling salesman problem (TSP), a typical discrete combinatorial problem. Although providing rapid convergence to the solution, TSP frequently converges to a local minimum. Stochastic simulated annealing is a highly effective means of obtaining an optimal solution capable of preventing the local minimum. This important feature is embedded into a Hopfield neural network to derive a new technique, i.e., mean field annealing. This work applies the Hopfield neural network and the normalized mean field annealing technique, respectively, to resolve a multiprocessor problem (known to be a NP-hard problem) with no process migration, constrained times (execution time and deadline) and limited resources. Simulation results demonstrate that the derived energy function works effectively for this class of problems.


Parental psychiatric disorder: effects on children.
A 4-year prospective study was undertaken of the families of 137 newly referred English speaking psychiatric patients with children at home aged under 15 years. The group comprised a representative sample of such patients living in one inner London borough. Teacher questionnaires were obtained yearly for all children of school age in the families, and for age-, sex- and classroom-matched controls. Detailed standardized interviews were undertaken yearly with parent-patients and with their spouses. A comparison was also made with a control group of families in the general population with 10-year-old children. Patients' families differed in terms of a higher rate of psychiatric disorder in spouses and a much higher level of family discord. Both parental mental disorder and marital discord tended to persist over the 4-year period, but persistence of both was much more marked when the parent had a personality disorder. The children of psychiatric patients had an increased rate of persistent emotional/behavioural disturbance, which tended to involve disorders of conduct. The psychiatric risk to the children was greatest in the case of personality disorders associated with high levels of exposure to hostile behaviour. Boys showing temperamental risk features were most vulnerable to the ill-effects associated with parental mental disorder.


Surface modified of polyacrylonitrile nanofibers by TiO2/MWCNT for photodegradation of organic dyes and pharmaceutical drugs under visible light irradiation.
This work describes the fabrication of two composite nanofibers systems containing polyacrylonitrile polymer (PAN), Multiwall carbon nanotubes (MWCNT) and Titania (TiO2) nanoparticles. Photodegradation experiments were performed to study the effect of various parameters including pH, catalyst dose, pollutant concentration and reaction time for three model compounds, methylene blue (MB), indigo carmine (IC), and ibuprofen (IBU) under visible light. Morphology and structure of the modified composite nanofibers were characterized by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric analysis (TGA), Photoluminescence (PL) spectroscopy, Raman spectra, and X-ray Photoelectron Spectra (XPS) analyses. The photocatalytic performance was achieved in a rather short time visible light (<30 min) and under low power intensity (125 W) compared to earlier reports. Kinetics data fitted well using pseudo-first order model to describe the mechanism of photocatalytic degradation processes. The stability and flexibility of the fabricated composite nanofibers allow their application in a continuous flow system and their re-use after several cycles.


The codon 31 polymorphism of the p53-inducible gene p21 shows distinct differences between major ethnic groups.
The codon 31 polymorphism of the p53-inducible protein p21 was studied with respect to allele frequency variations between some major ethnic groups. The frequency of the Al (Arg) allele showed highly significant variations ranging from 4% in Caucasians (Swedes) to 50% in Chinese. Compared to Caucasians, a relatively high frequency was found in African Blacks (29%) and Indians (16%). Furthermore, Finns and Mordvinians also had higher frequencies (9-10%) than west Europeans (French and Swedes), consistent with an Asiatic Mongoloid influence known to exist in Finno-Ugrian tribes. The geographic allele frequency patterns of p53 and its effector protein p21 were quite different. The p21 A1 mutations in African, Asiatic and European populations were identical at the DNA level. The geographical distribution of the A1 allele suggests an independent origin in Africa and Asia. The very pronounced ethnic differentiation of tumour suppressor genes and the fact that tumour suppressor genes may be teratogenes suggest that these polymorphisms are maintained by natural selection, probably operating in the intrauterine period.


Clinacanthus nutans Mitigates Neuronal Apoptosis and Ischemic Brain Damage Through Augmenting the C/EBPβ-Driven PPAR-γ Transcription.
Clinacanthus nutans Lindau (C. nutans) is a traditional herbal medicine widely used in Asian countries for treating a number of remedies including snake and insect bites, skin rashes, viral infections, and cancer. However, the underlying molecular mechanisms for its action and whether C. nutans can offer protection on stroke damage in brain remain largely unknown. In the present study, we demonstrated protective effects of C. nutans extract to ameliorate neuronal apoptotic death in the oxygen-glucose deprivation model and to reduce infarction and mitigate functional deficits in the middle cerebral artery occlusion model, either administered before or after hypoxic/ischemic insult. Using pharmacological antagonist and siRNA knockdown approaches, we demonstrated ability for C. nutans extract to protect neurons and ameliorate ischemic injury through promoting the anti-apoptotic activity of peroxisome proliferator-activated receptor-gamma (PPAR-γ), a stress-induced transcription factor. Reporter and chromatin immunoprecipitation promoter analysis further revealed C. nutans extract to selectively increase CCAAT/enhancer binding protein (C/EBP)β binding to specific C/EBP binding site (-332~-325) on the PPAR-γ promoter to augment its transcription. In summary, we report a novel transcriptional activation involving C/EBPβ upregulation of PPAR-γ expression to suppress ischemic neuronal apoptosis and brain infarct. Recognition of C. nutans to enhance the C/EBPβ → PPAR-γ neuroprotective signaling pathway paves a new way for future drug development for prevention and treatment of ischemic stroke and other neurodegenerative diseases.


In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits.
In vivo corneal absorption of the dipeptide prodrugs of acyclovir (ACV) was evaluated using microdialysis in rabbits. A corneal well was placed on the cornea of the anesthetized New Zealand White rabbits with implanted linear probes into the aqueous humor. Two hundred microliters of a 1% solution of L-valine-ACV (VACV), glycine-valine-ACV (GVACV), valine-valine-ACV (VVACV), and valine-tyrosine-ACV (VYACV) was placed in the corneal well and was allowed to diffuse for a period of 2 h, following which the drug solution was aspirated and well removed. Samples were collected every 20 min throughout the infusion and postinfusion phases and were analyzed by HPLC to obtain the aqueous humor concentrations. Absorption rate constants of all the compounds were found to be lower than the elimination rate constants. GVACV exhibited highest absorption rate (ka) compared with other prodrugs, but all the prodrugs showed similar terminal elimination rate (lambda(z)). The time of maximum absorption (Tmax) of ACV after administration of VACV and the dipeptide prodrugs did not vary significantly (p < 0.05). GVACV exhibited the highest concentration (Cmax) and area under curve (AUC) upon absorption (p < 0.05) compared to VACV, VVACV, and VYACV. Dipeptide prodrugs of ACV were absorbed through the cornea at similar rates but to varying extents. The dipeptide prodrug GVACV owing to its enhanced absorption of ACV seems to be a promising candidate for the treatment of ocular HSV infections.


Finding the mitral annular lines from 2-D + 1-D precordial echocardiogram using graph-search technique.
The apical four-chamber view echocardiogram collected by a transthoracic transducer can be used to evaluate the left ventricle volume. In the diastole, the left ventricle and left atrium become one chamber. In this case, the left ventricle and left atrium need to be separated using a "mitral annular line" so the volume of the left ventricle can be estimated. In this paper, a nearly automatic method for identifying the mitral annular lines from two-dimensional (2-D) + one-dimensional (1-D) precordial four-chamber view echocardiogram is presented. This method employs the optical flow technique and graph-search approach. The mitral annular line sequence is found by finding the shortest path in a weighted directed graph. The vertices in the graph are candidates for the mitral annular lines. The weights on the directed edges are determined using the optical flow technique. The proposed method requires only a physician to provide a point that is always in the left ventricular chamber. Experimental results show that the average error for the left ventricle volume obtained based on the computed mitral annular lines is 3%.


Control of brain microcirculation by endothelium.
Pial arterioles of mice are studied by in vivo TV microscopy. Focal endothelial injury is produced by a laser/Evans blue technique. Moderate damage results in local platelet aggregation. Very slight damage, without electron microscopic evidence of injury, results in loss of many endothelium derived vasoactive factors. These include "EDRFs" for acetylcholine, bradykinin and calcium ionophore, and "EDCFs" for histamine and serotonin. In the cases of acetylcholine, histamine and serotonin, each agonist possesses an additional opposing action which is independent of endothelium. The latter action is unmasked by the endothelial injury. The balance between simultaneously acting endothelium dependent and endothelium independent actions is a determinant of the response to an agonist with two opposing actions. This balance is partly dependent upon initial tone. Thus the effect of the agonist depends on initial tone. One of the determinants of initial tone may be basal release of one or more EDRFs or EDCFs. Evidence in pial arterioles for the basal release of EDRF for acetylcholine, comes from our data showing that L-NMMA constricts these arterioles. L-NMMA is a known inhibitor of synthesis of "classical" EDRF from L-arginine. The response to L-ARG is relaxation. Both the response to L-NMMA and the response to L-ARG are abolished by laser/dye injury of the endothelium. Thus these agents are really acting via an endothelial mechanism in brain arterioles, just as has been reported for their actions in conductance vessels. Finally mild injury associated with loss of "EDRFs" is also accompanied by a reduced ability of pial arteriolar endothelium to repell activated platelets.


Formation of furan along with HO₂ during the OH-initiated oxidation of 2,5-DHF and 2,3-DHF: an experimental and computational study.
Experimental characterization of products during OH-initiated oxidation of dihydrofurans (DHF) confirms the formation of furan accompanied by the formation of HO2 to be a significant channel in 2,5-DHF (21 ± 3%), whereas it is absent in 2,3-DHF. Theoretical investigations on the reaction of OH with these molecules are carried out to understand this difference. All possible channels of reaction are studied at M06-2X level with 6-311G* basis set, and the stationary points on the potential energy surface are optimized. The overall rate coefficients calculated using conventional TST with Wigner tunneling correction for 2,5-DHF and 2,3-DHF are 2.25 × 10(-11) and 4.13 × 10(-10) cm(3) molecule(-1) s(-1), respectively, in the same range as the previously determined experimental values. The branching ratios of different channels were estimated using the computed rate coefficients. The abstraction of H atom, leading to dihydrofuranyl radical, is found to be a significant probability, equally important as the addition of OH to the double bond in the case of 2,5-DHF. However, this probability is very small in the case of 2,3-DHF because the rate coefficient of the addition reaction is more than 10 times that of the abstraction reaction. This explains the conspicuous absence of furan among the products of the reaction of OH with 2,3-DHF. The calculations also indicate that the abstraction reaction, and hence furan formation, may become significant for OH-initiated oxidation of 2,3-DHF at temperatures relevant to combustion.


The challenge of non-adherence to early rehabilitation after coronary artery bypass surgery: Secondary results from the SheppHeartCABG trial.
Attending and maintaining a cardiac rehabilitation programme is a challenge. The purpose of this study was to explore associations between non-adherence to early coronary artery bypass graft rehabilitation and sociodemographic and clinical baseline data. Coronary artery bypass graft patients were randomised 1:1 to either four weeks of comprehensive early rehabilitation or usual care. Outcomes were assessed at three time-points points: baseline, discharge and four weeks post-coronary artery bypass graft. Differences in sociodemographic and clinical baseline data in adherent versus non-adherent patients were tested using the Pearson χ2 test for categorical variables. To test associations between non-adherence to exercise training and sociodemographic and clinical baseline data, multivariate logistic regression was used to estimate the odds ratio for in-hospital training and post-discharge training adjusted for age, sex and left ventricular ejection fraction. Non-adherence to in-hospital versus post-discharge exercise training was 31% (n=48) versus 53% (n=81). Female non-adherence was 20% versus 70%. Non-adherence to in-hospital versus post-discharge mindfulness was 87% versus 70%. Male non-adherence to mindfulness was 85% versus 70%. Non-adherence to psycho-educational consultations was 3%, most of whom were men. Patients with university level education were more adherent to in-hospital exercise training than patients with lower educational level (odds ratio=3.14 (95% confidence interval; 1.16-8.51), p=0.02). Diabetic patients were more non-adherent to exercise training after discharge (3.74 (1.54-9.08), p=0.004) as were overweight patients (0.37 (0.17-0.80), p=0.01). This study demonstrated wide acceptance of psycho-educational consultations in post-coronary artery bypass graft patients. Adherence to physical rehabilitation was low especially after discharge from hospital and the opportunity to attend a mindfulness programme was not used.


Barriers that prevent implementation of research findings in nursing: education-research hospitals case.
Using research results in nursing practices and basing nursing practices to evidence have been viewed as an important factor in increasing care quality. The aim of this research was to identify the barriers arising from utilizing research findings perceived by nurses. The research was conducted with participation of 748 nurses. The study is descriptive in nature, and the 'Barriers Scale' and a question form developed by the researchers were used as data collection instruments. The data were gathered through face-to-face interviews after the necessary permissions were taken. A total of 54.3% of the nurses are ≤ 30 years old, and 49.6% of them are graduates of high school-foundation degree. The nurses (63.8%) indicated the most important barrier as 'there is not enough time to read about research at work'. According to the results of this study, providing the nurses with both financial and information support after graduation is an important factor in facilitating research and using research results. Depending on the results of our study, we recommend that the number of publications in nursing and the opportunities of access to these publications be increased, and there should be more management support for research, and nurses should be provided with time.


[Investigation of the activity of the preparation cerbiden against Candida spp].
Antifungal activity of a new complex antibiotical preparation cerbiden obtained from medical plant Bidens cernua L. of the Asteraceae family, was investigated in vitro against the clinical and museum strains of Candida spp. High cerbiden activity against clinical and museum strains of Candida albicans, C. tropicalis, C. krusei, C. parapsilosis, C. guilliermondii, sensitive and resistant to nystatin, amphotericin B and clotrimazole was determined.


Head and neck cancer in India: need to formulate uniform national treatment guideline?
In a large and diverse country like India, there is a wide variation in the availability of infrastructure and expertise to treat head-neck cancer patients. Lack of consistent adherence to evidence-based management is the biggest problem. There is an unmet need to evaluate the existing treatment practices to form the basis for development of effective and uniform treatment policies. Prospective case series. A group of previously treated, potentially curable patients presenting to our institution (from April 2009 to March 2011) were evaluated for appropriateness of initial treatment based on National Comprehensive Cancer Network or Tata Memorial Hospital guidelines. Data regarding treatment center, protocol and accuracy of delivered treatment and their eventual outcome were analyzed. Descriptive. Amongst 450 newly registered patients, 77(17%) were previously treated with curative intent and 69(89%) of them were inappropriately treated. Seventeen (25%) patients were treated in clinics while 12(17%) in cancer centers and 34(50%) in corporate hospitals. Fourteen (20%) patients received chemotherapy, 22(32%) received radiotherapy and 14(20%) underwent surgery while 19(28%) patients received multimodality treatment. Disease stage changed to more advanced stage in 40(58%) patients and curative intent treatment could be offered only to 33(48%) patients. Amongst 56 patients available for outcome review, 18(32%) patients were alive disease-free, 20(36%) had died and 18(32%) were alive with disease. Large numbers of potentially curable patients are inappropriately treated and their outcome is significantly affected. Many initiatives have been taken in the existing National Cancer Control Program but formulation of a uniform national treatment guideline should be prioritized.


Chronic intermittent hypoxia increases rat sternohyoid muscle NADPH oxidase expression with attendant modest oxidative stress.
Chronic intermittent hypoxia (CIH) causes upper airway muscle dysfunction. We hypothesized that the superoxide generating NADPH oxidase (NOX) is upregulated in CIH-exposed muscle causing oxidative stress. Adult male Wistar rats were exposed to intermittent hypoxia (5% O2 at the nadir for 90 s followed by 210 s of normoxia), for 8 h per day for 14 days. The effect of CIH exposure on the expression of NOX subunits, total myosin and 4-hydroxynonenal (4-HNE) protein adducts in sternohyoid muscle was determined by western blotting and densitometry. Sternohyoid protein free thiol and carbonyl group contents were determined by 1D electrophoresis using specific fluorophore probes. Aconitase and glutathione reductase activities were measured as indices of oxidative stress. HIF-1α content and key oxidative and glycolytic enzyme activities were determined. Contractile properties of sternohyoid muscle were determined ex vivo in the absence and presence of apocynin (putative NOX inhibitor). We observed an increase in NOX 2 and p47 phox expression in CIH-exposed sternohyoid muscle with decreased aconitase and glutathione reductase activities. There was no evidence, however, of increased lipid peroxidation or protein oxidation in CIH-exposed muscle. CIH exposure did not affect sternohyoid HIF-1α content or aldolase, lactate dehydrogenase, or glyceraldehyde-3-phosphate dehydrogenase activities. Citrate synthase activity was also unaffected by CIH exposure. Apocynin significantly increased sternohyoid force and power. We conclude that CIH exposure upregulates NOX expression in rat sternohyoid muscle with concomitant modest oxidative stress but it does not result in a HIF-1α-dependent increase in glycolytic enzyme activity. Constitutive NOX activity decreases sternohyoid force and power. Our results implicate NOX-dependent reactive oxygen species in CIH-induced upper airway muscle dysfunction which likely relates to redox modulation of key regulatory proteins in excitation-contraction coupling.


Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: a European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study.
In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and age at treatment. The Life Situation Questionnaire was sent to 1,700 women treated in European Organisation for Research and Treatment of Cancer and Groupe d'Étude des Lymphomes de l'Adulte trials between 1964 and 2004. Women treated between ages 15 and 40 years and currently not using hormonal contraceptives (n = 460) were selected to assess occurrence of POF. Cumulative POF risk was estimated using the life-table method. Predictive factors were assessed by Cox regression analysis. Median follow-up was 16 years (range, 5 to 45 years). Cumulative risk of POF after alkylating chemotherapy was 60% (95% CI, 41% to 79%) and only 3% (95% CI, 1% to 7%) after nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine; epirubicin, bleomycin, vinblastine, and prednisone). Dose relationship between alkylating chemotherapy and POF occurrence was linear. POF risk increased by 23% per year of age at treatment. In women treated without alkylating chemotherapy at age younger than 32 years and age 32 years or older, cumulative POF risks were 3% (95% CI, 1% to 16%) and 9% (95% CI, 4% to 18%), respectively. If menstruation returned after treatment, cumulative POF risk was independent of age at treatment. Among women who ultimately developed POF, 22% had one or more children after treatment, compared with 41% of women without POF. Nonalkylating chemotherapy carries little to no excess risk of POF. Dose-response relationships for alkylating chemotherapy and age at treatment are both linear. Timely family planning is important for women at risk of POF.


Enzymatic hydrolysis of oleuropein from Olea europea (olive) leaf extract and antioxidant activities.
Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC50 = 41.82 μg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods.


Histochemical localization of copper in the gastrointestinal tract of the rat.
Three histochemical reactions for the localization of copper were applied to liver and different parts of the gastrointestinal tract of normal as well as of rats poisoned with a solution of copper. Variable quantities of copper were demonstrated in the livers of all the poisoned rats and in 21 out of 24 sections of jejunum. Rubeanic acid counterstained with 0.5% Cresyl violet gave the best results. Copper was not demonstrable in the livers or the gastrointestinal tract of normal rats. As the metal was concentrated in the upper jejunum, it is likely that this is the site of absorption. Detection of this metal may assist in the diagnosis of hepatolenticular degeneration.


A prospective evaluation of ventilator-associated conditions and infection-related ventilator-associated conditions.
The Centers for Disease Control and Prevention has shifted policy away from using ventilator-associated pneumonia (VAP) and toward using ventilator-associated conditions (VACs) as a marker of ICU quality. To date, limited prospective data regarding the incidence of VAC among medical and surgical ICU patients, the ability of VAC criteria to capture patients with VAP, and the potential clinical preventability of VACs are available. This study was a prospective 12-month cohort study (January 2013 to December 2013). We prospectively surveyed 1,209 patients ventilated for ≥ 2 calendar days. Sixty-seven VACs were identified (5.5%), of which 34 (50.7%) were classified as an infection-related VAC (IVAC) with corresponding rates of 7.0 and 3.6 per 1,000 ventilator days, respectively. The mortality rate of patients having a VAC was significantly greater than that of patients without a VAC (65.7% vs 14.4%, P < .001). The most common causes of VACs included IVACs (50.7%), ARDS (16.4%), pulmonary edema (14.9%), and atelectasis (9.0%). Among IVACs, 44.1% were probable VAP and 17.6% were possible VAP. Twenty-five VACs (37.3%) were adjudicated to represent potentially preventable events. Eighty-six episodes of VAP occurred in 84 patients (10.0 of 1,000 ventilator days) during the study period. The sensitivity of the VAC criteria for the detection of VAP was 25.9% (95% CI, 16.7%-34.5%). Although relatively uncommon, VACs are associated with greater mortality and morbidity when they occur. Most VACs represent nonpreventable events, and the VAC criteria capture a minority of VAP episodes.


Hope and fear for new classes of type 2 diabetes drugs: is there preclinical evidence that incretin-based therapies alter pancreatic morphology?
Incretin-based therapies appear to offer many advantages over other approaches for treating type 2 diabetes. Some preclinical studies have suggested that chronic activation of glucagon-like peptide 1 receptor (GLP1R) signalling in the pancreas may result in the proliferation of islet β-cells and an increase in β-cell mass. This provided hope that enhancing GLP1 action could potentially alter the natural progression of type 2 diabetes. However, to date, there has been no evidence from clinical trials suggesting that GLP1R agonists or dipeptidyl peptidase-4 (DPP4) inhibitors can increase β-cell mass. Nevertheless, while the proliferative capacity of these agents remains controversial, some studies have raised concerns that they could potentially contribute to the development of pancreatitis and hence increase the risk of pancreatic cancer. Currently, there are very limited clinical data to directly assess these potential benefits and risks of incretin-based therapies. However, a review of the preclinical studies indicates that incretin-based therapies probably have only a limited capacity to regenerate pancreatic β-cells, but may be useful for preserving any remaining β-cells in type 2 diabetes. In addition, the majority of preclinical evidence does not support the notion that GLP1R agonists or DPP4 inhibitors cause pancreatitis.