Functional Consequences of RNA 5'-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation.
Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5'-terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication. In this study, we assessed the consequences of the genomic deletions observed in vivo for coxsackievirus B3 biology. Using cell extracts from HeLa cells, as well as transfection of luciferase replicons in two types of cardiomyocytes, we demonstrated that coxsackievirus RNAs harboring 5' deletions ranging from 7 to 49 nucleotides in length can be translated nearly as efficiently as those of wild-type virus. However, these 5' deletions greatly reduced the synthesis of viral RNA in vitro, which was detected only for the 7- and 21-nucleotide deletions. Since 5' stem-loop I RNA forms a ribonucleoprotein complex with cellular and viral proteins involved in viral RNA replication, we investigated the binding of the host cell protein PCBP2, as well as viral protein 3CDpro, to deleted positive-strand RNAs corresponding to the 5' end. We found that binding of these proteins was conserved but that ribonucleoprotein complex formation required higher PCBP2 and 3CDpro concentrations, depending on the size of the deletion. Overall, this study confirmed the characteristics of persistent CVB3 infection observed in heart tissues and provided a possible explanation for the low level of RNA replication observed for the 5'-deleted viral genomes-a less stable ribonucleoprotein complex formed with proteins involved in viral RNA replication.IMPORTANCE Dilated cardiomyopathy is the most common indication for heart transplantation worldwide, and coxsackie B viruses are detected in about one-third of idiopathic dilated cardiomyopathies. Terminal deletions at the 5' end of the viral genome involving an RNA secondary structure required for RNA replication have been recently reported as a possible mechanism of virus persistence in the human heart. These mutations are likely to disrupt the correct folding of an RNA secondary structure required for viral RNA replication. In this report, we demonstrate that transfected RNAs harboring 5'-terminal sequence deletions are able to direct the synthesis of viral proteins, but not genomic RNAs, in human and murine cardiomyocytes. Moreover, we show that the binding of cellular and viral replication factors to viral RNA is conserved despite genomic deletions but that the impaired RNA synthesis associated with terminally deleted viruses could be due to destabilization of the ribonucleoprotein complexes formed.


Computed tomography, radiology and echocardiography in cats naturally infected with Aelurostrongylus abstrusus.
Objectives The aims of the study were to describe the radiographic and computed tomographic features in cats naturally infected with Aelurostrongylus abstrusus, and to identify signs of pulmonary hypertension with echocardiography. Methods Fourteen cats positive on Baermann test for A abstrusus were included in the study. All cats underwent thoracic radiography, CT and echocardiography. Results The most common clinical signs were coughing (10/14) and dyspnoea (5/14). Radiographic findings included a generalised unstructured interstitial pulmonary pattern (8/14), mixed bronchointerstitioalveolar pattern (3/14) and bronchointerstitial pattern with bronchial wall thickening (3/14). Sternal lymphadenopathy was detected on thoracic radiographs in six cats. On CT, features were mixed bronchointerstitioalveolar pattern with ground-glass appearance in six cats, interstitioalveolar with multiple pulmonary nodules in five, interstitial ground-glass infiltrates in three, regional lymph node enlargement in 11 (10 sternal, three cranial mediastinal and three tracheobronchial lymph nodes) and subpleural thickening in four. None of the thoracic radiographs revealed subpleural thickening. In all cases, pulmonary vessels were normal in terms of size, shape and attenuation on both radiography and CT. Pulmonary hypertension and cardiac abnormalities were not observed in any cat during echocardiography. Conclusions and relevance CT provided a more thorough characterisation of pulmonary and mediastinal lesions compared with thoracic radiographs in cats naturally infected with A abstrusus. Although feline aelurostrongylosis has been previously associated with histopathological lesions in lung arteries, in this cohort clinical evidence of pulmonary hypertension was not documented.


From investigational product to active reference: evolution of oral sumatriptan efficacy versus placebo for the treatment of acute migraine episodes and potential impact in comparative analyses.
Background: The relative efficacy and safety can vary among drugs over time. Sumatriptan, a first choice drug for acute migraine, can illustrate this phenomenon. Objective: To assess the evolution of the relative efficacy and tolerability of oral sumatriptan against placebo between its approval in 1991 and 2006. Methods: A systematic literature review of randomized controlled trials (RCTs) of adults suffering from acute migraine episodes was performed using Medline. Meta-analyses estimated odds ratios of the occurrence of pain-free at 2 hours and of any adverse event. Results: Out of the 67 RCTs identi.fied, pain-free at 2 hours and adverse events were reported in 25 and 28 studies, respectively. For pain-free, the relative effect of sumatriptan increases considerably over time, despite an increase in the absolute placebo effect. The odds ratio (95% CI) equaled 3.13 (1.67-5.86) around approval (1991-1994) and increased up to 4.14 (3.67-4.67) on the following decade. No specific variation was observed in the relative tolerability effect of sumatriptan over placebo over time. Conclusions: The relative effect of sumatriptan evolved substantially over time. This phenomenon may impact the results of network meta-analysis and indirect comparisons performed to evaluate the potential of a new drug, compared to widely prescribed older drugs.


Characteristics and outcomes of medically managed patients with non-ST-segment elevation acute coronary syndromes: Insights from the multinational EPICOR Asia study.
Many patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are medically managed without coronary revascularization. The reasons vary and may impact prognosis. EPICOR Asia (NCT01361386) is a prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8 countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non-significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3) significant CAD (CAG+ CAD+). We compared baseline differences between patients medically managed and patients undergoing revascularization, and also between the medically managed groups. Adverse events were reported and compared up to 2years. Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339 (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups, respectively. There were marked differences in the proportion of medically managed patients among the 8 countries/regions (13-81%). Medically managed patients had higher mortality at 2years compared with revascularization (8.7% vs. 3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more likely to have pre-existing cardiovascular disease, and had the highest 2-year mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality differences persisted after adjusting for other patient risk factors. Medically managed NSTE-ACS patients are a heterogeneous group with different risk stratification and variable prognosis. Identification of reasons underlying different management strategies, and key factors adversely influencing long-term prognosis, may improve outcomes.


[Interaction of beta-carotene on lipid peroxidation induced by cigarette smoke].
To study the interaction of beta-carotene on lipid peroxidation induced by the smoke of cigarette. Rat type II pneumocytes were isolated, cultured and then exposed to particles extracted from cigarette smoke and/or beta-carotene for 24 h. Malondialdehyde (MDA) in the cells was measured by TBA method. On the other hand, serum MDA of mice given beta-carotene supplements and/or exposed to cigarette smoke for 10 days was measured. The particles extracted from cigarette smoke increased the content of MDA in the rate type II pneumocytes, and the lipid peroxidation was antagonized by adding 0.5 microgram/ml of beta-carotene to the cells simultaneously. The results from the in vivo study showed that serum MDA levels were increased in the cigarette smoke-treated groups, and the lipid peroxidation was reduced by treating mice with 2.5 mg per kg body weight of beta-carotene. beta-carotene had an antagonistic effect on lipid peroxidation induced by cigarette smoke. The effective dosage of beta-carotene was 0.5 microgram/ml for rat pneumocytes and 2.5 mg/kg BW weight for mice.


The Ponseti technique and improved ankle dorsiflexion in children with relapsed clubfoot: a retrospective data analysis.
This study quantifies the change in passive ankle range of motion following modified Ponseti casting in children with relapsed idiopathic clubfoot. Fifty-three cases (feet) were retrospectively reviewed, with 6-month follow-up data available for 72% of participants. The median improvement in dorsiflexion was 15° (95% confidence interval: 12.5°-17.5°, P≤0.05), with 85% achieving dorsiflexion≥10°. At the 6-month follow-up, dorsiflexion remained significantly improved and 12 feet (32%) presented with subsequent relapse. Nine were referred for further casting and three were recommended for extra-articular surgery. Repeat modified Ponseti management clinically and statistically improves passive ankle dorsiflexion in relapsed idiopathic clubfoot.


[Essay on the epistemological relationship between probability and scientific method].
In the XIX century, regularities in statistics of events were perceived in Medicine and Human Sciences. These regularities raised the possibility of forecasting what considered to be impredictable, and so, probabilistics laws became an alternative to the strictly-causal laws. This work presents a brief historical review of probability calculus and its applications. Some philosophical thoughs, regarding the use of probabilistics models and decision analysis in Medicine, are also discussed.


zeste, a nonessential gene, potently activates Ultrabithorax transcription in the Drosophila embryo.
The GAGA, NTF-1, and zeste proteins have been purified previously from Drosophila embryo extracts and shown to activate the Ultrabithorax (Ubx) promoter in vitro. Here, differently mutated Ubx-promoter constructs containing binding sites for none, one, or all three of these transcription factors have been introduced into Drosophila by P-element transformation. Binding sites for each factor activate dramatically different patterns of transcription. In zeste mutant embryos, the activation by zeste protein-binding sites is essentially abolished. These genetic data, when considered with our earlier biochemical experiments, demonstrate that zeste directly and potently activates Ubx transcription in vivo. Surprisingly, previous genetic experiments indicate that zeste is a nonessential gene shown only to act in a dispensable regulatory process termed transvection. In our transgenic experiments, zeste is not activating transcription by transvection. We propose that the function of zeste in Drosophila is much broader than assumed previously, and that it is a member of a redundant system of transcription factors that regulate and maintain the expression of Ubx and other Drosophila genes.


Dysregulated wound healing in the pathogenesis of urogynecologic mesh complications.
To test the hypothesis that dysregulated wound healing is associated with Urogynecologic mesh complications, we collected vaginal cell secretions using vaginal swabs after polypropylene mesh implantation in patients with (N = 39) and without (N = 40) complication. A customized multiplex immunoassay measured markers of inflammation (MCP-1, IGFBP-1, IL-2, IL-10, IL-17, PDGF-BB, bFGF, IL-1b, IL-6, IL-12p70, TNF-α), neuroinflammation (IL-1RA, TGF-β, IL-15, IL-18, IL-3, M-CSF), angiogenesis (VEGF), and matrix proteins (fibronectin, tenasin c, thrombospondin-2, lumican) between groups. Patients with complications were younger, heavier, implanted with mesh longer, and more likely to be ever smokers. A 5 kg/m2 BMI increase and ever-smoking were associated with a 2.4-fold and sixfold increased risk of complication, respectively. Patients with the highest tertile of bFGF, fibronectin, thrombospondin-2, TNF-β, or VEGF had an odds ratio (OR) of 11.8 for having a mesh complication while ≥ 3 elevated had an OR of 237 while controlling for age, BMI, and smoking. The highest tertile of bFGF, thrombospondin-2, and fibronectin together perfectly indicated a complication (P < 0.0001). A receiver-operator curve for high bFGF, thrombospondin-2, and fibronectin showed excellent discrimination between complications and controls (AUC 0.87). These data provide evidence of dysregulated wound healing in mesh complications. Modifiable factors provide potential targets for patient counseling and interventions.


[Does orthodontic treatment contribute to oral health?].
The first part of this article is an edited Dutch summary of the paper "Oral-health-related benefits of orthodontic treatment" by Donald J. Burden in the special issue''Orthodontics: quality of care, quality of life'' in Seminars in Orthodontics (June 2007). Burden carried out a systematic review of the literature on some, historically claimed, beneficial influences of orthodontic treatment, such as reduced susceptibility to dental caries, periodontal disease, temporomandibular dysfunction, and traumatic injury. Based on the results of this review, Burden concludes that the oral health benefits of orthodontic intervention have not been demonstrated. The second part is a critical and balanced commentary on the content of the paper and on Burden's conclusions.


The TATA-box sequence in the basal promoter contributes to determining light-dependent gene expression in plants.
A prototype 13-bp TATA-box sequence, TCACTATATATAG, was mutated at each nucleotide position and examined for its function in the core promoter. Specific nucleotides in the first TATA, the second TATA, as well as the flanking sequences influenced promoter function in transient transformation of tobacco (Nicotiana tabacum var Petit Havana) leaves. The effect of a given mutation on reporter gene expression in light versus dark was variable and sometimes contrasting. Some mutations, like T(7) or A(8)-->C or G, completely inactivated the expression of the minimal promoter in light but not in dark. In general, the sequence requirement for dark expression was less stringent than that for light expression. The selective effect of TATA-box mutations on light versus dark expression was exerted on core promoter function in the chromatin-integrated state also. Even in the presence of an upstream light response activator element, TATA-box mutations influenced modulation of the promoter by light. An A at the eighth position was specifically involved in the red light response of the promoter. Selectivity in gene expression was associated with a high level of transcript initiation from a site that was not active in the dark. Nuclear proteins from dark- and light-grown seedlings showed that the sequence variation within the TATA-box governs the formation of alternative transcriptional complexes. The experiments give direct evidence for the role of a core TATA-box sequence in determining the level as well as selectivity of gene expression in plants.


Synthesis, characterisation, and biodistribution of radioiodinated C-hydroxy-carboranes.
The synthesis, radiolabelling and biodistribution of iodinated C-hydroxy-nido-carborane ligands is described. Microwave heating by using NaF in aqueous ethanol was used to prepare {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate], nido-carboranol} and {sodium [7-hydroxy-7,8-dicarba-nido-undecaborate-8-carboxylic acid], nido-salborin} in 97 and 90 % yield, respectively. Radioiodination of these nido-carboranes was completed by using both (125)I and (123)I, and the products were obtained in high radiochemical purity (>99 %) and yield (72 to 87 %). The structures of the radiolabelled products were validated through comparison to authentic standards. Biodistribution studies in BALB/c mice showed low accumulation of the labelled compounds in the liver and intestines, which are sites where labelled carboranes typically localise. The labelled cluster bearing hydroxy and carboxylic acid groups on the two carbon vertices demonstrated preferential clearance through the kidneys and low thyroid uptake. This compound had substantially reduced non-specific binding than the deshydroxy analogue making it an attractive bifunctional ligand for preparing targeted molecular imaging and therapy agents.


Microfluidics for real-time direct monitoring of self- and co-assembly biomolecular processes.
Molecular self-assembly is a major approach for the fabrication of functional supramolecular nanomaterials. This dynamic, straightforward, bottom-up procedure may result in the formation of various architectures at the nano-scale, with remarkable physical and chemical characteristics. Biological and bio-inspired building blocks are especially attractive due to their intrinsic tendency to assemble into well-organized structures, as well as their inherent biocompatibility. To further expand the morphological diversity, co-assembly methods have been developed, allowing to produce alternative unique architectures, enhanced properties, and improved structural control. However, in many cases, mechanistic understanding of the self- and co-assembly processes is still lacking. Microfluidic techniques offer a set of exclusive tools for real-time monitoring of biomolecular self-organization, which is crucial for the study of such dynamic processes. Assembled nuclei, confined by micron-scale pillars, could be subjected to controlled environments aiming to assess the effect of different conditions on the assembly process. Other microfluidics setups can produce droplets at a rate of over 100 s-1, with volumes as small as several picoliters. Under these conditions, each droplet can serve as an individual pico/nano-reactor allowing nucleation and assembly. These processes can be monitored, analyzed and imaged, by various techniques including simple bright-field microscopy. Elucidating the mechanism of such molecular events may serve as a conceptual stepping-stone for the rational control of the resulting physicochemical properties.


Revising the global biogeography of annual and perennial plants.
There are two main life cycles in plants-annual and perennial1,2. These life cycles are associated with different traits that determine ecosystem function3,4. Although life cycles are textbook examples of plant adaptation to different environments, we lack comprehensive knowledge regarding their global distributional patterns. Here we assembled an extensive database of plant life cycle assignments of 235,000 plant species coupled with millions of georeferenced datapoints to map the worldwide biogeography of these plant species. We found that annual plants are half as common as initially thought5-8, accounting for only 6% of plant species. Our analyses indicate that annuals are favoured in hot and dry regions. However, a more accurate model shows that the prevalence of annual species is driven by temperature and precipitation in the driest quarter (rather than yearly means), explaining, for example, why some Mediterranean systems have more annuals than desert systems. Furthermore, this pattern remains consistent among different families, indicating convergent evolution. Finally, we demonstrate that increasing climate variability and anthropogenic disturbance increase annual favourability. Considering future climate change, we predict an increase in annual prevalence for 69% of the world's ecoregions by 2060. Overall, our analyses raise concerns for ecosystem services provided by perennial plants, as ongoing changes are leading to a higher proportion of annual plants globally.


Structure and Surface Relaxation of CeO2 Nanoparticles Unveiled by Combining Real and Reciprocal Space Total Scattering Analysis.
We present a combined real and reciprocal space structural and microstructural characterization of CeO2 nanoparticles (NPs) exhibiting different crystallite sizes; ~3 nm CeO2 NPs were produced by an inverse micellae wet synthetic path and then annealed at different temperatures. X-ray total scattering data were analyzed by combining real-space-based Pair Distribution Function analysis and the reciprocal-space-based Debye Scattering Equation method with atomistic models. Subtle atomic-scale relaxations occur at the nanocrystal surface. The structural analysis was corroborated by ab initio DFT and force field calculations; micro-Raman and electron spin resonance added important insights to the NPs' defective structure. The combination of the above techniques suggests a core-shell like structure of ultrasmall NPs. These exhibit an expanded outer shell having a defective fluorite structure, while the inner shell is similar to the bulk structure. The presence of partially reduced O2-δ species testifies to the high surface activity of the NPs. On increasing the annealing temperature, the particle dimensions increase, limiting disorder as a consequence of the progressive surface-to-volume ratio reduction.


Pellagra among chronic alcoholics: clinical and pathological study of 20 necropsy cases.
Twenty cases of pellagra, diagnosed on neuropathological grounds, were found amont 74 necropsy cases of chronic alcoholism. Although these patients had presented with various mental, neurological and gastrointestinal symptoms, the diagnosis of pellagra had not been established clinically because, in the majority, there were no skin lesions. It is emphasised that whenever chronic alcoholics exhibit certain mental, neurological or gastrointestinal symptoms, one should strongly suspect pellagra even in the absence of skin lesions (pellagra sine pelle agra).


Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin.
Observational evidence is accumulating that the onset of age-related maculopathy, the leading cause of legal blindness in the Western World, could be delayed, or even averted, with antioxidant supplements. Lutein (L) and zeaxanthin (Z) are two hydroxy-carotenoids with antioxidant activity which accumulate at the macula, where they are collectively known as macular pigment (MP). It has been shown that MP is entirely of dietary origin, and that L and Z levels in serum, diet, and retina correlate. However, the nature of the relationships between L and Z in foodstuffs, blood, and macula is confounded by many variables including processes which influence digestion, absorption, and transport of the compounds in question, and accumulation and stabilization of the carotenoids in the tissues. If macular pigment is protective for age-related maculopathy, a clear understanding of the mechanisms whereby L and Z arrive at the target tissue (retina) from their source (foodstuff) is essential. In this paper, we review the literature germane to this growing area of interest.


Effects of ω-3 Fatty Acids and Catechins on Fatty Acid Synthase in the Prostate: A Randomized Controlled Trial.
Animal and human studies suggest fish oil and green tea may have protective effect on prostate cancer. Fatty acid synthase (FAS) has been hypothesized to be linked to chemoprotective effects of both compounds. This study evaluated the independent and joint effects of fish oil (FO) and green tea supplement (epigallocatechin-3-gallate, EGCG) on FAS and Ki-67 levels in prostate tissue. Through a double-blinded, randomized controlled trial with 2 × 2 factorial design, 89 men scheduled for repeat prostate biopsy following an initial negative prostate biopsy were randomized into either FO alone (1.9 g DHA + EPA/day), EGCG alone (600 mg/day), a combination of FO and EGCG, or placebo. We used linear mixed-effects models to test the differences of prostate tissue FAS and Ki-67 by immunohistochemistry between pre- and post-intervention within each group, as well as between treatment groups. Results did not show significant difference among treatment groups in pre-to-post-intervention changes of FAS (P = 0.69) or Ki-67 (P = 0.26). Comparing placebo group with any of the treatment groups, we did not find significant difference in FAS or Ki-67 changes (all P > 0.05). Results indicate FO or EGCG supplementation for a short duration may not be sufficient to produce biologically meaningful changes in FAS or Ki-67 levels in prostate tissue.


Cyanosis of the hands following the use of alphaprodine in dental anaesthesia.
A case is presented of asymptomatic cyanosis of the hands, seen four hours after dental surgery under intravenous, local and inhalational anaesthesia. Alphaprodine hydrochloride, a synthetic opiate and one of the agents used, may produce dilatation of the venous bed with passive venous pooling. Such a mechanism is thought to have occurred in this case, manifesting as cyanosis. A weakly positive intradermal skin test to alphaprodine suggests immediate type hypersensitivity as a possible underlying cause.


Oligomeric structure and tissue distribution of ficolins from mouse, pig and human.
Mouse plasma ficolin was purified by GlcNAc affinity and anion-exchange chromatography. Gel-filtration chromatography and gradient sedimentation indicated that mouse plasma ficolin is a 12-mer of approximately 35 kDa subunits, and electron microscopy showed the same parachute-like structure previously characterized for the pig ficolin 12-mer. Whereas the predominant form in pig plasma is a 24-mer, mouse and human plasma ficolin showed only the 12-mer form. We conclude that mouse plasma ficolin corresponds to the recently described ficolin A. We have identified a second mouse ficolin gene, ficolin B, which means that pig and mouse each have two ficolin genes, and human has three. One ficolin gene in all species is expressed in liver and is the primary source of plasma ficolin. Expression of this gene in other tissues, and expression of the second ficolin gene, appears to vary in different species.


[Can we prevent eating disorders?].
This paper reviews experience and empirical findings with respect to preventing eating disorders. In essence, the evidence is quite disappointing; no studies have shown major and lasting effects. This is because of methodological flaws, errors in programme designs and imprecise or unrealistic outcome measures. Some developments stand out as more promising: first, developing universal, preventive strategies that take into account knowledge about how to change attitudes and behaviour; second, replacing short-lived classroom educational programmes with strategies involving parents and the community at large. Within such an ecological and health promoting paradigm the focus is not to prevent serious eating disorders, but to modify the culture of body dissatisfaction. This focus can be integrated into preventing obesity in order to reduce the risk of conflicting public messages.


Supplementing broiler diets with bacterial selenium nanoparticles enhancing performance, carcass traits, blood indices, antioxidant status, and caecal microbiota of Eimeria tenella-infected broiler chickens.
Nanomedicine is a critical therapeutic approach for treating most poultry illnesses, particularly parasitic infections. Coccidiosis is a severe protozoan infection affecting poultry; the emergence of drug-resistant Eimeria strains demands the development of new, safe therapies. Consequently, the objective of this work was to investigate the efficacy of the biosynthesized selenium nanoparticles (SeNPs) by Paenibacillus polymyxa (P. polymyxa) against Eimeria tenella (E. tenella) experimental infection in broiler chickens. The prepared SeNPs absorbed the UV at 270 nm were spherical with a size of 26 nm, and had a surface negative charge of -25 mV. One hundred and fifty, 1-day-old male broiler chicks were randomly allocated into 5 groups (30 birds/group with triplicates each) as follows: T1: negative control (noninfected and nontreated with SeNPs); T2: delivered SeNPs (500 µg/kg diet) for 35 successive days, T3: E. tenella-infected (positive control birds), T4: E. tenella-infected and treated with SeNPs (500 µg/kg diet) and T5: E. tenella-infected chicks and treated with anticoccidial agent (sulfadimidine, 16% solution 8 mL/L of drinking water) for 5 successive days. At 14 d of age, each bird in infected groups was orally treated with 3 × 103 sporulated oocyst of E. tenella. SeNPs considerably decreased the number of oocysts in broiler feces compared to positive control and anticoccidial drug, followed by a substantial reduction of parasite phase count in the cecum (15, 10, and 8 for meronts, gamonts, and developing oocysts) when compared with positive control birds. The Eimeria experimental infection lowered the activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH) while increasing the stress parameters nitric oxide (NO) and malonaldehyde (MDA). Moreover, the production of proinflammatory (TNF-α and IL-6) and apoptotic genes (BcL2 and Cas-3) were significantly elevated. Administrating SeNPs to chicks significantly decreased oxidative stress, inflammation, and apoptotic markers in the cecum tissue. Therefore, growth performance, carcass weights, antioxidant enzymes, and blood properties of infected chicks were enhanced. The findings compared the protecting role of Se-nanoparticles against cecum damages in E. tenella-infected broilers.


Diabetes mellitus and impaired fasting glucose in ART-naïve patients with HIV-1, HIV-2 and HIV-1/2 dual infection in Guinea-Bissau: a cross-sectional study.
The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau. Patients were consecutively included. Demographic and lifestyle data were collected and one fasting blood glucose (FBG) measurement was used to diagnose DM (FBG≥7.0 mmol/L) and impaired fasting glucose (IFG) (FBG≥6.1 and <7.0 mmol/L). By June 2015, 953 newly diagnosed ART-naïve patients with HIV had been included in the study of whom 893 (93.7%) were fasting at the time of inclusion. Median age among the fasting patients was 37 years (IQR 30-46 years) and 562 (62.9%) were women. The prevalence of DM was 5.8% (52/893) while 5.6% (50/893) had IFG. DM was associated with family history of DM (OR 3.92, 95% CI 1.78 to 8.63), being 41-50 years (OR 2.98, 95% CI 1.18 to 7.49) or older than 50 years (OR 3.14, 95% CI 1.09 to 9.07) and Fula ethnicity (OR 2.72, 95% CI 1.12 to 6.62). DM prevalence was higher among younger patients compared with the background population in Bissau. Traditional risk factors for DM such as advancing age and a family history of DM apply also for ART-naïve patients with HIV.


[Gly482Ser polymorphism of the coactivator-1alpha of the activated receptor of peroxisome gamma proliferation in individuals from Maracaibo, Venezuela].
The aim of this study was to determine the association of the Gly482Ser polymorphism of the PGC-1 gene with insulin resistance and type 2 diabetes mellitus in subjects from the city of Maracaibo. The study was performed on 64 no-diabetic subjects (36 without insulin resistance and 28 with insulin resistance) and 13 with type 2 diabetes. A clinical and nutritional history was carried out and the evaluation of anthropometric parameters was included. Fasting serum glucose, fasting serum insulin, total cholesterol, HDL-C and LDL-C, were measured. The Gly482Ser polymorphism was detected by PCR-RFLP. It was found that the allelic frequencies for A and G were 0.36 and 0.64, respectively. The population was found in genetic equilibrium of Hardy Weinberg. The genotypes of the polymorphism Gly482Ser were not associated with insulin resistance and type 2 diabetes mellitus (OR = 1.320, p = 0.74; OR = 2, p = 0.47 respectively). Nevertheless, the diabetic subjects with the genotype AA presented values of LDL-C higher (p < 0.05) than the individuals with the genotypes GG and GA. The diabetics with the genotype GA showed significantly higher concentrations of triglycerides (>150 mg/dL) compared with the genotype GG. According to the results, the polymorphism Gly482Ser of the PGC-1 gene would be able to contribute to the cardiovascular risk in type 2 diabetics, while in the insulin resistant individuals, this polymorphism was not associated with cardiovascular risk factors.


Pharmacological and chemogenetic orexin/hypocretin intervention ameliorates Hipp-dependent memory impairment in the A53T mice model of Parkinson's disease.
Parkinson's disease (PD), classically defined as a progressive motor disorder accompanied with dopaminergic neuron loss and presence of Lewy bodies, is the second most common neurodegenerative disease. PD also has various non-classical symptoms, including cognitive impairments. In addition, inflammation and astrogliosis are recognized as an integral part of PD pathology. The hippocampus (Hipp) is a brain region involved in cognition and memory, and the neuropeptide orexin has been shown to enhance learning and memory. Previous studies show impairments in Hipp-dependent memory in a transgenic mouse model of Parkinson's disease (A53T mice), and we hypothesized that increasing orexin tone will reverse this. To test this, we subjected 3, 5, and 7-month old A53T mice to a Barnes maze and a contextual object recognition test to determine Hipp dependent memory. Inflammation and astrogliosis markers in the Hipp were assessed by immuno-fluorescence densitometry. The data show that early cognitive impairment is coupled with an increase in expression of inflammatory and astrogliosis markers. Next, in two separate experiments, mice were given intra-hippocampal injections of orexin or chemogenetic viral injections of an orexin neuron specific Designer Receptor Exclusively Activated by Designer Drug (DREADD). For the pharmacological approach mice were intracranially treated with orexin A, whereas the chemogenetic approach utilized clozapine N-oxide (CNO). Both pharmacological orexin A intervention as well as chemogenetic activation of orexin neurons ameliorated Hipp-dependent early memory impairment observed in A53T mice. This study implicates orexin in PD-associated cognitive impairment and suggests that exogenous orexin treatment and/or manipulation of endogenous orexin levels may be a potential strategy for addressing early cognitive loss in PD.


Changes in Hungarian academic psychology after the end of "people's democracy".
The paper surveys the last 30 years of Hungarian academic psychology. Around 1989-1990, the time of the great social changes Hungarian psychology was rather Westernized, but still a relatively small scientific field and applied profession. The opening and liberalization of politics made psychology in Hungary a booming profession and a rich research field. Education of psychologists was spreading, and becoming more Westernized in textbook usage and reading materials. Entrance numbers at two universities with 80 students were replaced by 2010 by 6 university programs and about 8000 incoming students. The training system is a Bologna type BA + MA + PhD system, The educational booming has its own problems. As all university subjects, psychology training is also underfinanced, with high teaching loads and a move by university management towards applied areas, neglecting basic research. The research activity is characterized by a fivefold increase of English language publications coming from Hungary over a 20 years period. University research was strengthened, and competitive grant systems were introduced, whth good success aretes by psychologists. Here again, managerial thinking questions many aspects of basic research and liberalized science management. These factors are peculiar to psychology, but they do have an impact on it. The paper gives some details about one chapter of academic psychology, cognitive psychology. Institutionally, support by the Soros foundation in the 90s for the university cognitive programs had as one consequence that three departments of cognition are active in Budapest today. Another aspect of insitutional development was the series of multidisciplinary conferences in Hungary (MAKOG), and Hungarian involvement in international graduate training programs in cognitive science. The most successful cognitive group, at Central European University (5 ERC grants, publications in leading journals) is recently chased out of Hungary by anti-Western and antiliberal legal moves. This would certainly have a detrimental effect on Hungarian cognitive psychology for quite a time.


[Cleidocranial dysostosis. Presentation of a case].
Cleidocranial dysostosis is a syndrome defined by three characteristic findings: clavicular aplasia, retarded cranial ossification, and autosomic dominant hereditary transmission, with completed penetrance and full expression. However, the diagnosis cannot only be made based on those finding, because the polymorphism and extension of the lesions of this disease is important. Therefore, in this disease we can see upset in the second teething, short stature or dwarf, persistence of the biconvex appearance of vertebral body, bone hypoplastic iliac, retarded pubis branch ossification, wedge shape distal phalanges or with brachymesophalangia of the forefinger and fifth finger. We describe a 20 years old man, with cleidocranial dysostosis, without familiar antecedent (probable mutation), that come to our center for treatment of denture pathology with disabled eating, because anomalous distribution and eruption. He had clavicle agenesis, cranial ossification upset with wormian bones, vertebral bodies biconvex, superior maxillary hypoplastic, and dental packed in the superior maxillary and jawbone. Cleidocranial dysostosis is a hereditary disease, which can be of spontaneous apparition (mutation), has a grand polymorphism, affect the osseous development, predominate in the middle line membranous bone and is an entity of radiologic diagnosis.


Activation by corticosteroids of steriod metabolizing enzymes in ovine placental explans in vitro.
A technique has been developed for the study of placetal steroid synethesis in tissue culture. Explants of sheep placentas recovered in the last third of gestation produced progesterone and converted labelled androstenedione into unconjugated and conjugated oestrogens. Cortisol added to the medium stimulated 17 alpha-hydroxylase and aromatizing enzyme activities. The results are discussed in relation to the proposal that the rise in secretion of fetal cortisol before parturition has a direct effect on the activation of placental enzymes catalysing the conversion of progesterone to eostrogens.


Type I Interferon and the Spectrum of Susceptibility to Viral Infection and Autoimmune Disease: A Shared Genomic Signature.
Type I interferons (IFN-I) and their cognate receptor, the IFNAR1/2 heterodimer, are critical components of the innate immune system in humans. They have been widely explored in the context of viral infection and autoimmune disease where they play key roles in protection against infection or shaping disease pathogenesis. A false dichotomy has emerged in the study of IFN-I where interferons are thought of as either beneficial or pathogenic. This 'good or bad' viewpoint excludes more nuanced interpretations of IFN-I biology - for example, it is known that IFN-I is associated with the development of systemic lupus erythematosus, yet is also protective in the context of infectious diseases and contributes to resistance to viral infection. Studies have suggested that a shared transcriptomic signature underpins both potential resistance to viral infection and susceptibility to autoimmune disease. This seems to be particularly evident in females, who exhibit increased viral resistance and increased susceptibility to autoimmune disease. The molecular mechanisms behind such a signature and the role of sex in its determination have yet to be precisely defined. From a genomic perspective, several single nucleotide polymorphisms (SNPs) in the IFN-I pathway have been associated with both infectious and autoimmune disease. While overlap between infection and autoimmunity has been described in the incidence of these SNPs, it has been overlooked in work and discussion to date. Here, we discuss the possible contributions of IFN-Is to the pathogenesis of infectious and autoimmune diseases. We comment on genetic associations between common SNPs in IFN-I or their signalling molecules that point towards roles in protection against viral infection and susceptibility to autoimmunity and propose that a shared transcriptomic and genomic immunological signature may underlie resistance to viral infection and susceptibility to autoimmunity in humans. We believe that defining shared transcriptomic and genomic immunological signatures underlying resistance to viral infection and autoimmunity in humans will reveal new therapeutic targets and improved vaccine strategies, particularly in females.


[Outcomes of disciplinary proceedings against gynaecologists: comparison between the periods 1980-1991 and 1992-2003].
In a study of the archives of the Chief Inspector for Healthcare in The Netherlands during the period 1992-2003, the number of complaints against gynaecologists submitted to disciplinary boards (n = 371) was found to be higher than during the period of 1980-1991 (n = 240). On the other hand, the number of complaints per gynaecologist had decreased from 6.3 complaints per 100 gynaecologists in 1992 to 2.6/100 in 2003. The number ofcomplaints declared legitimate relative to the number of submitted complaints remained the same in both periods (55/240 (23%) in 1980-1991 and 84/371 (23%) in 1992-2003), although the percentage ofcomplaints ruled as legitimate did increase during the course of the second period from 14 between 1992-1997 to 28 during the 1998-2003 period. Interesting points included the number of rulings regarding the death of an infant (40%), the interpretation of the cardiotocography recording, the need to keep medical records up to date (in particular the informed consent) and the fact that almost 50% of complaints ruled to be legitimate related to how the locum position was arranged, the role of the duty gynaecologist and that of the house officer.


Case report. Malignant change in an intracranial epidermoid cyst.
A malignant epidermoid tumor invading the fourth ventricle had histologic features that indicated malignant transformation in a benign epidermoid cyst. The computed tomographic (CT) findings correlated precisely with the histologic features, revealing both pathologic enhancement and a low attenuation zone. The spectrum of described CT findings in intracranial epidermoids is reviewed and contrasted with the appearance encountered in the present case.


Profile of cardiac complications of snake bite.
The present study was conducted in 30 cases of snake bite to understand fully the intricacies of the cardiac profile and to render help in the management of the problem arising out of them. All were subjected to routine and specific investigations (ECG, X-ray Chest, SGOT). The present study concluded that 57 per cent of patients of snake bite were in 2nd and 3rd decades of life. Viperine snake bite occurred in 93 per cent and elapide snake bite in 7 per cent of cases. Cardiotoxicity was seen in only 25 per cent patients with viperine bite. Seventy-six per cent of the patients presented within 24 hours of the bite. Seventy per cent of patients had haemorrhagic manifestations and 30 per cent had cardiotoxicity. The disturbance in heart rate was seen in 47 per cent, rhythm disturbance in 6.7 per cent, tachycardia in 36.7 per cent and bradycardia in 10 per cent cases. Hypertension was found in 6.7 per cent, hypotension in 16.7 per cent. Thirty per cent of patients had gallop rhythm and it persisted in 16.6 per cent patients till discharge. One patient had evidence of pulmonary edema and one had basal congestion. Cardiomegaly on chest X-ray was found in one patient and elevated SGOT titres were found in ten per cent. Common electrocardiographic changes were sinus tachycardia, sinus arrhythmia (6.6%), sinus bradycardia (10%), tall T-wave in V2 (3.3%), pattern suggestive of acute anterior wall infarction with reciprocal changes (3.3%), myocardial ischemia (10%), non-specific ST-T changes (16.7%) and atrioventricular block (3.3%). The mortality rate was 10 per cent and all these patients had bleeding manifestations and abnormal electrocardiograms.


Structural diversity and physical properties of paramagnetic molecular conductors based on bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) and the tris(chloranilato)ferrate(III) complex.
Electrocrystallization of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) in the presence of the tris(chloranilato)ferrate(III) [Fe(Cl2An)3](3-) paramagnetic chiral anion in different stoichiometric ratios and solvent mixtures afforded three different hybrid systems formulated as [BEDT-TTF]3[Fe(Cl2An)3]·3CH2Cl2·H2O (1), δ-[BEDT-TTF]5[Fe(Cl2An)3]·4H2O (2), and α‴-[BEDT-TTF]18[Fe(Cl2An)3]3·3CH2Cl2·6H2O (3). Compound 1 presents an unusual structure without the typical alternating organic and inorganic layers, whereas compounds 2 and 3 show a segregated organic-inorganic crystal structure where layers formed by Λ and Δ enantiomers of the paramagnetic complex, together with dicationic BEDT-TTF dimers, alternate with layers where the donor molecules are arranged in the δ (2) and α‴ (3) packing motifs. Compound 1 behaves as a semiconductor with a much lower conductivity due to the not-layered structure and strong dimerization between the fully oxidized donors, whereas 2 and 3 show semiconducting behaviors with high room-temperature conductivities of ca. 2 S cm(-1) and 8 S cm(-1), respectively. The magnetic properties are dominated by the paramagnetic S = 5/2 [Fe(Cl2An)3](3-) anions whose high-spin character is confirmed by electron paramagnetic resonance and magnetic susceptibility measurements. The correlation between crystal structure and conductivity behavior was studied by means of tight-binding band structure calculations, which support the observed conducting properties.


Improving Single-Nucleotide Polymorphism-Based Fetal Fraction Estimation of Maternal Plasma Circulating Cell-Free DNA Using Bayesian Hierarchical Models.
The recent advances in next-generation sequencing (NGS) technologies have enabled the development of effective high-throughput noninvasive prenatal screening (NIPS) assays for fetal genetic abnormalities using maternal circulating cell-free DNA (ccfDNA). An important NIPS quality assurance is quantifying the fetal proportion of the sampled ccfDNA. For methods using allelic read count ratios from targeted sequencing of single-nucleotide polymorphisms (SNPs), systematic biases and errors may reduce accuracy and diminish assay performance. We collected ccfDNA NIPS MiSeq sequencing data from an amplicon-based 92 SNP panel along with complementary low-depth whole-genome sequencing (WGS) on 243 normal male fetus pregnancies along with additional 144 nonpregnant female donor samples. Using fetal fraction estimates based on X and Y chromosome WGS coverage as gold standard, we compared an existing SNP-based approach, FetalQuant, to a more flexible Bayesian hierarchical modeling strategy that borrows information across interrogated SNPs to character SNP-level error rates and biases to improve fetal fraction estimates. Posterior distributions for SNP-level model parameters indicate most SNPs exhibited modest to moderate extrabinomial variation and a consistent underrepresentation of fetal alleles, with some extreme outliers in both regards. Fetal fraction estimates using FetalQuant, naive to these SNP properties, were relatively poor (R2 = 0.14, root mean squared error [RMSE] = 0.050), particularly when the true fetal fraction was low (<5%). In contrast, by quantifying SNP-level biases and error rates, our proposed approach demonstrated improved performance by reducing the bias and variability in fetal fraction estimates (R2 = 0.794, RMSE = 0.025). Using high-depth targeted SNP sequencing data, we identified a high degree of variability in distributional properties across SNP allelic read counts. These results highlight the benefits of leveraging hierarchical modeling for SNP-based fetal quantification assays (FQAs) and the need to properly calibrate FQAs dependent on NGS allelic ratio data.


A novel endogenous betaretrovirus in the common vampire bat (Desmodus rotundus) suggests multiple independent infection and cross-species transmission events.
The Desmodus rotundus endogenous betaretrovirus (DrERV) is fixed in the vampire bat D. rotundus population and in other phyllostomid bats but is not present in all species from this family. DrERV is not phylogenetically related to Old World bat betaretroviruses but to betaretroviruses from rodents and New World primates, suggesting recent cross-species transmission. A recent integration age estimation of the provirus in some taxa indicates that an exogenous counterpart might have been in recent circulation.


Treatment of patients with hemophilia A and inhibitors to factor FVIII with cimetidine.
In this study, cimetidine was used to treat patients with hemophilia A and inhibitors to factor VIII who presented with acute hemorrhages (Group A) and those without hemorrhages (Group B). The dose of cimetidine was 15 mg/kg/day. Group A consisted of five patients with inhibitors between 156 and > 10,000 Bethesda Units (BU), all with serious hemorrhagic problems. The control of hemorrhaging was effective in 100% of these patients, although inhibitor levels remained high (25-380 BU). Group B consisted of seven patients who did not have hemorrhages, whose inhibitor levels were 41-358 BU. Five of these patients no longer had anamnestic responses to Factor VIII after several months of treatment with cimetidine. No difference in the response to cimetidine was seen between HIV positive and HIV negative patients. The results suggest that cimetidine is useful to suppress inhibitors to Factor VIII in patients with hemophilia A.


Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy.
Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.


omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells.
Diets rich in omega-3 fatty acids have been shown to decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied. CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used. Cells were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid modifications confirmed with gas chromatography. Both human umbilical vein and hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion assays were performed in a standard fashion using (51)Cr-labeled cells to tumor necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial adhesion on the surface of control and fatty acid-modified cells. Gas chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057 nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/- 0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl-Lewis(x) expression with omega-3 treatment. These data indicate that omega-3 fatty acids may also be protective against the formation of hepatic metastases. The mechanism for this may be decreased endothelial cell adhesion which in turn may be due to decreased expression of the endothelial receptor sialyl-Lewis(x).


PCOS Forum: research in polycystic ovary syndrome today and tomorrow.
To summarize promising areas of investigation into polycystic ovary syndrome (PCOS) and to stimulate further research in this area. Summary of a conference held by international researchers in the field of polycystic ovary syndrome. Potential areas of further research activity include the analysis of predisposing conditions that increase the risk of PCOS, particularly genetic background and environmental factors, such as endocrine disruptors and lifestyle. The concept that androgen excess may contribute to insulin resistance needs to be re-examined from a developmental perspective, since animal studies have supported the hypothesis that early exposure to modest androgen excess is associated with insulin resistance. Defining alterations of steroidogenesis in PCOS should quantify ovarian, adrenal and extraglandular contribution, as well as clearly define blood reference levels by some universal standard. Intraovarian regulation of follicle development and mechanisms of follicle arrest should be further elucidated. Finally, PCOS status is expected to have long-term consequences in women, specifically the development of type 2 diabetes, cardiovascular diseases and hormone dependent cancers. Identifying susceptible individuals through genomic and proteomic approaches would help to individualize therapy and prevention. There are several intriguing areas for future research in PCOS. A potential limitation of our review is that we focused selectively on areas we viewed as the most controversial.


The effect of patient portals on quality outcomes and its implications to meaningful use: a systematic review.
The Health Information Technology for Economic and Clinical Health (HITECH) Act imposes pressure on health care organizations to qualify for "Meaningful Use". It is assumed that portals should increase patient participation in medical decisions, but whether or not the use of portals improves outcomes remains to be seen. The purpose of this systemic review is to outline and summarize study results on the effect of patient portals on quality, or chronic-condition outcomes as defined by the Agency for Healthcare Research and Quality, and its implications to Meaningful Use since the beginning of 2011. This review updates and builds on the work by Ammenwerth, Schnell-Inderst, and Hoerbst. We performed a systematic literature search in PubMed, CINAHL, and Google Scholar. We identified any data-driven study, quantitative or qualitative, that examined a relationship between patient portals, or patient portal features, and outcomes. We also wanted to relate the findings back to Meaningful Use criteria. Over 4000 articles were screened, and 27 were analyzed and summarized for this systematic review. We identified 26 studies and 1 review, and we summarized their findings and applicability to our research question. Very few studies associated use of the patient portal, or its features, to improved outcomes; 37% (10/27) of papers reported improvements in medication adherence, disease awareness, self-management of disease, a decrease of office visits, an increase in preventative medicine, and an increase in extended office visits, at the patient's request for additional information. The results also show an increase in quality in terms of patient satisfaction and customer retention, but there are weak results on medical outcomes. The results of this review demonstrate that more health care organizations today offer features of a patient portal than in the review published in 2011. Articles reviewed rarely analyzed a full patient portal but instead analyzed features of a portal such as secure messaging, as well as disease management and monitoring. The ability of patients to be able to view their health information electronically meets the intent of Meaningful Use, Stage 2 requirements, but the ability to transmit to a third party was not found in the review.


Bilayer ventilated labyrinthine metasurfaces with high sound absorption and tunable bandwidth.
The recent advent of acoustic metamaterials offers unprecedented opportunities for sound controlling in various occasions, whereas it remains a challenge to attain broadband high sound absorption and free air flow simultaneously. Here, we demonstrated, both theoretically and experimentally, that this problem can be overcome by using a bilayer ventilated labyrinthine metasurface. By altering the spacing between two constituent single-layer metasurfaces and adopting asymmetric losses in them, near-perfect (98.6%) absorption is achieved at resonant frequency for sound waves incident from the front. The relative bandwidth of absorption peak can be tuned in a wide range (from 12% to 80%) by adjusting the open area ratio of the structure. For sound waves from the back, the bilayer metasurface still serves as a sound barrier with low transmission. Our results present a strategy to realize high sound absorption and free air flow simultaneously, and could find applications in building acoustics and noise remediation.


Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer.
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis. The macropinocytic uptake of nab-paclitaxel induced macrophage immunostimulatory (M1) cytokine expression and synergized with IFNγ to promote inducible nitric oxide synthase expression in a TLR4-dependent manner. Nab-paclitaxel was internalized by tumor-associated macrophages in vivo, and therapeutic doses of nab-paclitaxel alone, and in combination with gemcitabine, increased the MHCII+CD80+CD86+ M1 macrophage population. These data revealed an unanticipated role for nab-paclitaxel in macrophage activation and rationalized its potential use to target immune evasion in pancreatic cancer. Cancer Immunol Res; 5(3); 182-90. ©2017 AACR.


Blood vessel detection using skin impedance tomography and spectroscopy.
Blood vessel detection is an essential method in a non-invasive circulatory monitoring system. However, only using camera-based image processing for finding a vein has many limitations due to the complexity of underneath tissue. Impedance tomography and spectroscopy can collect electrical characteristics map of the biological tissue precisely. The study developed instrumentation to measure the impedance with eight small electrodes, which can observe near vein area and show the conductivity map with small patches using tomographic reconstruction. The study examined the cephalic vein of a healthy human arm to confirm the feasibility of vein location recognition. The system could perform 86.8% pixel accuracy and achieve a mIoU score of 63.7% for vessel location segmentation in 5cm2 area observation. The system could identify a human blood vessel's electrical characteristic and visualize the passage.Clinical Relevance- This approach will support intravascular therapy by identifying the vessel location automatically and providing information to the vessel monitoring system in backend. In addition, the system would allow efficient data entry into the electronic medical record for management of hospitalized patients.


Regulatory mechanisms of one-carbon metabolism enzymes.
One-carbon metabolism is a central metabolic pathway critical for the biosynthesis of several amino acids, methyl group donors, and nucleotides. The pathway mostly relies on the transfer of a carbon unit from the amino acid serine, through the cofactor folate (in its several forms), and to the ultimate carbon acceptors that include nucleotides and methyl groups used for methylation of proteins, RNA, and DNA. Nucleotides are required for DNA replication, DNA repair, gene expression, and protein translation, through ribosomal RNA. Therefore, the one-carbon metabolism pathway is essential for cell growth and function in all cells, but is specifically important for rapidly proliferating cells. The regulation of one-carbon metabolism is a critical aspect of the normal and pathological function of the pathway, such as in cancer, where hijacking these regulatory mechanisms feeds an increased need for nucleotides. One-carbon metabolism is regulated at several levels: via gene expression, posttranslational modification, subcellular compartmentalization, allosteric inhibition, and feedback regulation. In this review, we aim to inform the readers of relevant one-carbon metabolism regulation mechanisms and to bring forward the need to further study this aspect of one-carbon metabolism. The review aims to integrate two major aspects of cancer metabolism-signaling downstream of nutrient sensing and one-carbon metabolism, because while each of these is critical for the proliferation of cancerous cells, their integration is critical for comprehensive understating of cellular metabolism in transformed cells and can lead to clinically relevant insights.


Clustered somatic mutations in and around first exon of non-rearranged c-myc in Burkitt lymphoma with t(8;22) translocation.
We have examined the restriction map of the c-myc gene in 15 BL cell lines carrying the variant t(8;22) translocation in which c-myc is known to remain on chromosome 8. Using 3 restriction enzymes cutting outside the c-myc domain (EcoRI, BamHI, HindIII), we found no evidence for a c-myc/Ig lambda rearrangement in 14 BL cell lines. In the last one, BL 37, the 3' flanking region was rearranged corresponding to the already identified breakpoint located 400 pb downstream from the c-myc gene (9). Using 4 restriction enzymes cutting inside the c-myc gene (PvuII, PstI, SacI, HincII) we looked for discrete abnormalities within the gene limits, and we found in 9 BL cell lines several abolished and created sites, compatible with multiple independent somatic mutations. They are significantly clustered in the 5' non coding region, with a striking prevalence at the end of exon 1. The role of mutations in the non-coding first exon region for the deregulation of c-myc expression is discussed.


First chemical synthesis of a scorpion alpha-toxin affecting sodium channels: the Aah I toxin of Androctonus australis hector.
Aah I is a 63-residue alpha-toxin isolated from the venom of the Buthidae scorpion Androctonus australis hector, which is considered to be the most dangerous species. We report here the first chemical synthesis of Aah I by the solid-phase method, using a Fmoc strategy. The synthetic toxin I (sAah I) was renatured in DMSO-Tris buffer, purified and subjected to thorough analysis and comparison with the natural toxin. The sAah I showed physico-chemical (CD spectrum, molecular mass, HPLC elution), biochemical (amino-acid composition, sequence), immunochemical and pharmacological properties similar to those of the natural toxin. The synthetic toxin was recognized by a conformation-dependent monoclonal anti-Aah I antibody, with an IC50 value close to that for the natural toxin. Following intracerebroventricular injection, the synthetic and the natural toxins were similarly lethal to mice. In voltage-clamp experiments, Na(v) 1.2 sodium channel inactivation was inhibited by the application of sAah I or of the natural toxin in a similar way. This work describes a simple protocol for the chemical synthesis of a scorpion alpha-toxin, making it possible to produce structural analogues in time.


Detection and Live-Cell Imaging of a Micro-RNA Associated with the Cancer Neuroblastoma.
The ability of a molecular beacon to detect miR-132, a microRNA associated with the childhood cancer neuroblastoma, is reported in solution and within live cells. The stem-loop structure comprises a sequence complementary to miR-132, modified with a 6-FAM dye and dabcyl quencher on either end. In the absence of the target, self-binding occurs bringing the luminophore and quencher into close proximity, significantly decreasing the emission intensity. In the presence of miR-132, the signal is greatly enhanced, with a linear increase in intensity for mole ratios of beacon-to-target between 0.25 and 2.00. The structure differentiates between target and mismatched nucleic acid sequences, e.g., in the presence of a single-base mismatch, no increase in emission intensity beyond the background is observed. The stem-loop can be introduced into neuroblastoma cancer cells by electroporation, allowing miR-132 to be imaged within live cells. miR-132 appears to be localized within the nucleus of the cells, where its concentration is of the order of 1 μM. Significantly, transfection of the cells with a miR-132 mimic causes the emission intensity to more than double, demonstrating the sensitivity of the approach to changes in miR-132 concentration in live cells. This behavior opens up significant theranostic applications, such as the possibility of rapidly identifying retinoic acid resistant patients as well as providing a means to monitor therapeutic efficacy.


A MOLECULAR PHYLOGENY OF ACROCHAETE AND OTHER ENDOPHYTIC GREEN ALGAE (ULVALES, CHLOROPHYTA)(1).
A molecular phylogeny was reconstructed from a culture collection of >150 isolates of epi-endophytic and endophytic green algae, based on nucleotide sequences of the plastid tufA and nuclear ITS2 loci. The cultures were isolated from a variety of algal hosts, notably the red algae Chondrus crispus, Mastocarpus stellatus, and Osmundea species, and the brown algae Chorda filum and Fucus serratus. The phylogeny revealed that in the Ulvales the majority of isolates fell into Acrochaete (Ulvellaceae), Ulva (Ulvaceae), Bolbocoleon (Bolbocoleaceae), and at least two unknown genera provisionally assigned to the Kornmanniaceae. Acrochaete was monophyletic. The genus was also more specious than previously described with 12 species, including up to six new species awaiting formal description. Isolates identified as Acrochaete repens, the type species of the genus, were polyphyletic. The remainder of the isolates were placed in the Ulotrichales. The results confirm that the endophytic habit supports a broad diversity of algal taxa and suggest that blade formation is a relatively recent innovation within the green algae.


Patient report improves posthospital discharge event capture in total joint replacement: a novel approach to capturing all posthospital event data.
Current approaches to quantifying total posthospital complications and readmissions following surgical procedures are limited because the United States does not have a single health care payer. Patients seek posthospital care in varied locations, yet hospitals can only quantify those returning to the same facility. Seeking information directly from patients about health care utilization following hospital discharge holds promise to provide data that is missing for surgeons and health care systems. Because total joint replacement (TJR) is the most common and costly elective surgical hospitalization, we examined the concordance between patients' self-report of potential short-term complications and their readmissions and our review of medical records in the initial hospital and surrounding facilities. Patients undergoing primary total hip or knee replacement from July 1, 2011, through December 3, 2012, at a large site participating in a national cohort of TJR patients were identified. Patients completed a six-month postoperative survey regarding emergency department (ED), day surgery (DS), or inpatient care for possible medical or mechanical post-TJR complications. We reviewed inpatient and outpatient medical records from all regional facilities and examined the sensitivity, specificity, and positive- and negative predictive values for patient self-report and medical records. There were 413 patients who had 431 surgeries and completed the six-month questionnaire. Patients reported 40 medical encounters (9 percent) including ED, DS or inpatient care, of which 20 percent occurred at hospitals different from the initial surgery. Review of medical records revealed 9 additional medical encounters that patients had not mentioned including five hospitalizations following surgery and four ED visits. Overall patient self-report of ED, DS, and inpatient care for possible complications was both sensitive (82 percent) and specific (100 percent). The positive predictive value was 100 percent and negative predictive value 98 percent. Patient self-report of posthospital events was accurate. Substantial numbers of patients required care at outlying hospitals (not where the TJR occurred). Methods that directly engage patients can augment current posthospital utilization surveillance to assure complete data.


ELECTRONIC OPTICS: Organic Lasers Promise New Lease on Light.
Many of today's lasers are made from ceramic chips that require expensive clean-room facilities to manufacture, and their color palette is somewhat limited. Researchers have long pinned their hopes on organic materials, which are typically easier and cheaper to process. Now, on page 599, a team reports that they've devised the first electrically powered solid state organic laser, a step that could open the floodgates for novel lasers that are cheaper and that shine in colors inorganics can't match.


Family donors are critical and legitimate in developing countries.
For many years, family blood donors have been considered less safe than volunteer non-remunerated blood donors and actively discouraged by international organisations and affluent countries support agencies for developing countries. In addition to safety, pressure and coercion was considered unethical. However these assumptions were not supported by evidence. To assemble recently collected evidence to reopen the assessment whether or not the ban of family blood donors is justified. Review of old and recent literature through Pubmed and references from identified articles. Viral marker data comparing confirmed seroprevalence in 1(st) time volunteer non-remunerated donors (VNRD) and family/replacement donors (FRD) corrected for gender and age, show no significant difference between the two groups. Evidence has been provided that for both VNRD and FAD benevolence is more appropriate than altruism. The two groups merge for psychological attitude to donation for which knowing someone needing transfusion is a powerful incentive to give blood. Excluding a life or death situation found in areas where severe blood shortage justifies replacement donation, pressures are exerted on both VNRD and FRD. There is no evidence of coercion of FRD. FRDs therefore meet all criteria for VNRD and are willing to become VNRD and to repeat donation. Ostracising FRD is illegitimate and damaging to the blood supply in resource poor areas. In some countries no difference is made between the two groups of donors representing similar populations asked to give blood in different circumstances. FRDs remain a critical source of volunteer, non-remunerated, blood meeting all classical criteria of VNRD that should be considered legitimate and indispensable at this point in time instead of discouraged.


Saturable CD14-dependent binding of fluorescein-labeled lipopolysaccharide to human monocytes.
We used rough lipopolysaccharide (ReLPS) to construct a fluorescein-labeled LPS (FITC-LPS) with a very high labeling efficiency that bound to isolated human monocytes in a CD14-dependent fashion and that in this respect behaved indistinctively from native LPS. The CD14-dependent binding could be inhibited either by a 1,000-fold excess of unlabeled LPS or by polymyxin B, bactericidal/permeability-increasing protein, cationic protein 18, or soluble CD14. Although this FITC-LPS preparation no longer possessed the ability to prime neutrophils for the production of reactive oxygen species or to stimulate human monocytes to produce tumor necrosis factor, activation of the Limulus amoebocyte lysate cascade was comparable to activation by native LPS. Binding to monocytes was enhanced by human pooled serum (HPS) or LPS-binding protein (LBP) for LPS concentrations up to 100 ng/ml and was completely CD14 dependent. For LPS concentrations exceeding 100 ng/ml, binding was still partially CD14 dependent, but not HPS or LBP dependent. CD14-dependent association of LPS with monocytes was shown to be totally saturable. In conclusion, we found an HPS- or LBP-dependent binding of FITC-LPS to monocytes that was CD14 dependent at up to 100 ng of LPS per ml, and saturation of binding was shown.


Gluconeogenesis from lactate in the developing rat. Studies in vivo.
1. The specific radioactivity of plasma l-lactate and the incorporation of (14)C into plasma d-glucose, liver glycogen and skeletal-muscle glycogen were measured as a function of time after the intraperitoneal injection of l-[U-(14)C]lactate into 2-, 10- and 30-day-old rats. 2. Between 15 and 60min after the injection of the l-[U-(14)C]lactate, the specific radioactivity of plasma lactate decreased with a half-life of 20-33min in animals at all three ages. 3. At all times after injection examined, the specific radioactivity of plasma glucose of the 2- and 10-day-old rats was at least fourfold greater than that of the 30-day-old rats. 4. Although (14)C was incorporated into liver glycogen the amount incorporated was always less than 5% of that present in plasma glucose. 5. The results are discussed with reference to the factors that may influence the rate of incorporation of (14)C into plasma glucose, and it is concluded that the rate of gluconeogenesis in the 2- and 10-day-old suckling rat is at least twice that of the weaned 30-day-old animal.


Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene.
Argininosuccinic aciduria (ASAuria) is an inborn error of metabolism caused by mutations in the argininosuccinate lyase (ASL) gene, which leads to the accumulation of argininosuccinic acid (ASA) in body fluids and severe hyperammonemia. A severe neonatal form and a milder late-onset variant are described. We report a novel ASL pseudogene located in the centromeric region of chromosome 7, 14 novel mutations in the ASL gene, and a novel intronic polymorphism found in a cohort of Italian patients. Our approach relied exclusively on genomic DNA analysis. We found seven missense mutations, two nonsense, three small insertions/deletions, and two splicing mutations. Only two patients harbored previously described mutations, and among the novel variants only two were present in more than one kindred. The pathogenicity of the splicing mutations was demonstrated by a functional splicing assay that employed a hybrid minigene. We also performed molecular modeling using the reported three-dimensional structure of ASL to predict the functional consequences of the missense mutations. There was no genotype-phenotype correlation. Patients with neonatal onset display developmental delay and seizures despite adequate metabolic control. Moreover, hepatomegaly, fibrosis, and abnormal liver function tests are common complications in these patients, but not in patients with the late infancy form. We stress the importance of mutation analysis in patients with ASAuria, to confirm the clinical diagnosis, and to perform DNA-based prenatal diagnosis in future pregnancies of these families.


Increased expression of IL-18 in cutaneous graft-versus-host disease.
Interleukin-18 (IL-18) is an 18-kDa cytokine produced by lipopolysaccharide (LPS)-activated macrophages or Kupffer cells. In addition, IL-18 is also produced by many different types of cells and tissues, including epidermal keratinocytes, the adrenal cortex, and the brain. IL-18 acts on the immune system to increase IFN-gamma production from T and NK cells to enhance NK cell cytotoxicity and to activate Th1 cell proliferation. It is considered that the tissue expression of cytokines and cell adhesion molecules such as ICAM-1 are common in graft-versus-host disease (GVHD). Recent evidence suggests that IL-18 is a cytokine relevant in the pathogenesis of GVHD. Despite the potential importance of IL-18 in GVHD, the distribution of IL-18 production in cutaneous GVHD has not been fully investigated. In this study, the expression of IL-18 in the cutaneous GVHD was investigated. Formalin-fixed, paraffin-embedded tissue sections were obtained, and immunohistochemical analysis was performed to detect IL-18 and ICAM-1 expression according to the acute and chronic GVHD. Immunohistochemical analysis confirmed the enhanced IL-18 expression levels in the early stage (grade 1) of acute GVHD and the late stage (sclerodermoid) of chronic GVHD compared to the other stages. In contrast, the ICAM-1 expression level was constant at all stages. Our findings indicate that IL-18 is a significant pathogenic indicator in cutaneous GVHD, and the tissue expression of IL-18 seems to be associated with the pathogenesis of acute and chronic GVHD.


Optimizing selective stimulation of peripheral nerves with arrays of coils or surface electrodes using a linear peripheral nerve stimulation metric.
We present a PNS oracle, which solves these computation time and linearity problems and is, therefore, well-suited for fast optimization of voltage distributions in contact electrode arrays and current drive patterns in non-contact magnetic coil arrays. The PNS oracle metric for a nerve fiber is computed from an electric field map using only linear operations (projection, differentiation, convolution, scaling). Due to its linearity, this PNS metric can be precomputed for a set of coil or electrode segments, allowing rapid PNS prediction and comparison of any possible coil or electrode stimulation configuration constructed from this set. The PNS oracle is closely related to the classical activating function and modified driving functions but is adjusted to better correlate with full neurodynamic modeling of myelinated mammalian nerves. We validated the PNS oracle in three MRI gradient coils and two body models and found good correlation between the PNS oracle and the full neurodynamic modeling approach (R 2 > 0.995). Finally, we demonstrated its potential utility by optimizing the driving currents and voltages of arrays of 108 magnetic coils or 108 contact electrodes to selectively stimulate target nerves in the lower leg. Peripheral nerve stimulation (PNS) by electromagnetic fields can be accurately simulated using coupled electromagnetic and neurodynamic modeling. Such simulations are slow and non-linear in the electric field, which makes it difficult to iteratively optimize coil and electrode configurations or drive patterns aiming to avoid PNS or to initiate it for therapeutic purposes.


Rod Lengthening With the Magnetically Controlled Growing Rod: Factors Influencing Rod Slippage and Reduced Gains During Distractions.
Prospective study. To identify the factors that are associated with rod slippage and to study the pattern of achieved length gain with a standard distraction methodology. Ability to achieve successful magnetically controlled growing rod (MCGR) distraction is crucial for gradual spine lengthening. Rod slippage has been described as a failure of internal magnet rotation leading to a slippage and an inability to distract the rod. However, its onset, significance, and risk factors are currently unknown. In addition, how this phenomenon pertains to actual distracted lengths is also unknown. A total of 22 patients with MCGR and at least six distraction episodes were prospectively studied. Patients with rod slippage occurring less than six distraction episodes were considered early rod slippage whereas those with more than six episodes or have yet to slip were grouped as late rod slippage. The association of parameters including body habitus, maturity status, age of implantation, total number of distractions, months of distraction from initial implantation, initial and postoperative Cobb angle, T1-T12, T1-S1, T5-T12 kyphosis, curve flexibility, instrumented length, and distance between magnets in dual rods and between the magnets and apex of the curve with early or late onset of rod slippage were studied. Differences between expected and achieved distraction lengths were assessed with reference to rod slippage episodes and rod exchanges to determine any patterns of diminishing returns. Patients had mean age of 7.1 years at diagnosis with mean follow-up of 49.8 months. A mean 32.4 distractions were performed per patient. Early rod slippage occurred in 14 patients and late rod slippage occurred in eight patients. Increased height, weight, body mass index, older age, increased T1-12 and T1-S1 lengths, and less distance between magnets were significantly associated with early rod slippage. Expected distraction lengths did not translate to achieve distraction lengths and reduced gains were only observed after achieving one-third of the allowable distracted length in the MCGR. Length gains return to baseline after rod exchange. This is the first study to specifically analyze the impact of rod slippage on distraction lengths and the risk factors associated with its onset and frequency. Increased body habitus and reduced distance between internal magnets significantly influenced rod slippage events. Diminishing returns in distracted length gains were only observed after a period of usage. 3.


Lower versus higher oxygen targets after resuscitation from out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials.
To update the existing evidence and gain further insight into effects of lower versus higher oxygen targets on the outcomes in patients resuscitated from out-of-hospital cardiac arrest (OHCA). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing lower versus higher oxygen targets on the outcomes among adults resuscitated from OHCA. The primary outcome was short-term survival (in hospital or within 30 days). Subgroup analyses were performed according to timing of study interventions. Seven RCTs with 1454 patients were finally included. The short-term survival did not differ between the two groups with a relative risk (RR) of 0.98 (95% CI, 0.86 to 1.11). There were no significant differences in survival at longest follow-up (RR, 1.01; 95% CI, 0.91 to 1.14), favorable neurological outcome (RR, 1.00; 95% CI, 0.91 to 1.11), length of intensive care unit stay (mean difference, -4.94 h; 95% CI, -14.83 to 4.96 h), or risk of re-arrest (RR, 0.68; 95% CI, 0.21 to 2.19). The quality of evidence ranged from moderate to very low. Current evidence suggests that targeting a lower or higher oxygen therapy in patients after resuscitation from OHCA results in similar short-term survival and other clinical outcomes.


Segmental costovertebral malformations: association with neural tube defects. Report of 3 cases and review of the literature.
Patients with spondylocostal dysostosis (SCD) have vertebral abnormalities and numerical or structural rib anomalies that produce thoracic asymmetry. Rib anomalies and dysmorphism are the typical features that differentiate this syndrome from spondylothoracic dysostosis (STD). Jarcho-Levin syndrome is a severe form with involvement of the whole vertebral column. Other associated findings such as congenital heart defects, abdominal wall malformations, genitourinary malformations and upper limb anomalies may be found; in addition, neural tube defects (NTDs) have been associated with this malformation. SCD is transmitted both in a recessive form and as a dominant defect. We report on 3 children with SCD; 2 also had NTDs. All of them were studied with X-rays and spinal magnetic resonance (MR), and over the same period they underwent multidisciplinary clinical functional evaluation. One of our cases with NTD also presented polythelia, which has not previously been described in patients with SCD. The common association of segmental costovertebral malformations with NTDs could be related to an early gastrulation genomic defect, or one after gastrulation, when there are two independent somitic columns. The latter sometimes progresses and then involves primary and secondary neurulation. Also, the association of SCD with NTDs could be related to the interaction of different genes, resulting in this complex phenotype. Therefore, additional genetical and embryological studies are necessary to provide evidence of an etiological link between SCD and NTD.


Radiographic assessment of progression in osteoarthritis.
We evaluated methods of grading radiologic progression of osteoarthritis (OA). Sets of radiographs were assessed separately by 8 readers who were blinded to the time sequence. Included were radiographs of patients with OA of the hands (24 pairs), hips (40 pairs), and knees (32 pairs). Most films were taken 12-60 months apart. The relative contribution of individual joints (such as particular interphalangeal joints), of observations (such as narrowing or spurs), and of a single joint compartment (such as the medial or lateral compartment of the knee) toward evidence of OA progression was evaluated, as well as the reliability and concordance of scoring, and the sensitivity in detecting change. In assessing OA of the hand, the greatest sensitivity was achieved by reading a single posteroanterior bilateral hand radiograph for narrowing, spurs, and erosions, and scoring 10 joints (second and third distal interphalangeal, second and third proximal interphalangeal, and trapeziometacarpal joints, bilaterally), using a scale of 0-3. In OA of the hip, a single anteroposterior radiograph assessed for joint space narrowing and cyst formation yielded the greatest sensitivity. In OA of the knee, an anteroposterior radiograph, with weight-bearing, assessed for narrowing, spurs, and sclerosis in both the medial and lateral compartments yielded the greatest sensitivity. These techniques will be useful to the investigator in designing experimental studies and to the clinician in determining the rate of disease progression in an individual patient.


Diabetic Neuropathy Prevalence and Its Associated Risk Factors in Two Representative Groups of Type 1 and Type 2 Diabetes Mellitus Patients from Bihor County.
Diabetic neuropathy has an important impact on the quality of life of affected individuals due to the presence of chronic symptoms like distal neuropathic pain, but it also influences the survival of diabetic patients, given that the clinical forms of diabetic neuropathy produce complications such as diabetic foot syndrome in distal peripheral neuropathy or life threatening arrhythmias in autonomic cardiac neuropathy. The prevalence of diabetic neuropathy in representative cohorts is very discordant in numerous studies, and our purpose was to evaluate the frequency of this microvascular complication in Bihor County and to determine some risk factors for its development in order to perform a more rigorous screening in certain risk groups. We formed two representative cohorts for type 1 and type 2 diabetes mellitus population in our county and applied a questionnaire with three subsets of questions for sensitive, motor and autonomic symptoms. Every patient was evaluated by using semi quantitative tests for distal neuropathy and two tests for determination of cardiac autonomic neuropathy. The prevalence of diabetic neuropathy was 28.70% in patients with type 1 diabetes mellitus and 50.70% in those with type 2 diabetes mellitus. Distal neuropathy was the most frequent clinical form, autonomic neuropathy having a low prevalence. The same risk factors were associated (p<0.01) with an increased risk of diabetic neuropathy in both type 1 and type 2 diabetes mellitus: age, diabetes duration, HbA1 c, hypertension, dyslipidaemia, and other microvascular complications. Screening for distal symmetric polyneuropathy can be easily done by using a symptom questionnaire and semi quantitative tests, and it is important to consider the fact that over 50% of type 2 diabetes patients in the representative cohort were affected by the complication. Control of modifiable risk factors can reduce the risk of neuropathy development considering the lower frequency of neuropathy in the groups with good glycaemic control, normal blood pressure and absence of dyslipidaemia.


Cervical preparation for second trimester dilation and evacuation.
Abortion during the second trimester of pregnancy accounts for 10-15% of abortions performed worldwide. Dilation and evacuation (D&E) is the preferred method of second-trimester abortion in most parts of the developed world. Cervical preparation is recommended for dilation and curettage (D&C) after 12 weeks gestation and is standard practice for D&E beyond 14 weeks gestation. Prostaglandins, osmotic dilators, and Foley balloon catheters have been used and studied as cervical preparation prior to second-trimester D&E. However, no consensus exists as to which cervical preparation method is superior with regards to safety, procedure time, need for additional dilation, ability to perform the procedure, or patient and provider acceptability. Despite the fact that the advent of osmotic dilation has improved the safety of the D&E procedure during the second trimester, it is unclear whether a certain type of osmotic dilator is superior to another or whether osmotic dilation with adjuvant prostaglandin is superior to osmotic dilation alone or to prostaglandins alone. This review evaluates cervical preparation methods for second-trimester surgical abortion with respect to differences in procedure time, dilation achieved, need for additional dilation, complications, ability to complete the procedure, patient pain scores, and patient and provider acceptability and satisfaction. We searched for trials of cervical preparation prior to second-trimester D&E. We included all randomized controlled trials that compared osmotic, mechanical, antiprogesterone, prostaglandin, or other medical agents of cervical preparation for second-trimester surgical abortion from 14-24 weeks of gestation. Data were abstracted by two authors and data entry was verified by a third author. Mean difference and Peto Odds Ratio were calculated. Osmotic dilators were found to be superior to prostaglandins with respect to cervical dilation throughout the second trimester and with respect to procedure time within the early second trimester. Addition of prostaglandins to osmotic dilators was not found to increase cervical dilation, except after 19 weeks gestation, however, no impact was seen on procedure time. Addition of Mifepristone to misoprostol was found to improve cervical dilation, yet increase procedure time and frequency of pre-procedural expulsions. Two-day cervical preparation was found to produce greater cervical preparation than one-day, but had no impact on procedure time. Serious complication rates or ability to complete the procedure did not differ significantly between any of the preparation methods reviewed. Cervical preparation with osmotic dilators and/or misoprostol before second-trimester D&E is safe and effective. Osmotic dilators appear to provide superior cervical dilation when compared to prostaglandins alone or when combined with prostaglandins, however this difference in cervical dilation does not appear to result in differences in procedure time or complication rates. There does not appear to be clear clinical benefit from two days of cervical preparation compared to one-day prior to second-trimester D&E below 19 weeks gestational duration. Mifepristone plus misoprostol was associated with high rates of pre-procedural expulsions and does not appear to be a useful method of cervical preparation before second-trimester dilation and evacuation. Same-day procedures appear to be a safe and reasonable option in the early second trimester, however, more research is needed to assess the effectiveness and safety of same-day procedures in the later second trimester.


Optical encryption using phase-shifting interferometry in a joint transform correlator.
We propose an optical encryption technique where the encrypted field and the decrypting key are obtained by three-step phase-shifting interferometry and registered as digital Fresnel holograms in a joint transform correlator architecture. Decryption can be achieved by digital or optical means. The technique allows the complete process to be achieved at high speed and data to be transfered via digital communication channels. Experimental implementation is performed in a system based on a programmable liquid-crystal TV display working in pure phase mode to represent the input data and to introduce the required phase shifts. A CCD is used to register the output data.


Viability of forest floor and canopy seed banks in Pinus contorta var. latifolia (Pinaceae) forests after a mountain pine beetle outbreak.
Seed banks are important for the natural regeneration of many forest species. Most of the seed bank of serotinous lodgepole pine is found in the canopy, but after an outbreak of mountain pine beetle (MPB), a considerable forest-floor seed bank develops through the falling of canopy cones. After large-scale mortality of pine stands from MPB, however, the viability of seeds in both the canopy and the forest-floor cone bank is uncertain. We sampled cones in five stands 3 yr after MPB (3y-MPB); five stands 6 yr after MPB (6y-MPB); and 10 stands 9 yr after MPB (9y-MPB), in central British Columbia, Canada. Seeds were extracted and viability tested using germination techniques. Forest-floor cones had seed with high germination capacity (GC): 82% for embedded (partly buried) closed cones vs. 45% for buried partly open cones. For canopy cones, GC steeply declined about 15 yr after cone maturation and by 25 yr, GC was 50%, compared with 98% in the first year. In the 3y- and 6y-MPB stands, seeds from cones that were 7 to 9 yr old had similar GC on dead and living trees; however, seeds from the dead trees had lower vigor than seeds from living trees. We demonstrate for the first time that a serotinous pine can form a viable soil seed bank by cone burial, which may facilitate natural regeneration if a secondary disturbance occurs. Seeds contained in 15-yr-old cones showed a steep decline in viability, which could limit regeneration if there is a long delay before a secondary disturbance.