The development of a community-based public health response to an outbreak of post-streptococcal glomerulonephritis in a First Nations community.
Post-streptococcal glomerulonephritis (PSGN) is a rare immune-mediated condition that typically occurs in children as a result of group A streptococcus (GAS) infection. PSGN is not considered a disease of public health significance, or reportable, in Canada. Higher incidence of PSGN has been described among Indigenous people in Canada. No national or provincial guidance exists to define or manage PSGN outbreaks. To describe an outbreak of seven paediatric cases of PSGN in a remote First Nations community in northwestern Ontario and the development of a community-wide public health response. Following a literature review, an intervention was developed involving screening of all children in the community for facial or peripheral edema or skin sores, and treatment with antibiotics if noted. Case, contact and outbreak definitions were also developed. The purpose of the response was to break the chain of transmission of a possible nephritogenic strain of streptococcus circulating in the community. Relevant demographic, clinical and laboratory data were collected on all cases. Seven paediatric cases of PSGN presented to the community nursing station between September 25 and November 29, 2017. Community-wide screening for skin sores was completed for 95% of the community's children, including 17 household contacts, and as a result, the last of the cases was identified. Nineteen adult household contacts were also screened. Ten paediatric contacts and two adult contacts with skin sores were treated with one dose of intramuscular penicillin, and six paediatric contacts received oral cephalexin. No further cases were identified following the screening. PSGN continues to occur in Indigenous populations worldwide at rates higher than in the overall population. In the absence of mandatory reporting in Canada, the burden of PSGN remains underappreciated and could undermine upstream and downstream public health interventions. Evidence-based public health guidance is required to manage outbreaks in the Canadian context. The community-based response protocol developed to contain the PSGN outbreak in this First Nations community can serve as a model for the management of future PSGN outbreaks.


Scanned conical illumination as a probe of electro-optic retro-reflection.
We describe a prototype element for use in probing electro-optic retro-reflection in sensor applications, illuminating a planar-aligned nematic liquid crystal electro-optic cell with convergent light having a single, tunable angle of incidence (tunable conical illumination). This illumination is generated using a 100X, high numerical aperture, long working-distance microscope objective under conditions of extreme spherical aberration. The electro-optic effect observed is multiple-beam optical interference between polarized reflections from the two bounding plates of the cell, rendered tunable with voltage-controlled refractive index changes induced by molecular reorientation of the liquid crystal. Characterization of the reflectivity vs. angle of incidence and applied voltage enables identification of conditions of high-contrast, low power, electro-optic reflectivity control applicable to fiber optics.


Versatile Dynamic Bioactive Lubricant-Infused Surface for Effective Isolation of Circulating Tumor Cells.
The rarity of circulating tumor cells (CTCs) and the complexity of blood components present major challenges for the efficient isolation of CTCs in blood. The coexisting matters could interfere with the detection of CTCs by adhering to the binding sites on the material surface, leading to the reduced accuracy of biomarker capture in blood. Herein, we developed dynamic bioactive lubricant-infused slippery surfaces by grafting the 1H,1H,2H,2H-heptadecafluorodecyl acrylate polymer and 3-acrylamidophenylboronic acid polymer brushes on quartz plates by UV light-initiated and then grafted cancer cell-binding peptides via reversible catechol-boronate chemistry between phenylboronic acid groups and 3,4-dihydroxy-l-phenylalanine groups of peptides for high-efficient capture of CTCs and nondestructive release of the desired cells in sugar response. Patterned dynamic bioactive lubricant-infused surfaces (PDBLISs) further exhibited the improved capture efficiency of CTCs and more effective antifouling properties for nonspecific cells and blood components. Moreover, the PDBLIS can efficiently capture rare cancer cells from the mimic of cancer patient's blood samples. We anticipate that the strategy we proposed would be used in further clinical diagnosis of complicated biofluids related to a variety of tumors and exhibit good prospects and potential in future liquid biopsies.


The influence of propagating and evanescent waves on the focusing properties of zone plate structures.
The field properties of Fresnel zone plates with wavelength-scale focal distances were numerically investigated using the finite-difference time-domain method. The fields in the focal planes are analyzed using the angular spectrum representation, and the components of the propagating and evanescent waves are reconstructed. It was found that, in the focal plane of silver zone plates, there were more evanescent waves and the propagating waves occurred at higher spatial frequencies relative to glass zone plates. The propagating and evanescent wave components vary with the material and the number of zones in the zone plate structures. Our findings suggest that more evanescent waves and higher spatial frequency components of propagating waves can shape the field and obtain a smaller focus.


Spray plasma device, a new method to process nanostructured layers. application to deposit ZnO thin layers.
The aim of this paper is to present a new plasma spray device to deposit nanostructured films. In this process, aqueous droplets of a starting material, in this case, a nitrate salt, of small and uniform size produced in an aerosol generator are injected into a low pressure plasma reactor. Droplets are then submitted to the reactivity of plasma and projected against a substrate where they form the final film. The reactor is designed to reduce the turbulence that results in coalescence of the particles and affects the uniformity of the deposited films. The plasma is produced by an inductive RF generator that avoids the contamination of the layers by electrodes. The control of plasma gas composition, i.e., argon and oxygen, permits adjustment of the concentration of reactive species leading to control the stoichiometry of the deposited layers. The ability of this process to produce nano scale zinc oxide films by the use of an aqueous solution containing Zn(NO3)2 is demonstrated. The films obtained under defined experimental conditions are smooth, colorless and transparent. SEM and AFM photographs show the formation of uniform layers with 20 to 60 nm in thickness. XRD patterns of deposited films showed that preferential c-axis orientation of crystallites depends highly on the concentration of Zn(NO3)2 in the starting solution. Willamson-Hall method in accordance with AFM photographs showed that the size of crystallites ranges between 24 and 34 nm.


Reconfigurable neuromorphic computing block through integration of flash synapse arrays and super-steep neurons.
Neuromorphic computing (NC) architecture inspired by biological nervous systems has been actively studied to overcome the limitations of conventional von Neumann architectures. In this work, we propose a reconfigurable NC block using a flash-type synapse array, emerging positive feedback (PF) neuron devices, and CMOS peripheral circuits, and integrate them on the same substrate to experimentally demonstrate the operations of the proposed NC block. Conductance modulation in the flash memory enables the NC block to be easily calibrated for output signals. In addition, the proposed NC block uses a reduced number of devices for analog-to-digital conversions due to the super-steep switching characteristics of the PF neuron device, substantially reducing the area overhead of NC block. Our NC block shows high energy efficiency (37.9 TOPS/W) with high accuracy for CIFAR-10 image classification (91.80%), outperforming prior works. This work shows the high engineering potential of integrating synapses and neurons in terms of system efficiency and high performance.


Total Synthesis of (±)-Grandilodine B.
The first total synthesis of the opened-type Kopsia alkaloid grandilodine B is reported. Four stereocenters of this alkaloid, three of them quaternary, are stereoselectively generated by a Diels-Alder reaction, a diastereoselective cyanation of tertiary alcohol, and a facial-selective nitrone 1,3-dipolar cycloaddition.


Circ_0027089 regulates NACC1 by targeting miR-136-5p to aggravate the development of hepatitis B virus-related hepatocellular carcinoma.
Hepatitis B virus (HBV) infection is the main trigger of hepatocellular carcinoma (HCC). Circular RNA plays an indispensable role in cancer development, and this study aimed to disclose the function and mechanism of circ_0027089 in HBV-related HCC. The expression levels of circ_0027089, miR-136-5p and nucleus accumbens associated protein 1 (NACC1) mRNA were measured by quantitative real-time PCR, and the protein level of NACC1 was detected by western blot. For functional analyses, cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry assay, and cell apoptosis was also assessed by caspase 3/7 activity. The capacities of migration and invasion were evaluated by wound healing assay and transwell assay, respectively. The predicted relationship between miR-136-5p and circ_0027089 or NACC1 was validated by dual-luciferase reporter assay and RNA binding protein immunoprecipitation assay. Animal experiments were performed in nude mice to explore the role of circ_0027089 in vivo. Circ_0027089 expression and NACC1 expression were elevated, while miR-136-5p expression was decreased in HBV-related HCC tissues and cells. In function, circ_0027089 knockdown inhibited HepG2.2.15 and HepAD38 (tet-off) cell proliferation, migration and invasion but induced cell cycle arrest and apoptosis, while circ_0027089 overexpression played the reversed effects. For mechanism exploration, miR-136-5p was a target of circ_0027089, and miR-136-5p deficiency could reverse the role of circ_0027089 knockdown. Circ_0027089 functioned as an oncogene to promote the development of HBV-related HCC by regulating NACC1 via competitively targeting miR-136-5p.


Antioxidant, anti-inflammatory and antiseptic molecular actions of gedunin against lipopolysaccharide-induced sepsis in experimental rats.
Sepsis is a life-threatening organ dysfunction without effective therapeutic options. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce sepsis. It is associated with oxidative stress, inflammation and multiple organ failure. Gedunin (GN) is a tetranortriterpenoid isolated from the Meliaceae family. Gedunin possesses numerous pharmacological properties, including antibacterial, anti-inflammatory, antiallergic, and anticancer activities. However, the molecular anti-inflammatory mechanism of GN in sepsis has not been established. The aim of the study was to explore the antioxidant and anti-inflammatory molecular actions underlying the antiseptic activity of GN in an LPS-induced rat model. Rats were randomized into 4 sets: group 1 (control) was given 1 mL of dimethyl sulfoxide (DMSO) by gavage, group 2 rats were treated with LPS (100 μg/kg body weight (BW), intraperitoneally (ip.)), group 3 rats were given LPS (100 μg/kg BW, ip.)+GN (50 mg/kg BW in DMSO), and rats in the group 4 were given GN (50 mg/kg BW in DMSO) alone. We studied hepatic markers, inflammatory cytokines and antioxidants using specific biochemical kits and analyzed their statistical significance. Histopathology of liver, lungs and kidney tissues was also explored. The mRNA levels and conducted protein investigations were performed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, respectively. Our findings revealed that GN significantly (p < 0.05) inhibited oxidative stress, lipid peroxides, toxic markers, pro-inflammatory cytokines, and histological changes, thereby preventing multi-organ impairment. Additionally, GN attenuated the HMGβ1/NLRP3/NF-κB signaling pathway and prevented the degradation of Iκβα. Gedunin is a promising natural antiseptic agent for LPS-induced sepsis in rats.


Public participation in local alcohol regulation: Findings from a survey of New Zealand communities.
In many high-income countries, the responsibility for alcohol regulation is being devolved from central to local governments. Although seeking public input is typically required by law, there remains little empirical evidence on whether and how the public is involved. We investigated public participation in local liquor licensing and related regulation in New Zealand. In 2007, we randomly sampled 2337 residents from the national electoral roll in seven communities and invited them to complete a postal questionnaire assessing their level of general community engagement, whether they had taken action on alcohol issues, and barriers to participation they perceived or encountered. A total of 1372 individuals responded (59% response). Fifty-two percent were current members of community organisations, and 40% had ever taken action on a local issue. Respondents considered alcohol to be a major problem locally, but only 4% had been involved in action to address a problem, whereas 18% had considered taking action. In their communities, 12% and 24%, respectively, felt they could influence the number or location of alcohol outlets. There was little variation across communities. Despite high levels of general community engagement and alcohol being widely regarded as a local problem, few community members reported acting on alcohol issues, and their self-efficacy to effect change was low.


A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.
The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile loading are used to tissue-engineer AC. Our goal is to provide a practical guide to their use and optimization of loading parameters. For each loading condition, we will also present and discuss benefits and limitations of bioreactor configurations that have been used. The intent is for this review to serve as a reference for including mechanical stimulation strategies as part of AC construct culture regimens.


Liquid Biopsy-Based Volatile Organic Compounds from Blood and Urine and Their Combined Data Sets for Highly Accurate Detection of Cancer.
Liquid biopsy is seen as a prospective tool for cancer screening and tracking. However, the difficulty lies in effectively sieving, isolating, and overseeing cancer biomarkers from the backdrop of multiple disrupting cells and substances. The current study reports on the ability to perform liquid biopsy without the need to physically filter and/or isolate the cancer cells per se. This has been achieved through the detection and classification of volatile organic compounds (VOCs) emitted from the cancer cells found in the headspace of blood or urine samples or a combined data set of both. Spectrometric analysis shows that blood and urine contain complementary or overlapping VOC information on kidney cancer, gastric cancer, lung cancer, and fibrogastroscopy subjects. Based on this information, a nanomaterial-based chemical sensor array in conjugation with machine learning as well as data fusion of the signals achieved was carried out on various body fluids to assess the VOC profiles of cancer. The detection of VOC patterns by either Gas Chromatography-Mass Spectrometry (GC-MS) analysis or our sensor array achieved >90% accuracy, >80% sensitivity, and >80% specificity in different binary classification tasks. The hybrid approach, namely, analyzing the VOC datasets of blood and urine together, contributes an additional discrimination ability to the improvement (>3%) of the model's accuracy. The contribution of the hybrid approach for an additional discrimination ability to the improvement of the model's accuracy is examined and reported.


Histamine is involved in gastric vasodilation during acid back diffusion via activation of sensory neurons.
Protective vasodilation during acid back diffusion into the rat gastric mucosa depends on activation of sensory neurons and mast cell degranulation with histamine release. We hypothesized that these two mediator systems interact and that histamine partly exerts its effect via sensory nerves. Gastric blood flow (GBF) and luminal histamine were measured in chambered stomachs, and mast cell numbers were assessed by morphometry. Ablation of sensory neurons and depletion of mast cells were produced by pretreatment with capsaicin or dexamethasone, respectively. Mucosal exposure to 1.5 M NaCl and then to pH 1.0 saline in ablated and control rats caused increased luminal histamine and reduced numbers of mast cells. Enterochromaffin-like cell marker pancreastatin remained unchanged. Only control rats responded with an increase in GBF. Capsaicin stimulation (640 microM) of the undamaged mucosa induced identical increase in GBF and unchanged mast cell mass in normal and dexamethasone-treated rats. Increase in GBF after topical exposure to histamine (30 mM) in rats pretreated with capsaicin or a calcitonin gene-related peptide (CGRP)(1) antagonist human CGRP(8-37) or exposed to the calcium pore blocker ruthenium red was less than one-half of that in control rats. These data suggest that mast cell-derived histamine is involved in gastric vasodilatation during acid back diffusion partly via sensory neurons.


Acute Effects of Sacubitril/Valsartan with Initial Initiation in Pediatric Patients in the Cardiac Intensive Care Unit.
There are very few objectively studied and proven medical interventions for the management of pediatric heart failure. Due to improvement in morbidity and mortality in the adult heart failure population, sacubitril/valsartan has started to be used in pediatric patients. The aim of this study was to characterize the acute cardiovascular effects of sacubitril/valsartan in the first 48 h after initiation. Single center retrospective study of pediatric patients in the cardiac intensive care unit who were initiated on sacubitril/valsartan for the first time over a three-year period. Clinical data was collected immediately prior to and within 48 h following initiation. A total of 16 patients with a mean age of 9.6 years were started on sacubitril/valsartan with a mean daily dose of 1.6 mg/kg/day in the first 48 h. Significant decreases were noted in N-terminal brain natriuretic peptide and vasoactive-inotrope score. No significant changes were noted in other clinical variables. The initiation of sacubitril/valsartan in a small cohort of pediatric patients with heart failure in the cardiac intensive care unit is associated with a significant decrease in N-terminal brain natriuretic peptide with a concurrent decrease in vasoactive-inotrope score and without significant change venous oxygen extraction ratio or other hemodynamic variables.


Bone GLA protein (BGP) levels and bone turnover in rheumatoid arthritis.
Bone GLA protein (BGP) and other biochemical indices of bone turnover were measured in 42 female patients with rheumatoid arthritis (RA) and in a group of normal subjects matched for sex and age. Mean serum BGP concentrations were significantly higher in patients with active arthritis than in patients with mild activity (p less than 0.01) and controls (p less than 0.01). No significant difference was found in serum BGP levels and in other parameters of bone turnover when the patients were stratified according to functional class or duration of disease. There was a correlation between BGP and alkaline phosphatase levels only in RA patients with high activity of disease. Our data suggest an accelerated bone turnover in patients with active RA. We infer that in such patients the impairment of bone metabolism is a determinant of RA-associated osteopenia. Disease activity rather than functional impairment or duration of arthritis should be regarded as a factor in the bone loss of RA.


Aedes albopictus production in urban stormwater catch basins and manhole chambers of downtown Shanghai, China.
The near-surface urban drainage system in Shanghai is highly complex, with hundreds of thousands of catch basins (CBs) and manhole chambers (MCs). Comparatively little is known about the breeding of mosquitoes in this vast system, especially for the locally predominant species Aedes albopictus. A cross-sectional mosquito sampling study was conducted from late July to early August of 2017 using 539 CBs and 309 MCs located in 10 communities of downtown Shanghai. We measured the water-holding status of the drainage systems and density of mosquito larvae. Mosquito species were examined on site and in the laboratory later. The CBs were characterized by a lower percentage of standing water compared to MCs (47.0% vs. 79.9%, respectively; X2 = 76.407, P<0.001), but CBs contained a higher percentage of stagnant water percent than MCs (45.2% vs. 35.3%, respectively; X2 = 11.465, P = 0.001). There were exclusively two species of mosquito larvae found in the drainage systems, Ae. albopictus and Culex pipiens complex. Compared with MCs, the structures of CBs were more conducive to larval production and yielded more larvae-positive samples (43.4% vs 14.2%, X2 = 53.136, P<0.001) and higher larval density (8.23 vs. 4.09 per dipper, t = 3.287, P = 0.001). Aedes albopictus was the predominant species in CBs, with a constituent ratio of 71.7%. Regarding structures with different features in different locations, CBs that had a vertical grate with an unsealed lid and MCs with plastic composite covers were the most favorable types for mosquito breeding, and residential neighborhoods yielded the highest number of Ae. albopictus. Aedes albopictus was the predominant species in both CBs and stormwater MCs, especially in residential neighborhoods. CBs, particularly those with vertical grates, were a major source of mosquito production in downtown Shanghai. MCs featured more running water and fewer larvae by percentage, and few larvae were found in Sewage MCs. However, due to the tremendous baseline amount, MCs were still an important breeding source of mosquitoes. We suggest that Aedes control in Shanghai should focus on CBs or other potential larvae habitats in and around residential neighborhoods. The use of permeable materials and completely sealed covers should be adopted in the construction of CBs and MCs henceforth.


Management consideration for patient with a large solitary fibrous tumor occupying the infratemporal fossa: A case report.
The solitary fibrous tumor (SFT) was first described as a mesenchymal tumor of fibroblastic type, present in the pleura. The head and neck area is the third most common site of SFT occurrence. Numb chin syndrome (NCS) is a rare neurological symptom. The current report describes the case of a 39-year-old female patient referred to the present hospital with NCS, which was later observed to be due to a large SFT in the infratemporal fossa. Computed tomography and magnetic resonance images were taken and subsequent examination of these images revealed a space occupying mass (52×50×40 mm) in the infratemporal fossa. An open biopsy was performed on the lower part of the right auricula following angiography assisted vascular embolization of the maxillary artery. Pathological diagnosis was verified as SFT. Despite the tumor size and anatomical site, the SFT was successfully reduced in size by treatment with intensity modulated radiation therapy (IMRT) alone, with no recurrence. IMRT treatment of SFT may be effective as a future potential option for locally advanced head and neck SFT.


Acute Exercise as an Intervention to Trigger Motor Performance and EEG Beta Activity in Older Adults.
Acute bouts of exercise have been shown to improve fine motor control performance and to facilitate motor memory consolidation processes in young adults. Exercise effects might be reflected in EEG task-related power (TRPow) decreases in the beta band (13-30 Hz) as an indicator of active motor processing. This study aimed to investigate those effects in healthy older adults. Thirty-eight participants (65-74 years of age) were assigned to an experimental (EG, acute exercise) or a control group (CG, rest). Fine motor control was assessed using a precision grip force modulation (FM) task. FM performance and EEG were measured at (1) baseline (immediately before acute exercise/rest), (2) during practice sessions immediately after, (3) 30 minutes, and (4) 24 hours (FM only) after exercise/rest. A marginal significant effect indicated that EG revealed more improvement in fine motor performance immediately after exercise than CG after resting. EG showed enhanced consolidation of short-term and long-term motor memory, whereas CG revealed only a tendency for short-term motor memory consolidation. Stronger TRPow decreases were revealed immediately after exercise in the contralateral frontal brain area as compared to the control condition. This finding indicates that acute exercise might enhance cortical activation and thus, improves fine motor control by enabling healthy older adults to better utilize existing frontal brain capacities during fine motor control tasks after exercise. Furthermore, acute exercise can act as a possible intervention to enhance motor memory consolidation in older adults.


Hippocampal insulin resistance and altered food decision-making as players on obesity risk.
There are increasing evidences that hippocampus can modulate the decision of what, when and how much to eat, in addition to its already recognized role in learning and memory processes. Insulin also has been linked to brain functions such as feeding behavior and the imbalance of its mechanism of action on hippocampus is being related to cognitive dysfunction. The discussion here is whether changes in insulin action could contribute to intake dysregulation and obesogenic behavior as a primary consequence of impairing hippocampal functioning, aside from the role of this hormone on obesity development through peripheral metabolic pathways. Excess intake of high-fat and high-sugar diets leads to insulin resistance, which disrupts hippocampal function. Hippocampal physiology is sensitive to signals of hunger and satiety, inhibiting the ability of food cues to evoke appetite and eating, therefore alterations in hippocampal integrity could affect food inhibitory control leading to increased intake and obesity.


Study on the control effect of local basement replacement on the stability of dump.
This study focuses on effectively controlling landslides at the boundary of a soft rock open-pit dump while ensuring safe increases in the dump's capacity and optimal utilization of external dump sites. To achieve this, the adoption of a local filling method for the dump base is proposed. By leveraging the concepts of limit equilibrium theory and equivalent shear strength parameters, the mathematical expression of the slope stability coefficient in the Morgenstern-Price method is derived and improved. This improved method is then applied to a real engineering example to determine the optimal basement replacement rate required to maintain slope stability. The findings reveal that the local filling of the base is well-suited for slopes susceptible to potential landslides associated with cutting layers, bedding layers, and swelling. For practical ease, it is advisable to choose the lowest step in the dump's slope for construction convenience. As the local replacement rate of the base increases, the slope's stability coefficient gradually improves, with the K-Fs ratio showing a prominent role in this process. Additionally, numerical simulation methods are employed to elucidate the mechanism of the dump's landslide following local basement replacement, thereby providing comprehensive evidence of the engineering applicability of this method. The research results demonstrate a promising practical application prospect for effectively controlling the stability of soft base dump slopes.


Acute Type A Aortic Dissection: Beyond the Diameter.
Aortic dissection is a life-threatening condition in which early diagnosis, treatment and close follow up are critical for survival. Between 60% and 70% of patients with acute aortic dissection are affected at the ascending aorta, classified as Stanford type A (TAD). Preventive surgery of the aorta in asymptomatic patients on the basis of aortic size alone remains controversial among patient populations without known risk factors for aortic dissection. In fact, many dissection patients do not appear to have markedly dilated aortas at the time of presentation. In contrast, previous studies have indicated that the incidence of aortic dissection did not decrease, regardless of elective aortic replacement therapy. An increased aortic size as a follow up parameter is not sufficient to predict aortic dissection and rupture. Here, published evidence is reported regarding the limited role of aortic size in the genesis of TAD. Currently, a need exists to develop new markers to prevent aortic complications, especially in patients with sporadic ascending aneurysms (S-TAAs). It is important to emphasize this interesting aspect to the scientific cardiothoracic surgery forum in an attempt to improve guidelines for this disease.


[Induction by formaldehyde of conformational changes from helix to globule in the myoglobin molecule].
The secondary structure of myoglobin, treated with formaldehyde, has been studied by absorption spectroscopy, circular dichroism and gel-chromatography. The chemical modification of protein leads to disturbance of the polypeptide alpha-helix and destruction of the heme environment. The unfolding of protein in the presence of formaldehyde is a reversible process, the rate of transition is conditioned by temperature and formaldehyde concentration. At certain temperature conditions and formaldehyde concentration it is possible to obtain completely unfolded protein. The denaturation of myoglobin in the presence of formaldehyde is not cooperative in contrast to classical denaturation by pH, temperature, urea and other agents. Presence of some aminoacids causes inhibition of conformational changes in the protein molecule. Possible mechanisms of denaturation of myoglobin in the presence of formaldehyde are discussed.


Interference of a methotrexate derivative with urinary oncopterin [N2-(3-aminopropyl)biopterin] measurement by high-performance liquid chromatography with fluorimetric detection.
We previously reported a HPLC assay method using fluorimetric detection for the simultaneous determination of urinary N2-(3-aminopropyl)biopterin (oncopterin, a natural pteridine newly found in urine from cancer patients), biopterin and neopterin. We now have observed that an unknown substance, which may be derived from methotrexate, in urine from a patient with stomach cancer interfered with the assay of oncopterin and demonstrated that oncopterin could be completely separated from the unidentified substance by HPLC using a Nucleosil 100-5SA strong cation-exchange column. Furthermore, oncopterin was not detectable by this HPLC-fluorimetric method in urine samples from patients with stomach cancer who were not treated with methotrexate. The content of urinary oncopterin from cancer patients is supposed to be very low, with less than 1 mumol/mol creatinine. The present results indicate that the peak found with elution from the C18 column was a methotrexate-derived compound and co-eluted with the analyte oncopterin.


The historical social positioning of nursing and medicine: implications for career choice, early socialization and interprofessional collaboration.
For almost half a century, research has identified that effective teamwork is essential in order to enhance care provision and health outcomes for patients. Although the value of teamwork is well-recognized in healthcare, the historically rooted dynamics of workplace relationships create a myriad of challenges to creating collaborative teams. Understanding the history of interpersonal dynamics between health professionals can provide direction for future interprofessional education and collaboration strategies. The aim of this paper is to provide a historical overview of the social positioning of nursing and medicine in the context of interprofessional collaboration. Few professions work as closely as nursing and medicine. Despite the well-recognized benefits of interprofessional collaboration, these two professions are often socially positioned in opposition to one another and depicted as adversarial. This analysis will seek to advance our understanding of the historical roots between these two professions and their relationships with and among each other in relation to career choice, early socialization and patient care delivery. An exploration of the historical social positioning of nursing and medicine can provide an enhanced understanding of the barriers to interprofessional collaboration and inform future successes in interprofessional education and practice among all health and social care professions.


Reduction of polyethylenimine-coated iron oxide nanoparticles induced autophagy and cytotoxicity by lactosylation.
Superparamagnetic iron oxide (SPIO) nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications. When covered with amphiphilic alkyl-polyethyleneimine (PEI), the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes. However, the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications. In this study, we used lactose to modify amphiphilic low molecular weight polyethylenimine (C12-PEI2K) at different lactosylation degree. It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells, comparing to the unsubstituted ones. Besides, we found the PEI induced cell autophagy can be reduced via lactose modification, indicating the increased cell viability might rely on down-regulating autophagy. Thus, our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.


Dipeptidyl Peptidase IV Inhibitory Peptides Derived from Oat (Avena sativa L.), Buckwheat (Fagopyrum esculentum), and Highland Barley (Hordeum vulgare trifurcatum (L.) Trofim) Proteins.
Peptides released from oat, buckwheat, and highland barley proteins were examined for their in vitro inhibitory effects on dipeptidyl peptidase IV (DPP4), an enzyme that deactivates incretin hormones involved in insulin secretion. All of the hydrolysates exhibited DPP4 inhibitory activities, with IC50 values ranging from 0.13 mg/mL (oat glutelin alcalase digestion) to 8.15 mg/mL (highland barley albumin tryptic digestion). The lowest IC50 values in gastrointestinal, alcalase, and tryptic digestions were 0.99 mg/mL (oat flour), 0.13 mg/mL (oat glutelin), and 1.83 mg/mL (highland barley glutelin). In all, 35 peptides of more than seven residues were identified in the tryptic hydrolysates of oat globulin using liquid chromatography-mass spectroscopy. Peptides LQAFEPLR and EFLLAGNNK were synthesized and their DPP4 inhibitory activities determined. LQAFEPLR showed high in vitro DPP4 inhibitory activity with an IC50 value of 103.5 μM.


[Reconstructive problems after radical vulvectomy in carcinoma: current trends].
The most recent techniques of vulvar reconstruction after radical excision for carcinoma are here reported and evaluated. The analysis of the different Authors' experiences leads to different indications and limits concerning each method. Therefore it is necessary for the surgeon to be able to apply different reconstructive solutions after considering the initial local and general conditions.


Comparison of trap types and colors for capturing emerald ash borer adults at different population densities.
Results of numerous trials to evaluate artificial trap designs and lures for detection of Agrilus planipennis Fairmaire, the emerald ash borer, have yielded inconsistent results, possibly because of different A. planipennis population densities in the field sites. In 2010 and 2011, we compared 1) green canopy traps, 2) purple canopy traps, 3) green double-decker traps, and 4) purple double-decker traps in sites representing a range of A. planipennis infestation levels. Traps were baited with cis-3-hexenol in both years, plus an 80:20 mixture of Manuka and Phoebe oil (2010) or Manuka oil alone (2011). Condition of trees bearing canopy traps, A. planipennis infestation level of trees in the vicinity of traps, and number of A. planipennis captured per trap differed among sites in both years. Overall in both years, more females, males, and beetles of both sexes were captured on double-decker traps than canopy traps, and more beetles of both sexes (2010) or females (2011) were captured on purple traps than green traps. In 2010, detection rates were higher for purple (100%) and green double-decker traps (100%) than for purple (82%) or green canopy traps (64%) at sites with very low to low A. planipennis infestation levels. Captures of A. planipennis on canopy traps consistently increased with the infestation level of the canopy trap-bearing trees. Differences among trap types were most pronounced at sites with low A. planipennis densities, where more beetles were captured on purple double-decker traps than on green canopy traps in both years.


Order-disorder transition in a model with two symmetric absorbing states.
We study a model of two-dimensional interacting monomers which has two symmetric absorbing states and exhibits two kinds of phase transition; one is an order-disorder transition and the other is an absorbing phase transition. Our focus is around the order-disorder transition, and we investigate whether this transition is described by the critical exponents of the two-dimensional Ising model. By analyzing the relaxation dynamics of "staggered magnetization," the finite-size scaling, and the behavior of the magnetization in the presence of a symmetry-breaking field, we show that this model should belong to the Ising universality class. Our results along with the universality hypothesis support the idea that the order-disorder transition in two-dimensional models with two symmetric absorbing states is of the Ising universality class, contrary to the recent claim [K. Nam et al., J. Stat. Mech.: Theory Exp. (2011) L06001]. Furthermore, we illustrate that the Binder cumulant could be a misleading guide to the critical point in these systems.


Contributions of stretch activation to length-dependent contraction in murine myocardium.
The steep relationship between systolic force production and end diastolic volume (Frank-Starling relationship) in myocardium is a potentially important mechanism by which the work capacity of the heart varies on a beat-to-beat basis, but the molecular basis for the effects of myocardial fiber length on cardiac work are still not well understood. Recent studies have suggested that an intrinsic property of myocardium, stretch activation, contributes to force generation during systolic ejection in myocardium. To examine the role of stretch activation in length dependence of activation we recorded the force responses of murine skinned myocardium to sudden stretches of 1% of muscle length at both short (1.90 microm) and long (2.25 microm) sarcomere lengths (SL). Maximal Ca(2+)-activated force and Ca(2+) sensitivity of force were greater at longer SL, such that more force was produced at a given Ca(2+) concentration. Sudden stretch of myocardium during an otherwise isometric contraction resulted in a concomitant increase in force that quickly decayed to a minimum and was followed by a delayed development of force, i.e., stretch activation, to levels greater than prestretch force. At both maximal and submaximal activations, increased SL significantly reduced the initial rate of force decay following stretch; at submaximal activations (but not at maximal) the rate of delayed force development was accelerated. This combination of mechanical effects of increased SL would be expected to increase force generation during systolic ejection in vivo and prolong the period of ejection. These results suggest that sarcomere length dependence of stretch activation contributes to the steepness of the Frank-Starling relationship in living myocardium.


Thermodynamic Modeling and Experimental Data Reveal That Sugars Stabilize Proteins According to an Excluded Volume Mechanism.
We present a new thermodynamic model to investigate the relative effects of excluded volume and soft interaction contributions in determining whether a cosolute will either destabilize or stabilize a protein in solution. This model is unique in considering an atomistically detailed model of the protein and accounting for the preferential accumulation/exclusion of the osmolyte molecules from the protein surface. Importantly, we use molecular dynamics simulations and experiments to validate the model. The experimental approach presents a unique means of decoupling excluded volume and soft interaction contributions using a linear polymeric series of cosolutes with different numbers of glucose subunits, from 1 (glucose) to 8 (maltooctaose), as well as an 8-mer of glucose units in the closed form (γ-CD). By studying the stabilizing effect of cosolutes along this polymeric series using lysozyme as a model protein, we validate the thermodynamic model and show that sugars stabilize proteins according to an excluded volume mechanism.


l-Carnitine Inhibits Lipopolysaccharide-Induced Nitric Oxide Production of SIM-A9 Microglia Cells.
Microglia are the resident immune effector cells of the central nervous system. They account for approximately 10-15% of all cells found in the brain and spinal cord, acting as macrophages, sensing and engaging in phagocytosis to eliminate toxic proteins. Microglia are dynamic and can change their morphology in response to cues from their milieu. Parkinson's disease is a neurodegenerative disease, associated with reactive gliosis, neuroinflammation, and oxidative stress. It is thought that Parkinson's disease is caused by the accumulation of abnormally folded alpha-synuclein protein, accompanied by persistent neuroinflammation, oxidative stress, and subsequent neuronal injury/death. There is evidence in the literature for mitochondrial dysfunction in Parkinson's disease as well as fatty acid beta-oxidation, involving l-carnitine. Here we investigate l-carnitine in the context of microglial activation, suggesting a potential new strategy of supplementation for PD patients. Preliminary results from our studies suggest that the treatment of activated microglia with the endogenous antioxidant l-carnitine can reverse the effects of detrimental neuroinflammation in vitro.


Weak measurement of magneto-optical Goos-Hänchen effect.
As a lateral shift of reflected light beam from the optical interface, the Goos-Hänchen (GH) effect led to various practical applications in biosensing and optical field manipulations. Magneto-optical (MO) effect of dielectric or metal may bring flexible modulation for GH effect, which can be regarded as the magneto-optical Goos-Hänchen (MOGH) effect. In this paper, the GH and MOGH effects in a BK7 prism/Fe/Au waveguide enhanced by surface plasmon resonance (SPR) are demonstrated experimentally for the first time. By weak measurement, the GH and MOGH shifts are further amplified to facilitate their applications. By contrast, the results of theory and experiment are basically consistent. The maximum MOGH shift of the proposed BK7/Fe/Au waveguide achieves 120 μm when optimum thicknesses are chosen. As MOGH effect exhibits a higher sensitivity to the refractive index of sample than GH shift, it can be applied in refractive index detection. The demonstrated MOGH effect with advantages of high sensitivity and convenient control opens avenues for future applications with biosensors and functionally optical devices.


A minor wound with a fatal course.
The authors report on a fatal case of severe tetanus in a 74-year old woman. Despite comprehensive intensive care management they could not achieve a satisfying control of the autonomic dysfunction caused by tetanus. By now there is no established therapy for the treatment of the autonomic dysfunction. This report demonstrates the dismal prognosis of severe tetanus in the older people, which is often complicated by cardiovascular comorbidity and underlines the importance of tetanus prevention by sufficient vaccination.


[Tricuspid Valve Replacement without Removing Transvenous Pacemaker Lead].
Transvenous pacemaker lead occasionally impairs tricuspid valve coaptation because of the direct injury like a perforation, the direct interference with the valve, or the adhesion between the pacemaker leads and the valve leaflets, resulting in severe tricuspid regurgitation. In these situation, tricuspid valve replacement (TVR) is selected after the exchange from transvenous lead to epicardial lead. However this procedure has some problems such as poor threshold of the endcardial lead, the injury and the difficulty in transvenous lead removal. We performed successful TVR without removing transvenous pacemaker lead after the fixation to the annulus of posterior leaflet in tricuspid valve. This technique is useful in a patient with tricuspid regurgitation due to the influence of the pacemaker lead.


Cancer as the main aging factor for humans: the fundamental role of 5-methoxy-tryptamine in reversal of cancer-induced aging processes in metabolic and immune reactions by non-melatonin pineal hormones.
Aging and advanced cancer are characterized by similar neuroendocrine and immune deficiencies; the most important of them consist of diminished nocturnal production of the pineal hormone melatonin (MLT) and decreased production of IL-2. At present, however, it is known that the pineal gland may produce indole hormones other than MLT. The most investigated of them is represented by 5-methoxy-tryptamine (5-MTT), which may exert antitumor, anticachectic, and immunomodulating effects under experimental conditions, in addition to those effects produced by MLT itself. In an attempt to obtain some preliminary data in human subjects about the potential therapeutic properties of 5-MTT, three different studies of 5-MTT have been carried out in advanced solid tumor patients. The first study of MLT plus 5-MTT included 14 thrombocytopenic cancer patients who did not respond to MLT alone. In the second study we have compared the clinical efficacy of MLT plus 5-MTT in a group of 25 untreatable metastatic cancer patients to the results obtained in a control group of 25 cancer patients receiving MLT alone. Finally, the third study of MLT plus 5-MTT included 14 untreatable metastatic cancer patients who did not respond to MLT alone. In all of these studies, MLT and 5-MTT were given orally at the level of 20 mg/day in the evening and at 5 mg/day during the period of maximum light. A normalization of platelet number was achieved by MLT plus 5-MTT in 5 of 14 (36%) thrombocytopenic cancer patients who did not respond to MLT alone. The percentage of disease control obtained by MLT plus 5-MTT in untreatable metastatic cancer patients was significantly higher than that achieved by MLT alone (15/25 [60%] vs. 8/25 [32%], P < 0.05). Finally, the association of 5-MTT with MLT induced disease stabilization in 4 of 14 (29%) untreatable metastatic cancer patients who did not respond to MLT alone.


Lymphomas and oncolytic virus therapy.
There are several well-documented cases in medical literature of the remission of leukemias and malignant lymphomas following natural human viral infections. In the hope of being able to reproduce these spontaneous tumor regressions, investigators have studied various viruses with distinct oncolytic properties. The first attempts to treat patients with oncolytic viruses took place > 80 years ago; however, it achieved little success. With modern technologies and current knowledge of viruses and cancer, there is an expectation for the discovery of efficient oncolytic viral therapies. This article will review the current knowledge of oncolytic viruses in relation to the treatment of lymphoma.


Ultrafast spectroscopic study of the photochemistry and photophysics of arylhalodiazirines: direct observation of carbene and zwitterion formation.
Ultrafast photolysis (lambdaex = 270, 350, or 360 nm) of bromophenyl, chlorophenyl, fluorophenyl, and fluoro-para-trifluoromethylphenyl diazirines produces transient species which absorb broadly in the UV and visible regions. Transient decay can be fit to either mono- or biexponential functions (tau1 approximately 0.3-10 ps, tau2 approximately 10-350 ps; dependent on solvent and halogen). Fluoro- and chlorophenylcarbene are formed within the time resolution of the spectrometer (300 fs, 270 nm excitation). Bromophenyl diazirine decay (270 nm excitation) correlates with the growth of bromophenylcarbene. Solvent and substituent effects on the slower decays of the transient absorptions are consistent with assigning the carriers of transient absorption in the visible region to ring-opened zwitterionic species.


Identification of a polar targeting determinant for Bacillus subtilis DivIVA.
The Bacillus subtilis protein DivIVA controls both the positioning of the vegetative cell division site and the polar attachment of the chromosome during sporulation. In vegetative growth DivIVA attracts the bipartite cell division inhibitor MinCD away from the cell centre and towards the cell pole. This process ensures the inactivation of old polar division sites and leaves the cell centre free for the assembly of a new cell division complex. During sporulation MinCD and DivIVA levels fall, but DivIVA remains at the cell poles and becomes involved in the migration of the chromosomes to the pole. In order to investigate polar targeting of DivIVA, we undertook a mutational analysis of the 164-amino-acid protein. These studies identified one mutant (divIVA(R18C)) that could not localize to the cell pole but which retained the ability to support both vegetative growth and 50% sporulation efficiency. Further analysis revealed that, in the absence of polar targeting, DivIVA(R18C) localized to the nucleoid during vegetative growth in a Spo0J/Soj-dependent manner and required Spo0J/Soj and MinD to orientate the chromosomes correctly during sporulation. We demonstrate that polar targeting of DivIVA(R18C) is not essential during vegetative growth because the mutant can recognize the cell division site and influences the localization of MinD. Similarly we show that DivIVA(R18C) can function during sporulation because it can support the Spo0J/Soj orientation of the chromosome. In addition, we establish that both residues 18 and 19 constitute a DivIVA polar targeting determinant.


Strategies against burnout and anxiety in medical education--implementation and evaluation of a new course on relaxation techniques (Relacs) for medical students.
Burnout and stress-related mental disorders (depression, anxiety) occur in medical students and physicians with a significantly higher prevalence than in the general population. At the same time, the learning of coping mechanisms against stress is still not an integral part of medical education. In this pilot study we developed an elective course for learning relaxation techniques and examined the condition of the students before and after the course. 42 students participated in the semester courses in 2012 and 2013 as well as in a survey at the start and end of each course. The students were instructed in autogenic training (AT) and progressive muscle relaxation according to Jacobsen (PMR) with the goal of independent and regular exercising. At the beginning and the end of the semester/course the students were interviewed using standardized, validated questionnaires on burnout (BOSS-II) and anxiety (STAI-G), depression (BDI), quality of life (SF-12) and sense of coherence (SOC-L9). We compared the results of our students participating in Relacs with results from eight semester medical students (n = 88), assessed with the same questionnaires at similar points of time within their semester. Participating students showed a significant decline in cognitive and emotional burnout stress and in trait anxiety. Furthermore, they showed a reduction in state anxiety and a conspicuous decrease in mean depression. The sense of coherence increased at the same time. A comparative cohort of medical students of 8th semester students, showed lower values for the specified measurement parameters at the beginning, but showed no progressive changes. Our course introducing AT and PMR led to a significant reduction of burnout and anxiety within the participating group of medical students. Even the course attendance for just one semester resulted in significant improvements in the evaluated parameters in contrast to those students who did not attend the course.


Association of antibodies to Opisthorchis viverrini with hepatobiliary disease in northeastern Thailand.
The association between Opisthorchis viverrini infection and hepatobiliary disease was studied in northeastern Thailand. Positive rates of O. viverrini infection and antibody titers to O. viverrini adult worm extracts, which were determined by enzyme-linked immunosorbent assay (ELISA), were compared among four groups: Thai patients with cholangiocarcinomas (CHCA), those with calculus cholecystitis (CCLT), endemic area victims of traffic accidents, and Japanese individuals used as negative controls. While no difference was observed between cases with CCLT and the accident victims, the CHCA group showed a significantly higher positivity rate for fluke infection and higher antibody titers than the other groups. Comparison of the positivity rates and ELISA titers among intrahepatic and extrahepatic CHCA subgroups showed that only females with intrahepatic tumors had a low positive rate and significantly lower titers, with no other significant variation being evident. From these observations, a strong association between high intensity of past and/or present O. viverrini infection and the genesis of CHCAs was apparent in the majority of cases. However, in addition to the fluke infection, other unknown exogenous or endogenous factor(s) were suggested in the female cases.


Large-scale identification of tubulin-binding proteins provides insight on subcellular trafficking, metabolic channeling, and signaling in plant cells.
Microtubules play an essential role in the growth and development of plants and are known to be involved in regulating many cellular processes ranging from translation to signaling. In this article, we describe the proteomic characterization of Arabidopsis tubulin-binding proteins that were purified using tubulin affinity chromatography. Microtubule co-sedimentation assays indicated that most, if not all, of the proteins in the tubulin-binding protein fraction possessed microtubule-binding activity. Two-dimensional gel electrophoresis of the tubulin-binding protein fraction was performed, and 86 protein spots were excised and analyzed for protein identification. A total of 122 proteins were identified with high confidence using LC-MS/MS. These proteins were grouped into six categories based on their predicted functions: microtubule-associated proteins, translation factors, RNA-binding proteins, signaling proteins, metabolic enzymes, and proteins with other functions. Almost one-half of the proteins identified in this fraction were related to proteins that have previously been reported to interact with microtubules. This study represents the first large-scale proteomic identification of eukaryotic cytoskeleton-binding proteins, and provides insight on subcellular trafficking, metabolic channeling, and signaling in plant cells.


The venous drainage of the heart in porcupines (Hystrix cristata).
The venous drainage of the heart in porcupines (Hystrix cristata) was investigated. Each of the five adult porcupines (three males, two females) was injected with a coloured latex mixture via the V. cava caudalis for the demonstration of the cardiac veins. The dissection of the specimens revealed that the venous drainage of the heart in porcupines was made by the V. cordis magna, V. distalis ventriculi sinistri, V. proximalis ventriculi sinistri, V. cordis caudalis (the left marginal vein), V. cordis media and Vv. cordis dextrae. The cardiac veins were observed in a subepicardial course on the heart except for the R. interventricularis paraconalis. The R. interventricularis paraconalis showed an intramyocardial course until the middle of the sulcus interventricularis paraconalis, and a subepicardial course after this point. The V. cordis magna and V. distalis ventriculi sinistri opened to the sinus coronarius. The V. cordis caudalis and the V. cordis media drained into the V. cava caudalis. The venous drainage of the conus arteriosus was made by the left V. coni arteriosi opening to the R. interventricularis paraconalis, and by the right V. coni arteriosi which continued to the Vv. cordis dextrae.


The contribution of axial fiber extensibility to the adhesion of viscous capture threads spun by orb-weaving spiders.
The viscous capture threads produced by over 4000 species of orb-weaving spiders are formed of regularly spaced aqueous droplets supported by a pair of axial fibers. These threads register increased stickiness when spans of increasing lengths contact a surface, indicating that adhesion is recruited from multiple droplets. This study examined threads produced by five species to test the hypothesis that axial fiber extensibility is crucial for this summation of adhesion. It did so by comparing the stickiness of unstretched threads with threads that had been elongated to reduce the extensibility of their axial fibers. As stretching these threads also increased the distance between their droplets, we measured the stickiness of stretched threads with contact plates whose widths were increased in proportion to the degree of thread elongation. We then accounted for the actual thread elongation achieved for each individual's threads and for differences in the five species' absolute thread extensibility. The results showed that in four species thread extensibility contributed positively to adhesion. For three species, thread extensibility and droplet volume together explained the mean per droplet adhesion of threads. Models based on these three species show that, as threads were elongated, increasing amounts of potential adhesion were lost to diminished axial fiber extensibility. These models indicate that approximately one-third of an unstretched viscous thread's stickiness accrues from the adhesive recruitment made possible by axial fiber extensibility.


Development of Myxobolus macrocapsularis (Myxosporea: Myxobolidae) in an oligochaete alternate host, Tubifex tubifex.
The development of Myxobolus macrocapsularis Reuss, 1906, a myxosporean parasite of the gills of common bream Abramis brama L., was studied in experimentally infected oligochaetes. In 3 experiments uninfected Tubifex tubifex Muller and Limnodrilus hoffmeisteri (Claparéde) were exposed to mature myxospores of M. macrocapsularis. In all experiments, typical triactinospores developed in T. tubifex specimens but no infection was found in L. hoffmeisteri. Triactinospores were released from oligochaetes 66 to 99 d after initial exposure. At that time pansporocysts containing 8 triactinospores were located in the gut epithelium of experimental oligochaetes, but free actinosporean stages were also found in the gut lumen of the oligochaetes. Each triactinospore had 3 pyriform polar capsules and a barrel-shaped sporoplasm with 32 secondary cells. The spore body joined the 3 caudal projections with a stout style.


Combining growth hormone releasing hormone-arginine and synacthen testing diminishes the cortisol response.
The GHRH/arginine test and short synacthen test (SST) have been validated as safe alternatives to the insulin tolerance test for the assessment of the GH reserve and hypothalamic-pituitary-adrenal axis integrity, respectively. However, these two tests are usually performed separately. The objective was to see whether the synacthen and GHRH/arginine tests could be combined to save time and blood samples and minimize inconvenience to patients. Twenty-four consecutive patients with adult onset pituitary disease requiring pituitary function testing were randomized to receive sequentially and in random order a SST, a GHRH/arginine test, and a combined SST and GHRH/arginine test on three different visits separated by at least 1 wk. There was no difference in basal cortisol or ACTH values for the SST done alone or during the combined test. However, when GHRH/arginine was given with synacthen, patients had a lower peak cortisol response with a mean difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P < 0.001), and one patient with a normal response on the SST had a subnormal cortisol response in the combined test. Similar lower peak cortisol responses were observed in males and females with combined test. The difference between the peak cortisol responses showed no significant correlation with age (r = 0.123; P = 0.58) or with the body mass index (r = -0.376; P = 0.09). There was no difference in GH measurements between the GHRH/arginine test done alone or in combination with the SST. Combining the SST and GHRH/arginine test results in a lower cortisol response to synacthen. For this reason, the combined test cannot be recommended to assess the integrity of cortisol and GH reserve using current diagnostic criteria.


piRNA-19128 regulates spermatogenesis by silencing of KIT in chicken.
Spermatogenesis is a complex process. Some studies have shown that Piwi-interacting RNAs (piRNAs) play an important role in spermatogenesis. To verify the evaluate between piRNAs and PIWI proteins in chicken and its possible role in spermatogenesis and reproductive stem cell proliferation and differentiation, we performed immunoprecipitation and deep sequencing analyses and determined the expression profiles of small RNAs in primordial germ cells (PGCs), spermatogonial stem cells (SSCs), spermatogonia (Sa) cells, and spermatozoa. Length analysis showed that piRNAs bound to PIWIL1 mainly contained 23-30 nt. Base preference analysis showed "1U-10A"; moreover, base preference of piRNAs was obvious in all of germline cells. Here we reported the TE family of gallus gallus, and targeted by piRNA. Target gene of piRNA annotation enrichment analysis identified candidate genes KIT, SRC, WNT4, and HMGB2. Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes were associated with steroid hormone biosynthesis, Notch signaling pathway, and melanogenesis. These results indicate that chicken piRNAs perform important regulatory roles during spermatogenesis similar to mice piRNAs. Chicken piRNAs interacted with PIWI proteins and regulated spermatogenesis and germ cell proliferation and differentiation. Further, we observed a negative correlation between piRNA-19128 and KIT expression. Results of dual-luciferase reporter assay confirmed that piRNA-19128 directly interacted with KIT, suggesting that it plays a key role in the regulation spermatogenesis by inhibiting KIT expression. Thus, the present study provides information on the length and base preference of chicken piRNAs and suggests that piRNA-19128 regulates spermatogenesis in chicken by silencing KIT.


Bacillus subtilis spoVIF (yjcC) gene, involved in coat assembly and spore resistance.
In systematic screening four sporulation-specific genes, yjcA, yjcB, yjcZ and yjcC, of unknown function were found in Bacillus subtilis. These genes are located just upstream of the cotVWXYZ gene cluster oriented in the opposite direction. Northern blot analysis showed that yjcA was transcribed by the SigE RNA polymerase beginning 2 h (t(2)) after the onset of sporulation, and yjcB, yjcZ and yjcC were transcribed by the SigK RNA polymerase beginning at t(4) of sporulation. The transcription of yjcZ was dependent on SigK and GerE. The consensus sequences of the appropriate sigma factors were found upstream of each gene. There were putative GerE-binding sites upstream of yjcZ. Insertional inactivation of the yjcC gene resulted in a reduction in resistance of the mutant spores to lysozyme and heat. Transmission electron microscopic examination of yjcC spores revealed a defect of sporulation at stage VI, resulting in loss of spore coats. These results suggest that YjcC is involved in assembly of spore coat proteins that have roles in lysozyme resistance. It is proposed that yjcC should be renamed as spoVIF.


Surveillance and sampling of disease vectors.
Improving the surveillance and sampling of vectors is associated with many issues, including: the relative merits of laboratory studies as against field studies of vector behaviour; the ability to track individual vectors; the cost-effectiveness of traps and confident interpretation of sampling data. In this paper, the authors offer examples of recent progress in these matters and suggestions for future progress, with an emphasis on the need for analytical approaches to be adopted more widely.


Mitral valve reconstruction by posterior cusp advancement using a pericardial graft. Long-term follow-up in nine patients.
Between December 1964 and March 1969, 11 posterior cusp advancement operations were carried out for patients with mitral valve disease in whom there was posterior cusp deficiency. Seven of the nine long-term survivors have required reoperation for recurrent mitral regurgitation, combined in six instances with stenosis of varying severity, the interval between the first and second operations ranging from five months to nine years (average 57-5 months). Histological examination of the pericardial grafts recovered at re-operation has been made and shows that after an initial period during which the graft retains near normal structure, there is a progressive degeneration with fibrous tissue replacement. This process takes place on both surfaces of the graft where there is evidence of vascularization in the zone between the graft remnant and the overlying and increasingly thick fibrous tissue covering. The conclusion drawn from the experience with this small series is that the long-term performance of pericardial grafts designed to restore function to the posterior cusp of the mitral valve is poor and unpredictable.


Brief report: pressure support ventilation during an ascent and on the summit of Mt. Everest? A theoretical approach.
At extreme altitude, air has an almost identical composition compared to air at sea level, while its pressure is altitude-dependently lower. When supplementary oxygen is used to achieve an acceptable inspiratory pressure of oxygen (PI(O2)) during climbing, the barometric pressure difference to lower altitudes is not compensated for. In this report, we tried theoretically to apply pressure support ventilation (PSV) to partially compensate for low barometric pressures. PSV is widely used for respiratory home care and is applicable via a nasal mask. Since there are light-weight units with long battery lives on the market, we speculated that these units may to some extent replace bottled oxygen. PSV was in theory applied at barometric pressures of 400 torr (Everest Base Camp), 284 torr (South Col), and 253 torr (summit of Mt. Everest). We found that during PSV at a mean airway pressure of 16.5 torr on the summit of Mt. Everest, a fraction of inspired oxygen (FI(O2)) of 0.34 sufficed to achieve an alveolar partial pressure (PA(O2)) of 67 torr. PSV increases PI(O2) by 3.5 torr, which in theory elevates the maximum oxygen consumption (V(O2max)) by 218 mL.min(-1) in an acclimatized climber in this setting. An additional benefit of PSV at extreme altitude may come from the unloading of the respiratory muscles.


Assessment of right ventricular function with Doppler echocardiographic indices derived from tricuspid annular motion: comparison with radionuclide angiography.
To assess right ventricular systolic function using indices derived from tricuspid annular motion, and to compare the results with right ventricular ejection fraction (RVEF) calculated from radionuclide angiography. Pulsed Doppler echocardiography indices were obtained from 10 patients with a normal RVEF (group 1) and from 20 patients whose RVEF was less than 45% (group 2). The patients in the two groups were similar in age, systolic blood pressure, and heart rate. There was a close correlation between the tricuspid annular motion derived indices (D wave integral (DWI), peak velocity of D wave (PVDW), and tricuspid plane systolic excursion (TPSE)) and RVEF (r = 0.72, 0.82, and 0.79, respectively). DWI was significantly higher in group 1 than in group 2. PVDW discriminated adequately between individuals with abnormal and normal right ventricular ejection fraction. The sensitivity and specificity of tricuspid annular motion derived indices were very good. Indices derived from tricuspid annular motion appear to be important tools for assessing right ventricular systolic function.


Efficiency of multiexciton generation in colloidal nanostructures.
Solar energy production, one of the world's most important unsolved problems, has the potential to be a source of clean, renewable energy if scientists can find a way of generating cheap and efficient solar cells. Generation of multiple excitons from single photons is one way to increase the efficiency of solar energy collection, but the process suffers from low efficiency in bulk materials. An increase of multiexciton generation efficiency in nanocrystals was proposed by Nozik in 2002 and demonstrated by Schaller and Klimov in 2004 in PbSe nanocrystals. Since then, scientists have observed efficient multiexciton generation in nanostructures made of many semiconductors using various measurement techniques. Although the experimental evidence of efficient carrier multiplication is overwhelming, there is no complete theory of this phenomenon. Researchers cannot develop such a theory without a self-consistent description of the Coulomb interaction and a knowledge of mechanisms of electron and hole thermalization in nanostructures. The full theoretical description requires the strength of the Coulomb interaction between exciton and multiexciton states and the thermalization rates, which both vary with the dimensionality of the confining potential. As a result, the efficiency of multiexciton generation depends strongly on the material and the shape of the nanostructure. In this Account, we discuss the theoretical aspects of efficient carrier multiplication in nanostructures. The Coulomb interaction couples single excitons with multiexciton states. Phenomenological many-electron calculations of the evolution of single-photon excitations have shown that efficient multiexciton generation can exist only if the rate of the Coulomb mixing between photo-created exciton and biexciton states is significantly faster than the rate of exciton relaxation. Therefore, to increase multiexciton generation efficiency, we need to either increase the exciton-biexciton mixing rate or suppress the exciton relaxation rate. Following this simple recipe, we show that multiexciton generation efficiency should be higher in semiconductor nanorods and nanoplatelets, which have stronger exciton-biexciton coupling due to the enhancement of the Coulomb interaction through the surrounding medium.


Asymmetric [4 + 2], [6 + 2], and [6 + 4] Cycloadditions of Isomeric Formyl Cycloheptatrienes Catalyzed by a Chiral Diamine Catalyst.
Novel asymmetric aminocatalytic cycloadditions are described between formyl cycloheptatrienes and 6,6-dimethylfulvene that lead to [4 + 2], [6 + 2], and [4 + 6] cycloadducts. The unprecedented reaction course is dependent on the position of the formyl functionality in the cycloheptatriene core, and each formyl cycloheptatriene isomer displays a distinct reactivity pattern. The formyl cycloheptatriene isomers are activated by a chiral primary diamine catalyst, and the activation mode is dependent on the position of the formyl functionality relative to the cycloheptatriene core. The [4 + 2] and [6 + 2] cycloadducts are formed via rare iminocatalytic inverse electron-demand cycloadditions, while the [4 + 6] cycloadduct is formed by a normal electron-demand cycloaddition. The reactivity displayed by the different formyl cycloheptatrienes was investigated by DFT calculations. These computational studies account for the different reaction paths for the three isomeric formyl cycloheptatrienes. The aminocatalytic [4 + 2], [6 + 2], and [4 + 6] cycloadditions proceed by stepwise processes, and the interplay between conjugation, substrate distortion, and dispersive interactions between the fulvene and aminocatalyst mainly defines the outcome of each cycloaddition.


Expression of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium: a histopathological study.
Our objective was to examine the expression rates of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium. A total of 94 endometrial frozen sections (carcinoma 48, hyperplasia 21, normal tissue 25) were examined immunohistochemically in terms of the expression rates of p53, Bcl-2 and Bax. All of the specimens in the non-malignant groups were positive for Bax, whereas this rate was 85.4% in the group with malignant specimens (p = .03). Conversely, p53 was expressed only in the cancerous group (77.1%, p < .001). The Bcl-2 expression rate was 54.2% in the cancer group, 76.2% in the group with hyperplasia and 60% in the group containing normal tissue (p = .23). Comparing to the non-malignant specimens, the mean Bcl-2/Bax were significantly higher in the malignant group. In conclusion, Bax under-expression, p53 over-expression and a high Bcl-2 to Bax ratio might be associated with endometrial carcinoma. Bcl-2, however, plays no significant role in this regard. Impact statement What is already known on this subject? The p53, Bcl-2 and Bax are the three major genes that regulate apoptosis. Some studies have suggested that these genes may play a role in the pathogenesis of endometrial carcinoma. The available reports, however, are old and inconclusive. What do the results of this study add? Comparing immunohistochemically obtained p53, the Bcl-2 and Bax expression rates between normal endometrial tissue, endometrial specimens with endometrial hyperplasia and specimens with carcinoma showed that Bax under-expression, p53 over-expression and a high Bcl-2 to Bax ratio were associated with malignancy. Using an up-to-date technique to examine the three major regulators of apoptosis at the same time, in a rather large sample size of both normal and abnormal endometrial tissue specimens simultaneously, are the major advantages of the present work. What are the implications of these findings for clinical practice and/or further research? According to our findings, the status of p53, Bcl-2 and Bax expression in the endometrial tissue can be used for risk stratification of endometrial carcinoma for both screening and preventive purposes.


The immune mechanism of intestinal tract Toll-like receptor in mediating EV71 virus type severe hand-foot-and-mouth disease and the MAPK pathway.
Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)-infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study. Peripheral vein blood samples were collected from each individual, and used to isolate peripheral blood mononuclear cells (PBMCs) for mRNA extraction and sera for measuring levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-6 and IL-10. The average expression levels of TLR3, TLR4, TLR7 and TLR8 mRNA in PBMCs of children with severe HFMD were significantly higher than those in the other children, the lowest values were found in the healthy control group (P<0.05). The expression levels of TLR2 and TLR9 mRNA were not significantly different (P>0.05) among the groups. Additionally, the expression levels of TNF-α, IFN-γ, IL-6 and IL-10 in the serum of the children in the severe group were significantly higher than those in the other two groups, and the lowest values were again found in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with the TNF-α, IFN-γ, IL-6 and IL-10 levels in the serum (P<0.05). Furthermore, the expression levels of the ERK, JNK and p38 mRNA in PBMCs of children in the severe group were significantly higher than those in the other two groups, with the lowest values being in the control group (P<0.05). Pearson correlation analysis showed that the TLR3, TLR4, TLR7 and TLR8 mRNA levels in PBMCs were positively correlated with ERK, JNK and p38 mRNA levels (P<0.05). The results of our study seem to indicate that the high expression levels of TLR3, TLR4, TLR7 and TLR8 induced in severe EV71 HFMD regulate the expression of cytokines by MAPK signaling pathway and negatively affect the ability of the organism to resolve the infection. Further studies are needed to test the hypothesis that immuno-modulation would be an effective treatment approach in pediatric cases of severe HFMD.


Advances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve.
Significant progress has been made for tissue imaging of proteins using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS). These advancements now facilitate mapping of a wide range of proteins, peptides, and post-translational modifications in a wide variety of tissues; however, the use of MALDI IMS to detect proteins from cardiac tissue is limited. This review discusses the most recent advances in protein imaging and demonstrates application to cardiac tissue, including the heart valve. Protein imaging by MALDI IMS allows multiplexed histological mapping of proteins and protein components that are inaccessible by antibodies and should be considered an important tool for basic and clinical cardiovascular research. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.


Photoabsorption spectra of a natural polyphenol compound for therapeutic applications: the protocatechuic acid in dilute water solution at room temperature.
The UV-Vis absorption spectra of the protocatechuic acid, a potential new drug for the treatment of cancerous tumors and central nervous diseases, is for the first time fully reproduced in water solution at room temperature; these results open up the routes to integrated experimental/simulated studies in order to identify characteristic spectroscopic features of such a molecule and its derivatives within different hosting receptors in nature.


Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite.
A method is described for the simultaneous determination of the carboxylic acid and N-acetyl-derivatives of primaquine, in plasma and urine. After oral administration of 45 mg primaquine, to five healthy volunteers, absorption was rapid, with peak primaquine levels of 153.3 +/- 23.5 ng/ml at 3 +/- 1 h, followed by an elimination half-life of 7.1 +/- 1.6 h, systemic clearance of 21.1 +/- 7.1 l/h, volume of distribution of 205 +/- 371 and cumulative urinary excretion of 1.3 +/- 0.9% of the dose. Primaquine underwent rapid conversion to the carboxylic acid metabolite of primaquine, which achieved peak levels of 1427 +/- 307 ng/ml at 7 +/- 4 h. Levels of this metabolite were sustained in excess of 1000 ng/ml for the 24 h study period, and no carboxyprimaquine was recovered in urine. N-acetyl primaquine was not detected in plasma or urine. Following [14C]-primaquine administration to one subject, plasma radioactivity levels rapidly exceeded primaquine concentrations. Plasma radioactivity was accounted for mainly as carboxyprimaquine . Though 64% of the dose was recovered over 143 h, as [14C]-radioactivity in urine, only 3.6% was due to primaquine. As neither carboxyprimaquine nor N- acetylprimaquine were detected in urine, the remaining radioactivity was due to unidentified metabolites.


Ribotypes of Polymyxa graminis in Wheat Samples Infected with Soilborne Wheat Viruses in China.
Polymyxa graminis is an obligate parasite and important vector of more than 14 soilborne plant viruses that pose a significant threat to cereal crops in Europe, North America, and Asia. Different ribotypes or formae speciales of P. graminis have been recognized and these may be associated with different cereal hosts or with transmission of different viruses. Two soilborne viruses infecting winter wheat in China have been reported and well studied (Wheat yellow mosaic virus [WYMV, genus Bymovirus] and Chinese wheat mosaic virus [CWMV, genus Furovirus]) but there has been no reported characterization of P. graminis isolates associated with them. In this study, the ribosomal DNA internal transcribed spacer (ITS) regions of P. graminis were examined from 63 wheat samples with apparent virus symptoms obtained from 16 sites within six Chinese provinces. Their associations with soilborne viruses were investigated. Ribotype I (P. graminis f. sp. temperata) and ribotype II (P. graminis f. sp. tepida) were confirmed in winter wheat regions of China for the first time. All 63 wheat root samples were infected with ribotype I of P. graminis and 11 were also infected with ribotype II. There was no obvious association between the ribotypes and infection by either WYMV or CWMV (or double infection). Phylogenetic analysis of the P. graminis ITS1-5.8S-ITS2 sequences revealed that ribotype I in China belongs to previously reported subgroup Ib, whereas ribotype II belongs to IIa. There was considerable sequence variation (pairwise distances from 0.0219 to 0.0319) between Chinese ribotype I isolates of different regions and previously reported ribotype I isolate Ken5 (accession number HE860055.1).


A report on a rare case of Klebsiella ozaenae causing atrophic rhinitis in the UK.
Ozena is a chronic disease of the nasal cavity characterised by atrophy of the mucosa and bone caused by Klebsiella ozaenae. It is endemic to subtropical and temperate regions affecting the lower socio-economic group, usually the poor who live in unhygienic conditions. It is a rare disease in the UK. There is usually a delay in diagnosis due to unfamiliarity of the disease. A 25-year-old Nigerian migrant presented with nasal obstruction with purulent nasal discharge. Isolation of the bacterium was found from cultures of nasal discharge, crusting and tissue biopsies. She was treated successfully with ciprofloxacin. It is important to consider this rare condition in cases of nasal obstruction even in non-endemic areas especially with the advances of modern travel.


Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and provide evidence for a role of XLαs in fetal development.
Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia (POH) when paternally inherited. Recent studies have suggested that mutations on the paternal, but not the maternal, GNAS allele could be associated with intrauterine growth retardation (IUGR) and thus small size for gestational age. The aim of the study was to confirm and expand these findings in a large number of patients presenting with either PHP-Ia or PPHP/POH. We collected birth parameters (ie, gestational age, weight, length, and head circumference) of patients with either PHP-Ia (n = 29) or PPHP/POH (n = 26) with verified GNAS mutations. The parental allele carrying the mutation was assessed by investigating the parents or, when a de novo mutation was identified, through informative intragenic polymorphisms. Heterozygous GNAS mutations on either parental allele were associated with IUGR. However, when these mutations are located on the paternal GNAS allele, IUGR was considerably more pronounced than with mutations on the maternal allele. Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2-13 than with exon 1/intron 1 mutations. These data indicate that a paternally derived GNAS transcript, possibly XLαs, is required for normal fetal growth and development and that this transcript affects placental functions. Thus, similar to other imprinted genes, GNAS controls growth and/or fetal development.


Sex differences in microvascular function and arterial hemodynamics in nondialysis chronic kidney disease.
Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of 1) Ringer's solution; 2) superoxide dismutase mimetic, Tempol; and 3) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin. Blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Central pulse pressure (mean ± SE; 62 ± 9 vs. 46 ± 3 mmHg; P = 0.01) and augmentation index (36 ± 3 vs. 26 ± 3%; P = 0.03) were higher in females. There was a trend for higher central systolic pressures in females (146 ± 9 vs. 131 ± 3 mmHg; P = 0.06). Females reported higher forward (39 ± 4 vs. 29 ± 2 mmHg; P = 0.004) and reflected (27 ± 3 vs. 19 ± 1 mmHg; P < 0.001) wave amplitudes. Cutaneous vascular function was impaired in females compared with males (77 ± 3 vs. 89 ± 1%, P = 0.001). Microvascular function was improved following the delivery of Tempol and apocynin in females but not in males. Female patients with CKD had poorer central hemodynamics and reduced microvascular function compared with their male counterparts. Oxidative stress may contribute to lower microvascular function observed in females.NEW & NOTEWORTHY There are limited data regarding the physiological mechanisms of potential sex differences in central hemodynamics and vascular function in chronic kidney disease (CKD). We report that older female patients with nondialysis CKD have higher central pulse pressures compared with male patients with CKD. In addition, older females with CKD have lower microvascular function compared with their male counterparts, and oxidative stress contributes to the lower microvascular function in older female patients with CKD.


How Do B-Learning and Learning Patterns Influence Learning Outcomes?
Learning Management System (LMS) platforms provide a wealth of information on the learning patterns of students. Learning Analytics (LA) techniques permit the analysis of the logs or records of the activities of both students and teachers on the on-line platform. The learning patterns differ depending on the type of Blended Learning (B-Learning). In this study, we analyse: (1) whether significant differences exist between the learning outcomes of students and their learning patterns on the platform, depending on the type of B-Learning [Replacement blend (RB) vs. Supplemental blend (SB)]; (2) whether a relation exists between the metacognitive and the motivational strategies (MS) of students, their learning outcomes and their learning patterns on the platform. The 87,065 log records of 129 students (69 in RB and 60 in SB) in the Moodle 3.1 platform were analyzed. The results revealed different learning patterns between students depending on the type of B-Learning (RB vs. SB). We have found that the degree of blend, RB vs. SB, seems to condition student behavior on the platform. Learning patterns in RB environments can predict student learning outcomes. Additionally, in RB environments there is a relationship between the learning patterns and the metacognitive and (MS) of the students.


Chimeric Leader Peptides for the Generation of Non-Natural Hybrid RiPP Products.
Combining biosynthetic enzymes from multiple pathways is an attractive approach for producing molecules with desired structural features; however, progress has been hampered by the incompatibility of enzymes from unrelated pathways and intolerance toward alternative substrates. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a diverse natural product class that employs a biosynthetic logic that is highly amenable to engineering new compounds. RiPP biosynthetic proteins modify their substrates by binding to a motif typically located in the N-terminal leader region of the precursor peptide. Here, we exploit this feature by designing leader peptides that enable recognition and processing by multiple enzymes from unrelated RiPP pathways. Using this broadly applicable strategy, a thiazoline-forming cyclodehydratase was combined with enzymes from the sactipeptide and lanthipeptide families to create new-to-nature hybrid RiPPs. We also provide insight into design features that enable control over the hybrid biosynthesis to optimize enzyme compatibility and establish a general platform for engineering additional hybrid RiPPs.


Repeated hospitalization for the same disease: a multiplier of national health costs.
In five typical hospitals, and a specialized treatment center, more than half of all patients--and 60 percent of all costs--were attributable to repeated admissions for the same disease. The fiscal and clinical nature of repeated hospitalization suggests changes for national health policy. These will require more sensitive identification of patients "at risk" of recidivism, and insurance mechanisms that relate more rationally and equitably to long-term needs.


Effect of surfactants on antibiotic resistance.
The effectiveness of surfactants as potentiators of antibiotic activity on several resistant strains of bacteria, selected from clinical sources and laboratory collections, was studied using a tube dilution assay. Bacterial strains included members of the Enterobacteriaceae and staphylococci. Cetyltrimethylammonium bromide (CTAB), Tween 80 (Tw80), a mixture of n-alkyldimethyl betaines (L14), and alpha-(2,4,5-trichlorophenoxy) propionic acid (TCP) were tested in combination with pencillin G (PenG), methicillin (Met), streptomycin (Sm), polymyxin B (PmB), and chlortetracycline (CTC). Growth response to the drug combinations was compared with the response to each drug alone. CTAB and L14 but not Tw80 or TCP were found to potentiate the activity of CTC on strains of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Studies on the inhibition of protein synthesis by CTC in cells of a strain of E. coli suggested that the surfactants increased the uptake of antibiotic into the cells. CTAB and L14 almost completely sensitized strains of P. mirabilis, Serratia marcescens, K. pneumoniae, and E. coli to PmB. With the exception of K. pneumoniae, TCP was also effective in potentiating the activity of PmB on the above strains whereas Tw80 showed potentiation only with a strain of E. coli. CTAB and L14 but not TCP or Tw80 potentiated the activity of PenG but not Met on strains of staphylococci. Studies of penicillinase in the cells suggested that the surfactants inhibited the formation of this enzyme possibly at the level of induction. None of the surfactants were found to potentiate the activity of Sm.


Molecular beacon probes combined with amplification by NASBA enable homogeneous, real-time detection of RNA.
Molecular beacon probes can be employed in a NASBA amplicon detection system to generate a specific fluorescent signal concomitantly with amplification. A molecular beacon, designed to hybridize within the target sequence, was introduced into NASBA reactions that amplify the genomic RNA of potato leafroll virus (PLRV). During amplification, the probe anneals to the antisense RNA amplicon generated by NASBA, producing a specific fluorescent signal that can be monitored in real-time. The assay is rapid, sensitive and specific. As RNA amplification and detection can be carried out in unopened vessels, it minimizes the risk of carry-over contaminations. Robustness has been verified on real-world samples. This homogeneous assay, called AmpliDet RNA, is a significant improvement over current detection methods for NASBA amplicons and is suitable for one-tube applications ranging from high-throughput diagnostics to in vivo studies of biological activities.


Complications following the Kasai operation for biliary atresia: European experience.
Biliary atresia is a rare but important disease of infancy having an incidence of about 1 in 16,000 births. In most infants the disease process involves both the intra- and extra hepatic parts of the biliary system (Fig. 1) and histologically it has been characterized as a panductular cholangiopathy. Destruction and disappearance of biliary structures is progressive.


Sexual problems before and after myocardial infarction: patients' needs for information.
Changes occur in an individual's lifestyle after a myocardial infarction (MI), including his or her sexual activity. This study evaluated problems related to post-MI sexual functioning and the information needs of MI patients. The study included 110 MI patients who had home visits within 2-5 months after their discharge from the hospital. Data were gathered through a questionnaire that was completed through personal interviews. The study sample was predominantly male (95.5%). All patients were married, and 25% were between the ages of 24 and 40 years. We identified unnecessary limitations in sexual activities and mistakes in the reorganization of activities, such as resumption of sexual activity and frequency and positions of sexual intercourse. We found that all 110 patients had insufficient information about their future sexual functioning.


Successful management of unruptured interstitial pregnancy in 17 consecutive cases by using laparoscopic surgery.
To analyse the optimal laparoscopic surgical techniques for the treatment of interstitial pregnancy to minimise bleeding during the operative procedure and the safety of the subsequent pregnancy. Advanced bipolar coagulator was used to achieve haemostasis. The mean gestational age was 55 ± 5.1 days. All 17 women with an interstitial pregnancy were successfully treated by laparoscopic surgery without any complication. No surgery was converted to laparotomy. The mean pre-operative beta-human chorionic gonadotropin (β-hCG) serum concentration was 14 696 ± 11 705 mIU/mL. This value decreased to 1911 ± 1769 mIU/mL at 3-day post-operation. Among women who underwent laparoscopic surgery, a cornual resection was performed in 16 (94.1%) cases. One (5.8%) woman underwent a laparoscopic evacuation of the conceptus and received a local injection of 10 mg methotrexate. The volume of blood loss was <25 mL in 16 cases. However, one woman experienced a rupture at the beginning of the operation and lost 250 mL of blood. The mean hospital stay was 4.5 days. Four of the nine women who chose to retain their reproductive function had subsequent normal pregnancies, but all received an elective caesarean delivery prior to labour. The laparoscopic management of women with unruptured interstitial pregnancy can frequently be performed without haemorrhage or complication using advanced bipolar coagulation. The small sample of successful subsequent pregnancies demonstrates the safety and effectiveness of this technique, but this finding should be confirmed by further investigations.