A mechanistic analysis of the inoculum requirement for the cultivation of mammalian cells on microcarriers.
For the cultivation of mammalian cells on microcarriers a minimum inoculum concentration is required to initiate cell attachment and subsequent cell growth. A critical cell number model has been proposed to elucidate the mechanism of the inoculum requirement. In this model it was hypothesized that after inoculation a critical number of cells per microcarrier is required for normal growth to occur; failure to acquire enough cells will impede cell growth. This critical cell number model was expressed mathematically and used to simulate cell distribution and growth on microcarriers under different cultivation conditions. By comparing the simulated growth kinetics with the experimental results, the actual critical cell number per microcarrier was identified. The critical number could be reduced by employing an improved medium for the cultivation.


[Elimination disorders in childhood. How to make children dry and clean].
Evacuation disorders include a number of disturbances in which genetic and environmental factors play a highly differentiated role. Behind enuresis nocturna is a genetic CNS development disorder; a differentiation is made between cases with and without diurnal bladder dysfunction. In the first line treatment involves the use of an alarm device, while desmopressin is a second-choice treatment. In children with diurnal enuresis, there is a range of functional disorders of continence to be considered including, in particular, idiopathic urge incontinence, urinary incontinence when micturition is suppressed, and detrussor sphincter dyscoordination. Prominent among the therapeutic options are cognitive-behavioral measures and biofeedback training. Encopresis may develop on the soil of acute constipation or underlying psychological factors. Treatment is symptom-oriented and also comprised behaviorial measures (toilet training), possibly dietary measures and, in the event of constipation, enemas or oral laxatives.


Influence of dietary crude protein concentration and source on potential ammonia emissions from beef cattle manure.
Emissions of ammonia, as well as other gases and particulates, to the atmosphere are a growing concern of livestock producers, the general public, and regulators. The concentration and ruminal degradability of CP in beef cattle diets may affect urinary and fecal excretion of N and thus may affect ammonia emissions from beef cattle feed yards. To determine the effects of dietary CP concentration and degradability on potential ammonia emissions, 54 steers were randomly assigned to nine dietary treatments in a 3 x 3 factorial arrangement of treatments. Treatments consisted of three dietary CP concentrations (11.5, 13, and 14.5%) and three supplemental urea:cottonseed meal ratios (100:0, 50:50, and 0:100 of supplemental N). Steers were confined to tie stalls, and feces and urine excreted were collected and frozen after approximately 30, 75, and 120 d on feed. One percent of daily urine and feces excretion were added to polyethylene chambers containing 1,550 g of soil. Chambers were sealed, and ammonia emissions were trapped in an acid solution for 7 d using a vacuum system. As the protein concentration in the diet increased from 11.5 to 13%, in vitro daily ammonia emissions increased (P < 0.01) 60 to 200%, due primarily to increased urinary N excretion. As days on feed increased, in vitro ammonia emissions also increased (P < 0.01). Potential ammonia losses were highly correlated (P < 0.01) to urinary N (r2 = 0.69), urinary urea-N (r2 = 0.58) excretion, serum urea-N concentration (r2 = 0.52), and intake of degradable protein N (r2 = 0.23). Although dietary composition can affect daily ammonia losses, daily ammonia emissions must be balanced with effects on animal performance to determine optimal protein concentrations and forms in the diet.


Endoscopic brachytherapy for obstructive colorectal cancer.
Palliation of obstructive colon cancer is often challenging. Treatment options include Yttrium aluminum garnet (YAG) laser, stent placement, and surgical intervention. High-dose-rate intraluminal brachytherapy (HDRILBT) has been used to relieve obstructive symptoms due to rectal, bronchial, and esophageal cancers. In this case report, we document the combined use of YAG laser and HDRILBT for the palliation of obstructive colon cancer at the hepatic flexure, not previously reported in the literature. The patient in this case report had a large colonic tumor at the hepatic flexure causing near complete obstruction. Stent insertion and surgery were not feasible. YAG laser was used once and 11 days later, two fractions of HDRILBT were given 1 week apart. Under endoscopic vision and fluoroscopic guidance, a 150-cm Teflon catheter was passed through the lumen of the partially obstructed bowel for purposes of HDRILBT. A total dose of 10Gy was delivered at 1cm from the center of the source axis using a high-dose-rate afterloader. After treatment with the first fraction of HDRILBT, the tumor size decreased and the colonic lumen was significantly more patent. The patient's symptoms were significantly relieved after two fractions. Her weight increased and she was medically fit enough to undergo further chemotherapy. Further HDRILBT was not indicated. The calculated biological effective dose for the total HDRILBT treatments was well below the dose tolerances for acute effects for normal colonic tissue. HDRILBT should be considered as a possible treatment option for obstructive colon cancers when stent placement or surgery is not possible.


Human kallikrein 13 expression in salivary gland tumors.
The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.


Muscle-Preserving Selective Laminectomy Maintained the Compensatory Mechanism of Cervical Lordosis After Surgery.
A retrospective single-center study. The aim of this study was to evaluate the compensatory mechanism of cervical lordosis (CL), the changes in cervical sagittal alignment, and range of motion (ROM) after muscle-preserving selective laminectomy (SL). CL increases as a compensatory mechanism for the adjustment of cervical sagittal balance or horizontal gaze. However, laminoplasty invades this mechanism and causes kyphosis in higher T1 (C7) slope patients. SL is a posterior surgery selecting the decompression laminae without disturbing the extensor musculature and facet joints. The clinical features and radiological findings of 125 cervical compressive myelopathy patients who underwent C6 single-level SL, C5-C6 two consecutive levels SL, C4-C6 three consecutive levels SL, and C3-C6 four consecutive levels SL were enrolled. Cervical spine lateral radiography was performed before surgery and at the final follow-up. The patients were divided into two groups according to the preoperative C7 slope. Postoperative cervical alignment change was compared between the higher and lower C7 slope groups. Subsequently, pre- and postoperative cervical alignment and cervical ROM were analyzed according to the number of consecutive laminae surgically treated. Patients with higher C7 slope had greater lordotic cervical alignment and larger C2-C7 sagittal vertical axis (SVA) pre- and postoperatively. No kyphotic alignment change was observed, even in the higher C7 slope group. C6 SL and C5-C6 SL did not affect C2-C7 angle, and did not increase C2-C7 SVA after surgery. Although C4-C6 SL and C3-C6 SL demonstrated postoperative slight increase in C2-C7 SVA, C2-C7 angle never decreased after surgery. Cervical ROM slightly reduced in the C4-C6 SL and C3-C6 SL groups; however, no reduction of ROM was observed in the C6 SL and C5-C6 SL groups. SL preserved the inherent compensatory CL that had been observed preoperatively and maintained cervical sagittal balance after surgery. 4.


The Anesthesia Records of Harvey Cushing and Ernest Codman.
Hundreds of thousands of anesthesia records are created each day. The earliest records were prepared by 2 medical students in late 19th-century Boston. Ernest Codman and Harvey Cushing went on to become prominent surgeons and contributed much to the safety of the surgical patient. Cushing's career is celebrated due to his associations with William Stewart Halsted, Peter Bent Brigham Hospital, Yale University, in New Haven, Connecticut, and his biography of Sir William Osler. Codman is remembered for introducing the morbidity and mortality conference as well as his drive to improve outcomes and patient safety. We analyze every anesthetic record created by Codman and Cushing and provide both a historical context and perspective on many ways in which their doggedness, brilliance, and insight anticipated many advances that enhanced safety for patients undergoing surgical procedures.


Deformation-induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude.
The onset of ventilator-induced lung injury (VILI) is linked to a number of possible mechanisms. To isolate the possible role of alveolar epithelial deformation in the development of VILI, we have developed an in vitro system in which changes in alveolar epithelial cell viability can be measured after exposure to tightly controlled and physiologically relevant deformations. We report here a study of the relative effect of deformation frequency, duration, and amplitude on cell viability. We exposed rat primary alveolar epithelial cells to a variety of biaxial stretch protocols, and assessed deformation-induced cell injury quantitatively, using a fluorescent cell viability assay. Deformation-induced injury was found to depend on repetitive stretching, with cyclic deformations significantly more damaging than tonically held deformations. In cyclically deformed cells, injury occurred rapidly, with the majority of cell death occurring during the first 5 min of deformation. Deformation-induced injury was increased with the frequency of sustained cyclic deformations, but was not dependent on the deformation rate during a single stretch. Reducing the amplitude of cell deformations by superimposing small cyclic deformations on a tonic deformation significantly reduced cell death as compared with large-amplitude deformations with the same peak deformation.


Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management.
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) respectively characterized by clonal erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus and risk of leukemic or fibrotic transformation. Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR or MPL mutations (so called driver mutations). In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Median survivals are approximately 15 years for PV and 18 years for ET; the corresponding values for patients age 40 or younger were 37 and 35 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life-expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET but risk of thrombosis is higher in JAK2 mutated cases. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. In PV, two risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors). In ET, four risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild-type), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild-type) and high (thrombosis history present or age > 60 years with JAK2 mutation). The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once-daily or twice-daily aspirin (81 mg), in the absence of contraindications. Very low risk ET might not require therapy while aspirin therapy is advised for low risk disease. Cytoreductive therapy is recommended for high-risk ET and PV, but it is not mandatory for intermediate-risk ET. First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs of choice are interferon-α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs. Controlled studies are needed to confirm the clinical outcome value of twice-daily vs once-daily aspirin dosing and the therapeutic role of pegylated interferons and direct oral anticoagulants.


Saliency-aware video compression.
In region-of-interest (ROI)-based video coding, ROI parts of the frame are encoded with higher quality than non-ROI parts. At low bit rates, such encoding may produce attention-grabbing coding artifacts, which may draw viewer's attention away from ROI, thereby degrading visual quality. In this paper, we present a saliency-aware video compression method for ROI-based video coding. The proposed method aims at reducing salient coding artifacts in non-ROI parts of the frame in order to keep user's attention on ROI. Further, the method allows saliency to increase in high quality parts of the frame, and allows saliency to reduce in non-ROI parts. Experimental results indicate that the proposed method is able to improve visual quality of encoded video relative to conventional rate distortion optimized video coding, as well as two state-of-the art perceptual video coding methods.


Knockdown of Drosophila hemoglobin suggests a role in O2 homeostasis.
Almost all insects are equipped with a tracheal system, which appears to be sufficient for O2 supply even in phases of high metabolic activity. Therefore, with the exception of a few species dwelling in hypoxic habitats, specialized respiratory proteins had been considered unnecessary in insects. The recent discovery and apparently universal presence of intracellular hemoglobins in insects has remained functionally unexplained. The fruitfly Drosophila melanogaster harbors three different globin genes (referred to as glob1-3). Glob1 is the most highly expressed globin and essentially occurs in the tracheal system and the fat body. To better understand the functions of insect globins, the levels of glob1 were modulated in Drosophila larvae and adults by RNAi-mediated knockdown and transgenic over-expression. No effects on the development were observed in flies with manipulated glob1 levels. However, the knockdown of glob1 led to a significantly reduced survival rate of adult flies under hypoxia (5% and 1.5% O2). Surprisingly, the glob1 knockdown flies also displayed increased resistance towards the reactive oxygen species-forming agent paraquat, which may be explained by a restricted availability of O2 resulting in decreased formation of harmful O2(-). In summary, our results suggest an important functional role of glob1 in O2 homeostasis, possibly by enhancing O2 supply.


Vector-encoded Helicobacter pylori neutrophil-activating protein promotes maturation of dendritic cells with Th1 polarization and improved migration.
Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori infection. Both HP-NAP protein and oncolytic viruses encoding HP-NAP have been suggested as immunotherapeutic anticancer agents and adjuvants for vaccination but with little known about its mode of action to activate adaptive immunity. Dendritic cells (DCs) are key players in bridging innate and adaptive immune responses, and in this study we aim to evaluate the effect of HP-NAP on DC maturation, migration, and induction of adaptive immune response. Maturation markers CD83, CD80, CD86, HLA-DR, CD40, and CCR7 were upregulated on human DCs after treatment with supernatants from HP-NAP adenovirus-infected cells. HP-NAP-activated DCs had a Th1 cytokine secretion profile, with high IL-12 and relatively low IL-10 secretion, and migrated toward CCL19. Ag-specific T cells were efficiently expanded by Ag-presenting HP-NAP-activated DCs, which is an important property of functionally mature DCs. Furthermore, intradermal injections of HP-NAP-encoding adenovirus in C57BL/6 mice enhanced resident DC migration to draining lymph nodes, which was verified by imaging lymph nodes by two-photon microscopy and by phenotyping migrating cells by flow cytometry. In conclusion, therapeutic effects of HP-NAP are mediated by maturation of DCs and subsequent activation of Ag-specific T cells in addition to provoking innate immunity.


Cation Binding to Xanthorhodopsin: Electron Paramagnetic Resonance and Magnetic Studies.
Xanthorhodopsin (xR) is a member of the retinal protein family and acts as a proton pump in the cell membranes of the extremely halophilic eubacterium Salinibacter ruber. In addition to the retinal chromophore, xR contains a carotenoid, which acts as a light-harvesting antenna as it transfers 40% of the quanta it absorbs to the retinal. Our previous studies have shown that the CD and absorption spectra of xR are dramatically affected due to the protonation of two different residues. It is still unclear whether xR can bind cations. Electron paramagnetic resonance (EPR) spectroscopy used in the present study revealed that xR can bind divalent cations, such as Mn2+ and Ca2+, to deionized xR (DI-xR). We also demonstrate that xR can bind 1 equiv of Mn2+ to a high-affinity binding site followed by binding of ∼40 equiv in cooperative manner and ∼100 equiv of Mn2+ that are weakly bound. SQUID magnetic studies suggest that the high cooperative binding of Mn2+ cations to xR is due to the formation of Mn2+ clusters. Our data demonstrate that Ca2+ cations bind to DI-xR with a lower affinity than Mn2+, supporting the assumption that binding of Mn2+ occurs through cluster formation, because Ca2+ cations cannot form clusters in contrast to Mn2+.


[Antioxidants in the treatment of patients with discoid lupus erythematosus].
The authors present the data of biochemical studies of lipid peroxidation in 63 patients with discoid lupus erythematosus, validating the use of antioxidants combined with prednisolone and delagil in the treatment of such patients.


[Oxidative and anti-oxidative effects of ambroxol on acute hydrochloric acid-induced lung injury in rats].
To evaluate the protective effect of ambroxol on acute hydrochloric acid-induced lung injury in rats. Thirty pathogen-free SD rats were randomly divided into 3 groups: Group A (n=10) served as control group, and received intracheal instillation of normal saline (NS, pH5.3, 1.2 ml/kg) with pre-treatment of intraperitoneal NS; Group B (n=10) received intracheal instillation of hydrochloric acid /NS (pH1.25, 1.2 ml/kg) with pre-treatment of intraperitoneal NS; and Group C received intracheal instillation of hydrochloric acid /NS (pH1.25, 1.2 ml/kg) with pre-treatment of intraperitoneal ambroxol (50 mg/kg/d, 3 days). Five hours after the instillation of the injury vehicle, the arterial gas was examined, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) in the blood and homogenate of harvested lung were assayed respectively. PaO2 in Group B was significantly lower than that in Group A and C (P < 0.01), and pH and PaCO2 in the 3 groups had little difference (P > 0.05). MDA in the lungs of Group B increased obviously, and levels of SOD in the lung and blood decreased significantly in Group B (Group B vs Group A, P < 0.01). Levels of SOD of Group C in the lung and blood were markedly higher than those of Group B (P < 0.01), MDA of Group C was obviously lower than that of Group B (P < 0.01), and MDA of blood in the 3 groups had no significant difference (P > 0.05). Ambroxol can inhibit lipid peroxidation and increase antioxidant activity, which may be one of the mechanisms in protecting lung tissue from hydrochloric acid-induced injury.


Analysis of bacterial diversity in the canine duodenum, jejunum, ileum, and colon by comparative 16S rRNA gene analysis.
The study aim was to describe the diversity of the intraluminal intestinal microbial community in dogs by direct sequence analysis of the 16S rRNA gene. Intestinal content was collected from the duodenum, jejunum, ileum, and colon from six healthy dogs. Bacterial 16S rRNA gene was amplified with universal bacterial primers. Amplicons were ligated into cloning vectors and near-full-length 16S rRNA gene inserts were analyzed. From a total of 864 clones analyzed, 106 nonredundant 16S rRNA gene sequences were identified. Forty-two (40%) sequences showed<98% sequence similarity to 16S rRNA gene sequences reported previously. Operation taxonomic units were classified into four phyla: Firmicutes, Fusobacteria, Bacteroidetes, and Proteobacteria. Clostridiales predominated in the duodenum (40% of clones) and jejunum (39%), and were highly abundant in the ileum (25%) and colon (26%). Sequences affiliated with Clostridium cluster XI and Clostridium cluster XIVa dominated in the proximal small intestine and colon, respectively. Fusobacteriales and Bacteroidales were the most abundant bacterial order in the ileum (33%) and colon (30%). Enterobacteriales were more commonly observed in the small intestine than in the colon. Lactobacillales occurred commonly in all parts of the intestine.


Regulation of casein kinase I epsilon and casein kinase I delta by an in vivo futile phosphorylation cycle.
Casein kinase I delta (CKIdelta) and casein kinase I epsilon (CKIepsilon) have been implicated in the response to DNA damage, but the understanding of how these kinases are regulated remains incomplete. In vitro, these kinases rapidly autophosphorylate, predominantly on their carboxyl-terminal extensions, and this autophosphorylation markedly inhibits kinase activity (Cegielska, A., Gietzen, K. F., Rivers, A., and Virshup, D. M. (1998) J. Biol. Chem. 273, 1357-1364). However, we now report that while these kinases are able to autophosphorylate in vivo, they are actively maintained in the dephosphorylated, active state by cellular protein phosphatases. Treatment of cells with the cell-permeable serine/threonine phosphatase inhibitors okadaic acid or calyculin A leads to rapid increases in kinase intramolecular autophosphorylation. Since CKI autophosphorylation decreases kinase activity, this dynamic autophosphorylation/dephosphorylation cycle provides a mechanism for kinase regulation in vivo.


Synthesis and biological evaluation of bis-CNB-GABA, a photoactivatable neurotransmitter with low receptor interference and chemical two-photon uncaging properties.
Photoactivatable "caged" neurotransmitters allow optical control of neural tissue with high spatial and temporal precision. However, the development of caged versions of the chief vertebrate inhibitory neurotransmitter, γ-amino butyric acid (GABA), has been limited by the propensity of caged GABAs to interact with GABA receptors. We describe herein the synthesis and application of a practically useful doubly caged GABA analog, termed bis-α-carboxy-2-nitrobenzyl-GABA (bis-CNB-GABA). Uncaging of bis-CNB-GABA evokes inward GABAergic currents in cerebellar molecular layer interneurons with rise times of 2 ms, comparable to flash duration. Response amplitudes depend on the square of flash intensity, as expected for a chemical two-photon uncaging effect. Importantly, prior to uncaging, bis-CNB-GABA is inactive at the GABAA receptor, evoking no changes in holding current in voltage-clamped neurons and showing an IC50 of at least 2.5 mM as measured using spontaneous GABAergic synaptic currents. Bis-CNB-GABA is stable in solution, with an estimated half-life of 98 days in the light. We expect that bis-CNB-GABA will prove to be an effective tool for high-resolution chemical control of brain circuits.


How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity.
Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.


PhpC modulates G-quadruplex-RNA landscapes in human cells.
Stabilizing DNA/RNA G-quadruplexes (G4s) using small molecules (ligands) has proven an efficient strategy to decipher G4 biology. Quite paradoxically, this search has also highlighted the need for finding molecules able to disrupt G4s to tackle G4-associated cellular dysfunctions. We report here on both qualitative and quantitative investigations that validate the G4-RNA-destabilizing properties of the leading compound PhpC in human cells.


Peek at the glass ceiling: gender distribution of leadership among emergency medicine residency programs.
A gender gap in faculty rank at academic institutions exists; however, data among graduate medical education (GME) programmes are limited. There is a need to assess gender disparities in GME leadership, as a lack of female leadership may affect recruitment, role modelling and mentorship of female trainees. This cross-sectional study aimed to describe the current state of gender in programme leadership (department chair, programme director (PD), associate/assistant PD (APD) and clerkship director (CD)) at accredited Emergency Medicine (EM) programmes in the USA to determine whether a gender gap exists. A survey was distributed to EM residency programmes in the USA assessing demographics and gender distribution among programme leadership. If no response was received, information was collected via the programme's website. Data were organised by position, region and length of the programme. We obtained data on the number of female EM physicians in practice and in training/fellowship in 2017 from the Association of American Medical Colleges. Data analysis was completed using descriptive statistics and χ2 analysis. Of the 226 programmes contacted, 148 responded to the survey (66.3%). Among US EM residency programmes, 11.2% of chairs, 34.6% of PDs, 40.5% of APDs and 46.5% of CDs are women. The percentage of female chairs is significantly lower than the percentage of women in practice or in training in EM. The percentage of female PDs did not differ from the percentage of women in practice or in training in EM. The percentage of female APDs and CDs was significantly higher than the percentage of women in practice but did not differ from the percentage in training. There was wide variability across regions. Four-year programmes had more women in PD and APD positions compared with 3-year programmes (p=0.01). While the representation of women in educational roles is encouraging, the number of women holding the rank of chairperson remains disproportionately low. Further studies are needed to evaluate reasons for this and strategies to increase gender equality in leadership roles.


Neuroimaging of central nervous system infections.
During the past decade, advances have been made in the technology used to image the pediatric central nervous system. Although computed tomography (CT) remains the first line of imaging for the sick child admitted to the emergency room with fever and altered mental status, magnetic resonance imaging (MRI) offers superior soft tissue imaging of central nervous system (CNS) infections and advanced techniques. MRI also is the standard of care for imaging spinal infections. CT remains superior for the detection of calcification and bony detail. With the advent of new MRI sequences such as T2-weighted fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and magnetic resonance spectroscopy (MRS), we are able to detect early and subtle abnormalities such as the vasculitis accompanying a meningitis and to identify patterns of signal alteration that can help us be more specific about the diagnosis in lesions with similar appearances.


Reactions of beta-Lysin with Purified Cytoplasmic Membranes of Bacillus megaterium.
The bactericidal activity of beta-lysin was inactivated when it reacted with purified protoplasmic membranes. This reaction caused the membranes to fragment and lose their unit structure.


Radioautographic localization of labelled proteins after incubation of guinea-pig islets of Langerhans with (3H)tryptophan.
An analysis was made by electron-microscopic radioautography of the distribution of silver grains over storage granules of A(2) and B cells after incubation of isolated guinea-pig islets of Langerhans for 17h in the presence of [(3)H]tryptophan. A significant concentration of labelled proteins was present in the A(2) cell, but not in the B-cell granules.


MicroRNA-224 is involved in transforming growth factor-beta-mediated mouse granulosa cell proliferation and granulosa cell function by targeting Smad4.
Many members of the TGF-beta superfamily are indicated to play important roles in ovarian follicular development, such as affecting granulosa cell function and oocyte maturation. Abnormalities associated with TGF-beta1 signaling transduction could result in female infertility. MicroRNAs (miRNAs), as small noncoding RNAs, were recently found to regulate gene expression at posttranscriptional levels. However, little is known about the role of miRNAs in TGF-beta-mediated granulosa cell proliferation and granulosa cell function. In this study, the miRNA expression profiling was identified from TGF-beta1-treated mouse preantral granulosa cells (GCs), and three miRNAs were found to be significantly up-regulated and 13 miRNAs were down-regulated. Among up-regulated miRNAs, miR-224 was the second most significantly elevated miRNA. This up-regulation was attenuated by treatment of GCs with SB431542 (an inhibitor of TGFbeta superfamily type I receptors, thus blocking phosphorylation of the downstream effectors Smad2/3), indicating that miR-224 expression was regulated by TGF-beta1/Smads pathway. The ectopic expression of miR-224 can enhance TGF-beta1-induced GC proliferation through targeting Smad4. Inhibition of endogenous miR-224 partially suppressed GC proliferation induced by TGF-beta1. In addition, both miR-224 and TGF-beta1 can promote estradiol release from GC, at least in part, through increasing CYP19A1 mRNA levels. This is the first demonstration that miRNAs can control reproductive functions resulting in promoting TGF-beta1-induced GC proliferation and ovarian estrogen release. Such miRNA-mediated effects could be potentially used for regulation of reproductive processes or for treatment of reproductive disorders.


Quantitative Monte Carlo-based brain dopamine transporter SPECT imaging.
Brain dopamine transporter imaging with I-123-labeled radioligands is technically demanding due to the small size of the imaging target relative to the spatial resolution of most SPECT systems. In addition, I-123 has high-energy peaks which can penetrate or scatter in the collimator and be detected in the imaging energy window. The aim of this study was to implement Monte Carlo (MC)-based full collimator-detector response (CDR) compensation algorithm for I-123 into a third-party commercial SPECT reconstruction software package and to evaluate its effect on the quantitative accuracy of dopaminergic-image analysis compared to a method where only the geometric component of the CDR is compensated. In this work, we utilized a full Monte Carlo collimator-detector model and incorporated it into an iterative SPECT reconstruction algorithm. The full Monte Carlo model reconstruction was compared to standard reconstruction using an anthropomorphic striatal phantom filled with different I-123 striatal/cortex uptake ratios and with clinical I-123 Ioflupane DaTScan studies. Reconstruction with the full model yielded higher (13-25%) striatal uptake ratios than the conventional reconstruction, but the uptake ratios were still much lower than the true ratios due to partial volume effect. Visually, images reconstructed with the full Monte Carlo model had better contrast and resolution than the conventional images, with both phantom and patient studies. Reconstruction with full Monte Carlo collimator-detector model yields higher quantitative accuracy than conventional reconstruction. Additional work to reduce the partial volume effect related errors would improve the accuracy further.


Venous anatomy of the superficial circumflex iliac artery perforator flap: A cadaveric and clinical study.
Reconstructive surgeons frequently face challenges with free tissue transfer when transplanted flaps are thicker than intended. This is especially pronounced in lower limb cases, where the soft tissue below the knee is thin. The supra-fascial superficial circumflex iliac perforator (SCIP) flap overcomes this problem, but venous congestion remains a concern. We aim to examine the venous anatomy of the SCIP flap through cadaveric dissections and clinical data analyses to enhance the understanding of the venous anatomy and reduce venous congestion in future procedures. Eight cadaveric groins underwent venous dye injection and dissection to identify the superficial circumflex iliac vein (SCIV) and venae comitantes (VC) vascular networks. The venous anatomy was studied for dominant drainage. From April 2015 to December 2019, we conducted 102 SCIP flap reconstructions, mainly using the superficial circumflex iliac artery's superficial branch. Clinical data were analyzed and correlated with cadaveric dissections. SCIP flaps were categorized into three groups: dual drainage (VC and SCIV) in group I, SCIV-only in group II, and VC-only in group III. Correlations between clinical cases and cadaveric dissections revealed the SCIV as an independent drainage system with oscillating links to the VC. The SCIV is approximately twice the diameter of the VC, and the area of each vascular network suggests codominance. No significant difference in flap loss or venous congestion rates was noted when SCIV was the sole drainage, compared with VC or dual drainage. The SCIP flap with one artery and SCIV anastomosis, exhibits low venous congestion rates. Surgeons should consider SCIV for safe SCIP flap reconstruction.


Positive and negative interactions with health professionals: a qualitative investigation of the experiences of informal cancer carers.
Empathic and informative interactions with health professionals are important for the well-being of people with cancer. However, there is a dearth of research examining the construction and experience of interactions with health professionals from the perspective of informal cancer carers. The aim of this study was to explore how cancer carers subjectively position their experiences of interactions with health professionals, in particular, their construction of experiences as positive or negative, and the perceived consequences of such interactions. Positioning theory is used to examine how the sociomedical construction of health professionals shapes carers' experiences of interactions with them. Semistructured interviews were carried out with 53 informal cancer carers across a range of cancer types and stages, analyzed using thematic decomposition. Carers positioned positive interactions as those involving health professionals who were warm and genuine, accessible and approachable, and who made carers feel accepted and comfortable. In the case of allied health professionals, the provision of a space for carers' cathartic release was also constructed positively. Negative interactions were positioned as those involving poor communication and a lack of empathy, poor or absent information provision, and absence of guidance about additional support. Positive experiences with health professionals were positioned by carers as leading to feelings of empowerment, value, and recognition, and negative interactions as leading to distress, anger, frustration, and feelings of isolation. It is important for health professionals to be supportive of carers' needs, to communicate in an empathic manner, to be approachable and accessible, and to recognize carers needs and concerns.


Institutional barriers to the orthopaedic clinician-scientist.
The clinician-scientist faces many career barriers that changes in medicine over the past two decades have accentuated. Political, socioeconomic, and cultural changes in medicine have increased financial pressures on physicians and hospitals, negatively impacting the ability of clinicians to pursue research activities. Examples of institutional barriers include pressure on physicians to increase clinical productivity to help offset rising costs and declining reimbursements, inadequate resources and structures to protect research time, a lack of consideration of the importance of spatial colocalization of interacting researchers and clinicians, insufficient focus on integrating clinician-scientists into research teams, and inadequate accessibility of administrative research infrastructure. Lack of mentorship and role models in orthopaedics also contributes to the barriers confronting the clinician-scientist. A number of steps could be taken by institutions to positively influence orthopaedic clinician-scientist career development. Creation of research teams in which orthopaedic clinician-scientists can collaborate effectively with other researchers is a critical step, as is providing protected time free of clinical responsibilities to be devoted to research. Increased attention to physical co-localization of the research activities of clinicians and scientists, and provision of research infrastructure at the department level are additional approaches that can be taken to ameliorate the institutional barriers to the orthopaedic clinician-scientist.


Household electricity access in Africa (2000-2013): Closing information gaps with model-based geostatistics.
Household electricity access data in Africa are scarce, particularly at the subnational level. We followed a model-based Geostatistics approach to produce maps of electricity access between 2000 and 2013 at a 5 km resolution. We collated data from 69 nationally representative household surveys conducted in Africa and incorporated nighttime lights imagery as well as land use and land cover data to produce maps of electricity access between 2000 and 2013. The information produced here can be an aid for understanding of how electricity access has changed in the region during this 14 year period. The resolution and the continental scale makes it possible to combine these data with other sources in applications in the socio-economic field, both at a local or regional level.


EPIDEMIOLOGIC EVALUATION OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 3B INFECTION IN AN AFRICAN ELEPHANT (LOXODONTA AFRICANA).
This epidemiologic study follows a 5-yr-old male African elephant ( Loxodonta africana ) during an episode of hemorrhagic disease (HD) due to elephant endotheliotropic herpesvirus 3B (EEHV3B) utilizing data from complete blood counts, electrophoresis and acute phase protein analysis, and polymerase chain reaction (PCR) of multiple body fluids during and after the clinical episode. The elephant presented with sudden onset of marked lethargy and inappetence followed by hypersalivation, hyperemia of the conjunctivae and focally on the tongue, and swellings on the head and ventrum. A moderate leukocytopenia with band neutrophilia, lymphopenia, monocytopenia, and thrombocytophilia was followed by a rise in all three cell types by day 10. Moderate increases in serum amyloid A and C-reactive protein were noted in the first weeks of illness. Conventional PCR of whole blood yielded a strong positive result for EEHV3B. Quantitative PCR revealed moderate viremia, which slowly returned to undetectable levels by day 35 of treatment. EEHV3B was shed in trunk wash samples starting at day 22 for 10 days at moderate levels, and then at low levels for up to 8.5 mo. All three female herd mates shed low levels of EEHV3B in trunk washes intermittently starting from day 28 of the calf's illness until over 7 mo afterward. The majority of saliva samples from the calf over the 8.5-mo period were also positive for EEHV3B. A subfraction of saliva samples from a female herdmate was positive from days 127-190 following disease onset in the calf. Four elephant gammaherpesviruses were detected sporadically from the calf and female herdmates during this same time period. Treatment was started at the onset of clinical signs and consisted of rectal and oral fluids and oral famciclovir. This is the first case of EEHV3B HD in an elephant species and the first thorough epidemiologic evaluation of EEHV HD in an African elephant.


Recent advances and uses of grape flavonoids as nutraceuticals.
Grape is one of the oldest fruit crops domesticated by humans. The numerous uses of grape in making wine, beverages, jelly, and other products, has made it one of the most economically important plants worldwide. The complex phytochemistry of the berry is characterized by a wide variety of compounds, most of which have been demonstrated to have therapeutic or health promoting properties. Among them, flavonoids are the most abundant and widely studied, and have enjoyed greater attention among grape researchers in the last century. Recent studies have shown that the beneficial health effects promoted by consumption of grape and grape products are attributed to the unique mix of polyphenolic compounds. As the largest group of grape polyphenols, flavonoids are the main candidates considered to have biological properties, including but not limited to antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, cardioprotective, neuroprotective, and hepatoprotective activities. Here, we discuss the recent scientific advances supporting the beneficial health qualities of grape and grape-derived products, mechanisms of their biological activity, bioavailability, and their uses as nutraceuticals. The advantages of modern plant cell based biotechnology as an alternative method for production of grape nutraceuticals and improvement of their health qualities are also discussed.


Clinical Management of Multiple Melanoma Brain Metastases: A Systematic Review.
The treatment of multiple brain metastases (MBM) from melanoma is controversial and includes surgical resection, stereotactic radiosurgery (SRS), and whole-brain radiation therapy (WBRT). Several new classes of agents have revolutionized the treatment of metastatic melanoma, allowing some subsets of patients to have long-term survival. Given this, management of MBM from melanoma is continually evolving. To review the current evidence regarding the treatment of MBM from melanoma. The PubMed database was searched using combinations of search terms and synonyms for melanoma, brain metastases, radiation, chemotherapy, immunotherapy, and targeted therapy published between January 1, 1995, and January 1, 2015. Articles were selected for inclusion on the basis of targeted keyword searches, manual review of bibliographies, and whether the article was a clinical trial, large observational study, or retrospective study focusing on melanoma brain metastases. Of 2243 articles initially identified, 110 were selected for full review. Of these, the most pertinent 73 articles were included. Patients with newly diagnosed MBM can be treated with various modalities, either alone or in combination. Level 1 evidence supports the use of SRS alone, WBRT, and SRS with WBRT. Although the addition of WBRT to SRS improves the overall brain relapse rate, WBRT has no significant impact on overall survival and has detrimental neurocognitive outcomes. Cytotoxic chemotherapy has largely been ineffective; targeted therapies and immunotherapies have been reported to have high response rates and deserve further attention in larger clinical trials. Further studies are needed to fully evaluate the efficacy of these novel regimens in combination with radiation therapy. At this time, the standard management for patients with MBM from melanoma includes SRS, WBRT, or a combination of both. Emerging data exist to support the notion that SRS in combination with targeted therapies or immune therapy may obviate the need for WBRT; prospective studies are required to fully evaluate the efficacy of these novel regimens in combination with radiation therapy.


Neurotransmitters: emerging targets in cancer.
Neurotransmitters are conventionally viewed as nerve-secreted substances that mediate the stimulatory or inhibitory neuronal functions through binding to their respective receptors. In the past decades, many novel discoveries come to light elucidating the regulatory roles of neurotransmitters in the physiological and pathological functions of tissues and organs. Notably, emerging data suggest that cancer cells take advantage of the neurotransmitters-initiated signaling pathway to activate uncontrolled proliferation and dissemination. In addition, neurotransmitters can affect immune cells and endothelial cells in the tumor microenvironment to promote tumor progression. Therefore, a better understanding of the mechanisms underlying neurotransmitter function in tumorigenesis, angiogenesis, and inflammation is expected to enable the development of the next generation of antitumor therapies. Here, we summarize the recent important studies on the different neurotransmitters, their respective receptors, target cells, as well as pro/antitumor activity of specific neurotransmitter/receptor axis in cancers and provide perspectives and insights regarding the rationales and strategies of targeting neurotransmitter system to cancer treatment.


Construction and Composition of the Squid Pen from Doryteuthis pealeii.
The pen, or gladius, of the squid is an internalized shell. It serves as a site of attachment for important muscle groups and as a protective barrier for the visceral organs. The pen's durability and flexibility are derived from its unique composition of chitin and protein. We report the characterization of the structure, development, and composition of pens from Doryteuthis pealeii. The nanofibrils of the polysaccharide β-chitin are arranged in an aligned configuration in only specific regions of the pen. Chitin is secreted early in development, enabling us to characterize the changes in pen morphology prior to hatching. The chitin and proteins are assembled in the shell sac surrounded by fluid that has a significantly different ionic composition from squid plasma. Two groups of proteins are associated with the pen: those on its surface and those embedded within the pen. Only 20 proteins are identified as embedded within the pen. Embedded proteins are classified into six groups, including chitin associated, protease, protease inhibitors, intracellular, extracellular matrix, and those that are unknown. The pen proteins share many conserved domains with proteins from other chitinous structures. We conclude that the pen is one of the least complex, load-bearing, chitin-rich structures currently known and is amenable to further studies to elucidate natural construction mechanisms using chitin and protein.


A novel approach for identifying causal models of complex diseases from family data.
Causal models including genetic factors are important for understanding the presentation mechanisms of complex diseases. Familial aggregation and segregation analyses based on polygenic threshold models have been the primary approach to fitting genetic models to the family data of complex diseases. In the current study, an advanced approach to obtaining appropriate causal models for complex diseases based on the sufficient component cause (SCC) model involving combinations of traditional genetics principles was proposed. The probabilities for the entire population, i.e., normal-normal, normal-disease, and disease-disease, were considered for each model for the appropriate handling of common complex diseases. The causal model in the current study included the genetic effects from single genes involving epistasis, complementary gene interactions, gene-environment interactions, and environmental effects. Bayesian inference using a Markov chain Monte Carlo algorithm (MCMC) was used to assess of the proportions of each component for a given population lifetime incidence. This approach is flexible, allowing both common and rare variants within a gene and across multiple genes. An application to schizophrenia data confirmed the complexity of the causal factors. An analysis of diabetes data demonstrated that environmental factors and gene-environment interactions are the main causal factors for type II diabetes. The proposed method is effective and useful for identifying causal models, which can accelerate the development of efficient strategies for identifying causal factors of complex diseases.


Epithelial inclusion cysts following radial keratotomy.
A 26-year old woman underwent radial keratotomy combined with concentric trephination (6.5 and 8 mm) six months prior to development of multiple epithelial inclusion cysts. A biopsy specimen from one enlarging cyst showed an absence of scarring in addition to the retention of epithelium within a radial incision wound. Adjacent keratocytes were abnormal and seemed to be undergoing degenerative changes. To our knowledge, this is the first report of a failure in corneal wound healing associated with microcystic degeneration of the epithelium following radial keratotomy.


Ab Initio Screening of Doped Mg(AlH4)2 Systems for Conversion-Type Lithium Storage.
In this work, we have explored the potential applications of pure and various doped Mg(AlH4)2 as Li-ion battery conversion electrode materials using density functional theory (DFT) calculations. Through the comparisons of the electrochemical specific capacity, the volume change, the average voltage, and the electronic bandgap, the Li-doped material is found to have a smaller bandgap and lower average voltage than the pure system. The theoretical specific capacity of the Li-doped material is 2547.64 mAhg-1 with a volume change of 3.76% involving the electrode conversion reaction. The underlying reason for property improvement has been analyzed by calculating the electronic structures. The strong hybridization between Lis-state with H s-state influences the performance of the doped material. This theoretical research is proposed to help the design and modification of better light-metal hydride materials for Li-ion battery conversion electrode applications.


Favorable prognostic role of tropomodulins in neuroblastoma.
Neuroblastoma is a pediatric tumor of the sympatoadrenal lineage of the neural crest characterized by high molecular and clinical heterogeneity, which are the main causes of the poor response to standard multimodal therapy. The identification of new and selective biomarkers is important to improve our knowledge on the mechanisms of neuroblastoma progression and to find the targets for innovative cancer therapies. This study identifies a positive correlation among tropomodulins (TMODs) proteins expression and neuroblastoma progression. TMODs bind the pointed end of actin filaments, regulate polymerization and depolymerization processes modifying actin cytoskeletal dynamic and influencing neuronal development processes. Expression levels of TMODs genes were analyzed in 17 datasets comprising different types of tumors, including neuroblastoma, and it was demonstrated that high levels of tropomodulin1 (TMOD1) and tropomodulin 2 (TMOD2) correlate positively with high survival probability and with favorable clinical and molecular characteristics. Functional studies on neuroblastoma cell lines, showed that TMOD1 knockin induced cell cycle arrest, cell proliferation arrest and a mature functional differentiation. TMOD1 overexpression was responsible for particular cell morphology and biochemical changes which directed cells towards a neuronal favorable differentiation profile. TMOD1 downregulation also induced cell proliferation arrest but caused the loss of mature cell differentiation and promoted the development of neuroendocrine cellular characteristics, delineating an aggressive and unfavorable tumor behavior. Overall, these data indicated that TMODs are favorable prognostic biomarkers in neuroblastoma and we believe that they could contribute to unravel a new pathophysiological mechanism of neuroblastoma resistance contributing to the design of personalized therapeutics opportunities.


Kisspeptin and Neurokinin B Signaling Network Underlies the Pubertal Increase in GnRH Release in Female Rhesus Monkeys.
Loss-of-function or inactivating mutations in the genes coding for kisspeptin and its receptor (KISS1R) or neurokinin B (NKB) and the NKB receptor (NK3R) in humans result in a delay in or the absence of puberty. However, precise mechanisms of kisspeptin and NKB signaling in the regulation of the pubertal increase in gonadotropin-releasing hormone (GnRH) release in primates are unknown. In this study, we conducted a series of experiments infusing agonists and antagonists of kisspeptin and NKB into the stalk-median eminence, where GnRH, kisspeptin, and NKB neuroterminal fibers are concentrated, and measuring GnRH release in prepubertal and pubertal female rhesus monkeys. Results indicate that (1) similar to those previously reported for GnRH stimulation by the KISS1R agonist (i.e., human kisspeptin-10), the NK3R agonist senktide stimulated GnRH release in a dose-responsive manner in both prepubertal and pubertal monkeys; (2) the senktide-induced GnRH release was blocked in the presence of the KISS1R antagonist peptide 234 in pubertal but not prepubertal monkeys; and (3) the kisspeptin-induced GnRH release was blocked in the presence of the NK3R antagonist SB222200 in the pubertal but not prepubertal monkeys. These results are interpreted to mean that although, in prepubertal female monkeys, kisspeptin and NKB signaling to GnRH release is independent, in pubertal female monkeys, a reciprocal signaling mechanism between kisspeptin and NKB neurons is established. We speculate that this cooperative mechanism by the kisspeptin and NKB network underlies the pubertal increase in GnRH release in female monkeys.


Occupational injuries and illnesses reported by zoo veterinarians in the United States.
A 14-page comprehensive survey was mailed to all 565 United States members of the American Association of Zoo Veterinarians to identify the frequency of physical injuries, radiation exposures, chemical exposures, allergic or irritant reactions, infections, and use of preventive measures, and 315 (55.8%) veterinarians responded. Significant findings include major animal-related injury (61.5%), back injury (55%), necropsy injury (44.1%), adverse formalin exposure (40.2%), animal allergy (32.2%), zoonotic infection (30.2%), and insect allergy (14.2%). We also found that gender, length of experience, and practice type affected the number and type of incidents encountered in practice. Females reported a higher rate of zoonotic infection, insect allergy, and adverse exposure to anesthetic gas, formalin, and disinfectants/sterilants. Zoo veterinarians with more years of experience were more likely to receive major animal-related injury and associated hospitalization, back injury, and lost work time associated with back injury. Full-time zoo veterinarians were more likely to report back injury and inadequate knowledge of occupational hazards. Results are compared with hazards reported by veterinarians working in other fields. The frequency of injuries reported demonstrates a greater need for comprehensive health and safety programs for zoo veterinarians.


Comparison of various methods of diagnosis of renal cystic masses.
Two hundred fifty patients with renal cystic masses were evaluated by several diagnostic modalities, including sonography, angiography, cystography, and cytology. This presentation demonstrates the relative advantages of these methods as well as their relative level of confidence and diagnostic accuracy. When the lesion fulfilled all of the sonographic criteria for a cyst, no further diagnostic evaluation was warranted. If sonographic criteria were not met, cyst aspiration appeared to be the most definitive procedure.


1.95 μm kHz-linewidth single-frequency fiber laser using self-developed heavily Tm3+-doped germanate glass fiber.
We demonstrated a kHz-linewidth single-frequency laser at 1.95 μm using the self-developed heavily Tm(3+)-doped single-mode germanate glass fiber with the net gain coefficient of 2.3 dB per centimeter. The maximum output power of the stable single longitudinal mode continuous wave laser is over 200 mW. The slope efficiency measured versus the absorbed pump power is 34.8%, the signal-to-noise ratio is higher than 68 dB and laser linewidth is less than 7 kHz. A wavelength-tuning from 1949.55 to 1951.23 nm was also demonstrated based on changing the tension on the fiber Bragg grating outside the cavity.


[Treatment of ulcerative colitis and familial polyposis].
Total colectomy with mucosal protectomy and ileal pouchoanal anastomosis (IPAA) is a promising surgical development for the treatment of ulcerative colitis and familial polyposis. It avoids the need for an ostomy to the exterior, removes all affected tissue and maintains reasonable bowel control by the anal sphincter. 58 patients who underwent IPAA (Group A) were compared with 40 who underwent total proctocolectomy with Kock's pouch (KP) or Brooke's ileostomy (BI), or ileorectostomy (Group B). The indications for surgery were intractable disease, recurrent acute colitis, nonresolving acute colitis, dysplasia, toxic megacolon, perforation, hemorrhage and malnutrition. In Groups A and B duration of operation was, respectively, 6.9 and 5 hours (p less than 0.001); postoperative complications were intestinal obstruction (8 cases versus 14, p less than 0.05), pelvic inflammation (4 vs 3), pouchitis (4 vs 2), and wound infection (3 vs 1). Additional complications in Group A were pouchovaginal fistula (2), and single cases of transient brachial plexus palsy, anastomal stenosis, and rectal prolapse. There were no sexual or urinary complications, no cases in which pouch resection was necessary, nor was there any postoperative mortality. Additional complications in Group B were pouchocutaneous fistula (3) and neurogenic bladder (1?). Among those with KP, there were 9 cases of nipple slippage and 2 cases needed total pouch resection. Among those with BI there were 3 cases of ileostomal prolapse. Mortality in Group B was 4. Total hospital stay in groups A and B, respectively, were 30 and 56 days (p less than 0.0005). Fecal output was 6.3 and 5.9 movements per day in Groups A and B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Proliferation patterns in a pig model of AV fistula stenosis: can we translate biology into novel therapies?
Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation failure for which there are currently no effective therapies. To understand the mechanisms involved, we have examined the pattern of cellular proliferation at different time points in a pig model of AVF stenosis. Immunohistochemical analysis of cellular proliferation was performed at 2, 7, 28, and 42 days. The distribution of cellular proliferation within the different layers of the vessel wall was also studied. An ANOVA analysis was used to identify differences between the magnitude of cellular proliferation at different time points and within different layers of the vessel wall. Adventitial proliferation occurred at 2 days and declined over time. Intimal and medial proliferation peaked at 7 days and then decreased over time. There was minimal proliferation in all three layers at the 28- and 42-day time points. An important finding was the presence of active myofibroblast proliferation within "neointimal buds" at the 7-day time point. Results suggest that there could be early adventitial activation, followed by a passage of these cells into the medial and intimal layers. These suggest that the application of perivascular antiproliferative (adventitial) therapies at the time of surgery could potentially reduce AVF maturation failure.


Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics.
Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.


Tick Saliva Protein Evasin-3 Allows for Visualization of Inflammation in Arteries through Interactions with CXC-Type Chemokines Deposited on Activated Endothelium.
Atherosclerosis is one of the leading causes of mortality in developed and developing countries. The onset of atherosclerosis development is accompanied by overexpression of several inflammatory chemokines. Neutralization of these chemokines by chemokine-binding agents attenuates atherosclerosis progression. Here, we studied structural binding features of the tick protein Evasin-3 to chemokine (C-X-C motif) ligand 1 (CXCL1). We showed that Evasin-3-bound CXCL1 is unable to activate the CXCR2 receptor, but retains affinity to glycosaminoglycans. This observation was exploited to detect inflammation by visualizing a group of closely related CXC-type chemokines deposited on cell walls in human endothelial cells and murine carotid arteries by a fluorescent Evasin-3 conjugate. This work highlights the applicability of tick-derived chemokine-binding conjugates as a platform for the development of new agents for inflammation imaging.


Microplastics in marine mussels, biological effects and human risk of intake: A case study in a multi-stressor environment.
This study documented seasonal levels of microplastics (MPs) and biomarkers (condition index, neurotoxicity, energy, oxidative stress) in mussels (Mytilus galloprovincialis), and water physico-chemical parameters in the Douro estuary (NE Atlantic coast), and estimated the human risk of MP intake (HRI) through mussels. Mussel stress was determined through the Integrated Biomarker Response (IBR). HRI was estimated from mussel MP concentrations and consumer habits. MPs were mainly micro-fibres (72 %) with varied chemical composition. Seasonal MP means (±SEM) in mussels ranged from 0.111 ± 0.044 (spring) to 0.312 ± 0.092 MPs/g (summer). Seasonal variations of mussel stress (IBR: 1.4 spring to 9.7 summer) and MP concentrations were not related. MeO-BDEs, PBDEs, temperature, salinity and other factors likely contributed to mussel stress variation. HRI ranged from 2438 to 2650 MPs/year. Compared to the literature, MP contamination in mussels is low, as well as the human risk of MP intake through their consumption.


Longitudinal evaluation of myocardial function in preterm infants with respiratory distress syndrome.
Preterm births and respiratory distress syndrome (RDS) are associated with pulmonary vascular disease and altered myocardial function. We serially assessed up to 1 year of age the effects of RDS on global and regional myocardial function of preterm infants, compared to preterm and term controls using conventional echocardiography parameters, tissue Doppler velocities and deformation analysis. A total of 120 infants (30 preterm [PT] with RDS, 30 PT controls without RDS, and 60 term controls) underwent conventional and tissue Doppler echocardiography within 72 hours of birth, at corrected term age for the preterm infants, at 1 month corrected, and at 1 year corrected age. At birth, compared to preterm and term controls, the PT-RDS group had decreased right ventricular (RV) long-axis function, systolic velocity, peak systolic strain, shorter pulmonary arterial acceleration time (PAAT), and lower ratio of PAAT to RV ejection time (PAAT:RVET). Preterm infants had left ventricular (LV) diastolic dysfunction at birth (lower early diastolic myocardial velocity, mitral E velocity, and mitral E:A ratio), and reduced long-axis systolic velocities and shortening. Differences between groups disappeared by 1 month corrected age, except PAAT:RVET which remained lower in the PT-RDS group. At 1 year, RV function was normal in PT-RDS apart from systolic strain rate, and LV function was normal apart from lower stroke volume and shortening, relative to body weight. PT-RDS had lower left and right ventricular systolic and diastolic function at birth which improved over time, suggesting postnatal maturation of cardiac function and resolution of lung disease.


A combined inelastic neutron scattering and simulation study of the 3He@C60 endofullerene.
The 3He@C60 endofullerene consists of a single 3He atom entrapped inside a C60 fullerene cage. The confining potential, arising from the non-covalent interaction between the enclosed He atom and the C atoms of the cage, is investigated by inelastic neutron scattering. These measurements allow us to obtain information in both energy (ω) and momentum (Q) transfers in the form of the dynamical structure factor S (Q, ω). Simulations of the S (Q, ω) maps are performed for a spherical anharmonic oscillator model. Good agreement between the experimental and simulated data sets is achieved.


The origin of the Japanese race based on genetic markers of immunoglobulin G.
This review addresses the distribution of genetic markers of immunoglobulin G (Gm) among 130 Mongoloid populations in the world. These markers allowed the populations to be clearly divided into 2 groups, the northern and southern groups. The northern group is characterized by high frequencies of 2 marker genes, ag and ab3st, and an extremely low frequency of the marker gene afb1b3; and the southern group, in contrast, is indicated by a remarkably high frequency of afb1b3 and low frequencies of ag and ab3st. Based on the geographical distribution of the markers and gene flow of Gm ag and ab3st (northern Mongoloid marker genes) from northeast Asia to the Japanese archipelago, the Japanese population belongs basically to the northern Mongoloid group and is thus suggested to have originated in northeast Asia, most likely in the Baikal area of Siberia.


MicroRNA and Their Potential Role in Conjunctival Disorders.
MicroRNAs (miRNAs) are the small noncoding RNA molecules which regulate target gene expression posttranscriptionally. They are known to regulate key cellular processes like inflammation, cell differentiation, cell proliferation, and cell apoptosis across various ocular diseases. Due to their easier access, recent focus has been laid on the investigation of miRNA expression and their involvement in several conjunctival diseases. The aim of this narrative review is to provide understanding of the miRNAs and describe the current role of miRNAs as the mediators of the various conjunctival diseases. A literature search was made using PubMed, Scopus, and Web of Science databases for studies involving miRNAs in the conjunctival pathological conditions. Original articles in the last 10 years involving both human and animal models were included. Literature search retrieved 27 studies matching our criteria. Pertaining to the numerous literatures, there is a strong correlation between miRNA and the various pathological conditions that occur in the conjunctiva. miRNAs are involved in various physiological processes such as cell differentiation, proliferation, apoptosis, development, and inflammation by regulating various signaling pathways, genes, proteins, and mediators. Pterygium was the most studied conjunctival disease for miRNA involvement, whereas miRNA research in allergic conjunctivitis is still in its early stages. Our review provides deep insights into the various miRNAs playing an important role in the various conjunctival diseases. miRNAs do have the potential to serve as noninvasive biomarkers with diagnostic, prognostic, and therapeutic implications. However, multitudinous studies are required to validate miRNAs as the reliable biomarkers in conjunctival pathologies and its targeted therapy.


Outcomes of Deceased Donor Kidney Offers to Patients at the Top of the Waiting List.
Transplant centers may accept or refuse deceased-donor kidneys that are offered to their patients at the top of the waiting list. We sought to determine the outcomes of deceased-donor kidney offers and their association with characteristics of waitlisted patients and organ donors. We examined all 7 million deceased-donor adult kidney offers in the United States from 2007 to 2012 that led to eventual transplantation. Data were obtained from the national organ allocation system through the United Network of Organ Sharing. The study cohort consisted of 178,625 patients waitlisted for a deceased-donor kidney transplant and 31,230 deceased donors. We evaluated offers made to waitlisted patients and their outcomes (transplantation or specific reason for refusal). Deceased-donor kidneys were offered a median of seven times before being accepted for transplantation. The most common reasons for refusal of an offer were donor-related factors, e.g., age or organ quality (3.2 million offers, 45.0%), and transplant center bypass, e.g., minimal acceptance criteria not met (3.2 million offers, 44.0%). After adjustment for characteristics of waitlisted patients, organ donors, and transplant centers, male (odds ratio [OR], 0.93; 95% confidence interval [95% CI], 0.91 to 0.95) and Hispanic (OR, 0.96; 95% CI, 0.93 to 0.99) waitlisted patients were less likely to have an offer accepted than female and white patients, respectively. The likelihood of offer acceptance varied greatly across transplant centers (interquartile ratio, 2.28). Transplant centers frequently refuse deceased-donor kidneys. Such refusals differ by patient and donor characteristics, may contribute to disparities in access to transplantation, and vary greatly across transplant centers. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_07_27_Huml.mp3.


Phenotypic selection on floral traits in an urban landscape.
Native species are increasingly living in urban landscapes associated with abiotic and biotic changes that may influence patterns of phenotypic selection. However, measures of selection in urban and non-urban environments, and exploration of the mechanisms associated with such changes, are uncommon. Plant-animal interactions have played a central role in the evolution of flowering plants and are sensitive to changes in the urban landscape, and thus provide opportunities to explore how urban environments modify selection. We evaluated patterns of phenotypic selection on the floral and resistance traits of Gelsemium sempervirens in urban and non-urban sites. The urban landscape had increased florivory and decreased pollen receipt, but showed only modest differences in patterns of selection. Directional selection for one trait, larger floral display size, was stronger in urban compared to non-urban sites. Neither quadratic nor correlational selection significantly differed between urban and non-urban sites. Pollination was associated with selection for larger floral display size in urban compared to non-urban sites, due to the differences in the translation of pollination into seeds rather than pollinator selectivity. Thus, our data suggest that urban landscapes may not result in sweeping differences in phenotypic selection but rather modest differences for some traits, potentially mediated by species interactions.


Hypothalamic corticotropin-releasing hormone is a mediator of the anorexigenic effect of leptin.
Leptin, ob gene product, inhibits feeding behavior and stimulates energy expenditure in rodents. Corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY), which act in the hypothalamus to influence energy homeostasis, may mediate the anorexic effect of leptin. The present studies were undertaken to examine the possible involvement of hypothalamic CRH in the anorexigenic action of leptin in male Wistar rats. Recombinant leptin (2 microg/rat), microinjected into the third ventricle, inhibited food intake at 2 h by 33.3% (P < 0.01) in rats that were deprived of food for 18 h. The intracerebroventricular injection of 2 microg leptin also increased hypothalamic CRH content (P < 0.05) at 2 h after its administration. Simultaneous intracerebroventricular administration of 5 microg/rat alpha-helical CRH 9-41 (alpha-hCRH), a CRH antagonist, with 2 microg/rat leptin attenuated the anorexic effect of leptin by 2 h. In contrast, single intracerebroventricular injection of alpha-hCRH did not affect food consumption in food-deprived rats. These results implicate hypothalamic CRH as an important mediator of the anorexic effect of leptin in food-deprived rats.


Structural evaluation of a novel pro-apoptotic peptide coupled to CNGRC tumor homing sequence by NMR.
Hunter-killer peptides (HKPs) are synthetic peptides that target specific cell types for apoptosis. These studies report functional and structural characteristics of HKP9, an hunter-killer peptide that specifically targets tumor vasculature with a new apoptotic sequence. Vesicle leakage experiments were performed as a model for membrane perturbing activity. Placement of the homing sequence reduces both cell toxicity and vesicle leakage activity. NMR studies elucidate the conformation and orientation of HKP9 in micelles. The positively charged end of the HKP9 killing sequence is solvent exposed; however, the central portion of the peptide is helical and buried in dodecylphosphorylcholine micelles. The homing sequence is less solvent exposed than in a previously reported tumor-homing peptide. The results suggest that solvent accessibility of the homing sequence should be considered in design of future peptides.


Neuropathic pain symptoms relative to overall pain rating.
The influence of sensory symptoms on overall simple pain ratings in neuropathic pain is not well understood. The goal of this study was to determine this relationship by using the Neuropathic Pain Questionnaire (NPQ) and Neuropathic Pain Scale (NPS) in patients who had neuropathic pain. Overall pain intensity ratings were assessed by means of Average and Worst Pain ratings from the Brief Pain Inventory. Ongoing average pain was rated as 5.7 and worst pain as 7.7 on 0 to 10 scale, and it was present in 96% of patients, whereas symptoms that are commonly studied in the laboratory, such as increased pain due to touch and due to heat, were much less frequent (64% and 38%, respectively). Worst pain was most highly correlated with shooting, stabbing, and distress symptom complex, which was in contrast to Average pain, which was most highly correlated with symptom complex consisting of a large number of items. Analysis of conceptually related thermal heat sensation types of pain, spontaneous "burning" pain and the evoked pain "increased due to heat," showed that spontaneous burning pain was reported at much higher frequency and intensity than the evoked increased pain due to heat. There was no statistically significant difference between descriptors from NPS and NPQ among subgroups of neuropathic pain, such as polyneuropathy, radiculopathy, or posttraumatic neuralgia, but this could be in part due to relatively small number of patients in these subgroups of neuropathic pain. Quantitative analysis, as performed in this study, is one of the steps in developing an approach for elucidating the relationship between neuropathic pain symptoms and underlying mechanisms. Assessment of neuropathic pain symptoms by means of specifically designed questionnaires provides significant insight into patients' pain experience, including pain overall, which is under many influences. Further research of this type can contribute to advances in mechanism-based diagnosis and treatment.


Highly photostable nanogels for fluorescence-based theranostics.
A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability. The fluorescent nanogels display excellent biodegradability and cytocompatibility owed to the facile synthesis scheme involving a solvent-and surfactant-free one-pot reaction, derived entirely from biocompatible monomers citric acid, maleic acid, L-cysteine, and poly(ethylene glycol). The resultant nanogels are less than 200 nm in diameter with a narrow size distribution and monodispersity, and demonstrate long-term structural stability in biological buffer for two weeks. To gauge potential in theranostic applications, the fluorescent nanogels were surface functionalized with biologically active RGD peptides and encapsulated with active anti-cancer drug Doxorubicin, resulting in a pH-responsive controlled drug release in acidic pH resembling tumor environments. The strong fluorescence of the nanogels enabled tracking of targeted drug delivery, showing that drug-loaded nanogels homed into the cytoplasmic regions of prostate cancer cells to significantly induce cell death. These photo-crosslinkable and biodegradable nanogels pose as a strong candidate for theranostic medicine, demonstrating versatile functionalization, high stability in biological buffers, and capacity for real-time fluorescence-based monitoring of targeted drug delivery.


PlcRa, a new quorum-sensing regulator from Bacillus cereus, plays a role in oxidative stress responses and cysteine metabolism in stationary phase.
We characterized a new quorum-sensing regulator, PlcRa, which is present in various members of the B. cereus group and identified a signaling heptapeptide for PlcRa activity: PapRa(7). We demonstrated that PlcRa is a 3D structural paralog of PlcR using sequence analysis and homology modeling. A comparison of the transcriptomes at the onset of stationary phase of a ΔplcRa mutant and the wild-type B. cereus ATCC 14579 strain showed that 68 genes were upregulated and 49 genes were downregulated in the ΔplcRa mutant strain (>3-fold change). Genes involved in the cysteine metabolism (putative CymR regulon) were downregulated in the ΔplcRa mutant strain. We focused on the gene with the largest difference in expression level between the two conditions, which encoded -AbrB2- a new regulator of the AbrB family. We demonstrated that purified PlcRa bound specifically to the abrB2 promoter in the presence of synthetic PapRa(7), in an electrophoretic mobility shift assay. We further showed that the AbrB2 regulator controlled the expression of the yrrT operon involved in methionine to cysteine conversion. We found that the ΔplcRa mutant strain was more sensitive to hydrogen peroxide- and disulfide-induced stresses than the wild type. When cystine was added to the culture of the ΔplcRa mutant, challenged with hydrogen peroxide, growth inhibition was abolished. In conclusion, we identified a new RNPP transcriptional regulator in B. cereus that activated the oxidative stress response and cysteine metabolism in transition state cells.


Prehospital emergency care training practices regarding lesbian, gay, bisexual, and transgender patients in Maryland (USA).
Prehospital Emergency Medical Services (EMS) providers are expected to treat all patients the same, regardless of race, gender identity, sexual orientation, or religion. Some EMS personnel who are poorly trained in working with lesbian, gay, bisexual, and transgender (LGBT) patients are at risk for managing such patients incompletely and possibly incorrectly. During emergency situations, such mistreatment has meant the difference between life and death. An anonymous survey was electronically distributed to EMS educational program directors in Maryland (USA). The survey asked participants if their program included training cultural sensitivity, and if so, by what modalities. Specific questions then focused on information about LGBT education, as well as related topics, that they, as program directors, would want included in an online training module. A total of 20 programs met inclusion criteria for the study, and 16 (80%) of these programs completed the survey. All but one program (15, 94%) included cultural sensitivity training. One-third (6, 38%) of the programs reported already teaching LGBT-related issues specifically. Three-quarters of the programs that responded (12, 75%) were willing to include LGBT-related material into their curriculum. All programs (16, 100%) identified specific aspects of LGBT-related emergency health issues they would be interested in having included in an educational module. Most EMS educational program directors in Maryland are receptive to including LGBT-specific education into their curricula. The information gathered in this survey may help guide the development of a short, self-contained, open-access module for EMS educational programs. Further research, on a broader scale and with greater geographic sampling, is needed to assess the practices of EMS educators on a national level.


Endoscopic endonasal management of medial orbital blowout fractures.
This study demonstrated that endoscopic endonasal sinus surgery is a successful technique for reducing medial orbital blowout fractures and does not cause complications. Twenty-three patients with isolated medial blowout fractures that did not involve the inferior wall underwent reduction surgery using the endoscopic endonasal approach. Surgery was indicated if the patient experienced persistent diplopia, ocular motility limitation, or enophthalmos. Septoplasty and submucous resection of the inferior turbinate bone were performed to access the fracture site safely in 3 and 15 patients, respectively. The bone fragments entrapping the orbital content or adhesions between the orbital contents and the sinus mucosa were dissected carefully from the fracture site. An ophthalmologist used the eye traction test to verify improvement in ocular motility. A temporary Silastic sheet was applied in three patients, but no permanent supporting material was used in any patient. No surgical or late complications were seen. Preoperative symptoms were resolved in 22 of the 23 (95.5%) patients 6 months after surgery. We concluded that the endoscopic endonasal reduction based on endoscopic endonasal sinus surgery techniques is safe, accurate, and an appropriate surgical intervention for medial orbital blowout fractures.


Toward Efficient Deep Learning for Graph Drawing (DL4GD).
Due to their great performance in many challenges, Deep Learning (DL) techniques keep gaining popularity in many fields. They have been adapted to process graph data structures to solve various complicated tasks such as graph classification and edge prediction. Eventually, they reached the Graph Drawing (GD) task. This paper is an extended version of the previously published (DNN)2 and presents a framework to leverage DL techniques for graph drawing (DL4GD). We demonstrate how it is possible to train a Deep Learning model to extract features from a graph and project them into a graph layout. The method proposes to leverage efficient Convolutional Neural Networks, adapting them to graphs using Graph Convolutions. The graph layout projection is learned by optimizing a cost function that does not require any ground truth layout, as opposed to prior work. This paper also proposes an implementation and benchmark of the framework to study its sensitivity to certain deep learning-related conditions. As the field is novel, and many questions remain to be answered, we do not focus on finding the most optimal implementation of the method, but rather contribute toward a better understanding of the approach potential. More precisely, we study different learning strategies relative to the models training datasets. Finally, we discuss the main advantages and limitations of DL4GD.


Psychiatric disorders revealing multiple sclerosis after 20 years of evolvement.
Previous research indicates that the onset of psychiatric disorders is sometimes associated with multiple sclerosis (MS) evolving several years later. However, information on why this might occur, and on the outcomes of such patients, is still lacking. We aim to discuss these limitations with the current paper. We describe a 51-year-old female who demonstrated severe anxiety disorder and depression years before developing MS neurological symptoms. The patient was treated for these psychiatric disorders over 20 years. In the last 3 years of her treatment, the patient demonstrated a choreic-type of movement disorder in all her limbs. This disorder is consistent with relapsing-remitting MS. Clinical and magnetic resonance imaging (MRI) examinations demonstrated aspects of MS, without MS being diagnosed conclusively. The visual evoked potential indicated a diagnosis of conduction abnormalities. The established diagnosis was slow relapsing MS. The patient underwent methylprednisolone bolus (1 g/day). This case-study suggests that health professionals should conduct a full neurological assessment when they find atypical psychiatric symptoms in a patient. This would make sure that patients receive a better standard of care, and thus experience a better quality of life.


Isolation and characterization of microsatellite markers from the marine isopods Serolis paradoxa and Septemserolis septemcarinata (Crustacea: Peracarida).
This study reports the successful isolation of highly informative microsatellite marker sets for two marine serolid isopod species. For Serolis paradoxa (Fabricius, 1775), 13, and for Septemserolis septemcarinata (Miers, 1875), eight polymorphic microsatellite markers were isolated using the reporter genome enrichment protocol. The number of alleles per locus (N(A) ) and the observed heterozygosity (H(O) ) encompass a wide range of variation within S. paradoxa (N(A) 3-31, H(O) 6-89%) and S. septemcarinata (N(A) 2-18, H(O) 9-94%). The suitability of the newly isolated markers for population genetic studies is evaluated.


Proficient manipulation of fibreoptic bronchoscope to carina by novices on first clinical attempt after specialized bench practice.
Proficient manipulation of the fibreoptic bronchoscope is an important component of competent bronchoscopic airway management. We studied the duration of specialized bench training necessary to achieve this proficiency and the subsequent transfer of this psychomotor skill to human subjects. Twenty-nine novice endoscopists undertook the training associated with a commercial non-anatomic endoscopic dexterity training system, Dexter. Bronchoscopic driving performance was assessed after each hour of self-directed training, using a global rating scale from 1 (unskilled) to 5 (expert) with a score of 3 linked to proficiency. The scale was applied to anonymized recordings of the endoscopic view as the bronchoscope was manipulated from the mouth to the carina of an anatomic manikin. Once bench proficiency was achieved, the ability of participants to perform the skill on volunteer co-participants was assessed. Ninety-six per cent of participants achieved proficiency on the manikin within 4 h of practice. Ninety-three per cent then drove the bronchoscope proficiently from the mouth to the carina of clinical volunteers on the first attempt. The endoscopic dexterity required to proficiently drive a bronchoscope in human subjects to an anatomic endpoint relevant to fibreoptic intubation is achievable after 2-4 h of specialized bench training. Training in the local environment may be more conducive to success than in time-limited workshops. Achieving a defined proficiency standard on bench models contributes to the development of basic bronchoscopic competence. This has the potential to protect patients from novice learning curves, optimize clinical education and efficiency, and assist compliance with difficult airway algorithms.


Robust Graphene/Poly(vinyl alcohol) Janus Aerogels with a Hierarchical Architecture for Highly Efficient Switchable Separation of Oil/Water Emulsions.
Given the complexity and diversity of actual oily sewages, developing multifunctional separation materials with features of high separation efficiency and low energy consumption for separating diverse oil/water emulsions is urgently needed, yet it remains a formidable challenge till now. Herein, a superior graphene/poly(vinyl alcohol) Janus aerogel (J-CGPA), showing an intriguing three-dimensional (3D) hierarchical architecture (a dense skin-layer and a larger internal cell network) and desirable asymmetric wettability, was exploited via a simple direct freeze-shaping technique and subsequent mussel-inspired hydrophilic modification. Benefiting from the controlled unilateral decoration of dopamine, the resultant aerogels displayed completely opposite superwettability on two antithetic sides, i.e., one side is highly hydrophobic (water contact angle (WCA), 143°), whereas the other side is superhydrophilic. On the basis of the favorable 3D hierarchical structure and binary cooperative superwetting properties, the Janus aerogels achieved a remarkable switchable separation performance for both highly emulsified oil-in-water and water-in-oil emulsions as well as stratified oil/water mixtures accompanied with outstanding separation efficiencies. Particularly, an ultrahigh permeation flux of 1306 L m-2 h-1 along with a high rejection efficiency of 99.7% was acquired solely under the driving of gravity (<1 kPa), which is 1-2 order of magnitude higher than that of pioneering two-dimensional Janus polymeric/inorganic membranes recently reported. Moreover, together with robust reusability, this novel 3D Janus aerogel indicates a promising practical application for high-performance oily wastewater remediation.


Managing abandoned farmland: the need to link biological and sociological aspects.
The lack of a particular use associated with abandoned farmland provides real opportunities with respect to the various land-use pressures occurring in productive territories. These environments remain generally poorly known and, because of this, require in-depth studies on the feasibility of management options, on biological as well as social grounds. This study, based on research on the biophysical potential and the perceptions by the owners of abandoned farmlands, analyzes the feasibility of silvicultural management options to improve forestry potential. Using a questionnaire, we surveyed abandoned farmland owners on different aspects of the status of their abandoned farmland in order to determine their willingness toward the management of these private lands. The land owners were also asked to express their interests and their constraints toward various types of interventions, with an emphasis on silvicultural work. The data were analyzed using multivariate methods to establish relationships between the questionnaire data and the characteristics of the land owners (socioeconomic profile and value system toward the environment). The results show that, in general, abandoned farmland is an unwanted space, is generally little used, is poorly known, and has little importance in the plans of its owners. We have found three types of owner profiles; the owners with a farmer's profile are those who are the most interested in managing their abandoned farmland, whether for agriculture or silviculture. The desire to improve abandoned farmland seems less important to owners with an ecocentric profile (high awareness of the environment) and to older owners. Finally, by associating the type of abandoned farmland owned and the characteristics of the owners, it is possible to propose different management options that reconcile the wishes of the owners as well as the biophysical potential of their abandoned farmland.


Effect of centrifugation on water recycling and algal growth to enable algae biodiesel production.
The latest research shows that algal biofuels, at the production levels mandated in the Energy Independence and Security Act of 2007, will place significant demands on water and compete with agriculture meant for food production. Thus, there is a great need to recycle water while producing algal biofuels. This study shows that when using a synthetic medium, soluble algal products, bacteria, and other inhibitors can be removed by centrifugation and enable water recycling. Average water recovery reached 84% and water could be recycled at least 10 times without reducing algal growth.


Probing the HIV-1 NCp7 Nucleocapsid Protein with Site-Specific Gold(I)-Phosphine Complexes.
In this work, we examined a series of thiophilic Au(I) compounds based on [Au(L)(PR3)] (L = Cl-, 4-dimethylaminopyridine (dmap); R= ethyl (Et), cyclohexyl (Cy)) for chemoselective auration of the C-terminal HIV nucleocapsid protein NCp7 F2 and the "full" HIV NCp7 (NC, zinc finger (ZnF)) as probes of nucleocapsid topography. The choice of phosphine allowed electronic and steric effects to be considered. The use of the heterocycle "leaving group" allowed us to study the effect of possible π-stacking with the essential tryptophan residue of NC on the reactivity and selectivity, mimicking the naturally occurring interaction between the zinc finger and nucleic acids. We also examined for comparison the "standard" gold-phosphine compound auranofin, which contains an S-bound glucose coordinated to the {Au(PEt3)} moiety. Both the nature of the phosphine and the nature of L affect the reactivity with the C-terminal NCp7 F2 and the "full" NC. 31P NMR spectroscopy showed the formation of long-lived {Au(PR3)}-ZnF species in all cases, but in the case of NCp7 F2, a selective interaction in the presence of the dmap ligand was observed. In the case of auranofin, an unusual Au-His (rather than Au-Cys) coordination was indicated on NC. The overall results suggest that it is useful to consider three aspects of zinc finger structure in considering the profile of chemical reactivity: (i) the zinc-bound cysteines as primary nucleophiles; (ii) the zinc-bound histidine as a "spectator" ligand; and (iii) ancillary groups not bound to Zn but essential for ZnF function such as the essential tryptophan in NCp7 F2 and NC. Modification of fully functional NC zinc finger by the Cy3P-containing species confirmed the inhibition of the NC-SL2 DNA interaction, as evaluated by fluorescence polarization.


Effects of Silica Coating by Physical Vapor Deposition and Repeated Firing on the Low-Temperature Degradation and Flexural Strength of a Zirconia Ceramic.
To examine the application of physical vapor deposition (PVD) silica coating as an approach to retard low temperature degradation (LTD) for dental applications. Accelerated aging characteristics of heat- and surface-treated zirconia material were also investigated by exposing specimens to hydrothermal treatment. The specimens (90 disc-shaped specimens [15 mm ×1.2 mm]) were divided into 9 groups (n = 10) according to the test protocol: Ctrl, control (no surface treatment); Ag, autoclave aging; GrAg, grinding + aging; SiAg, silica coating + aging; GrSiAg, grinding + silica coating + aging; 3FAg, 3-time firing + aging; Gr3FAg, grinding + 3-time firing + aging; 5FAg, 5-time firing + aging; Gr5FAg, grinding + 5-time firing + aging. Accelerated aging was performed in a steam autoclave (134°C, 2 bars) for 12 hours. Following each treatment protocol, X-ray diffraction (XRD) analysis was used to estimate the relative amount of monoclinic phase and corresponding transformed zone depth (TZD). Additionally, a biaxial flexure test was used to calculate the flexural strength. Statistical analysis was conducted with one-way ANOVA and Fisher's LSD test (p < 0.05). The tetragonal-to-monoclinic transformation was retarded by PVD silica coating only on ground surfaces. Ground and heat-treated specimens exhibited the lowest monoclinic content after aging. The biaxial flexural strength value of the GrAg group was significantly higher than the values in all of the other groups except the SiAg group. The flexural strength value of the GrSiAg group was significantly higher than that of the 3FAg group. There was no statistically significant difference between the other groups (p > 0.05). Grinding decreased the susceptibility of zirconia to LTD and increased the flexural strength. PVD silica coating and repeated firing decreased the monoclinic content only in ground specimens during aging.