Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension.
Prenatal environment has been shown to modify adult blood pressure profile, but the underlying mechanisms are not well understood. The role of renal immune cell infiltration, oxidative stress, and nitric oxide bioavailability in the pathogenesis was investigated. Adult hypertension in rat offspring was induced by maternal low protein diet. Oxidative stress was determined by quantitative immunoblotting for nitrotyrosine, and T-cell and macrophage content by immunostaining, in offspring kidneys before and after the onset of hypertension. Nitric oxide metabolites (NOx) were measured in 24-hour urines. A group of offspring was treated with the immunosuppressive drug mycophenolate mofetil (MMF) to reduce inflammation, or with the superoxide dismutase mimetic Tempol to reduce oxidative stress, for a 3-week period before the onset of hypertension. During the prehypertensive stage, at 4 weeks of age, the low protein diet pups exhibited an increase in kidney nitrotyrosine content and in number of immune cells, both of which persisted in untreated animals after hypertension was established, at 8 weeks of age. Urine NOx was increased at 4 weeks and unchanged at 8 weeks of age. Both MMF and Tempol treatment prevented the immune cell infiltration, the increase in kidney nitrotyrosine abundance, and the development of hypertension. The effect on blood pressure persisted throughout the 4- to 10-week observation period after discontinuation of the treatments. Renal oxidative stress and infiltrating immune cells may play a pathogenetic role in prenatally programmed hypertension. Nitric oxide bioavailability does not appear impaired.


Biological correlates before esophageal cancer screening and after diagnosis.
Almost 50% of the world's esophageal cancer (EC) cases occur in China, and the impact of cancer screening has long been a controversial topic. The study was designed to evaluate the biological correlates of EC screening and subsequent diagnosis in China. Based on the national cohort of esophageal cancer program, a prospective multicenter study in high-risk regions was conducted from 2017 to 2019. 61 participants received twice esophageal endoscopy screening and pathological biopsy successively (with a mean follow-up of 14.03 months). Box-Cox-power transformation and two-way repeated measures ANOVA were used to evaluate hormone cortisol and immunoglobulin (IgA, IgG, IgM) levels in plasma, reflecting their stress, immune function, and biological correlates before screening and after knowing the diagnosis. The median of cortisol, IgA, IgG, and IgM in pre-screening was 15.46 ug/dL, 1.86 g/L, 12.14 g/L, and 0.91 g/L, corresponding value at post-diagnosis was 15.30 ug/dL, 2.00 g/L, 12.79 g/L, and 0.94 g/L, respectively. No significant differences in biological indicators were found between normal and esophagitis and low-grade intraepithelial neoplasia before screening and after diagnosis. After normality transformation, cortisol, IgA, IgG and IgM levels were (0.25 ± 0.04) U/mL, (0.72 ± 0.13) (g/L), (2.44 ± 0.22) (g/L) and (0.98 ± 0.25) (g/L) before screening, (0.25 ± 0.05) U/mL, (0.70 ± 0.13) (g/L), (2.48 ± 0.21) (g/L) and (1.00 ± 0.25) (g/L) after diagnosis, respectively. Repeated Measures ANOVA showed that the main effects were significant on IgA levels between pre-screening and post-diagnosis (P = 0.019). No interaction effects on biological levels between pre-post screening and esophageal pathology, anxiety states (all P > 0.05). Little biological correlates were found both before screening and after diagnosis. Cortisol and IgA dropped less significantly, while IgM and IgA were increased slightly after diagnosis. Further multi-round longitudinal studies are needed to validate these results.


Sulfuric Acid-Catalyzed Dehydratization of Carbohydrates for the Production of Adhesive Precursors.
Carbohydrates and hexose-derived 5-hydroxymethylfurfural (5-HMF) are platform chemicals for the synthesis of sustainable binders. New, greener approaches aim at the development of production systems, which minimize process steps and avoid organic solvents or other auxiliaries that could interfere with subsequent resin synthesis. In our work, carbohydrate solutions rich in 5-hydroxymethylfurfural (5-HMF) were produced using a continuous-flow microreactor and diluted H2SO4 as the catalyst. After optimization of the process conditions (temperature, reaction time, catalyst content), a 5-HMF yield of 49% was obtained at a low reaction time of 0.6 min and a catalyst concentration of 1% at 175 °C and 17 bar pressure. Extensive rehydration of the product was avoided by efficient immediate cooling of the reaction solution. The stability of the reaction system was improved by increasing the inner diameter of the capillary in the flow reactor to 2 mm. Advantageously, the obtained reaction mixtures are used directly as precursors in the development of sustainable binder systems, without the need of additional purification, filtration, or extraction steps.


Teenage Mothers Today: What We Know and How It Matters.
Over the past two decades, births to U.S. teenagers have fallen and no longer follow overall fertility patterns. Yet the unique challenges faced by teenage mothers and their families justify continued research. Across disciplines, newer work has furthered our understanding of teenage motherhood today. In this article, I highlight four areas of progress: processes of selection into teenage motherhood, the broader consequences of teenage childbearing beyond the socioeconomic realm, heterogeneity of effects, and the application of life course principles. Emerging societal trends such as complex family structures, a stalled recovery from the recession for families of low socioeconomic status, and a rapidly evolving political environment for reproductive health care continue to challenge the lives of teenage mothers. Given that the consequences for teenagers of becoming mothers may change, continued research is needed. Shifts in policy to favor supporting teenage mothers and addressing the causes of both teenage pregnancy and social disadvantage may help improve the lives of these mothers and their families.


Pediatric pseudotumor cerebri.
Although PTC most frequently occurs in obese females of childbearing age, the syndrome occurs in children as well.(3),(5) Prepubertal children with PTC have a lower incidence of obesity compared with adults and there is no sex predilection. The onset of puberty is best defined by the onset of secondary sexual characteristics such has menarche, pubic hair, and breast development. Children with PTC have a higher incidence of associated conditions and cranial nerve deficits compared with adults. Similar to adult patients, children are at risk for the development of permanent visual loss. In rare instances, children initially diagnosed with PTC will be found to harbor an intracranial neoplasm such as gliomatosis cerebri. An intracranial pressure of 28 cm H2O has recently been established as the upper limit of normal in children.31 Treatment is indicated for the symptomatic management of headaches and to preserve vision. Most children respond to medications such as acetazolamide, furosemide, or topiramate. Surgical treatment such as ONSF and shunting procedures are indicated for children with severe headaches, visual loss, or both despite maximal tolerated medical treatment.


Voxel-based investigations of regional cerebral blood flow abnormalities in Alzheimer's disease using a single-detector SPECT system.
To evaluate the feasibility of using the Statistical Parametric Mapping (SPM) program for an automated, voxel-by-voxel assessment of regional cerebral blood flow (rCBF) deficits in Alzheimer's disease (AD) subjects relative to age-matched controls studied with a conventional, single-detector SPECT system. We used a databank of 99mTc-HMPAO images of 19 patients with a diagnosis of probable AD and 15 elderly healthy volunteers; data were acquired using an Orbiter-Siemens single-detector SPECT system. Using SPM, images were transformed spatially, smoothed (12mm), and the data were compared on a voxel-by-voxel basis with t-tests. There were significant rCBF reductions in AD patients relative to controls involving regions predicted a priori to be affected in AD, namely the left temporal and parietal neocortices, and the right posterior cingulate gyrus (p<0.05, corrected for multiple comparisons). The location of rCBF reductions in AD subjects in our study is consistent with the deficits detected in previous functional imaging studies of AD using higher-resolution devices. This suggests the potential usefulness of using SPM for the analysis of data acquired with single-detector SPECT systems, despite the limited sensitivity and spatial resolution of such equipment.


Three-dimensional changes in lymphatic architecture around VX2 tongue cancer--dynamics of growth of cancer.
Many questions remain regarding the mechanism of cervical lymph node metastasis via lymphatic vessels. We report here the three-dimensional dynamics of the lymphatic architecture around tumor during growth of implanted VX2 tongue cancer. The tongue and the deep cervical lymph nodes of rabbits were observed at 3, 7 and 10 days after transplantation of VX2 cancer cells (n = 5 in each group). Lymph node metastasis was confirmed histopathologically. Morphological changes of the collecting lymphatic vessels and lymphatic capillaries were observed, and the number and diameter of these lymphatic vessels were measured within 500 microns around the tumor using the combined method of 5'-nucleotidase (5'-Nase) staining and three-dimensional reconstruction imaging. The VX2 cells were uniformly detected in cervical lymph nodes of each rabbit of the 10-day group. The number of lymphatic capillaries and the diameters of collecting lymphatic vessels around the tumor in the 7- and 10-day groups were greater than in the 3-day group. These capillaries arose by sprouting from preexisting lymphatic vessels and showed a tree-like branching pattern. We conclude that the dynamics of the lymphatic architecture around the tumor, especially the increase in number of capillaries on preexisting lymphatic vessels outside the tumor margin, may be associated with lymph node metastasis.


Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142.
JBIR-141 (1) and JBIR-142 (2) were discovered as potent Foxo3a inhibitors that consist of three quite unique substructures, a 1-((dimethylamino)ethyl)-5-methyl-4,5-dihydrooxazole-4-carboxylic acid that is originated from Ala-Thr amino acid residues, a 3-acetoxy-4-amino-7-(hydroxy(nitroso)amino)-2,2-dimethylheptanoic acid, and an α-acyl tetramic acid fused with a 2-methylpropan-1-ol moiety. Their structures involving absolute configurations were determined by spectroscopic data, chemical degradation, anisotropy methods, and LC-MS analyses of diastereomeric derivatives. Compounds 1 and 2 exhibited specific inhibition against Foxo3a transcriptional activity with IC50 values of 23.1 and 166.2 nM, respectively.


Molecular properties that influence the oral bioavailability of drug candidates.
Oral bioavailability measurements in rats for over 1100 drug candidates studied at SmithKline Beecham Pharmaceuticals (now GlaxoSmithKline) have allowed us to analyze the relative importance of molecular properties considered to influence that drug property. Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count (sum of donors and acceptors) are found to be important predictors of good oral bioavailability, independent of molecular weight. That on average both the number of rotatable bonds and polar surface area or hydrogen bond count tend to increase with molecular weight may in part explain the success of the molecular weight parameter in predicting oral bioavailability. The commonly applied molecular weight cutoff at 500 does not itself significantly separate compounds with poor oral bioavailability from those with acceptable values in this extensive data set. Our observations suggest that compounds which meet only the two criteria of (1) 10 or fewer rotatable bonds and (2) polar surface area equal to or less than 140 A(2) (or 12 or fewer H-bond donors and acceptors) will have a high probability of good oral bioavailability in the rat. Data sets for the artificial membrane permeation rate and for clearance in the rat were also examined. Reduced polar surface area correlates better with increased permeation rate than does lipophilicity (C log P), and increased rotatable bond count has a negative effect on the permeation rate. A threshold permeation rate is a prerequisite of oral bioavailability. The rotatable bond count does not correlate with the data examined here for the in vivo clearance rate in the rat.


Mitogen-activated protein kinases (MAPK) as predictors of clinical outcome in serous ovarian carcinoma in effusions.
The objective was to investigate the expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and high-osmolarity glycerol response kinase (p38), their role in the biology of ovarian carcinoma, and their correlation with chemotherapy response. Sixty-four fresh-frozen effusions from patients diagnosed with serous ovarian carcinoma were studied using immunoblotting. Results were analyzed for possible association with expression of proliferation and apoptosis markers, patient age, disease stage, tumor grade, histological grade, chemotherapy status, and survival. p38 level correlated with younger age (P = 0.004), while that of JNK correlated with better tumor differentiation (P = 0.009). Higher expression of Pan-JNK (P = 0.018) and higher p-ERK activity (P = 0.014) were seen in postchemotherapy specimens, specifically related to treatment by platinum agents. pan-JNK expression was higher in specimens treated with both platinum agents (P = 0.038) and paclitaxel (P = 0.033). In univariate survival analysis, the level of pan-ERK (P = 0.002), pan-JNK (P = 0.045), and pan-p38 (P = 0.016), as well as p-ERK activity (P = 0.014) correlated with better overall survival. In Cox multivariate survival analysis, pan-ERK (P = 0.001), pan-p38 (P = 0.017), and p-ERK (P = 0.041) retained their predictive value. Our results present the first evidence of in vivo involvement of MAPKs in the clinical course of ovarian cancer and the possible effect of chemotherapy on intracellular signaling in this disease. The improved prognosis associated with expression and phosphorylation of all three mitogen-activated protein kinase families highlights the unique properties of cancer cells in effusions and may expand our understanding of the biology of ovarian carcinoma at this site, possibly affecting treatment strategies for this malignancy.


Marital relations among former prisoners of war: contribution of posttraumatic stress disorder, aggression, and sexual satisfaction.
In this study, the authors examined the marital adjustment, spousal aggression, and sexual satisfaction of prisoners of war (POWs) 3 decades after their release. More specifically, the authors examined the extent to which impaired marital relations among former POWs are an outcome of their captivity or of the posttraumatic stress disorder (PTSD) that some of them developed. The authors compared 25 former POWs with PTSD, 85 former POWs without PTSD, and 104 control veterans. The findings reveal that the marital problems of former POWs are more related to PTSD than to their captivity. PTSD is related to decreased marital satisfaction, increased verbal aggression, and heightened sexual dissatisfaction among former POWs.


Lateral flagella of Aeromonas species are essential for epithelial cell adherence and biofilm formation.
Mesophilic Aeromonas strains express a single polar flagellum in all culture conditions and produce lateral flagella on solid media. Such hyperflagellated cells demonstrate increased adherence. Nine lateral flagella genes, lafA-U for Aeromonas hydrophila, and four Aeromonas caviae genes, lafA1, lafA2, lafB and fliU, were isolated. Mutant characterization, nucleotide and N-terminal sequencing demonstrated that the A. hydrophila and A. caviae lateral flagellins were almost identical, but were distinct from their polar flagellum counterparts. The aeromonad lateral flagellins exhibited higher molecular masses on SDS-PAGE, and this aberrant migration was thought to result from post-translational modification through glycosylation. Mutation of the Aeromonas lafB, lafS or both A. caviae lateral flagellins caused the loss of lateral flagella and a reduction in adherence and biofilm formation. Mutations in lafA1, lafA2, fliU or lafT resulted in strains that expressed lateral flagella, but had reduced adherence levels. Mutation of the lateral flagella loci did not affect polar flagellum synthesis, but the polarity of the transposon insertions on the A. hydrophila lafTlU genes resulted in non-motility. However, mutations that abolished polar flagellum production also inhibited lateral flagella expression. We conclude that Aeromonas lateral flagella: (i) play a role in adherence and biofilm formation; (ii) are distinct from the polar flagellum; (iii) synthesis is dependent upon the presence of a polar flagellum filament; and (iv) that the motor proteins of the polar and lateral flagella systems appear to be shared.


Verification of organic feed identity by fatty acid fingerprinting.
The origin and authenticity of feed for laying hens is an important and fraud-susceptible aspect in the production of organic eggs. Chemical fingerprinting in combination with chemometric methods is increasingly used in conjunction with administrative controls to verify and safeguard the authenticity of food commodities. On the basis of fatty acid fingerprinting data of 36 organic and 60 conventional feeds, we have developed a chemometric classification model to discriminate between organic and conventional chicken feed. A two-factor partial least squares-discriminant analysis (PLS-DA) model was developed using 70% of the original data. External validation of the model with the remaining 30% of the data showed that all of the organic feeds and 90% of the conventional feeds (18 of 20) were correctly identified by the model. These results indicate that the PLS-DA model developed in this study could be routinely used to verify the identity of unknown or suspicious feed for laying hens.


Comparison of the Auditec and Rintelmann recordings of the NU-6.
Word discrimination scores were obtained for 30 normally hearing listeners using Auditec and Rintelmann recordings of the NU-6 presented at 60 and 70 dB SPL in quiet and in a background of multitalker noise at signal-to-noise (S/N) ratios of +12, +6, 0, and -6 dB. This was done to obtain normative data and to determine whether these two recordings of the same word lists were equivalent at conversational levels in quiet and in a noisy background. The word discrimination scores for each recording in quiet and at each S/N ratio were not significantly different when presented at 60 and 70 dB SPL. However, the word discrimination scores were significantly poorer as the S/N ratio became more severe, and the scores obtained with the Auditec recording were significantly poorer than those obtained with the Rintelmann recording at each S/N ratio. These differences between word discrimination scores using the Auditec and Rintelmann recordings were primarily attributed to the recorded level of the test word and secondarily attributed to carrier phrase and talker differences.


Observed inequality in urban greenspace exposure in China.
Given the important role of green environments playing in healthy cities, the inequality in urban greenspace exposure has aroused growing attentions. However, few comparative studies are available to quantify this phenomenon for cities with different population sizes across a country, especially for those in the developing world. Besides, commonly used inequality measures are always hindered by the conceptual simplification without accounting for human mobility in greenspace exposure assessments. To fill this knowledge gap, we leverage multi-source geospatial big data and a modified assessment framework to evaluate the inequality in urban greenspace exposure for 303 cities in China. Our findings reveal that the majority of Chinese cities are facing high inequality in greenspace exposure, with 207 cities having a Gini index larger than 0.6. Driven by the spatiotemporal variability of human distribution, the magnitude of inequality varies over different times of the day. We also find that exposure inequality is correlated with low greenspace provision with a statistical significance (p-value < 0.05). The inadequate provision may result from various factors, such as dry cold climate and urbanization patterns. Our study provides evidence and insights for central and local governments in China to implement more effective and sustainable greening programs adjusted to different local circumstances and incorporate the public participatory engagement to achieve a real balance between greenspace supply and demand for developing healthy cities.


Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure - United States, August 2018.
Zika virus infection can occur as a result of mosquitoborne or sexual transmission of the virus. Infection during pregnancy is a cause of fetal brain abnormalities and other serious birth defects (1,2). CDC has updated the interim guidance for men with possible Zika virus exposure who 1) are planning to conceive with their partner, or 2) want to prevent sexual transmission of Zika virus at any time (3). CDC now recommends that men with possible Zika virus exposure who are planning to conceive with their partner wait for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) before engaging in unprotected sex. CDC now also recommends that for couples who are not trying to conceive, men can consider using condoms or abstaining from sex for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) to minimize their risk for sexual transmission of Zika virus. All other guidance for Zika virus remains unchanged. The definition of possible Zika virus exposure remains unchanged and includes travel to or residence in an area with risk for Zika virus transmission (https://wwwnc.cdc.gov/travel/page/world-map-areas-with-zika) or sex without a condom with a partner who traveled to or lives in an area with risk for Zika virus transmission. CDC will continue to update recommendations as new information becomes available.


Saying 'No' to PrEP research in Malawi: what constitutes 'failure' in offshored HIV prevention research?
Between 2004 and 2005, the first multi-sited clinical trial tested whether an existing, marketed antiretroviral drug, Tenofovir (TDF), could prevent HIV transmission. Referred to as pre-exposure prophylaxis (PrEP), most of these trial sites prematurely closed down. Two sites located in Cambodia and Cameroon received international media attention. But little attention was drawn to sites in Malawi and Nigeria, where university ethicists and research scientists extensively debated PrEP. This article focuses on events that took place in Malawi where there was a prolonged dispute over the scientific rationales of PrEP and not trial specific ethics referred to as 'bioethics'. Specifically, the article discusses debates pertaining to three PrEP trial protocols that were refused ethics approval in Malawi between 2004 and 2009. It is argued that HIV science debates in Malawi are embedded in postcolonial politics--geopolitical histories and state and household economic dispossessions that have created the structural possibilities for Malawi to become an offshore destination for HIV clinical research. As such, ethics in this case does not pertain to trial or bioethical 'failures'. Rather, ethics is located at the scale of imperial relations that give rise to multiple, often invisible, research concerns and constraints.


The Persistent Issue of Simulator Sickness in Naval Aviation Training.
Virtual simulations offer nearly unlimited training potential for naval aviation due to the wide array of scenarios that can be simulated in a safe, reliable, and cost-effective environment. This versatility has created substantial interest in using existing and emerging virtual technology to enhance training scenarios. However, the virtual simulations themselves may hinder training initiatives by inducing simulator sickness among the trainees, which is a series of symptoms similar to motion sickness that can arise from simulator use. Simulator sickness has been a problem for military aviation since the first simulators were introduced. The problem has also persisted despite the increasing fidelity and sense of immersion offered by new generations of simulators. As such, it is essential to understand the various problems so that trainers can ensure the best possible use of the simulators. This review will examine simulator sickness as it pertains to naval aviation training. Topics include: the prevailing theories on why symptoms develop, methods of measurement, contributing factors, effects on training, effects when used shipboard, aftereffects, countermeasures, and recommendations for future research involving virtual simulations in an aviation training environment.Geyer DJ, Biggs AT. The persistent issue of simulator sickness in naval aviation training. Aerosp Med Hum Perform. 2018; 89(4):396-405.


Studies on luciferase from Photobacterium phosphoreum. VIII. FMN-H2O2 initiated bioluminescence and the thermodynamics of the elementary steps of the luciferase reaction.
Bacterial luciferase from Photobacterium phosohoreum was found to produce bioluminescence on reaction with FMN and H2O2 in the presence of aldehyde. This luminescence is presumably produced by the same X1 intermediate as that found in FMNH2-O2 initiated luminescence. From the ratio of the light intensities of the FMN-H2O2 initiated reactions, we calculated the association constant of the reaction, luciferase+FMN+H2O2in equilibriumX1, and estimated its temperature dependence. From these results we calculated the thermodynamic parameters of the reaction, luciferase+FMNH2+O2in equilibriumX1. We found that the free energy level of X1 is only 3.2 kcal below that of fr-e FMN and H2O2. We also estimated the thermodynamic parameters of other steps of the luminescent reaction. The values obtained showed that the formation of X1 from luciferase, FMNH2 and O2 involves a positive entropy change, but the intermediate is in a state stabilized against decomposition. Results also suggest a considerable degree of electronic rearrangement on formation of the excited-state molecule from the X1-aldehyde complex.


Bradykinin regulates cyclooxygenase-2 in rat renal thick ascending limb cells.
Cyclooxygenase-2 (COX-2) is constitutively expressed in a subset of thick ascending limb cells in the cortex and medulla and increases when the renin-angiotensin and kallikrein-kinin systems are activated. Although the contribution of angiotensin II to the regulation of COX-2 is known, the effects of bradykinin on COX-2 expression have not been determined in this nephron segment. We evaluated expression of B2 bradykinin receptors in thick ascending limb cells containing COX-2 and the effect of bradykinin on COX-2 expression in primary cultured medullary thick ascending cells. The presence of B2 receptors was studied in renal sections by immunohistochemistry with antibodies against B2, COX-2, and Tamm-Horsfall glycoprotein. B2 receptors were detected on the apical and basolateral portion of the thick ascending cells. These cells also contained COX-2, suggesting that COX-2 expression may be regulated via B2 receptor. Incubation of cultured medullary thick ascending cells with bradykinin (10(-7) to 10(-5) mol/L) induced a significant increase on COX-2 protein expression. Maximal expression of COX-2 was observed 4 hours after exposure to bradykinin (10(-7) mol/L), effect abolished by a B2 receptor antagonist (HOE-140; 10(-6) mol/L). Prostaglandin E2 production increased when these cells were challenged with bradykinin for 4 hours, indicating that COX-2 was enzymatically active. We have demonstrated (1) the presence of B2 receptors in thick ascending limb cells expressing COX-2 and (2) the stimulatory effect of bradykinin on COX-2 protein expression, via B2 receptors, in cultured medullary thick ascending cells. We suggest that bradykinin can affect ion transport in the thick ascending limb via a COX-2-mediated mechanism.


Lysobacter caeni sp. nov., isolated from the sludge of a pesticide manufacturing factory.
Strain BUT-8(T), a Gram-stain-negative, non-motile and rod-shaped aerobic bacterium, was isolated from the activated sludge of a herbicide-manufacturing wastewater treatment facility. Comparative 16S rRNA gene sequence analysis revealed that strain BUT-8(T) clustered with species of the genus Lysobacter and was closely related to Lysobacter ruishenii DSM 22393(T) (98.3 %) and Lysobacter daejeonensis KACC 11406(T) (98.7 %). The DNA G+C content of the genomic DNA was 70.6 mol%. The major respiratory quinone was ubiquinone-8, and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an aminolipid. The major cellular fatty acids were iso-C15 : 0, iso-C16 : 0, iso-C17 : 0, iso-C11 : 0, iso-C11 : 0 3OH and summed feature 9 (comprising iso-C17 : 1ω9c and/or C16 : 010-methyl). The DNA-DNA relatedness between strain BUT-8(T) and its closest phylogenetic neighbours was below 70 %. Phylogenetic, chemotaxonomic and phenotypic results clearly demonstrated that strain BUT-8(T) belongs to the genus Lysobacter and represents a novel species for which the name Lysobacter caeni sp. nov. is proposed. The type strain is BUT-8(T) ( = CCTCC AB 2013087(T) = KACC 17141(T)).


Fibrin glue aneurysm sac embolization at the time of endografting.
To describe the procedural details for primary prevention of type II endoleak with fibrin glue injection into the aneurysm sac at the time of endografting. After deployment of the main stent-graft component, the angiographic pigtail catheter is withdrawn, leaving the 0.035-inch standard guidewire between the endograft and the native aorta. Through a brachial-femoral arterial guidewire loop, an 11-cm-long, 6-F introducer is advanced over the wire into the contralateral iliac artery. After deployment of the contralateral iliac extension, a 23-cm, 5-F sheath is advanced over the wire into the aneurysm sac. The wire and vessel dilator are removed, leaving the cannula in the sac. To prevent distal embolization of the sealant, a balloon is inflated in the contralateral limb to secure it to the native vessel before 5 mL of fibrin sealant are injected into the sac via a double-syringe delivery system inserted through the sheath. The balloon is left in place for 1 minute after sealant injection. In 64 consecutive patients in whom this technique has been used, sac embolization has been successful. There have been no intraoperative complications or in-hospital mortality. Over a mean follow-up of 9.3+/-4.4 months (range 1-18), only 1 lumbar endoleak has been detected on surveillance imaging. This preventive strategy appears to be an effective approach and the best therapeutic choice for preventive management of type II endoleak.


Early diagnostics of temporomandibular joint structural elements injures caused by traumatic mandibular bone fractures.
A rapidly increasing number of mandibular condylar fractures and some complications related to injuries of temporomandibular elements make this study important. Intra-articular disorders lead to secondary pathological findings such as osteoarthritis, deforming osteoarthrosis, and temporomandibular joint ankylosis that limits mouth opening, mastication, swallowing, breathing, and decreased/lost working capacity or disability. Early diagnosis of intra-articular disorders can prevent from long-lasting functional complications caused by temporomandibular joint injuries. This study was performed for the purpose of early detection and investigation of organic pathological changes in the cartilaginous and osseous tissues of the temporomandibular joint caused by traumatic fractures of the mandibular condyle. Twenty patients underwent a general clinical examination, magnetic resonance imaging (MRI), and immune-enzyme testing for biochemical markers of connective tissue injury (pyridinoline and deoxypyridinoline) in urine. Disk dislocation, deformation, adhesion, perforation or squeeze, tension or disruption of ligaments, and injury of articular surfaces are among complications of mandibular fractures that can be revealed on MRI. As regards biochemical findings, we revealed a sharp rise in the levels of pyridinoline and deoxypyridinoline before treatment and a lack of stabilization within 21 days of treatment.


Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational study.
Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an emerging acute kidney injury (AKI) biomarker. We evaluated the performance of urinary TIMP-2 in an adult mixed ICU by comparison with other biomarkers that reflect several different pathways of AKI. In this study, we prospectively enrolled 98 adult critically ill patients who had been admitted to the adult mixed ICU. Urinary TIMP-2 and N-acetyl-β-D-glucosaminidase (NAG) and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and erythropoietin (EPO) were measured on ICU admission. We evaluated these biomarkers' capability of detecting AKI and its severity as determined by using the Kidney Disease Improving Global Outcomes serum creatinine criteria, as well as its capacity to predict in-hospital mortality. The impact of sepsis, the leading cause of AKI in ICUs, was also evaluated. We found AKI in 42 patients (42.9%). All biomarkers were significantly higher in AKI than in non-AKI. In total, 27 patients (27.6%) developed severe AKI. Urinary TIMP-2 was able to distinguish severe AKI from non-severe AKI with an area under the receiver operating characteristic curve (AUC-ROC) of 0.80 (95% confidence interval, 0.66 to 0.90). A total of 41 cases (41.8%) were complicated with sepsis. Although plasma NGAL and IL-6 were increased by sepsis, urinary TIMP-2 and NAG were increased not by sepsis, but by the presence of severe AKI. Plasma EPO was increased only by septic AKI. In-hospital mortality was 15.3% in this cohort. Urinary TIMP-2 and NAG, and plasma NGAL, were significantly higher in non-survivors than in survivors, although plasma IL-6 and EPO were not. Among the biomarkers, only urinary TIMP-2 was able to predict in-hospital mortality significantly better than serum creatinine. Urinary TIMP-2 can detect severe AKI with performance equivalent to plasma NGAL and urinary NAG, with an AUC-ROC value higher than 0.80. Furthermore, urinary TIMP-2 was associated with mortality. Sepsis appeared to have only a limited impact on urinary TIMP-2, in contrast to plasma NGAL.


Children with Metopic Ridge.
The premature closure of the metopic suture results in metopic synostosis, also known as trigonocephaly. However, there is a group of children who have only a frontal metopic ridge, obvious with inspection and fingertip palpation, without the clinical features of trigonocephaly. This study aims to report a group of children with metopic ridge with a special emphasis on the definition and the diagnostic features. Thirty-eight children with a diagnosis of metopic ridge were followed up with clinical examinations and photographs in the pediatric neurosurgery outpatient clinic between January 2010 and November 2015. Children were between 3 and 30 (mean=14) months of age at diagnosis. Twenty-five (65.8%) of the children were boys and 13 (34.2%) were girls. A midline metopic ridge without fronto-orbital trigonocephalic deformity was the only diagnostic criterion. The parents" concern about the metopic deformity at initial diagnosis was a common feature in every case. Seven (18.4%) of the children had a sibling with either metopic ridge (n=4) or trigonocephaly (n=3). None of the children had worsened or had received surgery in the follow-up period. The metopic ridge is a pathology of the metopic suture and is a concern for parents in the context of craniosynostosis. Radiological investigation and craniosynostosis surgery are unnecessary in children with a metopic ridge.This clinical entity may be considered the mildest form of metopic synostosis.


Compound heterozygosity for Hb S and Hb S-Oman: Case report.
The haematological and clinical findings of a three year old Omani girl, phenotypically compound heterozygote for Hb S and Hb S Oman, are presented, further substantiated by family studies. The necessity of reviewing cases with sickle cell haemoglobin in Oman is stressed.


Antibiotic-Resistant Salmonella in the Food Supply and the Potential Role of Antibiotic Alternatives for Control.
Salmonella enterica is one of the most ubiquitous enteropathogenic bacterial species on earth, and comprises more than 2500 serovars. Widely known for causing non-typhoidal foodborne infections (95%), and enteric (typhoid) fever in humans, Salmonella colonizes almost all warm- and cold-blooded animals, in addition to its extra-animal environmental strongholds. The last few decades have witnessed the emergence of highly virulent and antibiotic-resistant Salmonella, causing greater morbidity and mortality in humans. The emergence of several Salmonella serotypes resistant to multiple antibiotics in food animals underscores a significant food safety hazard. In this review, we discuss the various antibiotic-resistant Salmonella serotypes in food animals and the food supply, factors that contributed to their emergence, their antibiotic resistance mechanisms, the public health implications of their spread through the food supply, and the potential antibiotic alternatives for controlling them.


A near field optical image of a gold surface: a luminescence study.
This paper addresses recent experimental findings about luminescence of a gold tip in near-field interaction with a gold surface. Our electrochemically etched gold tips show a typical, intrinsic luminescence that we exploit to track the plasmon resonance modeled by a Lorentzian oscillator. Our experimental device is based on a spectrometer optically coupled to an atomic force microscope used in tuning fork mode. Our measurements provide evidence of a strong optical coupling between the tip and the surface. We demonstrate that this coupling strongly affects the luminescence (intensity, wavelength and FHWM) as a function of the tip position in 2D maps. The fluctuation of these parameters is directly related to the plasmonic properties of the gold surface and is used to qualify the optical near field enhancement (which subsequently plays the predominant role in surface enhanced spectroscopies) with a very high spatial resolution (typically around 20 nm). We compare these findings to the independently recorded near-field scattered elastic Rayleigh signal.


Lower urinary tract symptoms in men: self-perceptions and the concept of bother.
To explore the meaning that men attach to their experiences of having lower urinary tract symptoms (LUTS) and to understand 'bother' in the context of those meanings. Sixteen men with symptoms suggestive of LUTS and/or an enlarged prostate were recruited from the outpatient urology clinic of a London teaching hospital. They were assessed before or shortly after their first appointment, during which demographic information, including age, occupation, marital status and ethnicity, was obtained and an individualized repertory grid was completed. Each man also completed the International Prostate Symptom Score, which included an item measuring overall bother, and the Hospital Anxiety and Depression Scale. Most participants held very negative views about what it meant to have prostate problems and viewed them as being associated with old age. Nevertheless, they also had reasonably high levels of self-esteem. However, there was evidence that these had been higher before they had prostate problems, and that self-esteem might decline over time. Bother was related to symptom scores and to anxiety. Also, a perception that other people, particularly their partner, saw them in a more negative light because of their symptoms was associated with higher levels of bother. The findings suggest that men attempt to preserve a sense of a relatively youthful and intact 'self' in the face of advancing years and a progressive disease that was viewed as being associated with old age. Overall, these men had a reasonably secure self-image and they deployed a range of cognitive strategies to maintain this. Bother appears to be a combination of symptom severity, psychological distress, negative evaluations of the condition and beliefs about the reactions of others. Reducing anxiety and challenging negative stereotypes and expectations that others would view them negatively if their problems were known might reduce bother. Attending to these factors could enable watchful waiting to be optimized by reducing bother. Trials to evaluate interventions drawing on these principles would be valuable.


Dictyosome-like structures present in human testicular cells.
Dictyosome-like structures (DLS) are present in human spermatocytes and spermatids. They display morphological and developmental characteristics similar to those of other species that contain DLS.


Cognitive Change After Elective Surgery in Nondemented Older Adults.
The authors report the results of repeated cognitive function tests administered over 10 months to 82 patients between the ages of 55 and 82 who underwent elective surgery. The Mini-Mental State Exam (MMSE) score, 10 months after surgery, was modeled by a multivariate linear regression that included the baseline demographics, baseline cognitive functions, and immediate postoperative MMSE scores. Immediate postoperative MMSE scores were highly significant to 10-month postoperative MMSE scores not explained by baseline variables. The results suggest that immediate postoperative cognitive change may predict later postoperative cognitive decline.


Bond strength and interfacial morphology of two adhesive systems to deciduous dentin: in vitro study.
This study evaluated the bond strength and the interfacial morphology of composite restorations (SMP: Scotchbond Multi-Purpose - 3M; CSE: Clearfil SE Bond - Kuraray) in primary dentin. There is no statistical difference between groups. Fracture modes revealed a weak zone in the demineralized dentin (SMP) and in the hybrid layer (CSE). The interfacial morphology was similar in both groups. The demineralized zone in bond structures has a negative influence in adhesive restorations over the time.


Impact of rapid identification of positive blood cultures using the Verigene system on antibiotic prescriptions: A prospective study of community-onset bacteremia in a tertiary hospital in Japan.
Rapid identification of positive blood cultures is important for initiation of optimal treatment in septic patients. Effects of automated, microarray-based rapid identification systems on antibiotic prescription against community-onset bacteremia (COB) remain unclear. We prospectively enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission) over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram-negative bacteria (GN) in the same patient were counted separately. For GP bacteremia, patients with ≥2 sets of positive blood cultures were included. The primary study objective was evaluating the rates of antibiotic prescription changes within 2 days of rapid identification using the Verigene system. Bacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes, respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6% [95%CI:21.3-34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8-45.2%]) after conventional identification and susceptibility testing. Prescription changes after Verigene identification were more frequent in GP (17/41[41.5%]) than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by Verigene test, bacterial identification agreement between the two tests was high (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted targeted antimicrobial resistance. The durations between the initiation of incubation and reporting of the results for the Verigene system and conventional test was 28.3 h (IQR: 25.8-43.4 h) and 90.6 h (68.3-118.4 h), respectively. In only four of the seven episodes of COB in which two isolates were identified by conventional tests, the Verigene test correctly identified both organisms. We observed a high rate of antibiotic prescription changes after the Verigene test in a population with COB especially in GP. The Verigene test would be a useful tool in antimicrobial stewardship programs among patients with COB.


Preference for Averageness in Faces Does Not Generalize to Non-Human Primates.
Facial attractiveness is a long-standing topic of active study in both neuroscience and social science, motivated by its positive social consequences. Over the past few decades, it has been established that averageness is a major factor influencing judgments of facial attractiveness in humans. Non-human primates share similar social behaviors as well as neural mechanisms related to face processing with humans. However, it is unknown whether monkeys, like humans, also find particular faces attractive and, if so, which kind of facial traits they prefer. To address these questions, we investigated the effect of averageness on preferences for faces in monkeys. We tested three adult male rhesus macaques using a visual paired comparison (VPC) task, in which they viewed pairs of faces (both individual faces, or one individual face and one average face); viewing time was used as a measure of preference. We did find that monkeys looked longer at certain individual faces than others. However, unlike humans, monkeys did not prefer the average face over individual faces. In fact, the more the individual face differed from the average face, the longer the monkeys looked at it, indicating that the average face likely plays a role in face recognition rather than in judgments of facial attractiveness: in models of face recognition, the average face operates as the norm against which individual faces are compared and recognized. Taken together, our study suggests that the preference for averageness in faces does not generalize to non-human primates.


Monoclonal antibodies recognizing epitopes of calretinins: dependence on Ca2+-binding status and differences in antigen accessibility in colon cancer cells.
Monoclonal antibodies are very helpful tools to investigate the localization and sometimes even the function of specific proteins in cells and tissues. By generating monoclonal antibodies against calretinin-22k (CR-22k), a C-terminally truncated isoform of calretinin (CR) as a result of alternative splicing of the CR mRNA, we envisaged that screening multiple monoclonal antibodies would allow the identification of CR-22k as well as CR. Both proteins share the first 178 amino acids, but have different C-termini. All three antibodies 10C10, 6B3 and 2H4 recognize recombinant CR-22k and the specificity to also recognize CR was demonstrated in brain extracts of different species and human tumour cells, which express CR. All monoclonal antibodies did not crossreact with the closely related protein calbindin D-28k. Antibody binding was depending on the Ca2+-binding status of both forms of calretinin. Generally, the Ca2+-bound form was better recognized than the Ca2+-free form. Carboxy- and amino-terminally truncated CR proteins were expressed in E. coli in order to characterize the epitopes recognized by the three antibodies. Additionally, tryptic and cyanogen bromide fragments were produced to further narrow down the sequences recognized by the three antibodies. 10C10 recognizes an epitope consisting of the linker region between EF-hand domains I and II and the N-terminal part of EF-hand II, while the others (6B3, 2H4) bind to a region including the linker between EF-hand domains III and IV. These antibodies are valuable tools to further investigate the distribution and eventually the specific function of these two proteins in the nervous tissue and under pathological conditions, e.g. in colon tumours and mesotheliomas.


Frontal sinus mucopyelocele with orbital and intracranial extension.
This case report discusses a 52-year-old lady with nonaxial proptosis, diplopia and diminution of vision due to a mass lesion in the upper medial quadrant of the orbit. A computed tomography scan revealed a well-defined lesion in the frontal sinus area with orbital and intracranial extension. On exploring it was found to be a mucopyelocele of the frontal sinus. Surgical excision was done by an external approach. The symptoms and signs resolved completely within a week. Frontal sinus mucopyeloceles are benign and curable, and their early recognition and management is of paramount importance, because they can expand and cause orbital as well as intracranial complications.


Simulation of potassium extraction by continuous haemodiafiltration.
Prediction of potassium extraction rates by continuous haemodiafiltration (CHDF) is useful for safe management of potassium levels in patients with hyperkalaemia. For this purpose, we developed a formula to predict the quantity of potassium extracted by CHDF. We hypothesized that potassium concentration in efflux dialysate was completely saturated by the influx blood, and potassium concentration in efflux blood was calculated based on this hypothesis. To check the accuracy of the calculation, potassium concentration was measured in efflux blood, and values were compared to predicted concentrations. Predicted potassium concentrations demonstrated good correlation to the measured values (95% confidence range, -0.32 to 0.58 mmol/l). These results confirmed that our hypothesis is applicable to clinical use of CHDF. Based on our observations, we created a formula to accurately predict the amount of potassium (dK) extracted by CHDF: dK=(Cb-Cd)xQd+CbxQf-CsxQs (Cb: plasma potassium concentration; Cd: potassium concentration in a dialysate; Cs: potassium concentration in the replacement fluid; Qd: dialysis rate; Qf: filtration rate and Qs: infusion rate of replacement fluid).


First-principles investigation of exchange interactions in quasi-one-dimensional antiferromagnet CaV2O4.
The effects of orbital degrees of freedom on the exchange interactions in a quasi-one-dimensional spin-1 antiferromagnet CaV2O4 are systematically studied. For this purpose a realistic low-energy electron model with the parameters derived from the first-principles calculations is constructed in the Wannier basis for the t2g bands. The exchange interactions are calculated using both the theory of infinitesimal spin rotations near the mean-field ground state and the superexchange model, which provide a consistent description. The obtained behaviour of exchange interactions differs substantially from the previously proposed phenomenological picture based on magnetic measurements and structural considerations, namely: (i) despite the quasi-one-dimensional character of the crystal structure, consisting of the zigzag chains of the edge-sharing VO6 octahedra, the electronic structure is essentially three-dimensional, that leads to finite interactions between the chains; (ii) the exchange interactions along the legs of the chains appear to dominate; and (iii) there is a substantial difference in exchange interactions in two crystallographically inequivalent chains. The combination of these three factors successfully reproduces the behaviour of experimental magnetic susceptibility.


Desmoplastic ameloblastoma.
Desmoplastic ameloblastoma is a relatively rare variety of ameloblastoma and only very few cases have been reported so far. The present case is an elderly man who had reported with a swelling in the anterior mandible which turned up to be desmoplastic ameloblastoma. Proper diagnosis is necessary to report such a case, so that the actual incidence can be noted.


Enhanced recovery of Salmonella from apple cider and apple juice with universal preenrichment broth.
A comparison was made of the relative efficiencies of Universal Preenrichment (UP) broth and lactose broth for the recovery of a variety of Salmonella serovars from pasteurized and unpasteurized apple cider and pasteurized apple juice. Bulk portions of juice were contaminated with single Salmonella serovars at high and low levels of 0.4 and 0.04 CFU/mL, respectively. The juice was aged for a minimum of 5 days at 2-5 degrees C. On the day analysis was initiated, each of 20 test portions (25 mL) of the contaminated juice was preenriched in UP broth and in lactose broth. The Bacteriological Analytical Manual Salmonella culture method was followed thereafter. For pasteurized apple cider, UP broth recovered significantly (p < 0.05) more Salmonella-positive test portions than did lactose broth (112 and 75, respectively). For unpasteurized apple cider, UP broth recovered significantly more Salmonella-positive test portions than did lactose broth (326 and 221, respectively). For pasteurized apple juice, UP broth recovered more Salmonella-positive test portions than did lactose broth (93 and 81, respectively). However, this difference was not statistically significant. These results indicate that UP broth should replace lactose broth for the analysis of pasteurized and unpasteurized apple cider and pasteurized apple juice.


Na3V2(PO4)3@C as Faradaic Electrodes in Capacitive Deionization for High-Performance Desalination.
Among various desalination technologies, capacitive deionization (CDI) has rapidly developed because of its low energy consumption and environmental compatibility, among other factors. Traditional CDI stores ions within the electric double layers (EDLs) in the nanopores of the carbon electrode, but carbon anode oxidation, the co-ion expulsion effect, and a low salt adsorption capacity (SAC) block its further application. Herein, the Faradaic-based electrode is proposed to overcome the above limitations, offering an ultrahigh adsorption capacity and a rapid removal rate. In this paper, the open framework structure Na3V2(PO4)3@C is applied for the first time as a novel Faradaic electrode in the hybrid capacitive deionization (HCDI) system. During the adsorption and desorption process, sodium ions are intercalated/deintercalated through the crystal structure of Na3V2(PO4)3@C while chloride ions are physically trapped or released by the AC electrode. Different concentrations of feedwater are investigated, and a high SAC of 137.20 mg NaCl g-1 NVP@C and low energy consumption of 2.157 kg-NaCl kWh-1 are observed at a constant voltage of 1.0 V, a concentration of 100 mM, and a flow rate of 15 mL min-1. The outstanding performance of the Na3V2(PO4)3@C Faradaic electrode demonstrates that it is a promising material for desalination and that HCDI offers great future potential.


Integration of Homeopathy and Complementary Medicine in the Tuscan Public Health System and the Experience of the Homeopathic Clinic of the Lucca Hospital.
The healthcare programs of the Region of Tuscany (Italy) have started the process of integration of some types of complementary medicine (CM), including homeopathy, which began in 1996. The Homeopathic Clinic of Lucca was opened in 1998, followed by the Homeopathic Clinic for Women in 2003, and the Clinic for CM and Diet in Oncology in 2013. Observational longitudinal studies conducted on 5,877 patients (3,937 in the general clinic, 1,606 in the women's clinic and 334 in oncology) were consecutively examined from 2003 to 2016. The Outcome in Relation to Impact on Daily Living (ORIDL) was generally used to assess outcomes. Comparing the clinical conditions before and after homeopathic treatment, improvement was observed in 88.8% of general medicine patients with follow-up (45.1%); in particular, 68.1% of the patients had a major improvement in or resolution (ORIDL +2, +3, +4) of their condition. In women, an improvement was obtained in 74.1% cases and a major improvement in 61.2%. In cancer patients with homeopathic and integrative treatment, a significant improvement was observed for all the symptoms during anti-cancer therapy, particularly for hot flashes, nausea, depression, asthenia, and anxiety. These results suggest that homeopathy can effectively be integrated with allopathic medicine and that the Tuscan experience could provide a useful reference for developing national and European regulations on the use of CM and homeopathy in public healthcare.


The New Harvard Doctor of Public Health: Lessons From the Design and Implementation of an Innovative Program in Advanced Professional Leadership.
We documented lessons learned in the initial design and development of the new Harvard doctor of public health (DrPH) degree, an innovative professional public health doctorate designed to provide advanced education in the field of public health. Using data from program documents, personal participation in the development and administration of the degree, and initial students' results, we present key learnings from this experience and describe the program's goals and processes. Now entering its fifth year, the new Harvard DrPH program has enrolled about 70 students and graduated its first 2 classes in a program that combines advanced public health study with leadership development and field engagement. Development of this transformational innovation in advanced public health education required creative approaches to competency development and curriculum design, engagement of faculty to become supportive stakeholders, and substantial support for educational administration. Demand for a program of this type is strong. Continuous improvement is ongoing.


[Childhood blindness. VISION 2020 and experiences in an African city].
The struggle against childhood blindness is being given high priority by the WHO. In regions of the world countries where the income per head is low there are 5 times as many blind children as in wealthy countries (1.5/1000 vs 0.3/1000 children). In developing countries cataract is regarded as the main cause of blindness in both childhood and adulthood. If all cataracts that would lead to blindness were operated on, despite a comparatively smaller number of affected persons a similar number of sighted life-years could be achieved throughout the world to that for patients with senile cataract. The partnership between the Rostock Ophthalmological Department and St. Joseph's Hospital in Kinshasa focuses on the analysis and treatment of avoidable blindness in children. Its main concern is the introduction of appropriate procedures for cataract surgery, in most cases combined with the implantation of injectable synthetic intraocular lenses. In the last 7 years about 600 procedures have been jointly performed, including 400 of congenital cataract, mostly bilateral.


Functional analysis of clusterin/apolipoprotein J in cellular death induced by severe genotoxic stress.
Clusterin/apolipoprotein J (CLU) is a secreted heterodimeric glycoprotein that is reportedly upregulated during tumorigenesis, as well as during cell injury or death. Despite extensive efforts, CLU function during cellular death remains largely elusive. We are using as a model system to study CLU function three human osteosarcoma (OS) cell lines, namely, Sa OS, KH OS, and U-2 OS cells, induced to die after exposure to severe genotoxic stress mediated by the chemotherapeutic drug doxorubicin (DXR). We initially applied small interfering RNA (siRNA)-mediated specific knockdown of the CLU protein in OS cells. In all three cell lines, CLU knockdown resulted in increased sensitization to DXR-induced apoptosis. Supportively, moderate levels of forced transgene-mediated CLU stable overexpression in KH OS cells could rescue them from DXR-mediated apoptosis. In contrast, stable overexpression of high CLU levels in Sa OS and U-2 OS cells augmented apoptosis induced by cell exposure to severe DXR-mediated genotoxic stress. In summary, our data provide evidence that, although CLU is essential for cellular homeostasis, it may become highly cytotoxic in certain cellular contexts when it accumulates in high amounts intracellularly either by direct synthesis or by uptake from the extracellular milieu.


A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway.
The eukaryotic intra-S-phase checkpoint, which slows DNA synthesis in response to DNA damage, is poorly understood. Is DNA damage recognized directly, or indirectly through its effects on replication forks? Is the slowing of S phase in part because of competition between DNA synthesis and recombination/repair processes? The results of our genetic analyses of the intra-S-phase checkpoint in the fission yeast, Schizosaccharomyces pombe, suggest that the slowing of S phase depends weakly on the helicases Rqh1 and Srs2 but not on other recombination/repair pathways. The slowing of S phase depends strongly on the six checkpoint-Rad proteins, on Cds1, and on Rad4/Cut5 (similar to budding yeast Dpb11, which interacts with DNA polymerase epsilon) but not on Rhp9 (similar to budding yeast Rad9, necessary for direct damage recognition). These results suggest that, in fission yeast, the signal activating the intra-S-phase checkpoint is generated only when replication forks encounter DNA damage.


Increasing awareness with recognition of pulsatile tinnitus for nurse practitioners in the primary care setting: A case study.
Pulsatile tinnitus is a whooshing sound heard synchronous with the heartbeat. It is an uncommon symptom affecting fewer than 10% of patients with tinnitus. It often goes unrecognized in the primary care setting. Failure to recognize this symptom can result in a missed or delayed diagnosis of a potentially life-threatening condition known as a dural arteriovenous fistula. The purpose of this case study is to provide a structured approach to the identification of pulsatile tinnitus and provide management recommendations. A case study and review of pertinent literature. Pulsatile tinnitus usually has a vascular treatable cause. A comprehensive history and physical examination will alert the nurse practitioner (NP) when pulsatile tinnitus is present. Auscultation in specific areas of the head can detect audible or objective pulsatile tinnitus. Pulsatile tinnitus that is audible to the examiner is an urgent medical condition requiring immediate consultation and referral. Knowledge of pulsatile tinnitus and awareness of this often treatable condition directs the NP to perform a detailed assessment when patients present with tinnitus, directs appropriate referral for care and treatment, and can reduce the risk of delayed or missed diagnosis.


Strongyloides stercoralis: Global Distribution and Risk Factors.
The soil-transmitted threadworm, Strongyloides stercoralis, is one of the most neglected among the so-called neglected tropical diseases (NTDs). We reviewed studies of the last 20 years on S. stercoralis's global prevalence in general populations and risk groups. A literature search was performed in PubMed for articles published between January 1989 and October 2011. Articles presenting information on infection prevalence were included. A Bayesian meta-analysis was carried out to obtain country-specific prevalence estimates and to compare disease odds ratios in different risk groups taking into account the sensitivities of the diagnostic methods applied. A total of 354 studies from 78 countries were included for the prevalence calculations, 194 (62.4%) were community-based studies, 121 (34.2%) were hospital-based studies and 39 (11.0%) were studies on refugees and immigrants. World maps with country data are provided. In numerous African, Asian and South-American resource-poor countries, information on S. stercoralis is lacking. The meta-analysis showed an association between HIV-infection/alcoholism and S. stercoralis infection (OR: 2.17 BCI: 1.18-4.01; OR: 6.69; BCI: 1.47-33.8), respectively. Our findings show high infection prevalence rates in the general population in selected countries and geographical regions. S. stercoralis infection is prominent in several risk groups. Adequate information on the prevalence is still lacking from many countries. However, current information underscore that S. stercoralis must not be neglected. Further assessments in socio-economic and ecological settings are needed and integration into global helminth control is warranted.


The murdered child and his killers.
The authors studied 112 cases of child homicide in New York City in 1968-1969 to identify contributing social and psychiatric factors and to determine the fate of the surviving siblings and the degree of involvement of the city's social agencies with the families. There was a pattern of long-term familial child maltreatment extending to the siblings and continuing after the murders. The victims were usually illegitimate preschoolers; the assailants, usually the mothers or their paramours, had backgrounds of assaultiveness and social deviance and killed in impulsive rage. Reports of sexual abuse of victims or of suicide or psychosis among assailants were rare. The authors present case illustrations and offer guidelines for improved prevention by psychiatrists and social workers.


Mobile Health Initiatives to Improve Outcomes in Primary Prevention of Cardiovascular Disease.
Cardiovascular disease affects more than a third of American adults and is the leading cause of mortality in the USA. Over the last 40 years, several behavioral and medical risk factors have been recognized as major contributors to cardiovascular disease. Effective management of many of these risk factors, particularly behavioral risk factors, remains challenging. With the growth of mobile health (mHealth) technology, a variety of novel strategies are now available to facilitate the delivery of interventions directed at reducing these risk factors. In this review, we discuss recent clinical studies and technologic innovations leveraging smartphone devices, social media, and wearable health tracking devices to facilitate behavioral interventions directed at three important and highly prevalent behavioral risk factors for cardiovascular disease: smoking, physical inactivity, and sub-optimal nutrition. We believe this technology has significant potential to provide low-cost, scalable, and individualized tools to improve management of these important cardiovascular disease risk factors.


An electrochemical cell for the efficient turn around of wafer working electrodes.
We present a new design for an electrochemical cell for use with wafer working electrodes. The key feature of the design is the use of half turn thumb screws to form a liquid-tight seal between an o-ring and the sample surface. The assembly or disassembly of the cell requires a half turn of each thumb screw, which facilitates the quick turn around of wafer samples. The electrochemical performance of the cell is demonstrated by cyclic voltammetry and double step chronoamperometry measurements of the ferricyanide/ferrocyanide couple.


Preparation, electrochemical and spectral properties of N-methylated pyridylethynyl porphyrins.
A new series of electron-deficient porphyrins were prepared by attaching one or two N-methylated 2-, 3- or 4-pyridylethynyl groups to the 10,20-meso positions of (5,15-biphenylporphinato)zinc(II). Electrochemical studies showed significant changes in the reduction potentials of these porphyrins, and N-methyl-2-pyridylethyne is the strongest electron-withdrawing substituent in the series. UV-visible spectra demonstrated largely red-shifted absorptions, and N-methyl-4-pyridylethyne has the greatest impact to the porphyrin absorptions. Electrochemical, UV-visible and EPR results concluded that porphyrins Zn2 and Zn6 reversibly undergo two one-electron porphyrin-ring reductions to their anion radicals then dianions. The first reductions of porphyrins Zn1, Zn3, Zn4 and Zn5 were irreversible one-electron transfer processes. The instability of these reduction products was suggested to result from the eletrophilic attacks at the substituents.


[Review of quality control program for clinical microbiology developed by the Tokyo Metropolitan Government].
There are limitations or disadvantages in previous nation wide external quality control (QC) programs. Therefore, the Tokyo Metropolitan Government and the Tokyo Medical Association (TMA) initiated the first regional annual external QC program in 1982. The QC results in chemistry, hematology and immunology have shown rapid improvement. By contrast, some serious problems in microbiology have been revealed. The Tokyo Metropolitan external QC programs consist of so-called "open" and "blind" surveys. Simulated specimens were prepared for open and blind surveys and all laboratories were asked to examine the specimens using routine procedures. All participants were required to report not only their test results such as codes for computer analysis, but also to describe the process. Written answers included the following subjects, procedures, culture characteristics and others: number and type of selective media, incubation conditions, colonial morphology, microscopic and biochemical characteristics of the microorganisms, etc. The survey reports on the identification of some kinds of pathologic organism were inaccurate. Discrepancies between the number of media used for routine procedures and the number used in open survey were detected. Previous nationwide external QC programs using frozen-dried organisms have been valuable in promoting general improvement in clinical microbiology in Japan, but they have revealed only gross errors. Our 10-year experience has convinced us that additional important information is obtained when using simulated specimens for open and blind surveys. The turnaround time and other aspects of the reporting of results should be monitored. Due to possible legal ramifications of QC surveys, laboratories are now more afraid of making errors than before. The continuing education of laboratory personnel is essential.


Simultaneous cardiac output measurements by transtracheal Doppler, electromagnetic flow meter, and thermodilution during various hemodynamic states in pigs.
The transtracheal Doppler (TTD) method of cardiac output (CO) measurement was compared with thermodilution (TDL) and aortic electromagnetic flow meter (EFM). Simultaneous CO measurements with the three methods were obtained during various hemodynamic states in eight pigs. Cardiac output ranged from 1 to 3 L/min during the study. For 128 measurements, the mean difference +/- SD between TTD-TDL and TTD-EFM measurements was -0.037 +/- 0.24 L/min and -0.055 +/- 0.23 L/min, respectively. TDL-EFM mean difference +/- SD was -0.017 +/- 0.15 L/min. The limits of the agreement between TTD and the reference methods were 0.4 to -0.5 L/min. The limits of agreement between the reference methods were 0.3 to -0.3 L/min. Regression analysis yielded TTD = 0.383 + 0.779 TDL (r = 0.86); TTD = 0.351 + 0.788 EFM (r = 0.87); TDL = 0.077 + 0.95 EFM (r = 0.95). Only a change greater than 0.6 L/min in TTD CO could predict with 95% confidence a change in TDL or EFM CO. These results suggest that, in the CO range of this study, the TTD method does not accurately reproduce the CO measurements obtained by TDL or EFM.


WHO strategies for the programmatic management of drug-resistant tuberculosis.
Adequate management of drug-resistant tuberculosis (TB), including multidrug- (MDR) and extensively drug-resistant (XDR-) TB are within the priorities of the newly launched World Health Organization's End TB and Elimination Strategies. This manuscript presents the evidence on the MDR- /XDR-TB epidemiology and discusses how the five recommended priority actions can be applied at the programmatic level to tackle the epidemic: 1) prevent development of MDR-TB thorough high quality treatment of drug- susceptible TB; 2) expand rapid testing and detection of drug-resistant TB; 3) provide immediate access to effective treatment and proper care; 4) prevent transmission through infection control; 5) increase political commitment and financing. A non-systematic review using Pubmed was carried out in addition to additional relevant information taken from the abstracts of international scientific conferences. Expert commentary: Current and future control of MDR-TB significantly relies on the correct use of new diagnostics and new drugs from one side, and on the consistent application of the five core interventions at the programmatic level. In addition, it is mandatory to tackle the social determinants and socio-economic barriers favouring the MDR-TB, otherwise it will not be possible to reach the planned goals as well as TB Elimination.


Outcomes and complications after heart transplantation: a review.
In more than 35 years of experience with heart transplantation, improvements in patient selection, surgical techniques, organ preservation, and postoperative management have increased survival rates and reduced complications. However, a number of significant complications continue, limiting the benefit of heart transplantation as the long-term solution for patients. Current survival rates are 83% at 1 year and 72% at 5 years, with 50% of patients surviving 9.4 years or more. Recipient and donor characteristics influence survival outcome. Primary graft dysfunction is the most frequent cause of death during the first 30 days. The function of the transplanted heart allows return to pre-illness activities, though denervation limits peak exercise capacity. Advances in immunosuppressive medications have decreased the incidence and severity of rejection, though only recently have shown promise in attenuating the incidence of cardiac graft vasculopathy, the major complication limiting long-term graft function. This review addresses current outcomes and the short- and long-term complications of heart transplantation.


3D stereolithography printing of graphene oxide reinforced complex architectures.
Properties of polymer based nanocomposites reply on distribution, concentration, geometry and property of nanofillers in polymer matrix. Increasing the concentration of carbon based nanomaterials, such as CNTs, in polymer matrix often results in stronger but more brittle material. Here, we demonstrated the first three-dimensional (3D) printed graphene oxide complex structures by stereolithography with good combination of strength and ductility. With only 0.2% GOs, the tensile strength is increased by 62.2% and elongation increased by 12.8%. Transmission electron microscope results show that the GOs were randomly aligned in the cross section of polymer. We investigated the strengthening mechanism of the 3D printed structure in terms of tensile strength and Young's modulus. It is found that an increase in ductility of the 3D printed nanocomposites is related to increase in crystallinity of GOs reinforced polymer. Compression test of 3D GOs structure reveals the metal-like failure model of GOs nanocomposites.


Long-term stability of the chronic epidural wireless recorder WIMAGINE in tetraplegic patients.
Objective.The evaluation of the long-term stability of ElectroCorticoGram (ECoG) signals is an important scientific question as new implantable recording devices can be used for medical purposes such as Brain-Computer Interface (BCI) or brain monitoring.Approach.The long-term clinical validation of wireless implantable multi-channel acquisition system for generic interface with neurons (WIMAGINE), a wireless 64-channel epidural ECoG recorder was investigated. The WIMAGINE device was implanted in two quadriplegic patients within the context of a BCI protocol. This study focused on the ECoG signal stability in two patients bilaterally implanted in June 2017 (P1) and in November 2019 (P2).Methods. The ECoG signal was recorded at rest prior to each BCI session resulting in a 32 month and in a 14 month follow-up for P1 and P2 respectively. State-of-the-art signal evaluation metrics such as root mean square (RMS), the band power (BP), the signal to noise ratio (SNR), the effective bandwidth (EBW) and the spectral edge frequency (SEF) were used to evaluate stability of signal over the implantation time course. The time-frequency maps obtained from task-related motor activations were also studied to investigate the long-term selectivity of the electrodes.Mainresults.Based on temporal linear regressions, we report a limited decrease of the signal average level (RMS), spectral distribution (BP) and SNR, and a remarkable steadiness of the EBW and SEF. Time-frequency maps obtained during motor imagery, showed a high level of discrimination 1 month after surgery and also after 2 years.Conclusions.The WIMAGINE epidural device showed high stability over time. The signal evaluation metrics of two quadriplegic patients during 32 months and 14 months respectively provide strong evidence that this wireless implant is well-suited for long-term ECoG recording.Significance.These findings are relevant for the future of implantable BCIs, and could benefit other patients with spinal cord injury, amyotrophic lateral sclerosis, neuromuscular diseases or drug-resistant epilepsy.


[Clinical value of minimal residual disease detection by flow cytometry in childhood B-cell acute lymphoblastic leukemia].
To elevate the prognostic value of minimal residual disease (MRD) detection by four-color flow cytometry with the antibody panel in childhood B-cell acute lymphoblastic leukemia (B-ALL). The clinical data of 183 children with newly-diagnosed acute B-ALL and who accepted MRD detection between October 2010 and March 2012 was retrospectively reviewed. According to the detection time and result of MRD, the 183 children were classified into four groups: MRD negative (n=37) and positive (n=18) in the induction chemotherapy and MRD negative (n=113) and positive (n=15) in the maintenance chemotherapy. During both induction and maintenance chemotherapy, the percentage of patients at high and median risk in the MRD positive group was higher than in the MRD positive group (P<0.05). In the maintenance chemotherapy group, the 3- year cumulative incidence of relapse in MRD positive patients was higher than negative patients (P=0.04). The Cox's proportional hazards regression analysis showed that insensitive reaction for prednisone (RR=1.005, 95%CI: 0.864-1.170, P=0.032), bone marrow morphology that did not meet M1 on the 15th day (RR=6.454, 95%CI: 2.191-19.01, P=0.002) and MRD≥0.01% (RR=1.923, 95%CI: 0.750-4.933, P=0.043) were risk factors for relapse in children with B-ALL. The four-color flow cytometry with the antibody panel can distinguish from MRD positive patients from negative patients with B-ALL. The result of MRD detection, as prednisone sensitivity and bone marrow morphology on the 15th day, is also a independent prognostic factor in children with B-ALL.


[Value of preoperative planning in total hip arthroplasty].
Preoperative planning enables an assessment of the size of the implants needed before total hip replacement. Eggli and Müller demonstrated the reproduciblity of preoperative planning but did not evaluate its contribution to reducing limb length discrepancy. As femur lateralization and the position of the prosthetic center of rotation affect joint mechanics, it would be useful to assess their contribution to the efficacy of preoperative planning. We reviewed the files of 57 patients who underwent total hip arthroplasty for primary joint degeneration or necrosis limited to one hip. The healthy hip served as a control. The surgical plan was elaborated from the preoperative pelvis x-rays (AP and lateral views) and anatomic measurements on films obtained three months postoperatively. In 49 cases, preoperative planning predicted a restoration of the normal anatomy of the operated hip (center of rotation, femur lateralization, length of the operated limb). This objective was achieved in only 22.5% of the cases. Femur lateralization was the most difficult objective to achieve (59.2%). Equal limb length and good position of the center of rotation was achieved in 70% of the cases. For eight patients (14%) preoperative planning was not satisfactory, the implant offset not being adapted to the patient's anatomy. There are limits to preoperative planning, particularly for restitution of adequate femur lateralization. This difficulty appears to be related to three factors: inadequate adaptation of the implant to hip anatomy (14% of the cases in our experience), stiff rotation in degenerative hips inhibiting proper assessment of the length of the femoral neck, and relative imprecision of operative evaluation of femoral anteversion affecting femur lateralization and the level of the femoral cut. Although imperfect, preoperative planning is, in our opinion, essential before total hip arthroplasty in order to avoid major positioning errors and operative difficulties.


Peroxisome proliferator-activated receptor gamma in the colon: inflammation and innate antimicrobial immunity.
Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor, originally described in adipose tissue, which controls the expression of a large number of regulatory genes in lipid metabolism and insulin sensitization. Well known by endocrinologists, thiazolidinedionesare classical PPARγ synthetic agonists, which were currently used as insulin-sensitizing agents in the treatment of type 2 diabetes. Although the clinical benefits of thiazolidinediones in treating metabolic disorders have been clearly demonstrated, studies performed in animal models of colitis and in patients with ulcerative colitis have also revealed the key roles of PPARγ activation in the regulation of inflammation and immune response, notably in the colon through epithelial cells.


Acute esophageal and gastric injury: complication of Lugol's solution.
Several new technologies have been developed to improve the diagnostic capability of conventional endoscopic techniques. One of these most frequently used methods is chromoendoscopy with Lugol's solution in the esophagus to detect malignant lesions. This method has been used for several decades and is generally considered as a safe method, only a few cases of side effects having been reported. We describe a case of acute esophageal and gastric mucosal damage after application of Lugol's solution during endoscopy in an 84-year-old woman. Endoscopists should be aware of the potential for adverse reactions to iodine staining.


The Fusarium wilt resistance locus Fom-2 of melon contains a single resistance gene with complex features.
The soil-borne fungus Fusarium oxysporum f.sp. melonis causes significant losses in the cultivated melon, a key member of the economically important family, the Cucurbitaceae. Here, we report the map-based cloning and characterization of the resistance gene Fom-2 that confers resistance to race 0 and 1 of this plant pathogen. Two recombination events, 75 kb apart, were found to bracket Fom-2 after screening approximately 1324 gametes with PCR-based markers. Sequence analysis of the Fom-2 interval revealed the presence of two candidate genes. One candidate gene showed significant similarity to previously characterized resistance genes. Sequence analysis of this gene revealed clear polymorphisms between resistant and susceptible materials and was therefore designated as Fom-2. Analysis of susceptible breeding lines (BL) presenting a haplotype very similar to the resistant cultivar MR-1 indicated that a gene conversion had occurred in Fom-2, resulting in a significant rearrangement of this gene. The second candidate gene which shared high similarity to an essential gene in Arabidopsis, presented an almost identical sequence in MR-1 and BL, further supporting Fom-2 identity. The gene conversion in Fom-2 produced a truncated R gene, revealing new insights into R gene evolution. Fom-2 was predicted to encode an NBS-LRR type R protein of the non-TIR subfamily. In contrast to most members of this class a coiled-coil structure was predicted within the LRR region rather than in the N-terminal. The Fom-2 physical region contained retroelement-like sequences and truncated genes, suggesting that this locus is complex.


Mechanical properties of the human thoracic spine as shown by three-dimensional load-displacement curves.
The mechanical properties of the human spine are best described by load-displacement curves which include coupling effects. Three-dimensional load-displacement curves were obtained for all levels of the human thoracic spine using fresh cadaver spines in an atmosphere containing 100 per cent humidity at 22 degrees centigrade to stimulate a physiological environment. Six forces and six moments were applied, one at a time, to the center of the upper vertebra while its subadjacent fellow was fixed. Assuming sagittal plane symmetry, vertebral displacement was measured in three-dimensional space and load-displacement curves were plotted for the main as well as the coupled motions. The thirty-six curves necessary to define the mechanical characteristics of each motion segment completely were determined for all eleven thoracic levels. The curves showed that all the thoracic spine is a complex three-dimensional structure with coupled motion characteristics. Axial forces (compression/tension) resulted in significant horizontal displacements. Spine motion segments were more flexible in flexion than in extension. The spine was found to be least flexible during axial compression.


Functional proteomics study reveals that N-Acetylglucosaminyltransferase V reinforces the invasive/metastatic potential of colon cancer through aberrant glycosylation on tissue inhibitor of metalloproteinase-1.
N-Acetylglucosaminyltransferase-V (GnT-V) has been reported to be up-regulated in invasive/metastatic cancer cells, but a comprehensive understanding of how the transferase correlates with the invasive/metastatic potential is not currently available. Through a glycomics approach, we identified 30 proteins, including tissue inhibitor of metalloproteinase-1 (TIMP-1), as a target protein for GnT-V in human colon cancer cell WiDr. TIMP-1 was aberrantly glycosylated as characterized by the addition of beta1,6-N-acetylglucosamine, polylactosaminylation, and sialylation in GnT-V-overexpressing WiDr cells. Compared with normal TIMP-1, the aberrantly glycosylated TIMP-1 showed the weaker inhibition on both matrix metalloproteinase (MMP)-2 and MMP-9, and this aberrancy was closely associated with cancer cell invasion and metastasis in vivo as well as in vitro. Integrated data, both of TIMP-1 expression level and aberrant glycosylation, could provide important information to aid to improve the clinical outcome of colon cancer patients.


Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients.
The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (i.v.) administration of either 40 mg of parecoxib (n=25) or 2 g of proparacetamol (n=25) 15 min before discontinuation of total i.v. anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm x min in the proparacetamol group and 635 (26-1413) cm x min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p >or= 0.05), while mean morphine consumption was 5-3.5mg and 5-2.0 mg in the proparacetamol groups and parecoxib, respectively (p >or= 0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24 h after surgery. In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.


Comparison of the responses of auditory nerve fibers to consonant-vowel syllables with predictions from linear models.
The responses of cat auditory-nerve fibers to synthesized consonant-vowel syllables were compared with predictions from linear models based on individual fibers' threshold tuning curves. Comparisons with the linear predictions provided information about the specific effects of peripheral nonlinearities on the representation of speech sounds. Spectral peaks, such as the formants of vowels, were more prominently represented in synchronized discharge patterns than in the linear predictions. Suppression of responses to other spectral peaks and to stimulus components between spectral peaks accounted for the differences. While profiles of fibers' synchronized responses were usually dominated by a single formant, predicted linear responses often included broad responses having two or more formants as well as components near the fibers' characteristic frequencies. In contrast, when no stimulus peak fell within a fiber's response area, the agreement between the neural response and the linear prediction was quite good. The results suggest that one role for peripheral nonlinearities in the auditory system may be to enhance the neural representation of spectral features such as formants.


Melanoma of the external ear: A population-based study.
Primary melanoma of the external ear (PMEE) is rare and therefore well-suited for large population-based registry analysis. The objective of this study was to utilize the Surveillance, Epidemiology, and End Results (SEER) set of cancer registries to determine the incidence, treatment, and survival characteristics of PMEE. A retrospective cohort analysis of SEER data from 2004 to 2013 identified all cases of PMEE stage I-IV by AJCC 7th edition guidelines. Population-based incidence was calculated. Cancer-specific survival data by stage was assessed using Kaplan-Meier analysis and the relative effects of tumor characteristics were analyzed with Cox regression models. A total of 5481 patients were analyzed (mean age 66.7years, 86.5% male, 93.6% non-Hispanic white). The incidence of PMEE was 1.91 per 100,000 persons-per-year. At diagnosis, 68.1% were stage I, 15.2% were stage II, 4.7% were stage III, 1.5% were stage IV, and 10.8% were unknown. The five-year overall and cancer-specific survival was 78.8% and 90.0%, and, according to AJCC stage, was 85.7% and 95.3% for stage I (n=2287), 64.6% and 81.1% for stage II (n=453), 50.8% and 57.0% for stage III (n=154), 17.2% and 20.5% for stage IV (n=34), and 71.0% and 87.1% for unknown stage (n=330), respectively. The multivariable Cox model identified tumor characteristics that were independently associated with survival. This is the first study to characterize the epidemiology, presentation and outcome of PMEE using the SEER registries. Older age, increasing Breslow thickness, stage, presence of ulceration, positive lymph nodes and distant metastasis each independently predicted time to cancer-specific death.


Bromide as a Robust Backfiller on Gold for Precise Control of DNA Conformation and High Stability of Spherical Nucleic Acids.
Functionalization of a gold surface with DNA is often complicated by kinetic traps from unintended DNA base adsorption. Herein, we communicate that Br- serves as a robust backfilling agent displacing selected DNA bases on gold. Traditional thiol backfillers are too strong, while even 300 mM Br- is well tolerated. Conjugates prepared with Br- hybridize 10-fold faster and resist DNA release with better colloidal stability yielding highly sensitive probes. From colorimetric and Raman assays, adsorption affinity ranks as F- < T ≈ Cl- < C < G ≈ Br- < A < I-, allowing Br- to displace nonpoly-A sequences from gold. This well-controlled biointerface will impact biosensing, drug delivery, and directed assembly of nanomaterials.


Regulation of p70s6k/p85s6k and its role in the cell cycle.
Two to three-fold increases in the rate of protein synthesis are required both to enter the G1 phase of the cell cycle from G0 and to proceed to S phase in response to growth factors and mitogens. This increase is in part regulated via multiple phosphorylation of the 40S ribosomal protein S6 by the mitogen-stimulated p70s6k/p85s6k. At the protein synthesis level this event appears to be involved in specifically increasing the efficiency of translation of a family of essential mRNAs containing a polypyrimidine tract at their 5' transcriptional start site. The activation of p70s6k/p85s6k and maintenance of its activity throughout G1 is controlled via multiple phosphorylation events mediated by a complex signalling network acting on distinct sets of phosphorylation sites.


Frontal gel chromatography of interacting systems: theoretical and experimental evaluation of the shapes of elution profiles for systems of the type A + B in equilibrium C.
A theoretical and experimental study has been made of the advancing elution profile in frontal gel chromatography of interacting systems for which the elution volume of the complex is smaller than that of the larger reactant. First, Gilbert-Jenkins theory is used to delineate the form of the elution profile from the magnitudes of the elution volumes and concentrations of reacting species. This procedure resulted in the detection of a misinterpretation of certain patterns obtained in a gel chromatographic study of the interaction between myoglobin and ovalbumin. Second, a numerical computational procedure, which incorporates both axial dispersion and concentration-dependence of species elution volumes, is used to establish the influence of these two factors on boundary shapes for such systems. Third, frontal gel chromatography on Sephadex G-75 is used to compare experimental behavior with theoretical profiles predicted for the electrostatic interaction between cytochrome c and soybean trypsin inhibitor (pH 6.8, I 0.01). Results of these experiments serve as a guide for future conduct of experiments aimed at characterization of biologically important, reversible complex formation between proteins and/or other macromolecules.


Dietary Zinc Deficiency Induces Cav3.2-Dependent Nociceptive Hypersensitivity in Mice.
Cav3.2 channels belong to the T-type calcium channel (T-channel) family, i.e., low voltage-activated calcium channels, and are abundantly expressed in the nociceptors, playing a principal role in the development of pathological pain. The channel activity of Cav3.2 is suppressed by zinc under physiological conditions. We thus tested whether dietary zinc deficiency would cause Cav3.2-dependent nociceptive hypersensitivity in mice. In the mice fed with zinc deficient diet for 2 weeks, plasma zinc levels declined by more than half, and mechanical allodynia developed. The dietary zinc deficiency-induced allodynia was restored by T-channel inhibitors or by Cav3.2 gene silencing. These data demonstrate that zinc deficiency induces Cav3.2-dependent nociceptive hypersensitivity in mice, thereby suggesting that pain experienced by patients with diseases accompanied by zinc deficiency (e.g., chronic kidney disease) might involve the increased Cav3.2 activity.


The role of vagal function in the risk for cardiovascular disease and mortality.
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The understanding of the risk factors for CVD may yield important insights into the prevention, etiology, course, and treatment of this major public health concern. We review the evidence for the role of vagal function in the risk for cardiovascular disease and mortality. Using a broad range of indicators of vagal function including resting heart rate, heart rate recovery, heart rate variability, and baroreflex sensitivity we show that decreased vagal function is associated with an increased risk for morbidity and mortality. These effects are independent of traditional risk factors. Moreover, we show that decreased vagal function is associated with both traditional and emerging risk factors as well as modifiable and non-modifiable risk factors. Most importantly, we provide evidence to support the notion that decreased vagal function precedes the development of a number of risk factors and that modification of risk profiles in the direction of lower risk is associated with increased vagal function. We close with a brief overview of the neural concomitants of vagal function and suggest that a model of neurovisceral integration may provide a unifying framework within which to investigate the impact of risk factors, including psychosocial factors, on cardiovascular disease.


DDI pacing in the bradycardia-tachycardia syndrome.
The bradycardia-tachycardia syndrome is a subgroup within the larger category of sinus node dysfunction. Pacing is often required to treat either the protracted asystolic spells following the spontaneous termination of a paroxysmal supraventricular tachyarrhythmia or to protect the patient from pharmacologically exacerbated bradycardias. While the optimal pacing mode for this subset of patients remains debatable, recent reports have favored the use of atrial ventricular sequential pacing with intact atrial sensing (DDI). This paper reports our experience with a series of 30 consecutive patients in whom the DDI mode was utilized as part of the management of this syndrome. DDI pacing has been demonstrated to be safe, extremely effective, and easy to use in this group of patients.