Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.
In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors, and HIV RNA. Sixteen of 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment for group sequential testing, 1.8 to 499; unadjusted P<0.001). Pain diminished and ability to eat improved with thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each), and 6 of the 29 patients discontinued treatment because of toxicity. Thalidomide treatment increased HIV RNA levels (median increase, 0.42 log10 copies per milliliter; increase with placebo, 0.05; P=0.04). With thalidomide treatment there were unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF-alpha receptors. Thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection.


Root-level exposure reveals multiple physiological toxicity of triazine xenobiotics in Arabidopsis thaliana.
Herbicides are pollutants of great concern due to environmental ubiquity resulting from extensive use in modern agriculture and persistence in soil and water. Studies at various spatial scales have also highlighted frequent occurrences of major herbicide breakdown products in the environment. Analysis of plant behavior toward such molecules and their metabolites under conditions of transient or persistent soil pollution is important for toxicity evaluation in the context of environmental risk assessment. In order to understand the mechanisms underlying the action of such environmental contaminants, the model plant Arabidopsis thaliana, which has been shown to be highly responsive to pesticides and other xenobiotics, was confronted with varying levels of the widely-used herbicide atrazine and of two of its metabolites, desethylatrazine and hydroxyatrazine, which are both frequently detected in water streams of agriculturally-intensive areas. After 24h of exposure to varying concentrations covering the range of triazine concentrations detected in the environment, root-level contaminations of atrazine, desethylatrazine and hydroxyatrazine were found to affect early growth and development in various dose-dependent and differential manners. Moreover, these differential effects of atrazine, desethylatrazine and hydroxyatrazine pointed to the involvement of distinct mechanisms directly affecting respiration and root development. The consequences of the identification of additional targets, in addition to the canonical photosystem II target, are discussed in relation with the ecotoxicological assessment of environmental xenobiotic contamination.


Pulmonary tuberculosis in Italian children by age at presentation.
To evaluate the clinical characteristics, diagnostic methods and outcome of paediatric pulmonary tuberculosis (PTB) in relation to children's ages when observed. Children under 15, who had been admitted to the Children's Hospital with PTB were prospectively evaluated. Our sample included patients with a positive tuberculin skin test and signs or symptoms of tuberculosis (TB), including abnormal chest X-rays which suggested PTB. We collected demographic, clinical, radiographic and microbiological data from the patients, in addition to carrying out contact investigations in order to find a source case. All the patients involved in this study were subjected to anti-tuberculosis treatment. Sixty-two patients (44% under 5) were eligible for inclusion in our study. Children with presenting symptoms were younger than asymptomatic patients (p<0.05). A source case was found in 38 patients out of 62 children (62%) and children under 5 were more likely to have a source case than that found with older children (p<0.05). Ghon complex (infiltrate + adenopathy) tended to occur in young children (median age of 3.25, p<0.05). Fourteen children (23%) had clinical specimens which tested positive for Mycobacterium tuberculosis (MT), and 20 (32%) for MT DNA according to a polymerase chain reaction (PCR). Resistant strains to 1 or more anti-tuberculosis drugs were found in 5 children and in 4 adult sources. The patients with minimal or no radiographic change during therapy displayed symptoms for a longer period of time and were infected by a resistant strain (p<0.05). Improvements in case detection, case management and contact investigations are necessary for controlling paediatric TB, especially in young children. Given that any diagnosis of TB in children is supported by epidemiological and clinical evidence rather than isolating MT, detection of the source case is important in selecting appropriate treatment.


Treatment of a middle cerebral artery bifurcation aneurysm with the novel Contour Neurovascular System compatible with 0.021″ catheters.
For wide-necked intracranial aneurysms, endo-saccular flow disruption can be a viable alternative to coiling or flow diverters. The Contour Neurovascular System is an intrasaccular flow diverter device targeting the neck of the aneurysm. Until now, the system had to be delivered through a 0.027″ microcatheter. We report the first implantation and follow-up of the novel Contour 021 system compatible with 0.021″ microcatheters.Case presentation: A 54-year-old male patient presented with an unruptured right middle cerebral artery aneurysm at the right temporopolar branch. Existing medication included apixaban. An arteriogram showed a broad-based aneurysm. Due to its asymmetric geometry, neither the Woven EndoBridge nor stent-assisted coil embolisation were regarded as promising treatment strategies. To uphold the option of different treatment options, prasugrel 10 mg was initiated before treatment. Implantation was performed under general anaesthesia via femoral artery puncture. A 0.021″ Headway™ catheter was used for accessing the aneurysm. The Contour device was oversized to the equatorial plane. Deployment was successful with only one attempt without the need for re-sheathing. Follow-up catheter angiography was performed after three months, showing complete occlusion of the aneurysm. No procedure-related complications occurred. The 0.021 design of the Contour enlarges the subgroup of patients that can be treated with endo-saccular devices and will enable treatment of smaller and more distal aneurysms.


FTDR 2.0: a tool to achieve sub-ppm level recalibrated accuracy in routine LC-MS analysis.
Advances in proteomics research involve the use of high-precision and high-resolution mass spectrometry instruments. Although hardware improvements are the main impetus for the acquisition of high-quality data, enhancements in software tools are also needed. In this study, recalibration was verified as an important way to improve data accuracy. A new version tool, known as FTDR 2.0, was developed to recalibrate the mass-to-charge ratio error of most observed parent ions to the sub part per million level in routine experiments. First, many new parameters were introduced and screened as features online to reduce systematic error and to adapt to various data sets. Second, a support vector regression model was trained to characterize the complex nonlinear maps from features to mass-to-charge ratio measurement errors. Third, a specific mass-to-charge ratio error tolerance for each parent ion was estimated by considering the impact of signal intensity. FTDR 2.0 is a user-friendly tool that supports most commonly used data standards and formats. A C++ library and the source code are provided to support the redevelopment and integration into other mass spectrometry data processing tools. The performance of FTDR 2.0 was verified using several experimental data sets from different research programs. Recalibration with FTDR 2.0 has been proved to improve the peptide identification in qualitative, quantitative, and post-translational modification analyses.


β-Defensin 1 Is Prominent in the Liver and Induced During Cholestasis by Bilirubin and Bile Acids via Farnesoid X Receptor and Constitutive Androstane Receptor.
Knowledge about innate antimicrobial defense of the liver is limited. We investigated hepatic expression and regulation of antimicrobial peptides with focus on the human beta defensin-1 (hBD-1). Radial diffusion assay was used to analyze antimicrobial activity of liver tissue. Different defensins including hBD-1 and its activator thioredoxin-1 (TXN) were analyzed in healthy and cholestatic liver samples by qPCR and immunostaining. Regulation of hBD-1 expression was studied in vitro and in vivo using bile duct-ligated mice. Regulation of hBD-1 via bilirubin and bile acids (BAs) was studied using siRNA. We found strong antimicrobial activity of liver tissue against Escherichia coli. As a potential mediator of this antimicrobial activity we detected high expression of hBD-1 and TXN in hepatocytes, whereas other defensins were minimally expressed. Using a specific antibody for the reduced, antimicrobially active form of hBD-1 we found hBD-1 in co-localization with TXN within hepatocytes. hBD-1 was upregulated in cholestasis in a graded fashion. In cholestatic mice hepatic AMP expression (Defb-1 and Hamp) was enhanced. Bilirubin and BAs were able to induce hBD-1 in hepatic cell cultures in vitro. Treatment with siRNA and/or agonists demonstrated that the farnesoid X receptor (FXR) mediates basal expression of hBD-1, whereas both constitutive androstane receptor (CAR) and FXR seem to be responsible for the induction of hBD-1 by bilirubin. hBD-1 is prominently expressed in hepatocytes. It is induced during cholestasis through bilirubin and BAs, mediated by CAR and especially FXR. Reduction by TXN activates hBD-1 to a potential key player in innate antimicrobial defense of the liver.


Cultivation of recombinant Chinese hamster ovary cells grown as suspended aggregates in stirred vessels.
Recombinant Chinese hamster ovary (rCHO) cells capable of producing a prourokinase mutant (mPro-uk) grown as suspended aggregates in stirred vessels were described and characterized. The addition of chitosan to a mixture of DMEM and Ham's F12 (D-MEM/F-12) medium promoted cell aggregation and spheroid formation efficiently. Multicellular aggregates formed immediately after the rCHO cells were inoculated into the chitosan-added medium, and the mean diameter of the cell aggregates reflecting the aggregate size increased with culture time, shifting from 65 to 163 mum after 2 and 9 d of culture in spinner flasks. No significant difference in the metabolism performance of the rCHO cells was observed between suspended aggregates and anchored monolayers. However, the cells cultured as suspended aggregates showed a marked decrease in growth rate as evaluated from specific growth rate (mu). Replacing D-MEM/F-12 medium with CD 293 medium caused compact spherical cell aggregates to dissociate into small irregular aggregates and single cells without apparent effects on cell performance in subcultures. The perfusion culture of the rCHO cells grown as suspended aggregates in a 2-l stirred tank bioreactor for 15 d resulted in a maximum viable cell density of 5.6 x 10(6) cells ml(-1) and an mPro-uk concentration of about 2.6 x 10(3) IU ml(-1), and cell viability was remained at roughly 90% during the entire run.


Thin-layer chromatography of 1-dimethylaminonaphthalene-5-sulphonyl derivatives of amino acids present in superfusates of cat cerebral cortex.
1. Five new solvent systems are reported for the separation of 1-dimethylaminonaphthalene-5-sulphonylamino acids by thin-layer chromatography on silica gel. After two-dimensional chromatography with a suitable pair of these solvent systems, most of the 1-dimethylaminonaphthalene-5-sulphonyl derivatives were completely separated and could be located by their intense yellow fluorescence when viewed under u.v. light. 2. These techniques have been used to identify 21 amino acids present in superfusates of cat cerebral cortex, plasma and cerebrospinal fluid. 3. A method for the semiquantitative estimation of amino acids in biological fluids is described in which the fluorescent intensity of their separated 1-dimethylaminonaphthalene-5-sulphonyl derivatives was measured.


Exact solitary wave solutions for a discrete lambdaphi4 field theory in 1+1 dimensions.
We have found exact, periodic, time-dependent solitary wave solutions of a discrete phi4 field theory model. For finite lattices, depending on whether one is considering a repulsive or attractive case, the solutions are Jacobi elliptic functions, either sn (x,m) [which reduce to the kink function tanh (x) for m-->1 ], or they are dn (x,m) and cn (x,m) [which reduce to the pulse function sech (x) for m-->1 ]. We have studied the stability of these solutions numerically, and we find that our solutions are linearly stable in most cases. We show that this model is a Hamiltonian system, and that the effective Peierls-Nabarro barrier due to discreteness is zero not only for the two localized modes but even for all three periodic solutions. We also present results of numerical simulations of scattering of kink-antikink and pulse-antipulse solitary wave solutions.


Remote monitoring of videourodynamics using smart phone and free instant messaging software.
To evaluate the feasibility of using smart phones plus free instant messaging software for remote monitoring of videourodynamics. From November 2011 to October 2012, 85 females with voiding disorders were enrolled for videourodynamic tests. The patients were assigned to videourodynamics remotely monitored by the attending physician by using iPhone/iPad and Skype (group 1) and videourodynamics with the attending physician present (group 2). The procedural time and videourodynamic qualities, assessed by the frequency of adherence to the modified Sullivan criteria, in each group were recorded and compared. There were 44 and 41 patients in group 1 and group 2, respectively. The mean procedural time was comparable between group 1 and group 2 (56.3 vs. 54.4 min, P = 0.25). The frequencies of adherence to the modified Sullivan criteria were similar in each group. The qualities of videourodynamics under the attending physician's remote or direct monitoring were both appropriate. Based on the convenience of Internet, the popularity of smart phones and the intention to make the urologists use their time more efficiently, our study provides remote monitoring as an alternative way for performing videourodynamics.


ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis.
Extracellular signal-regulated kinase (ERK)1/2 signalling mediates communication between growth factor receptors and the cell nucleus and has been linked to several key events in the transformation process such as proliferation and invasion. We therefore sought to delineate the degree of phosphorylated ERK1/2 in breast cancer and potential links to upstream receptors such as VEGFR2, ErbB2, downstream targets, such as Ets-2, as well as clinico-pathological parameters, clinical outcome and response to tamoxifen. ERK1/2 phosphorylation was assessed by immunohistochemistry using a phospho-specific ERK1/2 antibody in three breast cancer cohorts including a total of 886 tumours arranged in tissue arrays. Cohort I consisted of 114 patients, cohort II of 248 postmenopausal patients randomized to either 2 years of tamoxifen or no adjuvant treatment and cohort III of 524 patients. Surprisingly, ERK1/2 phosphorylation correlated inversely with tumour size. Phosphorylated ERK1/2 was further associated with the presence of VEGFR2 (cohorts II and III) and the degree of phosphorylated Ets-2, indicating in vivo, a signalling cascade from VEGFR2 via ERK1/2 to Ets-2 phosphorylation. Interestingly, ERK1/2 phosphorylation correlated with better survival in untreated patients independently of lymph-node status and tumour size indicating that ERK1/2 signalling might be associated with a less aggressive phenotype. Finally, patients with oestrogen receptor positive and ERK1/2 phosphorylated tumours also had an impaired tamoxifen response.


Opposed effects of prostaglandin E2 on perfusion of rat renal cortex and medulla: interactions with the renin-angiotensin system.
While prostaglandin E(2) (PGE(2)) is an established renal vasodilator, studies of prostaglandin EP receptors suggest that it also has vasoconstrictor potential. Prostaglandin E(2) is much more abundant in the medulla than in the cortex, yet likely differences in effects between zones have not been defined. This study is focused on different vascular effects in the cortex and medulla and interaction with the renin-angiotensin system (RAS). In anaesthetized rats, the effects of cyclo-oxygenase blockade and of PGE(2) infused into the renal artery or renal interstitium were examined. Total renal blood flow was measured by ultrasonic renal artery probe, and local perfusion, separately, of the superficial cortex, outer- and inner medulla, as laser-Doppler fluxes. Indomethacin (5 mg kg(-1) i.v.) increased cortical perfusion (by approximately 10%) and decreased medullary perfusion (by approximately 20%). Renal artery infusion of PGE(2) (15-30 microg kg(-1) h(-1)) increased cortical and medullary perfusion only transiently. Previous inactivation of the RAS using losartan or captopril, and background infusion of exogenous angiotensin II, prevented the transient increase and enhanced the subsequent stable decrease in perfusion. Prostaglandin E(2) infused into the medullary interstitium (7-22 microg kg(-1) h(-1)) increased medullary perfusion by 13%, while cortical perfusion decreased by 6%. Misoprostol, an agonist of constrictor EP(3) receptors, decreased perfusion of the cortex and medulla, with both renal artery and medullary interstitial infusion. In conclusion, in rat renal cortex the dominating stable PGE(2) effect is vasoconstriction, most probably mediated by EP(3) receptors and unrelated to activation of the RAS. Prostaglandin E(2) applied to the cortical or medullary interstitium, a natural route for paracrine agents, induces medullary vasodilatation.


Fabrication and Characterization of a 20-MHz Microlinear Phased-Array Transducer for Intervention Guidance.
This paper describes the design and fabrication of a miniature ultrasonic phased-array transducer used for intervention guidance. Currently, ultrasound probes are often placed at the body surface of the patients, leading to several drawbacks including the limitation of penetration and image quality. In order to improve the reliability of the guiding process, we propose a miniature phased-array transducer that can be placed adjacent to the intervention device during the interventional procedure. In this paper, we report the work that has been carried out on the development of this miniature phased-array transducer. It comprised 48 elements housed in a 3-mm-diameter needle. A specially designed flexible circuit was used for accommodating the transducer array in the long, thin needle housing. The center frequency and the fractional bandwidth were approximately 20 MHz and 42%, respectively, with an average crosstalk lower than -30 dB. The axial and azimuth resolutions were approximately 80 and [Formula: see text], respectively. The imaging capability of the transducer was further evaluated by acquiring the B-mode images of a needle in a cow liver. The performance of the proposed phased-array transducer demonstrates the feasibility of such an approach for interventional guidance.


A pre-search estimation algorithm for MEDLINE strategies with qualifiers.
Inexperienced users of online medical databases often have difficulty formulating their queries. Systems designed to assist them usually do not estimate how effective the initial search strategy will be before performing an actual search. Consequently, the search may find an overwhelming number of citations, or retrieve nothing at all. We have developed an estimation algorithm to predict the outcome of a MEDLINE search. The portion of the algorithm described here estimates retrieval for strategies containing qualifiers. In test searches, the estimate reduced the trial-and-error of strategy formulation. However, the accuracy of the estimate fell short of expectations. Our results show that pre-search estimation for strategies with qualifiers cannot be performed effectively with only the occurrence data that is presently available. They further imply that automated search intermediaries can benefit from medical knowledge which expresses the relationships that exist between terms.


Implications and mechanism of action of gabapentin in neuropathic pain.
Gabapentin is an anti-epileptic agent but now it is also recommended as first line agent in neuropathic pain, particularly in diabetic neuropathy and post herpetic neuralgia. α2δ-1, an auxillary subunit of voltage gated calcium channels, has been documented as its main target and its specific binding to this subunit is described to produce different actions responsible for pain attenuation. The binding to α2δ-1 subunits inhibits nerve injury-induced trafficking of α1 pore forming units of calcium channels (particularly N-type) from cytoplasm to plasma membrane (membrane trafficking) of pre-synaptic terminals of dorsal root ganglion (DRG) neurons and dorsal horn neurons. Furthermore, the axoplasmic transport of α2δ-1 subunits from DRG to dorsal horns neurons in the form of anterograde trafficking is also inhibited in response to gabapentin administration. Gabapentin has also been shown to induce modulate other targets including transient receptor potential channels, NMDA receptors, protein kinase C and inflammatory cytokines. It may also act on supra-spinal region to stimulate noradrenaline mediated descending inhibition, which contributes to its anti-hypersensitivity action in neuropathic pain.


Trustworthy learning with (un)sure annotation for lung nodule diagnosis with CT.
Recent evolution in deep learning has proven its value for CT-based lung nodule classification. Most current techniques are intrinsically black-box systems, suffering from two generalizability issues in clinical practice. First, benign-malignant discrimination is often assessed by human observers without pathologic diagnoses at the nodule level. We termed these data as "unsure-annotation data". Second, a classifier does not necessarily acquire reliable nodule features for stable learning and robust prediction with patch-level labels during learning. In this study, we construct a sure-annotation dataset with pathologically-confirmed labels and propose a collaborative learning framework to facilitate sure nodule classification by integrating unsure-annotation data knowledge through nodule segmentation and malignancy score regression. A loss function is designed to learn reliable features by introducing interpretability constraints regulated with nodule segmentation maps. Furthermore, based on model inference results that reflect the understanding from both machine and experts, we explore a new nodule analysis method for similar historical nodule retrieval and interpretable diagnosis. Detailed experimental results demonstrate that our approach is beneficial for achieving improved performance coupled with trustworthy model reasoning for lung cancer prediction with limited data. Extensive cross-evaluation results further illustrate the effect of unsure-annotation data for deep-learning based methods in lung nodule classification.


Mechanism of the copper-free palladium-catalyzed Sonagashira reactions: multiple role of amines.
Amines used as bases in copper-free, palladium-catalyzed Sonogashira reactions play a multiple role. The oxidative addition of iodobenzene with [Pd(0)(PPh(3))(4)] is faster when performed in the presence of amines (piperidine>morpholine). Amines also substitute one ligand L in trans-[PdI(Ph)(L)(2)] (L=PPh(3), AsPh(3)) formed in the oxidative addition. This reversible reaction, which gives [PdI(Ph)L(R(2)NH)], is favored in the order AsPh(3)>PPh(3) and piperidine>morpholine. Two mechanisms are proposed for Sonogashira reactions, depending on the ligand and the amine. When L=PPh(3), its substitution by the amine in trans-[PdI(Ph)(PPh(3))(2)] is less favored than that of the alkyne. A mechanism involving prior coordination of the alkyne is suggested, followed by deprotonation of the ligated alkyne by the amine. When L=AsPh(3), its substitution in trans-[PdI(Ph)(AsPh(3))(2)] by the piperidine is easier than that by the alkyne, leading to a different mechanism: substitution of AsPh(3) by the amine is followed by substitution of the second AsPh(3) by the alkyne to generate [PdI(Ph)(amine)(alkyne)]. Deprotonation of the ligated alkyne by an external amine leads to the coupling product. This explains why the catalytic reactions are less efficient with AsPh(3) than with PPh(3) as ligand.


Neuronal substrates for initiation, maintenance, and structural organization of sleep/wake states.
Animals continuously alternate between sleep and wake states throughout their life. The daily organization of sleep and wakefulness is orchestrated by circadian, homeostatic, and motivational processes. Over the last decades, much progress has been made toward determining the neuronal populations involved in sleep/wake regulation. Here, we will discuss how the application of advanced in vivo tools for cell type-specific manipulations now permits the functional interrogation of different features of sleep/wake state regulation: initiation, maintenance, and structural organization. We will specifically focus on recent studies examining the roles of wake-promoting neuronal populations.


Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas.
Phospholipase C-gamma 1 (PLC-gamma 1) is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. However, the biological significance of this molecule in normal or malignant human epithelial cell proliferation is unknown. We determined the relative content of PLC-gamma 1 in primary human mammary carcinomas and in nonmalignant mammary tissues. By Western blot and immunohistochemistry, considerably higher levels of PLC-gamma 1 protein were detectable in the majority of carcinomas and in one of two benign fibroadenomas compared to normal breast tissues. In 18 of 21 carcinomas that contained high levels of PLC-gamma 1, the presence of phosphotyrosine on PLC-gamma 1 could also be detected. All carcinomas in which tyrosine phosphorylated PLC-gamma 1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB-2, two tyrosine kinases known to phosphorylate this enzyme. Thus, a high percentage of mammary carcinomas concomitantly display increased levels of receptor tyrosine kinases and a direct tyrosine phosphorylation substrate, thereby potentially amplifying two successive steps in a signal transduction pathway.


Hearing threshold levels according to age.
Over 2900 audiograms from employees of a large food and drinks manufacturing company are reviewed. Hearing threshold levels according to age are tabulated and these appear to be different from the previously recognized average hearing threshold levels. There was no selection of these cases and include all otological and other hearing defects. The hearing thresholds therefore represents an unbiased sample of an industrial population.


Inhibition of vascular endothelial growth factor-induced endothelial cell migration by ETS1 antisense oligonucleotides.
Vascular endothelial growth factor (VEGF) increased the level of ETS1 mRNA in human umbilical vein endothelial cells (HUVEC) and human lung microvascular endothelial cells (HMVEC-L) over 5-fold. Protein levels were shown to increase concordantly. VEGF was also found to stimulate the invasiveness of endothelial cells as measured by migration through Matrigel- or gelatin-coated membranes. The VEGF-induced invasiveness was inhibited by ETS1 antisense oligonucleotides but not by a sense control. In addition, the ETS1 antisense oligonucleotides reduced the levels of ETS1 and urokinase-type plasminogen activator mRNAs. The antisense oligonucleotides directed against the ETS1 gene thus altered a cellular property of endothelial cells that is correlated with the ability of the cells to migrate through basement membranes. Together, these observations demonstrate a direct role for the ETS1 gene in angiogenesis.


Testing Usability and Feasibility of a Mobile Educator Tool for Pediatric Diabetes Self-Management: Mixed Methods Pilot Study.
Mobile interventions hold promise as an intervention modality to engage children in improving diabetes self-management education, attitudes, and behaviors. This pilot study aimed to explore the usability, acceptability, and feasibility of delivering a mobile diabetes educational tool to parent-child pairs in a clinical setting. This mixed methods pilot study comprised two concurrent phases with differing study participants. Phase 1 used user testing interviews to collect qualitative data on the usability and acceptability of the tool. Phase 2 used a single-arm pre- and poststudy design to quantitatively evaluate the feasibility and preliminary efficacy of the intervention. Study participants (English-speaking families with youth aged 5-14 years with insulin-dependent diabetes) were recruited from an urban hospital in Massachusetts, United States. In phase 1, parent-child pairs were invited to complete the intervention together and participate in 90-min user testing interviews assessing the tool's usability and acceptability. Interview transcripts were analyzed using a directed content analysis approach. In phase 2, parent-child pairs were invited to complete the intervention together in the clinical setting. Measures included parental and child knowledge, attitudes, and behaviors related to diabetes management (self-report surveys) and child hemoglobin A1c levels (medical record extractions); data were collected at baseline and 1-month follow-up. Pre- and postoutcomes were compared using paired t tests and the Fisher exact test. A total of 11 parent-child pairs (N=22) participated in phase 1 of the study, and 10 parent-child pairs (N=20) participated in phase 2 of the study. Participants viewed the mobile educational tool as acceptable (high engagement and satisfaction with the layout, activities, and videos) and identified the areas of improvement for tool usability (duration, directions, and animation). The findings from this pilot study suggest that the mobile educational tool is an informative, engaging, and feasible way to deliver diabetes self-management education to parents and children in an urban hospital setting. Data will inform future iterations of this mobile diabetes educational intervention to improve usability and test intervention efficacy.


[Cryoablation for cardiac arrhythmias].
The development of radiofrequency ablation has revolutionized the treatment of certain arrhythmias such as supraventricular tachycardia. Radiofrequency ablation has now become first line therapy for arrhythmias such a atrioventricular nodal reentrant tachycardia and Wolf Parkinson White syndrome. A major drawback of these procedures, especially those that necessitate ablation close to the atriocentricular node, is the risk of inadvertent atrioventricular block. In the last few years a new technique, cryoablation, has been developed to treat supraventricular arrhythmias. One of the main advantages of this new energy source for ablation is the extremely low risk of atrioventricular block. This technique is therefore especially beneficial if ablation is planned in the vicinity of the atrioventricular node. This paper describes this new procedure along with the experience with the first cases of cryoablation in Iceland.


Candida kanchanaburiensis sp. nov., a new ascomycetous yeast species related to Pichia nakazawae isolated in Thailand.
Three yeast strains, ST-633, ST-634 and ST-635, isolated from the fruit body of a mushroom, Coprinus sp., and rotted fruit of guava collected in the western region of Thailand, were found to represent a hitherto undescribed species. This yeast is related to Pichia nakazawae var. akitaensis, P. nakazawae var. nakazawae and Pichia philogaea in the D1/D2 domain of 26S rDNA but 12 (2.3%), 13 (2.5%) and 15 (2.8%) nucleotides are different from these taxa, respectively, suggesting the distinctness of the Thai strains at species level. Since ascospore formation was not detected, it is described as a new species of Candida, Candida kanchanaburiensis. This species is distinguished from P. nakazawae by the ability to assimilate 2-ketogluconic acid and L-lysine, and inability to assimilate soluble starch.


Local regulation of Leydig cells by the seminiferous tubules. Effect of short-term cryptorchidism.
Unilateral cryptorchism was induced in adult rats for 24 h, and its effect on testicular morphology and intratesticular testosterone concentration after hCG-stimulation were studied. In seminiferous, tubules from abdominal testes an increased number of degenerating germ cells was noted in stages XIV-III of the spermatogenic cycle and Sertoli cells contained an increased amount of lipid droplets in stages XIV-VIII. However, germ cells and Sertoli cells from tubules at other stages of the cycle appeared unaffected. In scrotal testes the size of peritubular Leydig cells varied in phase with the spermatogenic cycle. The largest cells were found adjacent to stage VII-VIII and the smallest adjacent to stage XI-XII. In abdominal testes no stage-dependent variation in the size of peritubular Leydig cells was seen. Perivascular Leydig cells were of equal size in abdominal and scrotal testes. The testicular testosterone concentration following stimulation with a low dose of hCG was significantly lower in abdominal testes. It is suggested that the seminiferous tubules locally modulate Leydig cell function and that the stage specific stimulatory influence from stage VII-VIII is rapidly lost during experimental cryptorchidism.


[Psychopathology associated to attention deficit hyperactivity disorder in school age children].
Attention Deficit Hyperactivity Disorder (ADHD) represents a frequent and highly comorbid disorder in children and adolescents. Comorbidity differs according to ADHD subtype and gender and has been reported to have a direct effect on the severity of ADHD. A descriptive, cross-sectional study was designed to determine the patterns of ADHD comorbidity in 102 children, aged 6 to 12 years, who attend the outpatient services of a child psychiatric hospital in Mexico City. The evaluation was performed using the Child Behavior Checklist (CBCL). The sample had about five comorbid disorders. The hyperactive-impulsive subtype had more severe externalizing symptoms, while the combined subtype had a higher severity of anxious depressive symptoms, delinquent behavior and internalized symptoms. Somatic complaints were more frequent in boys. A linear regression analysis showed that the severity of attention problems was influenced by the severity of aggressive behavior. School age children who came to psychiatric attention services with ADHD are highly comorbid. The comorbidity increases the severity of attention problems, particularly in patients with the hyperactive-impulsive or combined subtypes.


Unprecedented Activation of CO2 by α-Amino Boronic Acids.
Efficient and environmentally benign transformation of carbon dioxide (CO2) into valuable chemicals is mainly obstructed by the lack of suitable catalysts. To date, various catalysts have already been investigated for the conversion of CO2 molecules, but still finding metal-free, simple, and environment-friendly catalysts is a topic of utmost interest among researchers. Thus, in this regard, the present work projects α-amino boronic acids (AABs) as a metal-free and simple catalyst for CO2 activation. The density functional theory (DFT)-based calculations have been carried out to explore the catalytic potential of AABs. The detailed electronic structure analysis of the considered AABs unveils the catalytic similarities with frustrated Lewis pairs (FLPs) in a gas phase. Interestingly, a peculiar catalytic action of AABs has been observed in the presence of solvents. The contrasting catalytic behavior of AABs in solvents has been extensively investigated by employing principal interacting orbital (PIO), intrinsic bond orbital (IBO), and natural bond orbital (NBO) analyses along the reaction paths. The results of the orbital studies provide concrete ground for the observed reaction mechanism. Further, the energetic analysis of the reaction of CO2 with AABs reveals that <5 kcal/mol energy is required for activation in a solvent phase, and the formed adducts are readily active. These observations show that AABs can be considered as an efficient catalyst for CO2 activation.


Aortic arch aneurysm complicated with coronary artery disease: still a surgical challenge?
Recent surgical strategies and outcomes for the simultaneous operation of aortic arch repair (AAR) and coronary artery bypass grafting (CABG) were reviewed. The surgical treatment of aortic arch aneurysm complicated with coronary artery arteriosclerosis has been a challenge. In spite of recent improvements in cerebral protection during AAR such as deep hypothermia and circulatory arrest with/without retrograde cerebral perfusion, or antegrade selective cerebral perfusion (SCP), additional CABG poses a considerable surgical risk resulting in extremely higher mortality rates when compared with solo AAR. To minimize the cardiac ischemic time, several techniques such as distal coronary artery anastomosis on the perfused fibrillating heart, and coronary artery perfusion through a cardioplegic line during AAR have been employed. Recently, open stent grafting instead of aortic distal anastomosis has been attempted to minimize the cardiopulmonary time and operative complexity. Our recent experience suggested off-pump coronary artery bypass and AAR with the aid of SCP decreased cardiac ischemic time and cardiopulmonary time followed by improved operative morbidity and mortality. Further less-invasive surgical modalities that enhance the adequate myocardial protection and minimize the adverse effect of cardiopulmonary bypass can improve the outcome of this demanding operation for these elderly patients with aortic arch aneurysm and coronary artery occlusive disease.


A Comparison of Potassium Titanyl Phosphate Laser and Pingyangmycin as Treatment for Adult Laryngeal Hemangioma.
Objective: To evaluate the curative effect of Potassium titanyl phosphate (KTP) laser and pingyangmycin injection for adult laryngeal hemangiomas (ALH). Methods: This was a retrospective study conducted on patients treated with either KTP laser or pingyangmycin injection to assess the efficacy of both treatment and compare the effects on different types of adult laryngeal hemangioma. Results: The ordinal logistic regression test showed the surgery methods had no effect on the therapeutic results. On the contrary, the shape of ALH and the interaction between surgical procedures and ALH shape affected the prognosis of the ALH. This meant that the shape of ALH might be a confounding factor affecting the therapeutic effect of ALH. Thus, the Cochran-Mantel-Haenszel test which is a stratification analysis was used to assess the interaction between surgical procedures and ALH shape. Then better results were achieved using the KTP laser for the plane and raised types of ALH. Conclusions: The selection of surgical procedures (the KTP laser or pingyangmycin injection approaches) affects the treatment of ALH. For plane and raised ALH, the KTP laser may be recommended.


Narcissism and social networking Web sites.
The present research examined how narcissism is manifested on a social networking Web site (i.e., Facebook.com). Narcissistic personality self-reports were collected from social networking Web page owners. Then their Web pages were coded for both objective and subjective content features. Finally, strangers viewed the Web pages and rated their impression of the owner on agentic traits, communal traits, and narcissism. Narcissism predicted (a) higher levels of social activity in the online community and (b) more self-promoting content in several aspects of the social networking Web pages. Strangers who viewed the Web pages judged more narcissistic Web page owners to be more narcissistic. Finally, mediational analyses revealed several Web page content features that were influential in raters' narcissistic impressions of the owners, including quantity of social interaction, main photo self-promotion, and main photo attractiveness. Implications of the expression of narcissism in social networking communities are discussed.


Quantification of microvascular cerebral blood flux and late-stage tumor compartmentalization in 9L gliosarcoma using flow enhanced MRI.
Measurements of tumor microvasculature are important to obtain an understanding of tumor angiogenesis and for the evaluation of therapies. In this work, we characterize the evolution of the microvascular flux at different stages of tumor growth in the 9L rat brain tumor model. The absolute quantification of cerebral blood flux is achieved with MRI at 7 T using the flow enhanced signal intensity (FENSI) method. FENSI flux maps were obtained between 5 and 14 days after glioma cell inoculation. Based on cerebral blood flux maps, we highlighted two main stages of tumor growth, below and above 3 mm, presenting distinct flux patterns and vascular properties. No significant difference emerged from the group analysis performed on the data collected at an early developmental stage (tumor size < 3 mm) when compared with healthy tissue. At a late developmental stage (tumor size > 3 mm), we observed a significant decrease in the cerebral blood flux inside the gliosarcoma (-33%, p < 0.01) and compartmentalization of the tumor (p < 0.05). FENSI flux maps delineated a low-flux tumor core (58 ± 17 μL/min/cm(2) ) and higher vascularized regions around the tumor periphery (85 ± 21 μL/min/cm(2) ). Histology was performed on 11 animals to finely probe the intratumor heterogeneity and microvessel density, and the results were compared with the information derived from FENSI flux maps. The hyper- and hypoperfused tumor regions revealed with FENSI at the late tumor developmental stage correlated well with the ratios of high and low blood vessel density (R(2) = 0.41) and fractional vascular surface (R(2) = 0.67) observed with fluorescence microscopy [cluster of differentiation 31 (CD31) staining].


Childhood acute lymphoblastic leukemia: genetic determinants of susceptibility and disease outcome.
The origin of acute lymphoblastic leukemia (ALL), the most common pediatric cancer, can be explained by a combination of genetic factors and environmental exposure. The environmental toxicants to which an individual is exposed are biotransformed and eliminated from the body after metabolic conversion mediated by Phase I and Phase II xenobiotic-metabolizing enzymes. Phase I enzymes catalyze hydroxylation, reduction and oxidation reactions of xenobiotics (carcinogens/drugs), often converting them into more active or toxic compounds. Phase II enzymes catalyze conjugation reactions (glucuronidation, acetylation, methylation), thereby converting the metabolites into non-reactive, water-soluble products that are eliminated from the organism. The genetic polymorphism underlying the variation in enzyme activity can modify susceptibility to diverse adult cancers, probably by influencing the activation and removal of toxicants or drugs. Here we present an overview of the role of genetic variants of certain Phase I and Phase II enzymes in the development of childhood ALL, a good model for such studies because of its short latency period. The genetic contribution to the development of ALL is examined by association studies that analyze the loci of Phase I enzymes (cytochrome P-450, myeloperoxidase) and Phase II enzymes (quinone-oxidoreductase, glutathione-S-transferase, N-acetyltransferase). The loci of the enzyme variants CYPlA1, CYP2E1, NQO1, GSTM1, GSTP1, NAT2 are associated with disease development, and evidence of gene-gene interactions has emerged as well. Despite the improvements in treatment, resistant cases of ALL remain a leading cause of cancer-related death in children. Although the underlying mechanism of drug resistance is not well understood, differences in the capacity of ALL patients to process drugs and environmental carcinogens could play a role by modifying the risk of recurrent malignancy, as well as the response to therapy. Therefore, polymorphic genes encoding carcinogen- and drug-metabolizing enzymes may not only increase the risk of ALL but also influence the risk of relapse in patients. We found that the prognosis of patients with CYPlA1 and NQO1 variants was worse than that of patients who lack these variants. We conclude that genotyping ALL patients for functional polymorphisms of candidate genes can become an important tool in predicting disease outcome.


Vitamin C status and perception of effort during exercise in obese adults adhering to a calorie-reduced diet.
Moderate energy restriction and exercise are recommended for effective weight loss. Obese individuals oxidize less fat and report a higher perceived exertion during exercise, characteristics that may negatively influence exercise behavior. Because vitamin C status has been linked to fatigability, we compared the effects of vitamin C supplementation on self-reported fatigue and on the respiratory exchange ratio and the Ratings of Perceived Exertion scale during moderate exercise in healthy obese adults adhering to a hypocaloric diet. Twenty adults (4 men and 16 women) were stratified and randomly assigned to receive 500 mg of vitamin C (VC) or placebo (CON) daily for 4 wk while adhering to a vitamin C-controlled, calorie-restricted diet. Feelings of general fatigue as assessed by the Profile of Mood States questionnaire were recorded on a separate day from the exercise session at weeks 0 and 4. Participants walked on a treadmill at an intensity of 50% predicted maximal oxygen consumption for 60 min at weeks 0 and 4, and heart rate, respiratory exchange ratio, and Ratings of Perceived Exertion were recorded. After 4 wk, the two groups lost similar amounts of weight (≈ 4 kg), and the respiratory exchange ratio was not altered by group. Heart rate and the Ratings of Perceived Exertion during exercise were significantly decreased in the VC versus the CON group (-11 versus -3 beats/min, P = 0.022, and -1.3 versus +0.1 U, P = 0.001, respectively), and the general fatigue score was decreased 5.9 U for the VC group versus a 1.9 U increase for the CON group (P = 0.001). These data provide preliminary evidence that vitamin C status may influence fatigue, heart rate, and perceptions of exertion during moderate exercise in obese individuals.


Working Toward a Gold Standard: The Severity of Ethanol Withdrawal Scale (SEWS) Versus the Clinical Institute Withdrawal Assessment Alcohol Scale (CIWA-Ar).
Proving the Severity of Ethanol Withdrawal Scale (SEWS) significantly reduces Alcohol Withdrawal Syndrome (AWS) treatment Time on Medication Protocol (TOMP). Head-to-head Quality Assurance outcome compared separate cohorts of SEWS or Clinical Institute Withdrawal Assessment Alcohol Scale, Revised (CIWA-Ar) data using Student's t and Wilcoxon tests. SEWS-driven treatment (n = 244) reduced TOMP to 2.2 days versus 3.4 days for CIWA-Ar (n = 137); P < 0.0001. The SEWS is the superior measure of AWS symptoms.


The permeability of the posterior blood ocular barrier after xenon photocoagulation: a study using fluorescein labelled dextrans.
Xenon photocoagulation burns in the rabbit fundus were studied angiographically with fluorescein labelled dextrans of molecular weights in the range 3000 to 150 000. Recent photocoagulation burns showed dye leakage to all molecular weights used. Angiograms 2 days after burns had been produced showed leakage of dextrans of molecular weights up to and including 70 000 but no leakage of dextran of 150 000 molecular weight. At 7 days after photocoagulation healed burns remained permeable to dextrans of molecular weight 3000 or 20 000, but in the majority of eyes such burns did not leak dextrans of over 40 000 molecular weight. The clinical significance of the selective nature of photocoagulative damage to the posterior blood ocular barrier is discussed.


Evaluation of low-dose hCG treatment for cryptorchidism.
The aim of this study was to evaluate the efficiency of low-dose hCG (human chorionic gonadotropin) (500 IU/week for 3 weeks) in the treatment of cryptorchidism and in the assessment of Leydig cell functions. We include 35 male patients who had been diagnosed with cryptorchidism by the pediatric endocrinology specialist in the study. Twenty-one cases (Group I) received 500 IU/week of hCG while 14 patients (Group II) received 1500 IU/m2 three times a week, both for three weeks. The percentage of testis descent was calculated for both groups for the right and left testes. Leydig cell functions were evaluated by the pre- and post-treatment measurement of plasma testosterone level in all cases. A delta testosterone greater than 100 was considered to be a sufficient response. Among our patients, 77% had unilateral and 23% bilateral cryptorchidism. Unilateral cryptorchidism was detected in 80.9% of Group I patients and 71.4% of Group II patients. The pre-treatment percentages for Group I of right- and left-sided cryptorchidism were 81% and 38.1%, respectively, which decreased to 23.8% and 9.5% after treatment. The pre-treatment percentages for Group II of right- and left-sided cryptorchidism were 57.1% and 71.4%, respectively, which decreased to 14.3% and 35.7% after treatment. The success rate of hCG treatment, as defined by the testis descending into the scrotum, was 66.7% for Group I and 57.1% for Group II (p > 0.05). There was no significant difference between the two groups when Leydig cell functions were assessed. In conclusion, it is possible to use low-dose hCG for the treatment of cryptorchidism and the assessment of Leydig cell functions.


Gastrointestinal Involvement in Patients with Mantle Cell Lymphoma: A Single Center Experience of Eighty-Five Patients.
The frequency of endoscopically apparent gastrointestinal tract (GI) involvement in patients with mantle cell lymphoma (MCL) at diagnosis is thought to be in the range of 30%. While reports on GI involvement in MCL patients exist, most series lack a strict GI assessment due to the often asymptomatic nature of GI involvement. Owing to the standardized staging routine at our institution including GI assessment at diagnosis, we have analyzed the rate and prognostic impact of GI involvement in MCL. In this retrospective single-center evaluation, we have investigated GI involvement in 85 consecutive patients with MCL. All data were collected from clinical records. MCL with and without endoscopically detectable GI involvement was reported in 29 (34%) patients and 56 patients (66%), respectively. The colon was involved in 21 (72%) and the stomach in 8 (28%). Eight of 29 patients (28%) had symptomatic GI involvement, and the primary diagnosis had been established in the GI tract in 3/29 (10%) of our patients. No statistical differences could be observed between both groups in terms of gender (p = 0.474), Eastern Cooperative Oncology Group (0.428), and MCL international prognostic index (0.543). Overall survival was longer in patients with GI involvement (116.0 vs. 74 months), but not statistically significant (p = 0.825). In our single center cohort, we did not find a clinical impact of GI involvement on the clinical course of MCL and no GI complications occurred during chemotherapy in these patients. As most patients were also asymptomatic, these data argue against a routine GI assessment in patients diagnosed with MCL.


Foetal and placental ornithine decarboxylase activity in the rat--effect of maternal undernutrition.
The activity of the enzyme ornithine decarboxylase and the accumulation of nucleic acids were examined in the rat foetus and placenta during normal development and during maternal undernutrition. Maternal undernutrition resulted in a reduced rate of increase in weight of both the foetus and placenta towards the end of gestation. In the placenta the failure to increase in weight was accompanied by a failure of DNA to increase. In the foetus the amount of DNA failed to increase over a short period and then made a compensatory response to return to a normal amount by the end of gestation. Undernutrition failed to affect RNA in either the foetus or placenta. These results differ from those obtained during maternal protein deficiency. The activity of foetal and placental ornithine decarboxylase was normal during much of gestation in the undernourished group. However, at the same time as the compensatory increase in foetal DNA, there was a marked increase in enzyme activity in both tissues. It is suggested that a single compensatory stimulus is responsible for the changes in both ornithine decarboxylase and DNA.


The adhesion of different cell types to cultured vascular endothelium: effects of culture density and age.
The adhesion of lymphocytes, macrophages and resuspended smooth muscle cells to freshly subcultured bovine aortic endothelial cells is considerably greater than their adhesion to in-situ aortic endothelium when tested in vitro. Experiments with endothelial monolayers of different cell density and maturity suggest that this can be explained, at least in part, by two factors--firstly, an inverse relationship between macrophage, polymorph and smooth muscle cell (but not lymphocyte) adhesion and endothelial cell density, and secondly, an inverse relationship between endothelial adhesiveness and time since a culture became confluent. These observations may help to clarify the relationship between endothelial adhesiveness in vitro and in vivo, and to explain why leucocytes tend to adhere to regenerating arterial endothelium.


3-[(Cyclo-hexyl-idene)amino]-1-(4-methyl-phen-yl)thio-urea.
In the title compound, C(14)H(19)N(3)S, the cyclo-hexane ring has a chair conformation. The almost planar amino-thio-urea unit (r.m.s. deviation = 0.0062 Å) is aligned at a dihedral angle of 45.23 (8)° with respect to the benzene ring. Inter-molecular N-H⋯N and N-H⋯S hydrogen bonding stabilizes the crystal structure.


Adsorption of cellulase from Trichoderma reesei on cellulose and lignacious residue in wood pretreated by dilute sulfuric acid with explosive decompression.
The adsorption of cellulase on cellulose and a lignacious residue was examined by using cellulase from Trichoderma reesei, hardwood pretreated by dilute sulfuric acid under high pressure, and a lignacious residue prepared by a complete enzymatic hydrolysis of the pretreated wood. A significant amount of cellulase was found to adsorb on the lignacious residue during the hydrolysis of the pretreated wood. Hence, the adsorption of enzyme on the lignacious residue as well as cellulose must be taken into account in the development of the hydrolysis kinetics. It was found that the adsorption of enzyme on cellulose and on the lignacious residue could be represented by Langmuir type isotherms. The data show that the pretreatment at a higher temperature results in more enzyme adsorption on the cellulose fraction and less on the lignacious residue fraction. The relationship between the hydrolysis rate and the amount of enzyme adsorbed is discussed.


Dry reforming of methane over gallium-based supported catalytically active liquid metal solutions.
Gallium-rich supported catalytically active liquid metal solutions (SCALMS) were recently introduced as a new way towards heterogeneous single atom catalysis. SCALMS were demonstrated to exhibit a certain resistance against coking during the dehydrogenation of alkanes using Ga-rich alloys of noble metals. Here, the conceptual catalytic application of SCALMS in dry reforming of methane (DRM) is tested with non-noble metal (Co, Cu, Fe, Ni) atoms in the gallium-rich liquid alloy. This study introduces SCALMS to high-temperature applications and an oxidative reaction environment. Most catalysts were shown to undergo severe oxidation during DRM, while Ga-Ni SCALMS retained a certain level of activity. This observation is explained by a kinetically controlled redox process, namely oxidation to gallium oxide species and re-reduction via H2 activation over Ni. Consequentially, this redox process can be shifted to the metallic side when using increasing concentrations of Ni in Ga, which strongly suppresses coke formation. Density-functional theory (DFT) based ab initio molecular dynamics (AIMD) simulations were performed to confirm the increased availability of Ni at the liquid alloy-gas interface. However, leaching of gallium via the formation of volatile oxidic species during the hypothesised redox cycles was identified indicating a critical instability of Ga-Ni SCALMS for prolonged test durations.


[The importance of capnometry and pulse oximetry in laparoscopic cholecystectomy].
Recently the number of surgical and gynaecological operations performed via laparoscope has increased. The authors looked for the answer whether the carbon dioxide insufflated into the abdominal cavity during laparoscopy could cause significant change in the amount of carbon dioxide expired per minute. They measured the concentrations of carbon dioxide at the end of expiration, the amount of carbon dioxide produced per minute and the oxygen saturation during ataranaesthesia, muscle relaxation, intratracheal intubation and controlled mechanical ventilation in 20 cases of laparoscopic cholecystectomy. According to the results the amount of carbon dioxide exhaled per minute increased 1-3 minutes after insufflation and its maximum value was reached within 15-30 minutes (120-140% of the basic value). The continuous pulsoxymetrical examination showed that the constant intraperitoneal pressure equal or higher than 13-15 Hgmm could lead to the increase of the intrapulmonal shunt-circulation due to dystelectasis of the pulmonary bases. This could be prevented by increasing the respiratory pause-pressure to the level corresponding to the intraperitoneal pressure. In order to decrease the intraoperative anaesthesiological risks associated with the procedure the authors propose the use of capnometer and pulsoxymeter for the mentioned operation; this will keep level up with the relatively small risks associated with the postoperative period of the laparoscopic operations.


[The problems and challenges in the current eye health management in China].
The core goal of "Thirteenth Five-Year Plan for National Eye Health (2016 to 2020)" is to obtain eye health. At present, there are still several problems hampering Chinese eye health management system development, including the lack of top policy design, system protection and financial investment, weak support from primary health care institutions, other medical disciplines and social forces, and insufficient digital information. To achieve effective eye health management, it is necessary to address the sustainability of eye health management, the integrity of eye health digital information data and the feasibility of eye health payment. It is recommended that eye health-related medical workers take positive actions to strengthen the digital information construction and service capacity construction of eye disease prevention and control network, carry out health promotion extensively, and conduct eye health management mode research and practice.(Chin J Ophthalmol, 2017, 53: 481-483).


Generalized temporal coupled-mode theory for a P T-symmetric optical resonator and Fano resonance in a P T-symmetric photonic heterostructure.
We have proposed generalized temporal coupled-mode theory for P T-symmetric optical resonator, and on this basis we have explained the Fano resonance in P T-symmetric photonic heterostructure. Our theoretical predictions agree very well with the simulated results obtained by transfer matrix method, which confirms the correctness of our theory. Compared with conventional Fano resonance in optical resonator with time-reversal symmetry, in this Fano resonance the amplitudes of scattering coefficients can be tuned in much larger range, which can be much larger than one, and tend to infinity at singular scattering point, where the rates of dissipation and accumulation are equal to each other and the difference of the phases of the coupling coefficients between output fields and resonant mode is equal to ±π/2. Not only that, the quality factor Q here can be negative out of accumulation, and approaches infinity at this singular scattering point. The phases of reflections jump π in the vicinity of the minima of corresponding amplitudes. We believe that we open a new door to study Fano resonance in non-Hermitian optics and inspire relevant study in other non-Hermitian wave systems.


Are comorbidities compatible with a molecular pathological classification of neurodegenerative diseases?
The purpose of this review is to provide an update on comorbidities in neurodegenerative conditions. The term comorbidity is used here to distinguish cases with overlapping pathogenic mechanisms, which includes combinations of neurodegenerative proteinopathies from cases with multimorbidity, which is defined as concomitant brain and systemic disorders with different pathogenic mechanisms. Comorbid proteinopathies are more frequent in both sporadic and hereditary neurodegenerative diseases than previously assumed. The most frequent additional proteinopathies are related to Alzheimer's disease, Lewy body disorder, and limbic predominant transactive response DNA-binding protein 43 proteinopathy, however, different forms of tau pathologies are also increasingly recognized. In addition to ageing, synergistic interaction of proteins, common disease pathways, and the influence of genetic variations are discussed as possible pathogenic players. Comorbid proteinopathies might influence the clinical course and have implications for biomarker and therapeutic development. As pure forms of proteinopathies are still observed, the notion of current molecular classification is justified. This corroborates elucidation of various pathogenic pathways leading to neurodegeneration. Assuming that single proteins and associated pathways are targeted in therapy trials, efforts are needed to better stratify patients and to select pure proteinopathy forms lacking unfavorable genetic constellations. Otherwise combined therapeutic strategies might be necessary for comorbid proteinopathies.


Computerized characterization of masses on mammograms: the rubber band straightening transform and texture analysis.
A new rubber band straightening transform (RBST) is introduced for characterization of mammographic masses as malignant or benign. The RBST transforms a band of pixels surrounding a segmented mass onto the Cartesian plane (the RBST image). The border of a mammographic mass appears approximately as a horizontal line, and possible speculations resemble vertical lines in the RBST image. In this study, the effectiveness of a set of directional textures extracted from the images before the RBST. A database of 168 mammograms containing biopsy-proven malignant and benign breast masses was digitized at a pixel size of 100 microns x 100 microns. Regions of interest (ROIs) containing the biopsied mass were extracted from each mammogram by an experienced radiologist. A clustering algorithm was employed for automated segmentation of each ROI into a mass object and background tissue. Texture features extracted from spatial gray-level dependence matrices and run-length statistics matrices were evaluated for three different regions and representations: (i) the entire ROI; (ii) a band of pixels surrounding the segmented mass object in the ROI; and (iii) the RBST image. Linear discriminant analysis was used for classification, and receiver operating characteristic (ROC) analysis was used to evaluate the classification accuracy. Using the ROC curves as the performance measure, features extracted from the RBST images were found to be significantly more effective than those extracted from the original images. Features extracted from the RBST images yielded an area (Az) of 0.94 under the ROC curve for classification of mammographic masses as malignant and benign.


Electron-attachment-induced DNA damage: instantaneous strand breaks.
Low energy electron-attachment-induced damage in DNA, where dissociation channels may involve multiple bonds including complex bond rearrangements and significant nuclear motions, is analyzed here. Quantum mechanics/molecular mechanics (QM/MM) calculations reveal how rearrangements of electron density after vertical electron attachment modulate the position and dynamics of the atomic nuclei in DNA. The nuclear motions involve the elongation of the P-O (P-O(3') and P-O(5')) and C-C (C(3')-C(4') and C(4')-C(5')) bonds for which the acquired kinetic energy becomes high enough so that the neighboring C(3')-O(3') or C(5')-O(5') phosphodiester bond may break almost immediately. Such dynamic behavior should happen on a very short time scale, within 15-30 fs, which is of the same order of magnitude as the time scale predicted for the excess electron to localize around the nucleobases. This result indicates that the C-O phosphodiester bonds can break before electron transfer from the backbone to the base.


Systematic search for zinc-binding proteins in Escherichia coli.
A systematic search for Escherichia coli proteins with the zinc-binding activity was performed using the assay of radioactive Zn(II) binding to total E. coli proteins fractionated by two methods of two-dimensional gel electrophoresis. A total of 30-40 radioactive spots were identified, of which 14 have been assigned from N-terminal sequencing. In addition to five known zinc-binding proteins, nine zinc-binding proteins were newly identified including: acetate kinase (AckA), DnaK, serine hydroxymethyltransferase (GlyA), transketolase isozymes (TktA/TktB), translation elongation factor Ts (Tsf), ribosomal proteins L2 (RplB), L13 (RplM) and one of S15 (RpsO), S16 (RpsP) or S17 (RpsQ). Together with about 20 known zinc-binding proteins, the total number of zinc-binding proteins in E. coli increased up to more than 30 species (or more than 3% of about 1000 proteins expressed under laboratory culture conditions). The specificity and affinity of zinc-binding were analysed for some of the zinc-binding proteins.


A new pullulan and a branched (1-->3)-, (1-->6)-linked beta-glucan from the lichenised ascomycete Teloschistes flavicans.
The polysaccharides formed on hot alkaline extraction of the ascomycetous lichen Teloschistes flavicans were fractionated to give two glucans, which were characterised by methylation analysis and 1D and 2D NMR spectroscopy. One was a branched beta-glucan containing (1-->3) and (1-->6) linkages, a structure which is more typical of basidiomycetes rather than ascomycetes, which have linear glucans. The other was an alpha-glucan with alternating (1-->4) and (1-->6) linkages, found for the first time in Nature. This structure can be classified as a pullulan, which has been isolated from the fungi Aureobasidium pullulans, Tremella mesenterica, and Cyttaria harioti, but has different ratios of the component glycosidic linkages. The significance of the presence of the isolated alpha- and beta-glucans is discussed.


Medical practices regarding hepatitis C virus infection in Europe.
Six hundred and ninety-three European Association for the Study of the Liver (EASL) members, belonging to one of the 15 European Union (EU) member-states, were surveyed, through a standardized 45-item questionnaire, on their medical practices regarding hepatitis C virus (HCV) infection. The response rate was 45%, roughly similar in all the countries concerned. Responders were classified into three groups according to their geographical origin: North, Centre and South. A consensus existed with regard to the necessity of HCV screening in well-defined situations, such as history of blood transfusion, haemodialysis, haemophilia or intravenous drug addiction (90% of positive answers) while opinions substantially differed for vertical and nosocomial transmission of HCV. For the prevention of sexual and vertical transmission, opinions differed greatly: 22% were in favour of barrier methods for HCV-positive subjects while 34% were against; 49% allowed breast-feeding for babies born to HCV-positive mothers while 14% were against. Conversely, there was relative homogeneity in the issue of domestic prevention (70% in favour of precautions). Algorithms for prescription of virological tests were inhomogeneous (recombinant immunoblot assay was used by 60%; polymerase chain reaction was requested by 77% when alanine amino-transferase (ALT) was elevated vs 89% when normal): medical evaluation varied according to ALT values: liver biopsy and liver ultrasonography were carried out in 90 and 91% vs 40 and 70% for increased and normal ALT, respectively. Thirty per cent of respondents advised patients to stop alcohol consumption and 60% advised moderation. Two-thirds of the responders did not take into account histological severity and virological parameters before initiating antiviral therapy. Eighty per cent of the participants claimed that they administered interferon (IFN) for 12 months. For most of the items studied, there was a large variation, not only between the three groups, but also within each group. Ninety-two per cent of the responders claimed that they were well trained on HCV but they were rather critical of the quality of the information diffused (satisfaction rate: 45%). Altogether, our survey demonstrates that preventive and medical practices towards HCV are not homogeneous throughout the EU; this suggests the need for a European consensus conference in this regard.


Detection of human papillomavirus DNA in prostate gland tissue by using the polymerase chain reaction amplification assay.
Human papillomavirus (HPV) is associated with specific benign and malignant lesions of the epithelial and mucosal surfaces. Of the sexually transmitted types, HPV type 16 (HPV 16) and HPV 18 are commonly associated with severe dysplasia and carcinoma of the uterine cervix. In men, genital HPV infections which have been studied are manifest as external lesions usually involving types other than 16 and 18. The nature of HPV 16 and 18 infections in men has not been explored. Since the most common neoplasias of the male genital tract involve the prostate gland, we assayed benign hyperplastic and cancerous prostate tumors for the presence of HPV DNA, using type-specific primers in polymerase chain reaction amplifications. Normal prostatic tissue obtained at autopsy was included in the survey. Amplified sequences specific for HPV 16 were found in 14 of 15 benign prostatic hyperplasias and in all of four carcinomas tested. In contrast, HPV 18 was identified in only three benign hyperplasias, which also contained HPV 16 DNA. Four of five normal prostates demonstrated no HPV infection; one contained HPV 16 sequences. The presence of these oncogenic HPV types in prostate tissues suggests a reservoir for sexual transmission; a potential role for the virus in the etiology of prostatic neoplasia remains to be demonstrated.


De novo transcriptome assembly of Sorghum bicolor variety Taejin.
Sorghum (Sorghum bicolor), also known as great millet, is one of the most popular cultivated grass species in the world. Sorghum is frequently consumed as food for humans and animals as well as used for ethanol production. In this study, we conducted de novo transcriptome assembly for sorghum variety Taejin by next-generation sequencing, obtaining 8.748 GB of raw data. The raw data in this study can be available in NCBI SRA database with accession number of SRX1715644. Using the Trinity program, we identified 222,161 transcripts from sorghum variety Taejin. We further predicted coding regions within the assembled transcripts by the TransDecoder program, resulting in a total of 148,531 proteins. We carried out BLASTP against the Swiss-Prot protein sequence database to annotate the functions of the identified proteins. To our knowledge, this is the first transcriptome data for a sorghum variety derived from Korea, and it can be usefully applied to the generation of genetic markers.


Structural and biochemical insights into a hyperthermostable urate oxidase from Thermobispora bispora for hyperuricemia and gout therapy.
Microbial urate oxidase has emerged as a potential source of therapeutic properties for hyperuricemia in arthritic gout and renal disease. The thermostability and long-term thermal tolerance of the enzyme need to be established to prolong its therapeutic effects. Here, we present the biochemical and structural aspects of a hyperthermostable urate oxidase (TbUox) from the thermophilic microorganism Thermobispora bispora. Enzymatic characterization of TbUox revealed that it was active over a wide range of temperatures, from 30 to 70 °C, with optimal activity at 65 °C and pH 8.0, which suggests its applicability under physiological conditions. Moreover, TbUox exhibits high thermostability from 10 to 65 °C, with Tm of 70.3 °C and near-neutral pH stability from pH 7.0 to 8.0 and high thermal tolerance. The crystal structures of TbUox revealed a distinct feature of the C-terminal loop extensions that may help with protein stability via inter-subunit interactions. In addition, the high thermal tolerance of TbUox may be contributed by the extensive inter-subunit contacts via salt bridges, hydrogen bonds, and hydrophobic interactions. The findings in this study provide a molecular basis for the thermophilic TbUox urate oxidase for application in hyperuricemia and gout therapy.


Twelve episodes of meningitis in the same patient!
Recurrent bacterial meningitis is potentially life-threatening; resultant complications and adverse events during management take their extra toll on the patient. A rare case with 12 consecutive episodes of pyogenic meningitis, probably the maximum number ever reported in the literature, has been presented. A minor head injury but with no subsequent cerebrospinal fluid (SCF) leak during childhood was the index event in this patient. High resolution computerized tomography (HRCT) scan of the base of the skull clearly revealed a bony dehiscence missed on numerous previous imagings. Culprit micro organisms involved in recurrence were Streptococcus pneumoniae and Neisseriae meningitides. Though surgical repair would have been definitive treatment, medical management with pneumococcal and meningococcal vaccination and prophylactic penicillin have been used in this patient to prevent further recurrences.


A test method for the evaluation of protective glove materials used in agricultural pesticide operations.
The ASTM Standard Test Method for Resistance of Protective Clothing Materials to Permeation by Liquids and Gases (F 739-85) and the recommended permeation cell have been modified to permit the testing of protective clothing materials for permeation by the low volatility, low water solubility active ingredients present in many pesticide formulations. The modification makes use of solid collection medium, a thin (0.02-in. thick) sheet of silicone rubber, to collect permeants. Those compounds permeating the protective material can then be desorbed into an appropriate solvent and analyzed using conventional methods and instruments. A series of permeation tests have been conducted using samples of 10 common, commercially available protective glove materials and the modified cell. Permeation of the active ingredient as well as carrier solvent components of several concentrated pesticide formulations containing low volatility, low water solubility active ingredients and aromatic hydrocarbon carrier solvents has been monitored. The relative breakthrough and the total mass of material permeating the glove materials appears to be strongly related to the concentration of the aromatic carrier solvent present in the formulations studied to date. The collection method was found to be less useful for monitoring the permeation of active ingredients, which have reasonably high water solubilities. The results obtained by using this method with samples of protective glove materials challenged by several concentrated pesticide formulations are described. For these formulations containing xylene boiling range aromatic solvents, gloves made of nitrile rubber, butyl rubber, and Silver Shield were most resistant to permeation; natural rubber and polyethylene glove materials were least resistant.


Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes.
In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation.


A two-strain hiv-1 mathematical model to assess the effects of chemotherapy on disease parameters.
Treatment of human immunodeficiency virus type 1 (HIV-1) infection during the symptomatic phase has significantly improved patient survival. We present a two-strain HIV mathematical model that captures the dynamics of the immune system and two HIV-1 variants under antiretroviral therapy. We explore the effects of chemotherapy on the dynamics of two viral strains and T lymphocytes with one mutant strain phenotypically resistant to drug effects. Model calculations show that there is a common pattern for CD4+ T cell count increase. There is a drastic increase of CD4+ T cells during the first few weeks of treatment, followed by a gradual increase, and these increases are strictly by clonal expansion of preexisting CD4+ T cells. Plasma HIV RNA dramatically decline to zero levels during the first week of drug administration. If drug efficacy is equal to or above a threshold efficacy, viral load remains at zero levels and if drug efficacy is less than the threshold efficacy, viral load gradually increases until it stabilizes. Viral rebound during treatment is entirely due to the recovery of CD4+ T cells. The results also reveal that there is a dynamic equilibrium between viral load and cytotoxic T lymphocyte (CTL) response in an infected individual during drug administration.


Cognitive Effects of High-Frequency rTMS in Schizophrenia Patients With Predominant Negative Symptoms: Results From a Multicenter Randomized Sham-Controlled Trial.
Cognitive impairments are one of the main contributors to disability and poor long-term outcome in schizophrenia. Proof-of-concept trials indicate that repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) has the potential to improve cognitive functioning. We analyzed the effects of 10-Hz rTMS to the left DLPFC on cognitive deficits in schizophrenia in a large-scale and multicenter, sham-controlled study. A total of 156 schizophrenia patients with predominant negative symptoms were randomly assigned to a 3-week intervention (10-Hz rTMS, 15 sessions, 1000 stimuli per session) with either active or sham rTMS. The Rey Auditory Verbal Learning Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Digit Span Test, and the Regensburg Word Fluency Test were administered before intervention and at day 21, 45, and 105 follow-up. From the test results, a neuropsychological composite score was computed. Both groups showed no differences in any of the outcome variables before and after intervention. Both groups improved markedly over time, but effect sizes indicate a numeric, but nonsignificant superiority of active rTMS in certain cognitive tests. Active 10-Hz rTMS applied to the left DLPFC for 3 weeks was not superior to sham rTMS in the improvement of various cognitive domains in schizophrenia patients with predominant negative symptoms. This is in contrast to previous preliminary proof-of-concept trials, but highlights the need for more multicenter randomized controlled trials in the field of noninvasive brain stimulation.


Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8).
We have identified the zinc-finger transcription factor Kruppel-like factor 4 (Klf4) among the transcription factors that are significantly downregulated in their expression during epithelial-mesenchymal transition (EMT) in mammary epithelial cells and in breast cancer cells. Loss and gain of function experiments demonstrate that the down-regulation of Klf4 expression is required for the induction of EMT in vitro and for metastasis in vivo. In addition, reduced Klf4 expression correlates with shorter disease-free survival of subsets of breast cancer patients. Yet, reduced expression of Klf4 also induces apoptosis in cells undergoing TGFβ-induced EMT. Chromatin immunoprecipitation/deep-sequencing in combination with gene expression profiling reveals direct Klf4 target genes, including E-cadherin (Cdh1), N-cadherin (Cdh2), vimentin (Vim), β-catenin (Ctnnb1), VEGF-A (Vegfa), endothelin-1 (Edn1) and Jnk1 (Mapk8). Thereby, Klf4 acts as a transcriptional activator of epithelial genes and as a repressor of mesenchymal genes. Specifically, increased expression of Jnk1 (Mapk8) upon down-regulation of its transcriptional repressor Klf4 is required for EMT cell migration and for the induction of apoptosis. The data demonstrate a central role of Klf4 in the maintenance of epithelial cell differentiation and the prevention of EMT and metastasis.


[Pilot study of the effectiveness of combination therapy with reduced dose alteplase and the glycoprotein IIb/IIIa antagonist tirofiban in acute myocardial infarct].
In a pilot study with a total of 43 patients (31 males, 12 females) at a mean age of 64.2 +/- 12.1 years, the efficacy of a combination of a reduced dosage of alteplase (50 mg) and tirofiban with a start infusion of 0.4 microgram/kg/min over half an hour and an infusion rate of 0.10 microgram/kg/min over 12 h (PRISM-PLUS, modified) in four patients and a bolus of 10 micrograms/kg over 3 minutes and an infusion rate of 0.15 microgram/kg/min over 24 h (RESTORE, modified) in 39 patients were tested in acute myocardial infarction with regard to patency of infarct vessel and TIMI flow according to coronary angiography after 60 minutes, 30-day mortality and bleeding complications. The use of tirofiban in the PRISM-PLUS dosage led to an infarct vessel patency of 25% with TIMI III flow in one case. There were no complications in the next 30 days in this group. The use of tirofiban in the RESTORE dosage led to an infarct-vessel patency of 87%, a TIMI III flow in 79%, a 30-day mortality of 2.6% and a slight PCI-associated bleeding complication in one case. The combination of alteplase in a reduced dosage and tirofiban with a single bolus and an infusion rate according to the RESTORE study with satisfactory efficacy and low complication rate seems to be useful in the management of acute myocardial infarction.


Transsexualism and Slater's Selective Vocabulary Test.
It has been shown elsewhere that transsexual males use a vocabulary which differs from that of normal males. This could be demonstrated by Slater's Selective Vocabulary Test. This test was administered to 56 male transsexuals and the 'd' score - a device to eliminate the influence of I.Q. - was calculated. The normal d score for males is zero and the higher the score the greater is the degree of femininity. An attempt was made to find factors which facilitate this abnormal development of the vocabulary in male transsexuals. In order to do this the cases were divided into a group of high and a group of low 'd' scores, and tested for correlations with a number of factors which seemed likely to influence the vocabulary development. No such correlations could be established.


Functional recovery of injured cavernous nerves achieved through endogenous nerve growth factor-containing bioactive fibrous membrane.
Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN) during prostatectomy is the main cause of postoperative erectile dysfunction (ED). In this study, the capability of a personalized bioactive fibrous membrane to regenerate injured CN was investigated. The fibrous membrane bioactivity is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. In a rat model of bilateral CN crush, the implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function, showing a significantly increased number of smooth muscle cells and content of endothelial and neuronal nitric oxide synthases (eNOS; nNOS). In addition, the bioactive fibrous membrane promotes nerve regeneration by increasing the number of myelinated axons and nNOS-positive cells, therefore reversing the CN fibrosis found in untreated rats or rats treated with a bare fibrous membrane. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments for CN injuries. It may constitute an effective treatment for prostate cancer patients suffering from ED after being subject to radical prostatectomy. STATEMENT OF SIGNIFICANCE: The present work introduces a unique strategy to address post-surgical ED resulting from CN injury during pelvic surgery (e.g., radical prostatectomy, radical cystoprostatectomy, abdominoperineal resection). It comprises a bioactive and cell-free fibrous implant, customized to enhance CN recovery. Pre-clinical results in a rat model of bilateral CN crush demonstrated that the bioactive fibrous implant can effectively heal injured CN, and restore penile structure and function. This implant selectively binds NGF from patient fluids (i.e. urine) due to its functionalized surface and high surface area. Moreover, its local implantation reduces adverse side effects. This tailored regenerative approach has the potential to revolutionize the treatment of ED in prostate cancer patients following radical prostatectomy, overcoming current treatment limitations.


Diabetes mellitus and anorexia nervosa: another view.
Two patients are described in whom diabetes mellitus and anorexia nervosa occurred together. The nature of the relationship between the two conditions is discussed. It is suggested that weight loss is not always the primary goal in such patients.


Benefits and applications of laser-induced sparks in real scale model measurements.
The characteristics of using a laser-induced spark as a monopole source in scale model measurements were assessed by comparison with an electric spark and a miniature spherical loudspeaker. Room impulse responses of first order directivity sources were synthesized off-line using six spatially distributed sparks. The source steering direction was scanned across the horizontal and vertical plane to assess the origin of early reflections. The results confirm that the characteristics of the laser-induced spark outperform those of typical sources. Its monopole characteristics enable the authors to synthesize room responses of directional sources, e.g., to obtain directional information about reflections inside scale models.


Midterm outcomes and durability of sinus segment preservation compared with root replacement for acute type A aortic dissection.
The durability of root repair for acute type A aortic dissection is not well studied in the context of aortic insufficiency and stability of the sinuses of Valsalva. We compared clinical and functional outcomes in patients undergoing root repair and replacement for acute type A aortic dissection. Of 716 patients undergoing surgery for acute type A aortic dissection, 585 (81.7%) underwent root repair and 131 (18.3%) underwent root replacement. Survival, cumulative incidence of reoperation, aortic insufficiency, and sinuses of Valsalva dilation were compared between the 2 groups. Survival at 1, 5, and 10 years was 84.1% versus 77.3%, 70.8% versus 69.2%, 57.6% versus 58.0% in the root repair and replacement groups, respectively (P = .69). Cumulative incidence of reoperation at 1, 5, and 10 years was 0.0% versus 0.8%, 1.4% versus 3.8%, and 3.4% versus 8.6% in the root repair and root replacement groups, respectively (P = .011). Multivariable Cox regression identified sinuses of Valsalva diameter 45 mm or more as a risk factor for proximal aortic reoperation (hazard ratio, 9.06; 95% confidence interval, 1.26-65.24). In a repeated-measures, linear, mixed-effects model, root replacement was associated with smaller follow-up of sinuses of Valsalva dimensions (β = -0.66, P < .001). In an ordinal longitudinal mixed model, root replacement was associated with lower severity of postoperative aortic insufficiency (β = -3.10, P < .001). Survival is similar, but the incidence of aortic insufficiency and root dilation may be greater after root repair compared with root replacement for acute type A aortic dissection.


The role of innate immunity in Alzheimer's disease.
The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the brain-resident macrophages, known as microglia, and their receptors as integral regulators of both the initiation and propagation of inflammation, Aβ accumulation, neuronal loss, and memory decline in AD. Emerging studies have also begun to reveal critical roles for distinct innate immune pathways in AD pathogenesis, which has led to great interest in harnessing the innate immune response as a therapeutic strategy to treat AD. In this review, we will highlight recent advancements in our understanding of innate immunity and inflammation in AD onset and progression. Additionally, there has been mounting evidence suggesting pivotal contributions of environmental factors and lifestyle choices in AD pathogenesis. Therefore, we will also discuss recent findings, suggesting that many of these AD risk factors influence AD progression via modulation of microglia and immune responses.


Twinkling artifact in color Doppler imaging of the orbit.
To show an artifact related to color Doppler flow imaging of the orbit. Three patients with strongly reflective structures in the orbit were selected from those routinely referred by clinicians for color Doppler ultrasonography of the orbit. Gray scale and color flow images were obtained with a 7.5-MHz linear array probe for a region with strongly reflective structures. A spectral display was acquired to confirm the presence of blood flow. One patient had a metallic foreign body just behind the bulb; another had calcification within the irregular mass of phthisis bulbi; and the third had hyperechoic drusen in the periphery of the intraocular melanoma. The color mosaic, suggesting the presence of blood flow, was detected beyond all hyperechoic structures. Close vertical bands with no outer wrapping were detected in the spectrum display, obtained by placing the sample volume on the region of color flow. The artificial color flow was recognized as a color Doppler twinkling artifact. The color flow beyond the strongly reflecting structures in the orbit might be mistakenly interpreted as real blood flow if an examiner is not familiar with the artifact. It should prompt further imaging with spectral Doppler ultrasonography.


Defect Engineering in Ultrathin SnSe Nanosheets for High-Performance Optoelectronic Applications.
Ultrathin lamellar SnSe is highly attractive for applications in areas such as photonics, photodetectors, photovoltaic devices, and photocatalysis, owing to its suitable band gap, exceptional light absorption capabilities, and considerable carrier mobility. On the other hand, SnSe nanosheets (NSs) still face challenges of being difficult to prepare and their devices having low photoelectric conversion efficiencies. Herein, ultrathin SnSe NSs with controlled Se defects were synthesized with high yield by a facial Li intercalation-assisted liquid exfoliation method. The loss of Se, a narrowing of the band gap, and an increase in lattice disorders involving vacancies, distortions, and phase transition were observed in SnSe NSs prepared with a long lithiation process. Comparing between the 24 and 72 h lithiation samples, the ones processed for a longer time displayed a faster recombination time due to more defect-induced mid-states. Inspiringly, enhancements of 4-10 times were observed for photodetector device parameters such as photocurrent, photoresponsivity, photoresponse speed, and specific detectivity of the 72 h lithiation SnSe NSs. Additionally, these devices show good stability and a broad detection range, from ultraviolet to the near infrared region. Our results provide a promising avenue for the mass production of SnSe NSs with high photoelectric performance and open up opportunities for applications in photonics, optoelectronics, and photocatalysis.


Nursing resource planning in Norway.
One explanation for nurses' reticence about becoming involved in money issues is that they often mistakenly associate economics with cutting costs or cost containment. Another is nursing's European heritage, where the nurses' morale obligation has historically been to the patient. However, if nursing as a service is to continue, nurses must learn to plan their nursing resources, cost their services and document their effectiveness in terms of interventions and patient outcomes. To help nurse administrators gather more and better data for resource planning, below is a look at a framework suggested by Martha Quivey and the future directions to be taken.


Ocular Surface Disease Index© and the five-item dry eye questionnaire: A comparison in Indian patients with dry eye disease.
To compare the suitability of the Ocular Surface Disease Index (OSDI) and the 5-item Dry Eye Questionnaire (DEQ-5) in Indian patients with dry eyes. This cross-sectional study evaluated the OSDI and DEQ-5 in patients with tear film abnormalities. Tear film breakup time, tear film height, Schirmer's I, lissamine green staining, and meibomian gland expressibility were performed on each patient. There were 101 patients with symptoms and/or signs of tear film abnormality. Both OSDI and DEQ-5 questionnaires significantly correlated (ρ = 0.566, P < 0.0001) with each other. The OSDI questionnaire showed a good correlation with all dry eye tests, whereas the DEQ-5 correlated significantly only with the tear film breakup time and the lissamine green score. None of the questionnaires correlated with meibomian gland expressibility. The Bland-Altman analysis revealed a marginal bias (-0.01 unit) for DEQ-5. The DEQ-5 scored higher in patients with mild symptoms. While 101 (100%) patients answered all the questions in the DEQ-5, only 19 (18.8%) patients answered all the questions in the OSDI questionnaire. The least responses were recorded in the vision-function-related and environmental trigger subscales of the OSDI. The OSDI and DEQ-5 scores showed a moderate correlation. The OSDI questionnaire correlated with a higher number of dry eye tests than the DEQ-5. The large number of skipped questions in the vision-function-related and environmental trigger subscales of the OSDI suggests that the questionnaire is not adequately adapted to the Indian population. Patients with a negative OSDI score should be reassessed with the DEQ-5 to exclude symptom positivity.