Evolution of Electrospinning in Liver Tissue Engineering.
The major goal of liver tissue engineering is to reproduce the phenotype and functions of liver cells, especially primary hepatocytes ex vivo. Several strategies have been explored in the recent past for culturing the liver cells in the most apt environment using biological scaffolds supporting hepatocyte growth and differentiation. Nanofibrous scaffolds have been widely used in the field of tissue engineering for their increased surface-to-volume ratio and increased porosity, and their close resemblance with the native tissue extracellular matrix (ECM) environment. Electrospinning is one of the most preferred techniques to produce nanofiber scaffolds. In the current review, we have discussed the various technical aspects of electrospinning that have been employed for scaffold development for different types of liver cells. We have highlighted the use of synthetic and natural electrospun polymers along with liver ECM in the fabrication of these scaffolds. We have also described novel strategies that include modifications, such as galactosylation, matrix protein incorporation, etc., in the electrospun scaffolds that have evolved to support the long-term growth and viability of the primary hepatocytes.


Preliminary investigation of the psychometric properties of the Korean version of the brief cognitive assessment tool-short form for Korean American nursing home residents.
The authors of the current article developed and investigated the psychometric properties of a Korean version of the Brief Cognitive Assessment Tool-Short Form (BCAT-SF-K) to better understand cognitive functioning of Korean American nursing home residents. In Step I, normative values were established for the BCAT-SF-K based on a sample of Korean American community-dwelling older adults (n = 34). In Step II, the authors confirmed construct validity for the BCAT-SF-K in a sample of Korean American nursing home residents (n = 26), described cognitive levels, and reported key demographics. In the nursing home sample, 84.6% of individuals had severe cognitive impairment, 7.7% had mild impairment, and 7.7% had normal cognition. The BCAT-SF-K appears to be a reliable cognitive screening measure for Korean American nursing home residents. Based on the current study's findings, Korean American nursing home residents are both older and more cognitively impaired than their American-born nursing home counterparts. Study findings are discussed in relation to improving care for these vulnerable nursing home residents.


Potential antitumor agents. 42. Structure-activity relationships for acridine-substituted dimethyl phosphoramidate derivatives of 9-anilinoacridine.
Replacement of the 1'-methanesulfonamide group of the 9-anilinoacridine class of antitumor agents with the 1'-(dimethyl phosphoramidate) group provides compounds that are generally more lipophilic and bind more tightly to DNA. On the average, the dimethyl phosphoramidates are twice as dose potent as the corresponding methanesulfonamide (AMSA) compounds against P388 leukemia in vivo, but also show about twice the acute toxicity and no resultant improvement in tumor cell selectivity (ILSmax values) is seen. A pairwise comparison of a range of acridine-substituted compounds shows that structure-activity relationships within each series are similar and dominated by the acridine substitution pattern.


Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation.
Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.


Salivary Myeloperoxidase, Assessed by 3,3'-Diaminobenzidine Colorimetry, Can Differentiate Periodontal Patients from Nonperiodontal Subjects.
Periodontal diseases, which result from inflammation of tooth supporting tissues, are highly prevalent worldwide. Myeloperoxidase (MPO), from certain white blood cells in saliva, is a biomarker for inflammation. We report our study on the salivary MPO activity and its association with severity of periodontal diseases among Thai patients. Periodontally healthy subjects (n = 11) and gingivitis (n = 32) and periodontitis patients (n = 19) were enrolled. Assessments of clinically periodontal parameters were reported as percentages for gingival bleeding index (GI) and bleeding on probing (BOP), whereas pocket depth (PD) and clinical attachment loss (CAL) were measured in millimeters and then made to index scores. Salivary MPO activity was measured by colorimetry using 3,3'-diaminobenzidine as substrate. The results showed that salivary MPO activity in periodontitis patients was significantly higher than in healthy subjects (p = 0.003) and higher than in gingivitis patients (p = 0.059). No difference was found between gingivitis and healthy groups (p = 0.181). Significant correlations were observed (p < 0.01) between salivary MPO activity and GI (r = 0.632, p < 0.001), BOP (r = 0.599, p < 0.001), PD (r = 0.179, p = 0.164), and CAL (r = 0.357, p = 0.004) index scores. Sensitivity (94.12%), specificity (54.55%), and positive (90.57%) and negative (66.67%) predictive values indicate that salivary MPO activity has potential use as a screening marker for oral health of the Thai community.


Infusing gerontology throughout the BSW curriculum.
How can social work educators ensure that all of their BSW students have the savvy and "know-how" to deal with the needs of our growing aging population? The development of broad-based, innovative gerontological learning opportunities in a BSW program in a small liberal arts and sciences college is presented in this article. Strategies for actively involving community representatives in curriculum changes and participatory learning experiences with students are shared. Ways to incorporate various disciplines in the BSW education are explored in addition to developing intergenerational projects, direct involvement of older persons in the educational process, and ways to unite field practice with theory.


[Prototype symbolization in hooded crows].
The ability in prototype symbolization was studied in four crows trained in matching concept. The experimental approach was characterized by the absence of direct training providing an association between the pictured arrays and Arabic numerals. Experimental sessions were divided into demonstrative and test phases. In the demonstrative phases, the sample and the reinforced stimulus belonged to the same category: if the sample was a pictured array, the reinforced stimulus was also the pictured array, if the sample was a numeral, the reinforced stimulus was likewise a numeral. Matching-to-sample competence was sufficient to perform this task successfully. In case of a correct choice a crow received some mealworms, their number was equal to the number of items in the pictured array or the Arabic numeral. In the test phases, the sample and the comparison stimuli were of different categories. If the sample was a pictured array, the comparison stimuli were numerals; if the sample was a numeral, the comparisons were the pictured arrays. Such tests required the birds to choose a numeric symbol corresponding to the pictured array or to choose the array of pictured items numerically equal to the Arabic symbol. All four crows performed this task successfully. Birds were able to set up a correspondence between the Arabic numeral from 1 to 4 and the number of elements in pictured arrays by way of mental juxtaposition of the earlier received information. Similar experiments showed that crows are likely to be able to perform mental operations with numerals analogous to simple arithmetic addition.


Controlled Growth of Gold Nanostars: Effect of Spike Length on SERS Signal Enhancement.
Two different types of gold nanostars (Au NS), namely, short-spiked nanostars (SSNS) and long-spiked nanostars (LSNS), are prepared by using a hexagonal lyotropic liquid-crystalline (LLC) phase as a template. The formation, size and length of spikes or arms of the resultant Au NS are controlled by preparation in either a hexagonal LLC phase or an isotropic phase. These NS are anchored onto indium tin oxide (ITO) electrodes through a self-assembled monolayer of 3-mercaptopropyltrimethoxysilane, which acts as a linker molecule. Structural and morphological characterisations of SSNS- and LSNS-anchored ITO electrodes are performed by means of microscopic and spectroscopic analyses. Further electrochemical techniques, namely, cyclic voltammetry and electrochemical impedance spectroscopy, are also used to confirm the immobilisation of these Au NS on ITO electrodes and to study the electrochemical characteristics. These studies clearly reveal the formation of star-shaped, branched, anisotropic nanostructures of gold during the template preparation method and these Au NS are successfully anchored onto ITO electrodes through a covalent immobilisation strategy. Furthermore, the SERS activity of these Au NS is analysed by using glutathione and crystal violet as analytes and by employing glass and ITO as substrates. It is interesting to note that SSNS show a significant enhancement in SERS signals relative to those of LSNS.


Crystal structures and vibrational spectroscopy of copper(I) thiourea complexes.
Several synthetic strategies using copper(I) starting materials or copper(II) compounds and an in situ sulfite reductant have been used to systematically explore the chemistry of copper(I) complexes with thiourea and substituted thiourea ligands. This has resulted in the discovery of several new complexes and methods for the bulk synthesis of some previously reported complexes that had been prepared adventitiously in small quantity. The new complexes are (tu = thiourea, dmtu = N,N'-dimethylthiourea, etu = ethylenethiourea): [I(4)Cu(4)(tu)(6)].H(2)O, [Cu(4)(tu)(10)](NO(3)).tu.3H(2)O, [BrCu(dmtu)(3)], [ICu(dmtu)(3)](2), [BrCu(etu)(2)](2), [ICu(etu)(2)], [ICu(etu)(2)](3). [I(4)Cu(4)(tu)(6)].H(2)O has an adamantanoid structure, with four terminal iodide ligands and six doubly bridging tu ligands. In contrast to this, [Cu(4)(tu)(10)](NO(3)).tu.3H(2)O contains a tetranuclear cluster in which four of the tu ligands are terminal and the other six are doubly bridging. [BrCu(dmtu)(3)] is a mononuclear complex with tetrahedral coordination of copper by one bromide and three dmtu ligands, whereas [Cu(dmtu)(3)](2)I(2) has a centrosymmetric dimeric cation with two uncoordinated iodides, four terminal dmtu and two doubly bridging dmtu ligands, [(dmtu)(2)Cu(mu-S-dmtu)(2)Cu(dmtu)(2)]I(2). A reversal of this monomer to dimer trend from bromide to iodide is seen for the etu counterparts: [BrCu(etu)(2)](2) is a centrosymmetric dimer with two doubly bridging etu ligands, [(etu)BrCu(mu-S-etu)(2)CuBr(etu)], whereas [ICu(etu)(2)] is a trigonal planar monomer, although the novel [I(3)Cu(3)(etu)(6)] is also defined. Infrared and Raman spectra of the synthesized complexes were recorded and the metal-ligand vibrational frequencies have been assigned in many cases. The results confirm previously observed correlations between the vibrational frequencies and the corresponding bond lengths for complexes of the unsubstituted tu ligand. A mechanochemical/infrared method was used to synthesize [I(3)Cu(3)(etu)(6)] from CuI and etu, and to demonstrate the polymorphic transition from [ICu(etu)(2)] to [I(3)Cu(3)(etu)(6)].


Anomalous pressure in fluctuating shear flow.
We investigate how the pressure in fluctuating shear flow depends on the shear rate S and on the system size L by studying fluctuating hydrodynamics under shear conditions. We derive anomalous forms of the pressure for two limiting values of the dimensionless parameter lambda=SL(2)/nu, where nu is the kinematic viscosity. In the case lambda << 1, the pressure is not an intensive quantity because of the influence of the long-range spatial correlations of momentum fluctuations. In the other limit lambda >> 1, the long-range correlations are suppressed at large distances, and the pressure is intensive. In this case, however, there is the interesting effect that the nonequilibrium correction to the pressure is proportional to S(3/2), which was previously obtained with the projection operator method [K. Kawasaki and J. D. Gunton, Phys. Rev. A 8, 2048 (1973)].


Adult-to-adult living donor liver transplantation for acute liver failure in China.
To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation (AALDLT) for acute liver failure (ALF). Between January 2005 and March 2010, 170 living donor liver transplantations were performed at West China Hospital of Sichuan University. All living liver donor was voluntary and provided informed consent. Twenty ALF patients underwent AALDLT for rapid deterioration of liver function. ALF was defined based on the criteria of the American Association for the Study of Liver Diseases, including evidence of coagulation abnormality [international normalized ratio (INR) ≥ 1.5] and degree of mental alteration without pre-existing cirrhosis and with an illness of < 26 wk duration. We reviewed the clinical indications, operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors. The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis. Survival rates after operation were analyzed using the Kaplan-Meier method. Receiver operator characteristic (ROC) curve analysis was undertaken to identify the threshold of potential risk factors. The causes of ALF were hepatitis B (n = 18), drug-induced (n = 1) and indeterminate (n = 1). The score of the model for end-stage liver disease was 37.1 ± 8.6, and the waiting duration of recipients was 5 ± 4 d. The graft types included right lobe (n = 17) and dual graft (n = 3). The mean graft weight was 623.3 ± 111.3 g, which corresponded to graft-to-recipient weight ratio of 0.95% ± 0.14%. The segment Vor VIII hepatic vein was reconstructed in 11 right-lobe grafts. The 1-year and 3-year recipient's survival and graft survival rates were 65% (13 of 20). Postoperative results of total bilirubin, INR and creatinine showed obvious improvements in the survived patients. However, the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients. Multivariate analysis showed that waiting duration was independently correlated with increased mortality (P = 0.014). Furthermore, ROC curve revealed the cut-off value of waiting time was 5 d (P = 0.011, area under the curve = 0.791) for determining the mortality. The short-term creatinine level with different recipient's waiting duration was described. The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration < 5 d (66.7% vs 9.1%, P = 0.017). In addition, all donors had no residual morbidity. Furthermore, univariate analysis did not show that short assessment time induced the high morbidity (P = 0.573). Timely AALDLT for patients with ALF greatly improves the recipient survival. However, further systemic review is needed to investigate the optimal treatment strategy for ALF.


The Impact of Annual Audiograms on Employee's Habits and Awareness Regarding Hearing Protection and Noise Induced Hearing Loss, On and Off the Job.
Noise-induced hearing loss occurs among workers across a wide spectrum of industries. The purpose of this study was to investigate whether annual hearing testing contributed to a change in employees' habits and awareness and aimed to evaluate the use of hearing protection at work and at home. Employees enrolled in a university's hearing conservation program (HCP) were anonymously surveyed regarding their hearing protection habits and awareness of noise exposures on and off the job using a Likert-type scale. Approximately half were "very much" concerned about hearing loss over time. Evidence supports that annual testing, part of the workplace HCP, also led over half of participants to change their habits at work and at home. Awareness of noise exposures increased both at home and at work with annual testing. Overall, the HCP in this particular setting was associated with improved on-the-job and home hearing protection use.


Analysis of the Pseudomonas solanacearum polygalacturonase encoded by pglA and its involvement in phytopathogenicity.
A major endopolygalacturonase excreted by Pseudomonas solanacearum was purified to greater than 95% homogeneity and shown to have an isoelectric point of 9.0 and a subunit molecular mass of 52 kilodaltons (kDa). The gene encoding this enzyme (pglA) was isolated from a genomic library of P. solanacearum DNA based on its expression in Escherichia coli and shown to be contained on a 1.8-kilobase DNA fragment. The identity of the pglA gene product and the 52-kDa polygalacturonase was demonstrated by immunoadsorption and isoelectric focusing experiments. The cloned pglA gene was apparently expressed from its own promoter in E. coli and its product was partially secreted into the periplasm. The pglA gene was insertionally inactivated in vitro and used to mutate the chromosomal pglA gene of P. solanacearum by marker exchange mutagenesis. The resulting mutant strain was deficient in production of the 52-kDa polygalacturonase and took twice as long to wilt and kill tomato plants as the wild-type parent in plant bioassay experiments. Complementation in trans with the wild-type cloned pglA gene restored virulence to near wild-type levels. The data indicate that the pglA gene is important, but not absolutely necessary, for pathogenesis.


Subrutilane-A Hexacyclic Sesterterpene from Streptomyces subrutilus.
Mining of a terpene synthase from Streptomyces subrutilus resulted in the identification of the hexacyclic sesterterpene subrutilane, besides eight pentacyclic side products. Subrutilane represents the first case of a saturated sesterterpene hydrocarbon. Its structure, including the absolute configuration, was unambiguously determined through X-ray crystallographic analysis and stereoselective deuteration. The cyclisation mechanism to subrutilane and its side products was investigated in all detail by isotopic labelling experiments and DFT calculations. The subrutilane synthase (SrS) also converted (2Z)-GFPP into one major product. Additional compounds were obtained from the substrate analogues (7R)-6,7-dihydro-GFPP and (2Z,7R)-6,7-dihydro-GFPP with blocked reactivity at the C6-C7 bond. Interestingly, the early steps of the cyclisation cascade with (2Z)-GFPP and the saturated substrate analogues were analogous to those of GFPP, but then deviations from the natural cyclisation mode occur.


TLR4 mediates upregulation and sensitization of TRPV1 in primary afferent neurons in 2,4,6-trinitrobenzene sulfate-induced colitis.
Elevated excitability of primary afferent neurons underlies chronic pain in patients with functional or inflammatory bowel diseases. Recent studies have established an essential role for an enhanced transient receptor potential vanilloid subtype 1 (TRPV1) signaling in mediating peripheral hyperalgesia in inflammatory conditions. Since colocalization of Toll-like receptor 4 (TLR4) and TRPV1 has been observed in primary afferents including the trigeminal sensory neurons and the dorsal root ganglion neurons, we test the hypothesis that TLR4 might regulate the expression and function of TRPV1 in primary afferent neurons in 2,4,6-trinitrobenzene sulfate (TNBS)-induced colitis using the TLR4-deficient and the wild-type C57 mice. Despite having a higher disease activity index following administration of 2,4,6-trinitrobenzene sulfate, the TLR4-deficient mice showed less inflammatory infiltration in the colon than the wild-type mice. Increased expression of TLR4 and TRPV1 as well as increased density of capsaicin-induced TRPV1 current was observed in L4-S2 dorsal root ganglion neurons of the wild-type colitis mice till two weeks post 2,4,6-trinitrobenzene sulfate treatment. In comparison, the TLR4-deficient colitis mice had lower TRPV1 expression and TRPV1 current density in dorsal root ganglion neurons with lower abdominal withdrawal response scores during noxious colonic distensions. In the wild type but not in the TLR4-deficient dorsal root ganglion neurons, acute administration of the TLR4 agonist lipopolysaccharide increased the capsaicin-evoked TRPV1 current. In addition, we found that the canonical signaling downstream of TLR4 was activated in 2,4,6-trinitrobenzene sulfate-induced colitis in the wild type but not in the TLR4-deficient mice. These results indicate that TLR4 may play a major role in regulation of TRPV1 signaling and peripheral hyperalgesia in inflammatory conditions.


Predictability and Feasibility of Total Alloplastic Temporomandibular Joint Reconstruction using DARSN TM Joint Prosthesis for patients in Indian subcontinent-A prospective clinical study.
The aim of this study was to investigate the feasibility of a custom made alloplastic Temporomandibular Joint (TMJ) device design in patients undergoing temporomandibular (TM) Total Joint Reconstruction (TJR). TMJ disease with functional and anatomic distortion dictates the need for TJR. There are various materials to reconstruct a TMJ. However, various factors, such as cost, availability of prosthetic joint, limit its use to tertiary health care center. Hence, we have investigated the feasibility and efficacy of the custom made alloplastic TMJ prosthesis (DARSN TM Joint Prosthesis) with the advantage of being acceptable financially and the overall Quality of life (QoL) diagnosed with TMJ ankylosis and End Stage Joint Disease (ESJD) selected from the study population. The study group comprised of 20 patients with TMJ ankylosis or End Stage Joint Disease (ESJD) who needed TM TJR of which few subjects in the study population had history of failed previous surgery to the TMJ region. The patients underwent resection of the joint followed by TJR using the custom made alloplastic TMJ prosthesis. Various subjective and objective variables were evaluated such as the Jaw Function (JF), Inter-incisal opening (IO), Diet intake (DI), Quality of Life (QoL) using a Psychometric Modified Likert Scale and nutritional status of the patient using the Mid-Upper Arm Circumference (MUAC) as reference. All the subjective and objective variables showed significant improvement in the postoperative period as compared to the preoperative period. The JF score increased with a mean score of 6.25 (P<0.00001). Postoperative mean DI score was 3.15 (P<0.00001) and IO increased up to 29-38mm in 95% of the study population. The study population exhibited an improved overall QoL and nutritional status post-operatively. Follow up period of 1 year showed significant functional improvement among the study population. The results shows that the custom made alloplastic joint replacement is safe and effective and reliable alternative to treat patients with TMJ disease which restricts the normal function to a greater degree requiring TM TJR.


Molecular analysis of PRRT2 gene in a case of paroxysmal kinesigenic dyskinesia patient.
Paroxysmal kinesigenic dyskinesia (PKD) is an abnormal involuntary movement that is episodic or intermittent, with sudden onset, and the attacks are induced by sudden movement. Mutations in proline-rich transmembrane protein 2 (PRRT2) gene have been implicated in the cause of this disorder. This study presents a case of PKD on the basis of clinical findings supported and evidences obtained through a mutational analysis. Sequencing of all the exons of PRRT2 gene revealed a frameshift mutation (p.R217Pfs*8) in exon 2 and a novel transition mutation (c.244C > T) in 5'-untranslated region (UTR). Though mutations in PRRT2 gene are well-established in PKD, this study for the first time presents a novel transition mutation in the exon 2 region.


IDH1 Mutation in Gliomas in Mosul City - Iraq.
IDH1 (isocitrate dehydrogenase 1) mutation might be encounter in the low grade glioma and directs the progression of the tumor to a higher grade. To assess the frequency of IDH1 mutations in gliomas and to correlate the IDH1 positivity with the type and grade of tumors, the age and sex of the patients. A retro- and prospective case series study. One hundred and nine cases of intracranial gliomas were collected between 2008 and 2014 from Mosul Private Laboratories and Al-Jamboree Teaching Hospitals in Mosul. IDH1 mutations were assessed immunohistochemically using anti-IDH1 R132H mouse monoclonal antibody. IDH1 mutation was perceived in 34.86% of gliomas. In adult gliomas, the secondary glioblastoma and the low-grade astrocytoma had the greatest values of IDH1 positivity (88.88% and 62.5% respectively), followed by oligoastrocytoma/oligodendroglioma (50.0%), and anaplastic astrocytoma (47.36%). The primary glioblastomsa showed 17.64% IDH1 positivity. Males and females expressed the IDH1 equally. While, there was no role of IDH1 in pediatric gliomas. IDH1 mutation is commonly present in adult gliomas particularly in low-grade gliomas, and secondary glioblastoma, with equal sex distribution, but it has no role in pediatric gliomas.


UC-VEGF-SMC Three Dimensional (3D) Nano Scaffolds Exhibits Good Repair Function in Bladder Damage.
We constructed a UC-VEGF-SMC three dimensional (3D) scaffold to explore its effect on blood vessel regeneration and bladder repair function in a rabbit model with bladder injury. Rabbit adipose tissue-derived stem cells (ADSCs) were cultured to construct pluripotent stem cell systems that can be induced to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs). Reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, MTT assay and HE staining were used in our study. Rabbit models were divided into an experimental group, control group and sham group. The bladder histology, urodynamics, smooth muscle function, stent degradation rate, urothelial permeability and biomechanical determination of rabbits were detected after grafting the scaffold. Correct stem cells based on the ADSC surface marker and found that CD90 and CD105 were positive and that CD34 and CD45 were negative. RT-PCR showed that ADSC-iPS cells expressed the marker gene of embryonic stem cells (ESCs), which indicated that Sox2, Klf4, Oct4 and c-Myc were inserted into the iPS nucleus and that the ADSC-iPS system was constructed successfully. Immunofluorescence and MTT assays indicated that iPS differentiated into mature SMCs and UCs. ELISA and HEMC culturing methods revealed that vascular endothelia growth factor (VEGF) could promote the growth of HMECs. Rabbit bladder repair function (urodynamics, smooth muscle function, urothelial permeability and biomechanical determination) was stronger in the experimental group than in the control group. UC-VEGF-SMC 3D nano scaffold exhibits good repair function for bladder damage, which may helpful for treatment of damaged bladders.


Potentiation of immunosuppressive effects of cyclosporin A by 1 alpha,25-dihydroxyvitamin D3.
Both cyclosporin A (CsA) and 1 alpha,25-dihydroxyvitamin D3 (vitamin D3) inhibit T-cell functions. Because CsA has a dose-related systemic toxicity, there is a need for approaches by which the dosage of CsA could be reduced while maintaining the required immunosuppression. Therefore, we examined for any potentiating effect of vitamin D3 on CsA-induced suppression of T cell functions in vitro. Peripheral blood mononuclear cells were stimulated with phytohemagglutinin in the presence or absence of various concentrations of CsA (1.6-13.2 micrograms/ml) or vitamin D3 (10(-10)-10(-7) M) or both together and [3H]thymidine incorporation (TdR), interleukin 2 (IL-2) production, IL-2 receptor (IL-2R) expression, and the response to exogenous recombinant IL-2 (rIL-2) on TdR were measured. IL-2 production was measured on CTLL cell line and IL-2R expression with anti-Tac monoclonal antibody using FACScan. There was a dose-dependent inhibition of TdR, IL-2 production, and IL-2R expression by CsA. Vitamin D3 inhibited TdR and IL-2 production in a dose-dependent manner but had no significant (P greater than 0.1) effect on IL-2R expression. Recombinant IL-2 had no effect on CsA-induced inhibition of TdR, whereas rIL-2 completely reversed the vitamin D3-induced inhibition of TdR. A significantly (P less than 0.05) increased inhibition of TdR and IL-2 production was observed when two agents were used together as compared to expected inhibition by the addition of each agent separately. A consistent synergism was observed between all concentrations of CsA used and vitamin D3 (10(-8) and 10(-7) M). This study shows that the potentiation of immunosuppressive effects of CsA by vitamin D3 could be used as an approach to reduce the dosage of CsA in clinical use without compromising immunosuppression, thus preventing or minimizing the dose-related toxic effects of CsA.


Elaboration and evaluation of alginate foam scaffolds for soft tissue engineering.
Controlling microarchitecture in polymer scaffolds is a priority in material design for soft tissue applications. This paper reports for the first time the elaboration of alginate foam-based scaffolds for mesenchymal stem cell (MSC) delivery and a comparative study of various surfactants on the final device performance. The use of surfactants permitted to obtain highly interconnected porous scaffolds with tunable pore size on surface and in cross-section. Their mechanical properties in compression appeared to be adapted to soft tissue engineering. Scaffold structures could sustain MSC proliferation over 14 days. Paracrine activity of scaffold-seeded MSCs varied with the scaffold structure and growth factors release was globally improved in comparison with control alginate scaffolds. Our results provide evidence that exploiting different surfactant types for alginate foam preparation could be an original method to obtain biocompatible scaffolds with tunable architecture for soft tissue engineering.


Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms.
Malignant tumors remain one of the main sources of morbidity and mortality around the world. A chemotherapeutic approach to cancer treatment poses a multitude of challenges, primarily due to the low selectivity and genotoxicity of the majority of chemotherapeutic drugs currently used in the clinical practice, often leading to treatment-induced tumors formation. Highly selective antitumor drugs can largely resolve this issue, but their high selectivity leads to significant drawbacks due to the intrinsic tumor heterogeneity. In contrast, plant polyphenols can simultaneously affect many processes that are involved in the acquiring and maintaining of hallmark properties of malignant cells, and their toxic dose is typically much higher than the therapeutic one. In the present work we describe the mechanisms of the action of polyphenols on cancer cells, including their effects on genetic and epigenetic instability, tumor-promoting inflammation, and altered microbiota.


The response range of the blue-cone pathways: a source of vulnerability to disease.
Retinal disease preferentially affects the sensitivity of the "blue"-cone pathways. This vulnerability to disease may be due, in part, to a more limited response range. A psychophysical technique, the probe-flash paradigm, was used to test this hypothesis. The data suggest that the S-cone pathways have a more limited response range than the L-cone pathways. Explanations for blue-cone vulnerability are discessed in the context of this finding.


Professional and Personal Development After Psychoanalytic Training: Interviews with Early Career Analysts.
After analytic training, graduates position their newly acquired identity as "psychoanalyst" in the context of their broader career, contemplating whether to start new analytic cases, adapting their new knowledge base to psychotherapy practice, and deciding how to focus their professional and personal interests going forward. Using questionnaires and interviews, the Columbia Postgraduate Analytic Practice Study (CPAPS) has prospectively tracked the career trajectory of 69 of 76 graduates (91%) from the Columbia University Center for Psychoanalytic Training and Research since 2003. In this paper grounded theory is used to identify developmental themes in interviews with analysts who have been followed for at least ten years. Recent graduates are negotiating the following challenges: developing a sense of competence, navigating relationships with colleagues and former supervisors as situations change and roles shift, transitioning into becoming mentors, and balancing the competing responsibilities of professional and personal life. Disillusionment about aspects of training, analytic practice, analysis as a treatment, institute politics, and the field in general emerges as a stark reality, despite a high level of career satisfaction. Educational recommendations include making career development opportunities available and providing a realistic view of both practice realities and expectations of analytic treatment outcome.


Emotion and Implicit Timing: The Arousal Effect.
This study tested the effects of emotion on implicit time judgment. The participants did not receive any overt temporal instructions. They were simply trained to respond as quickly as possible after a response signal, which was separated from a warning signal by a reference temporal interval. In the testing phase, the inter-signal interval was shorter, equal or longer than the reference interval and was filled by emotional pictures (EP) of different arousal levels: high, moderate, and low. The results showed a U-shaped curve of reaction time plotted against the interval duration, indicating an implicit processing of time. However, this RT-curve was shifted toward the left, with a significantly lower peak time for the high-arousal than for the low-arousal EP. This emotional time distortion in an implicit timing task suggests an automatic effect of emotion on the internal clock rate.


Cardiac Troponin T and creatine kinase MB fraction levels among patients with acute ischemic stroke in Nigeria.
Stroke has been a global burden, with increasing morbidity and mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction are reported to be elevated in patients admitted with acute ischaemic stroke and high level of these biomarkers indicated more severe stroke and neurologic deficit in some of the patients. To evaluate the serum levels cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in patients with acute ischaemic stroke and relate the analytes to severity of stroke. Patients with clinical diagnosis of ischaemic stroke diagnosed, confirmed by brain Computerized Tomography scan and equal number of apparently healthy age and sex-matched were recruited. Serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) were analysed using ELISA method and Stroke severity was determined using National Institute of Health Stroke Score (NIHSS). Mean serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in stroke patients were found to be higher than age sex matched control (p<0.05). NIHS Score of 12.2 ± 5.43 and 9.78 ± 3.97 were observed in Patients with elevated and normal cTnT respectively (p=0.009) while NIHS Score were similar in patients with elevated and normal CK-MB (p = 0.772). The mean values of serum cTnT and CK-MB were higher in acute ischaemic stroke patients compared to controls. Serum cardiac Troponin t level may be a significant biomarker of the severity of stroke.


Diagnosing Recurrent DVT of the Leg by Two Different Non-Contrast-Enhanced Magnetic Resonance Direct Thrombus Imaging Techniques: A Pilot Study.
Introduction Magnetic resonance direct thrombus imaging (MRDTI) is a promising technique to improve the diagnostic management of patients with a suspected ipsilateral recurrent deep vein thrombosis (DVT) by direct visualization of a thrombus. Another magnetic resonance imaging (MRI) technique, T1-weighted turbo spin-echo spectral attenuated inversion recovery (TSE-SPAIR), has the potential to image a thrombus directly with a high spatial resolution as well. The main aim of this pilot study was to investigate if adding the TSE-SPAIR sequence to an MRDTI sequence performed in patients with suspected recurrent DVT may increase the diagnostic confidence of expert MRDTI readers. Methods Fifteen patients with suspected acute recurrent DVT were included in this study. The TSE-SPAIR sequence was scanned directly after the MRDTI scan but not used to guide clinical decision making, and both scans were adjudicated post hoc two times separately by three independent expert MRDTI readers. Diagnostic confidence was scored on a 4-point Likert scale: (1) poor (definite diagnosis impossible), (2) fair (evaluation of major findings possible), (3) good (definite diagnosis possible), and (4) excellent (exact diagnosis possible). Results The diagnostic confidence of expert readers increased when adding the TSE-SPAIR sequence on top of the MRDTI sequence from "good" (median, 3.0; interquartile range [IQR], 2.66-3.0) to "excellent" (median, 3.67; IQR 3.33-3.67; p = 0.001). Evaluation of the scans in the reversed order 5 months after initial reading showed similar results. Diagnostic accuracy for proximal DVT of both scan techniques was good. Conclusion The extra TSE-SPAIR sequence may help increase diagnostic confidence of radiologists in cases of uncertain diagnosis in patients with suspected ipsilateral recurrent DVT.


One-year intensive characterization on PM2.5 nearby port area of Thessaloniki, Greece.
The chemical characterization of particulate matter (PM) 2.5 fraction was studied during a 1-year sampling campaign conducted at a site near Thessaloniki's port area. PM2.5 collected samples were chemically analyzed for polycyclic aromatic hydrocarbons, minerals, and trace elements (Pb, Ni, Cu, V, Mn, Cr, Zn, Mg, K, Ti, Fe, Ca, and Al); water-soluble ions (Cl(-), NO3 (-), SO4 (2-), K(+), Na(+), NH4 (+), Mg(2+), Ca(2+)); and organic and elemental carbon. The average annual PM2.5 concentration (66.0 μg/m(3)) was at the highest level compared with other studies reported for the same city but different sampling sites. The average daily sum of the measured concentration of polycyclic aromatic hydrocarbons (PAHs) was 12.76 ng/m(3); this value decreased to 6.73 ng/m(3) for the warm period and reached the value of 19.8 ng/m(3) for the cold period. The average concentration of benzo[a]pyrene during the sampling period was 0.75 ng/m(3), which is below the European Union limit value of 1.0 ng/m(3). The ionic content comprised, on average, 22.6 % of the PM2.5 mass, with sulfate and ammonium being the most abundant species (31 and 26 %, respectively, of measured ions during the whole sampling period). The annual mean concentrations of organic carbon (OC) and elemental carbon (EC) were 10.5 ± 6.3 and 2.3 ± 1.5 μg/m(3), respectively. The OC/EC ratio ranged from 1.6 to 9.9, suggesting that there is a significant influence of residential wood burning for heating as well as ship and vehicle emissions to the sampling area. Finally, the elemental composition of associated PM2.5 was dominated by Ca, Fe, and Al. Although conclusions based only on PM2.5 measurements cannot entirely estimate all harbor sources' contribution, there is evidence to support that port activities affect the city's air quality and vice versa.


Urology in the USA.
The Mayo Clinic in the USA offers information to professionals and patients. Nursing teams focus on technical aspects of care whereas urological nurse practitioners take an holistic approach.


Role of the cytokine-induced SH2 domain-containing protein CIS in growth hormone receptor internalization.
The cytokine-inducible SH2 domain-containing protein CIS inhibits signaling from the growth hormone (GH) receptor (GHR) to STAT5b by a proteasome-dependent mechanism. Here, we used the GH-responsive rat liver cell line CWSV-1 to investigate the role of CIS and the proteasome in GH-induced GHR internalization. Cell-surface GHR localization and internalization were monitored in GH-stimulated cells by confocal immunofluorescence microscopy using an antibody directed against the GHR extracellular domain. In GH naïve cells, GHR was detected in small, randomly distributed granules on the cell surface and in the cytoplasm, with accumulation in the perinuclear area. GH treatment induced a rapid (within 5 min) internalization of GH.GHR complexes, which coincided with the onset of GHR tyrosine phosphorylation and the appearance in the cytosol of distinct granular structures containing internalized GH. GHR signaling to STAT5b continued for approximately 30-40 min, however, indicating that GHR signaling and deactivation of the GH.GHR complex both proceed from an intracellular compartment. The internalization of GH and GHR was inhibited by CIS-R107K, a dominant-negative SH2 domain mutant of CIS, and by the proteasome inhibitors MG132 and epoxomicin, which prolong GHR signaling to STAT5b. GH pulse-chase studies established that the internalized GH.GHR complexes did not recycle back to the cell surface in significant amounts under these conditions. Given the established specificity of CIS-R107K for blocking the GHR signaling inhibitory actions of CIS, but not those of other SOCS/CIS family members, these findings implicate CIS and the proteasome in the control of GHR internalization following receptor activation and suggest that CIS-dependent receptor internalization is a prerequisite for efficient termination of GHR signaling.


Complete Genome Sequences of Lactococcus lactis subsp. lactis bv. diacetylactis FM03 and Leuconostoc mesenteroides FM06 Isolated from Cheese.
Here, the genome sequences of Lactococcus lactis subsp. lactis bv. diacetylactis FM03 and Leuconostoc mesenteroides FM06, both isolated from cheese, are presented. FM03 and FM06 contain 7 and 3 plasmids, respectively, that carry genes encoding functions important for growth and survival in dairy fermentations.


Does cochlear reimplantation affect speech recognition?
Although cochlear implantation has been proven to be a very effective method of rehabilitation for post-lingually deaf adults and pre-lingually deaf children, as electronic devices, cochlear implants are occasionally subject to damage or breakdowns. In these cases, reimplantation would be necessary. The aim of this study was to find out whether or not there are any negative effects on speech abilities after reimplantation with the same type of multichannel digital implant in the same ear. Seven patients were provided with a digital multi-channel cochlear implant. One subject suffered manipulative damage to the implant, and in six subjects an implant failure was observed. All reimplantations were performed on the same ear as the initial implantation. with the same implant type. Parameters such as insertion depth and number of active channels were the same in all subjects before and after reimplantation. Immediately following the revision surgery, three patients attained the same level of hearing that they had with their original implants. Three months following reimplantation, five subjects achieved almost the same scores that they had before reimplantation. The results showed that cochlear implant patients undergoing re-implantation can anticipate achieving nearly the same level of speech recognition as they had with their original implant. Nevertheless, patients need to be aware of potential problems before undergoing reimplantation so that expectations are not too high.


Progressive Model-Driven Approach for 3D Modeling of Indoor Spaces.
This paper focuses on the 3D modeling of the interior spaces of buildings. Three-dimensional point clouds from laser scanners can be considered the most widely used data for 3D indoor modeling. Therefore, the walls, ceiling and floor are extracted as the main structural fabric and reconstructed. In this paper, a method is presented to tackle the problems related to the data including obstruction, clutter and noise. This method reconstructs indoor space in a model-driven approach using watertight predefined models. Employing the two-step implementation of this process, the algorithm is able to model non-rectangular spaces with an even number of sides. Afterwards, an "improvement" process increases the level of details by modeling the intrusion and protrusion of the model. The 3D model is formed by extrusion from 2D to 3D. The proposed model-driven algorithm is evaluated with four benchmark real-world datasets. The efficacy of the proposed method is proved by the range of [77%, 95%], [85%, 97%] and [1.7 cm, 2.4 cm] values of completeness, correctness and geometric accuracy, respectively.


Association between adipokines and critical illness outcomes.
Adipose tissue is an endocrine organ that plays a critical role in immunity and metabolism by virtue of a large number of hormones and cytokines, collectively termed adipokines. Dysregulation of adipokines has been linked to the pathogenesis of multiple diseases, but some questions have arisen concerning the value of adipokines in critical illness setting. The objective of this review was to evaluate the associations between blood adipokines and critical illness outcomes. PubMed, CINAHL, Scopus, and the Cochrane Library databases were searched from inception through July 2016 without language restriction. Studies reporting the associations of adipokines, leptin, adiponectin, resistin, and/or visfatin with critical illness outcomes mortality, organ dysfunction, and/or inflammation were included. A total of 38 articles were selected according to the inclusion/exclusion criteria of the study. Significant alterations of circulating adipokines have been reported in critically ill patients, some of which were indicative of patient outcomes. The associations of leptin and adiponectin with critical illness outcomes were not conclusive in that blood levels of both adipokines did not always correlate with the illness severity scores or risks of organ failure and mortality. By contrast, studies consistently reported striking increase of blood resistin and visfatin, independently of the critical illness etiology. More interestingly, increased levels of these adipokines were systematically associated with severe inflammation, and high incidence of organ failure and mortality. There is strong evidence to indicate that increased levels of blood resistin and visfatin are associated with poor outcomes of critically ill patients, including higher inflammation, and greater risk of organ dysfunction and mortality. Systematic review, level III.


International standardisation of the test of masticating and swallowing solids in children.
The Test of Masticating and Swallowing Solids (TOMASS) is a validated assessment tool measuring the efficiency of solid bolus intake by four quantitative parameters: discrete bites, masticatory cycles, swallows and time to ingest a single cracker. A normative database for adults (20-80+ years) has previously been established. The objective of this study was to investigate the applicability and reliability of the TOMASS in children and adolescents (TOMASS-C) and to establish the normative database for this younger population. We collected data from 638 participants (male: 311, female: 327) in five age groups (4-18 years) with five different but very similar test crackers in four countries. Significant effects of bolus type (cracker), age group and gender on the TOMASS parameters were identified, requiring stratification of the TOMASS-C database by these variables. Intra-rater reliability was excellent (ICC > 0.94) for all parameters; inter-rater reliability was moderate for "number of swallows" (ICC = 0.54), good for "bites" (ICC = 0.78) and "time" (ICC = 0.82), and excellent for "masticatory cycles" (ICC = 0.96). The "Test of Masticating and Swallowing Solids in Children (TOMASS-C)" was identified to be a reliable diagnostic tool for the comprehensive measurement of discrete oral stage components of solid bolus ingestion, standardised by a large normative database that covers age groups from preschoolers to young adults. While differences between gender groups were less pronounced than in the adult population, previous results relating to changes in masticatory and swallowing as a function of age are confirmed by our data.


Reversible Switching of Single-Molecule Magnetic Behaviour by Desorption/Adsorption of Solvent Ligand in a New Dy(III)-Based Metal Organic Framework.
Two metal-organic frameworks (MOFs), [Dy(BDC)(NO3)(DMF)2] n (1, H2BDC = terephthalic acid) and [Dy(BDC)(NO3)] n (1a), were synthesized. The structures of MOFs 1 and 1a are easy to be reversibly transformed into each other by the desorption or adsorption of coordination solvent molecules. Accordingly, their magnetic properties can also be changed reversibly, which realizes our goals of manipulating on/off single-molecule magnet behaviour. MOF 1 behaves as a single-molecule magnet either with or without DC field. Contrarily, no slow magnetic relaxation was observed in 1a both under zero field and applied field.


Contrast sensitivity loss in multiple sclerosis. Selectivity by eye, orientation, and spatial frequency measured with the evoked potential.
Multiple sclerosis can produce highly selective losses in visual function. Psychophysical studies have demonstrated contrast sensitivity deficits for spatial frequencies or for stimulus orientations. Using real-time lock-in retrieval of the visual evoked potential, the authors measured contrast sensitivity in 15 cases with probable or definite multiple sclerosis and acuities of 20/40 or better. Sine-wave grating contrast threshold determinations for three spatial frequencies (1, 4, and 8 cycles/deg) and four orientations (0, 45, 90, and 135 deg) revealed contrast deficits in at least one spatial frequency and orientation in every case. In most cases the visual losses were spotty or multifocal, and not the same in both eyes. Some cases with highly selective patterns of orientation or spatial frequency losses were observed and are discussed in terms of involvement of cortical functional architecture in the disease.


Visible/Infrared Dissociation of NO3: Roaming in the Dark or Roaming on the Ground?
We present a DC slice imaging study of roaming dynamics in the photodissociation of the nitrate radical, NO3, contrasting pure visible excitation with a combination of visible and CO2 laser excitation at 10.6 μm. Images of specific rotational levels of NO are seen to reflect dissociation on the ground and first excited electronic states, as reported in previous work. The branching is obtained for specific rotational levels by comparison to quasiclassical trajectory calculations of the dynamics on these two surfaces. The results for the visible dissociation are found to be very similar to the combination of visible and infrared, raising questions about the nature of the coupling of these surfaces, the extent to which roaming takes place on both, and how the final product branching is determined.


Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*).
We have isolated a novel cDNA from the human fetal brain cDNA library with homology to the Mg2+ -dependent serine/threonine protein phosphatase 2C (PP2C) family. The cDNA is 3055 bp in length, and the predicted coding region encodes a 360-amino-acid protein, which shows 99% identity to the PP2C epsilon from rat and mouse. Then we term it human PP2C epsilon gene. The gene is mapped to chromosome 3q26.1 and contains 4 exons. RT-PCR analysis shows that the PP2C epsilon is widely expressed in human tissues and the expression levels in heart, placenta, lung, liver, kidney, and pancreas are relatively high.


Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients.
The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation.


Successful radiofrequency catheter ablation of sustained ventricular tachycardia postmyocardial infarction in man guided by a multielectrode "basket" catheter.
Currently, analysis of sustained ventricular tachycardia postmyocardial infarction in man is limited by the time required for single point activation mapping and the difficulty in obtaining information during hemodynamically unstable arrhythmias. To overcome these limitations, we developed a multielectrode "basket" catheter for endocardial recording and pacing. This report describes the first clinical use of such a catheter to guide successful radiofrequency ablation of incessant sustained ventricular tachycardia postmyocardial infarction. This system may significantly shorten the time required for VT analysis and improve the results of radiofrequency catheter ablation for VT postmyocardial infarction.


Measuring side effects after radiotherapy for pharynx cancer.
Data on side effects after radiotherapy is needed to establish the benefits and drawbacks of new treatments, but side effects are not quantified as easily as survival or local control. Side effects may be quantified using physical measures. Unfortunately, only few endpoints exist where a physical measure is obtainable, and the case of a patient-relevant measure is even rarer. Radiotherapy is often followed by complex symptoms not easily quantifiable by the observer. Quantitative patient reported side effects can be retrieved using validated questionnaires, but this kind of data is often difficult to interpret and the correlation with clinically observable or measurable changes not straightforward. The exploitation of the possibilities of highly conformal radiotherapy and multimodality treatment depends on a better understanding of the correlation between dose, volume, modifying factors, and side effects. Using pharynx cancer as an example, the purpose of this article is to summarize the possibilities and limitations of different methods for measurement of radiotherapy-induced side effects.


Conservative management of postoperative chylous fistula with octreotide and peripheral total parenteral nutrition.
Postoperative chylous fistula after neck dissection is an uncommon complication associated with significant patient morbidity. Octreotide acetate is a somatostatin analogue established in the treatment of chylothorax; however, its utility in the management of cervical chylous fistulae has not been fully evaluated. The investigators hypothesized that chylous fistula can be managed by a combination of octreotide and peripheral total parenteral nutrition (TPN). A retrospective review of cases compiled at our institution from 2009 to 2015 was conducted. Ten patients, all men, were identified as having a postoperative chylous fistula after a neck dissection. All patients were treated with peripheral TPN and intravenous octreotide. Mean age of the patients was 63.0 years (range 49 to 82). Five (50.0%) had a neck dissection for the management of metastatic nasopharyngeal carcinoma and had previous neck irradiation. In 8 (80%) patients, chylous fistula occurred in the left neck. Seven (70.0%) of the leaks occurred within the first 2 postoperative days. Eight (80%) leaks were controlled using TPN and octreotide, with 2 (20%) patients requiring surgical intervention. No factors were significant in the successful conservative management of chylous fistulae. One patient with a chylous fistula of 1,800 ml/day was managed successfully without surgical intervention. The results of this case series suggest that chylous fistulae may be managed conservatively with octreotide and TPN. However, long-term evaluation is needed to define if and when surgical intervention is required for control.


Chondroma of the tongue. Report of two cases.
Lingual chondromas are very rare tumors. It can be assumed that chondromas of the tongue develop from heterotopic embryonal cartilage. Chondromas are usually seen on the lateral borders of the tongue. Because chondrosarcomas can appear in this location, wide excision of the lesions should be performed. The CO2 laser facilitates the excision, providing a dry surgical field. Two cases of lingual chondroma are presented and their probable cause discussed.


Influenza burden in children newborn to eleven months of age in a pediatric emergency department during the peak of an influenza epidemic.
The aim of this study was to determine the burden of influenza-related diseases in children 0 to 11 months of age during the peak of the 2001 to 2002 influenza epidemic. This was a prospective study at the Pediatric Emergency Department of Edouard Herriot tertiary teaching hospital in Lyon, France. The study included 304 infants 0 to 11 months of age. Consecutive patients were systematically enrolled during the 4 weeks of the influenza epidemic peak (Weeks 3 to 6, 2002). Influenza viruses were detected by antigen detection and virus culture from nasal swabs. Structured telephone interviews were conducted on Days 8 and 15 after virus detection. There was also a 6-month survey into the medicoadministrative database to detect late complications that required delayed hospitalization of influenza-positive children. Influenza virus was detected in 99 (33%) of 304 patients (A/H3N2 in 30% and B in 3%). Nonrespiratory symptoms were the dominant clinical manifestations in 30% of influenza-positive children. One child with influenza presented with febrile seizures. Twenty (20%) children with influenza were hospitalized. Parents reported recovery from the illness in 63 and 94% of children on Days 8 and 15, respectively. The median length of an influenza episode was 8 days. Our results confirm the high prevalence of influenza-related morbidity in infants during the epidemic peak. One child in three consulting to the pediatric emergency room had a virologically confirmed influenza infection regardless of the body temperature. Every fifth child with influenza was admitted to hospital, which corresponds to an admission rate of 237 per 100 000 children 0 to 11 months of age.


Style Transfer Via Texture Synthesis.
Style transfer is a process of migrating a style from a given image to the content of another, synthesizing a new image, which is an artistic mixture of the two. Recent work on this problem adopting convolutional neural-networks (CNN) ignited a renewed interest in this field, due to the very impressive results obtained. There exists an alternative path toward handling the style transfer task, via the generalization of texture synthesis algorithms. This approach has been proposed over the years, but its results are typically less impressive compared with the CNN ones. In this paper, we propose a novel style transfer algorithm that extends the texture synthesis work of Kwatra et al. (2005), while aiming to get stylized images that are closer in quality to the CNN ones. We modify Kwatra's algorithm in several key ways in order to achieve the desired transfer, with emphasis on a consistent way for keeping the content intact in selected regions, while producing hallucinated and rich style in others. The results obtained are visually pleasing and diverse, shown to be competitive with the recent CNN style transfer algorithms. The proposed algorithm is fast and flexible, being able to process any pair of content + style images.


[Trans-labyrinthine approach for the resection large and giant acoustic nerve neuromas].
The standard translabyrinthine approach for acoustic neuromas removal was introduced by W. House in 1964. After several years of experience the original translabyrinthine approach has been progressively modified into the current "enlarged" approach by extending the area of bone removal. This increased surgical field has made the translabyrinthine approach suitable for the removal of tumours of all sizes. We present our serie of 71 large (52) and giant (19) neuromas of the VIIIth nerve removed through a translabyrinthine approach between 1993 and 1998 at the ENT Department of Legnano.


Comprehensive analysis of differential expression profiles reveals potential biomarkers associated with the cell cycle and regulated by p53 in human small cell lung cancer.
Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database. Furthermore, microarray data was analyzed by using the clustering analysis tool GoMiner. Protein-protein interaction (PPI) networks of DEGs were constructed using the STRING online database. Protein expression was determined from the Human Protein Atlas, and SCLC gene expression was determined using Oncomine. In total, 153 DEGs were obtained. Functional enrichment analysis suggested that the majority of DEGs were associated with the cell cycle. CCNB1, CCNB2, MAD2L1 and CDK1 were identified to contribute to the progression of SCLC through combined use of GO, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and a PPI network. mRNA and protein expression were also validated in an integrative database. The present study indicated that the formation of SCLC may be associated with cell cycle regulation. In addition, the four crucial genes CCNB1, CCNB2, MAD2L1 and CDK1, which are downstream of p53, may have important roles in the occurrence and progression of SCLC, and thus may be promising potential biomarkers and therapeutic targets.


The plastid transcription machinery and its coordination with the expression of nuclear genome: Plastid-Encoded Polymerase, Nuclear-Encoded Polymerase and the Genomes Uncoupled 1-mediated retrograde communication.
Plastid genes in higher plants are transcribed by at least two different RNA polymerases, the plastid-encoded RNA polymerase (PEP), a bacteria-like core enzyme whose subunits are encoded by plastid genes (rpoA, rpoB, rpoC1 and rpoC2), and the nuclear-encoded plastid RNA polymerase (NEP), a monomeric bacteriophage-type RNA polymerase. Both PEP and NEP enzymes are active in non-green plastids and in chloroplasts at all developmental stages. Their transcriptional activity is affected by endogenous and exogenous factors and requires a strict coordination within the plastid and with the nuclear gene expression machinery. This review focuses on the different molecular mechanisms underlying chloroplast transcription regulation and its coordination with the photosynthesis-associated nuclear genes (PhANGs) expression. Particular attention is given to the link between NEP and PEP activity and the GUN1- (Genomes Uncoupled 1) mediated chloroplast-to-nucleus retrograde communication with respect to the Δrpo adaptive response, i.e. the increased accumulation of NEP-dependent transcripts upon depletion of PEP activity, and the editing-level changes observed in NEP-dependent transcripts, including rpoB and rpoC1, in gun1 cotyledons after norflurazon or lincomycin treatment. The role of cytosolic preproteins and HSP90 chaperone as components of the GUN1-retrograde signalling pathway, when chloroplast biogenesis is inhibited in Arabidopsis cotyledons, is also discussed. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.


The reliability of pre-transplant donor renal biopsies (PTDB) in predicting the kidney state. A comparative single-centre study on 154 untransplanted kidneys.
Pre-transplant donor biopsy (PTDB) is a common practice in marginal donors, taking for granted that it represents the whole kidney state, but its reliability has not yet been thoroughly investigated. This prompted us to carry out a comparative study on a needle biopsy group (NBG) and a wedge biopsy group (WBG) and their corresponding untransplanted kidneys. One hundred and fifty-four biopsies and matched kidneys were scored for four morphologic indexes, i.e. tubular atrophy, interstitial fibrosis, vascular damage and global glomerulosclerosis. Categorical indexes were statistically evaluated for concordance with the k index, and the percentage of sclerotic glomeruli with correlation and linear regression analysis. Agreement between biopsies and kidneys was similar in both NBG and WBG with high scores for vascular damage (k 0.74 and 0.75) and intermediate ones for tubular atrophy (k 0.54 and 0.50). Agreement as to fibrosis and glomerular sclerosis was intermediate in the WBG (k 0.56 and 0.55) and poor in the NBG (k 0. 34 and 0.18). Vascular damage was underscored and glomerulosclerosis overscored in both groups, whereas interstitial fibrosis was underscored in the NBG and overscored in WBG. The agreement for the total score, i.e. the sum of the single indexes, was high in the NBG (k 0.73) and intermediate in WBG (k 0.57). Agreement for glomerulosclerosis and total score rose consistently in both groups along with the increasing number of biopsy glomeruli. There was an agreement as to biopsy and kidney evaluation for fitness for transplantation in 85% of NBG and 81% of WBG. PTDB supplies reliable data on the actual kidney state, with better results for needle biopsy. Although the biopsy size plays a role, samples with over 10 glomeruli suffice for clinical purposes. Vascular damage is the most faithful single parameter, whereas global glomerulosclerosis estimation requires some caution.


The spread of coronavirus disease 2019 (COVID-19) via staff work and household networks in residential aged-care services in Victoria, Australia, May-October 2020.
Morbidity and mortality from coronavirus disease 2019 (COVID-19) have been significant among elderly residents of residential aged-care services (RACS). To prevent incursions of COVID-19 in RACS in Australia, visitors were banned and aged-care workers were encouraged to work at a single site. We conducted a review of case notes and a social network analysis to understand how workplace and social networks enabled the spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) among RACS. Retrospective outbreak review. Staff involved in COVID-19 outbreaks in RACS in Victoria, Australia, May-October 2020. The Victorian Department of Health COVID-19 case and contact data were reviewed to construct 2 social networks: (1) a work network connecting RACS through workers and (2) a household network connecting to RACS through households. Probable index cases were reviewed to estimate the number and size (number of resident cases and deaths) of outbreaks likely initiated by multisite work versus transmission via households. Among 2,033 cases linked to an outbreak as staff, 91 (4.5%) were multisite staff cases. Forty-three outbreaks were attributed to multisite work and 35 were deemed potentially preventable had staff worked at a single site. In addition, 99 staff cases were linked to another RACS outbreak through their household contacts, and 21 outbreaks were attributed to staff-household transmission. Limiting worker mobility through single-site policies could reduce the chances of SARS-CoV-2 spreading from one RACS to another. However, initiatives that reduce the chance of transmission via household networks would also be needed.


Lipoprotein-associated phospholipase A2 A379V variant is associated with body composition changes in response to exercise training.
Lipoprotein-associated PLA2 (Lp-PLA2) hydrolyses the sn-2 position of glycerophospholipids, in particular platelet activating factor (PAF), generating significant amounts of Lyso-PAF which in turn, via a remodelling pathway, can generate arachidonic acid (AA) from alkyl-acyl-glycerophosphorylcholine. AA is a precursor for prostaglandin synthesis, which regulates adipogenesis through the peroxisome proliferator-activated receptor subfamily. AA may also modulate skeletal muscle growth. We investigated the association of the PLA2G7 A379V variant with changes in body composition in a longitudinal study of 123 male Caucasian army recruits over 10 weeks of intensive physical training. There was no effect of genotype on baseline measures. However, after exercise training, homozygosity for the 379V allele was associated with a decrease in percentage adipose tissue mass (-3.61+/-1.14%), compared to AV (-1.67+/-0.38%) and AA (-1.09+/-0.24%) genotypes (p=0.01), and a significant mean increase (3.51+/-1.17%) in percentage lean mass, compared to AV (1.64+/-0.38%) and AA (1.10+/-0.24%) recruits (p=0.02). The association of this genotype with changes in body composition after training suggests a novel role for Lp-PLA2.


Transport properties of rigid, symmetrical oligomeric structures composed of prolate, ellipsoidal subunits.
We have calculated translational and rotational diffusion coefficients and intrinsic viscosities of oligomeric structures composed of n identical subunits having a prolate ellipsoidal shape with axial ratio p. Results are presented for p = 1-6 for a variety of structures with n = 1-6. We compare our results with those obtained by a different modeling procedure, proposed by other workers, in which the monomeric subunit is represented as a string of touching, colinear spheres. If n and an estimate of p are known, the structure of the oligomer can be. in most cases, unambiguously determined by comparison of the experimental oligomer-to-monomer ratios of a given property with the numerical results of this work. As examples of the applicability of our results, we examine the relationship between structure and properties for neurophysin. bovine serum albumin, hemoglobin and phycocyanin.


Adrenal crisis in metastatic breast cancer.
A female patient with oestrogen receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive lobular breast cancer presented with progressive disease on CT scan. Some days after initiation of antineoplastic chemotherapy and anti-HER2 targeted antibody therapy, the patient presented with profuse diarrhoea, neutropaenia, nausea and weakness. Although Clostridium difficile was rapidly tackled as a causative agent of gastrointestinal complaints, clinical situation did not markedly improve despite proper antimicrobial treatment. The patient reported profound lack of energy, while nausea, vomiting and loose stools still persisted. Additionally slightly exaggerated pigmentation of nonsunexposed skin and mucosal areas led us to the assumption of proopiomelanocortin-derived peptide hypersecretion. The combination of highly elevated adrenocorticotropic hormone and low basal cortisol levels taken from a morning blood sample established the diagnosis of adrenal insufficiency due to metastatic burden, leading to a near Addison crisis by gastrointestinal complications of chemo-immune therapy. Administration of hydrocortisone immediately relieved general symptoms .


Lymphedema following taxane-based chemotherapy in women with early breast cancer.
Taxanes can cause fluid accumulation by increasing extracellular fluid (ECF). Taxane-based regimens are standard of care for early breast cancer, but it is unknown whether they increase the risk of lymphedema. The aim of this study was to describe the incidence of lymphedema, generalized limb edema, and associated symptoms in women receiving adjuvant taxane-based chemotherapy. Women (n=63) recruited after axillary surgery for early breast cancer were assessed prior to anthracycline-based, prior to taxane-based chemotherapy, and 3 weeks and 6 months after completing taxane-based chemotherapy. At each assessment, the inter-limb ECF ratios and intra-limb intracellular fluid to ECF ratios were determined using bioimpedance spectroscopy. Inter-limb arm volume ratios were calculated from arm circumferences measurements. Self-rated symptoms of swelling and pain in the arm on the side of surgery were recorded. In the 53 women who completed assessments, taxane-based chemotherapy increased the ECF volume in both upper and lower limbs, which was not observed after anthracycline-based chemotherapy. The arm on the side of surgery was preferentially affected, indicated by elevated ECF ratios at 3 weeks and 6 months after completing taxane-based chemotherapy with 32% and 23% meeting the criteria for lymphedema at these time-points, respectively. Edema resolved by 6 months following completion of chemotherapy except in the arm on the side of surgery. The incidence of lymphedema in the arm on the side of surgery following taxane-based chemotherapy was increased persisting at least 6 months after ceasing chemotherapy. However, generalized swelling in the legs and opposite arm resolved by 6 months after chemotherapy.


The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis.
Systematic review and meta-analysis. To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, -14.5 mmHg, 95% CI -19.2, -9.9; -7.0 mmHg 95% CI -9.2, -4.8, respectively), lower triglycerides (-10.9 mg/dL, 95% CI -19.7, -2.1), total cholesterol (-9.9 mg/dL, 95% CI -14.5, -5.4), high-density lipoprotein (-1.7 mg/dL, 95% CI -3.3, -0.2) and low-density lipoprotein (-5.8 mg/dL, 95% CI -9.0, -2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (-10.3 mmHg, 95% CI -13.4, -7.1; -5.3 mmHg 95% CI -7.5, -3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.


Longitudinal Average Glucose Levels and Variance and Risk of Stroke: A Chinese Cohort Study.
Diabetes is a known independent risk factor for stroke. However, whether higher glucose levels (126-139.9 mg/dl) can increase the risk of stroke in people without diabetes is still unknown. Moreover, as a fluctuating parameter, long-term glucose levels may also be related to the risk of stroke outcome. It is important to explore the correlation between long-term average blood glucose, as well as its variability, and stroke. We used 40,975 clinical measurements of glucose levels and 367 measurements of glycated hemoglobin A1c levels from 12,321 participants without stroke to examine the relationship between glucose levels and the risk of stroke. Participants were from the Weitang Geriatric Diseases study, including 5,707 men and 6,614 women whose mean age at baseline was 60.8 years; 1,011 participants had diabetes, and 11,310 did not. We estimated the long-term average blood glucose level based on the multilevel Bayesian model and fit in Cox regression models, stratified according to diabetes status. Over a median follow-up period of 5 years, stroke developed in 279 of the 12,321 participants (244 without diabetes and 35 with). For people with an average glucose level of 126-139.9 mg per deciliter, compared with 90-99.9 mg per deciliter, the adjusted hazard ratio (HR) for total stroke was 1.78 (95% confidence interval (CI), 1.16-2.75), and the HR for levels higher than 140 mg per deciliter was 1.89 (95% CI, 1.09-3.29). Among those without diabetes whose glucose level was higher than 140 mg per deciliter, compared with 90-99.9 mg per deciliter, the adjusted HRs for total stroke and fatal stroke were 3.66 (95% CI, 1.47-9.08) and 5 (95% CI, 1.77-14.15), respectively. For a glucose standard deviation level higher than 13.83 mg per deciliter, compared with that lower than 5.91 mg per deciliter, the adjusted HR for total stroke was 2.31 (95% CI, 1.19-4.48). Our results suggest that higher average glucose levels (126-139.9 mg/dl) and variance may be risk factors for stroke, even among people without diabetes diagnosis.


From hotel to home.
In the heart of Manhattan, the Common Ground organisation helps the city's low paid and homeless to find health care and work. Man of these people have complex needs, including mental health and drug and alcohol problems.


Intraoperative integrated diagnostic system for malignant central nervous system tumors.
The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Since majority of adult malignant brain tumors are gliomas and primary central nervous system lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. Additionally, diffuse gliomas require molecular information on single nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen section (FS) diagnosis through incorporation of a quantitative polymerase chain reaction (qPCR)-based genotyping assay. FS evaluation, including GFAP and CD20 rapid immunohistochemistry, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined based on the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patientswith glioma and 18/19 (94.7%) with PCNSL. The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.


A meta-analysis of gray matter volume abnormalities in HIV patients.
HIV infection is known to have significant effects on central nervous system. This study conducted a meta-analysis of whole voxel-based morphometry (VBM) in HIV patients (N = 435) and HIV-uninfected controls (N = 397). This study observed a reduction of limbic lobe, cingulate gyrus, frontal lobe, middle frontal gyrus, sub-lobar, insula, inferior frontal gyrus and superior frontal gyrus volume in HIV patients. These morphological differences may be responsible for cognitive decline in HIV patients, as these brain regions are closely related to motor and memory functions. These results contribute to a better understanding of the neural mechanisms underlying brain injury in HIV patients and could help develop targeted brain targets, provide more personalized treatment and predict neurodevelopmental outcomes.


Peak expiratory flow rate in an elderly population.
A population survey was conducted in 1982-1983 among 3,812 persons aged 65 years and older residing in East Boston, Massachusetts, a geographically defined urban community. Three measurements of peak expiratory flow rate were obtained by using calibrated mini-Wright meters. Peak expiratory flow rate was strongly related to age, sex, smoking, and years smoked. After adjustment for these factors, low peak expiratory flow rate was associated with chronic respiratory symptoms (cough, wheeze, shortness of breath, exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea; p less than 0.0001) and with certain cardiovascular variables (history of stroke, p = 0.0014; angina, p = 0.05; and high pulse rate, p = 0.004). No significant associations were found with history of myocardial infarction or systolic and diastolic blood pressures. Peak expiratory flow rate was positively related to education (p less than 0.0001) and income (p less than 0.0001). Peak expiratory flow rate also was strongly related (p less than 0.0001) to measures of functional ability and physical activity, self-assessment of health, and simple measures of cognitive function. The correlations of peak expiratory flow rate with pulmonary symptoms and other indices of chronic disease raise the possibility that peak expiratory flow rate will predict mortality in an elderly population.


COVID-19 crisis management of German ICU clinicians in leadership - a metaphor analysis.
The COVID-19 pandemic coincided with an already long-standing crisis in health systems around the world characterized by economic pressure and increasing staff shortage. "Crisis" became a global metaphor to convey collective experiences of the COVID-19 threat. Little is known on how crisis metaphors influence thought and speech on crisis management and the challenging staff situation of intensive care unit (ICU) clinicians in leadership positions and how they act. Therefore, we were interested in (1) which metaphorical concepts ICU clinicians in leadership use to express experiences and strategies in dealing with coinciding crises, (2) how these change over time, and (3) how metaphors in speech reveal self-images of crisis management. We conducted a systematic metaphor analysis focusing on data from three participants of a qualitative interview study with twenty-four healthcare professionals in ICUs in Germany. The participants were interviewed at two time points between April 2020 and March 2021. We identified and reconstructed metaphorical concepts of three interviewees (ICU clinicians in leadership) with regard to the pandemic management, and developed a typology based on the dimensions of mood, modus operandi, location, and scope. The typology consists of eight self-images (protagonists) for the crisis management of ICU clinicians in leadership, such as the figure of the soldier ("to unite everyone behind this flag"), the distributor ("sometimes it is a crazy patchwork [wahnsinniges Gestückel]") or the critic ("we are the fool for everything"). They embody different qualities of a leader and refer to intra- and inter-role conflicts within multiple crisis conditions. Metaphor analysis reveals different self-images of ICU leadership clinicians in relation to crisis management. This illustrates that thinking and perceptions of crisis management may strongly differ between and within leaders and may change over the course of crises. Our findings highlight the need both to improve knowledge on challenges associated with leadership in crises and preparedness, and to support clinicians in their leadership by recognizing and addressing differences and changes in leaders' self-image.


Antibiotic dosing in patients with renal insufficiency or receiving dialysis.
Many patients are admitted to the hospital with renal insufficiency or renal insufficiency develops during their hospital stay. Many of these patients have bacterial infections requiring antimicrobial therapy. Antibiotic dosing in patients with varying degrees of renal insufficiency or hepatic failure is a therapeutic challenge to the clinician. The physician must be aware of the pharmacokinetics of the antibiotic in renal insufficiency as well as with intact renal function. Most antibiotics are eliminated via either hepatic or renal mechanisms, and the clinician should use this knowledge to select an antibiotic with the proper spectrum for the patient. This article presents practical guidelines for patients with hepatic insufficiency or various degrees of renal failure as well as for patients receiving peritoneal dialysis or hemodialysis. The guidelines presented provide the clinician with an approach that is easy to use and remember for determining the appropriate dose and dosing interval in patients with impaired hepatic or renal dysfunction.


The cadmium-mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots.
Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA-QDs) were investigated. After incubation with different concentrations of MAA-QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA-QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium-mercaptoacetic acid complex (Cd-MAA) that is formed in the solution of MAA-QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd-MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles.


50+ Years of Protein Folding.
The ability of proteins to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured rates of spontaneous folding of single-domain globular proteins range from microseconds to hours: the difference - 10-11 orders of magnitude - is the same as between the lifespan of a mosquito and the age of the Universe. This review (based on the literature and some personal recollections) describes a winding road to understanding spontaneous folding of protein structure. The main attention is given to the free-energy landscape of conformations of a protein chain - especially to the barrier separating its unfolded (U) and the natively folded (N) states - and to physical theories of rates of crossing this barrier in both directions: from U to N, and from N to U. It is shown that theories of both these processes come to essentially the same result and outline the observed range of folding and unfolding rates for single-domain globular proteins. In addition, they predict the maximal size of protein domains that fold under solely thermodynamic (rather than kinetic) control, and explain the observed maximal size of "foldable" protein domains.


Ultrastructural and immunological demonstration of the nodulation of the European Alnus glutinosa (L.) Gaertn. host plant by the North-American Alnus crispa var. mollis Fern. root nodule endophyte.
The inoculation of the European Alnus glutinosa (L.) Gaertn. host plant by a crushed-nodule inoculum, prepared with the North-American Alnus crispa var. mollis Fern. root nodule, was successful. Fluorescein- and ferritin-labelled antibodies, specific against the A. crispa var. mollis root nodule endophyte (Lalonde et al. 1975), demonstrated the idenity of this endophyte in the resulting nodules. The nodulation process of this abnormal host-endophyte system was studied by light and electron microscopy. An excretion of host blebs containing electron-dense polysaccharide material, resulting in the formation of exo-encapsulation threads containing presumptive endophytic bacterial cells, was associated with deformed root hairs. Originating from an exoencapsulation thread, the endophyte penetrates the root hair cell and then migrates as a hypha toward the cortical cells of the root. Its migration in the cortical cells of the primary nodule results in the induction of a lateral root which develops as the true nodule. The ultrastructure of the A. crispa var. mollis endophyte developing in the primary and true nodule of the abnormal A. glutinosa host was similar to the one induced inside its normal A. crispa var. mollis host. The actinomycetal intruder was a branched and septate hypha able to produce septate vesicles. The endophyte was always encapsulated in an electron-dense polysaccharide material surrounded by a host plasma membrane envelope. However, in this abnormal host-endophyte system, the number of primary nodules formed per root system was drastically reduced, and their appearance was delayed by 1 to 2 weeks. The delayed nodules were effective in fixing nitrogen and able to support satisfactory plant growth in a nitrogen-free medium.


Detection of mRNA encoding receptors by in situ and Northern hybridization.
The ability to measure mRNA encoding protein is attractive, since, provided certain criteria are met, the investigator can be confident of highly selective detection. In addition, changes in mRNA expression as well as their precise cellular localization, provides the scientist with important information that may not be evident by the detection of the translated protein. Hence, the combined approach of assessing mRNA and protein expression will often allow a more precise hypothesis to be formulated. In the present chapter, we describe methods we have optimized for the detection of mRNA following extraction from tissue or cells (Northern hybridization) and the detection of specific mRNA transcripts within their synthesising cells (in situ hybridization).


Theoretical prediction of the structure and hardness of TiB4 tetraborides from first-principles calculations.
To search for a novel transition metal boride superhard material, the structural configuration, hardness and bonding state of the boron rich TiB4 tetraborides are studied using the first-principles method. Similar to the TMB4 tetraboride, four tetraborides, orthorhombic (Immm), orthorhombic (Cmcm), tetragonal (P4/mbm) and hexagonal (P63/mmc) phases, are predicted based on the phonon dispersion and thermodynamic model. The stable TiB4 with orthorhombic (Immm and Cmcm) is first predicted. In particular, the theoretical hardness of Cmcm and Immm TiB4 is 53.3 GPa and 35.6 GPa, respectively. We predict that orthorhombic (Cmcm) TiB4 is a potential superhard material. Here, the calculated lattice parameters of the Cmcm TiB4 are a = 5.2230 Å, b = 3.0627 Å and c = 9.8026 Å. The calculated lattice parameters of the Immm TiB4 are a = 5.0374 Å, b = 5.6542 Å and c = 3.0069 Å. Naturally, the high hardness of Cmcm TiB4 is related to the octagon B-B cage structure, which is composed of three different B-B covalent bonds. Although the B-B cage structure is formed in Immm TiB4, the hard discrepancy is that the bond strength of the B-B covalent bond in Immm TiB4 is weaker than the bond strength of the B-B covalent bond in Cmcm TiB4. In addition, the Debye temperature of the Cmcm TiB4 is higher than those of the other three TiB4 tetraborides. The high-temperature thermodynamic properties of TiB4 tetraboride are determined by the vibration in the B atom and B-B covalent bond. Therefore, our study indicates that a novel orthorhombic (Cmcm) TiB4 superhard material is found.


Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis.
Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a(+), S100a(+) Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methylaminolevulinate (MAL) based photodynamic therapy (PDT) resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence.Although spontaneous regression of cutaneous Langerhans cell histiocytosis is observed, the rapid effect of photodynamic therapy after several failures of other treatment suggests that photodynamic therapy was successful. As far as we know this is the first report of photodynamic therapy for refractory skin lesions. Larger series are needed to determine whether photodynamic therapy deserves a place in the treatment of multiresistant cutaneous Langerhans cell histiocytosis.


Silver(III)⋅⋅⋅Silver(III) Interactions that Stabilize the syn Form in a Porphyrin Dimer Upon Oxidation.
The interaction between two AgII porphyrins, connected covalently through a highly flexible ethane bridge, in a metalloporphyrin dimer has been investigated upon stepwise oxidation. X-ray structure determination of one and two-electron oxidized complexes has clearly revealed only metal-centered oxidation that results in short Ag-N (porphyrin) distance with large distortion in the porphyrin macrocycle. The 2e-oxidized complex exhibits significant metallophilic interaction in the form of a close AgIII ⋅⋅⋅AgIII contact that brings two porphyrin rings more cofacial with syn-conformation, which would otherwise stabilize in an anti-form. The interaction also leads to an intense emission peak at 546 nm at 77 K in the photoluminescence study.