Microbial Proteases Applications.
The use of chemicals around the globe in different industries has increased tremendously, affecting the health of people. The modern world intends to replace these noxious chemicals with environmental friendly products for the betterment of life on the planet. Establishing enzymatic processes in spite of chemical processes has been a prime objective of scientists. Various enzymes, specifically microbial proteases, are the most essentially used in different corporate sectors, such as textile, detergent, leather, feed, waste, and others. Proteases with respect to physiological and commercial roles hold a pivotal position. As they are performing synthetic and degradative functions, proteases are found ubiquitously, such as in plants, animals, and microbes. Among different producers of proteases, Bacillus sp. are mostly commercially exploited microbes for proteases. Proteases are successfully considered as an alternative to chemicals and an eco-friendly indicator for nature or the surroundings. The evolutionary relationship among acidic, neutral, and alkaline proteases has been analyzed based on their protein sequences, but there remains a lack of information that regulates the diversity in their specificity. Researchers are looking for microbial proteases as they can tolerate harsh conditions, ways to prevent autoproteolytic activity, stability in optimum pH, and substrate specificity. The current review focuses on the comparison among different proteases and the current problems faced during production and application at the industrial level. Deciphering these issues would enable us to promote microbial proteases economically and commercially around the world.


Biochemical and structural properties of mouse kynurenine aminotransferase III.
Kynurenine aminotransferase III (KAT III) has been considered to be involved in the production of mammalian brain kynurenic acid (KYNA), which plays an important role in protecting neurons from overstimulation by excitatory neurotransmitters. The enzyme was identified based on its high sequence identity with mammalian KAT I, but its activity toward kynurenine and its structural characteristics have not been established. In this study, the biochemical and structural properties of mouse KAT III (mKAT III) were determined. Specifically, mKAT III cDNA was amplified from a mouse brain cDNA library, and its recombinant protein was expressed in an insect cell protein expression system. We established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60 degrees C. In addition, mKAT III is active toward a number of other amino acids. Its activity toward kynurenine is significantly decreased in the presence of methionine, histidine, glutamine, leucine, cysteine, and 3-hydroxykynurenine. Through macromolecular crystallography, we determined the mKAT III crystal structure and its structures in complex with kynurenine and glutamine. Structural analysis revealed the overall architecture of mKAT III and its cofactor binding site and active center residues. This is the first report concerning the biochemical characteristics and crystal structures of KAT III enzymes and provides a basis toward understanding the overall physiological role of mammalian KAT III in vivo and insight into regulating the levels of endogenous KYNA through modulation of the enzyme in the mouse brain.


The calcium sensor CBL10 mediates salt tolerance by regulating ion homeostasis in Arabidopsis.
Calcium serves as a critical messenger in many adaptation and developmental processes. Cellular calcium signals are detected and transmitted by sensor molecules such as calcium-binding proteins. In plants, the calcineurin B-like protein (CBL) family represents a unique group of calcium sensors and plays a key role in decoding calcium transients by specifically interacting with and regulating a family of protein kinases (CIPKs). We report here that the CBL protein CBL10 functions as a crucial regulator of salt tolerance in Arabidopsis. Cbl10 mutant plants exhibited significant growth defects and showed hypersensitive cell death in leaf tissues under high-salt conditions. Interestingly, the Na(+) content of the cbl10 mutant, unlike other salt-sensitive mutants identified thus far, was significantly lower than in the wild type under either normal or high-salt conditions, suggesting that CBL10 mediates a novel Ca(2+)-signaling pathway for salt tolerance. Indeed, the CBL10 protein physically interacts with the salt-tolerance factor CIPK24 (SOS2), and the CBL10-CIPK24 (SOS2) complex is associated with the vacuolar compartments that are responsible for salt storage and detoxification in plant cells. These findings suggest that CBL10 and CIPK24 (SOS2) constitute a novel salt-tolerance pathway that regulates the sequestration/compartmentalization of Na(+) in plant cells. Because CIPK24 (SOS2) also interacts with CBL4 (SOS3) and regulates salt export across the plasma membrane, our study identifies CIPK24 (SOS2) as a multi-functional protein kinase that regulates different aspects of salt tolerance by interacting with distinct CBL calcium sensors.


Interleukin-3 gene expression in irradiated mouse bone marrow.
The expression of endogenous interleukin-3 (IL-3) gene in mouse bone marrow after whole body irradiation was assessed by immunocytochemistry, in situ hybridization (ISH), and in situ reverse transcription PCR (IS RT-PCR). The results showed obvious injury to the bone marrow followed by recovery 4 weeks after radiation. IL-3 protein was increased in the cytoplasm of recovering hematopoietic cells, especially at 21 days after radiation, while the mRNA was negative, except at 15 days when the mRNA was weakly positive by ISH. IS RT-PCR showed that IL-3 mRNA was strongly positive in the cytoplasm of recovering hematopoietic cells, especially at 10 to 15 days after radiation. We postulate that endogenous IL-3 gene may accelerate hematopoietic recovery in irradiated bone marrow and that IS RT-PCR may objectively report the regulation of IL-3 gene expression.


Suppression of ethanol and lipopolysaccharide-induced liver injury by extracts of Hydrangeae Dulcis Folium in rats.
In female SD rats that were injected with 4 g/kg BW ethanol p.o. followed by a 5 mg/kg BW lipopolysaccharide (LPS) i.v. injection, serum glutamic pyruvic transaminases (GPT) activity increased to about eight times that of normal rats. In this model, rats that had been fed a diet containing 1% Hydrangeae Dulcis Folium (HDF) extracts for fifteen days showed significantly lower serum GPT activity (380.0+/-58.2 IU/l) than the control group (3527.0+/-774.1 IU/l). HDF's efficacy was far superior to milk thistle in this model (2950.0+/-915.9 IU/l). When mouse macrophages were treated with HDF extracts at 50 microg/ml, TNF-alpha production induced by LPS was suppressed to about 10% of the control. Rat serum TNF-alpha levels induced by LPS was decreased to 58.7% of the control by administering 1000 mg/kg BW HDF extract p.o. These results indicate that HDF prevents alcohol-induced liver injury through the inhibition of TNF-alpha production.


Remarkable Response of Toripalimab Combined with Chemotherapy in Sarcomatoid Carcinoma of Palatine Tonsil: A Case Report.
Sarcomatoid carcinoma (SaCa) of the palatine tonsil is a rare and aggressive subset of head and neck (H&N) cancer which is characterized by insensitivity to surgery and radiotherapy and a poor prognosis. Immunotherapy has led advances in the treatment of melanoma and H&N cancer, but the combined effects of immunotherapy and chemotherapy have not been sufficiently investigated. Herein, we report the case of 29-year-old Chinese women with local advanced non-resectable SaCa of the palatine tonsil who exhibited a substantial partial response to toripalimab and chemotherapy followed by radiation therapy. To the best of our knowledge, this is the first report of its successful application in this context. Toripalimab combined with chemotherapy may be an effective approach for locally advanced H&N cancer in rare categories of patients, which was the first application as far as we know.


A two-color infrared-vacuum ultraviolet laser pulsed field ionization photoelectron study of NH3.
We have observed fully rotationally resolved transitions of the photoelectron vibrational bands 2(4), 2(5), 1(1)2(1), and 1(1)2(3) for ammonia cation (NH3+) by two-color infrared (IR)-vacuum ultraviolet (VUV)- pulsed field-ionization photoelectron (PFI-PE) measurements. By preparing an intermediate rovibrational state of neutral NH(3) with a known parity by IR excitation followed by VUV-PFI-PE measurements, we show that the photoelectron parity can be determined unambiguously. The IR-VUV-PFI-PE measurement of the 2(4) band clearly reveals the formation of both even and odd l states for the photoelectrons, where l is the orbital angular momentum quantum number. This observation is consistent with the conclusion that the lack of inversion symmetry for NH3 and NH3+ allows odd/even l mixings, rendering the production of both odd and even l states for the photoelectrons. Evidence is also found, indicating that the photoionization transitions with DeltaK=0 are strongly favored compared to that with DeltaK=3. For the 2(5), 1(1)2(1), and 1(1)2(3) bands, only DeltaK=0 transitions for the production of even l photoelectron states from the J'K'=2(0) rotational level of NH3(nu1=1) are observed. The preferential formation of even l photoelectron states for these vibrational bands is attributed to the fact that the DeltaK=0 transitions for the formation of odd l photoelectron states from the 2(0) rotational level of NH3(nu1=1) are suppressed by the constraint of nuclear-spin statistics. In addition to information obtained on the photoionization dynamics of NH3, this experiment also provides a more precise value of 3232+/-10 cm-1 for the nu1+ (N-H stretch) vibrational frequency of NH3+.


Fast-ion orbit sensitivity of neutron emission spectroscopy diagnostics.
Fast ions in fusion plasmas often leave characteristic signatures in the plasma neutron emission. Measurements of this emission are subject to the phase-space sensitivity of the diagnostic, which can be mapped using weight functions. In this paper, we present orbit weight functions for the TOFOR and NE213 neutron diagnostics at the Joint European Torus, mapping their phase-space sensitivity in 3D orbit space. Both diagnostics are highly sensitive to fast ions that spend a relatively large fraction of their orbit transit times inside the viewing cone of the diagnostic. For most neutron energies, TOFOR is found to be relatively sensitive to potato orbits and heavily localized counter-passing orbits, as well as trapped orbits whose "banana tips" are inside the viewing cone of TOFOR. For the NE213-scintillator, the sensitivity is found to be relatively high for stagnation orbits.


Botulinum toxin injection site localization for the tibialis posterior muscle.
Thirty-one cadaveric lower limbs were dissected to identify the innervation of the tibialis posterior muscle to aid localization of the injection site for botulinum toxin for the treatment of an equinovarus deformity. A posterior midline surface-anatomy axis was defined from the level of the head of the fibula proximally to the intermalleolar axis distally. The nerve to tibialis posterior branched from the tibial trunk 13.4% down this axis and entered the muscle 22.1% along the same axis, within 1 cm of the midline. We also report the use of ultrasound for muscle localization at the level of the anatomically defined motor point.


Heterogeneity in the transforming growth factor beta response of esophageal cancer cells.
The role of the transforming growth factor beta (TGFbeta) pathway in the development and progression of esophageal cancers is poorly understood. As an initial step in clarification of this issue, the functional status of the TGFbeta pathway was evaluated in a panel of esophageal cancer derived cell lines. Both adenocarcinoma and squamous cell carcinoma derived lines were represented. Although the TGFbeta pathway was intact and functional in four of the five cell lines, only one of them was growth inhibited by TGFbeta. In one cell line, the loss of a growth inhibitory response to TGFbeta could be explained by decreased expression of Smad 4 and a general inability to activate TGFbeta responsive promoters. In the other three cell lines, TGFbeta was able to activate transcription of TGFbeta responsive promoters, but unable to downregulate transcription of c-myc. Taken together these findings indicate that a selective loss in the ability of TGFbeta to regulate expression of a key component of the growth inhibitory pathway may contribute to the poor prognosis of esophageal cancers.


Survival, classifications, and desmosomal plaque genes in non-small cell lung cancer.
Novel biomarkers are required to improve prognostic predictions obtained with lung cancer staging systems. This study of 62 surgically-treated Non-Small Cell Lung Cancer (NSCLC) patients had two objectives: i) to compare the predictive value of T-stage classifications between the 6(th) and 7(th) editions of the Tumor, Node, and Metastasis staging system (TNM); and ii) to examine the association of Pkp1 and/or Krt15 gene expression with survival and outcomes. Multivariate and Kaplan-Meier survival analyses were performed, examining the relationship of survival with T-stage, recurrence, and TNM-stage (by each TNM edition) and with the single/combined expression of Pkp1 and/or Krt15 genes. Five-year survival rates only significantly differed as a function of T-stage in patients without recurrence when estimated using the 6(th) edition of the TNM classification and only in patients in pathologic TNM-stage IA using the 7(th). Overall survival for patients with elevated expression of both genes was 13.5 months in those with adenocarcinoma and 34.6 months in those with squamous cell carcinoma. Overall survival was 30.4 months in patients with Pkp1 gene upregulation and 30.9 months in those with Krt15 gene upregulation. In conclusion, survival estimations as a function of T-staging differed between the 6(th) and 7(th) editions of TNM. Overall survival differed according to the expression of Pkp1 and/or Krt15 genes, although this relationship did not reach statistical significance.


Surface functionalization of carbon micro coils and their selective immobilization on surface-modified silicon substrates.
Surface functionalization of carbon micro coils (CMCs) was performed by acid treatment at different times. Nitric acid oxidation produced CMC with acidic functional groups, although morphology of CMCs was modified after the oxidation. The selective immobilization of as-prepared CMC from an aqueous dispersion was examined on differently surface-modified silicon substrates. It was confirmed that the acid-treated CMC was selectively immobilized on a silicon substrate by chemical bonding with amine-terminated self-assembled monolayers on a silicon substrate, while the pristine CMC was not.


Bone morphogenetic protein 4 is involved in cusp formation in molar tooth germ of mice.
In order to clarify the role of BMP4 in the development of the tooth crown, we employed the antisense technique on molar tooth germs removed from the mandibles of embryonic 13.5-d-old mice. In the tooth germ explants incubated for 14 d with antisense oligodeoxynucleotide (AS-ODN) against Bmp4 (a) cusps were not formed, whereas dentin matrix was secreted in the whole region of the crown, (b) inner enamel epithelial (IEE) cells remained in the undifferentiated state in the occlusal region of the crown, though they differentiated in the proximal region (lateral surface region of tooth crown), and (c) insufficient growth of the dental papilla was observed. A 5-bromo-2'-deoxyuridine (BrdU) uptake experiment showed that, although a site-specific proliferation of IEE cells occurred in the occlusal region in the control explants, it was not found in the AS-ODN-treated explants. In the proximal region, however, the proliferation of IEE cells was detected evenly in all explants treated with or without AS-ODNs. These results suggest that AS-ODN against Bmp4 inhibited the differentiation and the site-specific proliferation of IEE cells in the occlusal region of molar tooth germs, resulting in the suppression of cusp formation. Our data thus suggest that BMP4 is involved in cusp formation and differentiation of ameloblasts in the occlusal region of molars.


Osteomyelitis in adolescents.
Osteomyelitis in adolescents is a serious disease with the potential for lifelong disability. Microbial invasion of the bone typically results from hematogenous seeding. Staphylococcus aureus is the most common cause of acute hematogenous osteomyelitis. The clinical presentation and management of osteomyelitis in children and adolescents is changing with the emergence of invasive community-acquired methicillin-resistant S aureus infections. Antibiotic treatment should target S aureus including community-acquired methicillin-resistant strains. In some cases, surgical debridement is indicated, especially in cases of chronic osteomyelitis or osteomyelitis associated with septic arthritis. Early diagnosis and subsequent appropriate medical and surgical intervention is critical for avoiding chronic bone destruction and, thus, preventing permanent disability. A multidisciplinary approach involving the pediatrician, infectious disease specialist, and orthopedic surgeon is essential for achieving the best outcome for the patient.


Stepwise hydration of the cyanide anion: a temperature-controlled photoelectron spectroscopy and ab initio computational study of CN-(H2O)n, n=2-5.
We report the study of microsolvated CN(-)(H(2)O)(n) (n=1-5) clusters in the gas phase using a combination of experimental and computational approaches. The hydrated cyanide clusters were produced by electrospray and their structural and energetic properties were probed using temperature-controlled photoelectron spectroscopy (PES) and ab initio electronic structure calculations. Comparison between the low temperature (LT,T=12 K) and the room-temperature (RT) spectra shows a 0.25 eV spectral blueshift in the binding energy of the n=1 cluster and a significant spectral sharpening and blueshift for n=2 and 3. The experimental results are complemented with ab initio electronic structure calculations at the MP2 and CCSD(T) levels of theory that identified several isomers on the ground state potential energy function arising from the ability of CN(-) to form hydrogen bonds with water via both the C and N ends. In all cases the N end seems to be the preferred hydration site for the water network. The excellent agreement between the low temperature measured PES spectra and the basis set- and correlation-corrected [at the CCSD(T) level of theory] calculated vertical detachment energies, viz., 3.85 versus 3.84 eV (n=0), 4.54 versus 4.54 eV (n=1), 5.20 versus 5.32 eV (n=2), 5.58 versus 5.50 eV (n=3), and 5.89 versus 5.87 eV (n=4), allow us to establish the hydration motif of cyanide. Its microsolvation pattern was found to be similar to that of the halide anions (Cl(-), Br(-), and I(-)) as well as other diatomic anions having cylindrical symmetry such as NO(-), resulting to structures in which the ion resides on the surface of a water cluster. The exception is CN(-)(H(2)O)(2), for which one water molecule is bound to either side of the anion resulting in a quasilinear structure. For the n=3 cluster the anion was found to freely "tumble" on the surface of a water trimer, since the inclusion of zero-point energy even at T=0 K stabilizes the configuration of C(3) symmetry with respect to the one having the anion tilted toward the water cluster. For n=4 this motion is more restricted since the corresponding barrier at RT is 1.2 kcal/mol. It is also possible that at RT other isomers (lying within approximately 0.6 kcal/mol above the global minima) are also populated, resulting in the further broadening of the PES spectra.


Case Report: Severe Rhabdomyolysis and Multiorgan Failure After ChAdOx1 nCoV-19 Vaccination.
Severe skeletal muscle damage has been recently reported in patients with SARS-CoV-2 infection and as a rare vaccination complication. On Apr 28, 2021 a 68-year-old man who was previously healthy presented with an extremely severe rhabdomyolysis that occurred nine days following the first dose of SARS-CoV-2 ChAdOx1 nCov-19 vaccination. He had no risk factors, and denied any further assumption of drugs except for fermented red rice, and berberine supplement. The clinical scenario was complicated by a multi organ failure involving bone marrow, liver, lung, and kidney. For the rapid increase of the inflammatory markers, a cytokine storm was suspected and multi-target biologic immunosuppressive therapy was started, consisting of steroids, anakinra, and eculizumab, which was initially successful resulting in close to normal values of creatine phosphokinase after 17 days of treatment. Unfortunately, 48 days after the vaccination an accelerated phase of deterioration, characterized by severe multi-lineage cytopenia, untreatable hypotensive shock, hypoglycemia, and dramatic increase of procalcitonin (PCT), led to patient death. Physicians should be aware that severe and fatal rhabdomyolysis may occur after SARS-CoV2 vaccine administration.


Effect of unfiltered cigarettes on marginal bone loss of dental implants: A single center 4-year retrospective clinical study.
This retrospective clinical study evaluated, by radiographic analysis, the effect of unfiltered and filtered tobacco cigarette smoking on marginal bone loss (MBL) in the subjects with dental implants. In a 4-year retrospective clinical study, 419 dental implants were placed in 188 subjects aged 23-76 years who underwent implant-supported fixed prosthetic restorations. The effects of gender, implant length, implant diameter, implant location, and use of unfiltered and filtered tobacco cigarettes on marginal bone were investigated. MBL was analyzed on the mean, mesial, and distal surfaces of dental implants on periapical radiographs. The results of the data were statistically analyzed with ANOVA and Tukey test. A significant correlation was found between MBL difference and gender, implant length, and implant location (P< 0.05). Smokers had significantly higher MBL than nonsmokers, both within and between groups (P< 0.05). There was a significant difference in MBL in the mesial region in unfiltered cigarette smokers compared to filtered cigarette smokers (P= 0.013). There was a significant increase in MBL in the mesial and distal region compared to heavy smokers of cigarettes without filters (>20 cigarettes/day) and heavy smokers of cigarettes with filters (>20 cigarettes/day) (P< 0.05). In this study, tobacco smoking had a negative effect on marginal bone loss. There was a significant increase in marginal bone loss on the mesial and distal surfaces, especially in unfiltered heavy tobacco smokers (>20 cigarettes/day).


Indigenous sovereignty, data sourcing, and knowledge sharing for health.
In this article, we consider the impacts of the COVID-19 pandemic on Indigenous Peoples (IPs) by reporting on information-gathering work across two non-governmental and Indigenous organisations to compensate where federal systems failed. Strategies IPs have employed to understand and respond to the pandemic, and described here, include: collaborative efforts across communities intra- and inter-nationally; open-source data platforms; and small-scale epidemiological research. Our review exposes the informational politics faced by Indigenous organisations and communities, and their struggle to pursue needed resources or protections while avoiding the critiques of 'post-neoliberal' and 'science denialism'. We conclude by suggesting ways that Indigenous communities improve our understanding of their needs during public health crises, and maintain both informational and medical self-governance.


Translation and validation of stroke impact scale-16 in Urdu for Pakistan.
To translate and validate the Urdu version of stroke impact scale-16 for Pakistani society. The prospective cohort study was conducted from February 2018 to February 2020 after approval from the ethics review board of The University of Lahore, Lahore, Pakistan, and copmprised patients with mild to moderate stroke who were recruited from five public and two private hospitals of the Punjab province. Established guidelines were followed to translate the Stroke Impact Scale-16. The patients were concurrently evaluated on Barthel Index, Stroke Rehabilitation Assessment of Movement, Modified Rivermead Mobility Index, Modified Rankin Scale, Short Form 36 Health Survey Questionnaire and the Hospital Anxiety and Depression Scale to assess the validity of Stroke Impact Scale-16, and spearmen correlation coefficient was used to determine the correlation among the scales. Analysis of variance was employed to determine the discriminant validity. Intraclass correlation coefficient, weighted kappa, Cronbach's alpha and item-total correlation were calculated to establish the stability and consistency of Stroke Impact Scale-16. Data was analysed using SPSS 25. Of the 90 patients, 50(55.5%) were females and 40(45.5%) were males. The subjects were aged 50-80 years. The correlation of Stroke Impact Scale-16 was strong with the established tools and ranged from 0.78 to 0.91. The discriminant validity was also significant (p<.001) across all Modified Rankin Scale levels. The Intraclass correlation coefficient was 0.94 and Cronbach's alpha was 0.91 for test-retest reliability and internal consistency, respectively. All corrected item-total correlation values exceeded the priori minimum standard (>0.40) and ranged from 0.51 to 0.68. The weighted kappa for item reliability also achieved priori criteria (>0.40) and ranged from 0.53 to 0.88. With slight modifications, the Urdu version of Stroke Impact Scale-16 was found to have satisfactory psychometric properties and can be used in clinical and research settings for stroke survivors in Pakistan.


Analysis of "Artificial Pancreas (AP) Systems for People With Type 2 Diabetes: Conception and Design of the European CLOSE Project".
In an article in Journal of Diabetes Science and Technology, Schliess and coauthors describe the conception and design of the European Automated Glu cose Contro l at H ome for People with Chronic Di sease (CLOSE) initiative for the implementation of artificial pancreas (AP) systems for people with diabetes. The CLOSE consortium aims to develop integrated AP solutions (APplus) tailored to the needs of individuals with type 2 diabetes (T2D) by developing superior risk- and cost-benefit scenarios for AP operation to achieve acceptance by users and caregivers and a high likelihood for reimbursement. CLOSE is integrating the AP platform into the center of a comprehensive product and service package specifically tailored to defined T2D patient groups and care environments, leading to an interactive collaboration with users, health care providers, and other stakeholders in diabetes care. This is a very ambitious but well-conceived and delineated project which takes into consideration most of the relevant factors that may influence AP implementation in T2D care.


[Liraglutide in the treatment of obesity : a multidisciplinary approach].
Liraglutide, which has been prescribed for several years for the treatment of type 2 diabetes, is now proposed for the management of patients with BMI between 28 and 35 kg/m2 in the presence of metabolic comorbidity or BMI ≥ 35 kg/m2. Its reimbursement by the health insurance is conditioned on weight loss results and time limited. Careful preparation of the patient and his commitment to lifestyle changes are essential for the success and good tolerance of the treatment. The introduction of this treatment requires a multidisciplinary follow-up to ensure optimal results. The place of liraglutide in the pharmacopeia of obesity, a chronic disease that requires long-term treatment, should be clarified.


A monoclonal antibody detecting unusual Thy-1 determinants.
20-10-5S is a monoclonal antibody produced by the fusion of C3H anti-C3H.SW splenocytes with the SP2/0 cell line. The antibody appears to react with Thy-1 determinants by several criteria including cytotoxicity patterns, functional assays, genetic analyses, and competitive binding experiments. However, the antibody and the determinants it detects are unusual in that: 1) 20-10-5S is autoreactive; 2) the antibody shows allospecificity for Thy-1.2 vs Thy-1.1 antigens only on peripheral lymphocytes and not on thymocytes; and 3) the antibody reacts only with determinants on murine T cells and not with antigens on brain tissue or on rat thymocytes. It therefore seems that 20-10-5S reacts with murine T cell-specific Thy-1 determinants that are lost or modified during maturation of the cells on which they are expressed.


A Reduced Set of Features for Chronic Kidney Disease Prediction.
Chronic kidney disease (CKD) is one of the life-threatening diseases. Early detection and proper management are solicited for augmenting survivability. As per the UCI data set, there are 24 attributes for predicting CKD or non-CKD. At least there are 16 attributes need pathological investigations involving more resources, money, time, and uncertainties. The objective of this work is to explore whether we can predict CKD or non-CKD with reasonable accuracy using less number of features. An intelligent system development approach has been used in this study. We attempted one important feature selection technique to discover reduced features that explain the data set much better. Two intelligent binary classification techniques have been adopted for the validity of the reduced feature set. Performances were evaluated in terms of four important classification evaluation parameters. As suggested from our results, we may more concentrate on those reduced features for identifying CKD and thereby reduces uncertainty, saves time, and reduces costs.


TP53 and RET may serve as biomarkers of prognostic evaluation and targeted therapy in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. Genomic analysis is conducted to identify genetic alterations in driver genes which are all druggable targets for cancer therapy. In the present study, we performed an exome sequencing of 45 driver genes in 100 paired samples from HCC patients including tumors and matched adjacent normal tissues using Illumina HiSeq 2000 platform. Non-synonymous mutations were ascertained using the iPLEX MassARRAY system and Sanger sequencing. Clinicopathological relevance with genetic variations was assessed using SPSS software. The prognostic analyses of patients with gene mutation status were summarized using Kaplan-Meier curves. Sixty-one non-synonymous somatic mutations were identified in 43% of the HCC patients. The most frequent mutations were: TP53 (20%), RET (6%), PLCE1 (5%), PTEN (4%) and VEGFR2 (3%). Patients with mutations in TP53 had a lower overall survival (OS) (P=0.002) than those without mutations. Recurrent mutations in the Ret proto‑oncogene (RET) were associated with poor outcomes for both disease‑free survival (DFS) (P=0.028) and OS (P=0.001) in HCC patients. The mutational status of sorafenib-targeted genes were associated with decreased DFS (P=0.039), and decreased OS (P=0.15) without statistical significance. Mutual exclusion of TP53 and RET mutations were observed in the present study. In conclusion, patients with TP53 mutations, RET mutations and sorafenib-targeted gene mutations were demonstrated to be associated with poor HCC prognosis, which suggests that both TP53 and RET may serve as biomarkers of prognostic evaluation and targeted therapy in HCC.


Anxious-depressive comorbidity: effects on HPA axis and CNS noradrenergic functions.
Psychiatric comorbidity is all too common. An important example is the high comorbidity frequency of depressive and anxiety disorders, 25%-50%, much higher than the 5% or less expected by chance. Possible reasons for this comorbidity include definitional, environmental, and biological factors. Few previous studies have assessed, with proper methodology, potential biological changes associated with this co-occurrence. We assessed both hypothalamic-pituitary-adrenocortical axis (HPA) responses to the Trier Social Stress Test and growth hormone (GH) responses to clonidine, a centrally active alpha-2 adrenoreceptor agonist, in 15 persons with major depression without anxiety, 15 with an anxiety disorder without depression, 18 comorbid for anxiety and depression, and 48 individually matched control subjects. Individuals with depression only were normal on both tests, while those with anxiety only had normal HPA responses but blunted GH responses. Comorbid individuals showed elevated HPA responses and only those comorbid persons with anxiety symptoms predominant also showed blunted GH responses. Controls and anxiety-only subjects showed significant correlations between the results of the two tests. This association was disrupted by the presence of depression with or without comorbidity. Comorbidity is fundamental to understanding the pathophysiologies of depression and anxiety.


Inorganic Surface Engineering to Enhance Perovskite Solar Cell Efficiency.
The photoconversion efficiency of perovskite solar cells (PSCs) is enhanced by the deposition of inorganic nanoparticles (NPs) at the interface between the compact TiO2 electron-selective contact and the mesoporous TiO2 film. The NPs used are core/shell Au@SiO2, where a thin SiO2 coating protects the Au core from the direct chemical interaction with CH3NH3PbI3 halide perovskite used as light-harvesting material. The samples prepared with Au@SiO2 NPs exhibit a higher external quantum efficiency in the complete wavelength range at which perovskite presents light absorption and not just at the wavelengths at which Au@SiO2 NPs present their absorption peak. This fact rules out a direct plasmonic process as responsible for the enhancement of cell performance. A detailed characterization by photoluminescence, impedance spectroscopy, and open-circuit voltage decay unveils a modification of the interfacial properties with an augmentation of the interfacial electrostatic potential that increases both photovoltage and photocurrent. This article highlights the dramatic role of interfaces in the performance of PSCs. The use of reduced quantities of highly stable inorganic compounds to modify the PSC interface instead of the extensively used organic compounds opens the door to a new surface engineering based on inorganic compounds.


Responsiveness and interpretability of the Hand Eczema Severity Index.
The Hand Eczema Severity Index (HECSI) is used to measure the severity of hand eczema. It is unclear what HECSI scores mean and what is the minimally important change (MIC). Furthermore, its responsiveness has not been studied. To study the responsiveness and interpretability of the HECSI. This was a prospective study covering two time points: baseline and after 4-12 weeks. Responsiveness was assessed using a criterion approach, with at least one-step improvement on the 'Photographic guide for severity of hand eczema' as the anchor for important improvement. Interpretability of single scores was determined by defining severity bands based on agreement with the anchor. For change scores, the smallest detectable change (SDC) was calculated in patients indicating no change and the MIC was obtained in patients indicating that they had changed using three methods: mean cutoff, receiver operating characteristic (ROC) curve and 95% limit. In total, 294 patients participated (160 male, mean age 44·9 years). HECSI scores improved or deteriorated in parallel with the anchor. The area under the ROC curve was 0·86 (95% confidence interval 0·81-0·91). The final severity band for single scores had a κ-coefficient of agreement of 0·694: clear, 0; almost clear, 1-16; moderate, 17-37; severe, 38-116; very severe, ≥ 117. The SDC in 93 unchanged patients was 40·3 points. The obtained MIC values were all smaller than the SDC. The HECSI has good responsiveness. This study gives meaning to HECSI scores, which can be applied to clinical decision making and the design of clinical trials. We recommend that an improvement of 41 points on the HECSI is regarded as the minimally measurable true change. What's already known about this topic? The Hand Eczema Severity Index (HECSI) is one of the most widely used measurement instruments to measure the severity of hand eczema. The HECSI has good reliability, but its responsiveness and interpretability have not been studied. What does this study add? This study shows good responsiveness of the HECSI. A severity grading for single scores is proposed. The smallest detectable change and minimally important change for improvement are determined. What are the clinical implications of this work? The obtained values help to interpret HECSI scores in daily practice and clinical studies, and may facilitate researchers in the calculation of sample sizes for clinical trials.


Age-dependent variations of cancellous bone in response to ovariectomy in C57BL/6J mice.
The ovariectomized (OVX) mouse model has been widely accepted to be suitable for the study of postmenopausal osteoporosis. However, whether C57BL/6J mice, a commonly used genetic background mouse strain, is an appropriate model for postmenopausal osteoporosis remains controversial. The present study investigated the effect of the OVX model on alterations in bone density and microarchitecture in C57BL/6J female mice of different ages. C57BL/6J mice were divided into 8-, 12- and 16-week-old groups (OVX8, OVX12 and OVX16) from the beginning of OVX. At 8 weeks post-surgery, the mice were anesthetized and micro-computed tomography was used to analyze the bone density and microarchitecture. The results revealed that OVX-induced loss of cancellous bone was greatest in OVX8, moderate in OVX12, and only a weak bone loss was observed in the OVX16 group when compared with the SHAM16 control group. In addition, the effect of genetic backgrounds in response to the OVX model were examined. Several other strains of mice, including inbred (BALB/c) and outbred (ICR and Kunming), were used in the present study, all of which were subjected to OVX at 8 weeks of age. The present findings revealed that the highest rate of bone loss was detected in C57BL/6J female mice. In addition, treatment with estrogen (17β-estradiol, 30 µg/kg five times per week) led to a significant increase in bone density in C57BL/6J mice compared with the other strains of mice. Therefore, these results may provide novel insights into the age- and strain-associated effect of OVX on regulating turnover of bone in female mice. The present findings also suggest 8-week-old C57BL/6J mice as an animal model for postmenopausal osteoporosis and preclinical testing of potential therapies for this disease.


Dystrophin Dp71 is critical for the clustered localization of potassium channels in retinal glial cells.
The Müller cell is the principal glial cell of the vertebrate retina. The primary conductance in Müller cells is the inwardly rectifying potassium channel Kir4.1 (BIR10 and KAB-2), which is highly concentrated at the endfeet at the vitreal border and to processes enveloping blood vessels. Such asymmetric and clustered distribution of Kir4.1 channels in Müller cells is thought to be critical for the buffering of extracellular potassium concentration in retina. Herein we investigated whether the distribution and functional properties of Kir4.1 channels are dependent on expression of the Dp71, a dystrophin isoform expressed in Müller cells. Kir4.1 distribution was determined in mouse retinal sections and whole mounts using anti-Kir4.1 antibodies and confocal microscopy. In Müller cells from wild-type mice, Kir4.1 is highly clustered in their endfeet and perivascular processes. In contrast, in Müller cells from the mdx(3Cv) mouse, which lacks the expression of Dp71, the Kir4.1 immunoreactivity is evenly distributed throughout the cell membrane. Surface expression of Kir4.1 is not affected in mdx(3Cv) Müller cells as current density of barium-sensitive inward currents in mdx(3Cv) Müller cells are not different from wild type. Focal extracellular potassium increases in isolated Müller cells shows that Kir channels in the mdx(3Cv) cells, as opposed to wild type, are less prominently concentrated in their endfeet. In summary, our data indicate that Dp71 is critical for the clustering but not membrane expression of Kir4.1 in mouse Müller cells. These results point to a new role for dystrophin in glial cells.


Magnitude and quality of vaccine-elicited T-cell responses in the control of immunodeficiency virus replication in rhesus monkeys.
While a diversity of immunogens that elicit qualitatively different cellular immune responses are being assessed in clinical human immunodeficiency virus vaccine trials, the consequences of those varied responses for viral control remain poorly understood. In the present study, we evaluated the induction of virus-specific T-cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitude and the functional profile of the virus-specific CD8(+) T cells by measuring gamma interferon, interleukin-2, and tumor necrosis factor alpha production. We found that the different vectors generated virus-specific T-cell responses of different magnitudes and with different functional profiles. Heterologous prime-boost vaccine regimens induced particularly high-frequency virus-specific T-cell responses with polyfunctional repertoires. Yet, immediately after a pathogenic simian-human immunodeficiency virus (SHIV) challenge, no significant differences were observed between these cohorts of vaccinated monkeys in the magnitudes or the functional profiles of their virus-specific CD8(+) T cells. This finding suggests that the high viral load shapes the functional repertoire of the cellular immune response during primary infection. Nevertheless, in all vaccination regimens, higher frequency and more polyfunctional vaccine-elicited virus-specific CD8(+) T-cell responses were associated with better viral control after SHIV challenge. These observations highlight the contributions of both the quality and the magnitude of vaccine-elicited cellular immune responses in the control of immunodeficiency virus replication.


Collaborative Biosynthesis of Maleimide- and Succinimide-Containing Natural Products by Fungal Polyketide Megasynthases.
Fungal polyketide synthases (PKSs) can function collaboratively to synthesize natural products of significant structural diversity. Here we present a new mode of collaboration between a highly reducing PKS (HRPKS) and a PKS-nonribosomal peptide synthetase (PKS-NRPS) in the synthesis of oxaleimides from the Penicillium species. The HRPKS is recruited in the synthesis of an olefin-containing free amino acid, which is activated and incorporated by the adenylation domain of the PKS-NRPS. The precisely positioned olefin from the unnatural amino acid is proposed to facilitate a scaffold rearrangement of the PKS-NRPS product to forge the maleimide and succinimide cores of oxaleimides.


The properties of hyaluronan and its role in wound healing.
Hyaluronan occurs naturally in the body. It appears to have an important role in wound healing and is essential to scarless healing in a fetus. Hyaluronan has now been developed as a wound dressing. This paper will examine the literature to assess the dressing's usefulness in difficult-to-heal, chronic wounds, which present a great challenge to tissue viability experts.


Nervous control of mammalian salivary glands.
In the production and flow of saliva, sympathetic and parasympathetic nerves generally cooperate, although variations between the different salivary glands are considerable, particularly in the sympathetic innervation. In the submandibular gland of the dog, sympathetic impulses cause secretion via beta-adrenoceptors, and since sympathetic motor effects are elicited via alpha-adrenoceptors it is possible to study separately motor and secretory effects in this gland. Such experiments indicate that myoepithelial contractions serve to accelerate the salivary flow and to support the secreting acinar cells and prevent back-flow of fluid from the luminal system into the glandular tissues. The contractions are elicited reflexly from the oral mucosa together with secretion. A potentiation interaction between sympathetic and parasympathetic nerves occurs in the formation of the primary saliva. In parotid glands of rabbits and rats such an interaction has been demonstrated in the secretion of amylase.


Does testosterone mediate the trade-off between nestling begging and growth in the canary (Serinus canaria)?
Nestling birds solicit food from their parents with vigorous begging displays, involving posturing, jostling and calling. In some species, such as canaries, begging is especially costly because it causes a trade off against nestling growth. Fitness costs of begging like this are predicted by evolutionary theory because they function to resolve conflicts of interest within the family over the provision of parental investment. However, the mechanism that links these costs with nestling behaviour remains unclear. In the present study, we determine if the relationships between nestling androgen levels, nestling begging intensities and nestling growth rates are consistent with the hypothesis that testosterone is responsible for the trade-off between begging and growth. We test this idea with a correlational study, using fecal androgens as a non-invasive method for assaying nestling androgen levels. Our results show that fecal androgen levels are positively correlated with nestling begging intensity, and reveal marked family differences in each trait. Furthermore, changes in fecal androgen levels between 5 and 8 days after hatching are positively associated with changes in nestling begging intensity, and negatively associated with nestling growth during this time. Although these correlational results support our predictions, we suggest that that experimental manipulations are now required to test the direct or indirect role of testosterone in mediating the trade-off between begging and growth.


Effect of therapeutic plasma exchange on plasma levels and total removal of adipokines and inflammatory markers.
Aside from well-established inflammatory mediators adipokines have recently been found to play an important role in a variety of immunologic diseases. Therapeutic plasma exchange (TPE) is an established treatment modality for the acute removal of pathophysiological relevant disease mediators. The aim of this study was to determine adipokine removal during TPE therapy. 21 Caucasian patients (10 females, 11 males) with an indication for TPE using albumin as exchange fluid received two consecutive TPE sessions. Blood samples for measurement of resistin, leptin, sICAM-1, sCD40L, MCP-1, and sTNF-R were drawn before and at the end of each TPE session. Samples from the total removed plasma were collected at the end of every treatment. We found a significant reduction in pre- vs. post-TPE plasma concentrations for sICAM-1 (517 ± 246 vs. 260 ± 159 ng/ml, p < 0.0001), sTNF-R (8.1 ± 6.4 vs. 5.7 ± 3.9 ng/ml, p < 0.05), and resistin plasma levels (14.3 ± 6.9 vs. 9.5 ± 4.7 ng/ml, p < 0.001). Solely sICAM-1 reduction persisted for 25 ± 5 h between the first and second TPE treatment, while the other investigated mediators increased to baseline levels. Substantial amounts of all measured mediators could be recovered from the removed plasma. TPE provides a persistent reduction in sICAM-1 levels and temporarily affects several adipokine and cytokine plasma levels. Our findings are of importance not only for the interpretation of blood levels of cytokines in patients undergoing TPE but provide solid evidence that TPE markedly decreases sICAM-1.


An approach to the mechanism of the potent antiglucocorticoid: 17 beta-hydroxy-11 beta-4-dimethylaminophenyl-17 alpha-propynyl-estra-4,9-dien-3-one.
The effects of a new synthetic steroid, 17 beta-hydroxy-11 beta-4-dimethyl-aminophenyl-17 alpha-propynyl-estra-4,9-dien-3-one, classified under reference R38486 in the Roussel-Uclaf nomenclature [1], were investigated in two established rat hepatoma cell lines in order to gain information on the mechanism of action. The induction of tyrosine aminotransferase (TAT) and alanine aminotransferase (AAT) was totally abolished when R38486 was added with dexamethasone either on a 1-1 basis or on a 10-fold excess depending on the differentiation state of the cell. Binding studies showed a high affinity for the glucocorticoid receptor; however our "whole cell" study with [3H] R38486 indicates that only a low amount of antagonist-receptor complexes was translocated into the nucleus. Nuclear fractionation experiments showed that R38486, like the other antagonists studied, was located in the chromatin fraction where it may exert some definite role. Our observations based on whole cell experiments using physiological doses of glucocorticoid analogs indicate that the binding of activated antiglucocorticoid-receptor complexes to nuclear acceptor sites represents a physiologically significant process. Moreover the differences in the nuclear binding of antagonist-receptor- as compared to agonist-receptor-complexes may set off the machinery of antagonistic action.


Screening for Diguanylate Cyclase (DGC) Inhibitors Mitigating Bacterial Biofilm Formation.
The majority of bacteria in the natural environment organize themselves into communal biofilms. Biofilm formation benefits bacteria conferring resistance to harmful molecules (e.g., antibiotics, disinfectants, and host immune factors) and coordinating their gene expression through quorum sensing (QS). A primary signaling molecule promoting bacterial biofilm formation is the universal second messenger cyclic di-GMP. This dinucleotide predominantly controls the gene expression of motility, adhesins, and capsule production to coordinate biofilm formation. Cyclic di-GMP is synthesized by diguanylate cyclases (DGCs) that have a GGDEF domain and is degraded by phosphodiesterases (PDEs) containing either an EAL or an HD-GYP domain. Since high cellular c-di-GMP concentrations are correlated with promoting the ability of bacteria to form biofilms, numerous research endeavors to identify chemicals capable of inhibiting the c-di-GMP synthesis activity of DGCs have been performed in order to inhibit bacterial biofilm formation. This review describes currently identified chemical inhibitors that disturb the activity of DGCs and the methods of screening and assay for their discovery.


Spectral amplitude and phase measurement of a 40 GHz free-running quantum-dash modelocked laser diode.
We present a linear self-referenced measurement of the spectral amplitude and phase of a free-running quantum-dash modelocked laser diode. The technique is suitable for measuring optical signals with repetition rates up to 100 GHz. In contrast to many other linear techniques it requires no external electronic clock synchronized to the signal under test. Using this method we are able to compensate for the intracavity dispersion of the diode to demonstrate 500 fs pulses at a repetition rate of 39.8 GHz. We also use the technique to characterize the dependence of the diode's intracavity dispersion on the applied current.


Acute and long-term results of bipolar radiofrequency catheter ablation of refractory ventricular arrhythmias of deep intramural origin.
Successful bipolar radiofrequency catheter ablation (RFCA) of refractory ventricular arrhythmias (VAs) has been reported. However, the efficacy, safety, and long-term outcomes of bipolar RFCA of VAs are not fully determined. The purpose of this study was to evaluate the effectiveness and safety of bipolar RFCA in treating refractory VAs during long-term follow-up. Eighteen patients who underwent bipolar RFCA for ventricular tachycardia (VT) at 7 institutions were retrospectively investigated. Underlying heart diseases included remote myocardial infarction (n = 3 [17%]) and nonischemic cardiomyopathy (n = 15 [83%]). Although unipolar RFCA was performed in all patients, either it failed to suppress VT or VT recurred. The interventricular septum, left ventricular free wall, and left ventricular summit were targeted for bipolar RFCA. Acute success (VT termination and/or noninducibility) was achieved with bipolar RFCA in 16 patients (89%). Complications during the procedure included complete atrioventricular block (n = 2) and coronary artery stenosis (n = 1). One patient underwent chemical ablation after bipolar RFCA failure. At 12-month follow-up, VT reoccurred in 8 patients (44%). However, in patients with recurrence, VT burden had decreased: only 4 patients underwent re-RFCA, and only 1 of the 4 required chemical ablation. In the remaining 4 patients, re-RFCA was not required, as VT was controlled by medication or an implantable cardioverter-defibrillator. Bipolar RFCA is useful for acute suppression of refractory VT. Although VT recurrence rates during long-term follow-up were relatively high, we observed a significant reduction in VT burden.


[Advances in cardiovascular medicine through molecular imaging].
We will witness a change of paradigm in cardiovascular imaging, which is empowered by advances in imaging technology, biochemistry, molecular biology and nanotechnology. Instead of simply following the physical distribution of established contrast agents, we now have the opportunity to noninvasively image biological processes such as enzyme activity, interaction with cell surface markers, gene expression and cell migration. These advancements open up new avenues in basic cardiovascular research and will greatly speed up the pace of discovery. Patient management will profit as well: cardiovascular molecular imaging will strengthen personlized and prophylactic medicine through timely and precise diagnostics. In our review we describe selected molecular imaging strategies in atherosclerosis, myocardial ischemia and healing.


[Correlations of centrosome abnormality and genomic instability to tumor].
Genomic instability, including whole chromosome loss or gain, ploidy change, and a variety of chromosome aberration, is a characteristic of tumor cells. Centrosome abnormality is also found in several kinds of tumors. Abnormal centrosome can cause multipolar spindle formation, chromosome mis-segregation, and unequal distribution, and finally leads to cancers. Therefore, abnormal centrosome is common in tumor cells, and centrosome amplification is probably an early event in the origination and development of cancer.


Physical wounding and ethylene stimulated embryogenic stem cell proliferation and plantlet regeneration in protocorm-like bodies of Phalaenopsis orchids.
Phalaenopsis orchids have been regenerated by inducing protocorm-like bodies (PLBs) from etiolated leaf sections. However, the physiological and molecular mechanisms of secondary PLB development and subsequent proliferation have not been explored. Bisectionally cutting primary PLBs resulted in more secondary PLBs at 5 weeks, suggesting an embryogenic stem cell property imposed by wounding of primary PLB tissues. The ethylene precursors ethephon and 1-aminocyclopropanecarboxylic acid and the ethylene perception inhibitor silver nitrate increased PLB formation, while aminoethoxyvinylglycine decreased PLB formation. Ethylene content in wounded PLB explants increased over culture time in media containing ethylene precursors or inhibitors. mRNA levels of PhACS2, PhACS3, and PhACO were increased by ethephon and decreased by ethylene inhibitors. Expression of genes in the ethylene signaling pathway was enhanced following ethylene-precursor treatment and was mitigated by ethylene inhibitors during PLB proliferation. Transcription of PhETR and PhEIN3, as well as PhERS, PhCTR, and PhGTP, was significantly increased 12 h after ethylene treatment. Ethylene and physical wounding stimulated secondary PLB formation in Phalaenopsis, probably through ethylene biosynthesis and signal transduction.


MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.
The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.


Tunneling as a stochastic process: a path-integral model for microwave experiments.
Delay time results obtained in microwave experiments at frequencies above and below the cutoff frequency of different waveguide sections are interpreted on the basis of wave propagation in the presence of dissipative effects. Kac's original suggestion was the starting point for the formulation of a stochastic model, which has now been substantially improved, also in relation to the transition-elements theory of Feynman-Hibbs. In this way, an approach to the problem is provided, which is completely distinct from the ones formulated elsewhere.


[Arthroscopic treatment of popliteal cyst excision in combination with debridement of the knee under local anesthesia].
To evaluate the arthroscopic treatment effectiveness of popliteal cyst excision in combination with debridement of the knee under local anesthesia by comparing with continuous epidural anesthesia. Between June 2002 and January 2013, 145 patients with popliteal cyst underwent arthroscopic popliteal cyst excision in combination with debridement of the knee under local anesthesia (local anesthesia group). In addition, 51 patients with popliteal cyst were treated with the same surgery under continuous epidural anesthesia between February 2000 and August 2005 served as control group. No significant difference was found in gender, age, side, disease duration, or cyst size between 2 groups (P > 0.05). Then, anesthesia time, analgesia effect, anesthesia satisfaction, operation time, bleeding volume, and anesthesia complication were compared between 2 groups. The guidelines of Rauschning and Lindgren were used to assess the effectiveness, and recurrence rate was recorded. Results All incisions healed primarily, no neurological or vascular injury was found. The patients were followed up 1 year and 1 month to 8 years (mean, 3.7 years) in local anesthesia group, and 8 years to 13 years and 7 months (mean, 10.8 years) in control group. Local anesthesia group had shorter anesthesia time, higher visual analogue scale (VAS) score, shorter operation time, and lower bleeding volume (P < 0.05) than control group. Anesthesia satisfaction was reduced in local anesthesia group, but there was no significant difference (χ2 = 0.071, P = 1.000). The anesthesia complication incidence of control group (15.7%, 8/51) was significantly higher than that of local anesthesia group (0) (P = 0.000). Recurrence was found in 12 patients of local anesthesia group (curative ratio 9.7%) and in 5 patients of control group (curative ratio 90.2%), showing no significant difference (χ2 = 0.111, P = 0.774). According to the guidelines of Rauschning and Lindgren, there were 131 cases of grade 0, 13 cases of grade I, and 1 case of grade II in local anesthesia group, and 37 cases of grade 0, 12 cases of grade I, and 2 cases of grade II in control group; significant differences in grading were shown between at pre- and post-operation in 2 groups (Z = -10.683, P = 0.000; Z = -6.385, P = 0.000), and between 2 groups at post-operation (Z = -3.145, P = 0.002). Compared with under continuous epidural anesthesia, arthroscopic treatment of popliteal cyst excision under local anesthesia can obtain better results. Under local anesthesia, the condition of nerve and vessel can be timely and dynamically observed. Arthroscopic treatment of popliteal cyst excision in combination with debridement of the knee has the advantages of less trauma, lower recurrence rate, and satisfactory results.


Shear-induced structural changes of a smectic-A phase: a computer simulation study.
We have carried out a Monte Carlo simulation of a thin sample of the smectic-A phase of the Gay-Berne mesogen GB(4.4,20.0,1,1) sandwiched between two plates and subject to shear. The smectic layers are perpendicular to the confining plates and are pinned at the boundaries. The thickness of the samples studied ranges from about three to twenty molecules. The layers tilt progressively with increasing shear, but rearrange themselves at a critical shear. At this critical shear the layers melt near the center of the sample and reform with a reduced tilt consistent with the layer pinning at the walls. The pseudodynamics of this process as the smectic layers melt and are reformed have been followed during the simulation. The critical layer tilt at which slippage takes place tends to a constant value for thick samples, but for very thin samples the critical shear tends toward half a smectic layer, with a significantly reduced translational order near the sample center just before the critical shear. The simulation results are consistent with the predictions of the mean field theory of this phenomenon developed by Mottram et al.


The Effect of the Thermosensitive Biodegradable PLGA⁻PEG⁻PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement.
The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA⁻PEG⁻PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA⁻PEG⁻PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA⁻PEG⁻PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.


Combined ribotyping and random multiprimer DNA analysis to probe the population structure of Listeria monocytogenes.
To improve our understanding of the genetic links between strains originating from food and strains responsible for human diseases, we studied the genetic diversity and population structure of 130 epidemiologically unrelated Listeria monocytogenes strains. Strains were isolated from different sources and ecosystems in which the bacterium is commonly found. We used rRNA gene restriction fragment length polymorphism analysis with two endonucleases and random multiprimer DNA analysis with seven oligonucleotide primers to study multiple genetic features of each strain. We used three clustering methods to identify genetic links between individual strains and to determine the precise genetic structure of the population. The combined results confirmed that L. monocytogenes strains can be divided into two major phylogenetic divisions. The method used allowed us to demonstrate that the genetic structure and diversity of the two phylogenetic divisions differ. Division I is the most homogeneous and can easily be divided into subgroups with dissimilarity distances of less than 0.30. Each of these subgroups mainly, or exclusively, contains a single serotype (1/2b, 4b, 3b, or 4a). The serotype 4a lineage appears to form a branch that is highly divergent from the phylogenetic group containing serotypes 1/2b, 4b, and 3b. Division II contains strains of serotypes 1/2a, 1/2c, and 3a. It exhibits more genetic diversity with no peculiar clustering. The fact that division II is more heterogeneous than division I suggests that division II evolved from a common ancestor earlier than division I. A significant association was found between division I and human strains, suggesting that strains from division I are better adapted to human hosts.


Arabidopsis retains vertebrate-type telomerase accessory proteins via a plant-specific assembly.
The recent discovery of the bona-fide telomerase RNA (TR) from plants reveals conserved and unique secondary structure elements and the opportunity for new insight into the telomerase RNP. Here we examine how two highly conserved proteins previously implicated in Arabidopsis telomere maintenance, AtPOT1a and AtNAP57 (dyskerin), engage plant telomerase. We report that AtPOT1a associates with Arabidopsis telomerase via interaction with TERT. While loss of AtPOT1a does not impact AtTR stability, the templating domain is more accessible in pot1a mutants, supporting the conclusion that AtPOT1a stimulates telomerase activity but does not facilitate telomerase RNP assembly. We also show, that despite the absence of a canonical H/ACA binding motif within AtTR, dyskerin binds AtTR with high affinity and specificity in vitro via a plant specific three-way junction (TWJ). A core element of the TWJ is the P1a stem, which unites the 5' and 3' ends of AtTR. P1a is required for dyskerin-mediated stimulation of telomerase repeat addition processivity in vitro, and for AtTR accumulation and telomerase activity in vivo. The deployment of vertebrate-like accessory proteins and unique RNA structural elements by Arabidopsis telomerase provides a new platform for exploring telomerase biogenesis and evolution.


The use of free gingival soft tissue to improve the implant/soft-tissue interface.
Various techniques for the placement of different types of dental implants have evolved to the point where predictable bone-to-implant integration occurs if proper surgical technique is followed. The soft-tissue adaptation to the implant abutment is the first line of defense to prevent the development of peri-implantitis and subsequent bone loss. Given that there is a tenuous protective seal around dental implants, the rationale for soft-tissue augmentation around dental implants to provide an improved, tightly adapted implant/soft-tissue interface definitely exists.


Fibrocytes are not an essential source of type I collagen during lung fibrosis.
Progressive fibrosis involves accumulation of activated collagen-producing mesenchymal cells. Fibrocytes are hematopoietic-derived cells with mesenchymal features that potentially have a unique and critical function during fibrosis. Fibrocytes have been proposed as an important direct contributor of type I collagen deposition during fibrosis based largely on fate-mapping studies. To determine the functional contribution of hematopoietic cell-derived type I collagen to fibrogenesis, we use a double-transgenic system to specifically delete the type I collagen gene across a broad population of hematopoietic cells. These mice develop a robust fibrotic response similar to littermate genotype control mice injured with bleomycin indicating that fibrocytes are not a necessary source of type I collagen. Using collagen-promoter GFP mice, we find that fibrocytes express type I collagen. However, fibrocytes with confirmed deletion of the type I collagen gene have readily detectable intracellular type I collagen indicating that uptake of collagen from neighboring cells account for much of the fibrocyte collagen. Collectively, these results clarify several seemingly conflicting reports regarding the direct contribution of fibrocytes to collagen deposition.


Right hemisphere superiority for executive control of attention.
Over forty years have passed since the first evidence showing the unbalanced attentional allocation of humans across the two visual fields, and since then, a wealth of behavioral, neurophysiological, and clinical data increasingly showed a right hemisphere dominance for orienting of attention. However, inconsistent evidence exists regarding the right-hemisphere dominance for executive control of attention, possibly due to a lack of consideration of its dynamics with the alerting and orienting functions. In this study, we used a version of the Attentional Network Test with lateralized presentation of the stimuli to the left visual field (processed by the right hemisphere, RH) and right visual field (processed by the left hemisphere, LH) to examine visual field differences in executive control of attention under alerting and orienting of attention. Analyses of behavioral performance (reaction time and error rate) showed a more efficient executive control (reduced conflict effect) in the RH compared to the LH for the reaction time, under conditions of increased alerting and of informative spatial orienting. These results demonstrate the right-hemisphere superiority for executive control, and that this effect depends on the involvement of the alerting and orienting functions.


The sensitivity and specificity of a colorimetric microbiological caries activity test (Cariostat) in preschool children.
The purpose of this study was to test the ability of a colorimetric test, Cariostat (Sankin, Tokyo, Japan) to identify preschool children with dental caries. Three- to 5-year-old children (N = 153) from seven preschool programs in Saskatoon, Canada, were examined for dental caries using a mirror and explorer. A caries severity index (csi) was calculated for each subject. In all subjects buccal plaque samples were obtained, incubated, and scored as per the manufacturer's instructions for the Cariostat test. In 98 of 153 children whole stimulated saliva was also collected and population counts of Streptococcus mutans (CFU/ml of saliva) were determined. The test group exhibited mean dft = 1.03, mean dfs = 1.53, and mean csi = 0.46 while 66.67% of subjects were caries free and had no restorations. The S. mutans count was found to be significantly correlated (P < 0.001) with dft, dfs, and csi. Significant differences (P < 0.001) were found between Cariostat groups with respect to dft, dfs, and csi. The sensitivity of the Cariostat test was found to be 98% while the specificity was found to be 14%.


'Bats below the bridge': is a potentially treatable neurovascular disorder being underdiagnosed in accident and emergency departments?
Basilar artery thrombosis (BATS) is a progressive disorder which may present with fluctuating neurological signs of varying degrees of severity. Unless the diagnosis is considered, the confused young patient may be thought to be under the influence of drugs or to be psychologically ill, and indeed the Munchausen syndrome may be considered. The more elderly patient may be diagnosed simply as having had a cerebrovascular accident. This paper presents the cases of three patients admitted through the accident and emergency (A&E) department of St Mary's Hospital, London with basilar artery thrombosis during a 6-month period. All these patients demonstrated the classic triad for this syndrome of: (1) long tract neurological signs, (2) impaired conscious level, and (3) complex ocular signs. The concern is that, for patients with more subtle signs, a diagnosis of BATS may not be considered, and a neurological opinion may be thus delayed and no treatment with anticoagulants or thrombolytic agents would be given. Two of the three patients were treated with anticoagulants and improved, while in the third patients anticoagulation was judged inappropriate and the patients died from progression of the disease with respiratory complications.


Implementation and Assessment of a Pharmacy Educational Program Concerning Laboratory Monitoring for Medications.
The pharmacist's role in monitoring medication therapy, including the ability to order laboratory tests as a delegated medical function, has increased dramatically over the past 20 years. To implement and assess the impact of an intervention designed to educate pharmacists about appropriate medication-related laboratory monitoring and clinical interpretation of results. This pilot project had a pretest-posttest study design. The intervention was an educational program comprising 8 self-directed learning modules, each with a corresponding seminar. Evaluation of the program included scoring of the appropriateness and significance of clinical interventions related to laboratory monitoring, pre- and post-program test scores, and participants' subjective assessments of their abilities to order and assess the results of medication-related laboratory investigations. Descriptive statistics, the Wilcoxon signed rank test, the Student t-test, and the paired Student t-test were used where appropriate. Associations were assessed with the Pearson or Spearman rho correlation coefficient. All statistical tests were 2-tailed, and the p value for significance was established a priori at 0.05. There was no statistically significant difference with regard to the appropriateness (p = 0.70) or significance (p = 0.94) of clinical interventions undertaken before and after the educational program. Among the 21 pharmacists who completed the program, the average test score (± standard deviation) was 27.2 ± 8.1 before the program, increasing to 39.2 ± 8.7 after the program (p < 0.001). There was a statistically significant improvement in the perceived level of knowledge for each individual module (p < 0.05 for all). The establishment of an educational program led to improvements in both subjective and objective measures of knowledge and perceived abilities to order and assess the results of medication-related laboratory tests.


Ability of a Urine Assay of Type II Collagen Cleavage by Collagenases to Detect Early Onset and Progression of Articular Cartilage Degeneration: Results from a Population-based Cohort Study.
To evaluate the association of a sandwich assay for cartilage collagenase-mediated degradation, the C2C human urine sandwich assay (IB-C2C-HUSA), with early and late knee cartilage pathology and with progression of cartilage damage. A population-based cohort with knee pain, age 40-79 years, was evaluated at baseline (n = 253) and after mean 3.3 years (n = 161). We evaluated the IB-C2C-HUSA and a related competitive inhibition assay (C2C). The C2C assay was applied to serum (sC2C) and urine (uC2C). Based on knee radiographs and magnetic resonance imaging (MRI), 3 subgroups [no cartilage pathology, preradiographic cartilage pathology, and radiographic osteoarthritis (ROA)] were evaluated cross-sectionally for association with biomarker levels. Longitudinally, we evaluated whether baseline assays predict subsequent progression of cartilage degeneration, defined by MRI cartilage loss. Cross-sectionally, statistically significant differences were seen in the 3 subgroups for IB-C2C-HUSA (p < 0.001), with the highest levels seen in ROA, and for sC2C (p = 0.023), while no differences were seen for uC2C (p = 0.501). Baseline IB-C2C-HUSA levels were higher in progressors vs nonprogressors (p = 0.003). In logistic regression analysis, only baseline IB-C2C-HUSA was associated with an increased risk of progression of cartilage damage (OR 1.78, 95% CI 1.03-3.09). The IB-C2C-HUSA degradation assay detects the generation of a pathology-related cartilage collagen peptide(s) that increase(s) with onset of degeneration of knee articular cartilage. The baseline values are associated with progression of cartilage degeneration over 3 subsequent years. This assay may have value in clinical OA trials. Further, it points to collagenase activity as a therapeutic target for controlling degeneration of articular cartilage.


ADP receptors--targets for developing antithrombotic agents.
Platelet P2 receptors--P2Y1, P2Y12, and P2X1--constitute the means by which adenine nucleotides can activate platelets. Coactivation of the Galphaq-coupled P2Y1 and Galphai2-coupled P2Y12 receptors is necessary for ADP-mediated platelet activation, which forms the basis of using P2 antagonists as antithrombotic drugs. P2Y1 receptor antagonists inhibit platelet activation, while P2Y1 knockout mice show longer bleeding times than normal mice but few other problems; however, its ubiquitous expression in other tissues renders P2Y1 questionable as an antithrombotic target. The P2Y12 receptor is expressed nearly exclusively in platelets and brain, making it an attractive antithrombotic target. Antagonists for the P2Y12 receptor have been developed that either require metabolic activation to covalently inhibit P2Y12 and are irreversible, or simply are competitive in nature and thus reversible. Ticlopidine and clopidogrel are irreversible P2Y12 antagonists and have been repeatedly proven as clinical antithrombotic agents. In addition, a recently reported P2Y12 antagonist, CS-747, shows promise as a future antithrombotic drug. The AR-C series of compounds represent reversible P2Y12 antagonists and have been used extensively to characterize the function of P2Y12 in platelets. Clinical studies show that AR-C69931MX is as effective as clopidogrel; furthermore, the combination of AR-C69931MX (cangrelor) and clopidogrel confers greater antagonism of P2Y12 than either antagonist alone. The P2X1 receptor is a calcium channel that functions to potentiate agonist-induced platelet shape change, and its inhibition or loss has little if any effect on hemostasis. A combination of P2Y1 and P2Y12 antagonists may represent an additional course of antithrombotic treatment.


A new era in home care.
Profound changes in policy and reimbursement are ushering in a new era in home care. The transition from fee-for-service reimbursement to prospective payment/managed care and the mandate for outcomes assessment provide opportunities to expand innovative home care models. The authors describe 3 such models: community-based long-term care (exemplified by PACE, Program of All-inclusive Care for the Elderly), home-based primary care (exemplified by the Veterans Administration Home-Based Primary Care program), and disease management programs (exemplified by Group Health Cooperative of Puget Sound). Professional qualifications for the new era, including certification and graduate education for advanced practice nursing, also are described.


The difference between LSMC and replicating portfolio in insurance liability modeling.
Solvency II requires insurers to calculate the 1-year value at risk of their balance sheet. This involves the valuation of the balance sheet in 1 year's time. As for insurance liabilities, closed-form solutions to their value are generally not available, insurers turn to estimation procedures. While pure Monte Carlo simulation set-ups are theoretically sound, they are often infeasible in practice. Therefore, approximation methods are exploited. Among these, least squares Monte Carlo (LSMC) and portfolio replication are prominent and widely applied in practice. In this paper, we show that, while both are variants of regression-based Monte Carlo methods, they differ in one significant aspect. While the replicating portfolio approach only contains an approximation error, which converges to zero in the limit, in LSMC a projection error is additionally present, which cannot be eliminated. It is revealed that the replicating portfolio technique enjoys numerous advantages and is therefore an attractive model choice.


Methods to estimate the proportion of plant and fungal RNA in an arbuscular mycorrhiza.
Arbuscular mycorrhizas are endosymbiotic associations formed between obligately biotrophic arbuscular mycorrhizal (AM) fungi and plant roots. The fungus and plant coexist in intimate contact as the fungus grows within the cortex of the root. RNA isolated from arbuscular mycorrhizas contains transcripts from both eukaryotic genomes. It is essential to be able to estimate the relative levels of fungal and plant RNA so that changes in plant and fungal gene expression can be evaluated during development of the AM symbiosis. Here we describe the design and use of specific plant and fungal internal transcribed spacer sequences and 18S rRNA probes to distinguish and quantify the relative levels of RNA of plant and fungal origin in samples from arbuscular mycorrhizas. We present two different methods. The first employs the most traditional method of transcript level analysis, namely northern blot analysis. The second one uses ribonuclease protection assays, which permit the analysis of transcript levels in a very small amount of tissue and are proving to be suitable for the analysis of gene expression in AM fungi. Analysis of tissues from a developing mycorrhiza showed that the relative levels of fungal RNA increased gradually as colonization of the root system progressed, reaching 5-12% in the most highly colonized samples.


A Pilot Study of Synchronization of Respiration-Induced Motions in the Duodenum and Stomach for the Primary Tumor in Radiation Therapy for Pancreatic Cancer Using 4-Dimensional Computed Tomography.
We investigated the synchronization of respiration-induced motions at the primary tumor and organs at risk at radiation planning for pancreatic cancer. Four-dimensional computed tomography images were acquired under the condition of shallow free breathing in patients with pancreatic cancer. The gross tumor volume (GTV), duodenum (DU), and stomach (ST) were contoured. The center of mass was computed for each 4-dimensional volume of interest. The respiration dependence of coordinates for the center of each volume of interest was computed relative to its location at the 50% (maximum exhalation) phase. Based on the shift of the GTV, we investigated the synchronization of respiration-induced motions between each contouring target. We examined the differences in the volume averaged dose to the ST and DU in each respiratory phase. Nine patients with pancreatic cancer were analyzed in this study. The mean maximum 3-dimensional excursions at the GTV, DU, and ST were 9.6, 9.8, and 11.4 mm, respectively. At phase 0% and 90% (inhale phases), mean distance changes in the positional relationship with the GTV were 0.3 and 0.7 mm respectively for the DU and -2.5 and -2.4 mm respectively for the ST. There was no significant respiration associated change (RAC) between each respiratory phase in the DU (P = .568), and there was a significant RAC in the ST (P < .001). There was a significant RAC of the volume averaged dose to the ST (P = .023). Our results indicate that the DU but not the ST might move synchronously with GTV due to respiration.


[Elderly case of systemic lupus erythematosus who showed lupus peritonitis as the initial symptom].
A 64-year-old woman who admitted because of abdominal pain and ascites. She was diagnosed as having systemic lupus erythematosus (SLE) and lupus peritonitis based on anti ds-DNA antibody, ANA positive, serositis and renal dysfunction. She was successfully treated by intravenous pulse therapy with methylprednisolone, but her enteritis recurred after switching to oral administration. She recovered following pulse therapy with methylprednisolone and extracorporeal apheresis. This case was characterized by a rather old age of onset and the peculiar initial symptoms of peritonitis.


Platinum(II) Metallomesogens: New External-Stimuli-Responsive Photoluminescence Materials.
New dicatenar isoquinoline-functionalized pyrazoles, [Hpz(R(n,n)iq) ] (R(n,n)=C6 H3 (OCn H2n+1 )2 ; n=4, 6, 8, 10, 12, 14, 16, 18), have been strategically designed and synthesized to induce mesomorphic and luminescence properties into the corresponding bis(isoquinolinylpyrazolate)platinum(II) complexes [Pt(pz(R(n,n)iq) )2 ]. Thermal studies reveal that all platinum(II) compounds exhibit columnar mesophases over an exceptionally wide temperature range, above 300 °C in most cases. The photophysical behavior was also investigated in solution and in the solid state. As a consequence of the formation of Pt⋅⋅⋅Pt interactions, the weak greenish emission of the platinum derivatives turns bright orange in the mesophase. Additionally, the complexes are sensitive to a great variety of external inputs, such as temperature, mechanical grinding, pressure, solvents, and vapors. On this basis, they are used as dopant agents of a polyvinylpyrrolidone or poly(methyl methacrylate) polymer matrix to achieve stimuli-responsive thin films.


Using Frankencerts for Automated Adversarial Testing of Certificate Validation in SSL/TLS Implementations.
Modern network security rests on the Secure Sockets Layer (SSL) and Transport Layer Security (TLS) protocols. Distributed systems, mobile and desktop applications, embedded devices, and all of secure Web rely on SSL/TLS for protection against network attacks. This protection critically depends on whether SSL/TLS clients correctly validate X.509 certificates presented by servers during the SSL/TLS handshake protocol. We design, implement, and apply the first methodology for large-scale testing of certificate validation logic in SSL/TLS implementations. Our first ingredient is "frankencerts," synthetic certificates that are randomly mutated from parts of real certificates and thus include unusual combinations of extensions and constraints. Our second ingredient is differential testing: if one SSL/TLS implementation accepts a certificate while another rejects the same certificate, we use the discrepancy as an oracle for finding flaws in individual implementations. Differential testing with frankencerts uncovered 208 discrepancies between popular SSL/TLS implementations such as OpenSSL, NSS, CyaSSL, GnuTLS, PolarSSL, MatrixSSL, etc. Many of them are caused by serious security vulnerabilities. For example, any server with a valid X.509 version 1 certificate can act as a rogue certificate authority and issue fake certificates for any domain, enabling man-in-the-middle attacks against MatrixSSL and GnuTLS. Several implementations also accept certificate authorities created by unauthorized issuers, as well as certificates not intended for server authentication. We also found serious vulnerabilities in how users are warned about certificate validation errors. When presented with an expired, self-signed certificate, NSS, Safari, and Chrome (on Linux) report that the certificate has expired-a low-risk, often ignored error-but not that the connection is insecure against a man-in-the-middle attack. These results demonstrate that automated adversarial testing with frankencerts is a powerful methodology for discovering security flaws in SSL/TLS implementations.


Pass-band reconfigurable spoof surface plasmon polaritons.
In this paper, we introduce a new scheme to construct the band-pass tunable filter based on the band-pass reconfigurable spoof surface plasmon polaritons (SPPs), whose cut-off frequencies at both sides of the passband can be tuned through changing the direct current (DC) bias of varactors. Compared to traditional technology (e.g. microstrip filters), the spoof SPP structure can provide more tight field confinement and more significant field enhancement, which is extremely valuable for many system applications. In order to achieve this scheme, we proposed a specially designed SPP filter integrated with varactors and DC bias feeding structure to support the spoof SPP passband reconfiguration. Furthermore, the full-wave simulated result verifies the outstanding performance on both efficiency and reconfiguration, which has the potential to be widely used in advanced intelligent systems.


The Saline Load Test is Effective at Diagnosing Traumatic Arthrotomies of the Wrist.
The saline load test has previously been shown to be an effective tool to diagnose traumatic arthrotomies, but no studies have assessed the test's efficacy in the wrist. The purpose of this study was to investigate the amount of fluid required during a saline load test to detect intra-articular wrist involvement of traumatic wounds with high sensitivity. A cadaveric study was conducted using 7 thawed, fresh-frozen forequarter amputations from 7 different donors (3 male, 4 female). Specimen age (mean: 67.7 y, range: 52 to 80 y), laterality (1 right, 6 left), body weight (mean: 164.3 lbs, range: 100 to 223 lbs), and wrist range of motion (ROM) was assessed before testing. The wrist capsule was punctured with an 11-blade scalpel through the 6R radiocarpal portal site under fluoroscopic guidance to ensure the injury was intra-articular. A 19-G needle was then placed through the 3,4 radiocarpal portal site and confirmed with fluoroscopy to ensure intra-articular placement. Normal saline was then injected at a steady rate into the 3,4 radiocarpal portal site until extravasation of the saline was observed from the 6R radiocarpal arthrotomy site. The volume of saline required for extravasation from the 6R radiocarpal arthrotomy was recorded as the volume required to detect the arthrotomy. A plot of saline volumes (by percentile) was created, and a logarithmic distribution was calculated. A Wilcoxon rank-sum test was used to compare injection volumes between male and female specimens, and Pearson Coefficients were used to determine any correlations between injection volume and ROM. The average amount of saline that resulted in extravasation was 4 mL (range: 2 to 7 mL). In order to identify 75%, 90%, 95%, and 99% of the simulated wrist arthrotomies, 5 (95% confidence interval: 3-7), 6 (4-9), 7 (4-10), and 9 (5-14) mL were required, respectively. Pretest ROM did not correlate with saline volume. This study demonstrates the efficacy of the saline load test in detecting traumatic arthrotomies of the wrist joint with 95% sensitivity after loading 7 mL of saline. Prompt and accurate diagnosis of traumatic arthrotomies is paramount to guide management and optimize postinjury outcomes.


Automated system for training and assessing string-pulling behaviors in rodents.
String-pulling tasks have been used for centuries to study coordinated bimanual motor behavior and problem solving. String pulling is rapidly learned, ethologically grounded, and has been applied to many species and disease conditions. Typically, training of string-pulling behaviors is achieved through manual shaping and baiting. Furthermore, behavioral assessment of reaching, grasping, and pulling is often performed through labor intensive manual video scoring. No system, to our knowledge, currently exists for the automated shaping and assessment of string-pulling behaviors. Here we describe the PANDA system (Pulling And Neural Data Analysis), an inexpensive hardware and software system that utilizes a continuous string loop connected to a rotary encoder, feeder, microcontroller, high-speed camera, and analysis software for assessment and training of string-pulling behaviors and synchronization with neural recording data. We demonstrate this system in unimplanted rats and rats implanted with electrodes in motor cortex and hippocampus and show how the PANDA system can be used to assess relationships between paw movements and single-unit and local-field activity. We also found that automating the shaping procedure significantly improved overall performance, with rats regularly pulling >100 meters during a 15-minute session. In conclusion, the PANDA system will be of general use to researchers investigating motor control, motivation, and motor disorders such as Parkinson's disease, Huntington's disease, and stroke. It will also support the investigation of neural mechanisms involved in sensorimotor integration.


Wastewater-based epidemiological evaluation of the effect of air pollution on short-acting beta-agonist consumption for acute asthma treatment.
Asthma, one of the most common chronic diseases in the world and a leading cause of hospitalization among children, has been associated with outdoor air pollution. We applied the wastewater-based epidemiology (WBE) approach to study the association between the use of salbutamol, a short-acting beta-agonist used to treat acute bronchospasm, and air pollution in the population of Milan, Italy. Composite 24-h samples of untreated wastewater were collected daily and analyzed for human metabolic residues of salbutamol by liquid chromatography tandem mass spectrometry. Corresponding daily outdoor concentrations of particular matter up to 10µm (PM10) and 2.5µm (PM2.5) in aerodynamic diameter, nitrogen dioxide, ozone, sulfur dioxide, and benzene were collected from the public air monitoring network. Associations at different lag times (0-10 days) were assessed by a log-linear Poisson regression model. We found significant direct associations between defined daily doses (DDD) of salbutamol and mean daily concentrations of PM10 and PM2.5 up to nine days of lag time. The highest rate ratio, and 95% confidence interval (CI), of DDD of salbutamol was 1.06 (95% CI: 1.02-1.10) and 1.07 (95% CI: 1.02-1.12) at seven days of lag time and for an increase of 10 μg/m(3) of PM10 and PM2.5, respectively. Reducing the mean daily PM10 concentration in Milan from 50 to 30μg/m(3) means that 852 (95% CI: 483-1504) daily doses of salbutamol per day would not be used. These results confirm the association between asthma and outdoor PM10 and PM2.5 and prove the potential of the WBE approach to quantitatively estimate the relation between environmental exposures and diseases.


Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals.
A series of antisense oligonucleotides (ASOs) containing either 2'-O-methoxyethylribose (MOE) or locked nucleic acid (LNA) modifications were designed to investigate whether LNA antisense oligonucleotides (ASOs) have the potential to improve upon MOE based ASO therapeutics. Some, but not all, LNA containing oligonucleotides increased potency for reducing target mRNA in mouse liver up to 5-fold relative to the corresponding MOE containing ASOs. However, they also showed profound hepatotoxicity as measured by serum transaminases, organ weights and body weights. This toxicity was evident for multiple sequences targeting three different biological targets, as well as in mismatch control sequences having no known mRNA targets. Histopathological evaluation of tissues from LNA treated animals confirmed the hepatocellular involvement. Toxicity was observed as early as 4 days after a single administration. In contrast, the corresponding MOE ASOs showed no evidence for toxicity while maintaining the ability to reduce target mRNA. These studies suggest that while LNA ASOs have the potential to improve potency, they impose a significant risk of hepatotoxicity.


Direct comparison of off-axis holography and differential phase contrast for the mapping of electric fields in semiconductors by transmission electron microscopy.
To provide a direct comparison, off-axis holography and differential phase contrast have been performed using the same microscope on the same specimens for the measurement of active dopants and piezoelectric fields. The sensitivity and spatial resolution of the two techniques have been assessed through the study of a simple silicon p-n junction observed at different bias voltages applied in-situ. For an evaluation of limitations and artefacts of the methods in more complicated systems a silicon pMOS device and an InGaN/GaN superlattice with 2.2-nm In0.15Ga0.85N quantum wells is investigated. We demonstrate the effects of dynamical scattering on the electric field measurements in the presence of local strain-induced sample tilts and its dependence on parameters like the convergence angle.


BEX2 promotes tumor proliferation in colorectal cancer.
BEX2 has been suggested to promote the tumor growth in breast cancer and glioblastoma, while inhibit the proliferation of glioma cells. Thus, the role of BEX2 in tumor was still in debate. Additionally, the biological functions of BEX2 in colorectal cancer (CRC) have not yet been clarified. Here, we reported that BEX2 was overexpressed in advanced CRC from both the GSE14333 database and fresh CRC tissue specimens, and positively correlated with clinical staging. Knockdown of BEX2 significantly decreased the in vitro proliferation of SW620 colorectal cancer cells, suppressed subcutaneous xenograft growth and enhanced the survival of mice with cecal tumors. These effects were mainly mediated by the JNK/c-Jun pathway. Knockdown of BEX2 inhibited JNK/c-Jun phosphorylation, while BEX2 overexpression activated JNK/c-Jun phosphorylation. Moreover, the administration of the JNK-specific inhibitor SP600125 to SW620 with BEX2 overexpression abolished the effect of BEX2 on SW620 cell proliferation. This study reveals that BEX2 promotes colorectal cancer cell proliferation via the JNK/c-Jun pathway, suggesting BEX2 as a potential candidate target for the treatment of CRC.


The importance of emotional intelligence.
Nurse managers who exhibit high emotional intelligence (EI) can elicit higher nurse-retention rates, better patient satisfaction and optimal organisational outcomes, and those who are emotionally intelligent tend consistently to model the positive behaviour that is expected of healthcare staff.