Identification of key biomarkers and immune infiltration in renal interstitial fibrosis.
Renal interstitial fibrosis (RIF) is the common final pathway that mediates almost all progressive renal diseases. However, the underlying mechanisms of RIF have not been fully elucidated. Therefore, the current study aimed to explore the etiology of RIF and identify the key targets and immune infiltration patterns of RIF. Ribonucleic acid (RNA)-seq data of RIF and normal samples were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to screen relevant modules associated with RIF. Differentially expressed genes (DEGs) between the RIF and normal samples were identified using the limma package. Machine learning methods were used to identify hub gene signatures related to RIF. Further biochemical approaches including quantitative polymerase chain reaction (qPCR), immunoblotting and immunohistochemistry experiments were performed to verify the hub signatures in the RIF samples. Single sample gene set enrichment analysis (ssGSEA) was used to analyze the proportions of 28 immune cells in RIF and normal samples. WGCNA showed 121 RIF-related genes. A total of 523 DEGs were found between the RIF and normal samples. By overlapping these genes, we obtained 78 RIF-related genes, which were mainly enriched in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with immunity and inflammation. Integrative analysis of machine learning methods showed prominin 1 (PROM1), tryptophan aspartate-containing coat protein (CORO1A), interferon-stimulated exonuclease gene 20 (ISG20), and tissue inhibitor matrix metalloproteinase 1 (TIMP1) as hub gene signatures in RIF. Further, receiver operating curve (ROC) curves implied the diagnostic role of ISG20 and CORO1A in RIF. The expression levels of ISG20 and CORO1A were significantly higher in fibrotic tubular cells and renal tissues based on biochemical approaches. The immune microenvironment was found to be markedly altered in the RIF samples, as 21 differentially infiltrated immune cells (DIICs) were found between RIF and normal samples. This study is the first to find that ISG20 and CORO1A are key biomarkers and to examine the landscape of immune infiltration in RIF. Our findings provide novel insights into the mechanisms and treatment of patients with RIF.


[Antibiotic prophylaxis for infective endocarditis: current approaches].
This review addresses current views on prevention of infectious endocarditis (IE). History of establishing the concept of antibacterial prophylaxis (ABP), major approaches, and substantiation of changes in ABP in recent years are described. Recent international and national guidelines are highlighted, specifically, guidelines of the European Society of Cardiologists, American Heart Association/American College of Cardiology, and the Japanese Circulation Society. The review presents critical evaluation of previously approved international guidelines, including analysis of the effect of partial or complete ABP restriction on IE morbidity and incidence of complications. Special attention is paid to awareness of practitioners, particularly dentists, about ABP issues in their practice. Aspects of validity and key features of preventive approaches in implanting cardiac electronic devices and transcatheter aortic valve implantation are discussed.


Peptide-Like Molecules (PLMs): A Journey from Peptide Bond Isosteres to Gramicidin S Mimetics and Mitochondrial Targeting Agents.
Peptides are natural ligands and substrates for receptors and enzymes and exhibit broad physiological effects. However, their use as therapeutic agents often suffers from poor bioavailability and insufficient membrane permeability. The success of peptide mimicry hinges on the ability of bioisosteres, in particular peptide bond replacements, to adopt suitable secondary structures relevant to peptide strands and position functional groups in equivalent space. This perspective highlights past and ongoing studies in our group that involve new methods development as well as specific synthetic library preparations and applications in chemical biology, with the goal to enhance the use of alkene and cyclopropane peptide bond isosteres.


Oligothiophene-bridged bis(arylene ethynylene) small molecules for solution-processible organic solar cells with high open-circuit voltage.
A new series of conjugated oligothiophene-bridged bis(arylene ethynylene) small molecules have been designed, synthesized, and characterized by photophysical, electrochemical and computational methods. These compounds were found to have optimal LUMO levels that ensure effective charge transfer from these compounds to [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM). They were utilized as good electron-donor materials that can be blended with electron-acceptor PC70BM in the fabrication of solution-processed molecular bulk heterojunction (BHJ) solar cells. All of these BHJ devices showed very high open-circuit voltage (V(oc)) of 0.90-0.97 V, and the best power conversion efficiency achieved was 3.68%. The high V(oc) is consistent with the deeper low-lying HOMO level and is relatively insensitive to the donor : acceptor blend ratio. The spin-coated thin films of these small molecules showed p-channel field-effect charge transport with the hole mobilities of up to 2.04×10(-4) cm(2) V(-1) s(-1). These compounds illuminate the potential of solution-processible small-molecular aryl acetylide compounds for efficient power generation in photovoltaic implementation.


Generation of liver disease-specific induced pluripotent stem cells along with efficient differentiation to functional hepatocyte-like cells.
The availability of disease-specific induced pluripotent stem cells (iPSCs) offers a unique opportunity for studying and modeling the effects of specific gene defects on human liver development in vitro and for testing small molecules or other potential therapies for relevant liver disorders. Here we report, for the first time, the derivation of iPSCs by the retroviral transduction of Yamanaka's factors in serum and feeder-free culture conditions from liver-specific patients with tyrosinemia, glycogen storage disease, progressive familial hereditary cholestasis, and two siblings with Crigler-Najjar syndrome. Furthermore, they were differentiated into functional hepatocyte-like cells efficiently. These iPSCs possessed properties of human embryonic stem cells (hESCs) and were successfully differentiated into three lineages that resembled hESC morphology, passaging, surface and pluripotency markers, normal karyotype, DNA methylation, and differentiation. The hepatic lineage-directed differentiation showed that the iPSC-derived hepatic cells expressed hepatocyte-specific markers. Their functionality was confirmed by glycogen and lipid storage activity, secretion of albumin, alpha-fetoprotein, and urea, CYP450 metabolic activity, as well as LDL and indocyanin green uptake. Our results provide proof of principal that human liver-disease specific iPSCs present an exciting potential venue toward cell-based therapeutics, drug metabolism, human liver development and disease models for liver failure disorders.


Differential characteristics in the chemical composition of bananas from Tenerife (Canary Islands) and Ecuador.
The contents of moisture, protein, ash, ascorbic acid, glucose, fructose, total sugars, and total and insoluble fiber were determined in cultivars of bananas (Gran Enana and Pequeña Enana) harvested in Tenerife and in bananas (Gran Enana) from Ecuador. The chemical compositions in the bananas from Tenerife and from Ecuador were clearly different. The cultivar did not influence the chemical composition, except for insoluble fiber content. Variations of the chemical composition were observed in the bananas from Tenerife according to cultivation method (greenhouse and outdoors), farming style (conventional and organic), and region of production (north and south). A highly significant (r = 0.995) correlation between glucose and fructose was observed. Correlations of ash and protein contents tend to separate the banana samples according to origin. A higher content of protein, ash, and ascorbic acid was observed as the length of the banana decreased. Applying factor analysis, the bananas from Ecuador were well separated from the bananas produced in Tenerife. An almost total differentiation (91.7%) between bananas from Tenerife and bananas from Ecuador was obtained by selecting protein, ash, and ascorbic acid content and applying stepwise discriminant analysis. By selecting the bananas Pequeña Enana and using discriminant analysis, a clear separation of the samples according to the region of production and farming style was observed.


Resonance attractors of spiral waves in excitable media under global feedback.
The dynamics of spiral waves on a circular domain is studied by numerical integration of an excitable reaction-diffusion system with a global feedback. A theory based on the Fourier expansion of the feedback signal is developed to explain the existence and the stability of resonance attractors of spiral waves on domains of different sizes. The theoretical analysis predicts the existence of a discrete set of stable attractors with radii depending on the time delay in the feedback loop. These predictions are in good quantitative agreement with performed numerical simulations.


Prevalence of abnormal cervical cytology among subfertile Saudi women.
Since cervical cancer is reportedly the seventh most frequent cancer in women in Saudi Arabia and the eighth most frequent cancer among women aged between 15 and 44 years, we wanted to determine the prevalence of abnormal cervical cytology among subfertile women attending the reproductive medicine unit of a tertiary care center in Saudi Arabia. This was a retrospective, cross-sectional, hospital-based study. A Pap smear was done for 241 of 493 (48.9%) subfertile women from January 2008 through February 2009. The Pap smear was normal in 166 of 241 patients (67.9%), abnormal in 71 (29.5%), and unsatisfactory for evaluation in 4 (1.7%). According to the revised Bethesda system, epithelial cell abnormality was found in 7 (2.9%), inflammation in 55 (22.8%), and infection in 9 (3.7%) patients. Epithelial cell abnormalities were further classified as atypical squamous cells of undetermined significance (ASC-US) (n=3, 42.8%), atypical squamous cells of high grade (ASC-H) (n=1, 14.3%), low-grade squamous intraepithelial lesion (LSIL) (n=2, 28.5%), and glandular cell abnormalities (AGS) (n=1, 14.3%). The high prevalence of abnormal cervical cytology in our subfertile women accentuates the need for screening in patients eligible for in vitro fertilization. In addition, a well-organized screening program for cervical cell abnormalities at the national level should be implemented to allow identification of subfertile women at risk so that potentially life-saving measures can be undertaken early.


Extracorporeal shock-wave lithotripsy and garlic consumption: a lesson to learn.
The first case of a kidney haematoma after extracorporeal shock-wave lithotripsy (SWL) in a patient with nephrolithiasis who was taking aged garlic extraction is reported. Patient was treated conservatively without the need of any intervention. Urologists should be aware that herbal products including garlic, ginkgo, and ginseng have been associated with potential increased bleeding. The present case emphasises the need to specifically seek out a history of herbal use in presurgical patients. It is suggested that herbal medications should be discontinued up to 15 days prior to urologic surgery or SWL to minimise the risk of complications.


Randomized controlled trial of barbed polyglyconate versus polyglactin suture for robot-assisted laparoscopic prostatectomy anastomosis: technique and outcomes.
Transperitoneal robot-assisted laparoscopic prostatectomy (RALP) urethrovesical anastomosis is a critical step. Although the prevalence of urine leaks ranges from 4.5% to 7.5% at high-volume RALP centers, urine leaks prolong catheterization and may lead to ileus, peritonitis, and require intervention. Barbed polyglyconate sutures maintain running suture line tension and may be advantageous in RALP anastomosis for reducing this complication. To compare barbed polyglyconate and polyglactin 910 (Vicryl, Ethicon, Somerville, NJ, USA) running sutures for RALP anastomosis. This was a prospective, randomized, controlled, single-surgeon study comparing RALP anastomosis using either barbed polyglyconate (n = 45) or polyglactin 910 (n = 36) sutures. RALP anastomosis using either barbed polyglyconate or polyglactin 910 sutures was studied. Operative time, cost differential, perioperative complications, and cystogram contrast extravasation by anastomosis suture type were measured. Although baseline characteristics and overall operative times were similar, barbed polyglyconate sutures were associated with shorter mean anastomosis times of 9.7 min versus 9.8 min (p = 0.014). In addition, anastomosis with barbed polyglyconate rather than polyglactin 910 sutures was associated with more frequent cystogram extravasation 8 d postoperatively (20.0% vs 2.8%; p = 0.019), longer mean catheterization times (11.1 d vs 8.3 d; p = 0.048), and greater suture costs per case ($51.52 vs $8.44; p < 0.001). After 8 of 29 (27.6%) barbed polyglyconate anastomosis sites demonstrated postoperative day 8 cystogram extravasation, we modified our technique to avoid overtightening, reducing cystogram extravasation to 1 (6.3%) of 16 subsequent barbed polyglyconate anastomosis sites. Potential limitations include small sample size and the single-surgeon study design. Compared to traditional sutures, barbed polyglyconate is more costly and requires technical modification to avoid overtightening, delayed healing, and longer catheterization time following RALP.


Effects of isoflurane with and without dexmedetomidine or remifentanil on heart rate variability before and after nociceptive stimulation at different multiples of minimum alveolar concentration in dogs.
To evaluate the influence of 3 anesthetic protocols and multiples of minimum alveolar concentration (MAC) on heart rate variability (HRV) with and without nociceptive stimulation in dogs. 6 healthy adult Beagles. Each dog was anesthetized 3 times: with isoflurane alone, with isoflurane and a constant rate infusion of dexmedetomidine (IsoD; 3 μg/kg/h, IV), and with isoflurane and a constant rate infusion of remifentanil (IsoR; 18 μg/kg/h, IV). Individual MAC was determined via supramaximal electrical stimulation. Sinus rhythm-derived intervals between 2 adjacent R-R intervals were exported from ECG recordings. Selected HRV time and frequency domain variables were obtained (at 2-minute intervals) and analyzed offline with signed rank tests before and after stimulation at 0.75, 1.0, and 1. 5 MAC for each anesthetic session. The isoflurane session had the overall lowest prestimulation SDNN (SD of all R-R intervals) values. Prestimulation SDNN values decreased significantly with increasing MAC in all sessions. For the IsoD session, SDNN (milliseconds) or high-frequency power (milliseconds(2)) was inversely correlated with MAC (Spearman rank correlation coefficient for both variables, -0.77). In the isoflurane and IsoR sessions, heart rate increased significantly after stimulation. In the IsoD session, poststimulation SDNN was increased significantly, compared with prestimulation values, at 0.75 and 1.0 MAC. On the basis of SDNN and high-frequency power values, anesthetic levels between 0.75 and 1.5 MAC within the same anesthetic protocol could be differentiated, but with a large overlap among protocols. Usefulness of standard HRV variables for assessment of anesthetic depth and nociception in dogs is questionable.


Traditional Use and Current Status of Phytotherapy in Pediatrics.
Phytotherapy offers a favorable benefit-risk quotient, which when combined with other factors, makes it eminently suitable for pediatrics. Approximately 14 indications for external application and 30 for internal use of phytotherapy discussed in the handbook carefully outline potential usefulness and limits and take into account the clinical experience of several pediatricians.


Ultrafine particles in urban air and respiratory health among adult asthmatics.
Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (<0.1 microm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases. To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for six months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution were examined by multivariate regression models. Daily mean number concentration of particles, but not particle mass (PM10 (particle mass <10 microm), PM2.5-10, PM2.5, PM1), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use. Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.


The impact of home hemodialysis in children with severe cardiac failure.
When faced with patients with deteriorating cardiac disease, nephrologists tend to accept that heart disease is unmodifiable, accepting mediocrity and opting for stabilization. Likewise cardiac patients with persistent renal failure are presented with a poor renal prognosis and prepared for renal transplantation. We present three dialysis dependent children with moderate-to-severe cardiac failure in whom home hemodialysis normalized the cardiac function and restored renal function. These cases highlight the medical benefits of home hemodialysis in severe cardio-renal cases but not without acknowledgement of the resource, commitment, and safety challenges that accompanies them.


Primary study on imaging in transient ischemic attacks.
Although transient ischemic attacks (TIA) is a clinical diagnosis, imaging findings are important for its diagnosis and treatment. This study evaluated the value and limitations of conventional CT, CT cerebral perfusion imaging and transcranial Doppler sonography (TCD) in patients with TIA. Conventional CT, CT cerebral perfusion imaging and TCD were performed in 20 patients with TIA. After regular CT examination, 40-second dynamic scans were performed on selected slice, while 40 ml of non-ionic contrast materials was bolus-injected through antecubital vein with power injector. These dynamic images were processed with the perfusion software package on workstation. Cerebral blood flow (CBF) and time to peak (TTP) were measured in specific regions of the brain. TCD was also performed in 20 patients with TIA. Comparative analysis was made on the basis of the results of conventional CT, CT cerebral perfusion imaging and TCD. In the 20 patients with TIA, conventional CT turned out to be normal. However, persisting abnormal perfusion changes corresponding to clinical symptoms were found in 13 cases with the prolonged TTP. The other 7 cases were normal. TTP of the affected side (11.6 +/- 3.0) s was significantly prolonged (t = 4.782, P < 0.01) in comparison with the contralateral side (8.8 +/- 1.5) s. The difference in CBF was not statistically significant (t = 1.912, P = 0.073) between the affected side [(223.9 +/- 19.6) ml.min(-1).L(-1)] and the contralateral side [(227.7 +/- 19.8) ml.min(-1).L(-1)]. TCD revealed severe stenosis or occlusion of the carotid artery in 10 patients, arteriosclerosis in 6 patients, blood speed decrease in 2 patients, vasospasm in 1 patient. Conventional CT can exclude intracerebral diseases. Perfusion CT provides valuable hemodynamic information and shows the extent of perfusion disturbances. TCD can demonstrate abnormalities of the involved arteries in patients with TIA. The combination of these three imaging methods can provide more diagnostic information.


Expression of WTH3 in breast cancer tissue and the effects on the biological behavior of breast cancer cells.
The aim of the present study was to investigate the expression of WTH3 in tumor and normal breast tissue. The mRNA and protein expression levels of WTH3 were detected using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. In addition, matrix metalloproteinase (MMP)-2 protein expression was measured. The effect of WTH3 expression on the proliferation activity of breast cancer cells was detected using a Cell Counting Kit-8 assay. Furthermore, the effects of WTH3 on the invasion and migration ability of the breast cancer cells was investigated. The results revealed that WTH3 was able to significantly inhibit the proliferation of the MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, the invasion and migration assay demonstrated that WTH3 was able to inhibit the invasion and migration of breast cancer cells. Western blot analysis revealed that increased expression of WTH3 resulted in decreased expression levels of MMP-2, which has an important function in the metastasis of cancer cells. In conclusion, WTH3 expression differed between the tumor and normal breast tissues. WTH3 was able to inhibit the proliferation of breast cancer cells and decrease their invasion ability. Thus, WTH3 may be a promising target for breast cancer therapy in the future.


Oxygen therapy strategies and techniques to treat hypoxia in COVID-19 patients.
Hypoxia is one of the primary causes that leads to multiple organ injuries and death in COVID-19 patients. Aggressive oxygen therapy for the treatment of hypoxia is important in saving these patients. We have summarized the mechanisms, efficacy, and side effects of various oxygen therapy techniques and their status or the potential to treat hypoxia in COVID-19 patients. The benefit to risk ratio of each oxygen therapy technique and strategy to use them in COVID-19 patients are discussed. High flow nasal cannula oxygen (HFNO) should be considered a better choice as an early stage oxygen therapy. Supraglottic jet oxygenation and ventilation (SJOV) is a promising alternative for HFNO with potential benefits.


Partial characterization of fusicoccin binding to receptor sites on oat root membranes.
The possibility that fusicoccin (FC) binds to plasma membrane-associated ATPases of oat (cv. Victory) roots has been examined. Specific FC-binding in vitro is localized primarily on plasma membrane-enriched fractions. This FC-binding is greatly reduced by pretreatment of the membrane vesicles at temperatures above 45 C or with trypsin, and the same treatments cause the release of already bound FC. These results support the idea that the FC receptor is a protein located on the plasma membrane.Both active ATPases and FC-binding proteins were solubilized using 1% Triton X-100. When this material was fractionated using gel chromatography, the ATPase activity could be separated from the FC-binding proteins. The identity of the FC-binding proteins is discussed with regard to the extensive evidence which supports the involvement of plasma membrane-ATPase H(+)/K(+) pumps in FC-stimulated acidification and K(+) uptake.


Degradation of 316L stainless steel sternal wire by steam sterilization.
Sterilization is an important step prior to the implantation of medical devices inside the human body. In this work we studied the influence of steam sterilization cycles on the oxide film properties of stainless steel sternal wire. Characterization techniques such as open- circuit potential, potentiodynamic measurement, electrochemical impedance spectroscopy, cathodic stripping, transmission electron microscopy, atomic force microscopy and scanning electron microscopy were employed to investigate the cycles of steam sterilization on the corrosion behavior of sternal wire. The results showed that the oxide properties are a function of the number of steam sterilization cycles and deteriorate as the number of cycles increases. Steam sterilization might damage the implant integrity and heavy metals could be released to the surrounding tissues due to deterioration of the oxide film.


Generic Properties of Stochastic Entropy Production.
We derive an Itô stochastic differential equation for entropy production in nonequilibrium Langevin processes. Introducing a random-time transformation, entropy production obeys a one-dimensional drift-diffusion equation, independent of the underlying physical model. This transformation allows us to identify generic properties of entropy production. It also leads to an exact uncertainty equality relating the Fano factor of entropy production and the Fano factor of the random time, which we also generalize to non-steady-state conditions.


Synthesis of enantiomerically pure alpha-[14C]methyl-L-tryptophan.
A practical method for the preparation of large amounts of enantiomerically pure alpha-[14C]methyl-L-tryptophan using the enzymatic resolution of the corresponding D,L-methyl ester is reported. The radiolabelled alpha-methyl group was introduced using the alpha-methylation of the lithium enolate of the Schiff base of L-tryptophan methyl ester. Hydrolysis of the Schiff base with 1N HCl provided the D,L-methyl ester of alpha-[14C]methyl tryptophan. Enantioselective enzymatic hydrolysis of the L-methyl ester by alpha-chymotrypsin gave the enantiomerically pure alpha-[14C]methyl-L-tryptophan. The overall yield of this preparation was 33%.


Structure and properties of virions and virus-like particles derived from the coat protein of Alternanthera mosaic virus.
Plant viruses and their virus-like particles (VLPs) have a lot of advantages for biotechnological applications including complete safety for humans. Alternanthera mosaic virus (AltMV) is a potentially promising object for design of novel materials. The 3D structures of AltMV virions and its VLPs were obtained by single particle EM at ~13Å resolution. The comparison of the reconstructions and a trypsin treatment revealed that AltMV CPs possesses a different fold in the presence (virions) and absence of viral RNA (VLPs). For the first time, the structure of morphologically similar virions and virus-like particles based on the coat protein of a helical filamentous plant virus is shown to be different. Despite this, both AltMV virions and VLPs are stable in a wide range of conditions. To provide a large amount of AltMV for biotechnology usage the isolation procedure was modified.


Inferring primary tumor sites from mutation spectra: a meta-analysis of histology-specific aberrations in cancer-derived cell lines.
Next-generation sequencing technologies have led to profound characterization of mutation spectra for several cancer types. Hence, we sought to systematically compare genomic aberrations between primary tumors and cancer lines. For this, we compiled publically available sequencing data of 1651 genes across 905 cell lines. We used them to characterize 23 distinct primary tumor sites by a novel approach that is based on Bayesian spam-filtering techniques. Thereby, we confirmed the strong overall similarity of alterations between patient samples and cell culture. However, we also identified several suspicious mutations, which had not been associated with their cancer types before. Based on these characterizations, we developed the inferring cancer origins from mutation spectra (ICOMS) tool. On our cell line collection, the algorithm reached a prediction specificity rate of 79%, which strongly variegated between primary cancer sites. On an independent validation cohort of 431 primary tumor samples, we observed a similar accuracy of 71%. Additionally, we found that ICOMS could be employed to deduce further attributes from mutation spectra, including sub-histology and compound sensitivity. Thus, thorough classification of site-specific mutation spectra for cell lines may decipher further genome-phenotype associations in cancer.


Differentiation of Bacillus anthracis from Bacillus cereus by gas chromatographic whole-cell fatty acid analysis.
Three strains of Bacillus anthracis and seven strains of Bacillus cereus were grown on complex medium and on synthetic medium. Gas chromatographic analysis of whole-cell fatty acids of strains grown on complex medium gave nearly identical fatty acid patterns. Fatty acid patterns of strains grown on synthetic medium showed a high content of branched-chain fatty acids. Significant differences between the fatty acid patterns of the two species were found. Odd iso/anteiso fatty acid ratios were about equal in B. anthracis strains, whereas in B. cereus strains the fractions of iso acids were at least twice as high as the fractions of anteiso acids. The method described herein is used in our diagnostic laboratory to help differentiate between these two species.


Risk for inhalant initiation among middle school students: understanding individual, family, and peer risk and protective factors.
Because initiation of inhalants at an early age is associated with a range of health and behavioral problems, including an increased likelihood of inhalant dependence (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), we conducted discrete time survival analyses to determine the role of time-invariant and time-variant (over five waves) risk and protective factors as well as grade in inhalant initiation among middle school students. The current study uses data from 3,215 students who were initially surveyed as sixth graders in 2008-2009 and were resurveyed in seventh and eighth grades. Students were part of a larger substance use prevention trial conducted in greater Los Angeles. The sample is racially/ethnically diverse (54% Hispanic/Latino, 16% Asian, 14% White, 3% African American) and 51% male. Seventeen percent of youths initiated inhalants during middle school. Higher drug refusal self-efficacy, familism (i.e., values related to family), and parental respect were associated with decreased odds of inhalant initiation. Having a significant adult or older sibling who used substances was associated with increased risk of initiation, but adult influence declined linearly and by the end of seventh grade was no longer a risk factor. Self-rated popularity was associated with inhalant initiation in seventh grade only, and perceived substance use by peers was associated with inhalant initiation in sixth grade only. The influence of adults, siblings, and peers on inhalant use may be strongest in sixth and seventh grade. Interventions to prevent inhalant initiation should target sixth and seventh graders, address influence by family and peers, and provide skills training to improve drug refusal self-efficacy.


Pseudo-Spectral Damping Reduction Factors for the Himalayan Region Considering Recorded Ground-Motion Data.
Ground-motion prediction equations that are used to predict acceleration values are generally developed for a 5% viscous damping ratio. Special structures and structures that use damping devices may have damping ratios other than the conventionally used ratio of 5%. Hence, for such structures, the intensity measures predicted by conventional ground-motion prediction equations need to be converted to a particular level of damping using a damping reduction factor (DRF). DRF is the ratio of the spectral ordinate at 5% damping to the ordinate at a defined level of damping. In this study, the DRF has been defined using the spectral ordinate of pseudo-spectral acceleration and the effect of factors such as the duration of ground motion, magnitude, hypocenter distance, site classification, damping, and period are studied. In this study, an attempt has also been made to develop an empirical model for the DRF that is specifically applicable to the Himalayan region in terms of these predictor variables. A recorded earthquake with 410 horizontal motions was used, with data characterized by magnitudes ranging from 4 to 7.8 and hypocentral distances up to 520 km. The damping was varied from 0.5-30% and the period range considered was 0.02 to 10 s. The proposed model was compared and found to coincide well with models in the existing literature. The proposed model can be used to compute the DRF at any specific period, for any given value of predictor variables.


Selling second best: how infant formula marketing works.
Despite the clear policy intent to contain it, the marketing of formula milk remains widespread, powerful and successful. This paper examines how it works. The study comprised a mix of secondary analysis of business databases and qualitative interviews with marketing practitioners, some of whom had previously worked in formula marketing. The World Health Assembly Code aims to shield parents from unfair commercial pressures by stopping the inappropriate promotion of infant formula. In reality marketing remains widespread because some countries (e.g. the USA) have not adopted the Code, and elsewhere industry has developed follow-on and specialist milks with which they promote formula by proxy. The World Health Assembly has tried to close these loopholes by extending its Code to these products; but the marketing continues. The campaigns use emotional appeals to reach out to and build relationships with parents and especially mothers. Evocative brands give these approaches a human face. The advent of social media has made it easier to pose as the friend and supporter of parents; it is also providing companies with a rich stream of personal data with which they hone and target their campaigns. The formula industry is dominated by a small number of extremely powerful multinational corporations with the resources to buy the best global marketing expertise. Like all corporations they are governed by the fiduciary imperative which puts the pursuit of profits ahead of all other concerns. This mix of fiscal power, sophisticated marketing, and single-mindedness is causing great harm to public health. Formula marketing is widespread and using powerful emotional techniques to sell parents a product that is vastly inferior to breast milk. There is an urgent need to update and strengthen regulation.


Incorporation of Calcium Containing Mesoporous (MCM-41-Type) Particles in Electrospun PCL Fibers by Using Benign Solvents.
The electrospinning technique is a versatile method for the production of fibrous scaffolds able to resemble the morphology of the native extra cellular matrix. In the present paper, electrospinning is used to fabricate novel SiO2 particles (type MCM-41) containing poly(epsilon-caprolactone) (PCL) fibers. The main aims of the present work are both the optimization of the particle synthesis and the fabrication of composite fibers, obtained using benign solvents, suitable as drug delivery systems and scaffolds for soft tissue engineering applications. The optimized synthesis and characterization of calcium-containing MCM-41 particles are reported. Homogeneous bead-free composite electrospun mats were obtained by using acetic acid and formic acid as solvents; neat PCL electrospun mats were used as control. Initially, an optimization of the electrospinning environmental parameters, like relative humidity, was performed. The obtained composite nanofibers were characterized from the morphological, chemical and mechanical points of view, the acellular bioactivity of the composite nanofibers was also investigated. Positive results were obtained in terms of mesoporous particle incorporation in the fibers and no significant differences in terms of average fiber diameter were detected between the neat and composite electrospun fibers. Even if the Ca-containing MCM-41 particles are bioactive, this property is not preserved in the composite fibers. In fact, during the bioactivity assessment, the particles were released confirming the potential application of the composite fibers as a drug delivery system. Preliminary in vitro tests with bone marrow stromal cells were performed to investigate cell adhesion on the fabricated composite mats, the positive obtained results confirmed the suitability of the composite fibers as scaffolds for soft tissue engineering.


Caregivers experiences of managing medications for palliative care patients at the end of life: a qualitative study.
Informal caregivers are important in enabling palliative care patients to die at home, including their role in managing medications. Often these patients are taking multiple medications, imposing an unnecessary burden on those who are already struggling with oral intake. A literature review revealed that, while there are a number of qualitative studies published examining the experience of caregivers looking after patients at the end of life, there is a dearth of published studies specifically examining the impact of managing medications on caregivers. This study explores the experience of caregivers managing medications for patients dying at home, focusing on the impact of polypharmacy, the use of syringe drivers and the use of "as needed" medications for symptom control. Three focus groups were performed, involving bereaved caregivers of patients that had died at home, and were analysed using content thematic analysis. Themes that emerged include: the significant burden of polypharmacy; the positive impact of subcutaneous infusions; the value of being able to give medications as needed for symptom control; the importance of clear guidance to assist with medication management. Strategies are suggested that might ease the burden of medications at the end of life.


One more extreme near the critical micelle concentration: optical activity.
It is reported the discovery of optical activity of micellar solutions of sodium dodecyl sulfate, cetyltrimethylammonium bromide, and poly(oxyethilene)(4)dodecyl ether as typical representatives of anionic, cationic, and nonionic surfactants. The surfactants exhibit dextrorotation. Since the optical activity of the ionic surfactants appears only above the Krafft point, it should be ascribed to micellar aggregates. Optical rotation as a function of the surfactant concentration displays a pronounced maximum near the critical micelle concentration (the subsequent decrease of optical activity corresponds to formation of spherical micelles that cannot possess optical activity by symmetry). For sodium dodecyl sulfate, the maximum correlates well with extremes of other properties of surfactant solutions (foaminess, foam stability, Gibbs' and transversal elasticity of thin foam films), which was described earlier. Naturally, films and foams of sodium dodecyl sulfate solutions also demonstrate optical activity.


Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain.
Guanidinopropionic acid (GPA), an analogue of creatine (Cr), is known to inhibit Cr uptake by cells. The metabolic effects of chronic Cr depletion on brain, heart and soleus muscle of rats were studied. In GPA hearts and soleus muscle, total specific creatine kinase (CK) activity was decreased by approx. 40% compared to controls, whereas in brain this same activity was elevated by a factor of two. Immunoblot analysis of soleus mitochondria from GPA rats showed an approximate 4-fold increase in Mi-CK protein and a concomitant 3-fold increase in adenine nucleotide translocator (ANT) protein, when compared to control. In GPA-fed rats, the specific activities of adenylate kinase (ADK) and succinate dehydrogenase were significantly higher in brain and soleus (2-fold), but heart remained the same. However, hexokinase (HK) decreased by approx. 50% both in heart and soleus, indicating that muscle and brain follow different strategies to compensate the energy deficit caused by creatine depletion. Skinned muscle fibres from Cr-depleted soleus attained approx. only 70% maximum state 3 respiration with 0.1 M ADP in the presence of 10 mM Cr compared to 100% in control fibres. This defect in Cr stimulated respiration was also seen in isolated heart mitochondria, but was normal in those from brain. The observed deficit of Cr-stimulated respiration, the significant accumulation of Mib-CK and ANT, concomitant with the formation of Mib-CK rich intra-mitochondrial inclusions shown by electron microscopy, indicate that Mib-CK function and coupling to oxidative phosphorylation (OXPHOS), is impaired in these abnormal mitochondria. In addition, our results show tissue-specific metabolic compensations to Cr depletion.


Tissue engineering tools for modulation of the immune response.
Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine.


The Formation of beta, 1 --> 4 Glucan from UDP-alpha-d-Glucose Catalyzed by a Phaseolus aureus Enzyme.
Particulate enzyme preparations from Phaseolus aureus hypocotyls catalyze the formation of an alkali insoluble beta, 1 --> 4 linked [(14)C]-glucan using UDP-alpha-d [(14)C]-glucose as substrate. Particulate enzymes prepared from root tissue also catalyzed the production of beta, 1 --> 4 glucan. UDP-beta-d-[(14)C]-glucose would not serve as a substrate for these enzymes. The presence or absence of beta, 1 --> 4 glucan synthetase activity was independent of tissue source, substrate concentration, or homogenization method.The particulate enzyme also catalyzes the formation of a beta, 1 --> 3 linked glucan from UDP-d glucose which is usually soluble in hot alkali. The solubility of the beta, 1 --> 3[(14)C]-glucan decreased when the enzyme was obtained from hypocotyls germinated at a higher temperature. The water-soluble material resulting from the catalyzed reaction includes a large proportion of what appears to be [(14)C]-laminaribiose, and smaller proportions of [(14)C]-laminaritriose and [(14)C]-glucose. There is no detectable quantity of [(14)C]-cellobiose or [(14)C]-cellotriose in the water-soluble material.


A comparison of shaping ability using ProFile, GT file, and Flex-R endodontic instruments in simulated canals.
A total of 160 resin-simulated canal blocks with 20-degree or 30-degree curvature were prepared by ProFile rotary instruments, GT rotary files, and the balanced force technique with Flex-R files. Using an image analysis computer application, the pre- and postoperative images were stored and superimposed, and then the amount of material removed from the preoperative inner and outer curved walls was measured at five levels in the apical 5 mm of the canal. The time required for canal preparation, including irrigation, and the time taken to change instruments was recorded. At 1 mm from the apical end, the directions of canal transportation were most frequently toward the outer aspect of the curvature, with the only exception being the canals shaped by the balanced force technique in which more was removed from the inner aspect. The balanced force technique required more preparation time than the rotary instrumentation.


The effectiveness of aromatherapy on preoperative anxiety in adults: A systematic review and meta-analysis of randomized controlled trials.
Preoperative anxiety is very common in adults awaiting all types of surgical procedures, which can interfere with the start and completion of surgery and increase the risk of postoperative complications. In this context, many researchers and clinical practitioners have attempted to use aromatherapy to help adults reduce preoperative anxiety. To investigate systematically the efficacy of aromatherapy on preoperative anxiety in adults. A systematic review and meta-analysis of randomized controlled trials was undertaken. PubMed, Embase, Cochrane Library, Web of Science, PsycINFO and CINAHL were comprehensively searched from their inception to June 2020. Studies on the use of aromatherapy for treating preoperative anxiety in adults were included. Two reviewers assessed the risk of bias of the included studies independently using the Cochrane Collaboration 'Risk of Bias' tool. Overall meta-analysis and five subgroup analyses regarding the type of control, the type of aroma preparations, delivery mode, session length and surgery type were performed using RevMan 5.3. The Higgins' I2 (%) statistic was used to measure heterogeneity. A funnel plot and Egger's test were used to evaluate publication bias. Twenty studies comprising 1717 participants were included. The meta-analysis indicated that aromatherapy could significantly ameliorate preoperative anxiety (standard mean difference=-0.57, 95% confidence interval [-0.75, -0.39], p<0.00001) for adults awaiting surgical procedures, compared to placebo control, conventional care and no intervention. The subgroup analysis based on the surgery type showed that aromatherapy had a great improvement on preoperative anxiety for patients awaiting cardiac surgery and relatively low-risk surgery. Lavender oil, citrus species preparations and rose oil were the three most commonly used aroma preparations that could significantly improve preoperative anxiety. Most delivery modes of aromatherapy, including inhalation, massage, and oral administration, were effective. Moreover, short length (≤20 min per session) aromatherapy showed a better effect on preoperative anxiety (mean difference=-5.84, 95% confidence interval [-8.09, -3.59], p<0.00001) than aromatherapy lasting more than 20-minutes per session (mean difference=-2.15, 95% confidence interval [-3.81, -0.49], p = 0.01). Aromatherapy is an effective intervention for reducing preoperative anxiety in adults. Short-length aromatherapy inhalation seems to be more worthy of being recommended in clinical settings. More well-designed randomized controlled trials containing a wider range of surgical types and participants from more countries are needed to verify our findings before we can make strong recommendations.


[Bilateral multilocular cystic renal cell carcinoma: a case report].
A case of bilateral synchronous multilocular cystic renal cell carcinoma is reported. A 52-year-old man was admitted to our hospital for further examination of right renal mass which was found incidentally by ultrasonography. After he was examined by intravenous pyelography (IVP), computerized tomographic (CT) scan, magnetic resonance imaging (MIR) and angiography, right nephrectomy was performed under the diagnosis of right renal cancer. Histological diagnosis was multilocular cystic renal cell carcinoma. CT scan revealed a small left renal cystic lesion at that time. Ten months later enhanced CT scan revealed irregular septum in the cystic lesion. Under the diagnosis of left renal cancer, we carried out simple enucleation. Histological diagnosis was multilocular cystic renal cell carcinoma as in the right kidney. The patient has been followed up carefully. This is the third case of bilateral multilocular cystic renal cell carcinoma, which is regarded as the first synchronous one, reported in Japan.


Attachment insecurity predicts outcomes in an ACT-CBT group therapy for adults in a physical rehabilitation centre.
Adapting to chronic illness or disability is accompanied by acute and ongoing illness stressors. Psychological factors such as emotional distress and low self-efficacy are common experiences in chronic illness and disability and interfere with adaptation and psychosocial outcomes such as health-related quality of life. Transdiagnostic group psychotherapy may provide a parsimonious approach to psychological treatment in rehabilitation care by targeting shared illness stressors across mixed chronic illnesses and disabilities, and shared processes that maintain psychological symptoms. Attachment theory may explain individual differences in outcomes and help identify individuals at risk of poor health-related quality of life trajectories. Adults (N=109) participated in an 8-week process-based ACT-CBT psychotherapy group at a tertiary care physical rehabilitation centre between 2016 and 2020. Participants completed measures of emotional distress, self-efficacy, health-related quality of life, and attachment at pre- and post-treatment. Multilevel analyses indicated that patients improved on most outcomes at post-treatment. Attachment anxiety at pre-treatment was associated with more positive outcomes. Reliable change indices suggest clinically meaningful change for the majority of participants, but most were not recovered. Results provide proof-of-concept for the transdiagnostic group intervention and suggest that a longer course of treatment may be clinically indicated. Results warrant replication with larger and more diverse samples, and more robust designs.


Dental arch changes from 22 to 43 years of age: are they different in individuals with high versus low mandibular plane angle?
To investigate whether individuals with high and low mandibular plane angles, respectively, have different patterns of long-term dental arch changes in adulthood. The material comprised 16 low-angle (≤ 24.4 degree) and 10 high-angle individuals (≥38.7 degree). Mean age was 22.7 years when the first recordings were made (T1), and new recordings were made 10 (T2) and 20 (T3) years later. The individuals were orthodontically untreated except for three who had been out of retention for more than 5 years before T1. Lateral cephalograms and study casts were obtained on all three occasions. For the total observation period, the greatest mean changes were observed as a 1mm decrease of lower intercanine width and arch depths in both groups. Intermolar widths increased less than 0.5mm. Upper and lower crowding increased in the range of 0.5-0.7mm in the two groups. Only small changes occurred in overjet and overbite. Differences between groups were not significant except for lower anterior arch depth which decreased more in the low-angle group, and overjet which increased in the high- and decreased in the low-angle group. During both periods the changes were generally in the same direction. Changes in dental arch dimensions from third to fifth decade of life are small and generally similar in individuals with high versus low mandibular plane angles. The changes are for most variables in the same direction in the two periods examined. The only significant differences between the groups are the changes in lower arch depth and overjet.


Second monomer binding is the rate-limiting step in the formation of the dimeric PhoP-DNA complex.
PhoP, the response regulator of the PhoP/PhoQ system, regulates Mg(2+) homeostasis in Salmonella typhimurium. Dimerization of PhoP on the DNA is necessary for its regulatory function, and PhoP regulates the expression of genes in a phosphorylation-dependent manner. Higher PhoP concentrations, however, can activate PhoP and substitute for phosphorylation-dependent gene regulation. Activation of PhoP by phosphorylation is explained by self-assembly of phosphorylated PhoP (PhoP-p) in solution and binding of the PhoP-p dimer to the promoter. To understand the mechanism of PhoP dimerization on the DNA, we examined the interactions of PhoP with double-stranded DNAs containing the canonical PhoP box (PB). We present results from multiple biophysical methods, demonstrating that PhoP is a monomer in solution over a range of concentrations and binds to PB in a stepwise manner with a second PhoP molecule binding weakly. The affinity for the binding of the first PhoP molecule to PB is more than ∼17-fold higher than the affinity of the second PhoP monomer for PB. Kinetic analyses of PhoP binding reveal that the on rate of the second PhoP monomer binding is the rate-limiting step during the formation of the (PhoP)(2)-DNA complex. Results show that a moderate increase in PhoP concentration can promote dimerization of PhoP on the DNA, which otherwise could be achieved by PhoP-p at much lower protein concentrations. Detailed analyses of PhoP-DNA interactions have revealed the existence of a kinetic barrier that is the key for specificity in the formation of the productive (PhoP)(2)-DNA complex.


Micron Scale Spatial Measurement of the O2 Gradient Surrounding a Bacterial Biofilm in Real Time.
Bacteria alter their local chemical environment through both consumption and the production of a variety of molecules, ultimately shaping the local ecology. Molecular oxygen (O2) is a key metabolite that affects the physiology and behavior of virtually all bacteria, and its consumption often results in O2 gradients within sessile bacterial communities (biofilms). O2 plays a critical role in several bacterial phenotypes, including antibiotic tolerance; however, our understanding of O2 levels within and surrounding biofilms has been hampered by the difficulties in measuring O2 levels in real-time for extended durations and at the micron scale. Here, we developed electrochemical methodology based on scanning electrochemical microscopy to quantify the O2 gradients present above a Pseudomonas aeruginosa biofilm. These results reveal that a biofilm produces a hypoxic zone that extends hundreds of microns from the biofilm surface within minutes and that the biofilm consumes O2 at a maximum rate. Treating the biofilm with levels of the antibiotic ciprofloxacin that kill 99% of the bacteria did not affect the O2 gradient, indicating that the biofilm is highly resilient to antimicrobial treatment in regard to O2 consumption.IMPORTANCE O2 is a fundamental environmental metabolite that affects all life on earth. While toxic to many microbes and obligately required by others, those that have appropriate physiological responses survive and can even benefit from various levels of O2, particularly in biofilm communities. Although most studies have focused on measuring O2 within biofilms, little is known about O2 gradients surrounding biofilms. Here, we developed electrochemical methodology based on scanning electrochemical microscopy to measure the O2 gradients surrounding biofilms in real time on the micron scale. Our results reveal that P. aeruginosa biofilms produce a hypoxic zone that can extend hundreds of microns from the biofilm surface and that this gradient remains even after the addition of antibiotic concentrations that eradicated 99% of viable cells. Our results provide a high resolution of the O2 gradients produced by P. aeruginosa biofilms and reveal sustained O2 consumption in the presence of antibiotics.


Spatiotemporally Correlated Imaging of Interfacial Defects and Photocurrents in High Efficiency Triple-Cation Mixed-Halide Perovskites.
Triple-cation mixed-halide perovskites have attracted considerable attention due to their excellent photovoltaic properties and enhanced stability, though the power conversion efficiency (PCE) is still far below the theoretical expectation. In order to understand the microscopic mechanisms responsible for the gap, a Cs0.05 (FA0.85 MA0.15 )0.95 Pb(I0.85 Br0.15 )3 (CsFAMA)-based solar cell with respectful efficiency over 20% is examined, and distinct high- and low-current regions are observed in photoconductive atomic force microscopy (pc-AFM) mapping. Simulations attribute the difference in local photocurrents to interfacial donor defect densities at the NiO/CsFAMA interface, which is supported by electrochemical strain microscopy (ESM) mapping, revealing a negative correlation between ionic defects and photocurrents. The interfacial defects can be further manipulated by external bias upon relaxation study, resulting in reduced photocurrents accompanied by topography change when positive ions are driven toward the NiO/CsFAMA interface. It is also observed that both structure variation and photocurrent degradation upon accelerated aging test initiate at grain boundaries, which gradually expand at the expense of grain interior, suggesting that ionic defects are most active at grain boundaries. These findings render a direct correlation between interfacial defects and photocurrents while revealing degradation evolution, and if such interfacial defects heterogeneity can be mitigated, PCE toward the theoretical limit with enhanced stability can be envisioned.


MCT/LCT Mixed Oil Phase Enhances the Rheological Property and Freeze-Thawing Stability of Emulsion.
The main objective of this study was to investigate the effect of different oil phase compositions (medium-chain triglyceride (MCT) and long-chain triglyceride (LCT), the proportion of MCT is 0%, 5%, 10%, 15% and 20%, respectively) on the rheological properties and freeze-thaw stability of emulsions. The emulsions were characterized by differential scanning calorimetry (DSC), rheometer, stability analyzer, Malvern particle size meter and confocal microscope. Results showed that all emulsions exhibited a gel-like characteristic with a storage modulus higher than the loss modulus. The elastic modulus and complex viscosity of the emulsions increased with the increase of MCT proportions. During the heating from 4 °C to 80 °C, the complex viscosity of all emulsions decreased first and then remained unchanged at a continuous high temperature, indicating that the emulsions had good stability and internal structural integrity during the cooling and high-temperature processes. With the increase of MCT proportions, the freeze-thaw stability of the emulsions increased first and then decreased, and showed the optimum with 10% MCT. That could be referred for the production of a product with better freeze-thaw stability and rheological property in the food and cosmetic industries.


A special method of dilating tracheal stenosis following tracheostomy.
Several methods can be used to manage tracheal stenosis. For patients unfit for surgery, frequent dilatation with stent placement is the most common treatment. We here describe a simple and effective method using Bakes common bile duct dilators to dilate a tracheal stenosis in a patient with a tracheostomy.


[Research of the effect of cochlear implant and hearing aid on voice quality of hearing impaired children].
To discuss the effect of cochlear implant and hearing aid to voice quality. Four groups of randomly selected 73 subjects were compared. The groups comprised: cochlear implant children, children using hearing aids, normal hearing children and deaf children with no hearing instrumentation. The latter two groups were control groups. Each subject was required to phonate /ae/ about 3 s using 'voice assessment' to record the sound, and following voice acoustic variables were analysed: F0, SDF0, Jitter, Shimmer, NNE, HNR, SNR. Voice F0 of children with cochlear implant was significantly lower that the other three groups (P<0.05); there were no significant difference between hearing aid group, normal hearing group, and deaf children group with no intervention (P>0. 05); SDF0 of cochlear implant group and hearing aids group were significantly larger than the normal hearing group and deaf children group with no intervention (P<0.05), and the interaction of two factors (hearing and sex) was close to the critical level of significance (P>0.05), which means that cochlear implant and hearing aid could have affected the SDF0 of female children more than those of male children. There were no significant difference among all the four groups about voice quality variables: Jitter, Shimmer, NNE, HNR, SNR. Cochlear implant and hearing aid mainly change the voice F0 and/or SDF0, and have no effect on the voice quality variables.


Cytokine gene polymorphisms and susceptibility to cachexia.
Cachexia is a progressive deterioration of body habitus associated with chronic diseases. The finding that only a proportion of patients with chronic disease develop cachexia has prompted studies looking for genetic polymorphisms that may underlie differential susceptibility. The aim of this review is to explore how inflammation and gene polymorphisms influence susceptibility to cachexia. There has been evidence that certain cytokine gene polymorphisms are associated with cachexia. However, only the IL10 -1082 G allele, which is associated with an increased risk of developing cachexia has been replicated in more than one study. Variation in genes outwith inflammation pathways (e.g. genes involved in protein metabolism) is also likely to contribute the susceptibility of developing cachexia. The insertion/deletion angiotensin converting enzyme (ACE) gene polymorphism has recently been linked with lower lean body mass in cancer patients with cachexia. Although there is an increasing body of evidence of genetic susceptibility to cachexia, most studies so far have only focussed on a small number of polymorphisms and have small sample sizes. Large-scale candidate gene studies or genome-wide association studies are required to further elucidate the link between genotype and cachexia.


Surveillance Duplex Ultrasonography of Stent Grafts for Popliteal Aneurysms.
Stent grafts, also known as covered stents, have become an increasingly acceptable treatment for popliteal artery aneurysms. However, endovascular exclusion confers lower primary patency compared to traditional open bypass and exclusion. The purpose of this study was to evaluate whether duplex ultrasonography (DU) can reliably diagnose failing stent grafts placed for popliteal artery aneurysms prior to occlusion. Between June 5, 2007, and March 11, 2014, 21 stent grafts (Viabahn; Gore, Flagstaff, Arizona) were placed in 19 patients for popliteal artery aneurysms. All patients had at least 1 follow-up duplex scan postoperatively. Mean follow-up was 28.9 months (9-93 months). Postoperative DU surveillance was performed in our Intersocietal Accreditation Commission noninvasive vascular laboratory at 1 week postprocedure and every 6 months thereafter. Duplex ultrasonography measured peak systolic velocities (PSVs) and ratio of adjacent PSVs (Vr) every 5 cm within the stent graft and adjacent arteries. We retrospectively classified the following factors as "abnormal DU findings": focal PSV > 300 cm/s, uniform PSVs < 50 cm/s throughout the graft, and Vr > 3.0. These DU criteria were derived from laboratory-specific data that we previously published on failing stent grafts placed for lower extremity occlusive disease. Four of the 21 stent grafts presented with symptomatic graft thrombosis within 6 months of a normal DU. Three of these 4 patients presented with rest pain and underwent thrombectomy (2) or vein bypass (1), and 1 elected for nonintervention for claudication. Our results suggest that surveillance DU using criteria established for grafts placed for occlusive disease may not be useful for predicting stent graft failure in popliteal artery aneurysms.


Dynamics of halide ion-water hydrogen bonds in aqueous solutions: dependence on ion size and temperature.
We have carried out a series of molecular dynamics simulations to investigate the dynamics of X(-)-water (X = F, Cl, Br, and I) and water-water hydrogen bonds in aqueous alkali halide solutions at room temperature and also of Cl(-)-water and water-water hydrogen bonds at seven different temperatures ranging from 238 to 318 K. The hydrogen bonds are defined by using a set of configurational criteria with respect to the anion(oxygen)-oxygen and anion(oxygen)-hydrogen distances and the anion(oxygen)-oxygen-hydrogen angle for an anion(water)-water pair. The results of the hydrogen bond dynamics are obtained for two different cutoff values for the angular criterion. In both cases, similar dynamical behavior of the hydrogen bonds is found with respect to their dependence on ion size and temperature. The fluoride ion-water hydrogen bonds are found to break at a much slower rate than water-water hydrogen bonds, while the lifetimes of chloride and bromide ion-water hydrogen bonds are found to be shorter than those of fluoride ion-water ones but still longer than water-water hydrogen bonds. The short-time dynamics of iodide ion-water hydrogen bonds is found to be slightly faster, while its long-time dynamics is found to be slightly slower than the corresponding water-water hydrogen bond dynamics. Correlations of the observed dynamics of anion(water)-water hydrogen bonds with those of rotational and translational diffusion and residence times of water molecules in ion(water) hydration shells are also discussed. With variation of temperature, the lifetimes of both Cl(-)-water and water-water hydrogen bonds are found to show Arrhenius behavior with a slightly higher activation energy for the Cl(-)-water hydrogen bonds.


Copper-catalyzed radical approach to allenyl iodides.
A copper-catalyzed 1,4-addition reaction of sulfonyl iodides with 1,3-enynes affording various allenyl halides in high yields under mild conditions has been developed. Mechanistic studies showed that the reaction proceeds through a radical mechanism.


[Update on current care guidelines. The treatment of status epilepticus].
Status epilepticus is a medical emergency. Most epileptic seizures last for 1-4 minutes and seizures lasting over five minutes, should be treated as status epilepticus. EEG is essential for diagnostics and the monitoring of treatment effect. The treatment for status epilepticus, irrespective of aetiology, can be divided into first-aid medications, such as buccal midazolam or rectal diazepam, first-line medications such as intravenous diazepam or lorazepam, and second-line medications such as fosphenytoin and valproate for adults and phenobarbital for children. Third-line treatment is suppressive general anaesthesia, monitored by continuous EEG. Antiepileptic medication of patients with epilepsy should be carefully re-evaluated after episode of status epilepticus.


Occurrence and function of the orange carotenoid protein in photoprotective mechanisms in various cyanobacteria.
Excess light is harmful for photosynthetic organisms. The cyanobacterium Synechocystis PCC 6803 protects itself by dissipating the excess of energy absorbed by the phycobilisome, the water-soluble antenna of Photosystem II, into heat decreasing the excess energy arriving to the reaction centers. Energy dissipation results in a detectable decrease of fluorescence. The soluble Orange Carotenoid Protein (OCP) is essential for this blue-green light induced mechanism. OCP genes appear to be highly conserved among phycobilisome-containing cyanobacteria with few exceptions. Here, we show that only the strains containing a whole OCP gene can perform a blue-light induced photoprotective mechanism under both iron-replete and iron-starvation conditions. In contrast, strains containing only N-terminal and/or C-terminal OCP-like genes, or no OCP-like genes at all lack this light induced photoprotective mechanism and they were more sensitive to high-light illumination. These strains must adopt a different strategy to longer survive under stress conditions. Under iron starvation, the relative decrease of phycobiliproteins was larger in these strains than in the OCP-containing strains, avoiding the appearance of a population of dangerous, functionally disconnected phycobilisomes. The OCP-containing strains protect themselves from high light, notably under conditions inducing the appearance of disconnected phycobilisomes, using the energy dissipation OCP-phycobilisome mechanism.


Functional silencing of guanylyl cyclase/natriuretic peptide receptor-A by microRNA interference: analysis of receptor endocytosis.
Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) is the principal receptor for the regulatory action of atrial and brain natriuretic peptides (ANP and BNP) and an important effector molecule in controlling of extracellular fluid volume and blood pressure homeostasis. We have utilized RNA interference to silence the expression of GC-A/NPRA gene (Npr1), providing a novel system to study the internalization and trafficking of NPRA in intact cells. MicroRNA (miRNA)-mediated small interfering RNA (siRNA) elicited functional gene-knockdown of NPRA in stably transfected human embryonic kidney 293 (HEK-293) cells expressing a high density of recombinant NPRA. We artificially expressed three RNA polymerase II-driven miRNAs that specifically targeted the Npr1 gene, but shared no significant sequence homology with any other known mouse genes. Reverse transcription-PCR (RT-PCR) and Northern blot analyses identified two highly efficient Npr1 miRNA sequences to knockdown the expression of NPRA. The Npr1 miRNA in chains or clusters decreased NPRA expression more than 90% as compared with control cells. ANP-dependent stimulation of intracellular accumulation of cGMP and guanylyl cyclase activity of NPRA were significantly reduced in Npr1 miRNA-expressing cells by 90-95% as compared with control cells. Treatment with Npr1 miRNA caused a drastic reduction in the receptor density subsequently a deceased internalization of radiolabeled (125)I-ANP-NPRA ligand-receptor complexes. Only 12%-15% of receptor population was localized in the intracellular compartments of microRNA silenced cells as compared to 70%-80% in control cells.


Surface phenotype and functions of tumor-infiltrating dendritic cells: CD8 expression by a cell subpopulation.
Although the function and significance of tumor-infiltrating dendritic cells (TIDC) in the immune response to tumor have never been clearly demonstrated, their location suggests that they play a critical role in the presentation of tumor antigen to specific T cells. We studied the morphological and functional characteristics of interstitial dendritic cells (DC) located inside tumors obtained by injection of cancer cells into syngeneic rats. Single and double immunostaining of tumor sections revealed a dense network of cells which expressed class II major histocompatibility complex (MHC II) molecules. Cell morphology and surface markers were characteristic of DC populations in other tissues. These DC were in close contact with tumor cells and increased in number as the tumor grew larger. Unexpectedly, a subpopulation of morphologically characteristic TIDC expressed both CD8 and MHC II molecules. TIDC were purified from tumors by gradient centrifugation and immunobeads and characterized by morphology, ultrastructural study and surface markers studied by flow cytometry. TIDC were negative for the CD5 molecule (a pan T cell marker), and were not labeled with 3.2.3 monoclonal antibody (mAb) (an NK cell marker) or with Ki-M2R mAb (a macrophage marker). A subpopulation of TIDC expressed the CD8 molecule, confirming the in situ results. TIDC expressed high levels of class I and class II MHC molecules and the adhesion molecule ICAM-1. This expression is compatible with effective antigen presenting function. Purified TIDC triggered rapid and high levels of proliferation of tumor-immune T cells in vitro, demonstrating the potential of these cells to constitutively process and present tumor-associated antigens.


Inducing humoral and cellular responses to multiple sporozoite and liver-stage malaria antigens using exogenous plasmid DNA.
A vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection against Plasmodium falciparum malaria; however, a technology for formulating and delivering such a vaccine has remained elusive. Here, we report the preclinical assessment of an optimized DNA vaccine approach that targets four P. falciparum antigens: circumsporozoite protein (CSP), liver stage antigen 1 (LSA1), thrombospondin-related anonymous protein (TRAP), and cell-traversal protein for ookinetes and sporozoites (CelTOS). Synthetic DNA sequences were designed for each antigen with modifications to improve expression and were delivered using in vivo electroporation (EP). Immunogenicity was evaluated in mice and nonhuman primates (NHPs) and assessed by enzyme-linked immunosorbent assay (ELISA), gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay, and flow cytometry. In mice, DNA with EP delivery induced antigen-specific IFN-γ production, as measured by ELISpot assay and IgG seroconversion against all antigens. Sustained production of IFN-γ, interleukin-2, and tumor necrosis factor alpha was elicited in both the CD4(+) and CD8(+) T cell compartments. Furthermore, hepatic CD8(+) lymphocytes produced LSA1-specific IFN-γ. The immune responses conferred to mice by this approach translated to the NHP model, which showed cellular responses by ELISpot assay and intracellular cytokine staining. Notably, antigen-specific CD8(+) granzyme B(+) T cells were observed in NHPs. Collectively, the data demonstrate that delivery of gene sequences by DNA/EP encoding malaria parasite antigens is immunogenic in animal models and can harness both the humoral and cellular arms of the immune system.


[Effect of thoraco-laparoscopic esophagectomy on postoperative immune function of patients with esophageal carcinoma].
To investigate the effect of thoraco-laparoscopic esophagectomy on postoperative immune function of patients with esophageal carcinoma. Eighty-one patients undergoing radical esophagectomy in our hospital between January, 2017 and December, 2019 were enrolled in this study.According to the surgical approach, the patients were divided into endoscopic group (41 cases) and open surgery (3 incisions) group (40 cases).The immunological indicators (CD3+, CD4+, CD8+, and CD4+/CD8+ratio) of the patients were analyzed using double antibody sandwich enzyme-linked immunosorbent assay at 1 day before the surgery and on days 1, 4 and 7 after the surgery.The plasma levels of interleukin 6(IL-6) and cortisol, β-endorphin (β-EP) level, white blood cell count (WBC) and C-reactive protein (CRP) levels of the patients were measured before and on days 1 and 7 after the operation. No death occurred in either of the group after the operation.On days 4 and 7 after the operation, CD3+, CD4+, CD8+, and CD4+/CD8+ratio were significantly higher in patients undergoing thoracolaparoscopic surgery than in those receiving open surgery (P < 0.05).In both groups, the levels of cortisol, β-EP, WBC, CRP and IL-6 measured on days 1 and 7 postoperatively were significantly different from those before the operation (P < 0.05).At all the indicated postoperative time points, all the measured indicators, with the exception of IL-6 levels on postoperative day 7, which were comparable between the two groups, were significantly higher in the open surgery group than in the endoscopic group (P < 0.05). Thoraco-laparoscopic resection of esophageal cancer can reduce postoperative secretion of proinflammatory factors, alleviate inflammatory responses, and promote the recovery of immune functions to accelerate postoperative recovery of the patients.


Abuse experiences in a community sample of young adults: relations with psychiatric disorders, sexual risk behaviors, and sexually transmitted diseases.
This study documents significant associations among lifetime abuse experiences, psychiatric diagnoses, and sexual risk behaviors in a multiethnic community sample of young men and women (N = 1803) in South Florida. Self-report data were collected via structured interviews as part of a longitudinal follow-up of a larger school-based study. Participants were grouped according to extent of lifetime abuse experiences. Cumulative lifetime abuse experiences were associated with increased risk for a broad range of individual lifetime psychiatric disorders, as well as cumulative lifetime psychiatric disorders. Both cumulative abuse experiences and cumulative psychiatric disorders were independently associated with (a) higher levels of sexual risk behaviors and (b) higher risk for lifetime sexually transmitted diseases (STDs). Implications for selective prevention of sexual risk behaviors and STDs among young adults with histories of abuse and psychiatric disorders are discussed.


A new symmetry: A anti-B is anti-(B anti-A), and reverse enhancement.
Immune system network theory leads to a new symmetry, namely that the antibodies produced in an allogeneic A anti-B immune response (where A and B are, say, two different mouse strains), should have complementary shapes to the antibodies in a B anti-A response. That is, A anti-B is anti-(B anti-A). This symmetry is due to the existence of two readily separable populations of antibodies that are present in alloantisera: anti-foreign and anti-anti-self antibodies. The theoretical basis for the symmetry is described, and results indicating the presence of anti-anti-self antibodies in each of 12 alloantisera (six made in B10-congenic strains, and six made with the unrelated chains CBA, SJL, and C57BL/6) are reported. The finding that hyperimmune alloantisera routinely contain anti-anti-self antibodies suggests that network regulation plays an important role in maintaining self-tolerance during responses to allogeneic cells. We further show that A anti-B serum absorbed against B can specifically prolong the survival of A grafts in a B strain animal. We suggest that this result can be interpreted as being due to A anti-(B anti-A) antibodies preventing B anti-A cells from rejecting the A grafts. We call this phenomenon "reverse enhancement" because it involves the converse antiserum to that used in conventional enhancement of graft survival by specific antibodies.


Influence of Photoperiod and Leaf Age on Crassulacean Acid Metabolism in Portulacaria afra (L.) Jacq.
The possibility that Crassulacean acid metabolism (CAM) is subject to long day photoperiodic control in Portulacaria afra (L.) Jacq., a facultative CAM plant, was studied. Periodic measurements of (14)CO(2) uptake, stomatal resistance, and titratable acidity were made on plants exposed to long and short day photoperiods. Results indicates that waterstressed P. afra had primarily nocturnal CO(2) uptake, daytime stomatal closure, and a large diurnal acid fluctuation in either photoperiod. Mature leaf tissue from nonstressed plants under long days exhibited a moderate diurnal acid fluctuation and midday stomatal closure. Under short days, there was a reduced diurnal acid fluctuation in mature leaf tissue. Young leaf tissue taken from nonstressed plants did not utilize the CAM pathway under either photoperiod as indicated by daytime CO(2) uptake, lack of diurnal acid fluctuation, and incomplete daytime stomatal closure.The induction of CAM in P. afra appears to be related to the water status of the plant and the age of the leaf tissue. The photosynthetic metabolism of mature leaves may be partly under the control of water stress and of photoperiod, where CAM is favored under long days.


Improved Fractal Space Filling Curves Hybrid Optimization Algorithm for Vehicle Routing Problem.
Vehicle Routing Problem (VRP) is one of the key issues in optimization of modern logistics system. In this paper, a modified VRP model with hard time window is established and a Hybrid Optimization Algorithm (HOA) based on Fractal Space Filling Curves (SFC) method and Genetic Algorithm (GA) is introduced. By incorporating the proposed algorithm, SFC method can find an initial and feasible solution very fast; GA is used to improve the initial solution. Thereafter, experimental software was developed and a large number of experimental computations from Solomon's benchmark have been studied. The experimental results demonstrate the feasibility and effectiveness of the HOA.


[Treatment of patients with trophic ulcer].
The authors present the investigation of inpatient treatment of 137 patients with trophic ulcers of venous aethiology. All the patients were hospitalized in the "Road clinical hospital" on the Krasnoyarsk station. A comparative analysis of treatment results of the patients with trophic ulcers using different medical methods was made. The efficacy of combined use of low-frequency ultrasound and ozone therapy was proved.


Effect of remote ischemic preconditioning in the elderly patients with coronary artery disease with diabetes mellitus undergoing elective drug-eluting stent implantation.
There is conflicting evidence regarding the effectiveness of remote ischemic preconditioning (RIPC) in patients undergoing elective percutaneous coronary intervention (PCI). Therefore, we prospectively enrolled elderly patients with coronary heart disease (CHD) with diabetes mellitus (DM) undergoing elective drug-eluting stent (DES) implantation. They were randomized to receive RIPC within 2 hours before PCI (n = 102) or not (controls, n = 98). Baseline clinical characteristics were similar between the 2 groups. Despite a trend toward decline, the median high-sensitivity cardiac troponin I (hscTnI) level (P = .256) and the incidence of myocardial infarction (MI) type 4a (P = .106) in the RIPC group 16 hours after PCI procedure was not significantly different from the control group. The RIPC could attenuate the release of a myocardial biomarker but failed to show a significant effect on hscTnI level or MI type 4a incidence after PCI procedure in elderly patients with CHD having DM undergoing elective DES implantation.


Simultaneous measurement of six cytokines in a single sample of human tears using microparticle-based flow cytometry: allergics vs. non-allergics.
Tears play an essential role in maintaining corneal and conjunctival integrity by providing a tightly regulated, optimal extracellular environment critical to its numerous functions, which include anti-microbial defense, wound healing and inflammatory responses such as allergies. Elevated levels of inflammatory cytokines have been reported in tears from various ocular disease states. Characterization of tear cytokines has been limited by the small volume (microliter amounts) attainable. This limitation was addressed with the newly developed Becton Dickinson Cytometric Bead Array (CBA), which combines the principles of the "sandwich" immunoassay with the capability of flow cytometry for simultaneous measurement of the characteristics of multiple particles. This technique allows determination of six human cytokine (IFNgamma, TNFalpha, IL-2, IL-4, IL-5, IL-10) concentrations simultaneously in a single tear sample. Tears were collected from the inferior fornix of non-allergic (n=7) and allergic (n=9) donors. Each tear sample or cytokine standard was incubated with a mixture of capture Ab-bead reagent and detector Ab-phycoerythrin (PE) reagent, and analyzed using flow cytometry. All six cytokines were detectable in both non-allergic and allergic tears. Tears from allergic donors contained significantly less IL-10 (p=0.035), and had significant increases in the ratios of TNFalpha/IFNgamma, IL-5/IFNgamma and IL-5/IL-10 (p=0.0008, 0.0124 and 0.011, respectively). The small volume required (5-10 microl/test) by the Cytometric Bead Array allows measurement of all six cytokines from a single collection of tears. This decreases collection time, minimizing the confounding effect of stimulation on cytokine concentration in tears, as well as allowing calculation of cytokine ratios.


Homotropic cooperativity of monomeric cytochrome P450 3A4 in a nanoscale native bilayer environment.
Mechanistic studies of mammalian cytochrome P450s are often obscured by the phase heterogeneity of solubilized preparations of membrane enzymes. The various protein-protein aggregation states of microsomes, detergent solubilized cytochrome or a family of aqueous multimeric complexes can effect measured substrate binding events as well as subsequent steps in the reaction cycle. In addition, these P450 monooxygenases are normally found in a membrane environment and the bilayer composition and dynamics can also effect these catalytic steps. Here, we describe the structural and functional characterization of a homogeneous monomeric population of cytochrome P450 3A4 (CYP 3A4) in a soluble nanoscale membrane bilayer, or Nanodisc [Nano Lett. 2 (2002) 853]. Cytochrome P450 3A4:Nanodisc assemblies were formed and purified to yield a 1:1 ratio of CYP 3A4 to Nanodisc. Solution small angle X-ray scattering was used to structurally characterize this monomeric CYP 3A4 in the membrane bilayer. The purified CYP 3A4:Nanodiscs showed a heretofore undescribed high level of homotropic cooperativity in the binding of testosterone. Soluble CYP 3A4:Nanodisc retains its known function and shows prototypic hydroxylation of testosterone when driven by hydrogen peroxide. This represents the first functional characterization of a true monomeric preparation of cytochrome P450 monooxygenase in a phospholipid bilayer and elucidates new properties of the monomeric form.


Discovery of novel secreted virulence factors from Salmonella enterica serovar Typhimurium by proteomic analysis of culture supernatants.
Salmonella enterica serovar Typhimurium is a leading cause of acute gastroenteritis throughout the world. This pathogen has two type III secretion systems (TTSS) encoded in Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) that deliver virulence factors (effectors) to the host cell cytoplasm and are required for virulence. While many effectors have been identified and at least partially characterized, the full repertoire of effectors has not been catalogued. In this proteomic study, we identified effector proteins secreted into defined minimal medium designed to induce expression of the SPI-2 TTSS and its effectors. We compared the secretomes of the parent strain to those of strains missing essential (ssaK::cat) or regulatory (ΔssaL) components of the SPI-2 TTSS. We identified 20 known SPI-2 effectors. Excluding the translocon components SseBCD, all SPI-2 effectors were biased for identification in the ΔssaL mutant, substantiating the regulatory role of SsaL in TTS. To identify novel effector proteins, we coupled our secretome data with a machine learning algorithm (SIEVE, SVM-based identification and evaluation of virulence effectors) and selected 12 candidate proteins for further characterization. Using CyaA' reporter fusions, we identified six novel type III effectors and two additional proteins that were secreted into J774 macrophages independently of a TTSS. To assess their roles in virulence, we constructed nonpolar deletions and performed a competitive index analysis from intraperitoneally infected 129/SvJ mice. Six mutants were significantly attenuated for spleen colonization. Our results also suggest that non-type III secretion mechanisms are required for full Salmonella virulence.


[Clinical significances of combined detections of autoantibodies in patients with systemic lupus erythematosus].
To evaluate the clinical significances of combined detections of the autoantibodies ANA, ANAs and anti-dsDNA in patients with systemic lupus erythematosus (SLE). ANA was tested by indirect immunofluorescent method (IIF), ENA was tested by Western blot and anti-dsDNA was measured with radioimmunoassay in the serum samples from patients with SLE (n=90), and from the comparison group (n=74) and healthy control group (n=53). The sensitivity of anti-dsDNA, AnuA,anti-Sm in patients with SLE was 41.1%, 32.2% and 22.2%. The specificity of anti-dsDNA, AnuA, anti-Sm in SLE patients was all 97.3%. The positive likelihood ratios were 15.22, 11.93 and 8.22, respectively. The sensitivity and specificity reached 62.2% and 90.5%, respectively by combined determinations of anti-dsDNA, AnuA and anti-Sm. The combined examinations of anti-dsDNA, AnuA, anti-Sms can improve the sensitivity and efficiency of laboratory diagnosis of SLE.


Mechanical Behavior of Hybrid Glass/Steel Fiber Reinforced Epoxy Composites.
While conventional fiber-reinforced polymer composites offer high strength and stiffness, they lack ductility and the ability to absorb energy before failure. This work investigates hybrid fiber composites for structural applications comprised of polymer, steel fiber, and glass fibers to address this shortcoming. Varying volume fractions of thin, ductile steel fibers were introduced into glass fiber reinforced epoxy composites. Non-hybrid and hybrid composite specimens were prepared and subjected to monolithic and half-cyclic tensile testing to obtain stress-strain relationships, hysteresis behavior, and insight into failure mechanisms. Open-hole testing was used to assess the vulnerability of the composites to stress concentration. Incorporating steel fibers into glass/epoxy composites offered a significant improvement in energy absorption prior to failure and material re-centering capabilities. It was found that a lower percentage of steel fibers (8.2%) in the hybrid composite outperformed those with higher percentages (15.7% and 22.8%) in terms of energy absorption and re-centering, as the glass reinforcement distributed the plasticity over a larger area. A bilinear hysteresis model was developed to predict cyclic behavior of the hybrid composite.


[Amyotrophic lateral sclerosis and exposure to metals and other occupational/environmental hazardous materials: state of the art].
In recent years, scientific literature has been giving more and more importance to the study of the occupational/environmental exposure to risk agents related to the onset of Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex. Aim of this work is to verify the state of art about the eventual role of occupational/environmental exposure to risk agents. Selected articles, on the basis of keywords, year of publication and topics, are related to occupational and environmental exposure to xenobiotics, and, in particular, to the exposure to heavy metals that could lead to neuronal damage mechanisms involved in ALS onset. The review shows that although the scientific production has increased the interest in the evaluation of extra-genetic causes of ALS onset, there are still few studies concerning the careful study of the work activities of the individual patient, and the inferences that can be drawn to date about the possible connection between occupational exposure to risk factors and the onset of ALS are still lacking.


Selective Solvent-Assisted Linker Exchange (SALE) in a Series of Zeolitic Imidazolate Frameworks.
Solvent-assisted linker exchange (SALE) has recently emerged as an attractive strategy for the synthesis of metal-organic frameworks (MOFs) that are unobtainable via traditional synthetic pathways. Herein we present the first example of selective SALE in which only the benzimiadazolate-containing linkers in a series of mixed-linker zeolitic imidazolate frameworks (ZIF-69, -78, and -76) are replaced. The resultant materials (SALEM-10, SALEM-10b, and SALEM-11, respectively) are isostructural to the parent framework and in each case contain trifluoromethyl moieties. We therefore evaluated each of these materials for their hydrophobicity in condensed and gas phases. We expect that selective SALE will significantly facilitate the design of improved, and potentially complex, MOF materials with new and unusual properties.


32-Methyl-32-oxylanosterols: dual-action inhibitors of cholesterol biosynthesis.
Lanosterol 14 alpha-methyl demethylase (P-450DM) is the cytochrome P-450 monooxygenase which oxidatively removes the 14 alpha-methyl group of lanosterol. This demethylation is considered to be a rate-limiting step in the conversion of lanosterol to cholesterol. The intermediates in this transformation are known to bind very tightly to P-450DM and have been implicated in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity, the rate-limiting enzyme in overall cholesterol biosynthesis. Three 32-methylated analogs of the intermediates generated during the removal of the 14 alpha-methyl group by P-450DM, compounds 17a, 17b, and 18, have been prepared and their biochemical activities assessed. All three compounds were found to be direct inhibitors of P-450DM. These compounds were also shown to suppress HMGR activity by reducing the level of enzyme protein.


Purification and characterization of beta-N-acetylhexosaminidase from rice seeds.
N-Acetyl-beta-D-hexosaminidase (beta-HexNAc'ase) (EC 126.96.36.199) was purified from rice seeds (Oryza sativa L. var. Dongjin) using ammonium sulfate (80%) precipitation, Sephadex G-150, CM-Sephadex, and DEAE-Sephadex chromatography, sequentially. The activities were separated into 7 fractions (Fsub1;- F7sub7) by CM-Sephadex chromatography. Among them, F6 was further purified to homogeneity with a 13.0% yield and 123.3 purification-fold. The molecular mass was estimated to be about 52 kDa on SDS-PAGE and 37.4 kDa on Sephacryl S- 300 gel filtration. The enzyme catalyzed the hydrolysis of both p-nitrophenyl-N-acetyl-beta-D-glucosaminide (pNP-GlcNAc) and p-nitrophenyl-N-acetyl-beta-D-galactosaminide (pNPGalNAc) as substrates, which are typical properties of beta-HexNAc'ase. The ratio of the pNP-GlcNAc'ase activity to the pNP-GalNAc'ase activity was 4.0. However, it could not hydrolyze chitin, chitosan, pNP-beta-glucopyranoside, or pNP-beta-galactopyranoside. The enzyme showed K(M), V(max) and K(cat) for pNP-GlcNAc of 1.65mM, 79.49mM min(1), and 4.79 x 10(6) min(1), respectively. The comparison of kinetic values for pNPGlcNAc and pNP-GalNAc revealed that the two enzyme activities are associated with a single binding site. The purified enzyme exhibited optimum pH and temperature for pNPGlcNAc of 5.0 and 50 degrees C, respectively. The enzyme activity for pNP-GlcNAc was stable at pH 5.0-5.5 and 20-40 degrees C. The enzyme activity was completely inhibited at a concentration of 0.1 mM HgCl(2) and AgNO(3), suggesting that the intact thiol group is essential for activity. Chloramine T completely inhibited the activity, indicating the possible involvement of methionines in the mechanism of the enzyme.


Propagating the effects of missing data sources in a surveillance system.
Sporadically missing data sources in syndromic surveillance systems result in inaccurate counts and detection algorithm results. We examined how data quality issues relating to missing data sources propagate through a surveillance system and devised a method to track and visualize the resulting data quality issues.


Biological significance of tissue plasminogen activator content in brain tumors.
Fresh brain-tumor samples were obtained at operation and analyzed for their content of tissue type plasminogen activator (tPA) using an activity assay (gel chromatography zymogram) and an enzyme-linked immunospecific assay. The specimens were taken from 23 glioblastomas, 35 metastatic tumors, 42 meningiomas, 16 low-grade gliomas, and seven acoustic neurinomas; seven specimens were from normal brain. A strong correlation was found between the results of the two assays (r = 0.77, p less than 0.0001). There was a threefold difference in the tPA content of the benign tumors as compared to malignant tumors (p = 0.0006), the latter having less tPA. Histologically benign meningiomas contained higher tPA than malignant meningiomas (p = 0.01); however, the difference between low-grade gliomas and high-grade gliomas was less evident. Overall regression analysis data have shown an inverse relationship between the tissue content in tPA and the presence and degree of tumor necrosis and peritumoral brain edema (p = 0.004 and p = 0.0004, respectively). This finding was most consistent in the glioblastoma group where the correlation coefficient values were r = 0.53 and r = -0.55, respectively. There was no significant correlation between the tissue tPA content and the age and sex, steroid use, or plasma tPA of the patients or the duration of symptoms. In summary, this is the first demonstration of tPA in a large series of human brain tumors and in normal brain. The differences observed have clear biological significance and, although the source of tPA in tumor tissue is still unknown, a relative reduction in tPA in tumor tissue may play an integral role in the development of tissue necrosis and tissue edema. The lack of tPA in tumor necrosis was not due to tissue destruction and cell death since urokinase was readily detectable in that tissue.