[Effects of Electroacupuncture on Expression of Myocardial Chloride Channel-2 and CLCA Proteins in Mice with Acute Myocardial Ischemia].
To observe the influence of electroacupuncture stimulation (EA) of "Neiguan" (PC 6)/"Lieque" (LU 7) on ST segment of electrocardiogram (ECG) and the expression of myocardiac chloride channel (CLC)-2 and calcium (Ca2+)-activated chloride channel accessory (CLCA) proteins in acute myocardial ischemia (AMI) mice, so as to explore its mechanisms underlying improvement of AMI. Thirty ASIC 3-/- knock out mice were randomly divided into control, AMI model, EA-Neiguan (PC 6), EA-Lieque (LU 7) and EA-non-acupoint groups. The AMI model was induced by multiple subcuta-neous injection of isoprenaline (ISO, 0.5 g/L, 20 mg/kg). EA was applied to bilateral PC 6, LU 7, or non-acupoint[the mid-point between "Tianshu" (ST 25) and "Shenque" (CV 8)] for 20 min, once daily for 7 days. The ST segment of ECG of the standard Ⅱlimb-lead was recorded using a PowerLab data acquisition device, the change of myocardial histology observed by using microscope after HE staining, the activity of serum superoxide dismutase (SOD) detected using Colorimetric method, and the expression of CLC-2 and CLCA proteins of the left ventricle myocardium detected by Western blot. Outcomes of HE staining showed that the ischemic injury (sarcoplasm swelling and necrosis, etc.) of the left ventrical myocardial tissue after mo-deling was relatively milder in the EA-PC 6 group, not in the EA-non-acupoint group. The SOD activity was significantly lower in the model group than in the control group (P<0.01), and obviously increased in the EA-PC 6 group(P<0.01), but not in the EA-non-acupoint group (P>0.05). The expression levels of myocardial CLC-2 and CLCA proteins were significantly up-regulated in the model group compared with the control group (P<0.01) and markedly down-regulated in the EA-PC 6 group (not in the EA-non-acupoint group) in comparison with the model group(P<0.01), suggesting a specificity of effects of EA-PC 6 in improving myocardial injury and down-regulating CLC-2 and CLCA protein expression. EA of "Neiguan" (PC 6) can effectively suppress the increase of expression of CLC-2 and CLCA proteins in the left ventricle myocardium, which may contribute to its effect in relieving myocardial injury in mice.


Protein S-100B: a serum marker for ischemic and infectious injury of cerebral tissue.
The S-100B protein is released by injured astrocytes. After passage through a disintegrated blood-brain barrier (BBB) the molecule can be detected in the peripheral circulation. We investigated the association between the extent of brain injury and S-100B concentration in serum in cerebral injury caused by cerebral ischemia and cerebral fungal infection. Study I: The S-100B serum concentration was serially determined in 24 patients with ischemic stroke at 4, 8, 10, 24, 72 hours after the onset of symptoms. We observed that patients with brain lesions larger than 5 cm3 exhibited significantly increased serum levels of S-100B at 10, 24 and 72 hours compared to those with lesion volumes below 5 cm3. Furthermore, an association between S-100B serum concentration and neurological outcome was observed. Study II: In a mouse model of systemic fungal infection with Candida albicans we observed that serum levels of S-100B increased at day 1 after intravenous infection. At this time we could histologically demonstrate brain tissue injury by invading hyphae which had crossed the BBB. Furthermore, reactive astrogliosis was demonstrated by immunohistochemistry. On day 7 we found a significant decrease of S-100B serum level compared to day 1 and 4. This was associated with a demarcation of the fungi with leukocytes in brain tissue at this late phase of infection. No further invasion through the BBB was seen on day 7. In conclusion, serum levels of S-100B reflect the time course of tissue injury in cerebral ischemia and cerebral infection to a similar extent. Thus, S-100B may be a useful marker to assess cerebral tissue injury.


Cancer spread and micrometastasis development: quantitative approaches for in vivo models.
Death from cancer is usually due to metastasis. Fortunately, most cells that escape from a primary tumor fail to form metastases. Identifying reasons for this failure will help development of anti-metastatic therapies. Intravital videomicroscopy (IVVM) can be used to observe cancer cells injected into live animals. Co-injected microspheres can be used to assess cell survival. These techniques have been used to show that circulating tumor cells generally arrest in the microcirculation and may extravasate with high efficiency. While many tumor cells may survive in a secondary site, only a small subset form micrometastases and only a subset of these micrometastases persist to form vascularized macrometastases. Furthermore, solitary tumor cells may remain dormant for long periods of time in secondary sites. These findings suggest that metastatic growth and angiogenesis are prime targets for anti-metastatic therapy.


Abscission: the initial effect of ethylene is in the leaf blade.
The leaf blade of cotton (Gossypium hirsutum L. cv. Stoneville 213) was investigated as the initial site of ethylene action in abscission. Ethylene applied at 14 mul/l to intact 3-week-old plants caused abscission of the third true leaf within 3 days. However, keeping only the leaf blade of this leaf in air during ethylene treatment of the rest of the plant completely prevented its abscission for up to 7 days. This inhibition of abscission was apparently the result of continued auxin production in the blade since (a) the application of an auxin transport inhibitor to the petiole of the air-treated leaf blade restored ethylene sensitivity to the leaf in terms of abscission; (b) repeated applications of naphthaleneacetic acid to the leaf blade of the third true leaf, when the entire plant was exposed to ethylene, had the same preventive effect on abscission of this leaf as keeping its leaf blade in air; and (c) the inhibitory effect of ethylene on auxin transport in the petiole, which is reduced by auxin treatment, was also reduced by placing the leaf blade in air.The reverse treatment of exposing only the leaf blade of the third true leaf to 14 mul/l of ethylene, while the rest of the plant was kept in air, also did not cause abscission for up to 5 days. Auxin transport in the petioles of these leaves, however, was inhibited over 80% within 2 days and this effect presumably accounted for their increased sensitivity to ethylene during the subsequent exposures of the whole leaf to the gas.These results suggest that an initial and essential function of applied ethylene in abscission is to reduce the amount of auxin transported out of the leaf blade. This reduction together with the inhibitory effect of ethylene on auxin transport in the petiole reduces the auxin level at the abscission zone to a point where the cells in this region become responsive to the more direct action of the gas (e.g., enzyme induction and secretion). This sequence of events accounts for the lack of abscission unless ethylene is applied to both the leaf blade and the abscission zone.


Inhibition of granulocyte-macrophage colony-stimulating factor prevents dissemination and induces remission of juvenile myelomonocytic leukemia in engrafted immunodeficient mice.
Granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor alpha (TNFalpha) have been implicated in the pathogenesis of the fatal childhood disease termed juvenile myelomonocytic leukemia (JMML). We used a severe combined immunodeficient/nonobese diabetic (SCID/NOD) mouse model of JMML and examined the effect of inhibiting these cytokines in vivo with the human GM-CSF antagonist and apoptotic agent E21R and the anti-TNFalpha monoclonal antibody (MoAb) cA2 on JMML cell growth and dissemination in vivo. We show here that JMML cells repopulated to high levels in the absence of exogeneous growth factors. Administration of E21R at the time of transplantation or 4 weeks after profoundly reduced JMML cell load in the mouse bone marrow. In contrast, MoAb cA2 had no effect on its own, but synergized with E21R in virtually eliminating JMML cells from the mouse bone marrow. In the spleen and peripheral blood, E21R eliminated JMML cells, while MoAb cA2 had no effect. Importantly, studies of mice engrafted simultaneously with cells from both normal donors and from JMML patients showed that E21R preferentially eliminated leukemic cells. This is the first time a specific GM-CSF inhibitor has been used in vivo, and the results suggest that GM-CSF plays a major role in the pathogenesis of JMML. E21R might offer a novel and specific approach for the treatment of this aggressive leukemia in man.


Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma.
Acinic cell carcinoma (AcCC) is a morphologically distinctive salivary gland malignancy often associated with chromosome rearrangements leading to overexpression of the NR4A3 transcription factor. However, little is known about how NR4A3 contributes to AcCC biology. Detailed RNA-sequencing of 21 archived AcCC samples revealed fusion reads arising from recurrent t(4;9), t(9;12), t(8;9) or t(2;4) chromosomal translocations, which positioned highly active enhancers adjacent to the promoter of the NR4A3 gene or the closely related NR4A2 gene, resulting in their aberrant overexpression. Transcriptome analyses revealed several distinct subgroups of AcCC tumors, including a subgroup that overexpressed both NR4A3 and MSANTD3. A poor survival subset of the tumors with high-grade transformation expressed NR4A3 and POMC as well as MYB, an oncogene that is the major driver in a different type of salivary gland tumor, adenoid cystic carcinoma. The combination of NR4A3 and MYB showed cooperativity in regulating a distinct set of genes. In addition, the ligand binding domain of NR4A3 directly bound the Myb DNA binding domain. Transformation assays indicated that, while overexpressed NR4A3 was sufficient to generate transformed colonies, the combination of NR4A3 plus Myb was more potent, leading to anchorage-independent growth and increased cellular invasiveness. The results confirm that NR4A3 and NR4A2 are the main driver genes of AcCC and suggest that concurrent overexpression of NR4A3 and MYB defines a subset of AcCC patients with high-grade transformation that display exceptionally poor outcome.


Versatile and High-throughput Force Measurement Platform for Dorsal Cell Mechanics.
We present a high-throughput microfluidics technique facilitating in situ measurements of cell mechanics parameters at the dorsal side of the cell, including molecular binding strengths, local traction forces, and viscoelastic properties. By adjusting the flow rate, the force magnitude exerted on the cell can be modulated ranging from ~14 pN to 2 nN to perturb various force-dependent processees in cells. Time-lapse images were acquired to record events due to such perturbation. The values of various mechanical parameters are subsequently obtained by single particle tracking. Up to 50 events can be measured simultaneously in a single experiment. Integrating the microfluidic techniques with the analytic framework established in computational fluid dynamics, our method is physiologically relevant, reliable, economic and efficient.


A comparison of valdecoxib and naproxen in the treatment of rheumatoid arthritis symptoms.
The primary aim of this work was to compare the efficacy of valdecoxib 10, 20, and 40 mg QD with that of placebo and naproxen 500 mg BID in patients with rheumatoid arthritis (RA). The overall safety and tolerability profiles of valdecoxib and naproxen were also compared. A 12-week, multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled study was performed in patients with adult-onset RA whose disease was in a flare state after discontinuing NSAIDs or other analgesics. Patients were randomly assigned to valdecoxib 10, 20, or 40 mg QD, naproxen 500 mg BID, or placebo. The primary efficacy measures were the American College of Rheumatology (ACR) 20% responder index (ACR-20), physicians' assessments of tender/painful joint count and swollen joint count, and patients' and physicians' global assessments of disease activity. Adverse events, clinical laboratory data, and vital signs were assessed by the investigator and compared between treatment groups to evaluate overall tolerability and safety. A total of 1093 patients were randomized to receive either valdecoxib 10 mg QD (n=226), valdecoxib 20 mg QD (n=219), valdecoxib 40 mg QD (n=209), naproxen 500 mg BID (n=219), or placebo (n=220). At all time points, the proportion of ACR-20 responders was significantly higher in the valdecoxib groups than the placebo group at weeks 2 (10 mg, P<0.001; 20 mg, P=0.008; 40 mg, P= 0.004), 6 (all, P<0.001), and 12 (10 mg, P=0.006; 20 mg, P=0.004; 40 mg, P<0.001). Similarly, at all time points, the proportion of ACR-20 responders was significantly higher in the naproxen 500-mg group than the placebo group (all time points, P<0.001). In addition, mean changes in the number of tender/painful joint counts were significantly greater in the valdecoxib groups than the placebo group at weeks 2 (all, P<0.001), 6 (10 mg, P=0.002; 20 and 40 mg, P<0.001), and 12 (10 mg, P=0.004; 20 mg, P= 0.012; 40 mg, P<0.001). Naproxen treatment was also associated with greater reductions in tender/painful joint count than placebo (all, P<0.001). Mean changes in swollen joint count decreased at all time points in all groups, with significantly greater changes in the valdecoxib and naproxen treatment groups than the placebo group (valdecoxib 20 and 40 mg: week 6, P= 0.014 and P=0.003, respectively; naproxen: week 2, P=0.014; week 6, P=0.015; week 12, P=0.030). Physicians' global assessments of disease activity scores were significantly lower in the valdecoxib (10 mg: weeks 2 and 6, P<0.001; week 12, P=0.001; 20 and 40 mg: all weeks, P<0.001) and naproxen (all time points, P<0.001) treatment groups than the placebo group. Adverse events were reported by 45.5% patients in the placebo group, 51.8% in the valdecoxib 10 mg QD group, 58.0% in the valdecoxib 20 mg QD group, 56.9% in the valdecoxib 40 mg QD group, and 62.6% in the naproxen 500 mg BID treatment group. Valdecoxib 10, 20, and 40 mg QD were efficacious for treating the signs and symptoms of RA in these patients. The efficacy of valdecoxib 20 and 40 mg QD was not significantly different from that of naproxen 500 mg BID. Valdecoxib was generally well tolerated in this study.


Calcium and vitamin D metabolism in children with nephrotic syndrome.
Although abnormalities of calcium and vitamin D metabolism are recognized in children with nephrotic syndrome, longitudinal observations are not available in these patients during periods of relapse and remission. We report observations in 58 children (mean age 10.1 years) with nephrotic syndrome and normal glomerular filtration rate. Hypocalcemia, modest hyperparathyroidism, and strikingly low calcidiol levels were identified during episodes of relapse. Most alterations were transient, and normalized on remission. The plasma concentration of calcitriol, the most active metabolite of vitamin D, was found to be normal in both relapse and remission. In the presence of hypocalcemia and hyperparathyroidism, however, normal plasma calcitriol levels in relapse may be inappropriately low and reflect a state of relative deficiency. Concurrent glucocorticoid therapy did not modify the results. A corollary of our observations is that children with relapsing or protracted nephrotic syndrome are at risk of developing metabolic bone disease, even without impairment of glomerular filtration rate.


Inequality shaping processes and gated communities in US western metropolitan areas.
This paper investigates the social dimensions of gated communities (GCs) in US western metropolitan areas and how they contribute to segregation. We use geographically referenced data of GCs, and introduce a local metric based on social distance indices (SDI). This multivariate spatial analysis investigates homogeneity in three aspects: race and ethnicity, economic class and age between 2000 and 2010 census. The results indicate contrasting effects given different levels of geography. GCs significantly contribute to segregation patterns at a local level, and this has been locally reinforcing. Although socioeconomic segregation and ethnic status yield the most prevalent structure of local distance, gated enclaves are also significantly structured by age. The findings are considered in the context of a metropolitan decline in levels of segregation. Data also show that GCs are likely to be located within large racially homogeneous areas, and do not significantly contribute to racial segregation.


The Individual Rehabilitation Project as the core of person-centered rehabilitation: the Physical and Rehabilitation Medicine Section and Board of the European Union of Medical Specialists Framework for Rehabilitation in Europe.
To facilitate the interaction between the health professional and the patient, a framework to guide the rehabilitation process is needed. This framework would encompass three interwoven aspects: the rehabilitation management plan, Individual Rehabilitation Project (IRP), and rehabilitation cycle(s). All three framework aspects focus on the patient and on the aim of rehabilitation, i.e. to optimize a person's functioning across the continuum of care. An IRP is a multi-element, person-centered rehabilitation management scheme, in which rehabilitation is generally provided by a multiprofessional team under the leadership of a physical and rehabilitation medicine (PRM) physician, working in an interdisciplinary manner and together with the patient (or proxy). A reference system for operationalizing functioning and standardizing the process is the International Classification of Functioning, Disability and Health (ICF) - for assessing functioning needs, defining rehabilitation goals and outcomes. The objective of this paper is to present the IRP as a framework for rehabilitation in Europe (EUR-IRP). The specific aims are: 1) to introduce the IRP; and 2) to describe the framework components, elements and variables of the IRP. Demonstration projects (case studies) using the EUR-IRP will be conducted. The present paper presents the efforts to date for developing the EUR-IRP, a key part of the action plan of the PRM Section and Board of the European Union of Medical Specialists to implement the ICF systemwide across the care continuum. This paper serves as another step to bring together practice, science and governance in calling for contribution from rehabilitation clinicians and researchers and professional societies in PRM and beyond.


Modeling the scattering phase matrix of red clays.
This Letter focuses on modeling the optical properties of red clay. Specifically, the measured phase matrix element P22 of red clay shows a scattering-angle dependence that is quite different from those of other dust types, and has not been modeled successfully. The spheroidal particles cannot yield accurate agreement on all independent phase matrix elements of red clay simultaneously (failed for P22). The P22 element can be modeled well with the spheroidal model only by sacrificing the agreement on the other elements. However, the Koch-fractal model clearly outperforms the spheroidal model in reproducing all six phase matrix elements concurrently with a reasonable refractive index.


Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current.
Ventricular repolarization and contractile function are frequently abnormal in ventricular myocytes from human failing hearts as well as canine hearts with experimentally induced heart failure (HF). These abnormalities have been attributed to dysfunction involving various steps of the excitation-contraction coupling process, leading to impaired intracellular sodium and calcium homeostasis. We previously reported that the slow inactivating component of the Na(+) current (late I(Na)) is augmented in myocytes from failing hearts, and this appears to play a significant role in abnormal ventricular myocytes repolarization and function. We tested the effect of ranolazine, a novel drug being developed to treat angina, on (1) action potential duration (APD), (2) peak transient and late I(Na) (I(NaT) and I(NaL), respectively), (3) early afterdepolarizations (EADs), and (4) twitch contraction (TC), including after contractions and contracture. Myocytes were isolated from the left ventricle of normal dogs and of dogs with chronic HF caused by multiple sequential intracoronary micro-embolizations. I(NaT) and I(NaL) were recorded using conventional whole-cell patch-clamp techniques. APs were recorded using the beta-escin perforated patch-clamp configuration at frequencies of 0.25 and 0.5 Hz. TCs were recorded using an edge movement detector at stimulation frequencies ranging from 0.5 to 2.0 Hz. Ranolazine significantly (P<0.05) and reversibly shortened the APD of myocytes stimulated at either 0.5 or 0.25 Hz in a concentration-dependent manner. At a stimulation frequency of 0.5 Hz, 5, 10, and 20 microM ranolazine shortened the APD(90) (APD measured at 90% repolarization) from 516+/-51 to 304+/-22, 212+/-34 and 160+/-11 ms, respectively, and markedly decreased beat-to-beat variability of APD(90), EADs, and dispersion of APDs. Ranolazine preferentially blocked I(NaL) relative to I(NaT) in a state-dependent manner, with a approximately 38-fold greater potency against I(NaL) to produce tonic block (IC(50)=6.5 microM) than I(NaT) (IC(50)=294 microM). When we evaluated inactivated state blockade of I(NaL) from the steady-state inactivation mid-potential shift using a theoretical model, ranolazine was found to bind more tightly to the inactivated state than the resting state of the sodium channel underlying I(NaL), with apparent dissociation constants K(dr)=7.47 microM and K(di)=1.71 microM, respectively. TCs of myocytes stimulated at 0.5 Hz were characterized by an initial spike followed by a dome-like after contraction, which was observed in 75% of myocytes from failing hearts and coincided with the long AP plateau and EADs. Ranolazine at 5 and 10 microM reversibly shortened the duration of TCs and abolished the after contraction. When the rate of myocyte stimulation was increased from 1.0 to 2.0 Hz, there was a progressive increase in diastolic "tension," that is, contracture. Ranolazine at 5 and 10 microM reversibly prevented this frequency-dependent contracture.


Mechanism of PLC-mediated Kir3 current inhibition.
A large number of ion channels maintain their activity through direct interactions with phosphatidylinositol bisphosphate (PIP2). For such channels, hydrolysis of PIP2 causes current inhibition. It has become controversial whether the inhibitory effects on channel activity represent direct effects of PIP2 hydrolysis or of downstream PKC action. We studied Phospholipase C (PLC)-dependent inhibition of G protein-activated inwardly rectifying K+ (Kir3) channels. By monitoring simultaneously channel activity and PIP2 hydrolysis, we determined that both direct PIP2 depletion and PKC actions contribute to Kir3 current inhibition. We show that the PKC-induced effects strongly depend on PIP2 levels in the membrane. At the same time, we show that PKC destabilizes Kir3/PIP2 interactions and enhances the effects of PIP2 depletion on channel activity. These results demonstrate that PIP2 depletion and PKC-mediated effects reinforce each other and suggest that both of these interdependent mechanisms contribute to Kir3 current inhibition. This mechanistic insight may explain how even minor changes in PIP2 levels can have profound effects on Kir3 activity. We also show that stabilization of Kir3/PIP2 interactions by Gbetagamma attenuates both PKC and Gq-mediated current inhibition, suggesting that diverse pathways regulate Kir3 activity through modulation of channel interactions with PIP2.


The coronoid process as a cause of mandibular hypomobility--case reports.
In an attempt to draw the clinician's attention to the coronoid process site while evaluating the aetiology of the restriction of mandibular opening, four cases are illustrated. These cases represent a diversity of causes hampering the free rotational movement of the coronoid process in space during jaw function. Case 1 is an example of unilateral hyperplastic coronoid process and osteochondroma; case 2 shows unusually shaped short and divergent coronoid processes combined with a bucally displaced maxillary third molar on one side; cases 3 and 4 represent an anatomical variation of an extremely narrow vestibular space due to the close proximity of the medial aspect of the coronoid process to the distal molar. It is suggested that each clinical examination include the width of the buccal vestibular space while performing mandibular movements.


Spectrophotometric Analysis of the Cyanide Metabolite 2-Aminothiazoline-4-Carboxylic Acid (ATCA).
Methods of directly evaluating cyanide levels are limited by the volatility of cyanide and by the difficulty of establishing steady-state cyanide levels with time. We investigated the measurement of a stable, toxic metabolite, 2-aminothiazoline-4-carboxylic acid (ATCA), in an attempt to circumvent the challenge of directly determining cyanide concentrations in aqueous media. This study was focused on the spectrophotometric ATCA determination in the presence of cyanide, thiocyanate (SCN(-)), cysteine, rhodanese, thiosulfate, and other sulfur donors. The method involves a thiazolidine ring opening in the presence of p-(hydroxy-mercuri)-benzoate, followed by the reaction with diphenylthiocarbazone (dithizone). The product is spectrophotometrically analyzed at 625 nm in carbon tetrachloride. The calibration curve was linear with a regression line of Y = 0.0022x (R(2) = 0.9971). Interference of cyanide antidotes with the method was determined. Cyanide, thiosulfate, butanethiosulfonate (BTS), and rhodanese did not appreciably interfere with the analysis, but SCN(-) and cysteine significantly shifted the standard curve. This sensitive spectrophotometric method has shown promise as a substitute for the measurement of the less stable cyanide.


Comparative study of the blinking time between young adult and adult video display terminal users in indoor environment.
Investigate the average blinking time in conversation and in Video Display Terminal use of young adults and adults in the presbyopic age group. A transversal analytical study in a readily accessible sample consisting of Volkswagen do Brasil - Curitiba, Paraná employees was performed. The cohort group consisted of 108 subjects divided into two age groups: Group 1, the young adult group (age range 20-39): 77 employees, mean age of 30.09 +/- 5.09; Group 2, the presbyopic adult group, (age range 40-53): 31 employees, mean age of 44.17 +/- 3. Subjects under 18 years of age, with a history of ocular disorders, contact lens wearers and computer non-users were excluded. The subjects had their faces filmed for 10 minutes in conversation and VDT reading. Student's t-test was used and the statistical significance level was 95%. The average time between blinks in Group 1 for conversation and VDT reading was 5.16 +/- 1.83 and 10.42 +/- 7.78 seconds, respectively; in Group 2. 4,9 +/- 1.49 and 10.46 +/- 5.54 seconds. In both age groups, the time between blinks in VDT reading situations was higher (p<0.0001). There was no statistically meaningful difference for conversation and VDT reading situations when the two studied age groups were compared (p>0.05). There was an increase in the blinking time between young adults and the presbyopic group in VDT use situations when compared with reading situations. The difference in the blinking frequency between young adults and the presbyopic group in VDT use and reading situations was not statistically significant.


NT-proBNP in patients with out-of-hospital cardiac arrest: Results from the FINNRESUSCI Study.
To assess whether the established cardiovascular biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) provides prognostic information in patients with out-of-hospital cardiac arrest due to ventricular tachycardia or fibrillation (OHCA-VT/VF). We measured NT-proBNP levels in 155 patients with OHCA-VT/VF enrolled into a prospective multicenter observational study in 21 ICUs in Finland. Blood samples were drawn <6h of OHCA-VT/VF and later after 24h, 48h, and 96h. The end-points were mortality and neurological outcome classified according to Cerebral Performance Category (CPC) after one year. NT-proBNP levels were compared to high-sensitivity troponin T (hs-TnT) levels and established risk scores. NT-proBNP levels were higher in non-survivors compared to survivors on study inclusion (median 1003 [quartile (Q) 1-3 502-2457] vs. 527 [179-1284]ng/L, p=0.001) and after 24h (1913 [1012-4573] vs. 1080 [519-2210]ng/L, p<0.001). NT-proBNP levels increased from baseline to 96h after ICU admission (p<0.001). NT-proBNP levels were significantly correlated to hs-TnT levels after 24h (rho=0.27, p=0.001), but not to hs-TnT levels on study inclusion (rho=0.05, p=0.67). NT-proBNP levels at all time points were associated with clinical outcome, but only NT-proBNP levels after 24h predicted mortality and poor neurological outcome, defined as CPC 3-5, in models that adjusted for SAPS II and SOFA scores. hs-TnT levels did not add prognostic information to NT-proBNP measurements alone. NT-proBNP levels at 24h improved risk assessment for poor outcome after one year on top of established risk indices, while hs-TnT measurements did not further add to risk prediction.


Amplification of papillomaviral DNA sequences from a high proportion of feline cutaneous in situ and invasive squamous cell carcinomas using a nested polymerase chain reaction.
Squamous cell carcinomas (SCCs) are common skin tumours of cats. Previous studies have suggested that papillomaviral (PV) DNA is detectible within some feline SCCs. A PV DNA sequence has been previously amplified from five feline bowenoid in situ carcinomas (BISCs). Primers specific for this sequence were used in a nested polymerase chain reaction to compare PV detection rates in SCCs to rates within non-SCC skin lesions. Papillomaviral DNA was amplified from 20 of 20 BISC, 17 of 20 invasive SCC and 3 of 17 non-SCC controls. The rate of PV amplification from feline cutaneous SCCs was significantly higher than from non-SCC lesions. These results confirm that feline cutaneous SCCs are associated with PV infection. In humans, there is evidence that PVs promote SCC development within sun-exposed skin. The demonstrated association between PVs and feline cutaneous SCCs suggests, but does not prove, that PVs may also promote feline SCC development. If PVs are oncogenic in cats, prevention of PV infection may reduce feline cutaneous SCC development. To the authors' knowledge, this is the first time that PV DNA has been amplified from a non-SCC sample of feline skin.


Evaluating the correspondence of different cognitive batteries.
It is widely accepted that abilities are a meaningful level of abstraction for distinguishing among individuals with respect to their levels of cognitive functioning. However, relatively little is known about the extent to which different combinations of tests reflect the same cognitive abilities, or about the relation of cognitive abilities in one test battery with specific tests in another battery. Data from two cognitive batteries were analyzed to determine the correspondence of ability factors in the two batteries, and to evaluate the relative influence of cognitive abilities from one battery on the subtest scores in the other battery. Although the batteries involved different combinations of tests, correlations between the theoretically similar ability factors in the two batteries were very high (i.e., r > .84). Furthermore, with only a few exceptions, the primary influences on the subtest scores in one battery were from the theoretically relevant ability factor in the other battery.


Determination of intralumenal individual bile acids by HPLC with charged aerosol detection.
An isocratic HPLC charged aerosol detector (CAD) method was developed, validated, and applied for the determination of individual bile acids in human gastric and duodenal aspirates. The method requires a low volume of aspirates (50-100 microl) and minimal sample pretreatment. A Hypersil BDS RP-C(18) column (250 x 4.6 mm, 5 microm particle size) was equilibrated with a mobile phase composed of methanol-[ammoniun formate 20 mM, formic acid 0.5%, triethylamine 0.2% (pH 3)] 67:33 v/v. Its flow rate was 1 ml/min. The elution times for taurocholate, glycocholate, taurochenodeoxycholate, ursodeoxycholate, glycochenodeoxycholate, cholate, and glycodeoxycholate were approximately 9.9, 16.2, 18.2, 21.3, 31.6, 34.5, and 38.5 min, respectively. Calibration curves in the mobile phase were constructed in the concentration range of 0.5-500 microM. Limits of detection and quantification were in the range of 0.07-0.60 microM and 0.20-1.80 microM, respectively. This method was applied first, in gastric aspirates collected in the fasted state, in which bile acid presence is minimal and, second, in duodenal aspirates collected in the fed state, in which a large number of potentially interfering compounds exists. Intra-day relative standard deviation in fasted gastric aspirates and in fed duodenal aspirates was less than 2.2% and 6.0%, respectively.


Effects of Mindfulness-Based Stress Reduction (MBSR) on Stress, Heart Rate Variability, Affect, and Wellbeing among People with Schizophrenia.
Mindfulness-based stress reduction programs have been found to be effective in reducing the stress response and improving the psychological wellbeing of various populations. We aimed to confirm the effects of a mindfulness-based stress reduction program on perceived stress, heart rate variability, positive and negative affect, and subjective wellbeing of community-dwelling people with schizophrenia. The participants in this study were 26 people with schizophrenia (experimental group: 14, control group: 12) enrolled in two community mental health centers located in Gyeonggi Province in South Korea. In the experimental group, the mindfulness-based stress reduction program was applied once a week for 60 min over 8 weeks. The experimental group showed a significantly greater decrease in perceived stress and negative affect, as well as significantly greater improvement in heart rate variability than the control group. The mindfulness-based stress reduction program was an effective nursing intervention to reduce stress and negative affect in people with schizophrenia.


Effect of Extended Conjugation of N-Heterocyclic Carbene-Based Sensitizers on the Performance of Dye-Sensitized Solar Cells.
We report the synthesis, characterization, and photovoltaic properties of four ruthenium complexes (CI101, CBTR, CB111, and CB108) having various N-heterocyclic carbene ancillary ligands, pyridine-imidazole, -benzimidazole, -dithienobenzimidazole, and -phenanthroimidazole, respectively. These complexes were designed to investigate the effect of extended conjugation ordained from ring fusion on the power conversion efficiencies of the solar cells. The device sensitized by CB108, the pyridine-phenanthroimidazole conjugated complex, showed an improved efficiency (9.89%) compared to those of pyridine-benzimidazole conjugated system (CBTR, 9.72%) and the parent unfused ring system (CI101, 6.24%). Surprisingly, the sulfur-incorporated pyridine-dithienobenzimidazole system (CB111, 9.24%) exhibited a little lower efficiency than that of N719 (9.41%). The enhanced photovoltaic performance of CB108 was mainly attributed to the increase in electron lifetime and diffusion length confirmed by the electrochemical impedance spectroscopy.


Involvement of the ventrolateral medulla in the mediation of pressor responses of the rat to afferent vagal stimulation.
Electrical stimulation of afferent vagal fibres evoked a pressor response in rats after transection of the spinal cord. The pressor response was accounted for by an increased release of vasopressin because it was abolished by the intravenous injection of a vasopressin antagonist. Bilateral electrolytic lesions at the sites of the caudal ventrolateral medulla markedly reduced the pressor response to afferent vagal stimulation but not that to carotid occlusion. It is concluded that the area of the caudal ventrolateral medulla is involved in mediation of the vasopressin-induced pressor response to afferent vagal stimulation.


Waterlogging tolerance and recovery capability screening in peanut: a comparative analysis of waterlogging effects on physiological traits and yield.
Fifteen peanut varieties at the pod filling stage were exposed to waterlogging stress for 7 days, the enzyme activities and fluorescence parameters were measured after 7 days of waterlogging and drainage. The waterlogging tolerance and recovery capability of varieties were identified. After waterlogging, waterlogging tolerance coefficient (WTC) of relative electrolyte linkage (REL), malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and catalase (CAT) activity, non-photochemical quenching (NPQ) and photochemical quenching (qL) of leaves of most peanut varieties were increased, while the WTC of the soil and plant analysis development (SPAD) value, PS II actual quantum yield (Φ PS II ), maximum photochemical efficiency (Fv/Fm) were decreased. After drainage, the WTC of REL, MDA content, SOD and CAT activity of leaves were decreased compared with that of after waterlogging, but these indicators of a few cultivars were increased. Φ PS II , Fv/Fm and qL can be used as important indexes to identify waterlogging recovery capability. There was a significant negative correlation between recovery capability and the proportion of reduction in yield, while no significant correlation was found between waterlogging tolerance and the proportion of reduction in yield. Therefore, it is recommended to select varieties with high recovery capability and less pod number reduction under waterlogging in peanut breeding and cultivation.


The application of minerals in managing alcohol hangover: a preliminary review.
Despite the high prevalence and economic burden, biological mechanisms and effective treatments of alcohol hangover are not well understood. We have focused on oxidative stress and inflammatory responses which would substantially contribute to hangover physiology and symptoms based on preexisting research data. And, it is considered that minerals are one of the important components and influencing factors in antioxidant and anti-inflammatory system. Moreover, mineral deficient conditions show similar symptoms that occur in alcohol hangover. Herein we review some possible implications of various minerals, such as selenium, zinc, copper, vanadium, iron, and magnesium, according to suggested mechanisms and symptoms of alcohol hangover. Although, noticeable considerations and controlled trials will be required for general recommendations, we hope that our preliminary speculation would pave the way for further understanding and managing alcohol hangover.


Evaluation of the strain identity between isolates from caries lesions and root canals in early childhood caries cases.
Early childhood caries (ECC) has become a serious medical problem worldwide in the last decade. Bacterial microflora of the dental plaque and oral cavity is considered an important factor in the formation and progression of dental caries. The aim of this study was strain typing and comparison of bacterial isolates retrieved from caries lesions and root canal contents of the same teeth. In total, 18 pairs of presumptive streptococci and lactobacilli retrieved from dental caries and root canals isolated from ECC-affected children, were selected on the basis of biotyping results and rep-PCR fingerprinting with (GTG)5 primer. Strain typing was further done using the RiboPrinter microbial characterization system (DuPont Qualicon). The automated ribotyping determined 14 pairs of the strains (77.8 %) to be identical. The results obtained confirmed that identical bacterial strains colonized both the decayed dental surface and the necrotic content of the dental pulp cavity during the cariogenesis. Our finding supports the assumption that bacteria could penetrate through the damaged dental surface to the inner parts of the teeth.


Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not?
Because inflammation is appreciated as a unifying basis of many widely occurring diseases, the mechanisms involved in its natural resolution are of considerable interest. Using contained, self-limited inflammatory exudates and a systems approach, novel lipid-derived mediators and pathways were uncovered in the resolution of inflammatory exudates. These new families of local mediators control both the duration and magnitude of acute inflammation as well as the return of the site to homeostasis in the process of catabasis. This new genus of specialized proresolving mediators (SPM) includes essential fatty acid-derived lipoxins, resolvins, protectins, and, most recently, maresins. These families were named based on their unique structures and potent stereoselective actions. The temporally initiated biosynthesis of SPM and their direct impact on leukocyte trafficking and macrophage-directed clearance mechanisms provide clear evidence that resolution is an active, programmed response at the tissue level. Moreover, SPM that possess anti-inflammatory (ie, limiting PMN infiltration) and proresolving (enhance macrophage uptake and clearance of apoptotic PMN and microbial particles) actions as well as stimulating mucosal antimicrobial responses demonstrate that anti-inflammation and proresolution are different responses of the host and novel defining properties of these molecules. The mapping of new resolution circuits has opened the possibility for understanding mechanisms that lead from acute to chronic inflammation, or to the resolution thereof, as well as to potential, resolution-based immunopharmacological therapies.


Randomized placebo-controlled trial of a selective serotonin reuptake inhibitor in the treatment of nondepressed tinnitus subjects.
To assess the efficacy of a selective serotonin reuptake inhibitor (paroxetine) for relief of tinnitus. One hundred twenty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial. Paroxetine or placebo was increased to a maximally tolerated dose (up to 50 mg/day), and patients were treated for a total of 31 days at the maximal dose. Patients with chronic tinnitus were recruited from our university-based specialty clinic by referral from otolaryngologists and audiologists in the local community and by advertisement. Patients with psychotic or substance use disorders or suicidal ideation were excluded, as were those using psychoactive medications (this resulted in only 1 subject with major depression in the study) or any other medications that interact with paroxetine and those with inability to hear at one's tinnitus sensation level. Fifty-eight percent of patients were male, 92% were Caucasian, and the average age was 57. Tinnitus matching, the Tinnitus Handicap Questionnaire, the question: How severe (bothered, aggravating) is your tinnitus? Quality of Well-Being and other psychological questionnaires. Paroxetine was not statistically superior to placebo on the following tinnitus measures (tinnitus matching, 5- or 10-db drop, Tinnitus Handicap Questionnaire, quality of well-being measures, how severe, how bothered, positive change). There was a significant improvement in the single item question, How aggravating is your tinnitus? for those in the paroxetine group compared with the placebo group. These results suggest that the majority of individuals in this study did not benefit from paroxetine in a consistent fashion. Further work remains to be done to determine if subgroups of patients (e.g., those who tolerate higher doses, those who are depressed) may benefit.


Diagnosis and management of catecholamine secreting glomus tumors.
The clinical and diagnostic features of catecholamine secreting glomus tumors are reviewed. Three cases are reported, including the first documented case of a dopamine secreting glomus jugulare tumor. Based on this experience, the authors have outlined the indications for selective venous catheterterization studies and for pharmacologic blockage in the management of these patients. In addition to routine urinary screening, a high index of clinical suspicion is needed to avoid the complications associated with catecholamine secreting tumors.


Congenital anophthalmia and microphthalmia: epidemiology and orbitofacial rehabilitation.
To describe the prevalence of congenital anophthalmia and microphthalmia in Hospital Universitario La Paz, and to identify associated risk factors and evaluate cosmetic results in treated and nontreated patients. A retrospective, descriptive, cross-sectional study of patients treated with orbital expanding techniques (cases) and nontreated patients (controls) was carried out as a comparative case series study. A total of 36 patients with unilateral or bilateral anophthalmia or microphthalmia as main diagnosis were included; 52 epidemiological and management variables for each patient were analyzed. The study evaluated orbital growth and facial symmetry. The overall cosmetic result in the study's group of patients was satisfactory: 66.7% showed good or very good orbital growth, and 75% showed good or very good facial symmetry. Controls had better cosmetic outcome but showed more cataracts (P = 0.05), inferior colobomas (P = 0.026), and family history (P = 0.056) than the cases. Controls also showed significantly better orbital growth (P = 0.042) and facial symmetry (P = 0.014) than the cases. This study suggests that the mere presence of a globe (controls) still provides better orbitofacial development than the artificial stimulation (cases) currently available for patients with congenital anophthalmia and microphthalmia, who receive internal and external orbital rehabilitation.


Craniovertebral Junction Anomalies in Small Breed Dogs with Atlantoaxial Instability: A Multicentre Case-Control Study.
The main purpose of this study was to define criteria to systemically describe craniovertebral junction (CVJ) anomalies and to report the prevalence of CVJ anomalies in small breed dogs with and without atlantoaxial instability (AAI). Retrospective multicentre matched case-control study evaluating magnetic resonance imaging and computed tomographic images of small breed dogs with and without AAI for the presence of CVJ anomalies. One hundred and twenty-two dogs were enrolled (61 with and 61 without AAI). Only dogs with AAI had dens axis anomalies such as separation (n = 20) or a short-rounded conformation (n = 35). Patients with AAI were more likely to have atlantooccipital overlapping based on transection of McRae's line by the dorsal arch of the atlas (odds ratio [OR] = 5.62, p < 0.01), a transection of Wackenheim's clivus line (OR = 41.62, p < 0.01) and rostral indentation of the occipital bone (OR = 2.79, p < 0.05). Patients with AAI were less likely to have a larger clivus canal angle (OR = 0.94, p < 0.01) and larger occipital bone lengths (OR = 0.89, p < 0.05). Small breed dogs with AAI are more likely to have other CVJ anomalies such as atlantooccipital overlapping or dens anomalies. The grade of brachycephaly does not differ between patients with and without AAI. Certain objective criteria from human literature were found useful for the assessment of both AAI and atlantooccipital overlapping such as McRae's line, Wackenheim's clivus line, and clivus canal angle. The classification criteria used can help to evaluate CVJ anomalies in a more systematic way.


Glycation increases the vascular clearance rate of IgG in mice.
As elevated levels of glycated IgG have been detected in the plasma of diabetics we have investigated whether glycation of IgG affects its vascular clearance rate, using a mouse model system. Polyclonal mouse IgG was aseptically incubated for 14-19 days with 0.5 M glucose in 0.1 M phosphate buffer (pH 7.4) at 37 degrees C. As control, IgG was incubated under identical conditions but with no added glucose. After incubation, both forms were labelled with 125I and injected intravenously into BALB/c mice. The rate of vascular clearance of the glycated IgG was found to be significantly higher than the control IgG in the periods 5-24 h (P < 0.001, n = 6) and 24-48 h (P < 0.01, n = 6) after injection. After 2-3 days the mice were killed and the major organs were harvested. With glycated IgG there was a significant increase in the 125I accumulated in the kidney (P < 0.02). In later experiments, dual labelling with 131I and 125I allowed mixtures of glycated and unglycated IgG to be injected into the same mouse so that the vascular clearance of both forms of IgG could be followed simultaneously. These experiments confirmed that glycation of the IgG significantly increases its vascular clearance rate.


The Nutritional Status of Long-Term Institutionalized Older Adults Is Associated with Functional Status, Physical Performance and Activity, and Frailty.
Among older adults living in long-term nursing homes (LTNHs), maintaining an adequate functional status and independence is a challenge. Whilst a poor nutritional status is a potential risk factor for a decreased function in this population, its role is not fully understood. Here, using a transversal multicenter study of 105 older adults living in 13 LTNHs, we analyzed the associations between nutritional status, as measured by the Mini Nutritional Assessment (MNA), and the parameters of functional status, physical performance, physical activity, and frailty as well as comorbidity and body composition. The MNA scores were positively correlated with the Barthel Index, handgrip strength, Short Physical Performance Battery (SPPB) scores, absolute muscle power, and Assessment of Physical Activity in Frail Older People (APAFOP) scores and were negatively correlated with dynamic balance and frailty. In a multiple linear regression model controlling for gender and age, the APAFOP score (β = 0.386), BMI (β = 0.301), and Barthel Index (β = 0.220) explained 31% of the variance in the MNA score. Given the observed close relationship between the MNA score and functional status, physical performance and activity, and frailty, interventions should jointly target improvements in both the nutritional status and functional status of LTNH residents. Strategies designed and implemented by interdisciplinary professional teams may be the most successful in improving these parameters to lead to better health and quality of life.


Defective intrinsic fibrinolytic activity in a patient with severe factor XII-deficiency and myocardial infarction.
The paper reports the occurrence of myocardial infarctions in a patient with severe deficiency of blood coagulation factor XII (Hageman factor). Factor XII plays a central role in the intrinsic activation of fibrinolysis and consequently the defective intrinsic fibrinolytic activity detected in the present case casts some doubt on its role in the increased vulnerability to thrombotic accident.


[Observation of bone morphology in furcation defects of mandibular molars using cone beam computed tomography].
To observe mesial-distal bone morphology in classes II and III furcation involvements (FI) of mandibular molars using cone beam computed tomography (CBCT), to develop a classification system of mesial-distal bone morphology of furcation defects and to observe the intrabony defects on CBCT images. Based on the existing CBCT data, the mandibular molars with horizontal bone defects in furcation area were observed. One hundred and seventeen sites of 81 mandibular molars with class II or class III FIclassified on CBCT images were included. The classification system of mesial-distal bone morphology of furcation defects was developed. According to the location of the line drawn from mesial to distal alveolar bone crest (AC-line) of the tooth and bone level under furcation fornix, the bone morphology was classified into three types, including concave type, flat type and protruding type. The concave type was divided into two subtypes according to the location of AC-line and furcation fornix (Fx), which were subtype 1(AC-line coronal or equal to Fx)and subtype 2 (AC-line apical to Fx).The frequency of each type was calculated and analyzed. The intrabony defects was observed on sagittal CBCT images. In the 117 sites with FI, the flat type appeared with the highest rate (64.10%) and the protruding type appeared with the lowest rate (6.84%). The rates of subtype 1 and subtype 2 of concave type were 13.68% and 15.38%, respectively. The rate of subtype1 which was supposed to be beneficial for bone regeneration was 8.96% in class II FI and 20.00% in class III FI. Thirtyone intrabony defects were found among the 117 FI, 29 of which appeared in proximal aspect of the tooth and the left 2 appeared in furcation area. The highest frequency of the intrabony defects was found in subtype 1 of concave type. The classification of mesial-distal bone morphology on CBCT images may be helpful for clinicians to make accurate treatment plan before surgery and could be used in future studies to understand the influence of bone morphology on regenerative therapy for furcation defects.


[Ethnoterritorial heterogeneity of alcohol dependence formation in the native population of Siberia].
Clinical-dynamic parameters of heterogeneity of alcohol dependence in 155 tuvinian and russian patients with lucid and psychotic forms of the disease have been studied. A highly progressive form of alcoholism with late onset of systematic consumption of alcohol has been identified in tuvinians as compared with russians. The formation of withdrawal syndrome occurs at later age than in russians (37.7 and 29.6 years; p=0.00004), but its development is more rapid - in average 2-2.5 years of systematic alcohol consumption. Psychotic forms of alcoholism are more frequent in tuvinians with the earlier onset of systematic consumption of alcohol and manifestation of basic disease syndromes (by 7 and 5 years, respectively) than in those with lucid alcoholism. In conclusion, treatment and rehabilitation of patients of different ethnic groups should be based on clinical and social features of the disease.


Correlation between preoperative pressure pain assessments and anxiety and postoperative pain in impacted lower third molar surgery.
: The aim of this study was to evaluate correlations between anxiety and preoperative pressure pain assessments and postoperative pain and analgesic requirements in impacted lower third molar tooth surgery. This prospective study enrolled 60 patients who underwent impacted lower third molar surgery. The preoperative State-Trait Anxiety Inventory-I (STAI-I), pressure pain threshold, and pressure pain tolerance scores were measured. At 2, 4, 6, 12, and 24 hours, and at 6 days following surgery, the patients scored their pain on the visual analogue scale and recorded their analgesic drug usage. The data were evaluated, and the results were statistically analyzed. Of the 60 patients, 38 were female. Mean age was 24.62±7.42 years. The study found no relationship between preoperative pressure pain assessments and postoperative pain (P>0.05). There was also no relationship observed between preoperative STAI-I scores and postoperative pain (P>0.05). However, there was a positive correlation between operation time and total medication taken (P<0.05). Preoperative pressure pain threshold, pressure pain tolerance, and anxiety level had no significant effects on postoperative pain and analgesic requirements in impacted lower third molar surgery.


The synthesis and crystal structures of halogenated tolans p-X-C6H4-C[triple bond]C-C6F5 and p-X-C6F4-C[triple bond]C-C6H5(X=F, Cl, Br, I).
A series of halogenated, partially fluorinated tolans of general formula p-X-C6H4-C[triple bond]C-C6F5[X=I (1), Br (2), Cl (3), F (4)] and p-X-C6F4-C[triple bond]C-C6H5[X=I (5), Br (6)] have been prepared via palladium-catalysed Sonogashira cross-coupling, or for X=Cl (7), by nucleophilic aromatic substitution reactions. The single-crystal X-ray structures of 1-3 and 5-6 have been determined. The structures reveal that the molecular packing is characterized by either arene-perfluoroarene interactions (3), or halogen-halogen interactions (isomorphous 1 and 2), or neither (isomorphous 5 and 6). The structure of represents the first fully determined crystal structure of a compound that contains a halogen atom other than fluorine, in which arene-perfluoroarene interactions are present.


A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension.
Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment with a calcium channel blocker or to treatment with a combination of these drugs. The aim of the study was to evaluate the rate of decline in GFR in patients with chronic renal failure and hypertension treated with isradipine and spirapril as monotherapy and in combination. Sixty patients with chronic renal failure and hypertension were enrolled in the study. After enrollment, patients were followed prospectively for 6 months in the outpatient clinic on their usual antihypertensive medication, and then randomized to a double-blinded comparison of either spirapril 6 mg daily, isradipine 5 mg daily or spirapril 3 mg and isradipine 2.5 mg daily. After randomization, patients were followed for 21 months or until the need for dialysis. Every 3 months before and 3.5 months after randomization the glomerular filtration rate was measured by 51Cr-EDTA clearance and the effective renal plasma flow evaluated using the renal clearance of paraaminohippuric acid. Blood pressure and the decline in glomerular filtration rate did not differ between the groups before randomization. After randomization, the mean decline in the glomerular filtration rate was -0.32 ml/(min x month x 1.73 m2) in the spirapril group, -0.58 ml/(min x month x 1.73 m2) in the isradipine group and -0.14 ml/(min x month x 1.73 m2) in the combination group (p = 0.38). Twelve patients, 4 in each group, reached end-stage renal failure. No significant difference was found with respect to diastolic (p = 0.10) or systolic blood pressure (p = 0.08) during the treatment period, but a trend towards a better blood pressure control in the combination group was present. During treatment, the rate of decline in renal plasma flow did not differ significantly between the groups (p = 0.09), neither did the changes in filtration fraction (FF) (p = 0.58) nor the mean FF (p = 0.22) during the treatment. Our study indicated differences between the 3 treatment modalities in favor of combined therapy with respect to both the rate of decline in GFR and blood pressure control, but the differences where insignificant. Thus, the treatments might differ, but we were unable to confirm this because of large variation in GFR and small sample size.


Site-directed deletion mutants of a carboxyl-terminal region of human dihydrofolate reductase.
Substrate and inhibitor binding to dihydrofolate reductase (DHFR) primarily involves residues in the amino-terminal half of the enzyme; however, antibody binding studies performed in this laboratory suggested that the loop region located in the carboxyl terminus of human DHFR (hDHFR; residues 140-186) is involved in conformational changes that occur upon ligand binding and affect enzyme function (Ratnam, M., Tan, X., Prendergast, N.J., Smith, P.L. & Freisheim, J.H. (1988) Biochemistry 27, 4800-4804). To investigate this observation further, site-directed mutagenesis was used to construct deletion mutants of hDHFR missing 1 (del-1), 2 (del-2), 4 (del-4), and 6 (del-6) residues from loops in the carboxyl terminus of the enzyme. The del-1 mutant enzyme has a two-amino acid substitution in addition to the one-amino acid deletion. Deletion of only one amino acid resulted in a 35% decrease in the specific activity of the enzyme. The del-6 mutant enzyme was inactive. Surprisingly, the del-4 mutant enzyme retained a specific activity almost 33% that of the wild type. The specific activity of the del-2 mutant enzyme was slightly higher (38% wild-type activity) than that of the del-4 mutant. All three active deletion mutants were much less stable than the wild-type enzyme, and all three showed at least a 10-fold increase in Km values for both substrates. The del-1 and del-2 mutants exhibited a similar increase in KD values for both substrate and cofactor. The three active deletion mutants lost activity at concentrations of activating agents such as KCl, urea, and p-hydroxymercuribenzoate that continued to stimulate the wild-type enzyme. Antibody binding studies revealed conformational differences between the wild-type and mutant enzymes both in the absence and presence of bound folate. Thus, although the loops near the carboxyl terminus are far removed from the active site, small deletions of this region significantly affect DHFR function, indicating that the loop structure in mammalian DHFR plays an important functional role in its conformation and catalysis.


Ionic Interactions at the Crude Oil-Brine-Rock Interfaces Using Different Surface Complexation Models and DLVO Theory: Application to Carbonate Wettability.
The impact of ionic association with the carbonate surface and its influence toward carbonate wettability remains unclear and is an important topic of interest in the current literature. In this work, a triple layer model (TLM) approach was used to capture the electrokinetic interactions at both calcite-brine and oil-brine interfaces. The developed TLM was assembled against measured ζ-potential values from the literature, successfully capturing the trends and closely matching the ζ-potential magnitudes. The developed TLM was compared to a diffused layer model (DLM) presented in previous works, with the DLM showing a better match to the ζ-potential values for seawater brine solutions. The ζ-potential values predicted from both surface complexation models (SCMs) were used to calculate the total interaction energy (or potential) based on the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory. It was observed that low Mg2+ and high SO4 2- concentrations in modified composition brine (MCB) made the calcite-brine interface more negative. However, at the oil-brine interface, low Mg2+ made the oil-brine interface more negative but high SO4 2- concentrations slightly shifted the oil-brine ζ-potential toward negative. At the crude oil-brine-rock (COBR) interfaces, low Mg2+ and high SO4 2- concentrations in the MCB were observed to generate a greater repulsive interaction energy, which could trigger carbonate wettability alteration toward water wetness. The absolute sum of the ζ-potential at both interfaces was observed to be correlated to the total interaction potential at a 0.25 nm separating distance. Thus, an increase in the absolute sum of the ζ-potentials would generate a greater repulsive interaction potential and trigger wettability alteration. Therefore, these SCMs can be applied to design modified composition brine capable of triggering a repulsive interaction energy to alter carbonate wettability toward water wetness.


The Acceptability of Traditional Culture under the Background of Deep Learning.
The cultural values of a country impact its national psychology and identity. Citizens' values and public opinions are conveyed to state leaders over the media and other information channels, both directly and indirectly influencing decisions on foreign policy. The traditional cultural values that affect the psyche of the Chinese people are harmony, generosity, morality, courtesy, wisdom, honesty, loyalty, and filial piety. This study aims to analyze the attitudes of Chinese college students toward traditional culture. The reliability and effect factors of the traditional culture acceptability questionnaire are set in the context of deep learning. A questionnaire on traditional culture education of college students is compiled using the indicator evaluation methods, and the current situation of traditional culture education is investigated for college students. A total of 300 valid respondents are returned from five universities including Shanghai Jiaotong University, Fudan University, Yunnan University, Kunming University of Science and Technology, and Yunnan Normal University. Results show that 28% of college students believe that practical activities including visiting and learning and traditional festival commemoration are the most effective ways to educate traditional culture for them, which accounts for the largest percentage. Similarly, 19% of students suggest online publicity, while 16% believe that lecture reports are particularly important, and 12% of students advocate the teaching courses. In addition, about 23% of the students choose other methods, such as seminars, setting up Chinese culture festivals, and building cultural associations. The outcomes of this study provide data support for identifying the shortcomings in traditional cultural education and formulating strategies.


Engineering specific chemical modification sites into a collagen-like protein from Streptococcus pyogenes.
Recombinant bacterial collagens provide a new opportunity for safe biomedical materials. They are readily expressed in Escherichia coli in good yield and can be readily purified by simple approaches. However, recombinant proteins are limited in that direct secondary modification during expression is generally not easily achieved. Thus, inclusion of unusual amino acids, cyclic peptides, sugars, lipids, and other complex functions generally needs to be achieved chemically after synthesis and extraction. In the present study, we have illustrated that bacterial collagens that have had their sequences modified to include cysteine residue(s), which are not normally present in bacterial collagen-like sequences, enable a range of specific chemical modification reactions to be produced. Various model reactions were shown to be effective for modifying the collagens. The ability to include alkyne (or azide) functions allows the extensive range of substitutions that are available via "click" chemistry to be accessed. When bifunctional reagents were used, some crosslinking occurred to give higher molecular weight polymeric proteins, but gels were not formed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 806-813, 2017.


ADF10 shapes the overall organization of apical actin filaments by promoting their turnover and ordering in pollen tubes.
Here, we show that Arabidopsis ADF10 plays an important role in shaping the overall organization of apical actin filaments by promoting their turnover and ordering. ADF10 severs and depolymerizes actin filaments in vitro and is distributed throughout the entire pollen tube. In adf10 mutants, severing and monomer dissociation events for apical actin filaments are reduced, and the apical actin structure extends further toward the tube base than in wild-type tubes. In particular, the percentage of apical actin filaments that form large angles to the tube growth axis is much higher in adf10 pollen tubes, and the actin filaments are more randomly distributed, implying that ADF10 promotes their ordering. Consistent with the role of apical actin filaments in physically restricting the movement of vesicles, the region in which apical vesicles accumulate is enlarged at the tip of adf10 pollen tubes. Both tipward and backward movements of small vesicles are altered within the growth domain of adf10 pollen tubes. Thus, our study suggests that ADF10 shapes the organization of apical actin filaments to regulate vesicle trafficking and pollen tube growth.


HER2 testing in gastric cancer: a practical approach.
Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is approved by the European Medicines Agency for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry 3+ or immunohistochemistry 2+/fluorescence in situ hybridization-positive or immunohistochemistry 2+/silver in situ hybridization-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Approvals are underway in other countries, with recent approvals granted in the United States and Japan. Experience and data from trastuzumab use in breast cancer have highlighted the importance of quality HER2 testing and scoring to ensure accurate identification of patients eligible for treatment. HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity (focal staining) and incomplete membrane staining. Consequently, gastric cancer-specific HER2 testing protocols have been developed and standardized and it is imperative that these recommendations be adhered to. Given the predictive value of HER2 protein levels with response in the trastuzumab for GAstric cancer study (ToGA), immunohistochemistry should be the initial testing methodology and fluorescence in situ hybridization or silver in situ hybridization should be used to retest immunohistochemistry 2+ samples. Wherever possible, bright-field methodologies should be used as these are considered to be superior to fluorescent methodologies at identifying heterogeneous staining. Specific training is required before embarking on HER2 testing in gastric cancer, irrespective of the experience of HER2 testing in breast cancer. This paper provides the most up-to-date practical guidance on HER2 testing and scoring in patients with gastric and gastro-esophageal junction cancer, as agreed by a panel of expert pathologists with extensive experience of HER2 testing particularly reflecting the European Medicines Agency-approved indication. It is anticipated that these recommendations should ensure accurate and consistent HER2 testing, which will allow appropriate selection of patients eligible for treatment with trastuzumab.


Influence of manganese deficiency and toxicity on isoprenoid syntheses.
Twenty-eight day old wheat (Triticum aestivum L. cv Stacy) response to varying Mn concentration (10.1-10,000 micromolar) in nutrient solution was measured. Manganese concentrations in the most recently matured leaves (blade 1) were 0.21 to 19.03 mmol Mn per kilogram dry weight, respectively. Fresh and dry weights increased to a maximum at the 5 micromolar Mn nutritional level (0.37 millimole Mn per kilogram dry weight) and were decreased at Mn above and below this concentration. Blade 1 chloroplast pigment concentrations increased up to the 20 micromolar Mn nutritional level (1.98 millimole Mn per kilogram dry weight) and decreased at higher Mn concentrations. Thylakoid Mn content was above 1 mole Mn/100 mole chloroplast at Mn nutrition levels which resulted in greatly decreased plant growth. Total phytoene biosynthesis was decreased by Mn deficiency and toxicity. In vitro ent- kaurene synthesis was greatly influenced by Mn concentration with a maximal biosynthesis at 1 micromolar Mn and decreases at Mn levels above and below this concentration. In vivo blade 1 gibberellic acid equivalent concentrations were maximal at 20 parts per million Mn nutrition solution levels (1.98 millimole Mn per kilogram dry weight) and decreased at Mn tissue concentrations above and below this value; additionally, gibberellic acid concentrations were reciprocal to extracted C(20) alcohol concentrations. Mn influence on gibberellin and chloroplast pigment biosyntheses exactly matched the measured changes in growth.


MicroRNAs that affect prostate cancer: emphasis on prostate cancer in African Americans.
Although concerted efforts have been directed toward eradicating health disparities in the United States, the disease and mortality rates for African American men still are among the highest in the world. We focus here on the role of microRNAs (miRNAs) in the signaling pathways of androgen receptors and growth factors that promote the progression of prostate cancer to more aggressive disease. We explore also how differential expression of miRNAs contributes to aggressive prostate cancer including that of African Americans.


Effects of estradiol and its antagonist tamoxifen on motility and metabolism of human spermatozoa.
An investigation was conducted to evaluate the motility and metabolism of human spermatozoa incubated at 37 degrees Celsius for 3 hours in a krebs phosphate Ringer solution containing different concentrations of 17beta-estradiol and tamoxifen. 17beta-estradiol (17beta E2) stimulated significantly the motility of human spermatozoa. The oxidative metabolism and the intracellular ATP concentrations are enhanced with 10-20 mcg/ml of 17beta E2; the lactate production remains unchanged however. Tamoxifen, an antiestrogen, inhibited the motility of spermatozoa, and was toxic at high concentrations. Its effects on the energetic metabolism is dose-dependent; it increases the oxidative metabolism and decreases the lactate production and intracellular ATP at 3 mcg/ml.


Differentiating persistent from self-limiting symmetrical synovitis in an early arthritis clinic.
Early rheumatoid arthritis (RA) must be differentiated from benign self-limiting polyarthritis because of the risks associated with treatment of RA. Conventional, widely available clinical and laboratory variables, measured at first clinic visit, were studied for their ability to predict persistence in 112 patients with up to 6 months of joint symptoms. Those 65 patients with symmetrical peripheral polyarthritis were followed for 1 year: 36 who underwent spontaneous remission were classified self-limiting synovitis (SLS); the remaining 29 were termed persistent synovitis (PS). Univariate analysis suggested more severe disease in PS at presentation but showing considerable overlap with SLS, making clinical discrimination difficult. Multivariate analysis confirmed this overlap but identified a subset of most helpful variables. The RA latex was the most powerful variable, yet accounted for only 45% of the variability in outcome. Combining a positive RA latex with an ESR > 30 mm/h carried a relative risk for PS of 4.33, with specificity 94% but sensitivity only 69%. Self-limiting synovitis initially could not be distinguished from early RA: hence RA may exist in two forms, the traditional persistent form and a less well recognized abortive form.


Ribotypes of clinical Vibrio cholerae non-O1 non-O139 strains in relation to O-serotypes.
The emergence of Vibrio cholerae O139 in 1992 and reports of an increasing number of other non-O1 serogroups being associated with diarrhoea, stimulated us to characterize V. cholerae non-O1 non-O139 strains received at the National Institute of Infectious Diseases, Japan for serotyping. Ribotyping with the restriction enzyme BglI of 103 epidemiological unrelated mainly clinical strains representing 10 O-serotypes yielded 67 different typing patterns. Ribotype similarity within each serotype was compared by using the Dice coefficient (Sd) and different levels of homogeneity were observed (serotypes O5, O41 and O17, Sd between 82 and 90%: serotypes O13 and O141 Sd of 72; and O2, O6, O7, O11, O24 Sd of 62-66%). By cluster analysis, the strains were divided into several clusters of low similarity suggesting a high level of genetic diversity. A low degree of similarity between serotypes and ribotypes was found as strains within a specific serotypes often did not cluster but clustered with strains from other serotypes. However, epidemiological unrelated O5 strains showed identical or closely related ribotypes suggesting that these strains have undergone few genetic changes and may correspond to a clonal line. Surprisingly, 10 of 16 O141 strains studied contained a cholera toxin (CT) gene, including 7 strains recovered from stool and water samples in the United States. This is to our knowledge the first report of CT-positive clinical O141 strains. The closely related ribotypes shown by eight CT-positive strains is disturbing and suggest that these strains may be of a clonal origin and have the potential to cause cholera-like disease. Despite the low degree of correlation found between ribotypes and serotypes, both methods appears to be valuable techniques in studying the epidemiology of emerging serotypes of V. cholerae.


Click-Particle Display for Base-Modified Aptamer Discovery.
Base-modified aptamers that incorporate non-natural chemical moieties can achieve greatly improved affinity and specificity relative to natural DNA or RNA aptamers. However, conventional methods for generating base-modified aptamers require considerable expertise and resources. In this work, we have accelerated and generalized the process of generating base-modified aptamers by combining a click-chemistry strategy with a fluorescence-activated cell sorting (FACS)-based screening methodology that measures the affinity and specificity of individual aptamers at a throughput of ∼107 per hour. Our "click-particle display (PD)" strategy offers many advantages. First, almost any chemical modification can be introduced with a commercially available polymerase. Second, click-PD can screen vast numbers of individual aptamers on the basis of quantitative on- and off-target binding measurements to simultaneously achieve high affinity and specificity. Finally, the increasing availability of FACS instrumentation in academia and industry allows for easy adoption of click-PD in a broader scientific community. Using click-PD, we generated a boronic acid-modified aptamer with ∼1 μM affinity for epinephrine, a target for which no aptamer has been reported to date. We subsequently generated a mannose-modified aptamer with nanomolar affinity for the lectin concanavalin A (Con A). The strong affinity of both aptamers is fundamentally dependent upon the presence of chemical modifications, and we show that their removal essentially eliminates aptamer binding. Importantly, our Con A aptamer exhibited exceptional specificity, with minimal binding to other structurally similar lectins. Finally, we show that our aptamer has remarkable biological activity. Indeed, this aptamer is the most potent inhibitor of Con A-mediated hemagglutination reported to date.


The influence of group size on children's competitive behavior.
The present research was designed to test the hypothesis that children would compete more in tetrads than in dyads. Twenty-two pairs of male and 14 pairs of female target children (N = 72) played a competitive game in both tetrads and dyads. Consistent with the hypothesis, male target children competed more in tetrads than in dyads. This hypothesis was not supported for females, however. Analyses of the dynamics of tetrads and dyads further demonstrated that based on a global measure of smiling, the emotional atmosphere was less positive in tetrads than in dyads. The causes and consequences of interaction in different sized social groups are discussed.


Associations between refined athlete monitoring measures and individual match performance in professional Australian football.
The purpose of this study was to assess relationships between measures of training load, training response and neuromuscular performance and changes in individual match performance in professional Australian football. Data were collected from 45 professional Australian footballers from one club during the 2019 competition season. External load was measured by GPS technology. Internal load was measured via session rate of perceived exertion (sRPE). Perceptual wellness was measured via pre-training questionnaires (1-5 Likert scale rating of soreness, sleep, fatigue, stress and motivation). Percentage of maximum speed was calculated relative to individual maximum recorded during preseason testing. Rolling derivative training load measures (7-day and 28-day) were calculated. Principal Component Analysis (PCA) identified eight uncorrelated components. PCA factor loadings were used to calculate summed variable covariates and single variables were chosen from components based on practicality and statistical contribution. Associations between covariates and performance were determined via linear Generalised Estimating Equations. Performance was assessed via Player Ratings from a commercial statistics company. Seven-day total distance, IMA event count and sRPE load showed significant positive relationships with performance (18-23% increase in performance z-score). No other covariates displayed significant associations with performance. Individual relative increases in training load within the 7-day period prior to a match may be beneficial for enhancing individual performance.


The Mechanical Properties of Kevlar Fabric/Epoxy Composites Containing Aluminosilicates Modified with Quaternary Ammonium and Phosphonium Salts.
We investigated the effect of modified aluminosilicates, including bentonite from Armenia (BA) modified with quaternary ammonium salts (BAQAS) and phosphonium salts (BAQPS), on the mechanical properties and morphology of Kevlar/epoxy composites. The Kevlar/epoxy composites containing 1.0 or 3.0 wt.% modified bentonites were fabricated using the hand lay-up technique. The mechanical properties, including the tensile, flexural, and in-plane shear strength, were tested. Based on the obtained results, we found that the mechanical properties increased with modified bentonite loading. The best results were obtained for composites containing 3 wt.% BAQAS, as most of the mechanical properties were significantly improved (tensile strength 302.9 MPa (+30%), Young's modulus 16.3 GPa (+17%), flexural modulus 23.4 GPa (+12.5%), in-plane shear strength 22.8 MPa (+24.5%), and in-plane shear modulus 677.2 MPa (+42%)). The obtained improvements in the mechanical properties are attributed to the uniform dispersion of the filler, which was confirmed by the highest increase in the intergallery spacing, from 28.3 Å for BAQAS to 45.1 Å for the composite with 3 wt.% BAQAS. Scanning electron microscopy (SEM) analysis of the brittle fracture surface indicated that the addition of modified bentonite to the epoxy matrix changed the morphology of the Kevlar/epoxy/organoclay composites and improved the fiber-matrix interfacial adhesion.


Investigating a Signal of Acquired Hemophilia Associated with COVID-19 Vaccination: A Systematic Case Review.
Acquired hemophilia A (AHA), a rare but life-threatening disorder, most commonly occurs in older people and during pregnancy. During the coronavirus disease 2019 (COVID-19) vaccination campaign, an unexpected number of newly diagnosed AHA patients have been identified in clinical practice that were temporally related to COVID-19 vaccination. We present the result of a signal detection analysis aimed at exploring a possible association between COVID-19 immunization and occurrence of AHA. A disproportionality analysis on the World Health Organization (WHO) database was performed to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. Reports of AHA associated with any COVID-19 vaccine included in the WHO database were then integrated with those available on the Food and Drug Administration Vaccine Adverse Events Reporting System and those published in the medical literature. The WHO database included 146 reports of AHA. The information component (IC) was significant for the association of AHA with all COVID-19 vaccines (IC025: 1.1) and with the vaccine product BNT162b2 (IC025: 1.6). After duplicate exclusion, 96 unique cases of AHA following COVID-19 vaccines have been reviewed. Median time to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Overall, in 57% of the investigated cases, a preexisting condition predisposing to AHA was excluded. About 22% of cases occurred in subjects with age ≤65 years and there was no case associated with pregnancy. Mortality was 11%. Although we cannot exclude that the unexpected frequency of AHA diagnosis can be explained by a detection bias, the signal for COVID-19 vaccine-related AHA is robust and deserves further investigations.


[Selective enhancement of tumor blood flow and drug delivery to brain tumors in experimental rat gliomas under angiotensin II-induced hypertension].
Regional blood flow of brain tumors and normal brain tissue of rats before and during angiotensin II (AT II)-induced hypertension were measured using an electrolytic flowmeter and a laser flowmeter. Etoposide concentration in the tumor and brain tissue after intracarotid administration were also measured in brain tumor bearing rats with or without AT II-induced hypertension. A suspension of 5 x 10(5)/10 microliters 9L gliosarcoma cells was inoculated into the left caudate-putamen of CD Fischer 344 rats. Before induced hypertension, regional blood flow of the tumor (28.2 +/- 2.6 ml/100 g/min; mean +/- SEM) and the contralateral caudate-putamen (23.0 +/- 1.8 ml/100g/min) in the tumor bearing rats were significantly lower than that of the caudate-putamen (43.9 +/- 4.1 ml/100g/min) in the normal rats (p less than 0.01). Intravenous administration of AT II at a dose of 0.4-0.6 microgram/body/min increased the mean arterial blood pressure from 96.5 +/- 4.7 mmHg to 138.0 +/- 3.6 mmHg. AT II-induced hypertension resulted in an approximate 1.8(1.1 - 3.6)-fold increase in the regional tumor blood flow. On the other hand the regional blood flow of the contralateral caudate-putamen was slightly decreased at the rate of 6%. The mean concentration of etoposide with AT II-induced hypertension in the tumor tissue was 2.2-fold higher than that without AT II-induced hypertension. However, etoposide delivery to normal brain tissue was small. From these results, induced hypertension with intravenously administrated AT II selectively increase the tumor blood flow and drug delivery to brain tumor tissue. Intracarotid chemotherapy with AT II-induced hypertension might contribute to enhance therapeutic effect of malignant brain tumors.


Ipsilateral vascularised fibular transport for massive defects of the tibia.
The ipsilateral and contralateral fibulae have been used as a vascularised bone graft for loss of tibial bone usually by methods which have involved specialised microvascular techniques to preserve or re-establish the blood supply. We have developed a method of tibialisation of the fibula using the Ilizarov fixator system, ipsilateral vascularised fibular transport (IVFT), and have used it in five patients with massive loss of tibial bone after treatment of an open fracture, infected nonunion or chronic osteomyelitis. All had successful transport, proximal and distal union, and hypertrophy of the graft without fracture. One developed a squamous-cell carcinoma which ultimately required amputation of the limb. The advantage of IVFT is that the fibular segment retains its vascularity without the need for microvascular dissection or anastomoses. Superiosteal formation of new bone occurs if the tibial periosteal bed is retained. Other procedures such as corticotomy and lengthening can be carried out concurrently.


Vesicoureteral reflux is associated with increased risk of chronic kidney disease: A nationwide cohort study.
The association between vesicoureteral reflux (VUR) and chronic kidney disease (CKD) risk remains unestablished. We investigated the incidence of CKD in children with VUR in Taiwan and evaluated whether they had a higher risk of CKD than the general population. A nationwide population-based cohort study was conducted among children with VUR identified using Taiwan's National Health Insurance Research Database from 2000 to 2013. VUR was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We identified the children with VUR and randomly selected comparison children according to a 1:1 ratio, matching them by age, gender, index year and comorbidity using data from the National Health Insurance Research Database. In total, 8648 children with VUR and 8648 comparison children were included. All children were followed from the study date until a diagnosis of CKD, termination of insurance, or the end of 2013. Cox proportional hazards regressions were performed to compare the hazard ratios for CKD between the 2 cohorts. Incident cases of CKD were identified. After adjustment for potential confounders, the study cohort was independently associated with a higher risk of CKD (adjusted hazard ratio, 3.78; 95% confidence interval, 2.10-7.18). This population-based cohort study indicated that children with VUR have a higher risk of CKD than those without VUR.


Comparative microarray profile of the hepatopancreas in the response of "Huanghai No. 2" Fenneropenaeus chinensis to white spot syndrome virus.
White spot syndrome virus (WSSV) infects all shrimp species and is the greatest detriment to shrimp culture. To better understand the mechanism of molecular responses to WSSV infection in "Huanghai No. 2" Fenneropenaeus chinensis, a microarray technique was used. Microarray gene expression profiling of 59,137 unigenes identified Differentially Expressed Genes (DEGs) both in live and moribund shrimp at early, peak and late phases. In live shrimp, 1307, 1479 and 1539 DEGs were obtained in the early, peak and late phase, respectively. Meanwhile, 1536, 2181 and 1591 DEGs were obtained in moribund shrimp. Twenty known annotation genes are uniquely expressed in the late phase of live shrimp, including adhesion regulating molecule 1, arginine kinase, BUD31 homolog, and QM. Compared to WSSV-susceptible shrimp, 75 known annotation genes are uniquely expressed in WSSV-resistant shrimp, including arginine kinase, BUD31 homolog, clottable protein 2, caspase 2, cathepsin C, calnexin, HMGBb, Histone 3, and selenoprotein M. The gene expression patterns of the infected shrimp were altered by WSSV infection. To further confirm the expression of differentially expressed genes, real-time RT-PCR was performed to test six randomly selected genes. The data will provide valuable information to understand the immune mechanism of shrimp's response to WSSV.


[The systemic manifestations of ulcerative colitis].
To probe the relationship between location and extent of ulcerative colitis (UC) by analyzing its extra-intestinal manifestations. 392 UC cases in Peking Union Medical College Hospital from 1976 to 2000 were reviewed retrospectively. Chi-square test was used to test the difference between groups. 82 of 392 patients (20.9%) with UC had extra-intestinal manifestations, 34 (8.7%) of these patients had more than one extra-colonic organ involvement; It shows that the extensive colitis has highest incidence of extra-intestinal manifestations with UC than that of the left-sided colitis did, while the proctitis had the lowest incidence. There were no significant difference (P > 0.05) between the group of extensive colitis and that of left-side colitis; The incidence of extra-intestinal manifestations in severe cases was significantly greater than that in mild cases. There was a trend of increasing incidence from severe to moderate to mild type (P < 0.05); Most of the extra-intestinal manifestations were associated with active UC, except for AS, PSC, healed during SASP and/or steroid treatment. Extra-intestinal manifestations had a high incidence in UC. The most frequently involved organs were joints, hepatobiliary system, skin, mouth and eyes. The majority of them were associated with the active UC. The incidence of extra-intestinal manifestations with UC was closely related with the extent and severity of the lesions, and the most of the extra-intestinal manifestations occurred in the active phase of UC. But the incidence of extra-intestinal manifestations was not related to prognosis.


Inhibition of the photosynthetic capacity of isolated chloroplasts by ozone.
Isolated spinach chloroplasts have been used as a model system for studying the interaction of ozone, a component of photochemical smog, with plant membranes. Ozone bubbled into a suspension of isolated chloroplasts inhibits electron transport in both photosystems without uncoupling ATP production. Photosystem I (reduced 2,6-dichlorophenolindolphenol --> NADP(+)) is a little more sensitive than photosystem II (H(2)O --> 2,6-dichlophenolindolphenol). Ozone does not act as an energy transfer inhibitor, since the drop in ATP production and high energy intermediate (measured by amine-induced swelling) is nearly parallel to the decline in electron transport. A reasonable hypothesis is that ozone disrupts the normal pathway of energy flow from light-excited chlorophyll into the photoacts by a disruption of the components of the membrane but not a general disintegration of the membrane. In addition, ozone does not seem to penetrate into the grana region through the outer membrane of intact plastids, since ozone lowers the bicarbonate-supported O(2) evolution but does not affect the rate of ferricyanide reduction in the same plastids after osmotic disruption. This would indicate that the effect of ozone on green plants, at low concentrations, may be due to the interaction of ozone with the first membrane it contacts and not directly with internal metabolic processes.


Characteristics of two basolateral potassium channel populations in human colonic crypts.
The basolateral membrane of human colonic crypt cells contains Ca2+ and cAMP activated, Ba2+ blockable, low conductance (23 pS) K+ channels, which probably play an important part in intestinal Cl- secretion. This study has defined more clearly the basolateral K+ conductive properties of human colonic crypts using patch clamp recording techniques. High conductance (138 pS) K+ channels were seen in 25% of patches (one or two channels per patch), and significantly inhibited by the addition of 5 mM Ba2+, 1 mM quinidine or 20 mM tetraethylammonium chloride (TEA) to the cytosolic side of excised inside-out patches, whereas 1 mM diphenylamine-2-carboxylic acid (DPC) had no effect. In contrast, clusters of the 23 pS K+ channel (two to six channels per patch) were present in > 75% of patches, and channel activity was inhibited by quinidine and DPC, but not by TEA. Activity of the 138 pS K+ channel in inside-out patches was abolished almost completely by removal of bath Ca2+, but in contrast with its effect on the 23 pS K+ channel, addition of 0.1 mM carbachol had no effect on the 138 pS K+ channel in cell attached patches. It is concluded that human colonic crypt cells possess two discrete basolateral K+ channel populations, which can be distinguished by their responses to K+ channel blockers, and their different sensitivities to changes in intracellular Ca2+ concentration.


Complete Genome Analysis of Undecylprodigiosin Pigment Biosynthesizing Marine Streptomyces Species Displaying Potential Bioactive Applications.
Marine Streptomyces species are underexplored for their pigment molecules and genes. In this study, we report the genome of the undecylprodigiosin biosynthesizing gene cluster carrying Streptomyces sp. strain BSE6.1, displaying antioxidant, antimicrobial, and staining properties. This Gram-positive obligate aerobic bacterium was isolated from the coastal sediment of the Andaman and Nicobar Islands, India. Pink to reddish pigmented colonies with whitish powdery spores on both agar and broth media are the important morphological characteristics of this bacterium. Growth tolerance to NaCl concentrations was 2 to 7%. The assembled genome of Streptomyces sp. BSE6.1 contains one linear chromosome 8.02 Mb in length with 7157 protein-coding genes, 82 tRNAs, 3 rRNAs and at least 11 gene clusters related to the synthesis of various secondary metabolites, including undecylprodigiosin. This strain carries type I, type II, and type III polyketide synthases (PKS) genes. Type I PKS gene cluster is involved in the biosynthesis of red pigment undecylprodigiosin of BSE6.1, similar to the one found in the S. coelicolor A3(2). This red pigment was reported to have various applications in the food and pharmaceutical industries. The genome of Streptomyces sp. BSE6.1 was submitted to NCBI with a BioProject ID of PRJNA514840 (Sequence Read Archive ID: SRR10849367 and Genome accession ID: CP085300).


Silver-catalyzed one-pot synthesis of arylnaphthalene lactones.
Arylnaphthalene lignan lactones are valuable natural products with promising anticancer and antiviral properties. In an effort to simplify their synthesis, we investigated a one-pot multicomponent coupling reaction between phenylacetylene, carbon dioxide, and 3-bromo-1-phenyl-1-propyne. After the corresponding 1,6-diyne was generated in situ, cyclization afforded the desired product. The level of regioselectivity was enhanced through the tuning of electronic properties. The use of cinnamyl bromide which led to the formation of a 1,6-enyne intermediate was also studied.