Polynuclear Silver(I) Triazole Complexes: Ion Conduction and Nanowire Formation in the Mesophase.

Examples of polynuclear metallomesogens are few. Herein,1,2,4-triazole ligands were used to prepare mono- and polynuclear silver(I) triazole metallomesogens. Besides showing an SmA phase in the mesophase, two interesting properties were observed. First, higher ion conductivity is always found for the polynuclear complexes than for the mononuclear complexes with the same anion, an observation contrary to the knowledge that migration of a monomeric cation should be faster than that of a polymeric cation. Second, thermolysis of the polynuclear silver(I) triazole complexes in the assembled mesophase yielded Ag nanowires, in an excellent demonstration of the assembled nature of the polynuclear silver(I) ions in the thermolysis process.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

BACKGROUND: Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. AIM: To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. METHODS: Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. RESULTS: A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. CONCLUSIONS: Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens.

Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers.

BACKGROUND: The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear. AIM: To compare the rebleeding rate of high-dose and standard-dose PPI use after endoscopic haemostasis. METHODS: A total of 201 patients with bleeding ulcers undergoing endoscopic treatment with epinephrine injection and heater probe thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus, followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40 mg pantoprazole daily orally for 27 days. RESULTS: There were no statistical differences in mean units of blood transfused, length of hospitalisation ≦5 days, surgical or radiological interventions and mortality within 30 days between two groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence interval (CI) 1.3-11.1%] in the high-dose group, as compared to five patients (5.2%, 95% CI 0.6-9.7%) in the standard-dose group (P = 0.77). The stepwise Cox regression analysis showed end-stage renal disease, haematemesis, chronic obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76-204.14, 2.07-49.01, 1.66-50.00 respectively) were independent risk factors for rebleeding and Helicobacter pylori infection was associated with lower risk of rebleeding (hazard ratio: 0.20, 95% CI: 0.04-0.94). CONCLUSIONS: Following combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis and H. pylori Status, but not PPI dosage, are associated with rebleeding (http://www.Clinical Trials.gov.ID: NCT00709046).

Vertex and edge truncated octahedron gold crystals. N-alkylimidazole and silver(I) ion controlled morphology transformation.

Two interesting morphology transformations of Au crystals are observed through reacting a mixture of N-alkylimidazole (denoted as C(n)-im, where C(n) = C(n)H(2n+1), and n = 18 and 1), AgNO(3), and HAuCl(4) at 200 degrees C. The long chain C(18)-im with increasing AgNO(3) concentration leads to a progressive truncation of octahedrons at {100} vertices to produce cubes. On the other hand, increasing the concentrations of C(1)-im and AgNO(3), results in a progressive truncation of octahedrons at {110} edges to give rhombic dodecahedrons, which further transform to the unprecedented tetrahexahedrons. The phenomenon could be understood by considering that while both C(18)-im and C(1)-im function as a capping agent with preferential adsorption on Au {111} facets, Ag(+) adsorbs and is subsequently reduced to Ag on Au {110} facets for the sterically demanding C(18)-im, but on the Au {100} facets for C(1)-im. The competition between the growth of the facets protected by imidazole and Ag controls the morphology transformation via truncation of octahedrons at vertices or edges.

A novel motion compensation algorithm for acoustic radiation force elastography.

A novel method of physiological motion compensation for use with radiation force elasticity imaging has been developed. The method utilizes a priori information from finite element method models of the response of soft tissue to impulsive radiation force to isolate physiological motion artifacts from radiation force-induced displacement fields. The new algorithmis evaluated in a series of clinically realistic imaging scenarios, and its performance is compared to that achieved with previously described motion compensation algorithms. Though not without limitations, the new model-based motion compensation algorithm performs favorably in many circumstances and may be a logical choice for use with in vivo abdominal imaging.

Au(i)-benzimidazole/imidazole complexes. Liquid crystals and nanomaterials.

Three series of Au(I)-imidazole complexes with stoichiometries of [Au(Cn-bim)Cl], [Au(Cn-im)Cl], and [Au(Cn-im)2][NO3] x 2H2O (Cn-bim = N-CnH2n+1 -substituted benzimidazole and Cn-im = N-CnH2n+1-substituted imidazole) together with the compound of [Au(C18-bim)2][NO3] are synthesiszed. Typical structures of each series are determined by single crystal X-ray diffraction. The last series of compounds, are liquid crystals, and exhibit a wider mesophase range than their Ag(I) analogues. These Au(I) complexes form Au nanostructures both through chemical reduction or thermolysis. For the first time, N-long chain imidazole is utilized to stabilize colloidal Au in solution. Also for the first time, unique examples of simple thermolysis to produce large Au plates of nanothickness are demonstrated. Formation of a plate-like morphology through fusion of sphere-like nanoparticles at an early stage is evidenced by TEM images.

In vivo visualization of abdominal malignancies with acoustic radiation force elastography.

The utility of acoustic radiation force impulse (ARFI) imaging for real-time visualization of abdominal malignancies was investigated. Nine patients presenting with suspicious masses in the liver (n = 7) or kidney (n = 2) underwent combined sonography/ARFI imaging. Images were acquired of a total of 12 tumors in the nine patients. In all cases, boundary definition in ARFI images was improved or equivalent to boundary definition in B-mode images. Displacement contrast in ARFI images was superior to echo contrast in B-mode images for each tumor. The mean contrast for suspected hepatocellular carcinomas (HCCs) in B-mode images was 2.9 dB (range: 1.5-4.2) versus 7.5 dB (range: 3.1-11.9) in ARFI images, with all HCCs appearing more compliant than regional cirrhotic liver parenchyma. The mean contrast for metastases in B-mode images was 3.1 dB (range: 1.2-5.2) versus 9.3 dB (range: 5.7-13.9) in ARFI images, with all masses appearing less compliant than regional non-cirrhotic liver parenchyma. ARFI image contrast (10.4 dB) was superior to B-mode contrast (0.9 dB) for a renal mass. To our knowledge, we present the first in vivo images of abdominal malignancies in humans acquired with the ARFI method or any other technique of imaging tissue elasticity.

Liver ablation guidance with acoustic radiation force impulse imaging: challenges and opportunities.

Previous studies have established the feasibility of monitoring radiofrequency (RF) ablation procedures with acoustic radiation force impulse (ARFI) imaging. However, questions remained regarding the utility of the technique in clinically realistic scenarios and at scanning depths associated with abdominal imaging in adults. We address several of these issues and detail recent progress towards the clinical relevance of the ARFI technique. Results from in vitro bovine tissues and an in vivo ovine model are presented. Additional experiments were conducted with a tissue-mimicking phantom and parallel receive tracking techniques in order to further support the clinical feasibility of the method. Thermal lesions created during RF ablation are visualized with high contrast in both in vitro and in vivo hepatic tissues, and radial lesion growth can be monitored throughout the duration of the procedure. ARFI imaging is implemented on a diagnostic ultrasonic scanner, and thus may be a convenient option to guide RF ablation procedures, particularly when electrode insertion is also performed with sonographic guidance.

Magnetocardiography of animals in magnetically shielded environment with active compensation.

A high-Tc 1st-order electronic superconducting quantum interference device (SQUID) gradiometer system is constructed to study the magnetocardiogram (MCG) of rabbits in a moderately magnetically shielded environment with active compensation. In the noisy hospital environment, the noise cannot be completely reduced with the 1st-order gradiometer, therefore, a reference SQUID with active compensation was used to further reduce the noise level leaking into the room. The MCG system was equipped with a x-y translation bed. We used a low-pass filter with the cut off frequency at 44 Hz, a high-pass filter with the cut off frequency at 0.1 Hz and the 60 Hz notch filter to reduce the power line interference. The noise level of the 1st order gradiometer MCG system in this moderately magnetically shielded room was about 1 pT/square root of Hz1/2 at 1 Hz. The MCG of a normal rabbits was measured with this system and a MCG contour map and a current density distribution was constructed.

High-Tc SQUID magnetocardiography imaging system.

We set up a high-Tc SQUID system for magnetocardiography (MCG) in a moderately magnetically shielded room. The electronically balanced gradiometer consists of superconducting quantum interference device (SQUID) magnetometer. One reference SQUID was mounted above the sensing SQUID while the sensing SQUID is seated at the bottom of the cryostat. The baseline of the gradiometer is varied from 5 cm to 7 cm. The output of the MCG signal was filtered with the band pass filter (0.5 - 40 Hz) and the power-line filter. The MCG system was used to detect the magnetic signal of the human heart. Equivalent current sources were used to study the inverse problem.

Fine linkage and physical mapping suggests cross-over suppression with a retroposon insertion at the npc1 mutation.

Mouse Niemann-Pick disease type C1 (npc1), formerly designated spm (sphingomyelinosis), is an autosomal recessive lipid storage disorder. We generated a high-resolution linkage map in the 2.24-cM npc1 critical region by typing eight polymorphic markers in 2322 meioses (948 of these were previously reported). A minimal set of overlapping yeast artificial chromosomes (YACs) had previously been assembled (Hsu and Erickson 2000). The YAC 313-B-8, which covered this whole region, has been used to construct cosmid libraries. Three cosmid contigs were built, and one of them contained the npc1 locus. Two (CA)(n) microsatellites were identified, and the one new one was characterized, from the YAC-derived cosmids. The most proximal cosmid contig overlaps with markers near twirler (Tw). Both the physical map and genetic linkage map have been integrated to study the recombination frequencies in this particular region of the mouse genome, and recombination suppression due to the heterozygous insertion of DNA was suggested.

Construction of a long-range YAC physical map spanning the 10-cM region between the markers D18Mit109 and D18Mit68 on mouse proximal chromosome 18.

Four yeast artificial chromosome (YAC) contigs, physically approximately 8 Mb, have been constructed spanning a 10-cM region on mouse proximal chromosome 18 and include the sites of 21 known genes, including those near the twirler (Tw) locus and the recently isolated Niemann-Pick type C1 (npc1) gene, formerly designated as the spm locus. This physical map consists of 49 YAC clones that cover roughly 15% of the chromosome. The physical order of 38 microsatellite sequence-tagged sites (STSs) could be assembled and confirmed based on their presence or absence in individual YACs, from proximal D18Mit109 through distal D18Mit68. These YACs provide an important resource for the further characterization and identification of known and unknown genes. The physical map has been integrated with our previously published genetic linkage map and showed an average genetic to physical distance of cM/Mb > 1.1.

Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy.

Carbonic anhydrase II (CAII) deficiency in humans is associated with a syndrome of renal tubular acidosis, osteopetrosis, and cerebral calcification. A strain of mice of CAII deficiency due to a point mutation also manifests renal tubular acidosis. We report here that retrograde injection of cationic liposome complexed with a CAII chimeric gene, using a cytomegalovirus (CMV) promoter/enhancer as an expression cassette to drive human CAII cDNA, into the renal pelvis of CAII-deficient mice results in expression of CAII in the kidney. The levels of both the CAII gene and its corresponding mRNA were highest by day 3 after treatment, diminishing thereafter, but remaining detectable by 1 mo. After gene therapy, CAII-deficient mice restored the ability to acidify urine after oral administration of ammonium chloride. The ability to acidify urine was maintained at 3 wk after gene therapy, and was eventually lost by 6 wk. Immunohistochemistry studies using anti-CAII antibodies showed that CAII was expressed in tubular cells of the outer medulla and corticomedullary junction. The gene therapy was not associated with nephrotoxicity as assessed by blood urea nitrogen levels and renal histology. To our knowledge, this is the first successful gene therapy of a genetic renal disease. Our results demonstrate the potential of gene therapy as a novel treatment for hereditary renal tubular defects.

[A study of attitudes and behavior regarding fertility among newlyweds in Taipei City].

There are around 40,000 births in Taipei City each year. Of them about 40% are of the 1st parity. Of all deliveries, about 80% are born to mothers under 30 years old. There are about 20,000 marriages each year. Of all brides and grooms surveyed in the present study, 39.4% and 39.1% consider the ideal time to conceive being either as early as possible or within 1 year after the wedding. In actuality, 28.08% of the respondents were already pregnant before the wedding. Excluding the inteviewees who were married for over 1 year, 34.1% are currently pregnant, 6.98% have already given birth, and 0.15% have become pregnant again after a birth. This result is similar to the findings of the KAP conducted by the Center in 1980, which showed that 41.3% of the interviewees gave birth to their 1st child within 1 year after the wedding. The same survey of 1980 also finds that the interval between the 1st and the 2nd child is 1.94 years, though women in general consider the ideal interval to be 2.6 years. How to encourage those who are to be married and the newlyweds to prolong the intervals between the wedding and the 1st child and between the 1st and the 2nd child is an important task of the health educators. The present study interviews 1013 couples who registered their marriages in October 1983. Needs, targets, and contents of education programs are identified. Better ways to communicate with the newlyweds are also indicated. The purpose of the study, based on the findings, is to propose a model most suitable for the education in family planning of those who are to be married and who are just married, in order to provide them with better services and to further reduce the fertility of young people.

Vitamin E status of Chinese population in Taiwan.

Vitamin E status of Chinese population with different age groups was studied by determining plasma vitamin E levels (PE) and hydrogen peroxide-induced erythrocyte hemolysis (HPEH). The mean PE of 99 adults, ages 23 to 78, was 1.05 +/- 0.47 mg/100 ml. There was no significant difference between sexes. PE was negatively correlated with HPEH (P less than 0.01). There was a significant positive correlation (P less than 0.01) between PE and plasma cholesterol level. The mean PE of four young men of Yami tribesmen, ages 16 to 19, was 0.60 +/- 0.10 mg/100 ml. HPEH was low. After daily supplementation of 200 mg dl-alpha-tocopheryl acetate for 16 days, PE increased 54%, but the plasma cholesterol was not affected. The mean PE of 39 elementary school children ages 12 to 13, was 0.70 +/- 0.31 mg/100 ml. The mean PE of 20 newborn infants was 0.23 +/- 0.08 mg/100 ml. HPEH was as high as 56.5 +/- 31.9% indicating a state of vitamin E deficiency. PE of total population was positively correlated with age (P less than 0.01). It was concluded that the vitamin E status of Chinese population in Taiwan was comparable to that of population groups in many other parts of the world.