Covalent Triazine Frameworks Based on the First Pseudo-Octahedral Hexanitrile Monomer via Nitrile Trimerization: Synthesis,Porosity, and CO2 Gas Sorption Properties

Herein, we report the first synthesis of covalent triazine-based frameworks (CTFs) based on a hexanitrile monomer, namely the novel pseudo-octahedral hexanitrile 1,4-bis(tris(4′-cyano-phenyl)methyl)benzene 1 using both ionothermal reaction conditions with ZnCl₂ at 400 °C and the milder reaction conditions with the strong Brønsted acid trifluoromethanesulfonic acid (TFMS) at room temperature. Additionally, the hexanitrile was combined with different di-, tri-, and tetranitriles as a second linker based on recent work of mixed-linker CTFs, which showed enhanced carbon dioxide captures. The obtained framework structures were characterized via infrared (IR) spectroscopy, elemental analysis, scanning electron microscopy (SEM), and gas sorption measurements. Nitrogen adsorption measurements were performed at 77 K to determine the Brunauer-Emmett-Teller (BET) surface areas range from 493 m²/g to 1728 m²/g (p/p₀ = 0.01–0.05). As expected, the framework CTF-hex6 synthesized from 1 with ZnCl₂ possesses the highest surface area for nitrogen adsorption. On the other hand, the mixed framework structure CTF-hex4 formed from the hexanitrile 1 and 1,3,5 tricyanobenzene (4) shows the highest uptake of carbon dioxide and methane of 76.4 cm³/g and 26.6 cm³/g, respectively, at 273 K.     

Pulmonary vein isolation using second-generation single-shot devices: not all the same?

Introduction

Single-shot devices have been developed to simplify pulmonary vein isolation (PVI). Randomized studies of the second-generation cryoballoon (CB 2nd) demonstrated excellent results. There are limited data comparing results of circular pulmonary vein ablation catheter (PVAC) with conventional RF ablation or CB for PVI.

Objective

Using a sequential registry cohort and a prospective randomized study, we aimed to compare the acute and long-term results of CB 2nd and PVAC Gold.

Methods

In the registry, consecutive patients with paroxysmal atrial fibrillation (AF) undergoing their first PVI were included. The preferred method used was PVAC Gold in 2014 and CB 2nd in 2015. Subsequently, a randomized study (PVAC vs. CB 2nd) was performed. Ablation success was measured as freedom of AF or atrial tachycardias (AT) off antiarrhythmic drugs.

Results

In the registry cohort, PVAC Gold was used in 60 patients and CB 2nd in 56 patients (age 66?±?11 years, 52% male, LAD 43?±?6). In the randomized study, 20 patients were treated with PVAC Gold and 22 with CB 2nd (age 67?±?9; 43% men, LAD 40?±?7 mm). During a mean follow up of 13.2?±?3.6 months, success was 54% in PVAC Gold patients and 81% in CB 2nd cases (p?=?0.001). In the randomized study 12 months success was 50% versus 86%, p?<?0.05. Complications occurred rare in both groups.

Conclusions

Our registry data and the randomized study both suggest superiority of PVI using CB 2nd as compared with PVI using PVAC Gold.

     

Boiling Histotripsy Ablation of Renal Cell Carcinoma in the Eker Rat Promotes a Systemic Inflammatory Response

Boiling histotripsy (BH) is an experimental focused ultrasound technique that produces non-thermal mechanical ablation. We evaluated the feasibility, short-term histologic effects and the resulting acute inflammatory response to BH ablation of renal cell carcinoma (RCC) in the Eker rat. Genotyped Eker rats were monitored for de novo RCCs with serial ultrasound (US) imaging. When tumors were ≥8 mm, rats underwent ultrasound-guided extracorporeal ablation of the tumor with BH, a pulsed focused US technique that produces non-thermal mechanical ablation of targeted tissues, or a sham US procedure. Treatments targeted approximately 50% of the largest RCC with a margin of normal kidney. BH treated rats were euthanized at 1 (n?=?4) or 48 (n?=?4) h, and sham patients (n?=?4) at 48 h. Circulating plasma cytokine levels were assessed with multiplex assays before and at 0.25, 1, 4, 24 and 48 h following treatment. Kidneys were collected and processed for histologic assessment, immunohistochemistry and intrarenal cytokine concentration measurements. For statistical analysis Student's t-test was used. US-guided BH treatment was successful in all animals, producing hypoechoic regions within the targeted volume consistent with BH treatment effect. Grossly, regions of homogenized tissue were apparent with evidence of focal intra-parenchymal hemorrhage. Histologically, BH produced a sharply demarcated region of homogenized tumor and non-tumor tissue containing acellular debris. BH treatment was associated with significantly increased relative concentration of plasma TNF versus sham treatment (p < 0.05) and transient elevations in high-mobility group box 1 (HMGB1), IL-10 and IL-6 consistent with acute inflammatory response to trauma. Intrarenal cytokine concentrations followed the same trend. At 48 h, enhanced infiltration of CD8⁺ T cells was observed by immunohistochemistry in both the treated and un-treated contralateral RCC/kidneys in BH-treated animals versus sham treatment. BH treatment was well tolerated with transient gross hematuria and a perinephric hematoma developing in one subject each. The study demonstrates the feasibility of BH ablation of de novo RCC and suggests activation of the acute inflammatory cascade following treatment that appears to stimulate CD8+ T cell infiltration of both treated and untreated tumors. Longer duration chronic studies are ongoing to characterize the longevity and robustness of this response.     

Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.     

Staphylococcus aureus meningitis: experience with cefuroxime treatment during a 16 year period in a Danish region

Staphylococcus aureus is a rare cause of bacterial meningitis and there is no consensus on antibiotic treatment. Nafcillin is a common choice in countries where it is approved and marketed. High-dose cefuroxime has been the systemic treatment used in the study region, and a retrospective record review was conducted to determine its clinical efficacy. Cases of bacterial meningitis during 1984-1999 in the County of North Jutland, Denmark (approx. 490000 inhabitants), were identified in a regional bacteriology register. Inclusion of a case required either growth of S. aureus from > or = 2 specimens of cerebrospinal fluid (CSF), 1 positive CSF specimen with a CSF leucocyte count > 10(8)/l or 1 positive CSF specimen with a concurrent positive blood culture. A diagnosis of brain abscess required growth of S. aureus from aspirated pus. Staphylococcus aureus meningitis was confirmed in 45 patients, and 5 additional patients had a brain abscess. 44 cases were nosocomial (mortality 16%) and 6 were community acquired (mortality 83%). None of the isolates was methicillin resistant and 6 were penicillin susceptible. Intraventricular antibiotic treatment was given to 28 patients, systemic therapy included cefuroxime in 32 patients (64%) as either a primary or secondary choice, 6 (12%) were treated with penicillin G, 10 (20%) with penicillinase-resistant penicillin and 2 (4%) with cephalothin. Among 31 nosocomial cases treated systemically with cefuroxime the mortality was 10% (95% exact confidence limits 2-26%). In conclusion, cefuroxime seems to be a valid choice for S. aureus meningitis in the nosocomial setting.     

Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.     

血小板糖蛋白Ⅰbα因子突变(A156V)导致其与血管性血友病因子相互作用缺陷

目的　研究在流体切应力作用下表达突变的细胞与固着的血管性血友病因子 (vWF)相互作用中GPⅠbα突变 (A15 6V)的意义。方法　在GPⅠbαcDNA中直接诱发的突变克隆到哺乳类表达载体pDX的EcoRⅠ位点 ,随后将突变的cDNA转染在CHOβⅨ细胞。人的vWF通过甘氨酸和氯化钠沉淀及在Sepharose 4B柱分离的方法从血液冷沉淀制剂中纯化。纯化的vWF固着在盖玻片上 ,在平行板液流室中进行细胞滚动研究 ,用相差电视显微镜观察。结果　表达GPⅠb Ⅸ Ⅴ复合物的CHO细胞能粘附于并滚动在固着的vWF表面 ,当用表达A15 6V突变的细胞进行试验时 ,这些细胞虽然能粘附于并滚动在固着的vWF表面 ,但是它们滚动的速度明显快于其野生型 ,这表明突变的GPⅠbα与vWF之间的受体配体键的解离速度受损 ,单克隆抗体AN5 1与突变的GPⅠbα结合明显减少 ,表明A15 6V突变产生了GPⅠbα氨基端配体结合区的构象改变。结论　突变致使A15 6V突变细胞与固着的vWF产生较快的解离速度。突变的多肽在GPⅠbα氨基端配体结合区发生构象改变。平行板液流室在评价GPⅠbα与vWF之间相互作用中是一种有用的工具     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.