Diastolic Stress Testing Along the Heart Failure Continuum

Purpose of Review

This review summarizes recent developments highlighting the clinical utility of diastolic stress testing along the heart failure continuum.

Recent Findings

Invasive hemodynamic assessment of cardiac filling pressures during physiological stress is the gold-standard technique for unmasking diastolic dysfunction. Non-invasive surrogate techniques, such as Doppler ultrasound, have shown excellent agreement with invasive approaches and are now recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. While cycle exercise is often advocated, recent evidence supports the use of isometric handgrip as a viable alternative stressor.

Summary

Diastolic stress testing is a powerful tool to enhance detection of diastolic dysfunction, is able to differentiate between cardiac and non-cardiac pathology, and should be incorporated into routine clinical assessment.

     

Removal of free light chains in hemodialysis patients without multiple myeloma: a crossover comparison of three different dialyzers

Background

Immunoglobulin light chains are classified as middle molecule uremic toxins able to interact with B lymphocyte membranes leading to the activation of transmembrane signaling. The ensuing impairment of neutrophil function can contribute to the chronic inflammation state of uremic patients, and the increased risk of bacterial infections or vascular calcifications. The aim of this crossover observational study was to assess the difference in free light chain removal by three different hemodialysis filters in patients not affected by multiple myeloma.

Methods

Free light chain removal was compared in the polymethylmethacrylate (PMMA) membrane Filtryzer BK-F, the polyphenylene HFR17 filter and the conventional polysulfone filter F7HPS. Twenty chronic hemodialysis patients were enrolled: mean age was 67.7?±?17.0 years, M/F?=?14/6, dialysis vintage (months) 25.5?±?32.0. The patients were randomized into two groups of treatment lasting 6 weeks each. The dialysis sessions checked were the midweek sessions and the blood was drawn at times 0, 120’ and 240’. Kappa (k) and lambda (λ) light chain levels, β2microglobulin (β2M), C reactive protein (CRP) and albumin were checked.

Results

K light chain levels were 345.0?±?100.0 mg/L, λ light chains were 121.4?±?27.0 mg/L. The values of k light chains at times 120’ and 240’ were significantly lower with PMMA and HFR17 than those obtained with F7. The reduction ratio per session (RRs) for k light chains was 44.1?±?4.3% with HFR17, 55.3?±?3.4% with PMMA, 25.7?±?8.3% with F7 (p?=?0.018). The RRs for λ light chains was 30.3?±?2.9% with HFR17, 37.8?±?17.3% with PMMA, 14.0?±?3.9% with F7 (p?=?0.032). As to β2M, RRs was 42.4?±?3.2% with HFR17 vs. 33.9?±?2.8% with PMMA vs. 6.3?±?1.9% with F7 (p?=?0.022). The three filters tested showed no differences in CRP or albumin levels.

Conclusion

In terms of light chain and β2M removal, the PMMA and on-line HFR filters are similar and both are significantly more effective than the F7 filter in chronic dialysis patients.

Trial registration

The present trial was registered retrospectively (NCT02950389, 31/10/2016).

     

Spatial distribution and molecular characterization of Anopheles nivipes and Anopheles philippinensis (Diptera: Culicidae) in north-east India

Anopheles philippinensis-nivipes species of mosquitoes are considered secondary malaria vectors in the north-east India. However, difficulty in separating An. philippinensis and An. nivipes accurately on the basis of morphological identification, due to the overlapping female wing characters, has led to the paucity of information on their spatial distribution and vectorial importance, essential for understanding malaria disease epidemiology in areas under their influence. In view of this a study was undertaken to generate authentic information on distribution of An. philippinensis and An. nivipes in the north-east India using molecular tools. Between the two, An. nivipes was recorded as the dominant species in Assam, and Nagaland states whereas An. philippinensis was found predominant in the state of Mizoram and Arunachal Pradesh. Species differentiation based on female wing characters proved wrong in about 74% specimens of An. philippinensis but found accurate in case of An. nivipes. No intra-specific variation in second internal transcribed spacer (ITS2) region of ribosomal DNA(r-DNA) in either An. nivipes or An. philippinensis from different geographical areas of north-east India was noted.     

糖尿病及其血管并发症的介入治疗

糖尿病(diabetes mellitus,DM)根据发病机制的不同,可分为1型和2型．糖尿病介入治疗主要是针对1型DM由于胰岛β细胞缺乏造成胰岛素分泌绝对不足进行胰岛β细胞或者干细胞移植,从而增加胰岛素分泌的绝对量达到治疗DM的目的．DM的血管并发症介入治疗,最常见的是糖尿病足的治疗,使用经皮经腔血管成形术(percutaneous transluminal angioplasty,PTA)和血管内支架为糖尿病足及其他周围血管病变提供了一个新的治疗途径．     

Tamilnadia uliginosa (Retz) Tirveng and Sastre: Potential Application from Traditional Remedies to Modern Therapeutics

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Tamilnadia uliginosa (Retz) Tirveng and Sastre (Rubiaceae) is a small edible medicinal plant utilized in...     

Synthesis,radiolabeling and evaluation of a new positively charged 99mTc‐labeled fatty acid derivative for myocardial imaging

¹²³I‐labeled fatty acids and ¹⁸F‐FDG are used as metabolic markers for detecting myocardial abnormalities. However, a ^99mTc‐based molecule may find wider application. In the present work, a new ^99mTc‐labeled, uni‐positively charged, 16‐carbon fatty acid has been prepared and evaluated in normal Swiss mice. The results are then compared with the neutral analogue reported earlier. A 16‐cysteinyl hexadecanoic acid conjugate was synthesized in a six‐step synthetic procedure starting with 16‐bromohexadecanoic acid. The ligand upon incubation with [^99mTcN(PNP6)]²⁺ core formed the required positively charged complex in ～85% yield. The complex, which was obtained as a mixture of syn‐anti isomers, was purified by HPLC and the major fraction was used for in vivo studies in Swiss mice. The biodistribution studies in Swiss mice showed initial uptake similar to ¹²⁵I‐IPPA followed by rapid clearance from the myocardium till 10 min p.i. Thereafter, the rate of clearance was significantly decreased, an observation reported earlier for positively charged fatty acid complexes. In terms of absolute uptake, the positively charged complex performed better than the neutral analogue reported earlier. The positively charged fatty acid complexes, prepared using [^99mTcN(PNP)]²⁺ core, seems to be better candidates for the development of myocardial metabolic tracers than their neutral counterparts. Copyright © 2010 John Wiley & Sons, Ltd.     

High-performance water-borne fluorescent acrylic-based adhesive: synthesis and application

Water-borne adhesives have immense importance in cellulose-based materials, where their durability, handling, and strength remain to be a major concern. The present work demonstrates the development of three water-borne adhesives, namely, poly(1-vinyl-2-pyrrolidone-co-acrylic acid), poly(acrylonitrile-co-acrylic acid), and poly(1-vinyl-2-pyrrolidone-co-acrylonitrile-co-acrylic acid) applicable for cellulose-based materials. These acrylic-acid based adhesives were characterized by Fourier-transform infra-red spectroscopy, thermogravimetric analysis, X-ray diffraction, gel permeation chromatography, and universal testing machine. The synthesized polymer adhesives can be stored in the powder form for a longer period, thus utilizing less space. In order to use as adhesives, suitable formulations can be prepared in water. The adhesives show thermal stability up to 300 °C. Our studies show that poly(1-vinyl-2-pyrrolidone-co-acrylonitrile-co-acrylic acid) showed higher lap shear strength (ASTM D-906) than commercially available adhesives. In addition, these adhesives, being fluorescent in nature, can be detected under UV light and thus are applicable for the detection of fractured joints of any specimen. This property also helps in anti-counterfeiting applications, thus adding further to their utility.

Synthesis and application of a water-borne fluorescent acrylic adhesive, which can be stored as a powder for long-term use.     

Self-regulated viscous channel in the nuclear pore complex

The nuclear pore complex (NPC), the sole gateway for nucleocytoplasmic exchange in eukaryotic cells, allows for the passive diffusion of small molecules and transport-receptor-facilitated translocation of signal-dependent cargo molecules. Whether small molecules passively diffuse through a single central channel or through multiple holes of a hydrogel network is a subject of debate. Additionally, whether the passive and facilitated transport systems occupy distinct or overlapping physical regions of the NPC remains unclear. Here, we directly test these models using three-dimensional super-resolution fluorescence microscopy of human cells. This approach reveals that a single viscous central channel in the NPC acts as the sole pathway for passive diffusion of various small molecules; transport receptors and their cargo complexes take distinct transport routes in the periphery, which is occluded by phenylalanine-glycine filaments. Furthermore, the passive and facilitated passageways in the NPC are closely correlated, and their conformations can be simultaneously regulated by Importin β1 (a major transport receptor) and RanGTP (a critical regulator of transport directionality). These results strongly favor a self-regulated viscous channel configuration in native NPCs over the porous hydrogel meshwork model.