Diffusion tensor imaging analysis of rheumatoid arthritis patients with neuropsychiatric features to determine the alteration of white matter integrity due to vascular events

Clinical Rheumatology - The pathophysiology of neuropsychiatric manifestations in rheumatoid arthritis is not well known. The magnetic resonance imaging of the brain in rheumatoid arthritis...     

Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association

The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease‐associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL‐like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease‐causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL.     

Flow cytometric evaluation of platelet–leukocyte conjugate stability over time: methodological implications of sample handling and processing

Journal of Thrombosis and Thrombolysis - Platelet activation and subsequent aggregation is a vital component of atherothrombosis resulting in acute myocardial infarction. Therefore, quantifying...     

Prevalence, correlates, awareness, treatment, and control of hypertension in a middle-aged urban population in Kerala

BACKGROUND: Hypertension is an important cause of cardiovascular morbidity and mortality. METHODS AND RESULTS: We conducted a cross-sectional survey of 314 middle-aged subjects (163 men; age range 40-60 years, mean 49 years) in urban Thiruvananthapuram City. Kerala, to estimate the prevalence of hypertension, examine its correlates, and assess the degree of awareness, treatment, and control of high blood pressure. Blood pressure was measured by a nurse graduate using a mercury column sphygmomanometer and a standardized technique. We used multivariable analyses to examine the sociodemographic and clinical correlates of hypertension. The overall prevalence of hypertension in our sample was 54.5% (men 56.3%, women 52.3%). The factors associated with an increased prevalence of hypertension were higher body-mass index (odds ratio for a value in the top tertile of 2.33, 95% confidence interval: 1.2-4.4), and older age (odds ratio for the age group 55-60 years of 2.65, 95% confidence interval: 1.3-5.6). An occupation involving moderate or greater physical activity was inversely associated with the prevalence of hypertension (odds ratio 0.35, 95% confidence interval 0.13-0.94). Among hypertensives, 39% were aware of the condition, while 29% were treated with blood pressure-lowering medications. Adequate control of elevated blood pressure was achieved in only 30.6% of treated hypertensives. In our community-based sample, over half of all middle-aged individuals were hypertensive, but less than a third were under treatment. Adequate control of hypertension was achieved in less than a third of the treated individuals. CONCLUSIONS: These observations re-emphasize the need for hypertension awareness programs targeting the general public and the increased use of opportunistic blood pressure screening, and underscore the importance of measures to increase the knowledge of current guidelines for the detection and treatment of hypertension among healthcare providers.     

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.

     

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.     

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).

     

Relationship of Urologic Complications With Health-Related Quality of Life and Perceived Value of Health in Men and Women With Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) Cohort

OBJECTIVE

Limited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 ± 6.6 and 50.6 ± 7.2 years and duration of diabetes was 29.5 ± 4.8 and 29.8 ± 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R).

RESULTS

In both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (≤25th percentile) were 3.01 (1.90–4.75) times greater with erectile dysfunction and 2.65 (1.68–4.18) times greater with LUTS and in women, 2.04 (1.25–3.35) times greater with sexual dysfunction and 2.71 (1.72–4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures.

CONCLUSIONS

Sexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.     

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.