Synthesis of highly stable γ-Fe2O3 ferrofluid dispersed in liquid paraffin,motor oil and sunflower oil for heat transfer applications

This article aims at the synthesis of highly stable γ-Fe₂O₃ magnetic nanoparticles and their ferrofluids using different base liquids such as liquid paraffin, motor oil and sunflower oil for heat transfer applications. Phase and morphology of the synthesized nanoparticles were probed using XRD, SEM and FTIR spectroscopy. The average nanoparticle size of γ-Fe₂O₃ magnetic nanoparticles was found to be 13 nm. Stability of the ferrofluids was monitored by visually observing the aggregation nature of the nanoparticles for 180 days. The ferrofluid prepared using motor oil as a base fluid exhibited high stability (for more than 1 year) and a mean enhancement of 77% in thermal conductivity at 1.5 vol% nanoparticles was observed as compared to base fluid. The viscosity of the ferrofluids was also measured and found to be 18, 38 and 8 cP at 27 °C for the liquid paraffin based, motor oil based and sunflower oil based ferrofluid, respectively.

Highly stable ferrofluid for greater enhancement of thermal conductivity.     

Should the 6-Minute Walk Test Be Stopped If Oxyhemoglobin Saturation Falls Below 80%?

Objective

To examine the occurrence of adverse events in patients undergoing assessment for pulmonary rehabilitation when a 6-minute walk test (6MWT) continues despite desaturation below 80%.

Perioperative considerations during implantation of the subcutaneous defibrillator: State-of-the-art review

The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an important tool in the armamentarium of an electrophysiologist. Multiple randomized trials over the last decade have shown that S-ICDs are as efficacious as the transvenous ICDs and eliminate complications related to vascular access. In this review, we highlight issues unique to S-ICD implantation, focusing not only on the surgical implantation procedure, but also the pre- and postimplant management of the patient.     

Identification of TMC1 as a relatively common cause for nonsyndromic hearing loss in the Saudi population

Hearing loss (HL) is the most common sensory disorder worldwide and genetic factors contribute to approximately half of congenital HL cases. HL is subject to extensive genetic heterogeneity, rendering molecular diagnosis difficult. Mutations of the transmembrane channel‐like 1 (TMC1) gene cause hearing defects in humans and mice. The precise function of TMC1 protein in the inner ear is unknown, although it is predicted to be involved in functional maturation of cochlear hair cells. TMC1 mutations result in autosomal recessive (DFNB7/11) and sometimes dominant (DFNA36) nonsyndromic HL. Mutations in TMC1 are responsible for a significant portion of HL, particularly in consanguineous populations. To evaluate the importance of TMC1 mutations in the Saudi population, we used a combination of autozygome‐guided candidate gene mutation analysis and targeted next generation sequencing in 366 families with HL previously shown to lack mutations in GJB2. We identified 12 families that carried five causative TMC1 mutations; including three novel (c.362+3A > G; c.758C > T [p.Ser253Phe]; c.1396_1398delACC [p.Asn466del]) and two reported mutations (c.100C > T [p.Arg34Ter]; c.1714G > A [p.Asp572Asn]). Each of the identified recessive mutation was classified as severe, by both age of onset and severity of HL. Similarly, consistent with the previously reported dominant variant p.Asp572Asn, the HL phenotype was progressive. Eight families in our cohort were found to share the pathogenic p.Arg34Ter mutation and linkage disequilibrium was observed between p.Arg34Ter and SNPs investigated. Our results indicate that TMC1 mutations account for about 3.3% (12/366) of Saudi HL cases and that the recurrent TMC1 mutation p.Arg34Ter is likely to be a founder mutation.     

A comparison of warfarin monitoring service models

BackgroundWarfarin-related knowledge and patient satisfaction with warfarin monitoring services are generally high with respect to anticoagulation-related care received. Providing a cost-effective warfarin monitoring service while improving warfarin-related knowledge, patient safety and satisfaction can be challenging.ObjectivesTo compare ‘post and dose' service offered by the Calderdale Royal Hospital (CRH) and ‘face-to-face’ service offered by Huddersfield Royal Infirmary (HRI) in terms of costs of service delivery, patient satisfaction, warfarin-related knowledge and safety indicators.MethodsA cross-sectional sample of 160 patients on long-term warfarin therapy from anticoagulation (outpatient) clinics at CRH and HRI using interviewer-administered data collection form. International Normalized Ratio (INR), Time in Therapeutic Range (TTR) and Variance Growth Rate (VGR) values of last 12 months and the data on costs of service delivery, knowledge and satisfaction were collected.ResultsPatients monitored at HRI had higher mean VGR value (0.35 ± 0.62 vs. 0.17 ± 0.17, p = 0.092) and slightly lower mean TTR (68.70 ± 19.43 vs. 69.63 ± 17.71, p = 0.756) compared with CRH patients. Patients monitored in ‘post and dose’ were estimated at a price of £11.06 per patient per visit and each patient in face-to-face service only cost £9.70 per visit. Patients monitored at HRI had marginally higher overall knowledge score (65.22 ± 23.29 vs. 60.31 ± 20.93, p = 0.165) and overall satisfaction score (15.59 ± 3.16 vs. 15.05 ± 3.10, p = 0.279) compared with CRH patients. A positive and significant correlation was found between patients' knowledge and patient satisfaction (r = +0.327, p = 0.001).ConclusionAlthough, HRI provided monitoring service at a slightly lower cost than CRH, patients monitored at CRH had better anticoagulation control and favourable indicators. Warfarin-related knowledge needs to be improved to achieve further improvement in quality of warfarin use.     

Human Urinary Exosomes as Innate Immune Effectors

Exosomes are small extracellular vesicles, approximately 50 nm in diameter, derived from the endocytic pathway and released by a variety of cell types. Recent data indicate a spectrum of exosomal functions, including RNA transfer, antigen presentation, modulation of apoptosis, and shedding of obsolete protein. Exosomes derived from all nephron segments are also present in human urine, where their function is unknown. Although one report suggested in vitro uptake of exosomes by renal cortical collecting duct cells, most studies of human urinary exosomes have focused on biomarker discovery rather than exosome function. Here, we report results from in-depth proteomic analyses and EM showing that normal human urinary exosomes are significantly enriched for innate immune proteins that include antimicrobial proteins and peptides and bacterial and viral receptors. Urinary exosomes, but not the prevalent soluble urinary protein uromodulin (Tamm–Horsfall protein), potently inhibited growth of pathogenic and commensal Escherichia coli and induced bacterial lysis. Bacterial killing depended on exosome structural integrity and occurred optimally at the acidic pH typical of urine from omnivorous humans. Thus, exosomes are innate immune effectors that contribute to host defense within the urinary tract.Exosomes form as intraluminal vesicles of multivesicular bodies (MVBs), contain membrane and cytoplasmic proteins, have a cytoplasmic-side inward membrane orientation, and are released intact into the extracellular space (Figure 1A). First described in maturing ovine reticulocytes,¹ exosomes are released by many cell types² and have been conventionally regarded as a vehicle for shedding obsolete protein. However, emerging evidence has revealed a variety of exosomal functions, including the intercellular transfer of membrane receptors³ and RNA,^4–6 induction of immunity,⁷ antigen presentation,⁸ modulation of bone mineralization,⁹ and antiapoptotic responses.¹⁰Open in a separate windowFigure 1.Vesicles isolated from human urine are consistent with exosomes. (A) Exosomes are derived from the endocytic pathway (1–4) forming through invagination of the limiting membrane of the MVB (3). They are released into the urinary space from renal tubular epithelial cells through fusion of the MVB with the apical plasma membrane (4). (B and C) Exosomal isolation was confirmed by the identification by negative stain EM of nanovesicles (black arrows; characteristic mean 50-nm size distribution. (D) Uromodulin (white streaks in B and dark in C; open arrows in B and C) cofractionated with exosomes but was confirmed to be extraexosomal (5 nm gold-labeled; white arrows in C). (E) Western blot confirmed the presence of known exosomal constituents in vesicle preparations but did not confirm them in precipitated protein from exosome-depleted urine. (F) Immuno-EM with 5 (TSG101 and CD63) or 15 nm (AQP2) gold particle-labeled antibodies showed vesicular residency of known exosomal constituents (arrows). Vesicles were nonpermeabilized; thus, positive staining with an anti-CD63 antibody directed against an extracellular epitope indicated the cytoplasmic side inward membrane orientation characteristic of exosomes. EDUP, exosome-depleted urine protein; HKM, human kidney membrane; MW, molecular weight; TSG101, tumour susceptibility gene 101.Nanovesicles were first shown in human urine by Kanno and colleagues¹¹ and subsequently, were shown to represent exosomes.¹² Consistent with a renal tubular epithelial origin, renal tubular epithelial cells contain MVBs at the apical surface, and urine exosomes contain apical membrane proteins from every cell type along the nephron.^13,14 The array of functions ascribed to exosomes in other tissues has kindled recent interest in the functional significance of urinary exosomes. Hogan et al.¹³ suggested interaction of exosome-like vesicles with primary cilia of renal epithelial cells, and Street and coworkers¹⁵ showed in vitro uptake of exosomes by a renal cortical collecting duct cell line, leading to speculation that exosomes may provide intrarenal proximal-to-distal transapical renal tubular epithelial signaling through RNA transfer. However, most studies on urine exosomes to date have focused on biomarker discovery, resulting in the publication of several urine exosome protein compendia.^{12,13,16–21}Published reports of the urinary exosomal proteome have limited value in illuminating the potential functions of urinary exosomes for several reasons. First, protein identification by mass spectrometry (MS) has, until recently, yielded results with unacceptably low reproducibility and high false-positive rates,^22,23 and previous reports are not free of these limitations. Second, studies have often aimed to maximize the number of protein identifications and hence, biomarker candidates rather than applying or reporting rigorous protein identification thresholds. Third, most have relied on pooled samples from up to six donors and have not reported interindividual variability or reproducibility.Here, we sought, for the first time, to ascribe functionality to human urinary exosomes. We initially performed rigorous, conservative tandem MS analysis of separate human urinary exosomal samples to allow enrichment scoring²⁴ to elucidation of urine exosomal function.     

Antidiabetic potential of triterpenoid saponin isolated from Primula denticulate

Context: Primula denticulate Sm. (Primulaceae), commonly known as drumstick primula, is traditionally used to treat diabetes and urinary disorders. In the present study, a new triterpenoid saponin was isolated. Triterpenoids generally show antidiabetic activity. Considering its traditional use and chemical nature of the molecule, the present study was designed to evaluate the antidiabetic activity.

Objective: Antidiabetic activity of triterpenoid saponin (TTS) isolated from P. denticulate.

Materials and methods: A new TTS was isolated from the leaf of P. denticulate by column chromatography on CHCl₃/MeOH (8.5:1.5) fraction. It was further characterized by using NMR, UV, and IR spectroscopic methods. Ethanol and aqueous extracts of the leaf were also prepared. Antidiabetic study for TTS, ethanol extract, and aqueous extract was carried out in streptozotocin (STZ)-induced diabetic rats at doses of 200, 1000, and 1000?mg/kg body weight, respectively. A toxicity study was also performed.

Results: Isolated new TTS molecule was characterized as 3-O[β-d-xylopyranosyl-(1?→?2)-β-d-glucopyranosyl-(1?→?4)-α-l-arabinopyranosyloxy]-16α-hydroxy-13β,28-epoxy-olean-30-al by NMR, UV, and IR spectroscopic methods. This new TTS was found to be effective in lowering blood-glucose level in the experimental rat model, thus establishing its antidiabetic property (168.8?±?4.58) when compared with disease control (258.8?±?0.60). Its LD₅₀ value was found at a dose of 2000?mg/kg. The level of insulin was restored by TTS and ethanol extract up to 31.49?µU/ml and 38.90?µU/ml, respectively, when compared with disease control (18.45?µU/ml).

Discussion and conclusion: In conclusion, 3-O[β-d-xylopyranosyl-(1?→?2)-β-d-glucopyranosyl-(1?→?4)-α-l-arabinopyranosyloxy]-16α-hydroxy-3β,28-epoxy-olean-30-al possesses potential glucose lowering properties, i.e., antidiabetic potential against STZ-induced diabetic rats.