Emerging evidence has shown a strong association between neuropathic pain and chronic diseases. In recent years, the treatment of neuropathic pain has attracted more attention. Natural products, such ...as capsaicin and resiniferatoxin, have been well utilized to treat this disease. In this study, we aim to compare the regulatory effects of capsaicin and resiniferatoxin on pain-related genes as well as on genes with no direct association with pain. Public transcriptomic and microarray data on gene expression in the dorsal root ganglia and genes associated with TRPV1 (+) neurons were obtained from the GEO database and then analyzed. Differentially expressed genes were selected for further functional analysis, including pathway enrichment, protein-protein interaction, and regulatory network analysis. Pain-associated genes were extracted with the reference of two pain gene databases and the effects of these two natural drugs on the pain-associated genes were measured. The results of our research indicate that as compared to capsaicin, resiniferatoxin (RTX) regulates more non pain-associated genes and has a negative impact on beneficial genes (off-targets) which are supposed to alleviate nociception and hypersensitivity by themselves. So, based on this study, we may conclude that capsaicin may be less potent when compared to RTX, but it will elicit considerably less adverse effects too. Thereby confirming that capsaicin could be used for the efficient alleviation of neuropathic pain with possibly fewer side effects.
Summary
The subspecies fastigiata of cultivated groundnut lost fresh seed dormancy (FSD) during domestication and human‐made selection. Groundnut varieties lacking FSD experience precocious seed ...germination during harvest imposing severe losses. Development of easy‐to‐use genetic markers enables early‐generation selection in different molecular breeding approaches. In this context, one recombinant inbred lines (RIL) population (ICGV 00350 × ICGV 97045) segregating for FSD was used for deploying QTL‐seq approach for identification of key genomic regions and candidate genes. Whole‐genome sequencing (WGS) data (87.93 Gbp) were generated and analysed for the dormant parent (ICGV 97045) and two DNA pools (dormant and nondormant). After analysis of resequenced data from the pooled samples with dormant parent (reference genome), we calculated delta‐SNP index and identified a total of 10,759 genomewide high‐confidence SNPs. Two candidate genomic regions spanning 2.4 Mb and 0.74 Mb on the B05 and A09 pseudomolecules, respectively, were identified controlling FSD. Two candidate genes—RING‐H2 finger protein and zeaxanthin epoxidase—were identified in these two regions, which significantly express during seed development and control abscisic acid (ABA) accumulation. QTL‐seq study presented here laid out development of a marker, GMFSD1, which was validated on a diverse panel and could be used in molecular breeding to improve dormancy in groundnut.
Prions are often considered as anomalous proteins associated primarily with disease rather than as a fundamental source of diversity within biological proteomes. Whereas this longstanding viewpoint ...has its genesis in the discovery of the original namesake prions as causative agents of several complex diseases, the underlying assumption of a strict disease basis for prions could not be further from the truth. Prions and the spectrum of functions they comprise, likely represent one of the largest paradigm shifts concerning molecular-encoded phenotypic diversity since identification of DNA as the principle molecule of heredity. The ability of prions to recruit similar proteins to alternate conformations may engender a reservoir of diversity supplementing the genetic diversity resulting from stochastic mutations of DNA and subsequent natural selection. Here we present several currently known prions and how many of their functions as well as modes of transmission are intricately linked to adaptation from an evolutionary perspective. Further, the stability of some prion conformations across generations indicates that heritable prion-based adaptation is a reality.
•A new variational fully implicit combined field scheme for fluid–body interactions.•Square cylinder with sharp corners initiates lateral edge separation at 95<Re<100.•Rounded square cylinders ...undergo only vortex-induced motion at low Re.•Motion of the basic square is vortex-induced at low Re and galloping at high Re.•Removal of the corners drastically alters the flow and vibration characteristics.
We present a fully implicit combined field scheme based on Petrov–Galerkin formulation for fluid–body interaction problems. The motion of the fluid domain is accounted by an arbitrary Lagrangian–Eulerian (ALE) strategy. The combined field scheme is more efficient than conventional monolithic schemes as it decouples the computation of ALE mesh position from the fluid–body variables. The effect of corner rounding is studied in two-dimensions for stationary as well as freely vibrating square cylinders. The cylinder shapes considered are: square with sharp corners, circle and four intermediate rounded squares generated by varying a single rounding parameter. Rounding of the corners delays the primary separation originating from the cylinder base. The secondary separation, seen solely for the basic square along its lateral edges, initiates at a Reynolds number, Re between 95 and 100. Imposition of blockage lowers the critical Re marking the onset of secondary separation. For free vibrations without damping, Re range is 100–200 and mass ratio, m∗ of each cylinder is 10. The rounded cylinders undergo vortex-induced motion alone whereas motion of the basic square is vortex-induced at low Re and galloping at high Re. The flow is periodic for vortex-induced motion and quasi-periodic for galloping. The lower branch and desynchronization characterize the response of rounded cylinders. For the square cylinder, the components of response are the lower branch, desynchronization and galloping. Removal of the sharp corners of square cylinder drastically alters the flow and vibration characteristics.
Purpose
Nasotracheal intubation (NTI) is required for surgery in oropharyngeal (OP) carcinoma patients, but it may be challenging because of distorted anatomy, mucosal congestion, and increased risk ...of bleeding. Flexible bronchoscopy (FB)-guided NTI is preferred in these cases but has limitations. In this randomized controlled study, we sought to compare C-MAC
®
D-BLADE-guided videolaryngoscopy (VL) (Karl Storz SE & Co. KG, Tuttlingen, Germany) with FB for NTI under general anesthesia in patients with OP carcinomas.
Methods
We randomized a total of 100 patients with OP carcinoma and El-Ganzouri’s risk index (EGRI) < 7 to undergo NTI under general anesthesia with FB (
n
= 50) or C-MAC D-BLADE-guided VL (
n
= 50). The primary outcome was the total intubation time. We also recorded the time to glottis view, nasal intubation difficulty scale (NIDS) score, best percentage of glottis opening score, and complications.
Results
The median interquartile range (IQR) total intubation time was shorter with VL than with FB (total intubation time, 38 26–43 sec
vs
60 52–65 sec; difference, −20 sec 95% confidence interval (CI), −27 to −11;
P
< 0.001). Similarly, the median IQR time to glottis view was shorter with VL compared to FB (8 6–9 sec
vs
22 14–25 sec; difference, −13 sec 95% CI, −17 to −10;
P
< 0.001). The median NIDS score was higher with VL (difference, 2 95% CI, 2 to 3;
P
< 0.001). The incidences of airway trauma (two cases with FB
vs
seven with VL;
P
= 0.30) and postoperative sore throat (ten cases in both groups;
P
= 0.56) were similar.
Conclusion
Compared to FB, C-MAC D-BLADE-based VL reduced the total time for nasal intubation oropharyngeal carcinoma patients, potentially representing an acceptable alternative in selected cases.
Trial registration
CTRI.nic.in (2018/11/0162830); first submitted 8 November 2018.
Pseudomonas aeruginosa is an opportunistic pathogen implicated in a myriad of infections and a leading pathogen responsible for mortality in patients with cystic fibrosis (CF). Horizontal transfers ...of genes among the microorganisms living within CF patients have led to highly virulent and multi-drug resistant strains such as the Liverpool epidemic strain of P. aeruginosa, namely the LESB58 strain that has the propensity to acquire virulence and antibiotic resistance genes. Often these genes are acquired in large clusters, referred to as "genomic islands (GIs)." To decipher GIs and understand their contributions to the evolution of virulence and antibiotic resistance in P. aeruginosa LESB58, we utilized a recursive segmentation and clustering procedure, presented here as a genome-mining tool, "GEMINI." GEMINI was validated on experimentally verified islands in the LESB58 strain before examining its potential to decipher novel islands. Of the 6062 genes in P. aeruginosa LESB58, 596 genes were identified to be resident on 20 GIs of which 12 have not been previously reported. Comparative genomics provided evidence in support of our novel predictions. Furthermore, GEMINI unraveled the mosaic structure of islands that are composed of segments of likely different evolutionary origins, and demonstrated its ability to identify potential strain biomarkers. These newly found islands likely have contributed to the hyper-virulence and multidrug resistance of the Liverpool epidemic strain of P. aeruginosa.
BACKGROUND—Although adiposity is increasingly recognized as a risk factor for atrial fibrillation (AF), the importance of epicardial fat compared with other adipose tissue depots remains uncertain. ...We sought to characterize and compare the associations of AF with epicardial fat and measures of abdominal and overall adiposity.
METHODS AND RESULTS—We conducted a meta-analysis of 63 observational studies including 352 275 individuals, comparing AF risk for 1-SD increases in epicardial fat, waist circumference, waist/hip ratio, and body mass index. A 1-SD higher epicardial fat volume was associated with a 2.6-fold higher odds of AF (odds ratio, 2.61; 95% confidence interval CI, 1.89–3.60), 2.1-fold higher odds of paroxysmal AF (odds ratio, 2.14; 95% CI, 1.45–3.16) and, 5.4-fold higher odds of persistent AF (odds ratio, 5.43; 95% CI, 3.24–9.12) compared with sinus rhythm. Likewise, a 1-SD higher epicardial fat volume was associated with 2.2-fold higher odds of persistent compared with paroxysmal AF (odds ratio, 2.19; 95% CI, 1.66–2.88). Similar associations existed for postablation, postoperative, and postcardioversion AF. In contrast, associations of abdominal and overall adiposity with AF were less extreme, with relative risks per 1-SD higher values of 1.32 (95% CI, 1.25–1.41) for waist circumference, 1.11 (95% CI, 1.08–1.14) for waist/hip ratio, and 1.22 (95% CI, 1.17–1.27) for body mass index.
CONCLUSIONS—Strong and graded associations were observed between increasing epicardial fat and AF. Moreover, the strength of associations of AF with epicardial fat is greater than for measures of abdominal or overall adiposity. Further studies are needed to assess the mechanisms and clinical relevance of epicardial fat.
Quantum dots (QDs) comprise an emerging group of materials with innumerable number of possibilities in biological research including cellular labelling. Among the leading members in this category, ...ZnSe/ZnS quantum dots (QDs) hold greater attractive possibilities in imaging primarily due to their higher biocompatibility and dispersibility. Nevertheless, the inherent toxicity of ZnSe/ZnS QDs is not yet completely explored which largely compromise most of their biomedical application potential. Strong blue emitting water soluble QDs effectively synthesized by aqueous phase route. Synthesized QDs further subjected to various optical and physicochemical characterization. Approximately 5–6 nm sized ZnSe/ZnS QDs illuminated bluish green fluorescence under UV lamp. Present study addresses possible adverse effects of ZnSe/ZnS QDs in hepatic system using HepG2 cells; which is the routinely employed in vitroliver cell model. A bundle of assays wasperformed out to reveal the cytotoxic nature of ZnSe/ZnS QDs and the mechanism behind it. Herein, absorption, distribution, metabolism, excretion and toxicity (ADME and T) of ZnSe/ZnS in mice were profiled in detail followed by intravenous (i.v.) and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight. In a short review, it could be state that ZnSe/ZnS QDs did not exhibit any significant in vivo toxicity outcome in mice.
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•Synthesis of water dispersible ZnSe/ZnS QDs•Physico-chemical characterization•Evaluation of cytoplasmic enzyme•Evaluation of organ distribution of QDs•Analysis of elements from major organs by ICP-OES
This study uses a large firm-level data set covering more than 80 countries to explore the effects of firm size, city size, and government size on perceived and experienced corruption. Four points ...summarize our main findings, which seem instructive and new. First, there is a broad structural similarity in the major determinants of perceived and experienced corruption. Second, larger firms and larger government sizes reduce the perceptions and experiences of corruption. Third, larger cities raise corruption perceptions and experience. Fourth, when the sample is limited to large cities, the corruption-lowering effect of government size loses significance throughout, while firm size loses significance in experience regressions.
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