Cell-free DNA in the surveillance of heart transplant rejection

BackgroundCirculating cell-free deoxyribonucleic acid (cfDNA) is promptly materializing as a highly useful tool for the surveillance of solid-organ transplant rejection. Donor-specific fraction (DF) cfDNA is a potential marker of selective donor organ injury. It is emerging as a promising analytical target in the near future. The aim of this systematic review is to throw light on the importance of cfDNA and future perspective in detecting acute rejection in heart transplantation.MethodsAn exhaustive search was carried out for this review article on the basis of literature available including scientific databases of PubMed, Embase, and ClinicalTrials.gov. The search engines were systematically explored using the search terms “cell free DNA,” “Heart transplant,” and “Rejection” from inception until August 2020, and narrative analysis was accomplished. Majority of the studies described endomyocardial biopsy-proven acute rejection as reference standard.ResultsAfter initial screening of 331 articles, 11 studies were included and discussed in detail in the present review article. Majority of the studies showed prospective designs. A firm correlation was noted between acute rejection (identified on endomyocardial biopsy) and cfDNA levels by most of the studies.ConclusionscfDNA is a promising tool to replace repeated biopsies to detect rejection. The development in the area of digital droplet polymerase chain reaction and massive parallel sequencing, along with the overall reduction in cost of sequencing with its automation, has helped establish its role in the transplant population.     

Multi-walled carbon nanotube-induced inhalation toxicity: Recognizing nano bis-demethoxy curcumin analog as an ameliorating candidate

Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity.     

Cephalometric evaluation of the pharyngeal airway space after orthognathic surgery and distraction osteogenesis of the jaw bones

Objective:

Orthognathic surgeries and distraction osteogenesis (DO) of the jaw bones cause a change in the pharyngeal airway space (PAS). The aim of our study was to evaluate the magnitude of changes occurring in the pharyngeal airway after mandibular set-back surgeries and DO of maxilla/mandible.

Materials and Methods:

The study undertaken was a retrospective cephalometric study. Subjects included in our study had undergone mandibular set-back surgery or DO of maxilla/mandible. Lateral cephalograms of the subjects taken pre-operatively (T0), immediate post-operatively (T1) and after a minimum follow-up period of 6 months (T2) were studied. The cephalograms were traced manually and the following parameters were evaluated: Surface area of the PAS, pharyngeal airway width at the level of the base of the tongue, position of the hyoid bone and the tongue. Repeated measure ANOVA test was done to assess the presence of any significant changes in the proposed parameters at T0, T1 and T2. A correlation analysis was made between the mandibular/maxillary movements and the corresponding changes in the PAS.

Results:

Surgical movements of maxilla and mandible do have an effect on the pharyngeal airway.

Conclusion:

It was clearly evident that the effects of mandibular movements on the PAS and the hyoid bone is more significant than the maxillary movements.KEY WORDS: Distraction osteogenesis, orthognathic surgery, pharyngeal airway space     

A Comparison of Continuous and Interrupted Suturing in Laparoscopic Pyeloplasty

Background:

Laparoscopic pyeloplasty is one of the most common reconstructive procedures performed by urologists. Both continuous and interrupted sutures are being practiced for ureteropelvic anastomosis. The success rate and the complications associated with the suturing technique needs evaluation. We analyzed the results from of our patients who underwent laparoscopic pyeloplasty using both techniques.

Objective:

To review the outcome differences among patients undergoing laparoscopic pyeloplasty regarding suturing technique.

Materials and Methods:

All patients who underwent laparoscopic, transperitoneal dismembered pyeloplasty of the primary pelviureteric obstruction were analyzed. The primary outcome was successful pyeloplasty, as assessed by the resolution of symptoms and T½ <10 minutes. The secondary outcomes were the complication rate and the operative parameters. The difference in the parameters was assessed by Student t test analysis.

Results:

Of the 107 patients we studied, 65 had interrupted suturing and 42 had continuous suturing. The success rate was not significantly different among the 2 groups. The mean suturing time, postoperative drainage volume, postoperative hospital stay, and total cost of the procedure were significantly less in the continuous suturing group.

Conclusion:

The continuous suturing technique is preferred over the interrupted suturing technique for laparoscopic pyeloplasty because the success rates are equal and the postoperative stay, suturing time, drain output, and cost of the procedure are better.     

Dynamical facilitation governs glassy dynamics in suspensions of colloidal ellipsoids

One of the greatest challenges in contemporary condensed matter physics is to ascertain whether the formation of glasses from liquids is fundamentally thermodynamic or dynamic in origin. Although the thermodynamic paradigm has dominated theoretical research for decades, the purely kinetic perspective of the dynamical facilitation (DF) theory has attained prominence in recent times. In particular, recent experiments and simulations have highlighted the importance of facilitation using simple model systems composed of spherical particles. However, an overwhelming majority of liquids possess anisotropy in particle shape and interactions, and it is therefore imperative to examine facilitation in complex glass formers. Here, we apply the DF theory to systems with orientational degrees of freedom as well as anisotropic attractive interactions. By analyzing data from experiments on colloidal ellipsoids, we show that facilitation plays a pivotal role in translational as well as orientational relaxation. Furthermore, we demonstrate that the introduction of attractive interactions leads to spatial decoupling of translational and rotational facilitation, which subsequently results in the decoupling of dynamical heterogeneities. Most strikingly, the DF theory can predict the existence of reentrant glass transitions based on the statistics of localized dynamical events, called excitations, whose duration is substantially smaller than the structural relaxation time. Our findings pave the way for systematically testing the DF approach in complex glass formers and also establish the significance of facilitation in governing structural relaxation in supercooled liquids.The transformation of liquids into glasses is as ubiquitous as it is enigmatic. From the formation of obsidian during volcanic eruptions (1) and fabrication of superstrong metallic glasses (2) to exotic forms of slow dynamics in crystals of colloidal dimers (3) and Janus particles (4), glass formation pervades nature, industry, and academia. A vast majority of molecular glass-forming materials exhibit anisotropy in shape and interparticle interactions, which often has a profound influence on their glassy dynamics. The rapidly expanding repertoire of chemists has made it possible to design colloidal particles of desired shape and interactions that can serve as realistic experimental analogs of these molecular liquids (5). By contrast, prominent theories like the Adam–Gibbs (6) theory, random first-order transition (RFOT) theory (7, 8), and the dynamical facilitation (DF) theory (9, 10) have been tested predominantly on spherical glass formers with isotropic interactions, which exhibit gross features of glassy dynamics, but fail to capture the nuances of vitrification in complex systems.The discovery of growing static (11–16) and dynamic (17–21) length scales appears to support the thermodynamic perspective of the Adam–Gibbs and RFOT theories. However, the growth in static length scales over the dynamical range accessible to numerical simulations is often minuscule and much smaller than the corresponding growth in dynamic length scales (21, 22). This renders any causal connection between growing static length scales and growing timescales doubtful (22). Moreover, recent simulations (23) and colloid experiments (24) have shown that growing dynamical correlations in the form of string-like cooperative motion emerge naturally within the purely kinetic approach of the DF theory. To compound matters further, facilitation is present even within the RFOT framework, albeit as a consequence of slow dynamics rather than a cause (25). Thus, although DF has been shown to exist (23, 24, 26–29), its relative importance as a mechanism of structural relaxation is still debated (30–32). The application of the DF approach to complex glass formers will therefore not only enhance our understanding of glass transitions in these systems, but also help ascertain the relevance of facilitation in governing structural relaxation.Here, we apply the DF theory to elucidate glass formation in suspensions of colloidal ellipsoids with repulsive as well as attractive interactions. The DF theory claims that structural relaxation in glass-forming liquids proceeds via a process known as dynamical facilitation, whereby localized mobile regions, termed excitations, mediate motion in neighboring regions in a manner that conserves mobility (9, 10). We first show that the notions of localized excitations and facilitated dynamics can be extended even to orientational relaxation. Next, we demonstrate that the spatial decoupling of dynamical heterogeneities (DHs) observed in colloid experiments stems from the spatial decoupling of rotational and translational facilitation. Most importantly, the DF theory can predict the existence of recently observed reentrant glass transitions (33) from the density dependence of the concentration of excitations. Our findings not only highlight the importance of facilitated dynamics in anisotropic glass formers but also reinforce the claim that, in the broader context of the glass transition, facilitation dominates structural relaxation.     

In vitro Antibacterial Activity of Aqueous and Ethanol Extracts of Aristolochia indica and Toddalia asiatica Against Multidrug-Resistant Bacteria

Bacteria have developed multidrug resistance against available antimicrobial agents. Infectious diseases caused by these multidrug-resistant bacteria are major causes of morbidity and mortality in human beings. Synthetic drugs are expensive and inadequate for the treatment of diseases, causing side effects and ineffective against multidrug-resistant bacteria. The medicinal plants are promising to have effective antimicrobial property due to presence of phytochemical compounds like alkaloids, flavanoids, tannins and phenolic compounds. The present study aimed to find the antimicrobial activity of medicinal plants against multidrug-resistant bacteria. Multidrug-resistant bacteria were identified by Kirby-Bauer disc diffusion method. Production of β-lactamases (extended spectrum β-lactamases, metallo β-lactamase and AmpC β-lactamase) were identified by combination disc method. Antibacterial activity of aqueous and ethanol extract of Aristolochia indica and Toddalia asiatica were detected by agar well diffusion assay and minimum inhibitory concentration. All bacteria used in this study showed antibiotic resistance to ≥3 antibiotics. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Vibrio cholerae were found to be positive for β-lactamase production. Ethanol extract of Aristolochia indica showed more significant antibacterial activity against multidrug-resistant bacteria than Toddalia asiatica. Ethanol extracts of Aristolochia indica and Toddalia asiatica showed minimum inhibitory concentration values of 50-100 μg/ml and 100-200 μg/ml, respectively against multidrug-resistant bacteria. From this study, it was concluded that Aristolochia indica has more potential to treat multidrug-resistant bacteria than Toddalia asiatica.     

Environmental enrichment upregulates micro‐RNA‐183 and alters acetylcholinesterase splice variants to reduce anxiety‐like behavior in the little Indian field mouse (Mus booduga)

Environmental enrichment (EE) has an influential role in reducing behavioral reactivity to stress. We previously observed that EE reduces the anxiety‐like behavior in the field mouse Mus booduga accompanied by a reduction in the expression of molecules involved in the stress pathway. In this study, we demonstrate the effect of different housing condition on regulation of micro‐RNA‐183‐SC35‐mediated splicing of acetylcholinesterase (AChE). Adult male M. booduga were captured from an agricultural field and housed under nonenriched standard conditions (SC) for 7 days and considered as directly from the wild (DW). On day 8, individuals were randomly assigned to three groups; DW, SC, and EE. The DW group's anxiety‐like behavior was assessed in the elevated plus maze (EPM) and open field test (OFT). The SC and EE groups were transferred to their respective conditions and housed for another 30 days. The mice housed in EE showed less anxiety‐like behavior on EPM and in OFT compared with DW and SC mice. Interestingly, miR‐183 expression was increased following exposure to EPM in EE mice but not in SC mice. Subsequently, the upregulated miR‐183 expression suppresses the SC35 expression and shifting of splicing from AChE‐S (synaptic) to AChE‐R (read‐through) form, whereas standard housing condition downregulate miR‐183 and induces the splicing of AChE. The upregulated AChE‐R form possibly terminates ACh transmission, which is reflected in the level of anxiety‐like behavior. Overall, the present study suggests that EE effectively regulates the miR‐183 pathway to reduce anxiety‐like behavior. © 2012 Wiley Periodicals, Inc.