Nitrogen donor ligand for capping ZnS quantum dots: a quantum chemical and toxicological insight

Nanoparticles having strong optical and electronic properties are the most widely used materials in sensor development. Since the target analyte interacts directly with the surface of the material, the choice of ligand for functionalizing the surface of the material is the key for its further applications. The functionalized surface of the material makes it suitable for required applications as it controls the size of the particle during its growth from the solution phase. Biomolecule capped nanomaterials are favourable for various applications in bio-sensing. In the present work, an attempt has been made to explore the biologically active molecule imidazole as capping agent for ZnS semiconductor nanoparticles or quantum dots (QDs). This work explores the possibility of replacing conventional thiol-zinc bonding and hence paves new pathways for biomolecules having the possibility of being efficient capping agents. Computational chemistry has been used to study the mechanism of bonding between one of the nitrogen atoms of imidazole and the zinc ion of the ZnS QDs. The quantum chemical insight not only explores the most spontaneous interaction of zinc ion and imidazole molecule so as to act as an efficient capping agent but also explains the probable bonding site for nitrogen–zinc chemistry. The tailormade Mn doped ZnS QDs are one of the most promising materials for probe and sensor development. The ZnS core having non-toxicity and the emission in longer wavelength due to manganese makes this material highly useful biologically. The aqueous route of synthesis has been employed to obtain a highly homogeneous and pure material which was further characterized by UV (Ultra Violet spectroscopy), Spectrofluorometer, Transmission Electron Microscope and X-ray Diffraction. The toxicity at the cellular and genetic levels was also investigated to prove the potential of the imidazole capped Mn doped ZnS QD as a biocompatible material.

Nanoparticles having strong optical and electronic properties are the most widely used materials in sensor development.     

Contemporary Management of Adult Intussusception: Who Needs a Resection?

Background

Surgical resection is often recommended in adults with intestinal intussusception (AI) because of its potential association with malignancy. We provide a contemporary algorithm for managing AI by focusing on the probability of discovering a lead point.

Methods

This is a retrospective study of adult patients with computed tomography (CT)-confirmed intussusception who underwent operative management of AI between 1996 and 2011 at a single academic institution.

Results

Sixty-four patients were diagnosed with AI by CT scan and then managed operatively. The incidence of colonic (CI), small bowel (SBI), and retrograde intussusception (RI) was 14, 55, and 31 %, respectively. All patients with CI had a lead point, whereas none were found among patients with RI. Some 46 % of patients with SBI had a lead point. The probability of discovering a lead point in SBI was increased by past history of malignancy (RR, 3.7, p < 0.001), a mass seen on preoperative CT scan (RR, 2.9, p = 0.005), and age over 60 years (RR, 2.2, p = 0.07).

Conclusions

A pathologic lead point is likely with CI but not with RI. Patients with SBI who are over the age of 60 years and have a history of malignancy or a mass noted on CT scan have a higher likelihood of harboring a pathologic lead point.     

The effect of uterine fibroid embolization on lower urinary tract symptoms

Introduction and hypothesis

The objective was to determine the effect of uterine fibroid embolization (UFE) on lower urinary tract symptoms (LUTS) and quality of life (QoL).

Methods

This prospective study included women with symptomatic fibroids and LUTS who underwent UFE between March 2008 and May 2010. Subjects underwent pre-procedural pelvic magnetic resonance imaging (MRI) and completed the Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), Prolapse and Incontinence Sexual Questionnaire (PISQ-12), Uterine Fibroid Symptom Quality of Life questionnaire (UFS-QoL), and a standardized 48-h bladder diary at baseline and 3 months after the procedure. Patient Global Impression of Improvement (PGI-I) assessed post-procedural patient satisfaction. The primary outcome was subjective improvement in LUTS at 3 months, as measured by a decrease in UDI-6 score. Univariate analysis, paired t test and a stepwise regression analysis were appropriately conducted.

Results

Fifty-seven patients underwent UFE and completed bladder diaries and questionnaires. At 3 months after UFE, patients reported a significant decrease in UDI-6, IIQ-7, and UFS-QoL, indicating an improvement in urinary symptoms and QoL. Bladder diaries showed a significant reduction in daytime and night-time voids. No difference was found in incontinence episodes. Uterine volume, dominant fibroid size, fibroid location, and MRI-confirmed bladder compression did not affect the difference in UDI-6 scores. In a stepwise regression model, BMI had a significant impact on the change in UDI-6 score, with a decrease of 1.18 points for each 1 unit increase in BMI.

Conclusion

Uterine fibroid embolization significantly improves LUTS and urinary-related QoL. Obesity seems to attenuate this effect.     

Protective Effect of Alpha-Melanocyte-Stimulating Hormone (α-MSH) on the Recovery of Ischemia/Reperfusion (I/R)-Induced Retinal Damage in A Rat Model

The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism—and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.     

Theory of mind and empathy in patients at an early stage of relapsing remitting multiple sclerosis

Introduction

Early after having been diagnosed with relapsing remitting multiple sclerosis (RRMS), young patients coping with the new situation require good social support and interactions. Successful social interaction is critically dependent upon the ability to understand the minds of others and their feelings. Social cognition refers to the ability to understand the mind of others. Theory of mind (ToM) defines the capability to reason about mental states of others. Empathy describes the ability to have insight into emotional stages and feelings of others. Despite the knowledge of cognitive impairment, which can have profound effects on patients daily activities and quality of life in advanced stages of multiple sclerosis, little is known concerning social cognition in early stages of RRMS.

Methods

In this analysis, tests assessing executive functions (working memory, set shifting and inhibition) and instruments measuring theory of mind (the Movie for the Assessment of Social Cognition – MASC) and empathy (Baron-Cohen's Empathy Quotient) were administered to 25 young adult patients at an early stage of RRMS and to 25 healthy controls (HC). Patients and HC were carefully matched according to intellectual level, age, gender, handedness and education. An early stage of the disease was defined as being diagnosed with RRMS in the last 2 years and having an EDSS of 2 or lower.

Results

Patients had significantly more incorrect responses (“missing”) ToM (P < 0.04). Moreover, patients showed a significantly lower level of empathy in the self-rating questionnaire (P < 0.02). Of the cognitive tests and depression, ToM and Empathy Quotient (EQ) scores were only significantly correlated with the interference score of the stroop test.

Conclusions

Our findings suggest that theory of mind and empathy are deficient even at early stages of RRMS. Deficits in theory of mind and empathy might negatively influence interpersonal relationships in patients with RRMS.     

Isolated spontaneous septal myocardial infarction

Isolated occlusion of the septal perforating branch of the left anterior descending coronary artery is extremely rare. As a result, little is known about its electrocardiographic manifestations compared with those of an anteroseptal myocardial infarction. We present the case of an isolated septal myocardial infarction with ST-segment elevation.     

Toll-Like Receptor 2 Deficiency Increases Resistance to Pseudomonas aeruginosa Pneumonia in the Setting of Sepsis-Induced Immune Dysfunction

Background.?Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host's response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. Methods.?We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild-type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2?4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. Results.?Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2?4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor α and decreased release of interleukin 10. Conclusions.?In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung.     

Multisite phosphoregulation of Cdc25 activity refines the mitotic entrance and exit switches

Cyclin-dependent kinase 1 (Cdk1) kinase dephosphorylation and activation by Cdc25 phosphatase are essential for mitotic entry. Activated Cdk1 phosphorylates Cdc25 and other substrates, further activating Cdc25 to form a positive feedback loop that drives the abrupt G2/mitosis switch. Conversely, mitotic exit requires Cdk1 inactivation and reversal of Cdk1 substrate phosphorylation. This dephosphorylation is mediated, in part, by Clp1/Cdc14, a Cdk1-antagonizing phosphatase, which reverses Cdk1 phosphorylation of itself, Cdc25, and other Cdk1 substrates. Thus, Cdc25 phosphoregulation is essential for proper G2-M transition, and its contributions to cell cycle control have been modeled based on studies using Xenopus and human cell extracts. Because cell extract systems only approximate in vivo conditions where proteins interact within dynamic cellular environments, here, we use Schizosaccharomyces pombe to characterize, both experimentally and mathematically, the in vivo contributions of Cdk1-mediated phosphorylation of Cdc25 to the mitotic transition. Through comprehensive mapping of Cdk1 phosphosites on Cdc25 and characterization of phosphomutants, we show that Cdc25 hyperphosphorylation by Cdk1 governs Cdc25 catalytic activation, the precision of mitotic entry, and unvarying cell length but not Cdc25 localization or abundance. We propose a mathematical model that explains Cdc25 regulation by Cdk1 through a distributive and disordered phosphorylation mechanism that ultrasensitively activates Cdc25. We also show that Clp1/Cdc14 dephosphorylation of Cdk1 sites on Cdc25 controls the proper timing of cell division, a mechanism that is likely due to the double negative feedback loop between Clp1/Cdc14 and Cdc25 that controls the abruptness of the mitotic exit switch.     

Lymphoid aggregates in Crohn's colitis and mucosal immunity

Under normal conditions, the colorectal mucosa exhibits small numbers of scattered lymphocytes and plasma cells in the lamina propria and only few mucosal lymphoid aggregates (MLAs). In Crohn's colitis, the number of lymphocytes and plasma cells in the lamina propria and of MLA is substantially increased. In addition, multiple lymphoid aggregates are newly formed in the submucosa (submucosal lymphoid aggregate (SLA)) and deeper. The aim of the present study was to investigate the cellular immune response in MLA, in SLA, and in the lamina propria in Crohn's colitis. Fifty-nine colorectal biopsies/surgical specimens with or without inflammatory diseases were challenged with multiple myeloma 1 (MUM1) that highlights activated T cells, committed B cells, and plasma cells (aT/cB/PC). The number of MUM1-positive aT/cB/PC per high-power field (HPF) in MLA and in SLA was significantly lower in Crohn's colitis than in controls (p?<?0.05). In contrast, the number of MUM1-positive aT/cB/PC per HPF in the lamina propria was significantly higher in Crohn's colitis and in other forms of chronic colitis than in controls (p?<?0.05). The paucity of MUM1-positive cells in MLA and in SLA in Crohn's colitis might be caused by an increased number of MUM1-negative precursors. These precursors would eventually migrate into the lamina propria to differentiate into aT/cB/PC, complying thereby with the immunological mucosal demands generated by the on-going chronic inflammation.