Viruses, Vol. 8, Pages 38: Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections

Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV.

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Uncovering the financial ties of advocates for cancer drug approval https://t.co/gEZpBDoSF1

Uncovering the financial ties of advocates for cancer drug approval https://t.co/gEZpBDoSF1

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Electropolymerisation dynamics of a highly conducting metallopolymer: poly-[Os(4 `-(5-(2,2 `-bithienyl))-2,2 `: 6 `, 2 ``-terpyridine)(2)](2+)

The potential, time, and concentration dependence of the potentiostatic electropolymerisation of the thienyl-substituted transition metal complex [Os(bttpy)(2)(2+)] onto platinum disk microelectrodes is reported, bttpy is 4`-(5-(2,2-bithienyl))-2,2`:6`2``-terpyridine. Oxidative electropolymerisation of the thienyl bridges is highly efficient with an electropolymerisation efficiency of 36+/-3 observed across a wide range of potentials and monomer concentrations. The osmium centres are oxidised when polymerisation proceeds and the deposited polymer is highly conducting allowing high surface coverage films, up to 6 x 10(-7) mol cm(-2), to be deposited within 60 s. SEM imaging reveals that smooth films can be produced using moderate overpotentials for electrodeposition. Significantly, diffusional mass transport controls the rate of film deposition allowing the radial diffusion field found at microelectrodes to be exploited to favour film growth co-planar with the electrode surface. The electropolymerisation rate increases approximately linearly with increasing monomer concentration from approximately 8 to 400 muM and this first-order dependence likely arises from mass transport limitations. The rate of homogeneous charge transport through potentiostatically deposited films, characterised by (DC)-C-1/2, where D is the apparent charge transport diffusion coefficient and C is the concentration of osmium centres, is 3.5+/-0.5 x 10(-7) mol cm(-1) s(-1/2) and is largely insensitive to the deposition potential, and is very similar to that previously observed for potentiodynamically deposited films. This charge transport parameter is approximately two orders of magnitude larger than those found for non-conjugated bridges and is interpreted in terms of resonant superexchange across the quaterthienyl bridge. (C) 2003 Elsevier B.V. All rights reserved.

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Self-assembly of a novel pentanuclear centred-tetrahedral silver species

The reaction of 3,6-di(2-pyridyl)-4-trimethylsilyipyridazine with silver(I) tetrafluoroborate gives the pentanuclear complex cation [Ag5L4](5+), in which the silver centres are arranged as a centred tetrahedron.

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Electrochemical probing of ground state electronic interactions in polynuclear complexes of a new heteroditopic ligand

The synthesis and electronic properties of dinuclear ([(bipy)(2)Ru(I)M(terpy)][PF6](4)(bipy = 2,2`-bipyridine, terpy = 2,2`: 6`, 2``-terpyridine; M = Ru, Os)) and trinuclear ([(bipy)(2)Ru(I)(2)M][PF6](6) M = Ru, Os, Fe, Co) complexes bridged by 4`-(2,2`-bipyridin-4-yl)-2,2`: 6`, 2``-terpyridine (I) have been investigated and are compared with those of mononuclear model complexes. The electrochemical analysis using cyclic voltammetry and differential pulse voltammetry reveals that there are no interactions in the ground state between adjacent metal centres. However, there is strong electronic communication between the 2,2`-bipyridine and 2,2`: 6``

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Chiral induction in a ribose-decorated metallostar through intrinsic and interionic diastereomeric interactions

A ribose-functionalized bpy ligand has been prepared and shown to give modest diastereomeric excesses of Lambda-[FeL3](2+) complexes; interconversion of Delta and Lambda cations is relatively fast, and in CHCl3, the favored complexes with Delta- or Lambda-TRISPHAT counterions are homochiral, (Delta(+)Delta(-)) or (Delta(+)Lambda(-)). In the case of the Delta-TRISPHAT salt, a single diastereomer is observed (de greater than or equal to 96Publisher = AMER CHEMICAL SOC

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Regioselective metal-directed self-assembly of a prototype double helical hairpin dinuclear complex

A new type of covalently linked bis(oligopyridine) ligand, 4, has been prepared with a spacer group long enough to allow the formation of double helical M2L complexes; the solid-state structure of [Cu-2(4)][PF6](3) shows regioselective formation of the ``head-to-tail`` hairpin complex. (C) 2004 Published by Elsevier B.V.

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Self-assembled monolayers of Ru/Os dinuclear complexes: probing monolayer structure and interaction energies by electrochemical means

Monolayers of [Ru(bPY)(2)(mu-1)M(2)][PF6](4) salts (M = Os, Ru; bpy = 2,2`-bipyridine, 1 = 4`-(2,2`-bipyridin-4-yl)-2,2`:6`,2``-terpyridine, tpy = 2,2`:6`,2``-terpyridine, and 2= 4`-(4-pyridyl)-2,2`:6`,2``-terpyridine) were self-assembled on platinum and investigated by fast-scan electrochemistry. The electrochemistry of the complexes in solution and confined to the surface in self-assembled monolayers (SAMs) exhibited an almost ideal behavior. Scan-rate-dependent measurements of the peak current density (j(p)) were used to determine interaction energies within the monolayer. It is shown that the tpy coordination sites of the dinuclear complexes interact more strongly within the SAM than the bipyridine-coordinated fragments. This result was supported by peak potential shifts, which are due to interaction forces in SAMs. The alignment of the rodlike complexes relative to the surface is discussed, and the results of molecular mechanics calculations indicate that the species adopt a tilted orientation.

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Formation of a [2+2]-heterotetranuclear macrocycle from reaction of a platina-homoditopic ligand with iron(II)

Reaction of 4`-(2-propyn-1-oxy)-2,2`:6`,2``-terpyridine (HC= CCH(2)Oterpy) with trans-[PtI2(PEt3)(2)] regioselectively metallates the alkyne to give trans-[Pt(C=CCH(2)Oterpy)(2)(PEt3)(2)] which, when treated with Fe(II), gives a [2 + 2]-metallocycle.

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Conducting polymers containing in-chain metal centers: electropolymerization of oligothienyl-substituted M(tpy)(2) complexes and in situ conductivity studies, M = Os(II), Ru(II)

The electropolymerization of a series of Ru and Os bis-terpyridine complexes that form rodlike polymers with bithienyl, quaterthienyl, or hexathienyl bridges has been studied. Absorption spectroscopy, scanning electron microscopy, and cyclic voltammetry have been used to characterize the monomers and resulting polymer films. The absolute dc conductivity of the quaterthienyl-bridged Ru(tpy)(2) and Os(tpy)(2) polymers is unusually large and independent of the identity of the metal center at 1.6 x 10(-3) S cm(-1). The maximum conductivity occurs at the formal potential of each redox process, which typically is observed for systems where redox conduction is the dominant charge transport mechanism. Significantly, the dc conductivity of the metal-based redox couple observed in these polymers is 2 orders of magnitude higher than that of a comparable nonconjugated system.

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Conformational analysis of self-organized monolayers with scanning tunneling microscopy at near-atomic resolution

We describe the synthesis and a novel approach to the conformational analysis of 2,2`-bipyridines (bpy) bearing aromatic rich Frechet-type dendritic wedges of the first and second generation as substituents. The evaporation of solutions of these new ligands on graphite surfaces under ambient conditions results in the formation of self-organized monolayers. Scanning tunneling microscopy (STM) investigations of the monolayers under ambient conditions (air, 298 K) gave images at submolecular and near-atomic resolution. The analysis of the STM images includes the following processes: (i) identification and reproduction of potential homoconformational domains, (ii) exclusion of improper data using quality criteria for drift and feedback artifacts, (iii) compilation of running averages and checking for averaging artifacts, (iv) analysis of three-dimensional and contour plots, (v) calculation of the HOMO properties of the free molecules, and (vi) final conformational assignment based on all accessible information. Following this procedure, two different conformations could be assigned to domains observed in the monolayers of the first-gene ration (G1) and second-generation (G2) dendritic compounds. Homoconformational domains are observed side-by-side. The different conformations arise from syn or anti arrangements at the ether substituents. An additional conformational effect is found upon treating the G1 domains with HCl gas, when a partial rearrangement of the bpy from trans to cis occurs, concomitant with protonation.

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Hairpin helicates: a missing link between double-helicates and trefoil knots (pg 1168, 2005)

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Erratum

Med Princ Pract 2016;25:200

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Evaluation of Growth Hormone Stimulation Testing in Children

Abstract

Objective

To evaluate the use and interpretation of growth hormone (GH) stimulation tests used across the UK for diagnosing GH deficiency.

Background

Previous studies show poor consensus on the use of GH stimulation tests. Sex steroid priming and retesting in the transition period are areas not previously surveyed.

Design

Data were collected from tertiary paediatric endocrinologists, paediatricians with a specialist interest in endocrinology, and biochemists across the UK over six months through distributing electronic surveys.

Results

At least three different GH stimulation tests were used by 33% of departments. Glucagon and insulin doses varied most, and sampling frequency varied most using insulin. All laboratories use a recommended chemiluminescence immunoassay with an acceptable coefficient of variability. The GH peak for diagnosing GH deficiency varied from 6μg/L to 8μg/L. A wide range of clinical scenarios prompted retesting in the transition period, suggesting non-standardised current practice. Seventy-five percent of departments use sex steroid priming, but follow criteria variously combining bone age, chronological age and pubertal stage, together with variations in steroid type and dose.

Conclusions

Although a contentious diagnostic test, GH stimulation tests remain the gold standard for diagnosing GH deficiency. Our data suggest that together with variation in indication, protocol and interpretation, there is considerable variation in current practices pertaining to priming and retesting in transition. Given the current financial climate and the need for careful resource management, this study emphasises the considerable need for consensus in the investigation, diagnosis and long-term follow-up of these children, at least nationally if not internationally.

This article is protected by copyright. All rights reserved.

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Post-Gastric Bypass Hypoglycemia: A Review

Abstract

Bariatric surgery is a highly effective treatment for severe obesity, resulting in substantial weight loss and normalizing obesity-related comorbidities. However, long-term consequences can occur, such as post-bariatric surgery hypoglycemia. This is a challenging medical problem, and the number of patients presenting with it has been increasing. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it is the surgery most commonly associated with the development of post-bariatric surgery hypoglycemia. To date, the pathogenesis of this condition has not been completely established. However, various factors—particularly increased post-prandial glucagon-like peptide (GLP)-1 secretion—have been considered as crucial mediator. The mechanisms responsible for diabetic remission after bariatric surgery may be responsible for the development of hypoglycemia, which typically occurs 1–3 hours after a meal and is concurrent with inappropriate hyperinsulinemia. Carbohydrate-rich foods usually provoke hypoglycemic symptoms, which can typically be alleviated by strict dietary modifications, including carbohydrate restriction and avoidance of high-glycemic-index foods and simple sugars. Few patients require further medical intervention, such as medications, but some patients have required a pancreatectomy. Because this option is not always successful, it is no longer routinely recommended. Clinical trials are needed to further determine the pathophysiology of this condition as well as the best diagnostic and treatment approaches for these patients.

This article is protected by copyright. All rights reserved.

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Validation of a simulator for temporomandibular joint arthroscopy

Publication date: Available online 3 February 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): F. Monje Gil, C. Hernandez Vila, J.L. Moyano Cuevas, M. Lyra, J.B. Pagador, F.M. Sanchez Margallo
The traditional method of surgical training has followed the ‘observe, practice, and teach’ model, which is useful for open surgery, but is insufficient for minimally invasive surgery. This study presents the validation of a new simulator designed for TMJ arthroscopy training. A group of 10 senior maxillofacial surgeons performed an arthroscopy procedure using the simulator. They then completed a questionnaire analyzing the realism of the simulator, its utility, and the educational quality of the audiovisual software. The mean age of the 10 surgeons was 42.6 years, and they had performed a mean 151 arthroscopies. With regard to the realism of the simulator, 80% reported that it was of an appropriate size and design and 70% referred to the very realistic positions and relationships between the internal structures. Regarding its educational potential, 80% reported the simulator to be very useful for acquiring the basic skills and to acquire the sensation of depth during access to the TMJ. Finally, 90% reported the prototype to be very useful for TMJ arthroscopy training. These preliminary results showed a high degree of approval. The general opinion of the group of experts was that the experience was rewarding and inspiring, and that the prototype has the educational potential for the achievement of basic TMJ arthroscopy skills.



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The endoscopic modified Lothrop procedure: finally ready for prime time in the management of inflammatory sinus disease

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Cerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP-C

ABSTRACT

Background

Cerebellar ataxia is an exclusion criterion for the clinical diagnosis of progressive supranuclear palsy, but a variant with predominant cerebellar ataxia has been reported. The aims of this study were to estimate the frequency of progressive supranuclear palsy with predominant cerebellar ataxia in an autopsy series from the United States and to compare clinical, pathologic, and genetic differences between progressive supranuclear palsy with and without predominant cerebellar ataxia.

Method

We selected 100 consecutive patients with pathologically confirmed progressive supranuclear palsy who had been evaluated at the Mayo Clinic (referred to as the Mayo Clinic patient series) from our brain bank database (N = 1085). We next enriched in cases likely to have cerebellar ataxia by searching the remaining 985 cases for (1) an antemortem diagnosis of multiple system atrophy or (2) neuropathologic evidence of prominent degeneration of the cerebellum or cerebellar afferent nuclei. Subsequently, clinical, pathologic, and genetic features were compared between the two groups.

Results

One patient in the Mayo Clinic patient series (1%) met criteria for progressive supranuclear palsy with predominant cerebellar ataxia and had both cerebellar and mild midbrain atrophy on MRI. Four patients were identified with the targeted search. Four of the five patients were clinically misdiagnosed as multiple system atrophy. The severity of tau-related pathology and cerebellar degeneration were not different between the two groups. No differences were detected in tau genotypes.

Conclusion

Although our data cannot provide definitive information about how to make an accurate clinical diagnosis, they should serve to raise awareness of progressive supranuclear palsy with predominant cerebellar ataxia in the differential diagnosis of multiple system atrophy. © 2016 Movement Disorder Society

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Editorial

Publication date: Available online 3 February 2016
Source:Cellular Signalling
Author(s): George S. Baillie




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Role of OATP2A1 in PGE2 secretion from human colorectal cancer cells via exocytosis in response to oxidative stress

Publication date: Available online 2 February 2016
Source:Experimental Cell Research
Author(s): Taku Kasai, Takeo Nakanishi, Yasuhiro Ohno, Hiroaki Shimada, Yoshinobu Nakamura, Hiroshi Arakawa, Ikumi Tamai
Chronic inflammation induced by reactive oxygen species is associated with increased risk of developing colorectal cancer (CRC), and prostaglandin E2 (PGE2), which serves as a key mediator of inflammatory responses, plays an important role in CRC initiation and progression. Therefore, in the present study, we aimed to investigate the role of prostaglandin transporter OATP2A1/SLCO2A1 in the changes of PGE2 disposition in CRC cells in response to oxidative stress. H2O2 induced translocation of cytoplasmic OATP2A1 to plasma membranes in LoVo and COLO 320DM cells, but not in Caco-2 cells. The shift of subcellular OATP2A1 was abolished in the presence of anti-oxidant N-acetyl-l-cysteine or an inhibitor of protein kinase C, which evokes exocytosis. Exposure of LoVo cells to H2O2 caused an increase in the amount of extracellular PGE2 without changing the sum of intra- and extracellular PGE2. OATP2A1 knockdown decreased extracellular PGE2 in LoVo cells. In addition, extracellular PGE2 was significantly reduced by exocytosis inhibitor cytochalasin D, suggesting that H2O2-induced PGE2 release occurs in an exocytotic manner. Furthermore, mRNA expression of vascular endothelial growth factor (VEGF) was significantly reduced in LoVo cells by knockdown of OATP2A1. These results suggest that cytoplasmic OATP2A1 likely facilitates PGE2 loading into suitable intracellular compartment(s) for efficient exocytotic PGE2 release from CRC cells exposed to oxidative stress.

Graphical abstract

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Muir-Torre Syndrome Presenting as Sebaceous Adenocarcinoma and Invasive MSH6-Positive Colorectal Adenocarcinoma

Muir-Torre syndrome (MTS) is a rare genodermatosis, diagnosed by the presence of sebaceous neoplasms along with an internal malignancy, most commonly colorectal carcinomas. MTS is most commonly caused by microsatellite instabilities of the hMLH1 and hMSH2 mismatch repair genes, and is rarely caused by mutations of the hMSH6 gene. We describe the case of a 56-year-old male who presented with an enlarging mass on his back as well as hematochezia. The back mass was excised, and pathology confirmed microsatellite instability in MSH2 and MSH6. Abdominal CT and colonoscopy confirmed the presence of synchronous masses in the cecum, ascending colon, and the transverse colon. He refused any further workup or treatment, only to return 8 months later complaining of hematochezia and discomfort due to an enlarging mass protruding from the rectum. After consenting to surgical intervention, he agreed to outpatient chemotherapy treatment. The presence of sebaceous neoplasms should raise suspicion for the possibility of an associated internal malignancy.
Case Rep Oncol 2016;9:95-99

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Tonic-Clonic Seizure following Cytoreductive Surgery with Intraperitoneal Oxaliplatin: A Case Report and Review of the Literature

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal (IP) chemotherapy (HIPEC) is believed to improve outcomes in well-selected patients with peritoneal carcinomatosis. However, morbidity and mortality rates associated with this procedure are substantial. Here, we describe the case of a previously healthy young man who underwent CRS with hyperthermic IP oxaliplatin and developed one episode of tonic-clonic seizure on the second postoperative day.
Case Rep Oncol 2016;9:89-94

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Arsenic contamination of groundwater and its induced health effects in Shahpur block, Bhojpur district, Bihar state, India: risk evaluation

Abstract

The objective of this study was to determine the magnitude of groundwater arsenic contamination in Shahpur block of Bhojpur district, Bihar state, India and its health effects such as dermal, neurological, obstetric effects, and cancer risk. The School of Environmental Studies (SOES) collected 4704 tube-well water samples from all 88 villages of Shahpur, which were analyzed for arsenic. We found 40.3 and 21.1 % of the tube-wells had arsenic above 10 and 50 μg/l, respectively, with maximum concentration of 1805 μg/l. The study shows that 75,000, 39,000, and 10,000 people could be exposed to arsenic-contaminated water greater than 10, 50, and 300 μg/l, respectively. Our medical team examined 1422 villagers from Shahpur and registered 161 (prevalence rate, 11.3 %) with arsenical skin lesions. Arsenical skin lesions were also observed in 29 children of 525 screened. We analyzed 579 biological samples (hair, nail, and urine) from Shahpur and found that 82, 89, and 91 % of hair, nail, and urine, respectively, had arsenic above the normal levels, indicating many people in the study area are sub-clinically affected. Arsenical neuropathy was observed in 48 % of 102 arsenicosis patients. The study also found that arsenic exposed women with severe skin lesions had adversely affected their pregnancies. The carcinogenic and non-carcinogenic risks were also estimated based on the generated data. Safe drinking water supply is urgently required to combat arsenic situation in affected villages of Shahpur.

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Citric acid- and Tween ® 80-assisted phytoremediation of a co-contaminated soil: alfalfa ( Medicago sativa L.) performance and remediation potential

Abstract

A pot experiment was designed to assess the phytoremediation potential of alfalfa (Medicago sativa L.) in a co-contaminated (i.e., heavy metals and petroleum hydrocarbons) soil and the influence of citric acid and Tween^® 80 (polyethylene glycol sorbitan monooleate), applied individually and combined together, for their possible use in chemically assisted phytoremediation. The results showed that alfalfa plants could tolerate and grow in a co-contaminated soil. Over a 90-day experimental time, shoot and root biomass increased and negligible plant mortality occurred. Heavy metals were uptaken by alfalfa to a limited extent, mostly by plant roots, and their concentration in plant tissues were in the following order: Zn > Cu > Pb. Microbial population (alkane-degrading microorganisms) and activity (lipase enzyme) were enhanced in the presence of alfalfa with rhizosphere effects of 9.1 and 1.5, respectively, after 90 days. Soil amendments did not significantly enhance plant metal concentration or total uptake. In contrast, the combination of citric acid and Tween^® 80 significantly improved alkane-degrading microorganisms (2.4-fold increase) and lipase activity (5.3-fold increase) in the rhizosphere of amended plants, after 30 days of experiment. This evidence supports a favorable response of alfalfa in terms of tolerance to a co-contaminated soil and improvement of rhizosphere microbial number and activity, additionally enhanced by the joint application of citric acid and Tween^® 80, which could be promising for future phytoremediation applications.

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Report on the fifth meeting of INRA’s national network of ecotoxicologists, ECOTOX

Abstract

The fifth meeting of INRA’s national network of ecotoxicologists took place on 25 to 27 November 2014 in Biarritz, France. The main aim of the meeting was to bring together ecotoxicologists from INRA and associated partners, providing them ample opportunity to share and discuss their latest scientific results as well as the national policy of research in ecotoxicology and to precise perspectives for the network.

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GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate

Publication date: Available online 2 February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Stephan C. Jahn, Mohamed Hassan M. Solayman, Ryan J. Lorenzo, Taimour Langaee, Peter W. Stacpoole, Margaret O. James
Dichloroacetate (DCA), commonly used to treat metabolic disorders, is under investigation as an anti-cancer therapy due to its ability to reverse the Warburg effect and induce apoptosis in tumor cells. While DCA's mechanism of action is well-studied, other factors that influence its potential as a cancer treatment have not been thoroughly investigated. Here we show that expression of glutathione transferase zeta 1 (GSTZ1), the enzyme responsible for conversion of DCA to its inactive metabolite, glyoxylate, is downregulated in liver cancer and upregulated in some breast cancers, leading to abnormal expression of the protein. The cellular concentration of chloride, an ion that influences the stability of GSTZ1 in the presence of DCA, was also found to be abnormal in tumors, with consistently higher concentrations in hepatocellular carcinoma than in surrounding non-tumor tissue. Finally, results from experiments employing two- and three-dimensional cultures of HepG2 cells, parental and transduced to express GSTZ1, demonstrate that high levels of GSTZ1 expression confers resistance to the effect of high concentrations of DCA on cell viability. These results may have important clinical implications in determining intratumoral metabolism of DCA and, consequently, appropriate oral dosing.



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Iron overload enhances human mesenchymal stromal cell growth And Hampers matrix calcification

Publication date: Available online 3 February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Adriana Borriello, Ilaria Caldarelli, Maria Carmela Speranza, Saverio Scianguetta, Annunziata Tramontano, Debora Bencivenga, Emanuela Stampone, Aide Negri, Bruno Nobili, Franco Locatelli, Silverio Perrotta, Adriana Oliva, Fulvio Della Ragione
BackgroundIron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron-overload including liver, heart, joints, endocrine glands and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed. Because of the role of bone marrow mesenchymal stromal cells (BM-MSCs) in bone turnover and hematopoiesis, iron effects on primary BM-MSCs cultures were evaluated.MethodsPrimary human BM-MSCs cultures were prepared and the effects of iron on their proliferation and differentiation were characterized by biochemical analyses and functional approaches.ResultsAddition of iron to the culture medium strongly increased BM-MSCs proliferation and induced their accelerated S-phase entry. Iron enters BM-MSCs through both transferrin-dependent and transferrin-independent mechanisms. Inducing the accumulation of cyclins E and A, the decrease of p27Kip1 and the activation of MAPK pathway. Conversely, neither apoptotic signs nor up-regulation of reactive oxygen species were observed. Iron inhibited both differentiation of BM-MSCs into osteoblasts and in vitro matrix calcification. These effects result from the merging of inhibitory activities on BM-MSCs osteoblastic commitment and on the ordered matrix calcification process.ConclusionsWe demonstrated that BM-MSCs are a target of iron overload. Iron accelerates BM-MSCs proliferation and affects BM-MSCs osteoblastic commitment, hampering matrix calcification.General SignificanceOur study reports, for the first time, that iron, at concentration found in overloaded patient sera, stimulates the growth of BM-MSCs, the BM multipotent stromal cell component. Moreover, iron modulates the physiological differentiation of these cells, affecting bone turnover and remodeling.



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Occludin deficiency promotes ethanol-induced disruption of colonic epithelial junctions, gut barrier dysfunction and liver damage in mice

Publication date: April 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 4
Author(s): Hina Mir, Avtar S. Meena, Kamaljit K. Chaudhry, Pradeep K. Shukla, Ruchika Gangwar, Bhargavi Manda, Mythili K. Padala, Le Shen, Jerrold R. Turner, Paula Dietrich, Ioannis Dragatsis, RadhaKrishna Rao
BackgroundDisruption of epithelial tight junctions (TJ), gut barrier dysfunction and endotoxemia play crucial role in the pathogenesis of alcoholic tissue injury. Occludin, a transmembrane protein of TJ, is depleted in colon by alcohol. However, it is unknown whether occludin depletion influences alcoholic gut and liver injury.MethodsWild type (WT) and occludin deficient (Ocln^−/−) mice were fed 1–6% ethanol in Lieber–DeCarli diet. Gut permeability was measured by vascular-to-luminal flux of FITC-inulin. Junctional integrity was analyzed by confocal microscopy. Liver injury was assessed by plasma transaminase, histopathology and triglyceride analyses. The effect of occludin depletion on acetaldehyde-induced TJ disruption was confirmed in Caco-2 cell monolayers.ResultsEthanol feeding significantly reduced body weight gain in Ocln^−/− mice. Ethanol increased inulin permeability in colon of both WT and Ocln^−/− mice, but the effect was 4-fold higher in Ocln^−/− mice. The gross morphology of colonic mucosa was unaltered, but ethanol disrupted the actin cytoskeleton, induced redistribution of occludin, ZO-1, E-cadherin and β-catenin from the junctions and elevated TLR4, which was more severe in Ocln^−/− mice. Occludin knockdown significantly enhanced acetaldehyde-induced TJ disruption and barrier dysfunction in Caco-2 cell monolayers. Ethanol significantly increased liver weight and plasma transaminase activity in Ocln^−/− mice, but not in WT mice. Histological analysis indicated more severe lesions and fat deposition in the liver of ethanol-fed Ocln^−/− mice. Ethanol-induced elevation of liver triglyceride was also higher in Ocln^−/− mice.ConclusionThis study indicates that occludin deficiency increases susceptibility to ethanol-induced colonic mucosal barrier dysfunction and liver damage in mice.



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Betaine chemistry, roles, and potential use in liver disease

Publication date: Available online 2 February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Christopher R. Day, Stephen A. Kempson
Background. Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs.Scope of review. The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease.Major conclusions. A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices.General significance. The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease.



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The Usefulness of Intraoperative Cerebral C-Arm CT Angiogram for Implantation of Intracranial Depth Electrodes in Stereotactic Electroencephalography Procedure

Background: Stereotactic electroencephalography (SEEG) is an invasive diagnostic tool for localizing the epileptic zone in patients with medically refractory focal epilepsy. Despite technical and imaging advances in guiding the electrode placement, vascular injury is still one of its most serious complications. Object: To investigate the usefulness of intraoperative cerebral C-arm CT angiogram (CCTA) in avoiding intracranial hemorrhagic complications during SEEG electrode implantation. Methods: Trajectory data from 12 patients who underwent SEEG electrode implantation were studied in detail. This included an analysis of the implantation of 146 SEEG electrodes, which were guided by intraoperative CCTA, as well as the standard planning based on preoperative contrast-enhanced MRI. In addition, a prospective analysis of SEEG hemorrhagic complications using the studied methodology was performed in a total of 87 patients receiving 1,310 electrodes. Results: There was no complication related to the CCTA itself. Intraoperative CCTA entailed modification of the original trajectory based on the preoperative MRI in 27 of 146 electrode implantations (18.5%). In 10 of them, a severe vascular complication was adverted by intraoperative CCTA. The safety of this new approach was also confirmed by the analysis of postinterventional CT, which revealed a symptomatic hematoma caused by 1 single electrode out of the 1,310 implanted. Conclusions: This study showed that intraoperative CCTA in addition to preoperative MRI is useful in guiding a safer SEEG electrode implantation. The combination of both imaging modalities essentially minimizes the risk of serious hemorrhagic complications.
Stereotact Funct Neurosurg 2016;94:10-17

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Managing and Communicating Operational Workflow

Background: Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. Objective: To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). Methods: The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. Results: The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. Conclusions: The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings....

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Towards Creating the Perfect In Vitro Cell Model

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Simulation of Effective Slip and Drag in Pressure-Driven Flow on Superhydrophobic Surfaces

The flow on superhydrophobic surfaces was investigated using finite element modeling (FEM). Surfaces with different textures like grooves, square pillars, and cylinders immersed in liquid forming Cassie state were modeled. Nonslip boundary condition was assumed at solid-liquid interface while slip boundary condition was supposed at gas-liquid interface. It was found that the flow rate can be affected by the shape of the texture, the fraction of the gas-liquid area, the height of the channel, and the driving pressure gradient. By extracting the effective boundary slip from the flow rate based on a model, it was found that the shape of the textures and the fraction of the gas-liquid area affect the effective slip significantly while the height of the channel and the driving pressure gradient have no obvious effect on effective slip.

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Modeling and Characteristics Analysis for a Buck-Boost Converter in Pseudo-Continuous Conduction Mode Based on Fractional Calculus

In recent days, fractional calculus (FC) has been accepted as a novel modeling tool that can extend the descriptive power of the traditional calculus. Fractional-order descriptiveness can increase the flexibility and degrees of freedom of the model by means of fractional parameters. Based on the fact that real capacitors and inductors are “intrinsic” fractional order, fractional calculus is introduced into the modeling process to establish a fractional-order state-space averaging model of the Buck-Boost converter in pseudo-continuous conduction mode (PCCM). Orders of the model are considered as extra parameters, and these parameters have significant influences on the performance of the model. The inductor current, the inductor current ripple, the amplitude of the output voltage, and the transfer functions of the fractional-order model are all related to orders. The contrast simulation experiments are conducted to investigate the performance of integer-order and fractional-order Buck-Boost converters in PCCM. Results of numerical and circuit simulations demonstrate that the proposed theoretical analysis is effective; the fractional-order model of the Buck-Boost converter in PCCM has certain theoretical and practical significance for modeling and performance analysis of other electrical or electronic equipment.

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The IL-1β Receptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice

The cytokine interleukin-1β (IL-1β) is known to stimulate proinflammatory immune responses and impair β-cell function and viability, all critical events in the pathogenesis of type 1 diabetes (T1D). Here we evaluate the effect of SER140, a small peptide IL-1β receptor antagonist, on diabetes progression and cellular pancreatic changes in female nonobese diabetic (NOD) mice. Eight weeks of treatment with SER140 reduced the incidence of diabetes by more than 50% compared with vehicle, decreased blood glucose, and increased plasma insulin. Additionally, SER140 changed the endocrine and immune cells dynamics in the NOD mouse pancreas. Together, the data suggest that SER140 treatment postpones the onset of diabetes in female NOD mice by interfering with IL-1β activated pathways.

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Analysis of Effect of Heat Pipe Parameters in Minimising the Entropy Generation Rate

Heat transfer and fluid flow in the heat pipe system result in thermodynamic irreversibility generating entropy. The minimum entropy generation principle can be used for optimum design of flat heat pipe. The objective of the present work is to minimise the total entropy generation rate as the objective function with different parameters of the flat heat pipe subjected to some constraints. These constraints constitute the limitations on the heat transport capacity of the heat pipe. This physical nonlinear programming problem with nonlinear constraints is solved using LINGO 15.0 software, which enables finding optimum values for the independent design variables for which entropy generation is minimum. The effect of heat load, length, and sink temperature on design variables and corresponding entropy generation is studied. The second law analysis using minimum entropy generation principle is found to be effective in designing performance enhanced heat pipe.

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HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis

HCV (hepatitis C virus) is a member of the Flaviviridae family that contains a single-stranded positive-sense RNA genome of approximately 9600 bases. HCV is a major causative agent for chronic liver diseases such as steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma which are caused by multifactorial processes. Elevated levels of reactive oxygen species (ROS) are considered as a major factor contributing to HCV-associated pathogenesis. This review summarizes the mechanisms involved in formation of ROS in HCV replicating cells and describes the interference of HCV with ROS detoxifying systems. The relevance of ROS for HCV-associated pathogenesis is reviewed with a focus on the interference of elevated ROS levels with processes controlling liver regeneration. The overview about the impact of ROS for the viral life cycle is focused on the relevance of autophagy for the HCV life cycle and the crosstalk between HCV, elevated ROS levels, and the induction of autophagy.

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On the Coefficients of the Singularities of the Solution of Maxwell’s Equations near Polyhedral Edges

The solution fields of Maxwell’s equations are known to exhibit singularities near corners, crack tips, edges, and so forth of the physical domain. The structures of the singular fields are well known up to some undetermined coefficients. In two-dimensional domains with corners and cracks, the unknown coefficients are real constants. However, in three-dimensional domains the unknown coefficients are functions defined along the corresponding edges. This paper proposes explicit formulas for the computation of these coefficients in the case of two-dimensional domains with corners and three-dimensional domains with straight edges. The coefficients of the singular fields along straight edges of three-dimensional domains are represented in terms of Fourier series. The formulas presented are aimed at the numerical approximation of the coefficients of the singular fields. They can also be used for the construction of adaptive -nodal finite-element procedures for the efficient numerical treatment of Maxwell’s equations in nonsmooth domains.

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Human Breathing Rate Estimation from Radar Returns Using Harmonically Related Filters

Radar-based noncontact sensing of life sign signals is often used in safety and rescue missions during disasters such as earthquakes and avalanches and for home care applications. The radar returns obtained from a human target contain the breathing frequency along with its strong higher harmonics depending on the target’s posture. As a consequence, well understood, computationally efficient, and the most popular traditional FFT-based estimators that rely only on the strongest peak for estimates of breathing rates may be inaccurate. The paper proposes a solution for correcting the estimation errors of such single peak-based algorithms. The proposed method is based on using harmonically related comb filters over a set of all possible breathing frequencies. The method is tested on three subjects for different postures, for different distances between the radar and the subject, and for two different radar platforms: PN-UWB and phase modulated-CW (PM-CW) radars. Simplified algorithms more suitable for real-time implementation have also been proposed and compared using accuracy and computational complexity. The proposed breathing rate estimation algorithms provide a reduction of about 81% and 80% in the mean absolute error of breathing rates in comparison to the traditional FFT-based methods using strongest peak detection, for PN-UWB and PM-CW radars, respectively.

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The Mechanics of Brow-suspension Ptosis Repair: A Comparative Study of Fox Pentagon and Crawford Triangle Techniques.

Purpose: To perform quantitative analysis of the most commonly used brow-suspension configurations. Methods: The inflection positions for Fox pentagon and Crawford triangle configurations were marked on 49 healthy volunteers (male and female) and photographs taken in 3 states: "normal," "closed," and "raised." The skin marks were measured vectorially with respect to the medial canthus, and displacement changes were evaluated for "normal-to-closed" ("blinking") and from "closed-to-raised" ("eye-opening") states. The distance between a pair of inflection marks, representing the approximate path of sling configurations, were also measured and analyzed in relation to the mechanical properties of a variety of synthetic brow-suspension materials. Results: "Blinking" resulted in the greatest displacement in the medial eyelid incision, resulting in the greatest strain on the line connecting the medial eyelid and medial brow inflections. No significant differences in the strains for individual lines were found between the Fox and Crawford techniques, although the former shows a significantly lower overall strain in the whole loop than the latter. The displacements of some inflections and of the strains of a few lines differed significantly in men and women. Conclusions: Within the scope of this study, the blinking action was shown to result in the maximum strain of ~40%, which lies within the elastic region of stress-strain curves for some commonly used synthetic brow-suspension materials. No one method was statistically superior, although the Fox pentagon gave a significantly lower overall strain when the sling material was assumed to move somewhat around the inflections within a closed loop. (C) 2016 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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An Analysis of Conjunctival Map Biopsies in Sebaceous Carcinoma.

Purpose: To evaluate the need for standardized conjunctival map biopsies in periocular sebaceous carcinoma and to formulate recommendations regarding map biopsy number, location, size, and utility based on analysis of biopsy locations, results, and outcomes. Methods: Retrospective consecutive series of patients with sebaceous carcinoma treated at a tertiary care hospital from 1988 to 2013. Main outcome measures included conjunctival biopsy locations, number, size, and pathology. Results: A diffuse eyelid pattern was evident on presentation in 28/51 patients (54.9%) versus a solitary eyelid nodule in 23/51 (45.1%). Forty-five patients underwent a total of 429 conjunctival biopsies. The conjunctiva was negative in 277 specimens (64.6%), positive in 121 (28.2%), suspicious in 26 (6.1%), and nondiagnostic in 5 (1.2%). Intraepithelial conjunctival involvement was present in 36 patients (70.6%) of whom 23 (63.9%) presented with a diffuse eyelid appearance. There was no statistically significant correlation between primary tumor location and sites of positive biopsies or biopsy size. The pattern at presentation and location of primary tumor did not correlate with biopsy results. Clinical assessment regarding conjunctival involvement was incorrect in 10 of 23 patients (43.5%) with a solitary nodule. Despite primary tumor resection with clear margins confirmed on pathology, 5 of 45 (11%) patients had locally recurrent sebaceous carcinoma. Conclusions: Conjunctival biopsy size does not correlate with the presence of tumor in the biopsy. Primary tumor location and pattern of tumor at presentation do not correlate with conjunctival biopsy results. Irrespective of the clinical tumor features, standardized conjunctival map biopsies are essential in staging periocular sebaceous carcinoma. (C) 2016 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Comparison of Pharmacokinetics and Biodistribution of 10-Deacetylbaccatin III after Oral Administration as Pure Compound or in Taxus chinensis Extract: A Pilot Study

Planta Med
DOI: 10.1055/s-0035-1558207

Taxanes are a class of bioactive compounds isolated from the Taxus species. 10-Deacetylbaccatin III is one of the popular taxane compounds with antitumor activity, but the pharmacokinetic profile of this compound remains elusive. Previously, we prepared the taxane fractions from the twigs and leaves of Taxus chinensis var. mairei containing 20.4 % 10-deacetylbaccatin III. This study aimed to investigate the pharmacokinetics of 10-deacetylbaccatin III and biodistribution, and explore the potential changes when it was administered in the form of taxane extracts. A simple, sensitive, and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative determination of 10-deacetylbaccatin III in biosamples. The results showed that 10-deacetylbaccatin III, after oral dosing, displayed a quick absorption into the blood and distribution into major organs. Oral administration of 10-deacetylbaccatin III in the form of taxane mixtures led to a 16-fold increase in the systemic exposure of pure 10-deacetylbaccatin III, with the AUC0-U in the plasma increasing from 25.75 ± 11.34 to 231.36 ± 70.12 µg h/L (p < 0.0001). Moreover, the concentrations of 10-deacetylbaccatin III in major tissues were significantly enhanced when given in taxane extracts. These findings revealed pharmacokinetic interactions in the taxane components from T. chinensis var. mairei, which contributed to an enhanced systemic exposure of pharmacologically active taxanes.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Can We Be Less Radical with Surgery for Early Cervical Cancer?

Abstract

Although a rare cancer in the developed world due to the success of cervical screening programmes, cervical cancer remains one of the most common cancers diagnosed in women under the age of 35 years old. Radical hysterectomy and more recently radical trachelectomy have been highly effective in curing the majority of women with early stage disease. Many, however, are left with long-term ‘survivorship’ issues including bowel, bladder and sexual dysfunction. In view of these chronic co-morbidities, many clinicians now consider whether a less radical approach to surgery may be an option for some women. This review focuses on the current evidence for the safety of conservative surgery for early stage cervical cancer with regard to cure rates in comparison to standard management, as well as any improvement in short and long-term morbidity associated with a more conservative approach.

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Radiation Toxicity to the Cardiovascular System

Abstract

Radiation therapy is an important component of cancer treatment, and today, it is applied to approximately 50 % of malignancies, including valvular, myocardial, pericardial, coronary or peripheral vascular disease, and arrhythmias. An increased clinical suspicion and knowledge of those mechanisms is important to initiate appropriate screening for the optimal diagnosis and treatment. As the number of cancer survivors has been steadily increasing over the last decades, cardio-oncology, an evolving subspecialty of cardiology, will soon play a pivotal role in raising awareness of the increased cardiovascular risk and formulate strategies to optimally manage patients in this unique population.

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Did Ugo Foscolo suffer from chronic renal insufficiency?

Ugo Foscolo, was an Italian poet whose works rank among the masterpieces of Italian literature. Talented and well educated in philosophy, classics, and Italian literature, Foscolo gave literary expression to his ideological aspirations and to the numerous amorous experiences in odes, sonnets, plays, poems and an epistolary novel. Concurrent with his rich literary output, Foscolo’s correspondence represents a unique perspective from which to monitor his literary and political views and investigate aspects of his everyday life. Among other interesting information, one can find elements of Foscolo’s medical history which is generally unknown. Based on his testimonies we suggest that he suffered of longstanding bladder outlet obstruction presumably due to urethral stricture. In the present article we investigate the possibility that chronic bladder outlet obstruction and the consequent renal insufficiency was attributed to the death of Ugo Foscolo.

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Antibacterial activity of an acidic phospholipase A 2 (NN-XIb-PLA 2 ) from the venom of Naja naja (Indian cobra)

The resistance of bacteria against the use of conventional antibiotics has become a serious threat to public health and considering the associated side effect with antibiotics; new strategies to find and develop new molecules with novel modes of action has received grate attention in recent years. In this study, when the antibacterial potential of an acidic protein—NN-XIb-PLA 2 (Naja naja venom phospholipase A 2 fraction—XIb) of Naja naja venom was evaluated, it showed significant bactericidal action against the human pathogenic strains tested. It inhibited more effectively the gram positive bacteria like Staphylococcus aureus and Bacillus subtilis, when compared to gram negative bacteria like Escherichia coli, Vibrio cholerae, Klebsiell pneumoniae and Salmonella paratyphi. It inhibited the bacterial growth, with a MIC values ranging from 17 to 20 µg/ml. It was interesting to observe that NN-XIb-PLA 2 showed comparable antibacterial activity to the used standards antibiotics. It was found that their was a strong correlation between PLA 2 activities, hemolytic and antibacterial activity. Furthermore, it is found that in the presence of p-bromophenacyl bromide (p-BPB), there is a significant decrease in enzymatic activity and associated antibacterial activities, suggesting that a strong association exists between catalytic activity and antimicrobial effects, which thereby destabilize the membrane bilayer. These studies encourage further in dept study on molecular mechanisms of bactericidal properties of NN-XIb-PLA 2 and thereby help in development of this protein into a possible therapeutic lead molecule for treating bacterial infections.

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Formation of [2+2] diruthenium(II) metallomacrocycles from ligands containing 2,2 `: 6 `,2 ``-terpyridine domains linked through flexible polyethyleneoxy spacers

The syntheses of three ligands containing two terpy metal-binding domains linked through flexible polyethyleneoxy spacers are described. These ligands have been utilised as building blocks in a two-step process for the formation of a series of dinuclear ruthenium(II) metallomacrocycles of the type [Ru2L2](4+). Employing a two-step methodology allows the formation of homoleptic ([Ru2L2](4+)) and heteroleptic ([Ru2LL`](4+)) species in which the ligands differ in the length of the polyethyleneoxy spacer connecting each terpy motif. Homoleptic metallomacrocycles have been characterised through single crystal X-ray diffraction studies, while 2D-NMR spectroscopy has been employed for the characterisation of the heteroleptic species.

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Supramolecular self-assembly on a solid support: metal-directed complementarity

Resin immobilised (poly)-2,2`-bipyridines have been prepared and used as templates for the copper(II)- mediated assembly of alkene-functionalised 2,2`:6`,2 ``-terpyridines which undergo subsequent templated metathesis to form complementary poly-2,2`:6`,2 ``-terpyridine strands.

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Preparation and structural characterization of a dicopper prehelicate

In the reaction of 4`-(4-ethynylphenyl)-2,2`:6`,2``-terpyridine (3) with trans- [PtI2(PEt3)(2)] and CuI, ligand 3 scavenges Cu(I) and forms [Cu-2(PPh3)(2)(mu-I)(mu-3)]I, structural characterization of which shows that ligand 3 adopts a helical twist that parallels that found in related double helicates. (C) 2005 Elsevier B.V. All rights reserved.

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A case study in direct-space structure determination from powder X-ray diffraction data: Finding the hydrate structure of an organic molecule with significant conformational flexibility

The structure of the monohydrate crystalline phase of 3,5-bis((3,4,5-trimethoxybenzyl)oxy)benzyl alcohol has been determined directly from powder X-ray diffraction data using the direct-space genetic algorithm technique for structure solution followed by Rietveld refinement. This work raises several issues of a general nature concerning the assessment of results obtained in the structure determination of organic molecular solids from powder X-ray diffraction data and serves as a case study that may find wider relevance in this field.

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