bluuebunny/crossref_metadata_2025 huggingface dataset:
Durability of first antiretroviral treatment in HIV chronically infected patients: why change and what are the outcomes?
Authors: Moniz Patricia , Alçada Filipa , Peres Susana , Borges Fernando , Baptista Teresa , Claudia Miranda Ana , Antunes Isabel , Aldir Isabel , Ventura Fernando , Nina Jaime , Mansinho Kamal
Published: November 2014

Introduction

First antiretroviral therapy (ART) is often switched to simpler, more potent or better tolerated regimens [1, 2]. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached.

Materials and Methods

Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV‐1 and 2 infections, evaluate factors influencing ART change, second‐line ART and consequent virologic and immunologic responses. Patients had follow‐ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20).

Results

Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV‐1 infection (n=158). The mean age was 43.9 years (standard deviation±14.3), with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV‐1 patients (50%) followed by lopinavir/r (22%). In HIV‐2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5%) followed by therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann‐Whitney, Phi coefficient −0.161) and associated with the appearance of adverse reactions (p=0.04, Chi‐square). Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann‐Whitney). Patients started on ART before the year 2010 reduced the probability of inferior ART duration by 25.8%. After second‐line ART regimens, TCD4+ counts>500 cell/µL were increased by 38% and favourable virologic outcome achieved in 84%.

Conclusions

Adverse reactions were the main cause for ART switching, supporting a cautious approach when initiating regimens, particularly in older patients. All ART naive patients who changed initial therapy had favourable immunological and virologic responses.
Switching from an EFV‐based STR to a RPV‐based STR is effective, safe and improves HIV patients health status
Authors: Maggiolo Franco , Di Matteo Sergio , Bruno Giacomo , Astuti Noemi , Di Filippo Elisa , Valenti Daniela , Colombo Giorgio
Published: November 2014

Introduction

TDF/FTC/RPV has been shown effective in both naïve and PI‐pre‐treated patients. Less is known about a switch strategy in subjects receiving EFV.

Materials and Methods

We evaluated viro‐immunologic outcomes, Quality of Life (QoL) and costs of an unselected cohort of patients switching from a TDF/FTC/EFV STR (≥6 months duration) to a TDF/FTC/RPV STR. The considered outcome measures were quality‐adjusted life years (QALYs) as measured with the EQ5D questionnaire and the overall direct health costs. 64 patients with a baseline viral load<50 copies/mL were randomized to immediately switch therapy or to continue TDF/FTC/EFV for four months and then switch to TDF/FTC/RPV. Six patients in the deferred switch group did not actually change cART.

Results

Patients were mostly males (73.4%) with a mean age of 46 years, a baseline mean HIV‐RNA of 6.4 copies/mL and a mean baseline CD4 count of 588 cells/µL. For the considered follow‐up period, the mean cost per patient resulted 2,563 for TDF/FTC/RPV and 2,572 for TDF/FTC/EFV. Viremia remained undetectable and CD4 stable in all patients. Over time the mean QoL increased in the RPV arm ad slightly decreased in the EFV arm, after four months the mean per patient QALYs was 0.849 for RPV and 0.841 for EFV, respectively (Figure 1). A sharp increment of QoL was observed in the deferred‐switch arm after switch, too. VAS analysis of health status perception also increased overall from 82.78 to 83.79 due to the improvement in the RPV arm. Mean cholesterol levels improved in the RPV arm from 203 to 170 mg/dL, while an increment from 190 to 207 mg/dL was observed in the EFV arm. HDL levels lowered from 49 to 45 and rose from 53 to 54 mg/dL in the RPV and EFV arms, respectively. Triglycerides levels improved both in the RPV arm (from 138 to 112 mg/dL) and in the EFV arm (from 110 to 103 mg/dL).

Conclusions

Switching from TDF/FTC/EFV to TDF/FTC/RPV is a safe, well tolerated strategy that improves the overall health status of HIV‐treated patients. The switch does not expose patients to a risk of virologic failure due to possible PK interactions of the drugs. RPV compared to EFV proved to be cost‐effective showing lower cost and higher outcome measure values.
A clinical and pharmacokinetic study of the combination of etravirine plus raltegravir in HIV patients with expanded intolerance or resistance
Authors: Bañón Sara , Moreno Ana , Quereda Carmen , Gomez Cristina , Diaz de Santiago Alberto , Perez‐Elías María J , Moreno Santiago , Luis Casado Jose
Published: November 2014

Introduction

The combination of etravirine (ETR) plus raltegravir (RAL) could be an option for HIV patients with resistance, intolerance or important interactions with other drugs. However, there are few data on the efficacy, safety and pharmacokinetics of this dual therapy, taking into account the effect of HCV co‐infection or the possible induction of ETR in the drug metabolism of RAL.

Material and Methods

Cohort study of HIV patients initiating ETR plus RAL as dual therapy. Plasma trough levels of RAL were measured by LC/MS after at least one month on therapy.

Results

A total of 25 patients have been included in this combination since 2009. Mean age was 46 years, 72% were male, and 20 patients (80%) had HCV co‐infection (seven patients with fibrosis 3–4). Median nadir CD4+ count was 109 (60–209), and 21 patients had an HIV RNA level below 50 copies/mL. Median time on previous therapy was 473 months (IQR, 395–570), and reasons for this dual therapy was toxicity/intolerance in 19, and interactions in nine (two chemotherapy, three DAAs, two methadone, two other). After a median follow up of 722 days (473–1088: 53.3 patients‐year), there were no cases of blips or virological failure. Six patients (24%) discontinued therapy after more than 1.5 year on therapy, in four cases due to lost follow up and in two due to simplification after finishing the reason for interaction. There were no cases of liver toxicity, and only two patients increased slightly transaminases values (grade 1 and 2). Total cholesterol and triglycerides levels decrease significantly after initiation (TC, from 182 to 165 at one year; p=0.01; TG from 185 to 143 mg/dL; p=0.01). CT/HDL ratio decreases from 4.35 to 4.28 after six months. Geometric mean plasma trough level of RAL was 166 ng/mL (IQR, 40–249) and only one patient (6%) was below the in vitro IC50 of the wild type.

Conclusions

The combination of ETR plus RAL as dual therapy is effective and safe in patients with expanded intolerance or interactions. There are no significant pharmacokinetic interactions between both drugs.
Atazanavir/ritonavir monotherapy as maintenance strategy in HIV‐1 treated subjects with viral suppression: 96‐week analysis results of the MODAT study
Authors: Spagnuolo Vincenzo , Galli Laura , Bigoloni Alba , Nozza Silvia , d'Arminio Monforte Antonella , Antinori Andrea , Di Biagio Antonio , Rusconi Stefano , Guaraldi Giovanni , Di Giambenedetto Simona , Lazzarin Adriano , Castagna Antonella
Published: November 2014

Introduction

The 48‐week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r‐based triple therapy. The DSMB recommended stopping study enrollment but continuing follow‐up of enrolled patients. We present the 96‐week efficacy analysis.

Material and Methods

Multicentre, randomized, open‐label, non‐inferiority trial (non‐inferiority margin −10%). Treatment failure (TF) was defined as CVF (two consecutive HIV‐RNA >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients with CVF re‐introduced their previous NRTIs and remained in the study if HIV‐RNA <50 copies/mL within 12 weeks of re‐intensification.

Results

101 patients evaluated (Figure 1): 85% males, 21% HCV‐positive, median (IQR) age of 42 (36–48) years, baseline CD4+ 576 (447–743) cells/µL. In the 96‐week analysis (ITT; TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in the triple‐therapy arm (difference +1.3%, 95% CI −17.5–20.1). Fourteen patients in monotherapy and two in triple‐therapy arm had CVF; median HIV‐RNA was 136 (72–376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re‐intensified re‐suppressed. In monotherapy arm, TF was more frequent in HCV‐co‐infected patients (64% vs 28%; p=0.041). In the secondary analysis (ITT; re‐intensification=success), 82% (41/50) in monotherapy arm and 63% (32/51) in triple‐therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2–36.3). SAEs occurred in four (8%) patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm (one sepsis, one renal failure). Drug‐related adverse events (AEs) leading to discontinuation were three (6%) in the monotherapy arm (two AEs occurred in patients after successful re‐intensification) and 12 (23.5%) in the triple‐therapy (p=0.023).

Conclusions

Despite the small sample size, the primary 96‐week analysis showed that simplification to ATV/r monotherapy showed inferior efficacy to maintaining ATV/r triple‐therapy but appeared to be superior when re‐intensification was considered success.
Factors involved in treatment durability and immunological recovery in a cohort of HIV‐positive patients receiving atazanavir‐based regimens
Authors: Giacomelli Andrea , Oreni Letizia , Franzetti Marco , Di Cristo Valentina , Vergani Barbara , Morosi Manuela , Colella Elisa , Galli Massimo , Rusconi Stefano
Published: November 2014

Introduction

Since antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long‐term treatment.

Methods

We conducted a retrospective cohort study in HIV‐1‐positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time‐dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan‐Meier curve and Cox model.

Results

A total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV‐free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29–73) in ATV/r naïve patients, 36 months (95% CI 23–53) in unboosted ATV group and 35 months (95% CI 31–43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073–1.616 p=0.008) and patients with CD4<200 cells/µL at baseline (HR=1.433 95% CI 1.086–1.892 p=0.011) were at increased risk of regimen interruption, whereas starting therapy with a backbone containing abacavir (HR=0.725; 95% CI 0.533–0.987 p=0.041) resulted protective. In multivariate analysis no significant difference between the three regimens was observed regarding reaching a count of CD4 cells >500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852–0.982 p=0.014) and CD4<200 cells/µL at ATV start (HR=0.197; 95%CI 0.138–0.281 p<0.0001); conversely, females (HR=1.262; 95%CI 1.032–1.543 p=0.023) had a higher probability of CD4 recovery.

Conclusions

Antiretroviral regimens containing atazanavir with or without ritonavir were durable and well tolerated, an elevated viral load and CD4 <200 cells/µL at baseline resulted related to regimen discontinuation and reduced CD4 recovery.
Evaluating the Frequency, Co-occurrence, and Psychosocial Correlates of Childhood Multiple Victimization
Authors: Babchishin Lyzon K. , Romano Elisa
Published: November 2014

The current study was designed to contribute to our growing understanding of childhood multiple victimization (i.e., exposure to more than one type of victimization), which has been found to be the reality among most victimized children. Caregivers of school-aged children (N = 213) completed an online and anonymous questionnaire that assessed the victimization experiences (lifetime) and psychosocial functioning of their child, as well as collecting information on a number of socio-demographic factors. Results provide support for the ubiquitous nature of childhood multiple victimization (86.9%), as well as the common cooccurrence of lifetime victimization experiences (Mexposure= 6.58). Findings highlight the important association between victimization exposure and psychosocial functioning (e.g., anxiety, depression, aggression, posttraumatic stress). The practical and theoretical implications for the prevention of childhood victimization are also discussed.
Proteomic Analysis of Protein Deamidation
Authors: Hao Piliang , Sze Siu Kwan
Published: November 2014

Deamidation of asparagines and glutamines occurs spontaneously in proteins and results in protein degradation. Deamidation of asparaginyl residues in proteins produces a mixture of asparaginyl, n‐aspartyl, and isoaspartyl residues, which has been linked to the pathology of some neurodegenerative diseases. However, accurate proteomic analysis of deamidation is challenging since it occurs quickly during conventional proteomic sample preparation, and the co‐elution of the two resulting isomeric deamidated peptides in reversed‐phase liquid chromatography (RPLC) compromises their identification and quantification using RPLC‐MS/MS. To overcome these difficulties, a novel sample preparation protocol to minimize artificial deamidation has been developed alongside an offline RP‐ERLIC‐MS/MS (reversed‐phase chromatography fractionation followed by electrostatic repulsion‐hydrophilic interaction chromatography coupled with MS/MS) strategy to separate and quantify the three deamidation products from the same peptide on a proteome‐wide scale. These protocols are detailed in this unit. © 2014 by John Wiley & Sons, Inc.
T Cell Mediated Autoimmune Glomerular Disease in Mice
Authors: Ooi Joshua D. , Gan Poh‐Yi , Odobasic Dragana , Holdsworth Stephen R. , Kitching A. Richard
Published: November 2014

Many forms of glomerulonephritis are mediated by autoimmunity. While autoantibodies are often pathogenic, cell‐mediated immunity plays an important role in a number of forms of rapidly progressive glomerulonephritis. This unit describes the induction of cell‐mediated autoimmune glomerular disease in mice. One disease model, experimental anti‐glomerular basement membrane (GBM) disease, features autoreactivity to a well‐defined component of type IV collagen found in the GBM, α3(IV)NC1. The other models the cell‐mediated effector response in forms of renal vasculitis, where autoantibodies to myeloperoxidase result in systemic neutrophil activation, resulting in their localization to the glomerulus and the subsequent deposition of myeloperoxidase within glomerular capillaries. There, myeloperoxidase acts as a “planted” autoantigen and is recognized by effector autoreactive myeloperoxidase‐specific T cells. These models are useful both in defining mechanisms germane to the development of autoimmunity to α3(IV)NC1 and myeloperoxidase, and in dissecting the role of cell‐mediated responses in effecting glomerular injury. © 2014 by John Wiley & Sons, Inc.
Laser‐Assisted Generation of Human Induced Pluripotent Stem Cells
Authors: Liu Yang , Wu Dongmei , Lao Donglin , Peterson Cory , Hohenstein Elliott Kristi A. , Snyder Evan Y.
Published: November 2014

This unit describes a procedure for generating human induced pluripotent stem cells (hiPSCs) using the Laser‐Enabled Analysis and Processing (LEAP®) system, which combines high‐throughput cell imaging with laser‐mediated cell manipulation. Use of this system should not only improve the quality and uniformity of hiPSCs produced, but ultimately enable a more rapid, efficient, high‐throughput, and automated production process. © 2014 by John Wiley & Sons, Inc.
Laboratory Maintenance of Acinetobacter baumannii
Authors: Jacobs Anna C. , Zurawski Daniel V.
Published: November 2014

Acinetobacter baumannii has recently drawn great interest in the microbiology research community due to the increase in clinical antibiotic resistance of this organism, and persistence of this bacterial species in the hospital environment. This unit outlines protocols for the growth and maintenance of A. baumannii in the laboratory. © 2014 by John Wiley & Sons, Inc.
Induktion axialer Chiralität in einem Geländer‐Oligomer durch Längendiskrepanz der Oligomerstränge
Authors: Rickhaus Michel , Bannwart Linda Maria , Neuburger Markus , Gsellinger Heiko , Zimmermann Kaspar , Häussinger Daniel , Mayor Marcel
Published: November 2014

Helikale Moleküle zeigen einzigartige physikalische Eigenschaften, die auf ihre Chiralität zurückgehen. Wir beschreiben hier einen neuen Ansatz zum Aufbau von “Geländer”‐Oligomeren durch Verbindung zweier unterschiedlich langer Oligomerstränge. Dabei windet sich ein längerer Oligobenzylether‐Strang um ein kürzeres Oligophenyl‐Rückgrat, um die Längendiskrepanz auszugleichen. Das neue Geländer‐Oligomer (1) wurde durch Umwandlungen funktioneller Gruppen und Kreuzkupplungsschritte sowie interne nukleophile Cyclisierungen aufgebaut und vollständig charakterisiert, darunter durch Röntgenstrukturanalyse. Die Isolierung der reinen Enantiomere ermöglichte die Verfolgung des Racemisierungsprozesses mittels CD‐Spektroskopie.
Amine–Boranes: Green Hypergolic Fuels with Consistently Low Ignition Delays
Authors: Ramachandran P. Veeraraghavan , Kulkarni Ameya S. , Pfeil Mark A. , Dennis Jacob D. , Willits Jared D. , Heister Stephen D. , Son Steven F. , Pourpoint Timothée L.
Published: November 2014

Complexation of amines with borane converts them to hypergols or decreases their ignition delays (IDs) multifold (with white fuming nitric acid as the oxidant). With consistently low IDs, amine–boranes represent a class of compounds that can be promising alternatives to toxic hydrazine and its derivatives as propellants. A structure–hypergolicity relationship study reveals the necessary features for the low ID.
Synthesis, Crystal Structure of the Receptor Derived from Diethoxycarbonyl Glycoluril for Aromatic Amide Guest
Authors: Zhou Baohan , Xu Baoming , Ma Li , Wang Meixi , Chen Kun , Chen Yanguo
Published: November 2014

The receptor derived from the diethoxycarbonyl glycoluril was synthesized and characterized by IR, 1H NMR, MS techniques and X‐ray single crystal analysis. Single crystal X‐ray diffraction reveals that the receptor remains monomeric because of its bulky t‐Bu groups on the side walls. Its unique binding properties for aromatic amides were studied through 1H NMR and IR techniques.
Targeting a Dynamic Protein–Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex
Authors: Douse Christopher H. , Vrielink Nina , Wenlin Zhang , Cota Ernesto , Tate Edward W.
Published: November 2014

Motility is a vital feature of the complex life cycle of Plasmodium falciparum, the apicomplexan parasite that causes human malaria. Processes such as host cell invasion are thought to be powered by a conserved actomyosin motor (containing myosin A or myoA), correct localization of which is dependent on a tight interaction with myosin A tail domain interacting protein (MTIP) at the inner membrane of the parasite. Although disruption of this protein–protein interaction represents an attractive means to investigate the putative roles of myoA‐based motility and to inhibit the parasitic life cycle, no small molecules have been identified that bind to MTIP. Furthermore, it has not been possible to obtain a crystal structure of the free protein, which is highly dynamic and unstable in the absence of its natural myoA tail partner. Herein we report the de novo identification of the first molecules that bind to and stabilize MTIP via a fragment‐based, integrated biophysical approach and structural investigations to examine the binding modes of hit compounds. The challenges of targeting such a dynamic system with traditional fragment screening workflows are addressed throughout.
Biomechanical model of the thorax under blast loading: a three dimensional numerical study
Authors: Goumtcha Aristide Awoukeng , Thoral‐Pierre Karine , Roth Sébastien
Published: November 2014

Injury mechanisms due to high speed dynamic loads, such as blasts, are not well understood. These research fields are widely investigated in the literature, both at the experimental and numerical levels, and try to answer questions about the safety and efficiency of protection devices or biomechanical traumas. At a numerical level, the development of powerful mathematical models tends to study tolerance limits and injury mechanisms in order to avoid experimental tests which cannot be easily conducted. In a military framework, developing a fighter/soldier numerical model can help to the understanding of many traumas which are specific to soldier injuries, like mines, ballistic impacts or blast traumas. The aim of this study is to investigate the consequences of violent loads in terms of human body response, submitting a developed and validated three‐dimensional thorax finite element (FE) model to blast loadings. Specific formulations of FE methods are used to simulate this loading, and its consequence on the biomechanical model. Mechanical parameters such as pressure in the air field and also in internal organs are observed, and these values are compared to the experimental data in the literature. This study gives encouraging results and allows going further in soldier trauma investigations. Copyright © 2014 John Wiley & Sons, Ltd.
Diabetes mellitus with poor glycemic control increases bladder cancer recurrence risk in patients with upper urinary tract urothelial carcinoma
Authors: Tai Yi‐Sheng , Chen Chung‐Hsin , Huang Chao‐Yuan , Tai Huai‐Chin , Wang Sho‐Mon , Pu Yeong‐Shiau
Published: November 2014

Background

The association of diabetes mellitus and bladder cancer recurrence following radical nephroureterectomies (RNUs) in patients with upper urinary tract urothelial carcinoma (UTUC) was investigated.

Methods

Between January 1996 and March 2009, 538 patients with UTUC who received RNU and had no previous bladder cancer histories were enrolled. The clinicopathological characteristics were obtained and used for the analysis of metachronous bladder recurrence by using Cox proportional hazard model.

Results

The diabetic patients (N = 104, 19.3%) were elderly (72 vs 67 years, p < 0.001) and had more hypertension (56.7 vs 34.5%, p < 0.001) as compared with non‐diabetic patients. There was no significant difference in the rest of clinicopathological characteristics between patient groups. During the median follow‐up duration of 51 months, bladder recurrences were discovered in 47.1 and 33.1% of diabetic and non‐diabetic patients with UTUC, respectively. Poorly controlled diabetic patients (HbA1c ≥ 7.0%) exhibited a shorter duration of bladder cancer recurrence‐free survival as compared with those with good glycemic controlled diabetes mellitus and without diabetes mellitus (log‐rank test, p < 0.001 and <0.001, respectively). In the multivariate analysis, male gender [hazard ratio (HR) = 1.67, p = 0.017], ureteral tumour (HR = 1.61, p = 0.020), end‐stage renal disease (HR = 2.09, p = 0.030) and diabetes mellitus with poor glycemic control (HR = 2.10, p < 0.018) independently predicted bladder recurrence after RNU.

Conclusions

Diabetes mellitus with poor glycemic control (HbA1c ≥ 7.0%) increases the risk of subsequent bladder cancer recurrence. These results underscore the need for intensive glycemic control and close follow‐up for diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous determination of electrophoretic and dielectrophoretic mobilities of human red blood cells
Authors: Zhu Xiuzhen , Chen Yi
Published: November 2014

Electrophoresis and dielectrophoresis of cells can reveal many distinct cellular properties but are often conducted separately. Herein a simultaneous strategy was proposed, and a simple method was established by making cells migrate through a cross channel under a micro video for real‐time observation. The experiment can be performed within 0.044–1 s. In combination with digital calculation based on electromagnetic theory, the method was validated to be applicable to the determination of electrophoretic and dielectrophoretic mobilities, μEP and μDEP, of human blood erythrocytes, giving μEP = −(0.87 ± 0.16)× 10−4 cm2·V−1 · s−1 and μDEP = −(4.5 ± 1.3) × 10−8 cm4·V−2·s−1 by vector decomposition, or μEP = −(0.89 ± 0.14) × 10−4 cm2·V−1 · s−1 and μDEP = −(4.6 ±1.2) × 10−8 cm4·V−2 · s−1 by least squares fitting, all agreeing with published data. Hydrodynamic and EOFs were eliminated for better measurement. It was found that the location of cells had a serious impact on the measurement precision, and the upstream of the cross channel along the electric field was chosen for precise measurement. The method is also extendable to the study of other cells and particles.
Dementia diagnostic criteria in Down syndrome
Authors: Sheehan Rory , Sinai Amanda , Bass Nick , Blatchford Pippa , Bohnen Ingrid , Bonell Simon , Courtenay Ken , Hassiotis Angela , Markar Therese , McCarthy Jane , Mukherji Kamalika , Naeem Asim , Paschos Dimitrios , Perez‐Achiaga Natalia , Sharma Vijaya , Thomas David , Walker Zuzana , Strydom Andre
Published: November 2014

Objective

Dementia is a common clinical presentation among older adults with Down syndrome. The presentation of dementia in Down syndrome differs compared with typical Alzheimer's disease. The performance of manualised dementia criteria in the International Classification of Diseases (ICD)‐10 and Diagnostic and Statistical Manual of Mental Disorders‐IV‐Text Revision (DSM‐IV‐TR) is uncertain in this population.We aimed to determine the concurrent validity and reliability of clinicians' diagnoses of dementia against ICD‐10 and DSM‐IV‐TR diagnoses. Validity of clinical diagnoses were also explored by establishing the stability of diagnoses over time.

Methods

We used clinical data from memory assessments of 85 people with Down syndrome, of whom 64 (75.3%) had a diagnosis of dementia. The cases of dementia were presented to expert raters who rated the case as dementia or no dementia using ICD‐10 and DSM‐IV‐TR criteria and their own clinical judgement.

Results

We found that clinician's judgement corresponded best with clinically diagnosed cases of dementia, identifying 84.4% cases of clinically diagnosed dementia at the time of diagnosis. ICD‐10 criteria identified 70.3% cases, and DSM‐IV‐TR criteria identified 56.3% cases at the time of clinically diagnosed dementia. Over time, the proportion of cases meeting ICD‐10 or DSM‐IV‐TR diagnoses increased, suggesting that experienced clinicians used their clinical knowledge of dementia presentation in Down syndrome to diagnose the disorder at an earlier stage than would have been possible had they relied on the classic description contained in the diagnostic systems.

Conclusions

Clinical diagnosis of dementia in Down syndrome is valid and reliable and can be used as the standard against which new criteria such as the DSM‐5 are measured. Copyright © 2014 John Wiley & Sons, Ltd.
Can We Still be Friends? The Role of Exit Conversations in Facilitating Post‐Exit Relationships
Authors: Kulik Carol T. , Rae Belinda , Sardeshmukh Shruti R. , Perera Sanjeewa
Published: November 2014

Organizations might benefit from maintaining relationships with former employees, who could be rehired later or encouraged to refer job applicants and customers. We integrate the management literature on voluntary resignations and the communication literature on relationship dissolution to explore how conversations between an exiting employee and his or her manager facilitate (or constrain) post‐exit relationships. Employees who had recently resigned from full‐time jobs described their exit experiences in semistructured interviews with the research team. The results suggest two dominant patterns. When employees exited for external reasons (e.g., to pursue a program of study), they engaged in very direct communication strategies, elicited positive responses from their managers, and left with high interest in a post‐exit relationship. But when employees exited for internal reasons (problems within the employment relationship), they engaged in multiple exit cycles and moved from indirect communication strategies toward increasingly direct ones. Managerial responses to these strategies failed to capitalize on opportunities to nurture post‐exit relationships and sometimes generated a “vendetta effect” among exiting employees. The results suggest that managers might benefit from training in how to conduct effective exit conversations, particularly with employees who are leaving for internal reasons. © 2014 Wiley Periodicals, Inc.
Investigation of Heat Transfer in Serpentine Shaped Microchannel Using Al2O3/Water Nanofluid
Authors: Sivakumar [Research scholar] A. , Alagumurthi N. , Senthilvelan T.
Published: November 2014

An experimental investigation was conducted to explore the maximum heat transfer in a serpentine shaped microchannel by varying the hydraulic diameter, flow rates and with influence of Al2O3 nanofluid. Microconvection is an important area in heat transport phenomena. Surface area is one of the important factors in high heat transfer in a microchannel heat exchanger. In this study, serpentine shaped microchannels of hydraulic diameters 810, 830, 860, and 890 μm are analyzed for the optimizing the hydraulic diameter to get enhanced thermal performance of the microchannel. A copper material microchannel having length a of 70 mm is used. Flow rate also varied from 1 lpm (Litres per minute) to 3.5 lpm for optimization with nanofluid as a medium. From numerical study it is observed that as the hydraulic diameter decreases from 890 μm to 810 μm the pressure drop increases with a decrease in hydraulic diameter. Also as heat input to the microchannel increases from 5 watts to 70 watts. From analysis it is observed that the hydraulic diameter of the microchannel is a major factor in microchannel heat transfer which is dependent on flow rate of fluid in the microchannel. The results also show that suspended Al2O3 nanoparticles in fluids have enhanced heat transfer when compared to the base fluid.
In‐vitro investigations on laser‐induced smoke generation mimicking the laparoscopic laser surgery purposes
Authors: Khoder Wael Y. , Stief Christian G. , Fiedler Sebastian , Pongratz Thomas , Beyer Wolfgang , Hennig Georg , Rühm Adrian , Sroka Ronald
Published: November 2014

Intraoperative smoke‐generation limits the quality of vision during laparoscopic/endoscopic laser‐assisted surgeries. The current study aimed at the evaluation of factors affecting this phenomenon. As a first step, a suitable experimental setup and a test tissue model were established for this investigation. The experimental setup is composed of a specific sample container, a laser therapy component suitable for the ablation of model tissue at different treatment wavelengths (λ = 980 nm, 1350 nm, 1470 nm), a suction unit providing continuous smoke extraction, and a detection unit for smoke quantification via detection of light (λ = 633 nm) scattered from smoke particles. The ablation rate (AR) was calculated by dividing the ablated volume by the ablation time (60 sec). The laser‐induced scattering signal intensity of the smoke (SI) was determined from time‐charts of the signal intensity as a measure for vision, in addition a delay‐time tdelay could be derived defining the onset of SI after the laser was switched on. The ratio SI/AR is used as a measure for smoke generation in relation to the ablation rate. Additionally the light transmission of the tissue samples was used to estimate their optical properties. In this set‐up, smoke generation using λ = 980 nm as ablation laser wavelength was detected after a delay‐time tdelay = (121.6 ± 24.8) sec which is significantly longer compared to the wavelengths λ = 1350 nm with tdelay = (89.8 ± 19.3) sec and λ = 1470 nm with tdelay = (24.7 ± 5.4) sec. Thus, the delay

Experimental set‐up consisting of sample container, laser therapy component, suction unit and scattered‐light detection compartment.

time is wavelength‐dependent. The SI/AR ratio was significantly different (p < 0.001) for 1470 nm irradiation compared to 980 nm irradiation [SI/AR(1470) = (11.8 ± 2.6) · 103 vs. SI/AR(980) = (8.6 ± 2.0) · 103]. The ablation crater for 980 nm irradiation was comparable with 1470 nm irradiation, but the coagulation rim was thicker in the 980 nm case. In conclusion, it could be shown experimentally that smoke‐generation depends on the wavelength used for laser ablation.

magnified image

Experimental set‐up consisting of sample container, laser therapy component, suction unit and scattered‐light detection compartment.

time is wavelength‐dependent. The SI/AR ratio was significantly different (p < 0.001) for 1470 nm irradiation compared to 980 nm irradiation [SI/AR(1470) = (11.8 ± 2.6) · 103 vs. SI/AR(980) = (8.6 ± 2.0) · 103]. The ablation crater for 980 nm irradiation was comparable with 1470 nm irradiation, but the coagulation rim was thicker in the 980 nm case. In conclusion, it could be shown experimentally that smoke‐generation depends on the wavelength used for laser ablation.
Clarifying and illustrating the electronic energy transfer pathways in trimeric and hexameric aggregation state of cyanobacteria allophycocyanin within the framework of Förster theory
Authors: Ren Yanliang , Melhem Osama , Li Yongjian , Chi Bo , Han Xinya , Zhu Hao , Feng Lingling , Wan Jian , Xu Xin
Published: November 2014

Within the framework of the Förster theory, the electronic excitation energy transfer pathways in the cyanobacteria allophycocyanin (APC) trimer and hexamer were studied. The associated physical quantities (i.e., excitation energy, oscillator strength, and transition dipole moments) of the phycocyanobilins (PCBs) located in APC were calculated at time‐dependent density functional theory (TDDFT) level of theory. To estimate the influence of protein environment on the preceding calculated physical quantities, the long‐range interactions were approximately considered with the polarizable continuum model at the TDDFT level of theory, and the short‐range interaction caused by surrounding aspartate residue of PCBs were taken into account as well. The shortest energy transfer time calculated in the framework of the Förster model at TDDFT/B3LYP/6–31+G* level of theory are about 0.10 ps in the APC trimer and about 170 ps in the APC monomer, which are in qualitative agreement with the experimental finding that a very fast lifetime of 0.43–0.44 ps in APC trimers, whereas its monomers lacked any corresponding lifetime. These results suggest that the lifetime of 0.43–0.44 ps in the APC trimers determined by Sharkov et al. was most likely attributed to the energy transfer of α1‐84 ↔ β3‐84 (0.23 ps), β1‐84 ↔ α2‐84 (0.11 ps) or β2‐84 ↔ α3‐84 (0.10 ps). So far, no experimental or theoretical energy transfer rates between two APC trimmers were reported, our calculations predict that the predominate energy transfer pathway between APC trimers is likely to occur from α3‐84 in one trimer to α5‐84 in an adjacent trimer with a rate of 32.51 ps. © 2014 Wiley Periodicals, Inc.
Protein Kinase C Inhibitor, GF109203X Attenuates Osteoclastogenesis, Bone Resorption and RANKL‐Induced NF‐κB and NFAT Activity
Authors: Yao Jun , Li Jia , Zhou Lin , Cheng Jianwen , Chim Shek Man , Zhang Ge , Quinn Julian M.W. , Tickner Jennifer , Zhao Jinmin , Xu Jiake
Published: November 2014

Osteolytic bone diseases are characterized by excessive osteoclast formation and activation. Protein kinase C (PKC)‐dependent pathways regulate cell growth, differentiation and apoptosis in many cellular systems, and have been implicated in cancer development and osteoclast formation. A number of PKC inhibitors with anti‐cancer properties have been developed, but whether they might also influence osteolysis (a common complication of bone invading cancers) is unclear. We studied the effects of the PKC inhibitor compound, GF109203X on osteoclast formation and activity, processes driven by receptor activator of NFκB ligand (RANKL). We found that GF109203X strongly and dose dependently suppresses osteoclastogenesis and osteoclast activity in RANKL‐treated primary mouse bone marrow cells. Consistent with this GF109203X reduced expression of key osteoclastic genes, including cathepsin K, calcitonin receptor, tartrate resistant acid phosphatase (TRAP) and the proton pump subunit V‐ATPase‐d2 in RANKL‐treated primary mouse bone marrow cells. Expression of these proteins is dependent upon RANKL‐induced NF‐κB and NFAT transcription factor actions; both were reduced in osteoclast progenitor populations by GF109203X treatment, notably NFATc1 levels. Furthermore, we showed that GF109203X inhibits RANKL‐induced calcium oscillation. Together, this study shows GF109203X may block osteoclast functions, suggesting that pharmacological blockade of PKC‐dependent pathways has therapeutic potential in osteolytic diseases. J. Cell. Physiol. 230: 1235–1242, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Females remate more frequently when mated with sperm‐deficient males
Authors: Friesen Christopher R. , Uhrig Emily J. , Mason Robert T.
Published: November 2014

Polyandry is a source of sexual conflict and males often try to limit female promiscuity. Consequently, male manipulation of receptivity via antiaphrodisiacs and copulatory plugs that prevent female remating can be a source of sexual conflict. This sexual conflict may be intensified when females must remate for fertility insurance. Male red‐sided garter snakes produce a large, gelatinous copulatory plug that has been proposed to 1) physically prevent remating and 2) contain an antiaphrodisiac that reduces female receptivity. These males may become sperm depleted because of their dissociated reproductive pattern. If a female mates with a sperm deficient male and is also rendered unreceptive to further mating, then this represents a serious conflict. We tested whether female remating frequency is affected when females are mated with a male that produces a sperm‐less copulatory plug. We show that females are significantly more likely to remate after mating with vasectomized males than intact males, even though vasectomized males still produce a copulatory plug. These results suggest that the ejaculate material of the plug does not contain an antiaphrodisiac. Instead, females may use sperm as a cue for post‐copulatory mate assessment and seek to remate for the direct benefit of fertility insurance if they have mated with sperm‐depleted males. J. Exp. Zool. 321A: 603–609, 2014. © 2014 Wiley Periodicals, Inc.
Effect of different tumbling marinade treatments on the water status and protein properties of prepared pork chops
Authors: Gao Tian , Li Jiaolong , Zhang Lin , Jiang Yun , Song Lei , Ma Ruixue , Gao Feng , Zhou Guanghong
Published: November 2014

BACKGROUND

Recently, in consideration of the rapidly increasing demand for meat products and the trend towards fast food consumption, the prepared boneless pork chop, as a new style of value‐added product, is cut from pork loins and welcomed by consumers after marinating or further cooking. The effect of different tumbling marinade treatments (control group, CG; conventional static marinade, SM; vacuum continuous tumbling marinade, CT; vacuum intermittent tumbling marinade, IT) on the water status and protein properties of prepared pork chops was investigated.

RESULTS

The CT treatment significantly increased T22 peak area ratio compared with other treatments (P < 0.05). Histological microstructure results showed that CT treatment significantly increased solubility of salt‐soluble proteins and decreased muscle fiber diameter compared with other treatments (P < 0.05). The net enthalpy (ΔH) of IT treatment was significantly lower than SM treatment (P < 0.05), whereas the protein denaturation temperature (Tm3) and ΔH3 of CT treatment were lower than IT treatment.

CONCLUSION

These results suggest that CT treatment was more effective in improving the water mobility and distribution, promoting the denaturation of muscle protein and accelerating the marinade efficiency of pork chops compared with other treatments. Thus CT treatment should be adopted. © 2014 Society of Chemical Industry
Comparison of various capillary electrophoretic approaches for the study of drug–protein interaction with emphasis on minimal consumption of protein sample and possibility of automation†
Authors: Michalcová Lenka , Glatz Zdeněk
Published: November 2014

The binding ability of a drug to plasma proteins influences the pharmacokinetics of a drug. As a result, it is a very important issue in new drug development. In this study, affinity capillary electrophoresis, capillary electrophoresis with frontal analysis, and Hummel Dreyer methods with internal and external calibration were used to study the affinity between bovine serum albumin and salicylic acid. The binding constant was measured by all these approaches including the equilibrium dialysis, which is considered to be a reference method. The comparison of results and other considerations showed the best electrophoretic approach to be capillary electrophoresis‐frontal analysis, which is characterized by the high sample throughput with the possibility of automation, very small quantities of biomacromolecules, simplicity, and a short analysis time. The mechanism of complex formation was then examined by capillary electrophoresis with frontal analysis. The binding parameters were determined and the corresponding thermodynamic parameters such as Gibbs free energy ΔG0, enthalpy ΔH0, and entropy changes ΔS0 at various temperatures were calculated. The results showed that the binding of bovine serum albumin and salicylic acid was spontaneous, and that hydrogen bonding and van der Waals forces played a major role in the formation of the complex.
Remote Welding of Fillet Seams
Authors: Vogl Wolfgang , Oefele Florian
Published: November 2014

Scanner‐based remote welding is an established and highly efficient technique in production of car hang‐on parts and seats. However — without appropriate seam tracking — current scanner systems are constrained to welding of overlap joints only. While overlap joints are insensitive to position errors, the highly position‐critical fillet seams would allow smaller flanges and other process advantages, such as zero gap welding of galvanized material. In order to extend the application scope of remote welding to fillet seams, a fully coaxial approach for seam tracking through scan heads has been jointly developed. The system has been qualified for industrial use and implemented in serial production of BMW Mini doors.
Diode Lasers and Remote Welding
Authors: Luft Axel , Stittgen Tobias
Published: November 2014

For more than thirteen years, diode lasers are used in series body manufacturing. The first diode laser was installed for brazing tailgates in the Audi A3 in 2001. While nowadays diode lasers in car‐body construction are the industry standard for brazing, cutting and welding of aluminum and steel, a new promising technology in bodyshell work emerges: remote laser welding. What are the main advantages of this technology? What are potential applications? How can fiber‐coupled, high power diode lasers create added value in body‐in‐white (BIW) remote‐welding applications?
In vivo analysis of the vascular pattern of the superficial temporal artery based on digital subtraction angiography
Authors: Medved Fabian , Manoli Theodora , Medesan Raluca , Janghorban Esfahani Babak , Stahl Stéphane , Schaller Hans‐Eberhard , Brodoefel Harald , Ernemann Ulrike , Korn Andreas
Published: November 2014

Background

Existing anatomic descriptions of the superficial temporal artery (STA) are mainly based on cadaver studies and do not accurately reflect the in vivo situation. In this study, the anatomical course and branching pattern of the STA were analyzed with digital subtraction angiographies (DSAs).

Methods

DSAs of 93 Caucasian individuals between 16‐ and 79‐years old were retrospectively analyzed regarding the course and branching pattern of the STA as well as surgically relevant inner diameters and lengths of its main branches.

Results

In total, 11 variations in the branching pattern of the terminal STA were found. About 89% of the examined individuals demonstrated the classic variation in which the main trunk of the STA bifurcates into a single frontal and parietal branch. In 60% of cases with an existing bifurcation, the division of the main trunk of the STA was located above the zygoma. The mean inner diameters of the STA main trunk, the frontal branch and the parietal branch were 2.4 ± 0.6 mm, 1.3 ± 0.6 mm and 1.2 ± 0.4 mm, respectively. The surgically relevant “working lengths” of the frontal and parietal branches above the upper margin of the zygoma up to an inner diameter of 1 mm were 106.4 ± 62.1mm and 99.7 ± 40.9 mm, respectively.

Conclusions

The common variations of the branching pattern of the STA are described in this study. Furthermore, surgically relevant inner diameters and lengths of the main branches of the STA are determined. These findings should improve our understanding of the suitability and usefulness of the STA for various surgical procedures. © 2014 Wiley Periodicals, Inc. Microsurgery 35:380–386, 2015.