bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium tuberculosis of the RD
Rio
Genotype Is the Predominant Cause of Tuberculosis and Associated with Multidrug Resistance in Porto Alegre City, South Brazil
Authors: Dalla Costa Elis Regina , Lazzarini Luiz Claudio Oliveira , Perizzolo Paulo Fernado , Díaz Chyntia Acosta , Spies Fernanda S. , Costa Lucas Laux , Ribeiro Andrezza W. , Barroco Caroline , Schuh Sandra Jungblut , da Silva Pereira Marcia Aparecida , Dias Claudia F. , Gomes Harrison M. , Unis Gisela , Zaha Arnaldo , Almeida da Silva Pedro E. , Suffys Philip N. , Rossetti Maria L. R.
Published: January 2013

Spoligotyping has shown
Mycobacterium tuberculosis
strains to be composed of different lineages, and some of them are not just geographically restricted but also affect specific ethnic populations and are associated with outbreaks and drug resistance. We recently described a particular subtype within the Latin American-Mediterranean (LAM) family, called RD
Rio
, widespread in Brazil. Moreover, recent data also indicate that RD
Rio
is present in many countries on all continents and is associated with cavitary disease and multidrug resistance (MDR). To further explore the relationship between RD
Rio
and MDR, we conducted a study in a tuberculosis (TB) reference center responsible for the care of MDR patients in Rio Grande do Sul, the southernmost Brazilian state. From a collection of 237 clinical isolates, RD
Rio
alone was responsible for one-half of all MDR cases, including one large group composed of strains with identical IS
6110
-restriction fragment length polymorphism (RFLP) and having the LAM5 signature. We additionally had complete data records for 96 patients and could make comparisons between the presence and absence of RD
Rio
. No difference in clinical, radiological or laboratory features was observed, but a significantly greater number of cases with MDR were described in patients infected with an RD
Rio
strain (
P
= 0.0015). Altogether, RD
Rio
was responsible for 38% of all TB cases. These data support and confirmed previous findings that RD
Rio
is the main agent responsible for TB in Brazil and is associated with drug resistance. Considering that RD
Rio
is a globally distributed genotype, such findings raise concern about the increase in MDR in certain human populations.
The Cobas AmpliPrep/Cobas TaqMan HCV Test, Version 2.0, Real-Time PCR Assay Accurately Quantifies Hepatitis C Virus Genotype 4 RNA
Authors: Chevaliez Stéphane , Bouvier-Alias Magali , Rodriguez Christophe , Soulier Alexandre , Poveda Jean-Dominique , Pawlotsky Jean-Michel
Published: January 2013

Accurate hepatitis C virus (HCV) RNA quantification is mandatory for the management of chronic hepatitis C therapy. The first-generation Cobas AmpliPrep/Cobas TaqMan HCV test (CAP/CTM HCV) underestimated HCV RNA levels by >1-log
10
international units/ml in a number of patients infected with HCV genotype 4 and occasionally failed to detect it. The aim of this study was to evaluate the ability of the Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0 (CAP/CTM HCV v2.0), to accurately quantify HCV RNA in a large series of patients infected with different subtypes of HCV genotype 4. Group A comprised 122 patients with chronic HCV genotype 4 infection, and group B comprised 4 patients with HCV genotype 4 in whom HCV RNA was undetectable using the CAP/CTM HCV. Each specimen was tested with the third-generation branched DNA (bDNA) assay, CAP/CTM HCV, and CAP/CTM HCV v2.0. The HCV RNA level was lower in CAP/CTM HCV than in bDNA in 76.2% of cases, regardless of the HCV genotype 4 subtype. In contrast, the correlation between bDNA and CAP/CTM HCV v2.0 values was excellent. CAP/CTM HCV v2.0 accurately quantified HCV RNA levels in the presence of an A-to-T substitution at position 165 alone or combined with a G-to-A substitution at position 145 of the 5′ untranslated region of HCV genome. In conclusion, CAP/CTM HCV v2.0 accurately quantifies HCV RNA in genotype 4 clinical specimens, regardless of the subtype, and can be confidently used in clinical trials and clinical practice with this genotype.
Persistent Infection Caused by Hobi-Like Pestivirus
Authors: Decaro Nicola , Losurdo Michele , Lucente Maria Stella , Sciarretta Rossana , Mari Viviana , Larocca Vittorio , Elia Gabriella , Cavaliere Nicola , Martella Vito , Fasanella Antonio , Buonavoglia Canio
Published: January 2013

A calf persistently infected by Hobi-like pestivirus was monitored for about 6 months, displaying clinical signs typical of bovine viral diarrhea virus persistent infection and shedding the virus through all body secretions, with maximal titers detected in urine. This report provides new insights into the pathogenesis of the emerging pestivirus.
Rapid and Simultaneous Detection of
bla
KPC
and
bla
NDM
by Use of Multiplex Real-Time PCR
Authors: Milillo Michael , Kwak Yoon I. , Snesrud Erik , Waterman Paige E. , Lesho Emil , McGann Patrick
Published: January 2013

The increasing incidence of carbapenem nonsusceptibility among clinically important species is of global concern. Identification of the molecular mechanisms underlying carbapenem nonsusceptibility is critical for epidemiological investigations. In this report, we describe a real-time PCR-based assay capable of simultaneously detecting
bla
KPC
and
bla
NDM
, two of the most important carbapenemases, directly from culture in less than 90 min. The assay was validated with
bla
KPC
- and
bla
NDM
-carrying clinical isolates and demonstrated 100% concordance with the Carba NP test.
Circulating Antibodies and Macrophages as Modulators of Adenovirus Pharmacology
Authors: Khare Reeti , Hillestad Matthew L. , Xu Zhili , Byrnes Andrew P. , Barry Michael A.
Published: January 2013

Adenovirus serotype 5 (Ad5) naturally infects the liver after intravenous injection, making it a candidate for hepatocyte-directed gene transfer. While Ad5 can be efficient, most of the dose is destroyed by liver Kupffer cells before it can reach hepatocytes. In contrast, Ad5 bearing the hexon from Ad6 (Ad5/6) evades Kupffer cells. While Ad5/6 dramatically increases hepatocyte transduction in BALB/c mice, it has surprisingly little effect on C57BL/6 mice. To determine the source of this strain-specific difference, the roles of Kupffer cells, liver sinusoidal endothelial cells (LSECs), hepatocytes, scavenger receptors, clotting factors, and immunoglobulins were analyzed. The numbers of Kupffer cells and LSECs, the level of clotting factor X, and hepatocyte infectibility did not differ between different strains of mice. In contrast, high levels of immunoglobulins correlated negatively with Ad5 liver transduction in different mouse strains. Removal of immunoglobulins by use of Rag-deficient mice restored Ad5 transduction to maximal levels. Removal of Kupffer cells by predosing or by testing in colony-stimulating factor knockout mice restored Ad5 transduction in the presence of immunoglobulins. Partial reconstitution of IgM in Rag mice resulted in significant reductions in liver transduction by Ad5 but not by Ad5/6. These data suggest a role for IgM-mediated clearance of Ad5 via Kupffer cells and may explain the mechanism by which Ad5/6 evades these cells. These mechanisms may play a vital role in Ad pharmacology in animals and in humans.
Heart rate recovery and heart rate variability are unchanged in patients with coronary artery disease following 12 weeks of high-intensity interval and moderate-intensity endurance exercise training
Authors: Currie Katharine D. , Rosen Lee M. , Millar Philip J. , McKelvie Robert S. , MacDonald Maureen J.
Published: January 2013

Decreased heart rate variability and attenuated heart rate recovery following exercise are associated with an increased risk of mortality in cardiac patients. This study investigated the effects of 12 weeks of moderate-intensity endurance exercise (END) and a novel low-volume high-intensity interval exercise protocol (HIT) on measures of heart rate recovery and heart rate variability in patients with coronary artery disease (CAD). Fourteen males with CAD participated in 12 weeks of END or HIT training, each consisting of 2 supervised exercise sessions per week. END consisted of 30–50 min of continuous cycling at 60% peak power output (PPO). HIT involved ten 1-min intervals at 88% PPO separated by 1-min intervals at 10% PPO. Heart rate recovery at 1 min and 2 min was measured before and after training (pre- and post-training, respectively) using a submaximal exercise bout. Resting time and spectral and nonlinear domain measures of heart rate variability were calculated. Following 12 weeks of END and HIT, there was no change in heart rate recovery at 1 min (END, 40 ± 12 beats·min−1 vs. 37 ± 19 beats·min−1; HIT, 31 ± 8 beats·min−1 vs. 35 ± 8 beats·min−1; p ≥ 0.05 for pre- vs. post-training) or 2 min (END, 44 ± 18 beats·min−1 vs. 43 ± 19 beats·min−1; HIT, 42 ± 10 beats·min−1 vs. 50 ± 6 beats·min−1; p ≥ 0.05 for pre- vs. post-training). All heart rate variability indices were unchanged following END and HIT training. In conclusion, neither END nor HIT exercise programs elicited training-induced improvements in cardiac autonomic function in patients with CAD. The absence of improvements with training may be attributed to the optimal medical management and normative pretraining state of our sample.
Laccase–biosilica nanostructures — A miniaturized automatic approach
Authors: Passos Marieta L.C. , Lima José L.F.C. , Saraiva M. Lúcia M.F.S.
Published: January 2013

In the present work, an automatic generic tool for performing different syntheses of biosilica nanoparticles and the encapsulation of enzymes at the same time is described. Sequential injection analysis (SIA) allowed automation, since it enables the precise and exact control of fluidic manipulations as well as reaction conditions essential for achieving repeatable and reproducible hydrolysis, nucleation, and particle growth. An effective computer control of all the analytical parameters during run time ensured the testing of different templates, silicic acid precursors, and reaction conditions (flow rates, flow reversal, mixing, order of reagents added, pH, etc.) without physical reconfiguration of the flow setup. The effect of tetramethyl orthosilicate, sodium silicate, polyethylenimine, and protamine was evaluated not only for the morphology and size of obtained nanoparticles, but also for the stability and consequently the activity of laccase, the enzyme selected for this demonstration. This activity was evaluated using the spectrophotometric measurement (at 415 nm) of the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cationic radical, which results from the action of the encapsulated enzyme. The results obtained showed advantages, namely, reproducibility between all the samples used when compared with the small-scale batch-based process, and the absence of clogging due to the operational characteristics of the SIA technique. Besides the benign reaction conditions, such as ambient temperatures, physiological pH range, and aqueous solvents, this automatic procedure was shown to be a rapid, simple, and more sensitive alternative method for the enzyme immobilization that results in the physical entrapment of enzymes within silica nanospheres as they are formed.
CRITERIA FOR AN UPDATED CLASSIFICATION OF HUMAN TRANSCRIPTION FACTOR DNA-BINDING DOMAINS
Authors: WINGENDER EDGAR
Published: January 2013

By binding to cis-regulatory elements in a sequence-specific manner, transcription factors regulate the activity of nearby genes. Here, we discuss the criteria for a comprehensive classification of human TFs based on their DNA-binding domains. In particular, classification of basic leucine zipper (bZIP) and zinc finger factors is exemplarily discussed. The resulting classification can be used as a template for TFs of other biological species.
Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction
Authors: Balasubramanian Lavanya , Lo Chun-Min , Sham James S. K. , Yip Kay-Pong
Published: January 2013

It was previously demonstrated in isolated renal vascular smooth muscle cells (VSMCs) that integrin-mediated mechanotransduction triggers intracellular Ca2+ mobilization, which is the hallmark of myogenic response in VSMCs. To test directly whether integrin-mediated mechanotransduction results in the myogenic response-like behavior in renal VSMCs, cell traction force microscopy was used to monitor cell traction force when the cells were pulled with fibronectin-coated or low density lipoprotein (LDL)-coated paramagnetic beads. LDL-coated beads were used as a control for nonintegrin-mediated mechanotransduction. Pulling with LDL-coated beads increased the cell traction force by 61 ± 12% (9 cells), which returned to the prepull level after the pulling process was terminated. Pulling with noncoated beads had a minimal increase in the cell traction force (12 ± 9%, 8 cells). Pulling with fibronectin-coated beads increased the cell traction force by 56 ± 20% (7 cells). However, the cell traction force was still elevated by 23 ± 14% after the pulling process was terminated. This behavior is analogous to the changes of vascular resistance in pressure-induced myogenic response, in which vascular resistance remains elevated after myogenic constriction. Fibronectin is a native ligand for α5β1-integrins in VSMCs. Similar remanent cell traction force was found when cells were pulled with beads coated with β1-integrin antibody (Ha2/5). Activation of β1-integrin with soluble antibody also triggered variations of cell traction force and Ca2+ mobilization, which were abolished by the Src inhibitor. In conclusion, mechanical force transduced by α5β1-integrins triggered a myogenic response-like behavior in isolated renal VSMCs.
Skeletal muscle adaptation in response to mechanical stress in p130cas−/− mice
Authors: Akimoto Takayuki , Okuhira Kanako , Aizawa Katsuji , Wada Shogo , Honda Hiroaki , Fukubayashi Toru , Ushida Takashi
Published: January 2013

Mammalian skeletal muscles undergo adaptation in response to changes in the functional demands upon them, involving mechanical-stress-induced cellular signaling called “mechanotransduction.” We hypothesized that p130Cas, which is reported to act as a mechanosensor that transduces mechanical extension into cellular signaling, plays an important role in maintaining and promoting skeletal muscle adaptation in response to mechanical stress via the p38 MAPK signaling pathway. We demonstrate that muscle-specific p130Cas−/− mice express the contractile proteins normally in skeletal muscle. Furthermore, muscle-specific p130Cas−/− mice show normal mechanical-stress-induced muscle adaptation, including exercise-induced IIb-to-IIa muscle fiber type transformation and hypertrophy. Finally, we provide evidence that exercise-induced p38 MAPK signaling is not impaired by the muscle-specific deletion of p130Cas. We conclude that p130Cas plays a limited role in mechanical-stress-induced skeletal muscle adaptation.
Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis
Authors: Campanholle Gabriela , Ligresti Giovanni , Gharib Sina A. , Duffield Jeremy S.
Published: January 2013

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.
Involvement of N-type Ca2+channels in the fibrotic process of the kidney in rats
Authors: Mishima Keiichiro , Maeshima Akito , Miya Masaaki , Sakurai Noriyuki , Ikeuchi Hidekazu , Hiromura Keiju , Nojima Yoshihisa
Published: January 2013

N-type Ca2+channels are densely distributed in sympathetic nerves that innervate renal tubules. However, the role of N-type Ca2+channels in renal fibrosis remains unknown. To address this issue, we examined the difference between the effects of amlodipine (an L-type Ca2+channel blocker) and cilnidipine (a dual L/N-type Ca2+channel blocker) on fibrotic changes using a rat unilateral ureteral obstruction (UUO) model. The expression of both L-type and N-type Ca2+channels was significantly upregulated in UUO kidneys compared with that in contralateral kidneys. There were no significant differences in mean blood pressure among the rats tested. Both amlodipine and cilnidipine significantly attenuated fibrotic changes in UUO kidneys. The antifibrotic effect of cilnidipine was more potent than that of amlodipine. Amlodipine as well as cilnidipine reduced type III collagen deposition, α-smooth muscle actin (α-SMA) expression, and interstitial cell proliferation. In addition, cilnidipine significantly reduced deposition of type I collagen and macrophage infiltration in UUO kidneys. With the use of in vivo bromodeoxyuridine labeling, label-retaining cells (LRCs) were identified as a population of tubular cells that participate in epithelial-mesenchymal transition after UUO. Some LRCs migrated into the interstitium, expressed α-SMA and vimentin, and produced several extracellular matrixes in UUO kidneys. The number of interstitial LRCs was significantly decreased by cilnidipine but not amlodipine. These data suggest that N-type Ca2+channels contribute to multiple steps of renal fibrosis, and its blockade may thus be a useful therapeutic approach for prevention of renal fibrosis.
Status epilepticus enhances tonic GABA currents and depolarizes GABA reversal potential in dentate fast-spiking basket cells
Authors: Yu Jiandong , Proddutur Archana , Elgammal Fatima S. , Ito Takahiro , Santhakumar Vijayalakshmi
Published: January 2013

Temporal lobe epilepsy is associated with loss of interneurons and inhibitory dysfunction in the dentate gyrus. While status epilepticus (SE) leads to changes in granule cell inhibition, whether dentate basket cells critical for regulating granule cell feedforward and feedback inhibition express tonic GABA currents ( IGABA) and undergo changes in inhibition after SE is not known. We find that interneurons immunoreactive for parvalbumin in the hilar-subgranular region express GABAA receptor (GABAAR) δ-subunits, which are known to underlie tonic IGABA. Dentate fast-spiking basket cells (FS-BCs) demonstrate baseline tonic IGABA blocked by GABAAR antagonists. In morphologically and physiologically identified FS-BCs, tonic IGABA is enhanced 1 wk after pilocarpine-induced SE, despite simultaneous reduction in spontaneous inhibitory postsynaptic current (sIPSC) frequency. Amplitude of tonic IGABA in control and post-SE FS-BCs is enhanced by 4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3-ol (THIP), demonstrating the contribution of GABAAR δ-subunits. Whereas FS-BC resting membrane potential is unchanged after SE, perforated-patch recordings from FS-BCs show that the reversal potential for GABA currents ( EGABA) is depolarized after SE. In model FS-BCs, increasing tonic GABA conductance decreased excitability when EGABA was shunting and increased excitability when EGABA was depolarizing. Although simulated focal afferent activation evoked seizurelike activity in model dentate networks with FS-BC tonic GABA conductance and shunting EGABA, excitability of identical networks with depolarizing FS-BC EGABA showed lower activity levels. Thus, together, post-SE changes in tonic IGABA and EGABA maintain homeostasis of FS-BC activity and limit increases in dentate excitability. These findings have implications for normal FS-BC function and can inform studies examining comorbidities and therapeutics following SE.
TOPPER: Topology Prediction of Transmembrane Protein Based on Evidential Reasoning
Authors: Deng Xinyang , Liu Qi , Hu Yong , Deng Yong
Published: January 2013

The topology prediction of transmembrane protein is a hot research field in bioinformatics and molecular biology. It is a typical pattern recognition problem. Various prediction algorithms are developed to predict the transmembrane protein topology since the experimental techniques have been restricted by many stringent conditions. Usually, these individual prediction algorithms depend on various principles such as the hydrophobicity or charges of residues. In this paper, an evidential topology prediction method for transmembrane protein is proposed based on evidential reasoning, which is called TOPPER (topology prediction of transmembrane protein based on evidential reasoning). In the proposed method, the prediction results of multiple individual prediction algorithms can be transformed into BPAs (basic probability assignments) according to the confusion matrix. Then, the final prediction result can be obtained by the combination of each individual prediction base on Dempster’s rule of combination. The experimental results show that the proposed method is superior to the individual prediction algorithms, which illustrates the effectiveness of the proposed method.
Osteoprotegerin as a Marker of Atherosclerosis in Diabetic Patients
Authors: Augoulea Areti , Vrachnis Nikolaos , Lambrinoudaki Irene , Dafopoulos Konstantinos , Iliodromiti Zoe , Daniilidis Angelos , Varras Michail , Alexandrou Andreas , Deligeoroglou Efthymios , Creatsas George
Published: January 2013

Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients.
Prevalence of Osteoporosis and Its Associated Factors among Older Men with Type 2 Diabetes
Authors: Chen Hai-ling , Deng Li-li , Li Ju-fen
Published: January 2013

This study investigated the prevalence of osteoporosis and its associated factors in old men with T2DM to identify risk factors for low BMD. We enrolled 93 old men (≥60 years of age) with T2DM and 125 healthy old men (controls) and collected data of their lifestyle, medical history, bone densitometry, body weight, height, and blood pressure. Blood samples were collected for biochemical analyses. Urine samples were collected to determine 24 h urinary creatinine, albumin, and protein. Although no differences in age, blood pressure, waist-to-hip ratio, body mass index (BMI), and testosterone levels were observed, the prevalence of low BMD was significantly higher in the T2DM group compared to the control group. The risk of developing low BMD and fracture in T2DM subjects was increased by 46- and 26-fold, respectively, compared to control subjects. BMD of total spine and hip was positively correlated with BMI and negatively correlated with age, duration of diabetes, creatinine, and 24 h urinary albumin. So old men with T2DM have a greater risk of developing low BMD than old men without T2DM.
Graphs Whose Edge Set Can Be Partitioned into Maximum Matchings
Authors: Khare Niraj
Published: January 2013

This paper provides structural characterization of simple graphs whose edge set can be partitioned into maximum matchings. We use Vizing's classification of simple graphs based on edge chromatic index.
Tuberous Sclerosis Associated with Polycystic Kidney Disease: Effects of Rapamycin after Renal Transplantation
Authors: Rosado C. , García-Cosmes P. , Fraile P. , Vázquez-Sánchez F.
Published: January 2013

Tuberous sclerosis is rarely associated with autosomal dominant polycystic kidney disease in the so-called tuberous sclerosis complex. This association leads to an increased frequency of end-stage renal disease. We present a patient suffering from both syndromes, who received a renal graft and anticalcineurinic drugs as immunosuppressive agents. Progressive titration of the drug was necessary in order to attain the effective doses due to the enzymatic induction caused by concomitant treatment with antiepileptic drugs. These high doses resulted in nephrotoxicity. Immunosuppressor treatment was switched to rapamycin, whereby an improvement in renal function and other signs of tuberous sclerosis and polycystic kidney disease was observed. This case report highlights both the efficacy and safety of rapamycin as an immunosuppressor treatment and its capacity for controlling other symptoms of these genetic-related disorders.
Why the Treatment of Mental Disorders Is an Important Component of HIV Prevention among People Who Inject Drugs
Authors: Buckingham Elizabeth , Schrage Ezra , Cournos Francine
Published: January 2013

People who inject drugs are more likely to be HIV positive and to have a mental disorder than the general population. We explore how the detection and treatment of mental illness among people who are injecting drugs are essential to primary and secondary prevention of HIV infection in this population. Aside from opioid addiction, few studies have been conducted on the links between mental disorders and injection-drug use. However, independent of the injection-drug use literature, a growing number of studies demonstrate that untreated mental illness, especially depression and alcohol/substance use disorders, is associated with HIV-related risk behaviors, acquiring HIV infection, failure to access HIV care and treatment, failure to adhere to HIV care and treatment, and increased morbidity and mortality from HIV-related diseases and comorbidities. In our review of both the published literature and gray literature we found a dearth of information on models for providing care for both opioid addiction and other mental illnesses regardless of HIV status, particularly in low- and middle-income countries. We therefore make recommendations on how to address the mental health needs of HIV-positive people who inject drugs, which include the provision of opioid substitution therapy and integrated mental health, substance abuse, and HIV services.
Bartonella henselaeInfection: An Uncommon Mimicker of Autoimmune Disease
Authors: Maritsi Despoina N. , Zarganis Diagoras , Metaxa Zoi , Papaioannou Georgia , Vartzelis George
Published: January 2013

We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata), chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256) againstBartonellaconfirmed the diagnosis ofB. henselaeinfection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent.
A General Design Methodology for Synchronous Early-Completion-Prediction Adders in Nano-CMOS DSP Architectures
Authors: Olivieri Mauro , Mastrandrea Antonio
Published: January 2013

Synchronous early-completion-prediction adders (ECPAs) are used for high clock rate and high-precision DSP datapaths, as they allow a dominant amount of single-cycle operations even if the worst-case carry propagation delay is longer than the clock period. Previous works have also demonstrated ECPA advantages for average leakage reduction and NBTI effects reduction in nanoscale CMOS technologies. This paper illustrates a general systematic methodology to design ECPA units, targeting nanoscale CMOS technologies, which is not available in the current literature yet. The method is fully compatible with standard VLSI macrocell design tools and standard adder structures and includes automatic definition of critical test patterns for postlayout verification. A design example is included, reporting speed and power data superior to previous works.
Posterior Transpedicular Dynamic Stabilization versus Total Disc Replacement in the Treatment of Lumbar Painful Degenerative Disc Disease: A Comparison of Clinical Results
Authors: Oktenoglu Tunc , Ozer Ali Fahir , Sasani Mehdi , Ataker Yaprak , Gomleksiz Cengiz , Celebi Irfan
Published: January 2013

Study Design. Prospective clinical study.Objective. This study compares the clinical results of anterior lumbar total disc replacement and posterior transpedicular dynamic stabilization in the treatment of degenerative disc disease.Summary and Background Data. Over the last two decades, both techniques have emerged as alternative treatment options to fusion surgery.Methods. This study was conducted between 2004 and 2010 with a total of 50 patients (25 in each group). The mean age of the patients in total disc prosthesis group was 37,32 years. The mean age of the patients in posterior dynamic transpedicular stabilization was 43,08. Clinical (VAS and Oswestry) and radiological evaluations (lumbar lordosis and segmental lordosis angles) of the patients were carried out prior to the operation and 3, 12, and 24 months after the operation. We compared the average duration of surgery, blood loss during the surgery and the length of hospital stay of both groups.Results. Both techniques offered significant improvements in clinical parameters. There was no significant change in radiologic evaluations after the surgery for both techniques.Conclusion. Both dynamic systems provided spine stability. However, the posterior dynamic system had a slight advantage over anterior disc prosthesis because of its convenient application and fewer possible complications.
Synthesis, Characterization, and Anti-Inflammatory Activity of Newer Quinazolinone Analogs
Authors: Rajput Chatrasal Singh , Singhal Shiwani
Published: January 2013

A series of 3-[2′-(Substitutedbenzylideneamino)phenyl]-2-methyl-6-substituted quinazolin-4-ones (5–10), 3-[2′-(3″-chloro-2″-oxo-4″-substitutedphenylazetidin-1″-yl)phenyl]-2-methyl-6-substitutedquinazolin-4-ones (11–16), and 3-[2′-(2″-substitutedphenyl-4″-oxo-1″,3″-thiazolidin-3″-yl)phentl]-2-methyl-6-substitutedquinazolin-4-ones (17–22) have been synthesized in the present study. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, H1 NMR, and mass spectral data. All the newly synthesized compounds were screened for anti-inflammatory and analgesic activities.
Bilateral Adrenal Incidentalomas: A Case Report and Review of Diagnostic Challenges
Authors: Carlson Anders L. , Marney Annis M. , Anderson Scott R. , Gilbert Matthew P.
Published: January 2013

Incidentally discovered adrenal masses (incidentalomas) are common and present challenges both in diagnosis and management. When incidentally discovered adrenal masses are bilateral, a refined diagnostic approach is warranted since bilateral disease is more likely to be pathologic. We review a case of a 34-year-old man with incidentally discovered bilateral adrenal nodules. A comprehensive diagnostic strategy led to the diagnosis of bilateral pheochromocytoma caused by von Hippel-Lindau syndrome. He was successfully treated with bilateral laparoscopic adrenalectomy and has recovered well. While the initial diagnostic approach is similar to the unilateral incidentaloma, additional testing and/or genetic testing should be considered in the case of the bilateral adrenal mass.
Twist1 Induces CCL2 and Recruits Macrophages to Promote Angiogenesis
Authors: Low-Marchelli Janine M. , Ardi Veronica C. , Vizcarra Edward A. , van Rooijen Nico , Quigley James P. , Yang Jing
Published: January 2013

The transcription factor Twist1 induces epithelial–mesenchymal transition and extracellular matrix degradation to promote tumor metastasis. Although Twist1 also plays a role in embryonic vascular development and tumor angiogenesis, the molecular mechanisms that underlie these processes are not as well understood. Here, we report a novel function for Twist1 in modifying the tumor microenvironment to promote progression. We found that expression of Twist1 in human mammary epithelial cells potently promoted angiogenesis. Surprisingly, Twist1 expression did not increase the secretion of the common proangiogenic factors VEGF and basic fibroblast growth factor but rather induced expression of the macrophage chemoattractant CCL2. Attenuation of endogenous Twist1 in vivo blocked macrophage recruitment and angiogenesis, whereas exogenous CCL2 rescued the ability of tumor cells lacking Twist1 to attract macrophages and promote angiogenesis. Macrophage recruitment also was essential for the ability of Twist1-expressing cells to elicit a strong angiogenic response. Together, our findings show that how Twist1 recruits stromal macrophages through CCL2 induction to promote angiogenesis and tumor progression. As Twist1 expression has been associated with poor survival in many human cancers, this finding suggests that anti-CCL2 therapy may offer a rational strategy to treat Twist1-positive metastatic cancers. Cancer Res; 73(2); 662–71. ©2012 AACR.
Systems Analysis of BCL2 Protein Family Interactions Establishes a Model to Predict Responses to Chemotherapy
Authors: Lindner Andreas U. , Concannon Caoimhín G. , Boukes Gerhardt J. , Cannon Mary D. , Llambi Fabien , Ryan Deborah , Boland Karen , Kehoe Joan , McNamara Deborah A. , Murray Frank , Kay Elaine W. , Hector Suzanne , Green Douglas R. , Huber Heinrich J. , Prehn Jochen H.M.
Published: January 2013

Apoptotic desensitization is a hallmark of cancer cells, but present knowledge of molecular systems controlling apoptosis has yet to provide significant prognostic insights. Here, we report findings from a systems study of the intrinsic pathway of apoptosis by BCL2 family proteins and clinical translation of its findings into a model with applications in colorectal cancer (CRC). By determining absolute protein quantifications in CRC cells and patient tumor samples, we found that BAK and BAX were expressed more highly than their antiapoptotic inhibitors. This counterintuitive finding suggested that sole inhibition of effector BAX and BAK could not be sufficient for systems stability in nonstressed cells. Assuming a model of direct effector activation by BH3-only proteins, we calculated that the amount of stress-induced BH3-only proteins required to activate mitochondrial apoptosis could predict individual death responses of CRC cells to 5-fluorouracil/oxaliplatin. Applying this model predictor to protein profiles in tumor and matched normal tissue samples from 26 patients with CRCs, we found that differences in protein quantities were sufficient to model the increased tumor sensitivity to chemotherapy compared with normal tissue. In addition, these differences were sufficient to differentiate clinical responders from nonresponders with high confidence. Applications of our model, termed DR_MOMP, were used to assess the impact of apoptosis-sensitizing dugs in lowering the necessary dose of state-of-the-art chemotherapy in individual patients. Together, our findings offer a ready clinical tool with the potential to tailor chemotherapy to individual patients. Cancer Res; 73(2); 519–28. ©2012 AACR.
YM-155 Potentiates the Effect of ABT-737 in Malignant Human Glioma Cells via Survivin and Mcl-1 Downregulation in an EGFR-Dependent Context
Authors: Jane Esther P. , Premkumar Daniel R. , DiDomenico Joseph D. , Hu Bo , Cheng Shi-Yuan , Pollack Ian F.
Published: January 2013

Antiapoptotic proteins are commonly overexpressed in gliomas, contributing to therapeutic resistance. We recently reported that clinically achievable concentrations of the Bcl-2/Bcl-xL inhibitor ABT-737 failed to induce apoptosis in glioma cells, with persistent expression of survivin and Mcl-1. To address the role of these mediators in glioma apoptosis resistance, we analyzed the effects of YM-155, a survivin suppressant, on survival on a panel of glioma cell lines. YM-155 inhibited cell growth and downregulated survivin and Mcl-1 in a dose- and cell line–dependent manner. While U373, LN18, LNZ428, T98G, LN229, and LNZ308 cells exhibited an IC50 of 10 to 75 nmol/L, A172 cells were resistant (IC50 ∼ 250 nmol/L). No correlation was found between sensitivity to YM-155 and baseline expression of survivin or cIAP-1/cIAP-2/XIAP. However, strong correlation was observed between EGF receptor (EGFR) activation levels and YM-155 response, which was confirmed using EGFR-transduced versus wild-type cells. Because we postulated that decreasing Mcl-1 expression may enhance glioma sensitivity to ABT-737, we examined whether cotreatment with YM-155 promoted ABT-737 efficacy. YM-155 synergistically enhanced ABT-737–induced cytotoxicity and caspase-dependent apoptosis. Downregulation of Mcl-1 using short hairpin RNA also enhanced ABT-737–inducing killing, confirming an important role for Mcl-1 in mediating synergism between ABT-737 and YM-155. As with YM-155 alone, sensitivity to YM-155 and ABT-737 inversely correlated with EGFR activation status. However, sensitivity could be restored in highly resistant U87-EGFRvIII cells by inhibition of EGFR or its downstream pathways, highlighting the impact of EGFR signaling on Mcl-1 expression and the relevance of combined targeted therapies to overcome the multiple resistance mechanisms of these aggressive tumors. Mol Cancer Ther; 12(3); 326–38. ©2013 AACR.
Urgency, Detrusor Overactivity and Posterior Vault Prolapse in Women Who Underwent Pelvic Organ Prolapse Repair
Authors: Costantini Elisabetta , Lazzeri Massimo , Zucchi Alessandro , Mearini Luigi , Fragalà Eugenia , Del Zingaro Michele , Bini Vittorio , Porena Massimo
Published: January 2013

Introduction: We investigated the relationship between posterior vault prolapse and overactive bladder (OAB) symptoms or detrusor overactivity (DO) and their changes after surgical repair. Methods: Forty-three patients with vault prolapse and prevalent posterior compartment prolapse -underwent pelvic organ prolapse repair surgery: 28 received colposacropexy and 15 were treated by the vaginal approach. Subjective success was lack of prolapse-related symptoms or urgency. OAB symptoms, voiding symptoms and constipation were evaluated. Patient satisfaction was defined by a visual analog scale score (range 0-10). Objective anatomical success was defined as no vaginal prolapse of stage ≥2 at any vaginal site. Results: The median follow-up was 75 months (range 24-143). Preoperatively, 33/43 patients (76.74%) reported urgency. DO was found in 11/43 patients (25.6%), and 22/43 patients reported constipation. The anatomical outcome showed 2 persistent stage II rectoceles (6.9%). After surgery, OAB symptoms disappeared in 25/33 (75.88%) and persisted in 8 patients (24.2%); there was no de novo urgency. DO disappeared in 8/11 subjects (72.7%). Preoperative constipation was present in 17/33 patients with OAB symptoms (51.5%) and disappeared postoperatively in 13/17 patients (76.4%) (p < 0.013). De novo constipation appeared in 3 patients (associated with OAB in 2 patients). Conclusions: Prevalent posterior compartment pelvic organ prolapse and OAB/DO were often associated. After surgery, OAB symptoms and DO were significantly reduced.
Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With Decompensated Heart Failure
Authors: Brisco Meredith A. , Coca Steven G. , Chen Jennifer , Owens Anjali Tiku , McCauley Brian D. , Kimmel Stephen E. , Testani Jeffrey M.
Published: January 2013

Background—

Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment.

Methods and Results—

Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8;
P
<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8;
P
=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8;
P
=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1;
P
<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0;
P
=0.59; p interaction=0.03).

Conclusions—

An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.
Oxidative Stress and Sarcomeric Proteins
Authors: Steinberg Susan F.
Published: January 2013

Oxidative stress accompanies a wide spectrum of clinically important cardiac disorders, including ischemia/reperfusion, diabetes mellitus, and hypertensive heart disease. Although reactive oxygen species (ROS) can activate signaling pathways that contribute to ischemic preconditioning and cardioprotection, high levels of ROS induce structural modifications of the sarcomere that impact on pump function and the pathogenesis of heart failure. However, the precise nature of the redox-dependent change in contractility is determined by the source/identity of the oxidant species, the level of oxidative stress, and the chemistry/position of oxidant-induced posttranslational modifications on individual proteins within the sarcomere. This review focuses on various ROS-induced posttranslational modifications of myofilament proteins (including direct oxidative modifications of myofilament proteins, myofilament protein phosphorylation by ROS-activated signaling enzymes, and myofilament protein cleavage by ROS-activated proteases) that have been implicated in the control of cardiac contractility.
Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients With Atrial Fibrillation
Authors: Reddy Vivek Y. , Doshi Shephal K. , Sievert Horst , Buchbinder Maurice , Neuzil Petr , Huber Kenneth , Halperin Jonathan L. , Holmes David
Published: January 2013

Background—

The multicenter PROTECT AF study (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) was conducted to determine whether percutaneous left atrial appendage closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation.

Methods and Results—

Patients (n=707) with nonvalvular atrial fibrillation and at least 1 risk factor (age >75 years, hypertension, heart failure, diabetes, or prior stroke/transient ischemic attack) were randomized to either the Watchman device (n=463) or continued warfarin (n=244) in a 2:1 ratio. After device implantation, warfarin was continued for ≈45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups, respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy end point included stroke, systemic embolism, and cardiovascular death, and the primary analysis was by intention to treat. After 1588 patient-years of follow-up (mean 2.3±1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100 patient-years) in the Watchman and warfarin groups, respectively (relative risk, 0.71; 95% confidence interval, 0.44%–1.30% per year), which met the criteria for noninferiority (probability of noninferiority >0.999). There were more primary safety events in the Watchman group (5.5% per year; 95% confidence interval, 4.2%–7.1% per year) than in the control group (3.6% per year; 95% confidence interval, 2.2%–5.3% per year; relative risk, 1.53; 95% confidence interval, 0.95–2.70).

Conclusions—

The “local” strategy of left atrial appendage closure is noninferior to “systemic” anticoagulation with warfarin. PROTECT AF has, for the first time, implicated the left atrial appendage in the pathogenesis of stroke in atrial fibrillation.

Clinical Trial Registration:—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00129545.
Hybrid Biological-Digital Systems in Artistic and Entertainment Computing
Authors: van Eck Wim , Lamers Maarten H.
Published: January 2013

The authors give an overview of existing incorporations of biological systems for behavior generation within digital systems. The authors investigate digital systems that have artistic and/or entertainment goals, including computer games. The overview concludes with a reflection on the overall state of this hybrid approach.