bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Retrospective Evaluation of the Effectiveness and Safety of Ceftaroline Fosamil Therapy
Authors: Casapao Anthony M. , Davis Susan L. , Barr Viktorija O. , Klinker Kenneth P. , Goff Debra A. , Barber Katie E. , Kaye Keith S. , Mynatt Ryan P. , Molloy Leah M. , Pogue Jason M. , Rybak Michael J.
Published: February 2014

Ceftaroline has been approved for acute bacterial skin infections and community-acquired bacterial pneumonia. Limited clinical experience exists for use outside these indications. The objective of this study was to describe the outcomes of patients treated with ceftaroline for various infections. Retrospective analyses of patients receiving ceftaroline ≥72 h from 2011 to 2013 were included. Clinical and microbiological outcomes were analyzed. Clinical success was defined as resolution of all signs and symptoms of infection with no further need for escalation while on ceftaroline treatment during hospitalization. A total of 527 patients received ceftaroline, and 67% were treated for off-label indications. Twenty-eight percent (148/527) of patients had bacteremia. Most patients (80%) were initiated on ceftaroline after receipt of another antimicrobial, with 48% citing disease progression as a reason for switching. The median duration of ceftaroline treatment was 6 days, with an interquartile range of 4 to 9 days. A total of 327 (62%) patients were culture positive, and the most prevalent pathogen was
Staphylococcus aureus
, with a frequency of 83% (271/327). Of these patients, 88.9% (241/271) were infected with methicillin-resistant
S. aureus
(MRSA). Clinically, 88% (426/484) achieved clinical success and hospital mortality was seen in 8% (40/527). While on ceftaroline, adverse events were experienced in 8% (41/527) of the patients and 9% (28/307) were readmitted within 30 days after discharge for the same infection. Patients treated with ceftaroline for both FDA-approved and off-label infections had favorable outcomes. Further research is necessary to further describe the role of ceftaroline in a variety of infections and its impact on patient outcomes.
Mechanism of Action of 5-Nitrothiophenes against Mycobacterium tuberculosis
Authors: Hartkoorn Ruben C. , Ryabova Olga B. , Chiarelli Laurent R. , Riccardi Giovanna , Makarov Vadim , Cole Stewart T.
Published: February 2014

On using the streptomycin-starved 18b strain as a model for nonreplicating
Mycobacterium tuberculosis
, we identified a 5-nitrothiophene compound as highly active but not cytotoxic. Mutants resistant to 5-nitrothiophenes were found be cross-resistant to the nitroimidazole PA-824 and unable to produce the F
420
cofactor. Furthermore, 5-nitrothiophenes were shown to be activated by the F
420
-dependent nitroreductase Ddn and to release nitric oxide, a mechanism of action identical to that described for nitroimidazoles.
Role of the Polymorphic Immunodominant Molecule in Entry of Theileria parva Sporozoites into Bovine Lymphocytes
Authors: Toye Philip , Musoke Antony , Naessens Jan
Published: February 2014

Theileria parvais a tick-transmitted apicomplexan parasite that infects cattle and African buffalo. In cattle, it causes a fatal lymphoproliferative disease called East Coast fever. The polymorphic immunodominant molecule (PIM) is expressed by two stages of the parasite: the sporozoite, which is inoculated by the tick to infect mammalian lymphocytes, and the schizont, the established intralymphocytic stage. Here, we demonstrate that monoclonal antibodies (MAb) to PIM can reduce the ability of sporozoites to infect bovine lymphocytesin vitro. This reduction appears to be due to blocking of sporozoite attachment by binding of the MAb to several regions of PIM. Interestingly, one MAb, which recognizes an epitope in the central variable region of PIM, did not inhibit sporozoite infectivity. We also demonstrate that PIM antigen, as a recombinant molecule, can also reduce sporozoite infectivityin vitroby blocking both attachment and internalization of sporozoites. Electron microscopic studies showed that PIM is present in microspheres below the sporozoite surface and is transported to the parasite surface soon after contact with bovine lymphocytes. The results suggest that at least two sporozoite molecules, PIM and the previously described p67, are involved in the entry ofT. parvainto mammalian lymphocytes.
Putative Inv Is Essential for Basolateral Invasion of Caco-2 Cells and Acts Synergistically with OmpA To Affect
In Vitro
and
In Vivo
Virulence of Cronobacter sakazakii ATCC 29544
Authors: Chandrapala Dilini , Kim Kyumson , Choi Younho , Senevirathne Amal , Kang Dong-Hyun , Ryu Sangryeol , Kim Kwang-Pyo
Published: February 2014

Cronobacter sakazakii
is an opportunistic pathogen that causes neonatal meningitis and necrotizing enterocolitis. Its interaction with intestinal epithelium is important in the pathogenesis of enteric infections. In this study, we investigated the involvement of the
inv
gene in the virulence of
C. sakazakii
ATCC 29544
in vitro
and
in vivo
. Sequence analysis of
C. sakazakii
ATCC 29544
inv
revealed that it is different from other
C. sakazakii
isolates. In various cell culture models, an Δ
inv
deletion mutant showed significantly lowered invasion efficiency, which was restored upon genetic complementation. Studying invasion potentials using tight-junction-disrupted Caco-2 cells suggested that the
inv
gene product mediates basolateral invasion of
C. sakazakii
ATCC 29544. In addition, comparison of invasion potentials of double mutant (Δ
ompA Δinv
) and single mutants (Δ
ompA
and Δ
inv
) provided evidence for an additive effect of the two putative outer membrane proteins. Finally, the importance of
inv
and the additive effect of putative Inv and OmpA were also proven in an
in vivo
rat pup model. This report is the first to demonstrate two proteins working synergistically
in vitro
, as well as
in vivo
in
C. sakazakii
pathogenesis.
Role of F1C Fimbriae, Flagella, and Secreted Bacterial Components in the Inhibitory Effect of Probiotic Escherichia coli Nissle 1917 on Atypical Enteropathogenic E. coli Infection
Authors: Kleta Sylvia , Nordhoff Marcel , Tedin Karsten , Wieler Lothar H. , Kolenda Rafal , Oswald Sibylle , Oelschlaeger Tobias A. , Bleiß Wilfried , Schierack Peter
Published: February 2014

Enteropathogenic
Escherichia coli
(EPEC) is recognized as an important intestinal pathogen that frequently causes acute and persistent diarrhea in humans and animals. The use of probiotic bacteria to prevent diarrhea is gaining increasing interest. The probiotic
E. coli
strain Nissle 1917 (EcN) is known to be effective in the treatment of several gastrointestinal disorders. While both
in vitro
and
in vivo
studies have described strong inhibitory effects of EcN on enteropathogenic bacteria, including pathogenic
E. coli
, the underlying molecular mechanisms remain largely unknown. In this study, we examined the inhibitory effect of EcN on infections of porcine intestinal epithelial cells with atypical enteropathogenic
E. coli
(aEPEC) with respect to single infection steps, including adhesion, microcolony formation, and the attaching and effacing phenotype. We show that EcN drastically reduced the infection efficiencies of aEPEC by inhibiting bacterial adhesion and growth of microcolonies, but not the attaching and effacing of adherent bacteria. The inhibitory effect correlated with EcN adhesion capacities and was predominantly mediated by F1C fimbriae, but also by H1 flagella, which served as bridges between EcN cells. Furthermore, EcN seemed to interfere with the initial adhesion of aEPEC to host cells by secretion of inhibitory components. These components do not appear to be specific to EcN, but we propose that the strong adhesion capacities enable EcN to secrete sufficient local concentrations of the inhibitory factors. The results of this study are consistent with a mode of action whereby EcN inhibits secretion of virulence-associated proteins of EPEC, but not their expression.
Deregulated Balance of Omega-6 and Omega-3 Polyunsaturated Fatty Acids following Infection by the Zoonotic Pathogen Streptococcus suis
Authors: Lachance Claude , Segura Mariela , Dominguez-Punaro Maria C. , Wojewodka Gabriella , De Sanctis Juan B. , Radzioch Danuta , Gottschalk Marcelo
Published: February 2014

Streptococcus suisis an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused byS. suisis responsible for early high mortality in septic shock-like syndrome cases. Polyunsaturated fatty acids (PUFAs) may contribute to regulating inflammatory processes. This study shows that mouse infection byS. suisis accompanied by an increase of arachidonic acid, a proinflammatory omega-6 (ω-6) PUFA, and by a decrease of docosahexaenoic acid, an anti-inflammatory ω-3 PUFA. Macrophages infected withS. suisshowed activation of mitogen-activated protein kinase pathways and cyclooxygenase-2 upregulation. Fenretinide, a synthetic vitamin A analog, reducedin vitroexpression of inflammatory mediators. Pretreatment of mice with fenretinide significantly improved their survival by reducing systemic proinflammatory cytokines during the acute phase of anS. suisinfection. These findings indicate a beneficial effect of fenretinide in diminishing the expression of inflammation and improving survival during an acute infection by a virulentS. suisstrain.
The Copper-Responsive RicR Regulon Contributes to Mycobacterium tuberculosis Virulence
Authors: Shi Xiaoshan , Festa Richard A. , Ioerger Thomas R. , Butler-Wu Susan , Sacchettini James C. , Darwin K. Heran , Samanovic Marie I.
Published: February 2014

As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen
Mycobacterium tuberculosis
. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in
M. tuberculosis
, including the regulated in copper repressor (RicR) regulon, which is unique to pathogenic mycobacteria. In this work, we describe the contribution of each RicR-regulated gene to Cu resistance
in vitro
and to virulence in animals. We found that the deletion or disruption of individual RicR-regulated genes had no impact on virulence in mice, although several mutants had Cu hypersensitivity. In contrast, a mutant unable to activate the RicR regulon was not only highly susceptible to Cu but also attenuated in mice. Thus, these data suggest that several genes of the RicR regulon are required simultaneously to combat Cu toxicity
in vivo
or that this regulon is also important for resistance against Cu-independent mechanisms of host defense.

IMPORTANCE
Mycobacterium tuberculosis
is the causative agent of tuberculosis, killing millions of people every year. Therefore, understanding the biology of
M. tuberculosis
is crucial for the development of new therapies to treat this devastating disease. Our studies reveal that although host-supplied Cu can suppress bacterial growth,
M. tuberculosis
has a unique pathway, the RicR regulon, to defend against Cu toxicity. These findings suggest that Cu homeostasis pathways in both the host and the pathogen could be exploited for the treatment of tuberculosis.
Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus
Authors: Cotten Matthew , Watson Simon J. , Zumla Alimuddin I. , Makhdoom Hatem Q. , Palser Anne L. , Ong Swee Hoe , Al Rabeeah Abdullah A. , Alhakeem Rafat F. , Assiri Abdullah , Al-Tawfiq Jaffar A. , Albarrak Ali , Barry Mazin , Shibl Atef , Alrabiah Fahad A. , Hajjar Sami , Balkhy Hanan H. , Flemban Hesham , Rambaut Andrew , Kellam Paul , Memish Ziad A.
Published: February 2014

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10
−3
substitutions per site per year (95% credible interval [95% CI], 8.76 × 10
−4
; 1.37 × 10
−3
) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (
R
0
) for the virus that is less than 1.

IMPORTANCE
MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.
Mobile ependymoma diagnosed with cine MRI
Authors: Kotani Toshiaki , Okawa Akihiko , Akazawa Tsutomu , Sakuma Tsuyoshi
Published: February 2014

Migration of neurogenic spinal tumours is uncommon. However, such possible mobility should be kept in mind during surgery for neurogenic tumours whenever the lesion is not found at the anticipated level. Conventional static imaging techniques, such as myelography and MRI, have not documented dynamic motion of tumours. A 12-year-old boy was diagnosed with a neurogenic spinal tumour in the thoracolumbar region. To assess the migratory tendency of the tumour, cine MRI was performed to acquire dynamic images under postural change. Cine MRI showed that the tumour migrated up to the lower part of the T12 vertebra from the upper part of the L1 vertebra during a change in spinal posture from cervical flexion to extension. The tumour was completely removed and histological examination revealed the tumour to be an ependymoma. Cine MRI is useful for dynamically and non-invasively assessing the migratory tendency of spinal tumours.
Radiation-induced SVC syndrome
Authors: Mehta Sahil Viplov , Koo Douglas Junwoo
Published: February 2014

A 69-year-old woman with a history of Hodgkin's lymphoma at age 17 was admitted to our hospital with 3 weeks of progressive dyspnoea on exertion. Her medical history and physical exam were concerning for superior vena cava (SVC) syndrome and while her workup did indeed reveal such, its aetiology was not due to a compressive mass associated with malignancy. Rather, she developed chronic thromboses in the setting of radiation-induced venous fibrosis. This case report details her case and explains the key clinical concerns, pathophysiology and incidence of radiation-induced SVC syndrome.
DynaTAM: an online algorithm for performing simultaneously optimized proactive traffic control for freeways
Authors: Fang Jie , Hadiuzzaman Md. , Yin Elena , Qiu Tony Z.
Published: February 2014

Modern proactive control algorithms can perform real-time traffic state prediction and help determine control plans for active traffic control measures, such as ramp metering (RM) and variable speed limit (VSL). In this study, a control algorithm, DynaTAM (Dynamic Analysis Tool for Active Traffic Demand Management), is proposed for prediction-based, integrated optimization control. DynaTAM considers the correlations between the implemented control measures and determines the control plan for both RM and VSL at the same stage of optimization. The algorithm framework possesses a candidate control plan generator, which reduces the computational load of future optimizations and eliminates much of the uncertainty in the system performance. A field-data-based simulation study with different control scenarios is conducted to evaluate the performance of DynaTAM. The DynaTAM control algorithm is shown to not only effectively perform integrated and coordinated control using both RM and VSL, but also significantly improve the efficiency of traffic operations during peak hours.
Evidence supporting panmixia in Greenland halibut (Reinhardtius hippoglossoides) in the Northwest Atlantic
Authors: Roy Denis , Hardie David C. , Treble Margaret A. , Reist James D. , Ruzzante Daniel E.
Published: February 2014

Assessment of population structure is critical to the design and implementation of sound management and conservation strategies. However, population structure must be assessed using markers attuned to population genetic processes such as genetic drift and gene flow, which reflect actual levels of reproductive isolation among putative genetic clusters. This is critical for highly exploited, commercial species that form the backbone of regional and local economies. Here, we show extremely low levels of population genetic differentiation among Greenland halibut (Reinhardtius hippoglossoides) collected from throughout the Northwest Atlantic, which cannot be statistically differentiated from panmixia using 12 species-specific polymorphic microsatellite markers. In contrast, some previous studies have demonstrated significant differences among individuals collected from various parts of the species’ range using a variety of both genetic and nongenetic techniques. In accordance with other reports and consistent with the species’ life history, we demonstrate that the most parsimonious explanation reconciling observed patterns is a repeated high degree of local differentiation of new recruits and colonizers originating from a common gene pool. Such a scenario has important conservation implications in terms of devising more appropriate strategies balancing species persistence and replenishment with sustainable resource use.
Synthesis, photophysicochemical properties and TD-DFT calculations of tetrakis(2-benzoyl-4-chlorophenoxy) phthalocyanines
Authors: Yılmaz Yusuf , Mack John , Şener M. Kasım , Sönmez Mehmet , Nyokong Tebello
Published: February 2014

The synthesis of metal free, magnesium and zinc tetrakis(2-benzoyl-4-chlorophenoxy) phthalocyanine derivatives (2–4) is described along with their characterization by elemental analysis, IR, UV-visible absorption, and 1 H NMR spectroscopy and mass spectrometry. Trends observed in the fluorescence, triplet state, singlet oxygen and photodegradation quantum yields and the triplet state lifetimes are also analyzed. The compounds exhibit high solubility in a wide range of organic solvents and no evidence of aggregation was observed over a wide concentration range. The Zn ( II ) complex (4) was found to have a very high singlet oxygen quantum yield (ΦΔ = 0.78) in dimethylsulfoxide (DMSO) and a reasonably large triplet state quantum yield (ΦT = 0.82). The photophysical and photochemical properties clearly demonstrate that these compounds could prove useful in singlet oxygen applications such as photodynamic therapy (PDT). DFT and TD-DFT calculations were used to assess the impact of the positional isomerism of the 2-benzoyl-4-chlorophenoxy substituents on the electronic structures and optical spectroscopy.
Cecocolic Intussusception in Adult Caused by Acute Appendicitis
Authors: Kang Jeonghyun , Lee Kang Young , Sohn Seung-Kook
Published: February 2014

Intussusception in adult is rare. The etiology is different from that of childhood. The most common cause of intussusception in adult is known as malignancy. When dealing with adult intussusception, surgical resection is usually warranted for correct diagnosis and proper treatment. This is a case report of cecocolic intussusception caused by an acute appendicitis in adult. The causes of cecocolic intussusception were reported as appendiceal adenocarcinoma, appendiceal mucocele, appendiceal adenoma, or idiopathic. Although this patient underwent laparoscopic right hemicolectomy under suspicion of malignancy at cecum base, final pathologic diagnosis revealed only acute appendicitis. Thus, the present case emphasizes the importance of prior thorough examinations including colonoscopy when we encounter this rare kind of intussusception in adult.
Microbial Ecology of Anaerobic Digesters: The Key Players of Anaerobiosis
Authors: Ali Shah Fayyaz , Mahmood Qaisar , Maroof Shah Mohammad , Pervez Arshid , Ahmad Asad Saeed
Published: February 2014

Anaerobic digestion is the method of wastes treatment aimed at a reduction of their hazardous effects on the biosphere. The mutualistic behavior of various anaerobic microorganisms results in the decomposition of complex organic substances into simple, chemically stabilized compounds, mainly methane andCO2. The conversions of complex organic compounds toCH4andCO2are possible due to the cooperation of four different groups of microorganisms, that is, fermentative, syntrophic, acetogenic, and methanogenic bacteria. Microbes adopt various pathways to evade from the unfavorable conditions in the anaerobic digester like competition between sulfate reducing bacteria (SRB) and methane forming bacteria for the same substrate.Methanosarcinaare able to use both acetoclastic and hydrogenotrophic pathways for methane production. This review highlights the cellulosic microorganisms, structure of cellulose, inoculum to substrate ratio, and source of inoculum and its effect on methanogenesis. The molecular techniques such as DGGE (denaturing gradient gel electrophoresis) utilized for dynamic changes in microbial communities and FISH (fluorescentin situhybridization) that deal with taxonomy and interaction and distribution of tropic groups used are also discussed.
The Relation betweenHelicobacter pyloriInfection and Acute Bacterial Diarrhea in Children
Authors: Monajemzadeh Maryam , Abbasi Ata , Tanzifi Parin , Taba Taba Vakili Sahar , Irani Heshmat , Kashi Leila
Published: February 2014

Background.H. pyloriinfection leads to chronic gastritis in both children and adults. But recently, there are arising theories of its protective effect in diarrheal diseases.Aim. To explore the prevalence ofH. pyloriinfection in children with bacterial diarrhea and compare it with healthy controls.Patients and Methods. Two matched groups consisted of 122 consecutive children, aged 24–72 months old, with acute bacterial diarrhea, who had Shigellosis (N=68) and Salmonellosis (N=54) as patients group and 204 healthy asymptomatic children as control group enrolled in this study.Results. The prevalence ofH. pyloriinfection in healthy control children was significantly higher than in patients group, (odds ratio = 3.6, 95% CI: 1.33–9.5,P=0.007). In our study, only 2/54Salmonellainfected patients and 3/68 of Shigellosis had evidence ofH. pyloriinfection, while normal control children had 27/204 infected individuals.Conclusion.H. pyloriinfection may play a protective role against bacterial diarrhea in children. So it is important to consider all of the positive and negative aspects ofH. pyloriinfection before its eradication.
Animal Models in Studies of Cardiotoxicity Side Effects from Antiblastic Drugs in Patients and Occupational Exposed Workers
Authors: Lamberti Monica , Giovane Giancarlo , Garzillo Elpidio M. , Avino Franca , Feola Antonia , Porto Stefania , Tombolini Vincenzo , Di Domenico Marina
Published: February 2014

Cardiotoxicity is an important side effect of cytotoxic drugs and may be a risk factor of long-term morbidity for both patients during therapy and also for staff exposed during the phases of manipulation of antiblastic drugs. The mechanism of cardiotoxicity studied in vitro and in vivo essentially concerns the formation of free radicals leading to oxidative stress, with apoptosis of cardiac cells or immunologic reactions, but other mechanisms may play a role in antiblastic-induced cardiotoxicity. Actually, some new cytotoxic drugs like trastuzumab and cyclopentenyl cytosine show cardiotoxic effects. In this report we discuss the different mechanisms of cardiotoxicity induced by antiblastic drugs assessed using animal models.
Pulmonary Rehabilitation: The Reference Therapy for Undernourished Patients with Chronic Obstructive Pulmonary Disease
Authors: Samaras Nikolaos , Samaras Dimitrios , Chambellan Arnaud , Pichard Claude , Thibault Ronan
Published: February 2014

Chronic obstructive pulmonary disease (COPD) combines the deleterious effects of chronic hypoxia, chronic inflammation, insulin-resistance, increased energy expenditure, muscle wasting, and exercise deconditioning. As for other chronic disorders, loss of fat-free mass decreased survival. The preservation of muscle mass and function, through the protection of the mitochondrial oxidative metabolism, is an important challenge in the management of COPD patients. As the prevalence of the disease is increasing and the medical advances make COPD patients live longer, the prevalence of COPD-associated nutritional disorders is expected to increase in future decades. Androgenopenia is observed in 40% of COPD patients. Due to the stimulating effects of androgens on muscle anabolism, androgenopenia favors loss of muscle mass. Studies have shown that androgen substitution could improve muscle mass in COPD patients, but alone, was insufficient to improve lung function. Two multicentric randomized clinical trials have shown that the association of androgen therapy with physical exercise and oral nutritional supplements containing omega-3 polyinsaturated fatty acids, during at least three months, is associated with an improved clinical outcome and survival. These approaches are optimized in the field of pulmonary rehabilitation which is the reference therapy of COPD-associated undernutrition.
The Efficacy and Outcome of Ministernotomy Compared to Those of Standard Sternotomy for Aortic Valve Replacement
Authors: Skripochnik Edvard , Michler Robert E. , Hentschel Viktoria , Neragi-Miandoab Siyamek
Published: February 2014

Background. Benefits of ministernotomy have been reported but not yet fully established in the current literature. Ministernotomy may be associated with less bleeding, less need for transfusion, and reduced hospital length of stay. Methods. We retrospectively evaluated 347 patients who underwent aortic valve replacement between 2007 and 2011 at our institution. Results. Standard sternotomy was performed in 303 patients (154 males, 50.8% and 149 females, 49.2%) and ministernotomy in 44 patients (13 males, 30% and 30 females, 70%); most of the patients in ministernotomy group were female (75%) (P=.0095). The mean age for ministernotomy patients was 71.8±12.6 years and for sternotomy patients 67.4±13.8 years (P=.045). Significant preoperative morbidities (for ministernotomy and sternotomy, resp.) included stroke (11%, n=5 versus 18%, n=55; P=.39), PVD (23%, n=10 versus 16%, n=49; P=.29), COPD (25%, n=11 versus 17%, n=52; P=.21), renal failure (0.0%, n=0 versus 8.8%, n=26; P=.06), and previous heart surgery (9%, n=4 versus 9.5%, n=29; P=1.0). Intraoperative blood transfusion was required in 23% of ministernotomy patients (n=9) and 30% of sternotomy patients (n=91), P=.16. Major postoperative complications (for ministernotomy and sternotomy, resp.) included exploration for bleeding (4.5%, n=2 versus 6%, n=18; P=1) and adverse neurologic events (4.5%, n=2 versus 1.6%, n=5; P=.05). The length of stay (LOS) in the CCU was 75.4±57.1 hours for the ministernotomy group and 125.4±160.3 hours for the sternotomy group (P=.12). The LOS was slightly shorter following ministernotomy (9.00±7.78 days) compared to sternotomy (10.0±9.46 days) (P=.31). Perioperative mortality was 2.3% (n=1) for ministernotomy and 3.3% (n=10) for sternotomy (P=1.0). The 1-, 3-, and 7-year survival following ministernotomy was 93.8%, 93.8%, and 88.3%, respectively; following sternotomy, these rates were 87.7%, 83.7%, and 82.6%, respectively (95% CI 0.273 to 1.325, P=.20). Conclusion. Ministernotomy is less invasive and is associated with less perioperative and postoperative bleeding and reduced LOS in CCU and in hospital.
Alcohol Induced Mitochondrial Oxidative Stress and Alveolar Macrophage Dysfunction
Authors: Liang Yan , Harris Frank L. , Brown Lou Ann S.
Published: February 2014

An alcohol use disorder increases the risk of invasive and antimicrobial resistant community-acquired pneumonia and tuberculosis. Since the alveolar macrophage (AM) orchestrates the immune response in the alveolar space, understanding the underlying mechanisms by which alcohol suppresses AM phagocytosis is critical to improving clinical outcomes. In the alveolar space, chronic alcohol ingestion causes severe oxidative stress and depletes antioxidants which are critical for AM function. The mitochondrion is important in maintaining cellular redox balance and providing the ATP critical for phagocytosis. The focus of this study was to understand how alcohol triggers mitochondrial reactive oxygen species (ROS), stimulates cellular oxidative stress, and induces AM dysfunction. The current study also investigated the capacity of the mitochondrial targeted antioxidant, mitoTEMPOL (mitoT), in modulating mitochondrial oxidative stress, and AM dysfunction. Usingin vitroethanol exposure and AMs from ethanol-fed mice, ethanol promoted mitochondrial dysfunction including increased mitochondrial ROS, decreased mitochondrial membrane potential, and decreased ATP. Treatment with mitoT reversed these effects. Ethanol-induced decreases in phagocytosis and cell viability were also attenuated with mitoT. Therefore, antioxidants targeted to the mitochondria have the potential to ameliorate ethanol-induced mitochondrial oxidative stress and subsequent decreases in AM phagocytosis and cell viability.
Late Prevertebral and Spinal Abscess following Chemoradiation for Laryngeal Squamous Cell Carcinoma
Authors: Hindy Jawad , Shelef Ilan , Slovik Yuval , Joshua Ben-Zion
Published: February 2014

Objective. Advanced primary supraglottic tumors (i.e., T3 or T4) have traditionally been treated surgically and postoperative radiotherapy. In the last 2 decades, some patients were treated with chemoradiation avoiding surgery.Case Report. We describe a 55-year old female who presented with respiratory distress and paraplegia seven years after treatment for a T3N0M0 supraglottic squamous cell carcinoma. CT scan showed prevertebral and intraspinal air descending from C4 to D3 vertebras. Epidural and prevertebral abscesses were confirmed by neck exploration. Necrosis was observed in the retropharyngeal, prevertebral, and vertebral tissues.Conclusion. Prevertebral and spinal abscess may result from chemotherapy and radiotherapy to the head and neck. Physicians caring for head and neck cancer patients treated with chemotherapy and radiation should be aware of this rare severe complication.
Heliograph Imaging Based on Total Variation Constraint and Nonlocal Operator
Authors: Wang S. Z. , Xu L. Y. , Wang Y. , Zhang X. P.
Published: February 2014

Heliograph imaging is the process to reconstruct the solar image from sparse frequency domain data, and compressed sensing (CS) algorithm has shown potential power to accurately recover images from highly undersampled data. However, the available compressed sensing based models available for heliograph imaging are not able to reconstruct fine solar structures and often suffer from undesired convolutive artifacts. This paper presents an imaging model with total variation constraint and nonlocal operator based on compressed sensing theory, with particular objective to suppress convolutive artifacts and reconstruct fine structures. In particular, an efficient algorithm is presented to solve the formulated model. Finally, a set of simulations has been conducted by using both synthetic and real images, and the results demonstrate that our proposed algorithm has surprisingly lower reconstruction errors than other methods.
Assessment of Tissue Eosinophilia as a Prognosticator in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma—An Image Analysis Study
Authors: Jain Megha , Kasetty Sowmya , Sudheendra U. S. , Tijare Manisha , Khan Samar , Desai Ami
Published: February 2014

Association of tissue eosinophilia with oral squamous cell carcinoma has shown variable results ranging from favourable to unfavourable or even having no influence on prognosis. Also, very few studies have been done to know the role of eosinophils in premalignancy. So the present study investigated role of eosinophilic infiltration in oral precancer and cancer and its possible use as a prognosticator. 60 histopathologically proven cases (20 cases each of metastatic and nonmetastatic oral squamous cell carcinoma and oral leukoplakia with dysplasia of various grades) were included. Congo red is used as a special stain for eosinophils. Each specimen slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. As a result, a significant increase in eosinophil count was found in oral carcinomas compared to dysplasia. Nonmetastatic cases showed higher counts than metastatic carcinomas. So, it is concluded that eosinophilia is a favourable histopathological prognostic factor in oral cancer. Moreover, higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion thus suggesting that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for oral precancer and OSCC.
Pre- and Postoperative Evaluation by Photoplethysmography in Patients Receiving Surgery for Lower-Limb Varicose Veins
Authors: Saliba Júnior Orlando Adas , Giannini Mariangela , Mórbio Ana Paula , Saliba Orlando , Rollo Hamilton Almeida
Published: February 2014

Objective. To evaluate the effectiveness of surgery in treating primary varicose veins in the lower limbs by photoplethysmography (PPG) and duplex mapping (DM).Method. Forty-eight lower limbs were clinically evaluated according to the CEAP classification system and subjected to PPG and DM exams. Each limb had a venous refill time (VRT) of <20 seconds and a normal deep vein system (DVS) by DM.Results. The mean pre- and postoperative VRTs were 13.79 and 26.43 seconds, respectively (P<0.0001). After surgery, 42 limbs (87.50%) had normal results by PPG (VRT > 20 seconds). Four limbs (8.33%) showed improved VRTs, but the VRTs did not reach 20 seconds. In the 2 limbs (4.17%) that maintained their original VRTs, the DM exams showed the presence of insufficient perforating veins.Conclusion. In most cases, PPG allows for a satisfactory evaluation of the outcome of varicose vein surgery.
Do Foxp3+Regulatory T Cells (Treg Cells) Play a Role in the Immunopathogenesis of Primary/Idiopathic Minimal Change Disease?
Authors: Hue Susan Swee-Shan , Suhail Sufi Muhammad , Choo Jason Chon Jun , Yusof Nurhashikin , Loh Alwin Hwai-Liang , Salcido-Ochoa Francisco
Published: February 2014

Minimal change disease constitutes a major cause of nephrotic syndrome. It is regarded as a non-immune-complex mediated primary glomerulopathy and pathogenetically is characterised by podocyte injury and effacement of foot processes; therefore, it is also classified as a type of podocytopathy. T cell dysfunction with increased levels of a soluble glomerular permeability factor has been proposed to play a major role in the pathogenesis of minimal change disease. It has been therefore suggested that a dysfunction of regulatory T cells, the orchestrators of immune homeostasis, could be implicated in perpetuating T cell activation in this condition. However, the actual contribution of regulatory T cell dysfunction in the immunopathogenesis of primary minimal change disease is still largely unclear. We here propose a theoretical model based on the available evidence.
Prime Decomposition of Three-Dimensional Manifolds into Boundary Connected Sum
Authors: Zhang Meili , Deng Bo
Published: February 2014

In 2003 Matveev suggested a new version of the Diamond Lemma suitable for topological applications. We apply this result to different situations and get a new conceptual proof of theorem on decomposition of three-dimensional manifolds into boundary connected sum of prime components.
Identification and Prevention of Antiepileptic Drug Noncompliance: The Collaborative Use of State-Supplied Pharmaceutical Data
Authors: Hodges Joseph C. , Treadwell Janet , Malphrus Amy D. , Tran Xuan G. , Giardino Angelo P.
Published: February 2014

Background. Antiepileptic drugs (AEDs) noncompliance is associated with increased risk of seizures and morbidity in seizure disorder patients. Objective. To identify risk factors that correlated to higher levels of morbidity, measured by emergency room (ER) utilization by seizure disorder members taking AED. Methods. Patients with primary or secondary diagnosis of seizures, convulsions, and/or epilepsy and prescribed AEDs during an 11-month period were included in the study. Variables were analyzed using multivariate statistical analysis including logistic regression. Results. The study identified 201 members. No statistical significance (NS) between age, gender, number of tablets, type of drug, or other risk factors was associated with increased mortality. Statistical significance resulted with medication compliance review of 0–14 days, 15–60 days, and 61+ days between refills. 68% of patients with ER visit had noncompliance refill between 0 and 14 days compared to 52% of patients in non-ER group (P=0.04). Contrastingly, 15% of ER group had refills within 15–60 days compared with 33% of non-ER group (P=0.01). There was NS difference between two groups when noncompliance was greater than 60 days (P=0.66). Conclusions. The study suggests that careful monitoring of pharmaceutical refill information could be used to identify AED noncompliance in epileptic patients.
Targeted Delivery System of Nanobiomaterials in Anticancer Therapy: From Cells to Clinics
Authors: Jin Su-Eon , Jin Hyo-Eon , Hong Soon-Sun
Published: February 2014

Targeted delivery systems of nanobiomaterials are necessary to be developed for the diagnosis and treatment of cancer. Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular levels and to deliver anticancer drugs into the diseased sites. In particular, nanobiomaterial-based nanocarriers, so-called nanoplatforms, are the design of the targeted delivery systems such as liposomes, polymeric nanoparticles/micelles, nanoconjugates, norganic materials, carbon-based nanobiomaterials, and bioinspired phage system, which are based on the nanosize of 1–100 nm in diameter. In this review, the design and the application of these nanoplatforms are discussed at the cellular levels as well as in the clinics. We believe that this review can offer recent advances in the targeted delivery systems of nanobiomaterials regardingin vitroandin vivoapplications and the translation of nanobiomaterials to nanomedicine in anticancer therapy.
Dementia Coding, Workup, and Treatment in the VA New England Healthcare System
Authors: Cho Kelly , Gagnon David R. , Driver Jane A. , Altincatal Arman , Kosik Nicole , Lanes Stephan , Lawler Elizabeth V.
Published: February 2014

Growing evidence suggests that Alzheimer’s disease and other types of dementia are underdiagnosed and poorly documented. In our study, we describe patterns of dementia coding and treatment in the Veteran’s Administration New England Healthcare System. We conducted a retrospective cohort study with new outpatient ICD-9 codes for several types of dementia between 2002 and 2009. We examined healthcare utilization, medication use, initial dementia diagnoses, and changes in diagnoses over time by provider type. 8,999 veterans received new dementia diagnoses during the study period. Only 18.3% received a code for cognitive impairment other than dementia, most often “memory loss” (65.2%) prior to dementia diagnosis. Two-thirds of patients received their initial code from a PCP. The etiology of dementia was often never specified by ICD-9 code, even by specialists. Patients followed up exclusively by PCPs had lower rates of neuroimaging and were less likely to receive dementia medication. Emergency room visits and hospitalizations were frequent in all patients but highest in those seen by dementia specialists. Dementia medications are commonly used off-label. Our results suggest that, for the majority the patients, no prodrome of the dementia syndrome is documented with diagnostic code, and patients who do not see dementia specialists have less extensive diagnostic assessment and treatment.
The Application of Response Surface Methodology in the Study of Photodegraded Industrial Dairy Effluents by the Photo-Fenton Process: Optimization and Economic Viability
Authors: Loures Carla Cristina Almeida , Izário Filho Hélcio José , Oliveira Ivy dos Santos , Lamas Samanamud Gisella Rossana , Souza André Luiz de , Silva Messias Borges
Published: February 2014

This study presents results from an application of Photo-Fenton process for organic-load reduction in dairy effluents. Process efficiency was evaluated in terms of percentage dissolved organic carbon, chemical oxygen demand, and biochemical oxygen demand (DOC, COD, and BOD, resp.), whose initial values were 1658±145 mg O2 L−1, 9500±500 mg O2 L−1, and 2400 ± 100 mg O2 L−1, respectively. We applied a statistical design represented by Box-Behnken factorial design inclusive of Fenton's reagent, the power of applied radiation (W), and pH factors. The set temperature value was 30°C with a reaction time of 60 min. The maximum efficiency obtained was at pH=3.5, Fenton reagent in the proportion of 35 g H2O2 + 3.6 g Fe2+, and ultraviolet radiation potency of 28 W. The results obtained for DOC, COD, and BOD were 81%, 90.7%, and 78.8%, respectively. Regarding the cost/benefit evaluation, the variables and their levels should be the following: pH 3.5, 35.0 g H2O2/Fe2+ 3.6 g, and 28 W UV, obtaining a reduction in concentration of 79.5% DOC.
Regulatory T Cells and the Immune Aging Process: A Mini-Review
Authors: Jagger Ann , Shimojima Yasuhiro , Goronzy Jorg J. , Weyand Cornelia M.
Published: February 2014

Constant exposure to new and persisting antigens and the need to replace cellular attrition with newly built cells lead to profound remodeling of the immune system after the age of 50 years. The impact of the immunosenescence process varies amongst the different cellular subsets represented within the immune system. Emerging data suggest that progressive aging significantly affects frequencies, subset distribution and functional competence of regulatory T cells (Tregs). Given the central role of Tregs in immune homeostasis, age-related loss of Treg function would be predicted to cause excessive immunity, encountered in elderly humans as a syndrome of chronic, smoldering inflammation as well as the age-related increase in the risk for autoimmunity. Conversely, age-dependent gain of Treg activity would result in failing immunity, such as the rising risk of malignancies and infections amongst the elderly. Emerging data suggest that some Treg populations, specifically naturally occurring Tregs, seem to accumulate with advancing age, whereas inducible Tregs appear to be less available in the older host. More studies are necessary to elucidate functional competence of old Tregs, with an emphasis on comparing the efficacy of young and old Tregs for defined functional domains. Mechanisms of declining Treg inducibility are not understood, but may provide an opportunity for targeted immunomodulation in the elderly. On the horizon is the potential to develop novel therapeutic interventions that target Tregs to make the elderly more efficient in fighting cancers and infections and dampen the risk for senescence-associated inflammation.
Primär dermales Melanom bei einer Patientin mit multiplen Malignomen in der Vorgeschichte: Ein Fallbericht mit molekularer Charakterisierung
Authors: Sini Germana , Colombino Maria , Lissia Amelia , Maxia Sara , Gulino Marcello , Paliogiannis Panagiotis , Palomba Grazia , Palmieri Giuseppe , Cossu Antonio , Rubino Corrado
Published: February 2014

Einleitung: Das primär dermale Melanom (PDM) ist eine kürzlich beschriebene klinische Entität und für weniger als 1% aller Melanome verantwortlich. Histologisch ist es in der Dermis oder im Subkutangewebe lokalisiert. Es zeigt keine Verbindung zur darüber liegenden Epidermis. Die Differentialdiagnose erfolgt prinzipiell zusammen mit der des metastasierten kutanen Melanoms. Fallbericht: Eine 72-jährige europäischstämmige Frau mit multiplen Krebserkrankungen in der Vorgeschichte (metachrones bilaterales Mammakarzinom, Meningeom, klarzelliges Nierenzellkarzinom, uterine Fibromatose und intestinale adenomatöse Polyposis) wurde mit einer nodulären Läsion auf dem Rücken vorstellig. Nach Entfernung der Läsion zeigte der histologische Befund ein malignes PDM oder ein metastasiertes malignes Melanom. Bei der klinischen und instrumentellen Beurteilung der Patientin fand sich kein anderer Primärtumor, was auf die primitive Natur der Läsion hindeutete. Das Fehlen einer epithelialen Komponente sprach für die histologische Diagnose eines PDM. Anschließend erfolgte eine weiträumige chirurgische Exzision mit Sentinel-Lymphknotenbiopsie, die positiv für ein metastasiertes Melanom ausfiel. Schließlich wurde der Mutationsstatus der wichtigsten Gene, die die Proliferation, Apoptose und Zellalterung steuern, untersucht. In den Genen CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 und PTEN wurden keine pathogenen Mutationen nachgewiesen. Dies lässt vermuten, dass andere Signalwege und Veränderungen mit niedriger Frequenz daran beteiligt sind. Schlussfolgerungen: Die Differenzialdiagnose zwischen PDM und einer isolierten Melanommetastase basiert auf der Negativität von bildgebender Diagnostik und klinischen Befunden hinsichtlich anderer Primärläsionen. Diese Unterscheidung ist wichtig, da die 5-Jahres-Überlebensraten in solchen Fällen höher sind als in Fällen mit Metastasierung (80-100% vs. 5-20%).