bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer and Sexual Problems
Authors: Sadovsky Richard , Basson Rosemary , Krychman Michael , Morales Antonio Martin , Schover Leslie , Wang Run , Incrocci Luca
Published: January 2010

Introduction

There are many data on sexual problems subsequent to cancer and its treatment, although the likelihood of problems in specific individuals depends on multiple variables.

Aims

To gain knowledge about the risks of sexual problems among persons with cancer and to provide recommendations concerning their prevention and optimal treatment.

Methods

A committee of multidisciplinary specialists was formed as part of a larger International Consultation working with urologic and sexual medicine societies over a 2-year period to review the result of chronic illness management on sexual function and satisfaction. The aims, goals, data collection techniques, and report format were defined by a central committee.

Main Outcomes Measures

Expert consensus was based on evidence-based medical and psychosocial literature review, extensive group discussion, and an open presentation with a substantial discussion period.

Results

Cancer and cancer treatments have both direct and indirect effects on physiologic, psychological, and interpersonal factors that can all impact negatively on sexual function and satisfaction. Data on the likelihood of specific sexual problems occurring with cancer and its management vary depending on prediagnosis function, patient response, support from the treatment team, specific treatments used, proactive counseling, and efforts to mitigate potential problems. This summary details available literature concerning the pathophysiologic and psychological impacts of cancer diagnosis and treatment on sexual function, plus recommendations for their prevention and management.

Conclusions

Cancer and its management have a significant negative impact on sexual function and satisfaction. These negative effects can be somewhat mitigated by understanding prediagnosis sexual functioning level, counseling, careful treatment choices, and, when indicated, therapy post-treatment using educational, psychological, pharmacologic, and mechanical modalities.
Sexual Function in Chronic Illness
Authors: Basson Rosemary , Rees Peter , Wang Run , Montejo Angel Luis , Incrocci Luca
Published: January 2010

Introduction

Direct and indirect effects of chronic disease on sexual health are frequent and complex, but guidelines for their optimal management are lacking. With improved surgical and medical treatment of the underlying disease, the numbers of men and women needing assessment and management of associated sexual dysfunction are increasing.

Aim

To provide recommendations/guidelines for the clinical management of sexual dysfunction within the context of chronic illness.

Methods

An international consultation in collaboration with the major sexual medicine associations assembled 186 multidisciplinary experts from 33 countries into 25 committees. Nine experts from four countries compiled the recommendations of sexual dysfunction in chronic illness and cancer with four focusing on neurological, renal, and psychiatric disease and lower urinary tract symptoms (LUTS). Searches were conducted using Medline, Embase, Lilacs, and Pubmed databases.

Main Outcome Measures

Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.

Results

Some conclusions concerning prevalence and pathophysiology of sexual dysfunction in the context of neurological disorders, end-stage renal failure, LUTS, and psychiatric disease were made. Optimal assessment of the multiple factors affecting sexuality when one or both partners are chronically ill is outlined. Evidence-based recommendations for management are presented. Comorbid depression is frequent and independently determines prevalence of sexual dysfunction in many conditions.

Conclusions

There is need for more research and scientific reporting on prevalence, pathophysiology, and optimal treatment of sexual dysfunction associated with chronic illness. Screening for and managing comorbid depression is strongly recommended.
Women’s Sexual Desire and Arousal Disorders
Authors: Brotto Lori A. , Bitzer Johannes , Laan Ellen , Leiblum Sandra , Luria Mijal
Published: January 2010

Introduction

A committee of five was convened to update the chapter on women’s sexual dysfunctions from the perspective of diagnostic issues, pathophysiology, assessment, and treatment.

Aim

To review the literature since 2003 and provide recommendations based on evidence.

Methods

Research databases, conference proceedings, and articles in press were read for relevant new data on these topics for hypoactive sexual desire disorder (HSDD), female sexual arousal disorder (FSAD), female orgasmic disorder (FOD), and persistent genital arousal disorder (PGAD).

Main Outcome Measures

Recommendations by five experts from five countries were formulated with associated grades.

Results

The definitions of HSDD, FSAD, and FOD in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text-Revised are imperfect and have been criticized over the last decade. Proposed new criteria that take into account empirical findings and the diversity across women are recommended. There has been a flurry of new epidemiological studies on women’s sexual dysfunction; studies also assessing distress consistenly find a much lower prevalence of dysfunction if distress is considered. Assessment of sexual difficulties is best achieved through a biopsychosocial clinical interview of the woman and her partner (if possible); though laboratory investigations, a physical examination, psychophysiological measurement, and self-report questionnaires can often supplement the interview information. There are currently no approved pharmacological treatments for women’s sexual dysfunction in North America, though a number of promising agents have been studied. Evidence for the efficacy of psychological treatments is based on limited studies. There is an urgent need for more data on the assessment, etiology, and treatment of PGAD.

Conclusions

Specific recommendations for the assessment and treatment of women’s desire, arousal, and orgasm disorders are forwarded; however, more research into these domains is needed.
Women’s Sexual Pain Disorders
Authors: Van Lankveld Jacques J.D.M. , Granot Michal , Weijmar Schultz Willibrord C.M. , Binik Yitzchak M. , Wesselmann Ursula , Pukall Caroline F. , Bohm-Starke Nina , Achtrari Chahin
Published: January 2010

Introduction

Women’s sexual pain disorders include dyspareunia and vaginismus and there is need for state-of-the-art information in this area.

Aim

To update the scientific evidence published in 2004, from the 2nd International Consultation on Sexual Medicine pertaining to the diagnosis and treatment of women’s sexual pain disorders.

Methods

An expert committee, invited from six countries by the 3rd International Consultation, was comprised of eight researchers and clinicians from biological and social science disciplines, for the purpose of reviewing and grading the scientific evidence on nosology, etiology, diagnosis, and treatment of women’s sexual pain disorders.

Main Outcome Measure

Expert opinion was based on grading of evidence-based medical literature, extensive internal committee discussion, public presentation, and debate.

Results

A comprehensive assessment of medical, sexual, and psychosocial history is recommended for diagnosis and management. Indications for general and focused pelvic genital examination are identified. Evidence-based recommendations for assessment of women’s sexual pain disorders are reviewed. An evidence-based approach to management of these disorders is provided.

Conclusions

Continued efforts are warranted to conduct research and scientific reporting on the optimal assessment and management of women’s sexual pain disorders, including multidisciplinary approaches.
Silver Co‐Firable ZnTiNb2O8 Microwave Dielectric Ceramics with Li2O–ZnO–B2O3 Glass Additive
Authors: Li Kecheng , Wang Hong , Zhou Huanfu , Zhang Minghui , Yao Xi
Published: January 2010

The effects of Li2O–ZnO–B2O3 glass additive on the sintering behavior, phase formation, microstructure, and microwave dielectric properties of ZnTiNb2O8 ceramics have been investigated. The sintering temperature of ZnTiNb2O8 ceramics can be effectively reduced from 1200°C to 875°C by adding a small amount of Li2O–ZnO–B2O3 glass, while no obvious degradation of the microwave dielectric properties was induced. Typically, the 2.0 wt% Li2O–ZnO–B2O3 glass‐added ceramic sintered at 875°C has better microwave dielectric properties of ɛr=31.8, Q×f=25,013 GHz, and τf=−62 ppm/°C. In addition, the ceramics can be co‐fired well with an Ag electrode.
An early report from newly established laboratory‐based influenza surveillance in Lao PDR
Authors: Vongphrachanh Phengta , Simmerman James M. , Phonekeo Darouny , Pansayavong Vimatha , Sisouk Thongchanh , Ongkhamme Somvay , Bryce Gary T. , Corwin Andrew , Bryant Juliet E.
Published: January 2010

Please cite this paper as: Vongphrachanh P, Simmerman JM, Phonekeo D, Pansayavong V, Sisouk T, Ongkhamme S, Bryce GT, Corwin A, Bryant JE. An early report from newly established laboratory‐based influenza surveillance in Lao PDR. Influenza and Other Respiratory Viruses 4(2), 47–52.

Background  Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory‐based influenza surveillance system established in the Lao People’s Democratic Republic.

Methods  Three hospitals in the capital city of Vientiane began surveillance for influenza‐like illness (ILI) in outpatients in 2007 and expanded to include hospitalized pneumonia patients in 2008. Nasal/throat swab specimens were collected and tested for influenza and other respiratory viruses by multiplex ID‐TagTM respiratory viral panel (RVP) assay on a Luminex® 100× MAP IS instrument (Qiagen, Singapore).

Results  During January 2007 to December 2008, 287 of 526 (54·6%) outpatients with ILI were positive for at least one respiratory virus. Influenza was most commonly identified, with 63 (12·0%) influenza A and 92 (17·5%) influenza B positive patients identified. In 2008, six of 79 (7·6%) hospitalized pneumonia patients were positive for influenza A and four (5·1%) were positive for influenza B. Children <5 years represented 19% of viral infections in outpatients and 38% of pneumonia inpatients.

Conclusion  Our results provide the first documentation of influenza burden among patients with febrile respiratory illness and pneumonia requiring hospitalization in Laos. Implementing laboratory‐based influenza surveillance requires substantial investments in infrastructure and training. However, continuing outbreaks of avian influenza A/H5N1 in poultry and emergence of the 2009 influenza A(H1N1) pandemic strain further underscore the importance of establishing and maintaining influenza surveillance in developing countries.
Expenditure by conservation nongovernmental organizations in sub‐Saharan Africa
Authors: Brockington Dan , Scholfield Katherine
Published: January 2010

Evaluations of conservation performance and efficiency are still in their infancy. They will require understanding more about where conservation funds are actually spent, and how conservation sectors are structured. We present an overview of the work of conservation nongovernmental organizations (NGOs) in sub‐Saharan Africa from 2004 to 2006, based on an extensive survey and consultation exercise. We show that the distribution of funds within the sector is highly unequal, concentrated in a few organizations. Expenditure within the continent is uneven, highest in the south and lowest in the west. Only a small proportion of protected areas receive some form of support. At a country level, expenditure is well matched with species richness and threat, but the causes of those correlations are not clear. These results identify what we need to know about what conservation organizations actually do and thus advance the task of evaluating conservation effectiveness.
Late subsequent ocular morbidity in retinopathy of prematurity patients, with emphasis on visual loss caused by insidious ‘involutive’ pathology: an observational series
Authors: Fledelius Hans C. , Jensen Hanne
Published: January 2010

Purpose: This paper discusses late complications in eyes of surviving premature infants typically occurring years into the steady state attained after the initial ophthalmic events associated with preterm birth. The study focuses on insidious visual loss, as well as eventual vitreoretinal and anterior segment disorders.

Methods: We carried out a retrospective uncontrolled study of a case series (n = 31) of late complications to early ocular changes associated with very preterm delivery. The birth years of our subjects extended back to 1941, but only 15 more recent cases fulfilled contemporary criteria for a diagnosis of retinopathy of prematurity (ROP).

Results: Fourteen cases involvedvitreoretinalpathology (median observation time 14 years, range 6–46 years) with late detachment and/or vitreous haemorrhage. Twelve cases primarily involvedanterior segmentpathology (median observation time 37 years, range 7–58 years). Eyes in the latter category often showed features of early arrested growth and anterior traction, which, in four eyes, eventually led to enucleation or exenteration as a result of a blind and painful terminal state. The last five cases (observation periods 22–38 years) were labelled ‘miscellaneous’. Among the 31 patients, we identified a subgroup in whichinsidious visual losswas a common feature (n = 20). Initially, some of these cases showed evidence of cicatricial ROP and low vision from early in life. Others retained useful vision and did not present obvious ocular incidents related to the actual visual acuity decline.

Conclusions: Based on a variety of clinical ophthalmic preterm appearances, we propose the hypothesis that, in addition to increased structural vulnerability, a reduced functional reserve may pave the way for further abiotrophy or involution over time. This may manifest as reduced resistance to later ophthalmic events, such as disease or trauma, or simply the impact of age.
Colonization of fish skin is vital for Vibrio anguillarum to cause disease
Authors: Weber Barbara , Chen Chang , Milton Debra L.
Published: January 2010

Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities.
Clinical Safety of the 5 O'clock Portal in Shoulder Arthroscopy: A Prospective Study
Authors: Mehta Vishal M.
Published: January 2010

Background

The present study aimed to determine the rate of clinically significant neurovascular complications associated with the routine use of the 5 o'clock portal during arthroscopic Bankart repair.

Methods

Forty-eight consecutive patients underwent arthroscopic Bankart repair with the use of the 5 o'clock portal. These patients were followed at 2 weeks and 6 weeks postoperatively for subjective signs of neurovascular injury (i.e. numbness and tingling) as well as objective signs (i.e. intraoperative bleeding, radial pulse, capillary refill, sensation, motor strength, haematoma and oedema).

Results

Two out of 48 patients (4.2%) experienced transient neurological symptoms in an ulnar nerve distribution, which resolved by 6 weeks. There was no occurrence of clinically significant injury to the axillary nerve, axillary artery, musculocutaneous nerve, lateral cord of the brachial plexus or cephalic vein.

Conclusions

No clinically detectable neurovascular injuries were associated with the use of the 5 o'clock shoulder portal during Bankart repair.
Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease
Authors: Bacic Angela , Kogika Márcia M. , Barbaro Kátia C. , Iuamoto Cristina S. , Simões Denise M. N. , Santoro Marcelo L.
Published: January 2010

Background:Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD).

Objective:The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD.

Methods:Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD.

Results:UAC in dogs with CKD (range, 0.002–7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005–0.01; median, 0.002). Microalbuminuria (UAC 0.03–0.3) and macroalbuminuria (UAC>0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure ≥180 mmHg; in these dogs, UAC ratio (range, 0.006–7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure<180 mmHg (range, 0.002–4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC>1.0 usually had macroalbuminuria, those with UPC 0.5–1.0 usually had microalbuminuria, and those with UPC<0.5 usually lacked albuminuria.

Conclusions:UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC≤1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.
Hepatic Volume Measurements in Dogs with Extrahepatic Congenital Portosystemic Shunts before and after Surgical Attenuation
Authors: Kummeling A. , Vrakking D.J.E. , Rothuizen J. , Gerritsen K.M. , Van Sluijs F.J.
Published: January 2010

Background:In dogs with congenital portosystemic shunts (CPSS), the ability of the hypoplastic liver to grow is considered important for recovery after surgical shunt attenuation.

Objectives:This study investigated hepatic growth after extrahepatic shunt attenuation in dogs using magnetic resonance imaging (MRI) and computed tomography (CT).

Animals:Ten client‐owned dogs with single extrahepatic CPSS.

Methods:Abdominal MRI, CT, or both were performed before and 8 days, 1, and 2 months after shunt attenuation. Liver volumes were calculated from the areas of the MRI or CT images.

Results:Before surgery, median liver volume was 18.2 cm3/kg body weight. Liver volume increased significantly after surgery. Growth was highest between days 0 and 8 and decreased afterward. Median liver volume was 28.8 cm3/kg at 2 months after attenuation. No significant differences in growth were found between dogs with complete or partial shunt closure or between dogs with complete or incomplete metabolic recovery. Volumes measured from consecutively performed MRI and CT images correlated well (r= 0.980), but volumes from MRI images were significantly larger than volumes from CT images (6.8%;P= .008).

Conclusion and Clinical Importance:After shunt attenuation, rapid normalization of liver size was observed. Hepatic growth was not decreased in dogs after partial closure of CPSS or in dogs with subclinical, persistent shunting 2 months after surgery. CT is the preferred imaging method for volumetric estimation because of speed.
Serum Amyloid A and Haptoglobin Concentrations and Liver Fat Percentage in Lactating Dairy Cows with Abomasal Displacement
Authors: Guzelbektes H. , Sen I. , Ok M. , Constable P.D. , Boydak M. , Coskun A.
Published: January 2010

Background:There has been increased interest in measuring the serum concentration of acute phase reactants such as serum amyloid A [SAA] and haptoglobin [haptoglobin] in periparturient cattle in order to provide a method for detecting the presence of inflammation or bacterial infection.

Objectives:To determine whether [SAA] and [haptoglobin] are increased in cows with displaced abomasum as compared with healthy dairy cows.

Animals:Fifty‐four adult dairy cows in early lactation that had left displaced abomasum (LDA, n = 34), right displaced abomasum or abomasal volvulus (RDA/AV, n = 11), or were healthy on physical examination (control, n = 9).

Materials and Methods:Inflammatory diseases or bacterial infections such as mastitis, metritis, or pneumonia were not clinically apparent in any animal. Jugular venous blood was obtained from all cows and analyzed. Liver samples were obtained by biopsy in cattle with abomasal displacement.

Results:[SAA] and [haptoglobin] concentrations were increased in cows with LDA or RDA/AV as compared with healthy controls. Cows with displaced abomasum had mild to moderate hepatic lipidosis, based on liver fat percentages of 9.3 ± 5.3% (mean ± SD, LDA) and 10.8 ± 7.7% (RDA/AV). [SAA] and [haptoglobin] were most strongly associated with liver fat percentage,rs=+0.55 (P< .0001) andrs=+0.42 (P= .0041), respectively.

Conclusions and Clinical Importance:An increase in [SAA] or [haptoglobin] in postparturient dairy cows with LDA or RDA/AV is not specific for inflammation or bacterial infection. An increase in [SAA] or [haptoglobin] may indicate the presence of hepatic lipidosis in cattle with abomasal displacement.
Congenital Cardiac Defects in Neonatal Foals: 18 Cases (1992–2007)
Authors: Hall T.L. , Magdesian K.G. , Kittleson M.D.
Published: January 2010

Background:Literature available regarding congenital cardiac defects in foals is limited to reports of individual cases or small case series.

Objective:To describe the clinical, echocardiographic, and necropsy findings and breed predilection of congenital cardiac defects in neonatal foals.

Animals:Eighteen foals <15 days of age with 1 or more congenital cardiac defects.

Methods:Medical records of foals diagnosed with congenital cardiac defects at the William R. Pritchard Veterinary Medical Teaching Hospital were reviewed. Data collected included history, signalment, clinical signs, laboratory data, diagnostic and necropsy results, and outcome.

Results:Arabian foals represented 39% of cases with congenital cardiac defects and were significantly (P= .004) overrepresented (OR = 4.7 [CI: 1.8–12.4]) compared with the general hospital population. Ventricular septal defect (VSD) (14/18), tetralogy of Fallot (5/18), and tricuspid valve atresia (4/18) were the most common defects identified. A ≥3/6 heart murmur (14/14) accompanied by tachycardia (14/17), tachypnea (17/17), and cyanosis of mucous membranes (7/16) were the most common clinical signs. Concurrent congenital defects were common (9/18). Two foals, both with VSD, survived for ≥ 8 years after diagnosis and 1 was a successful performance horse.

Conclusions and Clinical Relevance:Arabian horses appear to have a predisposition for cardiac defects. The presence of a loud murmur (≥ 3/6), cyanotic membranes, and tachycardia or tachypnea in a neonatal foal should warrant thorough evaluation of the heart for congenital defects. Foals with cardiac defects should be closely evaluated for concurrent congenital defects in other body systems.
Mitochondria as the Target
Authors: Ray L. Bryan
Published: January 2010

Mammalian target of rapamycin (mTOR) protein is proposed to act at the mitochondrial membrane to control metabolism.
Science Signaling
Podcast: 5 January 2010
Authors: Yaffe Michael B. , VanHook Annalisa M.
Published: January 2010

Chief Scientific Editor Michael Yaffe reviews the year in
Science Signaling
.
Evaluation of New Thiazolide/Thiadiazolide Derivatives Reveals Nitro Group-Independent Efficacy against
In Vitro
Development of
Cryptosporidium parvum
Authors: Gargala Gilles , Le Goff Laetitia , Ballet Jean-Jacques , Favennec Loic , Stachulski Andrew V. , Rossignol Jean-François
Published: January 2010

Thirty-nine new thiazolide/thiadiazolide compounds were compared with the nitrothiazole nitazoxanide for activity against
Cryptosporidium parvum
development in HCT-8 cells. Twenty-seven agents exerted ≥90% inhibition. Agents with a lower 50% inhibitory concentration (IC
50
) than nitazoxanide were either NO
2
or halogen 5 substituted on the thiazole moiety. Other 5 substitutions such as methyl, C
3
H
7
, C
6
H
11
, H, SO
2
CH
3
, and SCH
3
negatively impacted activity. Five-substituted deacetylated analogues exhibited higher IC
50
s than their acetylated counterparts. Halogeno-thiazolide/thiadiazolides may provide valuable nitro-free alternatives to nitazoxanide.
Activity of Dalbavancin against
Bacillus anthracis In Vitro
and in a Mouse Inhalation Anthrax Model
Authors: Heine Henry S. , Purcell Bret K. , Bassett Jennifer , Miller Lynda , Goldstein Beth P.
Published: January 2010

Bacillus anthracis
, the causative agent of anthrax, can produce fatal disease when it is inhaled or ingested by humans. Dalbavancin, a novel, semisynthetic lipoglycopeptide, has potent activity, greater than that of vancomycin, against Gram-positive bacteria and a half-life in humans that supports once-weekly dosing. Dalbavancin demonstrated potent
in vitro
activity against
B. anthracis
(MIC range, ≤0.03 to 0.5 mg/liter; MIC
50
and MIC
90
, 0.06 and 0.25 mg/liter, respectively), which led us to test its efficacy in a murine inhalation anthrax model. The peak concentrations of dalbavancin in mouse plasma after the administration of single intraperitoneal doses of 5 and 20 mg/kg of body weight were 15 and 71 mg/kg, respectively. At 20 mg/kg, the dalbavancin activity was detectable for 6 days after administration (terminal half-life, 53 h), indicating that long intervals between doses were feasible. The mice were challenged with 50 to 100 times the median lethal dose of the Ames strain of
B. anthracis
, an inoculum that kills untreated animals within 4 days. The efficacy of dalbavancin was 80 to 100%, as determined by the rate of survival at 42 days, when treatment was initiated 24 h postchallenge with regimens of 15 to 120 mg/kg every 36 h (q36h) or 30 to 240 mg/kg every 72 h (q72h). A regimen of ciprofloxacin known to protect 100% of animals was tested in parallel. Delayed dalbavancin treatment (beginning 36 or 48 h postchallenge) with 60 mg/kg q36h or 120 mg/kg q72h still provided 70 to 100% survival. The low MICs and long duration of efficacy
in vivo
suggest that dalbavancin may have potential as an alternative treatment or for the prophylaxis of
B. anthracis
infections.
Pradimicin S, a Highly Soluble Nonpeptidic Small-Size Carbohydrate-Binding Antibiotic, Is an Anti-HIV Drug Lead for both Microbicidal and Systemic Use
Authors: Balzarini Jan , François Katrien O. , Van Laethem Kristel , Hoorelbeke Bart , Renders Marleen , Auwerx Joeri , Liekens Sandra , Oki Toshikazu , Igarashi Yasuhiro , Schols Dominique
Published: January 2010

Pradimicin S (PRM-S) is a highly water-soluble, negatively charged derivative of the antibiotic pradimicin A (PRM-A) in which the terminal xylose moiety has been replaced by 3-sulfated glucose. PRM-S does not prevent human immunodeficiency virus (HIV) adsorption on CD4
+
T cells, but it blocks virus entry into its target cells. It inhibits a wide variety of HIV-1 laboratory strains and clinical isolates, HIV-2, and simian immunodeficiency virus (SIV) in various cell culture systems (50% and 90% effective concentrations [EC
50
s and EC
90
s] invariably in the lower micromolar range). PRM-S inhibits syncytium formation between persistently HIV-1- and SIV-infected cells and uninfected CD4
+
T lymphocytes, and prevents dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-mediated HIV-1 and SIV capture and subsequent virus transmission to CD4
+
T cells. Surface plasmon resonance (SPR) studies revealed that PRM-S strongly binds to gp120 in a Ca
2+
-dependent manner at an affinity constant (

K
D

) in the higher nanomolar range. Its anti-HIV activity and HIV-1 gp120-binding properties can be dose-dependently reversed in the presence of an (α-1,2)mannose trimer. Dose-escalating exposure of HIV-1-infected cells to PRM-S eventually led to the isolation of mutant virus strains that had various deleted N-glycosylation sites in the envelope gp120 with a strong preference for the deletion of the high-mannose-type glycans. Genotypic resistance development occurred slowly, and significant phenotypic resistance occurred only after the sequential appearance of up to six mutations in gp120, pointing to a high genetic barrier of PRM-S. The antibiotic is nontoxic against a variety of cell lines, is not mitogenic, and does not induce cytokines and chemokines in peripheral blood mononuclear cells as determined by the Bio-Plex human cytokine 27-plex assay. It proved stable at high temperature and low pH. Therefore, PRM-S may qualify as a potential anti-HIV drug candidate for further (pre)clinical studies, including its microbicidal use.
In
Vitro
and
In Vivo
Activities of the Novel Anticytomegalovirus Compound AIC246
Authors: Lischka Peter , Hewlett Guy , Wunberg Tobias , Baumeister Judith , Paulsen Daniela , Goldner Thomas , Ruebsamen-Schaeff Helga , Zimmermann Holger
Published: January 2010

Human cytomegalovirus (HCMV) remains a serious threat for immunocompromised individuals, including transplant recipients and newborns. To date, all drugs licensed for the treatment of HCMV infection and disease target the viral DNA polymerase. Although these drugs are effective, several drawbacks are associated with their use, including toxicity and emergence of drug resistance. Hence, new and improved antivirals with novel molecular targets are urgently needed. Here we report on the antiviral properties of AIC246, a representative of a novel class of low-molecular-weight compounds that is currently undergoing clinical phase II studies. The anti-HCMV activity of AIC246 was evaluated
in vitro
and
in vivo
using various cell culture assays and an engineered mouse xenograft model. In addition, antiviral properties of the drug were characterized in comparison to the current gold standard ganciclovir. We demonstrate that AIC246 exhibits excellent
in vitro
inhibitory activity against HCMV laboratory strains and clinical isolates, retains activity against ganciclovir-resistant viruses, is well tolerated in different cell types (median selectivity index, 18,000), and exerts a potent
in vivo
efficacy in a mouse xenograft model. Moreover, we show that the antiviral block induced by AIC246 is reversible and the efficacy of the drug is not significantly affected by cell culture variations such as cell type or multiplicity of infection. Finally, initial mode-of-action analyses reveal that AIC246 targets a process in the viral replication cycle that occurs later than DNA synthesis. Thus, AIC246 acts via a mode of action that differs from that of polymerase inhibitors like ganciclovir.
Lactobacillus reuteri
2′-Deoxyribosyltransferase, a Novel Biocatalyst for Tailoring of Nucleosides
Authors: Fernández-Lucas Jesús , Acebal Carmen , Sinisterra José V. , Arroyo Miguel , de la Mata Isabel
Published: January 2010

A novel type II nucleoside 2′-deoxyribosyltransferase from
Lactobacillus reuteri
(
Lr
NDT) has been cloned and overexpressed in
Escherichia coli
. The recombinant
Lr
NDT has been structural and functionally characterized. Sedimentation equilibrium analysis revealed a homohexameric molecule of 114 kDa. Circular dichroism studies have showed a secondary structure containing 55% α-helix, 10% β-strand, 16% β-sheet, and 19% random coil.
Lr
NDT was thermostable with a melting temperature (

T
m

) of 64°C determined by fluorescence, circular dichroism, and differential scanning calorimetric studies. The enzyme showed high activity in a broad pH range (4.6 to 7.9) and was also very stable between pH 4 and 7.9. The optimal temperature for activity was 40°C. The recombinant
Lr
NDT was able to synthesize natural and nonnatural nucleoside analogues, improving activities described in the literature, and remarkably, exhibited unexpected new arabinosyltransferase activity, which had not been described so far in this kind of enzyme. Furthermore, synthesis of new arabinonucleosides and 2′-fluorodeoxyribonucleosides was carried out.
Identification by Suppression Subtractive Hybridization of
Frankia
Genes Induced under Nitrogen-Fixing Conditions
Authors: Yamaura Masatoshi , Uchiumi Toshiki , Higashi Shiro , Abe Mikiko , Kucho Ken-ichi
Published: January 2010

Frankia
is an actinobacterium that fixes nitrogen under both symbiotic and free-living conditions. We identified genes upregulated in free-living nitrogen-fixing cells by using suppression subtractive hybridization. They included genes with predicted functions related to nitrogen fixation, as well as with unknown function. Their upregulation was a novel finding in
Frankia
.
Isolation and Characterization of Bacteria Resistant to Metallic Copper Surfaces
Authors: Espírito Santo Christophe , Morais Paula Vasconcelos , Grass Gregor
Published: January 2010

Metallic copper alloys have recently attracted attention as a new antimicrobial weapon for areas where surface hygiene is paramount. Currently it is not understood on a molecular level how metallic copper kills microbes, but previous studies have demonstrated that a wide variety of bacteria, including
Escherichia coli
,
Staphylococcus aureus
, and
Clostridium difficile
, are inactivated within minutes or a few hours of exposure. In this study, we show that bacteria isolated from copper alloy coins comprise strains that are especially resistant against the toxic properties exerted by dry metallic copper surfaces. The most resistant of 294 isolates were Gram-positive staphylococci and micrococci,
Kocuria palustris
, and
Brachybacterium conglomeratum
but also included the proteobacterial species
Sphingomonas panni
and
Pseudomonas oleovorans
. Cells of some of these bacterial strains survived on copper surfaces for 48 h or more. Remarkably, when these dry-surface-resistant strains were exposed to moist copper surfaces, resistance levels were close to those of control strains and MICs for copper ions were at or below control strain levels. This suggests that mechanisms conferring resistance against dry metallic copper surfaces in these newly isolated bacterial strains are different from well-characterized copper ion detoxification systems. Furthermore, staphylococci on coins did not exhibit increased levels of resistance to antibiotics, arguing against coselection with copper surface resistance traits.
Synergistic Effects of Sodium Chloride, Glucose, and Temperature on Biofilm Formation by
Listeria monocytogenes
Serotype 1/2a and 4b Strains
Authors: Pan Youwen , Breidt Frederick , Gorski Lisa
Published: January 2010

Biofilm formation by
Listeria monocytogenes
is generally associated with its persistence in the food-processing environment. Serotype 1/2a strains make up more than 50% of the total isolates recovered from food and the environment, while serotype 4b strains are most often associated with major outbreaks of human listeriosis. Using a microplate assay with crystal violet staining, we examined biofilm formation by 18 strains of each serotype in tryptic soy broth with varying concentrations of glucose (from 0.25% to 10.0%, wt/vol), sodium chloride (from 0.5% to 7.0%, wt/vol) and ethanol (from 1% to 5.0%, vol/vol), and at different temperatures (22.5°C, 30°C, and 37°C). A synergistic effect on biofilm formation was observed for glucose, sodium chloride, and temperature. The serotype 1/2a strains generally formed higher-density biofilms than the 4b strains under most conditions tested. Interestingly, most serotype 4b strains had a higher growth rate than the 1/2a strains, suggesting that the growth rate may not be directly related to the capacity for biofilm formation. Crystal violet was found to stain both bacterial cells and biofilm matrix material. The enhancement in biofilm formation by environmental factors was apparently due to the production of extracellular polymeric substances instead of the accumulation of viable biofilm cells.
Population Polymorphism of Nuclear Mitochondrial DNA Insertions Reveals Widespread Diploidy Associated with Loss of Heterozygosity in Debaryomyces hansenii
Authors: Jacques Noémie , Sacerdot Christine , Derkaoui Meriem , Dujon Bernard , Ozier-Kalogeropoulos Odile , Casaregola Serge
Published: January 2010

Debaryomyces hansenii
, a yeast that participates in the elaboration of foodstuff, displays important genetic diversity. Our recent phylogenetic classification of this species led to the subdivision of the species into three distinct clades.
D. hansenii
harbors the highest number of nuclear mitochondrial DNA (NUMT) insertions known so far for hemiascomycetous yeasts. Here we assessed the intraspecific variability of the NUMTs in this species by testing their presence/absence first in 28 strains, with 21 loci previously detected in the completely sequenced strain CBS 767
T
, and second in a larger panel of 77 strains, with 8 most informative loci. We were able for the first time to structure populations in
D. hansenii
, although we observed little NUMT insertion variability within the clades. We determined the chronology of the NUMT insertions, which turned out to correlate with the previously defined taxonomy and provided additional evidence that colonization of nuclear genomes by mitochondrial DNA is a dynamic process in yeast. In combination with flow cytometry experiments, the NUMT analysis revealed the existence of both haploid and diploid strains, the latter being heterozygous and resulting from at least four crosses among strains from the various clades. As in the diploid pathogen
Candida albicans
, to which
D. hansenii
is phylogenetically related, we observed a differential loss of heterozygosity in the diploid strains, which can explain some of the large genetic diversity found in
D. hansenii
over the years.
Microscopic Detection of ViableStaphylococcus epidermidisin Peri-Implant Tissue in Experimental Biomaterial-Associated Infection, Identified by Bromodeoxyuridine Incorporation
Authors: Broekhuizen C. A. N. , Sta M. , Vandenbroucke-Grauls C. M. J. E. , Zaat S. A. J.
Published: January 2010

Infection of biomedical devices is characterized by biofilm formation and colonization of surrounding tissue by the causative pathogens. To investigate whether bacteria detected microscopically in tissue surrounding infected devices were viable, we used bromodeoxyuridine (BrdU), a nucleotide analogue that is incorporated into bacterial DNA and can be detected with antibodies. Infected human tissue was obtained postmortem from patients with intravascular devices, and mouse biopsy specimens were obtained from mice with experimental biomaterial infection.In vitroexperiments showed thatStaphylococcus epidermidisincorporated BrdU, as judged from staining of the bacteria with anti-BrdU antibodies. After incubation of bacteria with BrdU and subsequent staining of microscopic sections with anti-BrdU antibodies, bacteria could be clearly visualized in the tissue surrounding intravascular devices of deceased patients. With this staining technique, relapse of infection could be visualized in mice challenged with a low dose ofS. epidermidisand treated with dexamethasone between 14 and 21 days after challenge to suppress immunity. This confirms and extends our previous findings that pericatheter tissue is a reservoir for bacteria in biomaterial-associated infection. The pathogenesis of the infection and temporo-spatial distribution of viable, dividing bacteria can now be studied at the microscopic level by immunolabeling with BrdU and BrdU antibodies.
Neisseria gonorrhoeae
Survival during Primary Human Cervical Epithelial Cell Infection Requires Nitric Oxide and Is Augmented by Progesterone
Authors: Edwards Jennifer L.
Published: January 2010

Neisseria gonorrhoeae
is an obligate human pathogen that causes gonorrhea. We have shown previously that complement receptor 3 and Akt kinase play important roles in mediating cervical infection. At present, there are limited data to indicate how hormonally induced changes to the mucosal epithelia of the female genital tract mediate the course of gonococcal disease. Hence, I have expanded upon previous work to investigate the interaction of gonococci with primary human cervical epithelial (pex) cells under the variable estrogen and progesterone concentrations likely to be encountered
in vivo
throughout the female menstrual cycle. My data indicated that the ability of gonococci to survive and to replicate within pex cells was increased under progesterone-predominant conditions. Using bacterial survival, immunological, and kinase assays, I show that progesterone functioned in an additive manner with gonococcal phospholipase D to augment Akt kinase activity. This, in turn, resulted in a parallel increase in nitric oxide synthase expression. Nitric oxide production by pex cells was dependent upon Akt activity and was increased under progesterone-predominant conditions. Whereas both inducible and endothelial nitric oxide synthase contributed to nitric oxide production, only inducible nitric oxide synthase activity promoted gonococcal survival within pex cells. Collectively, these data provide the first clues as to how steroid hormones potentially modulate the course of gonococcal disease in women. In addition, these data demonstrate that host-derived nitric oxide likely is not protective against gonococci,
in vivo
; rather, nitric oxide may be required to sustain cervical bacterial disease.
The Apparent Malate Synthase Activity of
Rhodobacter sphaeroides
Is Due to Two Paralogous Enzymes, (3
S
)-Malyl-Coenzyme A (CoA)/β-Methylmalyl-CoA Lyase and (3
S
)- Malyl-CoA Thioesterase
Authors: Erb Tobias J. , Frerichs-Revermann Lena , Fuchs Georg , Alber Birgit E.
Published: January 2010

Assimilation of acetyl coenzyme A (acetyl-CoA) is an essential process in many bacteria that proceeds via the glyoxylate cycle or the ethylmalonyl-CoA pathway. In both assimilation strategies, one of the final products is malate that is formed by the condensation of acetyl-CoA with glyoxylate. In the glyoxylate cycle this reaction is catalyzed by malate synthase, whereas in the ethylmalonyl-CoA pathway the reaction is separated into two proteins: malyl-CoA lyase, a well-known enzyme catalyzing the Claisen condensation of acetyl-CoA with glyoxylate and yielding malyl-CoA, and an unidentified malyl-CoA thioesterase that hydrolyzes malyl-CoA into malate and CoA. In this study the roles of Mcl1 and Mcl2, two malyl-CoA lyase homologs in
Rhodobacter sphaeroides
, were investigated by gene inactivation and biochemical studies. Mcl1 is a true (3
S
)-malyl-CoA lyase operating in the ethylmalonyl-CoA pathway. Notably, Mcl1 is a promiscuous enzyme and catalyzes not only the condensation of acetyl-CoA and glyoxylate but also the cleavage of β-methylmalyl-CoA into glyoxylate and propionyl-CoA during acetyl-CoA assimilation. In contrast, Mcl2 was shown to be the sought (3
S
)-malyl-CoA thioesterase in the ethylmalonyl-CoA pathway, which specifically hydrolyzes (3
S
)-malyl-CoA but does not use β-methylmalyl-CoA or catalyze a lyase or condensation reaction. The identification of Mcl2 as thioesterase extends the enzyme functions of malyl-CoA lyase homologs that have been known only as “Claisen condensation” enzymes so far. Mcl1 and Mcl2 are both related to malate synthase, an enzyme which catalyzes both a Claisen condensation and thioester hydrolysis reaction.
Complete Genome Sequence of
Staphylococcus lugdunensis
Strain HKU09-01
Authors: Tse Herman , Tsoi Hoi Wah , Leung Sze Pui , Lau Susanna K. P. , Woo Patrick C. Y. , Yuen Kwok Yung
Published: January 2010

Staphylococcus lugdunensis
is a member of the coagulase-negative staphylococci and commonly found as part of the human skin flora. It is a significant cause of catheter-related bacteremia and also causes serious infections like native valve endocarditis in previously healthy individuals. We report the complete genome sequence of this medically important bacterium.
Traffic conflicts for road user safety studies
Authors: Brow Gerald R.
Published: January 2010

In this paper we advocate an approach to road safety studies in which traffic conflicts are used as indicators of roadway hazard. The critical traffic process event used to define conflict severity is the time to collision, modified by an observer's evaluation of the risk of collision. Field studies were done to assess the validity, reliability, and practicality of traffic conflicts. Experiments were conducted to test the threshold value of time to collision, and to examine a visual perception theory of crash avoidance behaviour. The experiments demonstrate that a time to collision threshold value of 1.5 s is a reasonable time-based index of hazard and that a visual perception model of breaking is a promising concept. The wider potential for traffic conflicts as a measure of driver risk, and as a basis for safety models, is discussed in the paper. The technique has been used for some 45 intersection safety studies. From the application to date it appears that the systematic observation of crash avoidance behaviour of drivers in unsafe conditions provides a useful tool for traffic engineering analysis of intersection traffic control and design problems. Key words: road safety, traffic conflicts, time to collision, driver risk, safety models.