bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive emotion reduces dyspnea during slow paced breathing
Authors: Allen Ben , Friedman Bruce H.
Published: January 2012

Slow breathing is used to induce cardiovascular resonance, a state associated with health benefits, but it can also increase tidal volume and associated dyspnea (respiratory discomfort). Dyspnea may be decreased by induced positive affect. In this study, 71 subjects (36 men, M = 20 years) breathed at 6 breaths per min. In condition one, subjects paced their breathing by inhaling and exhaling as a vertical bar moved up and down. In condition two, breathing was paced by a timed slideshow of positive images; subjects inhaled during a black screen and exhaled as the image appeared. Cardiac, respiratory, and self‐reported dyspnea and emotional indices were recorded. Tidal volume and the intensity and unpleasantness of dyspnea were reduced when paced breathing was combined with pleasant images. These results show that positive affect can reduce dyspnea during slow paced breathing, and may have applications for induced cardiovascular resonance.
Hypoxia regulation of ATP13A2 (PARK9) gene transcription
Authors: Xu Qian , Guo Hongling , Zhang Xiaojie , Tang Beisha , Cai Fang , Zhou Weihui , Song Weihong
Published: January 2012

J. Neurochem. (2012) 122, 251–259.

Parkinson’s disease (PD) is the second most common neurodegenerative disorders with a variable combination of motor and non‐motor symptoms. Mutations in several genes including ATP13A2 (PARK9) are reported to be associated with PD. The underlying mechanism of PD is not well defined, however, both genetic and environmental causes contribute to it. ATP13A2 gene locates in chromosome 1 and contains 29 exons encoding for a protein of 1180 amino acids with 10 transmembrane domains. Abnormal gene expression has been implicated in neurodegenerative disorders. The transcriptional regulation of the ATP13A2 gene is unknown. In this report, we cloned and functionally characterized the human ATP13A2 gene promoter. We showed that the promoter region of the human ATP13A2 gene contains hypoxia response elements which can bind to transcription factor hypoxia‐inducible factor 1α (HIF‐1α). Hypoxia up‐regulated ATP13A2 transcription via HIF‐1α in HEK293 and dopaminergic MN9D cells. Our study indicates that hypoxia signaling plays a very important role in the regulation of human ATP13A2 gene expression. Further study is needed to determine the role of hypoxia in the pathogenesis of PD and its interaction with other PD causative genes, which will provide insights to the role of hypoxia and dysregulation of gene expression in Parkinson’s disease.
A nocturnal Provespa wasp species as the probable pollinator of epiphytic orchid Coelogyne fimbriata
Authors: NAKASE Yuta , KATO Makoto
Published: January 2012

Many vespid wasps visit flowers to forage nectar. These hymenopterans sometimes contribute to flower pollination. However, none of the nocturnal wasp species is a known pollinator. We collected individuals of light‐attracted Provespa nocturna workers in a montane rainforest on Peninsular Malaysia: some wasps collected bore orchid pollinia on their thoraxes. Among 114 trapped individuals, four bore pollinaria and nine bore only viscidia, suggesting that pollinia had been successfully transported. Molecular barcoding of the pollinia (based on their ITS sequences) assigned the orchid to a species in Coelogyne fimbriata complex. These findings and our other analyses suggest that this nocturnal wasp contributes to pollination of an epiphytic nectarless orchid that probably releases olfactory attractants. This discovery sheds light on the importance of mutualistic relationships between the nocturnal social wasps and epiphytic orchids in Southeast Asian tropical rainforest canopies.
A thermoprotective role of the sodium channel β1 subunit is lost with the β1(C121W) mutation
Authors: Egri Csilla , Vilin Yuriy Y. , Ruben Peter C.
Published: January 2012

Purpose:  A mutation in the β1 subunit of the voltage‐gated sodium (NaV) channel, β1(C121W), causes genetic epilepsy with febrile seizures plus (GEFS+), a pediatric syndrome in which febrile seizures are the predominant phenotype. Previous studies of molecular mechanisms underlying neuronal hyperexcitability caused by this mutation were conducted at room temperature. The prevalence of seizures during febrile states in patients with GEFS+, however, suggests that the phenotypic consequence of β1(C121W) may be exacerbated by elevated temperature. We investigated the putative mechanism underlying seizure generation by the β1(C121W) mutation with elevated temperature.

Methods:  Whole‐cell voltage clamp experiments were performed at 22 and 34°C using Chinese Hamster Ovary (CHO) cells expressing the α subunit of neuronal NaV channel isoform, NaV1.2. Voltage‐dependent properties were recorded from CHO cells expressing either NaV1.2 alone, NaV1.2 plus wild‐type (WT) β1 subunit, or NaV1.2 plus β1(C121W).

Key Findings:  Our results suggest WT β1 is protective against increased channel excitability induced by elevated temperature; protection is lost in the absence of WT β1 or with expression of β1(C121W). At 34°C, NaV1.2 + β1(C121W) channel excitability increased compared to NaV1.2 + WT β1 by the following mechanisms: decreased use‐dependent inactivation, increased persistent current and window current, and delayed onset of, and accelerated recovery from, fast inactivation.

Significance:  Temperature‐dependent changes found in our study are consistent with increased neuronal excitability of GEFS+ patients harboring C121W. These results suggest a novel seizure‐causing mechanism for β1(C121W): increased channel excitability at elevated temperature.
Levetiracetam has an activity‐dependent effect on inhibitory transmission
Authors: Meehan Anna L. , Yang Xiaofeng , Yuan Li‐Lian , Rothman Steven M.
Published: January 2012

Purpose:  Previous work has shown that levetiracetam (LEV) binds the vesicular protein SV2A and reduces excitatory neurotransmitter release during trains of high‐frequency activity, most likely by accessing its binding site through vesicular endocytosis into excitatory synaptic terminals. Because there are differences in excitatory and inhibitory transmitter release mechanisms, and there are suggestions that neurons differ in their SV2A expression, we were curious whether LEV also reduces inhibitory transmission.

Methods:  We used patch‐clamp recording from CA1 neurons in rat brain slices to quantify the effects of LEV on inhibitory postsynaptic currents (IPSCs). We were able to elicit pure IPSCs by stimulating inhibitory terminals close to neuronal soma and blocking excitatory postsynaptic currents with specific antagonists.

Key Findings:  We found that LEV reduces inhibitory currents in a frequency‐dependent manner, with the largest relative effect on the later IPSCs in the highest frequency trains. However, in contrast to excitatory postsynaptic currents (EPSCs), LEV reduced IPSC trains after a briefer, 30 min incubation. When spontaneous activity during incubation was blocked with antagonists of excitatory transmission, LEV no longer reduced IPSCs. If slices were returned to LEV‐free artificial cerebrospinal fluid (ACSF) after LEV incubation, but prior to recording, the IPSC reduction failed to appear. However, if synaptic activity was limited by treating with excitatory transmitter antagonists, after the initial LEV exposure, LEV still diminished trains of IPSC. The concentration required to diminish IPSC trains was lower than for EPSCs.

Significance:  LEV exerts a qualitatively similar, frequency‐dependent effect on both IPSCs and EPSCs. The much shorter latency for IPSC reduction is consistent with the greater levels of spontaneous inhibition in brain slices, supporting the hypothesis that vesicular uptake is necessary for the entry of LEVs into terminals. The vesicular entry of LEV resembles the cell entry pathways for tetanus and botulinum neurotoxins, but is unique for small, neuroactive drugs. Although the reduction of IPSC trains by LEV initially seems counterintuitive for an antiepileptic drug, there are multiple reasons that disruption of γ‐aminobutyric acid (GABA) release could ultimately attenuate pathologic discharges.
Comparison of Bulk and Compound‐Specific δ13C Isotope Ratio Analyses for the Discrimination Between Cannabis Samples*
Authors: Muccio Zeland , Wöckel Claudia , An Yan , Jackson Glen P.
Published: January 2012

Abstract: Five marijuana samples were compared using bulk isotope analysis compound‐specific isotope ratio analysis of the extracted cannabinoids. Owing to the age of our cannabis samples, four of the five samples were compared using the isotope ratios of cannabinol (CBN), a stable degradation product of Δ9‐tetrahydrocannabinol (THC). Bulk δ13C isotope analysis discriminated between all five samples at the 95% confidence level. Compound‐specific δ13C isotope analysis could not distinguish between one pair of the five samples at the 95% confidence level. All the measured cannabinoids showed significant depletion in13C relative to bulk isotope values; the isotope ratios for THC, CBN, and cannabidiol were on average 1.6‰, 1.7‰, and 2.2‰ more negative than the bulk values, respectively. A more detailed investigation needs to be conducted to assess the degree fractionation between the different cannabinoids, especially after aging.
Characterization of the miRNA profile in UVB‐irradiated normal human keratinocytes
Authors: Zhou Bing‐rong , Xu Yang , Permatasari Felicia , Liu Wen‐li , Li Wei , Guo Xian‐fei , Huang Qiu‐hong , Guo Ze , Luo Dan
Published: January 2012

Abstract:  The aim of this study was to assess the effects of ultraviolet B (UVB) irradiation on microRNA (miRNA) expression in normal human keratinocytes. Global miRNA expression profiles of primary cultures of normal human keratinocytes 4 and 24 h postirradiation were studied using miRNA microarray with further confirmation by real‐time PCR. We found that upon 30 or 60 mJ/cm2 of UVB radiation, the expression of 44 miRNAs was up‐ or downregulated more than twofold compared with non‐irradiated keratinocytes. MiRNAs were either up‐ or downregulated after 4 h and then either returned to normal levels or remained affected after 24 h, resulting in four distinct patterns of miRNA expression change. It appears that acute exposure of keratinocytes to UVB radiation results in several specific patterns of miRNA response.
A meta‐analysis of the effects of detritus on primary producers and consumers in marine, freshwater, and terrestrial ecosystems
Authors: Hagen Elizabeth M. , McCluney Kevin E. , Wyant Karl A. , Soykan Candan U. , Keller Andrew C. , Luttermoser Kymberly C. , Holmes Eric J. , Moore John C. , Sabo John L.
Published: January 2012

Detritus is a central feature in marine, freshwater, and terrestrial ecosystems. Despite the ubiquity of detritus, ecologists have largely ignored its role in influencing food web structure. We used a meta‐analytic approach to ask three questions about how detritus affects food web structure in a wide variety of ecosystems. First, what is the effect strength of detritus on primary producers, detritivores, herbivores, and predators? Second, what functional role does detritus serve for consumers (energetic, habitat, or both)? Third, how does the effect of detritus on consumers vary between aquatic and terrestrial ecosystems? We found that detritus has strong positive effects on primary producers and consumers in a wide range of ecosystems types. Detritus has a positive direct effect on detritivores by providing both an energetic resource and habitat (refuge from predators). Detritus has equally strong positive effects on herbivores and predators, driven by a positive direct effect of habitat. Detritus has positive effects on consumers in both aquatic and terrestrial ecosystems with 1.7 times stronger effects in terrestrial ecosystems. These results suggest that detritus has strong effects on food‐web structure in a variety of ecosystem types. Even the portion of the food web that is linked most strongly to living plant tissue as its primary energy source is strongly positively affected.
No adverse effects of statins on muscle function and health‐related parameters in the elderly: An exercise study
Authors: Panayiotou G. , Paschalis V. , Nikolaidis M. G. , Theodorou A. A. , Deli C. K. , Fotopoulou N. , Fatouros I. G. , Koutedakis Y. , Sampanis M. , Jamurtas A. Z.
Published: January 2012

The aim of the present study was to investigate the effects of a repeated bout of eccentric exercise on health‐related parameters and muscle performance on subjects undergoing atorvastatin therapy. Twenty‐eight elderly men participated in the investigation and were assigned either in a control (n = 14) or in a statin therapy group (n = 14). All participants performed two isokinetic eccentric exercise bouts separated by 3 weeks. Muscle damage indices, resting energy expenditure, substrate metabolism, lipid and lipoprotein profile, as well as insulin sensitivity, were evaluated before and after eccentric. No differences in muscle function were observed between the two groups either at rest or after exercise. Eccentric exercise increased resting energy expenditure, increased fat oxidation, improved lipid profile, and increased insulin resistance 2 days after both eccentric exercise bouts. However, these changes appeared to lesser extent after the second bout. No differences were observed in the responses in the health‐related parameters in the control and in the statin therapy group. Eccentric exercise affected similarly the control and the atorvastatin‐treated individuals. The present results indicate that atorvastatin‐treated elderly individuals may participate in various physical activities, even high‐intensity muscle‐damaging activities, without negative impact on muscle function and adaptation.
New approach to analyze genetic and clinical data in bisphosphonate‐induced osteonecrosis of the jaw
Authors: Balla B , Vaszilko M , Kósa JP , Podani J , Takács I , Tóbiás B , Nagy Z , Lazáry Á , Lakatos P
Published: January 2012

Oral Diseases (2012) 18, 580–585

Objectives:  Osteonecrosis of the jaw (ONJ) is a major complication associated with long‐term use of bisphosphonates (BP). We aimed to investigate the effect of CYP2C8 rs1934951 SNP and its relationship to a number of clinical and biochemical factors in 46 Hungarian subjects with bisphosphonate‐induced ONJ.

Methods:  Blood samples were collected from each subject and genomic DNA was extracted. SNP analysis of CYP2C8 gene was carried out by predesigned TaqMan primer/probe sets. The genetic data together with clinical and biochemical variables were evaluated by chi‐square test, logistic regression, and principal component analysis (PCA).

Results:  The risk of mandibular localization of ONJ was 19.2‐fold higher in subjects with AG genotype than in normal GG genotype. PCA revealed strong positive correlations between maxillar localization of ONJ and a group of variables including intravenous BP application and serum lipid markers. Mandibular localization of ONJ was correlated positively with serum calcium, 25‐hydroxy‐vitamin D and PTH levels, oral BP application, and the length of BP therapy. The degree of the disease and the number of recurrences were correlated with the application of hormone‐deprivation therapy for breast cancer patients.

Conclusion:  The statistical approach applying PCA to our data may contribute to the better understanding of factors playing role in the development of bisphosphonate‐induced ONJ.
Effect of replacing corn with brown rice grain in a total mixed ration silage on milk production, ruminal fermentation and nitrogen balance in lactating dairy cows
Authors: MIYAJI Makoto , MATSUYAMA Hiroki , HOSODA Kenji , NONAKA Kazuhisa
Published: January 2012

Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design to determine the effects of substituting corn grain with brown rice (BR) grain in total mixed ration (TMR) silage on milk yield, ruminal fermentation and nitrogen (N) balance. The TMR silages were made from the ensiling of TMR containing (dry matter basis) 50.1% forage in rice silage and corn silage combination, and 49.9% concentrate. The grain portion of the diets contained 31.2% steam‐flaked corn, 31.2% steam‐flaked BR or an equal mixture of corn and BR. Dietary treatments did not affect dry matter intake, milk yield and milk fat, protein and lactose yields. The ruminal pH and total volatile fatty acid concentrations were not affected by dietary treatment. The urinary N excretion decreased linearly (P < 0.01) in response to increased levels of BR, with no dietary effect on N intake, N secretion in milk and fecal N excretion. Our results indicate that steam‐flaked BR is a suitable replacement for steam‐flaked corn in dairy cow diets, and that it can be included in rations to a level of at least 31.2% of dry matter without adverse effects on milk production, when cows were fed rice silage and corn silage‐based diets.
Educating diabetes camp counselors with a human patient simulator: A pilot study
Authors: Sullivan‐Bolyai Susan , Crawford Sybil , Johnson Kimberly , Huston Bonny , Lee Mary M.
Published: January 2012

Purpose.  The purpose of this study was to pilot test the feasibility and efficacy of a novel method of teaching camp counselors hypoglycemia management.

Design and Methods.  During orientation, counselors were assigned to the experimental (n= 21) or control (n= 15) group and received hypoglycemia education. The experimental group received supplemental education with a human patient simulator (HPS).

Results.  Baseline demographics, knowledge, and self‐efficacy were similar between groups. The experimental group had a significantly larger gain in diabetes knowledge than the control group. Within‐participant change in self‐efficacy did not differ by group. We observed a significant effect modification, with larger treatment‐related differences in the small subgroup with no previous diabetes exposure.

Practice Implications.  This feasibility study demonstrated the ease of teaching diabetes management to camp counselors using HPS.
Childcare health and health consultation curriculum: Trends and future directions in nursing education
Authors: Crowley Angela A. , Cianciolo Sandra , Krajicek Marilyn J. , Hawkins‐Walsh Elizabeth
Published: January 2012

Purpose.  The purpose of this study was to identify graduate and undergraduate nursing courses in health and health consultation in childcare and early education, and faculty awareness and interest in federal resources.

Design and Methods.  A questionnaire was sent electronically to 140 faculty in 45 schools of nursing.

Results.  Fifty‐nine faculty from 45 schools (42%) participated, and 80% reported at least one course related to childcare health and safety. Most faculty were not aware of federal initiatives to support childcare health and safety, and the role of nurse childcare health consultants; however, many were interested in receiving instructional materials.

Practice Implications.  Utilizing federal resources to augment nursing education in childcare health and safety curriculum may strengthen the workforce of nurses providing health consultation to early childhood programs.
Ability of centipedegrass (Eremochloa ophiuroides [Munro] Hack.) to spread by stolons: Effects of soil, fertilizer, shade and edging
Authors: Hirata Masahiko , Mizuno Shinnosuke , Tobisa Manabu
Published: January 2012

The ability of centipedegrass (Eremochloa ophiuroides [Munro] Hack.) to spread by stolons was evaluated in two experiments. Circular gaps (1 m diameter) were created in a monoculture of centipedegrass by removing the vegetation, and re‐invasion of the gaps by stolons originating from the surrounding vegetation was monitored for about 14 weeks. The treatments were three types of substrates (−F, river sand; 0F, original soil; +F, original soil + fertilizer) × two levels of light intensities (−L, 50% sunlight; L, full sunlight) in the gaps for Experiment 1, and four heights (0 [no wall], 1, 3 and 5 cm above ground) of walls edging the gaps for Experiment 2. A summer drought provided an opportunity to examine the effect of severe water stress on stolon development. In Experiment 1, the number of stolons re‐invading the gaps did not differ among the treatments. The elongation and branching of the re‐invading stolons were depressed in the −F gaps, showing no significant responses to the fertilizer application (+F) or shading (−L). In Experiment 2, the number, elongation and branching of re‐invading stolons decreased as the height of the edging wall increased. Across the two experiments, none of the treatments was successful in blocking centipedegrass spread by stolons. Even during the drought, the grass spread stolons on a substrate poor in nutrients and moisture, and over an edging of at least a 5 cm height. Such an ability of centipedegrass is favorable to rapid establishment of the grass after seeding or vegetative planting and also to quick self‐restoration of damaged or denuded patches formed in an established sward or turf. At the same time, the ability places a great difficulty in controlling the escape of the grass from planted areas to prevent or minimize naturalization and subsequent environmental impacts.
Owl monkeysAotusspp in the wild and in captivity
Authors: Fernandez‐Duque E.
Published: January 2012

Owl monkeysAotusspp have the potential to be a great model to accomplish a thorough integration of zoo and field research. Their most salient features are their nocturnal habits, monogamous social organization and paternal care, features that should make them of interest to the public. Following a brief historical perspective on our knowledge of owl monkey biology, I describe in detail, drawing from research with both captive and wild animals, those aspects that make owl monkeys unusual among primates and mammals. First, owl monkeys are the only anthropoids with nocturnal habits, and the study of their remarkable activity patterns has benefited enormously from an integrated approach that combined field research with research in semi‐natural conditions and the laboratory. Second, up until recently, our understanding of social monogamy and the involvement of the ♂♂ in infant care, two defining characteristics of the genus, have been primarily informed by studies of captive individuals. In the future, a truly integrated laboratory–field approach that focuses on certain areas that cannot be examined in only one or the other setting (e.g. reproductive biology, communication, energetics) will offer unique opportunities for synergistic interactions between zoo and field research that will have both intellectual and practical benefits.
Introduction of Asiatic golden cat Catopumatemminckii at Taronga Conservation Society Australia
Authors: Olsen D.
Published: January 2012

The Asiatic golden cat Catopuma temminckii is a difficult species to breed in captivity. This paper outlines two introductions and attempts made to breed the species at Taronga Conservation Society Australia. Unfortunately, both these attempts were unsuccessful. This paper will also detail the planning and processes undertaken, lessons learned and options for future trials with the hope of enabling a better understanding of the breeding behaviour of the Asiatic golden cat.
Transcriptional Factors for Epithelial–Mesenchymal Transition Are Associated with Mesenchymal Differentiation in Gliosarcoma
Authors: Nagaishi Masaya , Paulus Werner , Brokinkel Benjamin , Vital Anne , Tanaka Yuko , Nakazato Yoichi , Giangaspero Felice , Ohgaki Hiroko
Published: January 2012

Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial–mesenchymal transition (EMT). In the present study, we assessed 40 gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) gliosarcomas, but not in glial areas (P < 0.0001). Nuclear Twist expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) gliosarcomas, but glial tumor areas were largely negative except in four cases (P < 0.0001). Expression of MMP‐2 and MMP‐9 was also significantly more extensive in mesenchymal than in glial tumor areas. None of 20 ordinary glioblastomas showed Slug or Twist expression in >10% neoplastic cells. Thus, expression of Slug, Twist, MMP‐2 and MMP‐9 was characteristic of mesenchymal tumor areas of gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in gliosarcomas.
Clinical analysis of osteonecrosis of the femoral head induced by steroids
Authors: Zhao Feng‐chao , Li Zi‐rong , Guo Kai‐jin
Published: January 2012

Objective:  To explore the clinical characteristics of osteonecrosis of the femoral head (ONFH) induced by steroids.

Methods:  From January 2000 to October 2009, 497 hips in 270 cases of ONFH induced by steroids were studied. A questionnaire was administered when the patients were admitted; the questions concerned the underlying disease, duration of steroid usage, total dosage of steroid, incubation period (time interval between commencement of steroid therapy and onset of pain), severity of pain, location of initial complaint, primary diagnosis, time lag from onset of pain to final diagnosis and physical signs when admitted. The correlations between pain and Association Research Circulation Osseous (ARCO) stage, bone marrow edema (BME) and lesion size were analyzed.

Results:  The median of time between commencing steroid medication and developing ONFH for the 269 cases was 18 months (range, 2–384 months). 78.82% cases presented with pain within three years of steroid initiation, only 10.41% patients first complained of pain six or more years after commencing steroid therapy. Fifty‐six cases (20.82%) were misdiagnosed, lumbar disorders being the most frequent misdiagnoses. 79.29% of symptomatic hips presented with abnormal physical tests. Of 420 symptomatic hips, 166 hips were type C1, 223 hips type C2; 299 hips had collapsed; and there was BME in 209 hips.

Conclusion:  Most patients with ONFH induced by steroids complained of pain within 3 years of commencing steroid therapy. Pain was associated with lesion size, collapse and BME. Atypical location of pain, failure to perform a physical examination and MRI findings were the main causes of misdiagnoses.
Myosin I Links PIP
3
Signaling to Remodeling of the Actin Cytoskeleton in Chemotaxis
Authors: Chen Chun-Lin , Wang Yu , Sesaki Hiromi , Iijima Miho
Published: January 2012

A subset of myosin motor proteins binds the membrane phospholipid PIP
3
to link membrane and cytoskeletal dynamics.
Potassium Permeation
Authors: Vinson Valda
Published: January 2012

Structural features provide a basis for understanding gating and ion conduction of these channels.
Antigen Polarity in B Cell Differentiation
Authors: Mueller Kristen L.
Published: January 2012

Antigen distribution across activated B cells influences B-T lymphocyte interactions.
Muscling In on Fat
Authors: Wong Wei
Published: January 2012

Exercise triggers release of a myokine from skeletal muscle that induces the “browning” of white adipose tissue.
Oxygen and Two Friends
Authors: Gough Nancy R.
Published: January 2012

The cerebral vasculature responds to reduced oxygen through a pathway involving carbon monoxide and hydrogen sulfide.
Emergence of OXA-48-Type Carbapenemase-Producing Enterobacteriaceae in German Hospitals
Authors: Pfeifer Yvonne , Schlatterer Kathrin , Engelmann Elisabeth , Schiller Reinhold A. , Frangenberg Hans Reiner , Stiewe Doris , Holfelder Martin , Witte Wolfgang , Nordmann Patrice , Poirel Laurent
Published: January 2012

Nine carbapenem-resistant
Enterobacteriaceae
isolates collected from eight patients in five German hospitals were investigated. Six isolates produced the OXA-48 carbapenemase, and three isolates produced OXA-162, which is a point mutant form of OXA-48. Both carbapenemase genes were located on IncL/M-type conjugative plasmids. Insertion sequence IS
1999
(truncated or not by IS
1R
) was located upstream of the
bla
OXA-48
and
bla
OXA-162
genes in all of the isolates. Pulsed-field gel electrophoresis typing indicated the clonal transmission of an OXA-48-producing
Klebsiella pneumoniae
strain in two hospitals.
Cethromycin versus Clarithromycin for Community-Acquired Pneumonia: Comparative Efficacy and Safety Outcomes from Two Double-Blinded, Randomized, Parallel-Group, Multicenter, Multinational Noninferiority Studies
Authors: English Marci L. , Fredericks Christine E. , Milanesio Nancy A. , Rohowsky Nestor , Xu Ze-Qi , Jenta Tuah R. J. , Flavin Michael T. , Eiznhamer David A.
Published: January 2012

Community-acquired pneumonia (CAP) continues to be a major health challenge in the United States and globally. Factors such as overprescribing of antibiotics and noncompliance with dosing regimens have added to the growing antibacterial resistance problem. In addition, several agents available for the treatment of CAP have been associated with serious side effects. Cethromycin is a new ketolide antibiotic that may provide prescribing physicians with an additional agent to supplement a continually limited armamentarium. Two global phase III noninferiority studies (CL05-001 and CL06-001) to evaluate cethromycin safety and efficacy were designed and conducted in patients with mild to moderate CAP. Study CL05-001 demonstrated an 83.1% clinical cure rate in the cethromycin group compared with 81.1% in the clarithromycin group (95% confidence interval [CI], −4.8%, +8.9%) in the intent to treat (ITT) population and a 94.0% cethromycin clinical cure rate compared with a 93.8% clarithromycin cure rate (95% CI, −4.5%, +5.1%) in the per protocol clinical (PPc) population. Study CL06-001 achieved an 82.9% cethromycin clinical cure rate in the ITT population compared with an 88.5% clarithromycin cure rate (95% CI, −11.9%, +0.6%), whereas the clinical cure rate in the PPc population was 91.5% in cethromycin group compared with 95.9% in clarithromycin group (95% CI, −9.1%, +0.3%). Both studies met the primary endpoints for clinical cure rate based on predefined, sliding-scale noninferiority design. Therefore, in comparison with clarithromycin, these two noninferiority studies demonstrated the efficacy and safety of cethromycin, with encouraging findings of efficacy in subjects with
Streptococcus pneumoniae
bacteremia. No clinically significant adverse events were observed during the studies. Cethromycin may be a potential oral therapy for the outpatient treatment of CAP.
Single- and Multiple-Ascending-Dose Studies of the NS3 Protease Inhibitor Asunaprevir in Subjects with or without Chronic Hepatitis C
Authors: Pasquinelli Claudio , McPhee Fiona , Eley Timothy , Villegas Criselda , Sandy Katrina , Sheridan Pamela , Persson Anna , Huang Shu-Pang , Hernandez Dennis , Sheaffer Amy K. , Scola Paul , Marbury Thomas , Lawitz Eric , Goldwater Ronald , Rodriguez-Torres Maribel , DeMicco Michael , Wright David , Charlton Michael , Kraft Walter K. , Lopez-Talavera Juan-Carlos , Grasela Dennis M.
Published: January 2012

Hepatitis C virus (HCV) protease inhibitors combined with pegylated alfa interferon-ribavirin have demonstrated improved efficacy compared with pegylated alfa interferon-ribavirin alone for the treatment of chronic hepatitis C. Asunaprevir (BMS-650032), a novel HCV NS3 protease inhibitor in clinical development, was evaluated for safety, antiviral activity, and resistance in four double-blind, placebo-controlled, sequential-panel, single- and multiple-ascending-dose (SAD and MAD) studies in healthy subjects or subjects with chronic HCV genotype 1 infection. In SAD studies, subjects (healthy or with chronic HCV infection) were randomized to receive asunaprevir in dose groups of 10 to 1,200 mg or a placebo. In MAD studies, healthy subjects were randomized to receive asunaprevir in dose groups of 10 to 600 mg twice daily or a placebo for 14 days; subjects with HCV infection received asunaprevir in dose groups of 200 to 600 mg twice daily, or a placebo, for 3 days. Across all four studies, headache and diarrhea were the most frequent adverse events in asunaprevir recipients. Asunaprevir at doses of 200 to 600 mg resulted in rapid HCV RNA decreases from the baseline; maximal mean changes in HCV RNA over time were 2.7 and 3.5 log
10
IU/ml in the SAD and MAD studies, respectively. No enrichment of signature asunaprevir-resistant viral variants was detected. In conclusion, the novel NS3 protease inhibitor asunaprevir, when administered at single or multiple doses of 200 to 600 mg twice daily, is generally well tolerated, achieving rapid and substantial decreases in HCV RNA levels in subjects chronically infected with genotype 1 HCV.
Species-Specific Antifungal Susceptibility Patterns of Scedosporium and Pseudallescheria Species
Authors: Lackner Michaela , de Hoog G. Sybren , Verweij Paul E. , Najafzadeh Mohammad J. , Curfs-Breuker Ilse , Klaassen Corné H. , Meis Jacques F.
Published: January 2012

Since the separation of
Pseudallescheria boydii
and
P. apiosperma
in 2010, limited data on species-specific susceptibility patterns of these and other species of
Pseudallescheria
and its anamorph
Scedosporium
have been reported. This study presents the antifungal susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates (
n
= 332) from a wide range of sources and origins were identified down to species level and tested according to CLSI M38-A2 against eight antifungal compounds. Whereas
P. apiosperma
(geometric mean MIC/minimal effective concentration [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and
P. boydii
(geometric mean MIC/MEC values of 0.7, 1.3, 5.7, 13.8, 0.5, 1.4, 2.3, and 11.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) had similar susceptibility patterns, those for
S. aurantiacum
,
S. prolificans
, and
S. dehoogii
were different from each other. Voriconazole was the only drug with significant activity against
S. aurantiacum
isolates. The MIC distributions of all drugs except voriconazole did not show a normal distribution and often showed two subpopulations, making a species-based prediction of antifungal susceptibility difficult. Therefore, antifungal susceptibility testing of all clinical isolates remains essential for targeted antifungal therapy. Voriconazole was the only compound with low MIC values (MIC
90
of ≤2 μg/ml) for
P. apiosperma
and
P. boydii
. Micafungin and posaconazole showed moderate activity against the majority of
Scedosporium
strains.
Efficacy of Ertapenem for Treatment of Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae
Authors: Collins Vicki L. , Marchaim Dror , Pogue Jason M. , Moshos Judy , Bheemreddy Suchitha , Sunkara Bharath , Shallal Alex , Chugh Neelu , Eiseler Sara , Bhargava Pragati , Blunden Christopher , Lephart Paul R. , Memon Babar Irfan , Hayakawa Kayoko , Abreu-Lanfranco Odaliz , Chopra Teena , Munoz-Price L. Silvia , Carmeli Yehuda , Kaye Keith S.
Published: January 2012

Ertapenem is active against extended-spectrum-β-lactamase (ESBL)-producing
Enterobacteriaceae
organisms but inactive against
Pseudomonas aeruginosa
and
Acinetobacter baumannii
. Due to a lack of therapeutic data for ertapenem in the treatment of ESBL bloodstream infections (BSIs), group 2 carbapenems (e.g., imipenem or meropenem) are often preferred for treatment of ESBL-producing
Enterobacteriaceae
, although their antipseudomonal activity is unnecessary. From 2005 to 2010, 261 patients with ESBL BSIs were analyzed. Outcomes were equivalent between patients treated with ertapenem and those treated with group 2 carbapenems (mortality rates of 6% and 18%, respectively;
P
= 0.18).
Three-Dimensional Human Skin Equivalent as a Tool To Study Acinetobacter baumannii Colonization
Authors: de Breij Anna , Haisma Elisabeth M. , Rietveld Marion , El Ghalbzouri Abdelouahab , van den Broek Peterhans J. , Dijkshoorn Lenie , Nibbering Peter H.
Published: January 2012

Acinetobacter baumannii
can colonize body surfaces of hospitalized patients. From these sites, invasion into the host and spread to other patients and the hospital environment may occur. The eradication of the organism from the patient's skin is an important infection control strategy during epidemic and endemic episodes. In this study, a three-dimensional (3D), air-exposed human epidermal skin equivalent was exploited to study
Acinetobacter
skin colonization. We characterized the adherence of
A. baumannii
ATCC 19606
T
and
Acinetobacter junii
RUH2228
T
to and biofilm formation on the skin equivalent and the responses to these bacteria. Furthermore, we assessed the ability of the disinfectant chlorhexidine to decolonize the skin equivalents. The results revealed that both strains replicated on the stratum corneum for up to 72 h but did not invade the epidermis.
A. baumannii
, in contrast to
A. junii
, formed large biofilms on the stratum corneum. Bacterial colonization did not affect keratinocyte activation, proliferation, or differentiation, nor did it induce a strong inflammatory response. Disinfection with chlorhexidine solution resulted in complete eradication of
A. baumannii
from the skin, without detrimental effects. This 3D model is a promising tool to study skin colonization and to evaluate the effects of novel disinfectant and antimicrobial strategies.
Novel Plasmid and Its Variant Harboring both a
bla
NDM-1
Gene and Type IV Secretion System in Clinical Isolates of Acinetobacter lwoffii
Authors: Hu Hongyan , Hu Yongfei , Pan Yuanlong , Liang Hui , Wang Haiyan , Wang Xiumei , Hao Qinfang , Yang Xiaoli , Yang Xi , Xiao Xue , Luan Chunguang , Yang Yi , Cui Yujun , Yang Ruifu , Gao George F. , Song Yajun , Zhu Baoli
Published: January 2012

The spread of the
bla
NDM-1
gene is gaining worldwide attentions. This gene is usually carried by large plasmids and has been discovered in diverse bacteria since it was originally found in
Klebsiella pneumoniae
. Here we report the complete sequences of a
bla
NDM-1
-bearing plasmid, pNDM-BJ01, and its variant, pNDM-BJ02, isolated from clinical
Acinetobacter lwoffii
strains. The plasmid pNDM-BJ01 is 47.3 kb in size and cannot be classified into any known plasmid incompatibility group, thus representing a novel plasmid with an unknown maintenance mechanism. This plasmid contains both a
bla
NDM-1
gene and a type IV secretion system (T4SS) gene cluster. The T4SS is assigned to the P-type T4SS group, which usually encode a short, rigid pilus, and the
bla
NDM-1
gene is located within a composite transposon flanked by two insertion elements of IS
Aba125
. Plasmid pNDM-BJ02 is nearly identical to pNDM-BJ01 except that one copy of the IS
Aba125
element is missing, and it is therefore regarded as a variant of pNDM-BJ01. Sequence alignment indicated that this
bla
NDM-1
-containing composite transposon, which can also be captured by other mobile elements, was probably a product of multiple recombination events and can move as a whole by transposition.
In Vitro
Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic, against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species
Authors: Tyrrell Kerin L. , Citron Diane M. , Warren Yumi A. , Goldstein Ellie J. C.
Published: January 2012

TD-1792 is a multivalent glycopeptide-cephalosporin heterodimer antibiotic with potent activity against Gram-positive bacteria. We tested TD-1792 against 377 anaerobes and 34 strains of
Corynebacterium
species. Against nearly all Gram-positive strains, TD-1792 had an MIC
90
of 0.25 μg/ml and was typically 3 to 7 dilutions more active than vancomycin and daptomycin.
NLRP3 Inflammasome Is a Target for Development of Broad-Spectrum Anti-Infective Drugs
Authors: Thacker James D. , Balin Brian J. , Appelt Denah M. , Sassi-Gaha Sihem , Purohit Mitali , Rest Richard F. , Artlett Carol M.
Published: January 2012

We describe the molecular mode of action and pharmacodynamics of a new molecular entity (NME) that induces the NLRP3 inflammasome-mediated innate immune response. This innate response reduces the pathogen load in an experimentally induced methicillin-resistantStaphylococcos aureusinfection, enhances survival in an experimentally induced Gram-negative bacteremia, and overrides the escape mechanism of an obligate intracellular pathogen,viz.Chlamydia pneumoniae. Furthermore, the NME is more effective than standard-of-care antibiotic therapy in a clinically established multifactorial bacterial infection. Analysis of transcriptional regulation of inflammasome signaling genes and innate/adaptive immune genes revealed consistent and significant host changes responsible for the improved outcomes in these infections. These studies pave the way for the development of first-in-class drugs that enhance inflammasome-mediated pathogen clearance and identify the NLRP3 inflammasome as a drug target to address the global problem of emerging new infectious diseases and the reemergence of old diseases in an antibiotic-resistant form.
Optimal Meropenem Concentrations To Treat Multidrug-Resistant Pseudomonas aeruginosa Septic Shock
Authors: Taccone Fabio Silvio , Cotton Frédéric , Roisin Sandrine , Vincent Jean-Louis , Jacobs Frédérique
Published: January 2012

A patient with septic shock due to extensively drug resistant (XDR)
Pseudomonas aeruginosa
was cured by optimizing the meropenem (MEM) regimen to obtain at least 40% of the time between two administrations in which drug levels were four times higher than the MIC of the pathogen. As the standard drug dose did not achieve these optimal concentrations, the MEM regimen was progressively increased up to 12 g/day (3 g every 6 h in a 3-h extended infusion), which eventually resulted in sepsis resolution. High MEM dosage may represent a valuable therapeutic option for infection due to multidrug-resistant (MDR) strains, and drug monitoring would allow rapid regimen adjustment in clinical practice.
Novel Functions for Glycosyltransferases Jhp0562 and GalT in Lewis Antigen Synthesis and Variation in Helicobacter pylori
Authors: Pohl Mary Ann , Kienesberger Sabine , Blaser Martin J.
Published: January 2012

Lewis (Le) antigens are fucosylated oligosaccharides present in the
Helicobacter pylori
lipopolysaccharide. Expression of these antigens is believed to be important for
H. pylori
colonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(
1
,
3
)
galT
is essential for production of type 1 (Le
a
and Le
b
) antigens. The upstream gene
jhp0562
, which is present in many but not all
H. pylori
strains, is homologous to β-(
1
,
3
)
galT
but is of unknown function. Because
H. pylori
demonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5′ and 3′ ends. Chimeric β-(
1
,
3
)
galT
-like alleles can restore function in a β-(
1
,
3
)
galT
null mutant, but neither native nor recombinant
jhp0562
can. Mutagenesis of
jhp0562
revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(
1
,
3
)
galT
expression in all wild-type (WT) and mutant strains tested, whereas
jhp0562
was not expressed in
jhp0562
null mutants, as expected. Since
jhp0562
unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whether
galT
, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed that
galT
is essential for Le
b
production. In total, these results demonstrate that
galT
and
jhp0562
have functions that cross the expected Le synthesis pathways and that
jhp0562
provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.
Formylation of amines and alcohols using aminopropylated mesoporous SBA-15 silica (APMS) as an efficient and recyclable catalyst
Authors: Malakooti Reihaneh , Sobhani Sara , Razavi Nasrin , Shafiei Soheila , Mokhtari Rezvan
Published: January 2012

Aminopropylated mesoporous SBA-15 silica (APMS) is introduced as a new, recyclable and efficient catalyst for the formylation of a variety of amines and alcohols by using readily available formic acid under solvent-free conditions.
Multicentre multiobserver study of diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt–Jakob disease: a reliability and agreement study
Authors: Fujita Koji , Harada Masafumi , Sasaki Makoto , Yuasa Tatsuhiko , Sakai Kenji , Hamaguchi Tsuyoshi , Sanjo Nobuo , Shiga Yusei , Satoh Katsuya , Atarashi Ryuichiro , Shirabe Susumu , Nagata Ken , Maeda Tetsuya , Murayama Shigeo , Izumi Yuishin , Kaji Ryuji , Yamada Masahito , Mizusawa Hidehiro
Published: January 2012

Objectives

To assess the utility of the display standardisation of diffusion-weighted MRI (DWI) and to compare the effectiveness of DWI and fluid-attenuated inversion recovery (FLAIR) MRI for the diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD).

Design

A reliability and agreement study.

Setting

Thirteen MRI observers comprising eight neurologists and five radiologists at two universities in Japan.

Participants

Data of 1.5-Tesla DWI and FLAIR were obtained from 29 patients with sCJD and 13 controls.

Outcome measures

Standardisation of DWI display was performed utilising b0 imaging. The observers participated in standardised DWI, variable DWI (the display adjustment was observer dependent) and FLAIR sessions. The observers independently assessed each MRI for CJD-related lesions, that is, hyperintensity in the cerebral cortex or striatum, using a continuous rating scale. Performance was evaluated by the area under the receiver operating characteristics curve (AUC).

Results

The mean AUC values were 0.84 (95% CI 0.81 to 0.87) for standardised DWI, 0.85 (95% CI 0.82 to 0.88) for variable DWI and 0.68 (95% CI 0.63 to 0.72) for FLAIR, demonstrating the superiority of DWI (p<0.05). There was a trend for higher intraclass correlations of standardised DWI (0.74, 95% CI 0.66 to 0.83) and variable DWI (0.72, 95% CI 0.62 to 0.81) than that of FLAIR (0.63, 95% CI 0.53 to 0.74), although the differences were not statistically significant.

Conclusions

Standardised DWI is as reliable as variable DWI, and the two DWI displays are superior to FLAIR for the diagnosis of sCJD. The authors propose that hyperintensity in the cerebral cortex or striatum on 1.5-Tesla DWI but not FLAIR can be a reliable diagnostic marker for sCJD.