bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive continuous functional near‐infrared spectroscopy combined with electroencephalography recording of frontal lobe seizures
Authors: Nguyen Dang Khoa , Tremblay Julie , Pouliot Philippe , Vannasing Phetsamone , Florea Olivia , Carmant Lionel , Lepore Franco , Sawan Mohamad , Lesage Frédéric , Lassonde Maryse
Published: November 2012

Purpose: To investigate spatial and metabolic changes associated with frontal lobe seizures.

Methods: Functional near‐infrared spectroscopy combined with electroencephalography (EEG‐fNIRS) recordings of patients with confirmed nonlesional refractory frontal lobe epilepsy (FLE).

Key Findings: Eighteen seizures from nine patients (seven male, mean age 27 years, range 13–46 years) with drug‐refractory FLE were captured during EEG‐fNIRS recordings. All seizures were coupled with significant hemodynamic variations that were greater with electroclinical than with electrical seizures. fNIRS helped in the identification of seizures in three patients with more subtle ictal EEG abnormalities. Hemodynamic changes consisted of local increases in oxygenated (HbO) and total hemoglobin (HbT) but heterogeneous deoxygenated hemoglobin (HbR) behavior. Furthermore, rapid hemodynamic alterations were observed in the homologous contralateral region, even in the absence of obvious propagated epileptic activity. The extent of HbO activation adequately lateralized the epileptogenic side in the majority of patients.

Significance: EEG‐fNIRS reveals complex spatial and metabolic changes during focal frontal lobe seizures. Further characterization of these changes could improve seizure detection, localization, and understanding of the impact of focal seizures.
Postictal generalized EEG suppression is not associated with periictal cardiac autonomic instability in people with convulsive seizures
Authors: Lamberts Robert J. , Laranjo Sergio , Kalitzin Stiliyan N. , Velis Demetrios N. , Rocha Isabel , Sander Josemir W. , Thijs Roland D.
Published: November 2012

Purpose:  Postictal generalized EEG suppression (PGES) seems to be a pathophysiologic hallmark in ictal recordings of sudden unexpected death in epilepsy (SUDEP). It has recently been suggested that presence and duration of PGES might be a predictor of SUDEP risk. Little is known about the etiology of PGES.

Methods:  We conducted a retrospective case–control study in 50 people with convulsive seizures (CS) recorded on digital video–electroencephalography (EEG). One CS per individual was reviewed for presence and duration of PGES by two independent observers: Preictal and postictal heart rate (HR) (1 min before seizure onset and 1, 3, 5, 15, and 30 min after seizure end) and frequency domain measures of heart rate variability (HRV), including the ratio of low frequency (LF) versus high frequency (HF) power, were analyzed. The relationship between PGES and periictal autonomic changes was evaluated, as well as its association with several clinical variables.

Key Findings:  Thirty‐seven individuals (74%) exhibited PGES and 13 (26%) did not. CS resulted in a significant increase of periictal HR and the LF/HF ratio. PGES was associated with neither periictal HR (mean HR difference between PGES+ and PGES− seizures: −2 beats per minute [bpm], 95% confidence interval [CI] −10 to +6 bpm) nor HRV change. There was no association between the duration of PGES and periictal HR change. People with PGES were more likely to be asleep before seizure onset (odds ratio [OR] 4.7, 95% CI 1.2–18.3) and had a higher age of onset of epilepsy (median age 15 vs. 4 years).

Significance:  PGES was not associated with substantial changes in measures of cardiac autonomic instability but was more prevalent in CS arising from sleep.
Self‐Healing Behavior of Barium–Lanthanum–Borosilicate Glass and Its Reactivity with Different Electrolytes for SOFC Applications
Authors: Kaur Gurbinder , Pandey Om P. , Singh Kulvir
Published: November 2012

The diffusion couples of lanthanum‐based barium borosilicate glass with high‐ and low‐temperature electrolytes have been heat‐treated at 850°C and 800°C, respectively, for 5, 100 and 750 h. These prepared diffusion couples have been characterized using various techniques like X‐ray diffraction (XRD), scanning electron microscopy (SEM), X‐ray dot mapping, and electron probe microanalysis (EPMA). The thermodynamic parameters like frequency factor, crystallization constants, free volume, and bulk thermal expansion coefficients have been calculated to understand the behavior of glass. Interestingly, glass revealed self‐healing tendency with heat treatment duration.
Palaeoceanographic changes in the northern Barents Sea during the last 16 000 years – new constraints on the last deglaciation of the Svalbard–Barents Sea Ice Sheet
Authors: Kristensen Dorthe Klitgaard , Rasmussen Tine L. , Koç Nalan
Published: November 2012

The sediment core NP05‐71GC, retrieved from 360 m water depth south of Kvitøya, northwestern Barents Sea, was investigated for the distribution of benthic and planktic foraminifera, stable isotopes and sedimentological parameters to reconstruct palaeoceanographic changes and the growth and retreat of the Svalbard–Barents Sea Ice Sheet during the last ∼16 000 years. The purpose is to gain better insight into the timing and variability of ocean circulation, climatic changes and ice‐sheet behaviour during the deglaciation and the Holocene. The results show that glaciomarine sedimentation commenced c. 16 000 a BP, indicating that the ice sheet had retreated from its maximum position at the shelf edge around Svalbard before that time. A strong subsurface influx of Atlantic‐derived bottom water occurred from 14 600 a BP during the Bølling and Allerød interstadials and lasted until the onset of the Younger Dryas cooling. In the Younger Dryas cold interval, the sea surface was covered by near‐permanent sea ice. The early Holocene, 11 700–11 000 a BP, was influenced by meltwater, followed by a strong inflow of highly saline and chilled Atlantic Water until c. 8600 a BP. From 8600 to 7600 a BP, faunal and isotopic evidence indicates cooling and a weaker flow of the Atlantic Water followed by a stronger influence of Atlantic Water until c. 6000 a BP. Thereafter, the environment generally deteriorated. Our results imply that (i) the deglaciation occurred earlier in this area than previously thought, and (ii) the Younger Dryas ice sheet was smaller than indicated by previous reconstructions.
Inherited clast dispersal patterns: Implications for palaeoglaciology of the SE Keewatin Sector of the Laurentide Ice Sheet
Authors: Trommelen Michelle S. , Ross Martin , Campbell Janet E.
Published: November 2012

The net effect of ice‐flow shifts resulting in the dilution or reworking of clasts on a single preserved till sheet is often unknown yet has major implications for palaeoglaciology and mineral exploration. Herein, we analyse variations in till clast lithologies from a single till sheet, within palimpsest‐type Glacial Terrain Zones in NE Manitoba, Canada, to better understand sediment–landform relationships in this area of high landform inheritance. This near‐ice‐divide area is known to consist of a highly fragmented subglacial landscape, resulting from spatio‐temporal variations in intensity of reworking and inheritance throughout multiple glacial events (subglacial bed mosaic). We show that a seemingly homogenous ‘Keewatin’ till sheet is composed of local (>15 km) and continental‐scale (∼100‐km‐long carbonate train and 350–600 km long Dubawnt red erratic train) fan, irregular (amoeboid) or lobate palimpsest dispersal patterns. Local dispersal is more complex than the preserved local landform flowset(s) record, but appears consistent with the overall glacial history reconstructed from regional flowset and striation analyses. The resultant surface till is a spatial mosaic interpreted to reflect variable intensities in modification (overprinting) and preservation (inheritance) of a predominately pre‐existing till sheet. A multi‐faceted approach integrating till composition, regional landforms, ice‐flow indicators, and stratigraphic knowledge is used to map relative spatio‐temporal erosion/reworking intensity.
Prevalence of neurocysticercosis among people with epilepsy in rural areas of Burkina Faso
Authors: Millogo Athanase , Nitiéma Pascal , Carabin Hélène , Boncoeur‐Martel Marie Paule , Rajshekhar Vedantam , Tarnagda Zékiba , Praet Nicolas , Dorny Pierre , Cowan Linda , Ganaba Rasmané , Hounton Sennen , Preux Pierre‐Marie , Cissé Rabiou
Published: November 2012

Purpose:  To estimate the lifetime prevalence of neurocysticercosis (NCC)–associated epilepsy and the proportion of NCC among people with epilepsy in three Burkina Faso villages.

Methods:  Three villages were selected to represent three types of pig‐rearing methods: (1) Batondo, where pigs are left to roam; (2) Pabré, where pigs are mostly tethered or penned; and (3) Nyonyogo, where the majority of residents are Muslim and few pigs are raised. In Batondo and Nyonyogo, all concessions (a group of several households) were included. Half of the concessions in Pabré were randomly chosen. All households of selected concessions were included, and one person per household was randomly selected for epilepsy screening and serologic testing for cysticercosis. Self‐reported cases of epilepsy were also examined and confirmed cases included in analyses other than the estimate of NCC‐associated epilepsy prevalence. Epilepsy was defined as ever having had more than one episode of unprovoked seizures. Individuals with medically confirmed epilepsy had a computerized tomography (CT) scan of the brain before and after contrast medium injection. The diagnosis of NCC was made using a modification of the criteria of Del Brutto et al.

Key Findings:  Thirty‐nine (4%) of 888 randomly selected villagers and 33 (94%) of 35 self‐reported seizures cases were confirmed to have epilepsy by medical examination. Among the 68 participants with epilepsy who had a CT scan, 20 patients were diagnosed with definitive or probable NCC for a proportion of 46.9% (95% confidence interval [CI] 30.2–64.1) in Batondo and 45.5% (95% CI 19.0–74.1) in Pabré. No cases of NCC were identified in Nyonyogo.

Significance:  All the definitive and probable cases of NCC were from the two villages where pig breeding is common. Prevention policies intended to reduce the burden of epilepsy in this country should include measures designed to interrupt the life cycle of Taenia solium.
Beating the Clock: Strategic Management under the Threat of Direct Democracy
Authors: Ely Todd L. , Jacob Benoy
Published: November 2012

This article explores public sector responsiveness to voter‐led initiatives, specifically, the degree to which public managers attempt to lock in resources before they are constrained by a particular initiative. The authors posit that such behavior, which they term “beating the clock,” is a function of the potential impact of the proposed initiative, the degree to which managers can react to the initiative's central issues, and the perceived likelihood of passage. Although scholars have explored different responses to voter‐led initiatives, this particular form of strategic behavior has yet to be studied. Using longitudinal data on public debt issuance, hypotheses are tested in the context of a reform proposed through the initiative process in Colorado in 2010. Results show that the number of debt issues increased by roughly 150 percent in advance of a potentially binding election, indicating the ability to preempt formal initiative efforts in certain policy areas.
Mother‐Grandmother Conflict, Negative Parenting, and Young Children's Social Development in Multigenerational Families
Authors: Barnett Melissa A. , Mills‐Koonce W. Roger , Gustafsson Hanna , Cox Martha ,   Family Life Project Key Investigators
Published: November 2012

Mutigenerational households that include grandmothers and adult mothers caring for grandchildren are increasingly common. The influence, however, of mother‐grandmother relationship quality and grandmothers' parenting on grandchildren's social development remains largely unexplored in these three‐generation households. This study examines linkages among caregiver depressive symptoms, mother‐grandmother verbal conflict, observed parenting, and 36‐month‐old grandchildren's problem and prosocial behaviors among a subsample from the Family Life Project (N = 85) consisting of economically disadvantaged multigenerational families. The findings suggest that mother‐grandmother relationship conflict presents a risk to children's behavior directly and indirectly via mothers' negative parenting behaviors. Mothers seem to be more influenced by the mother‐grandmother relationship than grandmothers. These results highlight the importance of including mother‐grandmother conflict in mutigenerational families in family assessments and interventions.
Involvement in Childrearing and Mothers' and Fathers' Adjustment
Authors: Riina Elizabeth M. , Feinberg Mark E.
Published: November 2012

Combining social construction of gender and equity perspectives on parents' division of labor, this study extended research on associations between parents' childrearing involvement and adjustment by (a) differentiating between types of childrearing activities (task focused vs. relationship focused), (b) examining patterns of differences in these links for mothers versus fathers, and (c) testing whether gender‐role attitudes regarding family labor moderated these associations. One hundred sixty‐nine mothers and fathers reported on perceptions of their involvement in relationship‐focused and task‐focused childrearing, gender role attitudes, and their adjustment (parenting efficacy, depression, parenting stress, and role overload). Results indicated that fathers benefited from greater overall childrearing involvement, whereas higher relationship‐focused care was linked to more negative adjustment for mothers. Gender role attitudes moderated these links for fathers, such that traditional fathers who were more involved in childrearing reported better parental adjustment. The within‐couple complexities of involvement in childrearing and implications for parenting programs are discussed.
Mothers Who Do and Do Not Intend to Discuss Sexual Health With Their Young Adolescents
Authors: Byers E. Sandra , Sears Heather A.
Published: November 2012

This study distinguished two groups of mothers who have not communicated with their young adolescents about sexual health based on their intentions of having these discussions. We also compared these 2 groups to mothers who have had such communications. Overall, 29% of mothers had engaged in sexual discussions with their adolescent in some detail (active group), 22% intended to do so in the next 6 months (intender group), and 49% did not intend to do so in the next 6 months (nonintender group). Higher scores on variables consistent with the integrative model of behavioral prediction (parent knowledge, comfort, attitudes, perceptions of social norms, and self‐efficacy for sexual communication) differentiated the 3 groups: The active group had the highest scores, the nonintender group had the lowest scores, and the scores of the intender group fell in between. Group membership varied by sexual topic. Suggestions for enhancing parent‐adolescent sexual communication are discussed.
Effects of Fathers' Early Risk and Resilience on Paternal Engagement With 5‐Year‐Olds
Authors: Fagan Jay , Lee Yookyong
Published: November 2012

The present study examined whether fathers' additive risk and resilience when the child is an infant and age 5 predicted paternal engagement with children at age 5. Using data from the Fragile Families and Child Wellbeing study (N = 4,898), we found that the results confirmed the hypothesis that early risk has a negative effect and early resilience has a positive effect on engagement 4 years later. Later father risk had a stronger negative effect on nonresidential fathers than on residential fathers. The effect of early father risk on engagement at age 5 was moderated by father engagement during infancy. Implications for policy and practice are discussed.
The Self‐Directed Violence Classification System and the Columbia Classification Algorithm for Suicide Assessment: A Crosswalk
Authors: Matarazzo Bridget B. , Clemans Tracy A. , Silverman Morton M. , Brenner Lisa A.
Published: November 2012

The lack of a standardized nomenclature for suicide‐related thoughts and behaviors prompted the Centers for Disease Control and Prevention, with the Veterans Integrated Service Network 19 Mental Illness Research Education and Clinical Center, to create the Self‐Directed Violence Classification System (SDVCS). SDVCS has been adopted by the Department of Veterans Affairs and the Department of Defense. Another classification system, the Columbia Classification Algorithm for Suicide Assessment, has been recommended by the Food and Drug Administration. To facilitate the use of both systems, this article provides a “crosswalk” between the two classification systems.
The Components of Young Children's Emotion Knowledge: Which Are Enhanced by Adult Emotion Talk?
Authors: Salmon Karen , Evans Ian M. , Moskowitz Sophie , Grouden Melissa , Parkes Fiona , Miller Emily
Published: November 2012

This research adopted observational and experimental paradigms to investigate the relationships between components of emotion knowledge in three‐ to four‐year‐old children. In Study 1, 88 children were assessed on the Emotion Matching Task (Morgan, Izard, & King), and two tasks requiring the generation of emotion labels and causes. Most tasks were significantly associated with age and language ability, and similar tasks were significantly but moderately correlated. In Study 2, 58 of these children were allocated to one of three conditions: emotion cause talk, in which they received four sessions of training focusing on emotion labels and causes; non‐emotion cause talk, focusing on causal relationships in general; or were allocated to a no‐training control. Children in the emotion causes condition showed improvement in their use of emotion labels but not other components of emotion knowledge. The findings suggest that, in three‐ to four‐year‐old children, emotion knowledge is constituted by related but separable components and that training in emotion language targets separate rather than all aspects of emotion knowledge.
Young Children's Affective Responses to Acceptance and Rejection From Peers: A Computer‐based Task Sensitive to Variation in Temperamental Shyness and Gender
Authors: Howarth Grace Z. , Guyer Amanda E. , Pérez‐Edgar Koraly
Published: November 2012

This study presents a novel task examining young children's affective responses to evaluative feedback—specifically, social acceptance and rejection—from peers. We aimed to determine (1) whether young children report their affective responses to hypothetical peer evaluation predictably and consistently, and (2) whether young children's responses to peer evaluation vary as a function of temperamental shyness and gender. Four‐ to seven‐year‐old children (N = 48) sorted pictures of unknown, similar‐aged children into those with whom they wished or did not wish to play. Computerized peer evaluation later noted whether the pictured children were interested in a future playdate with participants. Participants then rated their affective responses to each acceptance or rejection event. Children were happy when accepted by children with whom they wanted to play, and disappointed when these children rejected them. Highly shy boys showed a wider range of responses to acceptance and rejection based on initial social interest, and may be particularly sensitive to both positive and negative evaluation. Overall, the playdate task captures individual differences in affective responses to evaluative peer feedback and is potentially amenable to future applications in research with young children, including pairings with psychophysiological measures.
Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C‐type units after painful nerve injury
Authors: Gemes Geza , Koopmeiners Andrew , Rigaud Marcel , Lirk Philipp , Sapunar Damir , Bangaru Madhavi Latha , Vilceanu Daniel , Garrison Sheldon R. , Ljubkovic Marko , Mueller Samantha J. , Stucky Cheryl L. , Hogan Quinn H.
Published: November 2012

Key points

The peripheral terminals of sensory neurons encode physical and chemical signals into trains of action potentials (APs) and transmit these trains to the CNS.

Although modulation of this process is thought to predominantly reside at synapses, there are also indications that AP trains are incompletely propagated past points at which axons branch. One such site is the T‐junction, where the single sensory neuron axon branches into peripheral and central processes.

In recordings from sensory neurons of dorsal root ganglia excised from adult rats, we identified use‐dependent failure of AP propagation between the peripheral and central processes that results in filtering of rapid AP trains, especially in C‐type neurons.

Propagation failure was regulated by membrane input resistance and Ca2+‐sensitive K+ and Cl− currents. Following peripheral nerve injury, T‐junction filtering is reduced in C‐type neurons, which may possibly contribute to pain generation.

Abstract  The T‐junction of sensory neurons in the dorsal root ganglion (DRG) is a potential impediment to action potential (AP) propagation towards the CNS. Using intracellular recordings from rat DRG neuronal somata during stimulation of the dorsal root, we determined that the maximal rate at which all of 20 APs in a train could successfully transit the T‐junction (following frequency) was lowest in C‐type units, followed by A‐type units with inflected descending limbs of the AP, and highest in A‐type units without inflections. In C‐type units, following frequency was slower than the rate at which AP trains could be produced in either dorsal root axonal segments or in the soma alone, indicating that the T‐junction is a site that acts as a low‐pass filter for AP propagation. Following frequency was slower for a train of 20 APs than for two, indicating that a cumulative process leads to propagation failure. Propagation failure was accompanied by diminished somatic membrane input resistance, and was enhanced when Ca2+‐sensitive K+ currents were augmented or when Ca2+‐sensitive Cl− currents were blocked. After peripheral nerve injury, following frequencies were increased in axotomized C‐type neurons and decreased in axotomized non‐inflected A‐type neurons. These findings reveal that the T‐junction in sensory neurons is a regulator of afferent impulse traffic. Diminished filtering of AP trains at the T‐junction of C‐type neurons with axotomized peripheral processes could enhance the transmission of activity that is ectopically triggered in a neuroma or the neuronal soma, possibly contributing to pain generation.
Single Amino Acid Substitutions Confer the Antiviral Activity of the TRAF3 Adaptor Protein onto TRAF5
Authors: Zhang Peng , Reichardt Anna , Liang Huanhuan , Aliyari Roghiyh , Cheng David , Wang Yaya , Xu Feng , Cheng Genhong , Liu Yingfang
Published: November 2012

Two single amino acid changes enable the adaptor protein TRAF5 to promote antiviral responses.
ADP Ribosylation in the ER Stress Response
Authors: Gough Nancy R.
Published: November 2012

The poly(ADP-ribose) polymerase PARP16 modifies two kinases involved in the unfolded protein response pathway to enhance their activity.
Coordinate Hyperproduction of SmeZ and SmeJK Efflux Pumps Extends Drug Resistance in Stenotrophomonas maltophilia
Authors: Gould Virginia C. , Okazaki Aki , Avison Matthew B.
Published: November 2012

A
Stenotrophomonas maltophilia
mutant that coordinately hyper-expresses three resistance nodulation division-type efflux pump genes,
smeZ
,
smeJ
, and
smeK
, has been identified. SmeZ is responsible for elevating aminoglycoside MICs; SmeJ and SmeK are jointly responsible for elevating tetracycline, minocycline, and ciprofloxacin MICs and conferring levofloxacin resistance. One clinical isolate with this same phenotype was identified from a sample of six, and the isolate also coordinately hyper-expresses
smeZ
and
smeJK
, confirming the clinical relevance of our findings.
Clonal Composition and Community Clustering of Drug-Susceptible and -Resistant Escherichia coli Isolates from Bloodstream Infections
Authors: Adams-Sapper Sheila , Diep Binh An , Perdreau-Remington Francoise , Riley Lee W.
Published: November 2012

Multidrug-resistant
Escherichia coli
strains belonging to a single lineage frequently account for a large proportion of extraintestinal
E. coli
infections in many parts of the world. However, limited information exists on the community prevalence and clonal composition of drug-susceptible
E. coli
strains. Between July 2007 and September 2010, we analyzed all consecutively collected Gram-negative bacterial isolates from patients with bloodstream infection (BSI) admitted to a public hospital in San Francisco for drug susceptibility and associated drug resistance genes. The
E. coli
isolates were genotyped for
fimH
single nucleotide polymorphisms (SNPs) and multilocus sequence types (MLSTs). Among 539 isolates,
E. coli
accounted for 249 (46%); 74 (30%) of them were susceptible to all tested drugs, and 129 (52%) were multidrug resistant (MDR). Only five MLST genotypes accounted for two-thirds of the
E. coli
isolates; the most common were ST131 (23%) and ST95 (18%). Forty-seven (92%) of 51 ST131 isolates, as opposed to only 8 (20%) of 40 ST95 isolates, were MDR (
P
< 0.0001). The Simpson's diversity index for drug-susceptible ST genotypes was 87%, while the index for MDR ST genotypes was 81%. ST95 strains were comprised of four
fimH
types, and one of these (
f-6
) accounted for 67% of the 21 susceptible isolates (
P
< 0.003). A large proportion (>70%) of both MDR and susceptible
E. coli
BSI isolates represented community-onset infections. These observations show that factors other than the selective pressures of antimicrobial agents used in hospitals contribute to community-onset extraintestinal infections caused by clonal groups of
E. coli
regardless of their drug resistance.
Novel Carbapenem Antibiotics for Parenteral and Oral Applications:
In Vitro
and
In Vivo
Activities of 2-Aryl Carbapenems and Their Pharmacokinetics in Laboratory Animals
Authors: Fujimoto Koichi , Takemoto Koji , Hatano Kazuo , Nakai Toru , Terashita Shigeyuki , Matsumoto Masahiro , Eriguchi Yoshiro , Eguchi Ken , Shimizudani Takeshi , Sato Kimihiko , Kanazawa Katsunori , Sunagawa Makoto , Ueda Yutaka
Published: November 2012

SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible
Staphylococcus aureus
,
Streptococcus pneumoniae
(including penicillin-resistant strains),
Streptococcus pyogenes
,
Enterococcus faecalis
,
Klebsiella pneumoniae
,
Moraxella catarrhalis
,
Haemophilus influenzae
(including β-lactamase-negative ampicillin-resistant strains), and
Neisseria gonorrhoeae
(including ciprofloxacin-resistant strains), with MIC
90
s of ≤1 μg/ml. Unlike tebipenem (MIC
50
, 8 μg/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as
Pseudomonas aeruginosa
(MIC
50
, ≥128 μg/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant
S. pneumoniae
and β-lactamase-negative ampicillin-resistant
H. influenzae
were equal or superior to that of tebipenem and greater than that of cefditoren. The therapeutic efficacies of intravenous administrations of SM-295291 and SM-369926 against experimentally induced infections in mice caused by penicillin-resistant
S. pneumoniae
and β-lactamase-negative ampicillin-resistant
H. influenzae
were equal or superior to that of tebipenem and greater than that of cefditoren, respectively, reflecting their
in vitro
activities. SM-295291 and SM-369926 showed intravenous pharmacokinetics similar to those of meropenem in terms of half-life in monkeys (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM-375769, which are medoxomil esters of SM-295291 and SM-369926, respectively, showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus, 2-aryl carbapenems are promising candidates that show an ideal broad spectrum for the treatment of community-acquired infections, including infections caused by penicillin-resistant
S. pneumoniae
and β-lactamase-negative ampicillin-resistant
H. influenzae
, have low selective pressure on antipseudomonal carbapenem-resistant nosocomial pathogens, and allow parenteral, oral, and switch therapies.
First Detection ofoqxABin Salmonella spp. Isolated from Food
Authors: Wong Marcus Ho Yin , Chen Sheng
Published: November 2012

Food-borne salmonellosis is an important public health problem worldwide and the second leading cause of food-borne illnesses in Hong Kong. In this study, the prevalence and antimicrobial resistance ofSalmonellain meat products in Hong Kong were determined. Interestingly, a plasmid-mediated quinolone resistance (PMQR) gene combination,oqxAB, which mediates resistance to nalidixic acid, chloramphenicol, and olaquindox, was for the first time detectable on the chromosomes of twoSalmonella entericaserovar Derby isolates. Further surveillance ofoqxABinSalmonellawill be needed.
Posaconazole Pharmacodynamic Target Determination against Wild-Type and
Cyp51
Mutant Isolates of Aspergillus fumigatus in an
In Vivo
Model of Invasive Pulmonary Aspergillosis
Authors: Lepak Alexander J. , Marchillo Karen , VanHecker Jaimie , Andes David R.
Published: November 2012

Invasive pulmonary aspergillosis (IPA) is a devastating disease of immunocompromised patients. Pharmacodynamic (PD) examination of antifungal drug therapy in IPA is one strategy that may improve outcomes. The current study explored the PD target of posaconazole in an immunocompromised murine model of IPA against 10
A. fumigatus
isolates, including 4
Cyp51
wild-type isolates and 6 isolates carrying
Cyp51
mutations conferring azole resistance. The posaconazole MIC range was 0.25 to 8 mg/liter. Following infection, mice were given 0.156 to 160 mg/kg of body weight of oral posaconazole daily for 7 days. Efficacy was assessed by quantitative PCR (qPCR) of lung homogenate and survival. At the start of therapy, mice had 5.59 ± 0.19 log
10
Aspergillus
conidial equivalents (CE)/ml of lung homogenate, which increased to 7.11 ± 0.29 log
10
CE/ml of lung homogenate in untreated animals. The infection was uniformly lethal prior to the study endpoint in control mice. A Hill-type dose response function was used to model the relationship between posaconazole free drug area under the concentration-time curve (AUC)/MIC and qPCR lung burden. The static dose range was 1.09 to 51.9 mg/kg/24 h. The free drug AUC/MIC PD target was 1.09 ± 0.63 for the group of strains. The 1-log kill free drug AUC/MIC was 2.07 ± 1.02. The PD target was not significantly different for the wild-type and mutant organism groups. Mortality mirrored qPCR results, with the greatest improvement in survival noted at the same dosing regimens that produced static or cidal activity. Consideration of human pharmacokinetic data and the current static dose PD target would predict a clinical MIC threshold of 0.25 to 0.5 mg/liter.
Azole Susceptibility and Transcriptome Profiling in Candida albicans Mitochondrial Electron Transport Chain Complex I Mutants
Authors: Sun Nuo , Fonzi William , Chen Hui , She Xiaodong , Zhang Lulu , Zhang Lixin , Calderone Richard
Published: November 2012

Mitochondrial dysfunction in pathogenic fungi or model yeast causes altered susceptibilities to antifungal drugs. Here we have characterized the role of mitochondrial complex I (CI) of
Candida albicans
in antifungal susceptibility. Inhibitors of CI to CV, except for CII, increased the susceptibility of both patient and lab isolates, even those with a resistance phenotype. In addition, in a
C. albicans
library of 12 CI null mutants, 10 displayed hypersusceptibility to fluconazole and were severely growth inhibited on glycerol, implying a role for each gene in cell respiration. We chose two other hypersusceptible null mutants of
C. albicans
, the
goa1
Δ and
ndh51
Δ mutants, for transcriptional profiling by RNA-Seq. Goa1p is required for CI activity, while Ndh51p is a CI subunit. RNA-Seq revealed that both the
ndh51
Δ mutant and especially the
goa1
Δ mutant had significant downregulation of transporter genes, including
CDR1
and
CDR2
, which encode efflux proteins. In the
goa1
Δ mutant, we noted the downregulation of genes required for the biogenesis and replication of peroxisomes, as well as metabolic pathways assigned to peroxisomes such as β-oxidation of fatty acids, glyoxylate bypass, and acetyl coenzyme A (acetyl-CoA) transferases that are known to shuttle acetyl-CoA between peroxisomes and mitochondria. The transcriptome profile of the
ndh51
Δ mutant did not include downregulation of peroxisome genes but had, instead, extensive downregulation of the ergosterol synthesis gene family. Our data establish that cell energy is required for azole susceptibility and that downregulation of efflux genes may be an outcome of that dysfunction. However, there are mutant-specific changes that may also increase the susceptibility of both of these
C. albicans
mutants to azoles.
Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection
Authors: Alhariri Moayad , Omri Abdelwahab
Published: November 2012

We sought to investigate alterations in quorum-sensing signal molecule
N
-acyl homoserine lactone secretion and in the release of
Pseudomonas aeruginosa
virulence factors, as well as the
in vivo
antimicrobial activity of bismuth-ethanedithiol incorporated into a liposome-loaded tobramycin formulation (LipoBiEDT-TOB) administered to rats chronically infected with
P. aeruginosa
. The quorum-sensing signal molecule
N
-acyl homoserine lactone was monitored by using a biosensor organism.
P. aeruginosa
virulence factors were assessed spectrophotometrically. An agar beads model of chronic
Pseudomonas
lung infection in rats was used to evaluate the efficacy of the liposomal formulation in the reduction of bacterial count. The levels of active tobramycin in the lungs and the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective in disrupting both quorum-sensing signal molecules
N
-3-oxo-dodeccanoylhomoserine lactone and
N
-butanoylhomoserine lactone, as well as significantly (
P
< 0.05) reducing lipase, chitinase, and protease production. At 24 h after 3 treatments, the CFU counts in lungs of animals treated with LipoBiEDT-TOB were of 3 log
10
CFU/lung, comparated to 7.4 and 4.7 log
10
CFU/lung, respectively, in untreated lungs and in lungs treated with free antibiotic. The antibiotic concentration after the last dose of LipoBiEDT-TOB was 25.1 μg/lung, while no tobramycin was detected in the kidneys. As for the free antibiotic, we found 6.5 μg/kidney but could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB reduced the production of quorum-sensing molecules and virulence factors and could highly improve the management of chronic pulmonary infection in cystic fibrosis patients.
Emergence and Spread of Plasmid-Borne
tet
(B)::IS
CR2
in Minocycline-Resistant Acinetobacter baumannii Isolates
Authors: Vilacoba Elisabet , Almuzara Marisa , Gulone Lucia , Traglia German Matías , Figueroa Silvia A. , Sly Gabriela , Fernández Analia , Centrón Daniela , Ramírez María Soledad
Published: November 2012

Resistance to minocycline has emerged in multidrug-resistant
Acinetobacter baumannii
isolates from Buenos Aires hospitals. Few reports about the description and dispersion of
tet
genes in this species have been published. We observed the presence of
tet
(B) in all minocycline-resistant isolates. This gene was found to be associated with the IS
CR2
mobile element, which may, in part, explain its dispersion.
Cloning and Characterization of Rainbow Trout Interleukin-17A/F2 (IL-17A/F2) and IL-17 Receptor A: Expression during Infection and Bioactivity of Recombinant IL-17A/F2
Authors: Monte Milena M. , Wang Tiehui , Holland Jason W. , Zou Jun , Secombes Christopher J.
Published: November 2012

Lower vertebrates have been found to possess genes that have similar homology to both interleukin (IL)-17A and IL-17F, which have been termed IL-17A/F. In fish species, several of these genes can be present, but, to date, very little is known about their functional activity. This article describes the discovery and sequence analysis of a rainbow trout (Oncorhynchus mykiss) IL-17A/F2 molecule and an IL-17RA receptor. In addition, the bioactivity of the trout IL-17A/F2 is investigated for the first time in any species. The predicted IL-17A/F2 and IL-17RA proteins consist of 146 and 966 amino acids (aa), respectively, with both molecules containing conserved family motifs. Expression analysis revealed high constitutive expression of trout IL-17A/F2 in mucosal tissues from healthy fish, suggesting a potential role in mucosal immunity. When the modulation of IL-17A/F2 and IL-17RAin vitrowas analyzed, it was observed that the two molecules were similarly affected. The expression of IL-17A/F2 was also induced in head kidney during bacterial, parasitic, and viral infections, revealing a possible function in defense against such pathogens. However, downregulation of IL-17RA was seen in some tissues and infections. The recombinant IL-17A/F2 protein was produced inEscherichia coliand was found to affect the expression of an antimicrobial peptide and the proinflammatory cytokines IL-6 and IL-8 in splenocytes. Consistent with mammalian IL-17 homologues, our expression and bioactivity results imply that trout IL-17A/F2 plays an important role in promoting inflammatory and host innate immune responses directed against different pathogen groups.
Assessing the limitations of the existing physician directory for measuring electronic health record (EHR) adoption rates among physicians in Connecticut, USA: cross-sectional study
Authors: Tikoo Minakshi
Published: November 2012

Objective

To assess the limitations of the existing physician directory in measuring electronic health record adoption rates among a cohort of Connecticut physicians.

Design

A population-based mailing assessed the number of physicians practising in Connecticut.

Measurements

Information about practice site, practises pertaining to storing of patient information, sources of revenue and preferred method for receiving survey. Practice status in Connecticut, measured by yes and no. Demographic information was collected on gender, year of birth, race and ethnicity.

Results

The response rate for the postcard mailing was 19% (3105/16 462). Of the 16 462 unduplicated consumers, 233 (1%) were retired and 5828 (35%) did not practise in Connecticut. Of the 3105 valid postcard responses we received, 2159 were for physicians practising in Connecticut. Nine (0.4%) of these responses did not specify a preferred method for receiving the full physician survey; 91 physicians refused to participate in the survey; 2159 surveys were sent out using each physician's requested method for receiving the survey, that is, web-based, regular mail or telephone. As of August 2012, 898 physicians had returned surveys, resulting in a response rate of 42%.

Limitations

The postcard response rate based on the unduplicated lists adjusted for exclusions, such as death, retired and do not practise in Connecticut, is 30%, which is low. We may be missing physicians’ population which could greatly affect the indicators being used to measure change in electronic health record adoption rates.

Conclusions

It is difficult to obtain an accurate physician count of practising physicians in Connecticut from the existing lists. States that are participating in the projects funded under various Office of the National Coordinator for Health Information Technology (ONC) initiatives must focus on getting an accurate count of the physicians practising in their state, since their progress is being measured based on this key number.
Could screening participation bias symptom interpretation? An interview study on women's interpretations of and responses to cancer symptoms between mammography screening rounds
Authors: Solbjør Marit , Skolbekken John-Arne , Sætnan Ann Rudinow , Hagen Anne Irene , Forsmo Siri
Published: November 2012

Objectives

To explore how women with negative mammography screening results, but who were later diagnosed with interval breast cancer, reacted when they observed breast symptoms that could indicate malignancy in-between screening rounds.

Design

Semistructured individual interviews with women who have been diagnosed with breast cancer during mammography screening intervals.

Setting

Two breast diagnostic units covering two counties in Norway.

Participants

26 women diagnosed with interval breast cancer.

Results

Women with a screening negative result react in two ways when experiencing a possible symptom of breast cancer. Among 24 women with a self-detected palpable lesion, 14 sought medical advice immediately. Their argument was to dispose of potential cancer as soon as possible. Ten women delayed seeking medical advice, explaining their delay as a result of practical difficulties such as holidays, uncertainty about the symptom, and previous experiences of healthcare services’ ability to handle diffuse symptoms. Also, a recent negative mammography scan led some women to assume that the palpable lesion was benign and wait for the next screening round.

Conclusions

Participating in mammography screening may contribute to a postponed reaction to breast cancer symptoms, although most women acted rapidly when detecting a palpable breast lesion. Furthermore, screening participation does not necessarily increase awareness of breast cancer symptoms.
General practitioner experience and perception of Child and Adolescent Mental Health Services (CAMHS) care pathways: a multimethod research study
Authors: Hinrichs Saba , Owens Matthew , Dunn Valerie , Goodyer Ian
Published: November 2012

Objectives

This is a pilot study with the objective of investigating general practitioner (GP) perceptions and experiences in the referral of mentally ill and behaviourally disturbed children and adolescents.

Design

Quantitative analyses on patient databases were used to ascertain the source of referrals into Child and Adolescent Mental Health Services (CAMHS) and identify the relative contribution from GP practices. Qualitative semistructured interviews were then used to explore challenges faced by GPs in referring to CAMHS.

Setting

GPs were chosen from the five localities that deliver CAMHS within the local Trust (Peterborough City, Fenland, Huntingdon, Cambridge City and South Cambridgeshire).

Participants

For the quantitative portion, data involving 19 466 separate referrals were used. Seven GPs took part in the qualitative interviews.

Results

The likelihood of a referral from GPs being rejected by CAMHS was over three times higher compared to all other referral sources combined within the Cambridge and Peterborough NHS Foundation Trust. Interviews showed that detecting the signs and symptoms of mental illness in young people is a challenge for GPs. Communication with referral agencies varies and depends on individual relationships. GPs determine whether to refer on a mixture of the presenting conditions and their perceived likelihood of acceptance by CAMHS; the criteria for the latter were poorly understood by the interviewed GPs.

Conclusions

There are longstanding structural weaknesses in the services for children and young people in general, reflected in poor multiagency cooperation at the primary care level. GP-friendly guidelines and standards are required that will aid in decision-making and help with understanding the referrals process. We look to managers of both commissioning and providing organisations, as well as future research, to drive forward the development of tools, protocols, and health service structures to help aid the recognition and treatment of mental illness in young people.
An exploratory study on the consequences and contextual factors of intimate partner violence among immigrant and Canadian-born women
Authors: Du Mont Janice , Forte Tonia
Published: November 2012

Objective

To compare immigrant and Canadian-born women on the physical and psychological consequences of intimate partner violence (IPV), as well as examine important sociodemographic, health and social support and network factors that may shape their experiences of abuse.

Method

National, population-based, cross-sectional survey conducted in 2009.

Participants

6859 women reported contact with a current or former partner in the previous 5 years, of whom 1480 reported having experienced emotional, financial, physical and/or sexual IPV. Of these women, 218 (15%) were immigrants and 1262 (85%) were Canadian-born.

Results

Immigrant women were less likely than Canadian-born women to report having experienced emotional abuse (15.3% vs 18.2%, p=0.04) and physical and/or sexual violence (5.1% vs 6.9%, p=0.04) from a current or former partner. There were no differences between immigrant and Canadian-born women in the physical and psychological consequences of physical and/or sexual IPV. However, compared with Canadian-born women, immigrant women reported lower levels of trust towards their neighbours (50.7% vs 41.5%, p=0.04) and people they work or go to school with (38.6% vs 27.5%, p=0.02), and were more likely to report having experienced discrimination based on ethnicity or culture (18.8% vs 6.8%, p<0.0001), race or skin colour (p=0.003) and language (10.1% vs 3.2%, p<0.0001). Immigrant women were less likely than Canadian-born women to report activity limitations (p=0.01) and medication use for sleep problems (14.1% vs 20.6%, p=0.05) and depression (11.5% vs 17.6%, p=0.05).

Conclusions

Our exploratory study revealed no differences between immigrant and Canadian-born women in the physical and psychological consequences of IPV. Abused immigrant women's lower levels of trust for certain individuals and experiences of discrimination may have important implications for seeking help for IPV and underscores the need for IPV-related intervention and prevention services that are culturally sensitive and appropriate.