bluuebunny/crossref_metadata_2025 huggingface dataset:
Do therapeutic imagery practices affect physiological and emotional indicators of threat in high self‐critics?
Authors: Duarte Joana , McEwan Kirsten , Barnes Christopher , Gilbert Paul , Maratos Frances A.
Published: October 2014

Objectives

Imagery is known to be a powerful means of stimulating various physiological processes and is increasingly used within standard psychological therapies. Compassion‐focused imagery (CFI) has been used to stimulate affiliative emotion in people with mental health problems. However, evidence suggests that self‐critical individuals may have particular difficulties in this domain with single trials. The aim of the present study was to further investigate the role of self‐criticism in responsiveness to CFI by specifically pre‐selecting participants based on trait self‐criticism.

Design

Using the Forms of Self‐Criticism/Self‐Reassuring Scale, 29 individuals from a total sample of 139 were pre‐selected to determine how self‐criticism impacts upon an initial instance of imagery.

Methods

All participants took part in three activities: a control imagery intervention (useable data N = 25), a standard CFI intervention (useable data N = 25), and a non‐intervention control (useable data N = 24). Physiological measurements (alpha amylase) as well as questionnaire measures of emotional responding (i.e., the Positive and Negative Affect Schedule, the Types of Positive Affect Scale, and the State Adult Attachment Scale) were taken before and after the different interventions.

Results

Following both imagery interventions, repeated measures analyses revealed that alpha amylase increased significantly for high self‐critics compared with low self‐critics. High self‐critics (HSC) also reported greater insecurity on entering the imagery session and more negative CFI experiences compared with low self‐critics.

Conclusions

Data demonstrate that HSC respond negatively to imagery interventions in a single trial. This highlights that imagery focused therapies (e.g., CFI) need interventions that manage fears, blocks, and resistances to the techniques, particularly in HSC.

Practitioner points

An initial instance of imagery (e.g., CFI) can be frightening for people who have a tendency to be self‐critical.

This research provides examples of physiological and emotional responses to imagery type therapies in high and low self‐critics, and associated clinical implications.

Therapists may find it helpful to be mindful that when introducing imagery based therapies, highly self‐critical patients need interventions that manage fears, blocks, and resistances to the techniques.
Interspecific differences in temperature response of mesophyll conductance: food for thought on its origin and regulation
Authors: FLEXAS JAUME , DIAZ‐ESPEJO ANTONIO
Published: October 2014

This article comments on: Temperature responses of mesophyll conductance differ greatly between species
Prophylactic effect of H2 blocker for anastomotic stricture after esophageal atresia repair
Authors: Murase Naruhiko , Uchida Hiroo , Kaneko Kenitiro , Ono Yasuyuki , Makita Satoshi , Yokota Kazuki
Published: October 2014

Background

Anastomotic stricture is the main complication after esophageal atresia (EA) repair. In this study, we assessed the efficacy of long‐term prophylactic H2 blocker treatment in preventing stricture.

Methods

Twenty‐seven patients who had undergone primary repair for EA (Gross type C) were reviewed retrospectively. The patients were analyzed in two groups: the H2 blocker group (n = 13), in which the patients were treated with prophylactic H2 blocker; and the control group (n = 14), in which they were not. To assess anastomotic stricture, contrast esophagography was performed and the number of patients who required balloon dilatation was recorded.

Results

Five patients (18.5%) required postoperative balloon dilatation within 1 year of primary repair. There was no difference in dilatation rate between the two groups. In the H2 blocker group, however, anastomotic stricture improved significantly in the late postoperative period relative to that in the early postoperative period. In contrast, in the control group, anastomotic stricture did not improve after a long postoperative period. The incidence of gastroesophageal reflux was 55.6%. Postoperative gastroesophageal reflux was a predisposing factor for balloon dilatation in the control group, but not in the H2 blocker group.

Conclusions

Long‐term treatment with prophylactic H2 blocker may prevent anastomotic stricture caused by gastroesophageal reflux in the late postoperative period after EA repair.
Evaluation rhythm problems in unexplained syncope etiology with implantable loop recorder
Authors: Ergul Yakup , Tanidir Ibrahim Cansaran , Ozyilmaz Isa , Akdeniz Celal , Tuzcu Volkan
Published: October 2014

Background

Syncope is a frequent complaint in children and adolescents and may be a significant sign of serious pathology. Although patient history, family history, and physical examination are sufficient to reach a diagnosis in most cases of syncope, the cause of syncope still cannot be determined after initial investigation in one‐third to half of all patients. The aim of this study was to evaluate the diagnostic yield of implantable loop recorder (ILR) in children with unexplained syncope.

Methods

A retrospective review was carried out of clinical data, indications, findings, and a final management strategy in patients who underwent ILR implantation.

Results

A total of 12 patients with a mean age of 9.4 ± 4.5 years underwent ILR (Reveal Plus; Medtronic) implantation. ILR implantation indication was syncope in all of the patients. Family history, routine cardiac assessment, including resting 12‐lead electrocardiogram, transthoracic echocardiography, 24 h Holter recording, and event recorder findings, were normal with the exception of one patient with (previously corrected) tetralogy of Fallot. After an average of 20 months (range, 1–36 months), six patients developed symptoms. ILR memory showed torsades de pointes–ventricular fibrillation (n = 3), catecholaminergic polymorphic ventricular tachycardia (n = 1), asystole and ventricular tachycardia (n = 1), and normal sinus rhythm (n = 1). At the time of writing six patients were still in follow up with no symptoms after an average of 25.2 months.

Conclusion

Implantable loop recorder plays an important role in the diagnosis of life‐threatening arrhythmias in which syncope is otherwise unexplained. ILR implantation should be remembered in children whose symptoms are strongly correlated with rhythm disturbances.
Brazilian Potato virus Y isolates identified as members of a new clade facilitate the reconstruction of evolutionary traits within this species
Authors: Janzac B. , Willemsen A. , Cuevas J. M. , Glais L. , Tribodet M. , Verrier J.‐L. , Elena S. F. , Jacquot E.
Published: October 2014

Potato virus Y (PVY) is a plant virus distributed worldwide that causes damage to several species of the Solanaceae family. It was established long ago that groups of PVY isolates defined by phylogenetic analyses correlate strongly with those demarcated by differential biological properties. Consequently, life‐history traits of this viral species can be inferred by phylogenetic analysis. In this study, characteristics of PVY isolates sampled in different tobacco fields in Brazil were analysed and most of the tested Brazilian PVY isolates were assigned to the recently described unconventional serogroup YU. The analysis of molecular diversity of the coat protein (CP) cistron from some YU isolates made it possible (i) to identify specific amino acid residues in the N‐terminal of the CP protein and (ii) to assign some YU isolates to a new PVY clade. The symptoms caused by isolates belonging to this new PVY ‘Brazilian’ clade and their ability to infect selected susceptible hosts led to the conclusion that neither veinal necrosis symptoms expressed on infected tobacco plants nor adaptation to potato or pepper hosts are ancestral characteristics of PVY. These observations suggest that PVY has gained a remarkable new biological property and broadened its host range over time.
It's not too late: The onset of the frontocentral P3 indexes successful response inhibition in the stop‐signal paradigm
Authors: Wessel Jan R. , Aron Adam R.
Published: October 2014

The frontocentral P3 event‐related potential has been proposed as a neural marker of response inhibition. However, this association is disputed: some argue that P3 latency is too late relative to the timing of action stopping (stop‐signal reaction time; SSRT) to index response inhibition. We tested whether P3 onset latency is a marker of response inhibition, and whether it coincides with the timing predicted by neurocomputational models. We measured EEG in 62 participants during the stop‐signal task, and used independent component analysis and permutation statistics to measure the P3 onset in each participant. We show that P3 onset latency is shorter when stopping is successful, that it is highly correlated with SSRT, and that it coincides with the purported timing of the inhibition process (towards the end of SSRT). These results demonstrate the utility of P3 onset latency as a noninvasive, temporally precise neural marker of the response inhibition process.
The Losses from Trade Restrictions: Policy Dynamics with Firm Selection and Endogenous Markup
Authors: Moon Soojae
Published: October 2014

In this paper, I explore the aggregate effects of trade restrictions in a two‐country, dynamic, general equilibrium (DGE) model with firm selection and variable adjustment of markup. As a response to the trade collapse in the global crisis of 2008 and 2009, temporary trade restrictions have emerged in several countries. With analyzing the dynamics of a negative macroeconomic shock in the home economy first, and the subsequent introduction of trade restrictions in the foreign economy second, I show that both economies are in a worse position than they were during the economic downturn. The follow‐ups to the recession and trade restrictions are investigated through three mechanisms: (1) variable markup as a new avenue of increasing competitive pressure for producers (e.g. more competitive firms lower their markups); (2) average individual firms' specific productivity cut‐off, which induces their optimum export choice (e.g. an increase in the export productivity cut‐off means exporting becomes more difficult than before.); and (3) the movement of international relative prices (e.g. the real exchange rate and terms of trade).
Associations between attachment‐related symptoms and later psychological problems among international adoptees: Results from the FinAdo study
Authors: Elovainio Marko , Raaska Hanna , Sinkkonen Jari , Mäkipää Sanna , Lapinleimu Helena
Published: October 2014

We examined the associations between attachment‐related symptoms (symptoms of reactive attachment disorder (RAD), symptoms of disinhibited social engagement disorder (DSED), and clinging) and later psychological problems among international adoptees. The study population comprised internationally adopted children (591 boys and 768 girls, 6–15 years) from the ongoing Finnish Adoption (FinAdo) study. Data were gathered with self‐administered questionnaires both from adoptive parents and from adoptees aged over 9 years. Attachment‐related symptoms were measured using of a short (8‐item) questionnaire and later behavioral/emotional problems were assessed using the Child Behavior Checklist (CBCL) and the Five to Fifteen (FTF) scale for attention‐deficit/hyperactivity disorder (ADHD) symptoms. RAD and DSED symptom subscales were associated with an increased risk of emotional and behavioral problems and ADHD. Especially the mixed type of attachment‐related symptoms was strongly associated with later emotional and behavioral problems.
A Suicide Prevention Campaign for Firearm Dealers in New Hampshire
Authors: Vriniotis Mary , Barber Catherine , Frank Elaine , Demicco Ralph ,   the New Hampshire Firearm Safety Coalition
Published: October 2014

A spate of suicides involving a just‐purchased firearm led a statewide coalition of firearm dealers, firearm rights advocates, and suicide prevention professionals to discuss the role of gun shops in preventing suicide. The group developed and mailed materials for (1) firearm retailers on avoiding sales to suicidal customers and (2) their customers on suicide and firearm safety. All storefront retailers were identified (n = 65), visited unannounced 6 months after receiving materials, and asked to complete a survey. Nearly half (48%) had at least one campaign product on display. Belief that reducing a suicidal person's access to firearms might save a life was associated with displaying materials (69% vs. 41%, p = .06). Public health and gun groups can successfully collaborate on suicide prevention activities.
The Gender Wage Gap in the United States and Cross Nationally
Authors: Misra Joya , Murray‐Close Marta
Published: October 2014

Scholarship in sociology and economics has long explored the gender wage gap. Recent research suggests that these inequalities are indicative of important differences not only between men and women, but among women and men, reflecting rising levels of income inequality among workers in the post‐industrial era. We argue that the most interesting debates in the gender wage gap – those exploring differences among subgroups by class, race, and/or parenthood status (such as the motherhood wage penalty), as well as those considering differences across countries – can bring new insights to the study of wage inequality, as well as to understandings of what drives gendered wage inequality.
Ideology in Action: Symbolic Localization of Kurdistan Workers' Party in Turkey
Authors: Gurbuz Mustafa E.
Published: October 2014

Revolutionary ideologies such as Marxism and Islamism often aim to transform dominant local structures, leading their proponents to find themselves torn between global ideologies and local politics. A critical question arises: What does happen when a revolutionary movement's ideology drastically contradicts with the movement's local pragmatic purposes? AnalyzingKurdistan Workers' Party(PKK) in Turkey, this article explores the complex process of ideological transformation under the forces of local competition. Drawing on Mikhail Bakhtin's dialogic approach, I introduce the concept ofsymbolic localizationto understand how revolutionary ideologies evolve through pragmatic concerns. Symbolic localization refers to a discursive process of collective reputation work in which social movement activists blend local cultural repertoires and their “we” identity in order to build recognition, legitimacy, and prestige in the eyes of local population. Three major mechanisms of the symbolic localization process are identified: moral authority building, public symbolism, and memory work.Symbolic localizationsuggests analyzing movement ideology as a discursive process and illuminates how political activists are shaped byrelationallocal engagements.
Cattle manure and inorganic nitrogen fertilizer application effects on soil hydraulic properties and maize yield of two soils of Murewa district, Zimbabwe
Authors: Dunjana N. , Nyamugafata P. , Nyamangara J. , Mango N.
Published: October 2014

This study set out to determine the effects of cattle manure and inorganic N‐fertilizer application on the hydraulic properties and maize yield of a clay and sandy soil in a smallholder farming area of Zimbabwe. Four fields classified as homefields (HF: more fertile and closer to homesteads) and outfields (OF: less fertile and further from the homesteads) were selected on clay and sandy soil. They were subjected to four treatments, control (no fertility amendment), 5, 15 and 25 t/ha cattle manure + 100 kg/ha N (as ammonium nitrate) for 7 years. A two‐way randomized complete block design was used with fertility and field type as the two factors. Clay soil hydraulic properties, which included density of macropores with a diameter >300 μm, unsaturated hydraulic conductivity, steady‐state infiltration rate, moisture retention under low suction and maize grain yield, were significantly improved (P < 0.05) by fertility management compared with the control and were generally comparable between the HF and OF. Fertility management significantly improved maize grain yield on sandy soils but did not enhance hydraulic parameters, thereby indicating poor responsiveness in structural build‐up. On the other hand, significantly different hydraulic parameters between the sandy soil HF and OF suggested effects of other factors not related to soil fertility and field type treatments. We therefore concluded that application of a high rate (25 t/ha) of cattle manure and inorganic N‐fertilizer is beneficial for fertility restoration to the degraded OFs with associated comparable hydraulic properties on HFs and OFs on clay soil, unlike on sandy soil.
Quality of surgical care in hospitals providing internship training in Kenya: a cross sectional survey.
Authors: Mwinga Stephen , Kulohoma Colette , Mwaniki Paul , Idowu Rachel , Masasabi John , English Mike ,   the SIRCLE Collaboration
Published: October 2014

Objective

To evaluate services in hospitals providing internship training to graduate doctors in Kenya.

Methods

A survey of 22 internship training hospitals was conducted. Availability of key resources spanning infrastructure, personnel, equipment and drugs was assessed by observation. Outcomes and process of care for pre‐specified priority conditions (head injury, chest injury, fractures, burns and acute abdomen) were evaluated by auditing case records.

Results

Each hospital had at least one consultant surgeon. Scheduled surgical outpatient clinics, major ward rounds and elective (half day) theatre lists were provided once per week in 91%, 55% and 9%, respectively. In all other hospitals, these were conducted twice weekly. Basic drugs were not always available (e.g. gentamicin, morphine and pethidine in 50%, injectable antistaphylococcal penicillins in 5% hospitals). Fewer than half of hospitals had all resources needed to provide oxygen. One hundred and forty‐five of 956 cases evaluated underwent operations under general or spinal anaesthesia. We found operation notes for 99% and anaesthetic records for 72%. Pre‐operatively measured vital signs were recorded in 80% of cases, and evidence of consent to operation was found in 78%. Blood loss was documented in only one case and sponge and instrument counts in 7%.

Conclusions

Evaluation of surgical services would be improved by development and dissemination of clear standards of care. This survey suggests that internship hospitals may be poorly equipped and documented care suggests inadequacies in quality and training.
Hemostatic analysis of dogs naturally envenomed by the African puffadder (Bitis arietans) and snouted cobra (Naja annulifera)
Authors: Nagel Susanna S. , Schoeman Johan P. , Thompson Peter N. , Wiinberg Bo , Goddard Amelia
Published: October 2014

Objective

To investigate hemostatic changes in dogs envenomed by cytotoxic (African puffadder) and neurotoxic snakes (snouted cobra) using thromboelastography (TEG) and plasma‐based coagulation assays.

Design

Prospective observational clinical study.

Setting

University teaching hospital.

Animals

Eighteen client‐owned dogs; 9 envenomed by African puffadder (Bitis arietans) and 9 by snouted cobra (Naja annulifera). Ten healthy dogs served as controls.

Interventions

None.

Measurements and Main Results

Blood was collected at presentation and 24 hours post envenomation. Platelet count, TEG, prothrombin time, activated partial thromboplastin time (aPTT), antithrombin activity, and fibrinogen (Fib) and C‐reactive protein (CRP) concentrations were measured. Outcomes were analyzed using linear mixed models at 5% significance. At presentation, R time was significantly prolonged in the puffadder group compared to the cobra (P = 0.01) and control groups (P = 0.05). Platelet count was significantly lower in the puffadder compared to the cobra (P = 0.04) and control groups (P = 0.001), respectively. Antithrombin activity was significantly decreased in the puffadder (P = 0.002) and cobra groups (P = 0.004) compared to the control group. Both prothrombin time and activated partial thromboplastin time were significantly prolonged in the cobra group compared to the control group (P = 0.03 for both). The TEG variables, maximum amplitude (MA) and G, were significantly increased 24 hours post envenomation in the puffadder group compared to their values at presentation (P = 0.05 for both). Fib and CRP concentrations were significantly increased 24 hours post envenomation in both snake‐envenomed groups.

Conclusions

Prolonged clot initiation was a common feature in puffadder‐envenomed dogs at presentation and this was likely venom induced. Snouted cobra‐envenomed dogs were normo‐ to hypercoagulable at presentation. Dogs from both puffadder and cobra groups progressed to a more hypercoagulable by 24 hours post envenomation, most likely due to marked inflammation as indicated by the increased Fib and CRP concentrations. TEG proved a sensitive tool for detecting abnormal hemostasis in snake‐envenomed dogs.
Fluid dynamics and intraocular pressure using venturi phacoemulsification machine in dogs ex vivo
Authors: Kang Seonmi , Park Sangwan , Noh Hyunwoo , Seo Kangmoon
Published: October 2014

Objective

To optimize fluid dynamics through measuring intraocular pressure (IOP) in a venturi phacoemulsification machine in dogs.

Procedures

In step I, flow and IOP of the test chamber were measured using a pressure transducer with the bottle height (BH) set at 50, 70, 100, and 120 cm and the vacuum from 30 to 450 mmHg. A 19‐gauge phaco and a 0.3‐mm irrigation/aspiration (I/A) handpiece were used. In step II, flow and IOP were measured in an enucleated canine eye with a 3.0‐ and a 3.2‐mm clear corneal incision (CCI), respectively. IOP was measured using the pressure transducer at a 30‐mmHg vacuum to allow corneal deformation, to define the fluidic parameters for preventing surge.

Results

Flow was directly proportional to the BH and vacuum, whereas IOP was directly proportional to the BH and inversely to the vacuum. Flow with an I/A handpiece was significantly less than with a phaco handpiece, explaining why IOP with an I/A handpiece was significantly higher than with a phaco handpiece. With the I/A handpiece, vacuum parameters less than 450 mmHg did not result in corneal deformation. IOP with a 3.2‐mm CCI was significantly lower than with a 3.0‐mm CCI, with the 3.2‐mm flow being greater than the 3.0‐mm flow.

Conclusions

BH during the I/A stage could be reduced to avoid unnecessary stress on the canine eye when using a venturi system. Although phacoemulsification with a 3.2‐mm CCI could induce lower IOP, a 3.0‐mm CCI might lessen the irrigation flow stress on the eye.
Effect of the relative time of emergence on the growth allometry ofGalium aparinein competition withTriticum aestivum
Authors: Klem Karel , Rajsnerová Petra , Novotná Kateřina , Urban Otmar , Marek Michal V.
Published: October 2014

The impact of the relative time of emergence on the growth allometry ofGalium aparineL. (cleavers) in competition withTriticum aestivumL. (spring wheat) was studied in a greenhouse experiment. The hypothesis that changes in growth allometry, particularly in the leaf area/height ratio, caused by a shift in the relative time of emergence, could lead to plants overcoming the competition or to competitive suppression was tested. The plant height, dry weight, total leaf area and vertical distribution were analyzed during the first 83 days of growth. The late emergence ofG. aparinesubstantially influenced the growth dynamics for the dry weight and total leaf area. The dynamics of height growth were affected only following a significant delay inG. aparineemergence. The ratio of dry weight to total leaf area was almost unaffected by the competition. By contrast, the allometric relationship between the plant height and total leaf area was highly sensitive to the relative time of emergence. The results suggest that height is the most important growth trait for the plants to resist increasing competition. Even though the plants responded to competition with elongation, the physiological costs linked with “shade avoidance” caused reductions in the dry weight and leaf area growth that resulted in the total suppression of the late‐emerging individuals, in particular when their emergence was >10 days after that of the crop.
From Asia to Europe across Siberia: phylogeography of the Siberian spined loach (Teleostei, Cobitidae)
Authors: Perdices Anabel , Vasil'eva Ekaterina , Vasil'ev Victor
Published: October 2014

We assessed the genetic variability of the Siberian spined loach Cobitis melanoleuca across its unusually broad distribution that encompasses areas greatly affected by Pleistocene glaciations. Due to extensive morphological variation among their populations, the taxonomic status of C. melanoleuca is complicated. It is unclear whether C. melanoleuca represents a single taxonomic unit or contains several species or subspecies. Our analyses showed low genetic variability in all populations without any phylogenetic structure. The absence of molecular distinctiveness indicates the conspecificity of all C. melanoleuca populations. Only a few common haplotypes shared by East Asian, Siberian and European populations were found at high frequency in the nuclear genes analysed. At the mitochondrial level, Siberian populations shared haplotypes with populations located at both extremes of the species’ range suggesting central populations as a source of current mitochondrial variability. Unimodal mismatch distributions and significant values from neutrality tests support a recent expansion of C. melanoleuca. Our time estimates suggest a postglacial colonisation of European waters around 1.0 MYA, indicating that C. melanoleuca may represent the last cobitid immigrant in Europe that used the northern route across Siberia to expand its range.
Spectre et géométrie conforme des variétés compactes à bord
Authors: Jammes Pierre
Published: October 2014

We prove that on any compact manifold $M^{n}$ with boundary, there exists a conformal class $C$ such that for any Riemannian metric $g\in C$ of unit volume, the first positive eigenvalue of the Neumann Laplacian satisfies ${\it\lambda}_{1}(M^{n},g)<n\,\text{Vol}(S^{n},g_{\text{can}})^{2/n}$. We also prove a similar inequality for the first positive Steklov eigenvalue. The proof relies on a handle decomposition of the manifold. We also prove that the conformal volume of $(M,C)$ is $\text{Vol}(S^{n},g_{\text{can}})$, and that the Friedlander–Nadirashvili invariant and the Möbius volume of $M$ are equal to those of the sphere. If $M$ is a domain in a space form, $C$ is the conformal class of the canonical metric.
Roughness of the SiC/SiO2 vicinal interface and atomic structure of the transition layers
Authors: Liu Peizhi , Li Guoliang , Duscher Gerd , Sharma Yogesh K. , Ahyi Ayayi C. , Isaacs-Smith Tamara , Williams John R. , Dhar Sarit
Published: October 2014

The SiC/SiO2 interface is generally considered to be the cause for the reduced electron mobility of SiC power devices. Previous studies have shown a correlation between the mobility and the transition layer width at the SiC/SiO2 interface. The authors investigated this interface with atomic resolution Z-contrast imaging and electron energy-loss spectroscopy, and discovered that this transition region was due to the roughness of the vicinal interface. The roughness of a vicinal interface consisted of atomic steps and facets deviating from the ideal off-axis cut plane. The authors conclude that this roughness is limiting the mobility in the channels of SiC MOSFETs.
Well-aligned NiSi/Si heterostructured nanowire arrays as field emitters
Authors: Lv Shasha , Li Zhengcao , Liao Jiecui , Zhang Zhengjun , Miao Wei
Published: October 2014

Nickel silicides are promising candidates in modern semiconductor devices as contact metals, metal gate electrodes, and source/drains in field effect transistors. A multistep template replication process was utilized to fabricate highly periodic and well-aligned silicon nanowires (SiNWs), and the size could be further reduced via dry oxidation and post chemical treatment. NiSi/Si heterostructured nanowire arrays were fabricated by nickel film deposition on SiNWs and then rapid thermal annealing at 550 °C. Field emission (FE) measurements illustrated that the turn-on field and field enhancement factor β of NiSi/Si heterostructures were 1.3 V/μm and ∼9000, better than that of the SiNWs, which were about 1.9 V/μm and ∼3900. These results are superior to the FE properties of other silicon-based nanomaterials. The excellent FE characteristics are attributed to the uniformly distributed nanowires with high aspect ratio and large proximity, high conductivity of uniform NiSi coating, and favorable morphological features with sharp and rough tips as hot emission spots. The single-crystalline silicon nanowires shelled with polycrystalline NiSi provide substantial opportunities for integration with Si devices to form active field emitters, and for exploration of the nickel silicides on other electrical and optical properties.
Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders
Authors: Santini Emanuela , Klann Eric
Published: October 2014

Pathways regulating translation and synaptic function may be interconnected in autism spectrum disorder.
Unhinging Muscle Injury
Authors: Gough Nancy R.
Published: October 2014

Blocking cleavage of LTBP4 (latent TGF-β binding protein 4) and TGF-β release decreases muscle pathology.
An Optimized Mouse Thigh Infection Model for Enterococci and Its Impact on Antimicrobial Pharmacodynamics
Authors: Rodriguez Carlos A. , Agudelo Maria , Gonzalez Javier M. , Vesga Omar , Zuluaga Andres F.
Published: October 2014

Negligible
in vivo
growth of enterococci and high-level dispersion of data have led to inaccurate estimations of antibiotic pharmacodynamics (PD). Here we improved an
in vivo
model apt for PD studies by optimizing the
in vitro
culture conditions for enterococci. The PD of vancomycin (VAN), ampicillin-sulbactam (SAM), and piperacillin-tazobactam (TZP) against enterococci were determined
in vivo
, comparing the following different conditions of inoculum preparation: aerobiosis, aerobiosis plus mucin, and anaerobiosis plus mucin. Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (
f
AUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (
fT
>MIC
) (SAM and TZP) and linked to the change in log
10
CFU/thigh. Only anaerobiosis plus mucin enhanced the
in vivo
growth, yielding significant PD parameters with all antibiotics. In conclusion, robust
in vivo
growth of enterococci was crucial for better determining the PD of tested antibacterial agents, and this was achieved by optimizing the procedure for preparing the inoculum.
Antimalarial Action of Artesunate Involves DNA Damage Mediated by Reactive Oxygen Species
Authors: Gopalakrishnan Anusha M. , Kumar Nirbhay
Published: October 2014

Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for
Plasmodium falciparum
malaria. It has been suggested that the cytotoxic effect of artemisinin is mediated by free radicals followed by the alkylation of
P. falciparum
proteins. The endoperoxide bridge, the active moiety of artemisinin derivatives, is cleaved in the presence of ferrous iron, generating reactive oxygen species (ROS) and other free radicals. However, the emergence of resistance to artemisinin in
P. falciparum
underscores the need for new insights into the molecular mechanisms of antimalarial activity of artemisinin. Here we show that artesunate (ART) induces DNA double-strand breaks in
P. falciparum
in a physiologically relevant dose- and time-dependent manner. DNA damage induced by ART was accompanied by an increase in the intracellular ROS level in the parasites. Mannitol, a ROS scavenger, reversed the cytotoxic effect of ART and reduced DNA damage, and modulation of glutathione (GSH) levels was found to impact ROS and DNA damage induced by ART. Accumulation of ROS, increased DNA damage, and the resulting antiparasite effect suggest a causal relationship between ROS, DNA damage, and parasite death. Finally, we also show that ART-induced ROS production involves a potential role for NADPH oxidase, an enzyme involved in the production of superoxide anions. Our results with
P. falciparum
provide novel insights into previously unknown molecular mechanisms underlying the antimalarial activity of artemisinin derivatives and may help in the design of next-generation antimalarial drugs against the most virulent
Plasmodium
species.
High-Content Screening Technology Combined with a Human Granuloma Model as a New Approach To Evaluate the Activities of Drugs against Mycobacterium tuberculosis
Authors: Silva-Miranda Mayra , Ekaza Euloge , Breiman Adrien , Asehnoune Karim , Barros-Aguirre David , Pethe Kevin , Ewann Fanny , Brodin Priscille , Ballell-Pages Lluís , Altare Frédéric
Published: October 2014

Tuberculosis remains a major health problem due to the emergence of drug-resistant strains of
Mycobacterium tuberculosis
. Some models have provided valuable information about drug resistance and efficacy; however, the translation of these results into effective human treatments has mostly proven unsuccessful. In this study, we adapted high-content screening (HCS) technology to investigate the activities of antitubercular compounds in the context of an
in vitro
granuloma model. We observed significant shifts in the MIC
50
s between the activities of the compounds under extracellular and granuloma conditions.
Stratification of the Impact of Inappropriate Empirical Antimicrobial Therapy for Gram-Negative Bloodstream Infections by Predicted Prognosis
Authors: Cain Sarah E. , Kohn Joseph , Bookstaver P. Brandon , Albrecht Helmut , Al-Hasan Majdi N.
Published: October 2014

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31;
P
= 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87;
P
= 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77;
P
= 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.
In Vitro
and Intracellular Activities of Peptide Deformylase Inhibitor GSK1322322 against Legionella pneumophila Isolates
Authors: Dubois Jacques , Dubois Maïtée , Martel Jean-François , Aubart Kelly , Butler Deborah
Published: October 2014

GSK1322322, a novel peptide deformylase inhibitor currently in development as an oral and intravenous agent for the treatment of hospitalized community-acquired bacterial pneumonia, showed poor
in vitro
activity against a panel of 50
Legionella pneumophila
strains, with MICs ranging from 1 to 16 μg/ml and an MIC
90
of 16 μg/ml, but very potent intracellular activity, with the minimum extracellular concentrations capable of inhibiting intracellular proliferation (MIECs) ranging from 0.12 to 2 μg/ml and 98% of the strains being inhibited by concentrations of ≤1 μg/ml.
Target-Based Resistance in Pseudomonas aeruginosa and Escherichia coli to NBTI 5463, a Novel Bacterial Type II Topoisomerase Inhibitor
Authors: Nayar Asha S. , Dougherty Thomas J. , Reck Folkert , Thresher Jason , Gao Ning , Shapiro Adam B. , Ehmann David E.
Published: October 2014

In a previous report (T. J. Dougherty, A. Nayar, J. V. Newman, S. Hopkins, G. G. Stone, M. Johnstone, A. B. Shapiro, M. Cronin, F. Reck, and D. E. Ehmann, Antimicrob Agents Chemother 58:2657–2664, 2014), a novel bacterial type II topoisomerase inhibitor, NBTI 5463, with activity against Gram-negative pathogens was described. First-step resistance mutations in
Pseudomonas aeruginosa
arose exclusively in the
nfxB
gene, a regulator of the MexCD-OprJ efflux pump system. The present report describes further resistance studies with NBTI 5463 in both
Pseudomonas aeruginosa
and
Escherichia coli
. Second-step mutations in
P. aeruginosa
arose at aspartate 82 of the gyrase A subunit and led to 4- to 8-fold increases in the MIC over those seen in the parental strain with a first-step
nfxB
efflux mutation. A third-step mutant showed additional GyrA changes, with no changes in topoisomerase IV. Despite repeated efforts, resistance mutations could not be selected in
E. coli
. Genetic introduction of the Asp82 mutations observed in
P. aeruginosa
did not significantly increase the NBTI MIC in
E. coli
. However, with the aspartate 82 mutation present, it was possible to select second-step mutations in topoisomerase IV that did lead to MIC increases of 16- and 128-fold. As with the gyrase aspartate 82 mutation, the mutations in topoisomerase IV did not by themselves raise the NBTI MIC in
E. coli
. Only the presence of mutations in both targets of
E. coli
led to an increase in NBTI MIC values. This represents a demonstration of the value of balanced dual-target activity in mitigating resistance development.
In Vitro
Efficacy of High-Dose Tobramycin against Burkholderia cepacia Complex and Stenotrophomonas maltophilia Isolates from Cystic Fibrosis Patients
Authors: Ratjen Anina , Yau Yvonne , Wettlaufer Jillian , Matukas Larissa , Zlosnik James E. A. , Speert David P. , LiPuma John J. , Tullis Elizabeth , Waters Valerie
Published: October 2014

Burkholderia cepacia
complex and
Stenotrophomonas maltophilia
infections are associated with poor clinical outcomes in persons with cystic fibrosis (CF). The MIC
50
based on planktonic growth and the biofilm concentration at which 50% of the isolates tested are inhibited (BIC
50
) of tobramycin were measured for 180
B. cepacia
complex and 101
S. maltophilia
CF isolates and were 100 μg/ml for both species. New inhalation devices that deliver high tobramycin levels to the lung may be able to exceed these MICs.
Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium
Authors: Cattoir Vincent , Isnard Christophe , Cosquer Thibaud , Odhiambo Arlène , Bucquet Fiona , Guérin François , Giard Jean-Christophe
Published: October 2014

Tigecycline (TIG) is approved for use for the treatment of complicated intra-abdominal infections, skin and skin structure infections, as well as pneumonia. Acquired resistance or reduced susceptibility to TIG has been observed in Gram-negative rods, has seldom been reported in Gram-positive organisms, and has not yet been reported in
Enterococcus faecium
. Using the serial passage method,
in vitro
mutant AusTig and
in vitro
mutants HMtig1 and HMtig2 with decreased TIG susceptibility (MICs, 0.25 μg/ml) were obtained from strains
E. faecium
Aus0004 and HM1070 (MICs, 0.03 μg/ml), respectively. In addition, two vancomycin-resistant
E. faecium
clinical isolates (EF16 and EF22) with reduced susceptibility to TIG (MICs, 0.5 and 0.25 μg/ml, respectively) were studied. Compared to the wild-type strains, the
in vitro
mutants also showed an increase in the MICs of other tetracyclines. An efflux mechanism did not seem to be involved in the reduced TIG susceptibility, since the presence of efflux pump inhibitors (reserpine or pantoprazole) did not affect the MICs of TIG. Whole-genome sequencing of AusTig was carried out, and genomic comparison with the Aus0004 genome was performed. Four modifications leading to an amino acid substitution were found. These mutations affected the
rpsJ
gene (
efau004_00094
, coding for the S10 protein of the 30S ribosomal subunit),
efau004_01228
(encoding a cation transporter),
efau004_01636
(coding for a hypothetical protein), and
efau004_02455
(encoding the
l
-lactate oxidase). The four other strains exhibiting reduced TIG susceptibility were screened for the candidate mutations. This analysis revealed that three of them showed an amino acid substitution in the same region of the RpsJ protein. In this study, we characterized for the first time genetic determinants linked to reduced TIG susceptibility in enterococci.
Lymphocytes Modulate Innate Immune Responses and Neuronal Damage in Experimental Meningitis
Authors: Hoffmann Olaf , Rung Olga , Held Josephin , Boettcher Chotima , Prokop Stefan , Stenzel Werner , Priller Josef
Published: October 2014

In bacterial meningitis, excessive immune responses carry significant potential for damage to brain tissue even after successful antibiotic therapy. Bacterial meningitis is regarded primarily as the domain of innate immunity, and the role of lymphocytes remains unclear. We studied the contribution of lymphocytes to acute inflammation and neurodegeneration in experimental Toll-like receptor 2-driven meningitis, comparing wild-type mice with RAG-1-deficient mice that have no mature T and B lymphocytes. At 24 h after intrathecal challenge with the synthetic bacterial lipopeptide Pam
3
CysSK
4
, RAG-1-deficient mice displayed more pronounced clinical impairment and an increased concentration of neutrophils, reduced expression of interleukin-10 (IL-10) mRNA, and increased expression of CXCL1 mRNA in the cerebrospinal fluid. Conversely, neuronal loss in the dentate gyrus was reduced in RAG-1-deficient mice, and expression of IL-10, transforming growth factor β and CCL2 mRNA by microglia was increased compared to wild-type mice. Adoptive transfer of wild-type lymphocytes reversed the enhanced meningeal inflammation and functional impairment observed in RAG-1-deficient mice. Our findings suggest compartment-specific effects of lymphocytes during acute bacterial meningitis, including attenuation of meningeal inflammation and shifting of microglial activation toward a more neurotoxic phenotype.
Cyclic Di-GMP-Mediated Repression of Swarming Motility by Pseudomonas aeruginosa PA14 Requires the MotAB Stator
Authors: Kuchma S. L. , Delalez N. J. , Filkins L. M. , Snavely E. A. , Armitage J. P. , O'Toole G. A.
Published: October 2014

The second messenger cyclic diguanylate (c-di-GMP) plays a critical role in the regulation of motility. InPseudomonas aeruginosaPA14, c-di-GMP inversely controls biofilm formation and surface swarming motility, with high levels of this dinucleotide signal stimulating biofilm formation and repressing swarming.P. aeruginosaencodes two stator complexes, MotAB and MotCD, that participate in the function of its single polar flagellum. Here we show that the repression of swarming motility requires a functional MotAB stator complex. Mutating themotABgenes restores swarming motility to a strain with artificially elevated levels of c-di-GMP as well as stimulates swarming in the wild-type strain, while overexpression of MotA from a plasmid represses swarming motility. Using point mutations in MotA and the FliG rotor protein of the motor supports the conclusion that MotA-FliG interactions are critical for c-di-GMP-mediated swarming inhibition. Finally, we show that high c-di-GMP levels affect the localization of a green fluorescent protein (GFP)-MotD fusion, indicating a mechanism whereby this second messenger has an impact on MotCD function. We propose that when c-di-GMP level is high, the MotAB stator can displace MotCD from the motor, thereby affecting motor function. Our data suggest a newly identified means of c-di-GMP-mediated control of surface motility, perhaps conserved amongPseudomonas,Xanthomonas, and other organisms that encode two stator systems.
The Rate of Osmotic Downshock Determines the Survival Probability of Bacterial Mechanosensitive Channel Mutants
Authors: Bialecka-Fornal Maja , Lee Heun Jin , Phillips Rob
Published: October 2014

Mechanosensitive (MS) channels allow cells to sense and respond to environmental changes. In bacteria, these channels are believed to protect against an osmotic shock. The physiological function of these channels has been characterized primarily by a standardized assay, where aliquots of batch-cultured cells are rapidly pipetted into a hypotonic medium. Under this method, it has been inferred many types of MS channels (MscS homologs in
Escherichia coli
) demonstrate limited effectiveness against shock, typically rescuing less than 10% of the cells when expressed at native levels. We introduce a single-cell-based assay which allows us to control how fast the osmolarity changes, over time scales ranging from a fraction of a second to several minutes. We find that the protection provided by MS channels depends strongly on the rate of osmotic change, revealing that, under a slow enough osmotic drop, MscS homologs can lead to survival rates comparable to those found in wild-type strains. Further, after the osmotic downshift, we observe multiple death phenotypes, which are inconsistent with the prevailing paradigm of how cells lyse. Both of these findings require a reevaluation of our basic understanding of the physiology of MS channels.
Analysis of the Dynamics of a Bacillus subtilis Spore Germination Protein Complex during Spore Germination and Outgrowth
Authors: Troiano Anthony J. , Zhang Jingqiao , Cowan Ann E. , Yu Ji , Setlow Peter
Published: October 2014

Germination ofBacillus subtilisspores is normally initiated when nutrients from the environment interact with germinant receptors (GRs) in the spores' inner membrane (IM), in which most of the lipids are immobile. GRs and another germination protein, GerD, colocalize in the IM of dormant spores in a small focus termed the “germinosome,” and this colocalization or focus formation is dependent upon GerD, which is also essential for rapid GR-dependent spore germination. To determine the fate of the germinosome and germination proteins during spore germination and outgrowth, we employed differential interference microscopy and epifluorescence microscopy to track germinating spores with fluorescent fusions to germination proteins and used Western blot analyses to measure germination protein levels. We found that after initiation of spore germination, the germinosome foci ultimately changed into larger disperse patterns, with ≥75% of spore populations displaying this pattern in spores germinated for 1 h, although >80% of spores germinated for 30 min retained the germinosome foci. Western blot analysis revealed that levels of GR proteins and the SpoVA proteins essential for dipicolinic acid release changed minimally during this period, although GerD levels decreased ∼50% within 15 min in germinated spores. Since the dispersion of the germinosome during germination was slower than the decrease in GerD levels, either germinosome stability is not compromised by ∼2-fold decreases in GerD levels or other factors, such as restoration of rapid IM lipid mobility, are also significant in germinosome dispersion as spore germination proceeds.