bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-site randomized controlled trial of a cognitive skills programme for male mentally disordered offenders: social–cognitive outcomes
Authors: Cullen A. E. , Clarke A. Y. , Kuipers E. , Hodgins S. , Dean K. , Fahy T.
Published: August 2011

Background

Cognitive skills programmes have been associated with improvements on psychometric measures and reductions in antisocial behaviour in mentally disordered offenders (MDOs). However, to date there have been no randomized controlled trials (RCTs) of such programmes with this population. In the first RCT of a cognitive skills programme with MDOs we aimed to determine if participation in the Reasoning and Rehabilitation (R&R) programme was associated with improvements in social–cognitive skills and thinking styles.

Method

A total of 84 men with a primary diagnosis of psychotic disorder and a history of violence were recruited from medium-secure forensic units and allocated to receive R&R (n=44) or treatment as usual (TAU;n=40). At baseline and post-treatment interviews, participants completed questionnaires to assess social problem-solving, criminal attitudes, anger experience, blame externalizing and perspective-taking. Researchers were not blind to group status.

Results

The R&R group demonstrated significant improvements on measures of social problem-solving relative to the TAU group, some of which were maintained at 12 months post-treatment. Only half of those allocated to receive R&R completed the full programme. Inpost-hocanalyses programme completers showed improvements in social problem-solving at the end of treatment and changes in criminal attitudes at 12 months post-treatment.

Conclusions

Among male MDOs, R&R participation was associated with improvements in social–cognitive skills, some of which were maintained for up to 12 months post-treatment. Our finding that programme completers do better may reflect pre-treatment patient characteristics. This study establishes that multi-site RCTs can be conducted in medium-secure forensic units.
Insight into the molecular basis for the kinetic differences between the two insulin receptor isoforms
Authors: Knudsen Louise , De Meyts Pierre , Kiselyov Vladislav V.
Published: August 2011

More than 20 years after the description of the two IR (insulin receptor) isoforms, designated IR-A (lacking exon 11) and IR-B (with exon 11), nearly every functional aspect of the alternative splicing both in vitro and in vivo remains controversial. In particular, there is no consensus on the precise ligand-binding properties of the isoforms. Increased affinity and dissociation kinetics have been reported for IR-A in comparison with IR-B, but the opposite results have also been reported. These are not trivial issues considering the reported possible increased mitogenic potency of IR-A, and the reported link between slower dissociation and increased mitogenesis. We have re-examined the ligand-binding properties of the two isoforms using a novel rigorous mathematical analysis based on the concept of a harmonic oscillator. We found that insulin has 1.5-fold higher apparent affinity towards IR-A and a 2-fold higher overall dissociation rate. Analysis based on the model showed increased association (3-fold) and dissociation (2-fold) rate constants for binding site 1 of IR in comparison with IR-B. We also provide a structural interpretation of these findings on the basis of the structure of the IR ectodomain and the proximity of the sequence encoded by exon 11 to the C-terminal peptide that is a critical trans-component of site 1.
Viscous damping of nanobeam resonators: Humidity, thermal noise, and a paddling effect
Authors: Chen Chao , Ma Ming , Zhe Liu Jefferson , Zheng Quanshui , Xu Zhiping
Published: August 2011

A nanobeam resonator is a key mechanical component of a nano-electromechanical system. Because of its small dimensions, the system can reach very high frequencies, but it is also very sensitive to its environment, as a large surface area of the material is exposed. Molecular dynamics (MD) simulations and theoretical analysis are used here to quantitatively predict the damping behavior of a nanobeam, including its critical damping conditions and lifetime, directly mapping fluid-structure properties and interaction into dynamics. We show here how the humidity defines the critical damping condition through viscous forces, marking the transition from the under-damping to the over-damping regime at elevated humidity. Phenomena such as thermal fluctuations and the paddling effect are also discussed with an explanation using a simple one-dimensional model.
Fusion-activated Ca
2+
entry via vesicular P2X
4
receptors promotes fusion pore opening and exocytotic content release in pneumocytes
Authors: Miklavc Pika , Mair Norbert , Wittekindt Oliver H. , Haller Thomas , Dietl Paul , Felder Edward , Timmler Melanie , Frick Manfred
Published: August 2011

Ca
2+
is considered a key element in multiple steps during regulated exocytosis. During the postfusion phase, an elevated cytoplasmic Ca
2+
concentration ([Ca
2+
])
c
leads to fusion pore dilation. In neurons and neuroendocrine cells, this results from activation of voltage-gated Ca
2+
channels in the plasma membrane. However, these channels are activated in the prefusion stage, and little is known about Ca
2+
entry mechanisms during the postfusion stage. This may be particularly important for slow and nonexcitable secretory cells. We recently described a “fusion-activated“ Ca
2+
entry (FACE) mechanism in alveolar type II (ATII) epithelial cells. FACE follows initial fusion pore opening with a delay of 200–500 ms. The site, molecular mechanisms, and functions of this mechanism remain unknown, however. Here we show that vesicle-associated Ca
2+
channels mediate FACE. Using RT-PCR, Western blot analysis, and immunofluorescence, we demonstrate that P2X
4
receptors are expressed on exocytotic vesicles known as lamellar bodies (LBs). Electrophysiological, pharmacological, and genetic data confirm that FACE is mediated via these vesicular P2X
4
receptors. Furthermore, analysis of fluorophore diffusion into and out of individual vesicles after exocytotic fusion provides evidence that FACE regulates postfusion events of LB exocytosis via P2X
4
. Fusion pore dilation was clearly correlated with the amplitude of FACE, and content release from fused LBs was accelerated in fusions followed by FACE. Based on these findings, we propose a model for regulation of the exocytotic postfusion phase in nonexcitable cells in which Ca
2+
influx via vesicular Ca
2+
channels regulates fusion pore expansion and vesicle content release.
Sensing membrane stress with near IR-emissive porphyrins
Authors: Kamat Neha P. , Liao Zhengzheng , Moses Laurel E. , Rawson Jeff , Therien Michael J. , Dmochowski Ivan J. , Hammer Daniel A.
Published: August 2011

Probes embedded within a structure can enable prediction of material behavior or failure. Carefully assembled composites that respond intelligently to physical changes within a material could be useful as intrinsic sensors. Molecular rotors are one such tool that can respond optically to physical environmental changes. Here, we propose to use molecular rotors within a polymersome membrane to report membrane stress. Using supermolecular porphyrin-based fluorophores as rotors, we characterize changes in the optical emission of these near-infrared (NIR) emissive probes embedded within the hydrophobic core of the polymersome membrane. The configuration of entrapped fluorophore depends on the available space within the membrane; in response to increased volume, emission is blue shifted. We used this feature to study how shifts in fluorescence correlate to membrane integrity, imparted by membrane stress. We monitored changes in emission of these porphyrin-based fluorophores resulting from membrane stress produced through a range of physical and chemical perturbations, including surfactant-induced lysis, hydrolytic lysis, thermal degradation, and applied stress by micropipette aspiration. This paper comprehensively illustrates the potential for supermolecular porphyrin-based fluorophores to detect intrinsic physical changes in a wide variety of environments, and suggests how molecular rotors may be used in soft materials science and biology as sensors.
Mesopores provide an amorphous state suitable for studying biomolecular structures at cryogenic temperatures
Authors: Huang Ya-Wen , Lai Yei-Chen , Tsai Chia-Jung , Chiang Yun-Wei
Published: August 2011

In nano-confinements, aqueous solutions can be found to remain in a liquid state at subfreezing temperatures. The finding provides a means of entering into previously inaccessible temperature regions for studying the dynamics and structure of bulk liquid. Here we show that studying biomolecular structures in nano-confinements improves the accuracy of cryostructures and provides better insight into the relationship between hydration water and biomolecules. Synthetic prion protein peptides are studied in two experimental conditions: (
i
) in confined nanochannels within mesoporous materials, and (
ii
) in vitrified bulk solvents, with a temperature range of 50–275 K, using cw/pulse ESR techniques. A large inhomogeneous lineshape broadening is only observed for the spectra from the vitrified bulk solvent below 70 K, suggesting a possible peptide clustering in the solution. The spin-counting and distance measurements by DEER-ESR provide further evidence that peptides are dispersed homogeneously in mesopores but heterogeneously in vitrified solvents wherein the biomolecular structure is disturbed due to heterogeneity in the bulk solvent structure. Our study demonstrates that the nanospace within mesoporous materials provides an amorphous environment that is better than vitrified bulk solvent for studying biostructures at cryogenic temperatures.
Chloroplast lipid droplet type II NAD(P)H quinone oxidoreductase is essential for prenylquinone metabolism and vitamin K
1
accumulation
Authors: Eugeni Piller Lucia , Besagni Céline , Ksas Brigitte , Rumeau Dominique , Bréhélin Claire , Glauser Gaétan , Kessler Felix , Havaux Michel
Published: August 2011

Lipid droplets are ubiquitous cellular structures in eukaryotes and are required for lipid metabolism. Little is currently known about plant lipid droplets other than oil bodies. Here, we define dual roles for chloroplast lipid droplets (plastoglobules) in energy and prenylquinone metabolism. The prenylquinones—plastoquinone, plastochromanol-8, phylloquinone (vitamin K
1
), and tocopherol (vitamin E)—are partly stored in plastoglobules. This work shows that NAD(P)H dehydrogenase C1 (NDC1) (At5g08740), a type II NAD(P)H quinone oxidoreductase, associates with plastoglobules. NDC1 reduces a plastoquinone analog in vitro and affects the overall redox state of the total plastoquinone pool in vivo by reducing the plastoquinone reservoir of plastoglobules. Finally, NDC1 is required for normal plastochromanol-8 accumulation and is essential for vitamin K
1
production.
WAVE regulatory complex activation by cooperating GTPases Arf and Rac1
Authors: Koronakis Vassilis , Hume Peter J. , Humphreys Daniel , Liu Tao , Hørning Ole , Jensen Ole N. , McGhie Emma J.
Published: August 2011

The WAVE regulatory complex (WRC) is a critical element in the control of actin polymerization at the eukaryotic cell membrane, but how WRC is activated remains uncertain. While Rho GTPase Rac1 can bind and activate WRC in vitro, this interaction is of low affinity, suggesting other factors may be important. By reconstituting WAVE-dependent actin assembly on membrane-coated beads in mammalian cell extracts, we found that Rac1 was not sufficient to engender bead motility, and we uncovered a key requirement for Arf GTPases. In vitro, Rac1 and Arf1 were individually able to bind weakly to recombinant WRC and activate it, but when both GTPases were bound at the membrane, recruitment and concomitant activation of WRC were dramatically enhanced. This cooperativity between the two GTPases was sufficient to induce WAVE-dependent bead motility in cell extracts. Our findings suggest that Arf GTPases may be central components in WAVE signalling, acting directly, alongside Rac1.
Augmin promotes meiotic spindle formation and bipolarity in
Xenopus
egg extracts
Authors: Petry Sabine , Pugieux Céline , Nédélec François J. , Vale Ronald D.
Published: August 2011

Female meiotic spindles in many organisms form in the absence of centrosomes, the organelle typically associated with microtubule (MT) nucleation. Previous studies have proposed that these meiotic spindles arise from RanGTP-mediated MT nucleation in the vicinity of chromatin; however, whether this process is sufficient for spindle formation is unknown. Here, we investigated whether a recently proposed spindle-based MT nucleation pathway that involves augmin, an 8-subunit protein complex, also contributes to spindle morphogenesis. We used an assay system in which hundreds of meiotic spindles can be observed forming around chromatin-coated beads after introduction of
Xenopus
egg extracts. Spindles forming in augmin-depleted extracts showed reduced rates of MT formation and were predominantly multipolar, revealing a function of augmin in stabilizing the bipolar shape of the acentrosomal meiotic spindle. Our studies also have uncovered an apparent augmin-independent MT nucleation process from acentrosomal poles, which becomes increasingly active over time and appears to partially rescue the spindle defects that arise from augmin depletion. Our studies reveal that spatially and temporally distinct MT generation pathways from chromatin, spindle MTs, and acentrosomal poles all contribute to robust bipolar spindle formation in meiotic extracts.
Electrophysiological evidence for the left-lateralized effect of language on preattentive categorical perception of color
Authors: Mo Lei , Xu Guiping , Kay Paul , Tan Li-Hai
Published: August 2011

Previous studies have shown that the effect of language on categorical perception of color is stronger when stimuli are presented in the right visual field than in the left. To examine whether this lateralized effect occurs preattentively at an early stage of processing, we monitored the visual mismatch negativity, which is a component of the event-related potential of the brain to an unfamiliar stimulus among a temporally presented series of stimuli. In the oddball paradigm we used, the deviant stimuli were unrelated to the explicit task. A significant interaction between color-pair type (within-category vs. between-category) and visual field (left vs. right) was found. The amplitude of the visual mismatch negativity component evoked by the within-category deviant was significantly smaller than that evoked by the between-category deviant when displayed in the right visual field, but no such difference was observed for the left visual field. This result constitutes electroencephalographic evidence that the lateralized Whorf effect per se occurs out of awareness and at an early stage of processing.
Rab3B protein is required for long-term depression of hippocampal inhibitory synapses and for normal reversal learning
Authors: Tsetsenis Theodoros , Younts Thomas J. , Chiu Chiayu Q. , Kaeser Pascal S. , Castillo Pablo E. , Südhof Thomas C.
Published: August 2011

Rab3B, similar to other Rab3 isoforms, is a synaptic vesicle protein that interacts with the Rab3-interacting molecule (RIM) isoforms RIM1α and RIM2α as effector proteins in a GTP-dependent manner. Previous studies showed that at excitatory synapses, Rab3A and RIM1α are essential for presynaptically expressed long-term potentiation (LTP), whereas at inhibitory synapses RIM1α is required for endocannabinoid-dependent long-term depression (referred to as “i-LTD”). However, it remained unknown whether i-LTD also involves a Rab3 isoform and whether i-LTD, similar to other forms of long-term plasticity, is important for learning and memory. Here we show that Rab3B is highly enriched in inhibitory synapses in the CA1 region of the hippocampus. Using electrophysiological recordings in acute slices, we demonstrate that knockout (KO) of Rab3B does not alter the strength or short-term plasticity of excitatory or inhibitory synapses but does impair i-LTD significantly without changing classical NMDA receptor-dependent LTP. Behaviorally, we found that Rab3B KO mice exhibit no detectable changes in all basic parameters tested, including the initial phase of learning and memory. However, Rab3B KO mice did display a selective enhancement in reversal learning, as measured using Morris water-maze and fear-conditioning assays. Our data support the notion that presynaptic forms of long-term plasticity at excitatory and inhibitory synapses generally are mediated by a common Rab3/RIM-dependent pathway, with various types of synapses using distinct Rab3 isoforms. Moreover, our results suggest that i-LTD contributes to learning and memory, presumably by stabilizing circuits established in previous learning processes.
Anti–IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss
Authors: Hsu Yu-Hsiang , Chen Wei-Yu , Chan Chien-Hui , Wu Chih-Hsing , Sun Zih-Jie , Chang Ming-Shi
Published: August 2011

IL-20 is a proinflammatory cytokine of the IL-10 family that is involved in psoriasis, rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about the role of IL-20 in bone destruction. We explored the function of IL-20 in osteoclastogenesis and the therapeutic potential of anti–IL-20 monoclonal antibody 7E for treating osteoporosis. Higher serum IL-20 levels were detected in patients with osteopenia and osteoporosis and in ovariectomized (OVX) mice. IL-20 mediates osteoclastogenesis by up-regulating the receptor activator of NF-κB (RANK) expression in osteoclast precursor cells and RANK ligand (RANKL) in osteoblasts. 7E treatment completely inhibited osteoclast differentiation induced by macrophage colony-stimulating factor (M-CSF) and RANKL in vitro and protected mice from OVX-induced bone loss in vivo. Furthermore, IL-20R1–deficient mice had significantly higher bone mineral density (BMD) than did wild-type controls. IL-20R1 deficiency also abolished IL-20–induced osteoclastogenesis and increased BMD in OVX mice. We have identified a pivotal role of IL-20 in osteoclast differentiation, and we conclude that anti–IL-20 monoclonal antibody is a potential therapeutic for protecting against osteoporotic bone loss.
Mechanism for modulation of gating of connexin26-containing channels by taurine
Authors: Locke Darren , Kieken Fabien , Tao Liang , Sorgen Paul L. , Harris Andrew L.
Published: August 2011

The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28–amino acid “tag” to the carboxyl-terminal domain (CT) of Cx26 (Cx26T) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26Tc) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26Tc/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32T and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function.
Efficacy of two Ni‐Ti systems and hand files for removing gutta‐percha from root canals
Authors: Mollo A. , Botti G. , Prinicipi Goldoni N. , Randellini E. , Paragliola R. , Chazine M. , Ounsi H. F. , Grandini S.
Published: August 2011

Mollo A, Botti G, Prinicipi Goldoni N, Randellini E, Paragliola R, Chazine M, Ounsi HF, Grandini S. Efficacy of two Ni‐Ti systems and hand files for removing gutta‐percha from root canals. International Endodontic Journal, 45, 1–6, 2012.

Aim  To compare the effectiveness of two Ni‐Ti systems and hand files for removing gutta‐percha and sealer from root canals.

Methodology  The root canals of 60 single‐rooted human teeth were prepared, filled with gutta‐percha and sealer (Pulp Canal Sealer; SybronEndo, Orange, CA, USA). Specimens were then divided into three groups (n = 20), and root filling material was removed using MTwo Retreatment Files (group 1); R‐Endo (group 2); K‐files and Gates‐Glidden drills (group 3). After retreatment, the efficacy of each technique was assessed using radiographs that were later digitized and the images analysed using AutoCAD 2004. The percentage of residual gutta‐percha was calculated for the whole canal as well as for the coronal, middle and apical thirds. Time required, apically extruded debris and the number of fractured instruments were also recorded. Data were statistically analysed using Kruskal–Wallis and Mann–Whitney U‐tests.

Results  All instrumentation techniques left gutta‐percha and sealer remnants inside the root canals. Ni‐Ti systems were significantly faster (P < 0.05) than the manual technique and significantly more effective (P < 0.05) in removing gutta‐percha particularly from the middle and apical thirds of the root canal. R‐Endo instrumentation was significantly more effective (P < 0.05) than MTwo retreatment files in removing gutta‐percha from the middle and apical thirds. R‐Endo instruments were associated with the least number of cases of apical extrusion. One MTwo instrument fractured.

Conclusions  The Ni‐Ti systems were more effective and faster than hand files, although all techniques left gutta‐percha and sealer remnants on the root canals.
Researching involvement in health care practices: interrupting or reproducing medicalization?
Authors: Donetto Sara , Cribb Alan
Published: August 2011

In this paper we reflect upon and problematize the ways in which ‘patient involvement’ is interpreted in a substantial proportion of the research literature on involvement and shared decision making. Drawing upon an analysis of this literature we raise concerns about the ‘medicalization of involvement’ embedded in, and reproduced by, some dominant research lenses, suggesting that this medicalization has powerful discursive and material effects. For example, we suggest that it tends to normalize and arguably trivialize intrinsically problematic and contentious concepts such as ‘patient preferences’ and, at the same time, to obscure the full range of possibilities for reciprocity in the exchanges between the medical world of the professional and the experiential and narrative world of the patient. We argue that richer conceptualizations of collaboration in clinical work are both possible and very much needed, and we indicate some examples of scholarly resources and perspectives that point towards richer and more defensible accounts of involvement. Overall we call for more attention to the idea of ‘epistemic involvement’ and much greater cross‐fertilization between different epistemological paradigms in this area of research.
Comparison of the hepatitis B virus core, surface and polymerase gene substitution rates in chronically infected patients
Authors: van de Klundert M. A. A. , Cremer J. , Kootstra N. A. , Boot H. J. , Zaaijer H. L.
Published: August 2011

Summary.  For phylogenetic comparison of hepatitis B virus (HBV) isolates, often a region of the HBV surface gene is analysed. Because the surface gene completely overlaps the polymerase gene, its evolution is constrained, and it may not be the best choice for genetic comparison of HBV isolates. Analysing serial sample pairs of 33 chronically HBV‐infected, untreated patients, with a cumulative follow‐up of 184 years, the synonymous and nonsynonymous substitution rates of a part of the overlapping HBV surface and polymerase genes were compared to those of a nonoverlapping part of the HBV core gene. The substitution rate of the HBV core gene was higher (8.15 × 10−4vs 4.57 × 10−4 substitutions/site/year) than that of the surface gene. The difference was mainly due to a significantly lower synonymous substitution rate in the surface gene, with dN/dS ratios of 0.412 in the core gene and 0.986 in the surface gene. Contrary to the core gene, the number of substitutions in the surface gene was higher in low viraemic hosts, who control HBV infection by suppressing replication. The number of substitutions in the core gene correlated more strongly with the duration of follow‐up. The overlapping HBV surface and polymerase genes experience strong negative selection, which limits the number of substitutions. Because the HBV core gene reflects the duration of infection more accurately, it is more suitable for the analysis of short‐term viral evolution and of hepatitis B transmission chains.
Contribution of the amygdala, but not orbitofrontal or medial prefrontal cortices, to the expression of flavour preferences in marmoset monkeys
Authors: Agustín‐Pavón Carmen , Parkinson John , Man Mei‐See , Roberts Angela C.
Published: August 2011

The development of food preferences contributes to a balanced diet, and involves both innate and learnt factors. By associating flavour cues with the reinforcing properties of the food (i.e. postingestive nutrient cues and innately preferred tastes, such as sweetness), animals acquire individual preferences. How the brain codes and guides selection when the subject has to choose between different palatable foods is little understood. To investigate this issue, we trained common marmoset monkeys (Callithrix jacchus) to respond to abstract visual patterns on a touch‐sensitive computer screen to gain access to four different flavoured juices. After preferences were stable, animals received excitotoxic lesions of either the amygdala, the orbitofrontal cortex or the medial prefrontal cortex. Neither the orbitofrontal nor the medial prefrontal cortex lesions affected pre‐surgery‐expressed flavour preferences or the expression of preferences for novel flavours post‐surgery. In contrast, amygdala lesions caused a shift in the preferences for juices expressed pre‐surgery such that, post‐surgery, juices were chosen according to their overall carbohydrate (simple sugars) content or ‘sweetness’. Subsequent tests revealed that amygdala‐lesioned animals only expressed juice preferences if they differed in ‘sweetness’. Unlike controls, orbitofrontal cortex‐lesioned and medial prefrontal cortex‐lesioned animals, they were unable to display preferences between juices matched for ‘sweetness’ i.e. 5% sucrose solutions aromatised with different essential oils. The most parsimonious explanation is that the amygdala contributes to the expression of food preferences based on learnt cues but not those based on an innate preference for sweetness.
The Gap Between Spanish Speakers’ Word Reading and Word Knowledge: A Longitudinal Study
Authors: Mancilla‐Martinez Jeannette , Lesaux Nonie K.
Published: August 2011

This longitudinal study modeled growth rates, from ages 4.5 to 11, in English and Spanish oral language and word reading skills among 173 Spanish‐speaking children from low‐income households. Individual growth modeling was employed using scores from standardized measures of word reading, expressive vocabulary, and verbal short‐term language memory. The trajectories demonstrate that students’ rates of growth and overall ability in word reading were on par with national norms. In contrast, students’ oral language skills started out below national norms and their rates of growth, although surpassing the national rates, were not sufficient to reach age‐appropriate levels. The results underscore the need for increased and sustained attention to promoting this population’s language development.
The experience of risk as ‘measured vulnerability’: health screening and lay uses of numerical risk
Authors: Gillespie Chris
Published: August 2011

As clinical and epidemiological research turns increasingly to statistical probabilities in the identification and management of disease, numerous risk factors have emerged that are applied to individual health surveillance. However, the application of statistical risk is interpreted differently by lay persons from the way it is by public health or medical professionals. This paper examines the experience of being designated as at risk of a serious health condition. Specifically, an examination of the experiences of people with elevated blood cholesterol levels and men with elevated prostate‐specific antigen (PSA) levels is presented in order to characterise the risk experience. This paper deals primarily with how being at risk symbolically alters health identities, with an introduction to the concept of measured vulnerability. Measured vulnerability refers to the capacity for scientifically‐derived statistical measures that are intended to tame randomness and provide certainty in managing risk to, instead, produce uncertainty and anxiety in those to whom the statistic is applied.
Female acne – a different subtype of teenager acne?
Authors: Preneau S. , Dreno B.
Published: August 2011

Above all, acne is considered an adolescent affection. However, in literature as in daily life, female acne is becoming more and more common. According to the articles that cover this subject, the prevalence is estimated from 40% to 50%. The objective of our work was to make an overview of new data about female acne at the clinical and epidemiological level to be precise if female acne has to be considered as a subtype of acne different from teenager acne. This review shows that the most frequently recognized age when speaking about female acne is 25 years old. Most commonly it is a light to moderate acne that mainly affects the face. Two clinical forms can be identified: an inflammatory form, the most frequent, made up of papulo‐pustules and nodules on the lower part of the face and a retentional form made up of blackheads and micro cysts with hyperseborrhoea. Concerning its evolution, it is characterized by three subtypes of which two are predominant: the most frequent form called ‘continue acne’ from adolescence to adult age and the less frequent form called ‘late onset acne’ that starts after 25 years of age. On a physiopathological level two main hypotheses can be proposed. Specific global assessment and therapeutic algorithm would be necessary for female acne, which in addition, in future would have to be considered separately from teenagers for the evaluation of a new drug.
Pharmacodynamic and pharmacokinetic basics of rivaroxaban
Authors: Kreutz Reinhold
Published: August 2011

Rivaroxaban, an oral, direct factor Xa inhibitor, is a small molecule drug capable of inhibiting not only free factor Xa with high selectivity but also prothrombinase‐bound and clot‐associated factor Xa in a concentration‐dependent manner. Clinical studies have demonstrated predictable anticoagulation and confirmed dose‐proportional effects for rivaroxaban in humans with a rapid onset (within 2–4 h) and a half‐life of 7–11 h and 11–13 h for young and elderly subjects, respectively. For a 10 mg dose, the oral bioavailability of rivaroxaban is high (80–100%) and is not affected by food intake. These favourable pharmacological properties underpin the use of rivaroxaban in fixed dosing regimens, with no need for dose adjustment or routine coagulation monitoring. Rivaroxaban has a dual mode of excretion with the renal route accounting for one‐third of the overall elimination of unchanged active drug. Rivaroxaban is a substrate of CYP3A4 and P‐glycoprotein and therefore not recommended for concomitant use with strong inhibitors of both pathways, e.g. most azole antimycotics and protease inhibitors. Rivaroxaban is currently approved for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery. Studies using 10 mg rivaroxaban once daily in this indication demonstrated its suitability for a wide range of patients regardless of age, gender or body weight. Further studies in the treatment of VTE, prevention of cardiovascular events in patients with acute coronary syndrome, prevention of stroke in those with atrial fibrillation and prevention of VTE in hospitalized medically ill patients have been reported or are ongoing.
Effect of Tibial Tuberosity Advancement on the Contact Mechanics and the Alignment of the Patellofemoral and Femorotibial Joints
Authors: Guerrero Tomás G. , Pozzi Antonio , Dunbar Nicholas , Kipfer Nicolas , Haessig Michael , Beth Horodyski Mary , Montavon Pierre M.
Published: August 2011

Objective

To evaluate the effect of tibial tuberosity advancement (TTA) on patellofemoral (PF) contact mechanics, and alignment of thePFand femorotibial (FT) joints in cranial cruciate ligament (CrCL)‐deficient stifles of dogs.

Study Design

Ex vivo biomechanical study.

Animals

Unpaired cadaveric hind limbs (n=9).

Methods

Digital pressure sensors placed in thePFjoint were used to measure contact force, contact area, peak and mean contact pressure, and peak pressure location with the limb under an axial load of 30% body weight and a stifle angle of 135°. TheFTandPFposes were obtained using a 2‐dimensional computer digitization technique. Each specimen was tested under normal,CrCL‐deficient, andTTA‐treated conditions. Data was normalized and analyzed, after testing for normality byWilk–Shapiro, using 1 sampleT‐test, pairedT‐test, andANOVA;P≤.05 was considered significant.Bonferroni's correction was used when needed.

Results

A significant cranioproximal tibial displacement and increase in patellar tilt were found in theCrCL‐deficient joints. BothFTandPFalignments were restored afterTTA. Contact areas and peak pressure did not vary between conditions. Peak pressure location displaced proximally from intact toCrCL‐deficient condition and returned to normal afterTTA. Total force measured in theCrCL‐deficient stifle andTTAconditions were significantly lower than in the control.

Conclusion

TTArestored the normalFTandPFalignment, and reduced the retropatellar force by about 20%.
Autoantibodies in Sjögren’s syndrome patients acutely inhibit muscarinic receptor function
Authors: Jin M , Hwang S‐M , Koo N‐Y , Kim B , Kho H‐S , Choi S‐Y , Song YW , Park K
Published: August 2011

Oral Diseases (2012) 18, 132–139

Objectives:  Autoantibodies from the sera of Sjögren’s syndrome patients (SS IgG) have been suggested to inhibit muscarinic receptor function. However, the acute nature of such an inhibitory effect remains controversial. In this study, we investigated the acute effects of SS IgG on muscarinic receptor function in human submandibular gland (HSG) cells.

Methods:  The effects of autoantibodies on muscarinic receptor function were studied using microspectrofluorimetry, whole‐cell patch clamp, immunofluorescence confocal microscopy, and a co‐immunoprecipitation assay.

Results:  Carbachol (CCh) was found to consistently increase intracellular calcium concentration ([Ca2+]i) and activate K+ current in HSG cells. However, pretreatment of the cells with SS IgG for 5 or 30 min significantly attenuated these responses, with a substantially more prominent effect after 30 min of treatment. Like CCh, adenosine 5′‐triphosphate (ATP) also increased [Ca2+]i and activated K+ currents in HSG cells, although pretreatment with SS IgG did not affect the cellular response to ATP. CCh was found to reorganize α‐fodrin in HSG cells in a Ca2+‐dependent manner. However, pretreatment with SS IgG prevented the cytoskeletal reorganization of α‐fodrin induced by CCh.

Conclusions:  SS IgG acutely and reversibly inhibited muscarinic receptor function, thereby inhibiting the Ca2+ mobilization necessary for the activation of K+ currents and α‐fodrin reorganization in HSG cells.
Evaluating the suitability of field beans as a substitute for soybean meal in early‐lactating dairy cow: Production and metabolic responses
Authors: TUFARELLI Vincenzo , KHAN Rifat Ullah , LAUDADIO Vito
Published: August 2011

Twenty‐four multiparous Holstein cows were utilized in a completely randomized design to examine the effect of feeding field beans (FB, Vicia faba L. var. minor) as substitute for soybean meal (SBM) on lactation performance and metabolic response during the early lactation period. Cows were individually divided into two equal groups and fed for 16 weeks on one each of the two experimental diets. The controls were fed pelleted concentrate contained 150 g/kg dry matter (DM) of SBM as the main protein source, whereas the experimental concentrate contained 345 g/kg DM of FB. Oat hay was offered ad libitum to cows and water was freely available. Blood samples were assayed for their content of: urea, glucose, triglycerides, cholesterol, total protein, albumin, calcium and phosphorus, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), nonesterified fatty acids (NEFA) and β‐hydroxybutyrate (BHBA). Inclusion of FB had no detectable effects on DM intake (DMI), body weight (BW), or body condition score (BCS). Neither milk yield nor quality were influenced by dietary treatment, except for milk urea nitrogen (MU) that was reduced in cows fed the FB diet (P < 0.05). Clotting properties of milk were not affected adversely by added dietary FB. Concentration of blood urea (BU) was lower in cows fed the FB diet than in those fed the control SBM diet (P < 0.05). These findings indicate that feeding FB in a lactation diet supported lactation performance similar to cows fed traditional SBM‐based diet, and the results may elicit great interest for countries where soybean utilization is adversely influenced by high supply costs.
When Do Challengers Succeed? Nongovernmental Actors, Administrative Agencies, and Legal Change: Shifting Rules for Oregon's Private Forests
Authors: Langridge Ruth
Published: August 2011

Regulatory regimes are notoriously resistant to change, so when less powerful actors manage to reshape long-established rules and gain increased access to a natural resource the interesting question is why? This article investigates relations between different claimant groups and the state in the reshaping of the regulations governing Oregon's private forestlands, how this process was mediated by broader political opportunities and constraints, and the conditions that supported a shift in the legal regime that benefited less advantaged interests. The intent is to deepen our understanding of the circumstances under which well-established rules of governance are altered. Analysis points to each of the following variables as significant for successful reform: (1) active challengers and their success in reframing issues to support their goals, (2) new political opportunities facilitating wider participation in the rulemaking process, and (3) concurrence between local and national aspirations supporting reform. While each condition is noteworthy, it is insufficient on its own. Rather, my study comparing two contested administrative rules suggests that a clear alignment of all three variables provides the strongest impetus for legislative and administrative rule changes at the state level benefiting less advantaged interests.
Temoporfin (Foscan®, 5,10,15,20‐Tetra(m‐hydroxyphenyl)chlorin)—A Second‐generation Photosensitizer†,‡
Authors: Senge Mathias O. , Brandt Johan C.
Published: August 2011

This review traces the development and study of the second‐generation photosensitizer 5,10,15,20‐tetra(m‐hydroxyphenyl)chlorin through to its acceptance and clinical use in modern photodynamic (cancer) therapy. The literature has been covered up to early 2011.
Neurovascular Decompression of the Rostral Ventrolateral Medulla Decreases Blood Pressure and Sympathetic Nerve Activity in Patients With Refractory Hypertension
Authors: Sasaki Susumu , Tanda Shuji , Hatta Tsuguru , Morimoto Satoshi , Takeda Kazuo , Kizu Osamu , Tamaki Shinji , Saito Mitsuru , Tamura Yoji , Kondo Akinori
Published: August 2011

J Clin Hypertens (Greenwich). 2011;13:818–820. ©2011 Wiley Periodicals, Inc.

Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49‐year‐old woman, had undergone continuous intravenous drip injections of calcium channel blockers and β‐blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin‐angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin‐angiotensin system.
KIOM-79 inhibits aldose reductase activity and cataractogenesis in Zucker diabetic fatty rats
Authors: Kim Junghyun , Kim Chan-Sik , Sohn Eunjin , Lee Yun Mi , Kim Jin Sook
Published: August 2011

Objectives

KIOM-79, a combination of four plant extracts, has a preventive effect on diabetic nephropathy and retinopathy in diabetic animal models. In this study, we have investigated the inhibitory effects of KIOM-79 on diabetic cataractogenesis.

Methods

We evaluated aldose reductase activity during cataractogenesis using Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. ZDF rats were treated orally with KIOM-79 (50 mg/kg body weight) once a day for 13 weeks.

Key findings

In vehicle-treated ZDF rats, lens opacity was increased, and lens fibre swelling and membrane rupture were observed. In addition, aldose reductase activity and aldose reductase protein expression in diabetic lens were markedly enhanced. However, the administration of KIOM-79 inhibited the development of diabetic cataract through the inhibition of aldose reductase activity and protein expression in diabetic lenses.

Conclusions

These observations suggested that KIOM-79 was useful against the treatment of diabetic cataractogenesis.
Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes
Authors: Chen Adrienne , Seifert H. Steven
Published: August 2011

The human pathogen
Neisseria gonorrhoeae
recruits and interacts extensively with polymorphonuclear leukocytes (PMNs) during infection.
N. gonorrhoeae
is able to survive the bactericidal activity of these innate immune cells and can actively modulate PMN functions
in vitro
. PMNs are short-lived cells which readily undergo apoptosis, and thus the effect of
N. gonorrhoeae
infection on PMN survival has implications for whether PMNs might serve as an important site of bacterial replication during infection. We developed and validated an HL-60 myeloid leukemia cell culture model for PMN infection and used both these cells and primary PMNs to show that
N. gonorrhoeae
infection alone does not induce apoptosis and furthermore that
N. gonorrhoeae
can inhibit both spontaneous apoptosis and apoptosis induced by the intrinsic and extrinsic apoptosis inducers staurosporine (STS) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), respectively.
N. gonorrhoeae
infection also results in the activation of NF-κB signaling in neutrophils and induces secretion of an identical profile of proinflammatory cytokines and chemokines in both HL-60 cells and primary PMNs. Our data show that the HL-60 cell line can be used to effectively model
N. gonorrhoeae-
PMN interactions and that
N. gonorrhoeae
actively inhibits apoptosis induced by multiple stimuli to prolong PMN survival and potentially facilitate bacterial survival, replication, and transmission.
Infection Intensity-Dependent Responses of Anopheles gambiae to the African Malaria Parasite Plasmodium falciparum
Authors: Mendes Antonio M. , Awono-Ambene Parfait H. , Nsango Sandrine E. , Cohuet Anna , Fontenille Didier , Kafatos Fotis C. , Christophides George K. , Morlais Isabelle , Vlachou Dina
Published: August 2011

Malaria remains a devastating disease despite efforts at control and prevention. Extensive studies using mostly rodent infection models reveal that successful
Plasmodium
parasite transmission by the African mosquito vector
Anopheles gambiae
depends on finely tuned vector-parasite interactions. Here we investigate the transcriptional response of
A. gambiae
to geographically related
Plasmodium falciparum
populations at various infection intensities and different infection stages. These responses are compared with those of mosquitoes infected with the rodent parasite
Plasmodium berghei
. We demonstrate that mosquito responses are largely dependent on the intensity of infection. A major transcriptional suppression of genes involved in the regulation of midgut homeostasis is detected in low-intensity
P. falciparum
infections, the most common type of infection in Africa. Importantly, genes transcriptionally induced during these infections tend to be phylogenetically unique to
A. gambiae
. These data suggest that coadaptation between vectors and parasites may act to minimize the impact of infection on mosquito fitness by selectively suppressing specific functional classes of genes. RNA interference (RNAi)-mediated gene silencing provides initial evidence for important roles of the mosquito G protein-coupled receptors (GPCRs) in controlling infection intensity-dependent antiparasitic responses.
Impact of Toll-Like Receptor 2 Deficiency on Immune Responses to Mycobacterial Antigens
Authors: Rahman Muhammad J. , Chuquimia Olga D. , Petursdottir Dagbjort H. , Periolo Natalia , Singh Mahavir , Fernández Carmen
Published: August 2011

In the present study, we addressed the question of whether Toll-like receptor 2 (TLR2)-mediated innate immunity can contribute to the development of acquired immune responses. We immunized TLR2−/−and wild-type (WT) mice three times subcutaneously with the mycobacterial antigen (Ag19kDa) (a TLR2 ligand) or Ag85A (not a TLR2 ligand). One week after the last immunization, sera and spleens were collected. To evaluate cellular responses, we measured gamma interferon (IFN-γ) afterin vitrorestimulation of spleen cells with antigen alone or antigen-pulsed bone marrow-derived macrophages (BMMAg) or pulmonary macrophages (PuMAg). Antibody responses were comparable in the two mouse strains, but we observed differences in the cellular responses. Recall responses to Ag85A were similar in the two strains, but responses to Ag19kDa given alone or presented by BMM or PuM were lower in TLR2−/−than in WT mice. The largest differences in cellular responses were observed when Ag19kDa was presented by PuM. To understand this, we analyzed phenotypic and functional differences between BMM and PuM upon stimulation with various ligands. Generally, PuM had a lower response to the TLR2 ligand Pam3Cys-Ser-(Lys)4trihydrochloride and to anti-CD40 than BMM, as measured by cytokine secretion and upregulation of costimulatory molecules. This might provide a partial explanation for the lower capacity of PuM when pulsed with Ag19kDa, also a TLR2 ligand. Altogether, our results revealed weaknesses in the T cell and antigen-presenting cell (APC) compartments of the Ag19kDa-immunized TLR2−/−mice but indicated that specific immune responses could be generated in the absence of TLR2 regardless of the characteristics of the antigen used.