Rational choice, context dependence, and the value of information in European starlings (Sturnus vulgaris).
Both human and nonhuman decision-makers can deviate from optimal choice by making context-dependent choices. Because ignoring context information can be beneficial, this is called a "less-is-more effect." The fact that organisms are so sensitive to the context is thus paradoxical and calls for the inclusion of an ecological perspective. In an experiment with starlings, adding cues that identified the context impaired performance in simultaneous prey choices but improved it in sequential prey encounters, in which subjects could reject opportunities in order to search instead in the background. Because sequential prey encounters are likely to be more frequent in nature, storing and using contextual information appears to be ecologically rational on balance by conditioning acceptance of each opportunity to the relative richness of the background, even if this causes context-dependent suboptimal preferences in (less-frequent) simultaneous choices. In ecologically relevant scenarios, more information seems to be more.


A sensitive ratiometric electrochemical biosensor based on DNA four-way junction formation and enzyme-assisted recycling amplification.
A simple ratiometric electrochemical biosensor is developed for sensitive detection of target DNA based on DNA four-way junction (DNA-4WJ) formation and enzyme-assisted recycling amplification. This biosensor can be easily fabricated by a one-step assembly of ratiometric probes and simply performed by a one-step incubation procedure. In the presence of target DNA, two unmodified DNA oligonucleotides may cooperatively hybridize with a hairpin probe in the triple-helix molecular beacon (THMB) to form a DNA-4WJ, which may cause conformational transduction and induce the change in the distance between two redox labeling probes and the electrode surface. The subsequent recognition and cleavage of DNA-4WJ quadripartite complexes by RNase HII may result in significant signal amplification. Due to the introduction of DNA-4WJ formation, enzyme-assisted recycling amplification and ratiometric measurement, this biosensor exhibits high sensitivity with a detection limit as low as 0.063 pM and a long dynamic range from 0.1 pM to 100 nM. Moreover, this biosensor demonstrates good performance with excellent selectivity, high reliability and good reproducibility, holding great potential for further applications in biomedical research and clinical diagnostics.


Retrospective evaluation of micro-focused ultrasound for lifting and tightening the face and neck.
Microfocused ultrasound (MFU) is an effective means for tightening and lifting lax facial and neck skin. To evaluate the safety and efficacy of MFU with visualization (MFU-V) for noninvasive treatment of facial and neck skin laxity 180 days after treatment and determine what lifestyle factors affect treatment outcomes. Healthy women (N = 48) previously treated with MFU-V on the face and upper neck were enrolled. Depending on when MFU-V treatment occurred, subjects completed 90- or 180-day follow-up visits or both. Digital images of each subject were obtained before treatment and at follow-up visits. Data were obtained at 90 (N = 16) and 180 days (N = 45), and physician Global Aesthetic Improvement Scale (GAIS) scores demonstrated that 81.3% and 77.7% patients achieved improvement, respectively. At 90 and 180 days, subject GAIS scores showed 75% and 77.8% of subjects perceived improvement, respectively. At 180 days, blinded reviewer assessments indicated that 67% of subjects showed improvement in appearance. There was no association between improvement and age, Fitzpatrick skin type, alcohol intake, or major illness. One minor adverse event was reported. Although the data obtained at 90 days must be interpreted cautiously because of the smaller number of patients, subjects achieved significant lifting and tightening of facial and neck skin up to 180 days after one MFU treatment.


Neural correlates of early-closure garden-path processing: Effects of prosody and plausibility.
Functional magnetic resonance imaging (fMRI) was used to investigate neural correlates of early-closure garden-path sentence processing and use of extrasyntactic information to resolve temporary syntactic ambiguities. Sixteen participants performed an auditory picture verification task on sentences presented with natural versus flat intonation. Stimuli included sentences in which the garden-path interpretation was plausible, implausible because of a late pragmatic cue, or implausible because of a semantic mismatch between an optionally transitive verb and the following noun. Natural sentence intonation was correlated with left-hemisphere temporal activation, but also with activation that suggests the allocation of more resources to interpretation when natural prosody is provided. Garden-path processing was associated with upregulation in bilateral inferior parietal and right-hemisphere dorsolateral prefrontal and inferior frontal cortex, while differences between the strength and type of plausibility cues were also reflected in activation patterns. Region of interest (ROI) analyses in regions associated with complex syntactic processing are consistent with a role for posterior temporal cortex supporting access to verb argument structure. Furthermore, ROI analyses within left-hemisphere inferior frontal gyrus suggest a division of labour, with the anterior-ventral part primarily involved in syntactic-semantic mismatch detection, the central part supporting structural reanalysis, and the posterior-dorsal part showing a general structural complexity effect.


To be, or not to be? The role of the unconscious in transgender transitioning: identity, autonomy and well-being.
The exponential rise in transgender self-identification invites consideration of what constitutes an ethical response to transgender individuals' claims about how best to promote their well-being. In this paper, we argue that 'accepting' a claim to medical transitioning in order to promote well-being would be in the person's best interests iff at the point of request the individual is correct in their self-diagnosis as transgender (i.e., the distress felt to reside in the body does not result from another psychological and/or societal problem) such that the medical interventions they are seeking will help them to realise their preferences. If we cannot assume this-and we suggest that we have reasonable grounds to question an unqualified acceptance in some cases-then 'acceptance' potentially works against best interests. We propose a distinction between 'acceptance' and respectful, in-depth exploration of an individual's claims about what promotes their well-being. We discuss the ethical relevance of the unconscious mind to considerations of autonomy and consent in working with transgender individuals. An inquisitive stance, we suggest, supports autonomous choice about how to realise an embodied form that sustains well-being by allowing the individual to consider both conscious and unconscious factors shaping wishes and values, hence choices.


Eosinophilic granulocytes and damage-associated molecular pattern molecules (DAMPs): role in the inflammatory response within tumors.
The development of a tumor over many years typically leads to reciprocal alternations in the host and the tumor, enabling tumor growth paradoxically in the setting of substantial necrosis and inflammation. When evaluating a tumor, it is important to assess 3 elements: (1) the quantity and quality of tumor-associated leukocytes, (2) their state of activation, and (3) tumor microenvironment. Peripheral blood eosinophilia and tumor-associated tissue eosinophilia are frequently associated with some tumor types and also found after immunotherapy with IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and antibody to CTLA-4. Within several tumor types including gastrointestinal tumors, tumor-associated tissue eosinophilia is associated with a significantly better prognosis. The converse is true in other tumor types such as differentiated oral squamous cell carcinoma. On the basis of the emergent data, tumor-associated eosinophils have at least 2 dominant nonoverlapping activities: (1) destructive effector functions potentially limiting tumor growth as well as causing recruitment and activation of other leukocytes, (2) immunoregulative and remodeling activities which suppress immune response and promote tumor proliferation. The mechanism by which eosinophils in particular are recruited into tumor tissue is largely unknown. Candidates for causing eosinophil chemotaxis into tumor tissue are the released damage-associated molecular pattern molecules (DAMPs) including the nuclear protein high mobility group box 1. High mobility group box 1 is released upon necrotic cell death and secreted by many cells, particularly during periods of nutrient, hypoxic, or oxidant stress. This overview on eosinophil biology in the context of cancer and necrosis, introduces intriguing and novel strategies targeting eosinophils to enable more effective biologic therapy for cancer patients.


Chemotherapy-induced Emesis: Experienced Burden in Life, and Significance of Treatment Expectations and Communication in Chemotherapy Care.
Because antiemetics have become more effective and integrative therapies such as acupuncture are used in combination with antiemetics, people receiving chemotherapy for cancer today might expect less emesis than in the past. It is not previously described if and how people receiving modern antiemetics during chemotherapy experience emesis. The objective of this study was to describe experiences regarding emesis among persons undergoing emetogenic chemotherapy, and how it affects their quality of life, daily life and work. A further aim was to describe views on the significance of treatment expectations and communication with healthcare personnel while undergoing chemotherapy for cancer. Fifteen participants (median age 62 years, n = 1 man and n = 14 women, with breast (n = 13) or colorectal (n = 2) cancer) undergoing adjuvant or neo-adjuvant highly or moderately emetogenic chemotherapy were interviewed individually. The data were then analyzed using inductive thematic analysis. Three themes described the participants' experiences: "Your whole life is affected, or continues as usual," covering descriptions of emesis limiting some participants' everyday lives, while others experienced no emesis at all or had found ways to manage it. Overall, participants described satisfaction with their antiemetic treatment. "Experiences and expectations more important than information", that is, the participants reported wanting all the information they could get about possible adverse effects of treatment, although they believed previous experiences were more important than information in creating expectations about treatment outcomes. The participants reported that being seen as a unique person was of utmost importance: "Meet me as I am." This creates trust in healthcare personnel and a feeling of safety and security in the situation. These findings underline the importance of person-centered care and support in creating positive treatment expectations. Future research is called for regarding the potential antiemetic effects of positive communication regarding strengthening positive treatment expectations during emetogenic chemotherapy.


Proton disorder and the dielectric constant of type II clathrate hydrates.
Computational studies are presented examining the degree of proton disorder in argon and molecular hydrogen sII clathrate hydrates. Results are presented using a variety of model potentials for the dielectric constant, the proton order parameter, and the molecular volume for the clathrate systems. The dielectric constant for the clathrate systems is found to be lower than the dielectric constant of ice in all models. The ratio of the clathrate to ice dielectric constant correlates well with the ratio of the densities, which is not the case for comparisons to the liquid, so that differences in the dielectric constants between ice and the clathrates are most likely due to differences in densities. Although the computed dielectric constant is a strong function of the model potential used, the ratio of the dielectric constant of ice to that of the clathrates is insensitive to the model potential. For the nonpolar guest molecules used in the current study, the degree proton of disorder is found to depend weakly on the identity of the guest but the dielectric constant does not appear to be sensitive to pressure or the type of guest.


Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity.
Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90-120 mg/kg) given to B6D2F1mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 microg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury.


Radiographic evaluation of dental age of adults using Kvaal's method.
It is a well-known fact that the assessment of the dental development can be related to an individual's age, but after the age of 21 years when the wisdom teeth also complete their development, there arises a need for an optimal age estimation procedure. With advancing age, there is a reduction in the size of the pulp due to secondary dentin deposition and a measurement of this reduction can also be used as a parameter to assess the age of the individuals, both in the living and dead. The purpose of the present study was to evaluate the feasibility of this approach in the estimation of age of adults, using Kvaal's method in the set sample. The material consisted of the digital long-cone intraoral periapical radiographs from 50 subjects of either sex in the age group of 15-60 years, who were selected after evaluation for the set inclusion and exclusion criteria. The pulp width and length from radiographs of 6 selected teeth, namely, maxillary central incisor, lateral incisor, and second premolar and mandibular lateral incisor, canine, and first premolar of either right or left side were measured using the RVG trophy software [Trophy® Windows is a software program supplied by Trophy Radiologie (Trophy Windows Version 5.03, Copyright 1993-2002,Trophy RVG patented by Trophy, Chicago)]. In order to compensate for the differences in magnification and angulation, various ratios were calculated and the mean of all ratios (M) was taken as the first predictor, while the difference between the mean of 2 width ratios and the mean of 2 length ratios (W - L) was taken as the second predictor. Different regression formulae for all 6 teeth, 3 maxillary teeth, 3 mandibular teeth, and each of the individual teeth were derived and the age was assessed. The assessed age was then co-related with the actual age of the patient using the Student's t test. The results showed that the coefficient of determination (R(2)) was the strongest (0.198) for the mandibular first premolar indicating that age can be estimated better with this particular tooth. No significant difference was observed between the estimated age and the actual age for all (P>0.05) except in mandibular lateral incisor and maxillary lateral incisor, where a significant difference was observed. To conclude, the results of the present study suggest the feasibility of Kvaal's method for age estimation in the set sample.


First Report of Bacterial Blight of Crucifers Caused by Pseudomonas cannabina pv. alisalensis in Australia.
In 1978 and 1979, Pseudomonas syringae pv. maculicola strains DAR 33362, DAR 33363, and DAR 33406 were isolated from diseased Brassica hirta, B. nigra, and B. napus var. napus, respectively, in Wagga Wagga and Armatree, NSW, Australia (2). Peters et al. (2) demonstrated that these strains were similar to P. syringae pv. maculicola ICMP 4326 (CFBP 1637), which was recently transferred to Pseudomonas cannabina pv. alisalensis (1). We evaluated these Australian strains to determine if they might also be P. cannabina pv. alisalensis. Amplification of DNA using the BOXA1R primer and PCR resulted in identical DNA fragment banding patterns for Australian strains DAR 33362 and DAR 33363 and P. cannabina pv. alisalensis ICMP 4326 and CFBP 6875. The third Australian strain, DAR 33406, was 90% similar to P. cannabina pv. alisalensis; in contrast, it was only 77% similar to P. syringae pv. maculicola. All strains of P. cannabina pv. alisalensis, including the pathotype strain (CFBP 6866) and all three Australian strains, were lysed by bacteriophage PBS1, which is specific for P. cannabina pv. alisalensis strains (1). To complete Koch's postulates, pathogenicity was evaluated on B. hirta, B. nigra, and B. napus var. napus. In two independent experiments, two plants of each species were inoculated with each Australian strain or a phosphate buffer control treatment. In separate experiments, pathogenicity was evaluated on the differential hosts radish (Raphanus sativus cv. Comet) and broccoli raab (Brassica rapa cv. Sorrento), and plants inoculated with the pathotypes of P. cannabina pv. alisalensis and P. syringae pv. maculicola served as additional control treatments. Inoculum was prepared by growing the bacteria on nutrient agar for 48 h (27°C), suspending the bacteria in 0.01 M phosphate buffer (pH 7.0), and adjusting each suspension to 0.6 OD at 600 nm (approximately 108 CFU/ml). Treatments were applied by spraying until runoff. DAR 33362, DAR 33363, and DAR 33406 caused typical bacterial blight symptoms on B. hirta, B. nigra, and B. napus var. napus. Infected leaves became yellow, followed by the development of small (<2 mm in diameter), angular, water-soaked, and eventually, shot-holed spots. Bacteria isolated from symptomatic tissue following surface disinfestation of tissue with sodium hypochlorite (0.525%) had identical characteristics (rep-PCR DNA fragment banding patterns and phage sensitivity) to the strains used to inoculate the plants. Additionally, DAR 33362, DAR 33363, and DAR 33406, as well as P. cannabina pv. alisalensis, caused symptoms on radish and broccoli raab while P. syringae pv. maculicola and the buffer control did not. These data support the transfer of the Australian crucifer strains, originally identified as P. syringae pv. maculicola, to P. cannabina pv. alisalensis. To our knowledge, this is the first report of a bacterial disease of crucifers caused by P. cannabina pv. alisalensis in Australia. Differentiation of these pathogens will inform crop rotation strategies for disease management. References: (1) C. T. Bull et al. Syst. Appl. Microbiol. 33:105, 2010. (2) B. J. Peters et al. Plant Pathol. 53:3, 2004.


Sources of airborne microorganisms in the built environment.
Each day people are exposed to millions of bioaerosols, including whole microorganisms, which can have both beneficial and detrimental effects. The next chapter in understanding the airborne microbiome of the built environment is characterizing the various sources of airborne microorganisms and the relative contribution of each. We have identified the following eight major categories of sources of airborne bacteria, viruses, and fungi in the built environment: humans; pets; plants; plumbing systems; heating, ventilation, and air-conditioning systems; mold; dust resuspension; and the outdoor environment. Certain species are associated with certain sources, but the full potential of source characterization and source apportionment has not yet been realized. Ideally, future studies will quantify detailed emission rates of microorganisms from each source and will identify the relative contribution of each source to the indoor air microbiome. This information could then be used to probe fundamental relationships between specific sources and human health, to design interventions to improve building health and human health, or even to provide evidence for forensic investigations.


A meta-analytic review of overgeneral memory: The role of trauma history, mood, and the presence of posttraumatic stress disorder.
A number of studies suggest that a history of trauma, depression, and posttraumatic stress disorder (PTSD) are associated with autobiographical memory deficits, notably overgeneral memory (OGM). However, whether there are any group differences in the nature and magnitude of OGM has not been evaluated. Thus, a meta-analysis was conducted to quantify group differences in OGM. The effect sizes were pooled from studies examining the effect on OGM from a history of trauma (e.g., childhood sexual abuse), and the presence of PTSD or current depression (e.g., major depressive disorder). Using multiple search engines, 13 trauma studies and 12 depression studies were included in this review. A depression effect was observed on OGM with a large effect size, and was more evident by the lack of specific memories, especially to positive cues. An effect of trauma history on OGM was observed with a medium effect size, and this was most evident by the presence of overgeneral responses to negative cues. The results also suggested an amplified memory deficit in the presence of PTSD. That is, the effect sizes of OGM among individuals with PTSD were very large and relatively equal across different types of OGM. Future studies that directly compare the differences of OGM among 4 samples (i.e., controls, current depression without trauma history, trauma history without depression, and trauma history and depression) would be warranted to verify the current findings.


The burden of the neurocognitive impairment associated with Plasmodium falciparum malaria in sub-saharan Africa.
The burden of Plasmodium falciparum malaria has been estimated traditionally in terms of infections and mortality. Neurocognitive sequelae have recently been identified that add to the burden caused by this parasite. We have attempted to provide estimates of the neurocognitive burden based upon more recent estimates of the population at risk and a detailed review of published studies in sub-Saharan Africa. There is little data on which to estimate the burden, and considerable limitations in extracting the data from the published studies to provide these estimates. However, we estimate that at least 1,300-7,800 children will have neurologic sequelae following cerebral malaria in stable endemic areas per year. The figure is likely to be considerably higher, since these estimates do not include neurocognitive impairment following non-cerebral malaria in children or adults in stable endemic areas, or populations in low stable or epidemic areas.


A laterally-coupled distributed feedback laser with equivalent quarter-wave phase shift.
We report the first laterally-coupled distributed feedback (LC-DFB) laser with a quarter-wave equivalent phase shift (EPS) realized by interference lithography (IL) and conventional photolithography. A specially designed sampled grating is fabricated on both sidewalls of a ridge waveguide to provide a quarter-wave EPS at the center of the cavity. The resulting laser exhibits stable single-mode lasing operation over a wide range of injection currents, with a side mode suppression ratio (SMSR) of 41.1 dB. This provides a practical, low-cost method to fabricate quarter-wave phase shifted DFB lasers with high performance without any epitaxial regrowth or the use of electron-beam lithography, thereby simplifying the fabrication of DFB lasers with stable and precise wavelengths, as single devices or as arrays in photonic integrated circuits.


Inhibitory control is associated with the activation of output-driven competitors in a spoken word recognition task.
Although lexical competition has been ubiquitously observed in spoken word recognition, less has been known about whether the lexical competitors interfere with the recognition of the target and how lexical interference is resolved. The present study examined whether lexical competitors overlapping in output with the target would interfere with its recognition, and tested an underestimated hypothesis that the domain-general inhibitory control contributes to the resolution of lexical interference. Specifically, in this study, a Visual World Paradigm was used to access the temporal dynamics of lexical activations when participants were moving the mouse cursor to the written word form of the spoken word they heard. By using Chinese characters, the orthographic similarity between the lexical competitor and target was manipulated independently of their phonological overlap. The results demonstrated that behavioral performance in the similar condition was poorer compared to that in the control condition, and that individuals with better inhibitory control (having smaller Stroop interference effect) exhibited weaker activation of orthographic competitors (mouse trajectories less attracted by the orthographic competitors). The implications of these findings for our understanding of lexical interference and its resolution in spoken word recognition were discussed.


Life course sun exposure and risk of prostate cancer: population-based nested case-control study and meta-analysis.
There is currently no means of primary prevention for prostate cancer. Increased exposure to ultraviolet-radiation may be protective, but the literature is inconclusive. We investigated associations of life course exposure to sunlight with prostate cancer. The study design was a UK-wide nested case-control study, based on 1,020 prostate specific antigen-detected cases and 5,044 matched population controls and a systematic review with meta-analysis. Men with olive/brown skin (OR = 1.47; 95% CI: 1.00 to 2.17), men who burnt rarely/never (OR = 1.11; 0.95 to 1.29) and men with the lowest levels of intense sun exposure in the 2 years prior to diagnosis (OR = 1.24; 1.03 to 1.50) had an increased prostate cancer risk. However, amongst men with prostate cancer, spending less time outside was associated with a reduced risk of advanced cancer (OR = 0.49; 0.27 to 0.89) and high Gleason grade (OR = 0.62; 0.43 to 0.91), and men who burnt rarely/never had a reduced risk of advanced cancer (OR = 0.71; 0.47 to 1.08). The meta-analysis provided weak evidence that men with the lowest (versus highest) sunlight exposure had an increased prostate cancer risk (4 studies, random-effects pooled relative risk = 1.13; 0.98 to 1.29) and higher advanced or fatal prostate cancer risk (6 studies, random-effects pooled relative risk = 1.14; 0.98 to 1.33). Our data and meta-analyses provide limited support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. The findings warrant further investigation because of their implications for vitamin D chemoprevention trials.


Transconjunctival single-plane sclerocorneal incisions versus clear corneal incisions in cataract surgery.
To compare a transconjunctival single-plane sclerocorneal incision with 2 tiny conjunctival cuts at both ends and a clear corneal incision (CCI) in cataract surgery. Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. Patients having routine cataract surgery were randomly divided into 2 groups based on incision type; that is, transconjunctival single-plane sclerocorneal or CCI. The incidence of intraoperative ballooning of the conjunctiva (chemosis) and the percentage of eyes that required stromal hydration to securely close the wound in each group were recorded and compared. Each group comprised 61 eyes (61 patients). No eye in the transconjunctival sclerocorneal group and 6 eyes (9.8%) in the CCI group developed intraoperative conjunctival chemosis (P = .027, Fisher exact probability test). Corneal stromal hydration was required in 2 eyes (3.3%) and 15 eyes (24.6%), respectively (P = .001). The transconjunctival single-plane sclerocorneal incision was effective and combined the merits of CCI incisions and sclerocorneal incisions.


Effect of Artemisia dracunculus Administration on Glycemic Control, Insulin Sensitivity, and Insulin Secretion in Patients with Impaired Glucose Tolerance.
To evaluate the effect of Artemisia dracunculus on glycemic control, insulin sensitivity, and insulin secretion in patients with impaired glucose tolerance (IGT). A randomized, double blind, placebo-controlled clinical trial was performed in 24 patients with diagnosis of IGT. Before and after the intervention, glucose and insulin levels were measured every 30 min for 2 h after a 75-g dextrose load, along with glycated hemoglobin A1c (A1C) and lipid profile. Twelve patients received A. dracunculus (1000 mg) before breakfast and dinner for 90 days; the remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests were used for statistical analyses. The institutional ethics committee approved the protocol. After A. dracunculus administration, there were significant decreases in systolic blood pressure (SBP; 120.0 ± 11.3 vs. 113.0 ± 11.2 mmHg, P < .05), A1C (5.8 ± 0.3 vs. 5.6% ± 0.4%, P < .05), AUC of insulin (56,136.0 ± 27,426.0 vs. 44,472.0 ± 23,370.0 pmol/L, P < .05), and total insulin secretion (0.45 ± 0.23 vs. 0.35 ± 0.18, P < .05), with a significant increase in high-density lipoprotein cholesterol (HDL-C) (1.3 ± 0.3 vs. 1.4 ± 0.3 mmol/L, P < .05). There were no significant differences after placebo administration. A. dracunculus administration for 90 days in patients with IGT significantly decreased SBP, A1C, AUC of insulin, and total insulin secretion with a significant increase in HDL-C levels.


Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.
Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP(-/-)Vim(-/-) mice. After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.


Mechanisms in the cycle of violence.
Two questions concerning the effect of physical abuse in early childhood on the child's development of aggressive behavior are the focus of this article. The first is whether abuse per se has deleterious effects. In earlier studies, in which samples were nonrepresentative and family ecological factors (such as poverty, marital violence, and family instability) and child biological variables (such as early health problems and temperament) were ignored, findings have been ambiguous. Results from a prospective study of a representative sample of 309 children indicated that physical abuse is indeed a risk factor for later aggressive behavior even when the other ecological and biological factors are known. The second question concerns the processes by which antisocial development occurs in abused children. Abused children tended to acquire deviant patterns of processing social information, and these may mediate the development of aggressive behavior.


Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study.
The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning.


Ambient air pollution and non-communicable respiratory illness in sub-Saharan Africa: a systematic review of the literature.
Aerosol pollutants are known to raise the risk of development of non-communicable respiratory diseases (NCRDs) such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, and allergic rhinitis. Sub-Saharan Africa's rapid pace of urbanization, economic expansion, and population growth raise concerns of increasing incidence of NCRDs. This research characterizes the state of research on pollution and NCRDs in the 46 countries of Sub-Saharan Africa (SSA). This research systematically reviewed the literature on studies of asthma; chronic bronchitis; allergic rhinitis; and air pollutants such as particulate matter, ozone, NOx, and sulfuric oxide. We searched three major databases (PubMed, Web of Science, and Scopus) using the key words "asthma", "chronic bronchitis", "allergic rhinitis", and "COPD" with "carbon monoxide (CO)", "sulfuric oxide (SO)", "ozone (O3)", "nitrogen dioxide (NO2)", and "particulate matter (PM)", restricting the search to the 46 countries that comprise SSA. Only papers published in scholarly journals with a defined health outcome in individuals and which tested associations with explicitly measured or modelled air exposures were considered for inclusion. All candidate papers were entered into a database for review. We found a total of 362 unique research papers in the initial search of the three databases. Among these, 14 met the inclusion criteria. These papers comprised studies from just five countries. Nine papers were from South Africa; two from Malawi; and one each from Ghana, Namibia, and Nigeria. Most studies were cross-sectional. Exposures to ambient air pollutants were measured using spectrometry and chromatography. Some studies created composite measures of air pollution using a range of data layers. NCRD outcomes were measured by self-reported health status and measures of lung function (spirometry). Populations of interest were primarily schoolchildren, though a few studies focused on secondary school students and adults. The paucity of research on NCRDs and ambient air pollutant exposures is pronounced within the African continent. While capacity to measure air quality in SSA is high, studies targeting NCRDs should work to draw attention to questions of outdoor air pollution and health. As the climate changes and SSA economies expand and countries urbanize, these questions will become increasingly important.


Injuries among World Cup freestyle skiers.
Limited knowledge exists on injuries among professional freestyle skiers. To describe the risk of injury and injury patterns among competitive World Cup (WC) freestyle skiers during the competitive season. Retrospective interviews were conducted with WC freestyle skiers from 20 nations in a cohort study at the end of the 2006-2007, 2007-2008 and 2008-2009 winter seasons, and all acute injuries occurring during the 4.5 month competitive season were recorded. If an athlete was not present, we interviewed his or her coach or medical personnel. A total of 291 acute injuries were recorded among 662 WC freestyle skiers. Ninety-three injuries (32%) were severe in nature, defined as >28 days absence from training/competition. This corresponds to 14 (95% CI 11.2 to 16.9) injuries per 100 athletes per season. The most frequently injured body part was the knee with 77 injuries (27%) and 37 of these were severe. The head was the next most commonly injured body part with 39 (13%) injuries. As many as 106 injuries (36%) occurred during WC/World Ski Championship competitions, corresponding to an injury rate of 15.6 injuries per 1000 runs (95% CI 12.7 to 18.6). There were no significant differences between men and women in either the injury rate or the rate seen for knee injuries. The injury rate among WC athletes in freestyle skiing is high, especially for severe injuries. The knee is the most commonly injured body part, also dominated by severe injuries. We found no significant difference in the injury rate related to sex.


Arabidopsis thaliana histone deacetylase 14 (HDA14) is an α-tubulin deacetylase that associates with PP2A and enriches in the microtubule fraction with the putative histone acetyltransferase ELP3.
It is now emerging that many proteins are regulated by a variety of covalent modifications. Using microcystin-affinity chromatography we have purified multiple protein phosphatases and their associated proteins from Arabidopsis thaliana. One major protein purified was the histone deacetylase HDA14. We demonstrate that HDA14 can deacetylate α-tubulin, associates with α/β-tubulin and is retained on GTP/taxol-stabilized microtubules, at least in part, by direct association with the PP2A-A2 subunit. Like HDA14, the putative histone acetyltransferase ELP3 was purified on microcystin-Sepharose and is also enriched at microtubules, potentially functioning in opposition to HDA14 as the α-tubulin acetylating enzyme. Consistent with the likelihood of it having many substrates throughout the cell, we demonstrate that HDA14, ELP3 and the PP2A A-subunits A1, A2 and A3 all reside in both the nucleus and cytosol of the cell. The association of a histone deacetylase with PP2A suggests a direct link between protein phosphorylation and acetylation.


Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes.
The objectives of the study were to determine whether thiazolidinedione (TZD) use is associated with an increased risk of fracture in men and women with type 2 diabetes mellitus and to compare the effects of pioglitazone and rosiglitazone. A research database of integrated pharmacy and medical claims was analysed using Cox models adjusted for age, gender, chronic obstructive pulmonary disease, asthma, osteoporosis, stroke, prior fracture and chronic disease score. Patients were followed for 540 days. There was a 39% higher [adjusted hazard ratio (HR), 1.39; 95% confidence interval (CI), 1.32-1.46] incidence of fractures in men and women exposed to a TZD (n = 69047; age = 56 +/- 5 years; 59% men; 48% rosiglitazone) compared with that in control patients (n = 75352; age = 56 +/- 5 years; 51% men). Men treated with a TZD had a higher likelihood of fracture than control patients (adjusted HR rosiglitazone, 1.47; 95% CI, 1.38-1.56; adjusted HR pioglitazone, 1.43; 95% CI, 1.34-1.52). The HRs associated with pioglitazone (adjusted HR, 1.43; 95% CI, 1.34-1.52) and rosiglitazone (adjusted HR, 1.47; 95% CI, 1.38-1.56) were almost identical. TZD use was associated with a higher fracture risk in women aged above and below 50 years and in men aged above 50 years. Our findings add support to the growing literature that TZD treatment is associated with an increased risk of fractures in both men and women, that effects of rosiglitazone and pioglitazone are similar and that fracture risk is increased even in younger women.


Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome.
Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate treatment. In patients, mutation of ARX, a transcription factor selectively expressed in neuronal precursors and adult inhibitory interneurons, impairs cell migration and causes a major inherited subtype of the disease X-linked infantile spasms syndrome. Using an animal model, the Arx((GCG)10+7) mouse, we determined that brief estradiol (E2) administration during early postnatal development prevented spasms in infancy and seizures in adult mutants. E2 was ineffective when delivered after puberty or 30 days after birth. Early E2 treatment altered mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and restored depleted interneuron populations without increasing GABAergic synaptic density. Postnatal E2 treatment may induce lasting transcriptional changes that lead to enduring disease modification and could potentially serve as a therapy for inherited interneuronopathies.


Circuits regulating pleasure and happiness: evolution and role in mental disorders.
Taking the evolutionary development of the forebrain as a starting point, the authors developed a biological framework for the subcortical regulation of human emotional behaviour which may offer an explanation for the pathogenesis of the principle symptoms of mental disorders. Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behaviour are essential for all free-moving animals to stay alive and to have offspring. Even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must therefore have been capable of generating these behaviours. Our earliest vertebrate ancestors, with a brain comparable with the modern lamprey, had a sophisticated extrapyramidal system generating and controlling all motions as well as a circuit including the habenula for the evaluation of the benefits of their actions. Almost the complete endbrain of the first land animals with a brain comparable with that of amphibians became assimilated into the human amygdaloid and hippocampal complex, whereas only a small part of the dorsal pallium and striatum developed into the ventral extrapyramidal circuits and the later insular cortex. The entire neocortex covering the hemispheres is of recent evolutionary origin, appearing first in early mammals. During the entire evolution of vertebrates, the habenular system was well conserved and maintained its function in regulating the intensity of reward-seeking (pleasure-related) and misery-fleeing (happiness-related) behaviour. The authors propose that the same is true in humans. Symptomatology of human mental disorders can be considered to result from maladaptation within a similar amygdalo/hippocampal-habenular-mesencephalic-ventral striatal system.


The Cochrane Lecture. The best and the enemy of the good: randomised controlled trials, uncertainty, and assessing the role of patient choice in medical decision making.
This lecture aimed to create a bridge to span the conceptual and ideological gap between randomised controlled trials and systematic observational comparisons and to reduce unwanted and unproductive polarisation. The argument, simply put, is that since randomisation alone eliminates the selection effect of therapeutic decision making, anything short of randomisation to attribute cause to consequent outcome is a waste of time. If observational comparison does have any significant part in evaluating medical outcomes, there is a grave danger of "the best", to paraphrase Voltaire, becoming "the enemy of the good". The first section aims to emphasise the advantages of randomised controlled trials. Then the nature of an essential precondition--medical uncertainty--is discussed in terms of its extent and effect. Next, the role of patient choice in medical decision making is considered, both when outcomes can safely be attributed to treatment choice and when they cannot. There may be many important situations in which choice itself affects outcome and this could mean that random comparisons give biased estimates of true therapeutic effects. In the penultimate section, the implications of this possibility both for randomised controlled trials and for outcome research is pursued and lastly there are some simple recommendations for reliable outcome research.


Technology use by older adults in the Netherlands and its associations with demographics and health outcomes.
Information and communications technology (ICT) has the potential to contribute to the quality of life of older adults. The aim of this study was to analyze the use of a broad array of ICT devices and services among Dutch older adults and to determine whether demographics and health outcomes are associated with this use. A questionnaire was dispensed among a group of Dutch older adults (≥65 years). A univariate analysis of covariance was used to analyse results. Two hundred ninety-one subjects filled out the questionnaire. Reported use of newer technologies was lower compared with older technologies. Increased age (p = 0.048, Confidence Interval [CI]: -0.73: -0.004), lower degree of education (p = 0.008, CI: -59.64: -5.59), birthplace outside of Europe (p = 0.024, CI: -21.99: -0.73), lower income (p = 0.005, CI: -46.44:25.38), less arthrosis of the hands (p = 0.042, CI: -1.38:21.11), and a lower physical functioning (p = 0.008, CI: 1.43:9.41) resulted in a lower ICT use score with an adjusted R2 of 0.311. Older adults are slower to adapt to newer technologies. It appears it is not the degree of physical restrictions, but rather the degree of adaptability to these restrictions that influence the use of ICT.


Cost Savings of Carpal Tunnel Release Performed In-Clinic Compared to an Ambulatory Surgery Center: Time-Driven Activity-Based-Costing.
Purpose: The purpose of our study was to investigate carpal tunnel release (CTR) performed in the clinic versus the ambulatory surgery center (ASC) to evaluate for potential cost savings. Methods: Patients who underwent either CTR in clinic under a local anesthetic or CTR in the ASC with sedation and local anesthetic were prospectively enrolled in a registry between 2014 and 2016. All patients completed a Visual Analog Scale (VAS) pain scale for procedural and postprocedure pain. Time-Driven Activity-Based Costing (TDABC) was utilized to quantify cost of both CTR in clinic and CTR in the ASC. Statistical analysis involved parametric comparative tests between patient cohorts for both the TDABC-cost and patient pain. Results: A total of 59 participants completed the postprocedure CTR survey during the study period, 23 (38.9%) in the ASC group and 36 (61.1%) in the clinic group. Overall time for the procedure from patient arrival to discharge was significantly longer for the ASC cases, averaging 215.7 minutes (range: 201-230) compared to 78.6 minutes (range: 59-98) in the clinic group (P < .01). Both procedural and postoperative VAS pain scores were comparable between clinic and ASC cohorts, procedural pain: 1.8 vs 1.9 (P = .91) and postoperative pain: 4.8 vs 4.9 (P = .88). TDABC analysis estimated ASC CTR procedures to cost an average of $557.07 ($522.06-$592.08) and clinic procedures to cost an average of $151.92 ($142.59-$161.25) (P < .05). Conclusions: CTR in the clinic setting results in significant cost savings compared to CTR in the ASC with no difference in pain scores during the procedure or postoperative period. Level of Evidence: Therapeutic Level II.


Outcome and haemato-toxicity of two chemotherapy regimens for childhood non-Hodgkin's lymphoma in a Kenyan hospital.
Effectiveness and toxicity of childhood cancer treatments have never been evaluated in Kenya since introduction of structured care in the early seventies. To evaluate effectiveness and toxicity of two treatment protocols for Non-Hodgkin's lymphoma (NHL). Historical cohort study using medical records. Kenyatta National Hospital, a tertiary care and medical teaching hospital. Children < or =15 years with diagnosis of non-Hodgkin's Lymphoma. Primary outcomes were median survival, event free survival and toxicity. Out of 101 records, only 26 (25.7%) met inclusion criteria. Baseline characteristics were similar in the two treatment arms. Median survival was 0.75 months (95% CI = 0.54-0.96) and 1.0 months (95% CI = 0.29-1.71) for short and long arm groups. There was no difference in event free survival and haematological toxicity. No clear difference in effectiveness and toxicity between the intensive-short and the less aggressive long course chemotherapy regimens was evident. Though lack of difference may be attributed to the small sample size, suboptimal supportive care for intensive treatment would increase risk of toxic deaths. As the short course protocol did not demonstrate obvious deterioration of median and event free survival, a strong case may be made for a randomised clinical trial within a context of improved supportive care.


Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits.
Age-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits. For each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression. Of the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27-20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 × 10-16 to 1.9 × 10-3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 × 10-7 to 3.0 × 10-4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis. We demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common.


Electronic Alteration on Oligothiophenes by o-Carborane: Electron Acceptor Character of o-Carborane in Oligothiophene Frameworks with Dicyano-Vinyl End-On Group.
We studied electronic change in oligothiophenes by employing o-carborane into a molecular array in which one or both end(s) were substituted by electron-withdrawing dicyano-vinyl group(s). Depending on mono- or bis-substitution at the o-carborane, a series of linear A1-D-A2 (1a-1c) or V-shaped A1-D-A2-D-A1 (2a-2c) oligothiophene chain structures of variable length were prepared; A1, D, and A2, represent dicyano-vinyl, oligothiophenyl, and o-carboranyl groups, respectively. Among this series, 2a shows strong electron-acceptor capability of o-carborane comparable to that of the dicyano-vinyl substituent, which can be elaborated by a conformational effect driven by cage σ*-π* interaction. As a result, electronic communications between o-carborane and dicyano-vinyl groups are successfully achieved in 2a.


Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(III) and as nitric oxide donors: syntheses, speciation studies and nitric oxide releasing investigations.
The synthesis and spectroscopic characterisation of novel mononuclear Ru(III)(edta)(hydroxamato) complexes of general formula [Ru(H2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-C1 and 3-Me-phenylhydroxamato), as well as the first example of a Ru(III)-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)].H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru(III) complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(mu-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru(III), are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru(III) involves initial formation of Ru(III)-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of Ru(III)-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids.


Comparative metabolite fingerprinting of the rumen system during colonisation of three forage grass (Lolium perenne L.) varieties.
The rumen microbiota enable ruminants to degrade complex ligno-cellulosic compounds to produce high quality protein for human consumption. However, enteric fermentation by domestic ruminants generates negative by-products: greenhouse gases (methane) and environmental nitrogen pollution. The current lack of cultured isolates representative of the totality of rumen microbial species creates an information gap about the in vivo function of the rumen microbiota and limits our ability to apply predictive biology for improvement of feed for ruminants. In this work we took a whole ecosystem approach to understanding how the metabolism of the microbial population responds to introduction of its substrate. Fourier Transform Infra Red (FTIR) spectroscopy-based metabolite fingerprinting was used to discriminate differences in the plant-microbial interactome of the rumen when using three forage grass varieties (Lolium perenne L. cv AberDart, AberMagic and Premium) as substrates for microbial colonisation and fermentation. Specific examination of spectral regions associated with fatty acids, amides, sugars and alkanes indicated that although the three forages were apparently similar by traditional nutritional analysis, patterns of metabolite flux within the plant-microbial interactome were distinct and plant genotype dependent. Thus, the utilisation pattern of forage nutrients by the rumen microbiota can be influenced by subtleties determined by forage genotypes. These data suggest that our interactomic approach represents an important means to improve forages and ultimately the livestock environment.


SV40 T antigen binds directly to the large subunit of purified DNA polymerase alpha.
Purified SV40 large T antigen and purified DNA polymerase alpha-primase form a complex detectable by ELISA and by a modified immunoblotting technique. The interaction is specific for the large catalytic subunit of polymerase alpha. The amino terminal 83 amino acids of T antigen are both necessary and sufficient for binding to the polymerase. However, antibody epitopes located in the carboxy terminal ATPase domain of T antigen are masked in the polymerase-T antigen complex, and complex formation is inhibited by an antibody directed against the carboxy terminus of T antigen, suggesting that this region of T antigen, though not required for binding, is in close proximity to the bound polymerase. The affinity of human DNA polymerase alpha for T antigen is approximately 10-fold greater than that of polymerase alpha from calf thymus, consistent with the interpretation that polymerase alpha is at least in part responsible for the primate-specific replication of SV40 DNA in vivo and in vitro. The results suggest that specific protein-protein interaction between DNA polymerase alpha and T antigen plays an important role in viral DNA replication.


Extraocular muscle afferent signals modulate visual attention.
Extraocular muscle afferent signals contribute to oculomotor control and visual localization. Prompted by the close links between the oculomotor and attention systems, it was investigated whether these proprioceptive signals also modulated the allocation of attention in space. A suction sclera contact lens was used to impose an eye rotation on the nonviewing, dominant eye. With their viewing, nondominant eye, participants (n = 4) fixated centrally and detected targets presented at 5° in the left or right visual hemifield. The position of the viewing eye was monitored throughout the experiment. As a control, visual localization was tested using finger pointing without visual feedback of the hand, whereas the nonviewing eye remained deviated. The sustained passive rotation of the occluded, dominant eye, while the other eye maintained central fixation, resulted in a lateralized change in the detectability of visual targets. In all participants, the advantage in speed and accuracy for detecting right versus left hemifield targets that occurred during a sustained rightward eye rotation of the dominant eye was reduced or reversed by a leftward eye rotation. The control experiment confirmed that the eye deviation procedure caused pointing errors consistent with an approximately 2° shift in perceived eye position, in the direction of rotation of the nonviewing eye. With the caveat of the small number of participants, these results suggest that extraocular muscle afferent signals modulate the deployment of attention in visual space.


On the formalization and reuse of scientific research.
The reuse of scientific knowledge obtained from one investigation in another investigation is basic to the advance of science. Scientific investigations should therefore be recorded in ways that promote the reuse of the knowledge they generate. The use of logical formalisms to describe scientific knowledge has potential advantages in facilitating such reuse. Here, we propose a formal framework for using logical formalisms to promote reuse. We demonstrate the utility of this framework by using it in a worked example from biology: demonstrating cycles of investigation formalization [F] and reuse [R] to generate new knowledge. We first used logic to formally describe a Robot scientist investigation into yeast (Saccharomyces cerevisiae) functional genomics [f(1)]. With Robot scientists, unlike human scientists, the production of comprehensive metadata about their investigations is a natural by-product of the way they work. We then demonstrated how this formalism enabled the reuse of the research in investigating yeast phenotypes [r(1) = R(f(1))]. This investigation found that the removal of non-essential enzymes generally resulted in enhanced growth. The phenotype investigation was then formally described using the same logical formalism as the functional genomics investigation [f(2) = F(r(1))]. We then demonstrated how this formalism enabled the reuse of the phenotype investigation to investigate yeast systems-biology modelling [r(2) = R(f(2))]. This investigation found that yeast flux-balance analysis models fail to predict the observed changes in growth. Finally, the systems biology investigation was formalized for reuse in future investigations [f(3) = F(r(2))]. These cycles of reuse are a model for the general reuse of scientific knowledge.


Effects of size of ingestively masticated fragments of plant tissues on kinetics of digestion of NDF.
Ingestively masticated fragments were collected and sized via sieving. Different sizes of esophageal masticate and ruminal digesta fragments, and ground fragments of larger masticated pieces were incubated in vitro, and undigested NDF remaining at intervals of up to 168 h of incubation was determined. The ruminal age-dependent time delay (tau) for onset of digestion of NDF was positively correlated (P < 0.004) with the mean sieve aperture estimated to retain 50% of the fragments between successive sieve apertures (MRA). Degradation rate of potentially degradable NDF (PDF) and level of indigestible NDF were not related (P > 0.10) to MRA of masticated and ground fragments. Estimates of tau were positively related to MRA, with slopes of bermudagrass < corn silage < ruminal fragments of corn silage. It was concluded that fragment size-, and consequently, ruminal age-dependent onset of PDF degradation of a mixture of different fragment sizes results in an age-dependent rate of degradation of the more rapidly degrading of two subentities of PDF. Models are proposed that assume a tau before onset of simultaneous degradation of PDF from two pools characterized as having gamma-modeled age-dependency and age-constant rates. The ruminal age-dependent pool seems to be associated with the faster-degrading pool, and its rate parameter increases with range in MRA in the population of fragments. Conceptually, the ruminal age-dependent rate parameter for PDF degradation seems to represent a composite of several effects: 1) effects of the size-dependent tau; 2) range in MRA of the population of ingestively masticated fragments; and 3) subentities of PDF that degrade via more rapid age-dependent rates compared with subentities of PDF that degrade via age-constant rates. The estimated fractional rates of ruminative comminution of ingestively masticated fragments (0.060 to 0.075/h) were of a magnitude similar to the mean fractional rates of PDF digestion (0.030 to 0.085/h), which implies that ruminative comminution may be first-limiting to fractional rate of PDF digestion. The in vivo roles of ingestive and ruminative mastication of fragments on PDF degradation must be considered in any kinetic system for estimating PDF digestion in the rumen. These results and others in the literature suggest that the rate of surface area exposure rather than intrinsic chemical attributes of PDF may be first-limiting to degradation rate of PDF in vivo.


Enzymatic production of bioactive docosahexaenoic acid phenolic ester.
Docosahexaenoic acid (DHA) is increasingly considered for its health benefits. However, its use as functional food ingredient is still limited by its instability. In this work, we developed an efficient and solvent-free bioprocess for the synthesis of a phenolic ester of DHA. A fed-batch process catalyzed by Candida antarctica lipase B was optimised, leading to the production of 440 g/L vanillyl ester (DHA-VE). Structural characterisation of the purified product indicated acylation of the primary OH group of vanillyl alcohol. DHA-VE exhibited a high radical scavenging activity in acellular systems. In vivo experiments showed increased DHA levels in erythrocytes and brain tissues of mice fed DHA-VE-supplemented diet. Moreover, in vitro neuroprotective properties of DHA-VE were demonstrated in rat primary neurons exposed to amyloid-β oligomers. In conclusion, DHA-VE synergized the main beneficial effects of two common natural biomolecules and therefore appears a promising functional ingredient for food applications.


Reshaping of the conformational search of a protein by the chaperone trigger factor.
Protein folding is often described as a search process, in which polypeptides explore different conformations to find their native structure. Molecular chaperones are known to improve folding yields by suppressing aggregation between polypeptides before this conformational search starts, as well as by rescuing misfolds after it ends. Although chaperones have long been speculated to also affect the conformational search itself--by reshaping the underlying folding landscape along the folding trajectory--direct experimental evidence has been scarce so far. In Escherichia coli, the general chaperone trigger factor (TF) could play such a role. TF has been shown to interact with nascent chains at the ribosome, with polypeptides released from the ribosome into the cytosol, and with fully folded proteins before their assembly into larger complexes. To investigate the effect of TF from E. coli on the conformational search of polypeptides to their native state, we investigated individual maltose binding protein (MBP) molecules using optical tweezers. Here we show that TF binds folded structures smaller than one domain, which are then stable for seconds and ultimately convert to the native state. Moreover, TF stimulates native folding in constructs of repeated MBP domains. The results indicate that TF promotes correct folding by protecting partially folded states from distant interactions that produce stable misfolded states. As TF interacts with most newly synthesized proteins in E. coli, we expect these findings to be of general importance in understanding protein folding pathways.


Vacuum bell therapy.
For specific therapy to correct pectus excavatum (PE), conservative treatment with the vacuum bell (VB) was introduced more than 10 years ago in addition to surgical repair. Preliminary results using the VB were encouraging. We report on our 13-year experience with the VB treatment including the intraoperative use during the Nuss procedure and present some technical innovations. A VB with a patient-activated hand pump is used to create a vacuum at the anterior chest wall. Three different sizes of vacuum bells, as well as a model fitted for young women, exist. The appropriate size is selected according to the individual patient's age and ventral surface. The device should be used at home for a minimum of 30 minutes (twice a day), and may be used up to a maximum of several hours daily. The intensity of the applied negative pressure can be evaluated with an integrated pressure gauge during follow-up visits. A prototype of an electronic model enables us to measure the correlation between the applied negative pressure and the elevation of the anterior chest wall. Since 2003, approx. 450 patients between 2 to 61 years of age started the VB therapy. Age and gender specific differences, depth of PE, symmetry or asymmetry, and concomitant malformations such as scoliosis and/or kyphosis influence the clinical course and success of VB therapy. According to our experience, we see three different groups of patients. Immediate elevation of the sternum was confirmed thoracoscopically during the Nuss procedure in every patient. The VB therapy has been established as an alternative therapeutic option in selected patients suffering from PE. The initial results up to now are encouraging, but long-term results comprising more than 15 years are so far lacking, and further evaluation and follow-up studies are necessary.


Assessment of the coronary venous system using 256-slice computed tomography.
To investigate the coronary venous system and its relation to adjacent structures using 256-slice computed tomography (CT). The study consisted of 102 patients who underwent coronary CT angiography (CTA) using 256-slice CT. For each patient, the coronary venous system and its relation to adjacent structures were evaluated. The appropriate locations and diameters of the posterior interventricular vein (PIV), posterior vein of the left ventricle (PVLV) and the left marginal vein (LMV) were detected. The paired student's t test was used to evaluate the difference between the diameter of the coronary sinus (CS) ostium in anteroposterior direction and that in superoinferior direction. The CS, great cardiac vein (GCV), PIV, and anterior interventricular vein (AIV) were visualized in all cases. It was possible to evaluate at least one main vein with adequate caliber and regular course for cardiac resynchronization therapy (CRT) in 96.1% of these cases. The diameter of the CS ostium in superoinferior direction (11.7±2.1 mm) was larger than that in anteroposterior direction (9.0±2.0 mm) (t = 13.511, P<0.05). For the majority of the cases, the CS-GCV was located above the level of the mitral valve annulus (MVA), while the left circumflex coronary artery (LCX) was coursed between the CS-GCV and the MVA. LMV had more intersection with the circumflex or circumflex marginal than PVLV. 256-slice CT provides superior noninvasive evaluation of the coronary venous system which has important clinical implications.


Acetylated LDL endocytosis by the human monocytic Mono Mac 6sr cells is not mediated by the macrophage type I and II scavenger receptors.
We recently reported that the human monocytic Mono Mac 6sr cell line constitutively takes up and degrades acetylated (acLDL) and oxidized LDL through receptor-specific pathways. The present studies were undertaken to further characterize the acLDL binding site on a functional and molecular basis. The degradation of acLDL increased during differentiation of Mono Mac 6sr cells with lipopolysaccharide (10 ng/mL, 72 hours) and low concentrations of phorbol 12-myristate 13-acetate (PMA; 0.1 to 1.0 ng/mL, 72 hours). Higher doses of PMA (5 or 10 ng/mL), however, decreased acLDL degradation. Scatchard plots of acLDL binding in untreated and LPS-differentiated Mono Mac 6sr cells were nonlinear and suggested the presence of more than one binding site. Although the ligand specificity of the acLDL receptor in Mono Mac 6sr cells resembles that of the macrophage type I and type II scavenger receptors, we did not detect mRNA of either receptor type in untreated or differentiated Mono Mac 6sr cells by means of Northern blotting and reverse transcription polymerase chain reaction. Furthermore, ligand blotting with 125I-acLDL failed to detect the 220-kD types I and II scavenger receptor protein. Thus, Mono Mac 6sr cells express an acLDL receptor that is distinct from the type I and type II scavenger receptor found in human monocyte-derived macrophages but that, like the latter, is induced during monocytic differentiation.


Quantitative Phylogenomics of Within-Species Mitogenome Variation: Monte Carlo and Non-Parametric Analysis of Phylogeographic Structure among Discrete Transatlantic Breeding Areas of Harp Seals (Pagophilus groenlandicus).
Phylogenomic analysis of highly-resolved intraspecific phylogenies obtained from complete mitochondrial DNA genomes has had great success in clarifying relationships within and among human populations, but has found limited application in other wild species. Analytical challenges include assessment of random versus non-random phylogeographic distributions, and quantification of differences in tree topologies among populations. Harp Seals (Pagophilus groenlandicus Erxleben, 1777) have a biogeographic distribution based on four discrete trans-Atlantic breeding and whelping populations located on "fast ice" attached to land in the White Sea, Greenland Sea, the Labrador ice Front, and Southern Gulf of St Lawrence. This East to West distribution provides a set of a priori phylogeographic hypotheses. Outstanding biogeographic questions include the degree of genetic distinctiveness among these populations, in particular between the Greenland Sea and White Sea grounds. We obtained complete coding-region DNA sequences (15,825 bp) for 53 seals. Each seal has a unique mtDNA genome sequence, which differ by 6 ~ 107 substitutions. Six major clades / groups are detectable by parsimony, neighbor-joining, and Bayesian methods, all of which are found in breeding populations on either side of the Atlantic. The species coalescent is at 180 KYA; the most recent clade, which accounts for 66% of the diversity, reflects an expansion during the mid-Wisconsinan glaciation 40~60 KYA. FST is significant only between the White Sea and Greenland Sea or Ice Front populations. Hierarchal AMOVA of 2-, 3-, or 4-island models identifies small but significant ΦSC among populations within groups, but not among groups. A novel Monte-Carlo simulation indicates that the observed distribution of individuals within breeding populations over the phylogenetic tree requires significantly fewer dispersal events than random expectation, consistent with island or a priori East to West 2- or 3-stepping-stone biogeographic models, but not a simple 1-step trans-Atlantic model. Plots of the cumulative pairwise sequence difference curves among seals in each of the four populations provide continuous proxies for phylogenetic diversification within each. Non-parametric Kolmogorov-Smirnov (K-S) tests of maximum pairwise differences between these curves indicates that the Greenland Sea population has a markedly younger phylogenetic structure than either the White Sea population or the two Northwest Atlantic populations, which are of intermediate age and homogeneous structure. The Monte Carlo and K-S assessments provide sensitive quantitative tests of within-species mitogenomic phylogeography. This is the first study to indicate that the White Sea and Greenland Sea populations have different population genetic histories. The analysis supports the hypothesis that Harp Seals comprises three genetically distinguishable breeding populations, in the White Sea, Greenland Sea, and Northwest Atlantic. Implications for an ice-dependent species during ongoing climate change are discussed.


Characterization of TP53 mutations in low-grade myelodysplastic syndromes and myelodysplastic syndromes with a non-complex karyotype.
Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized. 176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype. Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS. TP53 mutations often occurred in DNA-binding domains and the majority of cases had only one mutation, irrespective of their karyotype and MDS subtype. The variant allele frequency (VAF), however, was associated with karyotype complexity and the types of MDS with a lower VAF found in cases with a non-complex karyotype and low-grade MDS. A low (<20%) VAF was associated with a better survival, as well as low-grade subtype. In low-grade MDS and MDS with a non-complex karyotype, TP53 mutations showed a lower VAF. Patients with a lower VAF had a better survival. TP53 mutations are not the only prognostic factor in MDS patients with TP53 mutations as the VAF, blast counts and history of prior therapy also play important roles in prognosis.


Biomedical scientists' perceptions of ethical and social implications: is there a role for research ethics consultation?
Research ethics consultation programs are being established with a goal of addressing the ethical, societal, and policy considerations associated with biomedical research. A number of these programs are modelled after clinical ethics consultation services that began to be institutionalized in the 1980s. Our objective was to determine biomedical science researchers' perceived need for and utility of research ethics consultation, through examination of their perceptions of whether they and their institutions faced ethical, social or policy issues (outside those mandated by regulation) and examination of willingness to seek advice in addressing these issues. We conducted telephone interviews and focus groups in 2006 with researchers from Stanford University and a mailed survey in December 2006 to 7 research universities in the U.S. A total of 16 researchers were interviewed (75% response rate), 29 participated in focus groups, and 856 responded to the survey (50% response rate). Approximately half of researchers surveyed (51%) reported that they would find a research ethics consultation service at their institution moderately, very or extremely useful, while over a third (36%) reported that such a service would be useful to them personally. Respondents conducting human subjects research were more likely to find such a service very to extremely useful to them personally than respondents not conducting human subjects research (20% vs 10%; chi(2) p<0.001). Our findings indicate that biomedical researchers do encounter and anticipate encountering ethical and societal questions and concerns and a substantial proportion, especially clinical researchers, would likely use a consultation service if they were aware of it. These findings provide data to inform the development of such consultation programs in general.


A Comparative In Vitro Study of the Neuroprotective Effect Induced by Cannabidiol, Cannabigerol, and Their Respective Acid Forms: Relevance of the 5-HT1A Receptors.
Previous preclinical studies have demonstrated that cannabidiol (CBD) and cannabigerol (CBG), two non-psychotomimetic phytocannabinoids from Cannabis sativa, induce neuroprotective effects on toxic and neurodegenerative processes. However, a comparative study of both compounds has not been reported so far, and the targets involved in this effect remain unknown. The ability of CBD and CBG to attenuate the neurotoxicity induced by two insults involving oxidative stress (hydrogen peroxide, H2O2) and mitochondrial dysfunction (rotenone) was evaluated in neural cell cultures. The involvement of CB-1 and CB-2 or 5-HT1A receptors was investigated. The neuroprotective effect of their respective acids forms, cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), was also analyzed. MTT and immunocytochemistry assays were used to evaluate cell viability. No significant variation on cell viability was per se induced by the lower concentrations tested of CBD and CBG or CBDA and CBGA; however, high concentrations of CBD, CBDA, or CBGA were toxic since a 40-50% reduction of cell viability was observed. CBD and CBG showed neuroprotective effects against H2O2 or rotenone; however, both compounds were more effective in attenuating the rotenone-induced neurotoxicity. A high concentration of CBDA reduced the rotenone-induced neurotoxicity. WAY100635 (5-HT1A receptor antagonist) but not AM251 and AM630 (CB1 or CB2 receptor antagonists, respectively) significantly diminished the neuroprotective effect induced by CBG only against rotenone. Our results contribute to the understanding of the neuroprotective effect of CBD and CBG, showing differences with their acid forms, and also highlight the role of 5-HT1A receptors in the mechanisms of action of CBG.


A Multi-omics Approach to Unraveling the Microbiome-Mediated Effects of Arabinoxylan Oligosaccharides in Overweight Humans.
Long-term consumption of dietary fiber is generally considered beneficial for weight management and metabolic health, but the results of interventions vary greatly depending on the type of dietary fibers involved. This study provides a comprehensive evaluation of the effects of a specific dietary fiber consisting of a wheat-bran extract enriched in arabinoxylan-oligosaccharides (AXOS) in a human intervention trial. An integrated multi-omics analysis has been carried out to evaluate the effects of an intervention trial with an AXOS-enriched diet in overweight individuals with indices of metabolic syndrome. Microbiome analyses were performed by shotgun DNA sequencing in feces; in-depth metabolomics using nuclear magnetic resonance in fecal, urine, and plasma samples; and massive lipid profiling using mass spectrometry in fecal and serum/plasma samples. In addition to their bifidogenic effect, we observed that AXOS boost the proportion of Prevotella species. Metagenome analysis showed increases in the presence of bacterial genes involved in vitamin/cofactor production, glycan metabolism, and neurotransmitter biosynthesis as a result of AXOS intake. Furthermore, lipidomics analysis revealed reductions in plasma ceramide levels. Finally, we observed associations between Prevotella abundance and short-chain fatty acids (SCFAs) and succinate concentration in feces and identified a potential protective role of Eubacterium rectale against metabolic disease given that its abundance was positively associated with plasma phosphatidylcholine levels, thus hypothetically reducing bioavailability of choline for methylamine biosynthesis. The metagenomics, lipidomics, and metabolomics data integration indicates that sustained consumption of AXOS orchestrates a wide variety of changes in the gut microbiome and the host metabolism that collectively would impact on glucose homeostasis. (This study has been registered at ClinicalTrials.gov under identifier NCT02215343)IMPORTANCE The use of dietary fiber food supplementation as a strategy to reduce the burden of diet-related diseases is a matter of study given its cost-effectiveness and the positive results demonstrated in clinical trials. This multi-omics assessment, on different biological samples of overweight subjects with signs of metabolic syndrome, sheds light on the early and less evident effects of short-term AXOS intake on intestinal microbiota and host metabolism. We observed a deep influence of AXOS on gut microbiota beyond their recognized bifidogenic effect by boosting concomitantly a wide diversity of butyrate producers and Prevotella copri, a microbial species abundant in non-Westernized populations with traditional lifestyle and diets enriched in fresh unprocessed foods. A comprehensive evaluation of hundreds of metabolites unveiled new benefits of the AXOS intake, such as reducing the plasma ceramide levels. Globally, we observed that multiple effects of AXOS consumption seem to converge in reversing the glucose homeostasis impairment.


Phenotyping airways disease: an A to E approach.
The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic.


The Effects of Common Over-the-Counter Moisturizers on Skin Barrier Function: A Randomized, Observer-Blind, Within-Patient, Controlled Study.
Moisturizers possibly improve atopic dermatitis (AD) by restoration of skin barrier, although some have detrimental effects. The aim of the study was to estimate the effects of several routine moisturizers on barrier functions. This is a randomized, forearm-controlled, observer-blind study. Patients older than 12 years with clear to moderate AD were randomized to 1 of 4 moisturizers (Cetaphil Cream, Aveeno Eczema Therapy Moisturizing Cream, CeraVe Moisturizing Cream, Vaseline) applied to nonlesional skin of 1 forearm and no moisturizer to the opposite forearm for 4 weeks. Transepidermal water loss (TEWL), capacitance, pH, and TEWL after tape stripping were evaluated at weeks 0 and 4. In addition, participants without AD underwent baseline measurements only. Twenty patients with AD completed the study. Baseline measurements between the AD group and 10 non-AD controls were similar. After the intervention (AD group), mean TEWL improved in the treated forearm and worsened in the untreated one, but the difference was not significant. There was no significant change in pH or in TEWL after tape stripping. Capacitance significantly improved in the moisturizer forearm. The study was underpowered as recruitment fell short. The effects of moisturizers on nonlesional AD skin were small and need to be addressed when powering future studies. Broadening investigations beyond the classic barrier properties might be useful in future studies.


Sex-related similarities and differences in the neural correlates of beauty.
The capacity to appreciate beauty is one of our species' most remarkable traits. Although knowledge about its neural correlates is growing, little is known about any gender-related differences. We have explored possible differences between men and women's neural correlates of aesthetic preference. We have used magnetoencephalography to record the brain activity of 10 male and 10 female participants while they decided whether or not they considered examples of artistic and natural visual stimuli to be beautiful. Our results reveal significantly different activity between the sexes in parietal regions when participants judged the stimuli as beautiful. Activity in this region was bilateral in women, whereas it was lateralized to the right hemisphere in men. It is known that the dorsal visual processing stream, which encompasses the superior parietal areas, has been significantly modified throughout human evolution. We posit that the observed gender-related differences are the result of evolutionary processes that occurred after the splitting of the human and chimpanzee lineages. In view of previous results on gender differences with respect to the neural correlates of coordinate and categorical spatial strategies, we infer that the different strategies used by men and women in assessing aesthetic preference may reflect differences in the strategies associated with the division of labor between our male and female hunter-gatherer hominin ancestors.


Self-selected conscious strategies do not modulate motor cortical output during action observation.
The human motor system is active not only when actions are performed but also when they are observed. Experimenters often manipulate aspects of the action or context to examine factors that influence this "mirror" response. However, little is known about the role of the observer's own top-down intentions and motivation. In this exploratory study, we investigated whether observers are able to exert conscious control over their mirror response, when they are explicitly instructed to either increase or decrease mirroring. Transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) in a thumb abductor muscle as participants (n = 13) watched a video of a hand squeezing a rubber ball. The size of these MEPs, relative to the size of MEPs elicited during fixation cross observation, was taken as an index of mirroring. In an initial block of trials, participants were instructed to merely observe the actions presented. After the first block, the concept of mirroring was explained to the participants, and in the second and third blocks participants were instructed to either increase or decrease their mirror response. We did not instruct them about how to achieve this increase or decrease. Our results showed no difference in either facilitation or absolute motor excitability (i.e., nonnormalized MEP size) between the three blocks, indicating that individuals do not seem to be able to exert control over motor excitability during action observation, at least in the absence of a specific and maintained strategy.


Impact of icodextrin on clinical outcomes in peritoneal dialysis: a systematic review of randomized controlled trials.
Although icodextrin has been shown to augment peritoneal ultrafiltration in peritoneal dialysis (PD) patients, its impact upon other clinical end points, such as technique survival, remains uncertain. This systematic review evaluated the effect of icodextrin use on patient level clinical outcomes. The Cochrane CENTRAL Registry, MEDLINE, Embase and reference lists were searched (last search 13 September 2012) for randomized controlled trials of icodextrin versus glucose in the long dwell exchange. Summary estimates of effect were obtained using a random effects model. Eleven eligible trials (1222 patients) were identified. There was a significant reduction in episodes of uncontrolled fluid overload [two trials; 100 patients; relative risk (RR) 0.30, 95% confidence interval (CI) 0.15-0.59] and improvement in peritoneal ultrafiltration [four trials; 102 patients; mean difference (MD) 448.54 mL/day, 95% CI 289.28-607.80] without compromising residual renal function [four trials; 114 patients; standardized MD (SMD) 0.12, 95% CI -0.26 to 0.49] or urine output (three trials; 69 patients; MD -88.88, 95% CI -356.88 to 179.12) with icodextrin use for up to 2 years. There was no significant effect on peritonitis incidence (five trials; 607 patients; RR 0.97, 95% CI 0.76-1.23), peritoneal creatinine clearance (three trials; 237 patients; SMD 0.36, 95% CI -0.24 to 0.96), technique failure (three trials; 290 patients; RR 0.58, 95% CI 0.28-1.20), patient survival (six trials; 816 patients; RR 0.82, 95% CI 0.32-2.13) or adverse events. Icodextrin prescription improved peritoneal ultrafiltration, mitigated uncontrolled fluid overload and was not associated with increased risk of adverse events. No effects of icodextrin on technique or patient survival were observed, although trial sample sizes and follow-up durations were limited.


GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis.
GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma [HCC] and Of its treatment with sorafeNib) is a global, prospective, non-interventional study undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real-life practice, including Child-Pugh B patients who were excluded from clinical trials. Patients with unresectable HCC, for whom the decision to treat with sorafenib, based on the approved label and prescribing guidelines, had been taken by their physician, were eligible for inclusion. Demographic data and disease/medical history were recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at follow-up visits. The second interim analysis was undertaken when ~1500 treated patients were followed up for ≥ 4 months. Of the 1571 patients evaluable for safety, 61% had Child-Pugh A status and 23% Child-Pugh B. The majority of patients (74%) received the approved 800 mg initial sorafenib dose, regardless of Child-Pugh status; however, median duration of therapy was shorter in Child-Pugh B patients. The majority of drug-related AEs were grade 1 or 2, and the most commonly reported were consistent with previous reports. The incidence and nature of drug-related AEs were broadly similar across Child-Pugh, Barcelona Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the overall population. Consistent with the first interim analysis, overall safety profile and dosing strategy are similar across Child-Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.


New evidence on the impacts of early exposure to the 1918 influenza pandemic on old-age mortality.
This paper provides new evidence of the impacts of early life exposure to the 1918 pandemic on old-age mortality by analyzing data from the National Longitudinal Mortality Study (n ~ 220,000). The specifications used year and quarter of birth indicators to assess the effects of timing of pandemic exposure and used Cox proportional hazard models for all-cause mortality outcomes. The findings suggest evidence of excess all-cause mortality for cohorts born during 1918 and mixed evidence for cohorts born in 1917 and 1919. Therefore, contrary to some existing research, the results suggest no consistent evidence of the importance of specific windows of exposure by gestation period.


Pregnant women with bronchial asthma benefit from progressive muscle relaxation: a randomized, prospective, controlled trial.
Asthma is a serious medical problem in pregnancy and is often associated with stress, anger and poor quality of life. The aim of this study was to determine the efficacy of progressive muscle relaxation (PMR) on change in blood pressure, lung parameters, heart rate, anger and health-related quality of life in pregnant women with bronchial asthma. We treated a sample of 64 pregnant women with bronchial asthma from the local population in an 8-week randomized, prospective, controlled trial. Thirty-two were selected for PMR, and 32 received a placebo intervention. The systolic blood pressure, forced expiratory volume in the first second, peak expiratory flow and heart rate were tested, and the State-Trait Anger Expression Inventory and Health Survey (SF-36) were employed. According to the intend-to-treat principle, a significant reduction in systolic blood pressure and a significant increase in both forced expiratory volume in the first second and peak expiratory flow were observed after PMR. The heart rate showed a significant increase in the coefficient of variation, root mean square of successive differences and high frequency ranges, in addition to a significant reduction in low and middle frequency ranges. A significant reduction on three of five State-Trait Anger Expression Inventory scales, and a significant increase on seven of eight SF-36 scales were observed. PMR appears to be an effective method to improve blood pressure, lung parameters and heart rate, and to decrease anger levels, thus enhancing health-related quality of life in pregnant women with bronchial asthma.


Foodborne illness: is it on the rise?
Foodborne illness is a serious public health threat. The Centers for Disease Control and Prevention (CDC) estimates that 76 million foodborne illnesses, including 325,000 hospitalizations and 5,000 deaths, occur in the United States each year. Two recently published Foodborne Diseases Active Surveillance Network (FoodNet) reports showed that Salmonella, Campylobacter, Shigella, Cryptosporidium, and Shiga toxin Escherichia coli (STEC) O157 continue to be leading causes of both the number and incidence of laboratory-confirmed foodborne infections in the United States. According to the United States Department of Agriculture (USDA), foodborne illness costs the US economy $10-83 billion per year. Recent large foodborne outbreaks have led to claims that the number of foodborne disease outbreaks and concomitant illnesses has increased in recent years. However, a comparison of data from the CDC showed very little change in the incidence of foodborne illness caused by common pathogens between 2008 and the preceding 3 years (2005-2007). Nevertheless, despite intensified prevention efforts, foodborne illness remains a persistent problem in the United States. Food can become contaminated at any point in the farm-to-table continuum, as well as in consumers' own kitchens. Therefore, foodborne illness risk reduction and control interventions must be implemented at every step throughout the food preparation process, from farm to table. In addition, more effective food safety education programs for foodhandlers and consumers are needed. Strategies should take into account food safety-related trends including large-scale production and wide distribution of food, globalization of the food supply, eating outside of the home, emergence of new pathogens, and growing population of at-risk consumers.