Conductivity and phase morphology of carbon black-filled immiscible polymer blends under creep: an experimental and theoretical study.
Blends of carbon black (CB)-filled co-continuous immiscible polystyrene/poly(methyl-methacrylate) (PS/PMMA) with a PS/PMMA ratio of 50/50 and CB selectively located in the PS phase have been prepared by melt blending. The simultaneous evolution of conductivity and phase morphology of blend composites was investigated under shear and in the quiescent state at 200 °C. It was found that shear deformation had a significant influence on the conductivity of the unfilled PS/PMMA blend and its composites, which was attributed to the change of phase morphology during shear. After the shear stress of 10 kPa, the conductivity of PS/PMMA blends filled with 2 vol% of CB decreased by about two orders of magnitude and the phase morphology transformed from a fine co-continuous structure into a highly elongated lamellar structure. The deformation of phase morphology and the decrease of conductivity were weakened upon decreasing the shear stress or increasing the CB concentration. During subsequent recovery, pronounced phase structure coarsening was observed in the mixture and the conductivity increased as well. A simple model describing the behavior of conductivity under shear deformation was derived and utilized for the description of the experimental data. For the first time, the Burgers model was used to describe the conductivity, and the viscoelastic and viscoplastic parameters were deduced by fitting the conductivity under shear. The results obtained in this study provide a deeper insight into the evolution of phase structure in the conductive polymer blend composite induced by shear deformation.


Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells.
Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-β-expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL-17 expression but decreased TGF-β expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3+ (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper-17 responses that characterize this reaction.


Influence of chronic exposure to treated sewage effluent on the distribution of white blood cell populations in rainbow trout (Oncorhynchus mykiss) spleen.
Impairment of immune function in aquatic animals has been proposed as a possible consequence of low-level contamination of surface waters with anthropogenic substances such as through the discharge of wastewater into rivers, lakes, and oceans. The study at hand investigated the effects of chronic (32 weeks) exposure to sewage treatment plant (STP) effluent on the prevalence and distribution of different leucocyte populations in spleen samples of rainbow trout (Oncorhynchus mykiss). To simulate an infection, fish were injected intraperitoneally (ip) with inactivated Aeromonas salmonicida salmonicida, 6 weeks prior to the termination of the experiment. Immunohistological analysis revealed a marked decrease in thrombocyte numbers, an increase of monocytes, altered distribution of B-cells, and higher surface immunoglobulin expression, as well as activation of MHC class II expression in the spleen after exposure to 15% (v/v) effluent. The most prominent finding of the present study, however, was the occurrence of intraplasmatic deposits or inclusions with strong autofluorescence in spleen sections from effluent-exposed trout. In addition to effluent effects, injection of trout with A. salmonicida stimulated infiltration of monocytes, increased staining intensity on thrombocytes, and enhanced MHC class I expression in larger leucocytes surrounding melanomacrophage centres. In general, the current study demonstrates a marked, potentially adverse effect of STP effluent on spleen leucocytes and on the integrity of spleen tissue. The observed response suggests a constant unspecific stimulation of different leucocyte populations and is reminiscent of chronic inflammation.


ArsRS-Dependent Regulation of homB Contributes to Helicobacter pylori Biofilm Formation.
One elusive area in the Helicobacter pylori field is an understanding of why some infections result in gastric cancer, yet others persist asymptomatically for the life-span of the individual. Even before the genomic era, the high level of intraspecies diversity of H. pylori was well recognized and became an intriguing area of investigation with respect to disease progression. Of interest in this regard is the unique repertoire of over 60 outer membrane proteins (OMPs), several of which have been associated with disease outcome. Of these OMPs, the association between HomB and disease outcome varies based on the population being studied. While the molecular roles for some of the disease-associated OMPs have been evaluated, little is known about the role that HomB plays in the H. pylori lifecycle. Thus, herein we investigated homB expression, regulation, and contribution to biofilm formation. We found that in H. pylori strain G27, homB was expressed at a relatively low level until stationary phase. Furthermore, homB expression was suppressed at low pH in an ArsRS-dependent manner; mutation of arsRS resulted in increased homB transcript at all tested time-points. ArsRS regulation of homB appeared to be direct as purified ArsR was able to specifically bind to the homB promoter. This regulation, combined with our previous finding that ArsRS mutations lead to enhanced biofilm formation, led us to test the hypothesis that homB contributes to biofilm formation by H. pylori. Indeed, subsequent biofilm analysis using a crystal-violet quantification assay and scanning electron microscopy (SEM) revealed that loss of homB from hyper-biofilm forming strains resulted in reversion to a biofilm phenotype that mimicked wild-type. Furthermore, expression of homB in trans from a promoter that negated ArsRS regulation led to enhanced biofilm formation even in strains in which the chromosomal copy of homB had been deleted. Thus, homB is necessary for hyper-biofilm formation of ArsRS mutant strains and aberrant regulation of this gene is sufficient to induce a hyper-biofilm phenotype. In summary, these data suggest that the ArsRS-dependent regulation of OMPs such as HomB may be one mechanism by which ArsRS dictates biofilm development in a pH responsive manner.


Preliminary findings of cortical thickness abnormalities in blast injured service members and their relationship to clinical findings.
Though cortical abnormalities have been demonstrated in moderate and severe traumatic brain injured (TBI) patients, there have been no studies examining cortical changes following blast related mild TBI (mTBI). The purpose of this study was to determine the effects and functional relevance of blast mTBI on cortical thickness in a small cohort of carefully screened blast injured US Service Members (SM). Twelve SM with mTBI acquired through blast injury were compared to 11 demographically matched control SM without TBI. Both mTBI and control participants were active duty and had completed a combat deployment. Subjects underwent MRI examination and the T1 weighted anatomic images were processed using the FreeSurfer suite of tools. Cortical thickness maps were compared between groups and examined for relationships with time since injury (TSI). Utilizing a large database of functional imaging results (BrainMap), significant regions of interest (ROI) were used to determine the behavioral profiles most consistently associated with the specific ROI. In addition, clinical variables were examined as part of post-hoc analysis of functional relevance. Group comparisons controlling for age demonstrated several significant clusters of cortical thinning for the blast injured SM. After multiple comparisons correction (False Discovery Rate (FDR)), two left hemisphere clusters remained significant (left superior temporal (STG) and frontal (SFG) gyri). No clusters were significantly correlated with TSI after FDR correction. Behavioral analysis for the STG and SFG clusters demonstrated three significant behavioral/cognitive sub-domains, each associated with audition and language. Blast injured SMs demonstrated distinct areas of cortical thinning in the STG and SFG. These areas have been previously shown to be associated with audition and language. Post-hoc analyses of clinical records demonstrated significant abnormal audiology reports for the blast injured SM suggesting that the thinning in these ROIs might be related to injury to the external auditory system rather than direct injury to the brain from the blast. It is clear that additional replication is needed in much larger cohorts. Importantly, the combination of imaging tools and methods in this study successfully demonstrated the potential to define unique ROIs and functional correlates that can be used to design future studies.


Low-cost fabrication of large area sub-wavelength anti-reflective structures on polymer film using a soft PUA mold.
A soft lithographic approach using a modified polyurethane acrylate (PUA) mold for the fabrication of sub-wavelength antireflective structure on polymer film is reported. By introducing an intermediate transferring PUA mold generated by an anodized aluminum oxide membrane, there is no need either to heat nor to deposit metal as a seed layer. Therefore, the most costly and time-consuming master preparation step in the conventional process chain is not a necessity. The soft PUA mold provides a high resolution of 100 nm with an aspect ratio of 1.7 and a conformal contact with the substrate and reduces the pressure needed during the imprinting steps. It is numerically verified that the antireflective film with nanopores has a similar fascinating broadband antireflective effect compared with that of its complementary nanonipple one. In our experiment, the average transmission efficiency of the PET film with dual-side nanopores can be enhanced to 98.7% at normal incidence and 92.5% at an incident angle of 60° over a range of 400~800 nm of the spectrum. The proposed method is simple and cost-effective and the fabricated antireflective polymer film can be mounted on the surfaces of various optical devices for the reduction of Fresnel reflections.


Pregnancy-associated malaria: parasite binding, natural immunity and vaccine development.
Humans living in areas of high malaria transmission gradually acquire, during the early years of life, protective clinical immunity to Plasmodium falciparum, limiting serious complications of malaria to young children. However, pregnant women become more susceptible to severe P. falciparum infections during their first pregnancy. Pregnancy associated malaria is coupled with massive accumulation of parasitised erythrocytes and monocytes in the placental intervillous blood spaces, contributing to disease and death in pregnant women and developing infants. Indirect evidence suggests that prevention may be possible by vaccinating women of childbearing age before their first pregnancy. This review aims to introduce the reader to the implications of malaria infection during pregnancy and to analyse recent findings towards the identification and characterisation of parasite encoded erythrocyte surface proteins expressed in malaria-infected pregnant women that are likely targets of protective immunity and have potential for vaccine development.


[Inside-outside occipito-cervical fixation: technical report].
The clinical knowledgement of biomechanics of atlantoaxial complex have been proved that progressive instability has a mandatory occurrence after anterior decompression of the craniocervical junction. We report the occípitocervical fixation so called inside-outside technique, originally described by Pait et al. appliedin in two patients whom underwent odontoidectomy. The occipitalcervical fixation technique consist in the use of a titanium rod bended according with occipital cervical angle placed and fixed laterally over the cervical spine. The rod is fixed to the occipital bone by mean of placement a screw which flat portion is positioned onto the epidural space. In the cervical spine the rod is attached to transarticular screws placed at the superolateral quadrant of the articular mass. In the axis the screw is introduced through the pars interarticularis finishing at the axis body or the lateral mass of the atlas. This technique proved to be safe and easily applied in the patients whom underwent this surgical procedure.


The intensive care unit course and outcome in acute-on-chronic liver failure are comparable to other populations.
Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis, development of organ failure and high short-term mortality. Whether the outcome in patients admitted to the intensive care unit (ICU) with ACLF differs from other ICU populations is unknown. We compared the clinical course and host response in ICU patients with or without ACLF, matched for baseline severity of illness scores and characteristics. From the large prospective EPaNIC randomized control trial database (n = 4,640), 133 patients were identified with cirrhosis of whom 71 fulfilled the Chronic Liver Failure Consortium criteria for ACLF. These patients were matched for type and severity of illness and demographics to 71 septic and 71 medical ICU patients from the same database without chronic liver disease. Clinical, biochemical and outcome parameters were compared in this cohort study of 213 patients. In a subset of 100 patients, day 1 serum cytokines were quantified. The outcome of ACLF, when compared to septic or medical ICU patients, matched for baseline parameters of illness severity, was similar regarding length of ICU stay, development of new infections, organ failure and septic shock. ICU, hospital and 90-day mortality were similar between the groups. C-reactive protein and platelet levels were lower in patients with ACLF throughout the first week. Cytokines, including IL-10, IL-1β, IL-6, and IL-8, were similarly elevated in ACLF and septic ICU patients on day 1. However, TNF-α levels were higher in patients with ACLF. Patients with ACLF admitted to the ICU showed comparable clinical and ICU outcomes as ICU patients without chronic liver disease, but with similar baseline severity of illness characteristics. This suggests that ICU admission criteria should not be different in ACLF populations. Liver function may abruptly deteriorate in patients with chronic liver disease with cirrhosis, often resulting in these patients being admitted to an intensive care unit (ICU) with organ failure. Previous studies have indicated that this sudden deterioration, called acute-on-chronic liver failure is associated with very high mortality rates, which often resulted in deferred ICU care because of a perception of futility. Our study now shows that the ICU course and outcome are not different when patients with acute-on-chronic liver failure are compared to other ICU patients matched for severity of illness. This demonstrates that patients with acute-on-chronic liver failure deserve the same ICU care given to other ICU populations.


Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease.
Of 19 unselected patients with the diagnosis of amyotrophic lateral sclerosis (ALS) living in Suffolk County, New York (an area of high Lyme disease prevalence), 9 had serologic evidence of exposure to Borrelia burgdorferi; 4 of 38 matched controls were seropositive. Eight of 9 seropositive patients were male (8 of 12 male patients vs 2 of 24 controls). Rates of seropositivity were lower among patients with ALS from nonendemic areas. All patients had typical ALS; none had typical Lyme disease. Cerebrospinal fluid was examined in 24 ALS patients--3 (all with severe bulbar involvement) appeared to have intrathecal synthesis of anti-B burgdorferi antibody. Following therapy with antibiotics, 3 patients with predominantly lower motor neuron abnormalities appeared to improve, 3 with severe bulbar dysfunction deteriorated rapidly, and all others appeared unaffected. There appears to be a statistically significant association between ALS and immunoreactivity to B burgdorferi, at least among men living in hyperendemic areas.


Hexose/Pentose and Hexitol/Pentitol Metabolism.
Escherichia coli and Salmonella enterica serovar Typhimurium exhibit a remarkable versatility in the usage of different sugars as the sole source of carbon and energy, reflecting their ability to make use of the digested meals of mammalia and of the ample offerings in the wild. Degradation of sugars starts with their energy-dependent uptake through the cytoplasmic membrane and is carried on further by specific enzymes in the cytoplasm, destined finally for degradation in central metabolic pathways. As variant as the different sugars are, the biochemical strategies to act on them are few. They include phosphorylation, keto-enol isomerization, oxido/reductions, and aldol cleavage. The catabolic repertoire for using carbohydrate sources is largely the same in E. coli and in serovar Typhimurium. Nonetheless, significant differences are found, even among the strains and substrains of each species. We have grouped the sugars to be discussed according to their first step in metabolism, which is their active transport, and follow their path to glycolysis, catalyzed by the sugar-specific enzymes. We will first discuss the phosphotransferase system (PTS) sugars, then the sugars transported by ATP-binding cassette (ABC) transporters, followed by those that are taken up via proton motive force (PMF)-dependent transporters. We have focused on the catabolism and pathway regulation of hexose and pentose monosaccharides as well as the corresponding sugar alcohols but have also included disaccharides and simple glycosides while excluding polysaccharide catabolism, except for maltodextrins.


IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy.
One of the most important mechanisms by which cancer fosters its own development is the generation of an immune microenvironment that inhibits or impairs antitumor immune responses. A cancer permissive immune microenvironment is present in a large proportion of the patients with cancer who do not respond to immunotherapy approaches intended to trigger preexisting antitumor immune responses, for instance, immune checkpoint blockade. High circulating levels of IL8 in patients with cancer quite accurately predict those who will not benefit from checkpoint-based immunotherapy. IL8 has been reported to favor cancer progression and metastases via different mechanisms, including proangiogenesis and the maintenance of cancer stem cells, but its ability to attract and functionally modulate neutrophils and macrophages is arguably one of the most important factors. IL8 does not only recruit neutrophils to tumor lesions, but also triggers the extrusion of neutrophil extracellular traps (NET). The relevance and mechanisms underlying the contribution of both neutrophils and NETs to cancer development and progression are starting to be uncovered and include both direct effects on cancer cells and changes in the tumor microenvironment, such as facilitating metastasis, awakening micrometastases from dormancy, and facilitating escape from cytotoxic immune cells. Blockade of IL8 or its receptors (CXCR1 and CXCR2) is being pursued in drug development, and clinical trials alone or in combination with anti-PD-L1 checkpoint inhibitors are already ongoing.


Cognitive bias modification to prevent depression (COPE): study protocol for a randomised controlled trial.
Depression is a leading cause of disability worldwide and, although efficacious treatments are available, their efficacy is suboptimal and recurrence of symptoms is common. Effective preventive strategies could reduce disability and the long term social and health complications associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel, simple, and safe intervention that addresses attentional and interpretive biases associated with anxiety, dysphoria, and depression. The primary aim of this trial is to determine if CBM decreases the one-year onset of a major depressive episode among adults with subsyndromal depression. This randomised controlled trial will recruit 532 adults with subsyndromal symptoms of depression living in the Australian community (parallel design, 1:1 allocation ratio). Participants will be free of clinically significant symptoms of depression and of psychotic disorders, sensory and cognitive impairment, and risky alcohol use. The CBM intervention will target attentional and interpretive biases associated with depressive symptoms. The sessions will be delivered via the internet over a period of 52 weeks. The primary outcome of interest is the onset of a major depressive episode according the DSM-IV-TR criteria over a 12-month period. Secondary outcomes of interest include change in the severity of depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9), use of antidepressants or benzodiazepines, and changes in attention and interpretive biases. The assessment of outcomes will take place 3, 6, 9, and 12 months after randomisation and will occur via the internet. We propose to test the efficacy of an innovative intervention that is well grounded in theory and for which increasing empirical evidence for an effect on mood is available. The intervention is simple, inexpensive, easy to access, and could be easily rolled out into practice if our findings confirm a role for CBM in the prevention of depression. Australian and New Zealand Clinical Trials Registry ACTRN12613001334796. Date: 5th December 2013.


Morphology of renal afferent arterioles in spontaneously hypertensive rats.
We present a new perfusion technique that allows arteries down to the level of capillaries to be fixed while relaxed and under a known intravascular pressure. Through a catheter inserted into the right renal artery of 12-week-old male spontaneously hypertensive rats (n = 9) and control Wistar-Kyoto rats (n = 11), the kidney vessels were rinsed with human plasma, relaxed by papaverine, and perfused with a casting resin containing microspheres. The microspheres (12 microns) became trapped in the glomeruli of the kidney and, together with a closing of the venous outflow, they caused the flow through the kidney to stop, so that the intravascular pressure was raised to the level of the input perfusion pressure (100 mm Hg). The resin material was allowed to harden, and the kidney was immersion-fixed and prepared for histomorphometrical investigations. This technique made it possible to measure both the structurally determined lumen diameter and the corresponding media thickness under clearly defined conditions. The lumen diameter of afferent arterioles close to the glomeruli showed a 17% reduction in spontaneously hypertensive rats (15.4 +/- 0.6 microns; mean +/- SEM) compared with Wistar-Kyoto rat arterioles (18.5 +/- 0.3 microns, p < 0.001). However, this was not due to media hypertrophy, because media cross-sectional area was smaller (p < 0.001) in spontaneously hypertensive rats (210 +/- 6 microns 2) compared with Wistar-Kyoto rats (274 +/- 16 microns 2). We conclude that the lumen reduction in renal afferent arterioles in spontaneously hypertensive rats is not the result of an encroachment on the lumen by a hypertrophic media.


Stacking-Based Visualization of Trajectory Attribute Data.
Visualizing trajectory attribute data is challenging because it involves showing the trajectories in their spatio-temporal context as well as the attribute values associated with the individual points of trajectories. Previous work on trajectory visualization addresses selected aspects of this problem, but not all of them. We present a novel approach to visualizing trajectory attribute data. Our solution covers space, time, and attribute values. Based on an analysis of relevant visualization tasks, we designed the visualization solution around the principle of stacking trajectory bands. The core of our approach is a hybrid 2D/3D display. A 2D map serves as a reference for the spatial context, and the trajectories are visualized as stacked 3D trajectory bands along which attribute values are encoded by color. Time is integrated through appropriate ordering of bands and through a dynamic query mechanism that feeds temporally aggregated information to a circular time display. An additional 2D time graph shows temporal information in full detail by stacking 2D trajectory bands. Our solution is equipped with analytical and interactive mechanisms for selecting and ordering of trajectories, and adjusting the color mapping, as well as coordinated highlighting and dedicated 3D navigation. We demonstrate the usefulness of our novel visualization by three examples related to radiation surveillance, traffic analysis, and maritime navigation. User feedback obtained in a small experiment indicates that our hybrid 2D/3D solution can be operated quite well.


Effects of time averaging on optical scintillation in a ground-to-satellite atmospheric propagation.
Temporal natures for a variance of turbulence-induced log-intensity fluctuations are obtained. The variance of the optical fluctuation is reduced when the optical signals are integrated in a photodetector, and we express the index of reduction (called the time-averaging factor) by using an autocovariance function of the optical fluctuation. The optical fluctuations for a ground-to-satellite path are caused by both atmospheric turbulence and the beam-pointing jitter error of the optical transmitter. The turbulence-induced optical scintillation can be discriminated from the fluctuation that is due to the beam-pointing jitter error. The compared result from the probability density function of the optical signal reveals good agreement. The temporal autocovariance functions of optical scintillation are obtained and used to calculate the time-averaging factor. The analytically expected effects of time averaging are verified by the experimental results. The estimations contribute to the link budget design for the optical tracking channel through atmospheric turbulence.


IVORY Guidelines (Instructional Videos in Otorhinolaryngology by YO-IFOS): A Consensus on Surgical Videos in Ear, Nose, and Throat.
Otolaryngology instructional videos available online are often of poor quality. The objective of this article was to establish international consensus recommendations for the production of educational surgical videos in otolaryngology. DELPHI survey. Twenty-seven international respondents participated in this study from 12 countries. Consensus was reached after three rounds of questionnaires following the Delphi methodology. The proposals having reached the 80% agreement threshold in the third round were retained. The main recommendations are as follows: 1) Ethics: patients must be anonymized and unrecognizable (apart from plastic surgery if necessary). A signed authorization must be obtained if the person is recognizable. 2) Technical aspects: videos should be edited and in high-definition (HD) quality if possible. Narration or subtitles and didactic illustrations are recommended. 3) Case presentation: name of pathology and procedure must be specified; the case should be presented with relevant workup. 4) Surgery: surgical procedures should be divided into several distinct stages and include tips and pitfalls. Pathology should be shown if relevant. Key points should be detailed at the end of the procedure. 5) Organ-specific: type of approach and bilateral audiometry should be specified in otology. Coronal plane computed tomography scans should be shown in endonasal surgery. It is recommended to show pre- and postoperative videos in voice surgery and preoperative drawings and photos of scars in plastic surgery, as well as the ventilation method in airway surgery. International recommendations have been determined to assist in the creation and standardization of educational surgical videos in otolaryngology and head and neck surgery. 5 Laryngoscope, 131:E732-E737, 2021.


Molecularly engineered self-assembling membranes for cell-mediated degradation.
The use of peptide engineering to develop self-assembling membranes that are responsive to cellular enzyme activities is reported. The membranes are obtained by combining hyaluronan (HA) and a rationally designed peptide amphiphile (PA) containing a proteolytic domain (GPQGIWGQ octapeptide) sensitive to matrix metalloproteinase-1 (MMP-1). Insertion of an octapeptide in a typical PA structure does not disturb its self-assembly into fibrillar nanostructures neither the ability to form membranes with HA. In vitro enzymatic degradation with hyaluronidase and MMP-1 shows that membranes containing the MMP-1 substrate exhibit enhanced enzymatic degradation, compared with control membranes (absence of MMP-1 cleavable peptide or containing a MMP-1 insensitive sequence), being completely degraded after 7 days. Cell viability and proliferation is minimally affected by the enzymatically cleavable functionality of the membrane, but the presence of MMP-1 cleavable sequence does stimulate the secretion of MMP-1 by fibroblasts and interfere with matrix deposition, particularly the deposition of collagen. By showing cell-responsiveness to biochemical signals presented on self-assembling membranes, this study highlights the ability of modulating certain cellular activities through matrix engineering. This concept can be further explored to understand the cellular remodeling process and as a strategy to develop artificial matrices with more biomimetic degradation for tissue engineering applications.


Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy.
Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-associated myelopathy. Both diseases are usually preceded by a long clinically asymptomatic period. PCR amplification of the HTLV-I proviral integration sites shows that clonal expansion of HTLV-I-bearing T cells, rather than being an occasional phenomenon in nonmalignant disease, is the norm for both symptomatic and asymptomatic carriers. Sequencing of 100 molecular clones derived by PCR amplification of part of the envelope gene from two asymptomatic carriers revealed almost no genetic variation. Viral amplification via clonal expansion, rather than by reverse transcription, would explain this remarkable genetic stability.


More than 1,000 putative new human signalling proteins revealed by EST data mining.
Cloning procedures aided by homology searches of EST databases have accelerated the pace of discovery of new genes, but EST database searching remains an involved and onerous task. More than 1.6 million human EST sequences have been deposited in public databases, making it difficult to identify ESTs that represent new genes. Compounding the problems of scale are difficulties in detection associated with a high sequencing error rate and low sequence similarity between distant homologues. We have developed a new method, coupling BLAST-based searches with a domain identification protocol, that filters candidate homologues. Application of this method in a large-scale analysis of 100 signalling domain families has led to the identification of ESTs representing more than 1,000 novel human signalling genes. The 4,206 publicly available ESTs representing these genes are a valuable resource for rapid cloning of novel human signalling proteins. For example, we were able to identify ESTs of at least 106 new small GTPases, of which 6 are likely to belong to new subfamilies. In some cases, further analyses of genomic DNA led to the discovery of previously unidentified full-length protein sequences. This is exemplified by the in silico cloning (prediction of a gene product sequence using only genomic and EST sequence data) of a new type of GTPase with two catalytic domains.


Sleep habits and diabetes.
Sleep duration has been constantly decreasing over the past 50 years. Short sleep duration, sleep quality and, recently, long sleep duration have all been linked to poor health outcomes, increasing the risk of developing metabolic diseases and cardiovascular events. Beyond the duration of sleep, the timing of sleep may also have consequences. Having a tendency to go early to bed (early chronotype) compared with the habit of going to bed later (late chronotype) can interfere considerably with social schedules (school, work). Eventually, a misalignment arises in sleep timing between work days and free days that has been described as 'social jet lag'. The present review looks at how different sleep habits can interfere with diabetes, excluding sleep breathing disorders, and successively looks at the effects of sleep duration, chronotype and social jet lag on the risk of developing diabetes as well as on the metabolic control of both type 1 and type 2 diabetes. Finally, this review addresses the current state of knowledge of physiological mechanisms that could be linking sleep habits and metabolic health.


Parity-specific fertility intentions and uncertainty: the United States, 1970 to 1976.
A theoretical and analytic model of fertility intentions is proposed which treats "don't know" responses and other uncertain responses as distinct from more firm intentions. Methodologically, these analyses show that "don't know" responses need not be treated as missing data, but instead are both valid and meaningful responses. Furthermore, eliminating these uncertain respondents would have the negative effects of distorting across survey comparisons in intentions due to shifts in aggregate uncertainty, reducing the likelihood of accurately detecting shifts in fertility intentions, and lessening the representatives of the sample analyzed. Substantively, in conjunction with Morgan (1981), these results show that the sharp 1965-76 decline in the likelihood of intending more births at parities 2 through 5 occurred as women halted childbearing at minimal acceptable levels and postponed further childbearing. With time (or age), this delayed fertility became fertility about which the respondent was uncertain and, finally, fertility foregone. Since 1970, similar shifts are observed at parities 0 and 1, perhaps foreshadowing an increase in voluntary childlessness and one-child families.


Three-dimensional direct-write lithography into photopolymer.
We demonstrate a three-dimensional direct-write lithography system capable of writing deeply buried, localized index structures into diffusion-mediated photopolymer. The system is similar to that used for femtosecond writing in glass, but has a number of advantages including greater flexibility in the writing media and the ability to use low power, inexpensive, continuous-wave lasers. This system writes index structures both parallel and perpendicular to the writing beam in different types of photopolymers, providing control over the feature size and shape. We demonstrate that this system can be used to create single-mode waveguides that are deeply embedded in the photopolymer medium.


MicroRNA-493-5p-mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion.
Primary hepatic tumors mainly include hepatocellular carcinoma (HCC), which is one of the most frequent causes of cancer-related deaths worldwide. Thus far, HCC prognosis has remained extremely poor given the lack of effective treatments. Numerous studies have described the roles played by microRNAs (miRNAs) in cancer progression and the potential of these small noncoding RNAs for diagnostic or therapeutic applications. The current consensus supports the idea that direct repression of a wide range of oncogenes by a single key miRNA could critically affect the malignant properties of cancer cells in a synergistic manner. In this study, we aimed to investigate the oncogenes controlled by miR-493-5p, a major tumor suppressor miRNA that inactivates miR-483-3p oncomir in hepatic cancer cells. Using global gene expression analysis, we highlighted a set of candidate genes potentially regulated by miR-493-5p. In particular, the canonical MYCN protooncogene (MYCN) appeared to be an attractive target of miR-493-5p given its significant inhibition through 3'-UTR targeting in miR-493-5p-rescued HCC cells. We showed that MYCN was overexpressed in liver cancer cell lines and clinical samples from HCC patients. Notably, MYCN expression levels were inversely correlated with miR-493-5p in tumor tissues. We confirmed that MYCN knockdown mimicked the anticancer effect of miR-493-5p by inhibiting HCC cell growth and invasion, whereas MYCN rescue hindered miR-493-5p activity. In summary, miR-493-5p is a pivotal miRNA that modulates various oncogenes after its reexpression in liver cancer cells, suggesting that tumor suppressor miRNAs with a large spectrum of action could provide valuable tools for miRNA replacement therapies.


Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya.
Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4-9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2-65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1-19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6-73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population.


Characterisation of internal morphologies in electrospun fibers by X-ray tomographic microscopy.
Electrospun fabrics for use in, for example, tissue engineering, wound dressings, textiles, filters and membranes have attracted a lot of attention due to their morphological nanoscale architectures which enhance their physical properties. A thorough detailed internal morphological study has been performed on electrospun polystyrene (PS) fibers produced from dimethylformamide (DMF) solutions. Investigations by transmission electron microscopy (TEM) and thorough studies for the first time by synchrotron based X-ray tomographic microscopy (XTM) revealed that the individual electrospun PS fibers and beads have a graded density and in some cases even an internal porous structure.


Emerging functional markers for cancer stem cell-based therapies: Understanding signaling networks for targeting metastasis.
Metastasis is one of the most challenging issues in cancer patient management, and effective therapies to specifically target disease progression are missing, emphasizing the urgent need for developing novel anti-metastatic therapeutics. Cancer stem cells (CSCs) gained fast attention as a minor population of highly malignant cells within liquid and solid tumors that are responsible for tumor onset, self-renewal, resistance to radio- and chemotherapies, and evasion of immune surveillance accelerating recurrence and metastasis. Recent progress in the identification of their phenotypic and molecular characteristics and interactions with the tumor microenvironment provides great potential for the development of CSC-based targeted therapies and radical improvement in metastasis prevention and cancer patient prognosis. Here, we report on newly uncovered signaling mechanisms controlling CSC's aggressiveness and treatment resistance, and CSC-specific agents and molecular therapeutics, some of which are currently under investigation in clinical trials, gearing towards decisive functional CSC intrinsic or surface markers. One special research focus rests upon subverted regulatory pathways such as insulin-like growth factor 1 receptor signaling and its interactors in metastasis-initiating cell populations directly related to the gain of stem cell- and EMT-associated properties, as well as key components of the E2F transcription factor network regulating metastatic progression, microenvironmental changes, and chemoresistance. In addition, the study provides insight into systems biology tools to establish complex molecular relationships behind the emergence of aggressive phenotypes from high-throughput data that rely on network-based analysis and their use to investigate immune escape mechanisms or predict clinical outcome-relevant CSC receptor signaling signatures. We further propose that customized vector technologies could drastically enhance systemic drug delivery to target sites, and summarize recent progress and remaining challenges. This review integrates available knowledge on CSC biology, computational modeling approaches, molecular targeting strategies, and delivery techniques to envision future clinical therapies designed to conquer metastasis-initiating cells.


Control analysis of the role of triosephosphate isomerase in glucose metabolism in Lactococcus lactis.
Triosephosphate isomerase (TPI), which catalyses the conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P), was studied for its control on glycolysis and mixed acid production in L. lactis subspecies lactis IL1403 and L. lactis subspecies cremoris MG1363. Strains in which the TPI activity was modulated from 3%-225% (IL1403) or 13%-103% (MG1363) of the wild-type level were constructed by changing the expression of the tpiA gene. The enzyme was found to be present in high excess in the wild-type cells and 10% TPI activity still supported more than 70% of the wild-type glycolytic flux in both strains. Homolactic product formation was preserved throughout the range of TPI activities studied, although a slight increase in the amount of acetate and formate production was observed in the strains with strongly reduced TPI activity for both IL1403 and MG1363. The upstream metabolites glucose-6-phosphate, fructose-1,6-bisphosphate and DHAP in the IL1403 derivatives were essentially unchanged for TPI activities from 26% to 225%. At a TPI activity of 3%, the level of DHAP increased four times. The finding that an increased level of DHAP coincides with an increase in formate production is surprising and indicates that pyruvate formate lyase is not inhibited by DHAP under these conditions.


Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry.
The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma cells were located in a unique position in the correlation of forward light scattering, orthogonal light scattering, and immunofluorescent-labeled CD38. The identity of the sorted cell populations was confirmed by microscopic examination of Wright's stained slides and slides stained for cytoplasmic immunoglobulin using polyclonal antibodies reactive with light chains; ie, anti-kappa fluorescein isothiocyanate and anti lambda phycoerythrin (PE). The purity of the sorted plasma cells was greater than 97% (n = 4). The average frequency of plasma cells in normal bone marrow aspirates was low--0.25% of the nucleated cells (n = 7)--but surprisingly consistent between individuals (SD = .05; range 0.14% to 0.30%). A detailed analysis showed two distinct populations of plasma cells: (1) A population relatively smaller by forward light scattering expressed CD22, CD35, and sigE and was identified as early plasma cells (ie, lymphoplasmacytoid), and (2) a population larger by forward light scattering lacked these markers and was identified as mature plasma cells. The antigenic profile of the normal plasma cells was determined in two-color immunofluorescence studies. The expression of cell surface immunoglobulin G (IgG), IgA, IgE, IgD, IgM, and the cell surface antigens CD10, CD11b, CD13, CD11c, CD14, CD15, CD16, CD19, CD22, CD20, CD33, CD35, CD45, and HLA-DR was determined on the plasma cells. A significant heterogeneity in cell surface antigen expression was observed within the plasma cell population. Unexpectedly, myeloid-specific cell surface antigens such as CD33 and CD13 and the early B-cell antigen identified by CD10 were expressed on a proportion of plasma cells. These observations imply that the association of myeloid and early B-cell markers described in multiple myeloma may not be associated with the neoplasia but is a normal phenomenon.


Contraception: from accessibility to efficiency.
Despite the widespread use of medical contraception in France, the prevalence of abortion remains stable. A cross-sectional population-based survey was designed to study the characteristics of current contraceptive use in France, the different types of contraceptive failure, and the reasons reported for not using contraception. A representative sample of 14 704 French households was randomly selected from the telephone directory. All women who in the last 5 years had had an abortion or whose last pregnancy was unintended were selected (n = 1034), whilst a fraction (n = 1829) of the other women were randomly selected. Altogether, 2863 women answered the questionnaire. Only 2.7% of the women aged 18-44 years who did not wish to conceive and were sexually active did not use any contraception. However, 33% of pregnancies were estimated to be unplanned, of which 50% ended in an abortion. A total of 65% of the reported unplanned pregnancies occurred among women using contraception (21% the pill, 9% IUD, 12% condoms, 23% other method). The main reasons given for these contraceptive failures were the misuse of the methods or the failure of the partner to withdraw. Reasons for not using any contraception go beyond a simple lack of information. The importance of-and the reasons mentioned for-contraceptive failure show a misadaptation between women's contraceptive needs and the method they use. Improving the training of family planning providers remains a major goal to ensure that women use a contraceptive method that fits their social and sexual lifestyle.


Comparison of the Self-Adjusting File and Hedström File Used as Supplementary Instruments for the Remaining Filling Material Removal During Retreatment of C-Shaped Canals: A Micro-CT Study.
The aim of this study was to evaluate the use of Self-adjusting file (SAF) system and Hedström (H) file for removing remaining filling material (RFM) from C-shaped canals. 20 C-shaped mandibular second molars with C1 configurations were instrumented, filled with tagger´s hybrid technique. Samples were divided into 2 groups (n=10). Reciproc R25 and a Mtwo 35/04 file were used for retreatment in both groups. Then, a 2.0 SAF file (group I) and a #35 H file (group II) were used as supplementary steps for RFM removal. Micro-CT scanning was performed after every procedure. Total volumes were calculated and converted into percentages. Also, the minimum wall thickness at 3, 5, 7 mm from apex was calculated. The Prism 7.0 software was used as the analytical tool with a significance of 5%. Initial obturation removal was approximately 64% in group I and 67% in Group II. The apical third had the highest values of RFM. The use of a H file significantly reduced the RFM compared to SAF in the total canal length respectively (30% vs 18%) and at 1-3 mm and 3-6 mm when compared to the use of SAF. A statistically significant decrease of RFM and minimum wall thickness were observed in both groups (P<0.05). None of the retreatment techniques completely removed RFM. The apical region was the more unaffected area. Also, the SAF file was less effective than the H file in removing the RFM. Although C-shaped canals possesses thinner dentinal wall thickness, no excessive dentine removal was observed after each instrument use.


Applying an integrated refuge to manage western corn rootworm (Coleoptera: Chrysomelidae): effects on survival, fitness, and selection pressure.
The refuge strategy can delay resistance of insect pests to transgenic maize producing toxins from Bacillus thuringiensis (Bt). This is important for the western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), because of its history of adaptation to several management practices. A 2-yr study across four locations was conducted to measure the effects of integrated refuge (i.e., blended refuge) on western corn rootworm survival to adulthood, fitness characteristics, and susceptibility to Bt maize in the subsequent generation. The treatments tested in this study were as follows: a pure stand of Bt maize (event DAS-59122-7, which produces Bt toxins Cry34Ab1/Cry35Ab1), a pure stand of refuge (non-Bt maize), and two variations on an integrated refuge consisting of 94.4% Bt maize and 5.6% non-Bt maize. Within the two integrated refuge treatments, refuge seeds received a neonicotinoid insecticidal seed treatment of either 1.25 mg clothianidin per kernel or 0.25 mg thiamethoxam per kernel. Insects in the pure stand refuge treatment had greater survival to adulthood and earlier emergence than in all other treatments. Although fecundity, longevity, and head capsule width were reduced in treatments containing Bt maize for some site by year combinations, Bt maize did not have a significant effect on these factors when testing data across all sites and years. We found no differences in susceptibility of larval progeny to Bt maize in bioassays using progeny of adults collected from the four treatments.


Increased immune infiltration and chemokine receptor expression in head and neck epithelial tumors after neoadjuvant immunotherapy with the IRX-2 regimen.
IRX-2 is an injectable cancer immunotherapy composed of cytokines purified from stimulated normal-donor peripheral blood mononuclear cells. In a phase 2a trial (n = 27), neoadjuvant IRX-2 significantly increased lymphocyte infiltration (LI) into resected head and neck tumors and was associated with changes in fibrosis and necrosis. Event-free survival was 65% at 2 years, and overall survival 65% at 5 years. Overall survival was longer for patients with LI greater versus lower than the median. This substudy of the mechanisms responsible for the increase in LI with neoadjuvant IRX-2 employed multiplex immunohistochemistry (IHC) and transcriptome analysis to interrogate matched pre- and post-treatment tumor specimens from 7 available phase 2a trial patients. Multiplex IHC showed substantial increases in CD68-expressing cells (5 patients), T-cell density (4 patients), and PDL1 mean fluorescent intensity (4 patients). Consistent with IRX-2 activation of multiple immune cells, transcriptome analysis showed mean increases in expression of genes associated with NK cells, B cells, CD4+ T cells, CD8+ T cells, and dendritic cells, but not of genes associated with neutrophils. There were increases in mean expression of genes for most immune subsets, most markedly (2- to 3-fold) for B cells and dendritic cells. Mean increases in gene expression for chemokines suggest that tumor LI may be driven in part by IRX-2-induced production of chemo-attractants. Upregulation of checkpoint genes including PDL1 and CTLA4 along with increased T-cell infiltration suggests a functional antitumor immune response such that the efficacy of IRX-2 may be enhanced by combination with immune checkpoint inhibitors.


Vitamin C in human health and disease is still a mystery? An overview.
Ascorbic acid is one of the important water soluble vitamins. It is essential for collagen, carnitine and neurotransmitters biosynthesis. Most plants and animals synthesize ascorbic acid for their own requirement. However, apes and humans can not synthesize ascorbic acid due to lack of an enzyme gulonolactone oxidase. Hence, ascorbic acid has to be supplemented mainly through fruits, vegetables and tablets. The current US recommended daily allowance (RDA) for ascorbic acid ranges between 100-120 mg/per day for adults. Many health benefits have been attributed to ascorbic acid such as antioxidant, anti-atherogenic, anti-carcinogenic, immunomodulator and prevents cold etc. However, lately the health benefits of ascorbic acid has been the subject of debate and controversies viz., Danger of mega doses of ascorbic acid? Does ascorbic acid act as a antioxidant or pro-oxidant? Does ascorbic acid cause cancer or may interfere with cancer therapy? However, the Panel on dietary antioxidants and related compounds stated that the in vivo data do not clearly show a relationship between excess ascorbic acid intake and kidney stone formation, pro-oxidant effects, excess iron absorption. A number of clinical and epidemiological studies on anti-carcinogenic effects of ascorbic acid in humans did not show any conclusive beneficial effects on various types of cancer except gastric cancer. Recently, a few derivatives of ascorbic acid were tested on cancer cells, among them ascorbic acid esters showed promising anticancer activity compared to ascorbic acid. Ascorbyl stearate was found to inhibit proliferation of human cancer cells by interfering with cell cycle progression, induced apoptosis by modulation of signal transduction pathways. However, more mechanistic and human in vivo studies are needed to understand and elucidate the molecular mechanism underlying the anti-carcinogenic property of ascorbic acid. Thus, though ascorbic acid was discovered in 17th century, the exact role of this vitamin/nutraceutical in human biology and health is still a mystery in view of many beneficial claims and controversies.


Southern Blight of Jerusalem Artichoke Caused by Sclerotium rolfsii in California.
Jerusalem artichoke or sunchoke (Helianthus tuberosus) is a specialty vegetable that is grown commercially in California. The fleshy tubers are harvested and used as a fresh salad ingredient or cooked vegetable. During 2003, field plantings of Jerusalem artichoke in coastal California (Santa Cruz County) showed symptoms of an unfamiliar disease. Initial symptoms consisted of wilting of new shoots and leaves followed by browning and collapse of all foliage. Crown and lower stem tissues turned tan to brown. In advanced stages of the disease, crown and stem tissues were colonized internally and externally by white, cottony mycelium. Tan, spherical sclerotia that measured approximately 1 mm in diameter formed on the surfaces of the affected crowns and stems. Mycelia and sclerotia also grew on the soil adjacent to infected plants. Isolations from symptomatic crowns, mycelia, and sclerotia produced colonies that were identified as Sclerotium rolfsii. Pathogenicity was tested using two methods that included sclerotial inocula collected from five isolates grown on potato dextrose agar plates. With the first method, sclerotia of each isolate were applied to sets of tubers (10 tubers per isolate) prior to planting tubers into a soilless, peat moss-based medium in pots. With the second method, 3-week-old potted plants were inoculated by placing sclerotia of each isolate adjacent to stem tissue that was 3 cm below the surface of the soilless medium. Noninoculated controls were included for both methods. All plants were incubated in a greenhouse at 21 to 24°C. For the first method, by the third week after planting, 10 to 40% of plants did not emerge because the tubers were rotted and decayed. For the plants that did emerge, wilting of foliage and browning of crown and stem tissue occurred approximately 6 weeks after planting and by 10 weeks, all plants were diseased. S. rolfsii was reisolated from all necrotic tuber, crown, and stem tissues. For the second method, disease symptoms and signs of the pathogen occurred 5 weeks after inoculation and by week 10, 75% of test plants were symptomatic. S. rolfsii was again reisolated from all necrotic tuber, crown, and stem tissues. Symptoms were not observed on any of the noninoculated plants. To my knowledge, this is the first report of southern blight of Jerusalem artichoke in California. This disease has been reported on Jerusalem artichoke in several southern U.S. states (1,2). The two inoculation methods demonstrated that the pathogen could infect propagation organs (tubers) and also emergent stems of this host. References: (1) D. F. Farr et al. Fungi on Plants and Plant Products in the United States. The American Phytopathological Society, St. Paul, MN, 1989. (2) S. M. McCarter and S. J. Kays. Plant Dis. 68:299, 1984.


Reproductive interference between honeybee species in artificial sympatry.
Reproductive isolation between closely related species is often incomplete. The Western honeybee, Apis mellifera, and the Eastern hive bee, Apis cerana, have been allopatric for millions of years, but are nonetheless similar in morphology and behaviour. During the last century, the two species were brought into contact anthropogenically, providing potential opportunities for interspecific matings. Hybrids between A. mellifera and A. cerana are inviable, so natural interspecific matings are of concern because they may reduce the viability of A. cerana and A. mellifera populations - two of the world's most important pollinators. We examined the mating behaviour of A. mellifera and A. cerana queens and drones from Caoba Basin, China and Cairns, Australia. Drone mating flight times overlap in both areas. Analysis of the spermathecal contents of queens with species-specific genetic markers indicated that in Caoba Basin, 14% of A. mellifera queens mated with at least one A. cerana male, but we detected no A. cerana queens that had mated with A. mellifera males. Similarly, in Cairns, no A. cerana queens carried A. mellifera sperm, but one-third of A. mellifera queens had mated with at least one A. cerana male. No hybrid embryos were detected in eggs laid by interspecifically mated A. mellifera queens in either location. However, A. mellifera queens artificially inseminated with A. cerana sperm produced inviable hybrid eggs or unfertilized drones. This suggests that reproductive interference will impact the viability of honeybee populations wherever A. cerana and A. mellifera are in contact.


A unique case of a patient with partial trisomy 22 and lipodystrophy: is it a new syndrome due to an IGF-IR mutation?
A newborn male presented with intestinal malrotation, facial anomalies, hypertrichosis, hypertrophic, hyperpigmented nipples and enlarged genitals with a hyperpigmented scrotum. In addition, the patient displayed a marked lipodystrophy of trunk and limbs. His karyotype demonstrated a small supernumerary NOR-positive marker chromosome that was subsequently identified as del(22)(q12->qter). This extra structurally abnormal chromosome probably derives from a maternal balanced translocation, which was found by karyotype analysis of the mother. The patient's growth hormone (GH) serum levels were elevated, whereas serum insulin-like growth factor 1 (IGF-I) was almost undetectable. Molecular genetic analysis of the IGF-I and type 1 IGF receptor (IGF-IR) genes revealed a heterozygous mutation within exon 21 of the IGF-IR (Pro1257Ser). Findings in our patient correlate to a large extent with partial trisomy 22. Phenotypic variation from classical partial trisomy 22 syndrome may lie within the variability of this syndrome, originate from disturbances within the GH-IGF/IGF-IR axis or, alternatively, reflect the pathogenesis of a new syndrome due to the synergistical impact of the combination of the genetic aberrations. Additional studies are necessary to confirm or refute this hypothesis.


Quantification of heterogeneity as a biomarker in tumor imaging: a systematic review.
Many techniques are proposed for the quantification of tumor heterogeneity as an imaging biomarker for differentiation between tumor types, tumor grading, response monitoring and outcome prediction. However, in clinical practice these methods are barely used. This study evaluates the reported performance of the described methods and identifies barriers to their implementation in clinical practice. The Ovid, Embase, and Cochrane Central databases were searched up to 20 September 2013. Heterogeneity analysis methods were classified into four categories, i.e., non-spatial methods (NSM), spatial grey level methods (SGLM), fractal analysis (FA) methods, and filters and transforms (F&T). The performance of the different methods was compared. Of the 7351 potentially relevant publications, 209 were included. Of these studies, 58% reported the use of NSM, 49% SGLM, 10% FA, and 28% F&T. Differentiation between tumor types, tumor grading and/or outcome prediction was the goal in 87% of the studies. Overall, the reported area under the curve (AUC) ranged from 0.5 to 1 (median 0.87). No relation was found between the performance and the quantification methods used, or between the performance and the imaging modality. A negative correlation was found between the tumor-feature ratio and the AUC, which is presumably caused by overfitting in small datasets. Cross-validation was reported in 63% of the classification studies. Retrospective analyses were conducted in 57% of the studies without a clear description. In a research setting, heterogeneity quantification methods can differentiate between tumor types, grade tumors, and predict outcome and monitor treatment effects. To translate these methods to clinical practice, more prospective studies are required that use external datasets for validation: these datasets should be made available to the community to facilitate the development of new and improved methods.


Effect of advanced access scheduling on chronic health care in a Canadian practice.
To determine the effect of advanced access scheduling (AAS) on the care of patients with chronic disease within a Canadian family practice. Chart abstraction. A single family physician's practice in Brantford, Ont. Patient charts were reviewed for all patients with a history of hypertension, type 2 diabetes mellitus, or coronary artery disease during the years before and after implementation of AAS. The following information was extracted for each study patient: total number of appointments, number of appointments specific to chronic disease management, number of appointments for non-chronic disease, blood pressure (BP), and laboratory markers, including hemoglobin A(1c) (HbA(1c)) and low-density lipoprotein levels. For the year before and the year after implementation of AAS, the mean number of visits per patient was 4.3. The mean number of appointments for chronic disease management decreased significantly from 2.6 to 2.2 (P = .024), and the mean number of visits for non-chronic disease increased significantly from 1.7 to 2.1 (P = .001). The number of times clinical parameters of BP, HbA(1c), and low-density lipoprotein were measured decreased; however, there were no significant changes in actual BP or HbA(1c) levels. Following a 1-year period using AAS, use of the family health practice by patients with chronic disease was unchanged overall; however, AAS allowed for an increase in visits for non-chronic health conditions without significantly affecting the clinical parameters of BP or HbA(1c).


Expression of the human endogenous retrovirus HERV-W family in various human tissues and cancer cells.
We examined the structural genes (gag, pol and env) of the human endogenous retrovirus (HERV-W) family from 12 normal human tissues and 18 human cancer cell lines using RT-PCR. For the gag and pol genes, their expression patterns showed tissue or cell specificity, depending on the samples, whereas the env gene was expressed in all tissues and cancer cells examined. To identify active HERV-W elements in tissues and cancer cells, the RT-PCR products were cloned and sequenced. Ninety-five clones for the env gene, 55 clones for the pol gene and 17 clones for the gag gene of the HERV-W family were isolated from human tissues and sequenced, while 85 clones for the env gene, 61 clones for the pol gene and no clones for the gag gene of the HERV-W family were isolated and sequenced from cancer cells. Among these clones, 50 clones from tissues and 44 from cancer cells showed putative amino acids of the HERV-W env gene, while only two clones from cancer cells showed putative amino acids of the HERV-W pol gene. Phylogenetic analysis indicated that several clones identified previously from human monochromosomes had sister relationships with the clones from the different tissues and cancer cells. These data suggest that HERV-W elements are actively expressed in human tissues and cancer cells. These active HERV-W elements deserve further investigation as potential causative agents of various human diseases including cancers.


Vitamin A for preventing secondary infections in children with measles--a systematic review.
The objective of the present study was to determine whether vitamin A prevents pneumonia, diarrhoea and other infections in children with measles. A meta-analysis was carried out of randomized controlled trials identified through a systematic search of the medical literature for studies that used vitamin A to treat measles. A total of 492 children, aged from 6 months to 13 years, were supplemented with vitamin A, and 536 children were given placebo in six trials, five of which were conducted in hospitals and one in a community setting. The main outcome measures were: incidence of pneumonia, diarrhoea, croup, and otitis media; and duration of pneumonia, diarrhoea, fever and hospitalization. There was no significant reduction in the incidence of pneumonia or diarrhoea but there was a 47 per cent reduction in the incidence of croup (RR = 0.53; 95 per cent CI = 0.29-0.89) in children who were treated with 200 000 IU of vitamin A on 2 consecutive days. Only one study reported a 74 per cent reduction in the incidence of otitis media (RR = 0.26 95 per cent CI = 0.05-0.92). There was a statistically significant decrease in the duration of diarrhoea, pneumonia, hospital stay and fever in individual studies. It was concluded that vitamin A does have a beneficial effect on morbidity associated with measles and should be used as a treatment for hospitalized measles cases.


Simulation of ionisation clusters formed in nanometric volumes of the deoxyribose-substitute tetrahydrofuran.
To investigate the implications of using interaction cross sections of liquid water for the target volume when studying radiation action at the DNA level by particle track structure simulations. Absolute interaction cross sections for low energy electrons between 20 eV and 1 keV were measured for tetrahydrofuran (THF), which is a substitute for deoxyribose. From these data a complete interaction cross section data set was derived and integrated in our PTB Track structure Monte Carlo code 'PTra'. Simulations of electron track structure in THF and water were performed and ionisation cluster size distributions in nanometric target volumes were determined. From these a nanodosimetric estimate for the probability to produce a double strand break was derived. The probability distribution of ionisation cluster sizes was found to be shifted towards smaller values for a THF-filled target as compared to a water-filled one. For all electron energies investigated, the nanodosimetric estimates for double-strand break probability in the THF-filled target have lower values than for a target of liquid water. The preliminary results indicate that simulations based on cross sections of water would overestimate the initial direct radiation damage to the DNA.


Anticipatory reproduction and population growth in seed predators.
Mast seeding, the intermittent, synchronous production of large seed crops by a population of plants, is a well-known example of resource pulses that create lagged responses in successive trophic levels of ecological communities. These lags arise because seed predators are thought capable of increasing reproduction and population size only after the resource pulse is available for consumption. The resulting satiation of predators is a widely cited explanation for the evolution of masting. Our study shows that both American and Eurasian tree squirrels anticipate resource pulses and increase reproductive output before a masting event, thereby increasing population size in synchrony with the resource pulse and eliminating the population lag thought to be universal in resource pulse systems.


Addressing resource allocation issues in recommendations from clinical practice guideline panels: suggestions from an American College of Chest Physicians task force.
Most panels that develop clinical practice guidelines are poorly equipped to address resource allocation or cost issues associated with management options. This risks neglect, arbitrariness, lack of transparency, and methodological flaws in consideration of resource allocation. We provide recommendations for guideline panels to promote greater transparency and rigor. We suggest focusing on resource allocation issues for only a limited number of recommendations and provide criteria for selecting those in which economic considerations are likely to influence the direction or strength of the recommendation. Panels should involve a health economist to assist with the systematic review and critical interpretation of relevant economic analyses. They should carefully define the intended audience and may consider issuing alternative recommendations when available resources vary widely across target clinical settings. Targeting a limited number of recommendations for the consideration of resource allocation issues, and ensuring methodologically high-quality review, will best serve guideline panels, and the health-care providers and patients they hope to assist.


Nucleosome Stability Distinguishes Two Different Promoter Types at All Protein-Coding Genes in Yeast.
Previous studies indicate that eukaryotic promoters display a stereotypical chromatin landscape characterized by a well-positioned +1 nucleosome near the transcription start site and an upstream -1 nucleosome that together demarcate a nucleosome-free (or -depleted) region. Here we present evidence that there are two distinct types of promoters distinguished by the resistance of the -1 nucleosome to micrococcal nuclease digestion. These different architectures are characterized by two sequence motifs that are broadly deployed at one set of promoters where a nuclease-sensitive ("fragile") nucleosome forms, but concentrated in a narrower, nucleosome-free region at all other promoters. The RSC nucleosome remodeler acts through the motifs to establish stable +1 and -1 nucleosome positions, while binding of a small set of general regulatory (pioneer) factors at fragile nucleosome promoters plays a key role in their destabilization. We propose that the fragile nucleosome promoter architecture is adapted for regulation of highly expressed, growth-related genes.


Insulinoma induced hypoglycaemia in a Jamaican patient.
Herein reported is the case of a young woman who had hyperinsulinaemic hypoglycaemia which was biochemically consistent with an insulinoma. Initial imaging was negative and definitive treatment was delayed until repeat imaging localized the tumour several years later. This case demonstrates the importance of clinical judgment and biochemical testing in the diagnosis of insulinoma despite negative imaging.


Rupture of GORE-TEX neochordae 10 years after mitral valve repair.
The current non-resectional paradigm in mitral valve (MV) repair emphasizes the use of polytetrafluoroethylene (PTFE) for artificial chordal replacement. While excellent long-term durability of repair using PTFE neochordae has been established, there have been rare reports of neochordal rupture at various times after surgery. We report a case of artificial chordal rupture 10 years after anterior mitral leaflet repair, necessitating reoperation. This complication may have been precipitated by maldistributed intracardiac tensile forces as a consequence of a malpositioned annuloplasty band.


RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8⁺ T cells.
Dying cells initiate adaptive immunity by providing both antigens and inflammatory stimuli for dendritic cells, which in turn activate CD8(+) T cells through a process called antigen cross-priming. To define how different forms of programmed cell death influence immunity, we established models of necroptosis and apoptosis, in which dying cells are generated by receptor-interacting protein kinase-3 and caspase-8 dimerization, respectively. We found that the release of inflammatory mediators, such as damage-associated molecular patterns, by dying cells was not sufficient for CD8(+) T cell cross-priming. Instead, robust cross-priming required receptor-interacting protein kinase-1 (RIPK1) signaling and nuclear factor κB (NF-κB)-induced transcription within dying cells. Decoupling NF-κB signaling from necroptosis or inflammatory apoptosis reduced priming efficiency and tumor immunity. Our results reveal that coordinated inflammatory and cell death signaling pathways within dying cells orchestrate adaptive immunity.


Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort.
A genome-wide, whole brain approach to investigate genetic effects on neuroimaging phenotypes for identifying quantitative trait loci is described. The Alzheimer's Disease Neuroimaging Initiative 1.5 T MRI and genetic dataset was investigated using voxel-based morphometry (VBM) and FreeSurfer parcellation followed by genome-wide association studies (GWAS). One hundred forty-two measures of grey matter (GM) density, volume, and cortical thickness were extracted from baseline scans. GWAS, using PLINK, were performed on each phenotype using quality-controlled genotype and scan data including 530,992 of 620,903 single nucleotide polymorphisms (SNPs) and 733 of 818 participants (175 AD, 354 amnestic mild cognitive impairment, MCI, and 204 healthy controls, HC). Hierarchical clustering and heat maps were used to analyze the GWAS results and associations are reported at two significance thresholds (p<10(-7) and p<10(-6)). As expected, SNPs in the APOE and TOMM40 genes were confirmed as markers strongly associated with multiple brain regions. Other top SNPs were proximal to the EPHA4, TP63 and NXPH1 genes. Detailed image analyses of rs6463843 (flanking NXPH1) revealed reduced global and regional GM density across diagnostic groups in TT relative to GG homozygotes. Interaction analysis indicated that AD patients homozygous for the T allele showed differential vulnerability to right hippocampal GM density loss. NXPH1 codes for a protein implicated in promotion of adhesion between dendrites and axons, a key factor in synaptic integrity, the loss of which is a hallmark of AD. A genome-wide, whole brain search strategy has the potential to reveal novel candidate genes and loci warranting further investigation and replication.


Genetic and molecular analysis of vgU and vgW: two dominant vg alleles associated with gene fusions in Drosophila.
In the absence of a vg+ gene, extensive cell death occurs in third instar imaginal discs, which results in a complete loss of adult wing margin structures. Essentially all molecularly characterized vg alleles are associated with deletions or insertions of DNA into the vg locus. These alterations reduce or eliminate a 3.8-kb vg-specific transcript, resulting in recessive loss of function alleles. We report here the analysis of two dominant vg alleles which have been identified (vgU and vgW). The vgU allele is associated with a chromosomal inversion which splits the vg locus, resulting in a gene fusion between vg and the mastermind (mam) neurogenic locus. Reversion analysis of vgU indicates that sequences from the mam locus are required for vgU dominance. The vgW allele is also the result of a chromosomal inversion, in this case resulting in a gene fusion between vg and the homeobox-containing invected (inv) gene. It is also associated with novel dominant homeotic transformations. Revertant analysis indicates that sequences from inv are required for the dominant wing and dominant homeotic effects of vgW. The vg dominance does not appear to be mediated through a reduction of vg expression or a novel fusion transcript in either vgU or vgW. The results are consistent with a model in which inappropriate expression of inv causes the dominant homeotic effects seen in vgW.


Effect of the introduction of minimum lesion size on interobserver reproducibility using RECIST guidelines in non-small cell lung cancer patients.
We evaluated interobserver reproducibility for the response evaluation criteria in solid tumors (RECIST) guidelines and the influence of minimum lesion size (MLS) on reproducibility. The 110 consecutive patients with non-small cell lung cancer were treated with platinum-based chemotherapy. Five observers measured target lesions according to both the World Health Organization (WHO) criteria and RECIST. The percentage changes for unidimensional measurements (UD; RECIST type) and bidimensional measurements (BD; WHO type) were calculated for each patient. Interobserver reproducibility among five observers, that is 10 pairs, was expressed as the Spearman's correlation coefficient for the percentage changes, the proportion of agreement and the kappa statistics for response categories. The same analysis was carried out using MLS. BD was more reproducible than UD (Spearman rank correlation coefficient, 0.84 vs 0.81; proportion of agreement, 84.4% vs 82.5%; kappa value, 0.69 vs 0.61). When MLS was applied to UD, eligible cases decreased by 6.4% and the number of target lesions by 44.6%, whereas interobserver reproducibility for UD improved (Spearman rank correlation coefficient, 0.81-0.84; proportion of agreement, 82.5-84.2%; kappa value, 0.61-0.65). The introduction of MLS to UD could also improve intercriteria reproducibility between WHO and RECIST. It is important to apply the MLS when using RECIST for the comparable interobserver reproducibility attained with WHO.


Treatment of adult thoracolumbar spinal deformity: past, present, and future.
Care of the patient with adult spinal deformity (ASD) has evolved from being primarily supportive to now having the ability to directly treat and correct the spinal pathology. The focus of this narrative literature review is to briefly summarize the history of ASD treatment, discuss the current state of the art of ASD care with focus on surgical treatment and current challenges, and conclude with a discussion of potential developments related to ASD surgery.In the past, care for ASD was primarily based on supportive measures, including braces and assistive devices, with few options for surgical treatments that were often deemed high risk and reserved for rare situations. Advances in anesthetic and critical care, surgical techniques, and instrumentation now enable almost routine surgery for many patients with ASD. Despite the advances, there are many remaining challenges currently impacting the care of ASD patients, including increasing numbers of elderly patients with greater comorbidities, high complication and reoperation rates, and high procedure cost without clearly demonstrated cost-effectiveness based on standard criteria. In addition, there remains considerable variability across multiple aspects of ASD surgery. For example, there is currently very limited ability to provide preoperative individualized counseling regarding optimal treatment approaches (e.g., operative vs nonoperative), complication risks with surgery, durability of surgery, and likelihood of achieving individualized patient goals and satisfaction. Despite the challenges associated with the current state-of-the-art ASD treatment, surgery continues to be a primary option, as multiple reports have demonstrated the potential for surgery to significantly improve pain and disability. The future of ASD care will likely include techniques and technologies to markedly reduce complication rates, including greater use of navigation and robotics, and a shift toward individualized medicine that enables improved counseling, preoperative planning, procedure safety, and patient satisfaction.Advances in the care of ASD patients have been remarkable over the past few decades. The current state of the art enables almost routine surgical treatment for many types of ASD that have the potential to significantly improve pain and disability. However, significant challenges remain, including high complication rates, lack of demonstrated cost-effectiveness, and limited ability to meaningfully counsel patients preoperatively on an individual basis. The future of ASD surgery will require continued improvement of predictability, safety, and sustainability.


Electrically pumped silicon waveguide light sources.
We report simulations of electrically pumped waveguide emitters in which the emissive layer contains silicon nanoclusters and erbium ions. Plasmonic coupling to metallic or semi-metallic overlayers provides enhancement of the radiative rate of erbium ions, enabling high quantum efficiency emission. Using 2D and 3D finite difference time domain (FDTD) simulations we show that up to 75% of the light emitted from the active layer can be coupled into a nanowire silicon rib waveguide. Our results suggest that such devices, which can readily be fabricated using CMOS processing techniques, pave the way for viable waveguide optical sources to be realized in silicon photonics.


Applicability of Low-intensity Vibrations as a Regulatory Factor on Stem and Progenitor Cell Populations.
Persistent and transient mechanical loads can act as biological signals on all levels of an organism. It is therefore not surprising that most cell types can sense and respond to mechanical loads, similar to their interaction with biochemical and electrical signals. The presence or absence of mechanical forces can be an important determinant of form, function and health of many tissue types. Along with naturally occurring mechanical loads, it is possible to manipulate and apply external physical loads on tissues in biomedical sciences, either for prevention or treatment of catabolism related to many factors, including aging, paralysis, sedentary lifestyles and spaceflight. Mechanical loads consist of many components in their applied signal form such as magnitude, frequency, duration and intervals. Even though high magnitude mechanical loads with low frequencies (e.g. running or weight lifting) induce anabolism in musculoskeletal tissues, their applicability as anabolic agents is limited because of the required compliance and physical health of the target population. On the other hand, it is possible to use low magnitude and high frequency (e.g. in a vibratory form) mechanical loads for anabolism as well. Cells, including stem cells of the musculoskeletal tissue, are sensitive to high frequency, lowintensity mechanical signals. This sensitivity can be utilized not only for the targeted treatment of tissues, but also for stem cell expansion, differentiation and biomaterial interaction in tissue engineering applications. In this review, we reported recent advances in the application of low-intensity vibrations on stem and progenitor cell populations. Modulation of cellular behavior with low-intensity vibrations as an alternative or complementary factor to biochemical and scaffold induced signals may represent an increase of capabilities in studies related to tissue engineering.


Kin Recognition in a Clonal Fish, Poecilia formosa.
Relatedness strongly influences social behaviors in a wide variety of species. For most species, the highest typical degree of relatedness is between full siblings with 50% shared genes. However, this is poorly understood in species with unusually high relatedness between individuals: clonal organisms. Although there has been some investigation into clonal invertebrates and yeast, nothing is known about kin selection in clonal vertebrates. We show that a clonal fish, the Amazon molly (Poecilia formosa), can distinguish between different clonal lineages, associating with genetically identical, sister clones, and use multiple sensory modalities. Also, they scale their aggressive behaviors according to the relatedness to other females: they are more aggressive to non-related clones. Our results demonstrate that even in species with very small genetic differences between individuals, kin recognition can be adaptive. Their discriminatory abilities and regulation of costly behaviors provides a powerful example of natural selection in species with limited genetic diversity.


Crohn's disease: value of diagnostic imaging in the evaluation of anastomotic recurrence.
In patients who had previously undergone ileocolic resection due to Crohn's disease (CD) complications, anastomotic recurrence is a frequent event, which may lead to further surgical interventions. Optical colonoscopy with retrograde ileoscopy is currently the reference standard technique to confirm the clinical suspicion of anastomotic recurrence; however, the ileal side of ileocolic anastomoses may not be assessed due to technical complexities in approximately 1/3 of cases. Moreover, endoscopy allows for an investigation limited to the mucosal surface without demonstrating trans-mural involvement and/or penetrating complications (i.e. fistulas and abscesses). Imaging plays an important role in the assessment of both ileocolic and entero-enteric anastomoses in patients with CD. Conventional radiological methods (i.e. small bowel enteroclysis and small bowel follow through) can effectively depict the presence of aphthous ulcers and other mild and subtle mucosal abnormalities, but they are not precise for the diagnosis of transmural and extramural disease. CT - and MR- enterography accurately demonstrate both the extent of bowel wall involvement and the presence of penetrating complications. The main cross-sectional imaging findings observed in CD (including anastomotic recurrence) are small bowel wall thickening with bilaminar or trilaminar stratification, hyperdensity and oedema of the mesenteric fat, engorged mesenteric vasa recta ("comb sign"), sub-mucosal fibro-fatty infiltration and mesenteric adenopathy. Ultrasonography performed after distension of small bowel loops with anechoic contrast agents (Small Intestine Contrast Ultrasonography - SICUS -) is a non-invasive imaging technique which can detect early inflammatory alterations of the anastomosis. On the other hand ultrasonography is an operator-dependent technique and it lacks of a large anatomic field of view. Computed Tomography enterography, Crohn's disease, Ileocolic anastomosis, Magnetic Resonance Imaging.


Adhesion Properties of Freestanding Hydrophobin Bilayers.
Hydrophobins are a family of small-sized proteins featuring a distinct hydrophobic patch on the protein's surface, rendering them amphiphilic. This particularity allows hydrophobins to self-assemble into monolayers at any hydrophilic/hydrophobic interface. Moreover, stable pure protein bilayers can be created from two interfacial hydrophobin monolayers by contacting either their hydrophobic or their hydrophilic sides. In this study, this is achieved via a microfluidic approach, in which also the bilayers' adhesion energy can be determined. This enables us to study the origin of the adhesion of hydrophobic and hydrophilic core bilayers made from the class II hydrophobins HFBI and HFBII. Using different fluid media in this setup and introducing genetically modified variants of the HFBI molecule, the different force contributions to the adhesion of the bilayer sheets are studied. It was found that in the hydrophilic contact situation, the adhesive interaction was higher than that in the hydrophobic contact situation and could be even enhanced by reducing the contributions of electrostatic interactions. This effect indicates that the van der Waals interaction is the dominant contribution that explains the stability of the observed bilayers.


Parietal rTMS disrupts the initiation but not the execution of on-line adjustments to a perturbation of object size.
Previous studies have implicated the human parietal lobes in the on-line guidance of action. However, no study to date has examined at what stage in the on-line adjustment process do the parietal lobes play their most critical role. Repetitive transcranial magnetic stimulation (rTMS) was applied over the left intraparietal sulcus as participants reached to grasp a small or large illuminated cylinder. On some trials, the illumination could suddenly switch from the small to large cylinder, or vice-versa. Small-Large switches were associated with relatively early grip aperture adjustments, whereas Large-Small switches were associated with relatively late grip aperture adjustments. When rTMS was applied early in the movement, it disrupted on-line adjustments to Small-Large target switches, but not to Large-Small switches. Conversely, when rTMS was applied late in the movement, it disrupted adjustments to Large-Small target switches but not to Small-Large switches. The timing of the disruption by rTMS appeared linked to the initiation of the adjustment. It was concluded that the left parietal lobe plays a critical role in initiating an on-line adjustment to a change in target size, but not in executing that adjustment. The implications of these results for current views of on-line control are discussed.


Genome-scale comparison and constraint-based metabolic reconstruction of the facultative anaerobic Fe(III)-reducer Rhodoferax ferrireducens.
Rhodoferax ferrireducens is a metabolically versatile, Fe(III)-reducing, subsurface microorganism that is likely to play an important role in the carbon and metal cycles in the subsurface. It also has the unique ability to convert sugars to electricity, oxidizing the sugars to carbon dioxide with quantitative electron transfer to graphite electrodes in microbial fuel cells. In order to expand our limited knowledge about R. ferrireducens, the complete genome sequence of this organism was further annotated and then the physiology of R. ferrireducens was investigated with a constraint-based, genome-scale in silico metabolic model and laboratory studies. The iterative modeling and experimental approach unveiled exciting, previously unknown physiological features, including an expanded range of substrates that support growth, such as cellobiose and citrate, and provided additional insights into important features such as the stoichiometry of the electron transport chain and the ability to grow via fumarate dismutation. Further analysis explained why R. ferrireducens is unable to grow via photosynthesis or fermentation of sugars like other members of this genus and uncovered novel genes for benzoate metabolism. The genome also revealed that R. ferrireducens is well-adapted for growth in the subsurface because it appears to be capable of dealing with a number of environmental insults, including heavy metals, aromatic compounds, nutrient limitation and oxidative stress. This study demonstrates that combining genome-scale modeling with the annotation of a new genome sequence can guide experimental studies and accelerate the understanding of the physiology of under-studied yet environmentally relevant microorganisms.


Socioeconomic Inequality in Mortality from Road Traffic Accident in Iran.
Although the epidemiology of road traffic accidents (RTAs) and their determining factors have been extensively investigated and debated in Iran, yet there is no data regarding socioeconomic inequalities in mortality from RTA in Iranian context. Since effective interventions to control, management and diminish the negative influence of RTAs would require understanding of numerous contributing factors, including the inequalities We aimed to quantify for the first time the socioeconomic differential in mortality or injuries from RTAs. A cross-sectional study. Overall, 50755 died and injured people from RTA from Mar 2015 to Feb 2016 were evaluated. The data were taken from traffic police department in Iran. We calculated concentration index (CI) to measure socioeconomic inequality in traffic-related mortality & injury. Data were analyzed using Stata software. The mortality and injury rate from accidents was 1130.80 per 10000 accidents. The concentration index was negative for mortality rate (-0.11) of RTA, indicating the higher concentration of the rates among deprived groups. People with low socioeconomic level were more at risk for fatal accidents and injuries. Therefore, specific interventions on road safety should be delivered in the deprived drivers which uses from low safety level vehicles.


Comparative osseous and soft tissue morphology following cleft lip repair.
To quantify comparative improvement between osseous and soft tissue asymmetry following primary lip repair. Retrospective analysis of preoperative and postoperative computed tomography scans of infants with unilateral cleft lip and palate. Sixteen soft tissue landmarks were placed using an exploratory two-/three-dimensional image processing system and compared for asymmetry. Computed tomography scans were obtained on 26 patients (13 boys, 13 girls) of Chinese ethnicity (mean age = 0.25 years) prior to Millard lip repair. Nineteen of these contributed to follow-up comparative studies prior to palatoplasty at a mean age of 0.92 years. There were 18 left-sided and eight right-sided clefts. Euclidean distance matrix asymmetry analysis was used to determine the amount of soft tissue asymmetry pre- and postlip repair. Similar analyses of the same scans were performed for 41 osseous landmarks. Soft tissue landmarks had 36/39 (92%) preoperative and 13/39 (33%) postoperative asymmetric pairs. Osseous distances demonstrated 77/125 (61%) asymmetric pairs preoperatively and 60/125 (48%) postoperatively. Soft tissue and osseous distances of the lip region demonstrated 32% and 39% postoperative asymmetry, respectively. Soft tissue and osseous distances of the nasal region demonstrated 52% and 72% postoperative asymmetry, respectively. Soft tissue and osseous distances of the facial landmarks demonstrated 24% and 34% postoperative asymmetry, respectively. Primary lip repair appears to effect gains in symmetry in soft tissue and provides sufficient molding forces to cause correlating symmetry changes in underlying osseous structures.


Exercise programs may be effective in preventing a new episode of neck pain: a systematic review and meta-analysis.
What is the effectiveness of interventions that aim to prevent a new episode of neck pain? Systematic review and meta-analysis of randomised, controlled trials. People without neck pain at study entry. Any intervention aiming to prevent a future episode of neck pain. New episode of neck pain. Five trials including a total of 3852 individuals met the inclusion criteria. The pooled results from two randomised, controlled trials (500 participants) found moderate-quality evidence that exercise reduces the risk of a new episode of neck pain (OR 0.32, 95% CI 0.12 to 0.86). One of the meta-analysed trials included some co-interventions with the exercise. There was low-quality evidence from three randomised, controlled trials (3352 participants) that ergonomic programs do not reduce the risk of a new neck pain episode (OR 1.00, 95% CI 0.74 to 1.35). This review found moderate-quality evidence supporting the effectiveness of an exercise program for reducing the risk of a new episode of neck pain. There is a need for high-quality randomised, controlled trials evaluating interventions to prevent new episodes of neck pain. PROSPERO CRD42017055174. [de Campos TF, Maher CG, Steffens D, Fuller JT, Hancock MJ (2018) Exercise programs may be effective in preventing a new episode of neck pain: a systematic review. Journal of Physiotherapy 64: 159-165].