Association Mapping of Seedling Resistance to Tan Spot (Pyrenophora tritici-repentis Race 1) in CIMMYT and South Asian Wheat Germplasm.
Tan spot caused by Pyrenophora tritici-repentis (Ptr) is an important disease of wheat in many wheat producing areas of the world. A genome wide association study (GWAS) was conducted using 11,401 SNP markers of the Illumina Infinium 15K Bead Chip with whole genome coverage to identify genomic regions associated with resistance to tan spot in a diverse panel of 184 wheat genotypes originating from South Asia and CIMMYT. The GWAS panel was phenotyped for seedling resistance to tan spot with Ptr race 1 in two greenhouse experiments. Besides CIMMYT germplasm, several lines from South Asia (India, Bangladesh and Nepal) showed good degree of resistance to tan spot. Association mapping was conducted separately for individual experiments and for pooled data using mixed linear model (MLM) and Fixed and random model Circulating Probability Unification (FarmCPU) model; no significant MTAs were recorded through the MLM model, whereas FarmCPU model reported nine significant MTAs located on chromosomes 1B, 2A, 2B, 3B, 4A, 5A, 5B, 6A, and 7D. The long arms of chromosomes 5A and 5B were consistent across both environments, in which the Vrn-A1 locus was found in identified region of chromosome 5A, and MTA at IACX9261 on 5BL appears to represent the resistance gene tsn 1. MTAs observed on chromosomes 1B, 2A, 2B, 3B, 4A, 6A, and 7D have not been reported previously and are likely novel.


CD4(+) T Cell-Receptor Repertoire Diversity is Compromised in the Spleen but Not in the Bone Marrow of Aged Mice Due to Private and Sporadic Clonal Expansions.
Reduction in T cell receptor (TCR) diversity in old age is considered as a major cause for immune complications in the elderly population. Here, we explored the consequences of aging on the TCR repertoire in mice using high-throughput sequencing (TCR-seq). We mapped the TCRβ repertoire of CD4+ T cells isolated from bone marrow (BM) and spleen of young and old mice. We found that TCRβ diversity is reduced in spleens of aged mice but not in their BM. Splenic CD4+ T cells were also skewed toward an effector memory phenotype in old mice, while BM cells preserved their memory phenotype with age. Analysis of Vβ and Jβ gene usage across samples, as well as comparison of CDR3 length distributions, showed no significant age dependent changes. However, comparison of the frequencies of amino-acid (AA) TCRβ sequences between samples revealed repertoire changes that occurred at a more refined scale. The BM-derived TCRβ repertoire was found to be similar among individual mice regardless of their age. In contrast, the splenic repertoire of old mice was not similar to those of young mice, but showed an increased similarity with the BM repertoire. Each old-mouse had a private set of expanded TCRβ sequences. Interestingly, a fraction of these sequences was found also in the BM of the same individual, sharing the same nucleotide sequence. Together, these findings show that the composition and phenotype of the CD4+ T cell BM repertoire are relatively stable with age, while diversity of the splenic repertoire is severely reduced. This reduction is caused by idiosyncratic expansions of tens to hundreds of T cell clonotypes, which dominate the repertoire of each individual. We suggest that these private and abundant clonotypes are generated by sporadic clonal expansions, some of which correspond to pre-existing BM clonotypes. These organ- and age-specific changes of the TCRβ repertoire have implications for understanding and manipulating age-associated immune decline.


Greater Average Meal Planning Frequency Predicts Greater Weight Loss Outcomes in a Worksite-Based Behavioral Weight Loss Program.
Planning in behavioral weight loss (BWL) programs helps participants enact changes in eating and exercise, although the direct impact on weight loss is unclear. To examine how meal and exercise planning frequencies change in a BWL program and their relations to weight loss outcomes. Participants (N = 139) in a 40 week worksite-based BWL program completed a questionnaire regarding meal and exercise planning frequency at Weeks 0, 10, 20, 30, and 40 and were weighed weekly. Growth curve models were used to determine trajectories in meal and exercise planning frequency and to assess the role of an individual's average meal and exercise planning (between-person effect) and individual variation in planning (within-person effect) on body mass index (BMI). The best-fitting model, a linear random effect with a quadratic fixed-effect model, demonstrated that meal and exercise planning frequency increased over the course of the program with slowing growth rates. Between participants, higher average meal planning frequency (B = -0.029, t = -3.60), but not exercise planning frequency, was associated with greater weight loss. Within participants, exercise planning, but not meal planning, predicted a higher than expected BMI (B = 3.17, t = 4.21). Frequent meal planning should be emphasized as a continued, as opposed to intermittent, goal in BWL programs to enhance weight loss. Average exercise planning frequency does not impact weight loss in BWL programs; however, acute increases in exercise planning frequency may be a popular coping strategy during a weight loss setback or, alternatively, may lead to increased calorie consumption and weight gain.


Nicotinic acetylcholine receptor subtypes expression during rat retina development and their regulation by visual experience.
By acting through retinal nicotinic acetylcholine receptors (nAChRs), acetylcholine plays an important role in the development of both the retina and central visual pathways. Ligand binding and immunoprecipitation studies with subunit-specific antibodies showed that the expression of alphaBungarotoxin (alphaBgtx) and high-affinity epibatidine (Epi) receptors is regulated developmentally and increases until postnatal day 21 (P21). The increase in Epi receptors is caused by a selective increase in the subtypes containing the alpha2, alpha4, alpha6, beta2, and beta3 subunits. Immunopurification studies revealed three major populations of Epi receptors on P21: alpha6(*) receptors (26%), which contain the alpha6beta3beta2, alpha6alpha4beta3beta2, and alpha6alpha3/alpha2beta3beta2 subtypes; alpha4(non-alpha6)(*) receptors (60%), which contain the alpha2alpha4beta2 and alpha4beta2 subtypes; and (non-alpha4/non-alpha6)(*) receptors (14%), which contain the alpha2beta2/beta4 and alpha3beta2/beta4 subtypes. These three populations can be pharmacologically discriminated using alphaconotoxin MII, which binds the alpha6(*) population with high affinity. In situ hybridization showed that the transcripts for all of the subunits are heterogeneously distributed throughout retinal neurons at P21, with alpha3, alpha6, and beta3 transcripts preferentially concentrated in the ganglion cell layer, alpha5 in the inner nuclear layer, and alpha4 and beta2 distributed rather homogeneously. To investigate whether nAChR expression is affected by visual experience, we also studied dark-reared P21 rats. Visual deprivation had no effect on the expression of alphaBgtx receptors or the developmentally regulated Epi receptors containing the alpha2, alpha6, and/or beta3 subunits but significantly increased the expression of the Epi receptors containing the alpha4 and beta2 subunits. Overall, this study demonstrates that the retina is the rat neural region that expresses the widest array of nAChR subtypes. These receptors have a specific distribution, and their expression is finely regulated during development and by visual experience.


Diagnostic challenges related to myeloid/natural killer cells, a variant of myeloblasts.
The authors report herein two diagnostically challenging cases centered on the myeloid/natural killer (myeloid/NK) cells, a variant of myeloblasts, to illustrate the importance of advanced flow cytometric immunophenotyping and an updated understanding of surface markers in hematopoietic malignancies. Myeloid/NK cell acute leukemia is a very rare subtype of leukemia. Although its NK-cell nature is debatable, it represents a variant of leukemia with distinct morphological and immunophenotypical features. The first case is a de novo myeloid/NK-cell acute leukemia with a striking clinical, morphologic and immunophenotypic resemblance to acute promyelocytic leukemia (APL), but which could be distinguished by its CD11a, CD18, CD117 and CD9 expression. This case illustrates the importance of utilizing the APL surrogate surface phenotype of HLA-DR(low), CD11a(low) and CD18(low) by flow cytometric study to rule in/out APL immunophenotypically. In the second case, we show that myeloid/NK-cell blasts can present as a variant of blasts in a preleukemic disease as refractory anemia with excess blasts-1 (RAEB-1), where the blasts were negative for CD34, CD117 and HLA-DR. The recognition of such blast variant is important in appropriately classifying such preleukemic diseases by blast percentage.


Microhardness and morphological changes induced by Nd:Yag laser on dental enamel: an in vitro study.
The aim of this work was a scanning electron microscopy (SEM) evaluation of the hardness and morphological changes of enamel irradiated by neodymium: yttrium aluminium garnet (Nd:YAG) laser with different energy levels. Twenty-eight human teeth samples were divided into 4 groups: control, where enamel surface was not lased, and 3 test treated with 3 different levels of energy power 0.6, 1.2 and 2.4 Watt, respectively. In each group, 5 samples underwent Vickers micro-hardness test and 2 samples were processed for SEM. No significant differences between treated and non treated samples were found by micro-hardness test. However, by SEM, test samples showed a rougher enamel surface than control. Specifically, the 0.6 Watt treated samples showed vertical scratches and glass-like areas, while in the other 2 groups enamel surface was covered by craters and cracks. These findings suggest that enamel should be lased at a low energy level to preserve its integrity and reduce demineralization, and thus for dental caries prevention purposes; while high energy level creates a retentive surface suitable for sealant or composite anchorage.


The effect of fertiliser treatments on the severity of Fusarium head blight and mycotoxin biosynthesis in winter rye.
The fungi of the genus Fusarium cause Fusarium head blight (FHB), a devastating disease that reduces grain yield and quality. They also produce mycotoxins which may pose a serious threat to human and animal health. This study investigated the effects of NPK fertilisation, foliar application of Cu, Zn, and Mn, applied separately and in combination, and of the Nano-Gro® organic growth stimulator on the occurrence of FHB in cultivar Dańkowskie Diament rye based on the mycological analysis of kernels and on the concentrations of Fusarium mycotoxins in grain. The severity of FHB caused by seven species of the genus Fusarium was influenced by weather conditions in the analysed growing seasons. The applied fertilisation and the Nano-Gro® organic growth stimulator exerted varied effects on FHB development and the biosynthesis of Fusarium mycotoxins (deoxynivalenol, nivalenol, zearalenone and fumonisins) in grain. The greatest reduction in deoxynivalenol and nivalenol concentrations was noted in 2013, and the levels of moniliformin were lower in treated samples than in absolute control (untreated) samples in both years of the study. The severity of FHB positively correlated with the concentrations of zearalenone, deoxynivalenol, nivalenol, and moniliformin in the grain samples. Greater accumulation of ergosterol was noted in the rye grain harvested in 2013 than in 2012, and fertiliser treatment led to higher ergosterol concentrations than did control treatment.


Risk Factors for Complications, Longer Hospital Stay, and Readmission After Total Ankle Arthroplasty.
Studies have shown conflicting results regarding associations of preoperative comorbidities with outcomes after total ankle arthroplasty (TAA). Our aim was to analyze preoperative risk factors for complications, longer hospital stay, and readmission within 30 days after TAA. We conducted a retrospective study using the American College of Surgeons National Surgical Quality Improvement Program database. We included 294 patients who underwent TAA from 2009 through 2012. We used multivariate logistic regression to identify risk factors for complications, longer hospital stay, and hospital readmission. Surgical site infection was the most common complication. Diabetes was associated with greater odds of complications as was current smoker status. Notably, obesity was not associated with greater odds of complications. Age, chronic obstructive pulmonary disease, and diabetes mellitus were associated with longer hospital stays. Surgical site infection was the most common reason for hospital readmission. TAA has a low complication rate, with surgical site infection being the most common complication and the most common reason for hospital readmission. Patients with diabetes have greater odds of poor outcomes and prolonged hospital stays after TAA than patients without diabetes. Obesity was not associated with poor outcomes after TAA. Level III.


Stabilization of nontoxic Aβ-oligomers: insights into the mechanism of action of hydroxyquinolines in Alzheimer's disease.
The extracellular accumulation of amyloid β (Aβ) peptides is characteristic of Alzheimer's disease (AD). However, formation of diffusible, oligomeric forms of Aβ, both on and off pathways to amyloid fibrils, is thought to include neurotoxic species responsible for synaptic loss and neurodegeneration, rather than polymeric amyloid aggregates. The 8-hydroxyquinolines (8-HQ) clioquinol (CQ) and PBT2 were developed for their ability to inhibit metal-mediated generation of reactive oxygen species from Aβ:Cu complexes and have both undergone preclinical and Phase II clinical development for the treatment of AD. Their respective modes of action are not fully understood and may include both inhibition of Aβ fibrillar polymerization and direct depolymerization of existing Aβ fibrils. In the present study, we find that CQ and PBT2 can interact directly with Aβ and affect its propensity to aggregate. Using a combination of biophysical techniques, we demonstrate that, in the presence of these 8-HQs and in the absence of metal ions, Aβ associates with two 8-HQ molecules and forms a dimer. Furthermore, 8-HQ bind Aβ with an affinity of 1-10 μm and suppress the formation of large (>30 kDa) oligomers. The stabilized low molecular weight species are nontoxic. Treatment with 8-HQs also reduces the levels of in vivo soluble oligomers in a Caenorhabditis elegans model of Aβ toxicity. We propose that 8-HQs possess an additional mechanism of action that neutralizes neurotoxic Aβ oligomer formation through stabilization of small (dimeric) nontoxic Aβ conformers.


Animal factors affecting the meat quality of Australian lamb meat.
This paper integrates the key industry findings from the twelve preceding papers in this special edition of Meat science. In so doing, various animal factors important for the quality of Australian lamb meat are highlighted for sensory, visual appeal and human health attributes. Intramuscular fat concentration (IMF) was found to be a key element of eating quality that interacts both positively and negatively with a range of other factors. Shear force, IMF, colour stability and docosahexaenoic acid (DHA) will likely respond to genetic selection whilst other omega-3 fatty acids require nutritional intervention. Australian lamb meat can generally be regarded as a good source of the minerals iron and zinc; and a source of omega 3 fatty acids when finished on green pasture. Breeding priorities for meat quality will likely depend on breed type with improvement of meat colour stability more important for the wool focused Merino breed and improvement of sensory quality for the terminal sire breeds.


Test characteristics of ultrasonography for the detection of pneumothorax: a systematic review and meta-analysis.
A pneumothorax is a potentially life-threatening condition. Although CT scan is the reference standard for diagnosis, chest radiographs are commonly used to rule out the diagnosis. We compared the test characteristics of ultrasonography and supine chest radiography in adult patients clinically suspected of having a pneumothorax, using CT scan or release of air on chest tube placement as reference standard. We searched for English literature in MEDLINE and EMBASE and performed hand searches. Two independent investigators used standardized forms to review articles for inclusion, quality (QUADAS tool), and data extraction. We calculated κ agreement for study selection and evaluated clinical and quality homogeneity before meta-analysis. We reviewed 570 articles and selected 21 for full review (κ, 0.89); eight articles (total of 1,048 patients) met all inclusion criteria (κ, 0.81). All studies but one used the ultrasonographic signs of lung sliding and comet tail to rule out pneumothorax. Chest radiography data were available for 864 of 1,048 patients evaluated with ultrasonography. Ultrasonography was 90.9% sensitive (95% CI, 86.5-93.9) and 98.2% specific (95% CI, 97.0-99.0) for the detection of pneumothorax. Chest radiography was 50.2% sensitive (95% CI, 43.5-57.0) and 99.4% specific (95% CI, 98.3-99.8). Performance of ultrasonography for the detection of pneumothorax is excellent and is superior to supine chest radiography. Considering the rapid access to bedside ultrasonography and the excellent performance of this simple test, this study supports the routine use of ultrasonography for the detection of pneumothorax.


Identification of a gene expression signature for survival prediction in type I endometrial carcinoma.
Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favorable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and nonsurvivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were nonsurvivors. The tumors were analyzed with genome-wide expression array analysis, represented by 13,526 genes. Distinct differences in gene expression were found between the groups. A t-test established that 218 genes were significantly differentially expressed (p < 0.001) between the two survival groups, and in a cross-validation test 40 of the 45 (89%) tumors were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis, which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC > 2) was added the hierachical clustering yielded similar results. Stage I tumors are expected to have a favorable prognosis. However, in our tumor material there were six nonsurvivors with stage I tumors. Five out of six stage I nonsurvivors clustered in the nonsurvival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.


Acceptability, benefits, and challenges of video consulting: a qualitative study in primary care.
People increasingly communicate online, using visual communication mediums such as Skype and FaceTime. Growing demands on primary care services mean that new ways of providing patient care are being considered. Video consultation (VC) over the internet is one such mode. To explore patients' and clinicians' experiences of VC. Semi-structured interviews in UK primary care. Primary care clinicians were provided with VC equipment. They invited patients requiring a follow-up consultation to an online VC using the Attend Anywhere web-based platform. Participating patients required a smartphone, tablet, or video-enabled computer. Following VCs, semi-structured interviews were conducted with patients (n = 21) and primary care clinicians (n = 13), followed by a thematic analysis. Participants reported positive experiences of VC, and stated that VC was particularly helpful for them as working people and people with mobility or mental health problems. VCs were considered superior to telephone consultations in providing visual cues and reassurance, building rapport, and improving communication. Technical problems, however, were common. Clinicians felt, for routine use, VCs must be more reliable and seamlessly integrated with appointment systems, which would require upgrading of current NHS IT systems. The visual component of VCs offers distinct advantages over telephone consultations. When integrated with current systems VCs can provide a time-saving alternative to face-to-face consultations when formal physical examination is not required, especially for people who work. Demand for VC services in primary care is likely to rise, but improved technical infrastructure is required to allow VC to become routine. However, for complex or sensitive problems face-to-face consultations remain preferable.


Neuropsychiatric disturbance after aneurysmal subarachnoid hemorrhage.
Although aneurysmal subarachnoid hemorrhage (aSAH) accounts for only 3-5% of all strokes, a high degree of morbidity has been reported in this relatively young subset of patients. Neuropsychiatric disturbance has often been neglected in these reports. We aimed to investigate the pattern and pathological factors of chronic neuropsychiatric disturbance in aSAH patients. This cross-sectional observational four-center study was carried out in Hong Kong. Neuropsychiatric outcome (Neuropsychiatric Inventory Chinese Version [CNPI]) assessments were conducted cross-sectionally 1-4 years after ictus. Pathological factors considered were early brain injury as assessed by admission World Federation of Neurosurgical Societies grade, aneurysm treatment (clipping versus coiling), delayed cerebral infarction, and chronic hydrocephalus. One hundred and three aSAH patients' spouses or caregivers completed the CNPI. Forty-two (41%) patients were reported to have one or more domain(s) of neuropsychiatric disturbance. Common neuropsychiatric disturbance domains included agitation/aggression, depression, apathy/indifference, irritability/lability, and appetite/eating disturbance. Chronic neuropsychiatric disturbance was associated with presence of chronic hydrocephalus. A subscore consisting of the five commonly affected domains seems to be a suitable tool for aSAH patients and should be further validated and replicated in future studies.


Mental health of UK Armed Forces medical personnel post-deployment.
The mental health effects of deployment vary widely, and personnel in both combat and combat support roles, including medical personnel, may be adversely affected. To compare the mental health of deployed UK military medical staff in both forward and rear locations and to compare these two groups with other deployed military personnel. Participants were medics who had deployed to Iraq or Afghanistan and provided information about their deployed role, experiences during and on return from deployment and demographic and military factors. Health outcomes included common mental health problems (using 12-item General Health Questionnaire), post-traumatic stress disorder (PTSD, using 17-item Post-Traumatic Stress Disorder Checklist-Civilian Version), multiple physical symptoms and alcohol use (using 10-item Alcohol Use Disorders Identification Test). The sample comprised 321 medical personnel. The response rate was 56%. The mental health outcomes for forward located medics (FMs) were no different than those for rear located medics (RLMs). When comparing FMs and RLMs against all other military roles, a small but significant increase in PTSD symptoms in FMs was found. FMs were more likely to rate their work while deployed as being above their skills and experience, report exposure to more combat experiences and report a more challenging homecoming experience than RLMs. These results suggest that while the overall rates of self-reported mental health disorders were similar in FMs and RLMs, FMs reported more PTSD symptoms than all other roles, which may have been related to working in more hostile environments in more challenging roles while deployed and their experiences on returning home.


Zinc-induced inhibition of insulin secretion from isolated rat islets of Langerhans.
The present experiments indicate that ZnCl2 (0.015-0.50 mM) inhibits in a dose-dependent manner insulin secretion from isolated rat islets stimulated by D-glucose, L-leucine, and potassium. This inhibitory effect is partially reversed by washing and antagonized by high calcium concentrations in the medium. Zinc levels that inhibit insulin release do not affect 45calcium uptake, and zinc will not replace calcium in triggering insulin release. The conversion of 14C-D-glucose to 14CO2 by islets is not modified by zinc (0.12 mM or 0.50 mM) following either 2- or 0.5-h incubation periods, respectively. It is concluded that the inhibitory effect of zinc on insulin secretion may, in part, be mediated through interference with an intracellular function of calcium by the beta-cell.


The 21-aminosteroid U-74389G reduces cerebral superoxide anion concentration following fluid percussion injury of the brain.
We examined the effects of the 21-aminosteroid antioxidant U-74389G (16-desmethyl-tirilazad) on the concentration of extracellular superoxide anion following fluid percussion traumatic brain injury (TBI) measured by a cytochrome c-coated electrode and on local cerebral perfusion (CBFld) measured by laser Doppler flowmetry (LDF). U-74389G in a dose of 3 mg/kg reduced superoxide anion concentrations 60 min after TBI significantly but had no significant effect on CBFld. These results indicate that reduction of CBF after TBI can be dissociated from superoxide anion production. Persistent ischemia may limit neuroprotection efficacy and may contribute to divergent outcome results in clinical and animal trials using agents to modify reactive oxygen species.


[Histochemical characteristics of mast cells in hemangiomas].
Mast cells of hemangiomas localized in the skin and in the mucous membrane of the oral cavity, have a similar histochemical characteristics of protein and carbohydrate components. The histochemical characteristics of the carbohydrate component indicate either a high (as compared with the norm) degree of sulfating of heparin molecules, or quantitative accumulation of its molecules in the mast cells cytoplasm. Moreover, in mast cells there were revealed protein and a neutral carbohydrate component. An assumption is put forward that histochemical changes in mast cells in hemangiomas were of compensatory-adaptive character and were directed to prevent the thrombogenesis in hemangiomas.


Comparison of the type of substrate oxidation during exercise between pre and post pubertal markedly obese boys.
The aim of this study was to investigate, in markedly obese children, the effect of puberty on substrate oxidation during an acute bout of exercise. Two groups of markedly obese boys (7 pre pubertal, 8 post pubertal, matched for adiposity) performed an exercise-test designed for measuring carbohydrate and fat oxidation with indirect calorimetry, and consisting of five six-minute steady-state workloads at 20, 30, 40, 50, and 60 % of the theoretical maximal aerobic power. Fat oxidation (mg . min (-1)) is correlated to fat free mass (FFM) (r = 0.7, p = 0.02). When expressed in crude flow rate units, fat oxidation is slightly higher in PostP than PreP children (p < 0.05). However, when expressed per unit of FFM or as a percentage of total fuel oxidation, fat oxidation is lower in PostP than PreP children (p < 0.05). Multivariable analysis shows that the influence of age on the ability to oxidize fat at exercise is explained by the pubertal increase in FFM. In markedly obese children during puberty, the ability of each kg of FFM to oxidize fat at exercise decreases (- 28% at 20%Wmax th), but the pubertal increase in FFM overcomes this effect, resulting in an increase in whole body ability to oxidize fat at exercise (+ 17,3% at 20%Wmax th).


The drink remains the same: implicit positive associations in high but not moderate or non-caffeine users.
Research has demonstrated that high, but not low caffeine users exhibit an attentional bias to caffeine related stimuli. Separately, the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998) has been used to investigate the valence of implicit cognitions to drugs with some contradictory findings, though no work has addressed this issue with respect to caffeine. Here, we examined whether attentional bias would be found in high and moderate caffeine users using a pictorial version of the dot-probe task. A second aim was to explore differences in implicit cognitions between users and non-users. Fifteen high, moderate and non-caffeine users completed a picture dot-probe, IAT, and mood questionnaire following overnight caffeine deprivation. In the IAT, results demonstrated positive associations to caffeine related words for high but not moderate or non-users. Lower ratings for calmness were evident in both groups of caffeine compared to non-users. Dot-probe findings revealed an attentional bias among moderate caffeine users and non-users but not heavy users. The observed positive implicit associations to caffeine suggest that drug acceptability is the key in such perceptions.


Audible handheld Doppler ultrasound determines reliable and inexpensive exclusion of significant peripheral arterial disease.
To determine the accuracy of audible arterial foot signals with an audible handheld Doppler ultrasound for identification of significant peripheral arterial disease as a simple, quick, and readily available bedside screening tool. Two hundred consecutive patients referred to an interprofessional wound care clinic underwent audible handheld Doppler ultrasound of both legs. As a control and comparator, a formal bilateral lower leg vascular study including the calculation of Ankle Brachial Pressure Index and toe pressure (TP) was performed at the vascular lab. Diagnostic reliability of audible handheld Doppler ultrasound was calculated versus Ankle Brachial Pressure Index as the gold standard test. A sensitivity of 42.8%, a specificity of 97.5%, negative predictive value of 94.10%, positive predictive value of 65.22%, positive likelihood ratio of 17.52, and negative likelihood ratio of 0.59. The univariable logistic regression model had an area under the curve of 0.78. There was a statistically significant difference at the 5% level between univariable and multivariable area under the curves of the dorsalis pedis and posterior tibial models (p < 0.001). Audible handheld Doppler ultrasound proved to be a reliable, simple, rapid, and inexpensive bedside exclusion test of peripheral arterial disease in diabetic and nondiabetic patients.


Correlative Super-Resolution Optical and Atomic Force Microscopy Reveals Relationships Between Bacterial Cell Wall Architecture and Synthesis in Bacillus subtilis.
Understanding how bacteria grow and divide requires insight into both the molecular-level dynamics of ultrastructure and the chemistry of the constituent components. Atomic force microscopy (AFM) can provide near molecular resolution images of biological systems but typically provides limited chemical information. Conversely, while super-resolution optical microscopy allows localization of particular molecules and chemistries, information on the molecular context is difficult to obtain. Here, we combine these approaches into STORMForce (stochastic optical reconstruction with atomic force microscopy) and the complementary SIMForce (structured illumination with atomic force microscopy), to map the synthesis of the bacterial cell wall structural macromolecule, peptidoglycan, during growth and division in the rod-shaped bacterium Bacillus subtilis. Using "clickable" d-amino acid incorporation, we fluorescently label and spatially localize a short and controlled period of peptidoglycan synthesis and correlate this information with high-resolution AFM of the resulting architecture. During division, septal synthesis occurs across its developing surface, suggesting a two-stage process with incorporation at the leading edge and with considerable in-filling behind. During growth, the elongation of the rod occurs through bands of synthesis, spaced by ∼300 nm, and corresponds to denser regions of the internal cell wall as revealed by AFM. Combining super-resolution optics and AFM can provide insights into the synthesis processes that produce the complex architectures of bacterial structural biopolymers.


Arterial stiffness is increased in families with premature coronary artery disease.
A positive family history of premature coronary artery disease (CAD) is a risk factor for cardiovascular disease (CVD), independent of traditional risk factors. Therefore, currently used risk algorithms poorly predict risk in these individuals. Novel methods are thus needed to assess cardiovascular risk. Pulse-wave velocity (PWV) might be such a method, but it is unknown whether PWV is increased in first-degree relatives of patients with premature CAD. Observational case-control study. Academic hospital. Patients with premature CAD and a positive family history of premature CVD (n=50), their first-degree relatives without CVD (n=50) and unrelated controls (n=50). None. PWV was measured with using an Arteriograph system. Differences in PWV were assessed by a generalised linear model and multinomial logistic regression. Patients with premature CAD had a higher PWV compared with first-degree relatives and controls (9.69±2.90 m/s vs 8.15±1.96 m/s and 7.38±1.08 m/s; p<0.05 patients vs all groups). Linear regression showed all groups related to PWV, with patients having the highest PWV and controls the lowest (p<0.0001). Furthermore, PWV was associated with first-degree relatives (OR 1.32, 95% CI 1.02 to 1.72; p<0.05) and premature CAD (OR 1.72, 95% CI 1.32 to 2.24; p<0.05) compared with controls. These findings were independent of blood pressure and other traditional risk factors. Patients with premature CAD and their first-degree relatives had higher PWV compared with controls, independent of other risk factors. This holds promise for the future, in which arterial stiffness might play a role in risk prediction within families with premature CAD.


Phagocytosis by rat liver: relationships between phagosomes and lysosomes.
To study the transfer of phagocytosed components from phagosomes to lysosomes, we have investigated phagocytosis by rat liver of killed Staphylococcus aureus labelled with (125)I tyramine cellobiose. Lysosomes were identified by injecting the animals with Triton WR1339, a non ionic detergent that is endocytosed by the liver and accumulates in lysosomes, causing a marked decrease of their density; that allows these organelles to be well separated from other particles in a density gradient. Bacteria were quickly taken up by the liver; their uptake is followed by a slow degradation as ascertained by the increase of acid-soluble radioactivity in the homogenates with time. Triton WR1339 injection does not affect the uptake and the degradation of the particles. Differential centrifugation of homogenates shows that at any time after injection, most of the radioactivity is recovered in the mitochondrial fractions. Distributions of acid precipitable and acid soluble radioactivities amongst subcellular structures present in mitochondrial fractions were studied by isopycnic centrifugation in sucrose gradients, at increasing times after bacteria injection. Results show that: 1) acid-precipitable radioactivity is quasi-exclusively present in gradient fractions of high density, well separated from the fractions where there are recovered lysosomes; 2) with time, acid-soluble radioactivity is more and more associated with lysosomes, however, a significant proportion can be detected for many hours after injection, in gradient fractions where acid-precipitable radioactivity is located. The most plausible explanation of our observations is that phagocytosed particles are degraded in phagosomes and that the degradation products are delivered to lysosomes, probably by a vesicular process.


Enhanced formation of shiga toxin-producing Escherichia coli persister variants in environments relevant to leafy greens production.
Bacterial persistence is a form of phenotypic heterogeneity in which a subpopulation, persisters, has high tolerance to antibiotics and other stresses. Persisters of enteric pathogens may represent the subpopulations capable of surviving harsh environments and causing human infections. Here we examined the persister populations of several shiga toxin-producing Escherichia coli (STEC) outbreak strains under conditions relevant to leafy greens production. The persister fraction of STEC in exponential-phase of culture varied greatly among the strains examined, ranging from 0.00003% to 0.0002% for O157:H7 strains to 0.06% and 0.08% for STEC O104:H4 strains. A much larger persister fraction (0.1-11.2%) was observed in STEC stationary cells grown in rich medium, which was comparable to the persister fractions in stationary cells grown in spinach lysates (0.6-3.6%). The highest persister fraction was measured in populations of cells incubated in field water (9.9-23.2%), in which no growth was detected for any of the STEC strains examined. Considering the high tolerance of persister cells to antimicrobial treatments and their ability to revert to normal cells, the presence of STEC persister cells in leafy greens production environments may pose a significant challenge in the development of effective control strategies to ensure the microbial safety of fresh vegetables.


Developing a Parsimonious Frailty Index for Older, Multimorbid Adults With Heart Failure Using Machine Learning.
Frailty is associated with adverse outcomes in heart failure (HF). A parsimonious frailty index (FI) that predicts outcomes of older, multimorbid patients with HF could be a useful resource for clinicians. A retrospective study of veterans hospitalized from October 2015 to October 2018 with HF, aged ≥50 years, and discharged home developed a 10-item parsimonious FI using machine learning from diagnostic codes, laboratory results, vital signs, and ejection fraction (EF) from outpatient encounters. An unsupervised clustering technique identified 5 FI strata: severely frail, moderately frail, mildly frail, prefrail, and robust. We report hazard ratios (HRs) of mortality, adjusting for age, gender, race, and EF and odds ratios (ORs) for 30-day and 1-year emergency department visits and all-cause hospitalizations after discharge. We identified 37,431 veterans (age, 73 ± 10 years; co-morbidity index, 5 ± 3; 43.5% with EF ≤40%). All frailty groups had a higher mortality than the robust group: severely frail (HR 2.63, 95% confidence interval [CI] 2.42 to 2.86), moderately frail (HR 2.04, 95% CI 1.87 to 2.22), mildly frail (HR 1.60, 95% CI 1.47 to 1.74), and prefrail (HR 1.18, 95% CI: 1.07 to 1.29). The associations between frailty and mortality remained unchanged in the stratified analysis by age or EF. The combined (severely, moderately, and mildly) frail group had higher odds of 30-day emergency visits (OR 1.62, 95% CI 1.43 to 1.83), all-cause readmission (OR, 1.75, 95% CI 1.52 to 2.02), 1-year emergency visits (OR 1.70, 95% CI 1.53 to 1.89), rehospitalization (OR 2.18, 95% CI 1.97 to 2.41) than the robust group. In conclusion, a 10-item FI is associated with postdischarge outcomes among patients discharged home after a hospitalization for HF. A parsimonious FI may aid clinical prediction at the point of care.


Osteosarcopenia in rheumatoid arthritis treated with glucocorticosteroids - essence, significance, consequences.
Rheumatoid arthritis (RA) is one of the most common rheumatic diseases, associated with cooccurrence of serious side effects. This study discusses the problems associated with chronic RA, well-known as osteoporosis, but also recently recognized as sarcopenia. Relationships between sarcopenia and rheumatic diseases are not yet fully understood. Co-occurrence of osteoporosis and sarcopenia, referred to as osteosarcopenia, is becoming increasingly important. The overlap of the effects of RA and osteosarcopenia and the adverse effects of glucocorticosteroids leads to progressive impairment of the musculoskeletal system, increasing the risk of falls, fractures, institutionalization and death, and it is a source of dramatic socioeconomic burden on society. Very limited options for effective treatment of developed osteosarcopenia, as well as the severity of complications caused by it, advocates for the need of broad education and raising public awareness, especially among health care workers, in order to implement the prevention of osteosarcopenia as early as possible.


Longer Sleep Durations Are Positively Associated With Finishing Place During a National Multiday Netball Competition.
Juliff, LE, Halson, SL, Hebert, JJ, Forsyth, PL, and Peiffer, JJ. Longer sleep durations are positively associated with finishing place during a national multiday netball competition. J Strength Cond Res 32(1): 189-194, 2018-Sleep is often regarded as the single best recovery strategy available to an athlete, yet little is known about the quality and quantity of sleep in athletes during multiday competitions. This study objectively evaluated sleep characteristics of athletes during a national netball tournament. Using wrist actigraphy monitors and sleep diaries, 42 netballers from 4 state teams were monitored for the duration of a tournament (6 days) and 12 days before in home environments. Significant differences were found between teams based on final competition standings, suggesting enhanced sleep characteristics in athlete's whose team finished higher in the tournament standings. The top 2 placed teams when compared with the lower 2 placed teams slept longer (8:02 ± 36:43; 7:01 ± 27:33), had greater time in bed (9:03 ± 0:52; 7:59 ± 0:54) and reported enhanced subjective sleep ratings (2.6 ± 0.5; 2.3 ± 0.6). Sleep efficiency was no different between teams. A strong correlation (r = -0.68) was found indicating longer sleep durations during competition were associated with higher final tournament positions. Encouraging athletes to aim for longer sleep durations in competition, where possible, may influence the outcome in tournament style competitions.


Swelling of collagen intracanalicular implants.
Absorbable intracanalicular collagen implants are used to attempt to determine if permanent closure of the tear drainage system will diminish or alleviate the signs and symptoms of dryness. The rate of swelling of the collagen implants was measured in vitro in this study. Collagen implants were submersed in saline, Refresh Plus artificial tears or Tobrex antibiotic solution on a hanging drop microscope slide. The diameter of the collagen rod was measured over time using videotaping and image processing. The 0.3- and 0.4-mm diameter collagen implants swelled approximately 55% to 65% in Unisol 4 Preservative Free saline and Refresh Plus artificial tear solution, with the majority of the swelling occurring over the first 30 minutes. The 0.4-mm diameter implants took slightly longer to reach the fully swollen state than did the 0.3-mm implants. They swelled somewhat less in Tobrex Ophthalmic Solution. Collagen implants swell approximately 60%, with the majority of the swelling occurring in the first 30 minutes. Thus, it will take approximately 30 minutes after insertion of the implants for the full occlusive effect to occur.


[Allogeneic mesenchymal stromal cells in patients with ulcerative colitis: two years of observation].
The aim of the study was to determine the efficacy and safety of mesenchymal stromal cells (MSCs) of bone marrow in the treatment of patients with ulcerative colitis (UC). The study included 44 patients with ulcerative colitis (UC), which was implemented MSC transplantation, 40 patients with UC who received standard therapy with mesalazane (salofalka) 4-6 g/day and corticosteroids (prednisone)--1-2 mg/kg, azathioprine--1.5 mg/kg methotrexate 20-50 mg/m2, and 12 patients who underwent induction and maintenance of infliximab therapy. 2-3 days prior to the induction of MSCs abolish immunosuppressive doses of corticosteroids reduced to 15-20 mg/day dose of aminosalicylates was left at 2.0 g/day. To quantify the results using the average values of indices of Rahmilevich clinical activity, indices of endoscopic and histological activity scales Mayo and Gebs. The patients were observed for 24 months after transplantation. Were studied parameters of the humoral immune status (immunoglobulin A, G, M, autologous antibody), cytokine profile. Bone marrow cells were obtained from the donor's sternum or the iliac crest. By culturing the end of 5 to 6 weeks received a population of allogeneic donor's MSCs in the amount of (1.5-2) x 10(8) cells needed for transplant patient. Culture of MSCs injected in the drip i/v, single dose. In 34 (72.7%) patients with UC after the induction of MSCs was statistically significant compared with the group of patients treated with drugs only 5-aminosalicylic acid and corticosteroids, reducing the clinical and morphological indices of inflammatory activity. In 12 patients with UC include MSCs in the treatment program did not have a therapeutic effect. Application of MSC allowed to cancel corticosteroids in most patients with hormone-dependent and steroid resistance forms of UC, and in 7 to reduce the dose of prednisolone to 5 mg/day, limiting the use of drugs 5-ASA. According to the anti-inflammatory effectiveness of combined therapy with MSCs comparable to infliximab therapy. The use of MSCs can be evaluated as a new strategic direction for therapy UC. MSC, introduced in I/O, have powerful immunomodulatory effects, reduce the activity of autoimmune inflammation and stimulate the reparative process in the intestinal mucosa, thereby increasing the duration of remission, reduces risk of recurrence of disease, reduces the frequency of hospitalizations.


[Medical emergency care and patient contact at the Quart Rock Festival in Norway].
The annual Quart Rock Festival (1991-2007) was the largest rock festival in Norway. During festivals in 2004-06, a daily average of 3 000 personnel, guests and artists, and 10,000 visitors, 13,000 people, were present daily. The festival had a medical care organization recruited from primary care personnel. The team consisted of one general practitioner, one physiotherapist, two nurses from the municipality outpatient service, and lay personnel trained in first aid. We recorded all patient contacts at the festival in 2004, 2005, and 2006 in order to describe injuries requiring medical attention and the need for referrals. The total number of festival participants, including personnel, was 208,000 during the registration period. Of totally 1,349 patient contacts, 254 required consultation with a nurse and 191 with the attending physician. There were no deaths, cardiac or respiratory arrests or serious penetrating trauma. 33 contacts were related to intoxication: 24 due to alcohol, five to illegal drugs and four to unknown substances. Violence-related injuries were the cause of 18 contacts, of which none were serious. 49 patients were referred for follow-up, mostly to the municipality outpatient service or their own physician, and five patients were admitted to hospital. The transport-to-hospital-ratio was 0.24 per 10,000 participants. The results are similar to those in studies of rock festivals in other countries. The need for referrals was equal to or lower than in other studies. This indicates that the primary care-based medical organization at the Quart Festival was adequate.


Association of Variability in Body Mass Index and Metabolic Health With Cardiometabolic Disease Risk.
Background Metabolic syndrome is associated with high risk of cardiovascular disease, although risk may differ according to the specific conditions present and variability in those conditions. Methods and Results We defined obesity (body mass index [BMI] ≥30 kg/m2) and metabolic health (<2 nonobesity National Cholesterol Education Program Adult Treatment Panel III conditions) among 3632 Framingham Heart Study offspring cohort participants (mean age, 50.8 years; 53.8% women) who were followed up from 1987 to 2014. We defined participants whose variance independent of the mean for a metabolic syndrome-associated measure was in the top quintile as being "variable" for that measure. Variable metabolic health was defined as ≥2 variable nonobesity metabolic syndrome components. We investigated the interaction between obesity and metabolic health in their associations with cardiometabolic disease and cardiovascular disease using Cox proportional hazards regression. In addition, we estimated the associations of BMI variability and variable metabolic health with study outcomes within categories of obesity and metabolic health status, respectively. We observed 567 incident obesity (41 439 person-years), 771 incident metabolically unhealthy state (25 765 person-years), 272 incident diabetes mellitus (56 233 person-years), 503 incident hypertension (12 957 person-years), 589 cardiovascular disease (60 300 person-years), and 195 chronic kidney disease (47 370 person-years) events on follow-up. Obesity and being metabolically unhealthy were independently and positively associated with all outcomes. BMI variability, compared with stable BMI, was associated with 163%, 67%, 58%, and 74% higher risks of having obesity, becoming metabolically unhealthy, having diabetes mellitus, and having hypertension, respectively, among nonobese participants. Variable metabolic health, compared with stable metabolic health, was associated with a 28% higher risk of cardiovascular disease, among metabolically healthy participants. Conclusions We did not observe evidence for a positive interaction between obesity and metabolic health status with regard to study outcomes. BMI and metabolic health variability are associated with adverse health outcomes.


Women's Coverage, Utilization, Affordability, And Health After The ACA: A Review Of The Literature.
Women of working age (ages 19-64) faced specific challenges in obtaining health insurance coverage and health care before the Affordable Care Act. Multiple factors contributed to women's experiencing uninsurance, underinsurance, and increased financial burdens related to obtaining health care. This literature review summarizes evidence on the law's effects on women's health care and health and finds improvements in overall coverage, access to health care, affordability, preventive care use, mental health care, use of contraceptives, and perinatal outcomes. Despite major progress after the Affordable Care Act's implementation, barriers to coverage, access, and affordability remain, and serious threats to women's health still exist. Highlighting the law's effects on women's health is critical for informing future policies directed toward the continuing improvement of women's health care and health.


[The use of ultraviolet-irradiated plasma in the treatment of peritonitis].
Intravenous infusion of the one-group lyophilized donor plasma irradiated with ultraviolet rays was included in the complex treatment of 43 patients with acute purulent peritonitis. The species-specific composition of the microflora was studied in the different groups of patients according to the cause of peritonitis and the degree of microbial contamination of the purulent wounds in patients treated with and without ultraviolet plasma irradiation (UVPI). For prognosticating the course and outcome of the disease the authors used a complex of indices linked with the manifestation of neutrophil bactericidal activity and the level of exogenous intoxication. A positive effect of UVPI in the management of acute purulent appendicitis was noted, which was confirmed by clinical and microbiological tests.


Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses.
Coat color and pattern variations in domestic animals are frequently inherited as simple monogenic traits, but a number are known to have a complex genetic basis. While the analysis of complex trait data remains a challenge in all species, we can use the reduced haplotypic diversity in domestic animal populations to gain insight into the genomic interactions underlying complex phenotypes. White face and leg markings are examples of complex traits in horses where little is known of the underlying genetics. In this study, Franches-Montagnes (FM) horses were scored for the occurrence of white facial and leg markings using a standardized scoring system. A genome-wide association study (GWAS) was performed for several white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL) affecting the white marking score with p-values p≤10(-4) were identified. Three loci, MC1R and the known white spotting genes, KIT and MITF, were identified as the major loci underlying the extent of white patterning in this breed. Together, the seven loci explain 54% of the genetic variance in total white marking score, while MITF and KIT alone account for 26%. Although MITF and KIT are the major loci controlling white patterning, their influence varies according to the basic coat color of the horse and the specific body location of the white patterning. Fine mapping across the MITF and KIT loci was used to characterize haplotypes present. Phylogenetic relationships among haplotypes were calculated to assess their selective and evolutionary influences on the extent of white patterning. This novel approach shows that KIT and MITF act in an additive manner and that accumulating mutations at these loci progressively increase the extent of white markings.


Effects of salvianolic acid B on in vitro growth inhibition and apoptosis induction of retinoblastoma cells.
To observe the effects of salvianolic acid B (SalB) on in vitro growth inhibition and apoptosis induction of retinoblastoma HXO-RB44 cells. The effects of SalB on the HXO-RB44 cells proliferation in vitro were observed by MTT colorimetric method. The morphological changes of apoptosis before and after the treatment of SalB were observed by Hoechst 33258 fluorescent staining method. Apoptosis rate and cell cycle changes of HXO-RB44 cells were detected by flow cytometer at 48 hours after treated by SalB. The expression changes of Caspase-3 protein in HXO-RB44 cells were detected by Western Blot. SalB significantly inhibited the growth of HXO-RB44 cells, while the inhibition was in a concentration-and time-dependent manner. The results of fluorescent staining method indicated that HXO-RB44 cells showed significant phenomenon of apoptosis including karyorrhexis, fragmentation and the formation of apoptotic bodies, etc. after 24, 48 and 72 hours co-culturing of SalB and HXO-RB44 cells. The results of flow cytometer showed that the apoptosis rate and the proportion of cells in S phase were gradually increased at 48 hours and 72 hours after treated by different concentrations of SalB. Western Blot strip showed that the expression of Caspase-3 protein in HXO-RB44 cells was gradually increased with the increase of the concentration of SalB. SalB can significantly affect on HXO-RB44 cells growth inhibition and apoptosis induction which may be achieved through the up-regulation of Caspase-3 expression and the induction of cell cycle arrest.


A Retinotopic Spiking Neural Network System for Accurate Recognition of Moving Objects Using NeuCube and Dynamic Vision Sensors.
This paper introduces a new system for dynamic visual recognition that combines bio-inspired hardware with a brain-like spiking neural network. The system is designed to take data from a dynamic vision sensor (DVS) that simulates the functioning of the human retina by producing an address event output (spike trains) based on the movement of objects. The system then convolutes the spike trains and feeds them into a brain-like spiking neural network, called NeuCube, which is organized in a three-dimensional manner, representing the organization of the primary visual cortex. Spatio-temporal patterns of the data are learned during a deep unsupervised learning stage, using spike-timing-dependent plasticity. In a second stage, supervised learning is performed to train the network for classification tasks. The convolution algorithm and the mapping into the network mimic the function of retinal ganglion cells and the retinotopic organization of the visual cortex. The NeuCube architecture can be used to visualize the deep connectivity inside the network before, during, and after training and thereby allows for a better understanding of the learning processes. The method was tested on the benchmark MNIST-DVS dataset and achieved a classification accuracy of 92.90%. The paper discusses advantages and limitations of the new method and concludes that it is worth exploring further on different datasets, aiming for advances in dynamic computer vision and multimodal systems that integrate visual, aural, tactile, and other kinds of information in a biologically plausible way.


Incidence and risk factors of injuries and their impact on academic success: A prospective study in PETE students.
Injuries can have a major impact on the physical performance and academic career of physical education teacher education (PETE) students. To investigate the injury problem, risk factors, and the impact of injuries on academic success, 252 PETE students were followed during their first semester. Risk factor analysis was conducted by means of logistic regression analysis with a differentiation for upper body, lower body, acute, overuse, and severe injuries. An incidence of 1.26 injuries/student/semester was found. Most injuries involved the lower body (61%), were new injuries (76%), occurred acutely (66%), and were sustained during curricular gymnastics (25%) or extracurricular soccer (28%). Significant risk factors for lower body acute injuries were age (OR=2.14; P=.01), previous injury (OR=2.23; P=.01), and an injury at the start of the year (OR=2.56; P=.02). For lower body overuse injuries, gender (OR=2.85; P=.02) and the interval shuttle run test score (OR=2.44; P=.04) were significant risk factors. Previous injury (OR=2.59; P=.04) and injury at the start of the year (upper body: OR=4.57; P=.02; lower body: OR=3.75; P<.01) were risk factors for severe injuries. Injury-related time loss was positively related to total academic success (r=.20; P=.02) and success in theoretical courses (r=.24; P=<.01). No association was found between time loss and academic success for sport courses.


The art and science of patient storytelling-harnessing narrative communication for behavioral interventions: the ACCE project.
Narrative communication is an emerging form of persuasive communication used in health education to solicit actual patient stories. Eliciting a narrative is an open-ended process and may or may not map to desired intervention objectives or underlying behavioral constructs. In addition, incorporating actual, unscripted narratives into multimedia interventions is challenging. The authors evaluated a protocol of editing narratives for a multimedia intervention to promote smoking cessation in the African American community that maintains fidelity to the original message and was related to behavioral constructs from social cognitive theory. The authors used four steps: (a) narrative collection (videotaping), (b) narrative review (rating of content), (c) narrative editing (documentary style), and (d) pilot testing (usability and assessment of transportation). The authors videotaped 50 personal smoking cessation narratives. After coding for presence of theoretical constructs, perceived risks of smoking (present in 53% of narratives) was the most common related behavioral construct. Four narratives were chosen for inclusion in the DVD. Pilot testing showed viewers reported high level of transportation into the narrative. The authors found that some behavioral constructs were rare and difficult to solicit in this population but that the final product was engaging to the viewers. Lessons learned may be useful for other video-based behavioral interventions that incorporate personal narratives.


Loss of daylight vision in retinal degeneration: are oxidative stress and metabolic dysregulation to blame?
Retinitis pigmentosa is characterized by loss of night vision, followed by complete blindness. Over 40 genetic loci for retinitis pigmentosa have been identified in humans, primarily affecting photoreceptor structure and function. The availability of excellent animal models allows for a mechanistic characterization of the disease. Metabolic dysregulation and oxidative stress have been found to correlate with the loss of vision, particularly in cones, the type of photoreceptors that mediate daylight and color vision. The evidence that these problems actually cause loss of vision and potential therapeutic approaches targeting them are discussed.


Biosecurity interceptions of an invasive lizard: origin of stowaways and human-assisted spread within New Zealand.
Globalization, and the resultant movement of animals beyond their native range, creates challenges for biosecurity agencies. Limited records of unintentional introductions inhibit our understanding of the trade pathways, transport vectors and mechanisms through which hitchhiker organisms are spread as stowaways. Here, we adopt a phylogeographic approach to determine the source and human-mediated dispersal pathways of New Zealand's only invasive lizard, the delicate skink (Lampropholis delicata), intercepted by biosecurity agencies in New Zealand. Biosecurity agencies correctly predicted the source region of 77% of stowaways, which were usually solitary adults, arriving via air or sea pathways during the cooler months, evading initial border checks and alive when detected. New arrivals from Australia comprised 16% of detections originating from the region between Brisbane and Sydney. Our analyses indicate human-mediated dispersal has driven the post-border spread of L. delicata within New Zealand. Propagule pressure was substantially greater for L. delicata compared with the noninvasive, congeneric Lampropholis guichenoti. Our results highlight the transport pathways, spread mechanisms, and stowaway characteristics of Lampropholis lizards entering New Zealand, which could enhance current biosecurity protocols and prevent the establishment of additional lizard species.


Evidence on the efficacy of insert earphone and sound field VRA with young infants.
Visual reinforcement audiometry (VRA) with insert-earphone stimulus delivery provides a means of obtaining early ear-specific information on the auditory status of infants. The aim of this study was to investigate the efficacy of VRA in young infants, and to compare the use of sound field and insert-earphone stimulus presentation. VRA was performed on 41 normally developing infants aged between 20 and 42 weeks. Infants were tested in the sound field (n=22) and with insert earphones (n=19). Results showed significantly more minimum response levels (MRLs) obtained with sound field testing, and with older children. Nevertheless, in the insert-earphone group, 36% of those aged 32 weeks or more gave two or more MRLs, and 25% of the infants aged 25 weeks or less gave one or more MRLs. This study provides data from developmentally normal infants which confirms the efficacy of insert-earphones as well as sound field VRA with 32-42-week-olds, with reasonable expectation of success. The data in this study also suggest that VRA could be usefully employed for younger infants aged approximately 20-26 weeks where information, although less easily obtained, may be of particular value to early diagnosis and habilitation.


Techniques for the observation and measurement of red blood cell velocity in vessels of the guinea pig cochlea.
Fluorescence techniques combined with intravital microscopy provide a powerful approach to the study of cochlear blood microcirculation. In the current study, fluorescein isothiocyanate conjugated to high molecular weight dextrans was added to plasma to enhance the visual contrast of flowing blood in microscopic images from the guinea pig cochlea. Photometric signals, obtained from video pictures of the blood vessels, provided a means to continuously measure red cell velocity by using crosscorrelation algorithms to extract the time delay for moving features of the image. Alternatively, a small amount of fluorescently-labeled red blood cells (RBCs) were added to the vascular volume to serve as natural indicators of whole blood flow. The speed of these cells was measured by video photometric detection of the time required for the cells to pass between two predetermined positions in the television image. RBCs can be made fluorescent by chemical bonding of a fluorochrome to the cell membrane or by internal loading of the cell with an inert fluorochrome. Labeled RBCs provide a means to determine blood velocity in capillaries having extremely poor optical contrast, a situation which is generally the case for relatively thick tissues such as the lateral wall of the membranous labyrinth.


Not without a fair fight: failed abductions of females in wild hamadryas baboons.
In contrast to other papionin monkeys, hamadryas baboons are characterized by female-biased dispersal. Given that hamadryas females do not disperse voluntarily, one mechanism for female transfer between bands is thought to be abductions during aggressive intergroup conflict. To date, however, no successful abductions have been witnessed. We describe three abduction events at the Filoha field site in Ethiopia, two interband and one intraband, in which the abductors successfully separated a female from her leader male for several minutes or hours. In each case, the original leader male located the abductor and retrieved the female, even if it involved entering the social sphere of another band. These observations suggest that a hamadryas leader male will risk injury and loss of additional females in his attempt to retrieve a female from an abductor unless the abductor has openly challenged the leader for possession of his female and physically defeated him.


Evidence of the importance of host habitat use in predicting the dilution effect of wild boar for deer exposure to Anaplasma spp.
Foci of tick-borne pathogens occur at fine spatial scales, and depend upon a complex arrangement of factors involving climate, host abundance and landscape composition. It has been proposed that the presence of hosts that support tick feeding but not pathogen multiplication may dilute the transmission of the pathogen. However, models need to consider the spatial component to adequately explain how hosts, ticks and pathogens are distributed into the landscape. In this study, a novel, lattice-derived, behavior-based, spatially-explicit model was developed to test how changes in the assumed perception of different landscape elements affect the outcome of the connectivity between patches and therefore the dilution effect. The objective of this study was to explain changes in the exposure rate (ER) of red deer to Anaplasma spp. under different configurations of suitable habitat and landscape fragmentation in the presence of variable densities of the potentially diluting host, wild boar. The model showed that the increase in habitat fragmentation had a deep impact on Habitat Sharing Ratio (HSR), a parameter describing the amount of habitat shared by red deer and wild boar, weighted by the probability of the animals to remain together in the same patch (according to movement rules), the density of ticks and the density of animals at a given vegetation patch, and decreased the dilution effect of wild boar on deer Anaplasma ER. The model was validated with data collected on deer, wild boar and tick densities, climate, landscape composition, host vegetation preferences and deer seropositivity to Anaplasma spp. (as a measure of ER) in 10 study sites in Spain. However, although conditions were appropriate for a dilution effect, empirical results did not show a decrease in deer ER in sites with high wild boar densities. The model showed that the HSR was the most effective parameter to explain the absence of the dilution effect. These results suggest that host habitat usage may weaken the predicted dilution effect for tick-borne pathogens and emphasize the importance of the perceptual capabilities of different hosts in different landscapes and habitat fragmentation conditions for predictions of dilution effects.


Effects of Diet and Social Housing on Reproductive Success in Adult Zebrafish, Danio rerio.
Zebrafish (Danio rerio) have proven their efficiency as an animal model for genetics and development, but their nutrition and housing requirements continue to elude researchers. Diet and housing density were predicted to affect weight change and reproductive success in 120 days postfertilization (dpf) zebrafish, and growth performance of their progeny. Fish were fed one of four diets, each utilizing a different primary protein source (fish meal [Zeigler™], algae, or insect), while being housed 3.3 or 6.6 fish/L for 3 weeks. Clutch size, viability, and larval development of their progeny were monitored out to 10 dpf. All diets were sent out for proximate nutrient analysis and fatty acid profiles to understand how diet compositions affect reproduction. We found that diet and housing proximity affected adult fish weight and larvae growth; diets composed of higher levels of protein and polyunsaturated fatty acids (specifically arachidonic acid [AA] and eicosapentanoic acid) allowed fish to gain weight and produce healthy larvae. Fish housed at higher densities produced smaller embryos, but larger larvae than those housed at lower densities. These findings imply that significant effects of a modified stimulus are exhibited after relatively short periods.


Design of light-trapping microscale-textured surfaces for efficient organic solar cells.
Organic photovoltaic (OPV) cells suffer from low charge carrier mobilities of polymers, which renders it important to achieve complete optical absorption in active layers thinner than optical absorption length. Active layers conformally deposited on light-trapping, microscale textured, grating-type surfaces is one possible approach to achieve this objective. In this report, we analyze the design of such grating-type OPV cells using finite element method simulations. The energy dissipation of electromagnetic field in the active layer is studied as a function of active layer thickness, and pitch and height of the underlying textures. The superiority of textured geometry in terms of light trapping is clearly demonstrated by the simulation results. We observe 40% increase in photonic absorption in 150 nm thick active layer, for textures with 2 microm pitch and 1.5 microm height.


Transcriptional induction of the conserved alternative sigma factor RpoS in Escherichia coli is dependent on BarA, a probable two-component regulator.
The stationary phase expression of many conserved, adaptive bacterial proteins is dependent on RpoS, a second vegetative sigma factor. The regulation of RpoS itself, however, is complex and not fully understood, particularly at the level of transcription. In this report, we show that the observed hydrogen peroxide sensitivity of a mutant defective in expression of barA, a bacterial virulence factor, can be explained by a reduction in catalase activity, an RpoS-controlled function. Levels of katE mRNA, encoding the major catalase of Escherichia coli, were much lower in the barA mutant, suggesting that BarA is required for the expression of this RpoS-regulated gene. Expression of another RpoS-regulated gene, osmY, was also found to be severely reduced in the barA mutant. Employing Western analyses with anti-RpoS antisera and Northern analyses using probes specific for rpoS, we found that BarA is required for the exponential phase induction of RpoS itself. Operon lacZ fusion expression studies and Northern analyses indicate that BarA itself is maximally expressed in early exponential phase cultures immediately preceding the transcriptional induction of RpoS. Results of primer extension studies indicate that exponential phase expression from the rpoSp1 promoter is reduced by more than 85% in a barA mutant but could be efficiently complemented by a plasmid-borne copy of barA in trans. These results suggest that regulatory signals that are operant in exponentially growing cultures play an important role in effecting stationary phase gene expression.


Is Biceps Femoris Aponeurosis Size an Independent Risk Factor for Strain Injury?
This study examined whether professional footballers with previous biceps femoris long head (BFLH) injury in the last 3-years present a smaller proximal aponeurosis (Apo-BFLH) size compared to footballers with no previous injury. We examined the Apo-BFLH and BFLH size using magnetic resonance imaging and tested the knee flexor maximal isometric strength in 80 thighs of 40 footballers. Apo-BFLH size parameters were processed using a semi-automated procedure. Outcomes were compared between thighs with (n=9) vs. without (n=71) previous BFLH injury. No differences were observed between injured and non-injured thighs for the Apo-BFLH and BFLH size parameters (p>0.05) except for Apo-BFLH volume, which was higher in the non-injured thighs of athletes with previous injury (3692.1±2638.4 mm3, p<0.006) compared to the left (2274.1±798.7 mm3) thighs of athletes without previous injury. A higher knee flexor isometric strength was observed in the injured limb of athletes with previous BFLH injury (196.5±31.9 Nm, p<0.003) compared to the left (156.2±31.4 Nm) and right (160.0±31.4 Nm) thighs of non-injured athletes. The present results suggest that BFLH proximal aponeurosis size should not be considered as an independent risk factor for strain injury.


Preparation of azidocalmodulin: a photoaffinity label for calmodulin-binding proteins.
A photoaffinity label for calmodulin-binding proteins was prepared from 125I-labeled calmodulin (125I-calmodulin) and methyl-4-azidobenzimidate. Azidocalmodulin containing one azido group per calmodulin retained its ability to stimulate the CA2+-sensitive phosphodiesterase purified from bovine heart muscle. The concentrations of calmodulin and azidocalmodulin required for half-maximal stimulation of phosphodiesterase activity were 170 and 230 pM, respectively. Azido-125I-calmodulin was used to photoaffinity label troponin I, myosin light chain kinase, and the Ca2+-sensitive phosphodiesterase. Formation of crosslinked complexes required the presence of Ca2+ or Mn2+ and was inhibited by excess unmodified calmodulin. The calmodulin-binding subunits all formed 1:1 complexes with calmodulin, and the molecular weights of the crosslinked products obtained with troponin I, the phosphodiesterase, and myosin light chain kinase were 43,000, 79,000, and 116,000, respectively. Photolysis experiments using azido-125I-calmodulin and bovine cerebral cortex membranes or detergent-solubilized membranes resulted in formation of a limited number of specifically labeled polypeptides. Azido-calmodulin appears to be an appropriate photoaffinity label for the identification and characterization of calmodulin-binding subunits.


In vitro evaluation of a nitinol based vein cuff for external valvuloplasty.
This study shows first in vitro tests of a nitinol based vein cuff developed for external valvuloplasty. In contrary to currently existing vein cuffs the tested model enables minimal invasive implantation and also maintains its round pre-shaped profile at body temperature (37 degrees C). The examination of the cuff surface structure by scanning electron microscopy, profilometry and X-ray photoelectron spectroscopy after sterilization with ethylene oxide and before cyto-compatibility testing revealed a nearly smooth surface (mean square roughness Rq 66 +/- 33 nm) which was primarily composed of nickel, oxygen, titanium, carbon and silicon where nickel was the least fraction (Ni: 0.7%, Ti: 1.7%, Si: 15.8%, O: 29.5%, C: 52.3%) of the surface elements. Si and C are supposed to be contaminations caused by a final cuff polishing with silicon carbide at the end of the manufacturing process. To evaluate cyto-compatibility initial cell adherence and cell activity were assessed. The results showed good initial cell adherence of L929 fibroblast-like cells on the cuff surface already after 24 h. The results also revealed no inhibitory effects on the activity of these cells (MTS test) later on. The test setup developed to analyse functionality in a dynamic mode was shown to be suited at blood pressures up to 300 mmHg. The cuff successfully limited dilation of varicose veins (Vena saphena magna) at physiological blood pressures (< 120 mmHg) and also in cases of hypertonia (300 mmHg) to the diameter determined by the cuff (4.0 mm) over thecomplete testing period. This indicates that the clasp based cuff closure mechanism is suited to close the cuff under variable physiological and pathological blood pressure conditions. The cuff structure only allowed minimal adaptation on the inhomogenously dilating vein profile in the both peripheral cuff modules. Both peripheral modules followed the vessel dilation in correlation to the applied pressure. At pressures within the physiological range </= 120 mmHg) the variation of the lateral arch module diameter was only marginal, whereas at 300 mmHg pressure the peripheral modules followed vein dilation up to a diameter of 5.0 to 5.5 mm. The cuff also maintained the pre-shaped round profile in the central and peripheral modules during the pressure increase and the consecutive cuff expansion. The study showed that the first nitinol based vein cuff for external valvuloplasty was processed well enough by electropolishing and sterilization to allow culturing of L929 fibroblast-like cells on the cuff surface as a test of general biocompatibility. The cuff also proved to limit dilation of varicose veins at physiological and pathological blood pressures in vitro. Further tests with primary cells from the venous wall will follow to test the specific biocompatibility before tests in vivo can be envisaged.


Electron microscopy for tumour diagnosis: is it redundant?
The histopathological diagnosis of tumours has been transformed by immunohistochemistry. Used with experience and judgement, a panel of antibodies or antisera, combined when necessary with antigen retrieval, will enable the accurate typing of most problematic tumours. This has led many histopathologists to question whether the electron microscope has any residual utility for tumour diagnosis; the machines are large, costly to purchase and maintain, and will accept only minute samples of tissue. The following articles by Mierau and by Eyden, both strong advocates, comment on the current and future role of electron microscopy in tumour diagnosis.


Patient-provider communication about sexual health among unmarried middle-aged and older women.
Although past studies have highlighted the importance of patient-provider communication about sexual health and intimate relationships (SHIR), much of the research has focused on young women's or married women's experiences when discussing SHIR with their providers. To describe experiences of unmarried, middle-aged and older women in communicating about SHIR with their health care providers. Qualitative interviews were conducted with 40 unmarried women aged 40-75 years. We compared the responses of 19 sexual minority (lesbian and bisexual) women and 21 heterosexual women. Women varied in their definitions of intimate relationships. Not all women thought providers should ask about SHIR unless questions were directly related to a health problem, and most were not satisfied with questions about SHIR on medical intake forms. However, the themes women considered to be important in communication about SHIR were remarkably consistent across subgroups (e.g. previously married or never married; sexual minority or heterosexual). Sexual minority women were more hesitant to share information about SHIR because they had had prior negative experiences when disclosing their sexual orientation or perceived that clinicians were not informed about relevant issues. Some women felt that providers should ask about SHIR only if questions relate to an associated health problem (e.g. sexually transmitted infection). When providers do ask questions about SHIR, they should do so in ways that can be answered by all women regardless of partnering status, and follow questions with non-judgmental discussions.


Targeting the Metastasis Suppressor, N-Myc Downstream Regulated Gene-1, with Novel Di-2-Pyridylketone Thiosemicarbazones: Suppression of Tumor Cell Migration and Cell-Collagen Adhesion by Inhibiting Focal Adhesion Kinase/Paxillin Signaling.
Metastasis is a complex process that is regulated by multiple signaling pathways, with the focal adhesion kinase (FAK)/paxillin pathway playing a major role in the formation of focal adhesions and cell motility. N-myc downstream regulated gene-1 (NDRG1) is a potent metastasis suppressor in many solid tumor types, including prostate and colon cancer. Considering the antimetastatic effect of NDRG1 and the crucial involvement of the FAK/paxillin pathway in cellular migration and cell-matrix adhesion, we assessed the effects of NDRG1 on this important oncogenic pathway. In the present study, NDRG1 overexpression and silencing models of HT29 colon cancer and DU145 prostate cancer cells were used to examine the activation of FAK/paxillin signaling and the formation of focal adhesions. The expression of NDRG1 resulted in a marked and significant decrease in the activating phosphorylation of FAK and paxillin, whereas silencing of NDRG1 resulted in an opposite effect. The expression of NDRG1 also inhibited the formation of focal adhesions as well as cell migration and cell-collagen adhesion. Incubation of cells with novel thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, that upregulate NDRG1 also resulted in decreased phosphorylation of FAK and paxillin. The ability of these thiosemicarbazones to inhibit cell migration and metastasis could be mediated, at least in part, through the FAK/paxillin pathway.


Identification of distinct amino acids as ADP-ribose acceptor sites by mass spectrometry.
ADP-ribosylation is a well-known post-translational protein modification, which regulates a variety of -cellular processes. The proteins able to catalyze mono- or poly ADP-ribosylation of proteins belong to the family of ADP-ribosyltransferases. A variety of nuclear proteins has been described to be ADP-ribosylated, including ARTD1 itself and histone proteins. Despite intensive research during the last 40 years, the acceptor amino acids in ARTD1 or histone proteins could be identified and confirmed only recently by MS/MS and by site-directed mutagenesis. The establishment of a standardized protocol including the specific enrichment of ADP-ribosylated proteins and peptides and subsequent mass spectrometric analysis allows the identification of ADP-ribose acceptor sites of modified proteins and to address the functional contribution of ADP-ribosylation in vitro as well as in vivo.


Development of experimental autoimmune encephalomyelitis critically depends on CD137 ligand signaling.
Multiple sclerosis (MS) is a degenerative autoimmune disease of the CNS. Experimental autoimmune encephalomyelitis (EAE) is a commonly used murine model for MS. Here we report that CD137 ligand (CD137L, 4-1BB ligand, TNFS9), a member of the TNF superfamily, is critical for the development of EAE. EAE symptoms were significantly ameliorated in CD137L(-/-) mice. In the absence of CD137L, myelin oligodendrocyte glycoprotein (MOG)-specific T-cells secreted lower levels of T(h)1/T(h)17 cell-associated cytokines. MOG-specific T-cells also trafficked less efficiently to the CNS in CD137L(-/-) mice, possibly as a consequence of reduced expression of vascular cell adhesion molecule-1 (VCAM-1), which regulates leukocyte extravasation. Thus, CD137L regulates many functions of MOG-specific T-cells that contribute to EAE and may represent a novel therapeutic target for the treatment of MS.


Percutaneous transluminal angioplasty and transaxillary first rib resection. A multidisciplinary approach to the thoracic outlet syndrome.
A 33-year-old man with the thoracic outlet syndrome complicated by recurrent upper extremity deep venous thrombosis underwent venographic and dynamic venous pressure studies that suggested both extrinsic and intrinsic venous obstruction. The patient was treated with transaxillary first rib resection and percutaneous transluminal angioplasty of the involved subclavian vein stenosis and is symptom-free at 16 months follow-up. To our knowledge this is the first case in which such a multidisciplinary approach to the thoracic outlet syndrome has been performed.


Achieving ideal computed tomographic scan length in patient with suspected urolithiasis.
The purposes of the study were to determine the frequency and magnitude of extension of computed tomographic (CT) scans performed for the evaluation of urolithiasis, to investigate the potential contributing factors for overscanning, and to establish potential landmarks to assist in estimating the location of the superior margin of the kidneys. This is a retrospective review of 300 CT studies performed for evaluation of urolithiasis. The total length of the scanned area, performing technologist, and the patient demographics were collected. We found that scanning beyond the defined z-axis boundaries is a common phenomenon in CT examinations in patients with suspected urolithiasis with a magnitude that correlates (P < 0.0001) with patient time and setting: greater in the emergent (78.3 mm) and inpatient (79.8 mm) settings as well as on-call hours (80.4 mm). Our study also shows the superior margin of T11 to be consistently within 3 mm of the superior margin of the kidney but not below it. Overextension along the z axis is a ubiquitous phenomenon. The appropriate prescription of scan length, however, is an easy, efficient, costless, and universally applicable strategy. In patients with suspected urolithiasis, the superior margin of T11 represents a potential landmark to assist in estimating the upper margin of the kidneys.


Prediction of an impaired myocardial work using infarct size in acute myocardial infarction.
The relationship between myocardial infarct size (MIS) on late gadolinium-enhanced cardiac MRI (LGE MRI) and myocardial work (MW) indices assessed with MW echocardiography (MWE) has not been well characterized. This study aimed to determine an impaired MW using MIS in patients with acute myocardial infarction. Left ventricular (LV) two-dimensional speckle-tracking echocardiography, MWE, and LGE MRI were performed in 33 patients with ST-segment elevation myocardial infarction and in 30 age- and sex-comparable controls. LV global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) and MIS were acquired, respectively. MIS was negatively correlated with GWI (r = -0.60, P = 0.005), GCW (r =- 0.66, P = 0.002) and GWE (r = -0.71, P = 0.0004), but positively correlated with GLS (r = 0.68, P = 0.001). With the receiver operating characteristic curve, the cutoff value of MIS for the prediction of an impaired GLS was 16.5% [area under the curve (AUC) = 0.867)], an impaired GWI was 19.2% (AUC = 0.727), an impaired GCW was 19.2% (AUC = 0.725), an increased GWW was 15.8% (AUC = 0.656), an impaired GWE was 15.8% (AUC = 0.880). MIS is a strong predictor of impaired MW. Timely reduction of infarct size is essential to improve myocardial function.


Defects in innate and adaptive immunity in patients with sepsis and health care associated infection.
Recent advances in sepsis therapy exclusively involve improvements in supportive care, while sepsis mortality rates remain disturbingly high at 30%. These persistently high sepsis mortality rates arise from the absence of sepsis specific therapies. However with improvements in supportive care, patients with septic shock commonly partially recover from the infection that precipitated their initial illness, yet they frequently succumb to subsequent health care associated infections. Remarkably today the pathophysiology of sepsis in humans, a common disease in western society, remains largely a conundrum. Conventionally sepsis was regarded as primarily a disorder of inflammation. More recently the importance of immune compromise in the pathophysiology of sepsis and health care associated infection has now become more widely accepted. Accordingly a review of the human evidence for this novel sepsis paradigm is timely. Septic patients appear to exhibit a complex and long-lasting immune deficiency state, involving lymphocytes of both the innate and adaptive immune responses that have been linked with mortality and the occurrence of health care associated infection. Such is the pervasive nature of immune compromise in sepsis that ultimately immune modulation will play a crucial role in sepsis therapies of the future.


Equilibrium, hysteresis and kinetics of cadmium desorption from sodium-feldspar using rhamnolipid biosurfactant.
In this study, the sorption/desorption equilibruim and the desorption kinetics of Cd by rhamnolipid biosurfactant from Na-feldspar as a soil component were investigated. The linear, Langmuir and Freundlich isotherms adequately fitted the equilibrium sorption data with regression coefficients ranging from 0.9836 - 0.9879. However, both the sorption/desorption equilibria were well characterized by the Freundlich model. The extent of hysteresis was quantified based on the differences obtained from sorption and desorption isotherms regarding the quantity of Cd(II) sorbed, the Freundlich exponent, concentration-dependent metal distribution coefficients, and the irreversibility index based on the metal distribution coefficient. The kinetics of desorption of Cd from Na-feldspar was investigated using 77 mM rhamnolipid and at pH 6.8. The first-order, an empirical first-order desorption model (two-coefficient), Lagergren-pseudo-first-order, pseudo-second-order, Elovich and modified Freundlich models were used to describe the kinetic data to estimate the rate constants. To determine the rate-controlling step, the intra-particle diffusion model was also applied to the desorption process. The desorption kinetics of Cd(II) on Na-feldspar was represented better by the pseudo-second-order, Elovich and modified Freundlich equations with correlation coefficients ranging from 0.9941- 0.9982 than by first-order equations. The rate-controlling stage was suggested to be mainly the surface reaction mechanism.


Update on toll-like receptor ligands and allergy: implications for immunotherapy.
Innate responses to microbes are mediated in large part via toll-like receptors (TLRs) that recognize a diverse family of ligands produced by viruses, bacteria, and fungi. Great effort has been directed toward translating this knowledge into the development of therapies for the prevention and treatment of diseases, including those fueled by allergic (Th2-biased) hypersensitivities. In this review, we consider the ways in which ligands for different TLRs influence the allergic phenotype. In addition, an update on safety and efficacy data from clinical trials of allergic patients treated with TLR9 ligand-based interventions is provided. Finally, recent experimental results that help elucidate how ambient TLR ligand exposures influence allergic risk and their relevance to the development of TLR ligand-based therapeutics are discussed. Investigations presented within this opinion paper suggest that several TLR ligands could have clinical utility in the treatment of allergic diseases, whereas other TLR ligands appear less attractive, as they facilitate development of Th2-biased hypersensitivities in murine studies.


Link between light and fatty acid synthesis: thioredoxin-linked reductive activation of plastidic acetyl-CoA carboxylase.
Fatty acid synthesis in chloroplasts is regulated by light. The synthesis of malonyl-CoA, which is catalyzed by acetyl-CoA carboxylase (ACCase) and is the first committed step, is modulated by light/dark. Plants have ACCase in plastids and the cytosol. To determine the possible involvement of a redox cascade in light/dark modulation of ACCase, the effect of DTT, a known reductant of S-S bonds, was examined in vitro for the partially purified ACCase from pea plant. Only the plastidic ACCase was activated by DTT. This enzyme was activated in vitro more efficiently by reduced thioredoxin, which is a transducer of redox potential during illumination, than by DTT alone. Chloroplast thioredoxin-f activated the enzyme more efficiently than thioredoxin-m. The ACCase also was activated by thioredoxin reduced enzymatically with NADPH and NADP-thioredoxin reductase. These findings suggest that the reduction of ACCase is needed for activation of the enzyme, and a redox potential generated by photosynthesis is involved in its activation through thioredoxin as for enzymes of the reductive pentose phosphate cycle. The catalytic activity of ACCase was maximum at pH 8 and 2-5 mM Mg2+, indicating that light-produced changes in stromal pH and Mg2+ concentration modulate ACCase activity. These results suggest that light directly modulates a regulatory site of plastidic prokaryotic form of ACCase via a signal transduction pathway of a redox cascade and indirectly modulates its catalytic activity via stromal pH and Mg2+ concentration. A redox cascade is likely to link between light and fatty acid synthesis, resulting in coordination of fatty acid synthesis with photosynthesis.


Behavioral trajectories of aging prairie voles (Microtus ochrogaster): Adapting behavior to social context wanes with advanced age.
Several studies using mice have examined the effects of aging on cognitive tasks, as well as sensory and motor functions. However, few studies have examined the influence of aging on social behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous and biparental rodent that live in small family groups and are now among the most popular rodent models for studies examining social behavior. Although the social behavioral trajectories of early-life development in prairie voles have been well-studied, how social behavior may change throughout adulthood remains unknown. Here we examined behavior in virgin male and female prairie voles in four different age groups: postnatal day (PND) 60-80, 140-160, 220-240, and 300-320. All animals underwent testing in a novel object task, a dominance test, a resident-intruder test, and several iterations of social approach and social interaction tests with varying types of social stimuli (i.e., novel same-sex conspecific, novel opposite-sex conspecific, familiar same-sex sibling/cagemate, small group of novel same-sex conspecifics). We found that age influenced neophobia and dominance, but not social approach behavior. Further, we found that young adult, but not older adult, prairie voles adapt prosocial and aggressive behavior relative to social context, and that selective aggression occurs in relation to age even in the absence of a pair bond. Our results suggest that prairie voles calibrate social phenotype in a context-dependent manner in young adulthood and stop adjusting behavior to social context in advanced age, demonstrating that social behavior is plastic not only throughout early development, but also well into adulthood. Together, this study provides insight into age-related changes in social behavior in prairie voles and shows that prairie voles may be a viable model for studying the cognitive and physiological benefits of social relationships and social engagement in advanced age.


Procalcitonin to guide antibiotic decision making.
There is convincing evidence linking antibiotic-stewardship efforts which include the infection marker procalcitonin (PCT) to more rational use of antibiotics with improvements in side-effects and clinical outcomes. This is particularly true in the setting of respiratory infection and sepsis. Yet, some recent trials have shown no benefit of PCT-guided care. Our aim was to discuss the benefits and limitations of using PCT for early infection recognition, severity assessment and therapeutic decisions in individual patients based on most the recent study data. Current evidence from randomized trials, and meta-analyses of these trials, indicates that PCT-guided antibiotic stewardship results in a reduction in antibiotic use and antibiotic side-effects, which translates into improved survival of patients with respiratory infections and sepsis. Notably, initial PCT levels have been found to be helpful in defining the risk for bacterial infection in the context of a low pretest probability for bacterial infections (i.e., patients with bronchitis or chronic bastructive pulmonary disease exacerbation). Monitoring of repeated PCT measurements over time has also been found helpful for estimating recovery from bacterial infection and prognosis in higher risk situations (i.e., pneumonia or sepsis) and results in early and safe discontinuation of antibiotic therapy. Some trials, however, did not find a strong effect of PCT guidance which may be explained by low protocol adherence, assessment using only a single rather than repeat PCT levels and lower antibiotic exposure in control group patients. Using PCT in the right patient population, with high-sensitivity assays and with adequate training of physicians is important to increase protocol adherence and reduce antibiotic exposure. Inclusion of PCT into antibiotic stewardship algorithms has the potential to improve the diagnostic and therapeutic management of patients presenting with respiratory illnesses and sepsis, and holds great promise to mitigate the global bacterial resistance crisis and move from a default position of standardized care to more personalized treatment decisions.