Euparyphium albuferensis and Echinostoma friedi (Trematoda: Echinostomatidae): experimental cercarial transmission success in sympatric snail communities.
Euparyphium albuferensis and Echinostoma friedi cercarial infectivity to four species of sympatric snails was examined under single- or multiple-choice laboratory conditions to show the level of parasite-snail host compatibility. Radix peregra, Lymnaeafuscus, Physella acuta and Gyraulus chinensis act as second intermediate hosts of both parasite species although different cercarial transmission success (CTS) was observed. In single-host experiments, R. peregra and P. acuta showed a high degree of compatibility with E. albuferensis, while only P. acuta in the case of E. friedi. In two-choice snail communities, a snail with high CTS increased the values of another with low compatibility, in both parasite species. In multiple-choice snail communities, high CTS of some hosts decreased, while low CTS of other hosts increased. The degree of parasite-host compatibility of each snail species could be determined by the presence of other snails in the community.


High-bandwidth transfer of phase stability through a fiber frequency comb.
We demonstrate phase locking of a 729 nm diode laser to a 1542 nm master laser via an erbium-doped-fiber frequency comb, using a transfer-oscillator feedforward scheme which suppresses the effect of comb noise in an unprecedented 1.8 MHz bandwidth. We illustrate its performance by carrying out coherent manipulations of a trapped calcium ion with 99 % fidelity even at few-μs timescales. We thus demonstrate that transfer-oscillator locking can provide sufficient phase stability for high-fidelity quantum logic manipulation even without pre-stabilization of the slave diode laser.


Poly(p-phenyleneethynylene)-based tongues discriminate fruit juices.
We describe a simple optoelectronic tongue, consisting of a positively charged, fluorescent poly(para-phenyleneethynylene), P2, that reacts to fruit juices, when employed at three different pH-values (pH 3, 7, 13). This minimal tongue identifies and discriminates 14 different commercially available apple juices, 6 different grape juices and 5 different black currant juices from each other. A similar, negatively charged fluorescent polymer, P1, also achieved discrimination, but the analyte concentration had to be increased by a factor of 50. A mixture of black currant juice and red grape juice is identified as red grape juice, for specific combinations of grape and black currant juices. A mixture of red and green grape juice passes as red grape juice in our sensing system when it contains more than 70% of red grape juice. The data were obtained by fluorescence quenching of the conjugated polymers and processed by linear discriminant analysis of the collected data.


The HRAS1 variable number of tandem repeats and risk of breast cancer.
Rare alleles at the HRAS1 variable number of tandem repeats (VNTRs) locus have been implicated in breast cancer risk. We assessed the association of rare HRAS1 alleles and breast cancer in a case-control study nested within the Nurses' Health Study cohort. Using PCR-based methods, 717 incident breast cancer cases and 798 controls were genotyped for the HRAS1 VNTRs. The prevalence of the rare alleles in breast cancer cases was not different compared with controls (10.7 versus 12.0%, respectively; P = 0.45, two-sided Cochran-Mantel-Haenzel chi(2) test). There was no evidence that women heterozygous (multivariate odds ratio, 0.97; 95% confidence interval, 0.73-1.27) or homozygous (multivariate odds ratio, 0.83; 95% confidence interval, 0.32-2.14) for rare alleles were at an increased risk of breast cancer or that a positive gene-dose effect existed. The results did not vary by menopausal status. Although as a group the rare alleles were not associated with breast cancer, one class of rare alleles between the common alleles of a3 and a4 was associated with a significantly increased risk. These results suggest that there is no overall association between rare alleles of the HRAS1 VNTR and breast cancer.


Toll-like receptors--taking an evolutionary approach.
The Toll receptor was initially identified in Drosophila melanogaster for its role in embryonic development. Subsequently, D. melanogaster Toll and mammalian Toll-like receptors (TLRs) have been recognized as key regulators of immune responses. After ten years of intense research on TLRs and the recent accumulation of genomic and functional data in diverse organisms, we review the distribution and functions of TLRs in the animal kingdom. We provide an evolutionary perspective on TLRs, which sheds light on their origin at the dawn of animal evolution and suggests that different TLRs might have been co-opted independently during animal evolution to mediate analogous immune functions.


The impact of a multidimensional exercise program on self-reported anxiety and depression in cancer patients undergoing chemotherapy: a phase II study.
Little is known about the role of exercise in improving cancer patients' mood while undergoing chemotherapy. In this phase II study changes in self-reported anxiety and depression and fitness (VO2max) are reported in relation to a 6-week, 9 h weekly, multidimensional exercise program. A total of 91 patients receiving chemotherapy, between 18 and 65 years old, completed a Hospital Anxiety and Depression Scale Questionnaire (HADS; response rate 91%, adherence rate 78%). Anxiety (p < 0.001) and depression (p = 0.042) was significantly reduced. The mean +/- SD of the change was -1.14 +/- 2.91 for anxiety and -0.44 +/- 2.77 for depression. Improvements in fitness were correlated with improvements in depression, chi2(1) = 3.966, p = 0.046, but not with improvements in anxiety, chi2(1) = 0.540, p = 0.462. The research suggests that exercise intervention may have a beneficial impact on psychological distress for cancer patients receiving chemotherapy with low to moderate levels of baseline psychomorbidity. The study furthermore indicates that changes in distress may be associated with disease status and levels of physical activity undertaken during disease. The study is followed up by an ongoing randomized clinical controlled trial to evaluate potential causal effects of exercise intervention on psychological distress and fitness in cancer patients undergoing chemotherapy.


Kidney-Derived c-Kit+ Cells Possess Regenerative Potential.
Kidney-derived c-Kit+ cells exhibit progenitor/stem cell properties in vitro (self-renewal capacity, clonogenicity, and multipotentiality). These cells can regenerate epithelial tubular cells following ischemia-reperfusion injury and accelerate foot processes effacement reversal in a model of acute proteinuria in rats. Several mechanisms are involved in kidney regeneration by kidney-derived c-Kit+ cells, including cell engraftment and differentiation into renal-like structures, such as tubules, vessels, and podocytes. Moreover, paracrine mechanisms could also account for kidney regeneration, either by stimulating proliferation of surviving cells or modulating autophagy and podocyte cytoskeleton rearrangement through mTOR-Raptor and -Rictor signaling, which ultimately lead to morphological and functional improvement. To gain insights into the functional properties of c-Kit+ cells during kidney development, homeostasis, and disease, studies on lineage tracing using transgenic mice will unveil their fate. The results obtained from these studies will set the basis for establishing further investigation on the therapeutic potential of c-Kit+ cells for treatment of kidney disease in preclinical and clinical studies. Stem Cells Translational Medicine 2018;7:317-324.


Morphological-compound dysgraphia in an aphasic patient: "A wild write through the lexicon".
We describe the case of a dysgraphic aphasic individual--S.G.W.--who, in writing to dictation, produced high rates of formally related errors consisting of both lexical substitutions and what we call morphological-compound errors involving legal or illegal combinations of morphemes. These errors were produced in the context of a minimal number of semantic errors. We could exclude problems with phonological discrimination and phonological short-term memory. We also excluded rapid decay of lexical information and/or weak activation of word forms and letter representations since S.G.W.'s spelling showed no effect of delay and no consistent length effects, but, instead, paradoxical complexity effects with segmental, lexical, and morphological errors that were more complex than the target. The case of S.G.W. strongly resembles that of another dysgraphic individual reported in the literature--D.W.--suggesting that this pattern of errors can be replicated across patients. In particular, both patients show unusual errors resulting in the production of neologistic compounds (e.g., "bed button" in response to "bed"). These patterns can be explained if we accept two claims: (a) Brain damage can produce both a reduction and an increase in lexical activation; and (b) there are direct connections between phonological and orthographic lexical representations (a third spelling route). We suggest that both patients are suffering from a difficulty of lexical selection resulting from excessive activation of formally related lexical representations. This hypothesis is strongly supported by S.G.W.'s worse performance in spelling to dictation than in written naming, which shows that a phonological input, activating a cohort of formally related lexical representations, increases selection difficulties.


Measuring and comparing brain cortical surface area and other areal quantities.
Structural analysis of MRI data on the cortical surface usually focuses on cortical thickness. Cortical surface area, when considered, has been measured only over gross regions or approached indirectly via comparisons with a standard brain. Here we demonstrate that direct measurement and comparison of the surface area of the cerebral cortex at a fine scale is possible using mass conservative interpolation methods. We present a framework for analyses of the cortical surface area, as well as for any other measurement distributed across the cortex that is areal by nature. The method consists of the construction of a mesh representation of the cortex, registration to a common coordinate system and, crucially, interpolation using a pycnophylactic method. Statistical analysis of surface area is done with power-transformed data to address lognormality, and inference is done with permutation methods. We introduce the concept of facewise analysis, discuss its interpretation and potential applications.


Immunoproliferative Small Intestinal Disease Associated with Overwhelming Polymicrobial Gastrointestinal Infection with Transformation to Diffuse Large B-cell Lymphoma.
Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy.


Effects of an enrofloxacin-silver sulfadiazine emulsion in the ears of rabbits with perforated tympanic membranes.
To determine whether an enrofloxacin-silver sulfadiazine emulsion (ESS) labeled for treatment of otitis externa in dogs has ototoxic effects in rabbits following myringotomy. 6 healthy adult New Zealand White rabbits. Rabbits were anesthetized for brainstem auditory-evoked response (BAER) tests on day 0. Myringotomy was performed, and BAER testing was repeated. Saline (0.9% NaCl) solution and ESS were then instilled in the left and right middle ears, respectively, and BAER testing was repeated prior to recovery of rabbits from anesthesia. Application of assigned treatments was continued every 12 hours for 7 days, and rabbits were anesthetized for BAER testing on day 8. Rabbits were euthanized, and samples were collected for histologic (6 ears/treatment) and scanning electron microscopic (1 ear/treatment) examination. Most hearing thresholds (11/12 ears) were subjectively increased after myringotomy, with BAER measurements ranging from 30 to 85 dB in both ears. All day 8 hearing thresholds exceeded baseline (premyringotomy) values; results ranged from 30 to 85 dB and 80 to > 95 dB (the upper test limit) in saline solution-treated and ESS-treated ears, respectively. All ESS-treated ears had heterophilic otitis externa, epithelial hyperplasia of the external ear canal, various degrees of mucoperiosteal edema, and periosteal new bone formation on histologic examination. Scanning electron microscopy revealed that most outer hair cells in the ESS-treated ear lacked stereocilia or were absent. Results supported that ESS has ototoxic effects in the middle ear of rabbits. Further research is needed to confirm these findings. Myringotomized laboratory rabbits may be useful to study ototoxicity of drugs used in human medicine.


Myocardial flow reserve (MFR) with positron emission tomography (PET)/computed tomography (CT): clinical impact in diagnosis and prognosis.
In recent years, radionuclide myocardial perfusion imaging (MPI) using positron emission tomography/computed tomography (PET/CT) has emerged as a robust tool for the diagnosis, risk stratification and management of patients with known or established coronary artery disease (CAD). Cardiac PET/CT imaging affords key advantages compared to single photon emission computed tomography (SPECT) that encompass: (I) improved diagnostic accuracy; (II) decreased radiation exposure due to the utilization of short-lived radiopharmaceuticals, and importantly; (III) the ability to quantify noninvasively myocardial blood flow (MBF) in absolute terms, that is in ml per minute per gram of tissue. Quantitative approaches that measure MBF with PET can facilitate the diagnosis of multivessel CAD and offer the opportunity to monitor responses to lifestyle and/or risk factor modification and to therapeutic interventions. The aim of this review is to focus on the potential clinical utility of MBF and will discuss: (I) basics aspects of PET clinical perfusion tracers and flow quantification parameters; (II) limitations of relative MPI, (III) summarize a classification of diseases where flow quantification may be of use; (IV) specifically, review data on the diagnosis and prognostic value of flow quantification.


Optimal nonlinear information processing capacity in delay-based reservoir computers.
Reservoir computing is a recently introduced brain-inspired machine learning paradigm capable of excellent performances in the processing of empirical data. We focus in a particular kind of time-delay based reservoir computers that have been physically implemented using optical and electronic systems and have shown unprecedented data processing rates. Reservoir computing is well-known for the ease of the associated training scheme but also for the problematic sensitivity of its performance to architecture parameters. This article addresses the reservoir design problem, which remains the biggest challenge in the applicability of this information processing scheme. More specifically, we use the information available regarding the optimal reservoir working regimes to construct a functional link between the reservoir parameters and its performance. This function is used to explore various properties of the device and to choose the optimal reservoir architecture, thus replacing the tedious and time consuming parameter scannings used so far in the literature.


Motivation for lifestyle changes to improve health in people with impaired glucose tolerance.
To identify factors that could have motivational significance for lifestyle change to facilitate the reduction of Impaired Glucose Tolerance (IGT) and, consequently, the risk of having type 2 diabetes. Eighteen people living in a municipality in central Norway participated in the study. A large-scale public health screening study had defined them as people with IGT. The participants took part in a semi-structured interview that focused on four aspects of everyday lifestyle: (1) structure and rhythm, (2) physical health, (3) physical activity and (4) social relations. The interviews showed that the participants in the study changed their priorities regarding daily living. Results indicated four domains of motivational factors that appeared as significant for lifestyle changes. The participants attributed great significance to their physical health and were strongly motivated to prevent disease development by improvement of everyday structure and rhythm, reduction of sickness risk, activity level and social relation. Research indicates, however, that lasting lifestyle changes take time and that health care support must be adapted to the individual in light of their social setting. Persons with IGT appear to benefit from lifestyle changes along four dimensions of motivational significance: Structure and rhythm, Sickness concerns, Activity levels, Social relations. This means that attention needs to be more carefully tailored the individual along these four dimensions than has been the case in traditional health care.


Impact of stochastic migration on species diversity in meta-food webs consisting of several patches.
The structure of space has an appreciable influence on the diversity and stability of ecosystems. So far, there are only few theoretical studies investigating the population dynamics of food webs consisting of many species that can migrate between several patches, and in most of these models migration is a continuous, deterministic process. However, when migration events are rare (for instance because the patches are far apart), migration is a stochastic process and should be modeled accordingly. We present computer simulations of a food web model of many species on a spatial network of several patches, combining deterministic local population dynamics with stochastic migration. We evaluate the influence of the migration rate and other model parameters on local and regional species diversity and on stability. We find that migration increases the number of surviving and coexisting populations by two effects. These are the rescue effect, which restores local populations that have gone extinct, and dynamical coexistence, which sustains local populations that could not persist in the absence of immigration. Both effects occur even when migration events are rare. Species diversity increases on local and regional scales with the frequency of migration events. Furthermore, we investigate the adiabatic limit in which population dynamics always reaches an equilibrium before the next migration event, and we investigate the possible long-term scenarios. While the final state often contains the same food web on all patches, we also find instances where two slightly different food webs coexist on different patches, even when initially each patch contained the same food web.


Management of duodenal ulcer bleeding resistant to endoscopy: surgery is dead!
Acute massive duodenal bleeding is one of the most frequent complications of peptic ulcer disease. Endoscopy is the first-line method for diagnosing and treating actively bleeding peptic ulcers because its success rate is high. Of the small group of patients whose bleeding fails to respond to endoscopic therapy, increasingly the majority is referred for embolotherapy. Indeed, advances in catheter-based techniques and newer embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the management of hemorrhage from peptic ulcers over the past decade. Embolization may be effective for even the most gravely ill patients for whom surgery is not a viable option, even when extravasation is not visualized by angiography. However, it seems that careful selection of the embolic agents according to the bleeding vessel may play a role in a successful outcome. The role of the surgeon in this clinical sphere is dramatically diminishing and will certainly continue to diminish in ensuing years, surgery being typically reserved for patients whose bleeding failed to respond all previous treatments. Such a setting has become extremely rare.


Genome wide screens in yeast to identify potential binding sites and target genes of DNA-binding proteins.
Knowledge of all binding sites for transcriptional activators and repressors is essential for computationally aided identification of transcriptional networks. The techniques developed for defining the binding sites of transcription factors tend to be cumbersome and not adaptable to high throughput. We refined a versatile yeast strategy to rapidly and efficiently identify genomic targets of DNA-binding proteins. Yeast expressing a transcription factor is mated to yeast containing a library of genomic fragments cloned upstream of the reporter gene URA3. DNA fragments with target-binding sites are identified by growth of yeast clones in media lacking uracil. The experimental approach was validated with the tumor suppressor protein p53 and the forkhead protein FoxI1 using genomic libraries for zebrafish and mouse generated by shotgun cloning of short genomic fragments. Computational analysis of the genomic fragments recapitulated the published consensus-binding site for each protein. Identified fragments were mapped to identify the genomic context of each binding site. Our yeast screening strategy, combined with bioinformatics approaches, will allow both detailed and high-throughput characterization of transcription factors, scalable to the analysis of all putative DNA-binding proteins.


Transfusion of fresher versus older red blood cells for all conditions.
Red blood cell transfusion is a common treatment for anaemia in many clinical conditions. One current concern is uncertainty as to the clinical consequences (notably efficacy and safety) of transfusing red blood cell units that have been stored for different durations of time before a transfusion. If evidence from randomised controlled trials were to indicate that clinical outcomes are affected by storage age, the implications for inventory management and clinical practice would be significant. To assess the effects of using fresher versus older red blood cells in people requiring a red blood cell transfusion. We ran the search on 29th September 2014. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO), PubMed (for e-publications), three other databases and trial registers. We included randomised controlled trials comparing fresher red blood cell transfusion versus active transfusion of older red blood cells, and comparing fresher red blood cell transfusion versus current standard practice. All definitions of 'fresher' and 'older'/'standard practice' red blood cells were included. Two review authors independently assessed trial quality and extracted from the trial report data on adverse red blood cell transfusion reactions, when reported. We included 16 trials (1864 participants) in the review. Eight trials (279 participants) compared transfusion of fresher red blood cells versus transfusion of older stored red blood cells ('fresher' vs 'older'). Eight trials (1585 participants) compared the transfusion of fresher red blood cells versus current standard practice ('fresher' vs 'standard practice'). Five trials enrolled neonates, one trial enrolled children and 12 trials enrolled adults. Overall sample sizes were small: only two trials randomly assigned more than 100 participants.We performed no meta-analyses for a variety of reasons: no uniform definition of 'fresher' or 'older' red blood cell storage; overlap in the distribution of the age of red blood cells; and heterogeneity in measurements and reporting of outcomes of interest to this review. We tabulated and reported results by individual trial. Overall risk of bias was low or unclear, with four incidences of high risk of bias: in allocation concealment (three trials) and in incomplete outcome data (one trial).No trial measured all of the outcomes of interest in this review. Four trials comparing 'fresher' with 'older' red blood cells reported the primary outcome: mortality within seven days (one study; 74 participants) and at 30 days (three trials; 62 participants). Six trials comparing 'fresher' with 'standard practice' red blood cells reported the primary outcome: mortality within seven days (three studies; 159 participants) and at 30 days (three trials; 1018 participants). All 10 trials reported no clear differences in mortality at either time point between intervention arms.Three trials comparing 'fresher' with 'standard practice' red blood cells reported red blood cell transfusion-associated adverse events. No adverse reactions were reported in two trials, and one incidence of cytomegalovirus (CMV) infection was described in the 'standard practice' arm in one trial.Overall the trials reported no clear difference between either of the intervention comparisons in long-term mortality (three trials; 478 participants); clinically accepted measures of multiple organ dysfunction (two trials: 399 participants); incidence of in-hospital infection (two trials; 429 participants); duration of mechanical ventilation (three trials: 95 participants); and number of participants requiring respiratory organ support (five trials; 528 participants) or renal support (one trial; 57 participants). The outcome 'physiological markers of oxygen consumption or alterations in microcirculation' was reported by 11 studies, but the measures used were highly varied, and no formal statistical analysis was undertaken. Several factors precluded firm conclusions about the clinical outcomes of transfusing red blood cell units that have been stored for different periods of time before transfusion, including differences in clinical population and setting, diversity in the interventions used, methodological limitations and differences in how outcomes were measured and reported.No clear differences in the primary outcome - death - were noted between 'fresher' and 'older' or 'standard practice' red blood cells in trials that reported this outcome. Findings of a large number of ongoing trials will be incorporated into this review when they are published.Updates of this review will explore the degree of overlap in trials between 'fresher', 'older' and 'standard practice' storage ages of red blood cells and will consider whether the size of any observed effects is dependent on recipient factors such as clinical background, patient age or clinical presentation.


Recovery of Rare Earth Elements and Yttrium from Passive-Remediation Systems of Acid Mine Drainage.
Rare earth elements and yttrium (REY) are raw materials of increasing importance for modern technologies, and finding new sources has become a pressing need. Acid mine drainage (AMD) is commonly considered an environmental pollution issue. However, REY concentrations in AMD can be several orders of magnitude higher than in naturally occurring water bodies. With respect to shale standards, the REY distribution pattern in AMD is enriched in intermediate and valuable REY, such as Tb and Dy. The objective of the present work is to study the behavior of REY in AMD passive-remediation systems. Traditional AMD passive remediation systems are based on the reaction of AMD with calcite-based permeable substrates followed by decantation ponds. Experiments with two columns simulating AMD treatment demonstrate that schwertmannite does not accumulate REY, which, instead, are retained in the basaluminite residue. The same observation is made in two field-scale treatments from the Iberian Pyrite Belt (IPB, southwest Spain). On the basis of the amplitude of this process and on the extent of the IPB, our findings suggest that the proposed AMD remediation process can represent a modest but suitable REY source. In this sense, the IPB could function as a giant heap-leaching process of regional scale in which rain and oxygen act as natural driving forces with no energy investment. In addition to having environmental benefits of its treatment, AMD is expected to last for hundreds of years, and therefore, the total reserves are practically unlimited.


Postpartum cervical repair in mice: a morphological characterization and potential role for angiogenic factors.
The cervix undergoes marked mechanical trauma during delivery of the baby at birth. As such, a timely and complete tissue repair postpartum is necessary to prevent obstetrical complications, such as cervicitis, ectropion, hemorrhage, repeated miscarriages or abortions and possibly preterm labor and malignancies. However, our knowledge of normal cervical repair is currently incomplete and factors that influence repair are unclear. Here, we characterize the morphological and angiogenic profile of postpartum repair in mice cervix during the first 48 h of postpartum. The key findings presented here are: (1) cervical epithelial folds and size are diminished during the first 48 h of postpartum repair, (2) hypoxic inducible factor 1a, vascular endothelial growth factor (VEGF), and VEGF receptor 1 expression are pronounced early in postpartum cervical repair, and (3) VEGF receptor 2 gene and protein expressions are variable. We conclude that postpartum cervical repair involves gross and microscopic changes and is linked to expression of angiogenic factors. Future studies will assess the suitability of these factors, identified in the present study, as potential markers for determining the phase of postpartum cervical repair in obstetrical complications, such as cervical lacerations.


Acupuncture for chronic pain: is acupuncture more than an effective placebo? A systematic review of pooled data from meta-analyses.
There is controversy as to whether or not acupuncture is more effective than placebo. To help clarify this debate, we synthesized the evidence gathered from systematic reviews on the pooled data of high-quality randomized controlled trials comparing acupuncture to sham acupuncture for chronic pain. Systematic reviews of acupuncture for the most commonly occurring forms of chronic pain (back, knee, and head) published between 2003 and 2008 were sourced from Ovid databases: Medline, Allied and Complementary Medicine database, Cochrane Library and Web of Science during December 2008. Eight systematic reviews with meta-analyses of pooled data were eligible for inclusion. Data were extracted for short- and longer-term outcomes for the most commonly occurring forms of pain. Two independent reviewers assessed methodological quality. For short-term outcomes, acupuncture showed significant superiority over sham for back pain, knee pain, and headache. For longer-term outcomes (6 to12 months), acupuncture was significantly more effective for knee pain and tension-type headache but inconsistent for back pain (one positive and one inconclusive). In general, effect sizes (standardized mean differences) were found to be relatively small. The accumulating evidence from recent reviews suggests that acupuncture is more than a placebo for commonly occurring chronic pain conditions. If this conclusion is correct, then we ask the question: is it now time to shift research priorities away from asking placebo-related questions and shift toward asking more practical questions about whether the overall benefit is clinically meaningful and cost-effective?


Thermodynamics-Based Molecular Modeling of α-Helices in Membranes and Micelles.
The Folding of Membrane-Associated Peptides (FMAP) method was developed for modeling α-helix formation by linear peptides in micelles and lipid bilayers. FMAP 2.0 identifies locations of α-helices in the amino acid sequence, generates their three-dimensional models in planar bilayers or spherical micelles, and estimates their thermodynamic stabilities and tilt angles, depending on temperature and pH. The method was tested for 723 peptides (926 data points) experimentally studied in different environments and for 170 single-pass transmembrane (TM) proteins with available crystal structures. FMAP 2.0 detected more than 95% of experimentally observed α-helices with an average error in helix end determination of around 2, 3, 4, and 5 residues per helix for peptides in water, micelles, bilayers, and TM proteins, respectively. Helical and nonhelical residue states were predicted with an accuracy from 0.86 to 0.96, and the Matthews correlation coefficient was from 0.64 to 0.88 depending on the environment. Experimental micelle- and membrane-binding energies and tilt angles of peptides were reproduced with a root-mean-square deviation of around 2 kcal/mol and 7°, respectively. The TM and non-TM states of hydrophobic and pH-triggered α-helical peptides in various lipid bilayers were reproduced in more than 95% of cases. The FMAP 2.0 web server (https://membranome.org/fmap) is publicly available to explore the structural polymorphism of antimicrobial, cell-penetrating, fusion, and other membrane-binding peptides, which is important for understanding the mechanisms of their biological activities.


A single-amino-acid substitution eliminates the stringent carbohydrate requirement for intracellular transport of a viral glycoprotein.
In this report, we have investigated the contribution of primary sequence to the carbohydrate requirement for intracellular transport of two closely related glycoproteins, the G proteins of the San Juan and Orsay strains of vesicular stomatitis virus. We used site-directed mutagenesis of the coding sequence to eliminate the two consensus sites for glycosylation in the Orsay G protein. Whereas the nonglycosylated San Juan G protein required at least one of its two asparagine-linked oligosaccharides for transport to the plasma membrane at 37 degrees C, a fraction of the Orsay G protein was transported without carbohydrate. Of the 10 amino acid differences between these two proteins, residue 172 (tyrosine in San Juan, aspartic acid in Orsay) played the major role in determining the stringency for the carbohydrate requirement. The rates at which the glycosylated and nonglycosylated Orsay G proteins were transported to the cell surface were the same, although a smaller fraction of the nonglycosylated protein was transported. These results suggest that the carbohydrate does not promote intracellular transport directly but influences a polypeptide folding or oligomerization step which is critical for transport.


Prediction of early recurrence of hepatocellular carcinoma after resection using digital pathology images assessed by machine learning.
Hepatocellular carcinoma (HCC) is a representative primary liver cancer caused by long-term and repetitive liver injury. Surgical resection is generally selected as the radical cure treatment. Because the early recurrence of HCC after resection is associated with low overall survival, the prediction of recurrence after resection is clinically important. However, the pathological characteristics of the early recurrence of HCC have not yet been elucidated. We attempted to predict the early recurrence of HCC after resection based on digital pathologic images of hematoxylin and eosin-stained specimens and machine learning applying a support vector machine (SVM). The 158 HCC patients meeting the Milan criteria who underwent surgical resection were included in this study. The patients were categorized into three groups: Group I, patients with HCC recurrence within 1 year after resection (16 for training and 23 for test); Group II, patients with HCC recurrence between 1 and 2 years after resection (22 and 28); and Group III, patients with no HCC recurrence within 4 years after resection (31 and 38). The SVM-based prediction method separated the three groups with 89.9% (80/89) accuracy. Prediction of Groups I was consistent for all cases, while Group II was predicted to be Group III in one case, and Group III was predicted to be Group II in 8 cases. The use of digital pathology and machine learning could be used for highly accurate prediction of HCC recurrence after surgical resection, especially that for early recurrence. Currently, in most cases after HCC resection, regular blood tests and diagnostic imaging are used for follow-up observation; however, the use of digital pathology coupled with machine learning offers potential as a method for objective postoprative follow-up observation.


Origin and detection of microstructural clustering in fluids with spatial-range competitive interactions.
Fluids with competing short-range attractions and long-range repulsions mimic dispersions of charge-stabilized colloids that can display equilibrium structures with intermediate-range order (IRO), including particle clusters. Using simulations and analytical theory, we demonstrate how to detect cluster formation in such systems from the static structure factor and elucidate links to macrophase separation in purely attractive reference fluids. We find that clusters emerge when the thermal correlation length encoded in the IRO peak of the structure factor exceeds the characteristic length scale of interparticle repulsions. We also identify qualitative differences between the dynamics of systems that form amorphous versus microcrystalline clusters.


Artifacts in plasma volume changes due to hematology analyzer-derived hematocrit.
This investigation quantified the effect of changes in plasma osmolality on the measurement of hematocrit (Hct) and the implications for the subsequent use of these data to calculate changes in plasma volume and application to the World Anti-Doping Agency Athlete Biological Passport. Two groups of eight male volunteers visited the laboratory after an overnight fast. In study 1, a 20-mL blood sample was collected and aliquoted into collection tubes containing saline of varying concentrations to alter the sample osmolality. In study 2, plasma osmolality was manipulated in vivo through prolonged exercise. Samples were analyzed for hemoglobin concentration and Hct using manual methods and using an automated hematology analyzer (AHA). Changes in blood, plasma, and red cell volumes were calculated. Although AHA Hct values did not change (P = 0.652), spun packed cell volume fell progressively as the osmolality of the sample increased (P < 0.001, study 1). Consequently, there was a significant increase in apparent plasma volume as osmolality increased (P < 0.001): regression analysis revealed that a 10 mOsm·kg change in plasma osmolality produced a difference of 0.8 Hct units and a 1.6% change in plasma volume. In study 2, exercise produced a 12 ± 3 mOsm·kg increase in plasma osmolality. No difference in Hct was apparent at rest (P = 0.659), but spun packed cell volume was 1.0 ± 0.9 Hct units lower during exercise compared with AHA data (P < 0.001). There was a difference in the degree of plasma volume change calculated, with a reduction of 8.7% ± 3.4% and 11.3% ± 3.5% reported with the manual and AHA methods, respectively (P = 0.002). Conditions or interventions that result in a marked change in plasma osmolality produce a discrepancy in Hct measured using an AHA, consequently introducing errors into any calculation of changes in plasma volume using these data. These findings may also have implications for the measurement of Hct by World Anti-Doping Agency-accredited laboratories.


A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates.
Malaria vaccine design and prioritization has been hindered by the lack of a mechanistic correlate of protection. We previously demonstrated a strong association between protection and merozoite-neutralizing antibody responses following vaccination of non-human primates against Plasmodium falciparum reticulocyte binding protein homolog 5 (PfRH5). Here, we test the mechanism of protection. Using mutant human IgG1 Fc regions engineered not to engage complement or FcR-dependent effector mechanisms, we produce merozoite-neutralizing and non-neutralizing anti-PfRH5 chimeric monoclonal antibodies (mAbs) and perform a passive transfer-P. falciparum challenge study in Aotus nancymaae monkeys. At the highest dose tested, 6/6 animals given the neutralizing PfRH5-binding mAb c2AC7 survive the challenge without treatment, compared to 0/6 animals given non-neutralizing PfRH5-binding mAb c4BA7 and 0/6 animals given an isotype control mAb. Our results address the controversy regarding whether merozoite-neutralizing antibody can cause protection against P. falciparum blood-stage infections, and highlight the quantitative challenge of achieving such protection.


S-adenosylmethionine prevents chronic alcohol-induced mitochondrial dysfunction in the rat liver.
An early event that occurs in response to alcohol consumption is mitochondrial dysfunction, which is evident in changes to the mitochondrial proteome, respiration defects, and mitochondrial DNA (mtDNA) damage. S-adenosylmethionine (SAM) has emerged as a potential therapeutic for treating alcoholic liver disease through mechanisms that appear to involve decreases in oxidative stress and proinflammatory cytokine production as well as the alleviation of steatosis. Because mitochondria are a source of reactive oxygen/nitrogen species and a target for oxidative damage, we tested the hypothesis that SAM treatment during alcohol exposure preserves organelle function. Mitochondria were isolated from livers of rats fed control and ethanol diets with and without SAM for 5 wk. Alcohol feeding caused a significant decrease in state 3 respiration and the respiratory control ratio, whereas SAM administration prevented these alcohol-mediated defects and preserved hepatic SAM levels. SAM treatment prevented alcohol-associated increases in mitochondrial superoxide production, mtDNA damage, and inducible nitric oxide synthase induction, without a significant lessening of steatosis. Accompanying these indexes of oxidant damage, SAM prevented alcohol-mediated losses in cytochrome c oxidase subunits as shown using blue native PAGE proteomics and immunoblot analysis, which resulted in partial preservation of complex IV activity. SAM treatment attenuated the upregulation of the mitochondrial stress chaperone prohibitin. Although SAM supplementation did not alleviate steatosis by itself, SAM prevented several key alcohol-mediated defects to the mitochondria genome and proteome that contribute to the bioenergetic defect in the liver after alcohol consumption. These findings reveal new molecular targets through which SAM may work to alleviate one critical component of alcohol-induced liver injury: mitochondria dysfunction.


Percutaneous coronary intervention vs coronary artery bypass grafting in the management of chronic stable angina: A critical appraisal.
Chronic stable angina is a clinical expression of myocardial ischemia associated with fixed atherosclerotic coronary stenosis, which prevents the adaptation of coronary circulation resulting in an increased oxygen requirement. We recommend that once the diagnosis of chronic stable angina is made, first every patient should be offered the optimal medical therapy, including ACE inhibitors, beta-blockers, statins, and nitrates. If the patients' symptoms are not controlled in spite of these drugs being used in maximum tolerated dosages, then these patients should be subjected to coronary angiography. If a patient shows a single-or double-vessel disease, then PCI should be offered. On the contrary, if the coronary angiogram shows a triple-vessel disease and left main disease, then one has to look for comorbidities that put the patient at a higher risk of CABG and the patient should be treated with PCI. Other patients with left main and triple-vessel disease having diabetes and left ventricular dysfunction should go directly for surgical revascularization. Overall, health related quality of life (HRQoL) is similar in both PCI and CABG.


Relationship of various infection control interventions to the prevalence of multidrug-resistant Pseudomonas aeruginosa among U.S. hospitals.
Health care-associated infections caused by antibiotic-resistant gram-negative bacteria, such as Pseudomonas aeruginosa, are an emerging and increasingly important public health threat. However, there are very few studies that examine the relationships between antimicrobial resistance strategies and interventions and the prevalence of antibiotic-resistant and multidrug-resistant strains of Pseudomonas. The membership of the Association for Professionals in Infection Control and Epidemiology was invited to participate in a Web-based survey of U.S. acute care hospital infection preventionists. A final sample of 225 completed responses was analyzed using correlational techniques. Resistance to gentamicin (r = 0.17, P = .01), imipenem (r = 0.18, P = .02), ceftazidime (r = 0.20, P = .03), and ciprofloxacin (r = 0.15, P = .03) all showed significant direct associations with epidemiologic investigation using molecular testing. A significant inverse relationship was found between resistance to ceftazidime and effective efforts in the identification and isolation of infected patients (r = -0.18, P = .02). The finding of significant direct relationships between antimicrobial resistance and epidemiologic investigations using molecular testing suggests that the increased burden of resistance is associated with molecular testing rather than the intervention driving down rates. Effective identification and isolation of infected patients appeared to be associated with lower resistance rates. Further research is needed to uncover causal relationships.


Preferential adsorption of amino-terminated silane in a binary mixed self-assembled monolayer.
The composition and structure of a binary mixed self-assembled monolayer (SAM) of 3-aminopropyltriethoxysilane (APS, NH(2)(CH(2))(3)Si(OCH(2)CH(3))(3)) and octadecyltrimethoxysilane (ODS, CH(3)(CH(2))(17)Si(OCH(3))(3)) on a silicon oxide surface have been characterized by water contact-angle measurements, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and sum frequency generation (SFG) vibrational spectroscopy. XPS demonstrated that APS in the mixed SAM is significantly enriched in comparison to that in solution, indicating the preferential adsorption of APS during the SAM formation. AFM observations showed that the mixed SAM becomes rougher. SFG revealed that the coadsorption of APS induced a conformation disordering in the ODS molecules present in the mixed SAM. The surface enrichment of APS has been explained in terms of differences in the surface adsorption rates of the two components as well as in the self-congregation states of APS molecules in the bulk solution. Furthermore, the structure of the water molecules on the mixed SAM surface in contact with the aqueous solutions at different pH's has also been studied. The results indicate that the mixed-SAM modified surface is positively charged at pH < 5 and negatively charged at pH > 7.


"Quite a Profoundly Strange Experience": An Analysis of the Experiences of Salvia divinorum Users.
Salvia divnorum (an intense hallucinogen) is currently illegal in New Zealand under the 2014 Psychoactive Substances Amendment Act. Despite this, there is a scarcity of research surrounding Salvia divinorum and its effects in a New Zealand context. To explore the experiences of Salvia divinorum users, an anonymous questionnaire was advertised through flyers placed in locations where young adults congregate. A total of 393 people took part in the online questionnaire in 2010-2011, while salvia was legally available in New Zealand; 167 respondents had used salvia. Thematic analysis was used to analyze the resulting open-ended questionnaire data and three key themes were identified: the effects of salvia; the importance of set and setting; salvia use and pleasure/not-pleasure. Recreational use of salvia was situated within a broader drug landscape, with participants being drug experienced and "drug wise" (Measham, Aldridge, and Parker 2001). Use of salvia also appeared to be intermittent, with its use referred to as a novel experience. Thus, the recent criminalization of salvia under the 2014 Act may see a significant decline in use as experienced drug users look elsewhere for novel drug experiences.


Predicting time to full-time care in AD: a new model.
To develop a model to predict the length of time before patients with Alzheimer's disease (AD) of varying severity require full-time care (FTC). A predictive model (equation) of time to FTC (defined as being institutionalised or dependent) was developed based on the London and South-East Region (LASER-AD) epidemiological study using a discrete time representation of the Cox continuous time proportional hazards model and complementary log-log specification. Of the 117 pre-FTC patients, 68 (58.1%) patients progressed to FTC during the 54-month follow-up period. Analysis of potential predictors showed that baseline cognitive state, impairment of activities of daily living (ADL) and neuropsychiatric symptoms were strong predictors of time to FTC. In addition, the rate of cognitive and ADL decline predicted time to FTC. The final model predicted 88.2% of observations. The model simulates and predicts progression of pre-FTC AD patients until the need for FTC based on assessments for cognitive, functional and behavioural domains. The main application of the model is to assess the cost effectiveness of AD therapies as potential adjuncts to a background AD treatment including disease-modifying treatments. The applicability of the predictive model to a specific setting should be carefully assessed, i.e. the patient population being examined should have similar characteristics as patients in the LASER-AD cohort.


In silico approach to predict pancreatic β-cells classically secreted proteins.
Pancreatic β-cells, residents of the islets of Langerhans, are the unique insulin-producers in the body. Their physiology is a topic of intensive studies aiming to understand the biology of insulin production and its role in diabetes pathology. However, investigations about these cells' subset of secreted proteins, the secretome, are surprisingly scarce and a list describing islet/β-cell secretome upon glucose-stimulation is not yet available. In silico predictions of secretomes are an interesting approach that can be employed to forecast proteins likely to be secreted. In this context, using the rationale behind classical secretion of proteins through the secretory pathway, a Python tool capable of predicting classically secreted proteins was developed. This tool was applied to different available proteomic data (human and rodent islets, isolated β-cells, β-cell secretory granules, and β-cells supernatant), filtering them in order to selectively list only classically secreted proteins. The method presented here can retrieve, organize, search and filter proteomic lists using UniProtKB as a central database. It provides analysis by overlaying different sets of information, filtering out potential contaminants and clustering the identified proteins into functional groups. A range of 70-92% of the original proteomes analyzed was reduced generating predicted secretomes. Islet and β-cell signal peptide-containing proteins, and endoplasmic reticulum-resident proteins were identified and quantified. From the predicted secretomes, exemplary conservational patterns were inferred, as well as the signaling pathways enriched within them. Such a technique proves to be an effective approach to reduce the horizon of plausible targets for drug development or biomarkers identification.


Recent advances in functionalized micro and mesoporous carbon materials: synthesis and applications.
Functionalized nanoporous carbon materials have attracted the colossal interest of the materials science fraternity owing to their intriguing physical and chemical properties including a well-ordered porous structure, exemplary high specific surface areas, electronic and ionic conductivity, excellent accessibility to active sites, and enhanced mass transport and diffusion. These properties make them a special and unique choice for various applications in divergent fields such as energy storage batteries, supercapacitors, energy conversion fuel cells, adsorption/separation of bulky molecules, heterogeneous catalysts, catalyst supports, photocatalysis, carbon capture, gas storage, biomolecule detection, vapour sensing and drug delivery. Because of the anisotropic and synergistic effects arising from the heteroatom doping at the nanoscale, these novel materials show high potential especially in electrochemical applications such as batteries, supercapacitors and electrocatalysts for fuel cell applications and water electrolysis. In order to gain the optimal benefit, it is necessary to implement tailor made functionalities in the porous carbon surfaces as well as in the carbon skeleton through the comprehensive experimentation. These most appealing nanoporous carbon materials can be synthesized through the carbonization of high carbon containing molecular precursors by using soft or hard templating or non-templating pathways. This review encompasses the approaches and the wide range of methodologies that have been employed over the last five years in the preparation and functionalisation of nanoporous carbon materials via incorporation of metals, non-metal heteroatoms, multiple heteroatoms, and various surface functional groups that mostly dictate their place in a wide range of practical applications.


Impact on the NHS and health of the UK's trade and cooperation relationship with the EU, and beyond.
The UK's relationship with the European Union (EU) is now embodied in two principal legal instruments: the EU-UK Trade and Cooperation Agreement, which formally entered into force on 1 May 2021; and the Withdrawal Agreement, with its Protocol on Ireland/Northern Ireland, which continues to apply. Using a 'building blocks' framework for analysis of national health systems derived from the World Health Organisation, this article examines the likely impacts in the UK of this legal settlement on the National Health Service (NHS), health and social care. Specifically, we determine the extent to which the trade, cooperation and regulatory aspects of those legal measures support positive impacts for the NHS and social care. We show that, as there is clear support for positive health and care outcomes in only one of the 17 NHS 'building blocks', unless mitigating action is taken, the likely outcomes will be detrimental. However, as the legal settlement gives the UK a great deal of regulatory freedom, especially in Great Britain, we argue that it is crucial to track the effects of proposed new health and social care-related policy choices in the months and years ahead.


Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia.
To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.


Obstructive Sleep Apnea Is Associated with Elevated High Sensitivity C-Reactive Protein Levels Independent of Obesity: Korean Genome and Epidemiology Study.
Obstructive sleep apnea syndrome (OSA) has been recognized as a common health problem, and increasing obesity rates have led to further remarkable increases in the prevalence of OSA, along with more prominent cardiovascular morbidities. Though previous studies have reported an independent relationship between elevated high sensitivity C-reactive protein (hsCRP) levels and OSA, the issue remains controversial owing to inadequate consideration of obesity and various confounding factors. So far, few population based studies of association between OSA and hsCRP levels have been published. Therefore, the purpose of the present study was to investigate whether OSA is associated with increased hsCRP levels independent of obesity in a large population-based study. A total of 1,835 subjects (968 men and 867 women) were selected from a larger cohort of the ongoing Korean Genome and Epidemiology Study (KoGES). Overnight polysomnography was performed on each participant. All participants underwent anthropometric measurements and biochemical analyses, including analysis of lipid profiles and hsCRP levels. Based on anthropometric data, body mass index (BMI) and waist hip ratio (WHR) were calculated and fat mass (FM) were measured by means of multi-frequency bioelectrical impedance analysis (BIA). Mild OSA and moderate to severe OSA were defined by an AHI >5 and ≥15, respectively. The population was sub-divided into 3 groups based on the tertile cut-points for the distribution of hsCRP levels. The percentage of participants in the highest tertile of hsCRP increased dose-dependently according to the severity of OSA. After adjustment for potential confounders and obesity-related variables (BMI, WHR, and body fat) in a multiple logistic model, participants with moderate to severe OSA had 1.73-, 2.01-, and 1.61-fold greater risks of being in the highest tertile of hsCRP levels than participants with non-OSA, respectively. Interaction between obesity (BMI ≥25kg/m2) and the presence of moderate-to-severe OSA was significant on the middle tertile levels of hsCRP (OR = 2.4), but not on the highest tertile, compared to the lowest tertile. OSA is independently associated with elevated hsCRP levels and may reflect an increased risk for cardiovascular morbidity. However, we found that OSA and obesity interactively contribute to individuals with general levels of hsCRP (<1.01 mg/dl). The short-term and long-term effects of elevated hsCRP levels on cardiovascular risk in the context of OSA remain to be defined in future studies.


Systemic prednisone administration selectively alters granulocyte subsets in nasal polyps from aspirin-exacerbated respiratory disease and chronic rhinosinusitis patients.
Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis. Despite the spectrum of NP conditions, cellular differences between NPs from patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) are poorly understood. NPs are associated with abundant eosinophils; the contributions of neutrophil and basophil granulocytes are less defined. We therefore sought to assess granulocyte subpopulations, and differential effects following prednisone pretreatment, within NPs of CRSwNP and AERD patients. NPs, adjacent ethmoid sinus tissue, and peripheral blood mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus surgery. Samples from 5 cohorts: CRSwNP ± prednisone (n = 6 each), AERD ± prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional flow cytometry to gate granulocyte populations. Specimens were also assessed using immunohistochemistry (IHC) staining. Systemic prednisone administration was associated with a lower frequency of eosinophils (p < 0.0001, n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils (p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone treatment. In contrast, steroids do not alter basophil proportions (p = 0.48, n = 6) within NPs from either group. No significant shift in granulocyte subsets after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs from the same patients. Immunohistochemistry (IHC) staining supported these findings. Granulocyte subpopulations are focally affected within NPs by systemic steroid exposure, without notable granulocyte alterations in the surrounding regional tissues. These data provide direct insights into the cellular effects of routine prednisone exposure in CRS patients, and highlight a unique microenvironment present within NP lesions.


Subcellular structure of endosperm protein in high-lysine and normal corn.
Optical microscopy shows that the protein network in endosperm cells of normal corn is composed of an amorphous matrix in which granules averaging about 2 microns in diameter are embedded. That these granules are rich in zein is demonstrated by their solubility in 80 percent ethanol. High-lysine corn, with submicroscopic granules clearly resolved only in the electron microscope, has a much lower content of zein than normal corn. The small size of subcellular protein granules in high-lysine maize as compared with normal corn correlates with the reported difference in zein content of the two types of corn.


Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.
Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.


Liquid-phase characterization of molecular interactions in polyunsaturated and n-fatty acid methyl esters by (1)H low-field nuclear magnetic resonance.
To identify and develop the best renewable and low carbon footprint biodiesel substitutes for petroleum diesel, the properties of different biodiesel candidates should be studied and characterized with respect to molecular structures versus biodiesel liquid property relationships. In our previous paper, (1)H low-field nuclear magnetic resonance (LF-NMR) relaxometry was investigated as a tool for studying the liquid-phase molecular packing interactions and morphology of fatty acid methyl esters (FAMEs). The technological potential was demonstrated with oleic acid and methyl oleate standards having similar alkyl chains but different head groups. In the present work, molecular organization versus segmental and translational movements of FAMEs in their pure liquid phase, with different alkyl chain lengths (10-20 carbons) and degrees of unsaturation (0-3 double bonds), were studied with (1)H LF-NMR relaxometry and X-ray, (1)H LF-NMR diffusiometry, and (13)C high-field NMR. Based on density values and X-ray measurements, it was proposed that FAMEs possess a liquid crystal-like order above their melting point, consisting of random liquid crystal aggregates with void spaces between them, whose morphological properties depend on chain length and degree of unsaturation. FAMEs were also found to exhibit different degrees of rotational and translational motions, which were rationalized by chain organization within the clusters, and the degree and type of molecular interactions and temperature effects. At equivalent fixed temperature differences from melting point, saturated FAME molecules were found to have similar translational motion regardless of chain length, expressed by viscosity, self-diffusion coefficients, and spin-spin (T 2) (1)H LF-NMR. T 2 distributions suggest increased alkyl chain rigidity, and reduced temperature response of the peaks' relative contribution with increasing unsaturation is a direct result of the alkyl chain's morphological packing and molecular interactions. Both the peaks' assignments for T 2 distributions of FAMEs and the model for their liquid crystal-like morphology in the liquid phase were confirmed. The study of morphological structures within liquids and their response to temperature changes by (1)H LF-NMR has a high value in the field of biodiesel and other research and applied disciplines in numerous physicochemical- and organizational-based properties, processes, and mechanisms of alkyl chains, molecular interactions, and morphologies.


Role of medullary I1-imidazoline and alpha 2-adrenergic receptors in the antihypertensive responses evoked by central administration of clonidine analogs in conscious spontaneously hypertensive rats.
The antihypertensive action of clonidine analogs are generally ascribed to stimulation of medullary alpha 2-adrenergic receptors. Several recent studies have implicated the newly characterized class of imidazoline receptors as playing a more important role in this regard. In this study, a series of doses of four imidazoline and two nonimidazoline antihypertensive drugs were administered by intracisternal (i.c.) injection to freely moving spontaneously hypertensive rats. All six drugs produced a dose-dependent fall in mean arterial pressure (MAP) and heart rate (HR). The most potent agents in lowering MAP were the imidazoline agents, particularly moxonidine, a drug that has high affinity for I1-imidazoline receptors, but relatively low affinity for alpha 2-adrenergic receptors. There was a high correlation between the apparent binding affinity (Ki) for I1-receptors on membranes derived from bovine rostral ventrolateral medulla and the relative potency for lowering MAP after i.c. injection in spontaneously hypertensive rats. In contrast, no correlation existed between binding affinity values for alpha 2-adrenergic receptors derived from the same source and the antihypertensive response. The results of these experiments are consistent with a role for medullary I1-imidazoline receptors in mediating the antihypertensive action of clonidine and related imidazoline compounds in conscious hypertensive animals. The nonimidazoline agent, guanfacine, although a clinically effective antihypertensive agent, was not efficacious after i.c. injection. This discrepancy may be explained by an opposing pressor action or by a depressor action mediated by alpha 2-adrenergic receptors at an alternate site when the drug is peripherally administered. In contrast, the other nonimidazoline antihypertensive agent azepexole was fully efficacious after i.c. injection of the highest doses. Further studies may be necessary to determine whether drugs such as azepexole have a receptor target other than I1 or alpha 2-adrenergic receptors. We conclude that antihypertensive efficacy within the lower brainstem of conscious animals is predicted by interaction with I1-imidazoline but not alpha 2-adrenergic receptors.


Orthographic star coordinates.
Star coordinates is a popular projection technique from an nD data space to a 2D/3D visualization domain. It is defined by setting n coordinate axes in the visualization domain. Since it generally defines an affine projection, strong distortions can occur: an nD sphere can be mapped to an ellipse of arbitrary size and aspect ratio. We propose to restrict star coordinates to orthographic projections which map an nD sphere of radius r to a 2D circle of radius r. We achieve this by formulating conditions for the coordinate axes to define orthographic projections, and by running a repeated non-linear optimization in the background of every modification of the coordinate axes. This way, we define a number of orthographic interaction concepts as well as orthographic data tour sequences: a scatterplot tour, a principle component tour, and a grand tour. All concepts are illustrated and evaluated with synthetic and real data.


Pattern of intake of food additives associated with hyperactivity in Irish children and teenagers.
A double-blind randomized intervention study has previously shown that a significant relationship exists between the consumption of various mixes of seven target additives by children and the onset of hyperactive behaviour. The present study set out to ascertain the pattern of intake of two mixes (A and B) of these seven target additives in Irish children and teenagers using the Irish national food consumption databases for children (n = 594) and teenagers (n = 441) and the National Food Ingredient Database. The majority of additive-containing foods consumed by both the children and teenagers contained one of the target additives. No food consumed by either the children or teenagers contained all seven of the target food additives. For each additive intake, estimates for every individual were made assuming that the additive was present at the maximum legal permitted level in those foods identified as containing it. For both groups, mean intakes of the food additives among consumers only were far below the doses used in the previous study on hyperactivity. Intakes at the 97.5th percentile of all food colours fell below the doses used in Mix B, while intakes for four of the six food colours were also below the doses used in Mix A. However, in the case of the preservative sodium benzoate, it exceeded the previously used dose in both children and teenagers. No child or teenager achieved the overall intakes used in the study linking food additives with hyperactivity.


Impact of exergaming on young children's school day energy expenditure and moderate-to-vigorous physical activity levels.
Although emerging research is demonstrating the potential health impact of exergaming, investigations have primarily been conducted in laboratory settings among small samples with short-term interventions. Information on the effectiveness of exergaming in underserved children's objective physical activity (PA) in population-based settings is also scarce. Moreover, most empirical studies have only included 1 type of exergame in the intervention. Therefore, this study's purpose was to investigate the long-term impact of a multigame exergaming intervention among underserved children integrated within school curricula. Specifically, this study examined the effect of exergaming on children's accelerometer-determined sedentary behavior (SB), light PA, moderate-to-vigorous PA (MVPA), and energy expenditure (EE) over 2 years as compared with regular physical education (PE) classes. A total of 261 second- and third-grade children (134 girls, 127 boys; mean age 8.27 years) were recruited from 2 Texas elementary schools. Children's pre-test 3-day SB, light PA, MVPA, and EE at school were assessed in the fall of 2012. Participants were assigned to 1 of 2 groups: (1) exergaming/PE group (125 min weekly of exergaming-based PA program) and (2) comparison group (125 min weekly of PE). PA (SB, light PA, and MVPA) and EE outcome variables were assessed again in 2013 (post-test) and 2014 (follow-up). Significant time effects were observed for SB (F(1, 162) = 25.0, p < 0.01, η 2 = 0.14), light PA (F(1, 162) = 9.6, p < 0.01, η 2 = 0.06), and MVPA (F(1, 162) = 6.2, p = 0.01, η 2 = 0.04) but not for EE (F(1, 162) = 0.63, p > 0.05, η 2 = 0.004). Subsequent pairwise comparisons revealed significant increases from pre- to post-test for light PA (p < 0.01), MVPA (p < 0.01), and EE (p = 0.02) with no changes in SB (p > 0.05). Conversely, significant decreases occurred in light PA (p < 0.01) from post-test to follow-up with no differences seen in MVPA (p = 0.08) and EE (p = 0.06) over the same time period. A significant increase was seen, however, for SB from post-test to follow-up. Exergaming PE can have the same positive effect on children's light PA, MVPA, and EE as regular PE. More research is necessary to discern how to promote long-term PA participation after conclusion of the intervention.


Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease.
Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Patients with advanced CKD (blood creatinine ≥ 1.7 mg/dL [≥ 150 μmol/L] in men or ≥ 1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.


Papillary meningioma: a rare but distinct variant of malignant meningioma.
Papillary meningiomas are rare meningeal tumors and are associated with aggressive clinical behavior as compared with other meningiomas. Because of their rare occurrence, they may pose a diagnostic dilemma to the unwary pathologist. We report a case of papillary meningioma in a 16-year-old boy. A 16-year-old boy presented with complaints of headache, progressively diminishing vision and more recently generalized seizures. MRI revealed a large bifrontal meningioma which showed presence of a predominantly papillary pattern with areas of focal necrosis, frequent mitoses and bone invasion. He underwent radical excision of the tumor and is free from recurrence or metastasis at 15 months follow-up. Papillary meningiomas are rare but well recognized variants of meningioma. They need to be differentiated from other intracranial tumors with a papillary pattern. They are malignant, frequently show bone and parenchymatous invasion and have the potential for extracranial metastasis. Their timely recognition could prevent local and distant metastasis and the mortality or morbidity associated with it.


Electrical stimulation therapy for dysphagia: a follow-up survey of USA dysphagia practitioners.
The aim of this study was to compare current application, practice patterns, clinical outcomes, and professional attitudes of dysphagia practitioners regarding electrical stimulation (e-stim) therapy with similar data obtained in 2005. A web-based survey was posted on the American Speech-Language-Hearing Association Special Interest Group 13 webpage for 1 month. A total of 271 survey responses were analyzed and descriptively compared with the archived responses from the 2005 survey. Results suggested that e-stim application increased by 47% among dysphagia practitioners over the last 10 years. The frequency of weekly e-stim therapy sessions decreased while the reported total number of treatment sessions increased between the two surveys. Advancement in oral diet was the most commonly reported improvement in both surveys. Overall, reported satisfaction levels of clinicians and patients regarding e-stim therapy decreased. Still, the majority of e-stim practitioners continue to recommend this treatment modality to other dysphagia practitioners. Results from the novel items in the current survey suggested that motor level e-stim (e.g. higher amplitude) is most commonly used during dysphagia therapy with no preferred electrode placement. Furthermore, the majority of clinicians reported high levels of self-confidence regarding their ability to perform e-stim. The results of this survey highlight ongoing changes in application, practice patterns, clinical outcomes, and professional attitudes associated with e-stim therapy among dysphagia practitioners.


Child and adult pedestrian impact: the influence of vehicle type on injury severity.
In the United States, the vehicle fleet is shifting from predominantly passenger cars (automobiles) to SUVs, light trucks, and vans (LTV). This study investigates how pedestrian severe injury and mortality are associated with vehicle type and pedestrian age. The Pedestrian Crash Data Study (PCDS) database for years 1994-1998 was used for a cross-sectional study design. Outcome measures were Injury Severity Score, Maximum Abbreviated Injury Score, Abbreviated Injury Scale, Pedestrian Mortality, Functional Capacity Index and Life Years Lost to Injury. Compared to children, adult pedestrians were more likely to sustain severe injury (OR = 2.81; 95% CI: 1.56-5.06) or mortality (OR = 2.91; 95% CI: 1.10-7.74) when examining all vehicle types. However, after adjusting for vehicle type and impact speed, this association was not statistically significant at p < 0.05. Compared to passenger cars, pedestrians struck by LTV were more likely to have severe injuries (OR = 1.31; 95% CI: 0.88-1.94) or mortality (OR = 1.40; 95% CI: 0.84-2.34) for all pedestrians. Adjusting for pedestrian age, this association was more obvious and significant at lower impact speeds ( < or = 30 km/h); odds ratios of severe injury and mortality were 3.34 (p< 0.01) and 1.87 (p= 0.07), respectively. Adults hit by LTV had the highest risk of injury and mortality. These findings indicate that pedestrian age, vehicle engineering design and impact speed are highly contributing to risks of pedestrian injury and mortality.


Spatial-temporal stratifications in natural populations and how they affect understanding and estimation of effective population size.
The concept of effective population size (N(e) ) is based on an elegantly simple idea which, however, rapidly becomes very complex when applied to most real-world situations. In natural populations, spatial and temporal stratifications create different classes of individuals with different vital rates, and this in turn affects (generally reduces) N(e) in complex ways. I consider how these natural stratifications influence our understanding of effective size and how to estimate it, and what the consequences are for conservation and management of natural populations. Important points that emerge include the following: 1 The relative influences of local vs metapopulation N(e) depend on a variety of factors, including the time frame of interest. 2 Levels of diversity in local populations are strongly influenced by even low levels of migration, so these measures are not reliable indicators of local N(e) . 3 For long-term effective size, obtaining a reliable estimate of mutation rate is the most important consideration; unless this is accomplished, estimates can be biased by orders of magnitude. 4 At least some estimators of contemporary N(e) appear to be robust to relatively high (approximately 10%) equilibrium levels of migration, so under many realistic scenarios they might yield reliable estimates of local N(e) . 5 Age structure probably has little effect on long-term estimators of N(e) but can strongly influence contemporary estimates. 6 More research is needed in several key areas: (i) to disentangle effects of selection and drift in metapopulations connected by intermediate levels of migration; (ii) to elucidate the relationship between N(b) (effective number of breeders per year) and N(e) per generation in age-structured populations; (iii) to perform rigorous sensitivity analyses of new likelihood and coalescent-based methods for estimating demographic and evolutionary histories.


Oseltamivir pharmacokinetics in critically ill adults receiving extracorporeal membrane oxygenation support.
Extracorporeal membrane oxygenation (ECMO) is known to affect pharmacokinetics and hence optimum dosing. The aim of this open label, prospective study was to investigate the pharmacokinetics of oseltamivir (prodrug) and oseltamivir carboxylate (active metabolite) during ECMO. Fourteen adult patients with suspected or confirmed H1N1 influenza were enrolled in the study. Oseltamivir 75 mg was enterally administered twice daily and blood samples for pharmacokinetic assessment were taken on day 1 and 5. A multi-compartmental model to describe the pharmacokinetics of oseltamivir and oseltamivir carboxylate was developed using a non-linear mixed effects modelling approach. The median (range) clearance of oseltamivir carboxylate was 15.8 (4.8-36.6) l/hour, lower than the reported mean value of 21.5 l/hour in healthy adults. The median (range) steady state volume of distribution of oseltamivir carboxylate was 179 (61-436) litres, much greater than healthy adults but similar to previous reports in critically ill patients. Substantial 'between subject' variability in systemic exposure to oseltamivir carboxylate was revealed; median (range) area under the curve and Cmax were 4346 (644-13660) ng/hour/ml and 509 (54-1277) ng/ml, respectively. Both area under the curve and Cmax were significantly correlated with serum creatinine (r2=0.37, P=0.02 and r2=0.29, P=0.02, respectively). Systemic exposure to oseltamivir carboxylate following the administration of enteral oseltamivir 75 mg twice daily in adult ECMO patients is comparable to those in ambulatory patients and far in excess of concentrations required to maximally inhibit neuraminidase activity of the H1N1 virus. Dosage adjustment for ECMO, per se, appears not to be necessary; however, doses should be reduced in patients with renal dysfunction.


Strategic control in decision-making under uncertainty.
Complex economic decisions - whether investing money for retirement or purchasing some new electronic gadget - often involve uncertainty about the likely consequences of our choices. Critical for resolving that uncertainty are strategic meta-decision processes, which allow people to simplify complex decision problems, evaluate outcomes against a variety of contexts, and flexibly match behavior to changes in the environment. In recent years, substantial research has implicated the dorsomedial prefrontal cortex (dmPFC) in the flexible control of behavior. However, nearly all such evidence comes from paradigms involving executive function or response selection, not complex decision-making. Here, we review evidence that demonstrates that the dmPFC contributes to strategic control in complex decision-making. This region contains a functional topography such that the posterior dmPFC supports response-related control, whereas the anterior dmPFC supports strategic control. Activation in the anterior dmPFC signals changes in how a decision problem is represented, which in turn can shape computational processes elsewhere in the brain. Based on these findings, we argue for both generalized contributions of the dmPFC to cognitive control, and specific computational roles for its subregions depending upon the task demands and context. We also contend that these strategic considerations are likely to be critical for decision-making in other domains, including interpersonal interactions in social settings.


Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load.
Distinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis when bacterial and Ag loads are high and after curative treatment, when Ag load is reduced. The frequencies of M. tuberculosis Ag-specific IFN-gamma-secreting T cells declined during 28 mo of follow-up with an average percentage decline of 5.8% per year (p = 0.005), while the frequencies of Ag-specific IL-2-secreting T cells increased during treatment (p = 0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma- and IL-2-secreting cells over 28 mo. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single-cell level revealed a codominance of IFN-gamma-only secreting and IFN-gamma/IL-2 dual secreting CD4(+) T cells in active disease that shifted to dominance of IFN-gamma/IL-2-secreting CD4(+) T cells and newly detectable IL-2-only secreting CD4(+) T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis that now requires validation in larger prospective studies.


Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells.
The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-E1 cells. Cells were cultured for 3 days at 37 degrees C in a CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10(-7)-10(-5) M) stimulated the proliferation of cells. AHZ (10(-6) and 10(-5) M) increased deoxyribonucleic acid (DNA) content in the cells with 48 hr-culture. This increase was completely blocked by the presence of cycloheximide (10(-6) M) or hydroxyurea (10(-3) M). Also, the presence of cycloheximide (10(-6) M) completely inhibited the AHZ (10(-5) M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10(-7) M), estrogen (10(-9) M) and insulin (10(-8) M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10(-5) M). Dibutyryl cyclic AMP (10(-4) M) and zinc sulfate (10(-5) M) did not cause a significant increase in cellular DNA content. The present results support the view that AHZ has a direct specific proliferative effect on osteoblastic cells in vitro and that this effect is dependent on protein synthesis.


From evaluating a Skilled Care Initiative in rural Burkina Faso to policy implications for safe motherhood in Africa.
Evaluation findings from a particular setting need to be generalized into policy implications if they are to find widespread use. Skilled attendance at delivery is widely regarded as one of the most important intervention strategies for safe motherhood in low-resource settings, particularly in Africa, but implementations of such strategies are often not rigorously evaluated or interpreted into future policy. Initiative for Maternal Mortality Programme Assessment (Immpact) has applied a package of research-based monitoring and evaluation tools to assess the Family Care International Skilled Care Initiative in Ouargaye District, Burkina Faso. This evaluation research aimed to generate reliable, evidence-based policies for accelerating safe motherhood programmes in Burkina Faso and elsewhere in Africa. Five policy priorities were identified as representing real chances of improving the safety of motherhood: (1) enhancing national coverage of delivery by professionally skilled attendants; (2) to provide a network of 24-h basic emergency obstetric care within 5 km; (3) to have an effective referral system, equipped and resourced to undertake a reasonable number of Caesarean sections; (4) to promote community mobilization activities as a lever to increasing delivery care utilization; and (5) to implement strategies to remove financial barriers to delivery care. To meet Millennium Development Goal five by 2015, both supply and demand side constraints on the provision of quality maternity care have to be addressed, which in turn need greater political commitment and funding.


Critical assessment of the emission spectra of various photosystem II core complexes.
We evaluate low-temperature (low-T) emission spectra of photosystem II core complexes (PSII-cc) previously reported in the literature, which are compared with emission spectra of PSII-cc obtained in this work from spinach and for dissolved PSII crystals from Thermosynechococcus (T.) elongatus. This new spectral dataset is used to interpret data published on membrane PSII (PSII-m) fragments from spinach and Chlamydomonas reinhardtii, as well as PSII-cc from T. vulcanus and intentionally damaged PSII-cc from spinach. This study offers new insight into the assignment of emission spectra reported on PSII-cc from different organisms. Previously reported spectra are also compared with data obtained at different saturation levels of the lowest energy state(s) of spinach and T. elongatus PSII-cc via hole burning in order to provide more insight into emission from bleached and/or photodamaged complexes. We show that typical low-T emission spectra of PSII-cc (with closed RCs), in addition to the 695 nm fluorescence band assigned to the intact CP47 complex (Reppert et al. J Phys Chem B 114:11884-11898, 2010), can be contributed to by several emission bands, depending on sample quality. Possible contributions include (i) a band near 690-691 nm that is largely reversible upon temperature annealing, proving that the band originates from CP47 with a bleached low-energy state near 693 nm (Neupane et al. J Am Chem Soc 132:4214-4229, 2010; Reppert et al. J Phys Chem B 114:11884-11898, 2010); (ii) CP43 emission at 683.3 nm (not at 685 nm, i.e., the F685 band, as reported in the literature) (Dang et al. J Phys Chem B 112:9921-9933, 2008; Reppert et al. J Phys Chem B 112:9934-9947, 2008); (iii) trap emission from destabilized CP47 complexes near 691 nm (FT1) and 685 nm (FT2) (Neupane et al. J Am Chem Soc 132:4214-4229, 2010); and (iv) emission from the RC pigments near 686-687 nm. We suggest that recently reported emission of single PSII-cc complexes from T. elongatus may not represent intact complexes, while those obtained for T. elongatus presented in this work most likely represent intact PSII-cc, since they are nearly indistinguishable from emission spectra obtained for various PSII-m fragments.


High-speed synthetic aperture microscopy for live cell imaging.
We present a high-speed synthetic aperture microscopy for quantitative phase imaging of live biological cells. We measure 361 complex amplitude images of an object with various directions of illumination covering an NA of 0.8 in less than one-thirteenth of a second and then combine the images with a phase-referencing method to create a synthesized phase image. Because of the increased depth selectivity, artifacts from diffraction that are typically present in coherent imaging are significantly suppressed, and lateral resolution of phase imaging is improved. We use the instrument to demonstrate high-quality phase imaging of live cells, both static and dynamic, and thickness measurements of a nanoscale cholesterol helical ribbon.


Antiviral activity of Bifidobacterium adolescentis SPM1005-A on human papillomavirus type 16.
Probiotic lactic acid bacteria (LAB) support a functional and balanced immune system, and contribute to immune modulatory effects in combatting microbial pathogens, including viruses. Most cervical cancers are associated with anogenital region infection with high-risk (HR) human papillomavirus (HPV). In this study, we analyzed the antiviral activity of Bifidobacterium adolescentis SPM1005-A in the SiHa cervical cancer cell line expressing HPV type 16. We assessed the cellular toxicity of B. adolescentis SPM1005-A in SiHa cells by the Trypan blue dye exclusion assay. Cells (3.6 × 105) in culture plates with or without B. adolescentis SPM1005-A in the same type of medium, were incubated with HPV type 16 at a concentration of 5.1 × 107 cfu/ml. For antiviral analysis, we performed quantitative real-time PCR (qRT-PCR) for E6 and E7 oncogene expressions and observed protein levels by immunoblotting. The qRT-PCR results showed that E6 and E7 mRNA levels decreased simultaneously. Western blot analysis revealed that the E6 protein expression slightly decreased after 24 and 48 h, but the level of E7 protein expression appear unaffected compared with that in the control. Decreased HPV16 E6 and E7 mRNA transcript and protein levels were not associated with cell morphology or significant cytotoxic effects. This study showed that B. adolescentis SPM1005-A had antiviral activity through suppression E6 and E7 oncogene expression. The results suggest that B. adolescentis SPM1005-A could be potential applications of HPV-associated cervical cancer prevention.


Genetic susceptibility to fungal infection in children.
Fungal infections have steadily increased in incidence, emerging as a significant cause of morbidity and mortality in patients with iatrogenic immunosuppression. Simultaneously, we have witnessed a growing population of newly described inherited immune disorders that have enhanced our understanding of the human immune response against fungi. In the present review, we provide an overview and diagnostic roadmap to inherited disorders which confer susceptibility to superficial and invasive fungal infections. Inborn errors of fungal immunity encompass a heterogeneous group of disorders, some of which confer fungal infection-specific susceptibility, whereas others also feature broader infection vulnerability and/or noninfectious manifestations. Infections by Candida, Aspergillus, endemic dimorphic fungi, Pneumocystis, and dermatophytes along with their organ-specific presentations provide clinicians with important clues in the assessment of patients with suspected immune defects. The absence of iatrogenic risk factors should raise suspicion for inborn errors of immunity in children and young adults with recurrent or severe fungal diseases. Expeditious diagnosis and prompt initiation of antifungal therapy and management of complications are paramount to achieve remission of fungal disease in the setting of primary immunodeficiency disorders.