Mediated Interactions and Photon Bound States in an Exciton-Polariton Mixture.
The quest to realize strongly interacting photons remains an outstanding challenge both for fundamental science and for applications. Here, we explore mediated photon-photon interactions in a highly imbalanced two-component mixture of exciton polaritons in a semiconductor microcavity. Using a theory that takes into account nonperturbative correlations between the excitons as well as strong light-matter coupling, we demonstrate the high tunability of an effective interaction between quasiparticles formed by minority component polaritons interacting with a Bose-Einstein condensate (BEC) of a majority component polaritons. In particular, the interaction, which is mediated by sound modes in the BEC can be made strong enough to support a bound state of two quasiparticles. Since these quasiparticles consist partly of photons, this in turn corresponds to a dimer state of photons propagating through the BEC. This gives rise to a new light transmission line where the dimer wave function is directly mapped onto correlations between the photons. Our findings open new routes for highly nonlinear optical materials and novel hybrid light-matter quantum systems.


Toll-like receptors on tumor cells facilitate evasion of immune surveillance.
The signal pathways that trigger tumor cell escape from immune surveillance are incompletely understood. Toll-like receptors (TLRs), which activate innate and adaptive immune responses, are thought to be restricted to immune cells. We show here that TLRs, including TLR4, are expressed on tumor cells from a wide variety of tissues, suggesting that TLR activation may be an important event in tumor cell immune evasion. Activation of TLR4 signaling in tumor cells by lipopolysaccharide induces the synthesis of various soluble factors and proteins including interleukin-6, inducible nitric oxide synthase, interleukin-12, B7-H1, and B7-H2, and results in resistance of tumor cells to CTL attack. In addition, lipopolysaccharide-stimulated tumor cell supernatants inhibit both T cell proliferation and natural killer cell activity. Blockade of the TLR4 pathway by either TLR4 short interfering RNA or a cell-permeable TLR4 inhibitory peptide reverses tumor-mediated suppression of T cell proliferation and natural killer cell activity in vitro, and in vivo, delays tumor growth and thus prolongs the survival of tumor-bearing mice. These findings indicate that TLR signaling results in a cascade leading to tumor evasion from immune surveillance. These novel functions of TLRs in tumor biology suggest a new class of therapeutic targets for cancer therapy.


Risk factors for pacemaker implantation following aortic valve replacement: a single centre experience.
To identify perioperative clinical predictors of permanent pacemaker implantation following aortic valve replacement. Prospective cohort study on 276 patients submitted for aortic valve replacement: 267 patients (mean (SD) age, 57.5 (14) years) with no conduction disturbances, and nine patients (67.7 (5) years) with severe conduction disturbances requiring permanent pacing; 65 perioperative variables (38 preoperative, eight intraoperative, and 19 postoperative) were considered. Nine patients (3.2%) had irreversible second or third degree atrioventricular (AV) block requiring permanent pacing. Risk factors for permanent pacing identified by univariate analysis were: preoperative: additional valvar disease, aortic regurgitation, myocardial infarction, pulmonary hypertension, anaemia, use of digitalis; intraoperative: cardiac arrest; postoperative: cardiac arrest, conduction disturbances, electrolytic imbalance, angiotensin converting enzyme inhibitor use. Multivariate logistic regression analysis identified preoperative aortic regurgitation (p < 0.005; odds ratio (OR) 6.6, 95% confidence interval (CI) 1.6 to 12.2), myocardial infarction (p < 0.0005; OR 15.2, 95% CI 6.3 to 19.9), pulmonary hypertension (p < 0.005; OR 12.5, 95% CI 3.2 to 18.3), and postoperative electrolyte imbalance (p < 0.01; OR 4.5, 95% CI 1.3 to 6.4). Irreversible AV block requiring permanent pacemaker implantation is an uncommon condition following aortic valve replacement. Previous aortic regurgitation, myocardial infarction, pulmonary hypertension, and postoperative electrolyte imbalance should be considered in order to identify patients at increased risk for advanced AV block.


Food restriction and refeeding in lambs influence muscle antioxidant status.
Compensatory growth, a frequent phenomenon observed in ruminants due to seasonal variation in food availability, affects protein metabolism including protein oxidation. These oxidation processes may have an impact on animal health as well as on meat protein degradation during post mortem aging (ie meat maturation). Sixteen male lambs were randomly divided into four groups. One group was fed ad libitum (C) and one group was food-restricted to 60% of the intake of the C group (R). The last two groups were restricted similarly to the R group and refed either ad libitum (RAL) or similarly to the C group (pair-feeding) (RPF). Muscles samples were taken immediately after slaughter. The present study showed that the restriction/refeeding pattern had no effect on protein oxidation in the muscles studied (longissimus dorsi (LD), semitendinosus (ST) and supraspinatus (SP)). However, total antioxidant capacity decreased after food restriction (-51%, -43%, P < 0.01 for ST and LD muscles, respectively) and re-increased only after ad libitum refeeding. This alteration in the total antioxidant status can partially be explained by the similar pattern of change observed in the glutathione concentration of the muscles (-25%, P < 0.05 for ST muscle and NS for the other muscles). However, none of the concentrations of other water-soluble antioxidants studied (carnosine, anserine, glutathione peroxidase and superoxide dismutase) were altered during compensatory growth. This study showed that an inappropriate feeding level following a nutritional stress induced alterations in the total antioxidant status (particularly that of glutathione), which may have consequences on animal health. Other consequences of a decrease of the animal antioxidant status in vivo could be an alteration of the protein oxidation processes during meat maturation.


Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.
Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.


The COSMIN checklist for assessing the methodological quality of studies on measurement properties of health status measurement instruments: an international Delphi study.
Aim of the COSMIN study (COnsensus-based Standards for the selection of health status Measurement INstruments) was to develop a consensus-based checklist to evaluate the methodological quality of studies on measurement properties. We present the COSMIN checklist and the agreement of the panel on the items of the checklist. A four-round Delphi study was performed with international experts (psychologists, epidemiologists, statisticians and clinicians). Of the 91 invited experts, 57 agreed to participate (63%). Panel members were asked to rate their (dis)agreement with each proposal on a five-point scale. Consensus was considered to be reached when at least 67% of the panel members indicated 'agree' or 'strongly agree'. Consensus was reached on the inclusion of the following measurement properties: internal consistency, reliability, measurement error, content validity (including face validity), construct validity (including structural validity, hypotheses testing and cross-cultural validity), criterion validity, responsiveness, and interpretability. The latter was not considered a measurement property. The panel also reached consensus on how these properties should be assessed. The resulting COSMIN checklist could be useful when selecting a measurement instrument, peer-reviewing a manuscript, designing or reporting a study on measurement properties, or for educational purposes.


Fluctuating expression of microRNAs in adenovirus infected cells.
The changes in cellular microRNA (miRNA) expression during the course of an adenovirus type 2 infection in human lung fibroblast were studied by deep RNA sequencing. Expressions of 175 miRNAs with over 100 transcripts per million nucleotides were changed more than 1.5-fold. The expression patterns of these miRNAs changed dramatically during the course of the infection, from upregulation of the miRNAs known as tumor suppressors (such as miR-22, miR-320, let-7, miR-181b, and miR-155) and down-regulation of oncogenic miRNAs (such as miR-21 and miR-31) early to downregulation of tumor suppressor miRNAs (such as let-7 family, mir-30 family, 23/27 cluster) and upregulation of oncogenic miRNAs (include miR-125, miR-27, miR-191) late after infection. The switch in miRNA expression pattern occurred when adenovirus DNA replication started. Furthermore, deregulation of cellular miRNA expression was a step-wise and special sets of miRNAs were deregulated in different phases of infection.


Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne.
Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.


Sociodemographic Determinants of Healthcare-Seeking Options and Alternative Management Practices of Childhood Diarrheal Illness: A Household Survey among Mothers in Iraq.
Diarrhea remains a significant cause of child morbidity and mortality in Iraq. The objective of this study was to examine the current practices of home-based management of diarrheal illnesses among Iraqi children. We surveyed mothers of children aged less than 5 years to identify the sociodemographic factors associated with maternal healthcare-seeking practices. A total of 500 mother-child pairs were interviewed in a cross-sectional household survey in Thi-Qar Governorate, southeastern Iraq, between March 2016 and February 2017. Logistic and multinomial regression models were used to infer sociodemographic predictors of the healthcare-seeking and alternative management practices adopted by the mothers. The interviewees reported that 35.2% of their children had diarrhea in the 2 weeks before the survey. The least likelihood of reported occurrence of diarrhea was among mother-child pairs where the mothers had received university education, as compared with mothers who were illiterate or received only primary or secondary education. Lower odds (odds ratio = 0.4, P-value < 0.001) of reported childhood diarrhea was revealed among mothers aged > 25 years than among those younger. Self-ordered medicine from a pharmacy was the most preferred alternative management option in almost half (52.4% [262/500]) of the interviewed mothers in Thi-Qar. Interestingly, 69.6% (348/500) of the mothers reported supplying their children suffering from diarrhea with antibiotics. Relative to mothers with university education, those with high school education had more likelihood of selecting medical center (relative risk ratio [rrr] = 2.4) and pharmacy (rrr = 3.7) as against no treatment. Lower maternal educational level, mothers' age < 25 years, and the district of residence were important factors associated with diarrhea occurrence among children younger than 5 years. In light of the findings from this study, intervention aimed at improving healthcare seeking for managing diarrhea in Iraqi children should jointly consider the influence of mothers age, education, as well as the level of economic status of the communities in which mothers of these children reside. The results of this study indicate the need for enhancing public health education to improve the maternal management of diarrheal disease and the avoidance of unnecessary use of antimicrobials.


[Surgery for oesophageal cancer: current controversies].
Any attempt to define the present role of surgery in the treatment of oesophageal cancer should integrate the dramatic changes that occurred within this disease over the last 2 decades: major shift in the histologic type of tumours, improved staging methods, spectacular reduction of operative risks, standardization of oncologic principles focusing on the completeness of resection, and development of multimodality therapeutic strategies. Surgery has still a pivotal role. Esophagectomy should be performed by trained surgeons in high-volume institutions. Radical surgery with en-bloc resection and 2 fields lymphadenectomy, should be encouraged in low-risk patients with subcarinal tumors. Although multimodality treatment strategy is commonly applied for locally advanced disease, few data support its superiority over surgical resection alone, followed by adjuvant therapy when appropriate. One may thus hypothesize that the risk/benefit ratio of such strategies is probably optimal in case of early stage tumors, and future studies may further clarify this issue. Conversely, locally advanced tumors, particularly those located in the upper mediastinum and the neck, may be managed alternatively without surgery. However, surgery remains an important tool to ensure optimal palliation of dysphagia, to achieve local control, and finally to improve quality of life. In that way, video-assisted techniques and/or trans hiatal approaches aiming to minimize the surgical insult may have a place in the treatment of patients who have substantially responded to induction therapy. Tumors located close to the pharyngo-oesophageal junction are best managed with chemotherapy and radiotherapy. Finally, salvage surgery may be considered in highly selected patients in case of non-response or local relapse without distant metastases.


Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.
Mechanical stimuli drive many physiological processes, including touch and pain sensation, hearing, and blood pressure regulation. Mechanically activated (MA) cation channel activities have been recorded in many cells, but the responsible molecules have not been identified. We characterized a rapidly adapting MA current in a mouse neuroblastoma cell line. Expression profiling and RNA interference knockdown of candidate genes identified Piezo1 (Fam38A) to be required for MA currents in these cells. Piezo1 and related Piezo2 (Fam38B) are vertebrate multipass transmembrane proteins with homologs in invertebrates, plants, and protozoa. Overexpression of mouse Piezo1 or Piezo2 induced two kinetically distinct MA currents. Piezos are expressed in several tissues, and knockdown of Piezo2 in dorsal root ganglia neurons specifically reduced rapidly adapting MA currents. We propose that Piezos are components of MA cation channels.


Methylparaben and butylparaben alter multipotent mesenchymal stem cell fates towards adipocyte lineage.
Paraben esters and their salts are widely used as preservatives in cosmetics, personal care products, pharmaceuticals, and foods. We previously reported that parabens promoted adipocyte differentiation in vitro and increased adiposity but suppressed serum marker of bone formation in vivo. Here, we investigated the effects of parabens (methylparaben and butylparaben) on modulating cell fate of multipotent stem cell line C3H10T1/2. Both parabens modulated adipogenic, osteogenic, and chondrogenic differentiation of C3H10T1/2 cells in vitro. Butylparaben markedly promoted adipogenic differentiation, but suppressed osteogenic and chondrogenic differentiation whereas methylparaben showed similar but less pronounced effects. Moreover, butylparaben, but not methylparaben, was shown to activate peroxisome proliferator-activated receptor (PPAR) γ whereas neither of the paraben was shown to activate glucocorticoid receptor (GR) responsive reporter in C3H10T1/2 cells. The adipogenic effects of butylparaben were significantly attenuated by PPARγ knockdown, but not by GR knockdown. In contrast, paraben's effects on osteoblast differentiation were affected by both knockdowns. Collectively, the results demonstrate opposing effects of parabens on adipogenic and osteoblastogenic/chondrogenic differentiation of multipotent stem cells. In light of the recent findings that parabens are detected in human placenta and milk, our studies provide rationales to study paraben exposure during early development of life in the future.


Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations.
Beginning in 1992, the Agency for Health Care Policy and Research and the National Institute of Mental Health funded the Schizophrenia Patient Outcomes Research Team (PORT) to develop and disseminate recommendations for the treatment of schizophrenia based on existing scientific evidence. These Treatment Recommendations, presented here in final form for the first time, are based on exhaustive reviews of the treatment outcomes literature (previously published in Schizophrenia Bulletin, Vol. 21, No. 4, 1995) and focus on those treatments for which there is substantial evidence of efficacy. The recommendations address antipsychotic agents, adjunctive pharmacotherapies, electroconvulsive therapy, psychological interventions, family interventions, vocational rehabilitation, and assertive community treatment/intensive case management. Support for each recommendation is referenced to the previous PORT literature reviews, and the recommendations are rated according to the level of supporting evidence. The PORT Treatment Recommendations provide a basis for moving toward "evidence-based" practice for schizophrenia and identify both the strengths and limitations in our current knowledge base.


Sexual Orientation Disparities in Preconception Health.
Objective: In the United States, there have been very few improvements in adverse birth outcomes, such as infant mortality, low birthweight, and preterm birth in recent years. Health promotion before pregnancy (e.g., preconception care) has been increasingly recognized as an important strategy by which to improve these reproductive outcomes. As of yet, no research has examined sexual orientation disparities in preconception health which has important implications for birth outcomes in the United States, since sexual minority women (SMW) are more likely to report stillbirths, low birthweight, and preterm infants than heterosexual women. Methods: This study addresses this gap by utilizing data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine sexual orientation disparities in women's preconception health 1 and 3 years before a live birth (n = 3,133). Results: Our findings suggest that, even after controlling for maternal characteristics, SMW are more likely to report adverse health conditions and behaviors before pregnancy relative to heterosexual women 1 year before the survey, including higher odds of binge drinking, other substance use, having a sexually transmitted infection diagnosis, and depression. Conclusions: Despite new public health policies aimed at improved preconception health, our findings suggest that SMW are even more vulnerable to poor preconception health than their heterosexual counterparts, which has important implications for maternal and child health. This study provides important evidence for the need to invest in the reproductive health of SMW, particularly in the context of pregnancy.


Polymerization in soft nanoconfinement of lamellar and reverse hexagonal mesophases.
This work describes the kinetics of thermal polymerization in nanoconfined domains of lyotropic liquid crystal (LLC) templates by using chemorheological studies at different temperatures. We investigate lamellar and reverse hexagonal LLC phases with the same concentration of the monomeric phase. Results show that the mesophase structures remain intact during thermal polymerization with very slight changes in the domain size. The polymerization rate decreases in the nanoconfined structure compared to the bulk state due to the segregation effect, which increases the local monomer concentration and enhances the termination rate. Additionally, the polymerization rate is faster in the studied reverse hexagonal systems compared to the lamellar ones due to their lower degree of confinement. A higher degree of confinement also induces a lower monomer conversion. Differential scanning calorimetry confirms the obtained results from chemorheology.


New nanocomposite hybrid inorganic-organic proton-conducting membranes based on functionalized silica and PTFE.
Two types of new nanocomposite proton-exchange membranes, consisting of functionalized and pristine nanoparticles of silica and silicone rubber (SR) embedded in a polytetrafluoroethylene (PTFE) matrix, were prepared. The membrane precursor was obtained from a mechanical rolling process, and the SiO₂ nanoparticles were functionalized by soaking the membranes in a solution of 2-(4-chlorosulfonylphenyl)ethyl trichlorosilane (CSPhEtCS). The membranes exhibit a highly compact morphology and a lack of fibrous PTFE. At 125 °C, the membrane containing the functionalized nanoparticles has an elastic modulus (2.2 MPa) that is higher than that of pristine Nafion (1.28 MPa) and a conductivity of 3.6×10⁻³ S cm⁻¹ despite a low proton-exchange capacity (0.11 meq g⁻¹). The good thermal and mechanical stability and conductivity at T>100 °C make these membranes a promising low-cost material for application in proton-exchange membrane fuel cells operating at temperatures higher than 100 °C.


Beyond the active site: the impact of the outer coordination sphere on electrocatalysts for hydrogen production and oxidation.
Redox active metalloenzymes play a major role in energy transformation reactions in biological systems. Examples include formate dehydrogenases, nitrogenases, CO dehydrogenase, and hydrogenases. Many of these reactions are also of interest to humans as potential energy storage or utilization reactions for photoelectrochemical, electrolytic, and fuel cell applications. These metalloenzymes consist of redox active metal centers where substrates are activated and undergo transformation to products accompanied by electron and proton transfer to or from the substrate. These active sites are typically buried deep within a protein matrix of the enzyme with channels for proton transport, electron transport, and substrate/product transport between the active site and the surface of the protein. In addition, there are amino acid residues that lie in close proximity to the active site that are thought to play important roles in regulating and enhancing enzyme activity. Directly studying the outer coordination sphere of enzymes can be challenging due to their complexity, and the use of modified molecular catalysts may allow us to provide some insight. There are two fundamentally different approaches to understand these important interactions. The "bottom-up" approach involves building an amino acid or peptide containing outer coordination sphere around a functional molecular catalyst, and the "top-down" approach involves attaching molecular catalyst to a structured protein. Both of these approaches have been undertaken for hydrogenase mimics and are the emphasis of this Account. Our focus has been to utilize amino acid or peptide based scaffolds on an active functional enzyme mimic for H2 oxidation and production, [Ni(P(R)2N(R('))2)2](2+). This "bottom-up" approach has allowed us to evaluate individual functional group and structural contributions to electrocatalysts for H2 oxidation and production. For instance, using amine, ether, and carboxylic acid functionalities in the outer coordination sphere enhances proton movement and results in lower catalytic overpotentials for H2 oxidation, while achieving water solubility in some cases. Amino acids with acidic and basic side chains concentrate substrate around catalysts for H2 production, resulting in up to 5-fold enhancements in rate. The addition of a structured peptide in an H2 production catalyst limited the structural freedom of the amino acids nearest the active site, while enhancing the overall rate. Enhanced stability to oxygen or extreme conditions such as strongly acidic or basic conditions has also resulted from an amino acid based outer coordination sphere. From the "top-down" approach, others have achieved water solubility and photocatalytic activity by associating this core complex with photosystem-I. Collectively, by use of this well understood core, the role of individual and combined features of the outer coordination sphere are starting to be understood at a mechanistic level. Common mechanisms have yet to be defined to predictably control these processes, but our growing knowledge in this area is essential for the eventual mimicry of enzymes by efficient molecular catalysts for practical use.


Comparative analysis between protist communities from the deep-sea pelagic ecosystem and specific deep hydrothermal habitats.
Protist communities associated with deep seawater and bivalves from six hydrothermal sites in the Pacific Ocean were characterized by microscopy and molecular rRNA gene surveys (18S rRNA) and compared with planktonic communities from Pacific deep-pelagic seawater (from 500 to 3000 m in depth). Genetic libraries from larger size fractions (>3 µm) of deep-pelagic water were mainly dominated by Dinophyceae, whereas small size fractions (<3 µm) mainly revealed radiolarians and Syndiniales. In contrast, more specific opportunistic detritivores and grazers, mostly belonging to Stramenopiles and Cercozoa, were detected from water surrounding vent chimneys. Protist communities were different in the pallial cavity of the giant hydrothermal bivalves Bathymodiolus thermophilus and Calyptogena magnifica, dominated by Ciliophora (primarily belonging to Phyllopharyngea, Oligohymenophorea and Oligotrichea) and Cercozoa. Interestingly, protist communities retrieved from the pallial cavity liquid of hydrothermal bivalves were remarkably homogeneous along the Southern East Pacific Rise, in contrast to bivalves collected on the Mid-Atlantic Ridge hydrothermal vents and cold seeps from the Gulf of Mexico. Hence, complex protist communities seem to occur inside hydrothermal bivalves, and these metazoa may constitute a stable micro-niche for micro-eukaryotes, including grazers, detritivores, symbionts and potential parasites. From these communities, new lineages within the ciliates may emerge.


Breeding for low cadmium accumulation cereals.
Cadmium (Cd) is an element that is nonessential and extremely toxic to both plants and human beings. Soil contaminated with Cd has adverse impacts on crop yields and threatens human health via the food chain. Cultivation of low-Cd cultivars has been of particular interest and is one of the most cost-effective and promising approaches to minimize human dietary intake of Cd. Low-Cd crop cultivars should meet particular criteria, including acceptable yield and quality, and their edible parts should have Cd concentrations below maximum permissible concentrations for safe consumption, even when grown in Cd-contaminated soil. Several low-Cd cereal cultivars and genotypes have been developed worldwide through cultivar screening and conventional breeding. Molecular markers are powerful in facilitating the selection of low-Cd cereal cultivars. Modern molecular breeding technologies may have great potential in breeding programs for the development of low-Cd cultivars, especially when coupled with conventional breeding. In this review, we provide a synthesis of low-Cd cereal breeding.


Database search based on Bayesian alignment.
The size of protein sequence database is getting larger each day. One common challenge is to predict protein structures or functions of the sequences in databases. It is easy when a sequence shares direct similarity to a well-characterized protein. If there is no direct similarity, we have to rely on a third sequence or a model as intermediate to link two proteins together. We developed a new model based method, called Bayesian search, as a means to connect two distantly related proteins. We compared this Bayesian search model with pairwise and multiple sequence comparison methods on structural databases using structural similarity as the criteria for relationship. The results show that the Bayesian search can link more distantly related sequence pairs than other methods, collectively and consistently over large protein families. If each query made one error on average against SCOP database PDB40D-B, Bayesian search found 36.5% of related pairs, PSI-Blast found 32.6%, and Smith-Waterman method found 25%. Examples are presented to show that the alignments predicted by the Bayesian search agree well with structural alignments. Also false positives found by Bayesian search at low cutoff values are analyzed.


Analysis of distribution patterns of gap junctions during development of embryonic chick facial primordia and brain.
Gap junction distribution in the facial primordia of chick embryos at the time of primary palate formation was studied employing indirect immunofluorescence localization with antibodies to gap junction proteins initially identified in rat liver (27 x 10(3) Mr, connexin 32) and heart (43 x 10(3) Mr, connexin 43). Immunolocalization with antibodies to the rat liver gap junction protein (27 x 10(3) Mr) demonstrated a ubiquitous and uniform distribution in all regions of the epithelium and mesenchyme except the nasal placode. In the placodal epithelium, a unique non-random distribution was found characterized by two zones: a very heavy concentration of signal in the superficial layer of cells adjacent to the exterior surface and a region devoid of detectable signal in the interior cell layer adjacent to the mesenchyme. This pattern was seen during all stages of placode invagination that were examined. The separation of gap junctions in distinct cell layers was unique to the nasal placode, and was not found in any other region of the developing primary palate. One other tissue was found that exhibited this pattern-the developing neural epithelium of the brain and retina. These observations suggest the presence of region-specific signaling mechanisms and, possibly, an impedance of cell communication among subpopulations of cells in these structures at critical stages of development. Immunolocalization with antibodies to the 'heart' 43 x 10(3) Mr gap junction protein also revealed the presence of gap junction protein in facial primordia and neural epithelium. A non-uniform distribution of immunoreactivity was also observed for connexin 43.


Origin and spread of beta-globin gene mutations in India, Africa, and Mediterranea: analysis of the 5' flanking and intragenic sequences of beta S and beta C genes.
Nucleotide polymorphisms of both the 5' flanking and intragenic regions of the human beta-globin gene were investigated by directly sequencing genomic DNA after amplification by the polymerase chain reaction in 47 subjects homozygous for the beta S or the beta C mutation. The sickle-cell mutation was found in the context of five different haplotypes defined by eight nucleotide substitutions and various structures of a region of the simple repeated sequence (AT) chi Ty. All subjects from the same geographic origin bear an identical chromosomal structure, defining the Senegal-, Bantu-, Benin-, Cameroon-, and Indian-type chromosomes. These results strengthen our previous conclusions about the multiple occurrence of the sickle-cell mutation. The Benin-type chromosome was also found among Algerian and Sicilian sickle-cell patients, whereas the Indian-type chromosome was observed in two geographically distant tribes, illustrating the spread of these sickle-cell genes. We also found that the intragenic sequence polymorphisms (frameworks) are not always in linkage disequilibrium with the BamH I polymorphism downstream from the beta-globin gene, as had been previously observed. Finally, we present a tentative phylogenetic tree of the different alleles at this locus. Some polymorphisms of this sequence might be contemporary with our last common ancestor, the great apes, that is, about 4-6 millions years old.


Reverse-Offset Printing of Polymer Resist Ink for Micrometer-Level Patterning of Metal and Metal-Oxide Layers.
Printed electronics has advanced during the recent decades in applications such as organic photovoltaic cells and biosensors. However, the main limiting factors preventing the more widespread use of printing in flexible electronics manufacturing are (i) the poor attainable linewidths via conventional printing methods (≫10 μm), (ii) the limited availability of printable materials (e.g., low work function metals), and (iii) the inferior performance of many printed materials when compared to vacuum-processed materials (e.g., printed vs sputtered ITO). Here, we report a printing-based, low-temperature, low-cost, and scalable patterning method that can be used to fabricate high-resolution, high-performance patterned layers with linewidths down to ∼1 μm from various materials. The method is based on sequential steps of reverse-offset printing (ROP) of a sacrificial polymer resist, vacuum deposition, and lift-off. The sharp vertical sidewalls of the ROP resist layer allow the patterning of evaporated metals (Al) and dielectrics (SiO) as well as sputtered conductive oxides (ITO), where the list is expandable also to other vacuum-deposited materials. The resulting patterned layers have sharp sidewalls, low line-edge roughness, and uniform thickness and are free from imperfections such as edge ears occurring with other printed lift-off methods. The applicability of the method is demonstrated with highly conductive Al (∼5 × 10-8 Ωm resistivity) utilized as transparent metal mesh conductors with ∼35 Ω□ at 85% transparent area percentage and source/drain electrodes for solution-processed metal-oxide (In2O3) thin-film transistors with ∼1 cm2/(Vs) mobility. Moreover, the method is expected to be compatible with other printing methods and applicable in other flexible electronics applications, such as biosensors, resistive random access memories, touch screens, displays, photonics, and metamaterials, where the selection of current printable materials falls short.


Collar height and heel counter-stiffness for ankle stability and athletic performance in basketball.
This study examined the effects of collar height and heel counter-stiffness of basketball shoes on ankle stability during sidestep cutting and athletic performance. 15 university basketball players wore customized shoes with different collar heights (high and low) and heel counter-stiffness (regular, stiffer and stiffest) for this study. Ankle stability was evaluated in sidestep cutting while athletic performance evaluated in jumping and agility tasks. All variables were analysed using two-way repeated ANOVA. Results showed shorter time to peak ankle inversion for both high collar and stiff heel counter conditions (P < 0.05), while smaller initial ankle inversion angle, peak inversion velocity and total range of inversion for wearing high collar shoes (P < 0.05). No shoe differences were found for performance variables. These findings imply that the collar height might play a larger role in lateral stability than heel counter-stiffness, while both collar height and counter-stiffness have no effect on athletic performance.


Neural mechanisms for voice recognition.
We investigated neural mechanisms that support voice recognition in a training paradigm with fMRI. The same listeners were trained on different weeks to categorize the mid-regions of voice-morph continua as an individual's voice. Stimuli implicitly defined a voice-acoustics space, and training explicitly defined a voice-identity space. The pre-defined centre of the voice category was shifted from the acoustic centre each week in opposite directions, so the same stimuli had different training histories on different tests. Cortical sensitivity to voice similarity appeared over different time-scales and at different representational stages. First, there were short-term adaptation effects: increasing acoustic similarity to the directly preceding stimulus led to haemodynamic response reduction in the middle/posterior STS and in right ventrolateral prefrontal regions. Second, there were longer-term effects: response reduction was found in the orbital/insular cortex for stimuli that were most versus least similar to the acoustic mean of all preceding stimuli, and, in the anterior temporal pole, the deep posterior STS and the amygdala, for stimuli that were most versus least similar to the trained voice-identity category mean. These findings are interpreted as effects of neural sharpening of long-term stored typical acoustic and category-internal values. The analyses also reveal anatomically separable voice representations: one in a voice-acoustics space and one in a voice-identity space. Voice-identity representations flexibly followed the trained identity shift, and listeners with a greater identity effect were more accurate at recognizing familiar voices. Voice recognition is thus supported by neural voice spaces that are organized around flexible 'mean voice' representations.


Head shaking does not alter vestibulo ocular reflex gain in vestibular migraine.
Vestibular Migraine (VM) is the most common cause of non-positional episodic vestibular symptoms. Patients with VM commonly report increased motion sensitivity, suggesting that vestibular responses to head movement may identify changes specific to VM patients. Here we explore whether the vestibulo-ocular reflex (VOR) gain alters in response to a clinical "headshake" maneuver in patients with VM. Thirty patients with VM in the inter-ictal phase, 16 patients with Benign Positional Paroxysmal Vertigo (BPPV) and 15 healthy controls were recruited. Patients responded to the question "Do you feel sick reading in the passenger seat of a car?" and completed a validated motion sickness questionnaire as a measure of motion sensitivity. Lateral canal vHIT testing was performed before and after headshaking; the change in VOR gain was calculated as the primary outcome. Baseline VOR gain was within normal limits across all participants. There was no significant change in VOR gain after headshaking in any group (p = 0.264). Patients were 4.3 times more likely to be in the VM group than in the BPPV group if they reported nausea when reading in the passenger seat of a car. We postulate that a headshake stimulus may be insufficient to disrupt cortical interactions and induce a change in VOR gain. Alternatively, changes in VOR gain may only be apparent in the acute phase of VM. Reading in the passenger seat of a car was considered uncomfortable in all VM patients suggesting that this specific question may be useful for the diagnosis of VM.


Quality of life outcomes from a randomized controlled trial of patient navigation in Latina breast cancer survivors.
Breast cancer survivorship is a life-long process involving challenges to health-care communities and individuals, especially Latinas. Patient Navigation has shown some success in meeting these challenges. The purpose of this study was to compare the effects of an enhanced Patient Navigation program (Intervention; PN+) vs Control (PN) over time on general cancer and breast cancer-specific quality of life (QoL) in Latina breast cancer survivors (BCS). We conducted a 2-year, two-arm randomized controlled trial of the "Staying Healthy" program among Latina BCS. The design compared PN+ vs PN over time. We recruited 60 patients into each study arm and randomized them by sequential numerical assignment. PN+ participants received culturally tailored educational materials and active, personalized Patient Navigation services, including phone calls, transportation, and care coordination. PN participants were navigated only upon request. Primary outcomes included general cancer (Functional Assessments of Cancer Therapy [FACTS]-G) and breast cancer-specific (FACT-B) QoL. PN+ participants had significantly improved QoL measures compared to PN at 6-month follow-up on all subscales (P-values .007-.04) except physical well-being (PWB; P = .11). Intervention effect size coefficient (standard error) for FACT-G overall was 7.9 (3.1); P = .01. For FACT-B, it was 10.9 (3.9); P = .006. Again, all subscales showed significant effects [range 1.7-3.1 (0.8-1.2); P-values .006-.04], except for PWB [1.5 (1.0); P = .16] and social/family well-being (SWB) [2.1 (1.1); P = .06]. There were no differences between groups at baseline. Multiple cultural, psychosocial, and socioeconomic variables contributing to these intervention effects will be addressed in future studies. As the national BCS population continues to increase, more Patient Navigation-focused partnerships among patients, health-care professionals, research groups, and community organizations are needed to improve BCS experiences. The Staying Healthy program has the potential to serve as a national survivorship care model for improving Latina BCS QoL.


Extracranial venous hemodynamics in multiple sclerosis: a case-control study.
A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of multiple sclerosis (MS). We performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria. We prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva maneuver. We recruited 42 patients with MS (mean age 39 ± 11 years, 17 men) and 43 control individuals (mean age 38 ± 12 years, 16 men). Very good/excellent intrarater and interrater agreement (κ values 0.82-1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. After performing Valsalva maneuver, we documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999). With established reproducibility of venous ultrasound testing, our data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.


Core histone hyperacetylation impacts cooperative behavior and high-affinity binding of histone H1 to chromatin.
Linker histones stabilize higher order chromatin structures and limit access to proteins involved in DNA-dependent processes. Core histone acetylation is thought to modulate H1 binding. In the current study, we employed kinetic modeling of H1 recovery curves obtained during fluorescence recovery after photobleaching (FRAP) experiments to determine the impact of core histone acetylation on the different variants of H1. Following brief treatments with histone deacetylase inhibitor, most variants showed no change in H1 dynamics. A change in mobility was detected only when longer treatments were used to induce high levels of histone acetylation. This hyperacetylation imparted marked changes in the dynamics of low-affinity H1 population, while conferring variant-specific changes in the mobility of H1 molecules that were strongly bound. Both the C-terminal domain (CTD) and globular domain were responsible for this differential response to TSA. Furthermore, we found that neither the CTD nor the globular domain, by themselves, undergoes a change in kinetics following hyperacetylation. This led us to conclude that hyperacetylation of core histones affects the cooperative nature of low-affinity H1 binding, with some variants undergoing a predicted decrease of almost 2 orders of magnitude.


Errata.
Could it be the thinning of the ozone layer (see p. 645) that has indirectly caused our baffling faux pas in recent issues? In reporting the formation by the National Academy of Sciences of a Committee on Environmental Research to be headed by Cornell President Emeritus Dale Corson (11 October, p. 192), we inexplicably fused the distinguished careers of physicist Corson and former Dartmouth president John Kemeny. It was the latter who headed the President's Commission that investigated the accident at Three Mile Island, whereas Corson's distinctions include heading the NAS's "Corson Panel" on scientific communications and national security and founding the Government-University-Industry Research Roundtable. Three weeks earlier (in "Mycomummy," 20 September, p. 1353), we misspelled Coccidioides, a fungus whose petrified spores were found in the ancient skeleton of a Sinaguan indian.


Dose-adjusted Lenalidomide Combined with Low-dose Dexamethasone Rescues Older Patients with Bortezomib-resistant Multiple Myeloma.
The aim of this study was to assess the safety and efficacy of lenalidomide (Len), with the dose adjusted according to the renal function, plus low-dose dexamethasone (Dex) in older patients with bortezomib (Bor)-resistant multiple myeloma (MM). The study included 68 consecutive patients 70 years of age or older diagnosed with MM at our institute and ineligible for high-dose melphalan therapy plus autologous stem cell transplantation. Fifteen older patients with relapsed or refractory MM (RRMM) previously treated with Bor-containing regimens were treated with the combination of Len plus low-dose Dex. The median treatment duration was 12 months (range, 9 to 43 months), with all patients responding to Len plus low-dose Dex. All patients showed significant renal dysfunction between the beginning and end of treatment; however, the renal function improved in all cases. Treatment with dose-adjusted Len combined with low-dose Dex is an effective and safe therapy for older RRMM patients exhibiting renal impairment after receiving Bor-based therapies.


Emerging regulators of vascular smooth muscle cell function in the development and progression of atherosclerosis.
After a period of relative senescence in the field of vascular smooth muscle cell (VSMC) research with particular regards to atherosclerosis, the last few years has witnessed a resurgence, with extensive research re-assessing potential molecular mechanisms and pathways that modulate VSMC behaviour within the atherosclerotic-prone vessel wall and the atherosclerotic plaque itself. Attention has focussed on the pathological contribution of VSMC in plaque calcification; systemic and local mediators such as inflammatory molecules and lipoproteins; autocrine and paracrine regulators which affect cell-cell and cell to matrix contacts alongside cytoskeletal changes. In this brief focused review, recent insights that have been gained into how a myriad of recently identified factors can influence the pathological behaviour of VSMC and their subsequent contribution to atherosclerotic plaque development and progression has been discussed. An overriding theme is the mechanisms involved in the alterations of VSMC function during atherosclerosis.


The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1α Gene Expression.
The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate concentrations, and exercise-associated biomarkers. Eighteen recreationally trained males (25 ± 5 y) were randomized to supplement 6 g/day of either betaine anhydrous (BET) or cellulose placebo (PLA) for 14 days. Subsequently, subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs (BFR [LL-BFR; 20% 1RM at 80% arterial occlusion pressure] and high-load [HL; 70% 1RM]). Toe-tip lactate concentrations were sampled before (PRE), as well as immediately (POST0), 30 min (POST30M), and 3 h (POST3H) post-exercise. Serum homocysteine (HCY), growth hormone (GH) and insulin-like growth factor-1 concentrations were additionally assessed at PRE and POST30M. Analysis failed to detect any significant between-supplement differences for total repetitions completed. Baseline lactate changes (∆) were significantly elevated from POST0 to POST30 and from POST30 to POST3H (p < 0.05), whereby HL additionally demonstrated significantly higher ∆Lactate versus LL-BFR (p < 0.001) at POST3H. Although serum ∆GH was not significantly impacted by supplement or condition, serum ∆IGF-1 was significantly (p = 0.042) higher in BET versus PLA and serum ∆HCY was greater in HL relative to LL-BFR (p = 0.044). Although these data fail to support a BFR-betaine synergy, they otherwise support betaine's anabolic potential.


Positional Differences in Absolute vs. Relative Training Loads in Elite Academy Soccer Players.
Weekly training loads are typically reported using absolute values and are not individualized according to competition positional demands (relative values). The aim of this study was to evaluate absolute and relative training loads and compare across playing positions during a full in-season in an elite soccer academy. 24 elite academy soccer players, categorized into five positions (CD: central defender [n = 4]; FB: full back [n = 5]; CM: central midfielder [n = 6]; WM: wide midfielder [n = 5]; FW: forward [n = 4]), were monitored using a global positioning system. Absolute training load was calculated using the total distance, the distance at moderate-speed ([15-20[ km·h-1), high-speed ([20-25[ km·h-1), sprint (> 25 km·h-1), the total number of accelerations (> 3 m·s-2) and decelerations (< -3 m·s-2). Relative training load was calculated by dividing absolute training loads by mean values from the competitive matches. Training loads were determined daily according to their distance from match day (MD). One-way ANOVAs were performed to evaluate differences between playing positions. Absolute moderate-speed distance was greater for WM compared to CD (p = 0.015, and p = 0.017), while the opposite was shown for relative values (p = 0.014, and p < 0.001) on MD-4 and MD-3, respectively. The absolute moderate-speed distance was not different between CD, FB, CM, and FW, whereas relative values were greater for CD on MD+2 and MD-4 (p < 0.05). FB and WM performed greater absolute high-speed distance than CD on MD-4 and MD-3 (p < 0.05) while no difference was highlighted for relative values.Our results demonstrated that in the present academy players, training load for CD was underestimated using absolute training loads for moderate and high-speed distances. In contrast, relative training loads highlighted WM as an underloaded position. Therefore, relative training loads are recommended as they contextualize training loads according to competitive demands and favor training individualization.


Site-directed mutagenesis of aldehyde dehydrogenase-2 suggests three distinct pathways of nitroglycerin biotransformation.
To elucidate the mechanism underlying reduction of nitroglycerin (GTN) to nitric oxide (NO) by mitochondrial aldehyde dehydrogenase (ALDH2), we generated mutants of the enzyme lacking the cysteines adjacent to reactive Cys302 (C301S and C303S), the glutamate that participates as a general base in aldehyde oxidation (E268Q) or combinations of these residues. The mutants were characterized regarding acetaldehyde dehydrogenation, GTN-triggered enzyme inactivation, GTN denitration, NO formation, and soluble guanylate cyclase activation. Lack of the cysteines did not affect dehydrogenase activity but impeded GTN denitration, aggravated GTN-induced enzyme inactivation, and increased NO formation. A triple mutant lacking the cysteines and Glu268 catalyzed sustained formation of superstoichiometric amounts of NO and exhibited slower rates of inactivation. These results suggest three alternative pathways for the reaction of ALDH2 with GTN, all involving formation of a thionitrate/sulfenyl nitrite intermediate at Cys302 as the initial step. In the first pathway, which predominates in the wild-type enzyme and reflects clearance-based GTN denitration, the thionitrate apparently reacts with one of the adjacent cysteine residues to yield nitrite and a protein disulfide. The predominant reaction catalyzed by the single and double cysteine mutants requires Glu268 and results in irreversible enzyme inactivation. Finally, combined lack of the cysteines and Glu268 shifts the reaction toward formation of the free NO radical, presumably through homolytic cleavage of the sulfenyl nitrite intermediate. Although the latter reaction accounts for less than 10% of total turnover of GTN metabolism catalyzed by wild-type ALDH2, it is most likely essential for vascular GTN bioactivation.


Tobacco use and preferences for wellness programs among health aides and other employees of an Alaska Native Health Corporation in Western Alaska.
This study assessed health behaviors and preferences for wellness programs among employees of a worksite serving Alaska Native-people. Village-based Community Health Aides/Practitioners (CHA/Ps) were compared with all other employees on health indicators and program preferences. Using a cross-sectional design, all 1290 employees at the Yukon Kuskokwim Health Corporation (YKHC) in Western Alaska were invited in 2015 to participate in a 30-item online survey. Items assessed health behaviors, perceived stress, resiliency, and preferences for wellness topics and program delivery formats. Respondents (n = 429) were 77% female and 57% Alaska Natives. CHA/Ps (n = 46) were more likely than all other employees (n = 383) to currently use tobacco (59% vs. 36%; p = 0.003). After adjusting for covariates, greater stress levels were associated (p = 0.013) with increased likelihood of tobacco use. Employees reported lower than recommended levels of physical activity; 74% had a Body Mass Index (BMI) indicating overweight or obese. Top preferences for wellness topics were for eating healthy (55%), physical activity (50%), weight loss (49%), reducing stress (49%), and better sleep (41%). CHA/Ps reported greater interest in tobacco cessation than did other employees (37% vs. 21%; p = 0.016). Preferred program delivery format among employees was in-person (51%). The findings are important because tailored wellness programs have not been previously evaluated among employees of worksites serving Alaska Native people. Promoting healthy lifestyles among CHAP/s and other YKHC employees could ultimately have downstream effects on the health of Alaska Native patients and communities.


Electronic and molecular properties of an adsorbed protein monolayer probed by two-color sum-frequency generation spectroscopy.
Two-color sum-frequency generation spectroscopy (2C-SFG) is used to probe the molecular and electronic properties of an adsorbed layer of the green fluorescent protein mutant 2 (GFPmut2) on a platinum (111) substrate. First, the spectroscopic measurements, performed under different polarization combinations, and atomic force microscopy (AFM) show that the GFPmut2 proteins form a fairly ordered monolayer on the platinum surface. Next, the nonlinear spectroscopic data provide evidence of particular coupling phenomena between the GFPmut2 vibrational and electronic properties. This is revealed by the occurrence of two doubly resonant sum-frequency generation processes for molecules having both their Raman and infrared transition moments in a direction perpendicular to the sample plane. Finally, our 2C-SFG analysis reveals two electronic transitions corresponding to the absorption and fluorescence energy levels which are related to two different GFPmut2 conformations: the B (anionic) and I forms, respectively. Their observation and wavelength positions attest the keeping of the GFPmut2 electronic properties upon adsorption on the metallic surface.


Errors in calculated oncotic pressure of dog plasma.
Several equations to calculate plasma oncotic pressure (pi) from the total protein concentration (C) have been previously described. These equations were derived empirically from samples with a wide range of C obtained by diluting or concentrating normal plasma samples. To test these equations over a range of naturally occurring C, we measured C and pi of plasma samples from 40 dogs. C ranged from 5.3 to 8.7 g/dl and averaged 6.5 +/- 0.1 (mean +/- SE) and pi averaged 17.9 +/- 0.3 mmHg. The regression equation was pi = 78.14 + 1.67 C (r = 0.74). pi increased with C much less than predicted with the commonly used equations. The albumin-to-globulin concentration ratios (A/G), determined in 27 of the dogs, decreased with increasing C (A/G = 1.56-0.128 C, r = 0.62). The lower A/G at the higher C's could cause the lower than predicted increase in pi with C, because the equations were developed from data in which A/G was constant.


Physical activity, heart rate, metabolic profile, and estradiol in premenopausal women.
To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical activity (LPA), resting heart rate (HR), blood pressure (BP), anthropometry, and serum glucose, lipids, and insulin [Norwegian Energy Balance and Breast Cancer Aspect (EBBA) study]. E2 was measured in daily saliva samples throughout an entire menstrual cycle. A clustered metabolic risk score [z metabolic syndrome (zMS); total cholesterol-high-density lipoprotein-cholesterol (HDL-C) ratio, insulin resistance, total fat tissue, BP, and triglycerides] was defined. Linear regression and linear mixed models were used, and confounding factors were tested. Physically active women had lower fat percentage (Ptrend = 0.003) and HRs (Ptrend = 0.003) than sedentary women. We estimated an increase in E2 of 1.27 pmol.L [95% confidence interval (CI), 0.06-2.47] for each 11.7 beats.min (1 SD) increase in HR, and this corresponds to the 7% change in mean concentration of E2 for the total group. Associations with E2 were also found for fat tissue, total cholesterol-HDL-C ratio, insulin resistance, and triglycerides. A dose-response relationship was observed among the three levels of LPA and HR and zMS (Ptrend = 0.03 for LPA; Ptrend = 0.004 for HR). Women in the highest tertile of the clustered metabolic risk score had average salivary E2profiles that were markedly higher, throughout the cycle, than those of the other groups, with a cycle peak-day difference in E2 of 22-28%. LPA and HR were associated with metabolic risk score, and this score was associated with daily level of E2, pointing to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk.


Syntheses of 11C- and 18F-labeled carboxylic esters within a hydrodynamically-driven micro-reactor.
Carboxylic esters were successfully labeled with one of two short-lived positron-emitters, carbon-11 or fluorine-18, within a hydrodynamically-driven micro-reactor. The non-radioactive methyl ester was obtained at room temperature; its yield increased with higher substrate concentration and with reduced infusion rate. Radioactive methyl ester was obtained from the reaction of (10 mM) with in 56% decay-corrected radiochemical yield (RCY) at an infusion rate of 10 microL min(-1), and when the infusion rate was reduced to 1 microL min(-1), the RCY increased to 88%. The synthesis of the non-radioactive fluoroethyl ester from and required heating of the micro-reactor on a heating block at 80 degrees C (14-17% RCY), whilst the corresponding radioactive from and was obtained in 10% RCY. The radioactive 'peripheral' benzodiazepine receptor ligand was obtained from the reaction of acid with labeling agent in 45% RCY at an infusion rate of 10 microL min(-1). When the infusion rate was reduced to 1 microL min(-1), the RCY increased to 65%. The results exemplify a new methodology for producing radiotracers for imaging with positron emission tomography that has many potential advantages, including a requirement for small quantities of substrates, enhanced reaction, rapid reaction optimisation and easy product purification.


Improving antibiotic adherence in treatment of acute upper respiratory infections: a quality improvement process.
Approximately 25 million people in the United States visit their primary care physician each year for acute respiratory infections (ARI). They are a common cause of unnecessary prescription of antibiotics; despite well-validated national treatment guidelines, around 73% of adults with ARI are prescribed antibiotics in the United States. Inappropriate use of antibiotics has profound implications. Our aim was to increase adherence to antibiotic guidelines for treatment of ARI in an internal medicine outpatient practice. We used a package of active and passive interventions to improve physician awareness of treatment guidelines; these included short sessions of didactic teaching, antibiotic guidelines posters in patient examination rooms and staff areas, clinical decision support (CDS) tools integrated into the electronic medical record system, guideline adherence report cards for providers, and reiteration of CDS tool use and guideline adherence at monthly group meetings. Process measures were the rate of use of CDS tools for the management of ARI and patient callbacks within 72 h for the same issue. Outcome measures were compliance with antibiotic prescribing guidelines. Our low-cost interventions led to a significant improvement in ARI treatment guideline adherence. There was improvement in compliance with treatment guidelines for sinusitis (90.90% vs. 57.58%, p<0.001), pharyngitis (64.28% vs. 25.00%, p=0.003), upper respiratory infection (96.18% vs. 73.68%, p=0.008), and the aggregated measure of ARI (91.25% vs. 78.6%, p<0.001). Rate of CDS tool usage was 40.5% with a 72-h callback rate of 0.05%. Simple, low-cost interventions can improve appropriate antibiotic use for ARI and change the prescribing habits of providers in an outpatient setting. Provider and patient education is a vital component of antibiotic stewardship. Simple interventions for common outpatient conditions can have a positive impact on patient outcomes and reduce unnecessary healthcare costs.


Intracorporeal Heat Distribution from Fully Implantable Energy Sources for Mechanical Circulatory Support: A Computational Proof-of-Concept Study.
Mechanical circulatory support devices, such as total artificial hearts and left ventricular assist devices, rely on external energy sources for their continuous operation. Clinically approved power supplies rely on percutaneous cables connecting an external energy source to the implanted device with the associated risk of infections. One alternative, investigated in the 70s and 80s, employs a fully implanted nuclear power source. The heat generated by the nuclear decay can be converted into electricity to power circulatory support devices. Due to the low conversion efficiencies, substantial levels of waste heat are generated and must be dissipated to avoid tissue damage, heat stroke, and death. The present work computationally evaluates the ability of the blood flow in the descending aorta to remove the locally generated waste heat for subsequent full-body distribution and dissipation, with the specific aim of investigating methods for containment of local peak temperatures within physiologically acceptable limits. To this aim, coupled fluid-solid heat transfer computational models of the blood flow in the human aorta and different heat exchanger architectures are developed. Particle tracking is used to evaluate temperature histories of cells passing through the heat exchanger region. The use of the blood flow in the descending aorta as a heat sink proves to be a viable approach for the removal of waste heat loads. With the basic heat exchanger design, blood thermal boundary layer temperatures exceed 50°C, possibly damaging blood cells and proteins. Improved designs of the heat exchanger, with the addition of fins and heat guides, allow for drastically lower blood temperatures, possibly leading to a more biocompatible implant. The ability to maintain blood temperatures at biologically compatible levels will ultimately allow for the body-wise distribution, and subsequent dissipation, of heat loads with minimum effects on the human physiology.


Epidemiology and effect on production parameters of an outbreak of inclusion body hepatitis in broilers.
In 2007, an inclusion body hepatitis (IBH) outbreak affected several broiler farms in Mississippi. Results of logistic regression analyses showed significant associations between IBH occurrence and high enzyme-linked immunosorbent assay geometric mean titers for infectious bursal disease virus. However, there was no association between IBH occurrence and chicken infectious anemia virus status. Results of linear regression model analyses showed significant associations between IBH occurrence with average weight and with cost deviation. Broiler meat production cost was $0.0058/kg more expensive to produce when IBH occurred. Although feed conversion was higher with IBH occurrence, the association was not significant. IBH onset in the first farms affected occurred between 19 and 30 days of age, whereas in the last farms affected, IBH onset occurred as early as 10 days.


Cultured human hepatocytes. Evidence for metabolism of low density lipoproteins by a pathway independent of the classical low density lipoprotein receptor.
Studies of low density lipoprotein (LDL) metabolism in nonhuman model systems have indicated that the mammalian liver has dual mechanisms for the uptake and regulation of the concentration of plasma LDL. Heretofore, direct evaluation of lipoprotein uptake mechanisms in human hepatocytes has not been possible. In order to compare hepatocyte LDL uptake with fibroblast LDL metabolism, human hepatocytes were isolated and cultured from small biopsy specimens obtained from normolipidemic and homozygous familial hypercholesterolemic patients. Cells cultured in serum-free culture medium retained the morphological and biochemical characteristics of hepatocytes for at least 7 days. The uptake and degradation of LDL by hepatocytes was compared to that of the cultured human fibroblasts. Like fibroblasts, hepatocytes bound, internalized, and degraded LDL. In both cell types, uptake approached saturation at a concentration of 50 micrograms of LDL protein/ml. Competition for LDL binding by LDL, high density lipoprotein, and modified LD revealed that the hepatocyte binding was specific for LDL. Cellular cholesterol loading by incubation in LDL-enriched culture medium resulted in diminished LDL uptake in both cell types. Chemical modification of LDL by acetoacetylation, acetylation, and reductive methylation abolished LDL uptake and degradation by fibroblasts. However, hepatocytes bound and degraded the modified LDL at 30-50% the level of native LDL. Homozygous familial hypercholesterolemic hepatocytes were devoid of the LDL receptor pathway but metabolized native LDL to the extent observed with modified LDL uptake by normal hepatocytes. In contrast to the classic LDL receptor pathway, the second or alternate pathway does not lead to regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity. These findings indicate the presence of two separate pathways of LDL uptake in human hepatocytes which have different effects on hepatocytic cholesterol metabolism.


Development and Evaluation of a Risk-Adjusted Measure of Intraoperative Hypotension in Patients Having Nonemergent, Noncardiac Surgery.
Intraoperative hypotension is common and associated with organ injury and death, although randomized data showing a causal relationship remain sparse. A risk-adjusted measure of intraoperative hypotension may therefore contribute to quality improvement efforts. The measure we developed defines hypotension as a mean arterial pressure <65 mm Hg sustained for at least 15 cumulative minutes. Comparisons are based on whether clinicians have more or fewer cases of hypotension than expected over 12 months, given their patient mix. The measure was developed and evaluated with data from 225,389 surgeries in 5 hospitals. We assessed discrimination and calibration of the risk adjustment model, then calculated the distribution of clinician-level measure scores, and finally estimated the signal-to-noise reliability and predictive validity of the measure. The risk adjustment model showed acceptable calibration and discrimination (area under the curve was 0.72 and 0.73 in different validation samples). Clinician-level, risk-adjusted scores varied widely, and 36% of clinicians had significantly more cases of intraoperative hypotension than predicted. Clinician-level score distributions differed across hospitals, indicating substantial hospital-level variation. The mean signal-to-noise reliability estimate was 0.87 among all clinicians and 0.94 among clinicians with >30 cases during the 12-month measurement period. Kidney injury and in-hospital mortality were most common in patients whose anesthesia providers had worse scores. However, a sensitivity analysis in 1 hospital showed that score distributions differed markedly between anesthesiology fellows and attending anesthesiologists or certified registered nurse anesthetists; score distributions also varied as a function of the fraction of cases that were inpatients. Intraoperative hypotension was common and was associated with acute kidney injury and in-hospital mortality. There were substantial variations in clinician-level scores, and the measure score distribution suggests that there may be opportunity to reduce hypotension which may improve patient safety and outcomes. However, sensitivity analyses suggest that some portion of the variation results from limitations of risk adjustment. Future versions of the measure should risk adjust for important patient and procedural factors including comorbidities and surgical complexity, although this will require more consistent structured data capture in anesthesia information management systems. Including structured data on additional risk factors may improve hypotension risk prediction which is integral to the measure's validity.


Sacrectomy with Posterior-Only Approach in Sacral Tumors: An Analysis of 26 Cases and Review of Literature.
Sacral masses can be removed using anterior, posterior, or combined approaches. Achieving total sacrectomy through a posterior-only approach results in a shorter procedure time, minimal tissue damage, and a reduced risk of complications. In this study, we aimed to share our experience with performing total sacrectomy using a posterior-only approach in 26 patients and to assess their clinical outcomes at our center. This retrospective study examines the clinical progression, surgical response, and outcomes of 26 patients with various sacral mass pathologies. We accessed patient information from our hospital records. The study included 14 men (54%) and 12 women (46%), with an average age of 49.8 years. Most cases had a normal body mass index, while 6 were overweight. Sacrectomy was performed at a high level in 12 patients and at a middle level in 14 patients. In addition to pain, motor deficits were observed in 9 patients, and sphincter dysfunction was found in 5. Preoperative embolization was conducted for 11 patients. The most prevalent lesions were chordoma (8 patients), malignant peripheral nerve sheath tumor (4 patients), giant cell tumor (3 patients), and solitary plasmacytoma (3 patients). Only 1 patient experienced a temporary partial motor deficit after surgery. There were no instances of cerebrospinal fluid leakage. Five patients experienced local recurrence, and 1 had distant metastasis. Performing sacrectomy for large or giant sacral tumors through a posterior approach is both feasible and safe, resulting in reduced morbidity and no significant change in overall survival.


Preliminary Outcomes of an Older Peer and Clinician co-Facilitated Pain Rehabilitation Intervention among Adults Aged 50 Years and Older with Comorbid Chronic Pain and Mental Health Conditions.
The present study aimed to examine the acceptability, feasibility, and preliminary effectiveness of an older peer and clinician co-facilitated Behavioral Activation for Pain Rehabilitation (BA-PR) intervention among adults aged 50 years and older with comorbid chronic pain and mental health conditions. This was a mixed-methods research design with eight participants aged 55 to 62 years old with mental health conditions including schizophrenia spectrum disorder, bipolar disorder, major depressive disorder, personality disorder, and adjustment disorder. The quantitative data were assessed from observational methods, a pain rating scale and related measures. We used semi-structured interviews for qualitative feedback on experiences with the BA-PR intervention after participation. Overall, the participants had positive experiences following receipt of the BA-PR intervention. The recruitment and adherence rates for participants were 72.7% and 100%, respectively. Approximately 75% of the participants remained enrolled in the study. Findings from a paired t-test showed the BA-PR intervention was linked to significantly reduced prescription opioid misuse risk, t (7) = 2.42, p < 0.05. There were also non-significant reductions in pain intensity and depression severity, in addition to improvements in active and passive pain coping strategies and behavioral activation.The BA-PR intervention is the first pain rehabilitation intervention specifically designed for middle-aged and older adults with comorbid chronic pain and mental health conditions. Our findings indicate promise for the BA-PR intervention to potentially reduce prescription opioid misuse risk, pain, and depressive symptoms. However, a quasi-experimental study is needed before rigorous effectiveness testing.


PDZ motifs in PTP-BL and RIL bind to internal protein segments in the LIM domain protein RIL.
The specificity of protein-protein interactions in cellular signaling cascades is dependent on the sequence and intramolecular location of distinct amino acid motifs. We used the two-hybrid interaction trap to identify proteins that can associate with the PDZ motif-rich segment in the protein tyrosine phosphatase PTP-BL. A specific interaction was found with the Lin-11, Isl-1, Mec-3 (LIM) domain containing protein RIL. More detailed analysis demonstrated that the binding specificity resides in the second and fourth PDZ motif of PTP-BL and the LIM domain in RIL. Immunohistochemistry on various mouse tissues revealed a submembranous colocalization of PTP-BL and RIL in epithelial cells. Remarkably, there is also an N-terminal PDZ motif in RIL itself that can bind to the RIL-LIM domain. We demonstrate here that the RIL-LIM domain can be phosphorylated on tyrosine in vitro and in vivo and can be dephosphorylated in vitro by the PTPase domain of PTP-BL. Our data point to the presence of a double PDZ-binding interface on the RIL-LIM domain and suggest tyrosine phosphorylation as a regulatory mechanism for LIM-PDZ associations in the assembly of multiprotein complexes. These findings are in line with an important role of PDZ-mediated interactions in the shaping and organization of submembranous microenvironments of polarized cells.


Imaging quality of multifocal intraocular lenses: automated assessment setup.
A new technique for the assessment of the optical quality of multifocal intraocular lenses (MIOLs) under monochromatic and polychromatic illumination is presented. The system provides, in a totally automated procedure, the modulation transfer function (MTF) of the lens under test for different axial positions of the object. The artificial eye admits different artificial corneas, to optimise the axial resolution in the sampling of the MTF of the MIOL under test, and different pupils, to test the dependence of the optical performance of the MIOL on the eye pupil diameter. The performance and sensitivity of the apparatus is tested with different commercial MIOLs. The through-focus MTF for a refractive MIOL was measured at different moments during the process of hydration of a hydrophilic lens. Next, to show the performance of our proposal, two commercial refractive and diffractive MIOLs were evaluated. We have designed a precise and robust optical method for testing MIOLs in vitro. The proposed method represents a valuable technical improvement to make the procedure of MIOL evaluation more versatile, efficient and trustworthy.


Syntrophic growth via quinone-mediated interspecies electron transfer.
The mechanisms by which microbial species exchange electrons are of interest because interspecies electron transfer can expand the metabolic capabilities of microbial communities. Previous studies with the humic substance analog anthraquinone-2,6-disulfonate (AQDS) suggested that quinone-mediated interspecies electron transfer (QUIET) is feasible, but it was not determined if sufficient energy is available from QUIET to support the growth of both species. Furthermore, there have been no previous studies on the mechanisms for the oxidation of anthrahydroquinone-2,6-disulfonate (AHQDS). A co-culture of Geobacter metallireducens and G. sulfurreducens metabolized ethanol with the reduction of fumarate much faster in the presence of AQDS, and there was an increase in cell protein. G. sulfurreducens was more abundant, consistent with G. sulfurreducens obtaining electrons from acetate that G. metallireducens produced from ethanol, as well as from AHQDS. Co-cultures initiated with a citrate synthase-deficient strain of G. sulfurreducens that was unable to use acetate as an electron donor also metabolized ethanol with the reduction of fumarate and cell growth, but acetate accumulated over time. G. sulfurreducens and G. metallireducens were equally abundant in these co-cultures reflecting the inability of the citrate synthase-deficient strain of G. sulfurreducens to metabolize acetate. Evaluation of the mechanisms by which G. sulfurreducens accepts electrons from AHQDS demonstrated that a strain deficient in outer-surface c-type cytochromes that are required for AQDS reduction was as effective at QUIET as the wild-type strain. Deletion of additional genes previously implicated in extracellular electron transfer also had no impact on QUIET. These results demonstrate that QUIET can yield sufficient energy to support the growth of both syntrophic partners, but that the mechanisms by which electrons are derived from extracellular hydroquinones require further investigation.


An automated protocol for assessing career rurality outcomes of Australian health professionals using retrospective data.
Addressing the imbalance of the health workforce between metropolitan and rural areas requires a clear understanding of trends in choices of work location of health care staff. Here, we provide an automated and highly reproducible protocol to examine the location of health care workers over multiple years using medical graduates as a case study. Data linkage cohort study. The study cohort examined was University of Wollongong Medical graduates from 2010 to 2021 who were registered to practice in Australia. The main outcome measure was graduate location of practice in Modified Monash regsions MM1 or MM2-7 across multiple postgraduate years. This protocol used R Markdown. An automated and reproducible protocol was used to analyse choices of work location for the University of Wollongong's medical graduates. Over 90% of graduates were registered with AHPRA. Around 25%-30% of graduates were found to work in MM2-7 regions across their careers, exceeding the national average. The protocol presented allows for a fast and reproducible analysis of work location by region for health care workers. This will allow comparisons of outcomes between universities or health professions.


Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction.
Recently, anecdotal reports via the FDA's MedWatch reporting system have documented rare but serious hyperglycaemia in elderly patients receiving gatifloxacin. One possible factor contributing to these events may be gatifloxacin overexposure, resulting from age-related decreases in renal function in elderly patients predisposed to glycaemic alterations. These analyses examine gatifloxacin exposure in 10 patients with severe hyperglycaemia, provide a pharmacokinetic-pharmacodynamic (PK-PD) rationale for a potential age-related dose reduction to avoid high exposures, and evaluate the likely impact of such a dose reduction on clinical efficacy in this specific patient population. First, a previously derived population pharmacokinetic model, with patient demographics, was used to estimate gatifloxacin AUC0-24 following a dosage regimen of 400 mg/24 h in 10 index patients with severe hyperglycaemia. Second, the population pharmacokinetic model and patient demographic data from 2696 patients aged > or =65 years from two New Drug Application (NDA) databases were used to estimate AUC0-24 following dosage regimens for gatifloxacin of 200 and 400 mg/24 h. Finally, Monte Carlo simulation was utilized to assess the probability of achieving PK-PD target exposures against Streptococcus pneumoniae in elderly patients using these regimens. The mean estimated AUC0-24 among severe hyperglycaemia cases was 74 mg.h/L (range 57-100). Gatifloxacin AUC0-24 exposures for the 400 mg regimen were predicted to be higher in patients aged > or =65 years and similar to the severe hyperglycaemia cases. The probability of AUC0-24 > or =60 and > or =70 in patients aged > or =65 years for the 200 mg regimen was 0.03 and <0.01, respectively, versus 0.51 and 0.35 for the 400 mg regimen, respectively. The probability of achieving PK-PD target exposures against S. pneumoniae in patients aged > or =65 years receiving the 200 mg regimen was 0.99. The probability of a patient aged > or =65 years having an AUC0-24 > or =60-70 mg.h/L is markedly lower following a 200 mg regimen relative to a 400 mg regimen, suggesting a decreased risk of severe hyperglycaemia in a predisposed patient. Moreover, a dose reduction does not appear to significantly modify the likelihood of achieving the PK-PD target of gatifloxacin against S. pneumoniae.


Interference of Temporally Distinguishable Photons Using Frequency-Resolved Detection.
We demonstrate quantum interference of three photons that are distinguishable in time by resolving them in the conjugate parameter frequency. We show that the multiphoton interference pattern in our setup can be manipulated by tuning the relative delays between the photons, without the need for reconfiguring the optical network. Furthermore, we observe that the symmetries of our optical network and the spectral amplitude of the input photons are manifested in the interference pattern. We also demonstrate time-reversed Hong-Ou-Mandel-like interference in the spectral correlations using time-bin entangled photon pairs. By adding a time-varying dispersion using a phase modulator, our setup can be used to realize dynamically reconfigurable and scalable boson sampling in the time domain as well as frequency-resolved multiboson correlation sampling.


Handling Class Imbalance in Machine Learning-based Prediction Models: A Case Study in Asthma Management.
A data-driven prediction tool has the potential to provide early warning of an asthma attack and improve asthma management and outcomes. Most previous machine learning (ML)-based studies for asthma attack prediction have reported a severe class imbalance, with major implications for model performance. We aimed to undertake a systematic comparison of several class imbalance handling techniques in the context of risk prediction models for asthma prognosis. We used data from 9,835 asthma patients extracted from the Medical Information Mart for Intensive Care (MIMIC) IV database and deployed five class imbalance handling methods based on synthetic minority oversampling technique (SMOTE) and cost function customisation. We then compared their performances in improving two-class classifier models developed using logistic regression (LR) and extreme gradient boosting (XGBoost) for three different prediction tasks with varying severity of class imbalance (proportion of majority class ranging from 90.86% to 98.98%). The cost function customisation technique substantially outperformed the SMOTE-based methods in all tasks. XGBoost combined with cost function customisation achieved the highest prediction performance for the outcome with the most extreme class imbalance ratio (AUC = 0.72). Our findings suggest that the cost function customisation-based approach to tackle class imbalance provides substantially better performance compared to oversampling in the context of asthma management.Clinical Relevance- This study underscores the challenge of class imbalance in the context of prediction tools to improve asthma management and outcomes and provides a methodological solution that addresses the challenge. Accurate asthma prediction tools can provide early warning and potentially prevent deterioration thereby improving the quality of life of patients with asthma.


Bacillus subtilis deoxyribonucleic acid gyrase.
Bacillus subtilis 168 was shown to contain a deoxyribonucleic acid (DNA) gyrase activity which closely resembled those of the enzymes isolated from Escherichia coli and Micrococcus luteus in its enzymatic requirements, substrate specificity, and sensitivity to several antibiotics. The enzyme was purified from the wild type and nalidixic acid-resistant and novobiocin-resistant mutants of B. subtilis and was functionally characterized in vitro. The genetic loci nalA and novA but not novB were shown to code for portions of the functional gyrase. Enzyme from the antibiotic-resistant mutants was resistant to the drug in vitro. The most striking observation was the remarkable similarity between the B. subtilis enzyme and other DNA gyrases, especially with respect to the oxolinic acid-induced DNA cleavage in the presence of sodium dodecyl sulfate. All of the enzymes appeared to possess the same specificity of cutting sites regardless of the source or type of DNA used. This result implies that gyrase binding to DNA is highly specific.


Modification of the Keller operation for increased functional capacity.
A technique for stabilization of the metatarsophalangeal joint maintaining propulsive power of the hallux and prevention of transfer lesions has been described. It utilizes the flexor hallucis longus tendon to maintain the integrity of the biomechanics of the first metatarsophalangeal joint while obviating the need for an interphalangeal joint fusion to prevent hallux flexus. The procedure is an adjunct to the medial and dorsal exostectomy, corrects for proximal and distal articular set angles, and provides for a rapid recovery of function of the metatarsophalangeal joint.


Symptomatic vs. Asymptomatic 20-40% Internal Carotid Artery Stenosis: Does the Plaque Size Matter?
Background: Around 9-15% of ischemic strokes are related to internal carotid artery (ICA)-stenosis ≥50%. However, the extent to which ICA-stenosis <50% causes ischemic cerebrovascular events is uncertain. We examined the relation between plaque cross-sectional area and length and the risk of ischemic stroke or TIA among patients with ICA-stenosis of 20-40%. Methods: We retrospectively identified patients admitted to the Department of Neurology, University Hospital of Würzburg, from January 2011 until September 2016 with ischemic stroke or TIA and concomitant ICA-stenosis of 20-40%, either symptomatic or asymptomatic. Plaque length and cross-sectional area were assessed on ultrasound scans. Results: We identified 41 patients with ischemic stroke or TIA and ICA-stenosis of 20-40%; 14 symptomatic and 27 asymptomatic. The plaque cross-sectional area was significantly larger among symptomatic than asymptomatic ICA-stenosis; median values (IQR) were 0.45 (0.21-0.69) cm2 and 0.27 (0.21-0.38) cm2, p = 0.03, respectively. A plaque cross-sectional area ≥0.36 cm2 had a sensitivity of 71% and a specificity of 76% for symptomatic compared with asymptomatic ICA-stenosis. In a sex-adjusted multivariate logistic regression, a plaque cross-sectional area ≥0.36 cm2 and a plaque length ≥1.65 cm were associated with an OR (95% CI) of 5.54 (1.2-25.6), p = 0.028 and 1.78 (0.36-8.73), p = 0.48, respectively, for symptomatic ICA-stenosis. Conclusion: Large plaques might increase the risk of ischemic stroke or TIA among patients with low-grade ICA-stenosis of 20-40%. Sufficiently powered prospective longitudinal cohort studies are needed to definitively test the stroke risk stratification value of carotid plaque length and cross-sectional area in the setting of current optimal medical treatment.


How Many Species of Insects and Other Terrestrial Arthropods Are There on Earth?
In the last decade, new methods of estimating global species richness have been developed and existing ones improved through the use of more appropriate statistical tools and new data. Taking the mean of most of these new estimates indicates that globally there are approximately 1.5 million, 5.5 million, and 7 million species of beetles, insects, and terrestrial arthropods, respectively. Previous estimates of 30 million species or more based on the host specificity of insects to plants now seem extremely unlikely. With 1 million insect species named, this suggests that 80% remain to be discovered and that a greater focus should be placed on less-studied taxa such as many families of Coleoptera, Diptera, and Hymenoptera and on poorly sampled parts of the world. DNA tools have revealed many new species in taxonomically intractable groups, but unbiased studies of previously well-researched insect faunas indicate that 1-2% of species may be truly cryptic.


1000-fold sample focusing on paper-based microfluidic devices.
We present an experimental and analytical study of a novel paper-based analytical device (μPAD) for isotachophoretic sample focusing. Guided by a simple heat transfer model, we further developed wax printing fabrication to enable the creation of shallow channels, which are critical in providing sufficient dissipation of Joule heat, and thus enable the use of high electric fields and short analysis time. This results in a device that is self-contained on a simple piece of filter paper and does not require any specialized enclosures or cooling devices to combat evaporation at high temperatures. Furthermore, we provide an analytical model for isotachophoretic sample accumulation in porous media, introduce a simple figure of merit for evaluating and comparing the efficiency of such devices, and present experimental validation in both paper and glass channels. Using this device we demonstrate the processing of 30 μL of sample achieving 1000-fold increase in peak concentration in 6 min. We believe that this method and device can serve as a guide to the design of low-cost, rapid and highly sensitive paper-based diagnostic platforms.


Perceptually-weighted evaluation criteria for segmentation masks in video sequences.
In order to complement subjective evaluation of the quality of segmentation masks, this paper introduces a procedure for automatically assessing this quality. Algorithmically computed figures of merit are proposed. Assuming the existence of a perfect reference mask (ground truth), generated manually or with a reliable procedure over a test set, these figures of merit take into account visually desirable properties of a segmentation mask in order to provide the user with metrics that best quantify the spatial and temporal accuracy of the segmentation masks. For the sake of easy interpretation, results are presented on a peaked signal-to-noise ratio-like logarithmic scale.


Effect of Sulfotyrosine and Negatively Charged Amino Acid of Leech-Derived Peptides on Binding and Inhibitory Activity Against Thrombin.
Hirudins, natural sulfo(glyco)proteins, are clinical anticoagulants that directly inhibit thrombin, a key coagulation factor. Their potent thrombin inhibition primarily results from antagonistic interactions with both the catalytic and non-catalytic sites of thrombin. Hirudins often feature sulfate moieties on Tyr residues in their anionic C-terminus region, enabling strong interactions with thrombin exosite-I and effectively blocking its engagement with fibrinogen. Although sulfotyrosines have been identified in various hirudin variants, the precise relationship between sulfotyrosine and the number of negatively charged amino acids within the anionic-rich C-terminus peptide domain for the binding of thrombin has remained elusive. By using Fmoc-SPPS, hirudin dodecapeptides homologous to the C-terminus of hirudin variants from various leech species were successfully synthesized, and the effect of sulfotyrosine and the number of negatively charged amino acids on hirudin-thrombin interactions was investigated. Our findings did not reveal any synergistic effect between an increasing number of sulfotyrosines or negatively charged amino acids and their inhibitory activity on thrombin or fibrinolysis in the assays, despite a higher binding level toward thrombin in the sulfated dodecapeptide Hnip_Hirudin was observed in SPR analysis.


Thermodynamics of vitreoretinal surgery.
To report in vivo the temperature variations occurring continuously inside the human eye during vitreoretinal surgery. Intraocular temperature was monitored during the entire surgical time in 14 eyes of 14 patients undergoing pars plana vitrectomy. A custom made 23-gauge thermoprobe was inserted through a sclerotomy at 3.5 mm from the limbus. Temperature in the anterior chamber and on the retinal surface was measured at one time point, whilst the temperature in the vitreous cavity was monitored throughout the entire surgery. Time points of particular interest in the vitreous cavity were: at baseline (inflow off - outflow off), at the beginning of the vitrectomy (inflow off - outflow on), at the end of vitrectomy (inflow on-outflow on), during the epiretinal procedures (inflow on-outflow off), under air infusion, under oil and under endolaser treatment ongoing. The mean temperature in the anterior chamber and on the nasal retinal side was 23.6 °C (SD 1.8)and 32.3 °C (SD 1.1), respectively. The mean vitreous temperature at baseline, before opening the infusion, was 33.6 °C (SD 1.4). The mean temperature at the beginning and the end of the vitrectomy was 26.8 °C (SD 1.0) and 24.8 °C (SD 0.8), respectively. During the epiretinal procedures, the mean temperature was 27.4 °C (SD 0.7). Under air infusion, the mean temperature increased to 29.2 °C (SD 1.2). The fluctuations in temperature were statistically different between the time points during the vitrectomy (p < 0.001). Vitreoretinal surgery induces measurable changes in temperature in the human eye, with significant fluctuations. In particular, the temperature in the vitreous cavity decreases when both the inflow and the outflow fluid lines are open, whilst it increases under air infusion.