Nanofabrication of Isoporous Membranes for Cell Fractionation.
Cell fractionations and other biological separations frequently require several steps. They could be much more effectively done by filtration, if isoporous membranes would be available with high pore density, and sharp pore size distribution in the micro- and nanoscale. We propose a combination of two scalable methods, photolithography and dry reactive ion etching, to fabricate a series of polyester membranes with isopores of size 0.7 to 50 μm and high pore density with a demonstrated total area of 38.5 cm2. The membranes have pore sizes in the micro- and submicro-range, and pore density 10-fold higher than track-etched analogues, which are the only commercially available isoporous polymeric films. Permeances of 220,000 L m-2 h-1bar-1 were measured with pore size 787 nm. The method does not require organic solvents and can be applied to many homopolymeric materials. The pore reduction from 2 to 0.7 μm was obtained by adding a step of chemical vapor deposition. The isoporous system was successfully demonstrated for the organelle fractionation of Arabidopsis homogenates and could be potentially extended to other biological fractionations.


Investigating the value of balance and proprioception scores to predict lower limb injuries in professional judokas.
We investigated the ability of balance and proprioception screening tests to predict lower limb injuries in professional male judokas. Fifty-three male judokas of the national teams (Mean ± SD, age 18.68 ± 3.08 years, weight 75.34 ± 11.62 kg, height 175.28 ± 7.24 cm) participated in this study. Limits of stability (LOS), single leg stability (SLS), and knee joint position sense (JPS) was recorded as the screening tests before starting the 10 month follow up. Lower limb injury was recorded all through the follow up. Fifteen lower limb sport injuries were recorded for 53 judokas during the follow-up recordings. Significant accuracy of SLS, overall bilateral ratio (AUC 0.646, 95% CI 0.452-0.839, p = 0.046), as well as JPS 60° bilateral ratio (AUC 0.657, 95% CI 0.480-0.834, p = 0.044), and LOS overall (AUC 0.696, 95% CI 0.551-0.840, p = 0.031) were revealed discriminating between injured and uninjured judokas. The optimum cut-off of SLS, overall bilateral ratio, JPS 60° bilateral ratio, and LOS overall associated with belonging to uninjured judokas group was ≤ 1.15%, ≤ 1.09%, and ≤ 1.09 respectively (sensitivity, 0.763, 0.711, 0.789 respectively; specificity, 0.600). Although the absolute unilateral balance and proprioception scores were almost the same between injured and non-injured judokas, the bilateral ratio of both these indices were different between the two groups. Lower limbs bilateral balance and proprioception asymmetries is a more important risk factor than the absolute unilateral balance and proprioception scores for sustaining lower limb injuries in professional male judokas. Medical professionals and coaches are suggested to use these findings as pre-participation screening tools identify injury-prone athletes.


Protein-Related Dietary Parameters and Frailty Status in Older Community-Dwellers across Different Frailty Instruments.
The present study investigated the associations between frailty status and (a) daily protein intake, (b) daily body weight-adjusted protein intake, (c) branched-chain amino acid (BCAA) consumption, (d) evenness of protein distribution across main meals, (e) number of daily meals providing at least 30 g of protein, and (f) number of daily meals providing at least 0.4 g protein/kg of body weight in community-dwelling older adults. The relationship between frailty status and protein-related dietary parameters was explored across different frailty assessment tools. Two hundred older adults were enrolled in the study. Participant frailty status was determined according to a modified Fried's frailty phenotype (mFP), the FRAIL scale, and the Study of Osteoporotic Fracture (SOF) index. Diet was assessed by 24-h dietary recall, while diet composition was estimated using a nutritional software. A frailty instrument-dependent relationship was observed between frailty status and protein-related dietary parameters. Protein consumption was associated with frailty status only in participants identified as frail according to the mFP. In addition, protein and BCAA intake was found to be greater in robust and pre-frail participants relative to their frail counterparts. Our findings suggest that the association between frailty and protein-related dietary parameters is tool dependent. Specifically, protein and BCAA consumption appears to be lower only in older adults identified as frail by the mFP.


Total hip arthroplasty for protrusio acetabuli: a 3- to 9-year follow up of the Heywood technique.
Thirty-five total joint arthroplasties (34 patients) were performed in patients who had protrusio acetabuli. Twenty-nine percent of the patients had acetabular protrusio of grade I, while 71% had grade II and grade III protrusio. The mean follow up was 4 years (range: 3 to 9). Cemented acetabular components were used in 11 hips; 24 hips received an uncemented porous coated acetabular component. The patient evaluations included preoperative and postoperative Harris Hip Ratings and standard radiographs. In all cases, the medial wall defect was reconstructed with the solid autogenous femoral head as described by Heywood. The mean preoperative Harris Hip Rating was 45 (range: 30 to 60 points), and the postoperative mean was 85 (range: 70 to 100 points). Radiographically, the preoperative protrusio measured a mean of 8.8 mm (range: 6 to 18 mm), and the mean postoperative placement of the femoral head was 10 mm lateral to Kohler's line (range: 6 to 13 mm). There were no acetabular component failures and no acetabular bone graft resorptions. All autogenous grafts were incorporated to the host radiographically by 1 year post-surgery. This study corroborates previous work which suggests that medial-placed bone grafting is not resorbed and consolidates with the host bone. We find this technique extremely useful in dealing with this technical problem.


Sequence map of the 2 Mb Giardia lamblia assemblage A chromosome.
The gut protozoan parasite, Giardia lamblia (Assemblage A), has 5 major chromosomes, 1 of which is 2 Mb, as determined from gel separations of whole chromosomes. We originally published a physical map of this chromosome and, now, using the sequence data from 46 chromosome-specific probes, have produced a sequence map of the 2 Mb chromosome. Comparison of the probe sequences with the Giardia genome database (http://GiardiaDB.org) has identified 4 scaffolds (CH991771, CH991780, CH991782, and CH991767) belonging to the 2 Mb, Assemblage A, chromosome. Because of the density of probe sequences, we have been able to predict the orientation of the scaffolds and have identified erroneous inclusions in scaffold CH991767. Exclusion of erroneously included sequences resulted in a 1.96 Mb chromosome sequence. This study brings together experimental data and the GiardiaDB data to compile the sequence of a whole chromosome.


A new outlook on the energetics of muscle contraction.
Analysis of experimental data on two muscles demonstrates that, in contracting striated muscle, the total rate of ATP splitting, nu(t) (number of ATP molecules split per active myosin head per second), comprises of three separate components: nu(p), which is required for the generation of the contractile force P which is equal to the external load; nu(v) which is devoted to the development of the velocity of shortening V; and nu(w), which is responsible for the production of the mechanical power (PV). Nu(p) is proportional to P and nu(v) to V, which means that the sliding distance is independent of P. The mechanical power was found to be equal to the free energy change associated with the hydrolysis of nu(w), which means that the thermodynamic efficiency of the power-producing component is practically 100%. It is concluded that ATP hydrolysis is actually three different reactions. The analysis leads to Hill's force-velocity relationship. Its empirical constants a and b are expressed by thermodynamic and molecular parameters. The constant a was found to be inversely proportional to the sliding distance. The same considerations and conclusions should apply also to other muscles and to the movement under load of microtubules interacting with, e.g. kinesin.


A survey of isozyme polymorphism in a Drosophila melanogaster natural population.
A survey of biochemical polymorphism among glucose- and non-glucose-metabolizing enzymes was carried out on the June 1973 collection from the South Amherst, Mass. Drosophila melanogaster natural population. Polymorphic levels are among the highest recorded for this species; polymorphism among glucose-metabolizing enzymes did not differ significantly from that among non-glucose-metabolizing enzymes. Two loci, G6Pd on the X and Est-6 on the 3rd chromosome, displayed significant excesses of heterozygotes. Adh on the 2nd and Idh, Odh and Ao on the 3rd chromosome showed significant heterozygote deficiencies. Idh is ten map units to the left of Est-6, Odh twelve map units to the right and Ao is seven units beyond Odh. Temperatures in the two-week June period prior to collection were exceedingly variable. Daily high/low ranged between 76 degrees/40 degrees and 97 degrees/65 degrees F. These results support the findings of Frydenberg and Simonsen (1973) that in some populations glucose-metabolizing enzymes tend to be as polymorphic as non-glucose-metabolizing ones. They also add to the evidence obtained from other plant and animal populations that increased biochemical polymorphism is associated with more variable and/or colder climates. The increase may in part be due to increased polymorphism among glucose-metabolizing enzymes. Comparisons utilizing published data on other D. melanogaster populations and on D. robusta indicate a clinal increase in heterozygosity among glucose-metabolizing enzymes as one moves northward.


Tandem sialoglycan-binding modules in a Streptococcus sanguinis serine-rich repeat adhesin create target dependent avidity effects.
Sialic acid-binding immunoglobulin-like lectins (Siglec)-like domains of streptococcal serine-rich repeat (SRR) adhesins recognize sialylated glycans on human salivary, platelet, and plasma glycoproteins via a YTRY sequence motif. The SRR adhesin from Streptococcus sanguinis strain SK1 has tandem sialoglycan-binding domains and has previously been shown to bind sialoglycans with high affinity. However, both domains contain substitutions within the canonical YTRY motif, making it unclear how they interact with host receptors. To identify how the S. sanguinis strain SK1 SRR adhesin affects interactions with sialylated glycans and glycoproteins, we determined high-resolution crystal structures of the binding domains alone and with purified trisaccharides. These structural studies determined that the ligands still bind at the noncanonical binding motif, but with fewer hydrogen-bonding interactions to the protein than is observed in structures of other Siglec-like adhesins. Complementary biochemical studies identified that each of the two binding domains has a different selectivity profile. Interestingly, the binding of SK1 to platelets and plasma glycoproteins identified that the interaction to some host targets is dominated by the contribution of one binding domain, whereas the binding to other host receptors is mediated by both binding domains. These results provide insight into outstanding questions concerning the roles of tandem domains in targeting host receptors and suggest mechanisms for how pathogens can adapt to the availability of a range of related but nonidentical host receptors. They further suggest that the definition of the YTRY motif should be changed to ϕTRX, a more rigorous description of this sialic acid-recognition motif given recent findings.


Lower extremity preference and knee extensor torques in intercollegiate soccer players.
The purpose of this study was to determine whether lower extremity preference influenced the relationship between the dominant and nondominant knee extensors of intercollegiate soccer players. Twelve recreational athletes and 12 soccer players completed isometric contractions at 60 degrees flexion, and concentric-eccentric contraction cycles at angular velocities of 60 degrees and 180 degrees/s through a range of motion from 90 degrees to 10 degrees knee flexion. Although the soccer players demonstrated greater peak and average torques, and greater differences between their dominant and nondominant legs, they responded similarly to recreational athletes during isometric, concentric and eccentric contractions and produced similar torque-velocity patterns. The concentric/eccentric ratios were similar for both legs and both groups, and decreased as angular velocity increased. The nondominant/dominant ratios of the soccer players, however, were significantly lower than those of the recreational athletes when calculated using peak torque (p less than .02) and nearly so when calculated using average torque (p less than .08). Nondominant/dominant ratios were not affected by the type of contraction or by the angular velocity. Further study is required to determine whether the small asymmetry (about 7%) in knee extensor strength of the soccer players is significant with respect to performance or injury rates, or may be inconsequential.


Relationship between brain R(2) and liver and serum iron concentrations in elderly men.
Studies of iron overload in humans and animals suggest that brain iron concentrations may be related in a regionally specific way to body iron status. However, few quantitative studies have investigated the associations between peripheral and regional brain iron in a normal elderly cohort. To examine these relationships, we used MRI to measure the proton transverse relaxation rate (R(2)) in 13 gray and white matter brain regions in 18 elderly men (average age, 75.5 years) with normal cognition. Brain R(2) values were compared with liver iron concentrations measured using the FerriScan MRI technique and serum iron indices. R(2) values in high-iron gray matter regions were significantly correlated (positively) with liver iron concentrations (globus pallidus, ventral pallidum) and serum transferrin saturation (caudate nucleus, globus pallidus, putamen) measured concurrently with brain R(2), and with serum iron concentrations (caudate nucleus, globus pallidus) measured three years before the current study. Our results suggest that iron levels in specific gray matter brain regions are influenced by systemic iron status in elderly men.


Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients.
A retrospective chart review was carried out on 344 patients with systemic sclerosis (SSc) followed prospectively for the occurrence of pulmonary hypertension (PHT). Seventeen patients (4.9%) were found to have PHT. Eight patients had isolated PHT, while in nine PHT was associated with restrictive lung disease (RLD). The subset with RLD developed PHT earlier, but had longer survival than patients with isolated PHT. Patients with limited scleroderma tend to develop isolated PHT, while in those with diffuse disease PHT is associated with RLD. Irrespective of disease type, PHT in SSc has an extremely poor prognosis with a median survival of 12 months following diagnosis.


Repeat Cardiovascular Risk Assessment after Four Years: Is There Improvement in Risk Prediction?
Framingham risk equations are widely used to predict cardiovascular disease based on health information from a single time point. Little is known regarding use of information from repeat risk assessments and temporal change in estimated cardiovascular risk for prediction of future cardiovascular events. This study was aimed to compare the discrimination and risk reclassification of approaches using estimated cardiovascular risk at single and repeat risk assessments. Using data on 12,197 individuals enrolled in EPIC-Norfolk cohort, with 12 years of follow-up, we examined rates of cardiovascular events by levels of estimated absolute risk (Framingham risk score) at the first and second health examination four years later. We calculated the area under the receiver operating characteristic curve (aROC) and risk reclassification, comparing approaches using information from single and repeat risk assessments (i.e., estimated risk at different time points). The mean Framingham risk score increased from 15.5% to 17.5% over a mean of 3.7 years from the first to second health examination. Individuals with high estimated risk (≥20%) at both health examinations had considerably higher rates of cardiovascular events than those who remained in the lowest risk category (<10%) in both health examinations (34.0 [95%CI 31.7-36.6] and 2.7 [2.2-3.3] per 1,000 person-years respectively). Using information from the most up-to-date risk assessment resulted in a small non-significant change in risk classification over the previous risk assessment (net reclassification improvement of -4.8%, p>0.05). Using information from both risk assessments slightly improved discrimination compared to information from a single risk assessment (aROC 0.76 and 0.75 respectively, p<0.001). Using information from repeat risk assessments over a period of four years modestly improved prediction, compared to using data from a single risk assessment. However, this approach did not improve risk classification.


[(N-AEPz)ZnCl4]Cl: A "Green" Metal Halide Showing Highly Efficient Bluish-White-Light Emission.
Benefiting from their structural flexibility and solution processability, organic-inorganic metal halide hybrids with efficient white-light emission present a great promise for solid-state lighting and display applications. However, most of these reported high-performance single-component white-light materials contain lead. Herein, we report a "green" organic zinc halide, [(N-AEPz)ZnCl4]Cl (1; N-AEPz = N-aminoethylpiperazine), exhibiting prominent bluish-white-light emission with a photoluminescence quantum efficiency as high as 11.52%. Such a value is among the highest in the reported metal halide white-light emitters. Mechanism studies disclose that the broad-band emission is ascribed to the synergistic work of organic salts and inorganic clusters. This work would incent research on single-component white-light materials for next-generation display and lighting technologies.


HEATED TOBACCO PRODUCTS: WE STILL NEED TO KNOW A BIT MORE.
The aim: This research aims to analyze the challenges we came across due to the rapid spread among the population (including young people) of tobacco heating devices. Materials and methods: Analysis of 20 literature sources containing information about tobacco heating systems was performed. The search for literary sources was carried out in two main scientific databases: Scopus and PubMed. The review included original articles, research, and official recommendations from medical associations. Conclusions: Tobacco heaters reduce harmful substances in the inhaled air compared to conventional tobacco cigarettes, but these new devices provide effective nicotine absorption, which prolongs a person's nicotine dependence and prevents smoking cessation. The main problem we face due to the rapid spreading of these devices - potentially tobacco heating systems can pose health risks and further research on such risks, especially long - term, are needed. Tobacco heating devices, regardless of their manufacturer and design, should be subject to restrictions similar to traditional cigarettes.


The Impact of Complementary and Alternative Medicine on Insomnia: A Systematic Review.
Insomnia is characterized by difficulty in maintaining sleep and early morning awakenings. Although pharmacotherapies and psychological interventions remain essential for conventional treatment, motivational factors and interest in using complementary and alternative therapies for insomnia have developed over the last two decades. This review aims to comprehensively explore the effects of complementary and alternative medicine (CAM) on improving sleep quality to guide evidence-based clinical decision-making and inform future research. Several electronic databases such as MEDLINE, PubMed, Scopus, EMBASE, Clinical key, Cochrane, and Research gate were explored to search the relevant articles. For the systematic review, CAM studies were classified under "manual practices," "natural practices," and "mind-body practices." A total of 35 clinical trials were selected for inclusion in the systematic review, comprising adult samples. The systematic review revealed 11 RCTs with manual practice, 12 with mind-body practice, and 12 with natural medicine practice. The methodological quality of the RCTs was measured using the modified Jadad scale, a scientific quality index of ≥ 5/10 (on the augmented Jadad scale). Effect sizes (Cohen's d) were calculated and reported in all placebo-controlled studies with the available data. Regardless of systematic reviews, and randomized controlled trials on CAM, acupuncture, acupressure, herbal medicine, yoga, and tai chi, for insomnia, most of the RCTs did not agree with the findings. Further RCT for insomnia should be developed by considering the current advanced studies in the field of CAM.


[Neurotic development in the clinical picture of stuttering].
On the basis of a clinical study of neurotic development in 79 patients suffering from stammering, the authors present a psychopathological analysis of the polymorphic picture of the disease with stable neurotic and pathocharacterological disturbances and with the presence of peculiar superworship formations. Five clinical variants of the neurotic development in stammering have been identified: astheno-depressive, sensitive, superworshiphypochondriac, obsessive-phobic and hysterical. The formation of the neurotic development is considered in the ontogenetic aspect. The authors analyze a complex interrelationship of constitutional, evolutional-biological and psychogenic factors.


Reactive convective-dissolution in a porous medium: stability and nonlinear dynamics.
We investigate the effects of a dissolution reaction, A(aq) + B(s) → C(aq), on the gravitational instability and nonlinear dynamic behaviour of a diffusive boundary layer in a porous medium. Our linear stability and numerical results reveal that, unexpectedly, even when the density contribution of the soluble product C is smaller than that of the dissolved solute A, the chemical reaction can destabilize the layer and accelerate the onset of convection. However, for a very light product, the reaction stabilizes the layer. We show that these widely disparate characteristics of the reactive-diffusive layer are outcomes of the nonlinear competition between two reaction effects, the destabilizing sharpening of the solute concentration gradient and associated increase in the solute diffusive flux, and the stabilizing replacement of the solute by a less dense product near the interface.


Radiofrequency Ablation of Hepatic Tumor: Subjective Assessment of the Perilesional Vascular Network on Contrast-Enhanced Computed Tomography Before and After Ablation Can Reliably Predict the Risk of Local Recurrence.
To determine whether simple, subjective analysis of the perilesional vascular network can predict the risk of local recurrence after radiofrequency ablation (RFA) of liver malignancies on contrast-enhanced computed tomography (CECT). Contrast-enhanced computed tomography's 103 patients (59 men and 44 women; mean age, 63 years (range, 31-84 years) with 134 lesions who underwent RFA between 2000 and 2010 were retrospectively analyzed. The primary tumors include colorectal carcinoma (58 patients), hepatocellular carcinoma (n = 13), breast carcinoma (n = 8), neuroendocrine tumor (n = 5), and others (n = 19). Three blinded radiologists independently reviewed the CECT (a triple phase liver protocol for hypervascular tumors and a single phase for the hypovascular tumors) before and 6 weeks after RFA and subjectively estimated the width of the ablative margin on a 3-point scale (optimal, 1; suboptimal, 2; and residual tumor, 3). Local recurrence was determined on follow-up CECT. The consensus score was 1 in 94, 2 in 28, and 3 in 12 lesions. κ among readers was 0.75. Local recurrence occurred in 3 lesions with a score of 1 and 12 lesions with a score of 2. The consensus score was a significant univariate predictor of local recurrence. Subjective estimation of the width of ablative margin can reliably predict the risk of local recurrence.


[Mid-third femoral shaft fracture in a patient with hypophosphatemic rickets treated with a locking centromedullary nail].
Residual deformities of hypophosphatemic rickets can be approached with a corrective osteotomy and fixation with a centromedullary nail, external fixators, Ilizarov devices, Kirschner's nails, cast devices, and plates, including epiphysiodesis. These methods may be used in case of fracture. The purpose of this work is to discuss the management of a 16-year-old patient with X-linked hypophosphatemic rickets at the end-stage of growth, who presented with a shaft fracture of the right femur, treated with alignment osteotomy and fixation, and alignment osteotomy of the contralateral femur in a single surgical stage. The patient currently has signs of delayed healing. The main complications of surgical treatment include recurrence of deformity and delayed healing, both of which, until now, can only be addressed by acting on the calcium and phosphorus metabolism. The patients with fractures caused by medium-impact mechanisms should undergo multidisciplinary management and the best implant for each case must be selected individually.


Morningness-Eveningness and Physical Activity in Adolescent Girls: Menarche as a Transition Point.
This study identified trajectories of morningness-eveningness (M-E) and physical activity when chronological (i.e., time since birth) versus gynecological (i.e., time since menarche) age is used to indicate maturation. Piecewise models were fit for girls (N = 262, ages 11-19) using chronological or gynecological age as the time metric. Girls stayed up later (i.e., eveningness) as they approach menarche. After menarche no change in M-E was observed. In contrast, no change in M-E was detected with chronological age. No change in physical activity was observed before menarche, and physical activity declined after menarche. With chronological age, physical activity declined as girls got older. Gynecological age may be more appropriate than chronological age as a metric for understanding changes in M-E and physical activity.


Radiopharmaceuticals for the visualization of infectious and inflammatory lesions.
Many radiopharmaceuticals have been introduced for the scintigraphic demonstration of infectious and inflammatory lesions and some of them are currently in clinical use. They can be classified into two major categories according to their specificity. Specific radiopharmaceuticals include in vitro labeled leukocytes, radio-labelled monoclonal antibodies, and receptor specific small proteins and peptides. Nonspecific radiopharmaceuticals include radiolabelled nanocolloids, liposomes, macromolecules such as human immunoglobulin, dextran and human serum albumin, various small molecules and ions. In this review article radiopharmaceuticals in their respective groups are discussed as to the efficacy, and other parameters such as the physical characteristics of the radionuclides used, radiochemistry involved, availability, cost and biodistribution, emphasizing recent developments.


Neurocranial osteology and neuroanatomy of a late Cretaceous titanosaurian sauropod from Spain (Ampelosaurus sp.).
Titanosaurians were a flourishing group of sauropod dinosaurs during Cretaceous times. Fossils of titanosaurians have been found on all continents and their remains are abundant in a number of Late Cretaceous sites. Nonetheless, the cranial anatomy of titanosaurians is still very poorly known. The Spanish latest Cretaceous locality of "Lo Hueco" yielded a relatively well preserved, titanosaurian braincase, which shares a number of phylogenetically restricted characters with Ampelosaurus atacis from France such as a flat occipital region. However, it appears to differ from A. atacis in some traits such as the greater degree of dorsoventral compression and the presence of proatlas facets. The specimen is, therefore, provisionally identified as Ampelosaurus sp. It was CT scanned, and 3D renderings of the cranial endocast and inner-ear system were generated. Our investigation highlights that, although titanosaurs were derived sauropods with a successful evolutionary history, they present a remarkably modest level of paleoneurological organization. Compared with the condition in the basal titanosauriform Giraffatitan brancai, the labyrinth of Ampelosaurus sp. shows a reduced morphology. The latter feature is possibly related to a restricted range of head-turning movements.


Highly Anisotropic in-Plane Excitons in Atomically Thin and Bulklike 1T'-ReSe2.
Atomically thin materials such as graphene or MoS2 are of high in-plane symmetry. Crystals with reduced symmetry hold the promise for novel optoelectronic devices based on their anisotropy in current flow or light polarization. Here, we present polarization-resolved optical transmission and photoluminescence spectroscopy of excitons in 1T'-ReSe2. On reducing the crystal thickness from bulk to a monolayer, we observe a strong blue shift of the optical band gap from 1.37 to 1.50 eV. The excitons are strongly polarized with dipole vectors along different crystal directions, which persist from bulk down to monolayer thickness. The experimental results are well reproduced by ab initio calculations based on the GW-BSE approach within LDA+GdW approximation. The excitons have high binding energies of 860 meV for the monolayer and 120 meV for bulk. They are strongly confined within a single layer even for the bulk crystal. In addition, we find in our calculations a direct band gap in 1T'-ReSe2 regardless of crystal thickness, indicating weak interlayer coupling effects on the band gap characteristics. Our results pave the way for polarization-sensitive applications, such as optical logic circuits operating in the infrared spectral region.


Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells.
Activation of Notch-1 is known to be associated with the development and progression of human malignancies including pancreatic cancer. Emerging evidence suggest that the acquisition of epithelial-mesenchymal transition (EMT) phenotype and induction of cancer stem cell (CSC) or cancer stem-like cell phenotype are interrelated and contributes to tumor recurrence and drug resistance. The molecular mechanism(s) by which Notch-1 contributes to the acquisition of EMT phenotype and CSC self-renewal capacity has not been fully elucidated. Here we show that forced over-expression of Notch-1 leads to increased cell growth, clonogenicity, migration and invasion of AsPC-1 cells. Moreover, over-expression of Notch-1 led to the induction of EMT phenotype by activation of mesenchymal cell markers such as ZEB1, CD44, EpCAM, and Hes-1. Here we also report, for the first time, that over-expression of Notch-1 leads to increased expression of miR-21, and decreased expression of miR-200b, miR-200c, let-7a, let-7b, and let-7c. Re-expression of miR-200b led to decreased expression of ZEB1, and vimentin, and increased expression of E-cadherin. Over-expression of Notch-1 also increased the formation of pancreatospheres consistent with expression of CSC surface markers CD44 and EpCAM. Finally, we found that genistein, a known natural anti-tumor agent inhibited cell growth, clonogenicity, migration, invasion, EMT phenotype, formation of pancreatospheres and expression of CD44 and EpCAM. These results suggest that the activation of Notch-1 signaling contributes to the acquisition of EMT phenotype, which is in part mediated through the regulation of miR-200b and CSC self-renewal capacity, and these processes could be attenuated by genistein treatment.


Electrified Au nanoparticle sponges with controlled hydrophilic/hydrophobic properties.
Molecularly imprinted Au nanoparticle (NP) composites for the selective binding of the electron acceptors N,N'-dimethyl-4,4'-bipyridinium, MV(2+) (1), or bis-N-methylpyridinium-4,4'-ethylene, BPE(2+) (2), are prepared by the electropolymerization of thioaniline-functionalized Au NPs in the presence of the electron acceptor molecules and the subsequent rinsing off of the imprint substrates. The electrochemical oxidation of the π-donor bisaniline units bridging the Au NPs yields the quinoid electron acceptor bridges, which are re-reduced to the bisaniline state. By the cyclic oxidation and reduction of the bridging units, they are reversibly switched between the π-acceptor and the π-donor states, thus allowing the electrochemically triggered uptake and release of the electron acceptors (1 or 2) to and from the imprinted sites. While the electron acceptors 1 or 2 bind to the imprinted sites via donor-acceptor interactions, these substrates are released from the Au NP matrices upon the oxidation of the bridges to the quinoid state. The electrochemically switched wettability of the imprinted composites is demonstrated upon the reversible uptake, or release, of the substrates to and from the matrices. While the association of 1 or 2 to the respectively imprinted composites generates hydrophilic surfaces (θ = 30 and 41°, respectively), the release of the substrates from the matrices yields surfaces of enhanced hydrophobicity (θ = 60 and 55°, respectively). The electrochemically switched wettability is selective to the imprinted substrates and is amplified in the presence of the imprinted matrices as compared to the non-imprinted composites. The association of MV(2+) or BPE(2+) to the imprinted sites is further electrochemically characterized.


Net effects of nitrogen fertilization on the nutritive value and digestibility of oat forages.
Applications of soil amendments containing N are part of routine forage-management strategies for grasses, with a primary goal of increasing forage yield. However, the effects of N fertilization on forage nutritive value, estimates of energy density, and in vitro dry matter or neutral detergent fiber disappearance sometimes have been erratic or inconsistent. Our objectives were to evaluate the effects of N fertilization on the nutritive value of a single cultivar (ForagePlus, Kratz Farms, Slinger, WI) of fall-grown oat fertilized at planting with 20, 40, 60, 80, or 100 kg of N/ha of urea or 2 rates of dairy slurry (42,300 or 84,600 L/ha). Nitrogen fertilization exhibited consistent effects on fiber components; forages fertilized with urea or dairy slurry had greater concentrations of fiber components compared with those harvested from unfertilized check plots (0 kg of N/ha), and fiber concentrations increased linearly with urea fertilization rate. In contrast, concentrations of water-soluble carbohydrates were greatest for unfertilized forages (21.2%), but declined linearly with urea fertilization, exhibiting a minimum of 13.5% at the 80 kg of N/ha urea application rate. Similarly, nonfiber carbohydrates also declined linearly, from 34.8% for unfertilized check plots to a minimum of 24.6% at the 80 kg of N/ha urea application rate. Fertilization with urea resulted in consistent linear increases in crude protein (CP), neutral detergent soluble CP, neutral detergent insoluble CP, and acid detergent insoluble CP; however, the partitioning of CP on the basis of association with specific fiber fractions could not be related to N fertilization when concentrations were expressed on a percentage of CP basis. The summative calculation of energy, expressed as total digestible nutrients was closely related to N fertilization rate during both the 2013 (y = -0.038x + 72.2; R2 = 0.961) and 2014 (y = -0.040x + 69.2; R2 = 0.771) production years. Following 30- or 48-h incubations in buffered rumen fluid, in vitro dry matter disappearance was greater for unfertilized forages compared with those fertilized with either urea or dairy slurry, and disappearance declined linearly with urea fertilization rate; however, these responses were not detected for neutral detergent fiber disappearance. Overall, the forage nutritive value of fall-grown oat declined mildly in response to N fertilization, but these responses were not nearly strong enough to offset the advantages obtained by improved forage yields.


Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells.
In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.


Terminating transient chaos in spatially extended systems.
In many real-life systems, transient chaotic dynamics plays a major role. For instance, the chaotic spiral or scroll wave dynamics of electrical excitation waves during life-threatening cardiac arrhythmias can terminate by itself. Epileptic seizures have recently been related to the collapse of transient chimera states. Controlling chaotic transients, either by maintaining the chaotic dynamics or by terminating it as quickly as possible, is often desired and sometimes even vital (as in the case of cardiac arrhythmias). We discuss in this study that the difference of the underlying structures in state space between a chaotic attractor (persistent chaos) and a chaotic saddle (transient chaos) may have significant implications for efficient control strategies in real life systems. In particular, we demonstrate that in the latter case, chaotic dynamics in spatially extended systems can be terminated via a relatively low number of (spatially and temporally) localized perturbations. We demonstrate as a proof of principle that control and targeting of high-dimensional systems exhibiting transient chaos can be achieved with exceptionally small interactions with the system. This insight may impact future control strategies in real-life systems like cardiac arrhythmias.


Best linear unbiased estimators for properties of digitized straight lines.
This paper considers the problem of measuring properties of digitized straight lines from the viewpoint of measurement methodology. The measurement and estimation process is described in detail, revealing the importance of a step called ``characterization'' which was not recognized explicitly before. Using this new concept, BLUE (Best Linear Unbiased) estimators are found. These are calculated for various properties of digitized straight lines, and are briefly compared to previous work.


Event-related potentials to intranasal trigeminal stimuli change in relation to stimulus concentration and stimulus duration.
Few data are available on the relation of EEG-derived trigeminal event-related potentials (ERPs) to stimulus duration or stimulus concentration. Thus, the aim of this study was to analyze the relation between ERP components and both stimulus duration and stimulus concentration. Twenty healthy young subjects participated. Trigeminal ERPs were recorded after stimulation with CO(2). Five concentrations (45 to 65% volume per volume CO(2)) and five stimulus durations (100 to 300 msec) were used. Trigeminal ERPs were quantified in terms of amplitudes and latencies of its major peaks N(410) (termed N1) and P(622) (termed P3). The relation between stimulus duration, concentration, and amplitudes or latencies of trigeminal ERP components could be described as a model of power, following the formula p = b + k.I g1.D(g2). A linear relationship was found between stimulus concentration, amplitude N1, and amplitude P3, and between stimulus duration and amplitude P3 respectively. Furthermore, a linear relationship was seen between intensity ratings, and stimulus duration and concentration. These data confirm that the different ERP components encode different stimulus characteristics. Specifically, later components of the trigeminal ERP encode not only stimulus concentration but, other than earlier ERP components, also encode stimulus duration. Thus, they reflect the integration of stimuli over relatively long periods of time.


Arabidopsis thaliana transgenics overexpressing IBR3 show enhanced susceptibility to the bacterium Pseudomonas syringae.
The gene, indole-3-butyric acid (IBA)-RESPONSE (IBR) 3, is thought to participate in peroxisomal β-oxidation of IBA to indole-3-acetic acid. Here we show that IBR3 may also play a role in Arabidopsis thaliana defence response to microbial pathogens. IBR3 is up-regulated during infection by virulent Pseudomonas syringae pv. tomato (Pst) DC3000 bacteria. Although mutant ibr3-4 did not show a pathogen phenotype, lines overexpressing IBR3 demonstrated enhanced susceptibility to Pst DC3000. Increased susceptibility phenotypes of IBR3 overexpressors were correlated with defective SA defence signalling and impairment of pattern-triggered immunity (PTI) activation. Notably, reactive oxygen species production was reduced in IBR3 overexpressors after treatment with the microbe-associated molecular patterns flg22 and efl26. Later PTI responses, such as accumulation of FRK1 transcripts and callose deposition were also reduced in transgenics overexpressing IBR3 after inoculation with the Type III secretion system deficient bacterial mutant Pst DC3000 hrcC or treatment with flg22 or elf26. Importantly, overexpression of IBR3 did not affect indole-3-acetic acid content or auxin-responsive gene expression. These results suggest a novel role for IBR3 in A. thaliana defence response against bacterial pathogens.


The use of percutaneous implants for the prosthetic rehabilitation of orbital defects in irradiated cancer patients: a report of clinical outcomes and complications.
This retrospective study evaluated the use of percutaneous craniofacial implants for the prosthetic rehabilitation of patients with a history of orbital exenteration and irradiation for oncologic tumors of the head and neck. A total of 24 implants were placed in six patients. All implants were determined to be osseointegrated at the time of uncovering. Three implants were subsequently resubmerged beneath the soft tissue because of positional interferences with prosthesis fabrication. The remaining 21 implants were ultimately used to retain six orbital prostheses. Two implants failed to maintain osseointegration during the follow-up period and were subsequently removed without complications. This represents an overall integration success rate of 90.5% over a mean follow-up period of 32.8 months (range = 11 to 68 months). The significance of these findings and their relationship to comparable reports in the literature are discussed.


UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy.
The corticotropin-releasing hormone (CRH) family of peptides, including urocortin (UCN) 1, 2 and 3, are established hypothalamic neuroendocrine peptides, regulating the physiological and behaviour responses to stress indirectly, via the hypothalamic-pituitary-adrenal (HPA) axis. More recently, these peptides have been implicated in diverse roles in peripheral organs through direct signalling, including in placental and pancreatic islet physiology. CRH has been shown to stimulate insulin release through activation of its cognate receptors, CRH receptor 1 (CRHR1) and 2. However, the physiological significance of this is unknown. We have previously reported that during mouse pregnancy, expression of CRH peptides increase in mouse placenta suggesting that these peptides may play a role in various biological functions associated with pregnancy, particularly the pancreatic islet adaptations that occur in the pregnant state to compensate for the physiological increase in maternal insulin resistance. In the current study, we show that mouse pregnancy is associated with increased circulating levels of UCN2 and that when we pharmacologically block endogenous CRHR signalling in pregnant mice, impairment of glucose tolerance is observed. This effect on glucose tolerance was comparable to that displayed with specific CRHR2 blockade and not with specific CRHR1 blockade. No effects on insulin sensitivity or the proliferative capacity of β-cells were detected. Thus, CRHR2 signalling appears to be involved in β-cell adaptive responses to pregnancy in the mouse, with endogenous placental UCN2 being the likely signal mediating this.


BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility.
Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1-/- macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1-/- mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection.


Synthesis of Macrolactams from Macrolactones Using Ru-/Ir-Catalytic System under Neutral Conditions.
Herein, we report the Ru-/Ir-catalyzed synthesis of valuable macrolactams from macrolactones and esters. The ring-opening of the macrolactones was efficaciously facilitated by the Ru catalyst to generate 32 amides in the first step. In the second step, intramolecular N-alkylative ring closure of amides with alcohols was succeeded by Ir catalyst to provide a series of 22 macrolactams and gave water as a byproduct. Moreover, this approach proceeded under neutral conditions and avoided the use of external additives.


Genome-wide association analysis of body conformation traits in Mexican Holstein cattle using a mix of sampled and imputed SNP genotypes.
In arid and semi-arid zones, animal health and production are closely correlated with body conformation traits. These selected traits, in turn, allow livestock to adapt unfavorable soil and environmental conditions. The primary objective of this study was to perform a genome-wide association analysis for a set of sampled and imputed SNPs with 16 conformation traits in a population of Holstein cows from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was performed as a low-cost optimization strategy. Results show eight SNPs associated with two conformation traits. The Udder Depth trait resulted in seven associated SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield, Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body Depth trait resulted in one associated SNP from chromosome 2, although no QTL relation was found. The discovery of genes associated with conformation traits may be indicative of the adaptive selection pressures the Holstein breed has undergone in response to the extreme weather conditions found in the northwestern areas of Mexico. Results of this study indicate that traits such as stature and body depth may be used as indicators of cows' potential genetic merits for milk, fat, and protein production.


Both predictability and familiarity facilitate contour integration.
Research has shown that contour detection is impaired in the visual periphery for snake-shaped Gabor contours but not for circular and elliptical contours. This discrepancy in findings could be due to differences in intrinsic shape properties, including shape closure and curvature variation, as well as to differences in stimulus predictability and familiarity. In a detection task using only circular contours, the target shape is both more familiar and more predictable to the observer compared with a detection task in which a different snake-shaped contour is presented on each trial. In this study, we investigated the effects of stimulus familiarity and predictability on contour integration by manipulating and disentangling the familiarity and predictability of snakelike stimuli. We manipulated stimulus familiarity by extensively training observers with one particular snake shape. Predictability was varied by alternating trial blocks with only a single target shape and trial blocks with multiple target shapes. Our results show that both predictability and familiarity facilitated contour integration, which constitutes novel behavioral evidence for the adaptivity of the contour integration mechanism in humans. If familiarity or predictability facilitated contour integration in the periphery specifically, this could explain the discrepant findings obtained with snake contours as compared with circles or ellipses. However, we found that their facilitatory effects did not differ between central and peripheral vision and thus cannot explain that particular discrepancy in the literature.


Cryoelectron-microscopy structure of the enteropathogenic Escherichia coli type III secretion system EspA filament.
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) utilize a macromolecular type III secretion system (T3SS) to inject effector proteins into eukaryotic cells. This apparatus spans the inner and outer bacterial membranes and includes a helical needle protruding into the extracellular space. Thus far observed only in EPEC and EHEC and not found in other pathogenic Gram-negative bacteria that have a T3SS is an additional helical filament made by the EspA protein that forms a long extension to the needle, mediating both attachment to eukaryotic cells and transport of effector proteins through the intestinal mucus layer. Here, we present the structure of the EspA filament from EPEC at 3.4 Å resolution. The structure reveals that the EspA filament is a right-handed 1-start helical assembly with a conserved lumen architecture with respect to the needle to ensure the seamless transport of unfolded cargos en route to the target cell. This functional conservation is despite the fact that there is little apparent overall conservation at the level of sequence or structure with the needle. We also unveil the molecular details of the immunodominant EspA epitope that can now be exploited for the rational design of epitope display systems.


Temporal lobe structures and facial emotion recognition in schizophrenia patients and nonpsychotic relatives.
Temporal lobe abnormalities and emotion recognition deficits are prominent features of schizophrenia and appear related to the diathesis of the disorder. This study investigated whether temporal lobe structural abnormalities were associated with facial emotion recognition deficits in schizophrenia and related to genetic liability for the disorder. Twenty-seven schizophrenia patients, 23 biological family members, and 36 controls participated. Several temporal lobe regions (fusiform, superior temporal, middle temporal, amygdala, and hippocampus) previously associated with face recognition in normative samples and found to be abnormal in schizophrenia were evaluated using volumetric analyses. Participants completed a facial emotion recognition task and an age recognition control task under time-limited and self-paced conditions. Temporal lobe volumes were tested for associations with task performance. Group status explained 23% of the variance in temporal lobe volume. Left fusiform gray matter volume was decreased by 11% in patients and 7% in relatives compared with controls. Schizophrenia patients additionally exhibited smaller hippocampal and middle temporal volumes. Patients were unable to improve facial emotion recognition performance with unlimited time to make a judgment but were able to improve age recognition performance. Patients additionally showed a relationship between reduced temporal lobe gray matter and poor facial emotion recognition. For the middle temporal lobe region, the relationship between greater volume and better task performance was specific to facial emotion recognition and not age recognition. Because schizophrenia patients exhibited a specific deficit in emotion recognition not attributable to a generalized impairment in face perception, impaired emotion recognition may serve as a target for interventions.


Minimally displaced tibial tuberosity avulsion fracture in nine skeletally immature large breed dogs.
The objective of this study was to describe the clinical and radiographic features, as well as the treatment and outcome of minimally displaced tibial-tuberosity-avulsion-fractures (MDTTAF). Signalment, history, diagnostics, therapy, and outcome were recorded. Follow-up was documented as re-examination, radiographic assessment or telephone conversation. Nine large breed dogs that were presented with lameness originating from the proximal tibia were included. All showed signs of pain when pressure was applied to the tibial tuberosity. There was no stifle instability or intra-articular disease. The main feature on mediolateral radiographs was a widened tibial-tuberosity-physis with reactive new bone and loss of edge definition of the epiphyseal and metaphyseal margins. Non-surgical treatment was chosen in eight dogs, and surgery in one dog. Radiographic follow-up showed progressive closure of the tibial-tuberosity-physis and healing. Clinical signs resolved at a median of 28 days (range: 14-120). Minimally displaced tibial-tuberosity-avulsion-fractures should be a differential diagnosis in skeletally immature large breed dogs older than nine months of age with signs of subtle pelvic-limb lameness, and signs of proximal tibial pain, but no evidence of stifle joint disease. Thorough clinical examination and critical review of bilateral radiographs are important to diagnose MDTTAF. The outcome in these cases suggests that the prognosis for MDTTAF is excellent. Age and size of the affected dogs in this study differ from an earlier publication that illustrated more severely displaced tibial tuberosity avulsion fractures, occurring mainly in terriers around five months of age.


Incidence and causes of blindness amongst the rural population.
A survey of blindness was conducted in a few union councils of the districts of Chittagong, Comilla and Noakhali in a population of 1,14,624 and 1,085 cases of blindness (842 adults and 243 children) were detected. The most common cause of blindness in the adults was cataract whereas in the children it was corneal affection. Trauma constituted 26.7% of blindness in the children and 10.2% in the adults. Glaucoma was responsible for 16.3% of blindness in the adults.


Infective endocarditis and mitral prolapse: a comparison with other types of endocarditis.
We compared clinical features, response to therapy, and outcome of infective endocarditis in ten patients with mitral valve prolapse and 23 patients with endocarditis involving other types of left-sided valvular lesions. Signs of endocarditis were more subtle in patients with mitral valve prolapse, and antimicrobial therapy was instituted later in those patients. Nevertheless, nine of ten patients with mitral valve prolapse and endocarditis responded optimally to antimicrobials; only five of 23 patients with other types of endocarditis responded similarly. Four patients with mitral valve prolapse experienced increasing valvular dysfunction during the year after treatment of endocarditis; one died. We conclude that endocarditis in patients with mitral valve prolapse is more responsive to antimicrobial therapy even though recognition of the infection often is delayed. However, mitral valve prolapse endocarditis is not a benign infection, because progressive valvular dysfunction is a frequent sequel.


Study of optimization of an LCD light guide plate with neural network and genetic algorithm.
This paper proposes an optimization method for designing a prism-pattern LCD light guide plate (LGP) using a neural-network optical model and a real-valued genetic algorithm to achieve excellent luminance uniformity in the exiting light. This newly developed method is proposed as a way of solving the complicated optimization work for non-image optics due to the numbers of ray tracing. First, a neural-network optical model is based on a back-propagation neural network. Then the neural-network optical model is incorporated into a real-valued genetic algorithm to optimize the distribution density of the prism pattern. The results show that the 13-point luminance uniformity reaches an outstanding 92.09%.


Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators.
The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.


Gastric cancer: overview of current therapies.
The worldwide results of surgical adjuvant therapy for gastric cancer are reviewed. Studies from Japan suggest that earlier initiation of chemotherapy results in significantly improved survival, even in advanced resectable disease. Sites of cancer recurrence were evaluated. Transperitoneal and lymph node metastases were the major causes of treatment failure. It is suggested that these sites of recurrence be targeted in future surgical adjuvant therapy trials through preoperative, intraoperative, and early postoperative systemic and intraperitoneal therapy to control microscopic residual disease at a time when the tumor burden is the smallest.


Sensitivity of monomeric and dimeric forms of bovine seminal ribonuclease to human placental ribonuclease inhibitor.
We have studied the inhibition of bovine pancreatic RNAase (RNAase A) and bovine seminal RNAase in its native dimeric form (RNAase BS-1) and in monomeric carboxymethylated form (MCM RNAase BS-1) by human placental RNAase inhibitor (RNAase inhibitor) in order to understand the effect of enzyme structure on its response to the inhibitor. Study of the inhibition as a function of inhibitor concentration revealed that RNAase A and MCM RNAase BS-1 were inhibited fully and the inhibitor-sensitivities of the two were comparable. But under identical inhibitor concentrations RNAase BS-1 was found to be virtually insensitive to the inhibitor; at higher (3-10-fold) inhibitor concentrations marginal inhibition of the native enzyme could be observed. When RNAase BS-1 was pretreated with 5 mM-dithiothreitol (DTT) and assayed, it exhibited greater inhibitor-sensitivity, presumably as a result of its partial monomerization on exposure to DTT. This DTT-mediated change in the response of RNAase BS-1 to the inhibitor did not, however, seem to occur either in the assay conditions (which included DTT) or even when the enzyme was pretreated with DTT in the presence of the substrate, suggesting an effect of the substrate on the enzyme behaviour towards the inhibitor. Independently, gel-filtration runs revealed that, although DTT treatment caused monomerization of RNase BS-1, this change did not take place when DTT treatment was carried out in the presence of the substrate. From our observations, we infer that differential inhibitor-sensitivity of the dimeric and monomeric forms of RNAase BS-1, the relative contents of the two forms and the influence of the substrate on them may be important determinants of the net enzyme activity in the presence of the inhibitor.


Synthesis and Characterization of Compounds Based on Carbazole and Sulfone Groups.
Two compounds containing carbazole and sulfone groups with different alkyl chain lengths have been designed and synthesized. The sulfone group has strong absorption characteristics and the alkoxy chain and carbazole group are electron-rich, forming D-δ-A-type symmetrical molecules. The molecules have the characteristics of charge transfer and high thermal stability, and the molecules stack to form a layered staggered stack, reducing the intermolecular π-π interactions. The target compounds also exhibit strong ultraviolet-fluorescent emission in the solid state at room temperature, and they are expected to be good luminescent materials.


Changes in the community structure and activity of betaproteobacterial ammonia-oxidizing sediment bacteria along a freshwater-marine gradient.
To determine whether the distribution of estuarine ammonia-oxidizing bacteria (AOB) was influenced by salinity, the community structure of betaproteobacterial ammonia oxidizers (AOB) was characterized along a salinity gradient in sediments of the Ythan estuary, on the east coast of Scotland, UK, by denaturant gradient gel electrophoresis (DGGE), cloning and sequencing of 16S rRNA gene fragments. Ammonia-oxidizing bacteria communities at sampling sites with strongest marine influence were dominated by Nitrosospira cluster 1-like sequences and those with strongest freshwater influence were dominated by Nitrosomonas oligotropha-like sequences. Nitrosomonas sp. Nm143 was the prevailing sequence type in communities at intermediate brackish sites. Diversity indices of AOB communities were similar at marine- and freshwater-influenced sites and did not indicate lower species diversity at intermediate brackish sites. The presence of sequences highly similar to the halophilic Nitrosomonas marina and the freshwater strain Nitrosomonas oligotropha at identical sampling sites indicates that AOB communities in the estuary are adapted to a range of salinities, while individual strains may be active at different salinities. Ammonia-oxidizing bacteria communities that were dominated by Nitrosospira cluster 1 sequence types, for which no cultured representative exists, were subjected to stable isotope probing (SIP) with 13C-HCO3-, to label the nucleic acids of active autotrophic nitrifiers. Analysis of 13C-associated 16S rRNA gene fragments, following CsCl density centrifugation, by cloning and DGGE indicated sequences highly similar to the AOB Nitrosomonas sp. Nm143 and Nitrosomonas cryotolerans and to the nitrite oxidizer Nitrospira marina. No sequence with similarity to the Nitrosospira cluster 1 clade was recovered during SIP analysis. The potential role of Nitrosospira cluster 1 in autotrophic ammonia oxidation therefore remains uncertain.


Comparison of magnetic resonance arthrography with arthroscopy for imaging of shoulder injuries: retrospective study.
BACKGROUND Arthroscopy is the established 'gold standard' diagnostic investigation for detection of shoulder disorders. We aimed to compare the diagnostic accuracy of arthroscopy with magnetic resonance arthrography (MRA) for detection of shoulder disorders. METHODS Patients who underwent arthroscopy by a single surgeon and preoperative MRA between February 2011 and March 2012 for shoulder instability were identified. MRAs were reported by experienced musculoskeletal radiologists. Labral tears, anterior labral tears, superior labral anterior posterior (SLAP) lesions, posterior labral tears, rotator-cuff tears (RCTs), osteoarthritis, loose bodies and Hill-Sachs lesions were identified. Sensitivity, specificity, positive predictive value and negative predictive value, positive likelihood ratio and negative likelihood ratio were calculated. RESULTS A total of 194 patients were identified. The sensitivity and specificity for anterior labral tears was 0.60 and 0.92, SLAP lesions was 0.75 and 0.81, posterior labral tears was 0.57 and 0.96, any labral tear was 0.87 and 0.76, Hill-Sachs lesions was 0.91 and 0.91, RCTs was 0.71 and 0.86, osteoarthritis was 0.72 and 0.95, and loose bodies was 0.22 and 0.96, respectively. The positive predictive value and negative predictive value for anterior labral tears were 0.88 and 0.71, SLAP lesions was 0.64 and 0.88, posterior labral tears was 0.74 and 0.45, any labral tear was 0.89 and 0.71, Hill-Sachs lesions was 0.66 and 0.98, RCTs was 0.47 and 0.95, osteoarthritis was 0.70 and 0.95, and loose bodies was 0.27 and 0.95, respectively. CONCLUSIONS MRA has high diagnostic accuracy for labral tears and Hill-Sachs lesions, but whether MRA should be the first-line imaging modality is controversial.


Acute endocarditis complicated by left ventricular pseudoaneurysm with acute bloody pericardial effusion: A case report.
Delay in seeking medical attention for high fever and inadequate diagnosis can lead to rapid progression of inflammation and spread to surrounding tissues and organs. Staphylococcus aureus is a common cause of systemic infections, and infectious endocarditis can swiftly become severe; therefore, careful management is required. A 54-year-old woman was admitted to our hospital with high fever and progressive loss of consciousness. Meningitis was suspected, and antibiotic treatment was initiated. Blood culture revealed methicillin-sensitive Staphylococcus aureus. Subsequently, the patient developed hypotension, bradycardia, and cardiac arrest and underwent emergency cardiopulmonary resuscitation. Transesophageal echocardiography performed during the procedure revealed significant vegetation at the posterior leaflet of the mitral valve, an abscess at the valve annulus, and a pseudoaneurysm of the left ventricular posterior wall. The patient underwent emergency small incision pericardiotomy drainage, and her blood pressure and heart rate stabilized. After pericardial drainage, acute renal failure, fulminant hepatitis, and disruption of coagulation function were observed, and she was treated with plasma exchange therapy and intravenous immunoglobulin. Resection of the huge vegetation, debridement, patch closure of the ventricular perforation, and mitral valve replacement were performed. Surgical findings showed massive vegetation in the posterior leaflet of the mitral valve, an annular abscess in the posterior leaflet of the mitral valve connected to the left ventricular posterior wall, and a pseudoaneurysm. Postoperatively, her pseudoaneurysm resolved and her cardiac function stabilized, while circulatory failure due to bacteremia progressed, and she gradually developed acidosis and unstable blood pressure. Plasma exchange and continuous hemodiafiltration were continued; however, she died of progressive multiorgan failure. Staphylococcus aureus bacteremia can cause fatal complications. Even when symptoms of meningitis are suspected, it is essential to examine the patient for endocarditis. Delayed diagnosis can lead to fatal endocarditis-related complications.


Towards an understanding of chronic pain mechanisms: the use of psychologic tests and a refined differential spinal block.
Forty patients with chronic pain below the waist level were evaluated in a multidisciplinary pain clinic using a refined differential spinal block (DSB) technique. The refinements consisted of verbal instructions to prevent biasing the patients, coupled with a thorough evaluation of verbal and physiologic responses to the block. When demographic and psychologic data were assessed according to pain mechanisms, a pattern of patient groups emerged along a chronic pain continuum. Stress, anxiety, depression, and hysteria, as well as the neurophysiologic and demographic factors, modified the responses to the block. Long-term follow-up of these patients, including repeat DSB procedures and confirmatory anatomic blocks of sympathetic and somatic nerves, validated these impressions. The findings indicate a link between pain mechanisms and psychosocial factors that may directly influence responses to DSB.


A comparison of newer tests for the diagnosis of onchocerciasis.
Samples of human serum, skin and urine, collected in Cameroon, were used to assess the value of some newer methods for the diagnosis of onchocerciasis. Parasite DNA was detected in skin snips and urine by PCR, and parasite antigen was detected in serum and urine by immunoblotting. Serum concentrations of IgG4 antibodies reacting with recombinant Onchocerca volvulus antigens (OC3.6 and OC9.3) were also measured, using an ELISA. The PCR-based tests of skin snips and the serological tests for antigen and antibody tests showed higher sensitivities (90%-100%) than the urine PCR (14%) or the urine antigen test (68%). Although antibody detection is much easier to perform than tests based on PCR or antigen detection, the latter have an advantage in that they are only positive in people with current infections. Thus, antibody testing may be more useful for screening populations for infection or exposure to O. volvulus, whereas PCR and antigen testing are potentially more useful for diagnosis of infections in individuals and for monitoring the success of therapy.


Echocardiographic RV-E/e' for predicting right atrial pressure: a review.
Right atrial pressure (RAP) is a key cardiac parameter of diagnostic and prognostic significance, yet current two-dimensional echocardiographic methods are inadequate for the accurate estimation of this haemodynamic marker. Right-heart trans-tricuspid Doppler and tissue Doppler echocardiographic techniques can be combined to calculate the right ventricular (RV) E/e' ratio - a reflection of RV filling pressure which is a surrogate of RAP. A systematic search was undertaken which found seventeen articles that compared invasively measured RAP with RV-E/e' estimated RAP. Results commonly concerned pulmonary hypertension or advanced heart failure/transplantation populations. Reported receiver operating characteristic analyses showed reasonable diagnostic ability of RV-E/e' for estimating RAP in patients with coronary artery disease and RV systolic dysfunction. The diagnostic ability of RV-E/e' was generally poor in studies of paediatrics, heart failure and mitral stenosis, whilst results were equivocal in other diseases. Bland-Altman analyses showed good accuracy but poor precision of RV-E/e' for estimating RAP, but were limited by only being reported in seven out of seventeen articles. This suggests that RV-E/e' may be useful at a population level but not at an individual level for clinical decision making. Very little evidence was found about how atrial fibrillation may affect the estimation of RAP from RV-E/e', nor about the independent prognostic ability of RV-E/e' . Recommended areas for future research concerning RV-E/e' include; non-sinus rhythm, valvular heart disease, short and long term prognostic ability, and validation over a wide range of RAP.


The results of thoracoscopic surgery for primary spontaneous pneumothorax.
To review our experience of video-assisted thoracoscopic surgery for the treatment of primary spontaneous pneumothorax. Longitudinal cohort study following up consecutive patients for 3 to 4.3 years. Thoracic Surgery Department, Chest Diseases Hospital, Kuwait. Seventy-two consecutive patients undergoing thoracoscopy for primary spontaneous pneumothorax from January 1994 to June 1996. The mean age of the patients was 25 years (range, 15 to 40 years), and 67 were men (93%). All patients were successfully treated using video-assisted thoracoscopic technique. Recurrent pneumothorax was the most frequent indication for surgery, occurring in 49 patients. The most common method of management was stapling of an identified bleb, which was done in 56 cases. Pleurodesis was achieved by gauze abrasion (n = 39) and apical pleurectomy (n = 33). Postoperative prolonged air leak occurred in five patients (6.9%). There were no deaths attributable to the procedure. The mean (+/-SD) postoperative hospital stay was 4 +/- 2 days. Mean follow-up is 42 months (range, 36 to 54 months) for all patients. Pneumothorax recurred in four patients (5.5%) in whom pleural abrasion was done. The recurrences occurred in the first year of follow-up, three required a reoperation, and one healed by rest without pleural drainage. Video-assisted thoracoscopic surgery is a safe procedure in the treatment of primary spontaneous pneumothorax. Apical pleurectomy is a more effective way of producing pleural symphysis. Long-term follow-up did not increase the rate of recurrence.


Clinical impact of women with gestational diabetes mellitus by the new consensus criteria: two year experience in a single institution in Japan.
There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values (2/3-AV) needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P < 0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists.


Novel insights into the Thaumarchaeota in the deepest oceans: their metabolism and potential adaptation mechanisms.
Marine Group I (MGI) Thaumarchaeota, which play key roles in the global biogeochemical cycling of nitrogen and carbon (ammonia oxidizers), thrive in the aphotic deep sea with massive populations. Recent studies have revealed that MGI Thaumarchaeota were present in the deepest part of oceans-the hadal zone (depth > 6000 m, consisting almost entirely of trenches), with the predominant phylotype being distinct from that in the "shallower" deep sea. However, little is known about the metabolism and distribution of these ammonia oxidizers in the hadal water. In this study, metagenomic data were obtained from 0-10,500 m deep seawater samples from the Mariana Trench. The distribution patterns of Thaumarchaeota derived from metagenomics and 16S rRNA gene sequencing were in line with that reported in previous studies: abundance of Thaumarchaeota peaked in bathypelagic zone (depth 1000-4000 m) and the predominant clade shifted in the hadal zone. Several metagenome-assembled thaumarchaeotal genomes were recovered, including a near-complete one representing the dominant hadal phylotype of MGI. Using comparative genomics, we predict that unexpected genes involved in bioenergetics, including two distinct ATP synthase genes (predicted to be coupled with H+ and Na+ respectively), and genes horizontally transferred from other extremophiles, such as those encoding putative di-myo-inositol-phosphate (DIP) synthases, might significantly contribute to the success of this hadal clade under the extreme condition. We also found that hadal MGI have the genetic potential to import a far higher range of organic compounds than their shallower water counterparts. Despite this trait, hadal MDI ammonia oxidation and carbon fixation genes are highly transcribed providing evidence they are likely autotrophic, contributing to the primary production in the aphotic deep sea. Our study reveals potentially novel adaptation mechanisms of deep-sea thaumarchaeotal clades and suggests key functions of deep-sea Thaumarchaeota in carbon and nitrogen cycling. Video Abstract.


Image-quality assessment method for digital phase-contrast imaging based on two-dimensional power spectral analysis.
With use of the phase shift of X-rays that occurs when they pass through an object, phase-contrast imaging (herein referred to as "phase imaging") can produce images different from those of conventional contact imaging (herein referred to as "conventional imaging"). For this reason, assessment of the image quality based on noise-equivalent quanta (NEQ) and detective quantum efficiency (DQE) which does not include object-based information may not be appropriate for comparison of image quality between phase and conventional images. As an alternative method, we conceived a new image-quality assessment method with images that contain information about an object. First, we constructed images with an object and without an object under the same imaging parameters; then, we obtained two-dimensional power spectra by Fourier transform of those images. Second, we calculated the radial direction distribution function with the power spectra, and the distribution of signal intensity, which we defined as a signal intensity distribution function (SIDF). In this way, differences in image quality were evaluated relatively based on the SIDF of the imaged object. In our study, we first confirmed that phase-imaging evaluation was not appropriate by comparing NEQ and DQE of conventional, magnification, and phase imaging. Further, comparing the image quality of projected plant seeds by employing conventional, magnification, and phase imaging, we found that the phase-imaging method provided a higher image quality regarding edge sharpness than did conventional and magnification imaging. Therefore, based on these results, our image assessment method is considered useful for evaluation of images which include object-based information.


Intestinal Ultrasound to Evaluate Treatment Response During Pregnancy in Patients With Inflammatory Bowel Disease.
Active disease in inflammatory bowel disease patients during pregnancy is associated with poor maternal and fetal outcomes. Objective evaluation of disease activity is a core strategy in IBD, and during pregnancy noninvasive modalities are preferred. We aimed to evaluate feasibility and accuracy of intestinal ultrasound (IUS) to objectify disease activity throughout pregnancy. Pregnant patients with known IBD were included and followed throughout pregnancy for clinical disease activity, with fecal calprotectin (FCP) and with IUS every trimester. Feasibility of IUS was assessed for all colonic segments and terminal ileum (TI). Intestinal ultrasound outcomes to detect active disease and treatment response were compared with clinical scores combined with FCP. In total, 38 patients (22 CD, 16 UC) were included, with 27 patients having serial IUS. Feasibility of IUS decreases significantly in third trimester for TI (first vs third trimester: 91.3% vs 21.7%, P < .0001) and sigmoid (first vs third trimester: 95.6% vs 69.5%, P = .023). Intestinal ultrasound activity showed moderate to strong correlation with clinical activity (r = 0.60, P < .0001) and FCP (r = 0.73, P < .0001). Throughout pregnancy, IUS distinguished active from quiescent disease with 84% sensitivity and 98% specificity according to FCP combined with clinical activity. IUS showed disease activity in >1 segment in 52% of patients and detected treatment response with 80% sensitivity and 92% specificity. IUS is feasible and accurate throughout pregnancy, although visualization of the sigmoid and TI decreases in the third trimester. IUS provides objective information on disease activity, extent, and treatment response, even during second and third trimester, and offers a noninvasive strategy to closely monitor patients during pregnancy.


Work-related road safety: an analysis based on U.K. bus driver performance.
The effects of age and experience on accident involvement for bus drivers were investigated, with special emphasis upon the first years of being an operator, using two methods. First, direct calculations between these variables were undertaken. Thereafter, a variant of the method of quasi-induced exposure (a ratio of culpable versus nonculpable accidents in the population) was used and referred to as the indirect method. These methods yielded fairly similar results, given that the samples used were drawn from the same population but only partly overlapping. It was found that experience had the strongest effect on accidents in the first year of driving, while age had a u-shaped association with accidents, that is, young and old drivers had more accidents, something that was more apparent when experience was held constant. These results show that, for bus drivers, experience is initially more important than age, but after two or three years, the effect is small. Thereafter, age is the more discernible variable, although it is a very weak factor in predicting crash risk.


Time-Dependent Effect of Sciatic Nerve Injury on Rat Plasma Lipidome.
Neuropathic pain is a condition affecting the quality of life of a substantial part of the population, but biomarkers and treatment options are still limited. While this type of pain is caused by nerve damage, in which lipids play key roles, lipidome alterations related to nerve injury remain poorly studied. Here, we assessed blood lipidome alterations in a common animal model, the rat sciatic nerve crush injury. We analyzed alterations in blood lipid abundances between seven rats with nerve injury (NI) and eight control (CL) rats in a time-course experiment. For these rats, abundances of 377 blood lipid species were assessed at three distinct time points: immediately after, two weeks, and five weeks post injury. Although we did not detect significant differences between NI and CL at the first two time points, 106 lipids were significantly altered in NI five weeks post injury. At this time point, we found increased levels of triglycerides (TGs) and lipids containing esterified palmitic acid (16:0) in the blood plasma of NI animals. Lipids containing arachidonic acid (20:4), by contrast, were significantly decreased after injury, aligning with the crucial role of arachidonic acid reported for NI. Taken together, these results indicate delayed systematic alterations in fatty acid metabolism after nerve injury, potentially reflecting nerve tissue restoration dynamics.


Application and Analysis of Bipolar Membrane Electrodialysis for LiOH Production at High Electrolyte Concentrations: Current Scope and Challenges.
The objective of this work was to evaluate obtaining LiOH directly from brines with high LiCl concentrations using bipolar membrane electrodialysis by the analysis of Li+ ion transport phenomena. For this purpose, Neosepta BP and Fumasep FBM bipolar membranes were characterized by linear sweep voltammetry, and the Li+ transport number in cation-exchange membranes was determined. In addition, a laboratory-scale reactor was designed, constructed, and tested to develop experimental LiOH production tests. The selected LiCl concentration range, based on productive process concentrations for Salar de Atacama (Chile), was between 14 and 34 wt%. Concentration and current density effects on LiOH production, current efficiency, and specific electricity consumption were evaluated. The highest current efficiency obtained was 0.77 at initial concentrations of LiOH 0.5 wt% and LiCl 14 wt%. On the other hand, a concentrated LiOH solution (between 3.34 wt% and 4.35 wt%, with a solution purity between 96.0% and 95.4%, respectively) was obtained. The results of this work show the feasibility of LiOH production from concentrated brines by means of bipolar membrane electrodialysis, bringing the implementation of this technology closer to LiOH production on a larger scale. Moreover, being an electrochemical process, this could be driven by Solar PV, taking advantage of the high solar radiation conditions in the Atacama Desert in Chile.


Error in byline.
In the Observation entitled "Paravascular Inner Retinal Defect Associated With High Myopia or Epiretinal Membrane," published online January 22, 2015, in JAMA Ophthalmology (doi:10.1001/jamaophthalmol.2014.5632), the fifth author's name should have been given as Abdallah A. Ellabban, and in the Affiliations and Author Contributions as Ellabban. This article was corrected online.


Long-term follow-up outcomes in a real-world study cohort after percutaneous patent foramen ovale closure.
In recent years, percutaneous closure of a patent foramen ovale (PFO) has gained widespread use. This study is an evaluation of the safety and efficacy of the Figulla and Amplatzer devices for PFO closure, including long-term follow-up results. A total of 305 patients (43.6% male; mean age: 43.25±10.98 years) who underwent percutaneous PFO closure between 2003 and 2019 were enrolled. The Risk of Paradoxical Embolism (RoPE) score was calculated to predict the recurrence risk of cerebrovascular events due to PFO. Transthoracic echocardiography was used during the procedure. The devices were successfully implanted in all patients. The in-hospital periprocedural complications recorded were atrial fibrillation in 1 patient (0.3%), supraventricular tachycardia in 1 patient (0.3%), and femoral hematoma in 3 patients (1%). The procedure time and fluoroscopy time was 21.92±2.93 minutes and 2.19±0.24 minutes, respectively. Recurrent ischemic stroke or transient ischemic attack (TIA) was observed in 7 (2.2%) patients during the median 85.77 months (25th-75th percentile: 10.21-108.00 months) follow-up. The RoPE score was significantly lower in patients with recurrent ischemic cerebral event (stroke or TIA) compared with asymptomatic patients (p<0.001). Kaplan-Meier curve analysis revealed that there was no significant difference between PFO device types (Amplatzer: 2.4% vs. Figulla: 3.3%) in terms of recurrent ischemic cerebral events during follow-up (log-rank; p=0.642). Percutaneous PFO closure was safe, feasible, and effective. Our study confirmed the efficacy and safety of transthoracic echocardiogram guidance during percutaneous closure of PFO, which shortens the procedure time. A lower RoPE score was related to the recurrence risk of ischemic cerebrovascular events.


Development of a dynamic prediction model for unplanned ICU admission and mortality in hospitalized patients.
Frequent assessment of the severity of illness for hospitalized patients is essential in clinical settings to prevent outcomes such as in-hospital mortality and unplanned admission to the intensive care unit (ICU). Classical severity scores have been developed typically using relatively few patient features. Recently, deep learning-based models demonstrated better individualized risk assessments compared to classic risk scores, thanks to the use of aggregated and more heterogeneous data sources for dynamic risk prediction. We investigated to what extent deep learning methods can capture patterns of longitudinal change in health status using time-stamped data from electronic health records. We developed a deep learning model based on embedded text from multiple data sources and recurrent neural networks to predict the risk of the composite outcome of unplanned ICU transfer and in-hospital death. The risk was assessed at regular intervals during the admission for different prediction windows. Input data included medical history, biochemical measurements, and clinical notes from a total of 852,620 patients admitted to non-intensive care units in 12 hospitals in Denmark's Capital Region and Region Zealand during 2011-2016 (with a total of 2,241,849 admissions). We subsequently explained the model using the Shapley algorithm, which provides the contribution of each feature to the model outcome. The best model used all data modalities with an assessment rate of 6 hours, a prediction window of 14 days and an area under the receiver operating characteristic curve of 0.898. The discrimination and calibration obtained with this model make it a viable clinical support tool to detect patients at higher risk of clinical deterioration, providing clinicians insights into both actionable and non-actionable patient features.


Response of pediatric uveitis to tumor necrosis factor-α inhibitors.
To evaluate the outcome of tumor necrosis factor-α inhibition (anti-TNF) for pediatric uveitis. We retrospectively assessed children (age ≤ 18 yrs) with noninfectious uveitis receiving anti-TNF at 5 uveitis centers and 1 pediatric rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at ≥ 2 consecutive ophthalmological examinations ≥ 28 days apart while taking no oral and ≤ 2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses. Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% CI 62%-87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI 51%-76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype among JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75%-80% lower rate of achieving quiescence under anti-TNF, independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis reactivated within 12 months of achieving quiescence in 14% of those continuing anti-TNF (95% CI 6%-31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI 1%-43%). Treatment with anti-TNF was successful and sustained in a majority of children with noninfectious uveitis, and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNF.


Role of CCR2 in macrophage migration into the liver during acetaminophen-induced hepatotoxicity in the mouse.
The biological effects of monocyte chemoattractant protein (MCP) 1 are mediated by binding to C-C chemokine receptor (CCR) 2. In the present studies, we used CCR2 knockout (CCR2-/-) mice to examine the role of MCP-1 in acetaminophen-induced macrophage accumulation in the liver, expression of inflammatory cytokines, and hepatotoxicity. We found that hepatic expression of CCR2 and MCP-1 was increased 10-fold and 20-fold, respectively, 12 to 72 hours after administration of acetaminophen to wild-type mice. Expression of these proteins was localized in centrilobular regions of the liver. Whereas MCP-1 was expressed by both hepatocytes and macrophages, CCR2 was identified in inflammatory macrophages. F4/80 is a marker of mature macrophages expressed in large quantities by Kupffer cells. In wild-type mice, a 75% decrease in F4/80-positive macrophages was observed 24 to 48 hours after administration of acetaminophen. In contrast, expression of macrosialin (CD68), a marker of activated macrophages, increased 2-fold 24 to 72 hours after administration of acetaminophen and was associated with inflammatory cells. Although there was a decrease in the overall severity of inflammation and in the number of macrosialin-positive macrophages 72 hours after administration of acetaminophen in CCR2-/- mice, the number of F4/80-positive cells did not change. Loss of CCR2 was also found to alter acetaminophen-induced expression of tumor necrosis factor alpha, monocyte chemoattractant protein 3, and KC/gro. However, the overall outcome of acetaminophen-induced hepatic injury was not affected. In conclusion, these data indicate that MCP-1 and CCR2 contribute to the recruitment of a subset of activated macrophages into the liver during acetaminophen-induced hepatotoxicity that may be important in resolution of tissue injury.


Low-loss air-core polarization maintaining terahertz fiber.
We propose a low-loss air-core polarization maintaining polymer fiber for terahertz (THz) wave guiding. The periodic arrangement of square holes with round corners in the cladding offers a bandgap effect for mode guiding. Numerical simulations show that the bandgap effect repels the modal power from the absorbent background polymers, resulting in a significant suppression of absorption loss of the polymers by a factor of more than 25. The phase-index birefringence of the proposed THz fiber is in the order of 10(-3).


A Comparative Analysis of Dietary Habits on Sensory Motor Association and Heart Rate Variability during Menstrual Cycle.
Dietary habits can make a big difference on both physical and mental aspects of the body. Menstrual disorder frequently affects the quality of life of adolescent and young adult women. Menstrual cycle irregularities may be associated with psychological stress, and endocrine disturbances. Monitoring of sensory-motor association and cardiovascular activity across the menstrual cycle has not been evaluated with dietary habits. The present study was carried out to bridge the relationship between dietary habits and endogenous sex hormone mediated sensory motor association and heart rate variability (HRV) among young females during different phases of menstrual cycle. The present study was carried out on healthy volunteered 100 female medical students in the age group of 19-25 years with regular menstrual cycle. Group I (n=45) vegetarians, Group II (n=25) eggetarians and Group III (n= 30) non-vegetarians, where n denotes the number of individuals in each group. Sensory-motor association (reaction time) and cardiovascular activity (HRV) was evaluated. We observed among all the dietary habits (vegetarians, eggetarians and non-vegetarians) the reaction time and HRV was comparable in follicular and menstrual phase, however it was significantly altered in luteal phase when compared to follicular and menstrual phase. Moreover, among all the dietary habits, non-vegetarians showed more significant alteration of reaction time and HRV in luteal phase when compared to vegetarians and eggetarians, as well as there was positive correlation between visual and auditory reaction time and negative correlation between LF and HF in luteal phase, among all the dietary habits. We concluded sensorimotor association and regulation of autonomic tone is modified in luteal phase comparable to follicular phase and menstrual phase; however non-vegetarian had showed more significant alterations as compared to eggetarians and vegetarians. These suggest that sympathetic nervous activities are predominant in the luteal phase as compared to follicular phase, and this sympathetic dominance is more among non-vegetarians, which may be due to their higher BMI. The alterations in the balance of ovarian hormones might be responsible for these changes. Long-term intake of vegetarian diets may facilitate vagal regulation of the heart without increasing the sympathetic modulations of the cardiovascular system.