Prospective study of 101 patients with suspected drink spiking.
To evaluate cases of suspected drink spiking presenting to the ED by the prospective collection of standardized relevant historical, clinical and laboratory data. A prospective observational study of 101 patients presenting to metropolitan hospital ED with suspected drink spiking within the previous 12 h. Clinical history, including details surrounding the alleged drink spiking incident, and examination. Blood ethanol concentration measurement, together with the analysis of urine and blood samples for illicit and sedative drugs. Of the 97 alleged drink spiking cases included, there were only 9 plausible cases. We did not identify a single case where a sedative drug was likely to have been illegally placed in a drink in a pub or nightclub. Illicit drugs were detected in 28% of the study group. Ethanol was commonly detected, with the mean number of standard drinks consumed being 7.7 +/- 3.9 SD, and the median blood ethanol concentration at the time of presentation was 0.096% (96 mg/dL). At follow-up there were no major sequelae and no police prosecutions. Thirty five per cent of patients still believed that they had been a victim of drink spiking irrespective of the results. Our study did not reflect the current public perception of drink spiking. Drink spiking with sedative or illicit drugs appears to be rare. If drink spiking does occur, ethanol appears to be the most common agent used. Of greater concern was the frequency of illicit drug use and excessive ethanol consumption within the study population, making it difficult to determine whether a person had truly had a drink spiked.


Sleep apnoea profile in preterm infants recovering from respiratory distress syndrome.
Polygraphic recordings were made on 10 preterm infants recovering from respiratory distress syndrome and 12 healthy preterm control infants at 40, 52, and 64 weeks' conceptual age to study the influence of respiratory distress syndrome on the development of the sleep apnoea profile. Two significant differences were found: infants with respiratory distress syndrome not only had a lower incidence of non-obstructive apnoea and periodic breathing at 40 weeks but also a persistently higher incidence of obstructive and mixed apnoea at 52 and 64 weeks' conceptual age; the latter finding being related to non-rapid eye movement sleep only. While the lower incidence of both types of apnoea at 40 weeks suggests an advanced maturation of respiratory drive, the persistence of obstructive and mixed apnoea related to non-rapid eye movement sleep may reflect the impact of respiratory distress syndrome on airway structures.


Lateropulsion in Right-Sided Stroke: Brain Anatomical Correlates of Severity and Duration.
Lateropulsion (LP) is a profound disorder of postural control that has a significant impact on neurorehabilitation. Knowledge of relevant brain areas could guide decisions on appropriate intervention methods. Although LP severity and duration are highly variable in individuals with LP, imaging studies on LP have not sufficiently considered these aspects. The aim of this study was to investigate the lesion location in individuals after stroke and the correlation with LP duration and severity. A retrospective case-control study using voxel lesion symptom mapping (VLSM) in 74 individuals with right-sided brain lesion (49 with and 25 without LP) was performed to analyze the correlation between lesion location and LP severity. Duration was investigated in a subsample of 22 individuals with LP. LP was diagnosed by means of the Scale for Contraversive Pushing. Individuals with LP showed significantly larger lesion sizes compared with the individuals with no LP. VLSM analysis of LP severity did not reveal statistically significant results. VLSM analysis showed a statistically significant association with longer LP duration for the inferior frontal gyrus, the hippocampus, the inferior parietal gyrus, the supramarginal gyrus, the angular gyrus, the temporal cortex, the sagittal stratum, and the superior longitudinal fasciculus. LP-relevant areas are located in the multisensory network. Areas of the frontoparietal network, which are related to spatial cognition, memory, and attention, were found to be relevant for duration and severity. The findings, especially those regarding duration involving the middle temporal cortex, could explain the better intervention outcomes for methods based more on implicit than on explicit knowledge of verticality.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A433).


Continuous droplet removal upon dropwise condensation of humid air on a hydrophobic micropatterned surface.
Combination of two physical phenomena, capillary pressure gradient and wettability gradient, allows a simple two-step fabrication process that yields a reliable hydrophobic self-cleaning condenser surface. The surface is fabricated with specific microscopic topography and further treatment with a chemically inert low-surface-energy material. This process does not require growth of nanofeatures (nanotubes) or hydrophilic-hydrophobic patterning of the surface. Trapezoidal geometry of the microfeatures facilitates droplet transfer from the Wenzel to the Cassie state and reduces droplet critical diameter. The geometry of the micropatterns enhances local coalescence and directional movement for droplets with diameter much smaller than the radial length of the micropatterns. The hydrophobic self-cleaning micropatterned condenser surface prevents liquid film formation and promotes continuous dropwise condensation cycle. Upon dropwise condensation, droplets follow a designed wettability gradient created with micropatterns from the most hydrophobic to the least hydrophobic end of the surface. The surface has higher condensation efficiency, due to its directional self-cleaning property, than a plain hydrophobic surface. We explain the self-actuated droplet collection mechanism on the condenser surface and demonstrate experimentally the creation of an effective wettability gradient over a 6 mm radial distance. In spite of its fabrication simplicity, the fabricated surface demonstrates self-cleaning property, enhanced condensation performance, and reliability over time. Our work enables creation of a hydrophobic condenser surface with the directional self-cleaning property that can be used for collection of biological (chemical, environmental) aerosol samples or for condensation enhancement.


Prevalent patterns of serotype-specific seroconversion in Mexican children infected with rotavirus.
The level of neutralizing antibodies to rotaviruses belonging to serotypes 1, 3, and 4 was determined in acute- and convalescent-phase sera from 36 Mexican children with rotaviral diarrhea. Most of the infants who seroconverted fell into one of the following three patterns: single seroconversion to serotype 1; seroconversion to serotypes 1 and 4; or seroconversion to all three serotypes tested. The heterotypic neutralizing antibody responses to rotavirus infections are discussed.


Content analysis of the core promoter region of human genes.
We analyzed an extended core promoter regions covering [-70,+60] segment relative to the transcription start site of human promoters contained in the Eukaryotic Promoter Database. The analysis was made by using the Match program ver. 1.9 with an optimized setting and the TRANSFAC Professional database ver. 7.2. This analysis revealed that the most common transcription factor binding site in the examined collection of core promoters appears to be initiator (characterized by GEN_INI), which is expected. The other less obvious sites found were Spz1, E2F-1, ZF5, and C/EBP. The 'cap' site was also in this most common group. Over-representation of these sites relative to the non-promoter background data ranged from 0.3167 to 32.1645. These sites were characterized by being present in more than 60% of promoter sequences. Interestingly, the TATA-box has been found in only 11.63% of all examined promoters. The study is complemented by separate analyses of promoter groups having different GC content. These additional analyses revealed that the most common promoter elements found also include AP-2, CdxA, Pax-2, SRY, STAT1 and STAT5A. It was also observed that a number of promoter elements show strong preference either for the GC-rich or the GC-poor core promoters.


Theoretical investigations on the formation and dehydrogenation reaction pathways of H(NH2BH2)(n)H (n = 1-4) oligomers: importance of dihydrogen interactions.
The H(NH(2)BH(2))(n)H oligomers are possible products from dehydrogenation of ammonia borane (NH(3)BH(3)) and ammonium borohydride (NH(4)BH(4)), which belong to a class of boron-nitrogen-hydrogen (BNH(x)) compounds that are promising materials for chemical hydrogen storage. Understanding the kinetics and reaction pathways of formation of these oligomers and their further dehydrogenation is essential for developing BNH(x)-based hydrogen storage materials. We have performed computational modeling using density functional theory (DFT), ab initio wave function theory, and Car-Parrinello molecular dynamics (CPMD) simulations on the energetics and formation pathways for the H(NH(2)BH(2))(n)H (n = 1-4) oligomers, polyaminoborane (PAB), from NH(3)BH(3) monomers and the subsequent dehydrogenation steps to form polyiminoborane (PIB). Through computational transition state searches and evaluation of the intrinsic reaction coordinates, we have investigated the B-N bond cleavage, the reactions of NH(3)BH(3) molecule with intermediates, dihydrogen release through intra- and intermolecular hydrogen transfer, dehydrocoupling/cyclization of the oligomers, and the dimerization of NH(3)BH(3) molecules. We find that the formation of H(NH(2)BH(2))(n+1)H oligomers occurs first through reactions of the H(NH(2)BH(2))(n)H oligomers with BH(3) followed by reactions with NH(3) and the release of H(2), where the BH(3) and NH(3) intermediates are formed through dissociation of NH(3)BH(3). We also find that the dimerization of the NH(3)BH(3) molecules to form cyclic c-(NH(2)BH(2))(2) is slightly exothermic, with an unexpected transition state that leads to the simultaneous release of two H(2) molecules. The dehydrogenations of the oligomers are also exothermic, typically by less than 10 kcal/(mol of H(2)), with the largest exothermicity for n = 3. The transition state search shows that the one-step direct dehydrocoupling cyclization of the oligomers is not a favored pathway because of high activation barriers. The dihydrogen bonding, in which protic (H(N)) hydrogens interact with hydridic (H(B)) hydrogens, plays a vital role in stabilizing different structures of the reactants, transition states, and products. The dihydrogen interaction (DHI) within the R-BH(2)(eta(2)-H(2)) moiety accounts for both the formation mechanisms of the oligomers and for the dehydrogenation of ammonia borane.


Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor alpha chain expression on activated B cells.
Mice lacking a functional gene for the Oct2 transcriptional activator display several developmental and functional deficiencies in the B lymphocyte lineage. These include defective B cell receptor (BCR) and Toll-like receptor 4 signaling, an absence of B-1 and marginal zone populations, and globally reduced levels of serum immunoglobulin (Ig) in naive and immunized animals. Oct2 was originally identified through its ability to bind to regulatory regions in the Ig loci, but genetic evidence has not supported an essential role for Oct2 in the expression of Ig genes. We describe a new Oct2-mediated role in B cells. Oct2 augments the ability of activated B cells to differentiate to antibody-secreting plasma cells (ASCs) under T cell-dependent conditions through direct regulation of the gene encoding the alpha chain of the interleukin (IL) 5 receptor. Ectopic expression of IL-5Ralpha in oct2-deficient B cells largely restores their ability to differentiate to functional ASCs in vitro but does not correct other phenotypic defects in the mutants, such as the maturation and specialization of peripheral B cells, which must therefore rely on distinct Oct2 target genes. IL-5 augments ASC differentiation in vitro, and we show that IL-5 directly activates the plasma cell differentiation program by enhancing blimp1 expression.


Two new species of Gomphidius from the Western United States and Eastern Siberia.
Study of the genus Gomphidius from recent material from Asia and North America has been carried out using traditional taxonomy combined with molecular systematics. Two new species of Gomphidius (G. borealis and G. pseudoflavipes) are described, one from Eastern Siberia and a second from rarely collected habitats in the Western United States. One taxon has the longest spores reported for the genus and the second species appears to be associated with a Siberian larch.


Treatment of venous malformations by direct injection with ethanol.
Venous malformations (VMs) may be discrete or extensive, and larger lesions may be difficult to remove with surgery. Incompletely removed lesions have a tendency to recur. We report our experience with ethanol ablation of VMs. All 12 patients (seven women; mean age, 37 years) were evaluated with magnetic resonance imaging before treatment. A total of 19 prior surgical excisions had been performed for seven of the patients. Symptoms were present in all 12 patients and included bleeding, pain, swelling, and limitation of exercise. The VMs were present in the lower extremities of seven patients, in the upper extremities of three patients, and in the flank and buttocks in two patients. The 12 patients have undergone 30 injection procedures, with six patients requiring one, three patients requiring two, two patients requiring three, and one patient having undergone 12 treatments. General anesthesia was used in 11 patients. Blood loss was minimal for all procedures, and 28 of the 30 procedures were technically successful. Skin ulceration was seen in approximately half of the treated VMs, all of which healed with local wound care. Focal VMs were injected in six patients and resolved with a single treatment in five patients. Patients were free of symptoms at a mean follow-up of 10 months. Extensive VMs were injected for discrete, symptomatic areas in five patients. These lesions all regressed and were asymptomatic at a mean follow-up of 23 months in all but one patient. However, these lesions required multiple treatments as additional areas became problematic. Ethanol sclerosis is a well-tolerated, safe, and effective adjunct to the management of VMs. Advantages of ethanol injection include the ability to treat a very localized area without an incision. Conversely, extensive lesions may be palliated as symptoms occur.


The effect of deep learning-based lesion segmentation on failure load calculations of metastatic femurs using finite element analysis.
Bone ranks as the third most frequent tissue affected by cancer metastases, following the lung and liver. Bone metastases are often painful and may result in pathological fracture, which is a major cause of morbidity and mortality in cancer patients. To quantify fracture risk, finite element (FE) analysis has shown to be a promising tool, but metastatic lesions are typically not specifically segmented and therefore their mechanical properties may not be represented adequately. Deep learning methods potentially provide the opportunity to automatically segment these lesions and change the mechanical properties more adequately. In this study, our primary focus was to gain insight into the performance of an automatic segmentation algorithm for femoral metastatic lesions using deep learning methods and the subsequent effects on FE outcomes. The aims were to determine the similarity between manual segmentation and automatic segmentation; the differences in predicted failure load between FE models with automatically segmented osteolytic and mixed lesions and the models with CT-based lesion values (the gold standard); and the effect on the BOne Strength (BOS) score (failure load adjusted for body weight) and subsequent fracture risk assessments. From two patient cohorts, a total number of 50 femurs with osteolytic and mixed metastatic lesions were included in this study. The femurs were segmented from CT images and transferred into FE meshes. The material behavior was implemented as non-linear isotropic. These FE models were considered as gold standard (Finite Element no Segmented Lesion: FE-no-SL), whereby the local calcium equivalent density of both femur and metastatic lesion was extracted from CT-values. Lesions in the femur were manually segmented by two biomechanical experts after which final lesion segmentation for each femur was obtained based on consensus of opinions between two observers. Subsequently, a self-configuring variant of the popular deep learning model U-Net known as nnU-Net was used to automatically segment metastatic lesions within the femur. For these models with segmented lesions (Finite Element with Segmented Lesion: FE-with-SL), the calcium equivalent density within the metastatic lesions was set to zero after being segmented by the neural network, simulating absence of load-bearing capacity of these lesions. The models (either with or without automatically segmented lesions) were loaded incrementally in axial direction until failure was simulated. Dice coefficient was used to evaluate the similarity of the manual and automatic segmentation. Mean calcium equivalent density values within the automatically segmented lesions were calculated. Failure loads and patterns were determined. Furthermore, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both groups by comparing the predictions to the occurrence or absence of actual fracture within the patient cohorts. The automatic segmentation algorithm performed in a none-robust manner. Dice coefficients describing the similarity between consented manual and automatic segmentations were relatively low (mean 0.45 ± standard deviation 0.33, median 0.54). Failure load difference between the FE-no-SL and FE-with-SL groups varied from 0 % to 48 % (mean 6.6 %). Correlation analysis of failure loads between the two groups showed a strong relationship (R2 > 0.9). From the 50 cases, four cases showed clear deviations for which models with automatic lesion segmentation (FE-with-SL) showed considerably lower failure loads. In the whole database including osteolytic and mixed lesions, sensitivity and NPV remained the same, but specificity and PPV decreased from 94 % to 83 %, and from 78 % to 54 % respectively from FE-no-SL to FE-with-SL. This study indicates that the nnU-Net yielded none-robust outcomes in femoral lesion segmentation and that other segmentation algorithms should be considered. However, the difference in failure pattern and failure load between FE models with automatically segmented osteolytic and mixed lesions were relatively small in most cases with a few exceptions. On the other hand, the accuracy of fracture risk assessment using the BOS score was lower compared to the FE-no-SL. In conclusion, this study showed that automatic lesion segmentation is a none-solved issue and therefore, quantifying lesion characteristics and the subsequent effect on the fracture risk using deep learning will remain challenging.


Impact of educational posters on the lay knowledge of school teachers regarding emergency management of dental injuries.
The purpose of this study was to investigate the knowledge of school teachers about the emergency management of dental trauma, after an educational poster campaign. A total of 1000 questionnaires were sent to 100 schools in the area where the poster had been distributed. This was compared to another 100 schools (1000 questionnaires) in an area, Where the poster had not been distributed. The questionnaire surveyed demographic data, basic knowledge of emergency management of tooth fracture, luxation and avulsion injuries. A total of 511 questionnaires were returned (25.5%) and analyzed. Results showed differences between the two assessed areas. Teachers, who worked in the area with poster distribution, had better knowledge in handling tooth injuries. For the management of tooth fractures the portion of teachers, who knew the correct handling procedure, was 78.9% (area with poster campaign) vs 72.1% (area with no poster campaign), for the management of tooth luxation it was 87% vs 84% and for the management of tooth avulsion it was 71% vs 54%. In the area with the poster campaign 49% (n = 90 out of 185) of the teachers stated to have gained some knowledge about this topic beforehand. Out of these, 75 teachers (75/90 = 83%), had gained their information from the educational poster. Out of the 75 teachers, who had seen a poster on this topic, 68 (68/75 = 91%) would have managed such an emergency correctly. The present study shows the positive effect of educational poster campaigns. It therefore should encourage professionals in this field to embark on similar projects.


Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.
Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.


Continuity between DSM-5 Section II and Section III personality traits for obsessive-compulsive personality disorder.
Obsessive-compulsive personality disorder (OCPD) is formally operationalized in Section II of the DSM-5 by a heterogeneous collection of 8 categorical criteria. Section III contains an alternative model operationalizing personality disorders via dimensional personality traits and associated impairment. The extent to which the personality traits used to define OCPD in Section III correspond with the Section II operationalization of the disorder is contested. The current study aims to contribute to the evidence base necessary to solidify the optimal trait profile for this disorder via a more fine-tuned examination of OCPD. The research questions were examined using a clinical sample of 142 Danish adults who completed the Structured Clinical Interview for DSM-IV Axis II Disorders and the Personality Inventory for DSM-5 to index both the Sections II and III (personality traits) operationalizations of OCPD, respectively. Bivariate correlations supported Rigid Perfectionism and Perseveration as traits relevant to OCPD; however, hierarchical regression analyses indicated that of the 4 traits used in the Section III operationalization of OCPD, only Rigid Perfectionism uniquely predicted OCPD (p < .05). In addition to Rigid Perfectionism, the conceptually relevant traits of Submissiveness, Suspiciousness, and (low) Impulsivity were also found to uniquely predict OCPD and its specific symptoms in a regression model. These findings indicate that the traits proposed in Section III are only partially aligned with the traditional, Section II conceptualization of OCPD, and may be augmented by incorporating Submissiveness, Suspiciousness, and (low) Impulsivity. In light of the current findings and existing literature, a modified constellation of traits to operationalize OCPD is likely justified.


Novel method to evaluate the risk of tumor adhesions and post-operative hemorrhage of meningiomas using 320 row CT-DSA: A clinical research study.
Meningioma is an extra-axial tumor that forms adhesions toward the brain surface in the course of its growth. Predicting adhesions between the tumor and the brain surface leads to better predictions of surgical results. There are few studies on brain-tumor adhesions or postoperative hemorrhage. This study aimed to assess tumor vascularity of the dura and cerebral surface, and predict surgical outcomes using four-dimensional computed tomography angiography (4D CTA). Using a dynamic contrast CT, we conducted a retrospective study of 27 patients with convexity (n = 15), falx (n = 6), and parasagittal (n = 6) meningiomas treated in our hospital from January 2016 to September 2018. We set the region of interest on the dural layer and cerebral surface side of meningiomas and calculated the mean CT value in each region. Distribution of blood flow in the tumor was classified into two groups: A, which has a higher CT value of the dural side than that of the brain surface side at every timing, and B, which meets the criteria other than those in group A. Demographic data, preoperative characteristic images, and postoperative complications were compared between the groups. Twelve and 15 patients were classified into groups A and B, respectively. The extent of adhesions against the cerebral cortex in group A was significantly less severe compared with that in group B (p = 0.038). The rate of postoperative hemorrhage occurrence in group B (53%) was significantly higher than that in group A (8%) (p = 0.04). There were no significant differences in the other preoperative characteristic images or perioperative parameters between groups A and B. A 320-row dynamic contrast CT scanner can detect meningiomas with a high probability of severe adhesion toward the brain surface and postoperative intraparenchymal hematoma.


Histopathological Analysis of Tumor Microenvironment and Angiogenesis in Pheochromocytoma.
Pheochromocytomas (PHEOs) are relatively rare catecholamine-producing tumors derived from adrenal medulla. Tumor microenvironment (TME) including neoangiogenesis has been explored in many human neoplasms but not necessarily in PHEOs. Therefore, in this study, we examined tumor infiltrating lymphocytes (CD4 and CD8), tumor associated macrophages (CD68 and CD163), sustentacular cells (S100p), and angiogenic markers (CD31 and areas of intratumoral hemorrhage) in 39 cases of PHEOs in the quantitative fashion. We then compared the results with pheochromocytoma of the adrenal gland scaled score (PASS), grading system for pheochromocytoma and paraganglioma (GAPP) and the status of intra-tumoral catecholamine-synthesizing enzymes (TH, DDC, and PNMT) as well as their clinicopathological factors. Intratumoral CD8 (p = 0.0256), CD31 (p = 0.0400), and PNMT (p = 0.0498) status was significantly higher in PHEOs with PASS <4 than PASS ≧4. In addition, intratumoral CD8+ lymphocytes were also significantly more abundant in well-than moderately differentiated PHEO according to GAPP score (p = 0.0108) and inversely correlated with tumor size (p = 0.0257). Intratumoral CD68+ cells were significantly higher in PHEOs with regular or normal histological patterns than those not (p = 0.0370) and inversely correlated with tumor size (p = 0.0457). The status of CD163 was significantly positively correlated with that of CD8 positive cells (p = 0.0032). The proportion of intratumoral hemorrhage areas was significantly higher in PHEOs with PASS ≧4 (p = 0.0172). DDC immunoreactivity in tumor cells was significantly positively correlated with PASS score (p = 0.0356) and TH status was significantly higher in PHEOs harboring normal histological patterns (p = 0.0236) and cellular monotony (p = 0.0219) than those not. Results of our present study did demonstrate that abundant CD8+ and CD68+ cells could represent a histologically low-scored tumor. In particular, PHEOs with increased intratumoral hemorrhage should be considered rather malignant. In addition, abnormal catecholamine-producing status of tumor cells such as deficient PNMT and TH and increased DDC could also represent more aggressive PHEOs.


Exploring chemical space in the search for improved azoheteroarene-based photoswitches.
In quest of improved photo switches, azoheteroarenes have emerged as a potential alternative to azobenzenes. However, to date the number and types of these species that have been subjected to study are insufficient to provide an in-depth understanding of the photochemical effects brought about by different substituents. Here, we computationally screen the optical properties and thermal stabilities of 512 azoheteroarenes that consist of eight different N-containing heteroarenes combined with 64 substitution patterns. The most promising compounds are identified and their properties rationalized based on the nature of the azoheteroarene core and the location and type of substitution patterns.


An interactive wireless communication system for visually impaired people using city bus transport.
Visually impaired people have difficulty accessing information about public transportation systems. Several systems have been developed for assisting visually impaired and blind people to use the city bus. Most systems provide only one-way communication and require high-cost and complex equipment. The purpose of this study is to reduce the difficulties faced by visually impaired people when taking city buses, using an interactive wireless communication system. The system comprised a user module and a bus module to establish a direct one-to-one connection. When the user inputs 4-digit numbers, the user module immediately sends out the information. If the bus module receives the matched bus number, it buzzes and the warning LED flashes to notify the bus driver that someone is waiting to board on the bus. User tests were conducted by two visually impaired people in a simulated vehicle and a city bus. The success rate of interactive wireless communication, recognizing the arrival of the bus and boarding the correct bus reached 100% in all of the tests. The interactive wireless communication aid system is a valid and low-cost device for assisting visually impaired people to use city buses.


A randomised clinical trial on the efficacy of oxytetracycline dose through water medication of nursery pigs on diarrhoea, faecal shedding of Lawsonia intracellularis and average daily weight gain.
Oral treatment with antimicrobials is widely used in pig production for the control of gastrointestinal infections. Lawsonia intracellularis (LI) causes enteritis in pigs older than six weeks of age and is commonly treated with antimicrobials. The objective of this study was to evaluate the efficacy of three oral dosage regimens (5, 10 and 20mg/kg body weight) of oxytetracycline (OTC) in drinking water over a five-day period on diarrhoea, faecal shedding of LI and average daily weight gain (ADG). A randomised clinical trial was carried out in four Danish pig herds. In total, 539 animals from 37 batches of nursery pigs were included in the study. The dosage regimens were randomly allocated to each batch and initiated at presence of assumed LI-related diarrhoea. In general, all OTC doses used for the treatment of LI infection resulted in reduced diarrhoea and LI shedding after treatment. Treatment with a low dose of 5mg/kg OTC per kg body weight, however, tended to cause more watery faeces and resulted in higher odds of pigs shedding LI above detection level when compared to medium and high doses (with odds ratios of 5.5 and 8.4, respectively). No association was found between the dose of OTC and the ADG. In conclusion, a dose of 5mg OTC per kg body weight was adequate for reducing the high-level LI shedding associated with enteropathy, but a dose of 10mg OTC per kg body weight was necessary to obtain a maximum reduction in LI shedding.


What do you know about reproductive medicine?--results of a German representative survey.
The use of reproductive medical treatments has become increasingly routine in recent years. This paper reports on a study of how different aspects of modern reproductive medicine are perceived by the German population. Findings from a nationally representative sample of 2110 men and women aged 18 to 50 are presented. Participants responded to a questionnaire seeking self-report information about attitudes and knowledge regarding different aspects of reproductive medicine. The majority of respondents had already heard or read something about reproductive medicine; knowledge gaps were prevalent in men and individuals with lower levels of education. The decrease in female fertility usually was underestimated, whereas both the number of involuntarily childless couples and the success rate of reproductive medical treatment were overestimated. One-third of participants would make use of reproductive medicine to have their own child. This study revealed inadequacies in the knowledge of the German general population regarding reproductive medicine. Despite the low interest and poor knowledge of the topic, a broad acceptance of reproductive medical methods was reported. The results illustrate the need for adequate information transfer regarding female fertility as well as success rate and risks of reproductive medical interventions.


Plant reproduction is altered by simulated herbicide drift to constructed plant communities.
Herbicide drift may have unintended impacts on native vegetation, adversely affecting individual species and plant communities. To determine the potential ecological effects of herbicide drift, small plant community plots were constructed using 9 perennial species found in different Willamette Valley (OR, USA) grassland habitats. Studies were conducted at 2 Oregon State University (Corvallis, OR, USA) farms in 2 separate years, with single and combined treatments of 0.01 to 0.2× field application rates (f.a.r.) of 1119 g ha-1 for glyphosate (active ingredient [a.i.] of 830 g ha-1 acid glyphosate) and 560 g ha-1 a.i. for dicamba. Plant responses were percentage of cover, number of reproductive structures, mature and immature seed production, and vegetative biomass. Herbicide effects differed with species, year, and, to a lesser extent, farm. Generally, 0.1 to 0.2× f.a.r. of the herbicides were required to affect reproduction in Camassia leichtlinii, Elymus glaucus, Eriophyllum lanatum, Festuca idahoensis, Iris tenax, and Prunella vulgaris. Eriophyllum lanatum also had a significant increase in percentage of immature seed dry weight with 0.01× f.a.r. of dicamba or the combination of glyphosate plus dicamba. Other species showed similar trends, but fewer significant responses. These studies indicated potential effects of low levels of herbicides on reproduction of native plants, and demonstrated a protocol whereby species growing in a constructed plant community can be evaluated for ecological responses. Environ Toxicol Chem 2017;36:2799-2813. Published 2017 SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.


Ultrastructural localization of acidic compartments in cells of isolated rabbit PCT.
Acidic intracellular compartments were identified in cells of isolated perfused rabbit proximal convoluted tubules (PCT) with the weak base, N-(3-[(2,4-dinitrophenyl)amino]propyl)-N-(3-aminopropyl)methylamine, dihydrochloride (DAMP), a congener of dinitrophenol (DNP) and immunogold staining at the ultrastructural level in Lowicryl-embedded tissue. DAMP is protonated upon entrance into an acidic compartment and binds to protein. Glutaraldehyde fixation cross-links the DAMP-protein complex to maintain the complex in its original environment. Monoclonal antibodies directed against DNP cross-react with DAMP to identify its location in tissue sections. Accumulation of colloidal gold-conjugated antibodies to the monoclonal anti-DNP antibodies, indicating the presence of an acidic environment, was found in large endocytic vacuoles (diam greater than 0.5 micron) and lysosomes, and to a lesser extent in endocytic vesicles. Qualitatively, activity greater than background was not found in other organelles, including the Golgi apparatus and the cell nuclei. The specificity of the technique was tested by treating tubules with the ionophore, monensin, to collapse the intracellular pH gradient. This treatment resulted in the complete disappearance of the specific localization of colloidal gold particles. Quantitative analysis of the number of colloidal gold particles per area of cross-sectioned cell organelle demonstrated that monensin especially affected those counts obtained over large endocytic vacuoles and lysosomes. The present ultrastructural observations, therefore, identify endocytic vesicles, endocytic vacuoles, and lysosomes as acidic intracellular compartments in isolated rabbit PCT. This technique affords the opportunity to identify the location of acidic compartments along the entire nephron at the ultrastructural level.


Noncompete clauses: a contract provision that has exhausted its usefulness?
Noncompete clauses (NCs) are common in many physician employment agreements, including those of radiologists. NCs restrict radiologists' ability to perform services for anyone other than their employers, not only during the term of employment but also for a period of time after employment ends. Although courts frown on the post-termination portion as a restraint of trade, in most states, NCs will be enforced if they are deemed reasonable in duration and geography. However the practice of radiology has changed. Teleradiology is common, and improvements in telecommunications and portable devices allow radiologists to perform their services virtually anywhere. In light of these changes, are NCs still necessary for radiologists? Eighty-six University of Maryland radiology residency alumni for whom e-mail information was available were asked to complete an online survey regarding whether they are subject to NCs, the key terms of their NCs, and their views on the continuing usefulness of NCs. A review of all state and federal cases published in the Westlaw law database in which radiologists' NCs were adjudicated was also performed. Twenty-one alumni from our residency program completed the survey, representing a 24.4% response rate; 57.1% of respondents are subject to NCs. Of that group, post-termination restrictions ranged from 1 to 2 years in duration, and geographic limitations ranged from 7 to >50 miles from the employer's practice. Respondents were split as to the impact of teleradiology, with 36.8% feeling that NCs are now more necessary and 26.3% feeling that NCs are less necessary. Searches of Westlaw revealed 7 cases on point, which upheld as reasonable NCs ranging from 1 to 5 years in duration and imposing geographic limitations of 15 to 40 miles from the employer's practice. Although the practice of radiology has undergone significant changes, this survey shows that NCs are still widely used and are still being enforced in many courts. It is unclear whether NCs still make sense in today's practice, but it may be important to modify them to explicitly address the practice of teleradiology. NCs are common and have been upheld in court, although radiologists are split on their usefulness in this era of teleradiology. Contracts should specifically address teleradiology in NC provisions.


Persistent nocardemia following renal transplantation. Association with pulmonary nocardiosis.
Pulmonary nocardiosis occurred in a renal homotransplant patient and was diagnosed by persistently positive blood cultures. Infection developed at a time when efforts were being made with moderate dosages of immunosuppressive drugs to prevent rejection of the transplant. The subsequent nocardemia lasted for one week. The remaining kidney function was preserved, and the patient had a very favorable outcome because of early diagnosis and prompt treatment with sulfisoxazole.


Prevention of immunotoxin-induced immunogenicity by coadministration with CTLA4Ig enhances antitumor efficacy.
Immunotoxins have shown promise as antitumor agents in clinical trials. However, they have not become part of standard cancer therapy because of factors that include their inherent immunogenicity, which limits the duration of therapy. To address this issue, we evaluated in preclinical models the concomitant use of the immunosuppressive agent CTLA4Ig and BR96 sFv-PE40, a single-chain immunotoxin that binds to carcinoma cells expressing Le(y). Cotreatment with CTLA4Ig, an inhibitor of the CD28/CTLA4-CD80/CD86 costimulation pathway, blocked the production of Abs against BR96 sFv-PE40 in immunocompetent rodents and dogs. It also blocked hypersensitivity reactions in rats carrying colon carcinoma allografts during a second course of BR96 sFv-PE40 therapy, and the cotreatment with CTLA4Ig resulted in enhanced antitumor activity. Cotreatment with CTLA4Ig also prevented hypersensitivity reactions induced by repeat dosing of BR96 sFv-PE40 (q3dx5) in dogs. The production of anti-BR96-sFv-PE40 Abs was decreased in CTLA4Ig-cotreated rodents and dogs resulting in increased plasma levels of BR96 sFv-PE40 relative to non-CTLA4Ig-cotreated animals. These data show that cotreatment of immunotoxins with CTLA4Ig, by inhibiting the production of anti-immunotoxin Abs, can extend the duration of BR96 sFv-PE40 therapy to give greater exposure, reduced toxicities, and increased efficacy.


Genetic and behavioural evidence of monogamy in a mammal, Kirk's dik-dik (Madoqua kirkii).
Little is known about the mating behaviour of monogamous mammals. Here, we present behavioural and genetic evidence of fidelity in a socially monogamous dwarf antelope, Kirk's dik-dik. DNA microsatellite analysis revealed no evidence of extra-pair paternity (EPP) in dik-diks: mothers' partners matched the paternal genotype in all 12 juveniles tested. One likely reason for the absence of EPP is that males guard their mates closely during oestrus and over-mark all female scent, thereby reducing the likelihood of other males attempting to mate. In addition, males may be limited in their ability to search for extra-pair populations (EPCs) by activities associated with pair-bond maintenance. Year-round, males maintained proximity within pairs, followed their females' activity patterns, and spent approximately 64% of their time with their partners. However, males did attempt to obtain EPCs when the opportunity arose, and genetic monogamy in dik-diks is probably best explained by the behaviour of females: in contrast to many monogamous female birds, female dik-diks do not appear to seek EPC partners. We propose that females avoid extra-pair males because they are unable to mate with them without instigating a potentially dangerous conflict.


Looming-eyes buoys fail to reduce seabird bycatch in the Icelandic lumpfish fishery: depth-based fishing restrictions are an alternative.
Bycatch in gillnets from lumpfish (Cyclopterus lumpus) fisheries is an important conservation issue in the north Atlantic, with up to 30 000 seabirds potentially killed each year. To date, no technical solutions exist to reduce the bycatch of seabirds in gillnet fisheries, but research on above-water bird deterrents as a form of bycatch mitigation has shown promising results. Here, we tested whether a floating device called 'looming-eyes buoy' (LEB) would consistently reduce the bycatch of seabirds in the Icelandic lumpfish fishery. We conducted 61 controlled trials with sets of normal gillnets and experimental nets equipped with LEBs. We compared both fish catch and bycatch between net types while accounting for exposure time, water depth and season, and found no effect of LEBs on both target lumpfish catch and bycatch. Our analysis indicated however a strong correlation between bycatch rates and fishing depths, suggesting that depth-based fishing restrictions could virtually eliminate the bycatch of seabirds in this fishery. We estimated that limiting fishing to waters more than 50 m deep could save between 5000 and 9300 seabirds every year, arrest the population decline of endangered black guillemots in Iceland, while having only a marginal effect on target fish catch.


Rotation equivariant and invariant neural networks for microscopy image analysis.
Neural networks have been widely used to analyze high-throughput microscopy images. However, the performance of neural networks can be significantly improved by encoding known invariance for particular tasks. Highly relevant to the goal of automated cell phenotyping from microscopy image data is rotation invariance. Here we consider the application of two schemes for encoding rotation equivariance and invariance in a convolutional neural network, namely, the group-equivariant CNN (G-CNN), and a new architecture with simple, efficient conic convolution, for classifying microscopy images. We additionally integrate the 2D-discrete-Fourier transform (2D-DFT) as an effective means for encoding global rotational invariance. We call our new method the Conic Convolution and DFT Network (CFNet). We evaluated the efficacy of CFNet and G-CNN as compared to a standard CNN for several different image classification tasks, including simulated and real microscopy images of subcellular protein localization, and demonstrated improved performance. We believe CFNet has the potential to improve many high-throughput microscopy image analysis applications. Source code of CFNet is available at: https://github.com/bchidest/CFNet. Supplementary data are available at Bioinformatics online.


[Clinical variants of Alzheimer disease].
The heterogeneity and variants of Alzheimer disease (AD) are reviewed. There are cases with a slow or fast evolution and with early or late onset. Most cases are sporadic but there are also hereditary forms. About 50% of patients show neuropsychiatric disorders (depression and psychoses). Some cases have a greater deficit of right or left hemispheric functions. Among the variants, there are forms that start as pure aphasias, predominantly prefrontal cases and posterior cortical forms. Occasionally AD may simulate other disorders such as supranuclear palsy, corticobasal ganglionar degeneration and Jacob-Creutzfeldt disease. Finally, there are mixed forms, in which AD is associated with cerebrovascular disease (very commonly) and with other diseases such as dementia with Lewy bodies. We conclude that AD is a heterogeneous disorder and, therefore, clinical diagnosis may be insufficient. Biological markers and specific imaging studies are needed for a correct clinical diagnosis.


Nucleotide substitution rate of mammalian mitochondrial genomes.
We present here for the first time a comprehensive study based on the analysis of closely related organisms to provide an accurate determination of the nucleotide substitution rate in mammalian mitochondrial genomes. This study examines the evolutionary pattern of the different functional mtDNA regions as accurately as possible on the grounds of available data, revealing some important "genomic laws." The main conclusions can be summarized as follows. (1) High intragenomic variability in the evolutionary dynamic of mtDNA was found. The substitution rate is strongly dependent on the region considered, and slow- and fast-evolving regions can be identified. Nonsynonymous sites, the D-loop central domain, and tRNA and rRNA genes evolve much more slowly than synonymous sites and the two peripheral D-loop region domains. The synonymous rate is fairly uniform over the genome, whereas the rate of nonsynonymous sites depends on functional constraints and therefore differs considerably between genes. (2) The commonly accepted statement that mtDNA evolves more rapidly than nuclear DNA is valid only for some regions, thus it should be referred to specific mitochondrial components. In particular, nonsynonymous sites show comparable rates in mitochondrial and nuclear genes; synonymous sites and small rRNA evolve about 20 times more rapidly and tRNAs about 100 times more rapidly in mitochondria than in their nuclear counterpart. (3) A species-specific evolution is particularly evident in the D-loop region. As the divergence times of the organism pairs under consideration are known with sufficient accuracy, absolute nucleotide substitution rates are also provided.


Permissive role of cAMP in the oscillatory Ca2+ response to inositol 1,4,5-trisphosphate in rat hepatocytes.
Rat hepatocytes respond to alpha-adrenergic stimulation by intracellular production of myo-inositol 1,4,5-trisphosphate (IP3) which stimulates the periodic release and reuptake of intracellular store (IS) Ca2+. The generation of these Ca2+ oscillations was investigated by simultaneously monitoring Ca2+ changes in the cytosol and IS by combined fluorescence microscopy and whole-cell patch clamp. Intracellular IP3 perfusion (1-50 microM in the pipette) produced three types of Ca2+ response: understimulation, oscillations and overstimulation, i.e. with Ca2+ levels not returning to baseline. In a total of 57 experiments, only three displayed oscillations during continuous IP3 infusion, in a narrow range of IP3 concentration centred around 5-8 microM in the pipette. In oscillating cells, cytosolic Ca2+ spikes were synchronized with transient Ca2+ depletions of the IS, consistent with a direct exchange of Ca2+ between the two compartments. Application of 8-Br-cAMP to cells infused with IP3 increased the probability of eliciting Ca2+ oscillations by a factor of 4-5 for IP3 concentrations in the range 1-10 microM, whereas IP3 concentrations above 10 microM always resulted in overstimulation. IP3 photorelease experiments and measurements of IS Ca2+ content indicated that 8-Br-cAMP enhanced the affinity of the IP3 receptor and increased the pool of releasable Ca2+. We propose that cAMP has a permissive role in the generation of IP3-induced Ca2+ oscillations by extending the window of IP3 concentrations able to elicit oscillations.


The biosynthesis of raffinose.
1. Reaction of UTP and alpha-d-galactose 1-phosphate with [U-(14)C]sucrose in the presence of a Vicia faba dormant-seed preparation yielded the trisaccharide raffinose. 2. UTP-alpha-d-galactose 1-phosphate-uridylyltransferase activity has been demonstrated in the bean preparation and evidence for the participation of UDP-galactose in the trisaccharide synthesis is presented. 3. UDP-galactose 4-epimerase is present in the dormant seed. 4. The biosynthesis of raffinose in relation to the metabolism of other carbohydrates in plants is discussed.


Description of the transcriptomes of immune response-activated hemocytes from the mosquito vectors Aedes aegypti and Armigeres subalbatus.
Mosquito-borne diseases, including dengue, malaria, and lymphatic filariasis, exact a devastating toll on global health and economics, killing or debilitating millions every year (54). Mosquito innate immune responses are at the forefront of concerted research efforts aimed at defining potential target genes that could be manipulated to engineer pathogen resistance in vector populations. We aimed to describe the pivotal role that circulating blood cells (called hemocytes) play in immunity by generating a total of 11,952 Aedes aegypti and 12,790 Armigeres subalbatus expressed sequence tag (EST) sequences from immune response-activated hemocyte libraries. These ESTs collapsed into 2,686 and 2,107 EST clusters, respectively. The clusters were used to adapt the web-based interface for annotating bacterial genomes called A Systematic Annotation Package for Community Analysis of Genomes (ASAP) for analysis of ESTs. Each cluster was categorically characterized and annotated in ASAP based on sequence similarity to five sequence databases. The sequence data and annotations can be viewed in ASAP at https://asap.ahabs.wisc.edu/annotation/php/ASAP1.htm. The data presented here represent the results of the first high-throughput in vivo analysis of the transcriptome of immunocytes from an invertebrate. Among the sequences are those for numerous immunity-related genes, many of which parallel those employed in vertebrate innate immunity, that have never been described for these mosquitoes. The sequences and annotations presented in this paper have been submitted to GenBank under accession numbers AY 431103 to AY 433788 (Aedes aegypti) and AY 439334 to AY 441440 (Armigeres subalbatus).


Making cognitive decision support work: Facilitating adoption, knowledge and behavior change through QI.
This paper evaluates the role of facilitation in the successful implementation of Computerized Decision Support (CDS). Facilitation processes include education, specialized computerized decision support, and work process reengineering. These techniques, as well as modeling and feedback enhance self-efficacy, which we propose is one of the factors that mediate the effectiveness of any CDS. In this study, outpatient clinics implemented quality improvement (QI) projects focused on improving geriatric care. Quality Improvement is the systematic process of improving quality through continuous measurement and targeted actions. The program, entitled "Advancing Geriatric Education through Quality Improvement" (AGE QI), consisted of a 6-month, QI based, intervention: (1) 2h didactic session, (2) 1h QI planning session, (3) computerized decision support design and implementation, (4) QI facilitation activities, (5) outcome feedback, and (6) 20h of CME. Specifically, we examined the impact of the QI based program on clinician's perceived self-efficacy in caring for older adults and the relationship of implementation support and facilitation on perceived success. The intervention was implemented at 3 institutions, 27 community healthcare system clinics, and 134 providers. This study reports the results of pre/post surveys for the forty-nine clinicians who completed the full CME program. Self-efficacy ratings for specific clinical behaviors related to care of older adults were assessed using a Likert based instrument. Self-ratings of efficacy improved across the following domains (depression, falls, end-of-life, functional status and medication management) and specifically in QI targeted domains and were associated with overall clinic improvements.


Temporal lobe volume predicts Wada memory test performance in patients with mesial temporal sclerosis.
The Wada test is widely used in the presurgical evaluation of potential temporal lobectomy patients to predict postoperative memory function. Expected asymmetry (EA), defined as Wada memory lateralized to the nonsurgical hemisphere, or a higher score after injection of the surgical hemisphere would be considered favorable in terms of postoperative memory outcome. However, in some cases, nonlateralized memory (NM) results, with no appreciable asymmetry, may occur because of impaired scores after both injections, often leading to denial of surgery. The reason for such nonlateralized Wada memory in patients with intractable temporal lobe epilepsy (TLE) remains unclear. Given that quantitative morphometric magnetic resonance imaging studies in TLE patients have shown bilateral regional atrophy in temporal and extratemporal structures, we hypothesized that the volume loss in contralateral temporal structures could contribute to nonlateralized Wada memory performance. To investigate this, we examined the relationship between the volume changes of temporal structures and Wada memory scores in patients with intractable TLE with mesial temporal sclerosis (MTS) using an age- and gender-matched control group. Memory was considered nonlateralized if the absolute difference in the total correct recall scores between ipsilateral and contralateral injections was <11%. Among 21 patients, Wada memory was lateralized in 15 and nonlateralized in 6 patients, with all the nonlateralized scores being observed in left TLE. The recall scores after ipsilateral injection were significantly lower in patients with an NM profile than an EA profile (23 ± 14% vs. 59 ± 18% correct recall, p ≤ 0.001). However, the recall scores after contralateral injection were low but similar between the two groups (25 ± 17% vs. 25 ± 15% correct recall, p=0.97). Compared to controls, all the patients showed greater volume loss in the temporal regions. However, patients with a NM profile showed significantly more volume loss than those with a lateralized memory profile in both contralateral and ipsilateral temporal regions (p<0.05). Left hemispheric Wada memory performance correlated positively with the size of the left mesial and neocortical temporal structures (r=0.49-0.63, p=0.005-0.04). Our study suggests that volume loss in the nonsurgical temporal structures is associated with nonlateralized Wada memory results in patients with intractable TLE.


Effects of Chinese Medicine Tong xinluo on Diabetic Nephropathy via Inhibiting TGF- β 1-Induced Epithelial-to-Mesenchymal Transition.
Diabetic nephropathy (DN) is a major cause of chronic kidney failure and characterized by interstitial and glomeruli fibrosis. Epithelial-to-mesenchymal transition (EMT) plays an important role in the pathogenesis of DN. Tong xinluo (TXL), a Chinese herbal compound, has been used in China with established therapeutic efficacy in patients with DN. To investigate the molecular mechanism of TXL improving DN, KK-Ay mice were selected as models for the evaluation of pathogenesis and treatment in DN. In vitro, TGF- β 1 was used to induce EMT. Western blot (WB), immunofluorescence staining, and real-time polymerase chain reaction (RT-PCR) were applied to detect the changes of EMT markers in vivo and in vitro, respectively. Results showed the expressions of TGF- β 1 and its downstream proteins smad3/p-smad3 were greatly reduced in TXL group; meantime, TXL restored the expression of smad7. As a result, the expressions of collagen IV (Col IV) and fibronectin (FN) were significantly decreased in TXL group. In vivo, 24 h-UAER (24-hour urine albumin excretion ratio) and BUN (blood urea nitrogen) were decreased and Ccr (creatinine clearance ratio) was increased in TXL group compared with DN group. In summary, the present study demonstrates that TXL successfully inhibits TGF- β 1-induced epithelial-to-mesenchymal transition in DN, which may account for the therapeutic efficacy in TXL-mediated renoprotection.


2-Nonanone is a Critical Pheromone Component for Cerambycid Beetle Species Native to North and South America.
An increasing body of evidence indicates that cerambycid beetles native to different continents may share pheromone components, suggesting that these compounds arose as pheromone components early in the evolution of the family. Here, we describe the identification and field testing of the pheromone blends of two species in the subfamily Cerambycinae that share 2-nonanone as an important component of their male-produced aggregation-sex pheromones, the South American Stizocera consobrina Gounelle (tribe Elaphidiini) and the North American Heterachthes quadrimaculatus Haldeman (tribe Neoibidionini). Along with 2-nonanone, males of S. consobrina also produce 1-(1H-pyrrol-2-yl)-1,2-propanedione, whereas males of H. quadrimaculatus produce 10-methyldodecanol. Field bioassays conducted in Brazil (targeting S. consobrina) and Illinois (targeting H. quadrimaculatus) demonstrated that adults of both species were attracted only by the blends of both their pheromone components, and not to the individual components. The use of the pyrrole as a critical component for the former species is further evidence that this compound is a common pheromone structure among cerambycines in different biogeographical regions of the world.


Associations between blood nutritional biomarkers and cerebral Amyloid-β: Insights from the COGFRAIL Cohort Study.
Understanding the relationship between blood nutrients and neurodegeneration could contribute to devising strategies for preventing Alzheimer's disease. We investigated the associations between fatty acids, vitamins D, B6, B12, folate, and homocysteine and the cerebral load of amyloid β (Aβ). This cross-sectional study included 177 older adults (70 to 96 years, 65% female) with objective cognitive impairment, pre-frail, or frail. Cerebral Aβ load was determined using PET Standardized Uptake Value ratios (SUVr). Fatty acids were assessed in erythrocytes, vitamins D and homocysteine in serum, and the other vitamins in plasma. Linear regression models corrected for multiple comparisons evaluated the associations between each nutrient and Aβ. The principal component factor followed by linear regression grouped the fatty acids strongly correlated (factor) and associated with Aβ. Higher concentrations of polyunsaturated fatty acids (PUFAs) clupanodonic acid (22:5n-3) (β: -0.13; p= 0.001), mead acid (20:3n-9) (β: -0.07; p= 0.036), and adrenic acid (22:4n-6) (β: -0.05; p=0.031) were associated with lower global Aβ load, while linoleic acid (18:2n-6) was associated with higher global Aβ load (β: 0.18; p= 0.042). Clupanodonic acid was inversely associated with Aβ in all cerebral regions except the thalamus. The factor composed of mead, clupanodonic, and arachidonic (20:4n-6) acids was associated with a lower global Aβ load (β: -0.02; p=0.002). Some erythrocyte PUFAs were inversely associated with Aβ load in the brain, and most of them were metabolites of the essential fatty acids linoleic and α-linolenic. Given the cross-sectional design, these results must be carefully interpreted, and longitudinal studies are needed.


The natural course of atrial septal defect in adults--a still unsettled issue.
Atrial septal defect is the most frequently encountered major congenital cardiac disorder in the adult population, with a prevalence of 0.2 to 0.7 per thousand. Several patients tolerate large unrepaired defects for 80 years or even longer without serious disability. However, it is assumed that, as a rule, atrial septal defect reduces life expectancy, the average age at death not exceeding 50 years. This estimation is based on studies derived mainly from necropsy series or from the admission profile of patients undergoing late operative repair. The onset of atrial fibrillation, with an incidence ranging from 13 to 52 percent among patients older than 40 years, as well as the progression of pulmonary arterial hypertension in up to 53 percent of patients, results in congestive heart failure and functional limitation. On the other hand, very few longitudinal studies thus far have directly and systematically followed the course of adults with unrepaired defects. Thus, many issues regarding the natural history and prognosis of atrial septal defect still remain unresolved. Follow-up series of older patients with nonoperated defects could yield valuable information even in an era when routine early surgical closure is increasingly being recommended.


Superficial ulcerating necrobiosis in rheumatoid arthritis. A variant of the necrobiosis lipoidica-rheumatoid nodule spectrum?
Although necrobiosis is not a precise term, it primarily refers to collagen changes found in association with the palisading granulomas seen in granuloma annulare, necrobiosis lipoidica diabeticorum (NLD), and rheumatoid nodules. While the pathogenesis of each of these conditions remains unknown, immune complex vasculitis and delayed hypersensitivity mechanisms have been postulated. Two patients are described, having "classic" rheumatoid arthritis with chronic, superficial, ulcerating, discrete lesions on their lower legs that histologically were interpreted as NLD. While the argument for a chance association of NLD and rheumatoid arthritis could be advanced, the occurrence of identical lesions in two patients with high-titer rheumatoid factor, rheumatoid nodules, and some clinical and microscopic evidence of a low-grade rheumatoid vasculitis suggests a new subset of patients with necrobiotic palisading granulomas.


[Physiopathologic mechanisms of ventricular remodelling].
Understanding of the pathophysiological mechanisms involved in ventricular remodeling is of the utmost importance for the clinical cardiologist. In the near future this knowledge will allow us not only to better understand the evolution of patients suffering from this process but also to design new therapeutic strategies for the prevention of ventricular remodeling. In this work some of the main pathophysiological mechanisms involved in ventricular remodeling are briefly reviewed.


[Sutures in skin surgery].
Dermatologists performing skin surgery mostly use the square knot. Other underused or even forgotten suturing techniques may still be helpful in some instances. We shall emphasize some simple techniques such as the horizontal mattress suture, the "cross stitch", the "corner stitch" (half buried mattress suture), the buried dermal suture, the buried vertical mattress suture, the continuous mattress suture and the running intradermal suture. In given circumstances, all of them may improve suturing and promote healing. Technical aspects, advantages and disadvantages of each type of suture will be briefly described.


Concordance and predictive value of two adverse drug event data sets.
Accurate prediction of adverse drug events (ADEs) is an important means of controlling and reducing drug-related morbidity and mortality. Since no single "gold standard" ADE data set exists, a range of different drug safety data sets are currently used for developing ADE prediction models. There is a critical need to assess the degree of concordance between these various ADE data sets and to validate ADE prediction models against multiple reference standards. We systematically evaluated the concordance of two widely used ADE data sets - Lexi-comp from 2010 and SIDER from 2012. The strength of the association between ADE (drug) counts in Lexi-comp and SIDER was assessed using Spearman rank correlation, while the differences between the two data sets were characterized in terms of drug categories, ADE categories and ADE frequencies. We also performed a comparative validation of the Predictive Pharmacosafety Networks (PPN) model using both ADE data sets. The predictive power of PPN using each of the two validation sets was assessed using the area under Receiver Operating Characteristic curve (AUROC). The correlations between the counts of ADEs and drugs in the two data sets were 0.84 (95% CI: 0.82-0.86) and 0.92 (95% CI: 0.91-0.93), respectively. Relative to an earlier snapshot of Lexi-comp from 2005, Lexi-comp 2010 and SIDER 2012 introduced a mean of 1,973 and 4,810 new drug-ADE associations per year, respectively. The difference between these two data sets was most pronounced for Nervous System and Anti-infective drugs, Gastrointestinal and Nervous System ADEs, and postmarketing ADEs. A minor difference of 1.1% was found in the AUROC of PPN when SIDER 2012 was used for validation instead of Lexi-comp 2010. In conclusion, the ADE and drug counts in Lexi-comp and SIDER data sets were highly correlated and the choice of validation set did not greatly affect the overall prediction performance of PPN. Our results also suggest that it is important to be aware of the differences that exist among ADE data sets, especially in modeling applications focused on specific drug and ADE categories.


Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center.
The Foveal Photocoagulation Study, a component of the Macular Photocoagulation Study, is designed to evaluate whether laser treatment can reduce the risk of severe visual loss in eyes with well-defined choroidal neovascular membranes associated with macular degeneration that extend through the foveal center. On one third of the 554 baseline angiograms of study patients enrolled in and whose eyes were graded in the study as of January 31, 1990, the Reading Center staff has noted an unusual pattern of hyperfluorescence in the late-transit frames that has not been described previously. This pattern, which we call "loculated fluid," consists of a well-demarcated area of hyperfluorescence that appears to represent pooling of fluorescein in a compartmentalized space anterior to the choroidal neovascular leakage. Although the loculated fluid may conform to a pattern of typical cystoid macular edema, it can also pool within an area deep to the sensory retina in a shape that does not bear any resemblance to cystoid macular edema. This pattern is important to recognize because it (1) should not be confused with the angiographic pattern or extent of choroidal neovascularization and (2) should be differentiated from a serous detachment or tear of the retinal pigment epithelium.


Cloning and characterization of a chitinase-encoding gene (chiA) from Aspergillus nidulans, disruption of which decreases germination frequency and hyphal growth.
We cloned a chitinase-encoding gene from Aspergillus nidulans by polymerase chain reaction using degenerated oligonucleotide primers designed from the conserved amino acid sequences among chitinases from yeasts and Rhizopus spp. The cloned gene, named chiA, encoded a polypeptide consisting of 660 amino acids. Disruption of chiA had no effect on hyphal or conidiophore morphology, but germination frequency and hyphal growth rate decreased substantially. Expression of chiA was investigated using Escherichia coli beta-galactosidase as a reporter enzyme. The beta-galactosidase activity was present during hyphal growth and increased twice as the conidiophores developed. In situ staining of beta-galactosidase activity found high expression in metulae, phialides, and conidia during conidiophore development, indicating that the expression of chiA is developmentally regulated. This is the first report to isolate a chitinase gene from A. nidulans and investigate its functions using the gene disruption technique and gene fusion methods in filamentous fungi.


Delineating the importance of serum opsonins and the bacterial capsule in affecting the uptake and killing of Burkholderia pseudomallei by murine neutrophils and macrophages.
Infection of susceptible hosts by the encapsulated Gram-negative bacterium Burkholderia pseudomallei (Bp) causes melioidosis, with septic patients attaining mortality rates ≥ 40%. Due to its high infectivity through inhalation and limited effective therapies, Bp is considered a potential bioweapon. Thus, there is great interest in identifying immune effectors that effectively kill Bp. Our goal is to compare the relative abilities of murine macrophages and neutrophils to clear Bp, as well as determine the importance of serum opsonins and bacterial capsule. Our findings indicate that murine macrophages and neutrophils are inherently unable to clear either unopsonized Bp or the relatively-avirulent acapsular bacterium B. thailandensis (Bt). Opsonization of Bp and Bt with complement or pathogen-specific antibodies increases macrophage-uptake, but does not promote clearance, although antibody-binding enhances complement deposition. In contrast, complement opsonization of Bp and Bt causes enhanced uptake and killing by neutrophils, which is linked with rapid ROS induction against bacteria exhibiting a threshold level of complement deposition. Addition of bacteria-specific antibodies enhances complement deposition, but antibody-binding alone cannot elicit neutrophil clearance. Bp capsule provides some resistance to complement deposition, but is not anti-phagocytic or protective against reactive oxygen species (ROS)-killing. Macrophages were observed to efficiently clear Bp only after pre-activation with IFNγ, which is independent of serum- and/or antibody-opsonization. These studies indicate that antibody-enhanced complement activation is sufficient for neutrophil-clearance of Bp, whereas macrophages are ineffective at clearing serum-opsonized Bp unless pre-activated with IFNγ. This suggests that effective immune therapies would need to elicit both antibodies and Th1-adaptive responses for successful prevention/eradication of melioidosis.


[Hantavirus cardiopulmonary syndrome in the Triângulo Mineiro and Alto Paranaíba regions, State of Minas Gerais, 1998-2005: clinical-epidemiological aspects of 23 cases].
The epidemiological, clinical, laboratory and treatment findings from 23 cases of hantavirus cardiopulmonary syndrome were analyzed. These cases were identified either serologically or immunohistochemically in hospitals in the municipality of Uberlândia, State of Minas Gerais. Fever (100%), dyspnea (100%) and myalgia (78%) were the symptoms most frequently observed in this sample. The most prevalent physical signs were hypotension (65%) and tachycardia (65%). The most common laboratory findings included thrombocytopenia (96%), hemoconcentration (83%) and leukocytosis (74%). Abnormal values for liver enzymes were found in all the patients tested and abnormalities in chest radiography were very frequent (95.6%). In 55.5% of the patients, orotracheal intubation and hemodynamic support were required. The present study confirmed the seasonal pattern of hantavirus cardiopulmonary syndrome in the Uberlândia region and the involvement of professional groups who are considered to be at low risk of infection, in the transmission cycle of the disease. The high lethality rate (39%) and the severity of the disease observed in this study may be related to attending to these patients at a late stage.


CORRELATES OF ATOPIC DERMATITIS CHARACTERISTICS IN MILITARY PERSONNEL.
Atopic dermatitis, despite its relatively wide distribution and low severity, was statistically often a disqualification condition for military service. The aim of our study is to determine correlations between characteristics of atopic dermatitis in military personnel. 144 people with atopic dermatitis were under our observation, 78 of them military personnel, 26 military family members and 40 civilians, 62 men and 82 women. We studied the following characteristics: gender, age, marital status, education, social status, place of service location, genetic anamnesis, recurrence during the year, laboratory indicators of attached infections, focus of localization, other skin diseases, comorbidities, compliance with hygienic conditions, wearing a military uniform, the frequency of changing bed linen. 3-5 times recurrence a year shows a reliable positive correlation with: wearing a uniform for 12-24 hours, SSA/eosinophilia, mycosis, pathology of the respiratory system, military personnel. Staphylococcus aureus is associated with other infections - St. hominis, fungus, also shows a reliable positive correlation: localization on the face and torso, wearing the uniform for 1 week and more. Staphylococcus hominis shows a reliable positive correlation: localization - torso, wearing uniform for 1 week or more,y. Shows a reliable positive correlation with fungus: localization scalp, neck, lower limb, military serviceman; reliable positive correlation with SSA/eosinophilia: increased IgE, localization on the upper limbs, mycosis, change of bed linen - once every 2 weeks; IgE - localization of dermatosis on the upper limbs and torso area, pathology of the digestive system, changing bed linen once every 2 weeks, military serviceman. It shows a reliable positive correlation with helminthiasis: Localization on the genitals, mycosis, pathology of the digestive system, change of bed linen once a month. Development and recurrence of atopic dermatitis in military personnel correlates with living conditions and infections. Determining the differences between civilian and military patient populations will allow clinicians to better investigate the risk factors that predispose to the manifestation of dermatitis in the military.


Predictive prognostic role of miR-181a with discrepancy in the liver and serum of genotype 4 hepatitis C virus patients.
microRNA (miRNA) expression in organs does not always represent their quantity in serum. A disparity in the expression of miR-181a has been reported in the tissues and serum of hepatocellular carcinoma (HCC) patients. Since hepatitis C virus (HCV) is a major cause of HCC and miR-181a has never been studied in HCV, the present study aimed to investigate the miR-181a expression profile in genotype 4 (GT4)-HCV patients to evaluate whether this pattern is also apparent in HCV. RNA was extracted from liver tissues, peripheral mononuclear cells (PBMCs) and serum samples from GT4-HCV-infected patients and healthy donors to evaluate the relative miR-181a expression using quantitative reverse transcription-polymerase chain reaction. miR-181a was significantly higher in the serum of naïve patients compared to controls, and an inverse correlation with the viral load and liver enzymes was apparent. By contrast, no difference in miR-181a expression was observed in the liver tissues and PBMCs of patients compared to controls. This expression observed in HCV is conflicting to that previously reported in HCC. The study also demonstrates a significant upregulation of miR-181a post-interferon/ribavirin treatment in the serum of sustained virological responders (SVRs) compared to non-responders and treatment-naïve SVRs. In conclusion, miR-181a may be considered to be a possible prognostic marker in GT4-HCV infection.


Protomer of Imipramine Captured in Cucurbit[7]uril.
Small molecules possessing multiple proton-accessible sites are important not only to many biological systems but also to host-guest chemistry; their protonation states are causal to boosting or hindering specific host-guest interactions. However, determining the protonation site is not trivial. Herein, we conduct electrospray ionization ion mobility spectrometry-mass spectrometry to imipramine, a known molecule with two protonation sites, based on the introduction of cucurbit[7]uril as a host molecule. For protonated imipramine, the proposed strategy allows clear distinction of the two protomers as host-guest complex ions and can be leveraged to capture the energetically less preferable protomer of the protonated imipramine.


Automated method for subtraction of fluorescence from biological Raman spectra.
One of the challenges of using Raman spectroscopy for biological applications is the inherent fluorescence generated by many biological molecules that underlies the measured spectra. This fluorescence can sometimes be several orders of magnitude more intense than the weak Raman scatter, and its presence must be minimized in order to resolve and analyze the Raman spectrum. Several techniques involving hardware and software have been devised for this purpose; these include the use of wavelength shifting, time gating, frequency-domain filtering, first- and second-order derivatives, and simple curve fitting of the broadband variation with a high-order polynomial. Of these, polynomial fitting has been found to be a simple but effective method. However, this technique typically requires user intervention and thus is time consuming and prone to variability. An automated method for fluorescence subtraction, based on a modification to least-squares polynomial curve fitting, is described. Results indicate that the presented automated method is proficient in fluorescence subtraction, repeatability, and in retention of Raman spectral lineshapes.


Structural Disorder at the Edges of Rubrene Crystals Enhances Singlet Fission.
Materials that undergo singlet fission are of interest for their use in light-harvesting, photocatalysis, and quantum information science, but their ability to undergo fission can be sensitive to local variations in molecular packing. Herein we employ transient absorption microscopy, molecular dynamics simulations, and electronic structure calculations to interrogate how structures found at the edges of orthorhombic rubrene crystals impact singlet fission. Within a micrometer-scale spatial region at the edges of rubrene crystals, we find that the rate of singlet fission increases nearly 4-fold. This observation is consistent with formation of a region at crystal edges with reduced order that accelerates singlet fission by disrupting the symmetry found in rubrene's orthorhombic crystal structure. Our work demonstrates that structural distortions of singlet fission materials can be used to control fission in time and in space, potentially offering a means of controlling this process in light harvesting and quantum information applications.


[Effect of certain factors on the variability of strains of pertussis microbes].
The population of degraded cells having stable changes in some phenotypical properties were isolated after subculturing some laboratory Bordetella pertussis strains in Bordet-Gengou culture medium and casein-charcoal agar with blood, treated with mitomycin C and allowed to proliferate in the spleen of mice injected intravenously with microbial suspensions. The characteristics indicative of cell degradation were the growth of large yellowish-white colonies appearing in 24 hours, the destruction of the agglutinogenic complex and toxic substances causing the atrophy of the spleen in mice, the increased capacity for active proliferation in the spleen. Electron-microscopic study revealed that the variants obtained by subculturing in culture media had the damaged membrane with the formation of cell-wall invaginations having rounded membrane-like formations on their surface, disappearing after treatment with mitomycin C; the treatment of the initial strains with mitomycin C resulted in cytoplasmic damage with the coagulation of the nucleoid.


A multispecies perspective on ecological impacts of climatic forcing.
1. In the prevailing context of concerns over climate change and its potential impacts on ecosystems, evaluating ecological consequences of climatic forcing has become a critical issue. 2. Historical data on the abundance of organisms have been extensively used to characterize the ecological effects of climatic forcing through specific weather and/or climatic variables, with most of the studies confined to single population models. 3. However, population responses to environmental fluctuations typically depend upon positive and negative feedbacks induced by interactions with other species. It is therefore important to integrate the insights gained from single population approaches into a multispecies perspective. 4. Here we combine the hierarchical Bayesian modelling approach with the state-space formulation to extend the scope of previously proposed models of population dynamics under climatic forcing to multi-species systems. 5. We use our model to analyse long-term macro-moth (Lepidoptera) community data from the Rothamsted Insect Survey network in the UK, using winter rainfall and winter temperature as environmental covariates. 6. The effects of the two weather variables were consistent across species, being negative for winter rainfall and positive for winter temperature. The two weather variables jointly explained 15-40% of the total environmental variation affecting the dynamics of individual species, and could explain up to 90% of covariances in species dynamics. 7. The contribution of interspecific interactions to community-level variation was found to be weak compared to the contributions of environmental forcing and intraspecific interactions.


Anthropogenic effects on bacterial diversity and function along a river-to-estuary gradient in Northwest Greece revealed by metagenomics.
Studies assessing the effects of anthropogenic inputs on the taxonomic and functional diversity of bacterioplankton communities in lotic ecosystems are limited. Here, we applied 16S rRNA gene amplicon and whole-genome shotgun sequencing to examine the microbial diversity in samples from the Kalamas River (Northwest Greece), a mid-size river that runs through agricultural and NATURA-protected areas, but also receives urban sewage from a large city through a manmade ditch. Samples from three different locations between the exit of the ditch and the estuary, during three different months showed that temporal differences of taxonomic and functional diversity were more pronounced than spatial ones, and <1% of total taxa were shared among all samples, revealing a highly dynamic ecosystem. Comparisons of gene diversity with other aquatic habitats showed that only the high flow winter samples resembled more to freshwater environments while samples during the decreased water flow months were dominated by sewage inputs and soil-related organisms. Notably, microbial human gut signals were detectable over background freshwater and soil/runoff related signals, even at tens of kilometers downstream the city. These findings revealed the significance of allochthonous inputs on the composition and dynamics of river bacterial communities, and highlighted the potential of metagenomics for source tracking purposes.


Dorsal muscle fatigue increases thoracic spine curvature in all-out recreational ergometer rowing.
The purpose of this study was to investigate fatigue-related changes in spinal kinematics, kinetics, and muscle activity of back muscles during a 2000 m all-out ergometer rowing performance. We analyzed ten male subjects with experience in both rowing and CrossFit exercises. We applied a novel kinematic method to describe spine curvature, determined bending moments at the spine using inverse dynamics and collected EMG data. We identified significant increases in spine curvature of the thoracic spine (i.e. vertebrae Th6 to Th11). Significant increases in peak moments were found only at the upper spine (i.e. Th2). We found no significant changes in EMG amplitudes, while the frequency analysis showed significant decreases in the mean frequencies (MNF) for the M. latissimus dorsi, the M. trapezius descendens and the M. deltoideus posterior. No significant changes on MNF were found for the Mm. erector spinae. We hypothesize that the significant increase in curvature for the thoracic spine is connected to the fatigued back muscles, especially the Mm. trapezius descendens, and might lead to an unbalanced loading of intervertebral discs and other structures. These findings are particularly important for athletes and coaches in CrossFit as strenuous rowing intervals are combined with technical exercises with high loads on the back and spine (e.g. power and Olympic lifting) leading to impaired muscular stabilization and potentially to an increased injury risk.


[Effect and mechanism of total flavonoids of Lichi Semen on CCl_4-induced liver fibrosis in rats, and prediction of Q-marker].
This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.


Survival after lung transplantation for cystic fibrosis in Sweden.
In Sweden, lung transplantation has been performed in patients with end-stage lung disease since 1990. We assessed survival after lung transplantation for cystic fibrosis (CF) with focus on early mortality and outcome for patients infected with certain multiresistant bacteria, considered a relative contraindication for lung transplantation. Review of CF and transplant databases and patient charts. The Kaplan-Meier method and log-rank test were used for survival analysis and group comparison. From November 1991 to December 2014, 115 transplantations were performed in 106 CF patients (9 retransplantations): 3 heart-lung, 106 double lung-, 1 double lobar- and 5 single lung transplantations, constituting 13% (115/909) of all lung-transplant procedures performed in Sweden. The mean age at surgery was 31 (SD 10, range 10-61) years and there were 48% females. Overall 1-year survival after lung transplantation for CF was 86.4%, 5-year survival was 73.7% and 10-year survival was 62.4%. The mean and median survival after transplantation were 13.1 (95% confidence interval (CI): 11-15.3) and 14.6 (95% CI: 9.3-19.8) years, respectively, and there was no significant difference for gender or transplant centre. Extracorporeal membrane oxygenation was used as a bridge to transplantation in 11 cases and five patients received reconditioned lungs. Vascular and infectious complications contributed to eight deaths within the first three postoperative months. The mean survival for 14 patients infected pretransplant with Mycobacterium abscessus or Burkholderia cepacia complex was 8.8 (95% CI: 6.1-11.6) years compared to 13.2 (95% CI: 10.9-15.8) years for patients negative for these bacteria. Nineteen patients (14% of all listed), of whom three were listed for retransplantation, died while waiting a median time of 94 days (range 4 days-2.5 years) after listing. Survival after lung transplantation in Sweden is good, also for patients with pretransplant infection with M. abscessus or B. cepacia complex, and comparable to international data.


Demographic associations for autoantibodies in disease-free individuals of a European population.
The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto)immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.


Diagnostic difficulty identifying Apophysomyces trapeziformis septic arthritis in a patient with multiple myeloma.
Mucormycosis is a rare fungal infection, but can cause substantial morbidity and mortality in both immunocompromised and immunocompetent patients. Apophysomyces is a mucormycetes species ubiquitous in nature, particularly in soil, decaying wood and other organic matter. Apophysomyces is known to cause cutaneous fungal infections, particularly after penetrating trauma. Septic arthritis is a rare clinical manifestation. We describe a case of Apophysomyces trapeziformis causing septic arthritis of the knee of a patient with multiple myeloma. He was treated multiple times for bacterial septic arthritis with minimal improvement. Surgical tissue specimens finally grew mucoraceous mould, and DNA sequencing and morphological assessment of spores identified the mould as A. trapeziformis. The patient was treated with amphotericin B and posaconazole, but ultimately required an above-the-knee amputation for definitive treatment. This case illustrates the need to evaluate for fungal infection in a persistent septic arthritis that is culture negative and refractory to empiric antibiotics, particularly in an immunocompromised individual. It also shows the importance of a thorough social history and adequate tissue specimens for culture.


CRISPR-Cas9 knockin mice for genome editing and cancer modeling.
CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated Kras(G12D) mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.


Fabrication of N-doped TiO2 coatings on nanoporous Si nanopillar arrays through biomimetic layer by layer mineralization.
Si/N-doped TiO2 core/shell nanopillar arrays with a nanoporous structure are fabricated through a simple protein-mediated TiO2 deposition process. The Si nanopillar arrays are used as templates and alternatively immersed in aqueous solutions of catalytic molecules (protamine, PA) and the titania precursor (titanium(iv) bis(ammonium lactato)dihydroxide, Ti-BALDH) for the layer by layer mineralization of a PA/TiO2 coating. After a subsequent calcination, a N-doped TiO2 layer is formed, and its thickness could be controlled by varying the cycles of deposition. Moreover, the nanoporous structure of the Si nanopillars strongly affects the formation of the TiO2 layer. The obtained Si/TiO2 nanocomposites show significantly improved solar absorption compared with commercially purchased TiO2 nanoparticles.


Cutaneous vasoproliferative lesions in goats.
Abstract. In a retrospective survey of caprine neoplastic disease, eight masses were diagnosed as cutaneous vascular tumors. The typical clinical presentation was a solitary raised, bleeding mass. No predilection with regard to age, breed, sex, or anatomic location was found. Reevaluation of the microscopic features of the masses resulted in diagnoses of hamartoma (2), hemangioma (4), and hemangiosarcoma (2). An endothelial cell origin was confirmed in all seven tumors tested immunohistochemically for factor VIII-related antigen. Although rarely reported, goats display a range of cutaneous vascular growth abnormalities similar to those observed in other domestic animals.