Paid paternity leave-taking in the United States.
Surprisingly few studies have focused on paternity leave-taking in the U.S. This study utilizes data from three national datasets to provide a comprehensive examination of the attitudes, practices, and predictors of paid paternity leave-taking in the U.S. Specifically, this study focuses on (a) describing attitudes towards fathers receiving a share of paid parental leave, (b) describing rates and lengths of paid paternity leave-taking, and (c) analyzing the extent to which economic capital, cultural capital, social capital, and father identities predict paternity leave-taking practices. The results indicate that most people support fathers receiving a share of paid parental leave in the U.S. Yet, rates of paid paternity leave-taking are relatively low and the majority of fathers who take paid leave take only one week or less. Economic capital, cultural capital, social capital, and father identities that prioritize engaged fathering are positively associated with taking paid leave and taking longer periods of leave. Overall, the results emphasize that the current structure of U.S. paternity leave policies seems to limit access to paid paternity leave and contribute to patterns of inequality due to more advantaged fathers having greater access and ability to take paid paternity leave than less advantaged fathers.


Structure of the Borrelia Bacteriophage φBB1 Procapsid.
Bacteriophages of Borrelia burgdorferi are a biologically important but under-investigated feature of the Lyme disease-causing spirochete. No virulent borrelial viruses have been identified, but all B. burgdorferi isolates carry a prophage φBB1 as resident circular plasmids. Like its host, the φBB1 phage is quite distinctive and shares little sequence similarity with other known bacteriophages. We expressed φBB1 head morphogenesis proteins in Escherichia coli which resulted in assembly of homogeneous prolate procapsid structures and used cryo-electron microscopy to determine the three-dimensional structure of these particles. The φBB1 procapsids consist of 415 copies of the major capsid protein and an equal combined number of three homologous capsid decoration proteins that form trimeric knobs on the outside of the particle. One of the end vertices of the particle is occupied by a portal assembled from twelve copies of the portal protein. The φBB1 scaffolding protein is entirely α-helical and has an elongated shape with a small globular domain in the middle. Within the tubular section of the procapsid, the internal scaffold is built of stacked rings, each composed of 32 scaffolding protein molecules, which run in opposite directions from both caps with a heterogeneous part in the middle. Inside the portal-containing cap, the scaffold is organized asymmetrically with ten scaffolding protein molecules bound to the portal. The φBB1 procapsid structure provides better insight into the vast structural diversity of bacteriophages and presents clues of how elongated bacteriophage particles might be assembled.


Agricultural Capacity to Increase the Production of Select Fruits and Vegetables in the US: A Geospatial Modeling Analysis.
The capacity of US agriculture to increase the output of specific foods to accommodate increased demand is not well documented. This research uses geospatial modeling to examine the capacity of the US agricultural landbase to increase the per capita availability of an example set of nutrient-dense fruits and vegetables. These fruits and vegetables were selected based on nutrient content and an increasing trend of domestic production and consumption. Geographic information system models were parameterized to identify agricultural land areas meeting crop-specific growing requirements for monthly precipitation and temperature; soil depth and type; cropland availability; and proximity to existing production centers. The results of these analyses demonstrate that crop production can be expanded by nearly 144,000 ha within existing national production centers, generating an additional 0.05 cup-equivalents of fruits and vegetables per capita per day, representing a 1.7% increase above current total F&V availability. Expanding the size of national crop production centers can further increase the availability of all F&V by 2.5%-5.4%, which is still less than the recommended amount. Challenges to increasing F&V production in the US include lack of labor availability, barriers to adoption among producers, and threats to crop yields from environmental concerns.


Comparison of direct immunofluorescence, modified acid-fast staining, and enzyme immunoassay techniques for detection of Cryptosporidium spp in naturally exposed kittens.
To evaluate a modified Ziehl-Neelsen acid-fast staining technique (mZN), a direct immunofluorescence detection procedure (DIF), and 3 commercial enzyme immunoassays (EIAs) for detection of Cryptosporidium oocysts in fecal specimens from kittens. Prospective study. 416 fecal specimens collected from 104 randomly selected domestic shorthair kittens (8 to 16 weeks of age) that were naturally exposed to Cryptosporidium spp. Fresh fecal specimens were collected once daily for 4 consecutive days and processed immediately. Sensitivities of mZN, DIF, and 3 commercial EIAs (EIA-1, EIA-2, and EIA-3) were estimated and compared. EIA-2 had the highest sensitivity on day 1 (89%), followed by EIA-1 (80%), and mZN (72%). EIA-3 had the lowest sensitivity on day 1 (15%). EIA-2, EIA-1, and mZN had similar sensitivities after 2 consecutive fecal examinations (approx 90%). Determination of specificities was compromised by the small number of cats that had negative results for all tests (n = 3). Results suggest that EIA-2 and EIA-1 had the highest sensitivities when only a single fecal specimen was examined; however, mZN and EIA-1 had similar sensitivities when 2 consecutive fecal specimens were examined. The higher costs of EIA-2 and EIA-1 may be offset by the tests' high sensitivity, simplicity of use, and ease of interpretation and by savings in technician time.


Association of retinal vessel calibre and visual outcome in eyes with diabetic macular oedema treated with ranibizumab.
The study aims to identify the association between the baseline retinal vascular calibre and visual outcome of patients with diabetic macular oedema (DMO) treated with intravitreal ranibizumab. The 1-M field (as defined in the ETDRS study) of the digital colour fundus photographs of DMO patients who had been treated primarily with ranibizumab in a clinical trial was assessed. Of the 84 patients, 25 had gradable retinal photographs that could be subjected to analyses by the Interactive Vessel Analysis (IVAN) software at baseline. The average retinal vascular calibre of the six largest venules (CRVE) and the six largest arterioles (CRAE) in the peripapillary area (0.5 and 1 disc diameter from the optic disc margin) was measured. The relationship between CRVE and CRAE at baseline and the change in visual acuity at month 12 was assessed using the Mann-Whitney U test. Ten eyes from 10 patients who had shown an improvement of ≥2 lines of best corrected visual acuity (BCVA) at month 12 had a wider baseline CRVE (248.3±24.5 μm) compared with the 15 eyes from 15 patients who did not show the improvement of ≥2 lines (226.6±44.8 μm, P<0.05). The baseline CRAE did not differ significantly in these patients (156.1±22.7 vs 142±17.5 μm, P=0.17). A wider baseline retinal venular calibre may be a predictor of better visual outcome in DMO eyes treated with ranibizumab. Further prospective studies with a larger sample size and a broader range of disease severity and visual acuity are needed to confirm this finding.


[The clinical instrumental evaluation of treatment efficacy in patients with concomitant atherosclerosis of the coronary, cerebral and peripheral arteries].
The loading tests, instrumental and biochemical methods were employed to study the effect of mildronate, dalargin, rokornal, gevilon, dibunol, emoxipine and plasmapheresis on the coronary, cerebral, peripheral circulation, the level of cholesterol, its fractions and triglycerides in 247 patients suffering from atherosclerosis. Mildronate, dalargin, rokornal, emoxipine and plasmapheresis were shown to exert a beneficial effect on the regional circulation, lipid metabolism and can be used in the treatment of patients with concomitant forms of atherosclerosis.


Muscle activation and energy expenditure of sedentary behavior alternatives in young and old adults.
The physiological mechanisms that underlie the metabolic benefits of breaking up sedentary behavior (SB) have yet to be determined. The purpose of this study is to compare energy expenditure (EE) and muscle activation (MA) responses to sitting and four SB alternatives in younger and older adults. Twenty-two adults, grouped by age (21-35 and 62-76 years), completed five randomly ordered 20 min tasks: (1) continuous sitting (Sit), (2) sitting on a stability ball (Ball), (3) continuous standing (Stand), (4) sitting interrupted by walking (S/W), and (5) sitting interrupted by standing (S/S). Muscle activation of two upper (trapezius and erector spinae) and two lower (rectus femoris and medial gastrocnemius) body muscles and total body EE were measured continuously. A linear mixed model using gender and age as a covariate with Bonferroni adjustment were used to determine significant differences between tasks. Collectively, S/W produced significantly higher MA and EE compared with Sit (p < 0.001). Stand and Ball provided significantly greater EE, but not MA, compared to Sit (p < 0.05), while S/S did not significantly change EE or MA compared to Sit. There were no net EE differences when comparing age groups across the tasks. Upper body MA was not consistent in both age groups across tasks. Specifically, during S/W the upper body MA of older adults (9.7 ± 1.5% MVC) was double that of young adults (4.8 ± 0.7% MVC, p = 0.006). Lower body MA responded similarly to all tasks in both age groups. Disrupting sitting with walking produced the largest increase in EE and MA compared to other SB alternatives in both age groups. These results are important considering the wide use of SB alternatives by researchers and public health practitioners.


Signal averaged P wave compared with standard electrocardiography or echocardiography for prediction of atrial fibrillation after coronary bypass grafting.
To define the clinical value of the signal averaged P wave (SAPW) and to compare it with the standard electrocardiogram (ECG), echocardiogram, and clinical assessment for the prediction of atrial fibrillation after coronary bypass grafting (CABG). Prospective validation cohort study. Regional cardiothoracic centre. 201 unselected patients undergoing first elective CABG were recruited over six months. Patients requiring concomitant valve surgery were excluded. Age, sex, cardiothoracic ratio, and cardioactive drugs were noted. P wave specific SAPW recordings, ECG, and M mode echocardiograms from which left atrial diameter was measured were performed within 24 hours of surgery. Filtered P wave duration (SAPWD), spatial velocity, and energy were calculated from the SAPW. From the ECG, lead II P wave duration, P terminal force in lead V1, total P wave duration, and isoelectric interval were measured. Patients had Holter monitoring for 48 hours postoperatively and daily ECGs until discharge. Two patients died (1%) and 10 were unsuitable for analysis (5%). Of the remaining 189, 51 (27%) had atrial fibrillation (AF) lasting > 1 hour at a mean of 2 (0.5 to 7) days after CABG. Of the variables examined, only SAPWD (AF group 148 (SD 12), v 142 (14) ms, P = 0.008) and male sex (AF group 96%, v 78%, P < 0.01) were significantly different. A prospectively defined SAPWD of > 141 ms predicted atrial fibrillation with positive and negative predictive accuracies of 34% and 83%. Logistic regression analysis identified both male sex and SAPWD as significant independent predictors of postoperative atrial fibrillation. Signal averaged P wave duration was a better predictor of atrial fibrillation after coronary bypass grafting than standard electrocardiographic or echocardiographic criteria. The predictive value of this test is such that it is likely to be useful in the design of prospective trials of prophylactic antiarrhythmic treatment but is of limited use using current techniques in the clinical management of individual patients.


[Immunological response of patient with chronic salphingo-oophoritis to interference currents used in electrical sleep and balneotherapy].
The study included 105 women of a reproductive age with chronic nonspecific salpingooophoritis. The women were transcerebrally exposed to interference currents (IC). The immunological examination revealed that IC have an immunocorrecting effect on both cellular and humoral links of the immune system, correct imbalance of the immunoregulatory subpopulations confirmed by increased immunoregulatory index. Inclusion of balneotherapy potentiates analgetic, anti-inflammatory effects of transcerebral IC therapy, regulates balance of immunoregulatory T-cell subpopulations due to better differentiation of T-lymphocytes in the thymus.


Neurogenesis drives stimulus decorrelation in a model of the olfactory bulb.
The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb--the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells--are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures.


Online aerosol mass spectrometry of single micrometer-sized particles containing poly(ethylene glycol).
The analysis of poly(ethylene glycol) (PEG)-containing particles by online single particle aerosol mass spectrometers equipped with laser desorption/ionization (LDI) is reported. We demonstrate that PEG-containing particles are useful in the development of aerosol mass spectrometers because of their ease of preparation, low cost, and inherently recognizable mass spectra. Solutions containing millimolar quantities of PEGs were nebulized and, after drying, the resultant micrometer-sized PEG-containing particles were sampled. LDI (266 nm) of particles containing NaCl and PEG molecules of average molecular weight<500 Da generated mass spectra reminiscent of mass spectra of PEG collected by other mass spectrometer platforms including the characteristic distribution of positive ions (Na+ adducts) separated by the 44 m/z units of the ethylene oxide units separating each degree of polymerization. PEGs of average molecular weight>500 Da were detected from particles that also contained the tripeptide tyrosine-tyrosine-tyrosine or 2,5-dihydroxybenzoic acid, which were added to nebulized solutions to act as matrices to assist LDI using pulsed 266 nm and 355 nm lasers, respectively. Experiments were performed on two aerosol mass spectrometers, one reflectron and one linear, that each utilize two time-of-flight mass analyzers to detect positive and negative ions created from a single particle. PEG-containing particles are currently being employed in the optimization of our bioaerosol mass spectrometers for the application of measurements of complex biological samples, including human effluents, and we recommend that the same strategies will be of great utility to the development of any online aerosol LDI mass spectrometer platform.


Lepidoptera and pyrrolizidine alkaloids Exemplification of complexity in chemical ecology.
Pyrrolizidine alkaloids (PAs) are defensive secondary metabolites found in numerous plant groups. Various insects belonging to different orders have special requirements for these compounds and sequester them from such plants for their own defense and often as pheromone precursors. The fitness of these insects depends on PAs and, in some cases, PAs even act as regulators of androconial organ development. This article discusses selected behavioral, chemical, physiological, and phylogenetic aspects of insect-PA relationships, and raises questions about the complex interactions of the variety of PA-related adaptations as they occur among a diverse array of species. Although many superficial similarities are recognized, few generalizations can yet be drawn. However, insect-PA relationships not only exemplify basic features of chemical ecology but illustrate a multiplicity of aspects and adaptations, which we should expect to find in any thorough study of insect-plant relationship.


The Stability of Physician-Specific Episode Costs for Urologic Cancer Surgery: Implications for Urologists Under the Merit-Based Incentive Program.
To evaluate the stability of physician-specific episode payments for prostatectomy, nephrectomy, and cystectomy in the context of value-based purchasing programs, such as the merit-based incentive payment system. We utilized Surveillance, Epidemiology and End Results-Medicare data to identify patients aged 66-99 who underwent a prostatectomy, nephrectomy, or cystectomy from 2008 to 2012. We calculated each surgeon's average 90-day episode payment by procedure. Next, we examined payment differences between the most and least expensive quartile providers. For the most expensive quartile of physicians in 2010, we examined their spending quartile in 2011. Finally, we evaluated the correlation in spending over time and across procedures. We identified 14,585 patients who underwent surgery by one of 1895 unique clinicians. Differences in payments between the highest and lowest quartiles were $5881, $17,714, and $40,288 for prostatectomy, nephrectomy, and cystectomy, respectively. Only 39%, 16%, and 13% of physicians that were in the highest spending quartile for prostatectomy, nephrectomy, and cystectomy in 2010 were also in the most expensive quartile in 2011. Although we observed weak correlation in year-to-year spending for prostatectomy (0.108, P = .033 to .270, P < .001), annual payments for nephrectomy and cystectomy were not significantly correlated. Finally, there was minimal correlation in surgeon spending across procedures. There is wide variation in physician-specific episode payments for prostatectomy, nephrectomy, and cystectomy. However, physician spending patterns are not stable over time or across procedures, raising concerns about the ability of the cost-based measures in merit-based incentive payment system to change physician behavior and reliably distinguish those providing less efficient or lower quality care.


Inhibition of microvascular endothelial cell proliferation by vitreous following retinal scatter photocoagulation.
Laser photocoagulation of pig retina induced breakdown of the blood-retinal barrier, with the appearance of serum proteins in the vitreous as determined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting techniques. Vitreous from lasered eyes inhibited the proliferation of cultured retinal microvascular endothelial cells in comparison with vitreous from non-lasered control eyes, and the inhibitory effect in the lasered eyes persisted for at least seven days. Inhibition was specific for endothelial cells, since no effect was observed when retinal pericytes or Tenon's fibroblasts were the target cells. These results suggest that indirect scatter photocoagulation may induce regression of neovascularisation by causing breakdown of the blood-retinal barrier and thus releasing into the vitreous serum components which result in inhibition of retinal microvascular endothelial cell growth.


The Potentials of Methylene Blue as an Anti-Aging Drug.
Methylene blue (MB), as the first fully man-made medicine, has a wide range of clinical applications. Apart from its well-known applications in surgical staining, malaria, and methemoglobinemia, the anti-oxidative properties of MB recently brought new attention to this century-old drug. Mitochondrial dysfunction has been observed in systematic aging that affects many different tissues, including the brain and skin. This leads to increaseding oxidative stress and results in downstream phenotypes under age-related conditions. MB can bypass Complex I/III activity in mitochondria and diminish oxidative stress to some degree. This review summarizes the recent studies on the applications of MB in treating age-related conditions, including neurodegeneration, memory loss, skin aging, and a premature aging disease, progeria.


Knockout of the 15 kDa selenoprotein protects against chemically-induced aberrant crypt formation in mice.
Evidence suggests that selenium has cancer preventive properties that are largely mediated through selenoproteins. Our previous observations demonstrated that targeted down-regulation of the 15 kDa selenoprotein (Sep15) in murine colon cancer cells resulted in the reversal of the cancer phenotype. The present study investigated the effect of Sep15 knockout in mice using a chemically-induced colon cancer model. Homozygous Sep15 knockout mice, and wild type littermate controls were given four weekly subcutaneous injections of azoxymethane (10 mg/kg). Sep15 knockout mice developed significantly (p<0.001) fewer aberrant crypt foci than controls demonstrating that loss of Sep15 protects against aberrant crypt foci formation. Dietary selenium above adequate levels did not significantly affect aberrant crypt foci formation in Sep15 knockout mice. To investigate molecular targets affected by loss of Sep15, gene expression patterns in colonic mucosal cells of knockout and wild type mice were examined using microarray analysis. Subsequent analyses verified that guanylate binding protein-1 (GBP-1) mRNA and protein expression were strongly upregulated in Sep15 knockout mice. GBP-1, which is expressed in response to interferon-γ, is considered to be an activation marker during inflammatory diseases, and up-regulation of GBP-1 in humans has been associated with a highly significant, increased five-year survival rate in colorectal cancer patients. In agreement with these studies, we observed a higher level of interferon-γ in plasma of Sep15 knockout mice. Overall, our results demonstrate for the first time, that Sep15 knockout mice are protected against chemically-induced aberrant crypt foci formation and that Sep15 appears to have oncogenic properties in colon carcinogenesis in vivo.


Supplemental role of the Ames mutation assay and gap junction intercellular communication in studies of possible carcinogenic compounds from diesel exhaust particles.
This study presents a new strategy for the carcinogenic evaluation of complex chemical mixtures based on genotoxic and nongenotoxic assays. We studied the ability of organic extracts of diesel exhaust particles (DEP) to induce point mutations in five different Salmonella typhimurium strains (Ames test) and to inhibit gap junction intercellular communication (GJIC) in rat liver epithelial cell lines. A crude extract of DEP was prepared by extraction with dichloromethane (DCM), and fractionated according to polarity into five fractions: aliphatic hydrocarbons, polycyclic aromatic hydrocarbons (PAH), nitro-PAH, dinitro-PAH, and polar compounds. Statistical experimental design, multivariate data analysis, and modeling were used to quantify the mutagenicity of individual and combined DEP fractions in the Ames assay. Quantitative determination of GJIC was carried out using a recently described combination of scrape loading and digital image analysis. Both assays responded to the DEP extract, but the responses were due to different fractions. The nitro-PAH fraction showed the strongest mutagenic potential, followed by the dinitro-PAH fraction. The effect on GJIC was due to the fraction containing the polar components, followed by the dinitro-PAH fraction. The extract was found to induce both basepair substitutions and frameshift mutations, through activation by bacterial nitroreductases. Hyperphosphorylation of connexin43, the major connexin in the epithelial cell lines, was less evident for DEP extract than for other communication inhibitors such as phorbol esters and growth factors, and consequently inhibitors of the protein kinase C (PKC) and mitogen-activated protein (MAP) kinase pathway were unable to counteract the inhibition by DEP extract. Since the Ames test is a well accepted method to screen for substances with genotoxic activity while inhibition of GJIC is associated with effect of tumor promoters and nongenotoxic carcinogens, it is not surprising but encouraging and interesting that the present data indicate that the two endpoints supplement each other as screening tests and in the evaluation of hazardous compounds in complex mixtures.


[MicroRNA-profiling in breast- and salivary gland-derived adenoid cystic carcinomas].
Adenoid cystic carcinoma is a salivary gland-derived malignant tumor, but rarely it can originate from the breast, too. The salivary gland-derived form shows a very aggressive clinical outcome, while adenoid cystic carcinoma of the breast has mostly a very good prognosis. The aim of the authors was to compare the miRNA-expression profile of breast- and salivary gland-derived cases. The miRNA-profiles of two salivary gland derived and two breast-derived adenoid cystic carcinoma tissues as well as one normal breast and one salivary gland tissues were analysed using the Affymetrix® Gene Chip. The expression of some miRNAs differed in the tumor tissues compared to their controls: the let-7b was overexpressed in salivary gland-derived adenoid cystic carcinoma, while decreased in breast-derived adenoid cystic carcinoma. In addition, the miR-24 was decreased in salivary gland-derived but overexpressed in breast-derived adenoid cystic carcinomas. The miR-181a-2* was only detected in salivary gland-derived adenoid cystic carcinomas. Through post-transcriptional regulation of the genes, the diverse expression of some miRNAs may partially explain the diverse clinical outcome of salivary gland-derived and breast-derived adenoid cystic carcinomas.


Differential expression and costimulatory effect of 4-1BB (CD137) and CD28 molecules on cytokine-induced murine CD8(+) Tc1 and Tc2 cells.
In this study we report that the relative expression of 4-1BB (CD137) and CD28 molecules can differentially be modulated on CD8(+) T cells by combinations of various cytokines and anti-cytokine antibodies. During allostimulation of naive CD8(+) T cells in the presence of IL-2, IFN-gamma, IL-12, and anti-IL-4, they evolved into IL-2, IFN-gamma-producing Tc1 cells and showed inability to upregulate 4-1BB expression but not CD28. On the other hand, the Tc2 cells, generated in the presence of allogeneic APCs, IL-2, IL-10, IL-4, and anti-IFN-gamma, demonstrated intact and elevated 4-1BB and CD28 molecules. Activation of Tc1 and Tc2 cells with anti-CD3 and plate-bound anti-4-1BB and anti-CD28 mAbs revealed differential proliferative and cytokine secretory patterns. The 4-1BB signaling in the context of anti-CD3 as first signal led to the increased secretion of IL-4 by the Tc2 cells and not by Tc1 cells, while CD28 triggering produced IL-4 from Tc2 and IL-2 and IFN-gamma from Tc1 cells. Flow cytometric analysis of cell surface expression on Tc1 and Tc2 cells strengthened our observation that 4-1BB expression but not CD28 is poorly expressed on Tc1 cells. Both of the polarized CD8(+) T cell subsets exhibited comparable cytotoxic abilities and perforin and granzyme expression. The regeneration of 4-1BB expression is possible on Tc1 cells when back cultured in a Tc2 cytokine environment, but its expression could not be significantly altered on the Tc2 population unless IL-12 was included in the system.


Advances in responses of microalgal-bacterial symbiosis to emerging pollutants in wastewater.
Nowadays, emerging pollutants are widely used and exist in wastewater, such as antibiotics, heavy metals, nanoparticle and microplastic. As a green alternative for wastewater treatment, microalgal-bacterial symbiosis has been aware of owning multiple merits of low energy consumption and little greenhouse gas emission. Thus, the responses of microalgal-bacterial symbiosis to emerging pollutants in wastewater treatment have become a hotspot in recent years. In this review paper, the removal performance of microalgal-bacterial symbiosis on organics, nitrogen and phosphorus in wastewater containing emerging pollutants has been summarized. The adaptation mechanisms of microalgal-bacterial symbiosis to emerging pollutants have been analyzed. It is found that antibiotics usually have hormesis effects on microalgal-bacterial symbiosis, and that microalgal-bacterial symbiosis appears to show more capacity to remove tetracycline and sulfamethoxazole, rather than oxytetracycline and enrofloxacin. Generally, microalgal-bacterial symbiosis can adapt to heavy metals at a concentration of less than 1 mg/L, but its capabilities to remove contaminants can be significantly affected at 10 mg/L heavy metals. Further research should focus on the influence of mixed emerging pollutants on microalgal-bacterial symbiosis, and the feasibility of using selected emerging pollutants (e.g., antibiotics) as a carbon source for microalgal-bacterial symbiosis should also be explored. This review is expected to deepen our understandings on emerging pollutants removal from wastewater by microalgal-bacterial symbiosis.


Midwives' views, experiences and feelings of confidence surrounding vaginal breech birth: A qualitative study.
to explore midwives' views, experiences and feelings of confidence surrounding vaginal breech birth (VBB). a qualitative study was conducted with 12 participants using three focus group discussions. Data were transcribed verbatim and thematic analysis was used to analyse the data. UK midwives were recruited from different geographical areas who worked in community areas, hospital areas and as independent practitioners. three themes were identified. Firstly, midwives viewed VBB in dimensions of normality, perceiving it to be an unusual norm on one hand while also acknowledging potential problems. Secondly, midwives expressed varied feelings of preparedness; the majority feeling inexperienced and under-prepared with VBB, yet more confident when supported by other colleagues. Lastly, midwives described restrictions on women's choice of VBB; perceiving other practitioners as limiting women's choices through coercion, yet providing a balanced choice themselves. there should be an opportunity for midwives to be mentored by a more experienced practitioner in VBB. Practice areas should develop a guideline for VBB which acknowledges the role of the midwife in facilitating normal breech birth. Balanced written and verbal information on VBB may further assist decision making for women considering a VBB. Education in VBB should focus on learning what is normal for VBB and must emphasise the importance of teamwork and understanding roles within multidisciplinary teams.


[Lhermitte's sign].
Besides Babinski's, Lhermitte's sign is likely the eponym mostly used in the neurological literature. We review here the history of this eponym as well as recent advances on its pathophysiology and treatment. Lhermitte's phenomenon is, on one hand, a symptom as it is spontaneously explained by patients, and, on the other hand, a sign as it may be triggered by flexion of the nape. Initially described after head and cervical spine trauma, firstly by Marie and then by Babinski, it was Jean Lhermitte who recognized on it an etiological specificity, namely, a demyelinating sign of cervical spinal posterior cords. He also made a pathophysiological interpretation of the phenomenon, namely, a stretching of posterior cords during flexion of the neck. All authors agree that this phenomenon is more common in multiple sclerosis, although it has been descibed in many other conditions. The history of how this sign was hatched, whose pathophysiology remains a mystery, is fascinating. And it is fascinating the fact that patients compare the phenomenon with a current, especially if we bear in mind that few people may have suffered an electrocution, mainly in that time when just a few ones could actually enjoy domestic electricity.


Polymers of sodium-N-undec-10-ene-1-oyl taurate and sodium-N-undec-10-ene-1-oyl aminoethyl-2-phosphonate as pseudostationary phases for electrokinetic chromatography.
The use of micelle polymers, a class of polysoaps with a polymerized hydrophobic interior and a charged hydrophillic exterior, as pseudostationary phases in electrokinetic chromatography has generated significant interest. Their stable structure has been shown to provide significant advantages over conventional micelles when used as pseudostationary phases. In previous studies, micelle polymers have had carboxylate and sulfate head groups. These chemistries have limitations: carboxylate micelle polymers precipitate out of solution at pH less than seven or eight and sulfate head groups are not stable to hydrolysis and are hydrolyzed during polymerization. Additionally, while the chemical selectivity of conventional micelles varies with head group chemistry, no significant differences in chemical selectivity were observed between analogous polymers with sulfate and carboxylate groups. To overcome the limitations of carboxylate and sulfate head groups, and to further investigate the chemical selectivity of micelle polymers, poly(sodium-N-undec-10-ene-1-oyl-taurate) and poly(sodium-N-undec-10-ene-1-oyl-ethyl-2-phosphonate) micellar polymers have been synthesized and characterized as pseudostationary phases. These polymers have amide functionality and stable, strongly acidic sulfonate and phosphonate head groups. These polymers did provide improved solubility at low pH, and are stable under the conditions studied. The chromatographic performance and chemical selectivity of the polymers has been studied by several methods, including linear solvation energy relationships. Poly(sodiumN-undec-10-ene-1-oyl-taurate) has greater electrophoretic mobility than other polymers of this type, and can be used for the separation of hydrophobic compounds. The polymers do exhibit unique selectivity, but the differences in selectivity are not significant for the majority of compounds studied.


Genomic signatures in the coral holobiont reveal host adaptations driven by Holocene climate change and reef specific symbionts.
Genetic signatures caused by demographic and adaptive processes during past climatic shifts can inform predictions of species' responses to anthropogenic climate change. To identify these signatures in Acropora tenuis, a reef-building coral threatened by global warming, we first assembled the genome from long reads and then used shallow whole-genome resequencing of 150 colonies from the central inshore Great Barrier Reef to inform population genomic analyses. We identify population structure in the host that reflects a Pleistocene split, whereas photosymbiont differences between reefs most likely reflect contemporary (Holocene) conditions. Signatures of selection in the host were associated with genes linked to diverse processes including osmotic regulation, skeletal development, and the establishment and maintenance of symbiosis. Our results suggest that adaptation to post-glacial climate change in A. tenuis has involved selection on many genes, while differences in symbiont specificity between reefs appear to be unrelated to host population structure.


Endothelial dysfunction in pulmonary arteries of patients with mild COPD.
To investigate whether endothelial dysfunction of pulmonary arteries (PA) is present in patients with mild chronic obstructive pulmonary disease (COPD) and to what extent it is related to the morphological abnormalities of PA, we studied 41 patients who underwent lung resection. Patients were divided into the following groups: nonsmokers (n = 7), smokers with normal lung function (n = 13), and COPD (n = 21). Endothelium-dependent relaxation mediated by nitric oxide was evaluated in vitro in PA rings exposed to cumulative concentrations of acetylcholine (ACh) and ADP. Structural abnormalities of PA were assessed morphometrically. PA of COPD patients developed lower maximal relaxation in response to ADP than both nonsmokers and smokers (P < 0.05 each) and a trend to reduced relaxation in response to ACh (P = 0.08). Maximal relaxation to ADP correlated with the degree of airflow obstruction (r = 0.48, P < 0. 01). Morphometrical analysis of PA revealed thicker intimas, especially in small arteries, in both smokers and COPD compared with nonsmokers (P < 0.05 each). We conclude that endothelial dysfunction of PA is already present in patients with mild COPD. In these patients, as well as in smokers with normal lung function, small arteries show thickened intimas, suggesting that tobacco consumption may play a critical role in the pathogenesis of pulmonary vascular abnormalities in COPD.


Adaptive Design of Fluorescence Imaging Systems for Custom Resolution, Fields of View, and Geometries.
Objective and Impact Statement: We developed a generalized computational approach to design uniform, high-intensity excitation light for low-cost, quantitative fluorescence imaging of in vitro, ex vivo, and in vivo samples with a single device. Introduction: Fluorescence imaging is a ubiquitous tool for biomedical applications. Researchers extensively modify existing systems for tissue imaging, increasing the time and effort needed for translational research and thick tissue imaging. These modifications are application-specific, requiring new designs to scale across sample types. Methods: We implemented a computational model to simulate light propagation from multiple sources. Using a global optimization algorithm and a custom cost function, we determined the spatial positioning of optical fibers to generate 2 illumination profiles. These results were implemented to image core needle biopsies, preclinical mammary tumors, or tumor-derived organoids. Samples were stained with molecular probes and imaged with uniform and nonuniform illumination. Results: Simulation results were faithfully translated to benchtop systems. We demonstrated that uniform illumination increased the reliability of intraimage analysis compared to nonuniform illumination and was concordant with traditional histological findings. The computational approach was used to optimize the illumination geometry for the purposes of imaging 3 different fluorophores through a mammary window chamber model. Illumination specifically designed for intravital tumor imaging generated higher image contrast compared to the case in which illumination originally optimized for biopsy images was used. Conclusion: We demonstrate the significance of using a computationally designed illumination for in vitro, ex vivo, and in vivo fluorescence imaging. Application-specific illumination increased the reliability of intraimage analysis and enhanced the local contrast of biological features. This approach is generalizable across light sources, biological applications, and detectors.


Spiral spectrum of a Laguerre-Gaussian beam propagating in anisotropic non-Kolmogorov turbulent atmosphere along horizontal path.
Close to the ground, it is generally known that atmospheric turbulence exhibits strong anisotropy, which affects the performance of applications such as free-space optical (FSO) communication. In this paper, we establish a theoretical model for calculating the spiral spectrum, also called the orbital angular momentum (OAM) spectrum, of a Laguerre-Gaussian (LG) beam after propagation through anisotropic turbulence along a horizontal link. This model isolates the effects of anisotropy from other parameters of the turbulence. On the basis of this model, the effects of the anisotropy on the probability density of the OAM spectrum and its corresponding modal crosstalk are studied through numerical examples. Our simulation results show that the width of the OAM spectrum will increase or slightly decrease depending on the specific nature of the anisotropy. In addition, it is demonstrated that the inner scale is more likely to cause modal crosstalk than the outer scale. Some strategies to reduce modal crosstalk in anisotropic turbulence are also discussed. Our results may be useful in OAM-based FSO communication at ground level.


[Cannabis--a drug with dangerous implications for mental health].
Accepting and forgiving attitudes to the use of cannabis in its various forms, such as marijuana or hashish, are not justified, as they may result in dangerous mental health consequences. A theoretical framework for this opinion is provided, including information on the various forms of cannabis available. Case studies presented exemplify possible complications resulting from use of cannabis or its derivatives.


Associations between Problematic Gambling, Gaming, and Internet Use: A Cross-Sectional Population Survey.
While pathological gambling, or gambling disorder, is an established diagnosis, a link to other potential behavioural addictions has been suggested. The present study aimed to investigate whether signs of problem gaming and problematic internet use are related to problem gambling in the general population, while including other potential risk factors. A cross-sectional study design, using an electronical questionnaire, administered through a marketing survey company for relative representativeness with respect to age and gender. Potential correlates of problem gambling were measured in binary analyses, and significant associations were entered in a logistic regression analysis controlling them for one another. Problem gambling, gaming, and internet use were measured through established screening instruments (the CLiP, the GAS, and the PRIUSS). Statistically significant associations were found between problem gambling and both problem gaming and problematic internet use, as well as with male gender. In logistic regression, problem gaming, problematic internet use, and male gender remained associated with problem gambling. After controlling for potential demographic risk factors, problem gaming and problematic internet use may be related to problem gambling, suggesting that these constructs may interact or may share similar risk factors. More research is needed to clarify factors mediating the links between these conditions.


Comprehensive characterization of toxins during progression of inhalation anthrax in a non-human primate model.
Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late-fulminant. We report the comprehensive characterization of anthrax toxins, including total protective antigen (PA), total lethal factor (LF), total edema factor (EF), and their toxin complexes, lethal toxin and edema toxin in plasma, during the course of inhalation anthrax in 23 cynomolgus macaques. The toxin kinetics were predominantly triphasic with an early rise (phase-1), a plateau/decline (phase-2), and a final rapid rise (phase-3). Eleven animals had shorter survival times, mean±standard deviation of 58.7±7.6 hours (fast progression), 11 animals had longer survival times, 113±34.4 hours (slow progression), and one animal survived. Median (lower-upper quartile) LF levels at the end-of-phase-1 were significantly higher in animals with fast progression [138 (54.9-326) ng/mL], than in those with slow progression [23.8 (15.6-26.3) ng/mL] (p = 0.0002), and the survivor (11.1 ng/mL). The differences were also observed for other toxins and bacteremia. Animals with slow progression had an extended phase-2 plateau, with low variability of LF levels across all time points and animals. Characterization of phase-2 toxin levels defined upper thresholds; critical levels for exiting phase-2 and entering the critical phase-3, 342 ng/mL (PA), 35.8 ng/mL (LF), and 1.10 ng/mL (EF). The thresholds were exceeded earlier in animals with fast progression (38.5±7.4 hours) and later in animals with slow progression (78.7±15.2 hours). Once the threshold was passed, toxin levels rose rapidly in both groups to the terminal stage. The time from threshold to terminal was rapid and similar; 20.8±7.4 hours for fast and 19.9±7.5 hours for slow progression. The three toxemic phases were aligned with the three clinical stages of anthrax for fast and slow progression which showed that anthrax progression is toxin- rather than time-dependent. This first comprehensive evaluation of anthrax toxins provides new insights into disease progression.


Intra-operative recording of motor tract potentials at the cervico-medullary junction following scalp electrical and magnetic stimulation of the motor cortex.
Activity in descending motor pathways after scalp electrical and magnetic brain stimulation of the motor cortex was recorded from the exposed cervico-medullary junction in six patients having trans-oral surgery of the upper cervical spine. Recordings during deep anaesthesia without muscle paralysis revealed an initial negative potential (D wave) at about 2 ms with electrical stimulation in five of the six patients. This was followed by a muscle potential which obscured any later waveforms. Magnetic stimulation produced clear potentials in only one patient. The earliest wave to magnetic stimulation during deep anaesthesia was 1-2 ms later than the earliest potential to electrical stimulation. Following lightening of the anaesthetic and the administration of muscle relaxants a series of later negative potentials (I waves) were more clearly seen to both electrical and magnetic stimulation. More I waves were recorded to magnetic stimulation during light anaesthesia than during deep anaesthesia. Increasing the intensity of electrical stimulation also produced an extra late I wave. At the highest intensity of magnetic stimulation the latency of the earliest potential was comparable to the D wave to electrical stimulation. The intervals between these various D and I waves corresponded to those previously described for the timing of single motor unit discharge after cortical stimulation.


Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils.
Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/-) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil-mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases.


Pattern of accessory regions and invasive disease potential in Streptococcus pneumoniae.
The invasive disease potential (IDP) of Streptococcus pneumoniae differs between serotypes, but the reason for this is unknown. A total of 47 pneumococcal isolates from 13 serotypes with different IDPs in humans that belonged to 37 multilocus sequence types were compared by whole genome microarrays and mutant analyses. Approximately 34% of the genes were variable, including 95 genes previously shown by signature-tagged mutagenesis (STM) to be required for invasive disease in mice. Many variable genes were localized to 41 accessory regions (ARs), of which 24 contained genes previously identified by STM as required for invasive disease. Only AR6 and AR34 were preferentially found in isolates of serotypes with high IDPs. Neither AR6, which carries a gene previously identified bySTMas required for invasive disease and encodes a 6-phospho-betaglucosidase, nor the putative adhesin expressed by AR34 was required for mouse virulence in TIGR4. Pneumococci possess a repertoire of ARs that differ between clones and even between isolates of the same clone. The ARs required for invasive disease in humans may be redundant, as no unique pattern distinguished the most invasive clones from others. The ARs that contained genes previously identified by STM as required for virulence in mice were frequently absent from invasive human isolates. Only 1 AR (AR6) was present in almost all isolates from the serotypes with the highest IDP (1, 4, and 7F), whereas it was missing from many others.


Sugarcane Molasses - A Potential Dietary Supplement in the Management of Iron Deficiency Anemia.
Iron deficiency anemia (IDA) is a serious public health problem that debilitates ∼1.6 billion people globally every year, the majority being pregnant women and children from developing countries. In India, for example, in spite of several operational programs at the national level using iron-folic acid and other allopathic interventions, IDA is still prevalent. Traditional medicines, such as Ayurveda, prescribe herbal formulations containing sugarcane derivatives for the management of pandu, a condition similar to IDA. This article reviews molasses, a sugar industry by-product, as a potential raw material to develop nutraceutical products for IDA. Molasses contains iron and its absorption enhancers, such as sulfur, fructose, and copper, which make it a potential dietary supplement for IDA. More research, product development, and evidence of safety and efficacy of molasses in IDA management can provide a tasty and cost-effective dietary supplement, particularly for children. However, there are challenges, such as competition for raw material from refined sugar manufacturers, quality control, etc., that need to be overcome.


Molecular mechanism underlying desensitization of the proton-activated chloride channel PAC.
Desensitization is a common property of membrane receptors, including ion channels. The newly identified proton-activated chloride (PAC) channel plays an important role in regulating the pH and size of organelles in the endocytic pathway, and is also involved in acid-induced cell death. However, how the PAC channel desensitizes is largely unknown. Here, we show by patch-clamp electrophysiological studies that PAC (also known as TMEM206/ASOR) undergoes pH-dependent desensitization upon prolonged acid exposure. Through structure-guided and comprehensive mutagenesis, we identified several residues critical for PAC desensitization, including histidine (H) 98, glutamic acid (E) 94, and aspartic acid (D) 91 at the extracellular extension of the transmembrane helix 1 (TM1), as well as E107, D109, and E250 at the extracellular domain (ECD)-transmembrane domain (TMD) interface. Structural analysis and molecular dynamic simulations revealed extensive interactions between residues at the TM1 extension and those at the ECD-TMD interface. These interactions likely facilitate PAC desensitization by stabilizing the desensitized conformation of TM1, which undergoes a characteristic rotational movement from the resting and activated states to the desensitized state. Our studies establish a new paradigm of channel desensitization in this ubiquitously expressed ion channel and pave the way for future investigation of its relevance in cellular physiology and disease.


Probiotic Lactobacillus spp. act Against Helicobacter pylori-induced Inflammation.
The bacterial species, Helicobacter pylori, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics. Lactobacillus spp., on the other hand, possess probiotic activities that have beneficial effects in humans. However, the mechanisms by which Lactobacillus spp. harbor favorable functions and act against H. pylori infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains, Lactobacillus rhamnosus and Lactobacillus acidophilus, termed GMNL-74 and GMNL-185, respectively, to inhibit H. pylori growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-H. pylori. In addition, an in vitro cell-based model revealed that the inhibition of H. pylori adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the Lactobacillus strains. In vivo studies demonstrated that colonization of H. pylori and induced inflammation in the mouse stomach were also alleviated by these Lactobacillus strains. Furthermore, the abundance of beneficial gut bacteria, including Bifidobacterium spp. and Akkermansia muciniphilia, were significantly increased in H. pylori-infected mice treated with GMNL-74 and GMNL-185. These results demonstrate that Lactobacillus spp. ameliorate H. pylori-induced inflammation and supports beneficial gut specific bacteria that act against H. pylori infection.


Spontaneous membrane transfer through homotypic synapses between lymphoma cells.
Formation of an immunological synapse by T, B, or NK cells is associated with an intercellular transfer of some membrane fragments from their respective target cells. This capture is thought to require effector cell activation by surface recognition of stimulatory ligand(s). However, spontaneous synaptic transfers between homotypic lymphoid cells has never been described. In this study, we show that without adding Ag, resting healthy lymphoid cells and several tumor cell lines are inactive. Conversely, however, some leukemia cell lines including the Burkitt's lymphoma Daudi continuously uptake patches of autologous cell membranes. This intercellular transfer does not involve cytosol molecules or exosomes, but requires cell contact. In homotypic Daudi cell conjugates, this occurs through immunological synapses, involves constitutive protein kinase C and mitogen-activated protein/extracellular signal-regulated kinase kinase activity and strongly increases upon B cell receptor activation. Thus, spontaneous homosynaptic transfer may reflect the hitherto unsuspected autoreactivity of some leukemia cell lines.


[Pulmonary manifestations of autoimmune diseases].
The lung is a unique interface between the antigen and the circulating blood volume. It is submitted to extrinsic/intrinsic challenges and is particularly vulnerable to circulating insulting agents. It is a site of intense immune surveillance, allowing antigen sampling to expand the immunologic repertoire through lymphocyte recirculation. In addition, local inflammatory reactions to antigens are generated. Imaging has an important role in diagnosis of patients with immunologic lung diseases. This group includes autoimmune lung diseases. There are many advantages of plain chest radiography but also significant limitations. It was a revolution in imaging of lung diseases with Computed Tomography (CT), being high resolution an important help in pulmonary interstitium study. This technique has a higher diagnostic accuracy than the conventional chest X-ray both in the detection and the diagnosis of lung diseases, such as autoimmune lung diseases.


Time course of regional function after coronary occlusions of 1- to 120-min duration.
The purpose of this study was to characterize the degree and duration of functional impairment in previously ischemic tissue following coronary artery occlusions of varying duration. Open-chest dogs with left ventricular pressure transducers and ultrasonic segment length crystals were subjected to coronary artery occlusions of 1 (n = 22), 5 (n = 8), 10 (n = 7), 15 (n = 8), 20 (n = 7), 30 (n = 6), 60 (n = 10), or 120 (n = 8) min and segment length motion was measured during 6 h of reperfusion. Active shortening was replaced by passive lengthening during coronary occlusion and regional myocardial blood flow within the ischemic zone was always less than 0.4 ml . min-1 . g-1. Following reperfusion, the improvement of ischemic segment length function was inversely proportional to the duration of coronary occlusion. Function in previously ischemic segment lengths recovered rapidly after 1- and 5-min coronary occlusions, but after occlusions of 10-20 min, there was slow, though incomplete, return of some degree of active shortening yet no evidence of myocardial infarction. With occlusions exceeding 20 min there was persistence of systolic passive lengthening for 6 h despite the absence of infarction in the segment lengths in which function was being evaluated, although infarcted tissue was present ranging from 16.5 +/- 2.6% of the area of ischemia in dogs with 60-min coronary occlusions to 37.2 +/- 4.6% of the area of ischemia in dogs with 120-min occlusions.


Comparison of expression, purification and characterization of a new pectate lyase from Phytophthora capsici using two different methods.
Pectate lyases (PELs) play an important role in the infection process of plant pathogens and also have a commercial significance in industrial applications. Most of the PELs were expressed as soluble recombinant proteins, while a few recombinant proteins were insoluble. The production of a large-scale soluble recombinant PEL would allow not only a more detailed structural and functional characterization of this enzyme but also may have important applications in the food industry. We cloned a new pectate lyase gene (Pcpel2) from Phytophthora capsici. Pcpel2 was constructed by pET system and pMAL system, and both constructs were used to express the PCPEL2 in Escherichia coli BL21 (DE3) pLysS. The expressed products were purified using affinity chromatography and gel filtration chromatography. The purity, specific activity and pathogenicity of the purified PCPEL2 expressed by the pMAL system were higher than the purified PCPEL2 expressed by the pET system. In addition, some other characteristics of the purified PCPEL2 differed from the two systems, such as crystallographic features. Purified PCPEL2 expressed by the pMAL system was crystallized by the hanging-drop vapour-diffusion method at 289 K, and initial crystals were grown. The two different methods and comparison presented here would be highly valuable in obtaining an ideal enzyme for the downstream experiments, and supply an useful alternative to purify some insoluble recombinant proteins.


Vaginal laparoscopically assisted radical trachelectomy in cervical clear cell adenocarcinoma.
Adenocarcinoma of the cervix is a rare condition that has shown an increase in incidence, especially in the 20- to 34-year-old group. Adenocarcinoma represents about 5-10% of all tumours in this area, and, among these, the clear cell type accounts for 4-9%. This type of tumour affects mainly postmenopausal women but also occurs in young women with a history of prenatal exposure to diethylstilbestrol (DES). The prognosis for adenocarcinoma of the cervix is poor overall and worse for the clear cell variety. This article discusses a case of clear cell adenocarcinoma of the cervix, unrelated to intrauterine exposure to DES, in a woman of childbearing age who wished to preserve her fertility and was therefore treated by radical vaginal trachelectomy and pelvic lymphadenectomy.


Simulation of small- and wide-angle scattering properties of glass-bead retroreflectors.
Retroreflective materials are extensively used as traffic signs and security patterns. These goods are often realized by spherical glass-beads attached to some reflective substrate. New applications, especially 3D projection, require the precise evaluation and design of the characteristics of light backscattered from retroreflective screens. Simulation of such materials is not straightforward due to the different optical processes taking place: direct retroreflection involving small-angle diffraction effects, and multiple scattering resulting in wide-angle diffuse light. We propose a new complex method to describe the backscattering properties of glass-bead retroreflectors that uniquely combines diffraction calculations with ray tracing based on the microscopic properties of the screen. We validated our simulation method by measurements performed on commercial retroreflective samples.


On the analysis of a recurrent neural network for solving nonlinear monotone variational inequality problems.
We investigate the qualitative properties of a recurrent neural network (RNN) for solving the general monotone variational inequality problems (VIPs), defined over a nonempty closed convex subset, which are assumed to have a nonempty solution set but need not be symmetric. The equilibrium equation of the RNN system simply coincides with the nonlinear projection equation of the VIP to be solved. We prove that the RNN system has a global and bounded solution trajectory starting at any given initial point in the above closed convex subset which is positive invariant for the RNN system. For general monotone VIPs, we show by an example that the trajectory of the RNN system can converge to a limit cycle rather than an equilibrium in the case that the monotone VIPs are not symmetric. Contrary to this, for the strictly monotone VIPs, it is shown that every solution trajectory of the RNN system starting from the above closed convex subset converges to the unique equilibrium which is also locally asymptotically stable in the sense of Lyapunov, no matter whether the VIPs are symmetric or nonsymmetric. For the uniformly monotone VIPs, the aforementioned solution trajectory of the RNN system converges to the unique equilibrium exponentially.


Somatic symptoms in adolescence as a predictor of severe mental illness in adulthood: a long-term community-based follow-up study.
Somatic symptoms are common and costly for society and correlate with suffering and low functioning. Nevertheless, little is known about the long-term implications of somatic symptoms. The objective of this study was to assess if somatic symptoms in adolescents with depression and in their matched controls predict severe mental illness in adulthood by investigating the use of hospital-based care consequent to different mental disorders. The entire school population of 16-17-year-olds in the city of Uppsala, Sweden, was screened for depression in 1991-1993 (n = 2300). Adolescents with positive screenings (n = 307) and matched non-depressed controls (n = 302) participated in a semi-structured diagnostic interview for mental disorders. In addition, 21 different self-rated somatic symptoms were assessed. The adolescents with depression and the matched non-depressed controls were engaged in follow-up through the National Patient Register 17-19 years after the baseline study (n = 375). The outcome measures covered hospital-based mental health care for different mental disorders according to ICD-10 criteria between the participants' ages of 18 and 35 years. Somatic symptoms were associated with an increased risk of later hospital-based mental health care in general in a dose-response relationship when adjusting for sex, adolescent depression, and adolescent anxiety (1 symptom: OR = 1.63, CI 0.55-4.85; 2-4 symptoms: OR = 2.77, 95% CI 1.04-7.39; ≥ 5 symptoms: OR = 5.75, 95% CI 1.98-16.72). With regards to specific diagnoses, somatic symptoms predicted hospital-based care for mood disorders when adjusting for sex, adolescent depression, and adolescent anxiety (p < 0.05). In adolescents with depression, somatic symptoms predicted later hospital-based mental health care in a dose-response relationship (p < 0.01). In adolescents without depression, reporting at least one somatic symptom predicted later hospital-based mental health care (p < 0.05). Somatic symptoms in adolescence predicted severe adult mental illness as measured by hospital-based care also when controlled for important confounders. The results suggest that adolescents with somatic symptoms need early treatment and extended follow-up to treat these specific symptoms, regardless of co-occurring depression and anxiety.


Screening of Vibrio isolates to develop an experimental infection model in the Pacific oyster Crassostrea gigas.
In an attempt to develop a reproducible experimental model of bacterial infection in Crassostrea gigas, oysters taken from very localised sub-populations suffering natural mortality outbreaks were used in cohabitation trials under laboratory conditions. From these trials, a collection of Vibrio strains was isolated from moribund and healthy oysters. In a second step, strains were experimentally tested for virulence by means of injection into healthy oysters. This screening revealed a span of virulence among isolated strains from none to medium. When pooling injected strains, results suggest increased virulence. Vibrio strains may have additive/synergistic action leading to higher C. gigas mortality rates in experimental challenges. Although the study initially aimed to develop a simple experimental model, a complex of interactions emerged between several bacterial strains during the pathogenic process in their molluscan host. Selected strains provide a suitable model of experimental disease for further studies and better understanding of bacterial interaction and pathogenesis in C. gigas.


Molecular dissection of host cell invasion by the apicomplexans: the glideosome.
Gliding motility is an essential and fascinating apicomplexan-typical adaptation to an intracellular lifestyle. Apicomplexan parasites rely on gliding motility for their migration across biological barriers and for host cell invasion and egress. This unusual substratedependent mode of locomotion involves the concerted action of secretory adhesins, a myosin motor, factors regulating actin dynamics and proteases. During invasion, complexes of soluble and transmembrane micronemes proteins (MICs) and rhoptry neck proteins (RONs) are discharged to the apical pole of the parasite, some protein acts as adhesins and bind to host cell receptors whereas others are involved in the moving junction formation. These complexes redistribute towards the posterior pole of the parasite via a physical connection to the parasite actomyosin system and are eventually released from the parasite surface by the action of parasite proteases.


Injectable bone cement containing carboxymethyl cellulose microparticles as a silver delivery system able to reduce implant-associated infection risk.
In the challenging quest for a solution to reduce the risk of implant-associated infections in bone substitution surgery, the use of silver ions is promising regarding its broad spectrum on planktonic, sessile as well as multiresistant bacteria. In view of controlling its delivery in situ at the desired dose, we investigated its encapsulation in carboxymethyl cellulose (CMC) microparticles by spray-drying and included the latter in the formulation of a self-setting calcium phosphate bone cement. We implemented an original step-by-step methodology starting from the in vitro study of the antibacterial properties and cytotoxicity of two silver salts of different solubility in aqueous medium and then in the cement to determine the range of silver loading able to confer anti-biofilm and non-cytotoxic properties to the biomaterial. A dose-dependent efficiency of silver was demonstrated on the main species involved in bone-implant infection (S. aureus and S. epidermidis). Loading silver in microspheres instead of loading it directly inside the cement permitted to avoid undesired silver-cement interactions during setting and led to a faster release of silver, i.e. to a higher dose released within the first days combining anti-biofilm activity and preserved cytocompatibility. In addition, a combined interest of the introduction of about 10% (w/w) silver-loaded CMC microspheres in the cement formulation was demonstrated leading to a fully injectable and highly porous (77%) cement, showing a compressive strength analogous to cancellous bone. This injectable silver-loaded biomimetic composite cement formulation constitutes a versatile bone substitute material with tunable drug delivery properties, able to fight against bone implant associated infection. STATEMENT OF SIGNIFICANCE: This study is based on two innovative scientific aspects regarding the literature: i) Choice of silver ions as antibacterial agent combined with their way of incorporation: Carboxymethylcellulose has never been tested into bone cement to control its drug loading and release properties. ii) Methodology to formulate an antibacterial and injectable bone cement: original and multidisciplinary step-by-step methodology to first define, through (micro)biological tests on two silver salts with different solubilities, the targeted range of silver dose to include in carboxymethylcellulose microspheres and, then optimization of silver-loaded microparticles processing to fulfill requirements (encapsulation efficiency and size). The obtained fully injectable composite controls the early delivery of active dose of silver (from 3 h and over 2 weeks) able to fight against bone implant-associated infections.


Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors.
A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver.


Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.


A prospective study of evaluation of operative duration as a predictor of mortality in pediatric emergency surgery: Concept of 100 minutes laparotomy in resource-limited setting.
Operative duration is an important but under-studied predictor of mortality in emergency laparotomies. The primary objective of this study was to quantify the effect of duration of emergency laparotomy in children on mortality; and to identify a rough cut-off duration of laparotomy to serve as a guide so that a laparotomy can be planned to optimize pediatric surgical patient outcome. This is a prospective study conducted in a government tertiary teaching institution over a period of 24 months. All children in the age group of 5-10 years presenting in the emergency department with Pediatric Risk of Mortality III score ≤8, undergoing emergency laparotomy in emergency operation theater, were included. In all, 213 children were included in the study. The mean time from presentation to shifting to the operating room was 3.7 h. The mean operative duration was 108 min. The mean operative time in survived patients was 102 min as compared to 135 min in expired patients (P < 0.05). The 30-day in-hospital mortality rate was 17.4%. After application of binary logistic regression analysis, it was found that time to laparotomy and operative duration were significant risk factors (<0.05) predicting post-operative mortality. Kaplan-Meier survival curve showed a decrease at a mean weighted operative duration of approximately 100 min. Receiver operating characteristic curve analysis yielded operative duration of 123.5 min at which Youden's index maximized. This 100-min duration of laparotomy might appear a long duration but in casualty setup of a government hospital with limited resources, there are so many hurdles for optimal working that completion of an emergency laparotomy in children in 100 min can be considered a realistic target for improving post-operative outcome. At an operative duration of <123.50 min, mortality rates within acceptable limits can be achieved.