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Atmospheric immersion freezing (IF), a heterogeneous ice nucleation process where an ice nucleating particle (INP) is immersed in supercooled water, is a dominant ice formation pathway impacting the hydrological cycle and climate. Implementation of IF derived from field and laboratory data in cloud and climate models is difficult due to the high variability in spatio-temporal scales, INP composition, and morphological complexity. We demonstrate that IF can be consistently described by a stochastic nucleation process accounting for uncertainties in the INP surface area. This approach accounts for time-dependent freezing, a wide range of surface areas and challenges phenomenological descriptions typically used to interpret IF. The results have an immediate impact on the current description, interpretation, and experiments of IF and its implementation in models. The findings are in accord with nucleation theory, and thus should hold for any supercooled liquid material that nucleates in contact with a substrate., Competing Interests: COMPETING INTERESTS The authors declare no competing interests.

Purpose: To evaluate the long-term outcome of fetuses with a diagnosis of isolated short long bones., Methods: A retrospective review was conducted of all cases diagnosed with short long bones above 20 weeks of gestation during 2010-2017 in a single tertiary center. Exclusion criteria included abnormal sonographic findings other than short long bones, suspected genetic syndromes, chromosomal abnormalities, and abnormal Doppler flow indices. Follow-up was carried out by telephone questionnaire., Results: During the study period, 54 (24.32%) women met inclusion criteria. Mean gestational age at delivery was 38.05 years (± 2.42 SD). Mean birth weight was 12-19th percentile according to the local fetal growth charts [2645 g (± 684 SD) 95% CI 2173-2980]. Median time for post-natal follow-up was 9.3 years (IQR 6.6-10.75). Growth below the 10th percentile was demonstrated in 27 (50%) children. 11 (20.37%) children were followed up by endocrinological clinics, of them 7 (12.96%) were treated with growth hormone. Three (5.6%) of the children were diagnosed with attention deficit hyperactivity disorder, an incidence that is considered lower than that of the general population (± 9%)., Conclusions: Prenatal fetal isolated short long bones diagnosed during the late second and third trimester is associated with short stature. No neurodevelopmental impact was observed in our study group.

Organic nitrates (ONs) are an important component of secondary organic aerosols that play significant roles in atmospheric chemical processes such as ozone formation and as a reservoir of nitrogen oxides (NO x ). However, hindered by the availability of analytical techniques, characteristics of ON molecules remain unclear in regions influenced by anthropogenic volatile organic compounds (VOCs) and pollution. In this study, we achieved isomeric identification of particle-phase ONs in such regions. Using gas chromatography and time-of-flight mass spectrometry with an electron capture negative ionization source, we established a systematic procedure for screening unknown ONs in fine particulate matter (PM) collected in Beijing based primarily on the characteristic fragment ions of NO 2 - and [M-NO 2 ] - /[M-NO 2 -H 2 ] - . We found 78 ON candidates, 12 of which were confirmed using synthesized standards. Seventy-three of these detected ONs might originate from anthropogenic VOC precursors especially alkenes. Significantly, we observed two isomers generated from straight-chain 1-alkenes, namely, 2-hydroxy-1-nitrate and 1-hydroxy-2-nitrate. The signal ratios of the two isomers suggested that these hydroxy nitrates are mainly produced photochemically rather than through nighttime reactions. This study provides a promising method for identifying ONs in atmospheric PM and elucidating their formation pathways.

Background: Carbonaceous aerosols emitted from indoor and outdoor biomass burning are major risk factors contributing to the global burden of disease. Wood tar aerosols, namely, tar ball particles, compose a substantial fraction of carbonaceous emissions, especially from biomass smoldering. However, their health-related impacts and toxicity are still not well known. This study investigated the toxicity of the water-soluble fraction of pyrolyzed wood tar aerosols in exposed mice and lung epithelial cells., Results: Mice exposed to water-soluble wood tar aerosols showed increased inflammatory and oxidative stress responses. Bronchial epithelial cells exposed to the same water-soluble wood tar aerosols showed increased cell death with apoptotic characteristics. Alterations in oxidative status, including changes in reactive oxygen species (ROS) levels and reductions in the expression of antioxidant genes related to the transcription factor Nrf2, were observed and were confirmed by increased levels of MDA, a lipid peroxidation adduct. Damage to mitochondria was observed as an early event responsible for the aforementioned changes., Conclusions: The toxicity and health effect-related mechanisms of water-soluble wood tar were investigated for the first time in the context of biomass burning. Wood tar particles may account for major responses such as cell death, oxidative stress, supression of protection mechnaisms and mitochondrial damaged cause by expsoure to biomass burning aerosols.

Purpose: To characterize age- and sex-related changes in corneal refractive parameters in myopic and hyperopic patients undergoing refractive surgery., Design: A retrospective cross-sectional study., Methods: Analysis of demographic and refractive parameters of myopic and hyperopic patients who underwent laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) between January 2000 and December 2014 at the Care-Vision Laser Centers, Tel-Aviv, Israel., Results: A total of 62,422 eyes of 31,211 patients were included. With advancing age, refractive surgery was performed for lower magnitudes of myopia and hyperopia. The magnitude of cylinder was higher in men than in women in both myopic and hyperopic patients. In comparison, women were significantly more myopic than men (spherical equivalent of -3.73 diopter [D] versus -4.07 D; P < 0.01). The myopic group sphere (r = 0.044; P < 0.001) had a positive correlation with age, whereas other parameters had a negative correlation with age: astigmatism (r = -0.09; P < 0.001), best-correct visual acuity (BCVA) (r = -0.04; P < 0.001), flat K (r = -0.09; P < 0.001), steep K (r = -0.06; P < 0.001), average K (r = -0.07; P < 0.001), and J0 (r = -0.05; P < 0.001). For hyperopic patients, astigmatism (r = 0.35; P < 0.001), BCVA (r = 0.11; P < 0.001), flat K (r = 0.30; P < 0.001), average K (0.14; P < 0.001), and central corneal thickness (r = 0.10; P < 0.001) correlated positively with age, whereas sphere (r = -0.23; P < 0.001), J0 (r = -0.31; P < 0.001), and overall blurring strength (r = -0.31; P < 0.001) had negative correlations with age., Conclusions: This large cohort study shows age- and sex-related refractive parameters among myopic and hyperopic patients seeking refractive surgery. These parameters can explain and predict trends in patients attending refractive surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Anterior urethral anomalies (AUA) which present as anterior urethral valve, stenosis or atresia, are a rare cause for congenital urinary tract obstruction. We present our AUA prenatal diagnosis case series., Methods: Fetuses presenting with prenatal findings suggestive for AUA according to postnatal reported clinical and imaging signs (urinary tract dilatation, dilated bladder, enlarged edematous fetal penis, dilatation of the fetal urethra and diverticula) were followed prospectively., Results: Six fetuses were diagnosed with AUA. Diagnosis was confirmed upon examination of the neonate or the abortus. All cases presented with variable degrees of urinary tract dilatation. Four fetuses who presented with additional congenital anomalies of the kidneys and urinary tract (CAKUT) developed intra-uterine or early postnatal renal failure, while two isolated AUA cases have a normal renal outcome., Conclusions: AUA is a rare diagnosis. However, high index of suspicion and careful sonographic assessment of the male fetal urethra in cases referred for urinary tract dilatation may enable appropriate parent counseling, optimal prenatal surveillance and timed postnatal urological intervention. As in other lower urinary tract obstructions, future renal function seems to correlate with associated CAKUT, therefore close follow up throughout pregnancy and meticulous sonographic assessment is recommended., (© 2019 John Wiley & Sons, Ltd.)

It has been hypothesized that the cytotoxicity of secondary organic aerosols (SOA) is mediated through the formation of reactive oxygen species (ROS) in the exposed cells. Here, lung epithelial cells (A549) residing at the air-liquid interface were exposed to proxies of anthropogenic and biogenic SOA that were photochemically aged under varying nitrogen oxide (NOx) concentrations in an oxidation flow reactor. The total organic peroxides and ROS radical content in the SOA were quantified by the iodometric spectrophotometric method and by continuous-wave electron paramagnetic resonance. The effect of the exposure was evaluated by measuring cell viability and cellular ROS production following the exposure. The results demonstrate that SOA that aged in the absence of NOx contained more ROS than fresh SOA and were more toxic toward the cells, while varying NOx conditions had no significant influence on levels of the ROS content in fresh SOA and their toxicity. Analysis of ROS in the exposed cells using flow cytometry showed a similar trend with the total ROS content in the SOA. This study provides a first and direct observation of such association.

Purpose: To determine the factors associated with clinically significant dry eye after keratorefractive surgery., Methods: This is a large database retrospective study that included consecutive cases of myopic laser in situ keratomileusis (LASIK) or photorefractive keratectomy performed between 2008 and 2016 at Care-Vision Laser Center, Israel. Patients were divided into 2 groups according to whether they developed clinically significant dry eye., Results: A total of 25,317 right eyes of 25,317 patients, with a mean age of 27.0 ± 8.3 years, were included. Postoperative dry eye developed in 1518 eyes (6.0%). The dry eye group was older (29.2 ± 9.0 vs. 27.6 ± 8.3 yrs, P < 0.001) and had a higher proportion of women (48.5% vs. 44.8%, P = 0.005), lower preoperative spherical equivalent (3.7 ± 2.0 vs. 4.0 ± 2.3D, P < 0.001), lower preoperative best-corrected visual acuity (0.019 ± 0.057 vs. 0.016 ± 0.064 Logarithm of the Minimum Angle of Resolution (LogMAR), P = 0.04), and lower proportion of preoperative soft contact lens wearers (40.6% vs. 45.5%, P < 0.001). In the postoperative dry eye group, a high proportion underwent LASIK (52.4% vs. 38.7%, P < 0.001) and were treated with a 7.0-mm (as opposed to 6.0 mm) optic zone (18.9% vs. 16.3%, P < 0.001). In multivariable analysis, older age [odds ratio (OR) 1.013, P < 0.001], female gender (OR 0.87, P = 0.009), lower preoperative refractive error (OR 1.05, P < 0.001), and LASIK (OR 0.67, P < 0.001) were associated with postoperative dry eye., Conclusions: Patients who are of older age, are of female gender, and have a lower preoperative refractive error and those undergoing LASIK are more likely to develop dry eye disease after keratorefractive surgery.

Purpose: To determine the trends in prevalence of myopia in Israeli young adults over approximately a generation, as well as associated factors and variation in the impact of these factors on myopia prevalence in this region over time., Design: Retrospective, cross-sectional study., Participants: One hundred four thousand six hundred eighty-nine consecutive persons 16 to 19 years of age born between 1971 and 1994 who had not yet enlisted in the Israeli Army but had completed the medical profiling process., Methods: Using data collected at a north Israel recruitment center, the prevalence of myopia over time was estimated, and a polynomial regression analysis was performed to assess significance of nonlinear trends. Associations of demographic and socioeconomic factors with myopia were assessed, and trends over time were analyzed using a factorial logistic regression., Main Outcome Measures: The primary outcome measure was factors associated with the prevalence of myopia over time. The secondary outcome measure was a description of the change in prevalence of myopia over time., Results: The prevalence of myopia increased 1.284-fold over 24 years from 20.4% among participants born between 1971 and 1982 to 26.2% among participants born between 1983 and 1994. A quite similar increase was observed among males (from 17.9% to 22.7%, respectively) and females (from 23.9% to 30.8%, respectively). The factors found to be associated with myopia were as follows: more recent date of birth, female gender, more years of education, being the eldest child, non-Israeli ethnic origin, and urban residence. However, there were significant trends over time in the effects of some of these factors, most notably an attenuation of the difference between participants of different religions in the recent birth-years period. Most of these associations and trends were observed in both males and females separately, with some gender-specific variations. Immigrants from Ethiopia who were raised in Israel were highly more likely to demonstrate myopia than those who arrived at an older age., Conclusions: This study demonstrated an increase in the prevalence of myopia and the possible associations of urbanization- and higher education-related factors among several subpopulations and the risk for myopia developing., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The understanding of engineered nanoparticle (ENP) fate and transport in soil-water environments is important for the evaluation of potential risks of ENPs to the ecosystem and human health. The effects of pyrite grains and three types of oxyanions-sulfate, phosphate, and arsenate-on the retention of citrate-coated gold nanoparticles (citrate-Au-NPs) were studied in partially saturated soil column experiments. The mobility of Au-NP was found to be in the order: Au-NP-sulfide (originating from pyrite) > Au-NP-sulfate > citrate-Au-NP > Au-NP-arsenate > Au-NP-phosphate. Chemical retention mechanisms, including hydrogen bonding and calcium bridging, are proposed and discussed. The retention of Au-NPs in soil columns increases with the increased ability of transformed Au-NP surfaces to create strong hydrogen bonding through adsorbed oxyanions with soil surfaces. Oxyanions were also found to reduce aggregation and aggregate size of Au-NPs upon interaction with Ca 2+ solution. While the effects of cationic substances on ENP transport and stability have been studied frequently, the results here demonstrate that anionic substances have a substantial effect on Au-NP transport and stability. Furthermore, this study highlights the importance of examining ENPs under environmentally relevant condition, and the significant effect of ENP transformations on their mobility in soils.

Consumer-level 3D printers emit ultrafine and fine particles, though little is known about their chemical composition or potential toxicity. We report chemical characteristics of the particles in comparison to raw filaments and assessments of particle toxicity. Particles emitted from polylactic acid (PLA) appeared to be largely composed of the bulk filament material with mass spectra similar to the PLA monomer spectra. Acrylonitrile butadiene styrene (ABS), extruded at a higher temperature than PLA, emitted vastly more particles and their composition differed from that of the bulk filament, suggesting that trace additives may control particle formation. In vitro cellular assays and in vivo mice exposure all showed toxic responses when exposed to PLA and ABS-emitted particles, where PLA-emitted particles elicited higher response levels than ABS-emitted particles at comparable mass doses. A chemical assay widely used in ambient air-quality studies showed that particles from various filament materials had comparable particle oxidative potentials, slightly lower than those of ambient particulate matter (PM 2.5 ). However, particle emissions from ABS filaments are likely more detrimental when considering overall exposure due to much higher emissions. Our results suggest that 3D printer particle emissions are not benign and exposures should be minimized.

Purpose: To determine the rate of obstetric and neonatal complications associated with intrahepatic cholestasis of pregnancy in twin versus singleton gestations., Methods: A retrospective cohort study including patients diagnosed with intrahepatic cholestasis of pregnancy at a single tertiary center between 2011 and 2016. Women were allocated into two groups: twin pregnancies (n = 56) and singleton pregnancies (n = 186). Obstetric and neonatal outcomes were compared between the two groups., Results: Intrahepatic cholestasis of pregnancy was diagnosed earlier in gestation in twin compared to singleton pregnancies (33.1 ± 2.8 vs. 35.1 ± 3.0 weeks, respectively; adjusted P < 0.001). Maternal serum levels of fasting total bile acids were significantly higher in twin pregnancies compared to singletons [27 (IQR 16-44) vs. 16 (IQR 10-26) µmol/L, respectively; P = 0.01]. None of the pregnancies in our cohort was complicated by fetal death. Apgar score at 5 min and umbilical artery and vein PH at delivery were comparable between the two groups., Conclusions: Intrahepatic cholestasis of pregnancy in twin pregnancies appears to be more severe compared to singletons, as reflected by an earlier presentation and higher levels of maternal serum total bile acids. Large prospective studies are required to customize a management strategy specific for women with twin pregnancies and intrahepatic cholestasis of pregnancy.

Purpose: To describe a new technique for sealing small corneal perforations after penetrating trauma., Methods: Corneal perforations in six eyes were sealed using a stromal cefuroxime hydration technique. This technique is identical to the current method used to seal leaking incisions upon completion of cataract surgery except for the use of cefuroxime instead of balanced salt solution. Additionally, cefuroxime was intentionally injected into the anterior chamber. A therapeutic contact lens was used after the hydration. Comparison was made in eight eyes with small traumatic corneal perforation that was sealed using therapeutic contact lenses without hydration., Results: This novel technique was applied in six cases, with leakage stopping immediately following hydration in each of these eyes. In cases presenting with a shallow or flat anterior chamber, this maneuver produced immediate reformation of the chamber. Of note, the corneal scars after hydration were minimal with little effect on visual acuity. When compared to eyes with small corneal perforations which were sealed with therapeutic contact lenses without hydration, all cases that were hydrated with cefuroxime were sealed immediately, as opposed to cases treated without hydration. Furthermore, the eyes that underwent hydration with cefuroxime had a worse average visual acuity on admission, a better average visual acuity 1 month post-trauma, and a shorter average length of hospitalization., Conclusions: This new technique offers five major advantages: (1) Immediate sealing of the corneal perforation is achieved. (2) Definitive treatment can be achieved at the slit lamp. (3) Since neither stitches nor glue is applied, healing is achieved with minimal scarring and discomfort. (4) Little equipment is required. (5) Injection of cefuroxime into the anterior chamber provides prophylaxis against infection.

Background: Assessment of pelvic configuration is an important factor in the prediction of a successful vaginal birth. However, manual evaluation of the pelvis is practically a vanishing art, and imaging techniques are not available as a real-time bed-side tool. Unlike the obstetrical conjugate diameter (OC) and inter spinous diameter (ISD), the pubic arch angle (PAA) can be easily measured by transperineal ultrasound. Objectives: Three-dimensional computed tomography bone reconstructions were used to measure the three main birth canal diameters, evaluate the correlation between them, and establish the normal reference range for the inlet, mid-, and pelvic outlet. Study design: Measurements of the PAA, obstetric conjugate (OC), and ISD were performed offline using three-dimensional post processing reconstruction in bone algorithm application of the pelvis on examinations performed for suspected renal colic in nonpregnant reproductive age woman. The mean of two measurements was used for statistical analysis which included reproducibility of measurements, regression curve estimation between PAA, OC, and ISD, and calculation of the respective reference range centiles for each PAA degree. Results: Two hundred ninety-eight women comprised the study group. The mean ± SD of the PAA, ISD, and OC were 104.9° (±7.4), 103.8 mm (±7.3), and 129.9 mm (±8.3), respectively. The intra- and interobserver agreement defined by the intraclass correlation coefficient (ICC) was excellent for all parameters (range 0.905-0.993). A significant positive correlation was found between PAA and ISD and between PAA and OCD (Pearson's correlation = 0.373 ( p  < .001), and 0.163 ( p  = .022), respectively). The best regression formula was found with quadratic regression for inter spinous diameter (ISD): 34.122778 + (0.962182*PAA - 0.002830*PAA 2 ), and linear regression for obstetric conjugate (OC): 110.638397 + 0.183156*PAA. Modeled mean, SD, and reference centiles of the ISD and OCD were calculated using the above regression models as function of the PAA. Conclusions: We report significant correlation between the three pelvic landmarks with greatest impact on the prediction of a successful vaginal delivery: the PAA which is easily measured sonographically and the ISD and OC which are not measurable by ultrasound. This correlation may serve as a basis for future studies to assess its utility and prognostic value for a safe vaginal delivery.

Ice-binding proteins (IBPs) are found in many organisms, such as fish and hexapods, plants, and bacteria that need to cope with low temperatures. Ice nucleation and thermal hysteresis are two attributes of IBPs. While ice nucleation is promoted by large proteins, known as ice nucleating proteins, the smaller IBPs, referred to as antifreeze proteins (AFPs), inhibit the growth of ice crystals by up to several degrees below the melting point, resulting in a thermal hysteresis (TH) gap between melting and ice growth. Recently, we showed that the nucleation capacity of two types of IBPs corresponds to their size, in agreement with classical nucleation theory. Here, we expand this finding to additional IBPs that we isolated from snow fleas (the arthropod Collembola), collected in northern Israel. Chemical analyses using circular dichroism and Fourier-transform infrared spectroscopy data suggest that these IBPs have a similar structure to a previously reported snow flea antifreeze protein. Further experiments reveal that the ice-shell purified proteins have hyperactive antifreeze properties, as determined by nanoliter osmometry, and also exhibit low ice-nucleation activity in accordance with their size.

Nowadays, knowledge regarding component-specific inflammatory effect of fine particulate matter (PM 2.5 ) is limited. In this study, an omics approach based on time-of-flight mass spectrometry was established to identify the key hydrophobic components of PM 2.5 associated with pro-inflammatory cytokines released by macrophages after in vitro exposure. Of 764 compounds, 62 components were robustly screened with firmly identified 37 specific chemicals. In addition to polycyclic aromatic hydrocarbons (PAHs) and their methylated congeners, novel oxygen- and nitrogen-containing PAHs and, especially, oxygenated PAHs (Oxy-PAHs) were identified. Interleukin (IL)-6 was associated with Oxy-PAHs of 1,8-naphthalic anhydride, xanthone, and benzo[ h ]quinolone, especially, whereas IL-1β and tumor necrosis factor (TNF)-α were associated with most species. Most species were related to IL-1β, which was significantly higher in the heating season, with a monotonic dose-response pattern mainly for Oxy-PAHs and a U-shaped dose-response pattern for primary species. On the basis of the identified components, four sources of pollution (coal combustion, traffic emissions, biomass burning, and secondary formation, traced by Oxy-PAHs such as 1,8-naphthalic anhydride and quinones) were resolved by the positive matrix factorization model. TNF-α was associated with primary sources, whereas IL-1β and IL-6 were associated with both primary and secondary sources, suggesting different inflammatory effects between primary and secondary sources when assessing the toxicity-driven disparities of known and unknown PM 2.5 components.

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing contagious disease. In the plague mouse model, a single immunization with the EV76 live attenuated Y. pestis strain rapidly induced the expression of hemopexin and haptoglobin in the lung and serum, both of which are important in iron sequestration. Immunization against a concomitant lethal Y. pestis respiratory challenge was correlated with temporary inhibition of disease progression. Combining EV76-immunization and second-line antibiotic treatment, which are individually insufficient, led to a synergistic protective effect that represents a proof of concept for efficient combinational therapy in cases of infection with antibiotic-resistant strains., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Polycyclic aromatic hydrocarbons (PAHs) are toxic organic trace components in atmospheric aerosols that have impacts on climate and human health. They are bound to airborne particles and transported over long distances. Observations of their distribution, transport pathways, and degradation are crucial for risk assessment and mitigation. Such estimates would benefit from online detection of PAHs along with analysis of the carrying particles to identify the source. Typically, laser desorption/ionization (LDI) in a bipolar mass spectrometer reveals the inorganic constituents and provides limited molecular information. In contrast, two-step ionization approaches produce detailed PAH mass spectra from individual particles but without the source-specific inorganic composition. Here we report a new technique that yields the single-particle PAH composition along with both positive and negative inorganic ions via LDI. Thus, the complete particle characterization and source apportionment from conventional bipolar LDI-analysis becomes possible, combined with a detailed PAH spectrum for the same particle. The key idea of the method is spatiotemporal matching of the ionization laser pulse to the transient component distribution in the particle plume after laser desorption. The technique is robust and field-deployable with only slightly higher costs and complexity compared to two-step approaches. We demonstrate its capability to reveal the PAH-distribution on different particle types in combustion aerosols and ambient air.

Objective: To determine the contribution of chromosomal microarray (CMA) and other advanced genetic tests to the genetic evaluation of fetal pleural effusion (FPE) and to identify parameters that might assist in predicting genetic abnormality., Methods: A retrospective study of FPE cases referred between 2013 and 2018 was conducted. Cases that underwent genetic evaluation were divided into two groups, chromosomally normal and genetically abnormal. The types and prevalence of genetic abnormalities were reported. Clinical and sonographic parameters were compared. Univariate and multivariate analyses were performed to determine an association between different parameters and genetic abnormality., Results: Sixty-two cases were included in the study. Forty-eight cases were genetically assessed (karyotype, CMA, whole exome sequencing, Noonan panel, or a combination). A clinically significant genetic abnormality was detected in 29.17% (14/48) of cases. Aneuploidy and single gene disorders were found in 78.6% (11/14) and 21.4% (3/14) of abnormal cases. Four additional cases had microdeletion/duplications detected, yet none were of clinical significance. Multivariate analysis indicated that the presence of anomalies was statistically associated with genetic abnormality (95% CI, 1.144-168.2; 0.039)., Conclusion: In our cohort, CMA did not demonstrate an additional clinical yield over karyotyping. The presence of anomalies was independently associated with underlying genetic abnormality., (© 2019 John Wiley & Sons, Ltd.)

Nrf2 is an important transcription factor implicated in the oxidative stress response, which has been reported to play an important role in the way by which air pollution particulate matter (PM 2.5 ) induces adverse health effects. This study investigates the mechanism by which Nrf2 exerts its protective effect in PM 2.5 induced toxicity in lung cells. Lung cells silenced for Nrf2 (shNrf2) demonstrated diverse susceptibility to various PM extracts; water extracts containing high levels of dissolved metals exhibited higher capacity to generate mitochondrial reactive oxygen species (ROS) and hence increased oxidative stress levels. Organic extracts containing high levels of polycyclic aromatic hydrocarbons (PAHs) increased mortality and reduced ROS production in the silenced cells. shNrf2 cells exhibited a higher basal mitochondrial respiration rate compared to the control cells. Following exposure to water extracts, the mitochondrial respiration increased, which was not observed with the organic extracts. shNrf2 cells exposed to the organic extracts showed lower mitochondrial membrane potential and lower mtDNA copy number. Nrf2 may act as a signaling mediator for the mitochondria function following PM 2.5 exposure., (Copyright © 2019. Published by Elsevier B.V.)

We have previously shown that the cell morphogenesis NlpD lipoprotein is essential for virulence of the plague bacteria, Yersinia pestis. To elucidate the role of NlpD in Y. pestis pathogenicity, we conducted a whole-genome comparative transcriptome analysis of the wild-type Y. pestis strain and an nlpD mutant under conditions mimicking early stages of infection. The analysis suggested that NlpD is involved in three phenomena: (i) Envelope stability/integrity evidenced by compensatory up-regulation of the Cpx and Psp membrane stress-response systems in the mutant; (ii) iron acquisition, supported by modulation of iron metabolism genes and by limited growth in iron-deprived medium; (iii) activity of the twin-arginine (Tat) system, which translocates folded proteins across the cytoplasmic membrane. Virulence studies of Y. pestis strains mutated in individual Tat components clearly indicated that the Tat system is central in Y. pestis pathogenicity and substantiated the assumption that NlpD essentiality in iron utilization involves the activity of the Tat system. This study reveals a new role for NlpD in Tat system activity and iron assimilation suggesting a modality by which this lipoprotein is involved in Y. pestis pathogenesis., Competing Interests: The authors have declared that no competing interests exist.

Several types of natural molecules interact specifically with ice crystals. Small antifreeze proteins (AFPs) adsorb to particular facets of ice crystals, thus inhibiting their growth, whereas larger ice-nucleating proteins (INPs) can trigger the formation of new ice crystals at temperatures much higher than the homogeneous ice nucleation temperature of pure water. It has been proposed that both types of proteins interact similarly with ice and that, in principle, they may be able to exhibit both functions. Here we investigated two naturally occurring antifreeze proteins, one from fish, type-III AFP, and one from beetles, TmAFP. We show that in addition to ice growth inhibition, both can also trigger ice nucleation above the homogeneous freezing temperature, providing unambiguous experimental proof for their contrasting behavior. Our analysis suggests that the predominant difference between AFPs and INPs is their molecular size, which is a very good predictor of their ice nucleation temperature.

Objective: The aim of this study was to compare the pregnancy outcome of two different management strategies: outpatient versus inpatient in women with prenatal diagnosis of vasa previa., Materials and Methods: This is a retrospective cohort study conducted at a single tertiary center. Women with a prenatally diagnosed vasa previa between January 2007 and June 2017 were included. Obstetric and neonatal outcomes were compared between two management strategies: elective admission at 34 weeks of gestation or outpatient management unless there were signs of labor or premature contractions., Results: A total of 109 women met the inclusion criteria: 75 (68.8%) women in the inpatient group and 34 (31.2%) in the outpatient group. Women in the inpatient group were more likely to receive antenatal steroids (57.3 vs. 26.4%, p  = 0.002) and were less likely to have an urgent cesarean section (34.6 vs. 58.8%, respectively, p  < 0.001) compared with outpatient group. There was no difference in the rate of neonatal complications (inpatient: 64.6% vs. outpatient: 52.7%, p  = 0.27) or neonatal anemia requiring transfusion (2.7 vs. 5.8%, respectively, p  = 0.5) between the groups., Conclusion: The rate of elective cesarean section and exposure to antenatal steroids was higher in patients with vasa previa who were admitted electively at 34 weeks of gestation compared with patients who were managed as outpatient., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The substantial availability of hypoxia-inducible factor 1 (HIF-1) for pathophysiological states, such as malignancies and ischemia, is primarily regulated post-translationally through the ubiquitin proteolytic system. The balance between degradation and stabilization of HIF-1α protein is determined by specific E3 ligases. In our search for new E3 ligases that might affect HIF-1α protein expression, we studied the effects of beta-transducin repeat-containing protein (β-TrCP) on the hypoxic pathway in cancer cells. β-TrCP is overexpressed in many tumors and regulates various cellular processes through mediating the degradation of important targets. Unexpectedly, we found that β-TrCP overexpression increases HIF-1α protein expression level as well as HIF-1 transcriptional activity by stabilizing HIF-1α protein and preventing its ubiquitination and proteasomal degradation in prostate cancer cells. By using a proteomic approach, we succeeded in demonstrating that β-TrCP interferes with the association between HIF-1α and HSP70/CHIP, a HIF-1α established E3 ligase complex. Whereas the E3 ligase activity of β-TrCP is well known, antagonizing another E3 ligase is a new mechanism of action of this important E3. We suggest that destroying or suppressing β-TrCP and thereby interrupting the HIF-1 pathway, could be valuable antitumor therapy., (© 2018 Wiley Periodicals, Inc.)

Diaphanospondylodysostosis (DSD) is a rare autosomal recessive skeletal disorder, characterized mainly by ossification defects in vertebrae, thorax malformations, renal cystic dysplasia and usually death in the perinatal period. DSD is caused by mutations in the bone morphogenetic protein-binding endothelial regulator (BMPER) gene. We describe the prenatal findings of a non-consanguineous Jewish couple (shared Balkan origin), with three affected fetuses that presented with malformations in the spine and chest, reduced ossification of the skull and spine, horseshoe kidney and increased nuchal translucency. The unique combination of these ultrasound (US) features raised the possibility of DSD, which was confirmed by whole exome sequencing (WES) performed on a single fetal DNA and familial segregation. In the three fetuses, a novel homozygous mutation in BMPER (c.410T > A; p.Val137Asp) was found. This mutation, which segregated in the family, was not found in 65 controls of Jewish Balkan origin, and in several large databases. Taken together, the combination of a detailed prenatal US examination and WES may be highly effective in confirming the diagnosis of a rare genetic disease, in this case DSD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Transport of indium and gallium is reported in laboratory column experiments using quartz sand as a model porous medium representative of a groundwater system. With increased use of indium and gallium in recent years, mainly in the semiconductor industry, concerns arise regarding their environmental effects. The transport and retention behavior of these two metals were quantified via batch and column experiments, and numerical modeling. The effect of natural organic matter on indium and gallium mobility was studied by addition of humic acid (HA). Measured breakthrough curves from column experiments demonstrated different binding capacities between indium and gallium, stronger for indium, with the presence of HA affecting retention dynamics. For indium, the binding capacity on quartz decreases significantly in the presence of HA, leading to enhanced mobility. In contrast, gallium exhibits slightly higher retention and lower mobility in the presence of HA. In all cases, the binding capacity of gallium to quartz is much weaker than that of indium. These results are consistent with the assumption that indium and gallium form different types of complexes with organic ligands, with gallium complexes appearing more stable than indium complexes. Quantitative modeling confirmed that metal retention is controlled by complex stability., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To evaluate a multiple regression-derived nomogram for myopia and myopic astigmatism photorefractive keratectomy (PRK)., Methods: Regression modeling derived a formula for spherocylindrical correction in wavefront-optimized PRK (nomogram II). Treatment outcomes between eyes with myopia and myopic astigmatism using the manufacturer's nomogram (nomogram I) in the years 2010-2013 were retrospectively compared with eyes treated using nomogram II in the years 2014-2015., Results: Overall 1100 eyes (of 561 patients) were operated using nomogram I and 791 eyes (of 406 patients) using nomogram II. Nomogram II achieved correction within ± 0.5 D of the attempted in 90% (95% CI 86.8-92.3%) of eyes with a spherical equivalent (SE) < |- 6|D, compared to 84% (95% CI 81.8-86.9%) in nomogram I. Overcorrection was reached in 14% (95% CI 10.1-18.3%) of eyes with SE ≥ |-6|D in nomogram II, compared to 22.6% (95% CI 18.1-27.2%) in nomogram I. Nomogram II achieved correction within ± 0.5 D of the attempted in 88.7% (95% CI 85.7-91.6%) of patients aged 18-23 years compared to 81.2% (95% CI 77.9-84.5%) in nomogram I; however, in 77% (95% CI 69.5-84.4%) versus 87.4% (95% CI 82.7-92.0%), respectively, among patients aged ≥ 30 years. In eyes with astigmatism ≥ 2 D, a postoperative astigmatism < 0.5 D was achieved in 89.4% (95% CI 83.0-95.7%) versus 72.9% (95% CI 64.3-81.5%), and a treatment efficacy index ≥ 0.9 was achieved in 100% versus 92.6% (95% CI 87.6-97.6%) with nomogram II versus nomogram I, respectively., Conclusion: There were several clinically significant benefits of the advanced nomogram in wavefront-optimized myopia PRK. On the other hand, there was a trend of lower accuracy in the older age group, warranting a second iteration.

Early sensing of bacterial infection and the immediate recruitment of neutrophils to the lung is a major and decisive stage of the innate immune response to pulmonary bacterial infections. This chapter details the preparation of lung tissue suspensions from mice infected intra-nasally (I.N.) with the plague bacterium Yersinia pestis to study in vivo neutrophil responses to the infection. The samples were used for the quantification of neutrophil levels and for the characterization of the pro-inflammatory response required for neutrophil recruitment to the lung. The specific requirements for performing the procedures under Biosafety Level 3 containment and the proper handling and sterilization of the samples are discussed.

Purpose: To analyze the correlation between central corneal thickness (CCT) and myopia in refractive surgery candidates., Materials and Methods: Patients that underwent myopic laser refractive surgery between January 2000 and December 2014 were included. Preoperative CCT was measured by ultrasonic pachymetry, and refractive status determined by manifest and cycloplegic refraction., Results: A total of 30,245 individuals were included. Mean age was 28.2 ± 8.6 years, and 45.9% were female. Mean refractive error was 4.02 ± 2.17 D (range 0.25-19.5), and the mean CCT measurement was 533.5 ± 35.5 µm (range 404-794). Younger individuals showed higher degree of myopia (p = 0.006). No difference in CCT was found between women and men (533.0 ± 35.1 and 533.6 ± 35.9 µm, respectively, p = 0.19). Though CCT showed no correlation with age (p = 0.226) participants above age 40 expressed higher CCT values (p < 0.001). No significant correlation was found between the CCT and cylinder (p > 0.05). An increase in mean keratometry was associated with a decrease in CCT (p < 0.001). There was a direct correlation between the degree of myopia and CCT (r = 0.94, p < 0.001). The result remained the same after adjusting for age group and gender in stepwise backward regression analysis (p < 0.001)., Conclusion: Central corneal thickness is correlated with the degree of myopia among adults undergoing refractive surgery.

For about four decades, hybridoma technologies have been the "work horse" of monoclonal antibody production. These techniques proved to be robust and reliable, albeit laborious. Over the years, several major improvements have been introduced into the field, but yet, antibody production still requires many hours of labor and considerable resources. In this work, we present a leap forward in the advancement of hybridoma-based monoclonal antibody production, which saves labor and time and increases yield, by combining hybridoma technology, fluorescent particles and fluorescence-activated cell sorting (FACS). By taking advantage of the hybridomas' cell-surface associated antibodies, we can differentiate between antigen-specific and non-specific cells, based on their ability to bind the particles. The speed and efficiency of antibody discovery, and subsequent cell cloning, are of high importance in the field of infectious diseases. Therefore, as a model system, we chose the protein LcrV, a major virulence factor of the plague pathogen Yersinia pestis, an important re-emerging pathogen and a possible bioterror agent., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

In recent years, numerous reports have tied cytomegalovirus retinitis (CMVR) with multiple systemic conditions in the absence of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). These range from reports in apparently healthy individuals, through conditions rendering limited immune dysfunction such as advanced age and diabetes mellitus, and finally severe immune dysfunction such as in haematological and rheumatological conditions. Reports are also emerging, suggesting that induced local ocular immunosuppression is a risk factor for CMVR. We herein present a comprehensive collection of the accumulated findings regarding CMVR in non-HIV patients. We summarize the spectrum of underlying morbidity that has been associated with CMVR, its clinical presentation, diagnostic methods and treatment choice in the attempt to suggest the optimal treatment strategy in this complicated and diverse patient population which is still currently lacking a consensus., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A 26-years-old woman, underwent an ultrasound examination at 13.4 weeks. A cystic structure was identified in the right lower abdomen. Gradually, the cystic mass was replaced by echogenic content and eventually attained the appearance of hyperechoic bowel. At 21.2 weeks, the anal sphincter could not be demonstrated which was consistent with the diagnosis of isolated anal agenesis. Amniocentesis revealed 46XY karyotype with normal comparative genomic hybridization. After termination of pregnancy at 23 weeks, an autopsy revealed an isolated high type anorectal malformation (ARM) without fistula. We reviewed all 14 cases reported in the literature of first trimester sonographic expression of ARM., (© 2018 Wiley Periodicals, Inc.)

Purpose: To investigate the correlation between the angle of progression and the clinical fetal head station (FHS) during the second stage of labor, and to build reference range., Materials and Methods: A prospective, observational study was conducted. Women carrying singleton term pregnancies were enrolled during the second stage of labor. FHS was assessed manually by a senior obstetrician, while the angle of progression (AOP) was assessed by transperineal ultrasound (TPU). Both examiners were blinded to each others results. The correlation between the sonographic AOP and the clinical FHS was analyzed., Results: Seventy patients comprised the study group. Clinical FHS demonstrated an excellent correlation with the sonographic measurement of AOP (Pearson's Correlation 0.642, p < 0.001). This correlation was best described by a cubic regression according to the formula: 123.800 + 10.290 × FHS -2.889 * FHS +0.910, (r 2  = 0.423, p < .001). After aggregation of the mean AOP per FHS, the relative predicted centiles values and standard deviation were calculated. The mean Z score between measured and predicted values of the AOP for a given FHS was 0.007 (range -0.13 to +0.006)., Conclusions: Our results demonstrate a significant correlation between the clinical FHS and the TPU measured AOP. These standardized sonographic values may serve the obstetrician as a reliable, objective auxiliary tool for the evaluation of the FHS during the second stage of labor.

Objective: The objective of this study is to determine the clinical significance of maternal and fetal ultrasound Doppler flow indices in postdates pregnancies., Methods: This prospective study comprised 120 low-risk pregnant women beyond 40 weeks of gestation. All participants underwent Doppler assessment including of fetal middle cerebral artery (MCA), umbilical, and uterine arteries. Perinatal outcomes were recorded and evaluated for possible associations with Doppler flow values. Adverse perinatal outcomes were defined as umbilical cord arterial pH <7.1, Apgar score <7 at 5 min, neonatal admission to a neonatal intensive care unit, and emergency cesarean section due to abnormal intrapartum cardiotocogram Results: Adverse perinatal outcome rate was 17.5% (n = 21). Doppler indices of umbilical artery, MCA, uterine artery and the cerebroplacental ratio (CPR) did not differ significantly between pregnant women with and without adverse perinatal outcomes. Neonatal birth weight was found to correlate negatively with umbilical artery Doppler indices, including the peak systolic to end diastolic ratio (p = .04), the resistance index (p = .02), and the pulsatility index (p = .01). Doppler values of the uterine artery, MCA and CPR did not correlate with neonatal birth weight., Conclusions: The contribution of maternal and fetal ultrasound Doppler to the prediction of adverse perinatal outcomes in low-risk postdates pregnancies is low. Hence, performing routine Doppler examination as part of postdates pregnancy assessments is unlikely to yield significant clinical benefit.

The generation of adaptive immunity by vaccination is usually a prolonged process that requires multiple dosing over several months. Hence, vaccines are administered for disease prevention a relatively long time prior to possible infection as opposed to post-exposure prophylaxis, which typically requires rapid intervention such as antibiotic therapy. The emergence of pathogens resistant to common antibiotic treatments has prompted the search for alternative therapeutic strategies. We previously demonstrated that vaccination of mice with the F1 capsular antigen of Yersinia pestis elicits specific and effective yet, unexpectedly, rapid anti-plague immunity. Here, we show by applying genetic and immunological approaches that the F1 antigen is targeted by peritoneal innate-like B1b cells that generate a prompt T-independent (TI) anti-F1 humoral response. The rapid F1-mediated defense response was diminished in Xid (Btk m ) mice in which B1 cell numbers and activity are limited. Binding of fluorophore-labeled F1 to peritoneal B1b cells was detected as soon as 6 h post vaccination, emphasizing the high speed of this process. By assessing the ability to achieve rapid immunity with monomerized F1, we show that the natural polymeric structure of F1 is essential for (i) rapid association with peritoneal B1b cells, (ii) early induction of anti-F1 titers and (iii) rapid TI immunity in the mouse model of bubonic plague. These observations shed new light on the potential of novel as well as well-known protective antigens in generating rapid immunity and could be implemented in the rational design of future vaccines., Competing Interests: The authors declare no competing interests.

Exposure to ambient fine particulate matter (PM 2.5 ) is a leading risk factor for the global burden of disease. However, uncertainty remains about PM 2.5 sources. We use a global chemical transport model (GEOS-Chem) simulation for 2014, constrained by satellite-based estimates of PM 2.5 to interpret globally dispersed PM 2.5 mass and composition measurements from the ground-based surface particulate matter network (SPARTAN). Measured site mean PM 2.5 composition varies substantially for secondary inorganic aerosols (2.4-19.7 μg/m 3 ), mineral dust (1.9-14.7 μg/m 3 ), residual/organic matter (2.1-40.2 μg/m 3 ), and black carbon (1.0-7.3 μg/m 3 ). Interpretation of these measurements with the GEOS-Chem model yields insight into sources affecting each site. Globally, combustion sectors such as residential energy use (7.9 μg/m 3 ), industry (6.5 μg/m 3 ), and power generation (5.6 μg/m 3 ) are leading sources of outdoor global population-weighted PM 2.5 concentrations. Global population-weighted organic mass is driven by the residential energy sector (64%) whereas population-weighted secondary inorganic concentrations arise primarily from industry (33%) and power generation (32%). Simulation-measurement biases for ammonium nitrate and dust identify uncertainty in agricultural and crustal sources. Interpretation of initial PM 2.5 mass and composition measurements from SPARTAN with the GEOS-Chem model constrained by satellite-based PM 2.5 provides insight into sources and processes that influence the global spatial variation in PM 2.5 composition.

CKIα ablation induces p53 activation, and CKIα degradation underlies the therapeutic effect of lenalidomide in a pre-leukemia syndrome. Here we describe the development of CKIα inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIα-induced p53 activation and its anti-leukemic activity. Oncogene-driving super-enhancers (SEs) are highly sensitive to CDK7/9 inhibition. We identified multiple newly gained SEs in primary mouse acute myeloid leukemia (AML) cells and demonstrate that the inhibitors abolish many SEs and preferentially suppress the transcription elongation of SE-driven oncogenes. We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. Leukemia progenitors are selectively eliminated by the inhibitors, explaining their therapeutic efficacy with preserved hematopoiesis and leukemia cure potential; they eradicate leukemia in MLL-AF9 and Tet2 -/- ;Flt3 ITD AML mouse models and in several patient-derived AML xenograft models, supporting their potential efficacy in curing human leukemia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sea spray aerosols (SSA), have a profound effect on the climate; however, the contribution of oceanic microbial activity to SSA is not fully established. We assessed aerosolization of the calcite units (coccoliths) that compose the exoskeleton of the cosmopolitan bloom-forming coccolithophore, Emiliania huxleyi. Airborne coccolith emission occurs in steady-state conditions and increases by an order of magnitude during E. huxleyi infection by E. huxleyi virus (EhV). Airborne to seawater coccolith ratio is 1:10 8 , providing estimation of airborne concentrations from seawater concentrations. The coccoliths' unique aerodynamic structure yields a characteristic settling velocity of ∼0.01 cm s -1 , ∼25 times slower than average sea salt particles, resulting in coccolith fraction enrichment in the air. The calculated enrichment was established experimentally, indicating that coccoliths may be key contributors to coarse mode SSA surface area, comparable with sea salt aerosols. This study suggests a coupling between key oceanic microbial interactions and fundamental atmospheric processes like SSA formation., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

P-glycoprotein (P-gp), an ATP-dependent efflux pump, is associated with the development of multidrug resistance in cancer cells. Antibody-mediated blockade of human P-gp activity has been shown to overcome drug resistance by re-sensitizing resistant cancer cells to anticancer drugs. Despite the potential clinical application of this finding, the epitopes of the three human P-gp-specific monoclonal antibodies MRK-16, UIC2 and 4E3, which bind to the extracellular loops (ECLs) have not yet been mapped. By generating human-mouse P-gp chimeras, we mapped the epitopes of these antibodies to ECLs 1 and 4. We then identified key amino acids in these regions by replacing mouse residues with homologous human P-gp residues to recover binding of antibodies to the mouse P-gp. We found that changing a total of ten residues, five each in ECL1 and ECL4, was sufficient to recover binding of both MRK-16 and 4E3 antibodies, suggesting a common epitope. However, recovery of the conformation-sensitive UIC2 epitope required replacement of thirteen residues in ECL1 and the same five residues replaced in the ECL4 for MRK-16 and 4E3 binding. These results demonstrate that discontinuous epitopes for MRK-16, UIC2 and 4E3 are located in the same regions of ECL1 and 4 of the multidrug transporter.

Obesity and exposure to particular matter (PM) have become two leading global threats to public health. However, the exact mechanisms and tissue-specificity of their health effects are largely unknown. Here we investigate whether a metabolic challenge (early nutritional obesity) synergistically interacts with an environmental challenge (PM exposure) to alter genes representing key response pathways, in a tissue-specific manner. Mice subjected to 7 weeks obesogenic nutrition were exposed every other day during the final week and a half to aqueous extracts of PM collected in the city of London (UK). The expression of 61 selected genes representing key response pathways were investigated in lung, liver, white and brown adipose tissues. Principal component analysis (PCA) revealed distinct patterns of expression changes between the 4 tissues, particularly in the lungs and the liver. Surprisingly, the lung responded to the nutrition challenge. The response of these organs to the PM challenge displayed opposite patterns for some key genes, in particular, those related to the Nrf2 pathway. While the contribution to the variance in gene expression changes in mice exposed to the combined challenge were largely similar among the tissues in PCA1, PCA2 exhibited predominant contribution of inflammatory and oxidative stress responses to the variance in the lungs, and a greater contribution of autophagy genes and MAP kinases in adipose tissues. Possible involvement of alterations in DNA methylation was demonstrated by cell-type-specific responses to a methylation inhibitor. Correspondingly, the DNA methyltransferase Dnmt3a2 increased in the lungs but decreased in the liver, demonstrating potential tissue-differential synergism between nutritional and PM exposure. The results suggest that urban PM, containing dissolved metals, interacts with obesogenic nutrition to regulate diverse response pathways including inflammation and oxidative stress, in a tissue-specific manner. Tissue-differential effects on DNA methylation may underlie tissue-specific responses to key stress-response genes such as catalase and Nrf2., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Since the advent of laparoscopy there have been attempts to minimize abdominal wall incisions. For this purpose smaller instruments have been produced. Our aim was to develop the first 3 mm percutaneous clip applier and to make it better than the standard clips of today., Material and Methods: The ClipTip clip is made of Nitinol and has a crocodile shaped jaws, which when apposed effectively seal vessels. The shaft operates as a retractable needle permitting percutaneous insertion. Closing, reopening and reclosing is possible. The physical properties of the device were compared to three commercially available clip appliers. Surgeries were performed on porcine animals by experienced surgeons., Results: In comparison to available clips, the superiority of the ClipTip is a combination of wide effective length alongside the ability to withstand strong forces. In live animal studies the Cliptip was inserted into the peritoneal cavity without any injuries. Vessels were ligated successfully and no clip dislodgement or leakage occurred., Conclusions: We developed the next generation clip applier with better properties. Advantages include its length, the needleoscopic caliber, non-crushing effect, locking mechanism and wide aperture. The device has performed safely and effectively in pre-clinical tests. Further studies are planned in humans.

Purpose: The aim of our study was to assess the agreement between pre- and post-natal measurements in prenatal isolated ventriculomegaly., Methods: Ninety-two women were referred for lateral ventricular abnormality and followed prospectively. Cases with at least one dilated lateral ventricle ≥10 mm and a normal work up (serological tests, detailed anatomical scan, fetal brain MR imaging, genetic counseling, and amniocentesis) were considered idiopathic ventriculomegaly and comprised the study group for post-natal follow up. Prenatal measurements were performed by ultrasound and MR imaging. Post-natal measurements were performed by cranial sonography at age of 1-3 months. Measurements were performed in the customary plane for each modality. Paired Student's t test was used to assess the mean difference between pre- and postnatal measurements., Results: Forty three cases comprised the study group for post-natal measurements. A statistically significant decrease in ventricular width (p < .001) was observed between pre- and post-natal measurements. On clinical follow up for 24 months, all cases were normal except three who demonstrated very mild neurological deficits., Conclusions: Our study indicates statistically significant regression of prenatal isolated ventriculomegaly in the post-natal period.

Objectives: No study thus far has evaluated the LUS thickness in active labor. In this study, we endeavored to assess the LUS during active labor., Methods: Using transabdominal sonography in the mid-sagittal position with a full urinary bladder, the thickness of the LUS was measured during active labor phase in women with or without a history of a previous cesarean section., Results: A total of 28 women with a previous cesarean delivery were compared to 29 women without a history of uterine surgery. The median LUS was significantly thinner in women with a uterine scar both during (4 versus 5 mm, p = .001) and between contractions (5 versus 7 mm, p = .011). Paired comparison of LUS thickness between and during contractions within each group showed that thinning of LUS during contraction was significant for both the previous CS group (p < .001) and the control group (p < .001). We found no correlation between LUS thickness and chances of successful TOLAC., Conclusions: In this study, we characterized for the first time the LUS during active labor. We found that LUS was significantly thinner in women after a previous CS and that the LUS was significantly thinner during contraction.

To describe the prenatal presentation, including ultrasonographic, histologic, and molecular findings, in 2 fetuses affected with LMOD3-related nemaline myopathy. Prenatal ultrasonographic examinations and histopathologic studies were performed on 2 fetuses with evidence of nemaline myopathy. To establish a molecular diagnosis, whole-exome sequencing was pursued for the affected fetuses. Nemaline myopathy is a common form of congenital myopathy manifesting with nonprogressive generalized muscle weakness, hypotonia, and electron-dense protein inclusions in skeletal myofibers. Although clinically, nemaline myopathy can be viewed as a common pathway phenotype, its molecular basis is heterogeneous, with mutations in 11 identified genes implicated in its pathogenesis so far. Whole-exome sequencing revealed that the affected fetuses were compound heterozygous for 2 newly reported pathogenic variants in the LMOD3 gene, which encodes leiomodin 3. To our knowledge, this article is the first report of LMOD3-related nemaline myopathy since the original reported cohort. We provide a detailed description of the prenatal imaging of these affected fetuses, which we hope, in combination with next-generation sequencing, may contribute to further diagnosis in additional families., (© 2018 by the American Institute of Ultrasound in Medicine.)

Objective: Bed rest or activity restriction is a common obstetrical practice, despite a paucity of data to support its efficacy. The aim of this study was to determine whether physical activity, as assessed by a smart band activity tracker, is associated with preterm birth in pregnant women at high risk for preterm delivery., Methods: This was a pilot prospective cohort study including pregnant women at high risk for preterm delivery between 24 and 32 weeks-of-gestation. Physical activity level was assessed by smart band activity. Patients with sonographic short cervical length (≤ 20 mm) were asked to wear the smart band activity tracker continuously for at least one week, including one weekend. Both physicians and patients were blinded to the data stored in the smart band activity tracker. No specific recommendations were given to participants as to the level or intensity of physical activity. The primary outcome was the rate of preterm birth (< 37 weeks-of-gestation). Secondary outcomes included the rate of delivery before 34 weeks of gestation and neonatal outcome. Parametric and nonparametric statistics were used for analysis., Results: Study population included 49 pregnant women: 37 women (75.7%) delivered preterm and 12 (24.5%) delivered at or after 37 weeks-of-gestation. The median steps per day was significantly lower in patients who delivered preterm (3576, IQR: 2478-4775 vs. 4554, IQR: 3632-6337, p = 0.02). Regression analysis revealed that the median number of steps per day was independently inversely associated with preterm birth, after adjustment for maternal age, body mass index, gestational age at recruitment, cervical length, cervical dilatation and plurality., Conclusion: This pilot study represents the first quantitative assessment of the association between physical activity and preterm birth. The results of this pilot study do not support the efficacy of decreased physical activity in the prevention of preterm birth in patients with sonographic short cervical length., Competing Interests: The authors have declared that no competing interests exist.

Exposure to air pollution can induce oxidative stress, inflammation and adverse health effects. To understand how seasonal and chemical variations drive health impacts, we investigated indications for oxidative stress and inflammation in mice exposed to water and organic extracts from urban fine particles/PM 2.5 (particles with aerodynamic diameter ≤ 2.5 μm) collected in Beijing, China. Higher levels of pollution components were detected in heating season (HS, winter and part of spring) PM 2.5 than in the non-heating season (NHS, summer and part of spring and autumn) PM 2.5 . HS samples were high in metals for the water extraction and high in polycyclic aromatic hydrocarbons (PAHs) for the organic extraction compared to their controls. An increased inflammatory response was detected in the lung and liver following exposure to the organic extracts compared to the water extracts, and mostly in the HS PM 2.5 . While reduced antioxidant response was observed in the lung, it was activated in the liver, again, more in the HS extracts. Nrf2 transcription factor, a master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response, and its related genes were induced. In the liver, elevated levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of cell damage and proliferation, indicating oxidative and toxic damage. In addition, expression of genes related to detoxification of PAHs was observed. Altogether, the study suggests that the acute effects of PM 2.5 can vary seasonally with stronger health effects in the HS than in the NHS in Beijing, China and that some secondary organs may be susceptible for the exposure damage. Specifically, the liver is a potential organ influenced by exposure to organic components such as PAHs from coal or biomass burning and heating., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Fine particulate matter (PM 2.5 ) air pollution poses a major risk to human health worldwide, and absorbed chemicals play a key role in determining the toxicity of PM 2.5 . After inhalation and entry into the lungs, PM 2.5 components induce pro-inflammatory cytokines (e.g., interleukin (IL)-1β) in pulmonary cells. To test whether PM 2.5 components induce IL-1β through signing pathways that include the toll-like receptor 4 (TLR4)/nuclear factor-κ-gene binding (NF-κB), nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3), we exposed the mouse macrophage cell-line RAW264.7 to both water and organic extracts of PM 2.5 sampled over a 1-year period in Beijing, China. Varying degrees of oxidative stress and inflammatory responses were induced following exposure, while organic extracts of PM 2.5 collected during the heating season induced more significant responses. This response is attributed to high concentrations of polycyclic aromatic hydrocarbons (PAHs) originating from coal combustion and biomass burning for domestic heating. The inhibition of signaling molecules suggested that increased IL-1β was associated with the TLR4/NF-κB pathway and NLRP3 inflammasome activation, with a slightly difference between water and organic extracts exposure groups, which was likely the result of different chemical components. Our study elucidated a potentially important mechanism by which PM 2.5 components could trigger pulmonary inflammation, thus improving our understanding of the deleterious effects of this important and prevalent form of air pollution., (Copyright © 2018 Elsevier Ltd. All rights reserved.)