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Objective: to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive. Design: We describe a non-consanguineous pedigree composed by several individuals with short stature, including 2 pediatric patients with typical diagnosis of isolated growth hormone deficiency (IGHD) and 4 other siblings with severe short stature, low serum IGF-1 and IGFBP-3, but normal stimulated GH levels, suggesting growth hormone insensitivity (GHI) in the latter group. Results: Patients with classical IGHD phenotype carried a heterozygous variant in GH1 : c.626G>A (p.R209H). Data from the extended pedigree suggested GH1 as the initial candidate gene, which showed the same pathogenic heterozygous GH1 variant in the four siblings with short stature and a biochemical pattern of GHI. Conclusions: We suggest considering GH1 sequencing in children with short stature associated to low IGF-1 and IGFBP-3 serum levels, even in the context of normal response to growth hormone provocative testing (GHPT). • Growth hormone provocative tests have many limitations. • Phenotype between GHD and GHI may overlap. • Genetic evaluation is an additional tool towards a definitive diagnosis of GHD. • GH1 p.R209H variant has markedly variable clinical and biochemical consequences. • It is advisable to explore GH1 in short children with low IGF-I and IGFBP-3, despite normal GHPT. [ABSTRACT FROM AUTHOR]

Background Management of vascular malformations requires microcatheter manipulation through distal tortuous arterial feeders <1 mm in diameter to permit safe and effective embolization at the fistula or nidus location. The ASAHI CHIKAI 008 microguidewire (ACM) recently introduced in the United States was used to evaluate microcatheter torque, support, and safety in distal microcatheter navigation. Methods The use of the ACM in conjunction with flow-directed and over-the-wire microcatheters was evaluated in 25 neuroendovascular cases performed by a single operator for endovascular microcatheter embolization of intracranial vascular malformations over a 1-year period. The study evaluated angiographic evidence of distal microcatheter positioning, subsequent obliteration of the fistula at the location, and any complications. Results The microguidewire was used in microcatheter embolization of 10 vein of Galen malformations, 11 brain and head and neck arteriovenous malformations, 2 spinal dural arteriovenous fistulas, and 2 cranial dural arteriovenous fistulas. Good flow-directed and over-the-wire microcatheter placement using the ACM was possible across the spectrum of cases achieving optimal catheterization and safe embolization in all. There were no microguidewire- or microcatheter-related vessel spasms, dissections, or perforations during combined or individual manipulation and no contrast or embolic extravasation on fluoroscopy or postembolization angiography. Conclusions The ACM is a safe, sturdy microguidewire that provides good torque in distal arterial anatomy, while providing microcatheter support and maintaining tip configuration on repeated use. [ABSTRACT FROM AUTHOR]

Abstract Epstein Barr virus (EBV) has a large DNA genome assumed to be stable, but also subject to mutational processes such as nucleotide substitution and recombination, the latter explored to a lesser extent. Moreover, differences in the extent of recombination events across herpes sub-families were recently reported. Given the relevance of recombination in viral evolution and its possible impact in pathogenesis, we aimed to fully characterize and quantify its extension in all available EBV complete genome by assessing global and local recombination rate values (⍴/bp). Our results provide the first EBV recombination map based on recombination rates assessment, both at a global and gene by gene level, where the mean value for the entire genome was 0.035 (HPDI 0.020–0.062) ⍴/bp. We quantified how this evolutionary process changes along the EBV genome, and proved it to be non-homogeneous, since regulatory regions depicted the lowest recombination rate values while repetitive regions the highest signal. Moreover, GC content rich regions seem not to be linked to high recombination rates as previously reported. At an intragenic level, four genes (EBNA3C, EBNA3B, BRRF2 and BBLF2-BBLF3) presented a recombination rate above genome average. We specifically quantified the signal strength among different recombination-initiators previously described features and concluded that those which elicited the greatest amount of changes in ⍴/bp, TGGAG and CCCAG, were two well characterized recombination inducing motifs in eukaryotic cells. Strikingly, although TGGAG was not the most frequently detected DNA motif across the EBV genome (697 hits), it still induced a significantly greater proportion of initiation events (0.025 events/hits) than other more represented motifs, p -value = 0.04; one tailed proportion test. Present results support the idea that diversity and evolution of herpesviruses are impacted by mechanisms, such as recombination, which extends beyond the usual consideration of point mutations. Highlights • We provide the first recombination rate map for the entire EBV genome. • Recombination landscape was heterogeneous among EBV genome at global and local level. • GC content was not a key feature influencing recombination in EBV. • Among recombination-inducing DNA motifs, TGGAG and CCCAG were the most meaningful. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a degenerative lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Cell therapy using different cell types, including mesenchymal stromal cells (MSCs), has been considered as a potential approach for the treatment of DMD. MSCs can be obtained from autologous sources such as bone marrow and adipose tissues or from allogeneic placenta and umbilical cord. The safety and therapeutic impact of these cells has been demonstrated in pre-clinical and clinical studies and their functions are attributed to paracrine effects that are mediated by secreted cytokines and extracellular vesicles. Here, we studied the therapeutic effects of placenta-derived MSCs (PL-MSCs) and their secreted exosomes using mouse and human myoblasts from healthy controls, Duchenne patients and mdx mice. Treatment of myoblasts with conditioned medium or exosomes secreted by PL-MSCs increased the differentiation of these cells and decreased the expression of fibrogenic genes in DMD patient myoblasts. In addition, these treatments also increased the expression of utrophin in these cells. Using a quantitative miR-29c reporter, we demonstrated that the PL-MSC effects were partly mediated by the transfer of exosomal miR-29c. Intramuscular transplantation of PL-MSCs in mdx mice resulted in decreased creatine kinase levels. PL-MSCs significantly decreased the expression of TGF-β and the level of fibrosis in the diaphragm and cardiac muscles, inhibited inflammation and increased utrophin expression. In vivo imaging analyses using MSCs labeled with gold nanoparticles or fluorescent dyes demonstrated localization of the cells in the muscle tissues up to 3 weeks post treatment. Altogether, these results demonstrate that PL-MSCs and their secreted exosomes have important clinical applications in cell therapy of DMD partly via the targeted delivery of exosomal miR-29c. [ABSTRACT FROM AUTHOR]

The objective of this study was to measure the impact of the mechanized chlorpyrifos, copper oxychloride and myclobutanil application in a small peach orchard, on humans (operators, bystanders and residents) and on the productive soil. The mean Potential Dermal Exposure (PDE) of the workers (tractor drivers) was 30.8 mL·h − 1 ± 16.4 mL·h − 1 , with no specific pesticide distribution on the laborers body. Although the Margin of Safety (MOS) factor for the application stage were above 1 (safe condition) for myclobutanil and cooper oxycloride it was below 1 for chlorpyrifos. The mix and load stage remained as the riskier operation. Pesticide found on the orchard soil ranged from 5.5% to 14.8% of the total chlorpyrifos, copper oxychloride and myclobutanil applied. Pesticide drift was experimentally measured, finding values in the range of 2.4% to 11.2% of the total pesticide applied. Using experimental drift values, bystander (for one application), resident (for 20 applications) and earthworm (for one application) risk indicators (RIs) were calculated for the chlorpyrifos plus copper oxychloride and for myclobutanil treatments for different distances to the orchard border. Earthworm RI was correlated with experimental Eisenia andrei ecotoxicological assays (enzymatic activities: cholinesterases, carboxylesterases and glutathione S-transferases; behavioral: avoidance and bait-lamina tests) with good correlation. [ABSTRACT FROM AUTHOR]

Horticulture makes intensive use of soil and extensive use of polyethylene (PE) sheeting and pesticides, producing an environment where the dynamics between soil and plastics can affect pesticide fate. We have determined that the presence of plastic residues in the horticultural soil of small production units equals 10% of the soil area, being meso and macro-sections the predominant fragment sizes. All soil samples were taken from different plots located in Cuartel V, Moreno district, in the suburbs of Buenos Aires city, Argentina. Laboratory experiments were conducted to see the relations among pesticide, soil and PE film. Endosulfan recovery from LDPE films (25 μm and 100 μm) was studied, observing evidence that indicated migration to the inside of the plastic matrix. To further analyze the dynamics of pesticide migration to soil and atmosphere, experiments using chlorpyrifos, procymidone and trifluralin were performed in soil–plastic–atmosphere microenvironments, showing that up to 24 h significant amounts of pesticides moved away from the PE film. To determine whether PE residues could act as potential pesticide collector in soil, column elution experiments were done using chlorpyrifos, procymidone and trifluralin. Results showed an important pesticide accumulation in the mulch film (584 μg–2284 μg pesticide/g plastic) compared to soil (13 μg–32 μg pesticide/g soil). Finally, chemical and photochemical degradation of deltamethrin adsorbed in PE film was studied, finding a protective effect on hydrolysis but no protective effect on photodegradation. We believe that a deeper understanding of the dynamics among soil, plastic and pesticides in horticultural productive systems may contribute to alert for the implications of PE use for plastic sheeting. [ABSTRACT FROM AUTHOR]

Background Single-ventricle patients undergoing surgical reconstruction experience a high rate of brain injury. Incidental findings on preoperative brain scans may result in safety considerations involving hemorrhage extension during cardiopulmonary bypass that result in surgical postponement. Methods Single-ventricle patients were studied with brain scans immediately preoperatively, as part of a National Institutes of Health study, and were reviewed by neuroradiology immediately before cardiopulmonary bypass. Results Of 144 consecutive patients recruited into the project, 33 were studied before stage I (3.7 ± 1.8 days), 34 before bidirectional Glenn (5.8 ± 0.5 months), and 67 before Fontan (3.3 ± 1.1 years) operations. Six operations (4.5%), 2 before stage I, 3 before bidirectional Glenn, and 1 before Fontan, were postponed because of concerning findings on brain magnetic resonance imaging. Five were due to unexpected incidental findings of acute intracranial hemorrhage, and 1 was due to diffuse cerebellar cytotoxic edema; none who proceeded to operation had these lesions. Prematurity and genetic syndromes were not present in any patients with a postponed operation. Four of 4 before bidirectional Glenn/Fontan with surgical delays had hypoplastic left heart syndrome compared with 44 of 97 who did not ( p = 0.048). After observation and follow-up, all eventually had successful operations with bypass. Conclusions Preoperative brain magnetic resonance imaging performed in children with single ventricles disclosed injuries in 4.5% leading to surgical delay; hemorrhagic lesions were most common and raised concerns for extension during the operation. The true risk of progression and need for delay of the operation due to heparinization associated with these lesions remains uncertain. [ABSTRACT FROM AUTHOR]

Abstract: Potential dermal exposure measurements of horticultural and floricultural field operators that handled concentrated pesticides showed a correlation with the types of formulations used (liquid or solid) during the mix and load stage. For liquid formulations, hand exposure was 22–62 times greater than that for solid ones. The dermal exposure mechanism was studied for this formulation under laboratory conditions, finding that the rupture of the aluminum seal of the pesticide container and the color of the liquid formulation are important factors. Additionally, significant external surface contamination of pesticide containers collected at horticultural farms was found. This could partially account for the differences between the exposure levels of field and laboratory experiments for liquid formulations. [Copyright &y& Elsevier]

Phthalic acid esters (PAEs) were determined in polyethylene covers used in horticultural production units located at Moreno and La Plata districts (Buenos Aires, Argentina), detecting 0.69–8.75 mg PAEs kg−1 plastic in greenhouse and tunnel films. The PAEs found were diisobutylphthalate (DIBP), dibutylphthalate (DBP) and diethylhexylphthalate (DEHP). DBP was chosen as a model molecule to carry out the photochemical degradation studies that led to the formation of monobutylphthalate (MBP) and phthalic acid (PA). DBP, MBP and PA migration from plastic covers was studied, finding that while DBP and MBP moved to soil and atmosphere in short times (<48 h), PA remained in the agricultural covers. Further experiments with DBP were made to explore the effect on migration of temperature (20 °C, 50 °C), film thickness (25 μm, 100 μm) and plastic ageing by solarization, observing that temperature increase, film thickness reduction and ageing by solarization favored DBP migration to the environment. DBP and MBP impact on soil were evaluated by avoidance and reproduction tests using Eisenia andrei as bioindicator. Both compounds reduced cocoon viability decreasing the number of juveniles at the lowest concentration assayed (0.1 mg kg−1 of soil). At higher DBP and MBP concentrations the reproductive parameters (number of total cocoons, hatchability and number of juveniles) also showed alterations compared with the controls. Carboxylesterases (CaE), cholinesterases (ChE) and glutathion-S-transferases (GST) activities were analyzed in E. andrei exposed to DBP; cholinesterases activities were reduced at 1 and 10 mg DBP kg−1 soil, and glutathione S-transferases activities were increased at 10 mg DBP kg−1 soil while no effect was observed on carboxylesterases activities. These results emphasize the need to continue studying the impact of PAEs and their photodegradation products on the environment. [Display omitted] • (0.69–8.75) mg PAEs.kg−1 of plastic covers were found in Argentinean orchards. • Dibutylphthalate (DBP) was one of the main PAEs found. • DBP photodegraded to monobutylphthalate (MBP) and phthalic acid (PA). • DBP and MBP migrate from plastic covers to the environment. • DBP and MBP in soil alter E. andrei reproduction behaviour. [ABSTRACT FROM AUTHOR]

Background: The effect of carotid endarterectomy on cognitive function is not fully understood. This study aims to characterize changes in cerebral blood flow after carotid endarterectomy and to determine if patients with improvement in cerebral blood flow have improved cognitive function after endarterectomy. Methods: Cerebral blood flow was measured preoperatively and 1 month postoperatively using phase contrast magnetic resonance angiography. Preoperative flow impairment was defined as ipsilateral flow at least 20% less than contralateral flow. Improvement in flow was defined as an absolute increase of at least 0.10 in flow ratio from pre- to postoperative assessments. Patients underwent cognitive testing preoperatively and at 1, 6, and 12 months postoperatively. Results: Twenty-four patients with unilateral carotid stenosis were enrolled from 3 sites. Preoperative internal carotid artery (ICA) and middle cerebral artery (MCA) flow impairment was observed in 50% and 22% of patients, respectively. Patients with preoperative flow impairment had an average of 0.25 and 0.16 absolute improvement in flow ratio in the ICA and MCA vessels, respectively; this was statistically significant for patients with baseline ICA flow impairment (P < .01). One hundred percent of patients with improvement in MCA flow had a significant improvement in attention compared to 56% of patients without MCA flow improvement (P = .06). Clinically significant improvements in all 4 cognitive domains were observed at 1 year (P < .01). Conclusions: Patients with baseline impairment of MCA blood flow were more likely to experience improvement in flow after revascularization. Improvement in MCA blood flow was associated with greater cognitive improvement in attention and executive functioning. [Copyright &y& Elsevier]

Abstract: Tripolar and other electrode configurations that use simultaneous stimulation inside the cochlea have been tested to reduce channel interactions compared to the monopolar stimulation conventionally used in cochlear implant systems. However, these “focused” configurations require increased current levels to achieve sufficient loudness. In this study, we investigate whether highly accurate recordings of the intracochlear electrical field set up by monopolar and tripolar configurations correlate to their effect on loudness. We related the intra-scalar potential distribution to behavioral loudness, by introducing a free parameter (α) which parameterizes the degree to which the potential field peak set up inside the scala tympani is still present at the location of the targeted neural tissue. Loudness balancing was performed on four levels between behavioral threshold and the most comfortable loudness level in a group of 10 experienced Advanced Bionics cochlear implant users. The effect of the amount of focusing on loudness was well explained by α per subject location along the basilar membrane. We found that α was unaffected by presentation level. Moreover, the ratios between the monopolar and tripolar currents, balanced for equal loudness, were approximately the same for all presentation levels. This suggests a linear loudness growth with increasing current level and that the equal peak hypothesis may predict the loudness of threshold as well as at supra-threshold levels. These results suggest that advanced electrical field imaging, complemented with limited psychophysical testing, more specifically at only one presentation level, enables estimation of the loudness growth of complex electrode configurations. [ABSTRACT FROM AUTHOR]

• A machine vision system for young sheep identification was developed. • Sheep identification was based on facial images. • This system can be utilised to identify individual sheep throughout a growth period of about 3 months – from age 2 to 5 months. • The system presented may be adapted to identify other livestocks and may replace conventional RFID identification. • The identification system is more animal welfare-friendly , and it had a lower cost. Biometric identification provides an important tool for precision livestock farming. This study investigates the effect of weight gain and sheep maturation on recognition performance. Sheep facial identification was implemented using two convolutional neural network (CNN) called Faster R-CNN, and ResNet50V2, equipped with the state-of-art Additive Angular Margin (ArcFace) loss function. The identification model was tested on 47 young sheep at different stages, during a 3-month growth period, when they were between 2 and 5 months old, throughout which the sheep gained approximately 30 kilograms in weight. Results revealed that when the model was trained and tested on images of sheep aged 2 months, the average accuracy of the group was 95.4%, compared with 91.3% when trained on images of sheep aged 2 months but tested on images of sheep aged 5 months. [ABSTRACT FROM AUTHOR]

Abstract: The mast cell specific monoclonal antibody, mAb BGD6, is a mast cell lineage marker [Jamur, M.C., Grodzki, A.C., Berenstein, E.H., Hamawy, M.M., Siraganian, R.P., Oliver, C., 2005. Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 105, 4282–4289]. In rat basophilic leukemia (RBL-2H3) cells, mAb BGD6 precipitates cell-surface proteins of ∼110 and 40–60kDa. An expression cloning strategy was used to identify proteins that interact with mAb BGD6. A RBL-2H3 cDNA library in plasmids was transfected into PEAK cells, which do not bind mAb BGD6, and positive cells were selected with mAb BGD6. The plasmids recovered from the positive cells were amplified; retransfected into PEAK cells and after several screening cycles a positive clone was identified. This clone showed almost complete identity to FcγRIIB (CD32), the low affinity IgG receptor. However, in contrast to the sequence in GenBank, this clone had an insert of 141bp which codes for a longer isoform of this molecule with an extra 47 aa in its cytoplasmic domain. In RBL-2H3 cells both isoforms were expressed, with higher expression of the shorter form. The mechanism of binding of mAB BGD6 on both RBL-2H3 and CD32 transfected PEAK cells was then examined. Intact mAb BGD6 bound to both RBL-2H3 and CD32 expressing PEAK cells, but F(ab′)2 fragments bound only to RBL-2H3 cells demonstrating that mAb BGD6 binds to FcγRIIB only through its Fc portion. On RBL-2H3 cells, the Fab of an anti-CD32 mAb partially inhibited the binding of intact mAb BGD6. The binding pattern of mAb BGD6 inhibited with anti-CD32 resembled that of the F(ab′)2 fragment of the antibody suggesting that the Fc portion of mAb BGD6 contributes to its binding on cells that have FcγRIIB. These results are consistent with a model where mAb BGD6 binds through its Fab portion to a ∼110kDa protein and the Fc tail interacts with FcγRIIB (CD32). [Copyright &y& Elsevier]

Abstract: We study superpotential perturbations of q deformed Yang–Mills for q a root of unity. This is a special case whose geometry is associated to an orbifold with three lines of codimension two singularities meeting at the origin. We perform field theory perturbations that leave only co-dimension three singularities of conifold type in the geometry. We show that there are two “fractional brane” solutions of the F-term equations for each singularity in the deformed geometry, and that the number of complex deformations of that geometry also matches the number of singularities. This proves that for this case there are no local or non-local obstructions to deformation. We also show that the associated Dijkgraaf–Vafa matrix model has a solvable sector, and that the loop equations in this sector encode the full deformed geometry of the theory. [Copyright &y& Elsevier]

Beginning with the planar limit of SYM theory, we study planar diagrams for field theory deformations of which are marginal at the free field theory level. We show that the requirement of integrability of the full one-loop dilatation operator in the scalar sector, places very strong constraints on the field theory, so that the only soluble models correspond essentially to orbifolds of SYM. For these, the associated spin chain model gets twisted boundary conditions that depend on the length of the chain, but which are still integrable. We also show that theories with integrable subsectors appear quite generically, and it is possible to engineer integrable subsectors to have some specific symmetry, however these do not generally lead to full integrability. We also try to construct a theory whose spin chain has quantum group symmetry as a deformation of the R-symmetry structure of SYM. We show that it is not possible to obtain a spin chain with that symmetry from deformations of the scalar potential of SYM.We also show that the natural context for these questions can be better phrased in terms of multi-matrix quantum mechanics rather than in four-dimensional field theories. [Copyright &y& Elsevier]

PURPOSE: To present the physics data supporting the validity of the clinical dose data from the RAD-IR study and to document the performance of dosimetry-components of these systems over time. MATERIALS AND METHODS: Sites at seven academic medical centers in the United States prospectively contributed data for each of 12 fluoroscopic units. All units were compatible with International Electrotechnical Commission (IEC) standard 60601-2-43. Comprehensive evaluations and periodic consistency checks were performed to verify the performance of each unit''s dosimeter. Comprehensive evaluations compared system performance against calibrated ionization chambers under nine combinations of operating conditions. Consistency checks provided more frequent dosimetry data, with use of each unit''s built-in dosimetry equipment and a standard water phantom. RESULTS: During the 3-year study, data were collected for 48 comprehensive evaluations and 581 consistency checks. For the comprehensive evaluations, the mean (95% confidence interval range) ratio of system to external measurements was 1.03 (1.00–1.05) for fluoroscopy and 0.93 (0.90–0.96) for acquisition. The expected ratio was 0.93 for both. For consistency checks, the values were 1.00 (0.98–1.02) for fluoroscopy and 1.00 (0.98–1.02) for acquisition. Each system was compared across time to its own mean value. Overall uncertainty was estimated by adding the standard deviations of the comprehensive and consistency measurements in quadrature. The authors estimate that the overall error in clinical cumulative dose measurements reported in RAD-IR is 24%. CONCLUSION: Dosimetric accuracy was well within the tolerances established by IEC standard 60601-2-43. The clinical dose data reported in the RAD-IR study are valid. [Copyright &y& Elsevier]

In this paper we study the conjectured dual operators to a near maximal giant graviton and their open string fluctuations in the large N limit. Using matrix model estimates we show that the spectrum of states near the D-brane operator is consistent with a Fock space of open plus closed string states. We also give an argument that these operators, in spite of having large R charge of order N, are amenable to being studied with standard perturbative techniques, which organize themselves in a 1/N expansion. Also the spectrum of operators dual to massless fluctuations on the D-brane is shown to be protected from weak to strong coupling at leading order, so it is possible to read the shape of the dual operator by understanding how the spherical harmonics of the D-brane fluctuations appear. [Copyright &y& Elsevier]

Purpose: To determine peak skin dose (PSD), a measure of the likelihood of radiation-induced skin effects, for a variety of common interventional radiology and interventional neuroradiology procedures, and to identify procedures associated with a PSD greater than 2 Gy.Materials and Methods: An observational study was conducted at seven academic medical centers in the United States. Sites prospectively contributed demographic and radiation dose data for subjects undergoing 21 specific procedures in a fluoroscopic suite equipped with built-in dosimetry capability. Comprehensive physics evaluations and periodic consistency checks were performed on each unit to verify the stability and consistency of the dosimeter. Seven of 12 fluoroscopic suites in the study were equipped with skin dose mapping software.Results: Over a 3-year period, skin dose data were recorded for 800 instances of 21 interventional radiology procedures. Wide variation in PSD was observed for different instances of the same procedure. Some instances of each procedure we studied resulted in a PSD greater than 2 Gy, except for nephrostomy, pulmonary angiography, and inferior vena cava filter placement. Some instances of transjugular intrahepatic portosystemic shunt (TIPS) creation, renal/visceral angioplasty, and angiographic diagnosis and therapy of gastrointestinal hemorrhage produced PSDs greater than 3 Gy. Some instances of hepatic chemoembolization, other tumor embolization, and neuroembolization procedures in the head and spine produced PSDs greater than 5 Gy. In a subset of 709 instances of higher-dose procedures, there was good overall correlation between PSD and cumulative dose (r = 0.86; P <.000001) and between PSD and dose-area-product (r = 0.85, P <.000001), but there was wide variation in these relationships for individual instances.Conclusions: There are substantial variations in PSD among instances of the same procedure and among different procedure types. Most of the procedures observed may produce a PSD sufficient to cause deterministic effects in skin. It is suggested that dose data be recorded routinely for TIPS creation, angioplasty in the abdomen or pelvis, all embolization procedures, and especially for head and spine embolization procedures. Measurement or estimation of PSD is the best method for determining the likelihood of radiation-induced skin effects. Skin dose mapping is preferable to a single-point measurement of PSD. [ABSTRACT FROM AUTHOR]

Purpose: To determine patient radiation doses for interventional radiology and neuroradiology procedures, to identify procedures associated with higher radiation doses, and to determine the effects of various parameters on patient doses.Materials and Methods: A prospective observational study was performed at seven academic medical centers. Each site contributed demographic and radiation dose data for subjects undergoing specific procedures in fluoroscopic suites equipped with built-in cumulative dose (CD) and dose-area-product (DAP) measurement capability compliant with International Electrotechnical Commission standard 60601-2-43. The accuracy of the dosimetry was confirmed by comprehensive measurements and by frequent consistency checks performed over the course of the study.Results: Data were collected on 2,142 instances of interventional radiology procedures, 48 comprehensive physics evaluations, and 581 periodic consistency checks from the 12 fluoroscopic units in the study. There were wide variations in dose and statistically significant differences in fluoroscopy time, number of images, DAP, and CD for different instances of the same procedure, depending on the nature of the lesion, its anatomic location, and the complexity of the procedure. For the 2,142 instances, observed CD and DAP correlate well overall (r = 0.83, P <.000001), but correlation in individual instances is poor. The same is true for the correlation between fluoroscopy time and CD (r = 0.79, P <.000001). The correlation between fluoroscopy time and DAP (r = 0.60, P <.000001) is not as good. In 6% of instances (128 of 2,142), which were principally embolization procedures, transjugular intrahepatic portosystemic shunt (TIPS) procedures, and renal/visceral artery stent placements, CD was greater than 5 Gy.Conclusions: Most procedures studied can result in clinically significant radiation dose to the patient, even when performed by trained operators with use of dose-reducing technology and modern fluoroscopic equipment. Embolization procedures, TIPS creation, and renal/visceral artery stent placement are associated with a substantial likelihood of clinically significant patient dose. At minimum, patient dose data should be recorded in the medical record for these three types of procedures. These data should include indicators of the risk of deterministic effects as well as the risk of stochastic effects. [ABSTRACT FROM AUTHOR]

• Genetic deletion of either Hs3st3a1 or Hs3st3b1 in mice reduces salivary epithelial morphogenesis. • Loss of 3- O -sulfotranserases reduces basement membrane sulfation and alters HS composition. • Loss of individual 3- O -sulfotransferases alters specific HS biosynthetic transcriptional programs, suggesting Hs3st3a1 regulates Hs3st3b1. • Deletion of Hs3st3a1 or Hs3st3b1 , which are highly expressed in myoepithelial cells, impairs basal salivary hypofunction. Heparan sulfate 3- O -sulfotransferases generate highly sulfated but rare 3- O -sulfated heparan sulfate (HS) epitopes on cell surfaces and in the extracellular matrix. Previous ex vivo experiments suggested functional redundancy exists among the family of seven enzymes but that Hs3st3a1 and Hs3st3b1 sulfated HS increases epithelial FGFR signaling and morphogenesis. Single-cell RNAseq analysis of control SMGs identifies increased expression of Hs3st3a1 and Hs3st3b1 in endbud and myoepithelial cells, both of which are progenitor cells during development and regeneration. To analyze their in vivo functions, we generated both Hs3st3a1−/- and Hs3st3b1−/- single knockout mice, which are viable and fertile. Salivary glands from both mice have impaired fetal epithelial morphogenesis when cultured with FGF10. Hs3st3b1−/- mice have reduced intact SMG branching morphogenesis and reduced 3- O -sulfated HS in the basement membrane. Analysis of HS biosynthetic enzyme transcription highlighted some compensatory changes in sulfotransferases expression early in development. The overall glycosaminoglycan composition of adult control and KO mice were similar, although HS disaccharide analysis showed increased N - and non-sulfated disaccharides in Hs3st3a1−/− HS. Analysis of adult KO gland function revealed normal secretory innervation, but without stimulation there was an increase in frequency of drinking behavior in both KO mice, suggesting basal salivary hypofunction, possibly due to myoepithelial dysfunction. Understanding how 3- O -sulfation regulates myoepithelial progenitor function will be important to manipulate HS-binding growth factors to enhance tissue function and regeneration. [ABSTRACT FROM AUTHOR]

Purpose: This case series describes patients with head and neck arteriovenous malformations who underwent oral and maxillofacial surgical procedures combined with interventional radiology techniques to minimize blood loss.Materials and Methods: Twelve patients underwent femoral cerebral angiography to visualize the extent of vascular malformation. Before the surgical procedures, surgical sites were devascularized by direct injection of hemostatic or embolic agents. Direct puncture sclerotherapy at the base of surgical sites was performed using Surgiflo or n-butylcyanoacrylate glue. Surgical procedures were carried out in routine fashion. A hemostatic packing of FloSeal, Gelfoam, and Avitene was adapted to the surgical sites.Results: Direct puncture sclerotherapy with Surgiflo or n-butylcyanoacrylate glue resulted in minimal blood loss intraoperatively. Local application of the FloSeal, Gelfoam, and Avitene packing sustained hemostasis and produced excellent healing postoperatively.Conclusion: Patients with arteriovenous malformations can safely undergo routine oral and maxillofacial surgical procedures with minimal blood loss when appropriate endovascular techniques and local hemostatic measures are used by the interventional radiologist and oral and maxillofacial surgeon. [ABSTRACT FROM AUTHOR]

Abstract: High affinity IgE receptor (FcɛRI)-induced activation of mast cells results in degranulation and generation of leukotrienes and cytokines. FcɛRI-induced mast cell activation was analyzed at a single cell basis using a rat basophilic leukemia (RBL-2H3) cell line transfected with a reporter plasmid containing three tandem NFAT (nuclear factor of activated T cells) binding sites fused to enhanced green fluorescent protein (GFP). Surprisingly, with this sensitive detection system, there is activation of IgE sensitized cells at concentrations of antigen as low as 10pg/ml, which was 10-fold lower than was detected by degranulation. There were differences in signaling pathways leading to degranulation compared to NFAT-mediated gene activation. Both signaling to NFAT activation and degranulation required Syk and calcineurin. However inhibitors of the phosphatidylinositol 3-kinase pathway blocked degranulation but did not NFAT activation. The results also indicate that NFAT was activated at lower intracellular signals compared to degranulation. Therefore, FcɛRI activation can result in nuclear signals in the absence of the release of mediators. [Copyright &y& Elsevier]

• In this study, high maternal educational level was associated with vaccine hesitancy. • Hesitancy was associated with incomplete MMR and HPV immunization series. • We identified three domains: Benefits , Harms and Confidence in the Health System. • Vaccine Hesitancy Scale is a reliable and valid tool. The WHO SAGE Working Group on Vaccine Hesitancy developed the Vaccine Hesitancy Scale (VHS) to identify and compare hesitancy in different global settings. The objectives of the study were to describe and analyze vaccine hesitancy and to validate the VHS in a group of parents in Buenos Aires city, Argentina. A cross-sectional survey was conducted in parents of 1–3 and 12–15 year-old children at three health centres in Buenos Aires City, between June 2018 and May 2019. Sociodemographic data were collected together with history of refusal and/or delay in children's vaccination (defined as hesitancy). The 10-item VHS using 5-point Likert-scale (higher scores indicating lower hesitancy) was administered and children's immunization record cards were verified. Link between hesitancy and socio-demographic variables, and hesitancy and vaccination status was analyzed for five specific vaccines. Cronbach's α was used to determine internal consistency reliability and factor analysis to confirm survey subdomains. Simple and multiple regression analysis was used to examine associations between VHS scores and hesitancy, and VHS scores and vaccination status. Six hundred parents were surveyed and 469 immunization cards verified; 11.5% (n = 69) parents were hesitant. High maternal educational level showed significant association with hesitancy (OR 2.66 95% CI: 1.20–5.9) in the adjusted model. Hesitancy was significantly associated with incomplete MMR vaccination in children (OR 4.43 95% CI: 1.08–8.20) and HPV vaccination in adolescents (OR 3.75 95% CI: 1.54–9.12). Cronbach's α was 0.66 and factor analysis identified three underlying constructs: "Benefits", "Harms" and "Confidence in healthcare system". High scores in VHS were associated with lack of hesitancy (OR 1.2 95% CI: 1.13–1.27) and complete vaccination status (OR 1.07 95% CI: 1.02–1.12). Hesitancy was associated with high maternal educational level, and incomplete MMR and HPV immunization status in children and adolescents. VHS was a reliable and valid tool in this population. [ABSTRACT FROM AUTHOR]