Increased plasma immunoreactive 6-keto-prostaglandin F1 alpha levels in newborns with idiopathic respiratory distress syndrome.
Serial plasma concentrations of immunoreactive 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable hydration product of prostacyclin (PGI2), were measured with radioimmunoassay during the first month of life in 25 preterm infants with idiopathic respiratory distress syndrome (IRDS) and 38 preterm controls with normal heart and lung function. The levels of 6-keto-PGF1 alpha (521 +/- 81 pg/ml, mean +/- S.E.) in the infants with IRDS were higher (P less than 0.05) than those in the controls (335 +/- 42 pg/ml) on the first day of life, but thereafter no difference was seen. The highest first day 6-keto-PGF1 alpha level (1448 pg/ml) was found in the infant who died because of severe IRDS at the age of 19 h. The plasma 6-keto-PGF1 alpha concentrations in the distressed infants correlated positively with the alveolar-arterial oxygen gradient and the need of additional oxygen, but negatively with the arterial pH. In addition, an inverse correlation between the first day concentrations of 6-keto-PGF1 alpha and the lowest arterial oxygen tension in infants needing assisted ventilation was found. The mode of delivery (Cesarean section versus vaginal delivery) the gestational age, birth weight, sex or Apgar scores of the infants were not related to the 6-keto-PGF1 alpha levels on the first day of life. Neither did maternal pre-eclampsia, diabetes mellitus, or antenatal glucocorticoid treatment have any effect on the 6-keto-PGF1 alpha concentrations in the newborns. Our data suggest that a surge of the vasodilatory and antiaggregatory PGI2 is released during the early stage of IRDS, possibly in an attempt to increase the pulmonary perfusion. Our results give further indirect evidence that hypoxia stimulates the PGI2 production. High plasma immunoreactive 6-keto-PGF1 alpha levels during the early phase of IRDS suggest an increased generation of the vasodilatory and antiaggregatory PGI2 in this syndrome. This may be an attempt to overcome the increased pulmonary vasconstriction in IRDS. When the PGI2 formation rapidly declines after the first day of life, a relative PGI2 deficiency may ensue.


Mechanical property determination of bone through nano- and micro-indentation testing and finite element simulation.
Measurement of the mechanical properties of bone is important for estimating the stresses and strains exerted at the cellular level due to loading experienced on a macro-scale. Nano- and micro-mechanical properties of bone are also of interest to the pharmaceutical industry when drug therapies have intentional or non-intentional effects on bone mineral content and strength. The interactions that can occur between nano- and micro-indentation creep test condition parameters were considered in this study, and average hardness and elastic modulus were obtained as a function of indentation testing conditions (maximum load, load/unload rate, load-holding time, and indenter shape). The results suggest that bone reveals different mechanical properties when loading increases from the nano- to the micro-scale range (microN to N), which were measured using low- and high-load indentation testing systems. A four-parameter visco-elastic/plastic constitutive model was then applied to simulate the indentation load vs. depth response over both load ranges. Good agreement between the experimental data and finite element model was obtained when simulating the visco-elastic/plastic response of bone. The results highlight the complexity of bone as a biological tissue and the need to understand the impact of testing conditions on the measured results.


HLA-DS molecules and their relation to supertypic specificities.
We have analyzed the structures of HLA-DS molecules from DR1, 2, 3, 4, 5, and 7 cell lines by two-dimensional gel electrophoresis and examined the relationship of HLA-DS molecules to those expressing the supertypic specificities MT1, MB3, and MT3. These studies have allowed us to conclude that the HLA-DS locus is as polymorphic as HLA-DR and that the MT1 and MB3 supertypic specificities reside on DS molecules. Furthermore, MT1 molecules from DR1, DR2, and DRw6 cell lines are structurally different as are MB3 molecules from DR4 and DR5 cell lines. In addition, studies using two MT3 specific reagents, a monoclonal antibody, 109d6, and an alloantiserum, Hon, suggest that MT3 is a cross-reactive determinant present on products of two different loci: a DS4 molecule and a DR7-like molecule.


Head injuries in accident and emergency departments at Scottish hospitals.
The features of 3500 patients with head injury who attended accident and emergency departments in Scotland during 1974 are described. These represented 10 per cent of all attenders at these departments. Recent alcohol consumption was noted in 25 per cent of adult males; this was commonest amongst those who were victims of assault or pedestrians involved in traffic accidents. Forty-one per cent of patients had scalp wounds; 58 per cent had radiographs of the skull taken and of these 2.7 per cent had fractures of the skull. Although 20 per cent of patients had altered consciousness at some time, only 5 per cent showed any evidence of impaired consciousness when seen at hospital. Twenty-three per cent of those attending were admitted to hospital. Criteria which are important when assessing whether a head-injured patient should be admitted to hospital are listed.


Mastering the Match: Recruiting a Successful Surgery Resident.
The objective of general surgery residency is to produce competent surgeons. At a minimum this requires being procedurally and clinically capable and able to pass the board exams. Recruitment is designed to select those residents who can successfully do so. But there is more to being a successful resident than that. In this review, we attempt to define a "successful resident" and how to attract them to your program. Resident applicants are still most concerned with matching to a program that will prepare them for a surgery career. Though there is variation of importance for different applicants, resident life, comradery, and relationships with faculty or mentors do factor into residency ranking. The program website remains the most utilized resource for applicants. However, social media (SM) has an increasing role in applicants' evaluation of a program. SM and the preinterview gathering seem to expose the subjective aspects of a program most effectively. Additional assessments evaluating personality, grit or career goals may assist in screening applicants for good "fit." In order to recruit successful residents, it is necessary to determine which applicant attributes are important to the program. Additionally, a program must maintain an updated website with clearly delineated resident expectations and program strengths. The screening and interview process must be maximized to target residents with career goals complimentary to available program opportunities. If SM is utilized, post should be frequent with relevant information pertaining to both resident life and educational or clinical opportunities.


Birefringence-derived scleral artifacts in optical coherence tomography images of eyes with pathologic myopia.
We investigated birefringence-derived scleral artifacts in optical coherence tomography (OCT) images of eyes with pathologic myopia. This study included 76 eyes of 42 patients with pathologic myopia. Five sets of OCT B-scan images of the macula were obtained using commercial swept-source OCT. A dataset of prototype swept-source polarization-diversity OCT images was used to identify polarization-dependent OCT images (i.e., complex averaging of OCT signals from two polarization channels) and polarization-independent OCT images (i.e., intensity averaging of two OCT signals). Polarization-dependent OCT images and commercial OCT images were assessed for the presence of birefringence-derived artifacts by comparison with polarization-independent OCT images. Both polarization-dependent OCT images and commercial OCT images contained scleral vessel artifacts. Scleral vessel artifacts were present in 46 of 76 eyes (60.5%) imaged by polarization-dependent OCT and 17 of 76 eyes (22.4%) imaged by commercial OCT. The proportion of images that showed scleral vessel artifacts was significantly greater among polarization-dependent OCT images than among commercial OCT images (P < 0.001). Additionally, polarization-dependent OCT images showed low-intensity band artifacts. This study demonstrated the existence of birefringence-derived scleral artifacts in commercial OCT images and indicated that polarization-diversity OCT is an effective tool to evaluate the presence of these artifacts.


Gain-of-function missense variant in SLC12A2, encoding the bumetanide-sensitive NKCC1 cotransporter, identified in human schizophrenia.
Perturbations of γ-aminobutyric acid (GABA) neurotransmission in the human prefrontal cortex have been implicated in the pathogenesis of schizophrenia (SCZ), but the mechanisms are unclear. NKCC1 (SLC12A2) is a Cl(-)-importing cation-Cl(-) cotransporter that contributes to the maintenance of depolarizing GABA activity in immature neurons, and variation in SLC12A2 has been shown to increase the risk for schizophrenia via alterations of NKCC1 mRNA expression. However, no disease-causing mutations or functional variants in NKCC1 have been identified in human patients with SCZ. Here, by sequencing three large French-Canadian (FC) patient cohorts of SCZ, autism spectrum disorders (ASD), and intellectual disability (ID), we identified a novel heterozygous NKCC1 missense variant (p.Y199C) in SCZ. This variant is located in an evolutionarily conserved residue in the critical N-terminal regulatory domain and exhibits high predicted pathogenicity. No NKCC1 variants were detected in ASD or ID, and no KCC3 variants were identified in any of the three neurodevelopmental disorder cohorts. Functional experiments show Y199C is a gain-of-function variant, increasing Cl(-)-dependent and bumetanide-sensitive NKCC1 activity even in conditions in which the transporter is normally functionally silent (hypotonicity). These data are the first to describe a functional missense variant in SLC12A2 in human SCZ, and suggest that genetically encoded dysregulation of NKCC1 may be a risk factor for, or contribute to the pathogenesis of, human SCZ.


Critical role for Tbx6 in mesoderm specification in the mouse embryo.
Tbx6 is a member of the T-box family of transcription factor genes. Two mutant alleles of this gene establish that Tbx6 is involved in both the specification and patterning of the somites along the entire length of the embryo. The null allele, Tbx6(tm1Pa), causes abnormal patterning of the cervical somites and improper specification of more posterior paraxial mesoderm, such that it forms ectopic neural tubes. In this study, we use this allele to further investigate the mechanism of action of the Tbx6 gene and investigate possible genetic interactions. We have tested the developmental and differentiation potential of Tbx6(tm1Pa)/Tbx6(tm1Pa) cells in ectopic sites, in vitro, and in chimeras in vivo. We have also documented cell proliferation and cell death in mutant tail buds in an attempt to explain the mechanism of tail bud enlargement in the Tbx6 mutant embryos. Our results indicate specific developmental restrictions on the differentiation of posterior cells lacking Tbx6, once they have traversed the primitive streak, but no restrictions in differentiation of anterior somites, or of Tbx6 null embryonic stem (ES) cells. We further demonstrate that Tbx6 null ES cells fail to populate posterior somites in chimeric embryos. To discover whether different T-box proteins interact on the same down stream targets in areas of expression overlap, we have explored potential interactions between Tbx6 and T (Brachyury) in genetic crosses. Our results reveal that the T(Wis) mutation is epistatic to the Tbx6(tm1Pa) mutation and that there is no apparent genetic interaction. However, homozygosity for Tbx6(tm1Pa) and heterozygosity for T(Wis) mutation shows a combinatorial interaction at the phenotypic level.


Optimised NQR pulse technique for the effective detection of Heroin Base.
The nuclear quadrupole resonance (NQR) method has been applied to Heroin Base (HB) to find an optimised multi-pulse technique for effective detection of HB. Experimental results of applying the proposed spin-locking multi-pulse (SLMP) technique to nitrogen-14 NQR in this sample are presented and convincingly demonstrate as a path towards efficient detection. A detection using a sequence of this character could be achieved over real-world scan volumes for screening of goods. All experiments were carried out at room temperature.


Songbirds: A novel perspective on estrogens and the aging brain.
Songbirds perform some remarkable feats of memory, including forming memories for songs and for complex spatial features of their environments. Research into the neural and hormonal control of these behaviors reveals discrete circuits that can retain considerable plasticity in adulthood. The songbird brain is also a prominent site of estrogen synthesis and a target of estrogen action. Estrogens contribute to the plasticity of the adult songbird brain and contribute to the bird's capacity to form and retrieve some memories. We describe the brain, behavior and endocrinology of songbirds and discuss these findings within the context of the neurology of the aging brain.


The electrochemical reaction controlled optical response of cholestrol oxidase (COx) conjugated CdSe/ZnS quantum dots.
This paper reports the enhanced performance of cholesterol oxidase (COx) conjugated CdSe/ZnS quantum dots (QDs) by using water-soluble mercaptoacitic acid (MAA) as linker. The functionalized MAA-CdSe/ZnS QDs conjugated in four different dilutions of cholesterol oxidase significantly affected QDs photoluminescence intensities, which affected the process of charge transfer from QDs to MAA. The conjugation of COx to MAA-QDs in increased dilutions resulted in the regain of PL intensities, which were attributed to the passivation of MAA HOMO/LUMO states. The electrochemical impedance spectroscopy and cyclic voltammetry of the conjugated QDs were performed to get study the charge transfer mechanism. The 1:1000 diluted COx conjugated MAA-CdSe/ZnS QDs was found to have the lowest charge transfer resistance of 228 Ω, the highest diffusion (~ 1.39 × 10-13 cm2/s) and charge transfer rates (~ 4.5 × 10-6 s-1) between the electrode and the redox species. The current study demonstrated the sensitivity of electrochemical and optical based detection on the alkaline.


[Hormone dependence of 5'-nucleotidase histochemically detected during the development of the epididymis of the rat after birth].
5'nucleotidase activity of the apical border of the epididymal epithelium appears towards the end of the second week during postnatal development. This activity is in correlation with the activity of testicular hormone. Bilateral castration modifies it and testosterone restores this activity.


Evaluation of a theta-defensin in a Murine model of herpes simplex virus type 1 keratitis.
To test the activity of a synthetic theta-defensin, retrocyclin (RC)-2, in a murine herpes simplex virus (HSV)-1 keratitis model. The in vitro antiviral activity of RC-2 against HSV-1 KOS was determined by yield reduction and viral inactivation assays. Efficacy in an experimental murine HSV-1 keratitis model was tested using pre- or postinfection treatment with 0.1% peptide in PBS with or without 2% methylcellulose. Viral titers in the tear film were determined by plaque assay. RC-2 inhibited HSV-1 KOS in vitro with an EC(50) of 10 microM (~20 microg/mL) in yield-reduction assays, but was not directly virucidal. RC-106 (a less active analogue) did not inhibit HSV-1 KOS in culture. Incubating the virus with RC-2 or applying the peptide in 2% methylcellulose to the cornea before viral infection significantly reduced the severity of ocular disease, but postinfection treatment with 0.1% RC-2 in PBS with or without 2% methylcellulose did not. Viral titers were significantly reduced on some days after infection in the preincubation and prophylaxis groups. RC-2 was active against HSV-1 KOS in cultures and showed protective activity in vivo when used in a prophylactic mode, but the peptide showed limited activity in a postinfection herpes keratitis model. These findings support data obtained from experiments with HIV-1, HSV-2, and influenza A, indicating that RCs inhibit the entry of viruses rather than their replication.


Nonradioactive, photobiotin-labelled DNA probes for the routine diagnosis of barley yellow dwarf virus.
Photobiotin was used to prepare biotinylated, nonradioactive nucleic acid probes for the detection of the RNA of barley yellow dwarf virus (BYDV) in plant extracts. A 1.7-kb cDNA of the PAV isolate of BYDV in the plasmid pUC8 vector was biotinylated and then used intact or as sonicated double-stranded DNA fragments. Simple methods were developed for the preparation of partially purified nucleic acid extracts of cereals and their spotting, after formaldehyde treatment, onto nitrocellulose membranes. After hybridization, biotin-labelled DNA bound to BYDV RNA on the nitrocellulose was detected with an avidin-alkaline phosphatase conjugate. BYDV RNA was readily detected with a sensitivity similar to that found with the same probe labelled with 32P by nick translation. Healthy plant extracts gave colourless spots.


A Click Chemistry-Based Artificial Metallo-Nuclease.
Artificial metallo-nucleases (AMNs) are promising DNA damaging drug candidates. Here, we demonstrate how the 1,2,3-triazole linker produced by the Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction can be directed to build Cu-binding AMN scaffolds. We selected biologically inert reaction partners tris(azidomethyl)mesitylene and ethynyl-thiophene to develop TC-Thio, a bioactive C3 -symmetric ligand in which three thiophene-triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X-ray crystallography and forms multinuclear CuII and CuI complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, CuII -TC-Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide- and peroxide-dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.


Directly probing surfactant adsorption on nanoscopic trenches and pillars.
Confinement causes a change in the amount of surfactant adsorbed and in the adsorption morphology. Two cationic surfactants, tetradecyltrimethylammonium bromide (TTAB) and cetylpyridinium chloride (CPC) were adsorbed at the silica-water interface. Atomic force microscopy (AFM) force curves were measured on 50 nm and 80 nm wide trenches. Force curves were also measured on silica pillars, and the results were quantified based on distance from the edge. Trenches: Adsorbed surfactants films in 50 nm and 80 nm trenches showed the same break-through values. However, compared to unconfined values, TTAB in trenches had decreased break-through and adhesion forces while CPC in trenches had increased break-through and adhesion forces, indicating that surfactant identity varies the confinement effect. Pillars: Near the edge, few surfactants adsorb, and those that do extend in the direction normal to the surface. While the experimental data agree qualitatively with previous coarse-grained molecular dynamic simulations, the length scales at which the phenomena are detected differ by ~ half-order of magnitude. Specifically, experimental data show measurable effects on adsorbed surfactant morphology at a distance from the edge 10-20 times the length of a surfactant molecule after accounting for the ~8 nm size of the probe.


Exploring the associations between winter maintenance operations, weather variables, surface condition, and road safety: A path analysis approach.
This paper aims to assess the effects of snow and ice control operations by investigating the interdependency between weather variables, maintenance operations, pavement friction, and collisions. Using a disaggregated event-based and location-specific framework, and employing the statistical techniques of Structural Equation Modeling and Path Analysis, all the significant direct and indirect effects of weather variables and maintenance operations on pavement friction and collision occurrence during snowstorms have been identified. It was revealed that precipitation, extremely low temperatures, and the potential of black ice formation all had significant negative direct effects on pavement friction and significant indirect negative effects on traffic safety. Moreover, the application of anti-icing agents and plowing operations have been shown to significantly improve pavement friction and in return improve traffic safety indirectly. To illustrate how the maintenance operations improve traffic safety, a hypothetical snowstorm example was considered. According to the model, anti-icing application was associated with a 14% reduction in collisions, plowing operations resulted in a 33% reduction in collisions, and combining the two tools reduced collisions per snowstorm by 42%. The findings of this paper can help transportation agencies make more informed decisions to promote an efficient mobilization of the existing winter road maintenance services and resources while improving the safety of the traveling public during the winter months.


Management of equine sarcoids.
Sarcoids are the most common cutaneous neoplasm of the horse, arising as a result of a neoplastic proliferation of fibroblasts associated with infection with bovine papillomavirus, most notably types 1 and 2. Although they do not metastasise, they are locally invasive and aggressive, and can lead to important welfare concerns, interfere with tack and therefore impede athleticism, and undoubtedly lead to a reduction in the value of affected horses. This review discusses the evidence behind the most commonly used treatments for equine sarcoids. The most commonly used treatments are discussed. No one treatment is universally successful, and there are many treatments with varying level of scientific evaluation and reported success rates.


Nicotinic cholinergic influences on sexual receptivity in female rats.
Drugs which alter nicotinic cholinergic transmission were administered to female rats to examine the neurochemical regulation of feminine sexual behavior. Nicotine (50, 100 or 200 micrograms/kg, IP) facilitated lordosis behavior 5 minutes after injection in estrogen-primed ovariectomized (OVX) rats. Pretreatment with the nicotinic antagonist, mecamylamine (MECA, 2.5 or 10 mg/kg) prevented this effect, while atropine pretreatment (30 mg/kg) reduced it. Mecamylamine pretreatment also reduced lordotic behavior induced by bilateral intracerebroventricular (ICV) injection of the cholinesterase inhibitor, eserine (5 micrograms/cannula). However, MECA treatment (5 or 10 micrograms/cannula, bilaterally, ICV, or 5 or 10 mg/kg, IP) did not reduce sexual receptivity in OVX rats made highly receptive with estrogen plus progesterone priming. By comparison with previously published results, MECA is apparently less effective than muscarinic antagonists in disrupting sexual receptivity in several paradigms. There appears to be a critical muscarinic link in the neural circuit for sexual receptivity, but there does not appear to be a comparable nicotinic link. In fact, the lordosis-facilitating effect of nicotine may be a pharmacological effect unrelated to the normal neurochemical regulation of sexual receptivity.


Comparative study of macrophage response in mice after DNA immunization and infection with herpes simplex virus type 1.
Functional activity of macrophages and intensity of T cell immune response in mice were studied after intravaginal and intraperitoneal infection with herpes simplex virus type 1 and DNA vaccination in combination with adjuvant treatment (recombinant granulocyte-macrophage colony-stimulating factor and glucosaminylmuramyl dipeptide). DNA vaccination induced a virus-specific T cell immune response with no macrophagic inflammatory reaction. Infection with herpes simplex virus type 1 was accompanied by sustained inflammation, but not by the T cell immune response.


Growth hormone therapy in a poorly growing child with hypophosphatemic rickets.
We treated a 10 6/12 year old prepubertal male with hypophosphatemic rickets, who was growing poorly despite appropriate treatment with calcitriol and phosphate, with exogenous growth hormone (for an initial trial period of 4 months, followed by 14 months of continuous treatment at a dose of 4 IU three times weekly) even though his growth hormone testing proved to be normal. His growth rate increased significantly during treatment with synthetic growth hormone (from a basal rate of 3.9 cm/yr to 9 cm/yr during the first 4 months of therapy and from 2.7 cm/yr to 6.0 cm/yr during next 14 months of treatment) and his predicted adult height increased as well. Slight metabolic changes were detected in this patient during treatment, with an increase in serum phosphorus and a decrease in twenty-four hour urine calcium concentrations. It would seem reasonable to evaluate the growth hormone status of children with hypophosphatemic rickets who are growing poorly despite appropriate therapy with calcitriol and phosphate and to consider a trial period of therapy with growth hormone in some of them.


Fluorescence-activated cell sorting of EGFP-labeled neural crest cells from murine embryonic craniofacial tissue.
During the early stages of embryogenesis, pluripotent neural crest cells (NCC) are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt 1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt 1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR). The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.


Oxygen transport through lung surfactant and the surfactant specific proteins.
At the very beginning of its migration pathway to any tissue, oxygen has to cross the lung surfactant surface layer (LSSL) and the underlying aqueous hypophase. The influence of human broncho-alveolar lavage and its lipid and specific protein components on oxygen transport were studied in vitro using sensitive electrochemical techniques. LSSL adsorbing from BAL at the dropping mercury electrode/saline interface shifted the peak potentials of oxygen reduction Ep towards more negative values. The magnitude of delta Ep was dependent on the quality of BAL. The kinetics of the oxygen transport were evaluated by measuring changes in the intensities of the reduction current. Storage of oxygen in BAL was several times higher than in saline and indicated the presence of one or more binding sites or promoters for oxygen among BAL components. The surfactant specific protein was found to be one of the binding sites (or promoters) for the oxygen. Since electron microscopic immuno-gold labelling demonstrated the presence of this protein in the LSSL, and electrochemically it proved to transport lipids from the surface layer to the subphase, it was suggested that Sp-A plays the role of an oxygen carrier.


A novel report on the distribution of microplastics in ocellated icefish (Chionodraco rastrospinosus) in the northern Antarctic Peninsula.
Plastics are ubiquitous in the global marine ecosystem; however, studies on microplastic (MPs) ingestion by fish in the remote Antarctic are extremely limited. We detected MPs in ocellated icefish (Chionodraco rastrospinosus)-a limitedly distributed but ecologically important species-in the northern Antarctic Peninsula. This is the first study reporting MPs distribution in the stomach, intestine, and gill of this species. Of 32 C. rastrospinosus individuals, 10 (31.3 %) individuals ingested MPs. Totally, 157 suspected microplastic particles were detected, and only 10 MPs were finally confirmed from the subsampled 38 highly suspected particles after FTIR detection, with an average of 0.36 particles per individual. The stomach, intestine, and gills of each fish contained 0.06 ± 0.24, 0.16 ± 0.36, and 0.09 ± 0.29 particles, respectively. Fibrous MPs with a diameter of <200 μm were predominant in all tissues, with blue MPs being the most common. Polyester and acrylic acid were the most frequently observed plastic polymers. MPs abundance in C. rastrospinosus was unrelated to biometrics.


Effect of gingival phenotype on the maintenance of periodontal health: An American Academy of Periodontology best evidence review.
Gingival thickness, keratinized tissue width, and bone morphotype are three important parameters used to categorize periodontal phenotypes. These elements all play an important role in the maintenance of periodontal health. The aim of this review is to explore the importance of converting thin phenotype into a thick phenotype for periodontal health maintenance. Three clinically relevant focused questions were defined to understand the role of gingival phenotype around teeth. 1) What are the factors affecting gingival phenotype (e.g., age, sex, dental arch, race, crown forms, etc.)? 2) Is there a difference between thin versus thick gingival phenotype in terms of gingival health? 3) Does the conversion of gingivae from a thin to thick gingival phenotype in sites without mucogingival defects help with periodontal health maintenance? Extensive electronic and manual literature search identified a total of 1,129 citations. After title, abstract, and full-text screenings, 30 articles were included in the present review. Twenty-five studies met the inclusion criteria and provided data for focused question 1. It was found that periodontal phenotype varies among different individuals and different areas of the mouth within the same individual. Asian individuals tend to have thinner gingival phenotype compared with white subjects. Eleven studies met the inclusion criteria for the focused question 2. Prevalence and severity of gingival recession was higher at the sites with thin gingiva compared with the sites with thicker gingiva. No studies provided data for focused question 3. Available evidence indicates that subjects with thin and narrow gingiva tend to have more gingival recession compared with those with thick and wide gingiva. Currently, there is no published evidence to support conversion of thin to thick gingival phenotype in sites without gingival recession or mucogingival deformity.


Bending strength of the femur in relation to non-invasive bone mineral assessment.
To analyze the importance of bone mineral for the strength of the distal diaphyseal femur, we studied 14 distal cadaver femora by quantitative computed tomography, (QCT) dual energy X-ray (DXA) absorptiometry and three-point bending. The femora were retrieved at autopsy from 10 male and 4 female donors aged median 74 yr (range 59-92 yr). Significant correlations were found between three bone mineral mass related parameters--QCT bone mass (density x slice area), DXA mineral density (BMD) and content (BMC)--and mechanical parameters. Second area moment equivalents correlated significantly with the mechanical properties of the distal femur. QCT density did not show the same high correlations. The results indicate that the structural strength of diaphyseal bone is determined more by its geometry than mineral density. Assessment of bone mass by QCT or DXA may become important not only for assessment of fracture risk but also for planning of internal fixation in the treatment of osteporotic fractures. Further studies are required to investigate the clinical importance of these observations.


Trends in the management of adult moyamoya disease in the United States: results of a nationwide survey.
Moyamoya disease is a rare, progressive, steno-occlusive disease of the distal branches of the carotid arteries associated with the development of a profuse basal collateral vascular network. In the United States, the disease occurs sporadically and literature on the topic in limited. With data lacking relative to moyamoya epidemiology and management, we report our survey results among a sample of neurovascular surgeons. A 16-question survey was sent as a hyperlink by electronic mail to 46 vascular neurosurgery centers and physicians who have published on this topic. Data included patient demographics, referral patterns, treatment, and follow-up. Response rate was 70%. Of 32 respondents, 72% evaluated 10 or fewer adults per year, usually referred by a neurologist within their referral pattern. Fifteen (47%) respondents reported that the disease had a bilateral occurrence between 50% and 75% of the time. Most respondents (88%) reported that fewer than 25% of their patients had a previous surgery for the disease. Symptomatology (91%) was the criterion to recommend surgery. Nineteen (59%) respondents regularly assessed cerebrovascular reserve by the addition of acetazolamide challenge to their imaging method of choice, typically single photon emission computed tomography. Treatment was antiplatelets (55%) in asymptomatic adults and superficial temporal artery-to-middle cerebral artery bypass for >75% of symptomatic patients, as assessed by 48% of respondents. Yearly follow-up included cerebral angiography for both superficial temporal artery-to-middle cerebral artery bypass and indirect revascularization. Our survey results quantify epidemiologic trends of moyamoya disease in the United States. Finding a lack of consensus in management strategies, we conclude that collaborative efforts may help to create guidelines for the management of this puzzling entity.


Fabrication of CoFe2O4-graphene nanocomposite and its application in the magnetic solid phase extraction of sulfonamides from milk samples.
In the present study, a graphene-based magnetic nanocomposite (CoFe2O4-graphene, CoFe2O4-G) was synthesized and used successfully as an adsorbent for the magnetic solid phase extraction (MSPE) of sulfonamides for the first time. The surface morphologies and structures of the CoFe2O4-G nanocomposite were investigated by scanning electron microscopy (SEM), FT-IR, UV-vis spectroscopy, X-ray diffraction (XRD) and vibration sample magnetometer (VSM). Five sulfonamides, including sulfamerazine, sulfamethizole, sulfadoxine, sulfamethoxazole and sulfisoxazole were used as model analytes to evaluate the enrichment properties of the prepared adsorbent in MSPE. After preconcentration, the adsorbent could be conveniently separated from the aqueous samples by an external magnet, and the analytes desorbed from adsorbent were determined by high performance liquid chromatography-ultraviolet detection (HPLC-UV). Extraction parameters including sample pH, amount of sorbent, extraction time and desorption conditions were optimized in detail. Under the optimal conditions, good linear relationships between the peak areas and the concentrations of the analytes were obtained. The linear ranges were 0.02-50.00 mg L(-1) with correlation coefficients (r)≧0.9982. The limits of detection were less than 1.59 μg L(-1). Good reproducibility was obtained. The relative standard deviations of intra- and inter-day analysis were less than 4.3% and 6.5%, respectively. The proposed method was successfully applied for the analysis of sulfonamides in milk samples. The average recoveries determined for two milk samples spiked at levels from 5 to 20 μg L(-1) were 62.0-104.3% with relative standard deviations less than 14.0%. In addition, the CoFe2O4-G could be reused after cleaning with acetone and ultrapure water successively.


Lower body function as a predictor of mortality over 13 years of follow up: Findings from Hispanic Established Population for the Epidemiological Study of the Elderly.
The objective of this research was to investigate the effect of lower body function on mortality over 13 years of follow-up study. Data from the Hispanic Established Population for the Epidemiological Study of the Elderly were used, and the Cox proportional hazard model of mortality on age sex, education, body mass index, Center for Epidemiological Studies Depression Scale, Mini-Mental State Examination, any activities of daily living, walk score and short physical performance battery was applied. Results showed lower body function to be a strong predictor of mortality over 13 years, as indicated by walk and short physical performance battery scores, as well as any activities of daily living, depression and cognitive function. Furthermore, overweight or obese participants tended to live significantly longer over the long term. Lower body function significantly impacts mortality at 2, 7 and 13 years of follow-up study, but this association decreases in magnitude over time. Geriatr Gerontol Int 2016; 16: 1324-1331.


Down regulation of c-myc, c-fos and erb-B during estrogen induced proliferation of the chick oviduct.
Oncogenes c-myc, H-ras, c-fos and erb-B were constitutively expressed in immature chick oviduct withdrawn from estrogen administration for 2.5 weeks after 10 d of primary estrogen stimulation. Following secondary estrogen stimulation of the withdrawn chicks, synthesis of egg white proteins is rapidly induced and remaining non-functioning tubular gland cells are stimulated to proliferate with a doubling time of 24 h. During first 12 h of secondary estrogen stimulation, H-ras mRNA levels doubled and did not increase further at 24 h and 48 h. The steady state levels of c-myc, erb-B and c-fos mRNA decreased 24 h following secondary estrogen stimulation. The levels of these oncogene RNAs in oviduct were similar at 48 h following secondary estrogen stimulation to those from immature chicks administered 10 d of primary estrogen stimulation. Thus elevated expression of c-myc and c-fos mRNA does not appear to be necessary components for sustained estrogen induced cell proliferation in the chick oviduct.


Correction: Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.
[This corrects the article DOI: 10.1371/journal.pone.0141089.].


Volatile profile of quinoa and lentil flour under fungal fermentation and drying.
Solid-state fermentation reportedly improves the nutritional and sensory properties of legumes and pseudocereals. This study examined changes in the volatile profile using HS-SPME-GC-MS of two varieties of lentil and quinoa flour fermented with Pleurotus ostreatus and dried using hot-air drying and lyophilisation. Fermentation significantly increased the volatile profile. Pardina lentil flour showed a 570% increase in its volatile profile, and 10 compounds were created. In white quinoa, the total area rose from 96 to 4500, and 30 compounds were created. Compounds such as 1-octen-3-ol, benzaldehyde, 3-octanone and hexanal were generated during fermentation, providing a sweet, grassy, cocoa flavour. Hot-air drying led to decrease of over 40% in total peak area. Dried fermented flour retained higher levels of compounds that provide a sweet, cocoa aroma. Air-drying temperature had no significant influence on the volatile profile. This a allows the inclusion of these flours in a wide variety of food products.


Exploiting Combinatorial Interactions to Expand NLR Specificity.
Intracellular nucleotide-binding leucine-rich repeat (NLR) receptors play central roles in human and plant innate immunity. In this issue of Cell Host & Microbe, Wang et al. (2015) show that a single plant NLR can detect diverse pathogen effectors by partnering with different scaffolding proteins, which can each recognize distinct effector targets.


Flavobacterium gliding motility and the type IX secretion system.
Cells of Flavobacterium johnsoniae crawl rapidly over surfaces in a process called gliding motility. These cells do not have flagella or pili but instead rely on a novel motility machine composed of proteins that are unique to the phylum Bacteroidetes. The motility adhesins SprB and RemA are propelled along the cell surface by the still poorly-defined gliding motor. Interaction of these adhesins with a surface results in translocation of the cell. SprB and RemA are delivered to the cell surface by the type IX secretion system (T9SS). T9SSs are confined to but common in the phylum Bacteroidetes. Transmembrane components of the T9SS may perform roles in both secretion and gliding motility.


Alteration of cell-wall composition of Fusarium oxysporum by copper stress.
A strain of Fusarium oxysporum tolerated copper in the growth medium at concentrations up to 600 mg/L. The optimum growth was obtained at 200 mg Cu/L. The mycelium acquired a blue color in the presence of copper. The copper content of isolated cell walls obtained from mycelium grown in the presence of 600 mg Cu/L was 1.5 times higher than that of cell walls obtained from mycelium grown at 200 mg Cu/L and it contained 2.2 and 3.3% copper at 200 and 600 mg Cu/L, respectively. The amount of protein and total sugars increased in both the mycelium and its isolated cell walls in the presence of copper in the growth medium, chitin was also increased in the cell wall, reaching its maximum amount at 200 mg Cu/L--about 2.4 times higher than without copper. Most of amino acid concentrations in the cell wall were increased in the presence of 200 mg Cu/L and decreased above this concentration. Isoleucine, leucine, tyrosine, phenylalanine, and arginine showed the highest increase at this concentration. The altered cell walls obtained from mycelium grown at 200 and 400 mg Cu/L could rebind individual metals more than the control cell walls could. Rebinding of individual metals was in the order Zn > Fe > Ni > Cu > Co. Rebinding of copper by isolated cell walls depended on pH and temperature.


Categorization framework to aid exposure assessment of nanomaterials in consumer products.
Exposure assessment is crucial for risk assessment for nanomaterials. We propose a framework to aid exposure assessment in consumer products. We determined the location of the nanomaterials and the chemical identify of the 580 products listed in the inventory maintained by the Woodrow Wilson International Center for Scholars, of which 37% used nanoparticles suspended in liquids, whereas <1% contained "free airborne nanoparticles". C(60) is currently only used as suspended nanoparticles in liquids and nanosilver is used more as surface bound nanoparticles than as particles suspended in liquids. Based on the location of the nanostructure we were able to further group the products into categories of: (1) expected, (2) possible, and (3) no expected exposure. Most products fall into the category of expected exposure, but we were not able to complete a quantitative exposure assessment mainly due to the lack of information on the concentration of the nanomaterial in the products--a problem that regulators and industry will have to address if we are to have realistic exposure assessment in the future. To illustrate the workability of our procedure, we applied it to four product scenarios using the best estimates available and/or worst-case assumptions. Using the best estimates available and/or worst-case assumptions we estimated the consumer exposure to be 26, 15, and 44 microg kg(-1) bw year(-1) for a facial lotion, a fluid product, and a spray product containing nanoparticles, respectively. The application of sun lotion containing 2% nanoparticles result in an exposure of 56.7 mg kg(-1) bw d(-1) for a 2-year-old child, if the amounts applied correspond to the European Commission recommendations on use of sunscreen.


Variability in Human Cone Topography Assessed by Adaptive Optics Scanning Laser Ophthalmoscopy.
To assess between- and within-individual variability of macular cone topography in the eyes of young adults. Observational case series. Cone photoreceptors in 40 eyes of 20 subjects aged 19-29 years with normal maculae were imaged using a research adaptive optics scanning laser ophthalmoscope. Refractive errors ranged from -3.0 diopters (D) to 0.63 D and differed by <0.50 D in fellow eyes. Cone density was assessed on a 2-dimensional sampling grid over the central 2.4 mm × 2.4 mm. Between-individual variability was evaluated by coefficient of variation (COV). Within-individual variability was quantified by maximum difference and root mean square (RMS). Cones were cumulated over increasing eccentricity. Peak densities of foveal cones are 168 162 ± 23 529 cones/mm(2) (mean ± SD) (COV = 0.14). The number of cones within the cone-dominated foveola (0.8-0.9 mm diameter) is 38 311 ± 2319 (COV = 0.06). The RMS cone density difference between fellow eyes is 6.78%, and the maximum difference is 23.6%. Mixed-model statistical analysis found no difference in the association between eccentricity and cone density in the superior/nasal (P = .8503), superior/temporal (P = .1551), inferior/nasal (P = .8609), and inferior/temporal (P = .6662) quadrants of fellow eyes. New instrumentation imaged the smallest foveal cones, thus allowing accurate assignment of foveal centers and assessment of variability in macular cone density in a large sample of eyes. Though cone densities vary significantly in the fovea, the total numbers of foveolar cones are very similar both between and within subjects. Thus, the total number of foveolar cones may be an important measure of cone degeneration and loss.


Pharmacokinetics of piritramide in newborns, infants and young children in intensive care units.
Piritramide is indicated for treatment of postoperative pain and analgosedation in the intensive care unit (ICU) setting. In an open prospective study the pharmacokinetics of piritramide were investigated in four groups: newborns (NB, age: 1-28 days) (n=8), infants 1 (IF1, age: 2-4 months) (n=7), infants 2 (IF2, age: 5-12 months) (n=14) and young children (YC, age: 2-4 years) (n=10). The recommended paediatric dose range for therapy of postoperative pain is 50-200 microg/kg. Piritramide was administered intravenously as a single dose by bolus injection of 50 microg/kg. Blood samples were collected at 0, 15, 45, 90 min and 3, 6, 9, 12 h after application, and urine samples were collected before application and during the following intervals: 1-2, 2-6, 6-12 h. Piritramide was measured in blood and urine by HPLC-ESI-MS. The following pharmacokinetic parameters: maximum plasma concentration (C(max)), distribution half-life (t 1/2 alpha), elimination half-life (t 1/2 beta), total clearance (Cl(t)) and median volume of distribution at equilibrium (Vd(ss)) were calculated using a non-compartment and a two-compartment model for the disposition of piritramide (TOPFIT and NONMEM-pharmacokinetic analysis). Newborns (NB) showed the highest maximum plasma concentrations (median+/-SD) C(max) (79+/-240 microg/l) compared to the other three groups (IF1 36+/-367, IF2 12+/-81 and YC 16+/-9 microg/l) without statistical significance. The median elimination half-lives (t 1/2 beta) were 702+/-720 min in NB, 157+/-102 min in IF1, 160+/-68 min in IF2 and 166+/-143 min in YC. For t 1/2 beta the difference between NB and the other three groups (IF1, IF2 and YC) was statistically significant (Mann-Whitney-U, P<0.05). Cl(t) was 15.9+/-16.7, 46.6+/-76.9, 235.5+/-454.1 and 338+/-168.1 ml/min in NB, IF1, IF2 and YC respectively. The total clearance increased exponentially with an elimination half-life of 702 min from 15.9 ml/min in NB to 46.6 ml/min in IF2. Differences between the NB/IF1 groups and IF2/YC groups were significantly significant (NB vs. IF2, NB vs. YC, IF1 vs. IF2 and IF1 vs. YC). Vd(ss) was 2.0+/-4.93, 1.7+/-2.5, 7.0+/-5.2 and 6.7+/-2.2 l/kg in NB, IF1, IF2 and YC respectively. In comparison to group IF1 the Vd(ss) was significantly larger in groups IF2 and YC (Mann-Whitney U, P<0.05). Newborns showed a high initial concentration and a distinct prolongation of the elimination half-life of piritramide compared to infants, young children and adults. Therefore, dosage needed to treat postoperative pain should be reduced, and the repetitive doses should be geared to the analgesic effects. In infants and young children the elimination of piritramide is increased compared to adults; therefore the duration of the effects of piritramide will be shortened, and dose intervals ought to be reduced. Subsequent clinical trials for detailed dose adjustment of piritramide in paediatric patients comparing pharmacokinetics and effectiveness are needed.


Traumatic Flap Complications After Femtosecond LASIK.
The purpose of this article was to evaluate the prognosis of traumatic flap dislocation or avulsion in a large series of laser-assisted in situ keratomileusis (LASIK) cases. Retrospective, consecutive, noncomparative case series analyzes the visual and anatomical results after flap dislocation or avulsion, caused by trauma occurred at least 1 month after LASIK. A total of 37,315 eyes of 19,602 patients were reviewed. A traumatic flap complication was observed in 9 eyes of 9 patients, with a maximum interval of 37 months after surgery. Flap dislocation with central full-thickness folds was found in 5 cases; flap lifting and repositioning achieved a full recovery of uncorrected visual acuity. In another case, a partially detached flap was repositioned by a microsponge without lifting; self-limiting localized epithelial ingrowth followed. In 3 eyes, a complete flap avulsion occurred and, after epithelialization, a moderate refractive change was observed, comprised between -0.25 and -1 diopters (D) of spherical equivalent, with astigmatism <1 D; in 1 eye, the resulting myopia was corrected by repeat femtosecond LASIK. Traumatic flap complications after femtosecond LASIK are rare but can occur even in the long term; they have a favorable anatomic and visual prognosis.


Phylogenetic diversity of nitrogen-utilizing genes in hydrothermal chimneys from 3 middle ocean ridges.
Nitrogen-metabolizing genes, including nitrogenase (nifH), periplasmic nitrate reductase (napA), and cytochrome cd 1-type nitrite reductase (nirS), were collected from hydrothermal chimney sulfides on 3 middle ocean ridges and compared for the first time. There was a clear phylogenetic distinction of these nifH genes between different hydrothermal ecosystems, which supported the colonization and potential adaptation by different nitrogen fixing microbes in those sulfides. In particular, in sulfides from low-temperature hydrothermal vents of the Southwest Indian Ocean Ridge, the prevalence of nifH genes appears to be attributed to sulfate-reducing bacteria, suggesting their ecological significance. Phylogenetic analysis of nitrate/nitrite reductase genes indicated that nitrate was a critical electron acceptor for sulfur- or metal-oxidizing bacteria in these hydrothermal ecosystems. Our results provided information about the compositions and diversity of the 3 important genes involved in nitrogen fixation and nitrate/nitrite reduction processes in hydrothermal ecosystems and is the first comprehensive genetic repertoire of genes related to potential nitrogen fixation and denitrification processes in various hydrothermal environments.


Association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone.
The association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone is still scarcely addressed in the literature. To evaluate whether the intensity of obstructive sleep apnea is associated with craniofacial alterations and the position of the hyoid bone in children with mixed dentition. 76 children aged 7 to 10 years old were examined by otorhinolaryngological evaluation, polysomnography, and orthodontic assessment, including cephalometry. The participants were divided in 3 groups: primary snoring, mild obstructive sleep apnea and moderate to severe obstructive sleep apnea. Cephalometric measures of the face and hyoid bone were assessed. These measures were compared among the different groups by unpaired Student's t test. Moreover, these measures were correlated with the patient's obstructive apnea and hypopnea index variable using Pearson's correlation test. Of the 76 children, 14 belonged to group 1, with primary snoring; 46 to group 2, with mild obstructive sleep apnea; and 16 to group 3, with moderate-severe obstructive sleep apnea. There was no difference between the groups regarding the craniofacial variables. Children with obstructive sleep apnea showed a longer distance from the hyoid bone to the mandibular plane when compared to the primary snoring group (p<0.05). Between the two obstructive sleep apnea subgroups, patients with moderate or severe disease showed significantly shorter horizontal distance between the hyoid bone and the posterior pharyngeal wall (p<0.05), when compared to the groups with mild obstructive sleep apnea. We also observed a significant positive correlation between obstructive apnea and hypopnea index and the distance from the hyoid to the mandibular plane (p<0.05) as well as a significant negative association between obstructive apnea and hypopnea index and the horizontal distance from the hyoid to the posterior pharyngeal wall (p<0.01). We did not observe any association between obstructive sleep apnea and linear lateral alterations of the face. In contrast, there is a direct association between obstructive sleep apnea severity and the inferior and posterior position of the hyoid bone in children aged 7 to 10 years old.


Therapeutic applications of electrospun nanofibers impregnated with various biological macromolecules for effective wound healing strategy - A review.
A Non-healing infected wound is an ever-growing global epidemic, with increasing burden of mortality rates and management costs. The problems of chronic wound infections and their outcomes will continue as long as their underlying causes like diabetic wounds grow and spread. Commercial wound therapies employed have limited potential that inhibits pivotal functions and tissue re-epithelialization properties resulting in wound infections. Nanomaterial based drug delivery formulations involving biological macromolecules are developing areas of interest in wound healing applications which are utilized in the re-epithelialization of skin with cost-effective preparations. Research conducted on nanofibers has shown enhanced skin establishment with improved cell proliferation and growth and delivery of bioactive organic molecules at the wound site. However, drug targeted delivery with anti-scarring properties and tissue regeneration aspects have not been updated and discussed in the case of macromolecule impregnated nanofibrous mats. Hence, this review focuses on the brief concepts of wound healing and wound management, therapeutic commercialized wound dressings currently available in the field of wound care, effective electrospun nanofibers impregnated with different biological macromolecules and advancement of nanomaterials for tissue engineering have been discussed. These new findings will pave the way for producing anti-scarring high effective wound scaffolds for drug delivery.


Tuning of water resistance and protein adsorption capacity of porous cellulose nanofiber particles prepared by spray drying with cross-linking reaction.
Porous particles composed of 2,2,6,6-tetramethylpiperidinyl-1-oxyl-oxidized cellulose nanofiber (TOCN) as building block, i.e., porous TOCN particles, are attracting attention due to their environmental friendliness, superior properties, such as easy handling, large surface area, and high adsorption capacity. However, the instability of TOCNs in aqueous environments limits their applications. An effective solution to improve water resistance of TOCN particles is to reduce the hydrophilicity of TOCNs by forming chemical bonds with a cross-linker. In this study, Carbodilite, a common, easy-to-use, commercially available cross-linker with carbodiimide groups, was used to investigate a chemical cross-linking strategy for porous TOCN particles prepared by spray drying. The water resistance of cross-linked TOCN particles was evaluated through morphological observation by SEM images. The presence of polycarbodiimide significantly increased water resistance of cross-linked TOCN particles up to 24 h. This study demonstrates the trade-off between water resistance and adsorption efficiency according to cross-linker concentrations. These data are useful for interface science of TOCNs in liquids, assisting in controlling specific properties of porous TOCN particles for particular applications in adsorption and separation.


Patterned photocrosslinking to establish stiffness anisotropies in fibrous 3D hydrogels.
Cells are known to constantly interact with their local extracellular matrix (ECM) and respond to a variety of biochemical and mechanical cues received from the ECM. Nonetheless, comprehensive understanding of cell-ECM interactions has been elusive. Many studies rely on analysis of cell behavior on 2D substrates, which do not reflect a natural cell environment. Further, lack of dynamic control over local stiffness anisotropies and fiber alignment hinders progress in studies in naturally derived fibrous 3D cultures. Here, we present a cell-safe method of patterned photocrosslinking, which can aid in studying biological hypotheses related to mechanotransduction in 3D hydrogels. As previously described by our group, ruthenium-catalyzed photocrosslinking (RCP) of selected ECM regions promotes localized increase in stiffness mediated by focused blue laser light in a confocal microscope. In this study, we further demonstrate that RCP can induce localized strain stiffening and fiber alignment outside of the selected crosslinked region and induce stiffness anisotropy biased towards the direction of fiber alignment. MDA-MB-231 cells are shown to respond to RCP-induced changes in local ECM architecture and display directional bias towards the direction of fiber alignment, as compared to control cells. Further, the effect of patterned crosslinking on a stiffness landscape is measured using multi-axes optical tweezers active microrheology (AMR) with backscattered laser beam illumination. AMR validates RCP as a suitable tool for creating distinct stiffness anisotropies which promote directed migration of cells, further underscoring the usefulness of RCP in cell-ECM studies. STATEMENT OF SIGNIFICANCE: Studies on cell-ECM interactions in 3D cultures have often been hindered by the lack of available tools to dynamically alter local ECM stiffness and fiber alignment. Here, we present a non-invasive, cell-safe and easily applicable method of patterned photocrosslinking, which can aid in studying biological hypotheses in fibrous 3D hydrogels. Ruthenium-catalyzed crosslinking (RCP) of selected fibrin ECM regions promotes localized increase in stiffness and creates distinct stiffness anisotropies in the presence of the focused blue laser light. Outside of the crosslinked region, RCP causes fiber alignment and strain stiffening in the ECM, verified using multi-axes optical tweezers active microrheology (AMR). Following RCP, human breast cancer MDA-MB-231 exhibit directed cell migration, validating usefulness of this method in cell-ECM studies.


Primary malignant fibrous histiocytoma of the diaphragm: report of a case.
We present herein the case of a 55-year-old man with primary malignant fibrous histiocytoma (MFH) of the diaphragm. He was admitted to our hospital with right anterior chest pain, where diagnostic imaging showed a huge tumor in the right diaphragm with a tumor thrombus in the vena cava, spreading to the left lobe of the liver and the pericardium. Although invasion into the right lung was identified at the time of surgery, the entire tumor was removed. Histopathological examination of the resected specimen revealed the characteristics of MFH. We discuss the clinical features of this patient in comparison with the few previous reports on MFH of the diaphragm.


Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains.
Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85alpha, phospholipase Cgamma1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding motifs were found to inhibit its association with c-Src, Fgr, and phospholipase Cgamma1 SH3 domains, but not the p85alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells.


A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection.
It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as 'post-COVID syndrome'. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illnesses following acute SARS-CoV-2 infection. We searched the scientific literature using MedLine, SCOPUS, Europe PubMed Central and medRxiv from December 2019 to July 2023. Two reviewers independently identified 45 eligible articles, which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. The study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptoms of any nature and duration was 10.8% compared with 4.9% in healthy controls. For seven studies at low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1%, with a median follow-up time of 18 weeks. We also identified a higher risk for future illnesses such as irritable bowel syndrome, dyspepsia, hepatic and biliary disease, liver disease and autoimmune-mediated illnesses such as inflammatory bowel disease and coeliac disease in historically SARS-CoV-2-exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal illness, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.


Identification of persons with incident ocular diseases using health care claims databases.
To assess the extent to which incidence rates calculated for common ocular diseases by using claims data may be overestimated according to the length of the disease-free look-back period used in the analysis. Retrospective longitudinal cohort analysis. Billing records of 2457 persons continuously enrolled for 11 years in a managed-care network were searched for International Classification of Diseases (ICD-9-CM) diagnoses of cataract, open-angle glaucoma (OAG), nonexudative age-related macular degeneration (ARMD), and nonproliferative diabetic retinopathy (NPDR) at eye-care visits in the first half of 2001, the second half of 2010, and 2011. For each condition, incidence rates calculated by using "look-back" periods ranging from 0.5-9 years were compared with best estimates from a gold-standard period of 9.5 years. With a 1-year disease-free look-back period, incidence was overestimated by 260% for cataract, 135% for OAG, 209% for ARMD, and 300% for NPDR. Expanding the disease-free look-back period to 3 years resulted in a reduction of incidence overestimation to 40% for cataract, 14% for OAG, 45% for ARMD, and 100% for NPDR. A 5-year look-back period yielded incidence rates that were overestimated by <30% for all 4 conditions. In our claims-data analysis of 4 common ocular conditions, a disease-free interval ≤1 year insufficiently distinguished newly diagnosed from pre-existing disease, resulting in grossly overestimated incidence rates. Using look-back periods of 3-5 years, depending on the specific diagnosis, yielded considerably more accurate estimates of disease incidence.


Effect of sacral-root stimulation on the motor cortex in patients with idiopathic overactive bladder syndrome.
It is presumed that idiopathic overactive bladder syndrome (OBS) is due to visceral hypersensitivity. Sacral-root stimulation can restore the bladder function, but its mechanism remains uncertain. It is well-known that long-term peripheral stimulation can induce brain plasticity. Hence, we investigated whether brain reorganization occurred along with clinical improvement after sacral-root stimulation. Because toe flexion is the index for monitoring wire placement, we used the flexor hallucis brevis (FHB) as the target muscle. Transcranial magnetic stimulation (TMS) was applied to study motor cortex excitability and the brain mapping of the muscle. Six patients with idiopathic OBS were included in the study. All demonstrated clinical improvement after sacral-root stimulation. Motor cortex excitability and the area of representation for the flexor hallucis brevis muscle increased for at least 30 min after sacral-root stimulation had terminated. Our results showed that cerebral activities changed after sacral-root stimulation. The improvement in urinary urgency and urgency perception was probably due in part to brain reorganization.


Inhibition of anterior capsule opacification and contraction by the elevated anterior rim of the intraocular lens optic.
To verify the anterior capsule opacification (ACO) and contraction (ACC) of the ZCB00V intraocular lens (IOL), made of the same material as the AR40e with a high ACC rate. Retrospective cohort study. We evaluated 35 patients at 1 week, 1, 3 and 6 months post phacoemulsification with either a ZCB00V (n = 35) or FY-60AD (n = 34) IOL implantation. The ACC rate was calculated using retroillumination images of the anterior segment, and the ACO was measured using anterior segment photographs and image analysis software. The contact grade between the IOL and anterior capsule was estimated from the Pentacam® images. The postoperative ACC rates (mean ± standard deviation) at 3 months were 1.03%±2.54% for the ZCB00V and, and 7.12%±9.47% for the FY-60AD. The ZCB00V-implanted eyes showed a significantly lower postoperative ACC at 1 week, 3 months, and 6 months (P < 0.01). On the other hand, the FY-60AD-implanted eyes had more pronounced ACO, and a significantly larger area of opacification (62.24%±21.32% vs. 16.90%±8.34%; P = 0.0005). Pentacam® analysis revealed a space between the anterior capsule and IOL surface in the ZCB00V-implanted eyes, whereas the anterior capsule firmly adhered to the IOL surface in the FY-60AD-implanted eyes. The ACC and ACO were significantly lower in eyes with ZCB00V IOLs compared to those with the FY-60AD. The anterior segment image analysis revealed that the elevated anterior rim of the ZCB00V IOL prevented adhesion between the anterior capsule and IOL optic surface, suggesting an open capsule effect.


[Surgical components in the management of severe obesity].
Bariatric surgery, combined with nutritional and psychological care and physical activity, is currently the most effective treatment for morbid obesity. The multidisciplinary team at the Caen Normandy obesity center explains the prerequisites of this therapeutic approach, and the monitoring and vigilance to be developed in partnership with the patient.


Measurement of Cochlear Implant Electrode Position From Intraoperative Post-insertion Skull Radiographs: A Validation Study.
To validate a method of measuring angular depth of insertion (aDOI) as well as positional depth of each electrode contact in a cochlear implant by using intraoperative postinsertion skull radiographs. Retrospective review. Tertiary referral center. Intraoperative postinsertion radiographs obtained from 18 cochlear implant recipients were chosen for analysis. One high-resolution computer tomography scan of the head with the electrode in place was also analyzed. One cadaveric temporal bone with an inserted electrode provided additional data for analysis. aDOI and position of each electrode contact were measured from the radiographs using readily available software. High-resolution computer tomography imaging of the cochlea and electrode were reconstructed in three dimensions and used to simulate head rotation during intraoperative radiographs. The cadaveric temporal bone was imaged by x-ray at various acquisition angles. We evaluated the error introduced in measuring aDOI by assessing intra- and inter-rater variability. We also evaluated the error introduced by x-ray acquisition at nonstandardized angles by analyzing the three-dimensional construct and the cadaveric temporal bone. The concordance correlation coefficients for intrarater (0.991) and inter-rater (0.996) variability in aDOI measurement were excellent. The error introduced by nonstandardized x-ray acquisition angles was only -12.5 degrees to +15.8 degrees even at the limits of clinically relevant head rotation. The intraoperative postinsertion radiograph is sufficient for estimating positional depth of electrode contacts and the aDOI. This measure is robust in the face of nonstandardized x-ray acquisition angles, and shows good intra- and inter-rater variability.


Aberrant neuronal differentiation and inhibition of dendrite outgrowth resulting from endoplasmic reticulum stress.
Neural stem cells (NSCs) play an essential role in development of the central nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. After neuronal death, neurogenesis is generally enhanced to repair the damaged regions. However, it is unclear whether ER stress directly affects neurogenesis-related processes such as neuronal differentiation and dendrite outgrowth. We evaluated whether neuronal differentiation and dendrite outgrowth were regulated by HRD1, a ubiquitin ligase that was induced under mild conditions of tunicamycin-induced ER stress. Neurons were differentiated from mouse embryonic carcinoma P19 cells by using retinoic acid. The differentiated cells were cultured for 8 days with or without tunicamycin and HRD1 knockdown. The ER stressor led to markedly increased levels of ER stress. ER stress increased the expression levels of neuronal marker βIII-tubulin in 8-day-differentiated cells. However, the neurites of dendrite marker microtubule-associated protein-2 (MAP-2)-positive cells appeared to retract in response to ER stress. Moreover, ER stress markedly reduced the dendrite length and MAP-2 expression levels, whereas it did not affect the number of surviving mature neurons. In contrast, HRD1 knockdown abolished the changes in expression of proteins such as βIII-tubulin and MAP-2. These results suggested that ER stress caused aberrant neuronal differentiation from NSCs followed by the inhibition of neurite outgrowth. These events may be mediated by increased HRD1 expression.


Efficacy and safety of 177Lu‑DOTATATE in patients with advanced pancreatic neuroendocrine tumours: data from the NETTER-R international, retrospective study.
NETTER-R aimed to determine the efficacy, safety and tolerability of 177Lu-DOTATATE in patients with progressive, advanced pancreatic neuroendocrine tumours (panNETs) using retrospective real-world data from multiple sites. This international study retrospectively included patients with panNETs treated with 177Lu-DOTATATE. The primary endpoint was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included overall survival (OS), safety and tumour response. In total, 110 patients with panNETs were studied; 65.5% received a cumulative dose of 177Lu-DOTATATE 29.6 GBq ± 10% (median: 7.4 GBq). In 62 patients with available RECIST v1.1 tumour response, the median PFS was 24.8 months (95% confidence interval [CI]: 17.5-34.5), and the objective response rate was 40.3% (95% CI: 28.1-53.6); all responses were partial. With a median follow up of 24.5 months (range: 2.0-123.4 months) after the first cycle of 177Lu-DOTATATE, the median OS in the full analysis set (n = 110) was 41.4 months (95% CI: 28.6-50.2). PFS (hazard ratio [HR]: 3.672; p = 0.0009) and OS (HR: 3.360; p < 0.0001) were longer in patients who received no chemotherapy prior to 177Lu-DOTATATE than those who did. No treatment-emergent adverse events (TEAEs) led to treatment discontinuation. Grade 3 anaemia, lymphopenia and thrombocytopenia occurred in 0.9%, 5.4% and 0.9% of patients, respectively. No acute leukaemia or myelodysplastic syndrome was reported. Six patients (5.5%) had renal TEAEs. All renal grade ≥ 3 events were transient and did not lead to treatment modification. These results reinforce the role of 177Lu-DOTATATE for the treatment of patients with advanced, somatostatin receptor-positive panNETs.


A patient with fibroepithelial polyp of the ureter-a rare condition mimicking malignancy: a case report.
A 61-year-old man presented with hematuria and intermittent right pelvic pain. Intravenous urography showed a tubular filling defect and ureteroscopy a tumor in the right mid ureter. Urine cytology and tumor biopsy showed nonmalignant results. Open surgery was performed, and an intraoperative frozen section revealed a fibroepithelial polyp of the right mid ureter. A fibroepithelial polyp is a rare benign lesion that can occur in childhood but is an important differential diagnosis of an upper urinary tract urothelial cell carcinoma in adults.


Muscope: a miniature on-chip lensless microscope.
We report the Muscope, a miniature lensless holographic microscope suitable for on-chip integration. The prototype of the Muscope measured approximately only 7 mm × 4 mm × 4 mm, and was capable of offering a sub-micron half-pitch resolution. We have used, for the first time, a microLED display as the light source in a microscope. The individual pixels of a microLED display chip are used as programmable, microscopic and intense LEDs which can be spatially moved in a two-dimensional plane with a 5 μm pitch. This unique feature set of the display was used to implement computational super-resolution and wide-field imaging without any extra hardware, unlike many other lensless microscopes. We also report a new method to evaluate the magnification in our setting. The Muscope surpasses the existing lensless microscopes in compactness, scalability for production, automated operation and system integration. It provides exciting opportunities for a new class of devices with in-built optical imaging and monitoring and/or sensing capabilities.


Acoustic and kinetic behaviour of definity in mice exposed to high frequency ultrasound.
Microbubble contrast agents have shown clinical potential for characterising blood flow using 1 to 10 MHz ultrasound; however, scaling their use for similar applications in the mouse with high frequency ultrasound (20 to 60 MHz) has not been addressed. The goal was to determine the utility of microbubbles for mouse imaging with 30 MHz ultrasound by investigating their attenuation and backscatter characteristics as a function of concentration in vitro and dose response in vivo. The agent was exposed to a 30 MHz, 20% bandwidth pulse with a peak negative pressure of 244 kPa. In vitro results showed that the attenuation and backscatter increased linearly for concentrations between 2.8 x 10(6) and 28 x 10(6) bubbles per mL of deionized water. In vivo experiments where performed in the jugular vein of CD-1 mice and time intensity curves were acquired for doses between 10 and 100 microL kg(-1). These doses corresponded to the range of concentrations used in vitro. In vivo results showed that the peak enhancement of the agent increased linearly for doses between 10 and 60 microL kg(-1), the duration of enhancement varied between 200 to 300 s and the integrated enhancement (area under the curve) increased linearly up to 100 microL kg(-1). A maximum enhancement of 13 dB over the blood pool was observed for a dose of 100 microL kg(-1). The intra- and inter-mouse variabilities were 10% to 40% and indicate that further optimisations are required. These results suggest that quantitative contrast flow studies in the mouse using high frequency ultrasound are possible for doses between 10 and 60 microL kg(-1).


Molecular mechanisms of caramel-like odorant-olfactory receptor interactions based on a computational chemistry approach.
Molecular mechanisms of caramel-like odorant-olfactory receptor interactions were investigated based on molecular docking and molecular dynamics simulations. The transmembrane regions TM-3, TM-5 and TM-6 of receptors were main contributors of amino acid residues in the docking. Molecular docking results showed that hydrogen bonding and pi-pi stacking were the key forces for the stabilization of caramel-like odorants. The binding energies were positively correlated with the molecular weight of caramel-like odorants. Residues Asn155 (84%, OR2W1), Asn206 (86%, OR8D1), Ser155 (77%, OR8D1), Asp179 (87%, OR5M3), Val182 (84%, OR2J2) and Tyr260 (94%, OR2J2) with high frequencies played an important role in the complexes formation. Odorants 4-hydroxy-5-methylfuran-3(2H)-one (16#) and methylglyoxal (128#) were screened by molecular field-based similarity analysis, which tended to bind to the receptors OR1G1 and OR52H1 respectively, resulting a caramel-like aroma perception. The obtained results are useful for better understanding the perception of caramel-like odorants and their high-throughput screening.


Factors associated with physical activity policy and practice implementation in British Columbia's childcare settings: a longitudinal study.
In 2016-17, the government of British Columbia (BC) enacted a mandatory policy outlining Active Play Standards (AP Standards) alongside a capacity building initiative (Appetite to Play) focused on implementing policies and practices to support physical activity in childcare centres. We aimed to identify factors at the provider and organizational levels as well as attributes of the Standards hypothesized to influence implementation (i.e., changes in policies and practices). We conducted surveys before (2016-2017) and after (2018-2019) enforcement of the AP Standards among 146 group childcare centres across BC. The 2018-19 surveys measured theoretically based constructs associated with implementation of policies and practices (9 childcare- and 8 provider- level characteristics as well as 4 attributes of the licensing standards). Characteristics that were associated in simple regression models were entered in multivariable regression models to identify factors associated with policy and practice changes related to fundamental movement skills (FMS), screen time, total amount of active play (AP) and total amount of outdoor AP from baseline to follow-up. In multivariable analyses, higher staff capacity (OR = 2.1, 95% 1.2, 3.7) and perceived flexibility of the standards (OR: 3.3, 95% 1.5, 7.1) were associated with higher odds of a policy change related to FMS. Higher staff commitment to the AP standards was associated with a higher odds of policy changes related to screen time (OR = 1.6, 95% CI: 1.1, 2.4) and amount of AP (OR: 1.5, 95% 1.0, 2.3). Higher institutionalization of PA policies was associated with a higher odds of policy changes related to the amount of AP (OR: 5.4, 95% CI: 1.5, 20). Higher self-efficacy was associated with a higher odds of policy changes related to outdoor AP (OR = 2.9, 95% 1.1, 7.8). Appetite to Play training was a positively associated with practice changes related to FMS (β = 0.5, 95% CI: 0.1, 0.9). A hierarchy of theoretically defined factors influenced childcare providers' implementation of the AP Standards in BC. Future research should test the feasibility of modifying these factors to improve the implementation of PA policy and practice interventions in this setting.


Phosphorylation by Aurora B kinase regulates caspase-2 activity and function.
Mitotic catastrophe (MC) is an important oncosuppressive mechanism that serves to eliminate cells that become polyploid or aneuploid due to aberrant mitosis. Previous studies have demonstrated that the activation and catalytic function of caspase-2 are key steps in MC to trigger apoptosis and/or cell cycle arrest of mitotically defective cells. However, the molecular mechanisms that regulate caspase-2 activation and its function are unclear. Here, we identify six new phosphorylation sites in caspase-2 and show that a key mitotic kinase, Aurora B kinase (AURKB), phosphorylates caspase-2 at the highly conserved residue S384. We demonstrate that phosphorylation at S384 blocks caspase-2 catalytic activity and apoptosis function in response to mitotic insults, without affecting caspase-2 dimerisation. Moreover, molecular modelling suggests that phosphorylation at S384 may affect substrate binding by caspase-2. We propose that caspase-2 S384 phosphorylation by AURKB is a key mechanism that controls caspase-2 activation during mitosis.


Patellar hypertension syndrome in adolescence: a three-year follow up.
Anterior knee pain is one of the major causes of knee pain in an adolescent population. It has been suggested that raised intraosseous pressure may play an important role in the development of anterior knee pain in the young patient. A prospective clinical multicentre study with 27 adolescent patients presenting with anterior knee pain was performed. After failure to respond to conservative treatment, all patients agreed to undergo minimally invasive intraosseous pressure measurements in local anaesthesia. All 27 patients demonstrated a positive "pain provocation test" as a response to increased intrapatellar pressure and were decompressed with a new intraosseous drilling technique. The repeat intraosseous pressure measurement in 27 patients 1 year postoperatively revealed a significant reduction from 43.3+/-13.4 preoperatively to 24.1+/-4.2 mmHg (p<0.001). The pain relief was documented in the form of a reduced VAS from 7.6+/-1.4 to 2.1+/-1.1 cm after 3 years (p<0.001). Patients with anterior knee pain and a positive "pain provocation test" were diagnosed as suffering from a hypertension syndrome of the patella. We conclude that simple extraarticular patellar decompression may offer a valuable new form of treatment in this select group of adolescent patients with anterior knee pain.


Indications and Patient Selection for Percutaneous Coronary Intervention of Chronic Total Occlusions.
The most common indication for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is angina relief, which translates into improved physical function and quality of life. As the risk of the procedure is higher compared with non CTO PCI, it is important for operators to understand the current state of literature and have a detailed discussion with patients regarding risks and benefits prior to the procedure. This article discusses indications for the procedure and how to appropriately select patients for CTO PCI, in hopes of inspiring the reader to consistently offer this approach to indicated patients regardless of anatomic complexity.


4'-Nitrobiphenyl thioglucoside as the Smallest, fluorescent photosensitizer with cancer targeting ligand.
We have previously developed a glucose-linked biphenyl photosensitizer that can pass through glucose transporters, aiming for cancer-selective photodynamic therapy (PDT). Its small size (MW: 435) will allow oral administration and a fast clearance avoiding photosensitivity. However, its fluorescence efficiency was quite low, causing difficulty in monitoring cellular uptake. We thus synthesized a series of monosaccharide-linked biphenyl derivatives with a sulfur atom replacing an oxygen atom, in search of a photosensitizer with a brighter fluorescence. Among them, 4'-nitrobiphenyl thioglucoside showed a fluorescence emission extending to near infra-red region with a strength three times greater than that of the previous compound. This compound was found to have a higher 1O2-producing efficiency (ΦΔ: 0.75) than the previous compound (ΦΔ: 0.65). The thioglucoside indicated a significant photodamaging effect (IC50: 250 μM) against cancer cells. Although the galactose and mannose analogs exerted similar photodamaging effects, they were moderately toxic in the dark at a concentration of 300 μM. The thioglucoside and thiomannoside were at least partially uptaken through glucose transporters as demonstrated by inhibition with cytochalasin B, whereas no inhibition was observed for the galactoside. The behavior of d-glucose toward the cellular uptakes of these photosensitizers was bipolar: inhibitory at a low concentration and recovery or acceleratory at a higher concentration. These results indicate that 4'-nitrobiphenyl thioglucoside is the smallest (MW: 393) cancer-targeting photosensitizer with a trackable fluorescence property.


Sheathless guide catheter in transradial percutaneous coronary intervention for ST-segment elevation myocardial infarction.
The aim of this study was to assess the safety and efficacy of sheathless guide catheters in transradial percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Transradial PCI for STEMI offers significant clinical benefits, including a reduced incidence of vascular complications. As the size of the radial artery is small, the radial artery is frequently damaged in this procedure using large-bore catheters. A sheathless guide catheter offers a solution to this problem as it does not require an introducer sheath. However, the efficacy and safety of sheathless guide catheters remain to be fully determined in emergent transradial PCI for STEMI. Data on consecutive STEMI patients undergoing primary PCI at the Sendai Kousei Hospital between September 2010 and May 2013 were analyzed. The primary endpoint was the rate of acute procedural success without access site crossover. Secondary endpoints included door-to-balloon time, fluoroscopy time, volume of contrast, and radial artery stenosis or occlusion rate. We conducted transradial PCI for 478 patients with STEMI using a sheathless guide catheter. Acute procedural success was achieved in 466 patients (97.5%). The median door-to-balloon time was 45 min (range, 15-317 min). The median fluoroscopy time was 16.4 min (range, 10-90 min). The median volume of contrast was 134 mL (range, 31-431 mL). Radial stenosis or occlusion developed in 14 (3.8%) of the 370 evaluable patients. This study showed that use of a sheathless guide catheter taking a transradial approach was effective and safe in primary PCI for STEMI. © 2015 Wiley Periodicals, Inc.


Analysis of clinical background in patients with vegetation-like echoes: importance of clinical information.
Detection of vegetation is important for diagnosing infective endocarditis. We analyzed clinical information from 58 patients with vegetation-like echoes on transthoracic echocardiography who had been referred to this institution for an echocardiographic examination during the past 5 years. Patients with healed vegetations were excluded. A vegetation-like echo was defined as a mass, a thread-like echo attached to the valve or endocardium, or both. Diagnosis of a vegetation-like echo required the concurrence of two cardiologists and one sonographer. Altogether, 44 patients were treated with antibiotics because their clinical courses were consistent with active infective endocarditis. Blood cultures were positive in 27 patients and negative in 17 patients. Follow-up data were available for 10 of the 14 patients who had no findings suggestive of active infective endocarditis. The size of the vegetation-like echo remained unchanged over a mean interval of 12.1 months, and no clinical signs or symptoms of active infective endocarditis appeared. In about one-fourth of the patients with a vegetation-like echo, it was not associated with infective endocarditis. Clinical information, in addition to detection of a vegetation-like echo, appears to be indispensable for diagnosing infective endocarditis.


EGFR-Induced and c-Src-Mediated CD47 Phosphorylation Inhibits TRIM21-Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion.
Tumor cells often overexpress immune checkpoint proteins, including CD47, for immune evasion. However, whether or how oncogenic activation of receptor tyrosine kinases, which are crucial drivers in tumor development, regulates CD47 expression is unknown. Here, it is demonstrated that epidermal growth factor receptor (EGFR) activation induces CD47 expression by increasing the binding of c-Src to CD47, leading to c-Src-mediated CD47 Y288 phosphorylation. This phosphorylation inhibits the interaction between the ubiquitin E3 ligase TRIM21 and CD47, thereby abrogating TRIM21-mediated CD47 K99/102 polyubiquitylation and CD47 degradation. Knock-in expression of CD47 Y288F reduces CD47 expression, increases macrophage phagocytosis of tumor cells, and inhibits brain tumor growth in mice. In contrast, knock-in expression of CD47 K99/102R elicits the opposite effects compared to CD47 Y288F expression. Importantly, CD47-SIRPα blockade with an anti-CD47 antibody treatment significantly enhances EGFR-targeted cancer therapy. In addition, CD47 expression levels in human glioblastoma (GBM) specimens correlate with EGFR and c-Src activation and aggravation of human GBM. These findings elucidate a novel mechanism underlying CD47 upregulation in EGFR-activated tumor cells and underscore the role of the EGFR-c-Src-TRIM21-CD47 signaling axis in tumor evasion and the potential to improve the current cancer therapy with a combination of CD47 blockade with EGFR-targeted remedy.


True bilateral nasopharyngeal angiofibroma: report and review.
This report describes the third case of a true bilateral Juvenile nasopharyngeal angiofibroma (JNA), i.e. two separate JNA arising from both sides simultaneously. The associated multiple recurrences in such a case have not yet been reported. A 21-year-man underwent transpalatal excision and recurred twice. The last 'neo-occurrence' encountered after 2 years was at a different site and was subsequently managed by post-embolization endoscopic resection. A complete report of its clinico-radiological features and management outcome is discussed.


Increased expression of pigment epithelium-derived factor in allergic rhinitis.
To investigate the expression of messenger RNA (mRNA) of the gene for pigment epithelium-derived factor (PEDF) (OMIM *172860) and PEDF protein and to localize the PEDF protein in the nasal mucosa of patients with allergic rhinitis and of control subjects. Investigation of PEDF mRNA and PEDF protein expression in the nasal mucosa using reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical staining. We used inferior turbinate mucosal samples from 10 patients with allergic rhinitis and 10 matched healthy control subjects. We extracted PEDF mRNA from the inferior turbinate mucosa samples and performed reverse transcription-polymerase chain reaction analysis. We used Western blotting to analyze differences in expression levels of PEDF protein between patients with allergic rhinitis and healthy controls, and the PEDF protein was localized immunohistochemically. The expression levels of PEDF mRNA and PEDF protein in the nasal mucosa were significantly increased in patients with allergic rhinitis compared with those in nonallergic controls. The PEDF protein was expressed in the epithelium and submucosal glands. We found that PEDF protein is expressed in the human nasal mucosa, and its expression is increased in allergic rhinitis. These results suggest a possible contribution of PEDF to the chronic inflammation of the nasal mucosa in allergic rhinitis.


Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trials.
To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women with a history of ET failure. Systematic review and meta-analysis. Not applicable. Infertile women undergoing IVF after one or more failed ET. We included all randomized controlled trials of women undergoing IVF after one or more failed ET, where the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with a 95% confidence interval (95% CI). The review protocol was registered in PROSPERO before starting the data extraction (CRD42017082777). Live birth rate (LBR), clinical pregnancy rate (PR), multiple PR, miscarriage rate, ectopic pregnancy (EP) PR. Ten studies were included (1,468 participants). The intervention group showed higher LBR (RR 1.38, 95% CI 1.05-1.80) and clinical PR (RR 1.34, 95% CI 1.07-1.67) in comparison to controls, without difference in terms of multiple PR, miscarriage rate, and EP PR. Double luteal ESI with pipelle was associated with the greatest effect on LBR (RR 1.54, 95% CI 1.10-2.16) and clinical PR (RR 1.30, 95% CI 1.03-1.65). The ESI was beneficial for patients with two or more previous ET failure, but not for women with a single previous failed ET. No effect was found in women undergoing frozen-thawed ET cycles. The ESI may improve IVF success in patients with two or more previous ET failures undergoing fresh ET. The ESI timing and technique seem to play a crucial role in determining its effect on embryo implantation.


Single-Dose Vaccination of Recombinant Chimeric Newcastle Disease Virus (NDV) LaSota Vaccine Strain Expressing Infectious Bursal Disease Virus (IBDV) VP2 Gene Provides Full Protection against Genotype VII NDV and IBDV Challenge.
Newcastle disease virus (NDV) and infectious bursal disease virus (IBDV) are the two most important and widespread viruses causing huge economic losses in the global poultry industry. Outbreaks of genotype VII NDV and IBDV variants in vaccinated poultry flocks call for genetically matched vaccines. In the present study, a genetic matched chimeric NDV LaSota vaccine strain expressing VP2 gene of IBDV variant, rLaS-VIIF/HN-VP2 was generated for the first time, in which both the F and HN genes of LaSota were replaced with those of the genotype VII NDV strain FJSW. The cleavage site of the FJSW strain F protein in the rLaS-VIIF/HN-VP2 genome was mutated to the avirulent motif found in LaSota. Expression of IBDV VP2 protein was confirmed by western blot. The rLaS-VIIF/HN-VP2 maintained the efficient replication ability in embryonated eggs, low pathogenicity and genetic stability comparable to that of parental LaSota virus. One dose oculonasal vaccination of one-week-old SPF chickens with rLaS-VIIF/HN-VP2 induced full protection against genotype VII NDV and IBDV lethal challenge. These results indicate that the rLaS-VIIF/HN-VP2 is a promising bivalent vaccine to prevent infections of IBDV and genotype VII NDV.


Field-free deterministic ultrafast creation of magnetic skyrmions by spin-orbit torques.
Magnetic skyrmions are stabilized by a combination of external magnetic fields, stray field energies, higher-order exchange interactions and the Dzyaloshinskii-Moriya interaction (DMI). The last favours homochiral skyrmions, whose motion is driven by spin-orbit torques and is deterministic, which makes systems with a large DMI relevant for applications. Asymmetric multilayers of non-magnetic heavy metals with strong spin-orbit interactions and transition-metal ferromagnetic layers provide a large and tunable DMI. Also, the non-magnetic heavy metal layer can inject a vertical spin current with transverse spin polarization into the ferromagnetic layer via the spin Hall effect. This leads to torques that can be used to switch the magnetization completely in out-of-plane magnetized ferromagnetic elements, but the switching is deterministic only in the presence of a symmetry-breaking in-plane field. Although spin-orbit torques led to domain nucleation in continuous films and to stochastic nucleation of skyrmions in magnetic tracks, no practical means to create individual skyrmions controllably in an integrated device design at a selected position has been reported yet. Here we demonstrate that sub-nanosecond spin-orbit torque pulses can generate single skyrmions at custom-defined positions in a magnetic racetrack deterministically using the same current path as used for the shifting operation. The effect of the DMI implies that no external in-plane magnetic fields are needed for this aim. This implementation exploits a defect, such as a constriction in the magnetic track, that can serve as a skyrmion generator. The concept is applicable to any track geometry, including three-dimensional designs.