Enthesis maturation in engineered ligaments is differentially driven by loads that mimic slow growth elongation and rapid cyclic muscle movement.
Entheses are complex attachments that translate load between elastic-ligaments and stiff-bone via organizational and compositional gradients. Neither natural healing, repair, nor engineered replacements restore these gradients, contributing to high re-tear rates. Previously, we developed a culture system which guides ligament fibroblasts in high-density collagen gels to develop early postnatal-like entheses, however further maturation is needed. Mechanical cues, including slow growth elongation and cyclic muscle activity, are critical to enthesis development in vivo but these cues have not been widely explored in engineered entheses and their individual contribution to maturation is largely unknown. Our objective here was to investigate how slow stretch, mimicking ACL growth rates, and intermittent cyclic loading, mimicking muscle activity, individually drive enthesis maturation in our system so to shed light on the cues governing enthesis development, while further developing our tissue engineered replacements. Interestingly, we found these loads differentially drive organizational maturation, with slow stretch driving improvements in the interface/enthesis region, and cyclic load improving the ligament region. However, despite differentially affecting organization, both loads produced improvements to interface mechanics and zonal composition. This study provides insight into how mechanical cues differentially affect enthesis development, while producing some of the most organized engineered enthesis to date. STATEMENT OF SIGNIFICANCE: Entheses attach ligaments to bone and are critical to load transfer; however, entheses do not regenerate with repair or replacement, contributing to high re-tear rates. Mechanical cues are critical to enthesis development in vivo but their individual contribution to maturation is largely unknown and they have not been widely explored in engineered replacements. Here, using a novel culture system, we provide new insight into how slow stretch, mimicking ACL growth rates, and intermittent cyclic loading, mimicking muscle activity, differentially affect enthesis maturation in engineered ligament-to-bone tissues, ultimately producing some of the most organized entheses to date. This system is a promising platform to explore cues regulating enthesis formation so to produce functional engineered replacements and better drive regeneration following repair.


Characterization of EP-receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice.
1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, and hyperalgesia as assessed by the hot plate test. We characterized prostaglandin E receptor subtypes (EP1-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues. 2. Sulprostone (EP1 < EP3) induced allodynia over a wide range of dosages from 50 pg to 5 micrograms kg-1. The maximal allodynic effect was observed at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. This sulprostone-induced allodynia showed a time course similar to that induced by PGE2. 3. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and 16,16-dimethyl PGE2 (EP1 = EP2 = EP3) were as potent as PGE2 in inducing allodynia, and more potent than sulprostone. Butaprost (EP2), 11-deoxy PGE1 (EP2 = EP3), MB 28767 (EP3), and cicaprost (prostaglandin I2 (IP-) receptor) induced allodynia, but with much lower scores. 13,14-Dihydro-15-keto PGE2, a metabolite of PGE2, did not induce allodynia. 4. 16,16-Dimethyl PGE2 as well as PGE2 induced hyperalgesia over a wide range of dosages (16,16-dimethyl PGE2: 5 pg-0.5 micrograms kg-1 PGE2: 50 pg-0.5 micrograms kg-1) with two apparent peaks at 0.5 ng kg-1 and 0.5 micrograms kg-1. Sulprostone (EP1 < EP3) and 17-phenyl-omega-trinor PGE2 (EP1 > EP3) showed a bell-shaped hyperalgesia at lower doses of 5 pg-5 ng kg-1 and 50 pg-50 ng kg-1, respectively. MB28767 (EP3)showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 Microg kg-1. Butaprost(EP2) induced hyperalgesia at doses higher than 50 ng kg-1.5. These results demonstrate that PGE2 may exert allodynia through the EP1-receptor and hyperalgesia through EP2- and EP3-receptors in the mouse spinal cord.


Nucleotide-induced states of myosin subfragment 1 cross-linked to actin.
Actomyosin interactions and the properties of weakly bound states in carbodiimide-cross-linked complexes of actin and myosin subfragment 1 (S-1) were probed in tryptic digestion, fluorescence, and thiol modification experiments. Limited proteolysis showed that the 50/20K junction on S-1 was protected in cross-linked acto-S-1 from trypsin even under high-salt conditions in the presence of MgADP, MgAMPPNP, and MgPPi (mu = 0.5 M). The same junction was exposed to trypsin by MgATP and MgATP gamma S but mainly on S-1 cross-linked via its 50K fragment to actin. p-Phenylenedimaleimide-bridged S-1, when cross-linked to actin, yielded similar tryptic cleavage patterns to those of cross-linked S-1 in the presence of MgATP. By using p-nitrophenylenemaleimide, it was found that the essential thiols of cross-linked S-1 were exposed to labeling in the presence of MgATP and MgATP gamma S in a state-specific manner. In contrast to this, the reactive thiols were protected from modification in the presence of MgADP, MgAMPPNP, and MgPPi at mu = 0.5 M. These modifications were compared with similar reactions on isolated S-1. Experiments with pyrene-actin cross-linked to S-1 showed enhancement of fluorescence intensity upon additions of MgATP and MgATP gamma S, indicating the release of the pyrene probe on actin from the sphere of S-1 influence. The results of this study contrast the "open" structure of weakly bound actomyosin states to the "tight" conformation of rigor complexes.


Optical design of the U7 undulator beamline at the Pohang Light Source.
The first insertion-device beamline at the Pohang Light Source is designed for high-resolution spectroscopy and spectromicroscopy. The beamline will contain a variable-included-angle plane-grating monochromator (VIA-PGM) using a grating substrate which has seven different grooves with different depths. The advantages of this scheme will be the fixed exit-slit position and the mechanical stability of the grating scan mechanism while changing the photon energy range. The beamline is designed to cover the photon energy range 20-2000 eV. The estimated spectral resolution, E/DeltaE, is above 8000 in the photon energy range below 500 eV, and above 4000 for the remaining photon energy range. The estimated flux at the end-station is of the order of 10(12) photons s(-1) (0.1% bandwidth)(-1).


Complex germline architecture: two genes intertwined on two loci.
The germline micronuclear genome of some ciliated protists can be scrambled, with coding segments disordered relative to the expressed macronuclear genome. Here, we report a surprisingly complex pair of genes that assemble from interwoven segments on two germline loci in the ciliate Uroleptus. This baroque organization requires two scrambled genes to be disentangled from each other from two clusters in the genome, one containing segments 1-2-4-5-6-8-11-13-15-16 and the other 7-9-3-10-12-14, with pieces 1-5 comprising the first gene and 6-16 the second gene. Both genes remain linked in the somatic genome on a 1.5-kb "nanochromosome." This study is the first to reveal that two genes can become scrambled during evolution with their coding segments intertwined. These twin scrambled genes underscore the beauty and exceptions of protist genome architecture, pointing to the critical need for evolutionary biologists to survey protist genomes broadly.


[Ultrastructural alteration of extraocular muscle proprioceptor in congenital idiopathic nystagmus].
Objective: To explore the ultrastructural alteration of extraocular muscle proprioceptor in congenital idiopathic nystagmus (CIN). Methods: Case-control study. Ten extraocular muscle samples were collected from five CIN children who underwent nystagmus surgeries in Beijing Children's Hospital from March 2015 to March 2016. Another ten extraocular muscle specimens were collected from five strabismus children in surgery at the same period as normal contrast. There were 3 male patients and 2 female patients of CIN with age of 61-147 months (median age: 91 months). The ultrastructure of extraocular muscle proprioceptors was compared between these two groups by transmission electron microscope. Results: Twenty-three proprioceptors were found in extraocular muscle specimens of CIN children, whereas thirty-three proprioceptors were detected in strabismus children. The ultrastructure of extraocular muscle proprioceptor of CIN altered greatly comparing with that of the control. Fourteen extraocular muscle proprioceptors of CIN were discovered much smaller and vacuolated not only at inner capsules but also at the space between inner and outer capsules with lipofuscins and myeloid bodies in the intrafusal muscle fibers. Sensory nerve fibers degenerated greatly with a lot of lipofuscins and myeloid bodies in these sensory nerve fibers. Demyelination also appeared in some severe cases. Nine extraocular muscle proprioceptors of CIN showed significant dissolving degeneration of myofibrils and proliferation of collagen fibrils. The normal structures could not be distinguished in these proprioceptors. And these structural disorders also appeared in extrafusal muscle fibers and nerve endings. Conclusion: The ultrastructure of extraocular muscle proprioceptor in CIN turned much smaller and had significantly structural disorder.(Chin J Ophthalmol, 2017, 53: 136-139).


Thickness-Dependent Light Transmittance and Temperature Rise in Dual-Cure Bioactive and Light-Cure Bulk-Fill Composite Resins.
This study aimed to assess the light transmittance (T) and temperature increase through different increments of dual-cure bioactive bulk-fill restorative material (ACTIVA), light-cure bulk-fill, and conventional composite resin materials. Cylindrical specimens with a diameter of 8 mm and heights of 1, 2, 3, and 4 mm of ACTIVA, Tetric-N-Ceram bulk-fill (TBF), Filtek One bulk-fill (FBF), and Filtek Z250 (FZ) (n = 6 per group, 96 in total) were light-cured with a visible blue low-intensity light-emitting diode (LED) (650-800 mW/cm2 irradiance). T, and the temperature increase, were measured using an optical power meter and a digital thermometer during curing. The T mean values ranged between 0.012 and 0.239 (76.02 to 98.81% light attenuation), while the temperature rise mean values ranged between 9.02 and 20.80 °C. The parameters, including material type (partial eta squared (ηp2) = 0.284, p < 0.0001), thickness (ηp2 = 0.284, p < 0.0001), and their interaction (ηp2 = 0.185, p = 0.047), significantly affected the T values, whereas only the material type (ηp2 = 0.352, p = 0.047) affected the temperature rise values. The T and temperature rise mean values were highest in ACTIVA increments of 1-mm increments, in particular, showing the highest T mean values, followed by similar increments of TBF. A significantly higher T was found in 1-mm increments compared to thicker increments for all materials (p < 0.0001), and a significant positive correlation existed between T and temperature rise values (r = 0.348, p = 0.001). These findings show that the bioactive material ACTIVA and TBF allow for better T than the other materials, with ACTIVA recording a higher temperature rise. However, the large light attenuation observed for all materials, irrespective of thickness, suggests that curing in more than one location with a low-intensity LED is necessary to optimize the curing process. Furthermore, incremental filling of bulk-fill materials using a low intensity LED could be beneficial.


A prospective evaluation of the sentinel node mapping algorithm in endometrial cancer and correlation of its performance against endometrial cancer risk subtypes.
Sentinel node mapping is emerging as the alternative to lymphadenectomy in endometrial cancer. The objective of our study is to validate of the sentinel node mapping surgical algorithm and also to compare the performance of the algorithm against endometrial cancer risk subtypes DESIGN: This is a prospective interventional study carried out at a Single University teaching hospital. All patients with apparent early stage endometrial cancer who underwent robotic assisted surgical staging were included. Intracervical injection of Indocyanine Green dye and sentinel node identification and biopsy was done for all study patients. The node positive rate when using SLN mapping alone versus SLN mapping algorithm were compared. The node positivity was compared against various risk subtypes of endometrial cancer. 69 patients were included in the study. In 95.7% patients SLN was detected with a bilateral detection rate of 87.9%. 10 patients had nodal positivity, among which 7 were identified by SLN mapping alone. The algorithm captured all 10 patients with positive LNs, yielding a node positivity rate of 14.9%, sensitivity and NPV of 100%. For SLN mapping alone the sensitivity was 77.8%, false negative rate (FNR) 22.2%, and NPV 96.6%. In low- and intermediate-risk subtypes SLN mapping as well as algorithm identified all node positive patients, but in high-risk endometrial cancers the SLN mapping technique alone had a sensitivity of 57.1% and false-negative rate of 42.9% when compared with 100% sensitivity for the SLN mapping algorithm. When doing SLN mapping and biopsy during endometrial cancer staging surgery it is essential that the steps mentioned in the SLN mapping algorithm are followed as SLN mapping alone seems to have a limitation in detecting positive nodes especially in high risk subtypes of endometrial cancer. Even with the lack of survival data, based on the performance of SLN mapping surgical algorithm (even if ultrastaging facility is not available), it seems to be a better technique in detecting metastatic nodes, giving prognostic information, and enabling accurate adjuvant treatment.


Cardiovascular morbidity and mortality in COPD.
COPD and cardiovascular disease (CVD) share common risk factors. We undertook to estimate rates of hospitalization and death from CVD in COPD patients relative to the general population. A cohort of patients > or = 55 years old receiving a first treatment for COPD between 1990 and 1997 was formed from the Saskatchewan Health databases. All hospitalizations and deaths between cohort entry and the end of 1999 were identified. The cohort included 5,648 individuals and generated 23,426 person-years (PY) of follow-up. The overall rates of cardiovascular morbidity and mortality were 177.2 and 41 per 1,000 PY, respectively. Cardiovascular morbidity and mortality rates were higher in the COPD cohort than in the general population (standardized rate ratios of 1.9 and 2.0, respectively). More hospitalizations for CVD than for COPD itself were reported. Among CVDs, heart failure represented the most frequent cause of hospitalization (58.8 per 1,000 PY). CVD and more specifically ischemic heart disease (19.6 per 1,000 PY) were reported as a more frequent cause of death than COPD itself (15.5 per 1,000 PY). CVD is more frequent in COPD patients than in the general population and may represent a burden greater than that of lung disease itself.


Synthesis of pyridopyrazine-1,6-diones from 6-hydroxypicolinic acids via a one-pot coupling/cyclization reaction.
A facile one-pot synthesis of 3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,6(2H)-diones (pyridopyrazine-1,6-diones) has been developed which employs a sequential coupling/cyclization reaction of 6-hydroxypicolinic acids and β-hydroxylamines. The transformation proceeds in good yield under mild conditions using O-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) to both carry out the amide formation and activate the hydroxyl group for intramolecular alkylation.


Testicular metastasis of colorectal carcinoma: an unusual presentation.
Metastasis of colorectal carcinoma to testis is rare. The authors report a case of 35-year-old man with right testicular mass. Contrast-enhanced CT scan (CECT) of testes showed testicular mass with ascitis and enlargement of retroperitoneal lymphnodes. Thus, a provisional diagnosis of disseminated primary testicular tumour was made. On subsequent high orchidectomy pathological examination revealed mucinous adenocarcinoma with CDX2 positivity thereby suggesting the possibility of metastasis from adenocarcinoma. Further, the diagnostic evaluation revealed a colorectal mass, which was inoperable (stage IV) and found to be primary colorectal mucinous adenocarcinoma. The authors conclude that occult colorectal carcinoma may rarely metastasise to testis and this unusual presentation may produce diagnostic dilemma. Although rare, metastases to testes should be considered as a differential diagnosis, especially where symptoms are unusual for primary malignancy.


Therapeutic Potential of Matrix Metalloproteinase Inhibition in Breast Cancer.
Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that cleave nearly all components of the extracellular matrix as well as many other soluble and cell-associated proteins. MMPs have been implicated in normal physiological processes, including development, and in the acquisition and progression of the malignant phenotype. Disappointing results from a series of clinical trials testing small molecule, broad spectrum MMP inhibitors as cancer therapeutics led to a re-evaluation of how MMPs function in the tumor microenvironment, and ongoing research continues to reveal that these proteins play complex roles in cancer development and progression. It is now clear that effective targeting of MMPs for therapeutic benefit will require selective inhibition of specific MMPs. Here, we provide an overview of the MMP family and its biological regulators, the tissue inhibitors of metalloproteinases (TIMPs). We then summarize recent research from model systems that elucidate how specific MMPs drive the malignant phenotype of breast cancer cells, including acquisition of cancer stem cell features and induction of the epithelial-mesenchymal transition, and we also outline clinical studies that implicate specific MMPs in breast cancer outcomes. We conclude by discussing ongoing strategies for development of inhibitors with therapeutic potential that are capable of selectively targeting the MMPs most responsible for tumor promotion, with special consideration of the potential of biologics including antibodies and engineered proteins based on the TIMP scaffold. J. Cell. Biochem. 118: 3531-3548, 2017. © 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.


Quantifying and Modeling Coordination and Coherence in Pedestrian Groups.
Coherent collective behavior emerges from local interactions between individuals that generate group dynamics. An outstanding question is how to quantify group coordination of non-rhythmic behavior, in order to understand the nature of these dynamics at both a local and global level. We investigate this problem in the context of a small group of four pedestrians walking to a goal, treating their speed, and heading as behavioral variables. To measure the local coordination between pairs of pedestrians, we employ cross-correlation to estimate coupling strength and cross-recurrence quantification (CRQ) analysis to estimate dynamic stability. When compared to reshuffled virtual control groups, the results indicate lower-dimensional behavior and a stronger, more stable coupling of walking speed in real groups. There were no differences in heading alignment observed between the real and virtual groups, due to the common goal. By modeling the local speed coupling, we can simulate coordination at the dyad and group levels. The findings demonstrate spontaneous coordination in pedestrian groups that gives rise to coherent global behavior. They also offer a methodological approach for investigating group dynamics in more complex settings.


Effects of a teen pregnancy prevention program on teens' attitudes toward sexuality: A latent trait modeling approach.
The purpose of this study was to examine the effects of program interventions in a school-based teen pregnancy program on hypothesized constructs underlying teens' attitudes toward sexuality. An important task related to this purpose was the validation of the constructs and their stability from pre- to postintervention measures. Data from 1,136 middle grade students were obtained from an earlier evaluation of an abstinence-based teen pregnancy prevention program (S. Weed, I. Ericksen, G. Grant, & A. Lewis, 2002). Latent trait structural equation modeling was used to evaluate the impact of the intervention program on changes in constructs of teens' attitudes toward sexuality. Gender was also taken into consideration. This investigation provides credible evidence that both 1st- and 2nd-order constructs related to measures of teens' attitudes toward risky sexual behavior are sufficiently stable and sensitive to detect program effects.


Characterization of skin blebs from intradermal jet injection: Ex-vivo studies.
This paper presents results from an ex-vivo study of intradermal jet injections, which is an attractive method to achieve both needle-free and fractional dose delivery of vaccines. Due to the fact that fluid properties of many novel therapeutics and vaccines can vary significantly, a key parameter for our study is the fluid viscosity, whilst the main focus is on determining the best correlation between the delivered volume and geometrical dimensions of the fluid deposit. For this we use a combination of top-view (skin wheal), underside (below the dermis), and cross-section (true skin bleb) perspectives and find that the top-view alone, as done in clinical practice, is insufficient to estimate the volume deposited in the dermis. Overall, the best correlation is found between the injection volume and cross-sectional diameter, however there is significant variation amongst the different fluids. For mean injection volumes of 60 μL the mean bleb diameter is ≈8 mm, with mean aspect ratio h¯/d=0.38, indicating the blebs are mostly oblate. However, the shape varies with viscosity and the higher viscosity does not spread laterally to the same degree as lower viscosity fluids. In addition, our high-speed video observations of the injection process, reveal some interesting dynamics of the jet injection method, and we modeled the bleb growth with an exponential saturation.


Development of a foundation for a case definition of post-treatment Lyme disease syndrome.
The study objective is to demonstrate the clinical and research utility of an operationalized definition of post-treatment Lyme disease syndrome (PTLDS), as proposed by the Infectious Diseases Society of America. Seventy-four patients with confirmed erythema migrans and 14 controls were enrolled. Patient-reported symptoms and health function (SF-36) were collected pre-treatment and at follow-up visits over 6 months post-treatment. Eight (11%) patients met our operationalized definition of PTLDS, which included self-reported symptoms of fatigue, widespread musculoskeletal pain or cognitive complaints, and functional impact as measured by a T score of <45 on the composite SF-36. No controls met the functional impact criteria. Forty-three (60% patients returned to their previous health status when measured at 6 months post-treatment. Twenty (28%) patients had either residual symptoms or functional impact, but not both, and did not meet criteria for PTLDS. This operationalized definition of PTLDS allows for identification of those patients who are treated for early Lyme disease and have significant post-treatment illness, as they have both residual symptoms and impact on daily life functioning. With further refinement and improvement of this operationalized definition, the true incidence of PTLDS can be determined and future studies can be designed to examine its pathophysiology and treatment.


A holistic conceptual framework model to describe medication adherence in and guide interventions in diabetes mellitus.
Nonadherence to medications in patients with diabetes, which results in poor treatment outcomes and increased healthcare costs, is commonly reported globally. Factors associated with medication adherence have also been widely studied. However, a clear and comprehensive, disease-specific conceptual framework model that captures all possible factors has not been established. This study aimed to develop a conceptual framework that addresses the complex network of barriers to medication adherence in patients with diabetes. Fourteen databases and grey literature sources were systematically searched for systematic reviews reporting barriers to medication adherence in patients with diabetes. A thematic approach was used to categorize all identified barriers from the reviews and to create a matrix representing the complex network and relations of the different barriers. Eighteen systematic reviews were identified and used for the development of the conceptual framework. Overall, six major themes emerged: patient-, medication-, disease-, provider-, system-, and societal-related factors. Each of these themes was further classified into different sub-categories. It was noted that most interactions were identified to be within the patient-related factors, which not only interact with other themes but also within the same theme. Patient's demographics as well as cultural beliefs were the most notable factors in terms of interactions with other categories and themes. The intricate network and interaction of factors identified between different themes and within individual themes indicate the complexity of the problem of adherence. This framework will potentially enhance the understanding of the complex relation between different barriers for medication adherence in diabetes and will facilitate design of more effective interventions. Future interventions for enhancing medication adherence should look at the overall factors and target multiple themes of barriers to improve patient outcomes.


The Nitrogenous Hamigerans: Unusual Amino Acid-Derivatized Aromatic Diterpenoid Metabolites from the New Zealand Marine Sponge Hamigera tarangaensis.
The NMR-directed isolation and structure elucidation of nine new nitrogenous hamigeran diterpenoids from the New Zealand marine sponge Hamigera tarangaensis are described. Featured in this set are the oxazole-containing hamigeran M (4) and eight compounds (5a-6a and 7a-8c) related to the constitutional structure of hamigeran D (1). Moderate cytotoxicity in the low-micromolar range against the HL-60 promyeloid leukemic cell line is reported for seven of the new compounds. The structural nature of these compounds suggests that their adducts are derived from an amino acid source and has allowed for revision of the configuration about C-18 of the archetypal compound, hamigeran D, from 1a to 1b. The existence of three constitutionally identical forms of hamigeran Q (8a-8c) requires the involvement of an allo-isoleucine stereoisomer and suggests the intriguing possibility of partial prokaryotic biogenesis of these unusual secondary metabolites.


Reduction of lipid-accumulation of oleaginous yeast Rhodosporidium toruloides through CRISPR/Cas9-mediated inactivation of lipid droplet structural proteins.
The basidiomycetous yeast Rhodosporidium toruloides is an important chassis organism for producing microbial lipids and terpenoids. However, excess carbon flux flows towards lipid synthesis than terpenoid synthesis. Thus, it is essential to limit lipid accumulation so that R. toruloides can be explored as an advanced cell factory for producing non-lipid derivatives. In this study, we knocked out two lipid droplet (LD) structural proteins (Ldp1 and Cals) of R. toruloides NP11 through the CRISPR/Cas9 system to reduce lipid production. The results showed that lipid content of LD protein-disrupted strains dropped by over 40%. LDP1-disrupted mutants harbored small-sized LDs. This study provided valuable information to study about microbial lipid metabolism and platform strains for constructing advanced cell factories.


Safety and efficacy of endoscopic submucosal dissection of rectal tumors extending to the dentate line.
Unique anatomical features render endoscopic resection for rectal tumors extending to the dentate line (RTDL) technically challenging. The aim of this study was to evaluate the feasibility of endoscopic submucosal dissection (ESD) for RTDLs. This retrospective study compared ESD for RTDLs with proximal rectal tumors between September 2002 and June 2012. En bloc resection rate, R0 resection rate, complications, and tumor recurrences were assessed. A total of 45 RTDLs (median age 69 years; 15 males; median lesion size 38.4 mm) and 94 proximal rectal tumors were identified. En bloc resection and R0 resection rates were 95.6 % (43/45) and 53.3 % (24/45), respectively. The perforation rate was 4.4 %. Compared with proximal rectal ESD, ESD for RTDLs showed longer procedure time (104 vs. 60 minutes; P < 0.001), lower R0 resection rate (53.3 % vs. 70.2 %; P = 0.019), and more frequent high grade fever (22.2 % vs. 4.3 %; P = 0.002). No residual adenoma was observed at the first surveillance colonoscopy. Recurrence rate did not differ significantly between the two groups. ESD for RTDLs demonstrated safety and effectiveness comparable to ESD in proximal rectal lesions.


Spatial Heterogeneity in the Tumor Microenvironment.
Recent developments in studies of tumor heterogeneity have provoked new thoughts on cancer management. There is a desperate need to understand influence of the tumor microenvironment on cancer development and evolution. Applying principles and quantitative methods from ecology can suggest novel solutions to fulfil this need. We discuss spatial heterogeneity as a fundamental biological feature of the microenvironment, which has been largely ignored. Histological samples can provide spatial context of diverse cell types coexisting within the microenvironment. Advanced computer-vision techniques have been developed for spatial mapping of cells in histological samples. This has enabled the applications of experimental and analytical tools from ecology to cancer research, generating system-level knowledge of microenvironmental spatial heterogeneity. We focus on studies of immune infiltrate and tumor resource distribution, and highlight statistical approaches for addressing the emerging challenges based on these new approaches.


Socioeconomic Factors Explain Racial Disparities in Invasive Community-Associated Methicillin-Resistant Staphylococcus aureus Disease Rates.
Invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) incidence in the United States is higher among black persons than white persons. We explored the extent to which socioeconomic factors might explain this racial disparity. A retrospective cohort was based on the Centers for Disease Control and Prevention's Emerging Infections Program surveillance data for invasive community-associated MRSA cases (isolated from a normally sterile site of an outpatient or on hospital admission day ≤3 in a patient without specified major healthcare exposures) from 2009 to 2011 in 33 counties of 9 states. We used generalized estimating equations to determine census tract-level factors associated with differences in MRSA incidence and inverse odds ratio-weighted mediation analysis to determine the proportion of racial disparity mediated by socioeconomic factors. Annual invasive community-associated MRSA incidence was 4.59 per 100000 among whites and 7.60 per 100000 among blacks (rate ratio [RR], 1.66; 95% confidence interval [CI], 1.52-1.80). In the mediation analysis, after accounting for census tract-level measures of federally designated medically underserved areas, education, income, housing value, and rural status, 91% of the original racial disparity was explained; no significant association of black race with community-associated MRSA remained (RR, 1.05; 95% CI, .92-1.20). The racial disparity in invasive community-associated MRSA rates was largely explained by socioeconomic factors. The specific factors that underlie the association between census tract-level socioeconomic measures and MRSA incidence, which may include modifiable social (eg, poverty, crowding) and biological factors (not explored in this analysis), should be elucidated to define strategies for reducing racial disparities in community-associated MRSA rates.


Structural and thermodynamic characterization of the self-adhesive properties of human P-cadherin.
Human P-cadherin is a promising therapeutic target against cancer. However, its characterization at the molecular level is still lacking. We report that human P-cadherin associated irreversibly in a distinct dimer configuration. Unexpectedly, the divalent cation Ca²⁺ was not necessary for dimerization, although it greatly stabilized the protein-protein complex.


Dexamethasone induced alterations in enzymatic and nonenzymatic antioxidant status in heart and kidney of rats.
This study was designed to investigate the alterations in thiobarbituric acid reactants (TBA-reactants) and enzymatic and nonenzymatic antioxidant levels induced by dexamethasone (Dex) in heart and kidney and to find out whether these alterations induced by Dex and its hypertensive effect had any role in the maintenance of hypertension in this model. Administration of dexamethasone induced severe loss of body weight, significant increase in heart and kidney weights and also marked electrocardiographic changes. The protein content in heart and kidney increased significantly during Dex administration and returned to near normalcy after withdrawal. Total activity of lactate dehydrogenase showed a significant increase in heart till day 8 of treatment, whereas in serum, it exhibited a significant decrease. The activity of CK in heart showed an increase till day 8 of treatment and approached normalcy thereafter. In serum, CK exhibited a decrease till day 8, remaining insignificant thereafter. CKMB in heart showed an insignificant increase initially, reaching normal levels on Dex withdrawal, whereas in serum, it showed a significant decrease throughout the experimental period. Mean arterial pressure (MAP) and heart rate increased significantly, while a significant elevation in the ST segment was noticed during administration as well as after withdrawal of Dex. The TBA-reactants levels were found to increase in heart and kidney during days 12 and 16 of administration with Dex and even after withdrawal of Dex, the levels were insignificantly elevated. The level of glutathione in heart and kidney increased from day 4 onwards and reached normalcy during the later stages of treatment and after withdrawal of Dex. The total sulfhydryl groups exhibited a significant increase in both heart and kidney throughout the experiment. The antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase exhibited a significant decrease in heart during Dex administration whereas, in kidney, they exhibited a significant increase during treatment and after withdrawal of Dex. Thus, Dex induced rise in mean arterial pressure, significant alterations in electrocardiographic parameters and also marked alterations in enzymatic and nonenzymatic antioxidant levels and in the TBA-reactants level in heart and kidney.


Cleft lip and palate risk factors among otorhinolaryngology: Head and neck surgery patients in two hospitals.
Cleft lip and/or palate is the most prevalent type of head and neck deformity, accounting for 65% of cases. The occurrence of this condition is influenced by both genetic and environmental factors. Cleft defects are classified into 2 types: syndromic cleft lip and palate syndrome and non-syndromic cleft lip and palate syndrome. Cleft lip with or without cleft palate is the most common type of cleft defect, and the surgical repair is the primary treatment option for patients. Our study was a retrospective case-control study that included 132 cases of patients with cleft defects and 132 healthy babies without cleft defects serving as controls. Personal information, including the name, age, and origin of the participants, was collected. Additionally, we collected information on all potential risk factors, including medical history, daily habits, consanguinity between parents, and family history. Information was collected in Excel and analyzed using the Statistical Package for Social Sciences and a Chi-Square test was performed to determine the results and their relationship to cleft lip and palate. Our study identified various risk factors that have a significant association with cleft lip and palate with a P-value <5% in addition to factors that are not considered risk factors. Using relative risk analysis, we were able to rank the top 5 most significant and influential risk factors. The most impactful factor was not taking folic acid during pregnancy. The primary risk factors associated with cleft lip and palate include a family history of the condition, lack of folic acid supplementation, maternal age over 35 years, and high temperatures exceeding 39 °C. Consequently, we recommend that mothers who intend to conceive should take folic acid supplements at a dose of 0.4 to 0.8 mg during the initial trimester of pregnancy. Additionally, we advise careful monitoring of all risk factors, particularly during the first trimester of pregnancy.


Technology and Dementia: The Future is Now.
Technology has multiple potential applications to dementia from diagnosis and assessment to care delivery and supporting ageing in place. To summarise key areas of technology development in dementia and identify future directions and implications. Members of the US Alzheimer's Association Technology Professional Interest Area involved in delivering the annual pre-conference summarised existing knowledge on current and future technology developments in dementia. The main domains of technology development are as follows: (i) diagnosis, assessment and monitoring, (ii) maintenance of functioning, (iii) leisure and activity, (iv) caregiving and management. The pace of technology development requires urgent policy, funding and practice change, away from a narrow medical approach, to a holistic model that facilitates future risk reduction and prevention strategies, enables earlier detection and supports implementation at scale for a meaningful and fulfilling life with dementia.


An aerobiological survey of allergens in al Khobar, Saudi Arabia.
A nationwide aerobiologic study is in progress in Saudi Arabia using Burkard 7-day volumetric spore traps to determine the major airborne allergens and their seasonal patterns. Eights months readings have been completed at Al-Khobar, an important coastal city on the Arabian Gulf. Pollen levels showed a double season. An autumnal peak reached its maximum in October rising sharply from the low summer values before falling during the short winter then rising again in springtime. Both local and imported flora were represented with chenopodiaceae, grasses and Ambrosia as the most common botanical groups, identification of the most significant individual species is still in progress. Fungal spores also show distinctive seasonal patterns. In descending rank order from the most common genera were Cladosporium, Ustilago, Alternaria, with Chaetomium and Ulocladium as consistent but minor components. Basiodiospores and Ascospores represented less than 10% of the total spore population, indicative of the dry nature of the climate. Desert dust added an important irritant to the Saudi atmosphere but a major contaminating factor to the aerobiological material being analysed.


Composition and properties of trypsin-cleaved elongation factor Tu.
Native elongation factor Tu from Escherichia coli, EF-Tu, is initially attacked by trypsin at three adjacent sites in the primary structure. These are arginine-44, arginine-58, and lysine-56. The rates of hydrolysis at the two arginine residues are about the same but that at the lysine residue is much slower. The products of the tryptic digestion have been analysed by Edman degradation and polyacrylamide gel electrophoresis. The peptide from alanine-45 to arginine-58 is eventually excised and does not complex with the remaining polypeptides (fragments A and D). The loss of this peptide does not lead to a concomitant loss of activity in stimulating polyphenylalanine synthesis. The latter is closely correlated with the further hydrolysis of the remaining fragment (A + D) complex. This complex resembles native EF-Tu in its ability to stimulate both polyphenylalanine synthesis and the binding of aminoacyl-tRNA to 70-S ribosomes, but does not form so stable a ternary complex with aminoacyl-tRNA and GTP as the native protein.


Rhizoctonia solani Infection Assay of Young Sugar Beet and Arabidopsis plantlets.
Rhizoctonia solani is a soil-borne fungus, which rarely produces any spores in culture. Hence, all inoculation procedures are based on mycelia, often as a coat on cereal kernels, placed in close vicinity to the plant to be infected. In this protocol, an inoculation method is described where the fungus is first allowed to infest a perlite-maize flour substrate for 10 days, followed by thorough soil mixing to generate uniform fungal distribution. Pre-grown seedlings are then replanted in the infested soil. Plant materials can be harvested, five (sugar beet) and ten days (Arabidopsis) post infection, followed by a rapid cleaning step ahead of any nucleic acid preparation. Commercial DNA or RNA extraction kits can be used or, if higher DNA yield is required, a CTAB extraction method. Our purpose was to develop a reliable and reproducible protocol to determine the infection levels in planta upon infection with R. solani. This protocol is less laborious compared to previous ones, improves the consistency of plant infection, reproducibility between experiments, and suits both a root crop and Arabidopsis. Graphic abstract: Plant infectionInoculation of R. solaniPreparation of inoculumPCR analysis Overview of the R. solani infection procedure.


Ethylene induced plant stress tolerance by Enterobacter sp. SA187 is mediated by 2-keto-4-methylthiobutyric acid production.
Several plant species require microbial associations for survival under different biotic and abiotic stresses. In this study, we show that Enterobacter sp. SA187, a desert plant endophytic bacterium, enhances yield of the crop plant alfalfa under field conditions as well as growth of the model plant Arabidopsis thaliana in vitro, revealing a high potential of SA187 as a biological solution for improving crop production. Studying the SA187 interaction with Arabidopsis, we uncovered a number of mechanisms related to the beneficial association of SA187 with plants. SA187 colonizes both the surface and inner tissues of Arabidopsis roots and shoots. SA187 induces salt stress tolerance by production of bacterial 2-keto-4-methylthiobutyric acid (KMBA), known to be converted into ethylene. By transcriptomic, genetic and pharmacological analyses, we show that the ethylene signaling pathway, but not plant ethylene production, is required for KMBA-induced plant salt stress tolerance. These results reveal a novel molecular communication process during the beneficial microbe-induced plant stress tolerance.


The frequency stabilization method of laser feedback interferometer based on external cavity modulation.
Laser frequency stabilization is one of the foremost factors that influence the accuracy of measurement using a laser feedback interferometer, especially when the system is in the presence of strong optical feedback. In this paper, we use external cavity modulation to demonstrate a simple and effective method of frequency stabilization for laser feedback interferometer with strong optical feedback. The external cavity modulation is realized by oscillating a feedback mirror driven by a piezoelectric ceramic, the stable feedback optical field is obtained that has strong performance of anti-disturbance. Meanwhile, we stabilize the laser frequency by the thermal frequency-stabilizing. These lead to the realization of stable laser feedback interferometer. The relative uncertainty of the frequency stabilization is less than 1 part in 10(7).


Trombolysis in acute stroke.
Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke. It has been available in the United States for over a decade and was approved for use in Israel at the end of 2004. To assess the implementation of intravenous rt-PA in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel. Patients with acute ischemic stroke admitted between January 2005 and June 2006 who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed. Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. The mean age of intravenously treated patients was 67 years (range 22-85 years), median baseline NIHSS score was 14 (25-75%, 10-18) and the median 'onset to drug time' was 150 minutes (25-75%, 120-178). Symptomatic intracerebral hemorrhage and orolingual angioedema each occurred in one patient (2.7%). Significant clinical improvement occurred in 54% of treated patients, and 38% of patients were independent at hospital discharge. The use of reperfusion therapy for acute ischemic stroke has increased in our center after the formal approval of rt-PA therapy to over 5%, with 'onset to drug time', safety and outcome after intravenous rt-PA treatment comparing favorably with worldwide experience. A prerequisite for the implementation of effective reperfusion therapy and expansion of the proportion of patients treated nationwide is the establishment of a comprehensive infrastructure.


Human serotonin transporter availability predicts fear conditioning.
Serotonin facilitates fear learning in animals. We therefore predicted that individual differences in the capacity to regulate serotonergic transmission in the human neural fear circuit would be inversely related to fear conditioning. The capacity to regulate serotonergic transmission was indexed by serotonin transporter availability measured with [(11)C]-DASB positron emission tomography. Results indicate that lower serotonin transporter availability in the amygdala, insula and dorsal anterior cingulate cortex predicts enhanced conditioned autonomic fear responses. Our finding supports serotonergic modulation of fear conditioning in humans and may aid in understanding susceptibility for developing anxiety conditions such as post-traumatic stress disorder.


EGCG inhibits recepteur d'origine nantais expression by suppressing Egr-1 in gastric cancer cells.
Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in epithelial tumor carcinogenesis. In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the induction of RON and tumor growth in human gastric cancer. EGCG inhibited phorbol 12-myristate 13-acetate (PMA)-induced RON expression and reduced RON transcriptional activity. However, (-)-epigalloca-techin (EGC), (-)-epicatechin gallate (ECG) and (-)‑epicatechin (EC) did not affect RON expression. Experiments with deleted and site-directed mutagenesis of the RON promoter indicated that Egr-1 binding sites in the RON promoter may be the EGCG‑response element acting as a cis-element in gastric cancer cells. EGCG also inhibited PMA-induced Egr-1 expression and DNA binding in a dose-dependent manner. Furthermore, gastric cancer cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by EGCG and siRNA-targeted RON and Egr-1. EGCG significantly reduced tumor growth in an in vivo tumor model, whereas RON expression was downregulated. These results suggest that EGCG may exert at least part of its anticancer effect by controlling RON expression through suppression of Egr-1 activation.


Cultural variation in the social organization of problem solving among African American and European American siblings.
This study examined the social organization of a problem-solving task among 15 African American and 15 European American sibling pairs. The 30 sibling pairs between the ages of 6 and 12 were video recorded constructing a marble track together during a home visit. African American siblings were observed to collaborate more often than European American siblings who were more likely to divide up the labor and direct each other in constructing the marble track. In addition, older European American siblings made more proposals of step plans than older African American siblings. The findings provide insights into the cultural basis of the social organization of problem solving across African American and European American siblings.


Sonographic Evaluation of Colonic Carcinoma in Comparison to Colonoscopy.
Colon cancer is one of the main causes of cancer death. Diagnosis requires the examination of the entire large bowel by means of radiological or endoscopic techniques. Though there is not a remarkable advancement in gastrointestinal (GI) tract evaluations, the modern radiological imaging methods emphasize the importance of ultrasonography (US) evaluations and stand US out as the scanning method in malignancies of the GI tract. The objective of this study is to investigate the role of ultrasonography in the diagnosis of cancers of the colon & it's accuracy in comparison to colonoscopy. This cross sectional analytical study included a total of 62 patients, including 38(61.29%) male and 24(38.71%) female patients who came at Mymensingh Medical College Hospital & Popular Diagnostic Center, Mymensingh from January 2013 to November 2015 & whose ultrasonography and endoscopic examinations were planned with suspicion of colon cancer. Considering the colonoscopic biopsy as a gold standard, the sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ultrasonography were evaluated manually. All patients underwent ultrasonography and colonoscopy and results were compared with histopathologic diagnosis. Malignancy was histopathologically identified in 37(59.68%) patients. The sensitivity of ultrasound to identify colon cancer was 86.48%, its specificity was 84%, positive predictive value and negative predictive value was 88.89% & 80.77% respectively. The sensitivity of endoscopic intervention was 100%, its specificity was 96% and positive predictive value was 93.7%. Likewise, a series of analytical and clinical parameters were evaluated, in an attempt to establish associated factors of a colon cancer by means of the statistical package SPSS 13.0 for Windows. Therefore, we believe that abdominal ultrasonography which is non-invasive, easily accessible, cost-efficient method may detect a colonic mass or wall thickening consistent with a colonic carcinoma with a high degree of accuracy.


Neonatal cholestasis due to primary sclerosing cholangitis.
Neonatal cholestasis is rarely caused due to primary sclerosing cholangitis, which is an inflammatory disease of the bile ducts, which results in obstructive fibrosis of the ducts. A 7-month-old male child presented with jaundice along with high-colored urine and clay-colored stools since birth. Liver biopsy showed mild bile duct proliferation with cholangioles showing bile and thrombi suggestive of primary sclerosing cholangitis.


Dopamine Receptor DRD2 Gene rs1076560, Personality Traits and Anxiety in the Polysubstance Use Disorder.
Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups-polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing-Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State-Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2×3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research.


Effect of the Interfacial Energy Landscape on Photoinduced Charge Generation at the ZnPc/MoS2 Interface.
Monolayer transition-metal dichalcogenide crystals (TMDC) can be combined with other functional materials, such as organic molecules, to form a wide range of heterostructures with tailorable properties. Although a number of works have shown that ultrafast charge transfer (CT) can occur at organic/TMDC interfaces, conditions that would facilitate the separation of interfacial CT excitons into free carriers remain unclear. Here, time-resolved and steady-state photoemission spectroscopy are used to study the potential energy landscape, charge transfer, and exciton dynamics at the zinc phthalocyanine (ZnPc)/monolayer (ML) MoS2 and ZnPc/bulk MoS2 interfaces. Surprisingly, although both interfaces have a type-II band alignment and exhibit sub-100 fs CT, the CT excitons formed at the two interfaces show drastically different evolution dynamics. The ZnPc/ML-MoS2 behaves like typical donor-acceptor interfaces in which CT excitons dissociate into electron-hole pairs. On the contrary, back electron transfer occur at ZnPc/bulk-MoS2, which results in the formation of triplet excitons in ZnPc. The difference can be explained by the different amount of band bending found in the ZnPc film deposited on ML-MoS2 and bulk-MoS2. Our work illustrates that the potential energy landscape near the interface plays an important role in the charge separation behavior. Therefore, considering the energy level alignment at the interface alone is not enough for predicting whether free charges can be generated effectively from an interface.


Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis.
Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility.


Depression in schizophrenia.
Depressive syndromes that occur during the course of schizophrenia are not clearly understood but have important implications for the treatment of the schizophrenic patient. In this review of the literature on depression secondary to schizophrenia, the author notes that lack of tested diagnostic criteria has led to a misunderstanding of its relatively high frequency and its association with poor outcome features such as impaired psychosocial functioning, schizophrenic relapse, and suicide. Differential diagnosis, including ruling out akinetic depression, is essential, he believes, partly because the concept of schizophrenic depression as postpsychotic is not supported by evidence. Clinical management must address such increased risk factors as relapse and suicide, but evidence indicates that secondary depression in schizophrenia does not respond to antidepressant medication.


Immediate skin grafting on microvascular free tissue transfers.
Clinical reports of pedicled muscle flaps and microvascular tissue transfers include two distinctly different strategies for skin grafting. Some authors describe immediate grafting, whereas others recommend a three- to 5-day interval between flap transfer and grafting. No systematic analysis of either strategy has been reported. We reviewed 51 consecutive successful free tissue transfers that involved immediate skin grafting. Ninety-six percent of the grafts survived without complication. Bot muscle and fascial flaps supported skin grafts. Skin grafts survived infected recipient sites, pedicle revisions, partial flap necrosis, and secondary operation. We conclude that immediate skin grafting on free tissue transfers is reliable.


Anisotropic shape evolution of large-size Cu nanocrystals prepared in nonionic microemulsion media.
We report the anisotropic shape evolution of colloidal copper nanocrystals (Cu NCs) in nonionic microemulsion media by adopting tetraethylammonium hydroxide as a reactant and capping agent in water phase. Relatively large-size Cu NCs were synthesized to confine the growth of Cu NCs below 100 nm. TEM images showed the triangular and hexagonal morphologies of Cu NCs ranging over 55-70 nm after 28 h, while they showed the spherical NCs dominantly under higher concentration of a reducing agent. The surface plasmon resonance (SPR) absorption band of anisotropic Cu NCs was centered at 571 nm with signal enhancement over time. The formation kinetics revealed that the gradual conversion of the Cu seeds into larger NCs during 28 h at room temperature. The NCs were characterized to be Cu rather than CuO or Cu2O by electron diffraction patterns, exhibiting relevant d-spacing figures consistent with the bulk Cu crystal.


Postflight Rash and Skin Sensitivity Following a Year-Long Spaceflight Mission.
BACKGROUND: While skin conditions are commonly reported in flight on the International Space Station (ISS), postflight skin complaints have generally been limited to foot sole sensitivity upon reloading after landing. In this case report, we describe the postflight skin findings in NASA's first year-long crewmember.CASE REPORT: The crewmember was a 51-yr-old astronaut who spent 340 d in space on this mission. His in-flight course was unremarkable except for medication use for congestion, likely secondary to microgravity-induced fluid shift and elevated CO₂ levels on the ISS, and an episode of contact dermatitis from electrodes for an experiment. He had a nominal landing in Kazakhstan. During his direct return to Houston, approximately 10 h after the Soyuz landing, he developed erythema and skin sensitivity in gravity-dependent areas. The skin findings persisted for 6 d and were successfully treated with nonsteroidal anti-inflammatory drugs, gabapentin, hydrotherapy, and massage.DISCUSSION: While vascular, allergic, and immunologic causes cannot be ruled out, we hypothesize that a prolonged lack of skin stimulation over the course of the year-long mission led to the crewmember's postflight rash and skin sensitivity. Previous studies have demonstrated alterations in cutaneous receptor feedback in the sole of the foot in spaceflight and, therefore, it is plausible that skin in other parts of the body can undergo similar changes if they are not stimulated as they normally would be on Earth. More work will be needed to better understand this phenomenon and test potential mitigations.Law J, Gilmore S, Kelly S. Postflight rash and skin sensitivity following a year-long spaceflight mission. Aerosp Med Hum Perform. 2020; 91(7):604-607.


Impact of an Urban Sanitation Intervention on Enteric Pathogen Detection in Soils.
Environmental fecal contamination is common in many low-income cities, contributing to a high burden of enteric infections and associated negative sequelae. To evaluate the impact of a shared onsite sanitation intervention in Maputo, Mozambique on enteric pathogens in the domestic environment, we collected 179 soil samples at shared latrine entrances from intervention (n = 49) and control (n = 51) compounds during baseline (preintervention) and after 24 months (postintervention) as part of the Maputo Sanitation Trial. We tested soils for the presence of nucleic acids associated with 18 enteric pathogens using a multiplex reverse transcription qPCR platform. We detected at least one pathogen-associated gene target in 91% (163/179) of soils and a median of 3 (IQR = 1, 5) pathogens. Using a difference-in-difference analysis and adjusting for compound population, visibly wet soil, sun exposure, wealth, temperature, animal presence, and visible feces, we estimate the intervention reduced the probability of detecting ≥1 pathogen gene by 15% (adjusted prevalence ratio, aPR = 0.85; 95% CI: 0.70, 1.0) and the total number of pathogens by 35% (aPR = 0.65; 0.44, 0.95) in soil 24 months following the intervention. These results suggest that the intervention reduced the presence of some fecal contamination in the domestic environment, but pathogen detection remained prevalent 24 months following the introduction of new latrines.


Prenatal diagnosis of a novel 7q31.31q31.33 microduplication with a favorable outcome.
Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Especially CNVs identified in prenatal cases need careful considerations and correct interpretation if those are harmless or harmful variants from the norm. Herein, we reported a paternally inherited duplication of 7.6 Mb in 7q31.3 with, surprisingly, a favorable outcome. GTG-banding and CMA on the DNA derived from uncultured amniocytes revealed a karyotype: 46,XX.arr[GRCh37] 7q31.31q31.33(118,601,001_126,177,044) × 3. Ultrasound examination showed no dysmorphisms or intrauterine growth restriction in the fetus and the father was clinically normal as well. Prenatal detection of a 7.6 Mb in 7q31.31 to 7q31.33 duplication in a female fetus turned out to be a yet unreported unbalanced chromosome abnormality. This is another example that parental testing and GTG-banding are necessary additional tests to be done in prenatal cases, before a reliable conclusion on the meaning of an aberration can be drawn.


Profiling T cell activation using single-molecule fluorescence in situ hybridization and flow cytometry.
Flow cytometric characterization of Ag-specific T cells typically relies on detection of protein analytes. Shifting the analysis to detection of RNA would provide several significant advantages, which we illustrate by developing a new host immunity-based platform for detection of infections. Cytokine mRNAs synthesized in response to ex vivo stimulation with pathogen-specific Ags are detected in T cells with single-molecule fluorescence in situ hybridization followed by flow cytometry. Background from pre-existing in vivo analytes is lower for RNAs than for proteins, allowing greater sensitivity for detection of low-frequency cells. Moreover, mRNA analysis reveals kinetic differences in cytokine expression that are not apparent at the protein level but provide novel insights into gene expression programs expected to define different T cell subsets. The utility of probing immunological memory of infections is demonstrated by detecting T cells that recognize mycobacterial and viral Ags in donors exposed to the respective pathogens.


Issues and Advances in Scaling up Sulfide-Based All-Solid-State Batteries.
ConspectusAll-solid-state batteries (ASSBs) are considered to be a next-generation energy storage concept that offers enhanced safety and potentially high energy density. The identification of solid electrolytes (SEs) with high ionic conductivity was the stepping-stone that enabled the recent surge in activity in this research area. Among the various types of SEs, including those based on oxides, sulfides, polymers, and hybrids thereof, sulfide-based SEs have gained discernible attention owing to their exceptional room temperature ionic conductivity comparable even to those of their liquid electrolyte counterparts. Moreover, the good deformability of sulfide SEs renders them suitable for reducing the interfacial resistance between particles, thereby obviating the need for high-temperature sintering. Nevertheless, sulfide-based ASSB technology still remains at the research stage without any manufacturing schemes having been established. This state of affairs originates from the complex challenges presented by various aspects of these SEs: their weak stability in air, questions surrounding the exact combination of slurry solvent and polymeric binder for solution-based electrode fabrication, their high interfacial resistance resulting from solid particle contacts, and limited scalability with respect to electrode fabrication and cell assembly. In this Account, we review recent developments in which these issues were addressed by starting with the materials and moving on to processing, focusing on new trials. As for enhancing the air stability of sulfide SEs, strengthening the metal-sulfur bond based on the hard-soft acid-base (HSAB) theory has yielded the most notable results, although the resulting sacrificed energy density and weakened anode interface stability would need to be resolved. Novel electrode fabrication techniques that endeavor to overcome the critical issues originating from the use of sulfide SEs are subsequently introduced. The wet chemical coating process can take advantage of the know-how and facilities inherited from the more established lithium-ion batteries (LIBs). However, the dilemmatic matter of contention relating to the polarity mismatch among the slurry solvent, SE, and binder requires attention. Recent solutions to these problems involved the exploration of various emerging concepts, such as polarity switching during electrode fabrication, fine polarity tuning by accurate grafting, and infiltration of the electrode voids by a solution of the SE. The process of using a dry film with a fibrous binder has also raised interest, motivated by lowering the manufacturing cost, maintaining the environment, and boosting the volumetric energy density. Finally, optimization of the cell assembly and operation is reviewed. In particular, the application of external pressure to each unit cell has been universally adopted both in the fabrication step and during cell operation to realize high cell performance. The effect of pressurization is discussed by correlating it with the interface stability and robust interparticle contacts. Based on the significant progress that has been made thus far, we aim to encourage the battery community to engage their wide-ranging expertise toward advancing sulfide-based ASSBs that are practically feasible.


Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model.
Alpha-1-antitrypsin (a1AT) deficiency is caused by homozygosity for the a1AT mutant Z gene and occurs in 1 in 2000 births. The Z mutation confers an abnormal conformation on the protein, resulting in an accumulation within the endoplasmic reticulum of hepatocytes rather than appropriate secretion. The accumulation of the mutant protein is strikingly heterogeneous within the liver. Homozygous ZZ children and adults have an increased risk of chronic liver disease, which is thought to result from this variable intracellular accumulation of the a1AT mutant Z protein. Previous reports have suggested that autophagy, mitochondrial injury, apoptosis, and other pathways may be involved in the mechanism of hepatocyte injury, although the interplay of these mechanisms in vivo is unclear. In this study, we examine a well-characterized in vivo model of a1AT mutant Z liver injury, the PiZ mouse, to better understand the pathways involved in this disease. The results show an increase in the stimulation of the apoptotic cascade in hepatocytes, the magnitude of which strongly correlates to the absolute amount of the a1AT mutant Z protein accumulated within the individual cell. Increases in apoptotic regulatory proteins are also detected. These data, combined with previous work, permit for the first time the construction of a hypothetical hepatocellular injury cascade for this disease involving mitochondrial injury, caspase activation, and apoptosis, which takes into account the heterogeneous nature of the mutant Z protein accumulation within the liver. Further development of this hypothetical cascade will focus future research on this and other metabolic liver diseases.


Kinase activities associated with mTOR.
Although mTOR is a member of the PI-kinase-related kinase family, mTOR possesses serine-threonine protein kinase activities, which phosphorylate itself and exogenous substrates. mTOR autophosphorylates in vitro and is phosphorylated in vivo on serine residues. Ser2481, which is located in a His-Ser-Phe motif near the conserved carboxyl-terminal mTOR tail, has been reported as an autophosphorylation site in vivo and in vitro. The significance of the autophosphorylation remains unclear. Another phosphorylation site on mTOR in vivo is Ser2448. This site appears not to be an autophosphorylation site but a site potentially phosphorylated by protein kinase B (PKB). mTOR immunopurified from culture cells or tissues phosphorylates in vitro p70 S6 kinase (p70) alpha and p70beta, mainly on Thr412 or Thr401, respectively, located in a Phe-Thr-Tyr motif. Another exogenous substrate phosphorylated by immunopurified mTOR in vitro is eIF4E-binding protein 1 (4E-BP1) at sites corresponding to those phosphorylated in vivo during insulin stimulation in a Ser/Thr-Pro motif. Recently, raptor, a 150-kDa TOR-binding protein that contains a carboxyl-terminal WD-repeat domain, was discovered as a scaffold for the mTOR-catalyzed phosphorylation of 4E-BP1 and for the mTOR-mediated phosphorylation and activation of p70alpha. Other potential substrates phosphorylated by mTOR are nPKCdelta, nPKCepsilon, STAT3, and p53. The requirement of raptor for binding to and phosphorylation by mTOR of these potential substrates would clarify their physiological importance in the mTOR signaling pathway.


Haloperidol-induced reduction of nigral substance P-like immunoreactivity: a probe for the interactions between dopamine and substance P neuronal systems.
Protracted blockade of dopamine receptors by haloperidol has been shown to cause a reduction in nigral content of substance P-like immunoreactivity (SPLI). This pharmacological effect is used to study the mechanisms whereby the dopaminergic and substance P systems interact. Data presented in this paper suggest that 1) blockade of dopamine postsynaptic receptors alters nigral SPLI levels associated with the substance P striatal-nigral loop, 2) destruction of the nigral-striatal dopaminergic pathway results in changes in nigral content of SPLI similar to that induced by haloperidol, 3) several weeks after nigral-striatal lesions, compensatory mechanisms mediate a return of nigral SPLI content to control levels and 4) substance P striatal-nigral circuits continue to respond to dopaminergic input after kainic acid lesions in the anterior striatum, whereas properly placed mechanical striatal-nigral lesions appear to be effective in preventing this interaction. The data support a dynamic role for striatal-nigral substance P fibers in the extrapyramidal circuitry and suggest that his pathway must be accounted for when studying the interactions of transmitter systems within this locomotor center.


Objective Derivation of the Morphology and Staging of Visual Field Loss Associated with Long-Term Vigabatrin Therapy.
The morphology and between-eye symmetry of the visual field loss associated with the antiepileptic drug vigabatrin (VAVFL) has received little attention. Our objective was to model the appearance and ensuing staging of VAVFL derived with the European Medicines Agency-approved perimetric protocol. This was a retrospective, cross-sectional, observational study that identified 123 adults who had received vigabatrin for refractory seizures and who had no evidence of co-existing retino-geniculo-cortical visual pathway abnormality. A further 38 adults with refractory seizures and identical inclusion criteria but no exposure to vigabatrin acted as controls. For each group, the median outcome at each stimulus location in each eye (of absolute loss, relative loss or Pattern Deviation probability level, as appropriate) was derived for each successive ten pairs of fields, ranked for severity. Between-eye symmetry was quantified by an index that accounted for severity of loss and that was referenced to the likelihood of the occurrence of symmetry due to chance. The modelled VAVFL was bilateral and highly symmetrical and was described by six stages that were all independent of the extent of vigabatrin exposure. The loss originated in the extreme temporal periphery and encroached centripetally along all meridians towards fixation. The initial appearance within the central field (Stage 2) occurred inferior-nasally. Subsequent stages exhibited increasing loss, which was greater nasally than temporally. Stage 6 described concentric loss extending to approximately 15° eccentricity from fixation. The model exhibited a consistent pattern of VAVFL. The staging of the loss could assist the risk:benefit analysis of vigabatrin for the treatment of epilepsy.


Sampling conventions for estimating ultrafine and fine aerosol particle deposition in the human respiratory tract.
To provide targets for personal samplers designed for estimating particle deposition at distinct locations in the body, accounting if necessary for inter- and intra-person variation. Ultrafine and fine aerosol sampling conventions are proposed for approximating the deposition efficiency for five distinct loci of the respiratory tract. The 2 × 5 = 10 conventions represent averages over variation in physical activity level, posture, sex, and breathing mode. Recognizing three approximate relationships among the 10 deposition efficiencies, the number of independent conventions is reduced to only seven, namely three ultrafine and four fine aerosol conventions. The ultrafine and fine conventions are defined as ideal sampling efficiencies in terms of thermodynamic (independent of particle density) and aerodynamic diameter, respectively. Addition of measured mass, surface area, or particle count from aerosol collected by sampler pairs in agreement with convention can be used to estimate dose (prior to clearance) at a particular locus in the mean over breathing conditions ranging from sitting, to light, or to heavy exercise, normal or mouth breathing, and male or female, with aerosol density effects partially corrected automatically by the separate aerodynamic and thermodynamic sampling. Linear combinations of the conventions can be used for yet simpler sampling, though with limited distinctness as to deposition locus. Alternatively to estimating simply a mean, the large inter- and intra-person variation (relative standard deviation of the order of 100%) corresponding to the wide range of breathing conditions can be approximately corrected by using 'arrays' of samplers in agreement with convention, given suitable profiling of the individual whose dose is to be assessed. The intent behind the proposed conventions is not to eliminate the current aerosol penetration conventions, which have found international application in exposure assessment particularly for determining compliance with standards on acceptable aerosol levels. The aim is to promote personal sampler design leading to more sharply defined health research than can be done at present.


Association between Dioxin and Diabetes Mellitus in an Endemic Area of Exposure in Taiwan: A Population-Based Study.
Dioxin has been recognized as an environmental endocrine disruptor, but epidemiology studies of its effects on type 2 diabetes mellitus (DM) found inconsistent results, especially in men. Therefore, we conducted a study in Taiwan to evaluate the association between exposure to dioxin and DM.We recruited participants in an area where the residents were exposed to dioxin released from a factory. Using 20 and 64 pg WHO98-TEQDF/g lipid as the cut-offs, we categorized participants into 3 groups according to the level of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the serum. We defined DM as a fasting plasma glucose level more than 126 mg/dl or an existing diagnosis.Of the 2898 participants, 425 patients of DM were identified, and we observed positive associations between dioxin and DM. After adjusting for age and body mass index (BMI), we found that a high serum dioxin level was an independent risk factor for DM (adjusted odds ratio [AOR] associated with 20-63 pg WHO98-TEQDF/g lipid = 2.1, 95% confidence interval [95% CI] 1.5-2.9; AOR for ≥64 pg WHO98-TEQDF/g lipid = 3.2, 95% CI 2.1-4.8). The findings are compatible with those in previous studies of PCDD/Fs. When we stratified the participants by sex, the serum dioxin level remained an independent risk factor for DM in both men and women.Exposure to dioxin is a risk factor for DM, independent of age and BMI in both men and women. Therefore, screening and intervention programs should be considered in endemic areas of exposure to dioxin.


Postpneumonectomy pulmonary edema. A retrospective analysis of incidence and possible risk factors.
To analyze the incidence of postpneumonectomy pulmonary edema (PPE) and to determine potential risk factors for PPE. A group of 197 patients was studied retrospectively, and the incidence of PPE was recorded over a 5-year period. Preoperative, perioperative, and postoperative clinical data were collected, and preoperative and postoperative chest radiographs were reviewed. A scoring system was used to distinguish between premanifest and manifest PPE. Postpneumonectomy patients with pulmonary edema, with no clinically evident cause, were considered to have PPE. The incidence of premanifest PPE was 12.2% (n = 24), and that of manifest PPE was 2.5% (n = 5). Mortality in the group of patients who developed manifest PPE was 100%. Two significant perioperative associations were found in the PPE group. One was the administration of fresh frozen plasma (FFP) transfusions (relative risk, 4.3; 95% confidence interval, 1.3 to 14.4 corrected for age and sex), while the other was higher mechanical ventilation pressures during surgery (relative risk, 3.0; 95% confidence interval, 1.2 to 7.3). Our data suggest that FFP transfusions form an important risk factor for PPE. The mechanism may be an increased permeability of the pulmonary vessels due to an immunologic reaction after multiple FFP transfusions. The significantly higher mechanical ventilation pressures we found in the PPE group may be explained as an early sign of the development of PPE.


Malnutrition and inflammation in peritoneal dialysis patients.
Malnutrition, cardiovascular disease, and heightened inflammation are highly prevalent in dialysis patients, and major contributors to morbidity and mortality. We have investigated the inter-relationship between malnutrition and inflammation, and their impact on morbidity and mortality in peritoneal dialysis (PD) patients. We enrolled 63 PD patients beginning in November 2000, and measured C-reactive protein (CRP) and various nutritional markers, including prealbumin. CRP level was elevated in 29% of the PD patients. Diabetics had higher CRP than non-diabetics (24 vs. 9.3 mg/L, P = 0.016). Patients who were hospitalized during the study had higher enrollment CRP (16 vs. 12.5 mg/L, P = 0.05) and lower enrollment albumin (3.5 vs. 3.9 g/dL, P = 0.002), blood urea nitrogen (BUN) (40 vs. 49 mg/dL, P = 0.034), and protein catabolic rate (nPCR) (0.88 vs. 1.0 g/kg/day, P = 0.02) than those who were not hospitalized. Enrollment level of CRP was inversely correlated with nutritional markers prealbumin (r = -0.5, P < 0.0001) and creatinine (r =-0.35, P < 0.01). After adjusting for age, race, gender, diabetes, and CRP level, prealbumin continued to correlate with other nutritional markers. There was a trend toward association of elevated CRP with all-cause mortality in PD patients. It is useful to incorporate prealbumin and CRP in the regular assessment of PD patients, whose survival may be improved by better management of malnutrition and inflammation.


Repeatedly Flashed Luminance Noise Can Make Objects Look Further Apart.
Luminance noise is widely used as mask in Experimental Psychology. But can luminance noise also affect where we perceive an object or change the perceived distance between objects? In this study, I investigated the effect of a repeatedly flashed luminance noise pattern on the perceived separation between two bars. Indeed, compared to conditions without dynamic luminance noise, the spacing between the bars was overestimated when the pattern flashed on-and-off in the background. The cause for this remarkably stable effect remains unknown. Potential relations to apparent motion, masking, attentional biases, and other visual illusions are discussed.


Structural and functional analogy between pneumolysin and proaerolysin.
Pneumolysin and proaerolysin are bacterial toxins that form pores in host cells by oligomerization. We propose that they may have similar structures despite a poor sequence identity. The crystal structure of proaerolysin reveals a protein composed of four domains, arranged in the shape of an elongated comma. Electron microscopy of the pneumolysin monomer shows a similar arrangement of domains. The sequence of pneumolysin recognizes the template of proaerolysin from a library of protein folds. A three-dimensional model of pneumolysin has been constructed by the comparative approach using the structure of proaerolysin. This model, together with results on the activity of site-specific mutants and the positions of antigenic sites, has been used to propose functional roles of individual domains.


The [U2 F12 ]2- Anion of Sr[U2 F12 ].
The D2h -symmetric dinuclear complex anion [U2 F12 ]2- of pastel green Sr[U2 F12 ] shows a hitherto unknown structural feature: The coordination polyhedra around the U atoms are edge-linked monocapped trigonal prisms, the UV atoms are therefore seven-coordinated. This leads to a U-U distance of 3.8913(6) Å. A weak UV -UV interaction is observed for the dinuclear [U2 F12 ]2- complex and described by the antiferromagnetic exchange Jexp of circa -29.9 cm-1 . The crystalline compound can be easily prepared from SrF2 and β-UF5 in anhydrous hydrogen fluoride (aHF) at room temperature. It was studied by means of single crystal X-ray diffraction, IR, Raman and UV/VIS spectroscopy, magnetic measurements, and by molecular as well as by solid-state quantum chemical calculations.


Cross-cultural adaptation of the delphi definitions of low back pain prevalence (German DOLBaPP).
Assessed dimensions of low back pain (LBP) vary in prevalence studies. This may explain the heterogeneity in frequency estimates. To standardize definitions of LBP, an English consensus with 28 experts from 12 countries developed the "Delphi Definitions of Low Back Pain Prevalence" (DOLBaPP). The optimal definition and the shorter minimal definition with the related questionnaires for online, paper, and face-to-face use and telephone surveys are suitable for population-based studies. The definitions have to be adapted to different languages and cultures to provide comparable frequency estimates. The objective was to culturally adapt and pre-test the English definitions and corresponding Delphi DOLBaPP questionnaire forms into German. The German DOLBaPP adaptation was conducted using the systematic approach suggested by Beaton et al. A pre-test of the Delphi DOLBaPP optimal paper questionnaire including an additional evaluation form was conducted in a sample of 121 employees (mainly office workers). In order to evaluate the comprehensibility, usability, applicability, and completeness of the adapted questionnaire, response to the questionnaire and 6 closed evaluation questions were analyzed descriptively. Qualitative methods were used for the 3 open questions of the evaluation form. The cultural adaptation of the DOLBaPP for a German-speaking audience required little linguistic adaptation. Conceptual equivalence was difficult for the expression "low back pain". The expert committee considered the face validity of the pre-final version of the related Delphi DOLBaPP questionnaires as good. In the pre-test, most participants (95%) needed less than 5 minutes to fill in the optimal Delphi DOLBaPP questionnaire. They were generally positive regarding length, wording, diagram, and composition. All subjects with LBP (n=61 out of 121 - 50.4%) answered the questions on functional limitation, sciatic pain, frequency and duration of symptoms as well as pain severity. The results indicate that the cross-cultural German adaptation of the DOLBaPP Definitions and the corresponding questionnaires was successful. The definitions can be used in epidemiological studies to measure the prevalence of LBP. Some critical issues were raised regarding the general features of the Delphi DOLBaPP questionnaires. Future research is needed to evaluate these instruments.


Humoral immune response of the small-spotted catshark, Scyliorhinus canicula.
Cartilaginous fishes are the oldest group in which an adaptive immune system based on immunoglobulin-superfamily members is found. This manuscript compares humoral immune function in small-spotted catshark (Scyliorhinus canicula) with that described for spiny dogfish (Squalus acanthias), another member of the Squalomorphi superorder, and nurse shark, the model for humoral immunity in elasmobranchs and a member of the Galeomorphi superorder. Although small-spotted catshark and nurse shark are separated by over 200 million years we found that immunoglobulin isoforms are well conserved between the two species. However, the plasma protein profile of small-spotted catshark was most similar to that of spiny dogfish, with low levels of pentameric IgM, and IgNAR present as a multimer in plasma rather than a monomer. We show that an antigen-specific monomeric IgM response, with a profile similar to that described previously for nurse sharks, can be raised in small-spotted catshark. Lacking polyclonal or monoclonal antibody reagents for detecting catshark IgNAR we investigated phage-display and recombinant Fc-fusion protein expression as alternative methods to look for an antigen-specific response for this isotype. However, we could find no evidence of an antigen-specific IgNAR in the animals tested using either of these techniques. Thus, unlike nurse sharks where antigen-specific monomeric IgM and IgNAR appear together, it seems there may be a temporal or complete 'uncoupling' of these isotypes during a humoral response in the small-spotted catshark.


[The discriminatory force of 3 sagittal measurement relations of the jaw bases].
The angle ANB relates the apical base not only to each other but also to point nasion and the profile. Furthermore, it is influenced by prognathism and inclination of the maxillo-mandibular complex. Both the angle AB/Occlusal plane and the "Wits" appraisal are based on elements within the maxillo-mandibular complex and not influenced by structures outside this complex. Cephalograms of 4 groups of 25 cases each comprising ideal occlusion, class-II/1, class-II/2 and class-III malocclusions were collected. Angle ANB, angle AB/Occlusal plane and "Wits" appraisal in 10 variations using points A and B according to Downs, As and Bs according to Herren and the occlusal plane using Incsup., Incinf. and Incinter and the molar point Mo (Hügli) were determined. By means of a discriminant analysis the discriminatory power of these variations were calculated. Variations using the points As and Bs and point Mo gave better results in separating 100 cases according to their relation of the apical bases. The results of the stepwise discriminant analysis reveal a high percentage of "right" classification. It is possible to draw borderlines in the continuum of values, allowing with high probability a classification of each case according to Angles classification when more than one measurement is utilized.


The Impact of the Length of the Common Intestinal Loop on Metabolic and Nutritional Outcomes of Patients with Severe Obesity Who Undergo of Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy: 5-Year Follow-Up.
Introduction: Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a recent bariatric surgery technique, highly effective in terms of weight loss. Nevertheless, data regarding the impact of SADI-S at mid-long term (after >5 years of follow-up) are scarce. Objectives: To evaluate the effect of lengths of common intestinal loop on the evolution of patients with morbid obesity (MO), who undergo SADI-S. Materials and Methods: Descriptive study (case series), including patients with MO who underwent SADI-S procedure between January 2012 and December 2015 with at least 5 years of follow-up. Patients were classified as "Old-SADI-S" (OS) when length of the common alimentary loop was <2.5 m and "New-SADI-S" (NS) when length was >2.5 m. Clinical parameters and nutritional parameters were included. Results: Twenty-nine cases were included (17 OS; 12 NS), 86.2% women and mean age 46.7 ± 1 years. After 12 months, OS had significantly lower body mass index (29.7 ± 4.8 kg/m2 versus 32.0 ± 5.1 kg/m2, P = .01), without significant differences in the resolution of comorbidities. Nevertheless, OS group had severe malabsorptive complications requiring surgical conversion of OS to NS in 7 patients after 8 months. At 5 years of follow-up, no significant difference was seen between the two groups and resolution of comorbidities was maintained during this period of time. Conclusions: SADI-S is effective in terms of weight loss and resolution of comorbidities at 5 years of follow-up, regardless of the length of the common intestinal loop. However, a common intestinal loop <2.5 m was associated with severe malabsorptive complications that determined the surgical re-conversion in all cases.


The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila.
During the development of Drosophila appendages from imaginal discs lineage restrictions appear that prevent dividing cells from crossing between regionally distinct compartments. These compartments correspond not only to regions of cell lineage restrictions but also to regions of specific gene expression. When compartments were first discovered, it was proposed that their formation relied on compartment-specific 'selector' gene activity; engrailed is thought to play such a role for the early-arising anterior-posterior restriction. Recent results suggest that the dorsally expressed transcription factor encoded by apterous may control dorsoventral identity in the wing. In this study we use mosaic analysis to show that apterous maintains the late-arising dorsoventral lineage restriction in a manner that strongly supports the selector gene hypothesis: loss of apterous function from dorsal cells after the formation of the boundary causes them to cross into the ventral compartment. Moreover, we show that apterous plays a role controlling patterns of gene expression in the developing wing disc. The PS1 and PS2 integrins are normally expressed in primarily dorsal-specific and ventral-specific patterns, respectively. We show that ectopic expression of apterous induces ectopic ventral expression of PS1 integrin and alpha PS1 mRNA, while loss of apterous can induce the ectopic dorsal expression of PS2 integrin. Thus, apterous plays a selector-like role both in terms of the control of lineage restrictions and the regulation of downstream gene expression.


Prevalence and epidemiological characteristics of methicillin-resistant Staphylococcus aureus isolated from cattle in Bangalore India as a part of the One Health approach.
In India, limited studies are available on the epidemiological aspects of methicillin-resistant Staphylococcus aureus (MRSA) infections in both animal and human settings. Herein, we investigated the prevalence, antimicrobial resistance profile and molecular characteristics of MRSA isolates recovered from cattle using the One Health approach. Out of 66 mecA-positive staphylococci, species-specific multiplex PCR detected 24 % (n=16) of isolates as MRSA. Maximum antibiotic resistance was seen against cloxacillin (94 %, n=15) and least for enrofloxacin and cephalothin (each 13 %, n=2). Overall, 13 % (n=2) of MRSA isolates were multidrug-resistant. Molecular characterization by SCCmec typing identified 88 % (n=14) of MRSA isolates as type V. Twelve isolates (75 %) belonged to novel spa-type t17242, of which 67 % (n=8) belonged to agr type I. MLST analysis revealed ST 1687 (50 %, n=8) as the most predominant sequence type. Circulation of different MRSA clones among the cattle populace offers a risk of transmission to humans through direct contact, food chain or environmental contamination. Thus, continuous monitoring of MRSA strains is imperative for early diagnosis and for establishing effective treatment strategies to restrain the disease burden caused by MRSA infections.


Rabi-like oscillation of photonic topological valley Hall edge states.
We investigate Rabi-like oscillations of topological valley Hall edge states by introducing two zigzag domain walls in an inversion-symmetry-breaking honeycomb photonic lattice. Such resonant oscillations are stimulated by weak periodic modulation of the lattice depth along the propagation direction that does not affect the overall symmetry and the band topology of the lattice. Oscillations are accompanied by periodic switching between edge states with the same Bloch momentum but located at different domain walls. Switching period and efficiency are the non-monotonic functions of the Bloch momentum in the Brillouin zone. We discuss how the efficiency of this resonant process depends on the detuning of modulation frequency from the resonant value. Switching of nonlinear edge states is also briefly discussed. Our work brings about an effective approach to accomplish resonant oscillations of the valley Hall edge states in time-reversal-invariant topological insulators.


DYNAMICS OF ECDYSONE SECRETION AND ACTION IN THE FLESHFLY SARCOPHAGA PEREGRINA.
1. Ecdysone is in a highly dynamic state after its injection or its secretion by the ring-gland of Sarcophaga peregrina. Hormonal activity is rapidly destroyed by an inactivating mechanism which is present in the tissues but not in the blood. 2. Inactivation is blocked by low temperatures or anaerobic conditions-a finding that implicates chemical and, more particularly, oxidative reactions. The mechanism in question could be demonstrated in larval fragments but not in crude or fractionated homogenates. 3. When injected into mature larvae, 1 µg of α-ecdysone loses 50% of its activity in 1 hour and 98% in 8 hours. Lower doses show even briefer "half-lives." 4. The rapid inactivation of ecdysone can account for its low titer in both the blood and tissues. Thus at the "critical period" for puparium formation, the entire larva contains only 2.5 nanograms, corresponding to only 7% of a Sarcophaga unit. 5. The evidence points to the accumulation, not of the hormone itself, but the covert biochemical and biophysical effects of the hormone. The covert effects undergo spatial and temporal summation within the target organs and finally discharge the overt developmental response. 6. The role of the blood is to serve, not as a reservoir, but as a pipeline through which ecdysone flows from the ring-gland to its sites of action and swift inactivation.


Paediatric acute rheumatic fever in developed countries: Neglected or negligible disease? Results from an observational study in Lombardy (Italy).
Acute Rheumatic Fever (ARF) is a multisystemic disease that results from an autoimmune reaction due to group A streptococcal infection. The disease affects predominantly children aged 5 to 15 years and although its incidence in developed Countries declined since the early 1900s, to date there is a paucity of data that confirm this epidemiological trend. The study aimed to assess the burden of ARF in term of hospitalization and to describe the characteristics of acute rheumatic fever (ARF) in the paediatric population of Lombardy. The study was carried out by analyzing hospital discharge records of patients resident of Lombardy and aged 0-17 years old who, from 2014 to 2016, were hospitalized with the diagnosis of ARF. The following variables have been studied: age, sex, municipality of residence, date of diagnosis of each patient, hospital of admission, and presentation of the disease. From 2014 to 2016, 215 patients were found to meet the inclusion criteria and diagnosed as affected from Acute Rheumatic Fever. The rate of hospitalization showed a slightly increasing trend from 3.42 in 2014 to about 5.0 in 2016. Moreover, ARF presented a typical seasonal trend with lower cases in the autumn and a peak of hospitalization in the spring. To date, ARF seems to be a rare but not negligible disease in southern central European countries, and in Lombardy we estimated an annual hospitalization rate of 4.24 cases per 100,000 children. The increasing trend found in our study suggests that the burden of the disease could be reduced by involving multidisciplinary health professionals who, in addition to the paediatrician of free choice, would promote evidence based medicine management of the disease during all its clinical phases.