Heart fatty acid binding protein as a marker for postmortem detection of early myocardial damage.
Depletion of heart fatty acid binding protein (H-FABP) from cardiomyocytes with varying post-ischemia intervals was studied in acute myocardial infarction (AMI) model of rat, and 22 human autopsy cases were studied with streptavidin-peroxidase conjugated method (S-P). It was observed that as early as 15 min after ischemia, the depletion of H-FABP could be detected in model rats. With the ischemic time prolonged, the depletion of H-FABP was more and more evident. In all human cases with myocardial infarction, absent H-FABP staining could be found in infarcted area. And in some suspected early myocardial infarction cases, depletion of H-FABP staining could be demonstrated in areas that showed normal hematoxylin-eosin (HE) staining. The blood samples from model rats before ligation, at varying post-ischemia intervals and various postmortem time were measured for plasma concentration of H-FABP with enzyme-linked immuno-sorbent assay (ELISA) method. At 15 min after myocardial ischemia, the concentration of H-FABP was 4 times higher (546.0+/-85.3 microg/l) than that of the baseline level (103.7+/-94.1 microg/l). With the continuation of ischemic time, the concentration of H-FABP increased and peaked at 4 h (1953.5+/-405.3 microg/l), then decreased. The plasma concentration of H-FABP decreased slightly with postmortem time, but was still significant higher at any postmortem intervals than that of baseline level within 48 h after death. The results suggest that H-FABP staining can detect very early ischemic damages in human myocardium and the elevated plasma concentration of H-FABP in rat was an indicator of AMI, which was not affected by autolysis.


A molecular phylogeny of the African widowbirds and bishops, Euplectes spp. (Aves: Passeridae: Ploceinae).
The elaborate male displays and plumage ornaments in the African widowbirds and bishops (Euplectes spp.) have inspired classic studies on mating systems and sexual selection. In order to study the extreme divergence in ornament design and expression in this group, we present and discuss a well-supported molecular phylogeny of the genus and its placement within the Ploceinae subfamily. Parsimony and Bayesian analyses were performed on 2557bp of mitochondrial DNA (ATP6, Cyt b, ND2 and ND3) and a nuclear intron (G3PDH). All 17 Euplectes species, and 31 of 51 suggested subspecies, were included, as well as eight Ploceinae outgroups from four genera (Amblyospiza, Ploceus, Quelea and Foudia). Our results show monophyly of Euplectes, but not of the intrageneric groupings of bishops and widowbirds. Most notably, the Red-collared Widowbird E. ardens belongs to a subclade of bishops, and not to the sister subclade of 'true' widowbirds. Furthermore, the two bishops E. afer and E. aureus represent lineages that branched off before this basal split, which also refutes the proposed superspecies of E. afer and E. diadematus. Also somewhat surprisingly, and despite the striking plumage similarities among the red bishops, E. franciscanus is not closely related to either E. nigroventris or E. orix (of which it until recently was considered a subspecies). Finally, the Mountain Marsh Widowbird E. psammocromius is likely closest to the Long-tailed Widowbird E. progne, and not, as previously thought, to the Marsh Widowbird E. hartlaubi.


Effects of visual and auditory guidance on bimanual coordination complexity.
Perceptual guidance of movement with simple visual or temporal information can facilitate performance of difficult coordination patterns. Guidance may override coordination constraints that usually limit stability of bimanual coordination to only in-phase and anti-phase. Movement dynamics, however, might not have the same characteristics with and without perceptual guidance. Do visual and auditory guidance produce qualitatively different dynamical organization of movement? An anti-phase wrist flexion and extension coordination task was performed under no specific perceptual guidance, under temporal guidance with a metronome, and under visual guidance with a Lissajous plot. For the time series of amplitudes, periods and relative phases, temporal correlations were measured with Detrended Fluctuation Analysis and complexity levels were measured with multiscale entropy. Temporal correlations of amplitudes and relative phases deviated from the typical 1/f variation towards more random variation under visual guidance. The same was observed for the series of periods under temporal guidance. Complexity levels for all time series were lower in visual guidance, but higher for periods under temporal guidance. Perceptual simplification of the task's goal may produce enhancement of performance, but it is accompanied by changes in the details of movement organization that may be relevant to explain dependence and poor retention after practice under guidance.


PTEN and AKT1 Variations in Childhood T-Cell Acute Lymphoblastic Leukemia
PTEN/AKT pathway deregulations have been reported to be associated with treatment response in acute leukemia. This study examined pediatric T-cell acute lymphoblastic leukemia (T-ALL) samples for PTEN and AKT1 gene variations and evaluated the clinical findings. Fifty diagnostic bone marrow samples of childhood T-ALL cases were investigated for the hotspot regions of the PTEN and AKT1 genes by targeted next-generation sequencing. A total of five PTEN variations were found in three of the 50 T-ALL cases (6%). Three of the PTEN variations were first reported in this study. Furthermore, one patient clearly had two different mutant clones for PTEN. Two intronic single-nucleotide variations were found in AKT1 and none of the patients carried pathogenic AKT1 variations. Targeted deep sequencing allowed us to detect both low-level variations and clonal diversity. Low-level PTEN/AKT1 variation frequency makes it harder to investigate the clinical associations of the variants. On the other hand, characterization of the PTEN/AKT signaling members is important for improving case-specific therapeutic strategies.


Negative regulation of HIF-1α by an FBW7-mediated degradation pathway during hypoxia.
Hypoxia inducible factor-1α (HIF-1α) stimulates expression of genes associated with angiogenesis and is associated with poor outcomes in ovarian and other cancers. In normoxia, HIF-1α is ubiquitinated and degraded through the E3 ubiquitin ligase, von Hippel-Lindau; however, little is known about the regulation of HIF-1α in hypoxic conditions. FBW7 is an E3 ubiquitin ligase that recognizes proteins phosphorylated by glycogen synthase kinase 3β (GSK3β) and targets them for destruction. This study used an ovarian cancer cell model to test the hypothesis that HIF-1α phosphorylation by GSK3β in hypoxia leads to interaction with FBW7 and ubiquitin-dependent degradation. Expression of constitutively active GSK3β reduced HIF-1α protein and transcriptional activity and increased ubiquitination of HIF-1α in hypoxia, whereas pharmacologic inhibition of GSK3 or expression of siGSK3β promoted HIF-1α stabilization and activity. A mechanism through FBW7 was supported by the observed decrease in HIF-1α stabilization when FBW7 was overexpressed and both the elevation of HIF-1α levels and decrease in ubiquitinated HIF-1α when FBW7 was suppressed. Furthermore, HIF-1α associated with FBW7γ by co-immunoprecipitation, and the interaction was weakened by inhibition of GSK3 or mutation of GSK3β phosphorylation sites. The relevance of this pathway to angiogenic signaling was supported by the finding that endothelial cell tube maturation was increased by conditioned media from hypoxic SK-OV-3 cell lines expressing suppressed GSK3β or FBW7. These data introduce a new mechanism for regulation of HIF-1α during hypoxia that utilizes phosphorylation to target HIF-1α for ubiquitin-dependent degradation through FBW7 and may identify new targets in the regulation of angiogenesis.


BCG immunotherapy: effects of dose and route of administration on survival of mice bearing established tumors.
Bacillus Calmette-Guérin (BCG) was administered in various doses by four different routes to C3H/HeJ mice bearing well-established syngeneic MC-42 fibrosarcomas. Injections of BCG into established primary tumors decreased survival of tumor-bearing mice as compared to saline-injected controls. Of the three dosage groups, high-dose (10(8) viable organisms) intralesional BCG was most detrimental. The injection of low-dose BCG (10(4) organisms) into established tumors or subcutaneously at a distant site also shortened host survival times. Other subcutaneous injections and injections of BCG into the peritoneal or pleural cavities had no significant effect on survival, regardless of dosage. The dose-dependent effects of BCG immunotherapy which may prolong or shorten survival are discussed.


Novel Role for γ-Catenin in the Regulation of Cancer Cell Migration via the Induction of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1).
γ-Catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully understood. In this study, we have identified a novel role for the affects of γ-catenin on non-small cell lung cancer (NSCLC) cell migration. Expression of γ-catenin in NSCLC cells resulted in reduced cell migration as determined by both scratch assays and trans-well cell migration assays. Moreover, the affects of γ-catenin on cell migration were observed to be p53-dependent. Mechanistically, the anti-migratory effects seen via γ-catenin were driven by the expression of hepatocyte growth factor activator inhibitor Type I (HAI-1 or SPINT-1), an upstream inhibitor of the c-MET signaling pathway. Furthermore, the re-expression of γ-catenin sensitized NSCLC cells to c-MET inhibitor-mediated growth inhibition. Taken together, we identify γ-catenin as a novel regulator of HAI-1, which is a critical regulator of HGF/c-MET signaling. Therefore, targeting γ-catenin-mediated HAI-1 expression might be a useful strategy to sensitize NSCLC to c-MET inhibitors.


The effect of derivatives of folic acid on the fluorodeoxyuridylate-thymidylate synthetase covalent complex in human colon xenografts.
This study was designed to examine the endogenous concentrations of 5,10-methylenetetrahydrofolate (CH2FH4) in human colorectal adenocarcinoma xenografts, and to determine the ability of other folate derivatives to increase the formation of the ternary covalent complex between CH2FH4, [6-3H]-5-fluorodeoxyuridylate (FdUMP) and thymidylate synthetase (TS, EC 22.214.171.124). Levels of CH2FH4 were determined by measuring the release of [3H]2O from [5-3H]-dUMP using TS from Lactobacillus casei. The reaction was linear from 1.9 X 10(-13) to 2.4 X 10(-11) mol of CH2FH4 assayed. Concentrations of CH2FH4 were low, ranging from 66 to 233 nM in cell water. Tetrahydrofolate (FH4) and dihydrofolate (FH2) increased complex formation, while 5-formyltetrahydrofolate (5-CHOFH4) and 5-methyltetrahydrofolate (5-CH3FH4) decreased the covalent binding of [6-3H]-FdUMP in vitro. Administration of FH4 or FH2 to tumor-bearing mice reduced subsequent formation of the covalent complex in vitro. Since 5-CH3FH4 is a major derivative of folate in mammalian tissues, its effect on the covalent binding of [6-3H]-FdUMP was examined further; even in the presence of homocysteine and cyanocobalamin (B12), the formation of the covalent complex was not increased. The fate of [5-14CH3]-FH4 was subsequently examined in vivo. In tumors at 1 hr after injection, 72% of the radiolabel remained as [5-14CH3]-FH4, while 17% had been converted to [14C]-methionine or incorporated into protein. By contrast, however, the incorporation of radiolabel into the protein fraction of liver was almost 30-fold greater at this time. At 4 hr, radioactivity in tumors (dpm/g) and in the fraction associated with [5-14CH3]-FH4 was decreased by over 60%, while metabolism was increased by only 13%. No polyglutamate forms of [5-14CH3]-FH4 were detected in tumors at 4 hr after treatment.


Immunological aspects of otitis media: present views on possibilities of immunoprophylaxis of acute otitis media in infants and children.
The article reviews, based on current knowledge of immunological events affecting the middle ear, the possibilities and prospects for the prevention of otitis media (OM) by immunologic measures. While pneumococcal capsular polysaccharide vaccines proved not to be effective against infant acute otitis media (AOM), pneumococcal conjugate vaccines provide good immunogenicity even in infants, and call for trials with better prospects of clinical efficacy. The other future approaches currently under development are vaccines against nontypable Haemophilus influenzae and Branhamella catarrhalis, anti-viral immunoprophylaxis, combinations of the above alternatives, or passive immunization. Also, the use of new routes or ways of immunization are under study. Furthermore, the ways to modify the present treatment practices of AOM to favour good immunologic responses in infants and children must be studied.


Dynamics of spontaneous vesicle formation in fluorocarbon and hydrocarbon surfactant mixtures.
The spontaneous self-assembly of unilamellar vesicles was investigated by means of time-resolved synchrotron small-angle X-ray scattering. The self-assembly process was initiated by rapid mixing of anionic surfactant micelles with either zwitterionic or cationic surfactant micelles in equimolar ratio using a stopped-flow device. For the zwitteranionic systems, transient disklike mixed micelles are observed as structural intermediates prior to the onset of vesiculation. These disklike micelles display an exponential growth law, and above a critical size they close to form unilamellar vesicles. In the catanionic system, the earliest observable structures within the mixing time of 4 ms are unilamellar vesicles. Nevertheless, in both systems a narrow distribution of the vesicle size was observed at the initial stages of their formation. The subsequent evolution of the vesicle size distribution depends on the subtle differences in the bilayer composition and properties.


Mo3 S13 2- Intercalated Layered Double Hydroxide: Highly Selective Removal of Heavy Metals and Simultaneous Reduction of Ag+ Ions to Metallic Ag0 Ribbons.
We demonstrate a new material by intercalating Mo3 S13 2- into Mg/Al layered double hydroxide (abbr. Mo3 S13 -LDH), exhibiting excellent capture capability for toxic Hg2+ and noble metal silver (Ag). The as-prepared Mo3 S13 -LDH displays ultra-high selectivity of Ag+ , Hg2+ and Cu2+ in the presence of various competitive ions, with the order of Ag+ >Hg2+ >Cu2+ >Pb2+ ≥Co2+ , Ni2+ , Zn2+ , Cd2+ . For Ag+ and Hg2+ , extremely fast adsorption rates (≈90 % within 10 min, >99 % in 1 h) are observed. Much high selectivity is present for Ag+ and Cu2+ , especially for trace amounts of Ag+ (≈1 ppm), achieving a large separation factor (SFAg/Cu ) of ≈8000 at the large Cu/Ag ratio of 520. The overwhelming adsorption capacities for Ag+ (qm Ag =1073 mg g-1 ) and Hg2+ (qm Hg =594 mg g-1 ) place the Mo3 S13 -LDH at the top of performing sorbent materials. Most importantly, Mo3 S13 -LDH captures Ag+ via two paths: a) formation of Ag2 S due to Ag-S complexation and precipitation, and b) reduction of Ag+ to metallic silver (Ag0 ). The Mo3 S13 -LDH is a promising material to extract low-grade silver from copper-rich minerals and trap highly toxic Hg2+ from polluted water.


Host plant pollen influences calling behavior and ovarian development of the sunflower moth, Homoeosoma electellum.
Females of the sunflower moth, Homoeosoma electellum held in the presence of pollen, or an ethanolic pollen extract, from the sunflower Helianthus annuus initiated calling behavior at a significantly younger age following emergence than those provided sucrose only. Furthermore, females with pollen subsequently spent more time calling, and had an increased rate of egg maturation, than those held without pollen. These effects were attributed to a kairomone as females held in the presence of, but denied direct access to, pollen behaved in the same manner as those in contact with pollen. The importance of this life history strategy for the exploitation of temporarily available resources, essential to the survival of neonate larvae, and on the dispersal of adults, is discussed.


Student access to primary health care and preventive health screening at a school-based health centre in South Auckland, New Zealand.
To determine where students usually access primary health care and compare the quality of preventive health services that students who use the school-based health centre (SBHC) receive to those who go elsewhere for health care. A convenience sample of 20 classes were selected and surveyed in 2003. Three hundred and forty-three students completed the Young Adult Health Care Survey using a web-based questionnaire. While most students (79%) access health care from their family doctor, a significant number (40%) of students attended the SBHC in the last 12 months. Overall, health screening and preventive counselling from health care providers was low. Students who used the SBHC were more likely to received private and confidential health care and preventive screening than students who go elsewhere for health care. School-based health care provides additional access to health care that does not appear to replace traditional family practice based health care. While the SBHC appears to deliver better quality preventive health services for adolescents compared to traditional primary health care, improvements are needed across all primary health care settings.


The haemodynamic effects of long term felodipine therapy in previously untreated essential hypertension.
Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of less than 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm-5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure.


"But-He'll Fall!": Children with Autism, Interspecies Intersubjectivity, and the Problem of 'Being Social'.
'Being autistic' or 'having Autism Spectrum Disorder' implies a limited range of 'being social,' but the in situ organization of interaction, what Maynard and Marlaire (Qual Soc 15(2):177-202, 1992) call the 'interactional substrate,' within which this delimitation enfolds is usually hidden from sight. Analysis of processes constituting different 'interactional substrates' provides a view of how one comes to be known by and to self and others as a certain kind of being who is available (or not) for acting and feeling in certain ways. People diagnosed with Autism Spectrum Disorder (American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013) are often described as 'being' impaired in intersubjective understanding of others. But the story of ASD as an impairment of sociality and intersubjectivity becomes more complicated when animals enter into the picture. I consider two interactional substrates: a psychological interview in a mental health clinic, and an animal-assisted activity in a child's neighborhood. I aim to elucidate the practical problems of 'being social' encountered by two children with ASD, both nine-year-old girls, within these two very differently organized interactional substrates. I consider ways in which 'being with' therapy animals provides a way of 'being social' through "sensory modalities of knowing" (Haraway, When species meet, 2008:371).


Morphology of the hypophysis of the freshwater teleost rhamdia hilarii (val., 1840).
The anatomical relationship between hypophysis and encephalon of the Bagre fish (Rhamdia hilarii, Val.) was studied. The subdivisions, morphology and the relative volume (%) of the different hypophyseal regions during the reproductive stage of the fish were also considered.


Durable protein lattices of clathrin that can be functionalized with nanoparticles and active biomolecules.
Biological molecules that self-assemble and interact with other molecules are attractive building blocks for engineering biological devices. DNA has been widely used for the creation of nanomaterials, but the use of proteins remains largely unexplored. Here, we show that clathrin can form homogeneous and extended two-dimensional lattices on a variety of substrates, including glass, metal, carbon and plastic. Clathrin is a three-legged protein complex with unique self-assembling properties and is relevant in the formation of membrane transport vesicles in eukaryotic cells. We used a fragment of the adaptor protein epsin to immobilize clathrin lattices on the substrates. The lattices span multiple square millimetres with a regular periodicity of 30 nm and can be functionalized via modified subunits of clathrin with either inorganic nanoparticles or active enzymes. The lattices can be stored for months after crosslinking and stabilization with uranyl acetate. They could be dehydrated and rehydrated without loss of function, offering potential applications in sensing and as biosynthetic reactors.


A triphenylene based zinc ensemble as an oxidation inhibitor.
The zinc complex of a new triphenylene based receptor is evaluated for its anti-oxidant activity which is better in comparison to that of commercially available anti-oxidants.


Clinical analysis of 40 multiple myeloma patients with extramedullary plasmacytoma of the head.
Objectives To investigate the clinical characteristics, survival and prognosis of patients with multiple myeloma (MM) and head extramedullary plasmacytoma (EMP). Methods Forty MM patients were enrolled in the study (18 men, 22 women; median age, 55 years). Results Median overall survival (OS) and progression-free survival (PFS) were 24 (5-78) months and 17 (2-36) months, respectively. The 2-, 3- and 5-year OS rates were 51%, 20% and 7%, respectively. The 2-year PFS was 15%. Median OS and PFS in patients administered velcade were 26 (18-50) and 22.5 (5-78) months, compared with 20 (10-30) and 13.5 (2-36) months in patients without velcade, respectively. Median OS was 23.5 (5-50) months in patients with EMP at MM diagnosis ( n = 25) and 36 (22-78) months in patients with head EMP diagnosed during the disease course ( n = 15). Sixteen MM patients had EMP invasion of the head only and 24 had invasion at multiple sites. Median OS was 25 (22-78) months in patients with EMP of the head only and 22 (5-78) months in patients with EMP invasion at multiple sites. Conclusion MM patients with head EMP show a more aggressive disease course and shorter OS and PFS. The prognosis of these patients is poor, especially in patients with head EMP at MM diagnosis, though combined chemotherapy and radiotherapy may prolong survival.


Bacterial agents and changes in drug susceptibilities in cases of chronic dacryocystitis, Southern China.
This study aimed to determine the susceptibility and the changes of bacterial agents of chronic dacryocystitis and determine the risk factors for bacterial prevalence and drug sensitivity to provide a reference for clinical selection of antibiotics. A case-control study was conducted using 112 patients with chronic dacryocystitis and 112 patients with non-infectious ophthalmopathy between August 2017 and April 2018. Lacrimal and conjunctival sac secretions were cultured for aerobic and anaerobic bacteria. Forty-five patients with chronic dacryocystitis between November 2014 and November 2015 were also included. Positive bacterial cultures were obtained from 61.9% and 50.9% of chronic dacryocystitis and non-infectious ophthalmopathy patients, but the detection rates for pathogenic bacteria were 18.3% and 2.7%, respectively (P > 0.001). Gram-negative and anaerobic bacteria were significantly more prevalent in the patient group compared with the control group (P = 0.001 and 0.005, respectively). Bacteria were detected at a significantly higher rate in patients with irritant symptoms (itch or foreign-body sensation) than in those without (OR = 9.333, P = 0.002), particularly Staphylococcus (OR = 9.783, P = 0.002). 11.6% (10/86) and 55.8% (48/86) showed resistance to levofloxacin and tobramycin, respectively. Compared with three years ago, the detection rate for Gram-positive cocci decreased from 51.1% to 27.8% (χ2 = 8.054, P = 0.005) CONCLUSIONS: Gram-positive cocci, Gram-negative bacilli, and anaerobic bacteria were the predominant pathogens. The prevalence of Gram-positive bacteria in cases of chronic dacryocystitis is decreasing.


Human lactoferrin exerts bi-directional actions on PC12 cell survival via ERK1/2 pathway.
Human lactoferrin (hLF) is a member of the transferrin family and is found in most body fluids of human. Recent study showed that hLF played some roles in the regulation of cell growth. However, the biological function of hLF in the central nervous system and neuronal cells is still unclear. The MTT was used to assay cell viability, ELISA tests were used to assay caspase activities, and TUNEL staining was used to test the cytotoxicity of hLF to the cells. Our result showed that 700 microg/ml hLF significantly reduced the cell viability and increased the caspase 3 and 8 activities in PC12 neuronal cells. TUNEL staining further showed that 700 microg/ml hLF was cytotoxic to the PC12 through apoptosis-mediated pathway. In addition, 700 microg/ml hLF significantly decreased the protein expressions of phosphorylated extracellular-signal-regulated kinase 1/2 (ERK1/2) and Bcl-2 in PC12 cells, whereas 50 microg/ml hLF significantly increased the phosphorylation of ERK1/2 which could be specifically inhibited by PD98059. Furthermore, 50 microg/ml hLF could not only up-regulate the Bcl-2 expression but also protect PC12 cells from FasL-induced apoptosis. In conclusion, hLF plays a crucial role in the regulation of apoptosis and anti-apoptosis in PC12 neuronal cells via ERK1/2 phosphorylation pathway.


Radiographic and endoscopic measurements of esophageal length in pediatric patients.
Knowledge of the length between the upper esophageal sphincter (UES) and the lower esophageal sphincter (LES) in pediatric patients is essential for intraluminal impedance and dual pH probe recordings. We measured the vertical distance between the true vocal cords (TVCs) and the LES in chest x-rays (CXRs) of 118 children (ages, 6 weeks to 13 years) and measured the vertical distance between the UES and the LES during endoscopy in 31 patients (ages, 14 months to 17 years) and correlated the measurements to height, weight, and age. Esophageal length correlated best with patient height (R = 0.96 by CXR, R = 0.88 by endoscopy) and less well with weight (R = 0.87, R = 0.67) and age (R = 0.94, R = 0.86). Linear regression analyses using radiographic measurements revealed that esophageal length (TVC to LES) can be estimated from a patient's height by the following equation: 1.048 + 0.167 x height (in centimeters). With the upper pH probe placed in the hypopharynx at the TVC level and the inferior probe placed in the esophagus 3 to 6 cm above the LES, the patients were divided into 6 groups corresponding to the currently available number of sizes of dual pH-impedance probes. With the patients' heights between 71.5 and 161.3 cm, 64.7% to 100% of patients were within 1 cm of the desired location with preselected probes. Confirmation of placement was performed with CXR. A pediatric patient's height can be used to estimate the esophageal length (TVC to LES) and facilitate the selection of dual pH-impedance probes. Our method decreases the risk of morbidity while increasing the accuracy of the study of extraesophageal reflux disease.


Excess risk for contralateral breast cancer in CHEK2*1100delC germline mutation carriers.
We detected a significant excess risk for CHEK2*1100delC mutation carriers to develop a contralateral breast tumor, OR = 6.5 (95% CI 1.5-28.8, p = 0.005). The highest percentage of mutation carriers was detected among those bilateral breast cancer patients who had received radiation treatment for their first breast tumor. These results warrant prolonged medical surveillance and may indicate a clinically important interaction between CHEK2 heterozygosity and radiation in the development of contralateral breast cancer.


Histologic Activity and Steroid Use History Are Risk Factors of Clinical Relapse in Ulcerative Colitis With Mayo Endoscopic Subscore of 0 or 1.
The treatment goal of ulcerative colitis (UC) has changed from the control of symptoms to mucosal healing, previously evaluated mainly by endoscopy. Recently, the importance of histologic activity has emerged. Therefore, this study aimed to investigate the risk of clinical relapse according to histologic activity in UC with a Mayo endoscopic subsccore (MES) of 0 or 1. In a retrospective cohort after our center's biopsy guideline for UC was instituted, 492 UC patients with an MES of 0 or 1 were enrolled and analyzed. The primary outcome was the development of a clinical relapse including changes in medication, hospitalization, colectomy, and the development of colorectal cancer during the follow-up period. During the median 549 days of follow-up, 92 (18.7%) patients had a clinical relapse. All the patients changed their medication, including 4 hospitalized patients. Histologic activity defined by a Geboes score of ≧3.1 (hazard ratio [HR], 1.732; P = .035) and steroid use history (HR, 1.762; P = .008) were independent factors associated with clinical relapse. When stratified, the 1- and 2-year incidence rates of clinical relapse were 4.1% and 10.6%, respectively, for patients with histologic improvement and no steroid use history, whereas the rates were 23.9% and 39.4% for patients with histologic activity and steroid use history. In UC with an MES of 0 or 1, histologic activity and steroid use history can be used to stratify the risk of clinical relapse.


Lower cognitive reappraisal capacity is related to impairments in attachment and personality structure in poly-drug use: an fMRI study.
Insecure attachment, impaired personality structure and impaired emotion regulation figure prominently in substance use disorders. While negative emotions can trigger drug-use and relapse, cognitive reappraisal may reduce emotional strain by promoting changes in perspective. In the present study, we explored behavioral and neural correlates of cognitive reappraisal in poly-drug use disorder by testing individuals' capability to generate cognitive reappraisals for aversive events (Reappraisal Inventiveness Test). 18 inpatients with poly-drug use disorder and 16 controls completed the Adult Attachment Scale, the Emotion Regulation Questionnaire, the Brief Symptom Inventory, the Wonderlic Personnel Test, and the Operationalized Psychodynamic Diagnosis Structure Questionnaire, as well as two versions of the Reappraisal Inventiveness Test (during fMRI and outside the lab). Compared to controls, polydrug inpatients reported impaired personality structure, attachment and emotion regulation abilities. In the Reappraisal Inventiveness Test, poly-drug inpatients were less flexible and fluent in generating reappraisals for anger-eliciting situations. Corresponding to previous brain imaging evidence, cognitive reappraisal efforts of both groups were reflected in activation of left frontal regions, particularly left superior and middle frontal gyri and left supplemental motor areas. However, no group differences in neural activation patterns emerged. This suggests that despite cognitive reappraisal impairments on a behavioral level, neural reflections of these deficits in poly-drug use disorder might be more complex.


Prolactin cell activity and sodium fluxes in tilapia (Oreochromis mossambicus) after long-term acclimation to acid water.
In tilapia exposed for 3 months to water of pH 4.5, prolactin cell activity, as estimated by ultrastructural morphometry and determination of prolactin synthesis in vitro, was significantly higher than in controls from neutral water. Sodium influx from the water was 50% lower than in the controls, indicating impaired branchial sodium uptake mechanisms. In contrast to predictions based on the results of short-term exposure to acid water--which is known to induce an increase of sodium efflux--the sodium efflux rate was reduced to 70% of the control value. It is concluded that tilapia are able to acclimate to acid water by successful control--probably via prolactin--of diffusional sodium losses across the integument, in particular the gill surface. This compensates for the impaired sodium uptake, and enables the fish to reestablish a positive sodium balance in acid water.


Computed tomographic study of the optimal safe implantation corridors in feline thoraco-lumbar vertebrae.
To define the implantation corridors in feline thoraco-lumbar vertebrae (T10-L7) using computed tomography (CT) for optimal safe placement of the implants (screws/pins) in spinal column stabilization. Computed tomographic study. Computed tomography images of feline spinal column (n = 10) were used to define the optimal safe implantation corridors (OSIC) in the transverse plane. The OSIC were defined as corridors allowing the greatest amount of bone purchase with safe margins for implantation of the bicortical implants. They were characterized by their insertion point, optimal angle (from the midsagital plane), maximum and minimum safe angles (from the same insertion points), length, and width. The OSIC are located within the vertebral bodies. Insertion points were situated at the level of the vertebro-costal joint or the base of the transverse process of the vertebral body for thoracic and lumbar vertebrae, respectively. The mean optimal angle of the OSIC was 90.2° with a maximum deviation angle from optimal angle of 10° dorsally and 8.8° ventrally in thoracic vertebrae, and 90.5° with a maximum deviation angle from the optimal angle of 8.4° dorsally and 7.6° ventrally in lumbar vertebrae. Corridors drilled in the vertebral body perpendicular to the midsagital plane (90°) or with a small angle (≤10°) of deviation from the optimal angle provide an optimal safe placement of bicortical implants. However, perpendicular implant placement may not always be feasible due to surrounding soft tissue structures.


Recovery after electrical injury.
A 14-month-old boy was seen following an accidental electrical injury received from a faulty domestic appliance. After initially showing marked clinical and electroencephalographic signs of cerebral damage, after one month there was a dramatic and continued improvement in both motor and sensory function. The importance of prolonged and optimistic resuscitation is stressed.


Fully automated mouse echocardiography analysis using deep convolutional neural networks.
Echocardiography (echo) is a translationally relevant ultrasound imaging modality widely used to assess cardiac structure and function in preclinical models of heart failure (HF) during research and drug development. Although echo is a very valuable tool, the image analysis is a time-consuming, resource-demanding process, and is susceptible to interreader variability. Recent advancements in deep learning have enabled researchers to automate image processing and reduce analysis time and interreader variability in the field of medical imaging. In the present study, we developed a fully automated tool, mouse-echocardiography neural net (MENN), for the analysis of both long-axis brightness (B)-mode and short-axis motion (M)-mode images of left ventricle. MENN is a series of fully convolutional neural networks that were trained and validated using manually segmented B-mode and M-mode echo images of the left ventricle. The segmented images were then used to compute cardiac structural and functional metrics. The performance of MENN was further validated in two preclinical models of HF. MENN achieved excellent correlations (Pearson's r = 0.85-0.99) and good-to-excellent agreement between automated and manual analyses. Further interreader variability analysis showed that MENN has better agreements with an expert analyst than both a trained analyst and a novice. Notably, the use of MENN reduced manual analysis time by >92%. In conclusion, we developed an automated echocardiography analysis tool that allows for fast and accurate analysis of B-mode and M-mode mouse echo data and mitigates the issue of interreader variability in manual analysis.NEW & NOTEWORTHY Echocardiography is commonly used in preclinical research to evaluate cardiac structure and function. Despite the broad applications across therapeutic areas, the analysis of echo data is laborious and susceptible to interreader variability. In this study, we developed a fully automated mouse-echocardiography neural net (MENN). Cardiac measurements from MENN showed excellent correlations with manual analysis. Furthermore, the use of MENN leads to >92% reduction in analysis time and potentially eliminates the interobserver variability issue.


Implanting two posterior chamber intraocular lenses in a case of microphthalmos.
A 31-year-old male with bilateral microphthalmos and a history of severe refractive amblyopia presented with early nuclear sclerosis. Intraocular lens calculations determined the patient would need about a 46.0 diopter power intraocular lens in both eyes to achieve satisfactory vision postoperatively. When no manufacturer could or was willing to make such a high-power lens, we chose to implant two lenses in each eye. The patient is satisfied with his postoperative vision and overall outcome.


An animal health example of managing and analyzing a large volume of data on a PC: Modeling body weight and age of over 13 million cats for explanatory and predictive purposes.
Large amounts of animal health data are available to researchers, but are often stored in different formats and information silos. Analysis of this existing information can provide new insights into the health and welfare of animals and possibly reduce the need to collect additional data. The objective of this study was to develop a method of managing and analyzing large amounts of data on a personal computer that can be run within 24 h to limit the time and resources spent deploying models on larger servers. This paper describes an overall approach that makes use of existing methods for data acquisition and modeling, but adapts and combines them in a way that allows manipulation and analysis of large volumes of data on a PC. This included a total of five steps: removing errors; removing data points outside the scope of a specific hypothesis; creating descriptive statistics; developing explanatory and/or predictive models; and assessing the fit or accuracy of the models created. The approach was developed using electronic medical records for 19,416,753 feline patients from 3972 anonymized veterinary clinics in the United States and Canada, recorded between January 1981 and June 2016. Data regarding patient signalment (age, sex, breed, reproductive status) and body weight were extracted from the records and used to create linear regression models to describe body weight in cats of different ages, breeds, genders and reproductive status. Ordinary least squares linear regression and stochastic gradient descent linear regression were compared to determine their effectiveness and suitability for creating predictive models with large datasets, using 10 fold cross validation. This approach could be used to build workflows to create models to determine exploratory and predictive properties of health parameters for animals and people. The ability to work with large datasets on a PC or equivalent technology was demonstrated. Significant interactions were present among sex, reproductive status and age. A peak in weight occurred between 6 and 9 years depending on the sex, reproductive status and breed. The predictive ability of the two models was similar, with both producing a root mean square error of 1.45 and a mean absolute error of 1.09, and mean error that was approximately zero on the validation dataset.


Malignant lesions in the anterior maxilla.
The anterior alveolar ridge of the maxilla is a frequent site for pathology, most of it involving underlying bone and readily observable radiologically. Although much of this disease presents as well-defined unilocular radiolucencies arising adjacent to the apices of non-vital anterior teeth, thus being periapical radiolucencies of inflammatory origin (PRIO), a minority reflects more serious disease such as neoplasia. The most serious of the latter are malignancies, most frequently squamous cell carcinomas (SCCs). Although the majority of SCCs arise from the oral or nasal mucosa and secondarily invade the underlying bone, a proportion arise from epithelial remnants of odontogenesis within the alveolus. These need to be readily distinguished from other more common benign lesions, and also non-Hodgkin lymphomas (NHL). The latter has been reported arising with the alveolus in addition to their more usual nodal and extranodal sites. The rarer malignancies that could arise within the anterior maxilla are addressed in the text with particular reference to the 2017 edition of the World Health Organisation Classification of Head and Neck Tumours.


Deep sequencing increases hepatitis C virus phylogenetic cluster detection compared to Sanger sequencing.
Effective surveillance and treatment strategies are required to control the hepatitis C virus (HCV) epidemic. Phylogenetic analyses are powerful tools for reconstructing the evolutionary history of viral outbreaks and identifying transmission clusters. These studies often rely on Sanger sequencing which typically generates a single consensus sequence for each infected individual. For rapidly mutating viruses such as HCV, consensus sequencing underestimates the complexity of the viral quasispecies population and could therefore generate different phylogenetic tree topologies. Although deep sequencing provides a more detailed quasispecies characterization, in-depth phylogenetic analyses are challenging due to dataset complexity and computational limitations. Here, we apply deep sequencing to a characterized population to assess its ability to identify phylogenetic clusters compared with consensus Sanger sequencing. For deep sequencing, a sample specific threshold determined by the 50th percentile of the patristic distance distribution for all variants within each individual was used to identify clusters. Among seven patristic distance thresholds tested for the Sanger sequence phylogeny ranging from 0.005-0.06, a threshold of 0.03 was found to provide the maximum balance between positive agreement (samples in a cluster) and negative agreement (samples not in a cluster) relative to the deep sequencing dataset. From 77 HCV seroconverters, 10 individuals were identified in phylogenetic clusters using both methods. Deep sequencing analysis identified an additional 4 individuals and excluded 8 other individuals relative to Sanger sequencing. The application of this deep sequencing approach could be a more effective tool to understand onward HCV transmission dynamics compared with Sanger sequencing, since the incorporation of minority sequence variants improves the discrimination of phylogenetically linked clusters.


Transabdominal sonographic appearance of adult colonic polyps.
To assess the ability of transabdominal ultrasound to detect adult colonic polyps and to describe their ultrasonographic appearance. Total colonoscopy was carried out for 729 consecutive patients over a 39-month period. Ultrasonographic examination of the abdomen was followed by specific examination of the colon. Colorectal ultrasound was carried out for patients with colonic polyps of the protruded type (exclusive of advanced cancers and polyps of the flat or depressed types), and cleansing liquid was administered preparatory to colonoscopic examination. In examining colonic polyps we wanted to determine the sensitivity and specificity of ultrasound for detecting colonic polyps, and the presence of power-Doppler flow signals, location, morphologic classification, and size of the polyps. Ultrasound identified no colonic polyps less than 10 mm in diameter in any of the 729 patients. Of the 732 deternimation (three patients had two polyps greater than 10 mm in diameter), ultrasound yielded a positive diagnosis in 16 cases, false-positive in four cases, false-negative in 40 cases, and negative in 672 cases. Sensitivity of the technique was 28.6% and specificity was 99.4% for detection of polyps greater than 10 mm in diameter. Doppler signals were detected in all positive cases. Most polyps that were false-negatives on ultrasound examination occurred in the rectum and sigmoid colon. Sensitivity increased with tumor size, and was as high as 82% (9/11) for polyps exceeding 25 mm in diameter. Fifty-seven percent of pedunculated polyps (type Ip) but no sessile polyps (type Is) were found using ultrasound. Colorectal ultrasound detected adult colonic polyps greater than 10 mm in diameter 16 of the 56 in present 729 patients, suggesting that this method may be of limited value in screening for colonic polyps.


Speed dependent descending control of freezing behavior in Drosophila melanogaster.
The most fundamental choice an animal has to make when it detects a threat is whether to freeze, reducing its chances of being noticed, or to flee to safety. Here we show that Drosophila melanogaster exposed to looming stimuli in a confined arena either freeze or flee. The probability of freezing versus fleeing is modulated by the fly's walking speed at the time of threat, demonstrating that freeze/flee decisions depend on behavioral state. We describe a pair of descending neurons crucially implicated in freezing. Genetic silencing of DNp09 descending neurons disrupts freezing yet does not prevent fleeing. Optogenetic activation of both DNp09 neurons induces running and freezing in a state-dependent manner. Our findings establish walking speed as a key factor in defensive response choices and reveal a pair of descending neurons as a critical component in the circuitry mediating selection and execution of freezing or fleeing behaviors.


How a time machine concept aids dementia care.
People with Alzheimer's disease may be able to recall events from their past clearly yet unable to remember events from minutes or hours ago. They often hold outdated beliefs about themselves, which can trigger challenging behaviour. This article explains how the simple analogy of the "time machine" can help staff in all settings to understand belief systems in dementia.


Rapid automated assay of anti-oxidation/radical-scavenging activity of natural substances by sequential injection technique (SIA) using spectrophotometric detection.
A PC-controlled sequential injection analysis (SIA) system equipped with a spectrophotometric diode-array detector is used for rapid monitoring and evaluation of antioxidation/radical scavenging activity of biological samples. The automated method is based on the known reaction of stable 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) with antioxidants in organic or aqueous-organic media resulting in bleaching of DPPH due to its "quenching" by the interaction with the analytes. The decrease of the absorbance of DPPH (compared to blank experiment carried out with water-ethanol 1:1 instead of the test solution) measured at 525 nm is related to concentration of an antioxidant in the test solution. With the optimised SIA procedure it is possible to detect down to micromolar concentrations of model antioxidants such as ascorbic acid, caffeic acid, (+)-catechin, (-)-epicatechin and rutin and to evaluate the concentration of these antioxidants in the micromolar to millimolar range. The sample throughput is 45 h(-1). Thanks to its rapidity and sensitivity, the proposed SIA method is suitable for performing routine screening tests for the presence of various antioxidants in large series of lyophilised herbal or mushroom extracts (the amount of sample needed for the analysis is several milligrams).


Transcriptional responses of Daphnia magna exposed to Akaki river water.
Pollution of the aquatic environment is a global problem, with industrial waste, farming effluents, sewage, and wastewater as the main contributors. Many pollutants are biologically active at low concentrations, resulting in sublethal effects, which makes it a highly complex situation and difficult to assess. In many places, such as the Akaki river in Ethiopia, the pollution situation has resulted in streams with minimal presence of invertebrates or vertebrates. As it is difficult to perform a complete chemical analysis of the waters, the present study focused on using gene expression analysis as a biological end point to determine the effects of Akaki river contaminants. The present study was conducted using the small planktonic crustacean Daphnia magna with toxicogenomic molecular markers. Daphnia magna neonates were exposed to Akaki water samples collected from two different sites on the river and analyzed for mortality and expression of genes involved in different biological pathways. Despite the poor quality of Akaki river water, 48 h acute toxicity tests showed no mortality. Interestingly, analysis of sublethal toxicogenomic responses showed that exposure to Akaki water altered the expression of 25 out of 37 genes involved in metal regulation, immune response, oxidative stress, respiration, reproduction, and development. The toxicogenomic data gives insight into the mechanisms involved in causing potential adverse effects to aquatic biota harboring the Akaki river system.


Application of PCR-TTGE and PCR-RFLP for intraspecific and interspecific characterization of the genus Saccharomyces using actin gene (ACT1) primers.
In this work the actin gene was used to establish phylogenetic relationships of wider and more diffuse species of the genus Saccharomyces in food ecology by temporal temperature gradient electrophoresis (TTGE) and amplified restriction fragment length polymorphism (RFLP) analysis. Results for DNA RFLP analysis varied considerably, and some enzymes showed a high intra- and interspecific power; however, comparison of experimental results with those provided by the National Center for Biotechnology Information database disclosed a number of interesting variations. Only some experimental results matched the theoretical ones. A theoretical study of melting temperatures using available information from partial sequences of the actin gene was done. Several Saccharomyces species and strains could be distinguished using different TTGE melting points. Some degree of discrimination was achieved under different conditions, in that the Saccharomyces strains tested were separated into groups like the results obtained by PCR-RFLP.


Automated differentiation of glioblastomas from intracranial metastases using 3T MR spectroscopic and perfusion data.
Differentiation of glioblastomas from metastases is clinical important, but may be difficult even for expert observers. To investigate the contribution of machine learning algorithms in the differentiation of glioblastomas multiforme (GB) from metastases, we developed and tested a pattern recognition system based on 3T magnetic resonance (MR) data. Single and multi-voxel proton magnetic resonance spectroscopy (1H-MRS) and dynamic susceptibility contrast (DSC) MRI scans were performed on 49 patients with solitary brain tumors (35 glioblastoma multiforme and 14 metastases). Metabolic (NAA/Cr, Cho/Cr, (Lip [Formula: see text] Lac)/Cr) and perfusion (rCBV) parameters were measured in both intratumoral and peritumoral regions. The statistical significance of these parameters was evaluated. For the classification procedure, three datasets were created to find the optimum combination of parameters that provides maximum differentiation. Three machine learning methods were utilized: Naïve-Bayes, Support Vector Machine (SVM) and [Formula: see text]-nearest neighbor (KNN). The discrimination ability of each classifier was evaluated with quantitative performance metrics. Glioblastoma and metastases were differentiable only in the peritumoral region of these lesions ([Formula: see text]). SVM achieved the highest overall performance (accuracy 98%) for both the intratumoral and peritumoral areas. Naïve-Bayes and KNN presented greater variations in performance. The proper selection of datasets plays a very significant role as they are closely correlated to the underlying pathophysiology. The application of pattern recognition techniques using 3T MR-based perfusion and metabolic features may provide incremental diagnostic value in the differentiation of common intraaxial brain tumors, such as glioblastoma versus metastasis.


Increased elongated and stabilized microtubules in psoriatic keratinocytes.
Microtubules (MT) occur in the keratinocytes as 20 nm broad tubular structures with an electron-lucent core surrounded by an electron-dense wall. The number and the length of the MT increased to the upper epidermal layers. In the normal keratinocytes the MT were relatively short (maximal length 2.2 microns) and slightly tortuous. Their outline was tenuous and irregular. Sometimes the MT were interrupted indicating a high fragility. In the upper layers of the psoriatic epidermis the MT reached a maximal length of 3.1 microns, showing a greater elongation than in the normal epidermis. The MT were stright and distinctly limited, most likely resulting from a higher grade of stabilization or polymerisation. By their interaction with the tonofilaments the MT may contribute to the stability of the cell shape, delaying the flattening of the psoriatic keratinocytes in the upper epidermal layers. Nowhere did the MT make direct contact with the cell membrane. At some places they did gain access to the cell membrane by short microfilaments.


Cocaine use disorder: A look at metabotropic glutamate receptors and glutamate transporters.
Glutamate transmission is an important mediator of the development of substance use disorders, particularly with regard to relapse. The present review summarizes the changes in glutamate levels in the reward system (the prefrontal cortex, nucleus accumbens, dorsal striatum, hippocampus, and ventral tegmental area) observed in preclinical studies at different stages of cocaine exposure and withdrawal as well as after reinstatement of cocaine-seeking behavior. We also summarize changes in the glutamate transporters xCT and GLT-1 and metabotropic glutamate receptors mGlu2/3, mGlu1, and mGlu5 based on preclinical and clinical studies with an emphasis on their role in cocaine-seeking. Glutamate transporters, such as GLT-1 and xc-, play a key role in maintaining glutamate homeostasis. In preclinical models, agents reversing cocaine-induced decreases in GLT-1 and xc- in the nucleus accumbens attenuate relapse. Very recent studies indicate that other mechanisms of action, such as reversing the mGlu2 receptor downregulation, contribute to these compounds' anti-relapse efficacy. In preclinical models, antagonism of mGlu5 receptors and stimulation of mGlu2/3 autoreceptors decrease relapse. Therefore, analysis of the above glutamatergic adaptations seems to be crucial because, so far, there are no prognostic biomarkers that can forecast relapse vulnerability in clinical practice, which would be helpful in alleviating or suppressing this phenomenon. Moreover, these receptor sites can be molecular targets for the development of effective medication for cocaine use disorder.


Dentin demineralization when subjected to BioPure MTAD: a longitudinal and quantitative assessment.
In the present study, the demineralizing ability of BioPure MTAD (Dentsply/Tulsa, Tulsa, OK), 17% EDTA, and 5% citric acid on radicular dentin was quantitatively and longitudinally analyzed. 3 mm thick disks were obtained at the root cervical third from 9 maxillary human molars, and a standardized smear layer was produced. Cosite images of the dentin surface were obtained after several cumulative demineralization times. Sixteen images were obtained in each dentin sample for each experimental time, at 1000x magnification. An image processing and analysis sequence measured sets of images, providing data of area fraction for thousands of tubules over time. Thus, it was possible to follow the demineralization phenomenon and quantitatively analyze the effect of the various substances. The nonparametric Kruskal-Wallis H-test was used to analyze the data. Based on the present results, it can be concluded that the demineralization kinetics promoted by both 5% CA and BioPure MTAD was significantly faster than by 17% EDTA.


Direct anterior approach versus direct lateral approach in total hip arthroplasty and bipolar hemiarthroplasty for femoral neck fractures: a retrospective comparative study.
In the current literature, there is no consensus on the best surgical approach in hip replacement for femoral neck fractures (FNFs). The aim of this study is to compare the direct anterior approach (DAA) and the direct lateral approach (DLA) in patients treated with bipolar hemiarthroplasty (BHA) and total hip arthroplasty (THA) for FNFs. Patients with displaced FNFs (Garden type III and IV) treated operatively using BHA and THA were enrolled. The surgical approach techniques DAA and DLA are compared. The analysed variables are: mean surgery time, number of blood units transfused perioperatively, percentage of patients transfused, perioperative complications, pain and functional outcomes at 1 and 6 months and mortality at 1, 3 and 12 months. Between 2015 and 2017, 37 patients underwent BHA by the DAA and 38 patients underwent BHA by the DLA, 69 patients underwent THA by the DAA and 60 patients underwent THA by the DLA. For THA, the DAA compared to the DLA had a higher mean surgery time (100.8 min vs. 97.7 min), a lower mean number of blood units transfused perioperatively (1.4 U vs. 1.9 U), a significantly lower percentage of patients transfused (53.6% vs. 71.7%), a higher rate of perioperative complications (10.1% vs. 1.6%), a lower pain referred and better functional outcomes in the first 6 postoperative months and a significantly lower mortality rate at 12 months (2.9% vs. 16.7%). For BHA, the advantages of the DAA over DLA are not as significant. The direct anterior approach in THA for FNFs provides significant benefits in the early post-operative period compared to the direct lateral approach in terms of functional recovery, residual pain, blood loss and mortality rate in the elderly active population. Level IV, retrospective cohort study.


Degenerative lumbar spondylolisthesis: review of current classifications and proposal of a novel classification system.
To review existing classification systems for degenerative spondylolisthesis (DS), propose a novel classification designed to better address clinically relevant radiographic and clinical features of disease, and determine the inter- and intraobserver reliability of this new system for classifying DS. The proposed classification system includes four components: 1) segmental dynamic instability, 2) location of spinal stenosis, 3) sagittal alignment, and 4) primary clinical presentation. To establish the reliability of this system, 12 observers graded 10 premarked test cases twice each. Kappa values were calculated to assess the inter- and intraobserver reliability for each of the four components separately. Interobserver reliability for dynamic instability, location of stenosis, sagittal alignment, and clinical presentation was 0.94, 0.80, 0.87, and 1.00, respectively. Intraobserver reliability for dynamic instability, location of stenosis, sagittal alignment, and clinical presentation were 0.91, 0.88, 0.87, and 0.97, respectively. The UCSF DS classification system provides a novel framework for assessing DS based on radiographic and clinical parameters with established implications for surgical treatment. The almost perfect interobserver and intraobserver reliability observed for all components of this system demonstrates that it is simple and easy to use. In clinical practice, this classification may allow subclassification of similar patients into groups that may benefit from distinct treatment strategies, leading to the development of algorithms to help guide selection of an optimal surgical approach. Future work will focus on the clinical validation of this system, with the goal of providing for more evidence-based, standardized approaches to treatment and improved outcomes for patients with DS.


Prediction of individual subject's age across the human lifespan using diffusion tensor imaging: a machine learning approach.
Diffusion tensor imaging has the potential to be used as a neuroimaging marker of natural ageing and assist in elucidating trajectories of cerebral maturation and ageing. In this study, we applied a multivariate technique relevance vector regression (RVR) to predict individual subject's age using whole brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) from a cohort of 188 subjects aged 4-85 years. High prediction accuracy as derived from Pearson correlation coefficient of actual versus predicted age (FA - r=0.870 p<0.0001; MD - r=0.896 p<0.0001; AD - r=0.895 p<0.0001; RD - r=0.899 p<0.0001) was achieved. Cerebral white-matter regions that contributed to these predictions include; corpus callosum, cingulum bundles, posterior longitudinal fasciculus and the cerebral peduncle. A post-hoc analysis of these regions showed that FA follows a nonlinear rational-quadratic trajectory across the lifespan peaking at approximately 21.8 years. The MD, RD and AD volumes were particularly useful for making predictions using grey matter cerebral regions. These results suggest that diffusion tensor imaging measurements can reliably predict individual subject's age and demonstrate that FA cerebral maturation and ageing patterns follow a non-linear trajectory with a noteworthy peaking age. These data will contribute to the understanding of neurobiology of cerebral maturation and ageing. Most notably, from a neuropsychiatric perspective our results may allow differentiation of cerebral changes that may occur due to natural maturation and ageing, and those due to developmental or neuropsychiatric disorders.


Comparison of the effects of continuous subcutaneous infusion and split-mixed injection of insulin on nerve function in type I diabetes mellitus.
Comparable groups of type I diabetic patients (n = 19) were matched for age, duration of diabetes, mean HbA1 values, insulin requirements, degree of neuropathy, and the mean of nerve conduction velocities (CV) in median, ulnar, and peroneal motor and median, ulnar, and sural sensory nerves. One group (n = 9) was managed with continuous subcutaneous infusion of (regular) insulin (CSII); the other (n = 10) with split-mixed injections of (intermediate and regular) insulin (SMII). After 12 months, glucose regulation was equally and significantly improved in both groups (P less than 0.005), although it was not sufficiently intense to normalize mean total glycosylated hemoglobin values in either group. Furthermore treatment produced no difference between groups in the values for mean amplitude of glycemic excursions, 12 month average of consecutive M-values or in clinical evaluation. However, in the CSII group, mean CV had increased 6.4% (2.75 + 0.56 m/s; mean +/- SEM) versus 1.3% (0.57 +/- 0.54 m/s) in the SMII group (P less than 0.005). Multivariate analysis on a nerve-by-nerve basis found significantly improved conduction in 2/6 nerves (median motor; ulnar sensory) in the CSII group compared to the SMII group. These results suggest that CSII may provide a more favorable microenvironment for nerve repair.


Critical behavior at a dynamic vortex insulator-to-metal transition.
An array of superconducting islands placed on a normal metal film offers a tunable realization of nanopatterned superconductivity. This system enables investigation of the nature of competing vortex states and phase transitions between them. A square array creates the eggcrate potential in which magnetic field-induced vortices are frozen into a vortex insulator. We observed a vortex insulator-vortex metal transition driven by the applied electric current and determined critical exponents that coincided with those for thermodynamic liquid-gas transition. Our findings offer a comprehensive description of dynamic critical behavior and establish a deep connection between equilibrium and nonequilibrium phase transitions.


Response of irrigated groundnuts (Arachis hypogaea L.) to urea fertilization in the central rainlands of the Sudan.
The response of 3 varieties of groundnuts, i.e.: Ashford (A), Barberton (B), and Corinte (C), to different doses of urea nitrogen under irrigation was studied for three years. As a result of extensive tissue analysis, the critical needs of Barberton and Corinte for nitrogen were found to be 1500 ppm NO3-N and 3.7% total-N. Variety Ashford, which outyielded both, did not respond to urea nitrogen. A linear correlation coefficient of r = 0.85 for pod and straw yields gave a pod to straw ratio of 0.72. Kernel protein and oil content were not affected by nitrogen. Larger nodule counts and their total-N indicated better yields.


Drag force as a function of cross section and angle of attack. A hydraulic laboratory dataset for numerical validation.
This data relates to a set of hydraulic laboratory experiments in which the flow around four cross-sections was investigated. Each cross section was examined at four angles of attack (0, 5, 10, 90°), seven velocities (0-0.7 m/s in 0.1 m/s steps) and two flow directions. The data is primarily from an array of load cell which monitored the loading on the cross-sections during testing in six degrees of freedom during testing. Video and photographs are also included.


Secular increase and geographical differences in hip fracture incidence in Norway.
In 1988 and 1989, 2790 hip fractures were reported from the urban population of Oslo (annual incidence per 10,000 in the age group 50 years and older: women 118.7, men 45.4). For the same period, 385 fractures were reported from the rural population of the county Sogn og Fjordane (annual incidence per 10,000 in the age-group 50 years and older: women 74.6, men 36.7). The hip fracture incidence in Oslo had increased for all sex and age groups above 50 years (except women 50-59 years) in the 10-year period 1978/79 to 1988/89. The incidence of hip fractures in Sogn og Fjordane was only 65% of the incidence in Oslo. These results support previous reports on a secular increase and geographical differences in hip fracture incidence.


Mulberroside A ameliorates CCl4-induced liver fibrosis in mice via inhibiting pro-inflammatory response.
Liver fibrosis is caused by a variety of pathogenic factors. It is mainly characterized by chronic liver damage mediated by the imbalance between extracellular matrix synthesis and degradation. If the injury factor cannot be removed for a long time, fibrosis will progress to cirrhosis or even cancer. The development of liver fibrosis is a very complex process which is related to the activation of hepatic stellate cells (HSCs), oxidative stress, and cytokines produced by immune cells. At present, screening of substances with anti-inflammatory activity from natural plant extracts has become a new research focus in the prevention and treatment of liver fibrosis. Mulberry twig is a commonly used traditional Chinese medicine. Pharmacological studies have shown that mulberry twig has anti-inflammatory and antioxidant activities. Thus, it is likely that Mulberry twig contains active substances with liver protection functions. The present study aimed to explore the effect of Mulberroside A (MulA), the main active ingredient from Mulberry twig, on acute liver injury induced by CCl4 in mice. MulA treatment could significantly alleviate the CCl4-induced liver injury, as evidenced by histological analysis and Masson staining. However, we observed that MulA inhibited the expressions of collagen I and α-SMA in livers of CCl4-treated mice but did not directly inhibit the proliferation and activation of HSCs. Finally, we analyzed the anti-inflammatory effect of MulA and demonstrated that it could markedly inhibit the pro-inflammatory cytokines release in liver tissues and in cultured macrophages, thereby alleviating liver fibrosis. Our findings suggest MulA as a potential therapeutic candidate for liver injury and inflammatory diseases.


Local stability identification and the role of a key aromatic amino acid residue in staphylococcal nuclease refolding.
Staphylococcal nuclease (SNase) is a model protein that contains one domain and no disulfide bonds. Its stability in the native state may be maintained mainly by key amino acids. In this study, two point-mutated proteins each with a single base substitution [alanine for tryptophan (W140A) and alanine for lysine (K133A)] and two truncated fragment proteins (positions 1-139 [SNase(1-139) or W140O] and positions 1-141 [SNase(1-141) or E142O]) were generated. Differential scanning microcalorimetry in thermal denaturation experiments showed that K133A and E142O have nearly unchanged DeltaH(cal) relative to the wild-type, whereas W140A and W140O display zero enthalpy change (DeltaH(cal) approximately 0). Far-UV CD measurements indicate secondary structure in W140A but not W140O, and near-UV CD measurements indicate no tertiary structure in either W140 mutant. These observations indicate an unusually large contribution of W140 to the stability and structural integrity of SNase.


Structural characterization of T-protein of the Escherichia coli glycine cleavage system by X-ray small angle scattering.
T-protein, one of the components of the glycine cleavage complex, catalyses the formation of ammonia and methylene-tetrahydrofolate from H-protein-bound intermediate. Native T-protein of the glycine cleavage system from E. coli was efficiently purified using a combination of hydrophobic interaction, gel permeation and ion exchange chromatography. Synchrotron radiation small angle X-ray solution scattering indicates that T-protein has an extended structure in solution. A low resolution model of the protein was constructed ab initio and tentative models of the tertiary structure were built using prediction methods constrained by the scattering data.


Matrix-specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells.
Interstitial collagen I stimulates microvascular endothelial cells to form solid cords that imitate precapillary structures found during angiogenesis. Time-lapse microscopy identified cell retraction and disruption of cell-cell contacts as early critical steps in collagen I-induced capillary morphogenesis. These early stages paralleled collagen I activation of Src kinase and GTPase Rho through beta1 integrins. The Src inhibitor PP2, dominant-negative Src, and Rho inhibitor exoenzyme C3 transferase each inhibited collagen I induction of actin stress fibers that mediate cell retraction and each inhibited capillary morphogenesis. Collagen I also disrupted VE-cadherin from intercellular junctions through a Src-dependent mechanism; both the Src inhibitor PP2 and dominant-negative Src preserved VE-cadherin localization to regions of cell-cell contact. An active Src mutant disrupted VE-cadherin and cell-cell contacts similarly to collagen I. In sharp contrast, laminin-1 did not induce capillary morphogenesis, and laminin-1 did not induce activation of Src or Rho. Rather, laminin-1 induced persistent activation of the GTPase Rac. Thus, these studies identify activation of Src and Rho as key mechanisms by which collagen I provokes capillary morphogenesis of microvascular endothelial cells, and they define marked differences between the functions of collagen I and laminin-1 in regulating endothelial cell morphogenesis.


Pre-exposure prophylaxis (PrEP) uptake and service delivery adaptations during the first wave of the COVID-19 pandemic in 21 PEPFAR-funded countries.
Mitigation measures for the first wave of the COVID-19 pandemic and burden on health systems created challenges for pre-exposure prophylaxis (PrEP) service delivery. We examined PrEP uptake in PEPFAR programs before and after the start of the COVID-19 pandemic. We studied two PEPFAR program monitoring indicators, using routine Monitoring, Evaluation, Reporting (MER) indicators capturing uptake of PrEP (PrEP_NEW) and overall use of PrEP (PrEP_CURR). We also analyzed descriptive program narratives to understand successes and challenges field teams encountered after the start of the COVID-19 pandemic. To assess changes in coverage of PrEP across 21 countries, we calculated the "PrEP to need ratio" (PnR) using a published methodology. We defined the pre-COVID time period as April 1, 2019 -March 31, 2020 and the COVID time period as April 1, 2020 -March 31, 2021. The total number of persons who initiated PrEP increased by 157% from 233,250 in the pre-COVID-19 period compared with 599,935 in the COVID-19 period. All countries, except five, noted significant increases in PrEP uptake. PrEP uptake among adolescent girls and young women (AGYW) increased by 159% from 80,452 AGYW in the pre-COVID-19 period to 208,607 AGYW in the COVID-19 period. There were 77,430 key populations (KP) initiated on PrEP in the pre-COVID-19 period and 209,114 KP initiated in the COVID-19 period (a 170% increase). The PnR increased 214% in the COVID-19 period across all PEPFAR-supported countries. Adaptations, such as multi-month dispensing (MMD) of PrEP; virtual demand creation activities; decentralized, community-based and virtual service delivery, were implemented to maintain PrEP services. PEPFAR programs continued to maintain and initiate new clients on PrEP despite the challenges posed by the COVID-19 pandemic. Adaptations such as MMD of PrEP and use of technology were vital in expanding service delivery and increasing PrEP coverage. This project has been supported by the U.S. President's Emergency Plan for AIDS Relief.


The use of high-affinity polyhistidine binders as masking probes for the selection of an NDM-1 specific aptamer.
The emergence of carbapenemase-producing multi-drug resistant Enterobacteriaceae poses a dramatic, world-wide health risk. Limited treatment options and a lack of easy-to-use methods for the detection of infections with multi-drug resistant bacteria leave the health-care system with a fast-growing challenge. Aptamers are single stranded DNA or RNA molecules that bind to their targets with high affinity and specificity and can therefore serve as outstanding detection probes. However, an effective aptamer selection process is often hampered by non-specific binding. When selections are carried out against recombinant proteins, purification tags (e.g. polyhistidine) serve as attractive side targets, which may impede protein target binding. In this study, aptamer selection was carried out against N-terminally hexa-histidine tagged New Delhi metallo-ß-lactamase 1. After 14 selection rounds binding to polyhistidine was detected rather than to New Delhi metallo-ß-lactamase 1. Hence, the selection strategy was changed. As one aptamer candidate showed remarkable binding affinity to polyhistidine, it was used as a masking probe and selection was restarted from selection round 10. Finally, after three consecutive selection rounds, an aptamer with specific binding properties to New Delhi metallo-ß-lactamase 1 was identified. This aptamer may serve as a much-needed detection probe for New Delhi metallo-ß-lactamase 1 expressing Enterobacteriaceae.


New photostable naphthalimide-based fluorescent probe for mitochondrial imaging and tracking.
Monitoring mitochondria morphological changes temporally and spatially exhibits significant importance for diagnosing, preventing and treating various diseases related to mitochondrial dysfunction. However, the application of commercially available mitochondria trackers is limited due to their poor photostability. To overcome these disadvantages, we designed and synthesized a mitochondria-localized fluorescent probe by conjugating 1,8-naphthalimide with triphenylphosphonium (i.e. NPA-TPP). The structure and characteristic of NPA-TPP was characterized by UV-vis, fluorescence spectroscopy, (1)HNMR, (13)CNMR, FTIR, MS, etc. The photostability and cell imaging were performed on the laser scanning confocal microscopy. Moreover, the cytotoxicity of NPA-TPP on cells was evaluated using (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results showed that NPA-TPP not only has high sensitivity and specificity to mitochondria, but also exhibits super-high photostability, negligible cytotoxicity and good water solubility. In short, NPA-TPP indicates great potential for targeting mitochondria and enables a real-time and long-term tracking mitochondrial dynamics changes.


Haeme-oxygenase 1 expression in rat pancreatic beta cells is stimulated by supraphysiological glucose concentrations and by cyclic AMP.
Increased expression of haeme-oxygenase 1 (HO1) and other antioxidant enzymes could improve pancreatic beta-cell survival under stressful conditions, including hyperglycaemia. However, how hyperglycaemia increases islet HO1 expression is not known. Rat islets were pre-cultured for 1 week in RPMI medium containing 10 mmol x l(-1) glucose (G10), and further cultured overnight in G5-G30 plus various test substances. Islet HO1 mRNA and protein expression was measured by semiquantitative RT-PCR, western blot, and immunohistochemistry. Islet HO1 mRNA expression was minimal after overnight culture in G10, slightly increased in G5, and increased by five- to ten-fold in G30 in parallel with a heterogeneous increase in beta-cell HO1 protein expression. The effect of G30 was fully inhibited by agents decreasing cytosolic Ca2+ (diazoxide, nimodipine), but was only slightly reproduced by agents raising Ca2+ (tolbutamide, 30 mmol x l(-1) potassium). It was also suppressed by the alpha2-adrenoceptor agonist clonidine, whereas dibutyryl-cyclic-AMP largely increased beta-cell HO1 expression. The induction of HO1 mRNA expression by G30 was independent from changes in medium insulin concentration, but was completely inhibited by a cocktail of antioxidants. In contrast to HO1, islet mRNA expression of glutathione peroxidase and constitutive haeme-oxygenase 2 were not affected by G30, nor by dibutyryl-cyclic-AMP. High glucose and dibutyryl-cyclic-AMP stimulate expression of HO1 in rat pancreatic beta cells. The inhibition of HO1 expression in G30 by nimodipine, clonidine, and antioxidants, suggests that Ca2+ influx and cyclic-AMP are necessary for the generation of oxidative stress by G30, or for the stimulation of beta-cell HO1 expression by increased oxidative stress.


Movement patterns of the C-stem femoral component: an RSA study of 33 primary total hip arthroplasties followed for two years.
We used roentgen stereophotogrammetric analysis to follow 33 C-stem femoral components for two years after primary total hip arthroplasty. All components migrated distally and posteriorly within the cement mantle. The mean distal migration was 1.35 mm (sd 0.62) at two years and the mean posterior migration was 1.35 mm (sd 0.69) at two years. All the femoral components rotated into retroversion with a mean rotation at two years of 1.9 degrees (sd 1.1). For all other directions, the prosthesis was stable up to two years. Compared with other tapered prostheses, the distal migration of the C-stem is the same, but posterior rotation and posterior migration are greater.


Decoding of speech information using EEG in children with dyslexia: Less accurate low-frequency representations of speech, not "Noisy" representations.
The amplitude envelope of speech carries crucial low-frequency acoustic information that assists linguistic decoding. The sensory-neural Temporal Sampling (TS) theory of developmental dyslexia proposes atypical encoding of speech envelope information < 10 Hz, leading to atypical phonological representations. Here a backward linear TRF model and story listening were employed to estimate the speech information encoded in the electroencephalogram in the canonical delta, theta and alpha bands by 9-year-old children with and without dyslexia. TRF decoding accuracy provided an estimate of how faithfully the children's brains encoded low-frequency envelope information. Between-group analyses showed that the children with dyslexia exhibited impaired reconstruction of speech information in the delta band. However, when the quality of speech encoding for each child was estimated using child-by-child decoding models, then the dyslexic children did not differ from controls. This suggests that children with dyslexia encode neither "noisy" nor "normal" representations of the speech signal, but different representations.


Sleep in herniorrhaphy patients.
The nocturnal sleep patterns of 10 elective herniorrhaphy patients were documented by continuous, 8 hour polygraphic recordings from night 1 of hospitalization until discharge on day 4 or 5. Subjects showed a dramatic loss of REM sleep and stages III and IV and major increases in time awake and drowsy for the first 2 postoperative nights, with a gradual return toward normal sleep over the hospitalization period. The significance for healing of the loss of stages REM, III, and IV is discussed, especially with regard to hospital procedures and the use of medications.


[Ischemic gangrene of the upper limb associated with COVID-19 infection: about 2 cases].
Clinical manifestations of COVID-19 have changed a lot, ranging from respiratory and Ear, Nose and Throat (ENT) symptoms to extra pulmonary thrombotic, neurological, cardiac and renal complications. We here report the case of two patients with SARS-CoV-2 pneumonia whose course was marked by prolonged upper limb ischemia. The association between venous, but also arterial, thrombotic complications and viral infection is now well established, and appears to be related to hypercoagulability.


Eutrophic waters, algal bloom and fish kill in fish farming areas in Bolinao, Pangasinan, Philippines.
The coastal waters of Bolinao, Pangasinan, Philippines experienced environmental changes over a 10-year period (1995-2005), the most significant effect of which was the major fish kill event in 2002 that coincided with the first reported Philippine bloom of a dinoflagellate Prorocentrum minimum. Days before the bloom, dissolved oxygen was < 2.0 mg/l in the waters that were stratified. These conditions may be linked to the uncontrolled proliferation of fish pens and cages to more than double the allowable limit of 544 units for Bolinao waters. Mariculture activities release organic matter from unconsumed feed and fecal material that accumulate in the water and sediments. In over 10 years, water quality conditions have become eutrophic with ammonia increasing by 56%, nitrite by 35%, nitrate by 90%, and phosphate by 67%. The addition of more fish pens and cages placed additional stress to this poorly flushed, shallow area that affected water quality due to changes in the water residence time.


Compensatory binding of an asparagine residue to the coordination-unsaturated type I Cu center in bilirubin oxidase mutants.
Met467, the axial ligand to type I Cu in a multicopper oxidase, Myrothecium verrucaria bilirubin oxidase was substituted with a non-coordinating Phe and Leu to transform the spectral and magnetic properties and oxidase activities of the enzyme into those of fungal laccases, but the mutated type I Cu center showed properties characteristic of phytocyanins, blue copper proteins with an axial coordination of Gln, due to compensatory binding of the distal Asn459 as evidenced by a double mutation.


Osteopetrosis: a case report including gross and microscopic findings in the mandible at autopsy.
A case of juvenile osteopetrosis in a 10-year-old girl, including the skeletal, hematologic, and neurologic features, is described. Ankylosis of cementum to bone was evident in histologic sections, providing a possible explanation for the delayed or impaired eruption of teeth. A summary of the literature on the pathogenesis of osteopetrosis is presented.


Satisfactory results of diaphragmatic plication for bilateral phrenic nerve paralysis.
Bilateral diaphragmatic plication was performed in a 44-year-old man who underwent complete resection of a thymoma infiltrating the right lung, bilateral brachiocephalic vein, pericardium, and bilateral phrenic nerves. The plication procedure allowed him to be weaned from the ventilator on postoperative day 4. He demonstrated no restrictive or obstructive pattern of lung function, and after respiratory rehabilitation he returned to work full time 5 weeks after the operation. The present results indicate that ventilatory movement of the thoracic cage can compensate for loss of bilateral diaphragmatic ventilation for at least 18 months.


Comparative effectiveness of budesonide/formoterol combination and tiotropium bromide among COPD patients new to these controller treatments.
Inhaled corticosteroid/long-acting β2-agonist combinations and/or long-acting muscarinic antagonists are recommended first-line therapies for preventing chronic obstructive pulmonary disease (COPD) exacerbation. Comparative effectiveness of budesonide/formoterol combination (BFC, an inhaled corticosteroid/long-acting β2-agonist combination) vs tiotropium (long-acting muscarinic antagonist) in the US has not yet been studied. Using US claims data from the HealthCore Integrated Research Environment, COPD patients (with or without comorbid asthma) ≥40 years old initiating BFC or tiotropium between March 1, 2009 and February 28, 2012 and at risk for exacerbation were identified and followed for 12 months. Patients were propensity score matched on demographics and COPD disease severity indicators. The primary outcome was time to first COPD exacerbation. Secondary outcomes included COPD exacerbation rate, health care resource utilization, and costs. The Cox proportional hazards model for time to first exacerbation yielded a hazard ratio (HR) of 0.78 (95% CI =[0.70, 0.87], P<0.001), indicating a 22% reduction in risk of COPD exacerbation associated with initiation of BFC versus tiotropium. A post hoc sensitivity analysis found similar effects in those who had a prior asthma diagnosis (HR =0.72 [0.61, 0.86]) and those who did not (HR =0.83 [0.72, 0.96]). BFC initiation was associated with lower COPD-related health care resource utilization and costs ($4,084 per patient-year compared with $5,656 for tiotropium patients, P<0.001). In COPD patients new to controller therapies, initiating treatment with BFC was associated with improvements in health and economic outcomes compared with tiotropium.


Suppression of phosphoenolpyruvate carboxykinase gene expression by reduced endogenous glutathione level.
Glutathione is a small tripeptide to maintain overall reducing environment in vivo. Reduced endogenous glutathione level has been associated with aging, obesity and diabetes. In this study, the direct impact of low endogenous glutathione level on energy homeostasis is investigated at molecular level. Depletion of endogenous glutathione in rat primary hepatocytes by BSO, an inhibitor of gamma-glutamylcysteine synthase, leads to reduced mRNA levels of several key enzymes in energy homeostasis, including phosphoenolpyruvate carboxylkinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. Supplementation of various reducing reagents, including N-acetylcysteine, DTT and glutathione, reverses the inhibitory effect of BSO on PEPCK mRNA level. The suppressive effect of BSO on PEPCK mRNA level is also reversed through co-treatment with either SB210290, a specific p38 kinase inhibitor, or wortmannin and LY294002, the well-established PI-3 kinase inhibitors, suggesting the involvement of these kinases in this process. These observations correlate well with the observations that reduced endogenous glutathione level and reduced gluconeogenesis coincide with aging process, implying a causal relationship between these changes in aged population. More importantly, this study suggests that endogenous glutathione level tightly associates with energy homeostasis at molecular level, identifying reduced endogenous glutathione level as a potential contributing factor to dysregulated metabolic processes in aging, obese and diabetic populations. In addition, the different responses of PEPCK expression to the alteration of endogenous glutathione level in rat hepatoma cells from primary hepatocytes raises caution against using established cell lines in examining the dysregulated metabolic process related to altered endogenous glutathione level.


A parallel colorimetric method for the rapid discovery and optimization of heterogeneous hydrodesulfurization catalysts.
A spectrophotometric based, parallel approach to screen heterogeneous catalysts for hydrodesulfurization has been developed. The method utilizes optical changes resulting from the hydrodesulfurization of 1,1'-binaphthothiophene to 1,1'-binaphthyl to determine catalyst activity. Hydrodesulfurization of 1,1'-binaphthothiophene to 1,1'-binaphthyl results in a loss of conjugation in the binaphthyl ring system. This results in a blue shift of more than 60 nm in the UV-vis spectrum. Since only small amounts of the HDS catalyst and 1,1'-binaphthothiophene are required, a large number of catalysts may be screened simultaneously. The synthesis of the 1,1'-binaphthothiophene and conditions for HDS catalyst screening are described.


Whole-Body MRI: Current Applications in Oncology.
The purpose of this article is to review current image acquisition and interpretation for whole-body MRI, clinical applications, and the emerging roles in oncologic imaging, especially in the assessment of bone marrow diseases. Whole-body MRI is an emerging technique used for early diagnosis, staging, and assessment of therapeutic response in oncology. The improved accessibility and advances in technology, including widely available sequences (Dixon and DWI), have accelerated its deployment and acceptance in clinical practice.


Risk factors for salvage surgery failure in oral cavity squamous cell carcinoma.
Locoregional recurrences of oral cavity squamous cell carcinoma (SCC) may be diagnosed during follow-up of surgically treated patients. Nevertheless, few studies have investigated factors that impact salvage surgery failure and the mortality rates of these patients. The objectives were to identify predictive factors of salvage surgery failure and mortality in patients who undergo surgical treatment for recurrent oral cavity SCC and to compare the overall survival rates of these patients with those of patients who undergo only one surgical treatment. Retrospective cohort study. Forty-six patients submitted to salvage surgery for local or locoregional recurrence. The presence of lymph node metastasis and positive surgical margins at the salvage surgery time were the only independent factors associated with both recurrence rates (hazard ratio [HR]: 5.04 and 2.82, respectively) and mortality (HR: 3.51 and 3.24, respectively). When the overall survival rates of the 199 patients who only underwent one surgical treatment were compared to those of the 46 patients subjected to salvage surgery, a similarity was evident when patients who underwent salvage surgery did not have a new disease recurrence (70.7% vs. 54.7%, respectively; P = .158). Likewise, patients with new recurrences after salvage surgery and patients who received palliative treatment for relapsed disease had similar overall survival rates (0.6% vs. 0.0%, respectively; P = .475). The presence of lymph node metastasis at the time of recurrence and positive surgical margins after the salvage surgery were associated with a worse overall survival rate in patients with oral cavity SCC relapse. 2b. Laryngoscope, 128:1113-1119, 2018.


Calcitonin gene-related peptide and neuropeptide Y in the raccoon cuneate nucleus.
Immunocytochemical methods were used to determine the distribution of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in the middle region of the adult raccoon cuneate nucleus. Extensive CGRP-immunoreactive fibers and darkly stained punctate structures, thought to be terminals, were concentrated in the dorsal cap and basal region of the middle cuneate nucleus. These regions receive input from the claws and the hairy skin of the paw and forearm. The NPY-immunoreactive fibers and terminals were also found within the dorsal cap of the cuneate nucleus, but were less abundant than CGRP. However, most of the NPY-immunostained fibers and terminals were found in the cluster region of the cuneate nucleus, which receives input from glabrous skin. No CGRP- or NPY-immunoreactive cell bodies were found in the raccoon middle cuneate nucleus. This description of the distribution of CGRP and NPY in the normal animal provides a baseline for future investigations into injury-induced neuropeptide plasticity in the raccoon middle cuneate nucleus.


Emergency arterio-venous loop for free-flap defect reconstruction of the lower thigh with a post-irradiated and heavily infected wound.
Although being a safe and standardised procedure, free-flap reconstruction can be harmful if unpredictable situations occur intraoperatively. The case presented reveals a situation in which an unscheduled interdisciplinary approach allowed to complete our reconstructive aim. An extensive defect at the thigh was planned for reconstruction by means of a free rectus abdominis flap. As the distant part of the flap showed a compromised perfusion during operation and had to be partially discarded, our colleagues from the vascular surgery department created an arterio-venous loop for anastomosis. This allowed a more distant positioning of the flap and ensured a complete defect reconstruction.


Utility of ultrasound for evaluating the appendix during the second and third trimester of pregnancy.
This study aims to retrospectively evaluate the right lower quadrant ultrasounds in women presenting during the second or third trimester of pregnancy for the frequency of appendix visualization and accuracy in diagnosing appendicitis. Institutional Review Board approval was obtained for this Health Insurance Portability and Accountability Act-compliant study. We reviewed imaging records from 99 consecutive pregnant women from 2001 to 2011 who presented during the second (≥14 weeks gestation) or third trimester for right lower quadrant ultrasound to evaluate the appendix. Visualization of the appendix as well as the size and compressibility, if identified, were recorded. The medical records and labs related to the initial patient presentation, subsequent management, and follow-up were reviewed for surgical and clinical outcomes. Pathology records were reviewed to determine if appendicitis was present when appendectomy was performed. Patients who underwent appendectomy were considered to have appendicitis based on pathology results, and patients managed non-operatively with symptom improvement and those with a normal appendix at pathology were considered to not have appendicitis. During the study period, 99 women meeting inclusion criteria presented to our institution for right lower quadrant ultrasound to evaluate the appendix during the second or third trimester of pregnancy. The mean gestational age at presentation was 23 weeks (±7 weeks). The mean maternal age was 28 years (±6.6 years). The appendix was not visualized in 97% (96/99) of right lower quadrant ultrasound examinations. Of the three studies in which the appendix was visualized, two were considered positive for appendicitis and one was considered negative. Eight patients in this group ultimately underwent appendectomy, including the two patients with positive right lower quadrant ultrasounds, and appendicitis confirmed at pathology in seven of these cases (87.5%). Right lower quadrant ultrasound successfully demonstrated an abnormal appendix in 28.7% (two of seven) of surgically confirmed cases; however, this technique did not detect appendicitis in 71% (five of seven) of patients with surgically proven disease due to nonvisualization of the appendix. Retrospective review of right lower quadrant ultrasounds performed during the second and third trimester of pregnancy suggests that this modality has limited utility for diagnosing appendicitis due to infrequent visualization of the appendix.


The impact of functional health literacy and acculturation on the oral health status of Somali refugees living in Massachusetts.
We assessed the impact of health literacy and acculturation on oral health status of Somali refugees in Massachusetts. Between December 2009 and June 2011, we surveyed 439 adult Somalis who had lived in the United States 10 years or less. Assessments included oral examinations with decayed, missing, and filled teeth (DMFT) counts and measurement of spoken English and health literacy. We tested associations with generalized linear regression models. Participants had means of 1.4 decayed, 2.8 missing, and 1.3 filled teeth. Among participants who had been in the United States 0 to 4 years, lower health literacy scores correlated with lower DMFT (rate ratio [RR] = 0.78; P = .016). Among participants who had been in the country 5 to 10 years, lower literacy scores correlated with higher DMFT (RR = 1.37; P = .012). Literacy was not significantly associated with decayed teeth. Lower literacy scores correlated marginally with lower risk of periodontal disease (odds ratio = 0.22; P = .047). Worsening oral health of Somali refugees over time may be linked to less access to preventive care and less utilization of beneficial oral hygiene practices.