Structural characterization of myotoxic ecarpholin S from Echis carinatus venom.
Phospholipase A(2) (PLA(2)), a common toxic component of snake venom, has been implicated in various pharmacological effects. Ecarpholin S, isolated from the venom of the snake Echis carinatus sochureki, is a phospholipase A(2) (PLA(2)) belonging to the Ser(49)-PLA(2) subgroup. It has been characterized as having low enzymatic but potent myotoxic activities. The crystal structures of native ecarpholin S and its complexes with lauric acid, and its inhibitor suramin, were elucidated. This is the first report of the structure of a member of the Ser(49)-PLA(2) subgroup. We also examined interactions of ecarpholin S with phosphatidylglycerol and lauric acid, using surface plasmon resonance, and of suramin with isothermal titration calorimetry. Most Ca(2+)-dependent PLA(2) enzymes have Asp in position 49, which plays a crucial role in Ca(2+) binding. The three-dimensional structure of ecarpholin S reveals a unique conformation of the Ca(2+)-binding loop that is not favorable for Ca(2+) coordination. Furthermore, the endogenously bound fatty acid (lauric acid) in the hydrophobic channel may also interrupt the catalytic cycle. These two observations may account for the low enzymatic activity of ecarpholin S, despite full retention of the catalytic machinery. These observations may also be applicable to other non-Asp(49)-PLA(2) enzymes. The interaction of suramin in its complex with ecarpholin S is quite different from that reported for the Lys(49)-PLA(2)/suramin complex(,) where the interfacial recognition face (i-face), C-terminal region, and N-terminal region of ecarpholin S play important roles. This study provides significant structural and functional insights into the myotoxic activity of ecarpholin S and, in general, of non-Asp(49)-PLA(2) enzymes.


Rapid development and rupture of a pneumatocele caused by pulmonary dissection in the early postoperative period of lung resection: a case report.
Air leakage after lung resection is a common complication usually caused by direct injury to the lung parenchyma. Herein we illustrate a case of pneumatocele that developed rapidly in the right middle lobe and ruptured 16 days after right upper lobectomy. A 73-year-old man with chronic obstructive pulmonary disease underwent thoracoscopic right upper lobectomy and partial thymectomy for primary lung cancer and thymic nodules, respectively. Although a small amount of air leakage was observed after the operation, air leakage completely improved on postoperative day (POD) 2, and the chest drain tube was removed on POD 3. The patient's condition was complicated with eosinophilic pneumonia. Steroid therapy was started on POD 13. Dyspnea suddenly developed immediately after defecation on POD 16. Computed tomography (CT) scan showed a large pneumatocele in the right middle lobe, which was not found by CT scan on POD 11. He underwent reoperation on POD 20, and a large thick-walled pneumatocele in the right middle lobe was directly sewn. Histopathologically, the wall of bulla consisted of thickened visceral pleura and thin lung parenchyma, suggesting that this pneumatocele was induced by dissection of subpleural lung parenchyma.


Phencyclidine is a negative allosteric modulator of signal transduction at two subclasses of excitatory amino acid receptors.
Phencyclidine (PCP) and some of its pharmacological congeners inhibit the signal transduction at specific excitatory amino acid receptors of cerebellar granule cells in primary cultures. These drugs do not bind to the transmitter recognition sites, and affinity of this specific binding site is increased by the presence of the transmitter bound to its recognition sites. PCP inhibits phosphatidylinositol phosphate hydrolysis mediated by Mg2+-sensitive glutamate receptors (GP1) but not that mediated by Mg2+-insensitive glutamate receptors (GP2). In addition, PCP inhibits Ca2+ influx and cGMP formation mediated by the activation of Mg2+-sensitive glutamate receptors (GC1) but not that mediated by Mg2+-insensitive glutamate receptors (GC2). In this cell culture the activation of phosphatidylinositol phosphate hydrolysis by muscarinic receptor agonists is not affected by PCP. Since PCP inhibits noncompetitively GP1 and GC1 signal transduction it may act as a negative allosteric modulator of signal transduction at both receptors. The pharmacological profile of PCP and its congeners delimits a class of drugs modulating allosterically the action of the primary transmitter at GP1 and GC1 receptors. These drugs need the presence of the transmitter to act and they cannot be termed inverse agonists because they are devoid of activity in the absence of the transmitter; moreover, they do not bind to the transmitter recognition site nor do they prevent the transmitter binding to its recognition sites.


Synthesis of a ring-oxygenated variant of the 2-carboxy-6-hydroxyoctahydroindole core of aeruginosin 298-A from glucose.
[reaction: see text] The design and synthesis of a new core structure, a ring-oxygenated variant of 2-carboxy-6-hydroxyoctahydroindole (Choi) from D-glucose, is reported. Choi, a rigid bicyclic unnatural amino acid, is the core structure of about 15 aeruginosins natural compounds. These compounds are thrombin, trypsin, and factor VIIa inhibitors and Choi is important for their biological activity. The ring-oxygenated variant of 2-carboxy-6-hydroxyoctahydroindole can potentially be used as a surrogate of Choi in the design and synthesis of aeruginosin-based thrombin inhibitors.


Metallophosphazene precursor routes to the solid-state deposition of metallic and dielectric microstructures and nanostructures on Si and SiO2.
We present a method for the preparation and deposition of metallic microstructures and nanostructures deposited on silicon and silica surfaces by pyrolysis in air at 800 degrees C of the corresponding metallophosphazene (cyclic or polymer). Atomic force microscopy studies reveal that the morphology is dependent on the polymeric or oligomeric nature of the phosphazene precursor, on the preparation method used, and on the silicon substrate surface (crystalline or amorphous) and its prior inductively couple plasma etching treatment. Microscale and nanoscale structures and high-surface-area thin films of gold, palladium, silver, and tin were successfully deposited from their respective newly synthesized precursors. The characteristic morphology of the deposited nanostructures resulted in varied roughness and increased surface area and was observed to be dependent on the precursor and the metal center. In contrast to island formation from noble metal precursors, we also report a coral of SnP(2)O(7) growth on Si and SiO(2) surfaces from the respective Sn polymer precursor, leaving a self-affine fractal structure with a well-defined roughness exponent that appears to be independent (within experimental error) of the average size of the islands. The nature of the precursor will be shown to influence the degree of surface features, and the mechanism of their formation is presented. The method reported here constitutes a new route to the deposition of single-crystal metallic, oxidic, and phosphate nanostructures and thin films on technologically relevant substrates.


Anomeric effect in N-azidomethylpyrrolidine: gas-phase electron diffraction and theoretical study.
Gas-phase electron-diffraction data and high-level quantum chemical calculations have been used to study the conformational behaviour of N-azidomethylpyrrolidine. The two most stable conformers with a relative abundance of about 80% at 298 K possess gauche orientation of the azidomethyl group around the C-N(pyr) bond (C-N(azido)gauche with respect to the endocyclic N(pyr)-C bond). This orientation is a strong manifestation of an anomeric effect. The influence of the anomeric effect is also reflected in shortening of the C-N(pyr) bond and lengthening of the C-N(azido) bond as compared to such bonds in other compounds.


Renal artery sympathetic nerve radiofrequency denervation.
Arterial hypertension is one of the most common chronic diseases in the western world, affecting more than 25% of the adult population. The aim of this study was to assess changes in arterial blood pressure (BP) levels in hypertensive patients, after ablation of nerve terminals in renal arteries, using radiofrequency energy during 24 months of follow-up. Thirty-two patients with diagnosed resistant hypertension (20 men and 12 women) underwent percutaneous catheter-based renal denervation of nerve terminals in renal artery walls. Mean BP value before ablation was [mm Hg]: systolic 174.92, diastolic 99.73 and pulse pressure 75.19. After procedure reduction value of BP was reported [mm Hg]: systolic 146.78; diastolic 87.14, pulse pressure 59.64 at 24-month follow-up (p < 0.05 for all). 30% of patients had systolic BP ≤ 140 mm Hg, 67% had diastolic BP ≤ 90 mm Hg, and optimum BP values ≤ 140/90 mm Hg were observed in 30% of patients. In our cohort of patients, percutaneous renal artery ablation procedure effectively reduces systolic, diastolic BP and pulse pressure. No adverse events during 24 months of follow-up were noted. These results were comparable with available data from SIMPLICITY I and II trials.


Surgical Treatment of an Invasive Thymoma with Intracaval and Intracardiac Extension.
A 53-year-old male with an invasive thymoma extending to the superior vena and right atrium, presenting as superior vena cava syndrome is herein reported. However invasive thymoma with this growth pattern is extremely rare. In this case, the tumor was successfully resected via median sternotomy with cardiopulmonary bypass. After 17 months of follow-up, the patient was still free from any signs and symptoms indicative of superior vena cava syndrome, but recurrent tumor in the right pleura was observed on the follow-up chest computed tomography.


A preliminary investigation into the psychometric properties of the Dublin Extrapersonal Neglect Assessment (DENA): A novel screening tool for extrapersonal neglect.
Extrapersonal neglect is one clinical manifestation that can occur following stroke. Existing neglect assessment procedures have been criticised for lengthy administration and do not assess how extrapersonal space is affected. This study investigated the psychometric properties of a new, time-efficient screening tool for extrapersonal neglect. Full ethical approval was granted and consent obtained from 50 participants with first-time stroke. Participants were screened for extrapersonal neglect on two consecutive days by two raters using the Dublin Extrapersonal Neglect Assessment (DENA) to test inter-rater reliability. Construct validity of the DENA was investigated by comparing the DENA to the Catherine Bergego Scale (CBS). Additional analyses were calculated between the DENA and the extrapersonal items of the CBS (CBS-E). The kappa statistic, intraclass correlation coefficients (ICCs) and Bland Altman analyses were calculated to determine excellent inter-rater reliability (ICC 0.971, κ = .876) and significant correlation between the DENA and the CBS and CBS-E (ICC 0.870, 0.934, κ = .793, .833, respectively). Bland Altman analyses demonstrated acceptable levels of agreement between the DENA raters, and the DENA and CBS, with no systematic differences evident. The DENA provides clinicians with a quick and psychometrically sound screening tool for extrapersonal neglect to ensure this impairment is addressed in stroke rehabilitation.


Ultrasensitive Biosensor for Detection of Mercury(II) Ions Based on DNA-Cu Nanoclusters and Exonuclease III-assisted Signal Amplification.
This paper describes a novel method for label-free mercury(II) ion detection based on exonuclease III-induced target signal recycling amplification using double-stranded DNA templated copper nanoclusters. The synthesized DNA-Cu nanoclusters were used with exonuclease III loop amplification technology for ultra-high sensitivity detection of mercury(II) ions, which were detected by significantly decreased fluorescence intensity. Under the optimal experimental conditions, there was a clear linear relationship between Hg2+ concentration in the range of 0.04 to 8 nM and fluorescence intensity. The detection limit for Hg2+ was 4 pM. In addition, the interference of other metal ions on the mercury(II) ion detection was also studied. To confirm the application of the fluorescent sensor, it was applied to determine the concentrations of mercury(II) ions in tap water, and the results showed that the method can be used to detect mercury(II) ions in water samples successfully.


Elevated Serum IGFBP-2 and CTGF Levels Are Associated with Disease Activity in Patients with Dermatomyositis.
Insulin-like growth factor-binding proteins (IGFBPs) and connective tissue growth factor (CTGF) participate in angiogenesis. Dermatomyositis (DM) is characterized by microvasculopathy-derived skin lesions. Here, we investigated the clinical significance of serum IGFBP and CTGF levels in DM patients. In this study, 65 DM patients and 30 healthy controls were enrolled. Serum IGFBP and CTGF levels were examined by ELISA, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation. Serum IGFBP-2, IGFBP-4, and CTGF levels were higher in DM patients than in healthy controls (median (quartile): 258.9 (176.4-326.1) ng/mL vs. 167.7 (116.1-209.4) ng/mL, p < 0.0001; 450.4 (327.3-631.8) ng/mL vs. 392.2 (339.0-480.2) ng/mL, p = 0.04; and 45.71 (38.54-57.45) ng/mL vs. 35.52 (30.23-41.52) ng/mL, p = 0.001, respectively). IGFBP-2 and CTGF levels were positively correlated with cutaneous (r = 0.257, p = 0.040 and r = 0.427, p = 0.015, respectively) and global (r = 0.380, p = 0.002 and r = 0.292, p = 0.019, respectively) disease activity in DM patients. Serum IGFBP-2 and CTGF levels were increased in patients with DM and correlated with cutaneous and global disease activity.


Hybrid single-mode laser based on graphene Bragg gratings on silicon.
We exploit distributed optoelectronic properties enabled by graphene Bragg gratings (GBGs) to realize a hybrid single-mode laser on silicon. This hybrid laser achieves single-mode, continuous-wave operation at 1540 nm with a remarkable side-mode suppression ratio of 48 dB, benefitting from the coupling of the GBGs. These results suggest that graphene thin films can be used as an essential and cost-saving component for hybrid photonic integration on silicon.


Sex ratio of human conceptuses.
The sex ratio in each developmental week was analyzed in 551 conceptuses from induced abortions for medical or social reasons in Southwest Finland. The ovulation age of the conceptuses varied from five to 24 weeks. There was a clear decrease in the sex ratios with increasing duration of pregnancy. The embryonic sex ratio was 164, the fetal ratio was 111, and the total ratio was 117. According to the regression analysis, the sex ratios at the ages of eight and 14 weeks were 119 and 105, respectively. The results suggest that higher mortality of male versus female conceptuses is restricted to the period of organogenesis. Seasonal or monthly variation in the sex ratio was not found in the present study.


Fibrin glue fixation of a digital osteochondral fracture: case report and review of the literature.
Surgical treatment options for digital osteochondral fractures are limited by the small amount of bone available for fixation and the propensity for digital stiffness with the introduction of hardware. Fibrin sealant is used in a variety of clinical settings as a biologic bonding agent and may circumvent the drawbacks of traditional fixation or simple excision for certain digital osteochondral injuries. Successful use of fibrin sealant fixation for a patient with an osteochondral fracture involving the proximal interphalangeal joint is documented, and the literature on fibrin sealant for osseous fixation is reviewed.


TORC1 inhibition induces lipid droplet replenishment in yeast.
Lipid droplets (LDs) are intracellular structures that regulate neutral lipid homeostasis. In mammals, LD synthesis is inhibited by rapamycin, a known inhibitor of the mTORC1 pathway. In Saccharomyces cerevisiae, LD dynamics are modulated by the growth phase; however, the regulatory pathways involved are unknown. Therefore, we decided to study the role of the TORC1 pathway on LD metabolism in S. cerevisiae. Interestingly, rapamycin treatment resulted in a fast LD replenishment and growth inhibition. The discovery that osmotic stress (1 M sorbitol) also induced LD synthesis but not growth inhibition suggested that the induction of LDs in yeast is not a secondary response to reduced growth. The induction of LDs by rapamycin was due to increased triacylglycerol but not sterol ester synthesis. Induction was dependent on the TOR downstream effectors, the PP2A-related phosphatase Sit4p and the regulatory protein Tap42p. The TORC1-controlled transcriptional activators Gln3p, Gat1p, Rtg1p, and Rtg3p, but not Msn2p and Msn4p, were required for full induction of LDs by rapamycin. Furthermore, we show that the deletion of Gln3p and Gat1p transcription factors, which are activated in response to nitrogen availability, led to abnormal LD dynamics. These results reveal that the TORC1 pathway is involved in neutral lipid homeostasis in yeast.


Formation of multiple BGK-like structures in the time-asymptotic state of collisionless Vlasov-Poisson plasmas.
The time-asymptotic state of a finite-amplitude perturbation in a collisionless and Maxwellian plasma is typically represented as a steady state of two nonlinearly superposed, counterpropagating Bernstein-Greene-Kruskal (BGK) modes. Using high-resolution Vlasov-Poisson simulations, we show that the plasma evolves self-consistently into a time-asymptotic state of multiple vortexlike structures that gradually fill the phase space and reduce filamentation. This occurs without the need for external forcing or the presence of an energetic plasma population. This finding suggests that the time-asymptotic regime of the plasma is rather akin to a nonlinear superposition of multiple BGK-like modes associated with nearly constant phase-speed waves. The electric field and the space-averaged particle distribution function exhibit a power-law broad spectrum, which is consistent with an energy cascade towards smaller scales in both position and velocity spaces.


Quantum Simulation of Three-Body Interactions in Weakly Driven Quantum Systems.
The realization of effective Hamiltonians featuring many-body interactions beyond pairwise coupling would enable the quantum simulation of central models underpinning topological physics and quantum computation. We overcome crucial limitations of perturbative Floquet engineering and discuss the highly accurate realization of a purely three-body Hamiltonian in superconducting circuits and molecular nanomagnets.


Impact of a Drug Abuse Resistance Education (D.A.R.E) program in preventing the initiation of cigarette smoking in fifth- and sixth-grade students.
An alarmingly high number of children become addicted to tobacco use. To teach children the skills to resist the influences surrounding the initiation of tobacco and other drug use, a Drug Abuse Resistance Education (D.A.R.E.) program is being implemented in three fourths of the schools in the United States. The purpose of this study is to examine the impact of this program in preventing smoking. A survey was conducted among 236 fifth and sixth graders in Nashville, Tennessee. Of the students included in the survey, 88% graduated from D.A.R.E. Approximately 11.6% of respondents had ever smoked cigarettes; 86% of them continued to smoke. The D.A.R.E. group had a significantly lower rate of smoking compared with their non-D.A.R.E. counterparts (8.7% vs. 28.0%; p = 0.0001). Logistic regression analysis shows that the D.A.R.E. group was five times (odds 4.9; p = 0.003; 95% CI: 1.7, 14.0) less likely to initiate smoking compared with the non-D.A.R.E. group. The D.A.R.E. group had a significantly (p = 0.002) higher knowledge score on the risk of smoking. The knowledge score has strong opposite correlation to smoking behavior (p = 0.00001). Students with top-quartile knowledge scores had a substantially lower rates of smoking (1.4% vs. 14.4%; p = 0.001). This finding is consistent for both African-American (0% vs. 19.6%; p = 0.001) and white children (1.9% vs. 13%; p = 0.001). The D.A.R.E. program may have an impact in preventing the initiation of smoking behavior.


Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population.
There is a high prevalence of delirium in older medical intensive care unit (ICU) patients and delirium is associated with adverse outcomes. We need to identify modifiable risk factors for delirium, such as medication use, in the ICU. The objective of this study was to examine the impact of benzodiazepine or opioid use on the duration of ICU delirium in an older medical population. Prospective cohort study. Fourteen-bed medical intensive care unit in an urban university teaching hospital. 304 consecutive admissions age 60 and older. None. The main outcome measure was duration of ICU delirium, specifically the first episode of ICU delirium. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a validated chart review method. Our main predictor was receiving benzodiazepines or opioids during ICU stay. A multivariable model was developed using Poisson rate regression. Delirium occurred in 239 of 304 patients (79%). The median duration of ICU delirium was 3 days with a range of 1-33 days. In a multivariable regression model, receipt of a benzodiazepine or opioid (rate ratio [RR] 1.64, 95% confidence interval [CI] 1.27-2.10) was associated with increased delirium duration. Other variables associated with delirium duration in this analysis include preexisting dementia (RR 1.19, 95% CI 1.07-1.33), receipt of haloperidol (RR 1.35, 95% CI 1.21-1.50), and severity of illness (RR 1.01, 95% CI 1.00-1.02). The use of benzodiazepines or opioids in the ICU is associated with longer duration of a first episode of delirium. Receipt of these medications may represent modifiable risk factors for delirium. Clinicians caring for ICU patients should carefully evaluate the need for benzodiazepines, opioids, and haloperidol.


Infective endocarditis: 35 years of experience at a children's hospital.
We review the predisposing conditions, the presenting signs and symptoms, as well as the risk factors and bacterial etiologies in children with infective endocarditis, focusing on hospital course and outcome. We conducted a retrospective analysis of 76 cases of endocarditis in 73 patients occurring at Children's Hospital of Pittsburgh from January 1958 through December 1992. The median age of the patients was 9 years (range, 1 month to 18 years). Predisposing conditions included congenital heart disease (62 patients) and rheumatic heart disease (four patients). Seventy-seven percent of the children with congenital heart disease had undergone cardiac surgery. After therapy with appropriate antibiotics was started, blood cultures for 67 patients (70 episodes of infective endocarditis) remained positive for a mean (+/-SD) of 0.7 +/- 1.41 days, and all patients who presented with fever (75 episodes in 72 patients) remained febrile for a mean (+/-SD) of 4.28 +/- 6.21 days. Secondary fever occurred in 39% of the children. Thirty (41%) of the 73 patients survived without any complications and 13 (18%) died. Fifteen children with complications required surgery. Children with endocarditis caused by Staphylococcus aureus were more likely than those with infection caused by viridans streptococci to have prolonged fever, secondary fever, and/or complications as well to require surgery.


Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents.
On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V-FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.


Protein synthesis and degradation in skeletal muscle of normal and dystrophic hamsters.
Dystrophic hamsters (BIO 53.58) had lower body weights and gastrocnemius muscle weights than normal hamsters (BIO RB). Dystrophic muscle contained less protein than normal muscle. The proportion of collagenous to noncollagenous protein remained unchanged. Loss of protein in the dystrophic muscle was the result of an increase in the rate of protein degradation. This was accompanied by higher activities of two lysosomal proteases, cathepsins B and D. The net effect of the increase in protein degradation was blunted by an increase in the rate of synthesis of total protein and myosin. The faster rate of synthesis in dystrophic muscle was partially due to an increase in the concentration of cellular RNA. Rates of peptide-chain initiation and protein synthesis decreased in muscles of normal hamsters perfused in the absence of insulin. In the presence of insulin, these processes were maintained at higher rates. However, the rate of protein synthesis in dystrophic muscle appeared less insulin-dependent than normal muscle. Protein degradation was inhibited by insulin in both types of muscle.


Perceptions of ICU Diary Utility and Feasibility in a Combat ICU.
Severely injured patients have difficulty recalling their intensive care unit (ICU) experience which may contribute to emotional trauma. An ICU patient journal contains a short summary of key events during the ICU stay, and has been shown to improve emotional well-being. This project evaluated the feasibility and perceptions of ICU journals in a combat ICU. A one-page survey was distributed to ICU nursing staff at Craig Joint Theater Hospital before and after the use of ICU journals as a process improvement initiative. 16 preimplementation and 10 postimplementation surveys were collected to determine the perception of the utility and feasibility of ICU journals, as well as changes to nursing job satisfaction. Overall, nurses had positive perceptions of ICU journaling; after implementation they felt it could also benefit nurses (31% vs. 80%, p = 0.002). ICU nurses that used journals were also more likely to feel their work makes a difference (90%, p = 0.012) and they could connect with their patient on a personal level (50%, p = 0.037). Primary barriers were time to journal and legal concerns. This study demonstrates with the right guidance, ICU journals can be incorporated into an ICU in a deployed environment and nursing staff feel they benefit the patient, family, unit, and staff.


A Wireless Handheld Pressure Measurement System for In Vivo Monitoring of Intraocular Pressure in Rabbits.
Intraocular pressure (IOP) is the leading modifiable risk factor for preventing vision loss in glaucoma patients. Direct and frequent IOP measurements are highly desirable to assess adequacy of treatment and prevent further vision loss. In this study, we report on successful in vivo measurements of intraocular pressure in rabbits using an optical IOP measurement system. The sensor was implanted during cataract surgery in two New Zealand white (NZW) rabbits and tested in vivo for ten weeks. Prior to implantation, the sensors were characterized in vitro in the physiologically relevant pressure range of 0-60 mmHg. A portable wireless handheld reader consisting of an internal beam splitter, a monochromatic light source, and a digital single-lens reflex (DSLR) camera was also designed and implemented to capture interference patterns from the sensor. The sensitivity and accuracy of the sensor was 30 nm/mmHg and ±0.2 mmHg, respectively. Ten weeks post-implantation, the two NZW rabbits continued to respond well to the implant with no observable inflammation, signs of infection, or biofouling. All IOP measurements were obtained using the portable DSLR handheld reader. Successful in vivo studies demonstrate biocompatibility of the IOP sensor and prove feasibility of the IOP measurement system. The system has the potential to be used in both clinical and patient point-of-care (home) settings to frequently and accurately measure pressure.


Peritonitis in patients with scrub typhus.
Various complications have been reported in scrub typhus cases including acute respiratory distress syndrome, encephalitis, pneumonia, pericarditis, acute renal failure, and acute hepatic failure. Few studies have reported on the gastrointestinal manifestations of scrub typhus. Typical gastrointestinal manifestations in patients with scrub typhus include abdominal pain, nausea, vomiting, hematemesis, melena, and diarrhea. The two cases presented in this study are the first reported cases of peritonitis associated with scrub typhus. This study shows that scrub typhus should also be included in the differential diagnosis of peritonitis in areas where Orientia tsutsugamushi is endemic.


Correction for ambiguous solutions in factor analysis using a penalized least squares objective.
Factor analysis is a powerful tool used for the analysis of dynamic studies. One of the major drawbacks of factor analysis of dynamic structures (FADS) is that the solution is not mathematically unique when only nonnegativity constraints are used to determine factors and factor coefficients. In this paper, a method to correct for ambiguous FADS solutions has been developed. A nonambiguous solution (to within certain scaling factors) is obtained by constructing and minimizing a new objective function. The most common objective function consists of a least squares term that when minimized with nonnegativity constraints, forces agreement between the applied factor model and the measured data. In our method, this objective function is modified by adding a term that penalizes multiple components in the images of the factor coefficients. Due to nonuniqueness effects, these factor coefficients consist of more than one physiological component. The technique was tested on computer simulations, an experimental canine cardiac study using 99mTc-teboroxime, and a patient planar 99mTc-MAG3 renal study. The results show that the technique works well in comparison to the truth in computer simulations and to region of interest (ROI) measurements in the experimental studies.


Tetrahydrocannabinols in clinical and forensic toxicology.
Cannabinoids are the natural constituents of marihuana (cannabis). The main of them are delta9-tetrahydrocannabinol (9THC)--psychoactive agent, cannabinol (CBN) and cannabidiol (CBD). Cannabis is administered either by smoking or orally. 9THC potency and duration of action as well as its and two of its major metabolites concentrations in organism highly depend on the route of administration. A single active dose of 9THC is estimated on 520 mg. 9THC is rapidly metabolised. It is hydroxylated to an active metabolite, I1 -hydroxy-delta9-tetrahydro-cannabinol (11-OH-THC), then oxidised to an inactive 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), which is conjugated with glucuronic acid and predominantly excreted in the urine. The maximum psychological effect persists for 4-6 h after administration despite of very low 9THC blood concentrations. 9THC plasma concentration declined to values of 2-3 ng/ml during 3-4 h after smoking. Such a low concentration of the active compound in human organism create a demand for use of sensitive analytical methods for detection and determination of 9THC and its metabolites. The most effective techniques for 9THC and related compounds determination in biological material are chromatographic ones (gas and liquid) with mass spectrometric detection and different ionization modes. 9THC and its two metabolites (11-OH-THC and THCCOOH) are present in blood and hair, 9THC in saliva, and THCCOOH in urine. 9THC and related compounds are determined in autopsy material, although deaths by overdose of cannabis are exceptionally rare. Fatalities happen most often after intravenous injection of hashish oil. 9THC and its metabolites determination in different biological materials gives the basis for a wide interpretation of analytical results for clinical and forensic toxicology purposes.


Avoidant restrictive food intake disorder: First do no harm.
This opinion piece offers some considerations, both medical and psychological, for the use of nasogastric tube (NGT) feedings in the treatment of avoidant restrictive food intake disorder (ARFID) in children and adolescents. Although there is empirical support for the use of NGT feedings in the treatment of anorexia nervosa, this evidence base does not exist for the treatment of ARFID. As such, there is need to delineate pragmatic considerations in the use of this procedure. Issues of medical necessity notwithstanding, we advise that the use of this procedure be considered more cautiously due to the oral sensitivities inherent in many individuals with ARFID and the potential psychological consequences. These sensitivities may make the experience of NGT feedings particularly aversive, with the potential of creating iatrogenic conditioned food aversions. This article encourages clinicians to give careful thought and attention when considering NGT feedings in children and adolescents with ARFID.


New challenges in the growth field.
When unlimited supplies of biosynthetic human growth hormone (hGH) became available in the late 1980s, the envisaged potential of its therapeutic applications was enormous in that it was hoped that perhaps most short children would be able to be made taller. However, this seems to have been far too simplistic a view and certainly in those children with various growth disorders treated with pharmacological doses of growth hormone (GH), the potential for increased final height does not appear to be fulfilled, with the exception of girls with Turner's syndrome. Further challenges in the growth field involve the manipulation of pubertal development during concomitant GH therapy.


Some psychophysical tasks measure ocular dominance plasticity more reliably than others.
In the recent decade, studies have shown that short-term monocular deprivation strengthens the deprived eye's contribution to binocular vision. However, the magnitude of the change in eye dominance after monocular deprivation (i.e., the patching effect) has been found to be different between different methods and within the same method. There are three possible explanations for the discrepancy. First, the mechanisms underlying the patching effect that are probed by different measurement tasks might exist at different neural sites. Second, the test-retest variability of the same test can produce inconsistent results. Third, the magnitude of the patching effect itself within the same observer can vary across separate days or experimental sessions. To explore these possibilities, we assessed the test-retest reliability of the three most commonly used tasks (binocular rivalry, binocular combination, and dichoptic masking) and the repeatability of the shift in eye dominance after short-term monocular deprivation for each of the task. Two variations for binocular phase combination were used, at one and many contrasts of the stimuli. Also, two variations for dichoptic masking were employed; the orientation of the mask grating was either horizontal or vertical. Thus, five different tasks were evaluated. We hoped to resolve some of the inconsistencies reported in the literature concerning this form of visual plasticity. In this study, we also aimed to recommend a measurement method that would allow us to better understand its physiological basis and the underpinning of visual disorders.


[Study on impact of ethanol extracts from Sedum sarmentosum in inhibiting STAT-3 signaling and inducing apoptosis of human hepatocellular carcinoma cell line HepG2].
To investigate the impact of ethanol extracts from Sedum sarmentosum (ESB) on STAT-3 signaling and its probable molecular mechanism in inducing apoptosis. MTT assay was used to detect the impact of ESB on HepG2 cell proliferation. FITC-Annexin V-FITC /PI double-labeling were used to investigate the impact on hepatoma carcinoma cell apoptosis. Western blot analysis was used to test the expression levels of cell apoptosis-related proteins Caspase-3, Caspase-9, PARP, P-STAT-3 (Tyr705) , STAT-3, Bcl-2, Mcl-1. ESB could notably inhibit proliferation of HepG2 cells, and induce HepG2 cell apoptosis, with the dose-dependent inhibitory effect. In addition, ESB could inhibit STAT-3 signaling, down-regulate Mcl-1 and Bcl-2 expressions, and induce degradation/activation of apoptosis-related proteins Caspase-3 and Caspase-9 and PARP degradation in a dose-dependent manner. ESB inhibits HepG2 cell proliferation and induces apoptosis by inhibiting STAT-3 signaling and Mcl-1 and Bcl-2 expressions.


Play in the treatment of adolescents.
I propose a view of the treatment process with adolescents which places interactive play at the center. The adolescent plays by creating a highly charged interpersonal drama with the analyst to work out specific developmental conflicts. These conflicts involve struggles for greater autonomy and the formation of a solid sense of identity in the face of regressive pulls. The analyst unwittingly is taken up in the play and uses his or her sense of involvement as material for interpretation to further the play or resolve periods of strain when play falters.


Fetuin-A is not associated with mortality in chronic kidney disease.
Fetuin-A is a serum protein that inhibits vascular calcification such that lower levels are associated with a higher prevalence of vascular calcification and mortality risk among end-stage renal disease populations. We analyzed data of 822 persons in the Modification of Diet in Renal Disease study, a randomized, controlled trial of persons with predominantly non-diabetic stage 3-4 chronic kidney disease (CKD). Serum fetuin-A levels were measured in baseline serum. Survival status and cause of death were determined by the National Death Index. Cox proportional hazard models evaluated the association of fetuin-A levels with all-cause and cardiovascular mortality. Glomerular filtration ranged from 13 to 55 ml per min per 1.73 m(2). During a median follow-up of 9.5 years, 25% of persons died from any cause and 12% died from a cardiovascular cause. Compared to the lowest tertile, no association was found between the highest fetuin-A tertile and all-cause or cardiovascular mortality. Similarly, no association was found between fetuin-A as a continuous variable and all-cause or cardiovascular mortality. Our study shows that serum fetuin-A levels are not related to all-cause or cardiovascular mortality among persons with predominantly non-diabetic stage 3 or 4 CKD.


Consecutive cyclic esotropia - A case report.
Cyclic esotropia, a rare condition of obscure etiology characterized by regularly alternating periods of esotropia and orthophoria. We present a case of a 7-year-old boy who underwent surgical correction for intermittent exotropia elsewhere and developed esotropia with cyclic pattern post-operatively. Initially the cycle was of half-day orthophoria and half-day esotropia, which later became one full day of esotropia and one day of orthophoria. During re-surgery, right lateral rectus was found to have a stretched scar which was resected and then advanced and medial rectus was recessed. Post-surgery the child was orthophoric without cyclic pattern.


[The company Willmar Schwabe in the Nazi era].
This essay follows the history of the Schwabe Company between 1933 and 1945 when it, like all other companies at the time, had to subject to the state-enforced conformity ('Gleichschaltung'). While Willmar Schwabe II (1878-1935), the company's second director, kept clear of Nazi politics, both of his sons, who succeeded him at an early age, became members of the Nazi party: Willmar III (1907-1983) probably from initial conviction and Wolfgang (1912-2000), who joined in 1937, more likely for opportunistic reasons. The two lay journals published by Schwabe--the Leipziger Populäre Zeitschrift für Homöopathie and the Biochemische Monatsblätter--embraced the Nazi ideology more thoroughly than the general homeopathic journal Allgemeine Homöopathische Zeitung, including above all contributions on racial hygiene. Our research has revealed that Schwabe only employed foreign workers from 1942 on, that their number was much lower, at 0.9 per cent in 1942 and 3.6 per cent in 1944, than that of other pharmaceutical companies and that their pay hardly differed from that of German workers. The sales and profit figures investigated have shown that the company did not profit exceptionally from the new Nazi health policies ('Neue Deutsche Heilkunde'): while its sales and profits rose in the Nazi era due to the increased use of medication among the civil population during wartime, the drugs produced by Schwabe remained marginal also during the war, as is apparent also from its modest deliveries to the army. All in all one can conclude that the company offered neither resistance nor particular support to the Nazi ideology.


Specific suppression of microgliosis cannot circumvent the severe neuropathology in peroxisomal β-oxidation-deficient mice.
An important hallmark of various neurodegenerative disorders is the proliferation and activation of microglial cells, the resident immune cells of the central nervous system (CNS). Mice that lack multifunctional protein-2 (MFP2), the key enzyme in peroxisomal β-oxidation, develop excessive microgliosis that positively correlates with behavioral deficits whereas no neuronal loss occurs. However, the precise contribution of neuroinflammation to the fatal neuropathology of MFP2 deficiency remains largely unknown. Here, we first attempted to suppress the inflammatory response by administering various anti-inflammatory drugs but they failed to reduce microgliosis. Subsequently, Mfp2-/- mice were treated with the selective colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 as microglial proliferation and survival is dependent on CSF1R signaling. This resulted in the elimination of >95% of microglia from control mice but only 70% of the expanded microglial population from Mfp2-/- mice. Despite microglial diminution in Mfp2-/- brain, inflammatory markers remained unaltered and residual microglia persisted in a reactive state. CSF1R inhibition did not prevent neuronal dysfunction, cognitive decline and clinical deterioration of Mfp2-/- mice. Collectively, the unaltered inflammatory profile despite suppressed microgliosis concurrent with persevering clinical decline strengthens our hypothesis that neuroinflammation importantly contributes to the Mfp2-/- phenotype.


Fgd5 is a Rac1-specific Rho GEF that is selectively inhibited by aurintricarboxylic acid.
Rho proteins are signalling molecules that control cellular dynamics, movement and morphological changes. They are activated by Rho guanine-nucleotide exchange factors (Rho GEFs) that transduce upstream signals into Rho-mediated activation of downstream processes. Fgd5 is a Rho GEF involved in angiogenesis and its target Rho protein for this process has been linked to Cdc42 activation. Here, we examined the function of purified Fgd5, specifically, which Rho proteins it activates and pinpoint the structural domains required for enzymatic activity. Using a GEF enzyme assay, we found that purified Fgd5 showed preferential activation of Rac1 and direct binding of Rac1 in pull-down and co-immunoprecipitation assays. Structural comparisons showed that the Fgd5 DH domain is highly similar to the Rac1 GEF, TrioN, supporting a role for Fgd5 as a Rac1 GEF. Compounds that bind to purified Fgd5 DH-PH protein were identified by screening a small molecule library via surface plasmon resonance. The effects of eleven ligands were further examined for their ability to inhibit the Fgd5 GEF enzymatic activity and Rac1 interaction. From these studies, we found that the compound aurintricarboxylic acid, and to a lesser extent mitoxantrone dihydrochloride, inhibited both Fgd5 GEF activation of Rac1 and their interaction. Aurintricarboxylic acid had no effect on the activity or binding of the Rac1 GEF, TrioN, thus demonstrating the feasibility of selectively disrupting Rho GEF activators. Abbreviations: a.a.: amino acid; ATA: aurintricarboxylic acid; DH: Dbl homology; DOCK: dictator of cytokinesis; Fgd: faciogenital dysplasia; GEF: guanine-nucleotide exchange factor; GST: glutathione S-transferase; LOPAC: library of pharmacologically active compounds; PH: pleckstrin homology; PDB: protein data bank; s.e.m.: standard error of the mean; SPR: surface plasmon resonance.


CPF-C1 analog with effective antimicrobial and antibiofilm activities against Staphylococcus aureus including MRSA.
The evolution of Staphylococcus aureus (S. aureus) with the ability to acquire and develop resistance to antibiotics has been described as a distinct strain emergence event. Methicillin-resistant S. aureus (MRSA) is responsible for most global S. aureus bacteremia cases. Bacterial biofilms are one of the primary reasons for drug resistance. Biofilms formed by S. aureus are the most common cause of biofilm-associated infections, which increase the difficulty of treatment. Antimicrobial peptides (AMPs) represent promising candidates for the future treatment of antibiotic-resistant bacterial and biofilm-associated infections. In this study, we designed and synthesized a series of analogs to increase the druggability of the natural antimicrobial peptide CPF-C1. Among the analogs, CPF-2 showed high antimicrobial activity against MRSA and multidrug-resistant S. aureus isolated from clinics. In the serum and physiological salt environment, CPF-2 also exhibited effective antimicrobial activity. Importantly, CPF-2 did not determine resistance and showed no hemolytic activity at the active concentration. Concerning the mechanism of action, CPF-2 produced a rapid bactericidal effect by interrupting the bacterial membranes. Even more surprisingly, CPF-2 showed an excellent ability to prevent and eradicate biofilms caused by S. aureus and MRSA not only in vitro but also in vivo. Our results suggested that CPF-2 has potential as a lead compound to treat infections caused by S. aureus and MRSA, including the associated biofilms.


Distribution of prostaglandins E2 and F2 alpha within the foetoplacental unit throughout human pregnancy.
The concentrations of prostaglandin E2 and F2 alpha have been measured by radioimmunoassay in portions of cord, placenta, amnion, chorion, decidua and myometrium. The samples were obtained at defined periods of pregnancy, and the results have been compared with those obtained from the analyses of endometrial and myometrial tissue removed from women during the secretory phase of a menstrual cycle. The results showed that during pregnancy the mean concentration of prostaglandin E2 was higher (27-518%) than the corresponding value for prostaglandin F2 alpha in all tissues. At term the concentration of prostaglandin E2 (ng/100 mg wet weight of tissue, mean +/- S.D.) was higher in the umbilical cord (5-54 +/- 0-88), decidua (4-02 +/- 1-78) and myometrium (4-19 +/- 1-06), than in the amnion (2-25 +/- 1-27), chorion (1-64 "/- 0-63) or placenta (1-04 +/- 0-25). During labour there was a significant rise (P less than 0.0005, Student's 't' test) in the concentration in decidua (10-76 +/- 4-45), and to a lesser extent (P less than 0-05) in the myometrium (5-84 +/- 2-65) and amnion (4-77 +/- 2-51). The overall concentration in decidua during the first trimester (3-09 +/- 1-02) was significantly lower (P less than 0-005) than in endometrial tissue(16-82 +/- 10-13). The concentration was lower in myometrial tissue from non-pregnant subjects (2-90 +/- 2-21), than in the corresponding tissue removed at term (4-19 +/- 1-06) or during labour 5-84 +/- 2-65). The results for prostaglandin F2 alpha showed a similar pattern, but the values were significantly lower in the umbilical cord, and the percentage changes in concentration in the decidua and myometrium were of a higher magnitude.


Production of the angiotensin converting enzyme (ACE) in cultures of rat peritoneal macrophages.
Some authors attributed an increase in ACE activity in sarcoidosis to high production of this enzyme by alveolar macrophages. In order to study the production of ACE by peritoneal rat macrophages, we measured the ACE activity, by a modified version of Friedland and Silverstein's technique, in cultures of rat peritoneal macrophages, with dexamethasone, with Complete Freund Adjuvent (C.F.A.) or sarcoidosis node extract (Kveim Antigen). ACE activity was not detected in cultures. Our results were discussed.


The Absorption Characteristics of Nonvolatile Components in a Water Extraction From Amomi fructus as Determined by In Situ Single-Pass Intestinal Perfusion and High-Performance Liquid Chromatography.
Amomi fructus is a famous traditional Chinese medicine (TCM) that can exert beneficial effects during the treatment of gastrointestinal diseases and is used widely in China and other countries in Southeast Asia. However, the nonvolatile active ingredients that are present in the water extractions from A. fructus used to treat gastrointestinal diseases have yet to be elucidated. The goal of this study was to identify the nonvolatile active ingredients of A. fructus. We used an in situ single-pass intestinal perfusion (SPIP) model to identify the active ingredients of A. fructus that play significant roles in gastrointestinal absorption. In addition, we developed a high-performance liquid chromatography (HPLC) method to identify key fractions in intestinal outflow perfusate. Nineteen components were identified in a water extraction from A. fructus; these exhibited different absorption capabilities in different intestinal segments. Of these, six components were determined by the newly developed HPLC method: catechin, vanillic acid, epicatechin, polydatin, isoquercitrin, and quercitrin. The current study aimed to identify the active ingredients present in water extractions prepared from A. fructus in a single-intestinal perfusate from rats. Our findings provide an experimental basis to explain the pharmacodynamic actions of A. fructus.


Characterization of physiochemical and anatomical features associated with enhanced phytostabilization of copper in Bruguiera cylindrica (L.) Blume.
Copper is an essential micronutrient for normal plant metabolism and it is involved in number of physiological processes in plants but at the same time, at concentrations above threshold level, it acts as a potential stress factor. In this study, the phytoremediation potential of Bruguiera cylindrica (L.) Blume with respect to Cu was evaluated for the first time. Various physiochemical and anatomical parameters were analyzed in three-month-old healthy plantlets of B. cylindrica on exposure to different concentrations of CuSO4 (0, 0.05, 0.15, and 0.25 mM)for 20 d. Higher uptake and accumulation of Cu in the roots indicates that the roots are the primary site of Cu accumulation and thus the plant perform as an excluder. Tolerance index values (TI > 60) reveals the phytoremediation potential of this plant. Metabolites are accumulated in plants to cope up with the oxidative damage due to Cu stress. Increased rate of proline and free amino acids content and soluble sugar content especially in leaves of B. cylindrica subjected to CuSO4 contributes toward higher osmolality so as to counter the reduced water transport from roots. Nonenzymatic antioxidants like ascorbic acid, glutathione, and phenolics are the ROS scavenging compounds in the Defense system of B. cylindrica toward higher concentrations of CuSO4, and of these, phenolics accumulation plays greater role in the antioxidative function in B. cylindrica in response to Cu stress. The histochemistry of B. cylindrica revealed the prominent occurrence of star-shaped calcium oxalate crystals when exposed to 0.25 mM CuSO4, and it seems to be a prominent defense mechanism under Cu stress. Also a remarkable finding was the accumulation of Cu in the xylem vessels of plants on exposure of 0.25 mM CuSO4 as compared to control. The infrared spectra were analyzed to compare the functional groups in the phenolics and carbohydrate constituents of control and CuSO4-treated B. cylindrica plantlets and it indicated that carboxyl and hydroxyl groups are involved in the Cu binding so as to achieve tolerance to Cu. Thus this study revealed the potential role of B. cylindrica as a promising candidate for phytostabilization of copper.


High-field, high-resolution, susceptibility-weighted magnetic resonance imaging: improved image quality by addition of contrast agent and higher field strength in patients with brain tumors.
To demonstrate intratumoral susceptibility effects in malignant brain tumors and to assess visualization of susceptibility effects before and after administration of the paramagnetic contrast agent MultiHance (gadobenate dimeglumine; Bracco Imaging), an agent known to have high relaxivity, with respect to susceptibility effects, image quality, and reduction of scan time. Included in the study were 19 patients with malignant brain tumors who underwent high-resolution, susceptibility-weighted (SW) MR imaging at 3 T before and after administration of contrast agent. In all patients, Multihance was administered intravenously as a bolus (0.1 mmol/kg body weight). MR images were individually evaluated by two radiologists with previous experience in the evaluation of pre- and postcontrast 3-T SW MR images with respect to susceptibility effects, image quality, and reduction of scan time. In the 19 patients 21 tumors were diagnosed, of which 18 demonstrated intralesional susceptibility effects both in pre- and postcontrast SW images, and 19 demonstrated contrast enhancement in both SW images and T1-weighted spin-echo MR images. Conspicuity of susceptibility effects and image quality were improved in postcontrast images compared with precontrast images and the scan time was also reduced due to decreased TE values from 9 min (precontrast) to 7 min (postcontrast). The intravenous administration of MultiHance, an agent with high relaxivity, allowed a reduction of scan time from 9 min to 7 min while preserving excellent susceptibility effects and image quality in SW images obtained at 3 T. Contrast enhancement and intralesional susceptibility effects can be assessed in one sequence.


Whitish vulvar tumors associated with macular symmetrical rash.
We present a woman with an unusual case of secondary syphilis after an unnoticed primary infection. She initially presented with multiple grayish plaques and nodules on the vulva associated with an erythematous macular symmetrical rash affecting the trunk and extremities. Despite the increasing incidence of sexually transmitted diseases such as syphilis, presentation with unusual manifestations can lead to a delayed diagnosis.


Formation of the atrioventricular septal structures in the normal mouse.
It is sometimes thought that formation of the atrioventricular septum is equated with fusion of the endocardial cushions and that failure of fusion can explain all deficiencies of atrioventricular septation. Clearly, this is simplistic, but the exact contribution of different primordia to atrioventricular septation is not well understood. To clarify this, we studied normal mouse embryos (days 10 to 15 of gestation), which were serially sectioned and examined by light microscopy. Another group of embryos was examined by scanning electron microscopy after microdissection. Our results show that development of the atrioventricular septal area is highly complex. Proper formation requires the following: remodeling of the inner heart curvature, rotation of the horns of the systemic venous sinus around the pulmonary portal, expansion of the right atrioventricular junction, formation of the muscular atrial and ventricular septa, bridging by the dextrodorsal outflow ridge and the superior endocardial cushion, fusion with the inferior margins of the venous valves, and formation of the mouth of the coronary sinus from the cranial muscular wall of the left sinus horn. Multiple primordia contribute to a central mesenchymal mass (the "septum intermedium"), including the mesenchyme on the leading edge of the primary atrial septum, the atrioventricular endocardial cushions, and the cap of mesenchyme on the spina vestibuli. Fusion of these components closes the ostium primum, completing atrial and atrioventricular septation. Additionally, the spina vestibuli has a mesodermal core, which contributes to the muscularization of the lower margin of the oval fossa. This contrasts with the formation of the upper rim, which occurs as a result of an infolding of the atrial wall itself.


Molecular chaperon produced by an intracellular symbiont.
Symbionin, that is selectively produced by an intracellular symbiont harbored by the aphid bacteriocyte, is structurally homologous to the Escherichia coli groEL protein, a heat shock protein functioning as a molecular chaperon. It was shown that symbionin has ATPase activity and, in the presence of Mg-ATP, is converted into lower molecular mass species. Like the groEL protein, symbionin was able to reconstitute dimeric ribulose 1,5-bisphosphate carboxylase/oxygenase holoenzyme from its unfolded subunits in vitro, suggesting that this protein functions as a molecular chaperon in the endosymbiont. The groES-homologous protein did exist in the endosymbiont, but its amount was small relative to that of symbionin.


Continuous axillary brachial plexus block--a clinical and anatomical study.
In order to decrease both the failure rate and inadvertent arterial puncture rate that may be associated with continuous axillary brachial plexus block, a new technique of insertion of the catheter in the axilla was studied in 52 patients and in 12 fresh cadavers. With the arm abducted, externally rotated, and flexed at the elbow, an 80-mm long catheter was inserted under the skin at a site located 40-mm below the axilla and medial to the biceps muscle. Injection of lidocaine and bupivacaine produced sensory and motor blockades of the median, radial, ulnar, and musculocutaneous nerves in 98% of the patients. Arterial puncture occurred in one. The catheter was left in situ up to 9 days without complications. In the anatomical study, injection of dye and molding solutions showed that the tip of the catheter lay not in the perivascular sheath, but in a virtual cavity that was very superficial, under the skin, and surrounding the perivascular space. The technique used was safe and had a high success rate. It is particularly useful in patients undergoing long operations and in patients in whom pain would otherwise prevent postoperative physiotherapy of the upper arm.


Helicobacter pylori infection increases the risk of developing preeclampsia: A meta-analysis of observational studies.
Helicobacter pylori has been previously linked with preeclampsia on the basis of altered angiogenesis and activation of inflammatory cytokines. The purpose of the present systematic review is to summarise current evidence concerning the correlation of the two diseases. We searched the Medline (1966-2017), Scopus (2004-2017), Clinicaltrials.gov (2008-2017) EMBASE (1980-2017), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases. We selected all observational studies (both prospective and retrospective) that reported the incidence of preeclampsia among women with H. Pylori infection. Statistical meta-analysis was performed with the RevMan 5.3 software. Fourteen studies were finally included in this review, which included a total number of 9787 women. Nine percentage of these had preeclampsia (879 women). The evaluation of studies with the ROBINS-I tool revealed low to moderate risk of bias. H. pylori IgG seropositivity was significantly more prevalent in preeclamptic than in healthy pregnant women (9391 women, OR: 2.32, 95% CI [1.55, 3.46]). The frequency of anti-CagA antibodies was also higher in pregnancies complicated with preeclampsia (3275 women, OR: 3.97, 95% CI [1.55, 10.19]). The findings of our study support that H. pylori infection doubles the risk of developing preeclampsia. The exact pathophysiological processes, however, remain poorly investigated and future experimental studies are needed to shed light on the underlying mechanisms.


Induction of protective immune responses against EV71 in mice by baculovirus encoding a novel expression cassette for capsid protein VP1.
EV71 is a major causative agent of hand, foot and mouth disease (HFMD) and is responsible for large outbreaks in various Asian Pacific countries. In the present study, we generated the recombinant baculovirus (Bac-VP1) encoding VP1 in a novel expression cassette. The transmembrane domain of hemagglutinin of the H3N2 influenza virus was included in the cassette as a minimal membrane anchor for VP1. The protective immunity of Bac-VP1 was investigated in a mouse model. The results showed that mice vaccinated with live Bac-VP1 had strong VP1 specific antibody responses. In an in vitro neutralization assay Bac-VP1 sera exhibited cross-neutralization against homologous and heterologous EV71 strains with a maximum titer of 1:512. Passive immunization studies confirmed that these sera were able to provide 100% protection against 5 MLD(50) of mouse adapted EV71 (B4 strain). This study revealed that baculovirus displaying VP1 with a HA transmembrane domain efficiently induced cross-neutralizing antibody responses in mice.


Crack cocaine and sex.
The impact of crack cocaine use on number of sex partners was examined using bivariate analyses and a logistic model on a national treatment cohort of 4939 individuals. Number of sex partners over the last 12 months was dichotomized as none/one versus multiple partners for the logistic analyses. The model included 11 independent variables not including prostitution or use of crack cocaine. For both genders, the bivariate analyses showed significant positive associations between crack use and number of partners regardless of type of sexual activity; those who used crack had more partners for all sexual activities queried, compared to those who did not. Cocaine, whether in powder or crack form, was positively associated with prostitution for both genders. For men the odds ratio for crack cocaine use ranged from 1.6 (heterosexual anal) to 5.5 (homosexual anal) and for women from 2.9 (heterosexual oral) to 4.1 (homosexual oral). If prostitution is added to the model the odds ratios are reduced for homosexual activities for men and reduced dramatically for all types of sexual activity for women.


Roughening of fracture surfaces: the role of plastic deformation.
Post mortem analysis of fracture surfaces of ductile and brittle materials on the microm-mm and the nm scales, respectively, reveal self-affine cracks with anomalous scaling exponent zeta approximately 0.8 in three dimensions and zeta approximately 0.65 in two dimensions. Attempts to use elasticity theory to explain this result failed, yielding exponent zeta approximately 0.5 up to logarithms. We show that when the cracks propagate via plastic void formations in front of the tip, followed by void coalescence, the void positions are positively correlated to yield exponents higher than 0.5.


Ultrasensitive label free electrical detection of insulin in neat blood serum.
Electrical assays potentially offer a highly sensitive, cheap, portable, automated, and multiplexed means of protein biomarker detection, characteristics with an ability to underpin both disease stratification and the development of point of care diagnostics. Most conveniently applied in a reagent free manner, all sensitive assays such as these suffer, however, from profound problems when applied in complex fluids such as blood serum. We report herein, the development, and clinical application, of a highly sensitive and selective electrical insulin biosensor based on a chemisorbed zwittorionic polymer support and a novel reagentless sensing technique based on phase monitoring electrochemical impedance spectroscopy. The polymer adlayer is exceptionally effective in both reducing background response and maintaining receptive antibody binding efficacy, while the non-Faradaic analysis avoids potential interference from background electro-active molecules. Applied to the detection of even a low molecular weight protein (here, insulin), a linear range from 0.1 to 200 pM and an unprecedented femtomolar detection limit are possible in undiluted blood serum.


Reverse temporalis muscle flap for the reconstruction of orbital exenteration defects.
Orbital exenteration is a surgical procedure that results in devastating functional and aesthetic losses. Many reconstructive techniques, ranging from spontaneous epithelialization to free flaps, have been described for orbital exenteration defects. The temporalis muscle flap is one of the most frequently used flaps to obliterate the orbital cavity, but only a small portion of the muscle can be used for this purpose because most of the muscle is used as the pedicle. The reverse temporalis muscle flap based on the superficial temporal vessels is a versatile flap by which the entire temporalis muscle can be elevated and carried to defects beyond the midline. The authors have used this flap for orbital reconstruction after exenteration in 6 patients with successful results. This flap enables placement of highly vascularized tissue that provides the reconstructive goals of primary healing, obliterates dead space with separation of the orbit from the nasal cavity or sinuses, provides the potential for early postoperative radiotherapy, and offers possible flaps that can be used in combination for complex, wide defects.


Selecting adhesives.
It can be seen, therefore, that attaining optimum performance and durability from a medical device is possible if the design of the joints in the device are carefully planned in conjunction with an informed selection of an adhesive.


Bedside laparoscopy in the ICU: report of four cases.
Patients in the intensive care unit (ICU) may suffer from life-threatening abdominal pathologies, which may necessitate a surgical intervention. Diagnosis may be difficult, as deep sedation and analgesia often mask symptoms, and physical examination is unreliable. Imaging studies are not accurate enough, and exploratory laparotomy carries significant morbidity and mortality rates in this patient population. The unstable patient is difficult to mobilize to the imaging department or to the operating room. Bedside laparoscopy may overcome these difficulties. We describe our initial experience with the use of bedside laparoscopy in critical patients with suspected abdominal pathology. The procedure was performed in four patients over a 4-month period and completed in all four. The findings were: turbid fluid consistent with viscus perforation in a patient with unexplained sepsis after cardiac surgery, sterile hemorrhagic fluid in a patient with malignancy and thrombotic thrombocytopenia purpura, a retroperitoneal mass from which biopsies were taken in a patient with sudden respiratory failure, and abdominal abscess in a patient after bowel resection for mesenteric embolism. None of these patients had a laparotomy after the laparoscopy. Patients 1 and 4 died a few hours after the procedure from sepsis, and patients 2 and 3 died several days later. Bedside laparoscopy in the ICU is feasible, informative, and accurate. It has a role in diagnosing abdominal pathologies and planning further treatment. It may avert a nontherapeutic laparotomy. Unfortunately, the prognosis in these patients is poor. Earlier use of this diagnostic modality may improve patient outcome.


A facile approach to construct hybrid multi-shell calcium phosphate gene particles.
The calcium phosphate (CaP) particles have attracted much attention in gene therapy. How to construct stable gene particles was the determining factor. In this study, hybrid multi-shell CaP gene particles were successfully constructed. First, CaP nanoparticles served as a core and were coated with DNA for colloidal stabilization. The xi-potential of DNA-coated CaP nanoparticles was -15 mV. Then polyethylenimine (PEI) was added and adsorbed outside of the DNA layer due to the electrostatic attraction. The xi-potential of hybrid multi-shell CaP particles was slightly positive. With addition of PEI, the hybrid multi-shell particles could condense DNA effectively, which was determined by ethidium bromide (EtBr) exclusion assay. The hybrid particles were spherical and uniform with diameters of about 150 nm at proper conditions. By simple modification of PEI, the hybrid multi-shell CaP gene particles were successfully constructed. They may have great potential in gene therapy.


[Factors associated with visual prognosis of acute retinal necrosis syndrome].
To investigate relevant factors affecting the prognosis of acute retinal necrosis syndrome (ARN). Case-series study. The clinical data of 41 patients (53 eyes) with ARN were retrospectively analyzed. Eyes were divided into two groups according to best corrected visual acuity at final visit. The groups were best corrected visual acuity better than 0.1 (group A, 28 eyes) and worse than 0.1 (group B, 25 eyes). Data were analyzed using the χ(2) test, Fisher exact test, Mann-Whitney test, bivariate correlation statistics, and multinomial logistic regression analysis. All patients were treated with systemic antivirus drugs and glucocorticoid. Ten eyes were treated with prophylactic laser retinopexy, 26 eyes underwent intravitreal ganciclovir, and 31 eyes underwent vitrectomy. All contralateral eyes of unilateral ARN patients were not involved after systemic antivirus treatment. Compared to group B (16.0%, 4/25), more eyes with best corrected visual acuity better than 0.1 at first visit were observed in group A (85.7%, 24/28) (χ(2) = 23.037, P = 0.000). Duration from onset of symptoms until first administration of antivirus drugs was shorter in group A [(15 ± 13) days] than in group B [(30 ± 34) days, Z = -2.414, P = 0.016]. Compared to group A (25.0%, 7/28; 10.7%, 3/28; 7.1%, 2/28; 39.3%, 11/28), more eyes in group B suffered from retinal detachment (80.0%, 20/25), occlusive central retinal vasculopathy (56.0%, 14/25), optic atrophy (36.0%, 9/25) and proliferative vitreoretinopathy (92.0%, 23/25) (χ(2) = 13.862, 10.440, 5.048, 13.749; P = 0.000, 0.001, 0.025, 0.000). Logistics regression analysis showed that visual prognosis were related to factors including best corrected visual acuity better at first visit (OR = 27.225, P = 0.003) and occlusive central retinal vasculopathy (OR = 0.065, P = 0.053). No difference in the number of eyes with increased intraocular pressure was observed between group A and group B (P > 0.05). Prophylactic laser retinopexy before retinal detachment and intravitreal ganciclovir were not associated with visual prognosis (P > 0.05). Worse visual acuity at first visit and occlusive central retinal vasculopathy are major relevant factors threatening visual prognosis.


Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms.
Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline. Here we investigate thirty-one aminoacyl-tRNA synthetases from infectious disease organisms by co-crystallization in the presence of their cognate amino acid, ATP, and/or inhibitors. Crystal structures were determined for a CysRS from Borrelia burgdorferi bound to AMP, GluRS from Borrelia burgdorferi and Burkholderia thailandensis bound to glutamic acid, a TrpRS from the eukaryotic pathogen Encephalitozoon cuniculi bound to tryptophan, a HisRS from Burkholderia thailandensis bound to histidine, and a LysRS from Burkholderia thailandensis bound to lysine. Thus, the presence of ligands may promote aaRS crystallization and structure determination. Comparison with homologous structures shows conformational flexibility that appears to be a recurring theme with this enzyme class.


Evaluation of the Quality of Yogurt Using Ginseng Extract Powder and Probiotic Lactobacillus plantarum NK181.
The objective of this study was to evaluate the composition, pH, titratable activity, microbial properties, and antioxidant effect of yogurt using ginseng extract powder (GEP), Lactobacillus plantarum NK181, and Streptococcus thermophilus as the starter culture. Different concentration of GEP (0%, 0.5%, 1%, 1.5%, and 2% (w/v)) were used in the yogurt. During yogurt fermentation, pH was decreased; however, titratable acidity and viable cell counts were increased. The addition of GEP to yogurt led to a decrease in moisture content and an increase in the fat, ash, and total solids content. The antioxidant effect using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, β-carotene bleaching, and ferric reducing antioxidant power (FRAP) assay gradually increased with added GEP. Overall, yogurt fermented with 1% GEP was acceptable in terms of cell viability and antioxidant effect. These results might provide information regarding development of ginseng dairy products with enhanced antioxidant activities and probiotic properties.


The weight-adjusted-waist index predicts all-cause and cardiovascular mortality in general US adults.
The authors examined the relationship between Weight-adjusted Waist Index (WWI) and all-cause and cardiovascular mortality among adults in the US. This prospective cohort study included 26,882 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 through 2014. WWI was calculated as waist circumference divided by the square root of weight. The main outcomes of this study were all-cause mortality and cardiovascular mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index records through December 31, 2015. Cox proportional hazard models and Kaplan-Meier analysis were used to estimate Hazard Ratios (HR) and 95% CIs for mortality for all causes and cardiovascular diseases. A total of 26,882 participants with a mean WWI of 10.89 ± 0.01, of whom 49.23% were male. The average follow-up time was 68.95 ± 1.07 months, and 1870 participants were determined as deceased (4.99%), including 349 cardiovascular death (0.88%). The Kaplan-Meier analysis demonstrated a significant difference in all-cause and cardiovascular mortality between patients with WWI <11.33 and ≥11.33 (both log-rank test p < 0.0001). The fully adjusted Cox proportional hazard model indicated that a higher WWI level (≥ 11.33) was associated with an increased 95% risk for cardiovascular mortality (HR = 1.95, 95% CI 1.30‒2.93) and 68% risk for all-cause death (HR = 1.68, 95% CI 1.41‒2.00) compared with the counterparts. Elevated WWI levels were associated with a higher risk of cardiovascular mortality and all-cause mortality independently.


Lycopene protects against atrazine-induced hepatic ionic homeostasis disturbance by modulating ion-transporting ATPases.
The aim of this study was to evaluate the possible chemoprotective role of lycopene (LYC) against atrazine (ATR)-induced ionic disorder and hepatotoxicity in mice. Male kunming mice were treated with LYC (5mg/kg) and/or ATR (50mg/kg or 200mg/kg) by lavage administration for 21days. Ionic disorder was assessed by determining the Na(+), K(+) and Ca(2+) content and the alteration in ATP enzymes (ATPases) including Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase and the mRNA levels of ATPase's subunits in liver. ATR caused the increases of alanine aminotransferase and aspartate aminotransferase activities and histological changes. LYC pretreatment significantly protected liver against ATR-caused alternation. The significant effect of ATR and LYC on the K(+) and Mg(2+) content in liver was not observed, but ATR increased hepatic Na(+)-K(+)-ATPase activity and decreased Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity. The mRNA expressions of Na(+)-K(+)-ATPase subunits were regulated significantly by ATR. A significant increase of Ca(2+) content and seven down-regulated mRNA expressions of Ca(2+)-ATPase subunits and a decrease of Ca(2+)-ATPase activity were observed in the ATR-treated mice. Notably, LYC modulated these ATR-induced alterations of ATPase activity and mRNA expression of their subunits. These results suggest that ATR presents hepatotoxicity via regulating hepatic ATPase's activities and their subunit transcriptions and inducing ionic disorder. LYC protects liver against ATR-induced hepatotoxicity, significantly. LYC modulated hepatic ionic homeostasis disturbance via regulation of ATPase activities and their subunits' (1a1, 1b3, 1b4 and 2b4) transcriptions. In summary, these effects play a critical role of LYC-mediated chemoprevention against ATR-induced hepatotoxicity.


Office and ambulatory blood pressure in patients with craniomandibular disorders.
To assess the physiologic response to daily life stress in patients with craniomandibular disorders (CMD), office and ambulatory blood pressure and heart rate were studied in 25 female patients and 25 controls. Significant differences (p < 0.05) were found between the groups for heart rate before the clinical examination and that in the patient group when compared before and after the clinical examination. Higher values were found for mean daytime systolic and diastolic blood pressure in the control group compared with the patient group (p < 0.05). The mean number of systolic blood pressure > or = 140 mmHg during 24 h and daytime was significantly higher (p < 0.05) in the control group than in the patient group. In this study the CMD patients with muscular diagnosis were not more stressed than healthy subjects in the daily activities as evaluated by ambulatory blood pressure measurements.


CCL2 is Modulated by Cytokines and PPAR-γ in Anaplastic Thyroid Cancer.
Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. We tested in "primary human anaplastic thyroid carcinoma (ATC) cells" (ANA) versus "normal thyroid follicular cells" (TFC): a) CCL2 secretion basally, after IFN-γ and/or TNF-α stimulation; b) PPARγ activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA. ANA produced basally CCL2, at a higher level versus TFC. IFN-γ or TNF-α dose-dependently induced the CCL2 release in 3/6 or 5/6 ANA, respectively, but in all TFC. IFN-γ+TNF-α induced a synergistic release of CCL2 in all TFC, but only in 1/6 ATC. TZDs exerted an inhibition of CCL2 release in 3/6 ANA, while had no effect in TFC. Pioglitazone inhibition of ANA proliferation was not associated with the effect on CCL2; NF-κB and ERK1/2 were basally activated in ANA, increased by IFN-γ+TNF-α, and pioglitazone inhibited IFN- γ+TNF-α activation. CCL2 serum levels were higher in 6 ATC patients than in 5 controls (813±345 versus 345±212, pg/mL; respectively; P<0.01, ANOVA). ANA produce CCL2 basally and after cytokines stimulation, with an extremely variable pattern of modulation, suggesting different types of deregulation in the chemokine modulation. Serum CCL2 is increased in ATC patients. Further studies will be necessary to evaluate if CCL2 might be used as a marker in the followup of ATC patients.


Surgery of liver tumours.
The liver is a segmental organ that allows resection through anatomically defined planes. The surgical management of an intrahepatic lesion, discovered either during investigation of hepatological symptoms or coincidentally, must involve an approach to investigation that carries a minimum risk and does not compromise subsequent excision of the lesion. Biopsy of an intrahepatic lesion found at laparotomy is essential, but attempts at early tissue diagnosis by percutaneous biopsy of operable tumours may lead to unnecessary morbidity and tumour spread. Preoperative studies often allow a firm pathological diagnosis to be made and ultrasonography, CT scanning and arteriography can be used to fully assess operability. Hepatocellular carcinoma (HCC) is the commonest primary liver cancer and is often found in association with cirrhosis and in patients with inadequate functional hepatic reserve. Surgical excision represents the only hope of cure for these patients and a 35% 5-year survival can be achieved by resection in the non-cirrhotic patient. Fibrolamellar HCC is less often associated with cirrhosis and is more often resectable with a better prognosis. Secondary tumours are often diffuse but about 5% of colorectal metastases are either solitary or confined to a resectable area of the liver. These tumours and secondary deposits from gastrointestinal endocrine tumours represent a small group of patients with potentially curable metastatic disease. Morbidity and mortality of operation depends on the extent of resection and the functional reserve of the liver. Local resections and resection for benign disease should carry no operative mortality. Major hepatic resection has a mortality of 3-5% and resection involving the structures at the hilus of the liver has an operative mortality of 10-12%. Liver transplantation in the management of neoplastic disease in the liver has yet to show any benefit over resectional surgery except where tumours have been discovered incidentally in the removed liver after transplantation for cirrhosis.


Integrating Ultrafiltration Membranes with Flocculation and Activated Carbon Pretreatment Processes for Membrane Fouling Mitigation and Metal Ion Removal from Wastewater.
The presence of metal ions in an aqueous medium is an ongoing challenge throughout the world. Processes employed for metal ion removal are developed continuously with the integration of these processes taking center stage. Herein, an integrated system consisting of flocculation, activated carbon (AC), and an ultrafiltration (UF) membrane was assessed for the removal of multiple metal ions contained in wastewater generated from a university chemistry research laboratory. The quality of the wastewater was established before and further determined after treatment with inductively coupled plasma optical emission spectrometry (ICP-OES) for metal content, total dissolved solids (TDS), turbidity, electrical conductivity (EC), and pH. Assessing the spent AC indicated minimal structural changes, indicating a potential for further reuse; for instance, the BET for both the pristine and spent AC exhibited type I isotherms with a mesoporous structure, indicating no major structural changes due to metal complexation. The relative performance of the integrated system indicated that the use of flocculation improved the water quality of metal-laden wastewater for safe disposal. The integrated treatment systems exhibited high removal efficiencies between 80 and 99.99% for all the metal ions except for Mn (<0.008 mg L-1) and Cr (<0.016 mg L-1) both at ca. 70%, indicative of the positive influence of the polyelectrolyte in the treatment process. The fabricated UiO-66-NH2@GO membranes (Z4 and Z5) exhibited high fouling resistance and reusability potential as well as relatively high pure water flux. Consequently, the integrated process employed for the treatment of laboratory metal-containing wastewater is promising as a generic approach to improving the quality of metal-containing wastewater to meet the standards of discharging limits in South Africa.


Genetic characteristics of Shiga toxin-producing E. coli O157, O26, O103, O111 and O145 isolates from humans, food, and cattle in Belgium.
In this study, we characterized 272 Shiga toxin-producing Escherichia coli (STEC) isolates from humans, food, and cattle in Belgium [O157 (n = 205), O26 (n = 31), O103 (n = 15), O111 (n = 10), O145 (n = 11)] for their virulence profile, whole genome variations and relationships on different genetic levels. Isolates of O157 displayed a wide variation of stx genotypes, heterogeneously distributed among pulsogroups (80% similarity), but with a concordance at the pulsosubgroup level (90% similarity). Of all serogroups evaluated, the presence of eae was conserved, whereas genes encoded on the large plasmid (ehx, espP, katP) occurred in variable combinations in O26, O103, and O145. The odds of having haemolytic uraemic syndrome was less for all genotypes stx2a, stx2c, stx1/stx2c, and stx1 compared to genotype stx2a/stx2c; and for patients aged >5 years compared to patients aged ≤ 5 years. Based on the genetic typing and by using epidemiological data, we could confirm outbreak isolates and suggest epidemiological relationships between some sporadic cases. Undistinguishable pulsotypes or clones with minor genotypic variations were found in humans, food, and cattle in different years, which demonstrated the important role of cattle as a reservoir of STEC O157, and the circulation and persistence of pathogenic clones.


Modified Ponseti method of management of neonatal club feet.
The aim of this study was to assess the outcome of a new protocol for the management of neonatal clubfeet that can be considered as a modification of the Ponseti method. The modifications consisted of performing the tenotomy of the Achilles tendon prior to the application of the first cast and using only one cast for a period of 3 weeks following tenotomy. We applied the modified method in 50 children (82 club feet) and assessed the degree of deformity using the Pirani and the Dimeglio scoring systems. The minimum follow-up period was 28 months (range: 24-32). The intermediate range follow-up results of this study showed that the modified Ponseti method was associated with a good outcome in 85% of cases of neonatal club feet with a Pirani score of 5 or less and a Dimeglio score of 15 or less. Persistently high Pirani or Dimeglio scores immediately after tenotomy and poor compliance with splintage were predictors of failure of the modified technique.


Possible involvement of placental proteases in bradykinin (BK) degradation.
The hydrolysis of bradykinin (BK) by human placental subcellular fractions and pregnancy sera was studied in the presence of inhibitors by measuring amino acids liberated from BK by high-performance liquid chromatography. The effects of the inhibitors DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the essential roles of the above three proteases in BK degradation: among the three proteases, kininase I and endopeptidase 24.11 appeared to be the most important in kininase action in the placenta microsomes, whereas kininase I and ACE appeared to be the most important in kininase action in the placental cytosol, lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical arterial blood, umbilical venous blood and maternal plasma revealed higher concentrations in the mother than in the fetus. The present data suggest that degradation of BK in the placenta and pregnancy serum might contribute to the gradient of BK between mother and fetus.


Pulcherrimin protects Bacillus subtilis against oxidative stress during biofilm development.
Pulcherrimin is an iron-binding reddish pigment produced by various bacterial and yeast species. In the soil bacterium Bacillus subtilis, this pigment is synthesized intracellularly as the colorless pulcherriminic acid by using two molecules of tRNA-charged leucine as the substrate; pulcherriminic acid molecules are then secreted and bind to ferric iron extracellularly to form the red-colored pigment pulcherrimin. The biological importance of pulcherrimin is not well understood. A previous study showed that secretion of pulcherrimin caused iron depletion in the surroundings and growth arrest on cells located at the edge of a B. subtilis colony biofilm. In this study, we identified that pulcherrimin is primarily produced under biofilm conditions and provides protection to cells in the biofilm against oxidative stress. We presented molecular evidence on how pulcherrimin lowers the level of reactive oxygen species (ROS) and alleviates oxidative stress and DNA damage caused by ROS accumulation in a mature biofilm. We also performed global transcriptome profiling to identify differentially expressed genes in the pulcherrimin-deficient mutant compared with the wild type, and further characterized the regulation of genes by pulcherrimin that are related to iron homeostasis, DNA damage response (DDR), and oxidative stress response. Based on our findings, we propose pulcherrimin as an important antioxidant that modulates B. subtilis biofilm development.


Contribution of the Individual Small Intestinal α-Glucosidases to Digestion of Unusual α-Linked Glycemic Disaccharides.
The mammalian mucosal α-glucosidase complexes, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), have two catalytic subunits (N- and C-termini). Concurrent with the desire to modulate glycemic response, there has been a focus on di-/oligosaccharides with unusual α-linkages that are digested to glucose slowly by these enzymes. Here, we look at disaccharides with various possible α-linkages and their hydrolysis. Hydrolytic properties of the maltose and sucrose isomers were determined using rat intestinal and individual recombinant α-glucosidases. The individual α-glucosidases had moderate to low hydrolytic activities on all α-linked disaccharides, except trehalose. Maltase (N-terminal MGAM) showed a higher ability to digest α-1,2 and α-1,3 disaccharides, as well as α-1,4, making it the most versatile in α-hydrolytic activity. These findings apply to the development of new glycemic oligosaccharides based on unusual α-linkages for extended glycemic response. It also emphasizes that mammalian mucosal α-glucosidases must be used in in vitro assessment of digestion of such carbohydrates.


A Rare Case of Nontraumatic Thoracic Compression Fracture in a 28-Year-Old Man.
A 28-yr-old African American man with a history of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome, tobacco use, and sickle cell trait was referred to a physiatrist at a multidisciplinary spine center with a 1-yr history of nontraumatic thoracic back pain that had significantly worsened over the previous 4 wks. In the context of recurrent infections requiring hospital admissions and the patient's immunosuppressed status, magnetic resonance imaging of his thoracic spine was obtained, showing an acute or subacute anterior compression deformity of the T7 vertebral body. He was subsequently provided with a hyperextension brace, physical therapy referral, and a trial of intranasal calcitonin. The patient reported significant improvement in pain at his 3-mo follow-up appointment and continued to show pain and functional improvement in physical therapy sessions up to 6 mos later.


Forensically Important Blow Flies Chrysomya pinguis, C. villeneuvi, and Lucilia porphyrina (Diptera: Calliphoridae) in a Case of Human Remains in Thailand.
This is the first study to report Chrysomya pinguis (Walker) and Lucilia porphyrina (Walker) (Diptera: Calliphoridae) as forensically important blow fly species from human cadavers in Thailand, in addition to Chrysomya villeneuvi (Patton) already known in Thailand. In 2016, a fully decomposed body of an unknown adult male was discovered in a high mountainous forest during winter in Chiang Mai province. The remains were infested heavily with thousands of blow fly larvae feeding simultaneously on them. Morphological identification of adults reared from the larvae, and molecular analysis based on sequencing of 1,247 bp partial mitochondrial cytochrome c oxidase subunit 1 gene (CO1) of the larvae and puparia, confirmed the above mentioned 3 species. The approving forensic fly evidence by molecular approach was described for the first time in Thailand. Moreover, neighbor-joining phylogenetic analysis of the CO1 was performed to compare the relatedness of the species, thereby affirming the accuracy of identification. As species of entomofauna varies among cases in different geographic and climatic circumstances, C. pinguis and L. porphyrina were added to the list of Thai forensic entomology caseworks, including colonizers of human remains in open, high mountainous areas during winter. Further research should focus on these 3 species, for which no developmental data are currently available.


Differential response to stem cell factor and Flt3 ligand by the FAB subtype in acute myeloid leukemia clonogenic cells.
Proliferative response of blast clonogenic cells to various hematopoietic growth factors (HGF), including stem cell factor (SCF) and flt3 ligand (FL) was investigated in 100 patients with acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) in myeloid crisis (MC). The frequency of spontaneous colony formation was significantly high in CML in MC (55%) and AML French-American-British (FAB) subtype M4 (48%) compared with M2 (16%). No spontaneous colony was formed in any of the patients with M1 and M3. The frequency of proliferative response to various HGF alone and in combination according to FAB subtype and CML in MC was as follows: that to granulocyte colony-stimulating factor (G-CSF) was lowest in M1 and CML in MC (50%) compared with other FAB subtypes (>or=86%), that to granulocyte-macrophage CSF (GM-CSF) was lowest in CML in MC (44%) compared with FAB subtypes (>or=74%), and that to interleukin-3 (IL-3) was lowest in CML in MC (30%) compared with FAB subtypes (>or=78%). SCF and FL stimulated blast colony formation in 11% and 17% of patients with M3, respectively, but there was no response to both, and in 60% and 57% of patients with CML in MC, respectively, with 14% showing a response to both. The frequency of proliferative response to both SCF and FL increased in the order of M1 (33%), M2 (63%), M4-5 (95%), and M6 (100%). The results are summarized as follows: absence of spontaneous colony formation and response to HGF other than SCF and FL, designated as HGF-dependent growth (M3); spontaneous colony formation and lowest response to HGF, designated as autonomous growth (CML in MC); and spontaneous colony formation and highest response to HGF including SCF and FL, designated as autocrine growth (M4-6). M1 and M2 were intermediate between CML in MC and M4-6. The relation between in vitro growth pattern of blast clonogenic cells and prognosis in AML FAB subtype and CML in MC is discussed.


Design, synthesis and biological studies of a library of NK1-Receptor Ligands Based on a 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyran core: Switch from antagonist to agonist effect by chemical modification.
A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for agonists), compared to the substance P (SP) effect, in IPone assay. A set of these amino compounds was found to inhibit the action of SP, and therefore can be considered as a new family of SP-antagonists. Interestingly, the acylation of the 2-amino position causes a switch from antagonist to agonist activity. The 5-phenylsulfonyl-2-amino derivative 17 showed the highest antagonist activity, while the 5-p-tolylsulfenyl-2-trifluoroacetamide derivative 20R showed the highest agonist effect. As expected, in the case of the 5-sulfinylderivatives, there was an enantiomeric discrimination in favor of one of the two enantiomers, specifically those with (SS,RC) configuration. The anticancer activity studies assessed by using human A-549 lung cancer cells and MRC-5 non-malignant lung fibroblasts, revealed a statistically significant selective cytotoxic effect of some of these 2-amino-4H-pyran derivatives toward the lung cancer cells. These studies demonstrated that the newly synthesized 4H-pyran derivatives can be used as a starting point for the synthesis of novel SP-antagonists with higher anticancer activity in the future.