Hospital admissions through the emergency department: does insurance status matter?
To assess the effect of insurance status on the probability of admission and subsequent health status of patients presenting to emergency departments. We performed a prospective cohort study of patients with common medical problems at five urban, academic hospital emergency departments in Boston and Cambridge, Massachusetts. The outcome measure for the study was admission to the hospital from the emergency department and functional health status at baseline and follow-up. During a 1-month period, 2,562 patients younger than 65 years of age presented with either abdominal pain (52%), chest pain (19%) or shortness of breath (29%). Of the 1,368 patients eligible for questionnaire, 1,162 (85%) completed baseline questionnaires, and of these, 964 (83%) completed telephone follow-up interviews 10 days later. Fifteen percent of patients were uninsured and 34% were admitted to the hospital from the emergency department. Uninsured patients were significantly less likely than insured patients to be admitted, both when adjusting for urgency, chief complaint, age, gender and hospital (odds ratio = 0.5, 95% confidence interval 0.3 to 0.7), and when additionally adjusting for comorbid conditions, lack of a regular physician, income, employment status, education and race (odds ratio = 0.4, 95% confidence interval 0.2 to 0.8). However, there were no differences in adjusted functional health status between admitted and nonadmitted patients by insurance status, either at baseline or at 10-day follow-up. Uninsured patients with one of three common chief complaints appear to be less frequently admitted to the hospital than are insured patients, although health status does not appear to be affected. Whether these results reflect underutilization among uninsured patients or overutilization among insured patients remains to be determined.


Interaction impact of biocompost on nutrient dynamics and relations with soil biota, carbon fractions index, societal value of CO2 equivalent and ecosystem services in the wheat-rice farming.
This experiment aimed to understand the recycled industrial biocompost interaction with fertilizers doses on soil nutrient dynamics, soil organic carbon (SOC) fraction indexes, microbial population, positive ecosystem services, carbon dioxide (CO2) societal values and economy in wheat (Triticum aestivum L.)-rice (Oryza sativa L.) production. Based on the field and lab data, a significant interaction was observed between the biocompost and fertilizer levels; the fertilizer doses (FD)3 × biocompost (BC)1 were observed 80.6 grain and 56.0% higher straw yield in the wheat-rice crops than FD0 × BC9. Based on the results of soil organic carbon (SOC), the treatment FD3 × BC1 was observed more very labile (5.06 g kg-1) and moderately labile (4.26 g kg-1) carbon (C) fractions. However, C liability and recalcitrant indexes were recorded as non-significant. Further, the interaction effects of FD3 × BC1 found 65.7% more CO2 sequestration over FD0 × BC9. In terms of microbial dynamics, at 45 days after sowing (DAS), the treatment FD3 × BC4 was found to be the highest soil bacteria (56.6 × 107), fungi (32.3 × 105), and actinomycetes (49.1 × 106 cfu g-1) population. Further, regarding ecosystem services, the FD3 × BC1 found a maximum of US$ 1236 and 322 ha-1 year-1 grain and straw-based ecosystem services, respectively. However, the treatment FD3 × BC1 observed the maximum societal value (US$ 2041 ha-1). In contrast, higher economic values of 77.9 and 138.8% gross and net returns were recorded in the FD3 × BC1 compared to FD0 × BC9 in the wheat-rice cropping sequence (WRCS), respectively. Therefore, the study's hypothesis was to know the impact of the biocompost with fertilizers doses to enhance the nutrient and microbial dynamics, increasing SOC fractions (active and passive) and pools, CO2 sequestration, and restoring the soil health in the WRCS.


Poly(methacylic acid-co-maleic acid) grafted nanofibrillated cellulose as a reusable novel heavy metal ions adsorbent.
A poly(methacrylic acid-co-maleic acid) grafted nanofibrillated cellulose (NFC-MAA-MA) aerogel was prepared via radical polymerization in an aqueous solution using Fenton's reagent. The ensuing aerogel, in the form of a rigid porous material, was characterized by FTIR and NMR and used as an adsorbent for the removal of heavy metals from aqueous solutions. It showed an efficient adsorption, exceeding 95% toward Pb(2+), Cd(2+), Zn(2+) and Ni(2+) when their concentration was lower than 10 ppm and ranged from 90% to 60% for a metal concentration higher than 10 ppm. Over 98% of the adsorbed metal ion was recovered using EDTA as a desorbing solution, and the subsequent washing allowed the aerogel to be reused repeatedly without noticeable loss of adsorption capacity. It was concluded that the (NFC-MAA-MA) aerogel may be used as a high capacity and reusable sorbent material in heavy-metal removing processes.


Muscle Ultrasound Changes and Physical Function of Critically Ill Children: A Comparison of Rectus Femoris Cross-Sectional Area and Quadriceps Thickness Measurements.
Quadriceps thickness (QT) and rectus femoris cross-sectional area (RFCSA) are both used to evaluate muscle changes in critically ill children. However, their correlation and association with physical function has not been compared. To compare QT with RFCSA changes, and their association with physical function in critically ill children. Secondary analysis of a prospective cohort study of children 0-18 years old admitted to a tertiary mixed PICU between January 2015 and October 2018 with PICU stay greater than 48 hours and greater than or equal to one organ dysfunction. Ultrasound QT and RFCSA were measured at PICU admission, PICU discharge, hospital discharge, and 6 months post-discharge. QT and RFCSA changes from baseline were compared with each other and with change in motor function, physical ability, and physical health-related quality of life (HRQOL). Two hundred thirty-seven images from 66 subjects were analyzed. RFCSA change was not significantly different from QT change at PICU (-8.07% [interquartile range (IQR), -17.11% to 4.80%] vs -4.55% [IQR, -14.32% to 4.35%]; p = 0.927) or hospital discharge (-5.62% [IQR, -15.00% to 9.42%] vs -8.81% [IQR, -18.67% to 2.39%]; p = 0.238) but was significantly greater than QT change at 6 months (32.7% [IQR, 5.74-109.76%] vs 9.66% [IQR, -8.17% to 25.70%]; p < 0.001). Motor function change at PICU discharge was significantly associated with RFCSA change (adjusted β coefficient, 0.02 [95% CI, 0.01-0.03]; p = 0.013) but not QT change (adjusted β coefficient, -0.01 [95% CI, -0.02 to 0.01]; p = 0.415). Similar results were observed for physical HRQOL changes at hospital discharge (adjusted β coefficient for RFCSA change, 0.51 [95% CI, 0.10-0.92]; p = 0.017 and adjusted β coefficient for QT change, -0.21 [-0.76 to 0.35]; p = 0.458). Physical ability was not significantly associated with RFCSA or QT changes at 6 months post-discharge. Ultrasound derived RFCSA is associated with PICU motor function and hospital discharge physical HRQOL changes, unlike QT, and may be more useful for in-hospital muscle monitoring in critically ill children.


Stakeholder perceptions of lowering the blood alcohol concentration standard in the United States.
This study sought to better understand the past change in the legal blood alcohol concentration (BAC) standard from 0.10% to 0.08% in the United States, as well as explore stakeholder perceptions about potential health and other impacts of further lowering the standard below 0.08%. In-depth interviews were conducted with representatives of 20 organizations considered to have an interest and investment in the potential impacts of strategies to decrease alcohol-impaired related crashes and injuries. Interviews were conducted by a trained moderator, using a structured guide. Themes from the interviews are presented for several discussion topics explored for both the earlier change in the legal BAC limit from 0.10% to 0.08% and a potential lowering of the limit below 0.08%. Topics included arguments for and against change; organizational position on the change; stakeholders on both sides of the issue; strategies to support or oppose the change; health and economic impacts; and enforcement and adjudication challenges. Collectively, results suggest that moving the BAC standard below the current level will require considerable effort and time. There was strong, but not complete, agreement that it will be difficult, and maybe infeasible in the short-term, for states to implement a BAC standard lower than 0.08%.


Butterfat fatty acids differentially regulate growth and differentiation in Jurkat T-cells.
Synthetic Conjugated Linoleic Acid mixture (CLA; c9,t11; t10,c12-18:2) has been previously shown to inhibit growth, and enhance apoptosis and IL-2 mRNA synthesis in human lymphoblastic Jurkat T-cells. In this study, two different butterfat types were evaluated and compared for their effects on Jurkat cell viability, oxidative stress, pro-apoptotic activity, and cytokine synthesis: the conventionally produced butterfat (CBF), and organic butterfat (OBF) containing significantly higher amounts of c9,t11 (Rumenic Acid, RA), trans-vaccenic acid (VA; t11-18:1), alpha-linolenic acid (ALA), and lower levels of linoleic acid (LA). Results from cell treatment with both butterfat mixtures showed comparable oxidative stress (superoxide production, intracellular GSH depletion,and lipid peroxides yield), NADPH oxidase activation, cytotoxicity (LDH release), and IL-2 transcript level, whereas the effects of enhanced growth-inhibitory and pro-apoptotic activities were associated with OBF treatment. To then investigate each butterfat-induced effect caused by RA, VA, LA, and ALA, cells were exposed to synthetic FA concentrations similar to those from the different butterfats. Higher oxidative stress (superoxide production, intracellular GSH depletion) was induced by alpha-linolenic (ALA) and linoleic (LA) incubation (P<0.01) and superoxide production was suppressed by specific PKCalpha inhibitor (Gö 6976) and linked to increased toxicity and IL-2 synthesis inhibition. By contrast, cell treatment with RA increased apoptosis and IL-2 synthesis. These results suggest that a supply of ALA and LA is responsible for BF-induced oxidative stress via PKCalpha-NADPH oxidase pathway, and that enhanced antiproliferative effects in OBF treated cells is essentially determined by RA-induced pro-apoptotic activity.


COVID-19 vaccination, implications for PET/CT image interpretation and future perspectives.
The present paper aims to systematically review the literature on COVID-19 vaccine-related findings in patients undergoing PET/CT. The search algorithms included the following combination of terms: "PET" OR "positron emission tomography" AND "COVID"; "PET" OR "positron emission tomography" AND "COVID" AND "vaccination"; "PET" OR "positron emission tomography" AND "COVID", AND "autoimmune". We selected 17 articles which were assessed for quality and included in the systematic analysis. The most frequent vaccine-related signs on PET/CT were the deltoid [18F]FDG uptake and axillary hypermetabolic lymph nodes, which were described in 8-71% and 7-90% of the patients, respectively. Similarly, frequency of these findings using other tracers than [18F]FDG was greatly variable. This large variability was related to the variability in time elapsed between vaccination and PET/CT, and the criteria used to define positivity. In addition, vaccine-related findings were detected more frequently in young and immunocompetent patients than in elderly and immunocompromised ones. Therefore, awareness on vaccination status (timing, patient characteristics, and concurrent therapies) and knowledge on patterns of radiopharmaceutical uptake are necessary to properly interpret PET/CT findings.


[Non-thyroid illness" or changed thyroid hormone parameter syndrome with non-thyroid illnesses].
The multiple effects of systemic illness on thyroid economy are commonly referred to "non-thyroidal illness" (NTI) or "sick euthyroid syndrome". The various aspects of this common syndrome are summarized in this article. Results of the relevant studies published during the past 25 years were evaluated. The influence of the underlying illness and of drug administration was especially emphasized. The most common abnormalities in NTI are 1. the "low-T3 syndrome" due to a decreased T3 generation from T4 by a reduced activity of 5'-deiodinase (a selenoprotein); 2. the "low-T3 low-T4 state", which is associated with a poor prognosis. The low T4-levels are related to a binding inhibitor that displaces T4 from its binding proteins. However, there exists some controversy regarding the character of this binding inhibitor. 3. The high-T4 state is often found in acute psychiatric and liver diseases. The nutritional status of the patients and drugs known to influence thyroid hormone parameters have to be considered when patients with NTI are evaluated. Some difficulties may arise, when there is evidence of coexisting thyroid disease. Here aside from further biochemical evaluation such as thyroid antibodies, thyroid ultrasound and a thyroid scan have to be performed. NTI is associated with various alterations in thyroid hormone parameters when no intrinsic thyroid hormone disease exists. The severity of NTI reflects clinical outcome and clinical amelioration is associated with normalization of thyroid hormone parameters. There is no need for specific therapeutic intervention such as the administration of thyroid hormones in patients with the various forms of the NTI-syndrome.


Three-body physics. Observation of the Efimov state of the helium trimer.
Quantum theory dictates that upon weakening the two-body interaction in a three-body system, an infinite number of three-body bound states of a huge spatial extent emerge just before these three-body states become unbound. Three helium (He) atoms have been predicted to form a molecular system that manifests this peculiarity under natural conditions without artificial tuning of the attraction between particles by an external field. Here we report experimental observation of this long-predicted but experimentally elusive Efimov state of (4)He3 by means of Coulomb explosion imaging. We show spatial images of an Efimov state, confirming the predicted size and a typical structure where two atoms are close to each other while the third is far away.


On-line two-dimensional countercurrent chromatography×high performance liquid chromatography system with a novel fragmentary dilution and turbulent mixing interface for preparation of coumarins from Cnidium monnieri.
This study describes a novel on-line two-dimensional countercurrent chromatography×high performance liquid chromatography (2D CCC×HPLC) system for one-step preparative isolation of coumarins from the fruits of Cnidium monnieri. An optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds. In order to address the solvent incompatibility problem between CCC and RP-HPLC, a novel fragmentary dilution and turbulent mixing (FD-TM) interface was successfully developed. In detail, the eluent from the first dimensional CCC column was divided into fractions to form 'sample-dilution' stripes in the two switching sample loops, by the dilution water from the makeup pump. Following this, a long, thin tube was applied to mix the CCC eluent with water by in-tube turbulence, to reduce the solvent effect. Each CCC fraction was alternately trapped on the two holding columns for further preparative HPLC separation. This nationally designed FD-TM strategy effectively reduced post-column pressure and allowed a higher water dilution ratio at the post end of CCC, leading to improved sample recovery and a robust 2D CCC×HPLC isolation system. As a result, in a single 2D separation run (6.5h), eight target compounds (1-8) were isolated from 0.5g crude extract of C. monnieri, in overall yields of 1.3, 2.0, 0.5, 0.5, 0.8, 1.5, 8.2, and 15.0%, with HPLC purity of 90.1, 91.1, 94.7, 99.1, 99.2, 98.2, 97.9, and 91.9%, respectively. We anticipate that this improved 2D CCC×HPLC system, based on the novel FD-TM interface, has broad application for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.


Improvement of racial disparities with respect to the utilization of minimally invasive radical prostatectomy in the United States.
Race represents an established barrier to health care access in the United States and elsewhere. We examined whether race affects the utilization rate of minimally invasive radical prostatectomy (MIRP) in a population-based sample of individuals from the United States. Within the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients in whom MIRP and open radical prostatectomy (ORP) were performed between 2001 and 2007. We assessed the proportions and temporal trends in race distributions between MIRP and ORP. Multivariable logistic regression analyses further adjusted for age, year of surgery, baseline Charlson Comorbidity Index, annual hospital caseload tertiles, hospital region, insurance status, and median zip code income. Of 65,148 radical prostatectomies, 3581 (5.5%) were MIRPs. African Americans accounted for 11.4% of patients versus 78.8% for Caucasians versus 9.9% for others. Between 2001 and 2007, the annual proportions of Caucasian patients treated with MIRP were 2.2%, 0.9%, 2.6%, 7.2%, 4.7%, 9.3%, and 11.6%, respectively (chi-square trend p<0.001). For the same years in African American patients, the proportions were 0.8, 0.3, 1.4, 4.4, 3.5, 9.0 and 8.4% (chi-square trend P < .001). In multivariable analyses relative to Caucasian patients, African American patients were 14% less likely to undergo MIRP (P = .01). After period stratification between years 2001-2005 versus 2006-2007, African Americans were 22% less likely to undergo a MIRP in the early period (P = .007) versus 11% less likely to have a MIRP in the contemporary period (P = .1). The racial discrepancies in MIRP utilization rates are gradually improving.


[Research properties of the exogenous recombinant human heat shock protein HSP70 on test rodents].
Our research with Sprague-Dawley rats demonstrates protective properties of recombinant human heat shock protein 70 kDa (exogenous rhHSP70) as a prevent therapy agent for gram-positive sepsis. In this study we investigate acute toxicity of rhHSP70 on CD-1 mice and demonstrate very low dangerous of the substance.


Effects of pravastatin on serum adiponectin levels in female patients with type 2 diabetes mellitus.
Pravastatin has been reported to elevate circulating adiponectin levels in patients with various insulin resistant state, hypertension, coronary artery disease, and hypercholesterolemia. This study aimed to evaluate whether pravastatin increase serum total and high molecular weight adiponectin levels and improve insulin sensitivity in female patients with type 2 diabetes mellitus and hypercholesterolemia. This study was designed as a multicenter, double-blind, placebo-controlled, factorial randomized trial (placebo and pravastatin at 20 or 40 mg per day). A total of 73 female patients with type 2 diabetes and hypercholesterolemia were enrolled. Changes in total and high molecular weight (HMW) serum adiponectin levels, the ratio of HMW adiponectin to total adiponectin, insulin sensitivity measured by homeostasis model assessment of insulin resistance (HOMA-IR) and lipid profiles were evaluated after 16 weeks in each group. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly reduced after 16 weeks in the pravastatin 20 mg and 40 mg treatment groups compared with the placebo group (P = 0.008 and P = 0.004, respectively). However, there were no significant differences between the 20 mg and 40 mg pravastatin treatment groups in terms of total adiponectin and HMW adiponectin serum levels, as well as insulin sensitivity (P = 0.348 and P = 0.991). In female patients with type 2 diabetes and hypercholesterolemia, 16 weeks pravastatin therapy did not affect on serum total adiponectin or HMW adiponectin levels.


HAPPI GWAS: Holistic Analysis with Pre- and Post-Integration GWAS.
Advanced publicly available sequencing data from large populations have enabled informative genome-wide association studies (GWAS) that associate SNPs with phenotypic traits of interest. Many publicly available tools able to perform GWAS have been developed in response to increased demand. However, these tools lack a comprehensive pipeline that includes both pre-GWAS analysis, such as outlier removal, data transformation and calculation of Best Linear Unbiased Predictions or Best Linear Unbiased Estimates. In addition, post-GWAS analysis, such as haploblock analysis and candidate gene identification, is lacking. Here, we present Holistic Analysis with Pre- and Post-Integration (HAPPI) GWAS, an open-source GWAS tool able to perform pre-GWAS, GWAS and post-GWAS analysis in an automated pipeline using the command-line interface. HAPPI GWAS is written in R for any Unix-like operating systems and is available on GitHub (https://github.com/Angelovici-Lab/HAPPI.GWAS.git). Supplementary data are available at Bioinformatics online.


The temperature dependence of the calcium paradox: enzymatic, functional and morphological correlates of cellular injury.
An isolated rat heart preparation was used to characterize the temperature dependence of the calcium paradox and also to assess the validity of various indices of hypothermic protection. Hearts were subjected to 10-min periods of calcium depletion at various degrees of hypothermia followed by 20 min of normothermic calcium repletion. Using enzyme or protein leakage during calcium repletion as an index of hypothermic protection during calcium depletion, paradox injury was reduced extensively by relatively moderate hypothermia. Thus, depletion at 29 degrees C reduced total creatine kinase leakage by 57 +/- 4% from 1585 +/- 24 IU/g dry wt to 677 +/- 63 IU/g dry wt and at 25 degrees C leakage was reduced by 85 +/- 4% from 1585 +/- 24 IU/g dry wt to 237 +/- 71 IU/g dry wt. However, upon calcium repletion there was no recovery of contractile function. It was not until the myocardial depletion temperature was reduced to 20 degrees C that some functional recovery occurred. Under these circumstances cumulative creatine kinase leakage was reduced to below 88 IU/g dry wt, 6% of its normothermic value and protein leakage was undetectable. Functional recovery was not complete until the temperature was reduced to 15 degrees C or below. Correlation of cumulative enzyme leakage with functional recovery suggested a narrow release threshold (50 to 100 IU/g dry wt) above which no recovery occurred and below which a full recovery could be confidently predicted. Morphological assessments an all-or-none phenomenon; thus although increasingly severe hypothermia progressively reduced the percent of cells that sustained damage (as opposed to the degree of damage in all cells), it was not until 100% of cells appeared ultrastructurally undamaged that functional recovery was observed. Calcium-free perfusion at 4 degrees C protected the intercalated discs from gross lesions and prevented the separation of the external lamina from the surface coat. Our results also stress the heterogeneity of tissue injury and hypothermic protection and in addition shed further light upon the component mechanisms contributing to calcium injury.


Structural identification of electron transfer dissociation products in mass spectrometry using infrared ion spectroscopy.
Tandem mass spectrometry occupies a principle place among modern analytical methods and drives many developments in the 'omics' sciences. Electron attachment induced dissociation methods, as alternatives for collision-induced dissociation have profoundly influenced the field of proteomics, enabling among others the top-down sequencing of entire proteins and the analysis of post-translational modifications. The technique, however, produces more complex mass spectra and its radical-driven reaction mechanisms remain incompletely understood. Here we demonstrate the facile structural characterization of electron transfer dissociation generated peptide fragments by infrared ion spectroscopy using the tunable free-electron laser FELIX, aiding the elucidation of the underlying dissociation mechanisms. We apply this method to verify and revise previously proposed product ion structures for an often studied model tryptic peptide, [AlaAlaHisAlaArg+2H](2+). Comparing experiment with theory reveals that structures that would be assigned using only theoretical thermodynamic considerations often do not correspond to the experimentally sampled species.


Hyaluronan constitutively regulates activation of COX-2-mediated cell survival activity in intestinal epithelial and colon carcinoma cells.
Hyaluronan is a major component of the pericellular matrix surrounding tumor cells, including colon carcinomas. Elevated cycooxygenase-2 levels have been implicated in several malignant properties of colon cancer. We now show for the first time a strong link between hyaluronan-CD44 interaction and cyclooxygenase-2 in colon cancer cells. First, we have shown that increased expression of hyaluronan synthase-2 induces malignant cell properties, including increased proliferation, anchorage-independent growth, and epithelial-mesenchymal transition in HIEC6 cells. Second, constitutive hyaluronan-CD44 interaction stimulates a signaling pathway involving ErbB2, phosphoinositide 3-kinase/AKT, beta-catenin, and cyclooxygenase-2/prostaglandin E(2) in HCA7 colon carcinoma cells. Third, the HA/CD44-activated ErbB2 --> phosphoinositide 3-kinase/AKT --> beta-catenin pathway stimulates cell survival/cell proliferation through COX-2 induction in hyaluronan-overexpressing HIEC6 cells and in HCA7 cells. Fourth, perturbation of hyaluronan-CD44 interaction by hyaluronan oligomers or CD44-silencing RNA decreases cyclooxygenase-2 expression and enzyme activity, and inhibition of cyclooxygenase-2 decreases hyaluronan production suggesting the possibility of an amplifying positive feedback loop between hyaluronan and cyclooxygenase-2. We conclude that hyaluronan is an important endogenous regulator of colon cancer cell survival properties and that cyclooxygenase-2 is a major mediator of these hyaluronan-induced effects. Defining hyaluronan-dependent cyclooxygenase-2/prostaglandin E(2)-associated signaling pathways will provide a platform for developing novel therapeutic approaches for colon cancer.


Conservative treatment versus elective repair of umbilical hernia in patients with liver cirrhosis and ascites: results of a randomized controlled trial (CRUCIAL trial).
To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. Patients with an umbilical hernia and liver cirrhosis and ascites were randomly assigned to receive either elective repair or conservative treatment. The primary endpoint was overall morbidity related to the umbilical hernia or its treatment after 24 months of follow-up. Secondary endpoints included the severity of these hernia-related complications, quality of life, and cumulative hernia recurrence rate. Thirty-four patients were included in the study. Sixteen patients were randomly assigned to elective repair and 18 to conservative treatment. After 24 months, 8 patients (50%) assigned to elective repair compared to 14 patients (77.8%) assigned to conservative treatment had a complication related to the umbilical hernia or its repair. A recurrent hernia was reported in 16.7% of patients who underwent repair. For the secondary endpoint, quality of life through the physical (PCS) and mental component score (MCS) showed no significant differences between groups at 12 months of follow-up (mean difference PCS 11.95, 95% CI - 0.87 to 24.77; MCS 10.04, 95% CI - 2.78 to 22.86). This trial could not show a relevant difference in overall morbidity after 24 months of follow-up in favor of elective umbilical hernia repair, because of the limited number of patients included. However, elective repair of umbilical hernia in patients with liver cirrhosis and ascites appears feasible, nudging its implementation into daily practice further, particularly for patients experiencing complaints. Clinicaltrials.gov , NCT01421550, on 23 August 2011.


Citalopram prevents sleep-deprivation-induced reduction in CaMKII-CREB-BDNF signaling in mouse prefrontal cortex.
Curtailment of sleep in modern society leads to a spectrum of neuropsychiatric disorders. However, the molecular mechanisms underlying the effects of sleep deprivation (SD) remain elusive and currently there is no effective therapy to alleviate these effects. Here, we aimed to examine SD-induced cellular and molecular alterations in mouse prefrontal cortex (PFC) and whether subchronic citalopram (CTM) treatment can negate these alterations. Three-month-old C57BL/6 J mice were divided into control (Ctrl), SD, CTM alone and CTM + SD groups. CTM and CTM + SD group mice were treated with CTM for five consecutive days at a dose of 10 mg/kg per day before the experimental procedure. SD and CTM + SD group mice were sleep-deprived for 24 h using an automated treadmill method. We found that 24 h SD causes a marked reduction in the levels of phosphorylated calcium/calmodulin kinase II (pCaMKII), phosphorylated cyclic AMP-responsive element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in mouse PFC. Patch clamp recording of pyramidal neurons from acute PFC slices revealed that SD decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), suggesting a SD-induced postsynaptic alteration. Interestingly, subchronic CTM treatment prevents such SD-induced reductions in pCaMKII, pCREB and BDNF levels, and in mEPSC amplitude. These data suggest that CTM offers neuroprotection against SD-induced molecular and electrophysiological alterations.


Clinical factors determining pregnancy outcome after microsurgical tubal reanastomosis.
To evaluate pregnancy rates after tubal microsurgical anastomosis. Retrospective study. Private tertiary care center. Two hundred sixty-one women undergoing tubal microsurgical anastomosis. Tubal anastomoses were performed by minilaparotomy using microsurgical principles and approximating proximal and distal tubal ends in a two-layer technique with 8-0 ethylon. Pregnancy outcome was analyzed for the technique of sterilization, location of anastomosis, tubal length, age, and semen parameters. After exclusion of 89 patients lost to follow-up (34%) and 8 who did not attempt to conceive, 164 of the 261 patients were analyzed.The overall intrauterine pregnancy rate was 72.5%, with a miscarriage rate of 18% and a tubal pregnancy rate of 7.7%. Related to age, the cumulative intrauterine pregnancy rate was, respectively, 81%, 67%, 50%, and 12.5% for patients <36, 36-40, 40-43, and >43 years. Mean time to pregnancy was respectively 6.9, 6.2, and 12.7 months, respectively, for patients aged <36, 36-39, and 40-43 years According to the type of sterilization, intrauterine pregnancies occurred in 72% after ring sterilization, 78% after clip sterilization, 68% after coagulation, and 67% after Pomeroy sterilization. Intrauterine pregnancies and ectopic pregnancies, respectively, occurred in 80% and 3.4% in the isthmo-isthmic, 63% and 18% in the isthmo-ampullar, 75% and 8.3% in the isthmo-cornual, 100% and 0% in the ampullo-ampullar, and 60% and 0% in the ampullo-cornual anastomosis groups. Tubal length after anastomosis did not influence the pregnancy rate. In case of fertile sperm, the pregnancy rate was found to be 80%, and it decreased to 50% in case of subfertile semen. Our results clearly demonstrate the validity of tubal microsurgical anastomosis, establishing a quasinormalization of the fertility potential and offering the opportunity for a spontaneous conception.


Effects of organic matter on polycyclic aromatic hydrocarbons in riverine sediments affected by human activities.
Organic matter (OM) is an important component of riverine environments and a major factor in the migration and transformation of hydrophobic organic substances, such as polycyclic aromatic hydrocarbons (PAHs), to sediments. We studied the distributions, sources, and correlations between PAHs and OM in sediments from the Duliujian and the Beiyun rivers in North China. Sixteen PAHs were detected in the surface sediments at total concentrations ranging from 356 to 4652 ng·g-1 dry weight, which caused a moderate to high level of pollution. The PAH distributions were significantly and positively correlated with OM (p < 0.01) and higher concentrations were detected downstream of areas affected by human activity. Petroleum, coal, and wood combustion were the main sources of PAHs in riverine sediments, and the sources of OM in sediment included terrestrial and aquatic higher plants, soil, and sewage discharge. The OM accumulated and aged along the river, with increases in the degree of aromaticity and condensation, which led to stronger adsorption of PAHs. Our results will help to promote the management and restoration of contaminated riverine sediments.


Genotype frequency and use of single nucleotide polymorphisms for detection of informative allele by polymerase chain reaction.
To determine genotype frequency of biallelic single nucleotide polymorphisms and its use in detection of informative allele in donor/recipient pairs (sibling pairs) having undergone haematopoietic stem cell transplantation with various haematological disorders using a PCR based method. This descriptive study was conducted at GRC Lab Rawalpindi from Jan 2018- Oct 2019.A total of twenty donor/ recipient pairs (sibling pairs) were studied for genotype frequency and informativeness of single nucleotide polymorphisms. Genomic DNA was extracted from the peripheral blood and amplification of single nucleotide polymorphisms was done by PCR based method. The amplified DNA was seen by electrophoresis on 6% polyacrylamide gel. A sharp band of DNA on the polyacrylamide gel indicated a positive reaction. At least two or more informative SNP markers were found in every sibling pair. Our results demonstrate that PCR amplification of polyacrylamide gel electrophoresis using single nucleotide polymorphism has allowed the successful screening and detection of informative allele in all the donor/recipient pairs. (Sibling pairs). This PCR based assay using SNPs appears to be a quick, simple, reliable and technically feasible method for a use in a Pakistani setting.


Isolation of gene-edited cells via knock-in of short glycophosphatidylinositol-anchored epitope tags.
We describe Surface Oligopeptide knock-in for Rapid Target Selection (SORTS), a novel method to select mammalian cells with precise genome modifications that does not rely on cell cloning. SORTS is designed to disrupt the target gene with an expression cassette encoding an epitope tag embedded into human glycophosphatidylinositol (GPI)-anchored protein CD52. The cassette is very short, usually less than 250 nucleotides, which simplifies donor DNA construction and facilitates transgene integration into the target locus. The chimeric protein is then expressed from the target promoter, processed and exposed on the plasma membrane where it serves as a marker for FACS sorting with tag-specific antibodies. Simultaneous use of two different epitope tags enables rapid isolation of cells with biallelic knock-ins. SORTS can be easily and reliably applied to a number of genome-editing problems such as knocking out genes encoding intracellular or secreted proteins, protein tagging and inactivation of HIV-1 provirus.


Lipid research picks up speed on the slopes of Taos.
The 2002 Keystone Symposium on "Regulation of Cellular Responses by Lipid Mediators" provided a lively and active forum to discuss research in lipid signaling. This meeting review can provide only a glimpse into the diversity of research presented. Here we have chosen to highlight a group of exciting presentations describing novel features of the temporal and spatial regulation of phosphoinositides and their downstream targets.


Parent/caregiver satisfaction with their child's Medicaid plan and behavioral health providers.
The experiences of children in FFS and MC managed care plans (n = 715) were examined through satisfaction ratings by their parents/caregivers about their behavioral health provider and their Medicaid behavioral health plan. Multivariate regression analyses compared satisfaction ratings among children enrolled in FFS versus MC while controlling for other known predictors of satisfaction including child and parent/caregiver demographic characteristics, behavioral health status, and child history of behavioral health service use. Caregiver satisfaction with their children's behavioral health provider did not differ significantly between those children in managed care plans and those in fee-for-service plans. However, satisfaction ratings for Medicaid FFS plans were significantly more positive than those for Medicaid MC plans.


Quantitative distribution of calcitonin gene-related peptide in the rat central nervous system.
Using an antiserum directed against human calcitonin gene-related peptide (hCGRP), which fully cross reacts with rat CGRP, a sensitive radioimmunoassay was developed. The antiserum was characterized by displacement curve characteristics and high performance liquid chromatography. The assay was applied to rat brain tissue and the concentration of CGRP for 48 microdissected brain areas is presented. Highest levels (1000-4500 fmol/mg protein) were found in the central amygdaloid, caudate putamen, and spinal trigeminal nerve nucleus and tract, substantia gelatinosa, and the dorsal horn of the spinal cord. Moderate levels (200-600 fmol/mg protein) were found in the bed nucleus of the stria terminalis, the subfornical organ, the paraventricular, arcuate, dorsomedial, dorsal parabrachial, ambiguus and tractus solitarii nuclei and in the median eminence. These results coincide with those previously obtained by immunohistochemistry. The widespread distribution in the brain suggests involvement of CGRP in a variety of behavioral functions.


Characterisation by 1H NMR spectroscopy of oligosaccharides derived from alkali-extractable wheat-flour arabinoxylan by digestion with endo-(1-->4)-beta-D-xylanase III from Aspergillus awamori.
Alkali-extractable wheat-flour arabinoxylan, treated with endo-(1-->4)-beta-D-xylanase III from Aspergillus awamori CMI 142717, was fractionated by Bio-Gel P-2 size exclusion chromatography at 60 degrees C. Column fractions, corresponding to oligosaccharides with degrees of polymerisation from 5 to 10, were collected, and subfractionated by high performance anion-exchange chromatography on CarboPac PA-1. The structures of the oligosaccharides thus obtained were elucidated by 1H NMR spectroscopy, showing chains of (1-->4)-linked beta-D-xylopyranosyl residues differently substituted at O-3 and/or O-2,3 with alpha-L-arabinofuranosyl groups. The structures were different from those obtained with endo-(1-->4)-beta-D-xylanase I of the same xylanolytic enzyme system.


The feeding behaviour of a sit-and wait-predator, Ranatra dispar (Heteroptera: Nepidae): optimal foraging and feeding dynamics.
The feeding behaviour of R. dispar was examined with respect to the proportion of prey contents used, the time between successive captures (intercatch interval) and the feeding time. The feeding process consisted of three stages. (1) Injection of venom, (2) breakdown of tissue/digestive stage and (3) extraction of food. The rate of extraction from an individual prey decreases as its contents are depleted, but was shown to increase significantly during the first 15 min before decreasing. Even after 30 min the extraction rate was still marginally higher than the initial extraction rate. This phenomenon is quite different to what has previously been reported for sucking bugs.There was a negative relationship between increasing prey density and prey depletion, with the predators being significantly more 'wasteful', (i.e. prey were discarded before all extractable food was removed) at the two higher prey densities compared with those at the lower densities. As the prey density decreased from 60 to 1 prey per container, so the resultant intercatch interval, feeding time, and the average dry weight extracted per prey increased. No correlation was found between individual intercatch interval and subsequent feeding time when examined throughout a sequence of eight captures. This is taken to support the optimal feeding model in which the predator reacts to the average profitability of the environment (i.e. mean intercatch interval) rather than as reflected by the amount of food in the gut. The effect of the changing rate of extraction of food during a meal allows Ranatra, when exposed to high prey density, to feed for less than half the time on each prey item that it spends at low densities, and yet still obtain 60% of available food.


Glomalin-related soil protein: The particle aggregation mechanism and its insight into coastal environment improvement.
Glomalin-related soil protein (GRSP), a ubiquitous microbial product, plays a crucial role in particle aggregation and metal adsorption, but the underlying mechanisms remain unknown. Here, GRSP fraction was extracted from estuarine ecosystems and systematically characterized to elucidate the aggregation mechanisms and its impact on coastal environment improvement. We found that GRSP fraction (gravimetric mass of extracted GRSP, 5.1-24.3 mg g-1) was a globally relevant novel bioflocculant and that protein (linked to Bradford protein assay, 1.64-4.37 mg g-1) was the active flocculant constituent. The zeta potential, FTIR, XPS, and 13C NMR analyses identified its key constituents and structure, and revealed that the charge neutralization and bridging were GRSP fraction aggregation mechanisms. Thermogravimetric-infrared spectrometry analysis showed that GRSP fraction was highly thermostable, and the main volatile pyrolysis products included H2O, CO2, CO, and CH4. The SEM-EDX and XPS Fe valence spectroscopy suggested that GRSP fraction contained rich Fe (11.91 ± 0.48%) and could form Fe-rich flocs with particles. We also found that GRSP fraction has a high adsorption capacity (76-95%) for Cu, Zn, Pb and Cd, and its flocculation properties provide new insights into metal adsorption. The analysis of particle aggregation mechanism and its metal adsorption capacity is of great significance to elucidate the role of GRSP fraction in coastal environment improvement.


Methyloxime-substituted aminopyrrolidine: a new surrogate for 7-basic group of quinolone.
Novel fluoroquinolones containing oxime functionalized aminopyrrolidines have been synthesized. They were found to possess potent antibacterial activities against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Among these compounds, LB20277 (compound 12) showed the most favorable in vivo efficacy and pharmacokinetic profile in animals. Based on these promising results, LB20277 was selected as a candidate for further evaluation.


Clinical probability and alveolar dead space measurement for suspected pulmonary embolism in patients with an abnormal D-dimer test result.
Most patients with suspected pulmonary embolism (PE) have a positive D-dimer test and undergo diagnostic imaging. Additional non-invasive bedside tests are required to reduce the need for further diagnostic tests. We aimed to determine whether a combination of clinical probability assessment and alveolar dead space fraction measurement can confirm or exclude PE in patients with an abnormal D-dimer test. We assessed clinical probability of PE and alveolar dead space fraction in 270 consecutive in- and outpatients with suspected PE and positive D-dimer. An alveolar dead space fraction < 0.15 was considered normal. PE was subsequently excluded or confirmed by venous compression ultrasonography, spiral computed tomography and a 3-month follow-up. Radiologists were unaware of the results of clinical probability and capnography. PE was confirmed in 108 patients (40%). Capnography had a sensitivity of 68.5% (95% confidence interval [CI]: 58.9-77.1%) and a specificity of 81.5% (95% CI: 74.6-87.1%) for PE. Forty-five patients (16.6%) had both a low clinical probability and normal capnography (sensitivity: 99.1%, 95% CI: 94.9-100%) and 34 patients (12.6%) had both a high clinical probability and abnormal capnography (specificity: 100%, 95% CI: 97.7-100%). Capnography alone does not exclude PE accurately. The combination of clinical probability and capnography accurately excludes or confirms PE and avoids further testing in up to 30% of patients.


Effect of niacin monotherapy on high density lipoprotein composition and function.
Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL's cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C - 20%, q < 0.01; and triglyceride - 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q < 0.05). Niacin did not impact HDL's ability to influence endothelial function. Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.


Molecular detection and targeting of EWSR1 fusion transcripts in soft tissue tumors.
Soft tissue tumors are a heterogeneous group of tumors, traditionally classified according to morphology and histogenesis. Molecular classification divides sarcomas into two main categories: (a) sarcomas with specific genetic alterations and (b) sarcomas showing multiple complex karyotypic abnormalities without any specific pattern. Most chromosomal alterations are represented by translocations which are increasingly detected. The identification of fusion transcripts, in fact, not only support the diagnosis but also provides the basis for the development of new therapeutic strategies aimed at blocking aberrant activity of the chimeric proteins. One of the genes most susceptible to breakage/translocation in soft tissue tumors is represented by Ewing sarcoma breakpoint region 1 (EWSR1). This gene has a large number of fusion partners, mainly associated with the pathogenesis of Ewing's sarcoma but with other soft tissue tumors too. In this review, we illustrate the characteristics of this gene/protein, both in normal cellular physiology and in carcinogenesis. We describe the different fusion partners of EWSR1, the molecular pathways in which is involved and the main molecular biology techniques for the identification of fusion transcripts and for their inhibition.


Resonant Raman quantification of zeaxanthin production from Flavobacterium multivorum.
Resonant Raman scattering was used as a novel, rapid, non-destructive optical technique to measure zeaxanthin levels in Flavobacterium multivorum ATCC 55238. Culture broth, after bacterial growth for 40 h, exhibited characteristic resonance Raman vibrational modes at 1159 cm(-1) (C-C stretch) and 1525 cm(-1) (C=C stretch) upon excitation at 488 nm. A striking correlation was observed between the carotenoid level as estimated by HPLC and by resonance Raman spectroscopy.


Mitoxantrone (dihydroxyanthracenedione) in acute leukemia. An evaluation of two treatment schedules by the Southwest Oncology Group.
Fifty-eight evaluable patients with acute leukemia were treated with Mitoxantrone (DHAD) according to two schedules: 14 mg/M2 as a single I.V. pulse dose administered three-week intervals, and 4 mg/M2/day for five days every three weeks. Six of 58 patients achieved a complete remission. One complete remission and 1 partial remission were observed among 26 patients treated with the single pulse schedule. Five (16%) complete remissions were attained among 32 patients treated on the daily x 5 schedule. Responses were observed only in patients with non-lymphoblastic leukemia. DHAD was very well tolerated with myelosuppression as the major toxicity. Nausea and vomiting were minimal. Subclinical cardiac toxicity occurred in two patients. This was identified by serial reductions in cardiac ejection fractions. DHAD appears to have significant activity in acute non-lymphoblastic leukemia with minimal toxicity.


A role for retinoic acid in homeostatic plasticity.
Prolonged changes in neuronal activity trigger compensatory modifications in synaptic function to restore firing rates to normal levels. In this issue of Neuron, Aoto et al. demonstrate that synthesis of retinoic acid offsets chronic network inactivity by increasing synaptic strength through upregulation of GluR1 receptors.


Modification of the Kock pouch urinary diversion in a child.
We constructed a continent ileal urinary reservoir (Kock pouch) in a 9-year-old boy. The length of bowel required to achieve a satisfactory outcome was scaled down for this young, small child.


The voltammetric study of 2-mercapto-5-phenylammino-1,3,4-thiadiazole using carbon paste electrodes.
A rapid and accurate voltammetric method for the quantitative determination of 2-mercapto-5-phenylammino-1,3,4-thiadiazole (MPATD) with carbon paste electrodes (CPE) has been developed. The study was made by cyclic voltammetry between -0.4 and +0.6 V with 50 mV s(-1) sweep rate in aqueous solution. After successive oxidation/reduction cycles we found a total oxidation of MPATD at +0.45 V. As the compound is oxidated, the reduction current peak increases at +0.13 V, indicating an irreversible process. Following only the oxidation process in the -0.1 to +0.6 V range, we investigated the optimum scan rates at different current densities and pH values (realised with buffers, pH between 1.0 and 10.0) with CPE versus Ag/AgCl reference electrode using linear sweep voltammetry. We found a good linear relation between the current peak height and concentration in a 2.5 x 10(-9)-1.25 x 10(-7) mol ml(-1). This method allows the quantitative detection of the MPATD as it or from dosage forms and biological media.


Impact of Staphylococcus aureus on the pathogenesis of chronic cystic fibrosis lung disease.
One of the first pathogens which can be isolated from the airways of cystic fibrosis (CF) patients is Staphylococcus aureus, which often persists in this hostile environment for many months or even years. The increase in infections due to the methicillin-resistant S. aureus (MRSA) worldwide and even more the emergence of community-acquired MRSA, which differ from nosocomial MRSA by lack of multiresistance and carriage of a phage-encoded toxin, Panton-Valentine leukocidin, attracts new attention to the epidemiology, pathogenesis, and impact of S. aureus in the background of CF. In this review, recent data and studies will be reported and discussed to give an overview of the latest research.


An mRNA atlas of G protein-coupled receptor expression during primary human monocyte/macrophage differentiation and lipopolysaccharide-mediated activation identifies targetable candidate regulators of inflammation.
G protein-coupled receptors (GPCRs) are among the most important targets in drug discovery. In this study, we used TaqMan Low Density Arrays to profile the full GPCR repertoire of primary human macrophages differentiated from monocytes using either colony stimulating factor-1 (CSF-1/M-CSF) (CSF-1 Mϕ) or granulocyte macrophage colony stimulating factor (GM-CSF) (GM-CSF Mϕ). The overall trend was a downregulation of GPCRs during monocyte to macrophage differentiation, but a core set of 10 genes (e.g. LGR4, MRGPRF and GPR143) encoding seven transmembrane proteins were upregulated, irrespective of the differentiating agent used. Several of these upregulated GPCRs have not previously been studied in the context of macrophage biology and/or inflammation. As expected, CSF-1 Mϕ and GM-CSF Mϕ exhibited differential inflammatory cytokine profiles in response to the Toll-like Receptor (TLR)4 agonist lipopolysaccharide (LPS). Moreover, 15 GPCRs were differentially expressed between these cell populations in the basal state. For example, EDG1 was expressed at elevated levels in CSF-1 Mϕ versus GM-CSF Mϕ, whereas the reverse was true for EDG6. 101 GPCRs showed differential regulation over an LPS time course, with 65 of these profiles being impacted by the basal differentiation state (e.g. GPRC5A, GPRC5B). Only 14 LPS-regulated GPCRs showed asynchronous behavior (divergent LPS regulation) with respect to differentiation status. Thus, the differentiation state primarily affects the magnitude of LPS-regulated expression, rather than causing major reprogramming of GPCR gene expression profiles. Several GPCRs showing differential profiles between CSF-1 Mϕ and GM-CSF Mϕ (e.g. P2RY8, GPR92, EMR3) have not been widely investigated in macrophage biology and inflammation. Strikingly, several closely related GPCRs displayed completely opposing patterns of regulation during differentiation and/or activation (e.g. EDG1 versus EDG6, LGR4 versus LGR7, GPRC5A versus GPRC5B). We propose that selective regulation of GPCR5A and GPCR5B in CSF-1 Mϕ contributes to skewing toward the M2 macrophage phenotype. Our analysis of the GPCR repertoire expressed during primary human monocyte to macrophage differentiation and TLR4-mediated activation provides a valuable new platform for conducting future functional analyses of individual GPCRs in human macrophage inflammatory pathways.


Role of the guanine nucleotide binding protein, Gαo, in the development of morphine tolerance and dependence.
The use of morphine and other opioids for chronic pain is limited by the development of analgesic tolerance and physical dependence. Morphine produces its effects by activating the μ opioid receptor, which couples to Gαi/o-containing heterotrimeric G proteins. Evidence suggests that the antinociceptive effects of morphine are mediated by Gαo. However, the role of Gαo in the development of morphine tolerance and dependence is unknown. The objective of the study is to evaluate the contribution of Gαo to the development of morphine tolerance and dependence in mice. 129S6 mice lacking one copy of the Gαo gene (Gαo +/-) were administered morphine acutely or chronically. Mice were examined for tolerance to the antinociceptive action of morphine using the 52 °C hot plate as the nociceptive stimulus and for dependence by evaluating the severity of naltrexone-precipitated withdrawal. Wild-type littermates of the Gαo +/- mice were used as controls. Changes in μ receptor number and function were determined in midbrain and hindbrain homogenates using radioligand binding and μ agonist-stimulated [35S]GTPγS binding, respectively. Following either acute or chronic morphine treatment, all mice developed antinociceptive tolerance and physical dependence, regardless of genotype. With chronic morphine treatment, Gαo +/- mice developed tolerance faster and displayed more severe naltrexone-precipitated withdrawal in some behaviors than did wild-type littermates. Morphine tolerance was not associated with changes in μ receptor number or function in brain homogenates from either wild-type or Gαo +/- mice. These data suggest that the guanine nucleotide binding protein Gαo offers some protection against the development of morphine tolerance and dependence.


Development of a Rapid LC-MS/MS Method for the Determination of Emerging Fusarium mycotoxins Enniatins and Beauvericin in Human Biological Fluids.
A novel method for the simultaneous determination of enniatins A, A1, B and B1 and beauvericin, both in human urine and plasma samples, was developed and validated. The method consisted of a simple and easy pretreatment, specific for each matrix, followed by solid phase extraction (SPE) and detection by high performance liquid chromatography-tandem mass spectrometry with an electrospray ion source. The optimized SPE method was performed on graphitized carbon black cartridges after suitable dilution of the extracts, which allowed high mycotoxin absolute recoveries (76%-103%) and the removal of the major interferences from the matrix. The method was extensively evaluated for plasma and urine samples separately, providing satisfactory results in terms of linearity (R² of 0.991-0.999), process efficiency (>81%), trueness (recoveries between 85% and 120%), intra-day precision (relative standard deviation, RSD < 18%), inter-day precision (RSD < 21%) and method quantification limits (ranging between 20 ng·L(-1) and 40 ng·L(-1) in plasma and between 5 ng·L(-1) and 20 ng·L(-1) in urine). Finally, the highly sensitive validated method was applied to some urine and plasma samples from different donors.


Implementation of a Neurotrauma Hotline for post-hospital continuity of care.
There are 4.8 million emergency department (ED) visits for traumatic brain injury (TBI) annually in the United States. Many of these patients do not receive educational information or follow-up care. Our institution implemented a Neurotrauma Hotline for TBI patients. This study describes our implementation and utilization of a Neurotrauma Hotline at a Level I trauma center. Callers and outcomes of calls to the hotline over a 12-month period were analyzed. Correlation analysis was done to assess relationship between hotline calls and TBI clinic volumes. There were 1205 calls to the hotline. Calls were most commonly from internal providers or patients, with 338 repeat callers. The call reason was frequently an appointment (36.8%) or advice (32.1%). There were 334 TBI clinic visits, and however, there was no statistically significant correlation between number of hotline calls and number of clinic visits (r = .417; P = .177). There was widespread utilization of our hotline. Other institutions wishing to adopt similar practices can expect that the majority of calls will be for appointment scheduling or clinical advice. Further work is needed to determine whether implementation of a Neurotrauma Hotline improves resource utilization and patient outcomes.


Successful live birth following hysteroscopic adhesiolysis under laparoscopic observation for Asherman's syndrome: A case report.
Asherman's syndrome is characterized by reduced menstrual volume and adhesions within the uterine cavity and cervix, resulting in inability to carry a pregnancy to term, placental malformation, or infertility. We present the case of a 40-year-old woman diagnosed with Asherman's syndrome who successfully gave birth to a live full-term neonate after hysteroscopic adhesiolysis under laparoscopic observation, intrauterine device insertion, and Kaufmann therapy. A 40-year-old woman (Gravida 3, Para 0) arrived at our hospital for specialist care to carry her pregnancy to term. She had previously undergone six sessions of dilation and curettage owing to a hydatidiform mole and persistent trophoblastic disease, followed by chemotherapy. She subsequently became pregnant twice, but both pregnancies resulted in spontaneous miscarriages during the first trimester. Her menstrual periods were very light and of short duration. Hysteroscopic adhesiolysis with concurrent laparoscopy was performed, and Asherman's syndrome was diagnosed. The uterine adhesions covered the area from the internal cervical os to the uterine fundus. Postoperative Kaufmann therapy was administered, and endometrial regeneration was confirmed using hysteroscopy. She became pregnant 9 mo postoperatively and delivered through elective cesarean section at 37 wk of gestation. The postpartum course was uneventful, and she was discharged on postoperative day 7. Hysteroscopic adhesiolysis with concurrent laparoscopy enables identification and resection of the affected area and safe and accurate surgery, without complications.


Noninvasive assessment of chorioretinal oxygenation changes in experimental carotid occlusion.
To demonstrate the capability of our optical imaging system to assess oxygenation changes in chorioretinal vasculatures due to experimentally induced carotid occlusion. Chorioretinal oxygenation was assessed by projecting a narrow laser line at an angle on the retina after intravenous injection of an oxygen sensitive probe and imaging phosphorescence emission. Optical section phosphorescence imaging was performed in rats, under steady-state conditions and during unilateral occlusion of the common carotid artery. Phosphorescence intensity was measured in the retinal vein, artery, capillaries, and choroid vascular areas. Oxygenation was defined as the inverse of phosphorescence intensity. Oxygenation changes in the four vascular areas were determined relative to initial preocclusion oxygenation values and compared to measured changes under steady-state conditions. Under steady-state conditions, phosphorescence intensity in chorioretinal vasculatures remained constant, displaying a change of < or = 8% over time. At 12 +/- 5 s from initiation of occlusion, oxygenation decreased in the retinal venous, arterial, capillary, and choroidal circulations by -41 +/-19%, -10 +/- 5%, -20 +/- 18%, -10 +/- 5%, respectively (p < or = 0.05; n = 6). At 30 +/- 10 s from initiation of occlusion, oxygenation change in the retinal vein, artery, capillaries, and choroid was -9 +/- 12%, -2 +/- 4%, -11 +/- 21%, -1 +/- 8%, respectively, and not statistically different as compared to steady-state oxygenation changes (p > or = 0.3; n = 6). Optical section phosphorescence imaging technique can be used to assess intravascular oxygenation changes and may be a valuable tool for studying disease-related oxygen dynamics in the chorioretinal vasculatures.


Starch structure in developing barley endosperm.
Barley spikes of the cultivars/breeding lines Gustav, Karmosé and SLU 7 were harvested at 9, 12 and 24 days after flowering in order to study starch structure in developing barley endosperm. Kernel dry weight, starch content and amylose content increased during development. Structural analysis was performed on whole starch and included the chain-length distribution of the whole starches and their β-limit dextrins. Karmosé, possessing the amo1 mutation, had higher amylose content and a lower proportion of long chains (DP ≥38) in the amylopectin component than SLU 7 and Gustav. Structural differences during endosperm development were seen as a decrease in molar proportion of chains of DP 22-37 in whole starch. In β-limit dextrins, the proportion of Bfp-chains (DP 4-7) increased and the proportion of BSmajor-chains (DP 15-27) decreased during development, suggesting more frequent activity of starch branching enzymes at later stages of maturation, resulting in amylopectin with denser structure.


Design of enhanced agonists through the use of a new virtual screening method: application to peptides that bind class I major histocompatibility complex (MHC) molecules.
A new screening procedure is described that uses docking calculations to design enhanced agonist peptides that bind to major histocompatibility complex (MHC) class I receptors. The screening process proceeds via single mutations of one amino acid at the positions that directly interact with the MHC receptor. The energetic and structural effects of these mutations have been studied using fragments of the original ligand that vary in length. The results of these docking studies indicate that the mutant affinity ranking of long peptides can be practically reproduced with a screening approach performed using fragments of six residues. Fragments of four and five residues could mimic, in some cases, the structural arrangement of the side chains of the full-length peptide. We have compared the structural and energetic results of the docking calculations with experimental data using three unrelated ligand peptides that differ greatly in their affinity for the MHC complex. Analysis of the affinity of the fragments led to the identification of three important parameters in the construction of fragments that mimic the structural and energetic properties of the full-length ligand: the length of the fragment; its intermolecular energy; and the number and localization, internal or terminal, of the anchor residues. The results of this new peptide-design methodology have been applied to suggest new peptides derived from the MUC1-8 peptide that could be used as murine vaccines that trigger the immune response through the MHC class I protein H-2K(b).


The balancing act: patient care time versus cost.
With demands to improve patients' clinical outcomes and decrease the escalating costs of inpatient care, nurse executives are focusing on how nurses spend their time rather than just raising staffing levels to positively impact patient outcomes. Because nursing wages constitute a high proportion of a hospital's budget, understanding the costs of nursing activities is critical to managing them. An activity-based costing approach was used in 14 medical-surgical nursing units to study nursing activities and their related costs. Time use for 4 patient care activities (assess, teach, treat, provide psychosocial support) and 2 support activities (coordinate care and manage clinical records) including the percent of non-value-added (NVA) time for each of these activities was identified through focus groups, interviews, and timed observations. Annualized wage costs were assigned to these activities to determine average wage-related costs of each activity as well as NVA-related costs. More than one-third of nurses' time was considered NVA, averaging dollars 757,000 per nursing unit in wage costs annually. Nurses spent more time on support activities (56%) than in providing patient care (44%), with the least amount of time being spent on patient teaching and psychosocial support. Findings indicate a huge opportunity to both improve clinical outcomes in these units and, at the same time, reduce costs by focusing on processes to reduce the high amount time spent performing NVA and support activities and increase patient care time, particularly patient teaching and psychosocial support.


Impact of universal varicella vaccination on 1-year-olds in Uruguay: 1997-2005.
Varicella vaccination was introduced at the end of 1999 into the Uruguayan immunisation schedule for children aged 12 months. Varilrix (Oka strain; GlaxoSmithKline Biologicals) has been the only vaccine used since then and coverage has been estimated to exceed 90% since the start of the universal varicella vaccination programme. We assessed the impact of the Uruguayan varicella vaccination programme during 2005, 6 years after its introduction. Information on hospitalisations was collected from the main paediatric referral hospital and information on medical consultations for varicella was collected from two private health insurance systems in Montevideo. The proportion of hospitalisations due to varicella and the proportion of ambulatory visits for varicella since the introduction of the vaccine were compared between 1999 and 2005 and 1997 and 1999 in the following age groups: <1 year, 1-4 years, 5-9 years and 10-14 years. By 2005, the proportion of hospitalisations due to varicella among children, was reduced by 81% overall and by 63%, 94%, 73% and 62% in the <1, 1-4, 5-9 and 10-14 years age groups, respectively. The incidence of ambulatory visits for varicella among children was reduced by 87% overall and by 80%, 97%, 81% and 65% in the <1, 1-4, 5-9 and 10-14 years age groups, respectively. The burden of varicella has decreased substantially in Uruguayan children since the introduction of the varicella vaccination, including those groups outside the recommended vaccination age. It is expected to decrease further as more cohorts of children are vaccinated and herd immunity increases.


Prospective evaluation of contrast-enhanced computed tomography for the detection of colonic diverticular bleeding.
To prospectively evaluate the role of contrast-enhanced computed tomography (CE-CT) in the detection of colonic diverticular bleeding (CDB). Consecutive patients who presented with hematochezia and were clinically suspected of CDB were prospectively enrolled. Those who could undergo both CE-CT and total colonoscopy, and who were finally diagnosed as CDB, were included in the analysis. Fifty-two cases were finally included in the analysis. The detection rate of CDB by CT was 15.4 % (8/52). Univariate analysis showed that the interval from the latest episode of hematochezia to the performance of CT and the presence of a past history of CDB were contributing factors for detection. The interval was 1.6 ± 4.6 h (mean ± SD) in patients detected by CT, and 3.4 ± 3.2 h in those without detection. The detection rate of CDB by total colonoscopy was 38.5 % (20/52). The overall detection rate was 46.2 % (24/52), which was superior to what CT or colonoscopy alone achieved. CE-CT may play a complementary role to colonoscopy in patients with suspected CDB, but is not recommended for all cases due to its low detection rate. Patients who can be examined within 2 h of last hematochezia would be candidates for urgent CT.


Two rTMS sessions per week: a practical approach for treating major depressive disorder.
Depression is one of the leading causes of disability in the world, and a disease that contributes greatly to the global burden of disease. Repetitive transcranial magnetic stimulation (rTMS) has proven to be a well-tolerated, effective treatment for depression. The present study was designed to evaluate the efficacy of an rTMS treatment scheme with a fewer number of sessions per week. In total 91 adult university students with major depressive disorder (MDD). This was a double-blind, randomized clinical trial in which 15 sessions of rTMS were given to each one of two treatment groups made up of adults with active MDD. One treatment group received two sessions per week, the other received five. The study protocol included their respective sham rTMS groups. The patients who received active rTMS also participated in a follow-up procedure that consisted of two sessions of active rTMS per month for three more months. Measurements by the Hamilton Rating Scale for Depression (HAMD) showed that the groups which received active rTMS had higher percentages of antidepressant response at 96 and 95.5% for five and two sessions/week, respectively, compared to the sham rTMS groups: 27.3 and 4.5% for five and two sessions/week, respectively. Observations at the end of the 3-month follow-up phase showed that the improvements in HAMD scores were maintained in both groups. This study contributes to demonstrating that rTMS with a more practical schedule of two sessions/week is an effective antidepressant treatment that could be considered the first choice for managing symptoms of depression.


Inactivation of gram-negative bacteria in milk and banana juice by hen egg white and lambda lysozyme under high hydrostatic pressure.
The effect of hen egg white lysozyme (HEWL) and bacteriophage lambda lysozyme (LaL) in combination with high pressure (HP) treatment on the inactivation of four gram-negative bacteria (Escherichia coli O157:H7, Shigella flexneri, Yersinia enterocolitica and Salmonella typhimurium), was studied in skim milk (pH 6.8; a(w) 0.997) and in banana juice (pH 3.8; a(w) 0.971). In the absence of lysozymes, S. flexneri was more sensitive to HP in milk than in banana juice, while the opposite was observed for the other three bacteria. In combination with HP treatment, LaL was more effective than HEWL on all bacteria in both milk and banana juice. Depending on the bacteria, inactivation levels in banana juice were increased from 0.4-2.7 log units by HP treatment alone to 3.6-6.5 log units in the presence of 224 U/ml LaL. Bacterial inactivation in milk was also enhanced by LaL but only by 0.5-2.1 log units. Under the experimental conditions used, LaL was more effective in banana juice than in milk, while the effectiveness of HEWL under the same conditions was not significantly affected by the food matrix. This effect could be ascribed to the low pH of the banana juice since LaL was also more effective on E. coli in buffer at pH 3.8 than at pH 6.8. Since neither LaL nor HEWL are enzymatically active at pH 3.8, we analysed bacterial lysis after HP treatment in the presence of these enzymes, and found that inactivation proceeds through a non-lytic mechanism at pH 3.8 and a lytic mechanism at pH 6.8. Based on these results, LaL may offer interesting perspectives for use as an extra hurdle in high pressure food preservation.


Cangrelor in Patients With Coronary Artery Disease Pretreated With Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study.
There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor. This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor. In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included VerifyNow P2Y12 reaction units (PRU), light transmittance aggregometry, vasodilator-stimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7 time points. Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. Compared with placebo, the use of cangrelor in patients pretreated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162).


Gender differences in risk of posttraumatic stress symptoms after disaster among older people: Differential exposure or differential vulnerability?
Women have been observed to have a higher risk of developing posttraumatic stress symptoms (PTSS) after disaster compared to men. In a study of survivors of an earthquake, we sought to investigate: whether there was differential exposure to disaster-related trauma by gender; whether women and men have differential vulnerability to trauma; and what factors could explain the gender difference in PTSS. Data from a cohort of community-dwelling older survivors of the 2011 Great East Japan Earthquake and Tsunami was used. Data were obtained before (2010) and 2.5-years after the disaster (n = 3,334). Women suffered 1.6 times higher prevalence of PTSS than men (31.0% vs. 19.4%). Women were more likely to experience loss of relatives (29.2% vs. 23.2%), while men were more likely to report loss of friends (17.1% vs. 14.5%) and separation from work (7.5% vs. 4.6%). We did not find evidence for differential vulnerability to disaster-related trauma. Indeed, the gender gap in PTSS was larger among individuals who did not experience trauma. Women experienced greater deterioration of non-kin instrumental support, which significantly mediated the association between gender and PTSS. We have no information on PTSS prior to the earthquake. Nor do we have clinician diagnoses of PTSD. Women experienced housing damages and loss of relatives more often than men, which explained ∼21% of the gender gap in PTSS after disaster. Women reported more non-kin support prior to the disaster, but they also experienced greater deterioration of it, which explained ∼21% of the gender gap.


Per-operative haemodynamic assessment of lower limb arterial surgery. Part 2: Modelling of the arterial system.
A simple lumped parameter model has been constructed to characterize the arterial system of the lower limb in man. It is found that such a simple model can represent the system and provide an excellent match with experimental blood flow and pressure data obtained during reconstructive arterial surgery. Based on the values of the model parameters, the model is able to predict the success and failure of surgery with the help of a discriminant function. The physical quantities of length and Young's Modulus of the model tube, however, are found to be outside the physiological range.


Lipocalin-2 production by astrocytes in response to high concentrations of glutamate.
Glutamate-induced excitotoxicity is mainly mediated by neuronal NMDA receptors; however, it is unclear how astrocytes are involved in this phenomenon. This study aimed to explore the effects of excess glutamate on astrocytes both in vitro and in vivo. We used astrocyte-enriched cultures (AECs), in which microglia were removed from mixed glial cultures, to investigate the effects of extracellular glutamate on these cells by microarray, quantitative PCR, ELISA, and immunostaining. We also examined the production of lipocalin-2 (Lcn2) by immunohistochemistry in the brains of mice after status epilepticus induced by pilocarpine and by ELISA in the cerebrospinal fluid (CSF) of patients characterised by status epilepticus. Microarray analysis identified Lcn2 as a factor upregulated in AECs by excess glutamate; glutamate addition increased Lcn2 in the cytoplasm of astrocytes and AECs released Lcn2 in a concentration-dependent manner. Lcn2 production was reduced by chemical inhibition of metabotropic glutamate receptor or siRNA knockdown of metabotropic glutamate receptor 3. Furthermore, Lcn2 was increased in the astrocytes of a status epilepticus mouse model and in the CSF of human patients. These results indicate that astrocytes stimulate Lcn2 production via metabotropic glutamate receptor 3 in response to high concentrations of glutamate.


Synthesis and cytotoxicity of oligomycin A derivatives modified in the side chain.
A novel way of chemical modification of the macrolide antibiotic oligomycin A (1) at the side chain was developed. Mesylation of 1 with methane sulfonyl chloride in the presence of 4-dimethylaminopyridine produced 33-O-mesyl oligomycin in 56% yield. Reactions of this intermediate with sodium azide produced the key derivative 33-azido-33-deoxy-oligomycin A in 60% yield. 1,3-Dipolar cycloaddition reaction with propiolic acid, methyl ester of propiolic acid, and phenyl acetylene resulted in 33-deoxy-33-(1,2,3-triazol-1-yl)oligomycin A derivatives substituted at N4 of the triazole cycle. The mesylated oligomycin A and 33-deoxy-33-azidooligomycin A did not inhibit F0F1 ATFase ATPase; however, 33-azido-33-deoxy-oligomycin A and the derivatives containing 4-phenyltriazole, 4-methoxycarbonyl-triazole and 3-dimethylaminoethyl amide of carboxyltriazole substituents demonstrated a high cytotoxicity against K562 leukemia and HCT116 human colon carcinoma cell lines whereas non-malignant skin fibroblasts were less sensitive to these compounds. Novel series of oligomycin A derivatives allow for the search of intracellular molecules beyond F0F1 ATP synthase relevant to the cytotoxic properties of this perspective chemical class.


The Occurrence of Seizure Clusters in Patients With Epilepsy Is Partly Determined by Epilepsy Severity: A Single-Center Retrospective Observational Study.
Purpose: This retrospective observational study aimed to investigate the self-reported prevalence of seizure clusters (SCs) in patients with epilepsy (PWE) and its relationship with clinical characteristics. Methods: We retrospectively analyzed data from consecutive PWE from our hospital in northeastern China. Data were collected from the databank of a tertiary epilepsy center. Logistic regression models were employed to investigate the relationships between the individual patient demographic/clinical variables and the occurrence of SC. Results: In total, 606 consecutive PWE were included in the final analysis, and 268 (44.2%) patients experienced at least one seizure cluster. In multivariate logistic regression models, age (OR: 1.014; 95% CI: 1.002-1.027; p = 0.02), seizure frequency (OR: 2.08; 95% CI: 1.555-2.783; p < 0.001), multiple seizure types (OR: 5.111; 95% CI: 1.737-15.043; p = 0.003), number of current anti-seizure medications (ASM) (OR: 1.533; 95% CI: 1.15-2.042; p = 0.004), drug-resistant epilepsy (OR: 1.987; 95% CI: 1.159-3.407; p = 0.013), and a history of status epilepticus (OR: 1.903; 95% CI: 1.24-2.922; p = 0.003) were independent variables associated with a history of SC in PWE. Conclusion: Seizure clusters (SCs) are common occurrences at our study center. The occurrence of SC in individuals with epilepsy, to some extent, is determined by the epilepsy severity.


Spindle cell pancreatic endocrine tumor associated with Cushing's syndrome.
A 59-yr old female presented with Cushing's syndrome due to ectopic ACTH production. At the time of initial diagnosis an obvious source for the Cushing's syndrome was not found and the patient was treated with bilateral adrenalectomy. Three years later she presented with hyperpigmentation and evidence of ACTH overproduction. This time a CT scan localized a mass to the tail of the pancreas and a distal pancreatectomy was performed. The mass was composed of compact plump spindle cells arranged in interlacing fascicles, was well circumscribed, and did not display angioinvasion. Although isolated punctate foci of necrosis were noted, the overall mitotic count was 1 per 10 high power fields. Immunohistochemistry showed the tumor to be positive for chromogranin, synaptophysin, and ACTH. This case highlights an unusual histological variant of pancreatic endocrine tumor (PET), namely, one composed almost exclusively of interlacing spindle-shaped cells. This raises a wide differential diagnosis and the use of immunohistochemistry is required to arrive at the correct diagnosis. ACTH-producing PET are usually aggressive lesions with metastases at the time of presentation and aggressive biological behavior. However, this case was characterized by an indolent clinical course.


Heavy multinodular cutaneous lymphoid infiltrates: clinicopathologic features and B-cell clonality.
Criteria for distinguishing between cutaneous lymphoid hyperplasia (CLH) and low-grade B-cell lymphoma are not well defined. We examined the hypothesis that the presence of a clonal B-cell population in heavy multinodular lymphoid infiltrates correlates with clinical presentation and outcome. We identified 29 patients with skin lesions characterized histologically by a heavy dermal lymphocytic infiltrate with a multinodular architecture and extension into deep dermis and subcutaneous fat. Clonality was assessed immunophenotypically by light-chain restriction and also by analysis for IgH-gene rearrangement using PCR on DNA extracted from paraffin blocks. Follow-up (mean 80 months; median 45 months) was obtained in all patients. Twenty-four patients (83%) presented with a solitary lesion: only four had solitary recurrences, and none developed multiple synchronous lesions or systemic B-cell lymphoma. However, 9/24 of these solitary lesions (38%) were clonal by light-chain restriction or IgH PCR; 5/29 patients (17%) presented with multiple recurrent lesions and continued to develop lesions during the period of follow-up; 3/5 patients (60%) with multiple lesions demonstrated a B-cell clone. No patient developed systemic B-cell lymphoma. Heavy, multinodular cutaneous lymphoid infiltrates have an excellent prognosis. Multiple lesions at presentation are the best predictor of recurrent multiple lesions confined to the skin. The presence of a clonal B-cell population does not correlate with clinical presentation or histology, nor does it predict development of further lesions or systemic lymphoma.


Anesthesia for pediatric airway surgery: recommendations and review from a pediatric referral center.
Pediatric airway surgery presents many significant challenges to the anesthesia provider. The clinical experience of the Massachusetts Eye and Ear Infirmary serves as a guide in this review to describe the clinical reasoning and perioperative management of the pediatric patient needing airway surgery, with specific emphasis on diagnostic procedures, trauma, laryngotracheal reconstruction, juvenile recurrent respiratory papillomatosis, and adenotonsillectomy.


Identification of altered dipeptidyl-peptidase activities as potential biomarkers for unipolar depression.
Changes in circulatory aminopeptidases [dipeptidyl-peptidase-IV (DPP-IV), Prolyl-oligopeptidase (POP) and Leucine aminopeptidase (LAP)] activities have been found to be associated with psychiatric illnesses and inflammatory diseases. The discriminatory indices of aminopeptidases activities were assessed by enzymatic assays in plasma samples from 240 unipolar depression (UD) patients and 264 matched controls. In addition the relationship between soluble and cellular DPP-IV activity was determined in plasma and blood cells from healthy subjects. Greater than 95% of the plasma DPP-IV activity could be blocked by inhibitors, demonstrating the specificity of the assay. Also, DPP-IV protein and activity levels were strongly correlated. In contrast, only 50% of the membrane-bound activity in blood cells was inhibited, which suggested that other similar peptidases may be present in these cells. UD patients had decreased plasma levels of DPP-IV and POP activities compared to healthy controls with a concomitant increase in LAP activity. Finally, testing of the LAP/DPP-IV ratio resulted in good discrimination of UD patients from controls with an area under the curve-receiver operating characteristic of 0.70. Further biological validation studies using different cohorts are warranted. The finding that plasma DPP-IV activity was decreased and LAP activity was increased in UD patients suggests the potential value for testing the levels of these enzymes for improved classification of patients. In addition, the changes in these enzymes, suggests that the proteolytic maturation of their proneuropeptide and prohormone subtrates may also be affected in UD, resulting in altered production of the associated bioactive peptides.


Complete Genome Sequences of Weissella cibaria Strains CMU, CMS1, CMS2, and CMS3 Isolated from Infant Saliva in South Korea.
Weissella cibaria strain CMU is used as a commercial oral care probiotic in South Korea. Here, we present the complete genome sequences of four W. cibaria strains (CMU, CMS1, CMS2, and CMS3) isolated from the saliva of an infant living in Gwangju, South Korea.


Lysosomal diseases: biochemical pathways and investigations.
This chapter summarizes our current knowledge of lysosomes and lysosomal proteins referring to recent reviews, general schemes for degradation of substrates, and various causes of lysosomal storage diseases (LSDs). It then discusses the main principles for laboratory diagnosis. Initial screening by study of accumulated substrates in urine is helpful for mucopolysaccharidoses and oligosaccharidoses. A majority of LSDs result from the deficient activity of one acid hydrolase (in some diseases, several). Establishment of the diagnosis in this group of disorders is based on the measurement of the particular enzymic activity. Pseudodeficiencies are a possible source of error. For defects in lysosomal membrane transporters such as cystinosin or sialin, study of substrate accumulation in readily available cells/fluids is still the method of choice. Demonstration of a metabolic block in living cells is rarely used today, except for Niemann-Pick C disease. For primary diagnosis of patients, molecular genetic testing is necessary when no functional tests exist (e.g., many ceroid lipofuscinoses, Danon disease) and it is the preferred strategy when functional tests are too elaborate. Genotyping patients already diagnosed by biochemical methods is, however, essential for genetic counseling in the family; it may also be useful for optimal management.


Resistance of succinic acid dimethyl ester insulinotropic action to exendin (9-39) amide.
Exendin (9-39) amide (Ex [9-39]) was recently proposed for use in the treatment of alimentary or reactive hypoglycaemia. It was indeed found to antagonise the insulinotropic action of GLP-1 in rats infused with the dimethyl ester of succinic acid (SAD). We have now investigated whether, under comparable experimental conditions, Ex (9-39) also opposes the insulin-releasing action of SAD itself. Since this was not the case, Ex (9-39) could be safely used to abolish the incretin effect of GLP-1 without interfering with the control of insulin secretion by circulating nutrients.


Neuroimaging reveals a potential brain-based pre-existing mechanism that confers vulnerability to development of chronic painful chemotherapy-induced peripheral neuropathy.
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists. This prospective, multicentre cohort study recruited from three sites across Scotland. Brain functional MRI (fMRI) scans (3 Tesla) were carried out on chemotherapy naïve patients at a single fMRI centre in Edinburgh, Scotland. Nociceptive stimuli (with a 256 mN monofilament) were administered during the fMRI. Development of chronic sensory/painful CIPN (CIPN+) was determined based upon European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 changes conducted 9 months after chemotherapy, and imaging data analysed using standard software. Of 30 patients recruited (two lung, nine gynaecological, and 19 colorectal malignancies), data from 20 patients at 9 months after chemotherapy was available for analysis. Twelve were classified as CIPN+ (mean age, 63.2[9.6] yr, 9.6; six female), eight as CIPN- (mean age 62.9 [SD 5.5] yr, four female). In response to punctate stimulation, group contrast analysis showed that CIPN+ compared with CIPN- had robust activity in sensory, motor, attentional, and affective brain regions. An a priori chosen region-of-interest analysis focusing on the periaqueductal grey, an area hypothesised as relevant for developing CIPN+, showed significantly increased responses in CIPN- compared with CIPN+ patients. No difference in subcortical volumes between CIPN+ and CIPN- patients was detected. Before administration of any chemotherapy or appearance of CIPN symptoms, we observed altered patterns of brain activity in response to nociceptive stimulation in patients who later developed chronic sensory CIPN. This suggests the possibility of a pre-existing vulnerability to developing CIPN centred on brainstem regions of the descending pain modulatory system.


Preparation and characterization of large dioctadecyldimethylammonium chloride liposomes and comparison with small sonicated vesicles.
Dioctadecyldimethylammonium chloride (DODAC) unilamellar liposomes with a mean external diameter of 0.5 micron and sharp gel-to-liquid-crystalline phase transition temperatures (Tc) were obtained by chloroform vaporization and compared with small sonicated DODAC vesicles. Sucrose, impermeant through large DODAC liposomes and sonicated vesicles, was used for internal volume determinations. The internal volumes for large DODAC liposomes and sonicated DODAC vesicles were 9.0 +/- 1.3 and 0.13 +/- 0.2 l/mol, respectively. Ideal osmometer behaviour, towards KCl (0-50 mM) and sucrose, was observed only for large DODAC liposomes. Sonicated DODAC vesicles were osmotically non-responsive towards sucrose and flocculated upon addition of KCl. At temperatures near the Tc, a steep increase in the initial shrinkage rate and a minimum for the total extent of shrinkage were observed for large DODAC liposomes. Large DODAC liposomes are proposed as an adequate synthetic membrane model.


Room-temperature C-H bond alkynylation by merging cobalt and photocatalysts.
A new protocol is developed for the mono- and bis-ortho-C-H alkynylation of easily accessible benzamide derivatives using alkynyl bromides at room temperature by merging cobalt and photocatalysts. The diverse reactivity of various alkynyl bromides towards the C-H alkynylation and competing C-H/N-H bond annulation reactions has been demonstrated to give the corresponding products in good yields with excellent functional group tolerance.


Distribution of misonidazole in human tumours and normal tissues.
Levels of misonidazole in human tumours, normal tissues and blood have been measured in patients given a 1g oral dose of drug before surgery or biopsy. The results show that 50--70% of the blood level was found in a wide range of tumours and that similar levels were found in adjacent normal tissues. Good penetration of drug was achieved within tumours, and up to 90--100% of the blood level was found in the necrotic cyst fluid at the centre of some tumours. CSF studies showed free diffusion into the CNS, which was confirmed by finding 50--70% of the blood level within brain tumours. A delay of passage of drugs into the CSF was noted, which was not found for drug diffusion into bile and saliva.


Status epilepticus severity influences the long-term outcome of neurogenesis in the adult dentate gyrus.
Status epilepticus (SE) is characterized by continual seizure activity that can vary widely in the intensity of convulsions. We induced seizures by applying continuous electrical stimulation to the hippocampus in adult rats to explore the effects of three different SE states on neurogenesis and neuronal death in the hippocampus. Rats exhibiting the most severe SE state (fully convulsive) demonstrated profound increases in cell proliferation in the dentate gyrus (DG) at 1 week post-insult, but the majority of the new neurons had died at 4 weeks. In contrast, rats exhibiting less severe SE states (ambulatory or masticatory, partial convulsive) had the same degree of cell proliferation at 1 week, but most new neurons survived at 4 weeks. As compared to partially convulsive SE rats, fully convulsive SE rats had significantly greater DG pathology. Our data indicate that SE of varying severity triggers similar short-term proliferation of neural progenitors, but that the long-term outcome of neurogenesis is influenced by the degree of insult-induced degeneration in the DG tissue environment.


Ingestion of microplastics by commercial fish off the Portuguese coast.
The digestive tract contents of 263 individuals from 26 species of commercial fish were examined for microplastics. These were found in 17 species, corresponding to 19.8% of the fish of which 32.7% had ingested more than one microplastic. Of all the fish that ingested microplastics, 63.5% was benthic and 36.5% pelagic species. A total of 73 microplastics were recorded, 48 (65.8%) being fibres and 25 (34.2%) being fragments. Polymers were polypropylene, polyethylene, alkyd resin, rayon, polyester, nylon and acrylic. The mean of ingested microplastics was 0.27 ± 0.63 per fish, (n=263). Pelagic fish ingested more particles and benthic fish ingested more fibres, but no significant differences were found. Fish with the highest number of microplastics were from the mouth of the Tagus river. Scomber japonicus registered the highest mean of ingested microplastics, suggesting its potential as indicator species to monitor and investigate trends in ingested litter, in the MSFD marine regions.


Nrf2-ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases.
Neurodegenerative diseases (NDDs) are predicted to be the biggest health concern in this century and the second leading cause of death by 2050. The main risk factor of these diseases is aging, and as the aging population in Western societies is increasing, the prevalence of these diseases is augmenting exponentially. Despite the great efforts to find a cure, current treatments remain ineffective or have low efficacy. Increasing lines of evidence point to exacerbated oxidative stress, mitochondrial dysfunction and chronic neuroinflammation as common pathological mechanisms underlying neurodegeneration. We will address the role of the nuclear factor E2-related factor 2 (Nrf2) as a potential target for the treatment of NDDs. The Nrf2-ARE pathway is an intrinsic mechanism of defence against oxidative stress. Nrf2 is a transcription factor that induces the expression of a great number of cytoprotective and detoxificant genes. There are many evidences that highlight the protective role of the Nrf2-ARE pathway in neurodegenerative conditions, as it reduces oxidative stress and neuroinflammation. Therefore, the Nrf2 pathway is being increasingly considered a therapeutic target for NDDs. Herein we will review the deregulation of the Nrf2 pathway in different NDDs and the recent studies with Nrf2 inducers as "proof-of-concept" for the treatment of those devastating pathologies.