Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.
Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children. Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo. Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074). These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children. Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.


Down-Regulation of Thioredoxin1 Is Involved in Death of Calu-6 Lung Cancer Cells Treated With Suberoyl Bishydroxamic Acid.
Suberoyl bishydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, can show an anticancer effect. In this study, we investigated the effects of SBHA on the growth inhibition and death of Calu-6 and NCI-H1299 cells in relation to reactive oxygen species (ROS) and antioxidant levels. SBHA inhibited the growth of Calu-6 and NCI-H1299 lung cancer cells with an IC50 of 50 µM at 72 h. This agent induced apoptosis in Calu-6 cells and triggered to a G2/M phase arrest in NCI-H1299 cells. Although it also reduced the growth of normal human pulmonary fibroblast (HPF) cells, the susceptibility of Calu-6 cells to SBHA was higher than that of HPF cells. In addition, SBHA did not affect the growth of human small airway epithelial cells (HSAEC). Regarding ROS and antioxidant levels, SBHA increased ROS level and glutathione (GSH) depletion in Calu-6 and NCI-H1299 cells whereas it decreased ROS levels in HPF and HSAEC. SBHA also decreased thioredoxin1 (Trx1) level in Calu-6 cells. Although the down-regulation of Trx1 intensified apoptosis and ROS level in SBHA-treated Calu-6 cells, the overexpression of Trx1 attenuated apoptosis and ROS level in these cells. This down-regulation of Trx1 did not affect apoptosis-signaling regulating kinase1 (ASK1) activation. In conclusion, the down-regulation of Trx1 by SBHA was closely involved in cell death in Calu-6 cells.


Sexual function after aortic surgery.
Male patients attending for follow up after aortic surgery have often commented that there has been a change in their sexual function. A survey of patients attending vascular outpatient clinic and private practice following aortic surgery was carried out by personal interview. Of those who were sexually active before operation, 40% thought that there had been a diminution in performance and 11% thought that there was some improvement. Similar results have been found in other centres. Aortic surgery carries a risk of diminution in sexual function as a consequence of the operation. It is the duty of the surgeon to warn patients of this risk when seeking informed consent.


Effect of phenolic compounds from pretreated sugarcane bagasse on cellulolytic and hemicellulolytic activities.
This work shows both cellulases and hemicellulases are inhibited and deactivated by water-soluble and acetone extracted phenolics from sugarcane bagasse pretreated at 10% (w/v) for 30 min in liquid hot water at 180 or 200°C. The dissolved phenolics in vacuum filtrate increased from 1.4 to 2.4 g/L as temperature increased from 180 to 200°C. The suppression of cellulose and hemicellulose hydrolysis by phenolics is dominated by deactivation of the β-glucosidase or β-xylosidase components of cellulase and hemicellulase enzyme by acetone extract at 0.2-0.65 mg phenolics/mg enzyme protein and deactivation of cellulases and hemicellulases by the water soluble components in vacuum filtrate at 0.05-2mg/mg. Inhibition was a function of the type of enzyme and the manner in which the phenolics were extracted from the bagasse.


In the Right Place at the Right Time: Is TMC1/2 the Transduction Channel for Hearing?
Recent papers suggest that TMC1 and TMC2 constitute the ion channels mediating hearing and balance. Kurima et al. (2015) now show these proteins are expressed in the right place and at the right time, bringing us closer to definitive identification.


Rising incidence of paediatric inflammatory bowel disease (PIBD) in Wessex, Southern England.
There has been a significant increase in the incidence of paediatric inflammatory bowel disease (PIBD) over the last 25 years although there is no recent data from England. We aimed to analyse changes in incidence within a defined English population over the last decade and compare this to recent and historical incidence data from comparable studies. The new diagnosis incidence of PIBD (age less than or equal to 16 years) was recorded from a prospective database for a geographically defined area within Southern England (2002-2012). Data were analysed for two separate time periods (cohort 1:2002-2006 and cohort 2:2008-2012) and compared to data from the British Paediatric Surveillance Unit (BPSU) survey in 1998/1999. Data were analysed by age, sex and disease type. There has been an increase in incidence of PIBD from 6.39/100,000/year during cohort 1 to 9.37/100,000/year during cohort 2 (p=0.0002). This compares with the BPSU incidence data in England (1998-1999) of 5.2/100,000/year. There was no statistically significant difference in median age of diagnosis between cohorts (p=0.46). The incidence of Crohn's disease (CD) was 3.8/100,000/year in cohort 1 rising to 5.85/100,000/year in cohort 2 (p=0.001). The incidence of ulcerative colitis (UC) was 2.01/100,000/year in cohort 1 rising to 2.62/100,000/year in cohort 2 (p=0.1458). Overall PIBD incidence is higher in males in cohort 1 (male-to-female ratio 1.35:1) and cohort 2 (male-to-female ratio 1.5:1). The incidence of PIBD continues to increase with a rise of almost 50% in the last decade in Southern England. The reasons for this increase remain unclear.


MRI of tibial stress fractures: relationship between Fredericson classification and time to recovery in pediatric athletes.
Tibial stress fractures are not uncommon in pediatric athletes. The severity of injury may be graded using magnetic resonance imaging (MRI). To determine whether Fredericson MRI grading of tibial stress fractures can differentiate times to recovery across different grades in pediatric athletes. A medical record search identified all athletes younger than 19 years old who had tibial stress fractures confirmed by MRI and were treated by sports medicine specialists in our clinic system over a 5-year period. Two pediatric radiologists graded MRI exams using the Fredericson system. Time to recovery (in days) was defined in four ways: pain onset to full participation, pain onset to zero pain, first treatment to full sport participation and first treatment to zero pain. Recovery times were compared to tibial stress fracture Fredericson MRI grade and to the use of a recovery device. Thirty-eight pediatric athletes (age range: 7-18 years, mean: 15.4±2.2 years) had 42 tibial stress fractures while participating in 12 different sports. About half (55%) were track and/or cross-country athletes. The mean time from diagnosis to report of no pain for all patients was 55.6±5.0 days. We found no significant difference in time to recovery across stress fracture grade or with the use of a recovery device. No differences were noted between Fredericson stress fracture grades and different time periods to recovery or between differences in recovery time and the return to full participation in sports, regardless of the use of assistive devices.


Preferential Metabolic Improvement by Intermittent Fasting in People with Elevated Baseline Red Cell Distribution Width: A Secondary Analysis of the WONDERFUL Randomized Controlled Trial.
Red cell distribution width (RDW) predicts cardiovascular outcomes, but it is unstudied with regard to intermittent fasting. In WONDERFUL trial subjects, the effect of the interaction between baseline RDW and intermittent fasting on changes in insulin and other cardiometabolic endpoints and the effect of fasting on changes in RDW were evaluated. The subjects enrolled were aged 21-70 years and were free of statins, anti-diabetes medications, and chronic diseases, and had ≥1 metabolic syndrome feature, as well as elevated low-density lipoprotein cholesterol. Subjects were randomized to 24-h, water-only fasting (twice per week for 4 weeks, once per week for 22 weeks) or 26 weeks of ad libitum eating. Subjects (N = 71; n = 38 intermittent fasting, n = 33 controls) had more substantial changes in insulin in intermittent fasting vs. controls (-3.45 ± 2.27 vs. 0.48 ± 3.55 mIU/L) when baseline RDW size distribution (RDW-SD) was ≥median (42.6 fL) than <median (-1.99 ± 2.80 vs. -1.08 ± 3.40 mIU/L) (p-interaction = 0.039). Results were similar but weaker for glucose, HOMA-IR, and metabolic syndrome score. RDW-SD (intermittent fasting: 1.27 ± 9.6 fL vs. control: -0.37 ± 1.76 fL, p = 0.34) was unchanged by fasting at 26 weeks. Intermittent fasting decreased insulin more in subjects with higher baseline RDW. RDW may identify individuals who derive the most health benefits from intermittent fasting and who have the most cause to adhere to a fasting regimen.


Radiation-induced abnormal cortical thickness in patients with nasopharyngeal carcinoma after radiotherapy.
Conventional MRI studies showed that radiation-induced brain necrosis in patients with nasopharyngeal carcinoma (NPC) in years after radiotherapy (RT) could involve brain gray matter (GM) and impair brain function. However, it is still unclear the radiation-induced brain morphological changes in NPC patients with normal-appearing GM in the early period after RT. In this study, we acquired high-resolution brain structural MRI data from three groups of patients, 22 before radiotherapy (pre-RT) NPC patients with newly diagnosed but not yet medically treated, 22 NPC patients in the early-delayed stage after radiotherapy (post-RT-ED), and 20 NPC patients in the late-delayed stage after radiotherapy (post-RT-LD), and then analyzed the radiation-induced cortical thickness alteration in NPC patients after RT. Using a vertex-wise surface-based morphometry (SBM) approach, we detected significantly decreased cortical thickness in the precentral gyrus (PreCG) in the post-RT-ED group compared to the pre-RT group. And the post-RT-LD group showed significantly increased cortical thickness in widespread brain regions, including the bilateral inferior parietal, left isthmus of the cingulate, left bank of the superior temporal sulcus and left lateral occipital regions, compared to the pre-RT group, and in the bilateral PreCG compared to the post-RT-ED group. Similar analysis with ROI-wise SBM method also found the consistent results. These results indicated that radiation-induced brain injury mainly occurred in the post-RT-LD group and the cortical thickness alterations after RT were dynamic in different periods. Our findings may reflect the pathogenesis of radiation-induced brain injury in NPC patients with normal-appearing GM and an early intervention is necessary for protecting GM during RT.


Molecular organization of the antifungal and anticancer drug 2-(2,4-dihydroxyphenylo)-5,6-dichlorobenzothiazole in solution and in monolayers: an effect of pH.
2-(2,4-Dihydroxyphenylo)-5,6-dichlorobenzothiazol (dHBBT) is a new anticancer, antifungal and antibacterial drug characterised also by cytostatic and anticancer activity. The effect of pH on the molecular organization of dHBBT in monomolecular layers and in solution has been studied by electronic absorption and FT-IR spectroscopies. The analysis of the spectroscopic data suggests that at neutral and at high pH values (pH 6-8) dHBBT appears in the anionic form that prevents the formation of dimers due to the electrostatic repulsion between the molecules.


[Diagnostic algorithm for transitory hip osteoporosis--including computerized tomography].
The radiological appearances and diagnostic procedures for transitory osteoporosis of the hip are described. The proposed algorithm includes computed tomography of the hip joint. By means of this method, effusion and thickening of the joint capsule can be recognized with certainty and the indications for diagnostic aspiration of the joint can be defined.


A phylogenetically distinct Middle East respiratory syndrome coronavirus detected in a dromedary calf from a closed dairy herd in Dubai with rising seroprevalence with age.
Middle East respiratory syndrome coronavirus (MERS-CoV) was detected by monoclonal antibody-based nucleocapsid protein-capture enzyme-linked immunosorbent assay (ELISA), RNA detection, and viral culture from the nasal sample of a 1-month-old dromedary calf in Dubai with sudden death. Whole genome phylogeny showed that this MERS-CoV strain did not cluster with the other MERS-CoV strains from Dubai that we reported recently. Instead, it formed a unique branch more closely related to other MERS-CoV strains from patients in Qatar and Hafr-Al-Batin in Saudi Arabia, as well as the MERS-CoV strains from patients in the recent Korean outbreak, in which the index patient acquired the infection during travel in the eastern part of the Arabian Peninsula. Non-synonymous mutations, resulting in 11 unique amino acid differences, were observed between the MERS-CoV genome from the present study and all the other available MERS-CoV genomes. Among these 11 unique amino acid differences, four were found in ORF1ab, three were found in the S1 domain of the spike protein, and one each was found in the proteins encoded by ORF4b, ORF5, envelope gene, and ORF8. MERS-CoV detection for all other 254 dromedaries in this closed dairy herd was negative by nucleocapsid protein-capture ELISA and RNA detection. MERS-CoV IgG sero-positivity gradually increased in dromedary calves with increasing age, with positivity rates of 75% at zero to three months, 79% at four months, 89% at five to six months, and 90% at seven to twelve months. The development of a rapid antigen detection kit for instantaneous diagnosis is warranted.Emerging Microbes & Infections (2015) 4, e74; doi:10.1038/emi.2015.74; published online 2 December 2015.


Residual plots for linear regression models with censored outcome data: A refined method for visualizing residual uncertainty.
Residual plots are a standard tool for assessing model fit. When some outcome data are censored, standard residual plots become less appropriate. Here, we develop a new procedure for producing residual plots for linear regression models where some or all of the outcome data are censored. We implement two approaches for incorporating parameter uncertainty. We illustrate our methodology by examining the model fit for an analysis of bacterial load data from a trial for chronic obstructive pulmonary disease. Simulated datasets show that the method can be used when the outcome data consist of a variety of types of censoring.


Spatial variation of the local tissue oxygen diffusion coefficient measured in situ in the cat retina and cornea.
A method for measuring the local oxygen diffusion coefficient (D) in an intact tissue, in situ, in a living cat is described. Values of D were calculated from nonlinear regression analysis of the polarographic (turn-on) transients using a semi-empirical model for the retina and a theoretical one for the cornea. Two types of microelectrodes were employed: in the retina, ones with extremely short recesses; and in the cornea, bare metal needles. The local D in the cat retina was practically homogeneous with a mean of 1.97 +/- 0.11.10(-5) cm2/s, at its body temperature of 37-38 degrees C, 70.6 +/- 3.3 percent of that in isotonic saline at 37 degrees C. In the cat corneal stroma, at its normal temperature in situ of 33 degrees C, D was also virtually homogeneous with a mean of 1.19 +/- 0.20.10(-5) cm2/s, 42.8 +/- 7.3 percent of that in isotonic saline at 37 degrees C.


Tramadol and hyoscine N-butyl bromide combined in infusion solutions: compatibility and stability.
More than two-thirds of patients with metastatic cancer experience pain. Tramadol is one of the most interesting and useful weak opioids used by palliative care units to treat moderate to moderately severe pain. Relief of distressful symptoms in terminally ill patients is of prime importance; a common practice is to administer opioid analgesics in conjunction with other drugs as hyoscine N-butyl bromide, which is very useful in reducing secretions in patients with inoperable malignant bowel obstruction. The pursuit for excellence in symptom control in patients unable to take oral medication has led to the administration of medications by other routes such as the subcutaneous route. The purpose of this study was to fulfill the lack of information regarding the compatibility and physical stability of tramadol hydrochloride and hyoscine N-butyl bromide combined in infusion solutions. The stability of nine admixtures (stored in polypropylene syringes) at 4 and 25 degrees C was assessed over a period of 15 days. Nonstatistically significant losses of tramadol HCl and a maximum loss of 7% for hyoscine N-butyl bromide were obtained. Therefore, tramadol HCl (dose range, 100-400 mg/day) can be formulated together in saline with hyoscine N-butyl bromide (dose range 40-80 mg/day) for s.c. infusion using a 60-ml drug infuser for a duration of 7 days.


Individual variations of prostanoid agonist responses in rabbit aorta: evidence for the independent regulation of prostanoid receptor subtypes.
1 The frequency and selectivity of individual variations of prostanoid agonist responses in aortic strips from a population of male rabbits was studied. Three levels of responsiveness to the thromboxane mimetic U46619 occurred: responders (R), intermediate responders (IR), and non-responders (NR). R could be subdivided into R1 and R2 based on an enhanced potency of prostaglandin F2 alpha (PGF2 alpha) in R2. In the total population (n = 92), the phenotype frequency was: R, 69%; IR, 11%; and NR, 20%. In a subgroup of this population in which R1 and R2 phenotypes were determined (n = 63), the phenotype frequency was: R1, 54%; R2, 19%; IR, 6%; and NR, 21%. 2 The four rabbit aorta phenotypes, R1, R2, IR, and NR, were characterized with respect to the rank orders of prostanoid agonist potency, agonist intrinsic activities, and the effects of the thromboxane receptor antagonist SQ29548. The rank order of prostanoid agonist potency was U46619 greater than PGF2 alpha greater than PGE2 in R1 and R2, and PGF2 alpha greater than or equal to PGE2 greater than U46619 in IR and NR. For each prostanoid agonist, the intrinsic activity was highest in R (R1 congruent to R2), intermediate in IR, and lowest in NR. In R1, SQ29548 inhibited all prostanoid agonist responses equally. The contractile effects of PGF2 alpha and PGE2 were partially resistant to inhibition by SQ29548 in R2. Prostanoid agonist responses were not inhibited by SQ29548 in IR. 3 The potency of histamine was equivalent in R1, R2, IR, and NR. 4 It is concluded that there are individual variations in the functional expression of thromboxane receptor sensitivity, i.e., prostanoid agonist responses inhibited by SQ29548. Also, there are individual variations in the functional expression of the sensitivity of a non-thromboxane receptor or receptors, i.e., prostanoid agonist responses not inhibited by SQ29548. It has been proposed by others that prostanoid receptors be termed P-receptors and that the prostanoid agonist to which they are most sensitive be indicated by a preceding letter, e.g., TP- for thromboxane receptor and FP- for PGF2 alpha-selective receptor. Accordingly, we proposed a working hypothesis that suggests the four phenotypes could result from the independent regulation of the functional expression of TP- and FP-receptor subtypes with (a) R2 containing both the TP- and FP-receptor subtypes in a fully functional state; (b) R1 containing only the functional TP-receptor; (c) IR containing only the functional FP-receptor; and (d) NR containing only a low efficacy FP-receptor system. 5 The mechanisms underlying the observed individual variations are unknown but could include changes in receptor number or affinity, changes in receptor-effector coupling, changes in a second messenger system, or changes in tissue degradative or uptake processes. Further study is needed to differentiate between these possibilities.


Fusion transcript loci share many genomic features with non-fusion loci.
Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies have shown extensively that these cells readily undergo fusion transcription. We used the FusionMap program to identify high-confidence fusion transcripts from RNAseq data. The RNAseq datasets were from our (N = 8) and other (N = 14) clinical prostate tumors with adjacent non-cancer cells, and from the LNCaP prostate cancer cell line that were mock-, androgen- (DHT), and anti-androgen- (bicalutamide, enzalutamide) treated. In total, 185 fusion transcripts were identified from all RNAseq datasets. The majority (76%) of these fusion transcripts were 'read-through chimeras' derived from adjacent genes in the genome. Characterization of sequences at fusion loci were carried out using a combination of the FusionMap program, custom Perl scripts, and the RNAfold program. Our computational analysis indicated that most fusion junctions (76%) use the consensus GT-AG intron donor-acceptor splice site, and most fusion transcripts (85%) maintained the open reading frame. We assessed whether parental genes of fusion transcripts have the potential to form complementary base pairing between parental genes which might bring them into physical proximity. Our computational analysis of sequences flanking fusion junctions at parental loci indicate that these loci have a similar propensity as non-fusion loci to hybridize. The abundance of repetitive sequences at fusion and non-fusion loci was also investigated given that SINE repeats are involved in aberrant gene transcription. We found few instances of repetitive sequences at both fusion and non-fusion junctions. Finally, RT-qPCR was performed on RNA from both clinical prostate tumors and adjacent non-cancer cells (N = 7), and LNCaP cells treated as above to validate the expression of seven fusion transcripts and their respective parental genes. We reveal that fusion transcript expression is similar to the expression of parental genes. Fusion transcripts maintain the open reading frame, and likely use the same transcriptional machinery as non-fusion transcripts as they share many genomic features at splice/fusion junctions.


An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials.
Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ12) and titanium dioxide nanoparticles (TiO2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ12 and TiO2 NM-105 particles showed good linearity (R2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12. This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials.


Calcium Channels in Retinal Function and Disease.
Voltage-gated Ca2+ (Cav) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. To meet the spatial and temporal demands of visual signaling, Cav channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. In this article, we review current concepts regarding the specific subtypes of Cav channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.


Induction and characterization of human glioma clones with different radiosensitivities.
To facilitate investigation of the molecular mechanisms of tumor cell radiosensitivities, we have generated a set of clones with different radiosensitivities from a human glioma cell line U-251 MG-Ho. Forty-four colonies were isolated by subjecting parent cells to the mutagen N-methylnitrosourea and then irradiating these cells with increasing doses of x-rays. About half of the clones displayed different radiosensitivities than the parent cells. We selected one of the most sensitive clones (X3i) and one of the most resistant clones (Y6) for further study. Isoeffective doses for these two clones differed by about a factor of 1.7; the relative radiosensitivities of both clones were stable for at least 30 cell culture passages. These two clones do not differ significantly in either the induction or repair of radiation-induced DNA double-strand breaks as measured by pulsed field gel electrophoresis. Radiation-induced apoptosis measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay and micronucleus formation were similar in both clones. However, potentially lethal damage repair was greater in the radioresistant Y6 clone than in the radiosensitive X3i clone as determined by colony-forming efficiency assay.


STAT1β enhances STAT1 function by protecting STAT1α from degradation in esophageal squamous cell carcinoma.
STAT1, which carries tumor suppressor functions in several models, consists of two isoforms, namely STAT1α and STAT1β. The biological function and significance of STAT1β has never been examined in human cancer. We examined STAT1β function in esophageal squamous cell carcinoma (ESCC) by transfecting a STAT1β gene into various ESCC cell lines. The interaction between STAT1α and STAT1β was examined by using co-immunoprecipitation and confocal microscopy. The prognostic significance of STAT1β expression, detectable by immunohistochemistry and western blot, was evaluated in a large cohort of ESCC patients. Enforced expression of STAT1β induced and prolonged the expression and phosphorylation of STAT1α in ESCC cells, and these effects were amplified by gamma-interferon (IFN-γ). We also found that STAT1β interacts with STAT1α and decreases STAT1α degradation by the proteasome. Moreover, STAT1β substantially increased the DNA binding and transcription activity of STAT1. STAT1β also sensitized ESCC cells to chemotherapeutic agents, including cisplatin and 5-flurouracil. Using western blot and immunohistochemistry, we found that STAT1β was frequently decreased in esophageal cancer, as compared to their adjacent benign esophageal epithelial tissue. Loss of STAT1β significantly correlated with lymph node metastasis, invasion and shorter overall survival in ESCC patients. Therefore, STAT1β plays a key role in enhancing the tumor suppressor function of STAT1α, in ESCC, in a manner that can be amplified by IFN-γ.


Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.
The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.


Neuronal properties underlying processing of visual information in the barnacle.
Generation of a transient, amplified response to the dimming of light in the visual system of the barnacle involves two synaptic stages. It is accomplished primarily by decrementally conducting neurones that are similar to bipolar cells of the vertebrate retina.


Sentinel lymph node biopsy procedure in squamous vulvar cancer. 10 years follow-up analysis.
Application of sentinel lymph node biopsy (SLNB) procedure in early-stage vulvar cancer and analysis of results, recurrences and complications. 40 patients with vulvar cancer and SLNB between 2008 and 2018 were retrospectively reviewed. During the surgical procedure the inguinofemoral lymph nodes were checked with a gamma probe to identify the sentinel nodes that were removed and referred for intraoperative pathological assessment. Subsequently, long-term patient follow-up was performed with analysis of complications, relapse and mortality. 40 patients (mean age: 72 years [47-86], the overall detection rate per patient was 95% and a total of 129 Sentinel Lymph Nodes (SLNs) were removed (3.22 SLN/patient). In 3 out of 25 patients with lateral tumour lesions drainage was bilateral and in 2 out of 15 with midline lesions drainage was unilateral. On lymphoscintigraphy, 16 out of 40 had bilateral drainage and 24 unilateral. A total of 119 SLN- and 10 SLN+ were obtained, in 8 out of 10 an inguinofemoral lymphadenectomy was performed. In the SLN- group, one case of lymphatic blockage and one false negative were included. In 12 out of 40 patients there were post-surgical complications, 4 of them lymphoedemas. In the median follow-up (40 months), 6 out of 10 with SLN+ (40% mortality) and 7 out of 30 SLN- (16% mortality) had recurrences. SLNB in vulvar cancer is the technique of choice for correct staging and locoregional therapy. Correct clinical lymph node staging is important before surgery in order to avoid potential blockage drainages which could induce a false negative SLN.


Flaxseed dietary fiber supplements for suppression of appetite and food intake.
We conducted two single-blinded randomized crossover acute studies with 24 and 20 subjects, respectively, to compare (I) CONTROL vs. Flax drink; and (II) Flax drink vs. Flax tablets. The subjects were exposed to one of the treatments after an overnight fast, and rated appetite sensation for 120 min using visual analog scales (VAS). Hereafter they consumed an ad libitum early lunch to assess energy intake. The treatments were iso-caloric and iso-volumeric: 300 mL drink; Flax drink: CONTROL drink with addition flax fiber extract (2.5 g of soluble fibers); and Flax tablet: CONTROL drink with flax fiber tablets (2.5 g of soluble fibers). Flax drink increased sensation of satiety and fullness compared to CONTROL and a significant decrease in subsequent energy intake was observed after the Flax drink compared to CONTROL (2937 vs. 3214 kJ). Appetite ratings were similar for Flax tablets and Flax drink as they did not differ by more than 1-4%. Subsequent energy intake was similar after the two treatments (3370 vs. 3379 kJ). A small dose of flaxseed fiber significantly suppresses appetite and energy intake. Furthermore, flaxseed fibers administered as drinks or tablets produce similar responses.


beta-Subunit of human chorionic gonadotropin, ultrasound, and ectopic pregnancy: a prospective study.
This prospective study shows that the beta-subunit of human chorionic gonadotropin (beta-hCG) "screen" and ultrasound provide for nearly 100% clinical accuracy in diagnosing ectopic pregnancy in suspected cases. During the 14 months from February, 1981, to April, 1982, 81 consecutive patients believed to have ectopic pregnancies were screened. Fifty-six had a negative beta-hCG screen, thus ruling out early pregnancy complications. No false negative results were found. Twenty-seven patients had a positive screen, and 16 of these had an ectopic pregnancy. Twenty of the 27 patients with a positive beta-hCG screen underwent pelvic ultrasound examination. All of those with a positive beta-hCG screen and no intrauterine pregnancy on ultrasound had ectopic pregnancies. With the use of these clinical aids, morbidity and tubal damage are reduced because delay in operating upon those with ectopic pregnancy is avoided. Unnecessary operation is avoided in those patients who do not have an ectopic pregnancy.


Organ donor management: Eight common recommendations and actions that deserve reflection.
Despite major advances in our understanding of the physiopathology of brain death (BD), there are important controversies as to which protocol is the most appropriate for organ donor management. Many recent reviews on this subject offer recommendations that are sometimes contradictory and in some cases are not applied to other critically ill patients. This article offers a review of the publications (many of them recent) with an impact upon these controversial measures and which can help to confirm, refute or open new areas of research into the most appropriate measures for the management of organ donors in BD, and which should contribute to discard certain established recommendations based on preconceived ideas, that lead to actions lacking a physiopathological basis. Aspects such as catecholamine storm management, use of vasoactive drugs, hemodynamic objectives and monitoring, assessment of the heart for donation, and general care of the donor in BD are reviewed.


Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for esophageal cancer.
We aimed to evaluate the safety, tolerability, and efficacy of combination preoperative chemoradiotherapy as first-line treatment in patients with advanced esophageal cancer. We performed a phase I dose-escalation trial of docetaxel at 25-40 mg/m(2) in four planned dose levels in 3-6 patient cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70 mg/m(2) on days 1 and 29) and 5-fluorouracil (70 mg/m(2)/day on days 1-4 and 29-32) and concurrent radiation therapy (40 Gy). The tumors were resected during weeks 10-13. This study included 7 patients with esophageal cancer. The dose-limiting toxicity was observed at a biweekly docetaxel dose of 30 mg/m(2) when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25 mg/m(2). Grade 3/4 hematological toxicity was observed in 71% of the patients and grade 3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86% (complete, 57% and partial, 29%). All patients underwent surgery, and there were no deaths as a result of postoperative complications. This preoperative chemoradiotherapy regimen using triplets is feasible but results in moderate toxicity. It is noteworthy that this regimen was associated with a high rate of pathological complete remission.


The initiation and early development of autoimmune diseases.
Our understanding of autoimmunity has changed considerably over the past years as a consequence of the demonstration that self-reactive B cells and T cells are not necessarily deleted from the immunological vocabulary. The critical event in initiating (or avoiding) autoimmune responses is presentation to T cells of the self-peptide-MHC antigen complex. Based on the premise that quantitative aspects are of paramount importance, we suggest that T-cell activity, MHC expression, and self-peptide binding determine the initiation of autoimmune responses.


[MicroRNA Expression Profiling of Diffuse Large B-Cell Lymphoma].
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers that differ in pathogenesis and prognosis. The main methods of treating NHL include chemotherapy, immunochemotherapy, and radiation therapy. However, a significant proportion of these tumors are chemoresistant or rapidly recur after a short chemotherapy-induced remission. In this regard, the search for alternative cytoreductive therapeutic methods is relevant. Aberrant expression of microRNA (miRNA) is one of the mechanisms responsible for the emergence and progression of malignant lymphoid neoplasms. We analyzed the profile of miRNA expression in the biopsy material from lymph nodes affected by diffuse large B-cell lymphoma (DLBCL). The key material of the study was histological preparations of lymph nodes obtained by excisional diagnostic biopsy and treated using conventional histomorphological formalin fixation methods. The study group consisted of patients with DLBCL (n = 52); the control group consisted of patients with reactive lymphadenopathy (RL) (n = 40). It was shown that the miR-150 expression level in DLBCL was reduced by more than 12 times (</>p = 3.6 x 10^(-15)) compared with RL. Bioinformatics analysis revealed the involvement of miR-150 in the regulation of hematopoiesis and lymphopoiesis. The data we obtained allow us to consider miR-150 as a promising therapeutic target with great potential in clinical practice.


Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation.
Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100-452 and 95-153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.


Influences of the Big Five personality traits on the treatment response and longitudinal course of depression in patients with acute coronary syndrome: A randomised controlled trial.
Influences of the Big Five personality traits on the treatment response and longitudinal course of depression in patients with acute coronary syndrome: A randomised controlled trial. This naturalistic observational study initially recruited 1152 ACS patients; 685 patients completed personality assessments at baseline, of whom 630 were followed-up one year later. Of the 294 patients with depression, 207 participated in a 24-week double blind trial of escitalopram or placebo. The remaining 87 patients who received medical treatment only and the 391 who had not depression were also followed in a one year naturalistic observational study. The Big five personality traits were assessed using the Big Five Inventory. The influences of personality on the Hamilton Depression Rating Scale score changes were analysed using a mixed-model repeated-measures analysis of covariance. A Cluster analysis identified two personality types: resilient and vulnerable. The vulnerable personality type was characterized by lower extraversion, agreeableness, and conscientiousness - but higher neuroticism - than the resilient type. This personality type was independently associated with a poorer outcome of depression in ACS patients during the 24-week treatment period and the one year longitudinal follow-up period compared to the resilient personality type, irrespective of treatment allocation. Recruitment from a single institution may limit generalisability. Personality traits were investigated 12-weeks after ACS; thus, the responses may have been influenced by the prior receipt of escitalopram. Personality types influences the treatment outcome and longitudinal course of depression in ACS patients independent of antidepressant treatment.


The effect of intravenous ketamine on depressive symptoms after surgery: A systematic review.
The development of depressive symptoms is an important complication experienced by patients postoperatively and is associated with poor clinical outcomes. Ketamine is a feasible treatment option for depressive symptoms after surgery due to its known antidepressant effect. This meta-analysis aimed to evaluate the current body of research regarding the effects of intravenous ketamine on depressive symptoms after surgery. A meta-analysis of randomized controlled trials. Perioperative care area. Adult surgical patients. Systematic literature search was performed in the CENTRAL, MEDLINE, and EMBASE databases, for randomized controlled trials comparing the effect of intravenous ketamine versus placebo on postoperative depressive symptoms as the primary outcome, with no language restrictions. Two independent reviewers screened records for inclusion, extracted data, and assessed risk of bias. Random effects models were used to pool overall estimates. Postoperative pain intensity was also examined. The GRADE approach was used to assess the quality of evidence. Out of 834 records screened, 9 studies met our inclusion criteria, comprising a total of 2468 patients. Compared with the control group, ketamine provided significant reduction of postoperative depression scale scores, by a standardized mean difference (SMD) of -0.89 (95% CI [-1.23, -0.73], P = 0.33, I2 = 13%; 4 studies) on postoperative day (POD) 1, SMD -0.51 (95% CI [-0.99, -0.04], P < 0.001, I2 = 93%; 4 studies) on POD 3, suggesting clinically relevant reduction in postoperative depressive symptoms. Postoperative depression scale scores on POD 7 were also reduced in patients receiving ketamine compared to the control group, with SMD -0.33 (95% CI [-0.52, -0.14], P = 0.36, I2 = 2%; 3 studies), but the minimal clinical difference of 0.5 SMD was not reached. No significant difference was observed in the postoperative depression scale over the long term at 30 days' follow-up (SMD -0.13, 95% CI [-0.25, 0.00], P = 0.07, I2 = 52%; 5 studies). A significant reduction of postoperative pain intensity on POD 1 was identified in patients following ketamine administration (SMD -1.29, 95% CI [-2.57, -0.01], P = 0.05, I2 = 98%; 5 studies). However, administration of ketamine resulted in a significantly increased risk of nausea and vomiting (RR 1.71, 95% CI [1.25, 2.33], P = 0.17, I2 = 35%; 6 studies), headache (RR 4.88, 95% CI [1.97, 12.06], P = 0.83, I2 = 0%; 4 studies), and hallucination (RR 34.94, 95% CI [8.59, 142.17], P = 0.44, I2 = 0%; 4 studies). The current evidence supports intravenous ketamine administration for the treatment of depressive symptoms after surgery. While ketamine administration has clinically significant side effects, future studies are needed in surgical populations at high risk of complications.


BLI-MS: Combining biolayer interferometry and mass spectrometry.
Biolayer interferometry (BLI) is a technology which allows to study the affinity between two interacting macro-molecules and to visualize their kinetic of interaction in real time. In this work, we combine BLI interaction measurement with mass spectrometry in order to identify the proteins interacting with the bait. We provide for the first time the proof of concept of the feasibility of BLI-MS in complex biological mixtures.


Organotropic mutagenesis in tissues of Chinese hamsters induced by chemical carcinogens.
In order to investigate the relationship between mutation and carcinogenesis in vivo, a method has been developed in which somatic mutation can be studied in specific organs of Chinese hamsters after acute dosing with chemical carcinogens. In preliminary experiments an increase in mutation was detected in cultures derived from lung tissue of hamsters after intraperitoneal dosing with the direct-acting mutagen and weak carcinogen, ethyl methanesulphonate, or with diethylnitrosamine, a carcinogen which requires metabolic activation before mutagenic activity can be demonstrated in vitro. Subsequent experiments have shown the induction of mutation in cells dereived from the bladder of animals dosed with diethylnitrosamine or methyl nitrosourea and in a variety of tissues from animals dosed with methane-sulphonates, 2-acetylaminofluorene and 3-methylcholanthrene.


Influence of maternal care on the developing brain: Mechanisms, temporal dynamics and sensitive periods.
Variation in maternal care can lead to divergent developmental trajectories in offspring with implications for neuroendocrine function and behavioral phenotypes. Study of the long-term outcomes associated with mother-infant interactions suggests complex mechanisms linking the experience of variation in maternal care and these neurobiological consequences. Through integration of genetic, molecular, cellular, neuroanatomical, and neuroendocrine approaches, significant advances in our understanding of these complex pathways have been achieved. In this review, we will consider the impact of maternal care on male and female offspring development with a particular focus on the issues of timing and mechanism. Identifying the period of sensitivity to maternal care and the temporal dynamics of the molecular and neuroendocrine changes that are a consequence of maternal care represents a critical step in the study of mechanism.


Multidirectional percutaneous drilling and autologous bone marrow injection for the treatment of femoral diaphyseal nonunions: a prospective interventional study.
To examine the outcomes of multidirectional percutaneous drilling and autologous concentrated bone marrow (BM) transplantation for atrophic femoral diaphyseal nonunion characterized by intact hardware and mechanical stability at the nonunion site. Fourteen patients (22-63 years of age) were admitted to our hospital with atrophic femoral diaphyseal nonunion. All patients were treated with a combination of multidirectional percutaneous drilling and autologous concentrated BM transplantation. Radiographic evaluation was conducted every month after transplantation until bone healing was achieved. Bony union was achieved in 13 of the 14 patients (92.9%) after an average of 3.9 months (range: 2.5-6 months). The average radiographic union scale in tibial (RUST) scale score improved significantly from the preoperative period (6.15±1.21) to follow-up (11.23±0.73; P<0.05). The mean follow-up after transplantation was 31.4±9.5 months (range: 18-50 months). At the final follow-up, the quality of function had improved significantly, allowing a return to normal activities. Combined multidirectional percutaneous drilling and autologous concentrated BM transplantation is an easy, safe, inexpensive, and efficacious method to treat atrophic femoral diaphyseal nonunion characterized by intact hardware and mechanical stability at the nonunion site.Trial registration number: ISRCTN29808592.


Heat Shock Protein 27 Enhances SUMOylation of Heat Shock Protein B8 to Accelerate the Progression of Breast Cancer.
Heat shock proteins (HSPs) are emerging as valuable potential molecular targets in breast cancer therapy owing to their diverse functions in cancer cells. This study investigated the potential role of heat shock protein 27 (HSP27, also known as HSPB1) in breast cancer through heat shock protein B8 (HSPB8). The correlation between HSP27 and HSPB8 was identified by using co-immunoprecipitation, immunoprecipitation, and SUMOylation assays. Through gain- and loss-of-function approaches in MCF-7 cells, the effect of HSP27 on HSPB8 expression, SUMOylation level, and protein stability of HSPB8, as well as on cell proliferation, migration, and stemness, was elucidated. A mouse xenograft model of breast cancer cells was established to verify the function of HSP27 in vivo. Results indicate that HSP27 and HSPB8 were highly expressed in breast cancer tissues and MCF-7 cells. HSP27 was also found to induce the SUMOylation of HSPB8 at the 106 locus and subsequently increased its protein stability, which resulted in accelerated proliferation, migration, and stemness of breast cancer cells in vitro along with increased tumor metastasis of breast cancer in vivo. However, these results could be reversed by the knockdown of HSPB8. Overall, HSP27 induces SUMOylation of HSPB8 to promote HSPB8 expression, thereby endorsing proliferation and metastasis of breast cancer cells. This study may provide insight for the development of new targets for breast cancer.


Successful use of infliximab therapy in sight-threatening corticosteroid-resistant Vogt-Koyanagi-Harada disease.
To report an experience with infliximab in severe corticosteroid-resistant Vogt-Koyanagi-Harada (VKH) disease. Interventional case series. The medical records of 2 adult patients were reviewed. Both patients had a visual acuity reduced to hand motion perception bilaterally after 1 month of high-dose corticosteroid therapy, due to multiple exudative retinal detachment involving the fovea. Visual acuity and OCT findings improved immediately after the first infliximab infusion, retinal detachments fully resolved after 1 month and visual acuity returned to normal within 6 months. Despite a negative pretreatment screening, one patient developed multivisceral tuberculosis, which led to infliximab discontinuation after the 7th infusion and was cured by a 9-month ambulatory antibiotic regimen. The other patient received 11 well-tolerated infliximab infusions. Respectively, 9 and 4 months after infliximab discontinuation both patients had normal vision and OCT findings. Infliximab showed tremendous therapeutic efficacy in sight-threatening corticosteroid-resistant VKH disease.


Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013.
Community-based and other epidemiologic studies within the United States have identified substantial disparities in health care among adults with epilepsy. However, few data analyses addressing their health-care access are representative of the entire United States. This study aimed to examine national survey data about adults with epilepsy and to identify barriers to their health care. We analyzed data from U.S. adults in the 2010 and the 2013 National Health Interview Surveys, multistage probability samples with supplemental questions on epilepsy. We defined active epilepsy as a history of physician-diagnosed epilepsy either currently under treatment or accompanied by seizures during the preceding year. We employed SAS-callable SUDAAN software to obtain weighted estimates of population proportions and rate ratios (RRs) adjusted for sex, age, and race/ethnicity. Compared to adults reporting no history of epilepsy, adults reporting active epilepsy were significantly more likely to be insured under Medicaid (RR=3.58) and less likely to have private health insurance (RR=0.58). Adults with active epilepsy were also less likely to be employed (RR=0.53) and much more likely to report being disabled (RR=6.14). They experience greater barriers to health-care access including an inability to afford medication (RR=2.40), mental health care (RR=3.23), eyeglasses (RR=2.36), or dental care (RR=1.98) and are more likely to report transportation as a barrier to health care (RR=5.28). These reported substantial disparities in, and barriers to, access to health care for adults with active epilepsy are amenable to intervention.


Cardioprotective Effect of Anisodamine Against Myocardial Ischemia Injury and its Influence on Cardiomyocytes Apoptosis.
Anisodamine is an ancient Chinese medicine derived from Tibet as a belladonna alkaloid, which is usually used for improvement of blood circulation in patients with organ phosphorus poisoning or shock. In this study, for the first time, we report its cardioprotective effects on preventing ischemia/reperfusion (I/R) injury of patients with acute myocardial infarction (AMI), and decreasing the myocardial infarction area and severity in heart of Sprague-Dawley (SD) rats. Our results suggest a potential molecular mechanism of anisodamine against the I/R injury in cardiomyocytes is associated with its anti-apoptotic effect. Anisodamine treatment decreases the expression of caspase-3 and caspase-8, and increases Bcl-2/Bax ratio in cardiomyocytes. Our data suggest that anisodamine can provide significant cardioprotection against I/R injury, potentially through the suppression of cardiomyocytes apoptosis.


Pancreatic polypeptide hypersecretion associated with a neuroendocrine carcinoma of the gallbladder.
The authors report a case of a suspected pure pancreatic polypeptide-secreting neuroendocrine carcinoma of the gallbladder. The tumor was initially interpreted as an adenocarcinoma of the gallbladder, but was found to have a neuroendocrine component after review. The pathology supports the view that a primitive epithelial stem cell can express both epithelial and neuroendocrine characteristics and can differentiate into both an adenocarcinoma and a neuroendocrine carcinoma. Upon recurrence, the tumor produced symptoms due to local growth, but eventually metastasized and led to the death of the patient within 4 years. The patient was treated with chemoembolization followed by the long-acting somatostatin analog octreotide acetate. The high serum level of pancreatic polypeptide may have contributed to cholestasis and cholelithiasis. Earlier measurement of serum hormone levels and identification of high pancreatic polypeptide levels may have suggested the presence of residual tumor and led to closer follow-up, imaging studies, and therapy.


Image Sharing Technologies and Reduction of Imaging Utilization: A Systematic Review and Meta-analysis.
Image sharing technologies may reduce unneeded imaging by improving provider access to imaging information. A systematic review and meta-analysis were conducted to summarize the impact of image sharing technologies on patient imaging utilization. Quantitative evaluations of the effects of PACS, regional image exchange networks, interoperable electronic heath records, tools for importing physical media, and health information exchange systems on utilization were identified through a systematic review of the published and gray English-language literature (2004-2014). Outcomes, standard effect sizes (ESs), settings, technology, populations, and risk of bias were abstracted from each study. The impact of image sharing technologies was summarized with random-effects meta-analysis and meta-regression models. A total of 17 articles were included in the review, with a total of 42 different studies. Image sharing technology was associated with a significant decrease in repeat imaging (pooled effect size [ES] = -0.17; 95% confidence interval [CI] = [-0.25, -0.09]; P < .001). However, image sharing technology was associated with a significant increase in any imaging utilization (pooled ES = 0.20; 95% CI = [0.07, 0.32]; P = .002). For all outcomes combined, image sharing technology was not associated with utilization. Most studies were at risk for bias. Image sharing technology was associated with reductions in repeat and unnecessary imaging, in both the overall literature and the most-rigorous studies. Stronger evidence is needed to further explore the role of specific technologies and their potential impact on various modalities, patient populations, and settings.


(p)ppGpp-mediated stress response induced by defects in outer membrane biogenesis and ATP production promotes survival in Escherichia coli.
Cellular growth requires a high level of coordination to ensure that all processes run in concert. The role of the nucleotide alarmone (p)ppGpp has been extensively studied in response to external stresses, such as amino acid starvation, in Escherichia coli, but much less is known about the involvement of (p)ppGpp in response to perturbations in intracellular processes. We therefore employed CRISPRi to transcriptionally repress essential genes involved in 14 vital processes and investigated whether a (p)ppGpp-mediated response would be induced. We show that (p)ppGpp is produced and required for a pertinent stress response during interference with outer membrane biogenesis and ADP synthesis specifically. When these processes were perturbed via the transcriptional repression of essential genes, wild type E. coli MG1655 ceased growing and entered a semi-dormant state, whereas isogenic (p)ppGpp0 cells continued to grow uncontrollably to the point of lysis. Furthermore, in vivo measurements revealed that the ATP levels were intrinsically offset in (p)ppGpp0 cells, further indicating a role for the alarmone in cellular energy homeostasis. In summary, our investigation suggests that (p)ppGpp acts as a coordinator of cell growth in response to imbalances in outer membrane biogenesis and adenosine ribonucleotide synthesis, elucidating novel roles for (p)ppGpp in bacterial physiology.


Investigation of antidepressant medication usage after bariatric surgery.
Many patients seeking bariatric surgery have a history of mood disorders and are actively prescribed antidepressants. While extensive documentation exists on the impact of weight loss surgery on reductions in cardiac, diabetic, and hypertensive medications, little is known about the impact of bariatric surgery on the use of antidepressant medications. A retrospective study of 439 patients who had undergone Roux-en-Y gastric bypass (RYGB) from January 2001 to November 2004 was examined for postoperative changes in the use of antidepressant medications. After RYGB, 23% of the patients had an increase in their antidepressant use, 40% continued to require the same antidepressant, 18% had a change in antidepressant medication, and only 16% had a decrease or discontinued their antidepressant. Unlike most medications, antidepressant usage did not decrease in the majority of patients after RYGB. These results highlight the prevalence of antidepressant prescription use in patients before and after RYGB and support the need for the careful monitoring of depressive symptoms.


Purification and characterization of aldolase from human erythrocytes.
A procedure has been developed for the purification of human erythrocyte aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 184.108.40.206.3). The process involves a specific substrate elution of the enzyme from phosphocellulose followed by a reverse ammonium sulfate fractionation. The preparation has been shown to be homogeneous by analytical ultracentrifugation, thin-layer electrophoresis, and polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme exhibits a specific activity of 16 I.U./mg protein, a Km of 7.1-10(-6) M for fructose 1,6-bisphosphate, and a substrate specificity (Fru-1,6-P2/Fru-1-P) of 40. The native protein in a tetramer of 158 000 molecular weight possessing identical or nearly identical subunits, an isoelectric point of 8.9, a diffusion coefficient of 4.68-10(-7) cm2/s, and a molecular radius of 4.56 nm. The study shows the enzyme to be a type A aldolase resembling other muscle forms in chemical and physical properties as well as amino acid composition.


Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling.
Trophoblast lineages, precursors of the placenta, are essential for post-implantation embryo survival. However, the regulatory network of trophoblast development remains incompletely understood. Here, we report that Cited1, a transcription coactivator, is a robust inducer for trophoblast-like state from mouse embryonic stem cells (ESCs). Depletion of Cited1 in ESCs compromises the trophoblast lineage specification induced by BMP signaling. In contrast, overexpression of Cited1 in ESCs induces a trophoblast-like state with elevated expression of trophoblast marker genes in vitro and generation of trophoblastic tumors in vivo. Furthermore, global transcriptome profile analysis indicates that ectopic Cited1 activates a trophoblast-like transcriptional program in ESCs. Mechanistically, Cited1 interacts with Bmpr2 and Smad4 to activate the Cited1-Bmpr2-Smad1/5/8 axis in the cytoplasm and Cited1-Smad4-p300 complexes in the nucleus, respectively. Collectively, our results show that Cited1 plays an important role in regulating trophoblast lineage specification through activating the BMP signaling pathway.


Type 2 diabetes mellitus as a possible risk factor for myasthenia gravis: a case-control study.
A certain number of myasthenia gravis (MG) patients clinically had type 2 diabetes mellitus (T2DM) prior to MG onset, which suggests that the onset of MG may correlate with the history of T2DM. This study aimed to examine the correlation between MG and T2DM. In a single-center, retrospective, 1:5 matched case-control study, all 118 hospitalized patients with a diagnosis of MG from 8 August 2014 to 22 January 2019 were enrolled. In total, four datasets with different sources of the control group were retrieved from the electronic medical records (EMRs). Data were collected at the individual level. A conditional logistic regression analysis was used to test the risk of MG associated with T2DM. The risk of MG was significantly associated with T2DM, and there were notable differences by sex and age. Whether compared to the general population, general hospitalized patients without autoimmune diseases (AIDs), or patients with other AIDs except MG, women aged over 50 years with T2DM had an increased risk of MG. The mean onset age of diabetic MG patients was more than that of the non-diabetic MG patients. This study demonstrates that T2DM is strongly associated with the subsequent risk of MG and varies significantly by sex and age. It reveals that diabetic MG may be a unique subtype that is different from the conventional MG subgroup classification. More clinical and immunological features of diabetic MG patients need to be explored in further studies.


Molecular cloning and expression of the xylanase gene of alkalophilic Bacillus sp. strain C-125 in Escherichia coli.
The gene for xylanase A of alkalophilic Bacillus sp. strain C-125 was cloned in Escherichia coli with pBR322. The plasmid pCX311 contained 2.6- and 2.0-kilobase-pair HindIII fragments. The characteristics of the purified pCX311-encoded xylanase were the same as those of purified xylanase A from alkalophilic Bacillus sp. strain C-125.


Toxicity evaluation of wastewater collected at different treatment stages from a pharmaceutical industrial park wastewater treatment plant.
The toxicity of water-receiving bodies, the effluent and other treatment stages in wastewater treatment plants has recently been of interest to the public due to the lack of a regulated toxicity-based index for wastewater discharge in China. This study aimed to evaluate the conventional pollution parameters and toxicities of wastewaters collected at different treatment stages from a pharmaceutical industrial park wastewater treatment plant through dehydrogenase activity (DHA) and bioluminescent bacteria (Vibrio qinghaiensis) tests. The results of an analysis of conventional parameters indicated that the total suspended solids (TSS), chemical oxygen demand (COD), total nitrogen (TN), ammonia nitrogen (NH3N), and total phosphorus (TP) were largely removed after various treatments. However, the TN, NH3N and COD still exceeded the regulated standards. The tested pharmaceutical park effluents were mainly polluted with organic pollutants and nitrogenous. The toxicity test results indicated that the toxicities could be markedly reduced after treatment, with the toxicities of two out of the six effluent samples at different treatment stages being greater than the influent toxicity. Spearman's rank correlation coefficients indicated a significantly positive correlation between the toxicity values obtained using the DHA and Vibrio qinghaiensis tests. Compared with the DHA measurement, the Vibrio qinghaiensis test was faster and more sensitive. Meanwhile, the toxicity indicators were significantly and positively correlated with the TSS, TN, TP and COD concentrations. These results may aid the understanding of the toxicity of pharmaceutical industrial park wastewaters and toxicity removal using the treatment techniques that are currently utilized in China.


Use of the New Zealand Intensive Medicines Monitoring Programme to study the levonorgestrel-releasing intrauterine device (Mirena).
To demonstrate how the Intensive Medicines Monitoring Programme (IMMP) can be used to monitor adverse events associated with an intrauterine device, using the levonorgestrel-releasing intrauterine device (Mirena) as an example. A long-term prospective observational cohort study using Prescription Event Monitoring (PEM) is currently being undertaken in women using Mirena in New Zealand. This report describes the method used and reports the early results for those women who used the device between March 1998 and March 2001. Adverse events were recorded by inserting doctors and general practitioners on registration forms and systematic follow-up questionnaires. Between March 1998 and March 2001, the IMMP received 3519 registration forms for insertions in 3452 women. 'Difficult insertion' was the most frequently reported event (3.6% of all insertions). Approximately, 2% of the Mirena insertions were carried out under GA and there were three uterine perforations (0.9 per 1000 insertions) in the total cohort. To date, follow-up questionnaires have been processed for 495 patients. The response rate for these was 83%. As adapted in the IMMP, PEM is an effective tool for the early post-marketing surveillance of an intrauterine device in real life clinical practice.


Structure of human vertebral lamellar bone in age-associated involution and osteoporosis.
We compared the structure of lamellar bone in anterolateral zones of vertebral bodies in adult and senile subjects in health and osteoporosis. The appearance of structural signs of age-related osteopenia and enlargement of coplanar consolidations of the bone matrix crystals were noted. Osteopenia was more pronounced in osteoporosis, while the structural organization of the mineral component did not differ from that in age-matched controls.


Hydrodynamic drag force exerted on activated sludge floc at intermediate Reynolds number.
We hung the activated sludge flocs on an elastic nylon stick and then subjected it to a uniform water flow and measured its displacement. The hydrodynamic drag force exerted on the floc was subsequently estimated, both for cationic flocculated flocs and for flocculated and then frozen/thawed flocs. A confocal laser scanning microscope (CLSM) was employed to probe the interior structure of flocs. Polyelectrolyte flocculation leads to a compact global structure, and hence high drag force exerted on the floc by water. The corresponding C(D)Omega value at Re=12-27 for flocs ranges from 1.58 to 3.61. Fast freezing would little affect the hydrodynamic drag force. Slow freezing, in contrast, considerably consolidated the floc structure and hence presented impermeable sphere-like behavior of the slowly frozen/thawed flocs.


Total mercury concentration in the fur of free-ranging giant otters in a large Neotropical floodplain.
The giant otter, Pteronura brasiliensis, (Zimmermann, 1780), is a semiaquatic carnivore that feeds mainly on fish. Mercury has high toxicity and high potential for bioaccumulation in tissues and biomagnification in organisms through food chains. Thus, as a top predator in the trophic chain, the giant otter has the potential to accumulate mercury by biomagnification. The objective of the present study was to measure the total mercury concentration in giant otter fur samples from an area in the southern Brazilian Pantanal. Fur samples from 19 otters from different social groups were collected from captured animals or were sampled with biopsy darts. Total mercury determination was performed by cold steam spectrophotometry. Mercury concentrations found in the giant otter fur were 7.15 ± 3.41 μg g-1 (2.01-12.06 μg g-1) dry weight. The values are above to the upper limit found in fur samples of otter species not exposed to contamination sources, which typically range from 1 to 5 μg g-1. The concentrations found in the study area indicate that even in the southern Pantanal, which is approximately 475 km from gold mining activity, mercury can be considered a threat for giant otters, as well as for riverside populations. It is also important to consider that other anthropogenic sources of mercury, such as pesticides used in agriculture, could affect this population.


Skryjelites auritus gen. et sp. nov. and Quasimolites quasimodo gen. et sp. nov.--two new middle Cambrian hyolithids (?Mollusca) from the Czech Republic.
Two new endemic genera and species of extinct group of Hyolitha, Skryjelites auritus gen. et sp. nov. and Quasimolites quasimodo gen. et sp. nov. are described and illustrated from the Buchava Formation of the Barrandian area (Czech Republic).


Planar or tetrahedral? A ternary 17-electron CBe5H4+ cluster with planar pentacoordinate carbon.
A 17-electron CBe5H4+ cluster features planar pentacoordinate carbon, owing to the 2π/6σ double aromaticity. The neutral CBe5H4 cluster has a tetrahedral configuration despite its 18-electron counting. The latter species is governed by σ conjugation.


High-resolution Structural Magnetic Resonance Imaging and Quantitative Susceptibility Mapping.
High-resolution 7-T imaging and quantitative susceptibility mapping produce greater anatomic detail compared with conventional strengths because of improvements in signal/noise ratio and contrast. The exquisite anatomic details of deep structures, including delineation of microscopic architecture using advanced techniques such as quantitative susceptibility mapping, allows improved detection of abnormal findings thought to be imperceptible on clinical strengths. This article reviews caveats and techniques for translating sequences commonly used on 1.5 or 3 T to high-resolution 7-T imaging. It discusses for several broad disease categories how high-resolution 7-T imaging can advance the understanding of various diseases, improve diagnosis, and guide management.


Open system gene expression profiling and identification of novel genes for targeted vaccine delivery.
Ongoing development of vaccines is limited by the techniques used to identify routes to immunization. Using open system gene expression profiling, researchers can now directly identify receptors used by M-cells in the transport of antigens to the mucosal immune system. These receptors will be ideal for targeted delivery of new synthetic vaccines. In addition, gene expression profiling will provide important new information on the biology of the M-cell and mucosal immune mechanisms.


BMP7 expression in esophageal squamous cell carcinoma and its potential role in modulating metastasis.
Our previous study showed that BMP7 revealed significantly higher levels in esophageal squamous cell carcinoma (ESCC) tissues with lymph node metastasis compared with non-lymph node metastasis, using gene expression profiling assays. The roles of BMP7 in ESCC is not fully understood. The aim of this study was to investigate the effect of BMP7 on lymph node metastasis of ESCC and to explore its potential mechanism. Expression of BMP7 in ESCC tissues was evaluated by immunohistochemistry. BMP7 were down-regulated by RNA interference. The protein and mRNA levels of BMP7 were detected by western blot and RT-PCR, respectively. High content screening and transwell assay were used to identify the metastatic ability of tumor cells. Positivity of BMP7 staining was 57.5 % in the tissues of primary carcinoma with lymph node metastasis compared to tissues without lymph node metastasis, and expression of BMP7 was significantly higher in the cell lines with highly metastatic capacity than that in the cell lines without metastatic ability. Suppression of endogenous BMP7 expression by siRNA in the highly metastatic cell lines resulted in significant reduction in ability of cell migration and invasion in both in vitro and in vivo studies. In addition, inhibition of BMP7 by siRNA also leads to up-regulation of E-cadherin and down-regulation of MMP-9 in the highly metastatic cell lines. These findings indicate that BMP7 modulates the expression of E-cadherin and MMP-9, and by which mechanism it may regulate cell migration and metastasis of ESCCs.


Comparative cytotoxicity of fumonisin B1 in two cell lines derived from normal human bronchial epithelial cells using four distinct bioassay techniques.
This study focuses on the cytotoxic effects of fumonisin B1 (FB1) on both immortalised and immortalised and subsequently transfected normal human bronchial epithelial (NHBE) cells of human origin using four bioassays. While the MTT, Neutral Red and hexosaminidase colorimetric assays showed little difference between the toxic effects on the two related cell lines, the clonogenic assay, measuring cell survival and proliferation, indicated that FB1 had a more toxic effect on the nontransfected cells. This kind ofin vitro approach using cells which retain many characteristics of normal cell growth and differentiation can go some way to developing evaluation models for food safety in the case of mycotoxin contamination without resorting totally to whole animal testing. Nevertheless, one or two cytotoxicity tests may be inadequate for a complete appraisal of toxic potential: rather, as wide a range of methodologies as feasible should be employed initially before meaningful conclusions may be drawn.


DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion.
The early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been identified. However, no functional characterization has been provided to date. Here, we have investigated the DJ-1-interacting transcripts, as well as the role of DJ-1 RNA-binding activity during ischemia and reperfusion. Among the identified DJ-1-interacting transcripts, we have distinguished a significant enrichment of mRNAs encoding mitochondrial proteins. The effects of DJ-1 depletion on mitochondrial protein expression and mitochondrial morphology were investigated using a CRISPR/Cas9 generated DJ-1 knockout (DJ-1KO) cell model. DJ-1 depletion resulted in increased MTND2 protein expression in resting cells; however, after exposure to I/R, MTND2 levels were significantly reduced with respect to wild type cells. Increased mitochondrial fission was consistently found in DJ-1KO cells after I/R exposure. MTND2 transcript binding to DJ-1 was increased during ischemia. Our results indicate that the RNA-binding activity of DJ-1 shield mitochondrial transcripts from oxidative damage.


Silk sericin alleviates aberrant photoperiod-induced alterations in testicular and adrenal steroidogenesis in adult mice.
Steroidogenesis is a complex process of sequential enzymatic reactions affected by climate change. Animals respond to altered day length, the so-called photoperiod, with changes in physiology. The study aimed to an evaluation of sericin effect in alleviating steroidogenesis disorders induced by disturbed photoperiod in mice. The animals were randomly divided into three groups according to the lighting cycle: a control group with a standard 12Light:12Dark cycle, a short-term photoperiod group with a 6Light:18Dark cycle, and a long-term photoperiod group with an 18Light:6Dark cycle. Both short and long-term groups were subdivided into two equal subgroups: The placebo and the sericin-treated subgroups received, for five weeks from prepubertal throughout adulthood, one intraperitoneal injection per week of the solvent and 1 g sericin/kg body weight, respectively. Selected oxidative stress parameters and testicular and adrenal steroidogenic capacities of adult mice were measured. After five weeks, the placebo group with impaired photoperiod showed a decrease in the quality and quantity of sperm and a reduction in testosterone, corticosterone, aldosterone, total antioxidant capacity, xanthine oxidase, and melatonin. At the same time, in these groups, there was an increase in the level of aromatase, malondialdehyde, cholesterol, and steroidogenic factor-1 (SF-1) expression in the adrenal cortex and an enhancement in histological lesions. Mice receiving sericin had parameters similar to the control group. Our findings reveal that silk sericin can reduce the stress caused by photoperiod disorders regarding testicular function, sex hormone levels, and sperm quantity and quality. Thus, sericin is a biocompatible protein with a promising potential for its use in the case of organisms living under an abnormal photoperiod.


The time course of the phosphorylation of proteins in the synaptic plasma membrane and the effect of certain cations.
The phosphorylation of proteins in the synaptic plasma membrane is a rather slow reaction taking several minutes to saturate all the phosphate acceptor sites. (The time for half the protein bound phosphate groups to turnover is about 1 min). A divalent cation is needed as a cofactor for the reaction. At high (0.5 mM) ATP concentrations Mg2+ is more effective than Mn2+ but at low (10 microM) ATP concentrations the reverse is the case. Zn2+ and Ca2+ support very little phosphorylation.


One strike and you're a lout: Cherished values increase the stringency of moral character attributions.
Moral dilemmas are inescapable in daily life, and people must often choose between two desirable character traits, like being a diligent employee or being a devoted parent. These moral dilemmas arise because people hold competing moral values that sometimes conflict. Furthermore, people differ in which values they prioritize, so we do not always approve of how others resolve moral dilemmas. How are we to think of people who sacrifice one of our most cherished moral values for a value that we consider less important? The "Good True Self Hypothesis" predicts that we will reliably project our most strongly held moral values onto others, even after these people lapse. In other words, people who highly value generosity should consistently expect others to be generous, even after they act frugally in a particular instance. However, reasoning from an error-management perspective instead suggests the "Moral Stringency Hypothesis," which predicts that we should be especially prone to discredit the moral character of people who deviate from our most deeply cherished moral ideals, given the potential costs of affiliating with people who do not reliably adhere to our core moral values. In other words, people who most highly value generosity should be quickest to stop considering others to be generous if they act frugally in a particular instance. Across two studies conducted on Prolific (N = 966), we found consistent evidence that people weight moral lapses more heavily when rating others' membership in highly cherished moral categories, supporting the Moral Stringency Hypothesis. In Study 2, we examined a possible mechanism underlying this phenomenon. Although perceptions of hypocrisy played a role in moral updating, personal moral values and subsequent judgments of a person's potential as a good cooperative partner provided the clearest explanation for changes in moral character attributions. Overall, the robust tendency toward moral stringency carries significant practical and theoretical implications.


Failure to detect a stimulatory effect of estradiol-17 beta on ovine fetal lung maturation.
It has been reported that estradiol-17 beta (E2) stimulates rat and rabbit fetal lung maturation; however, E2 was not directly administered to the fetus in these experiments. Therefore, we used the chronically instrumented fetal sheep to study the effects of 14 days of continuous E2 infusion on fetal lung maturation. Animals were instrumented on days 104-106 of gestation, then infused with either saline or E2 (100 micrograms/day) from 111 to 127 days of gestation. Fetal plasma concentrations of E2, estrone, and cortisol, and tracheal fluid phosphatidylcholine:sphingomyelin ratios and phosphatidylcholine flux were measured daily in E2-infused (n = 8) and saline-infused (n = 6) control animals. At 127 days of gestation, fetuses were sacrificed and lung tissue samples obtained for biochemical and morphological analyses. Plasma E2 levels rose from 0.045 +/- 0.001 (mean +/- SE) to 7.45 +/- 5.31 ng/ml (p less than 0.05) in E2-infused animals whereas levels remained less than 0.06 ng/ml in saline-infused animals. Plasma estrone concentrations also were significantly elevated by E2 infusion. Plasma cortisol concentrations increased from 0.58 +/- 0.08 to 0.88 +/- 0.40 microgram/dl in E2-treated fetuses during the last week of infusion whereas values in control animals were unchanged. The ratio of acetone-precipitated phosphatidylcholine to sphingomyelin and the flux of acetone-precipitated phosphatidylcholine in tracheal fluid were not affected by E2 infusion. Fetal lung tissue phospholipid content was also unaffected by E2 infusion. Furthermore, there was no consistent effect of E2 infusion on the histological structure of the fetal lung tissue as determined by morphometric methods.(ABSTRACT TRUNCATED AT 250 WORDS)


Persulfate activation during exertion of total oxidant demand.
Total oxidant demand (TOD) is a parameter that is often measured during in situ chemical oxidation (ISCO) treatability studies. The importance of TOD is based on the concept that the oxidant demand created by soil organic matter and other reduced species must be overcome before contaminant oxidation can proceed. TOD testing was originally designed for permanganate ISCO, but has also recently been applied to activated persulfate ISCO. Recent studies have documented that phenoxides activate persulfate; because soil organic matter is rich in phenolic moieties, it may activate persulfate rather than simply exerting TOD. Therefore, the generation of reactive oxygen species was investigated in three soil horizons of varied soil organic carbon content over 5-day TOD testing. Hydroxyl radical may have been generated during TOD exertion, but was likely scavenged by soil organic matter. A high flux of reductants + nucleophiles (e.g. alkyl radicals + superoxide) was generated as TOD was exerted, resulting in the rapid destruction of the probe compound hexachloroethane and the common groundwater contaminant trichloroethylene (TCE). The results of this research document that, unlike permanganate TOD, contaminant destruction does occur as TOD is exerted in persulfate ISCO systems and is promoted by the activation of persulfate by soil organic matter. Future treatability studies for persulfate ISCO should consider contaminant destruction as TOD is exerted, and the potential for persulfate activation by soil organic matter.


Long-term impact of the 2011 Great East Japan Earthquake and tsunami on functional disability among older people: A 3-year longitudinal comparison of disability prevalence among Japanese municipalities.
It has been unclear whether the prevalence of disability is higher in an area affected by natural disaster than in other areas even if more than one year has passed since the disaster. The aim of this ecological study was to examine whether the rate of increase in disability prevalence among the older population was higher in disaster-stricken areas during the 3 years after the Great East Japan Earthquake (GEJE) and tsunami. This analysis used public Long-term Care Insurance (LTCI) data covering 1570 municipalities. "Disaster areas" were considered to be the three prefectures most affected by the earthquake and tsunami: Iwate, Miyagi, and Fukushima. The outcome measure was the number of aged people (≥65 years) with LTCI disability certification. Rates of change in disability prevalence from January 2011 to January 2014 were used as the primary outcome variable, and compared by analysis of covariance between "coastal disaster areas", "inland disaster areas" and "non-disaster areas". The mean rate of increase in disability prevalence in coastal (14.7%) and inland (10.0%) disaster areas was higher than in non-disaster areas (6.2%) (P < 0.001). During the 3 years after the earthquake, the increase of disability prevalence from before the GEJE continued to be higher in the disaster-stricken areas.


Ecological balance emerges in implementing the water-energy-food security nexus in well-developed countries in Africa.
Although many African countries have made significant progress towards universal access to water, energy, and food resources (WEF), assessing the ecological response to the increasing productivity of these resources is not well researched, which carries the risk of ecological deficit, resource degradation, and inefficient policy responses to resource management. This study seeks to assess the ecological sustainability response to the high increase demand for WEF resources in well-developed African countries. The study developed new measurement metrics for the WEF production system, including three indicators of ecological footprint (EF), ecological biocapacity (EBC), and eco-balance. The overall analysis considers data from four distinct types of water and energy use activities, and eight distinct types of food consumption, in nine African countries with the highest WEF nexus performance. An evaluation tool for the Water, Energy, Food and Ecological Balance (WEFEB) nexus index is proposed as one of the study's outcomes. Despite having 100% access to WEF resources related to the SDG targets. The results reveal the significant levels of imbalance and large ecological deficits existing in many of the concerned countries, especially North Africa, Mauritius, and South Africa, which need to rethink their economic models. Projecting a sustained increase in resource demand so that each country achieves at least 1700 m3/capita/year as the minimum amount of water needed, most countries would suffer from a steady increase in ecological imbalance. According to the results, managing the ecological imbalances with increasing demand for WEF resources in well-developed African countries may require well-designed policies to effectively reduce certain types of human demand that have a large ecological footprint.


Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B.
The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001), respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2%, 83.3%, 90.6%, 73.5%, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9%, 80.0%, 87.2%, 60.0%, 3.59%, 0.35% and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100%, at the same time sensitivity declined to 63.2% and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7%, NPV to 86.4%, and LR- declined to 0.08. Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is contraindicated.


[Regulation of inflammatory responses by endothelial cells--understanding the molecular mechanism(s) and its therapeutic application to sepsis].
Endothelial cells are activated by shear-stress and inflammatory mediators that are capable of activating sensory neurons. Activated endothelial cells increase the production of nitric oxide and prostaglandins, thereby regulating inflammatory responses induced by various insults. Dysfunction of sensory neurons and excess inflammatory mediators released from activated neutrophils damage endothelial cells, thereby increasing inflammatory responses such as an increase in tumor necrosis factor production. Pulmonary endothelial dysfunction plays a critical role in the development of acute lung injury and shock, leading to multi-organ failure. Determination of soluble E-selectin in serum samples of patients with sepsis predicts the future development of acute lung injury. Therapeutic agents that are capable of stimulating sensory neurons or inhibiting leukocyte activation might be useful in the treatment of severe sepsis especially when these agents are administered in the early stage of severe sepsis.


Cloning a balanced translocation associated with DiGeorge syndrome and identification of a disrupted candidate gene.
DiGeorge syndrome (DGS), a developmental defect, is characterized by cardiac defects and aplasia or hypoplasia of the thymus and parathyroid glands. DGS has been associated with visible chromosomal abnormalities and microdeletions of 22q11, but only one balanced translocation--ADU/VDU t(2;22)(q14;q11.21). We now report the cloning of this translocation, the identification of a gene disrupted by the rearrangement and the analysis of other transcripts in its vicinity. Transcripts were identified by direct screening of cDNA libraries, exon amplification, cDNA selection and genomic sequence analysis using GRAIL. Disruption of a gene in 22q11.2 by the breakpoint and haploinsufficiency of this locus in deleted DGS patients make it a strong candidate for the major features associated with this disorder.


Primary bulbar conjunctival basal cell carcinoma: A clinical-pathologic report and literature review.
To enhance the characterization of primary bulbar conjunctival basal cell carcinoma (BCC) clinically and histologically, via report of a case and review of the relevant medical literature. We report the case of a 73-year-old man with no history of skin cancer who presented with a bulbar conjunctival nodule without connection to the eyelid or caruncle, originally thought to represent a pyogenic granuloma. After one month without improvement on topical prednisolone, excisional biopsy was performed, with routine histopathology and immunohistochemistry. The tumor was found histologically to be primary conjunctival BCC. Immunostaining exhibited negative Ber-EP4 and S100, mostly negative CK7 and EMA, and positive p63. Margins were negative, and the patient had no recurrence six months after excision. Primary conjunctival BCC must be considered in the differential diagnosis of a conjunctival lesion which may initially appear benign but does not behave as expected clinically. The location of the tumor in the case presented here refutes a prior postulate that primary conjunctival BCC arises from basal adnexal epithelium in the caruncle. Of the immunohistochemical findings, only the Ber-EP4 result differed from the typical immunostaining profile of cutaneous BCC. Further study is needed to determine the frequency of Ber-EP4 positivity in primary conjunctival BCC.


Comparative Effectiveness of Coalitions Versus Technical Assistance for Depression Quality Improvement in Persons with Multiple Chronic Conditions.
Prior research suggests that Community Engagement and Planning (CEP) for coalition support compared with Resources for Services (RS) for program technical assistance to implement depression quality improvement programs improves 6- and 12-month client mental-health related quality of life (MHRQL); however, effects for clients with multiple chronic medical conditions (MCC) are unknown. To explore effectiveness of CEP vs RS in MCC and non-MCC subgroups. Secondary analyses of a cluster-randomized trial. 93 health care and community-based programs in two neighborhoods. Of 4,440 clients screened, 1,322 depressed (Patient Health Questionnaire, PHQ8) provided contact information, 1,246 enrolled and 1,018 (548 with ≥3 MCC) completed baseline, 6- or 12-month surveys. CEP or RS for implementing depression quality improvement programs. Primary: depression (PHQ9 <10), poor MHRQL (Short Form Health Survey, SF-12<40); Secondary: mental wellness, good physical health, behavioral health hospitalization, chronic homelessness risk, work/workloss days, services use at 6 and 12 months. End-point regressions were used to estimate intervention effects on outcomes for subgroups with ≥3 MCC, non-MCC, and intervention-by-MCC interactions (exploratory). Among MCC clients at 6 months, CEP vs RS lowered likelihoods of depression and poor MHRQL; increased likelihood of mental wellness; reduced work-loss days among employed and likelihoods of ≥4 behavioral-health hospitalization nights and chronic homelessness risk, while increasing faith-based and park community center depression services; and at 12 months, likelihood of good physical health and park community center depression services use (each P<.05). There were no significant interactions or primary outcome effects for non-MCC. CEP was more effective than RS in improving 6-month primary outcomes among depressed MCC clients, without significant interactions.