Application of a spacer gel to optimize three-dimensional conformal and intensity modulated radiotherapy for prostate cancer.
The aim was to evaluate the impact of a spacer gel on the dose distribution, applying three-dimensional conformal (3D CRT) and intensity modulated radiotherapy (IMRT) planning techniques. The injection of a spacer gel (10 ml SpaceOAR™) was performed between the prostate and rectum under transrectal ultrasound guidance in 18 patients with prostate cancer. 3D CRT and IMRT treatment plans were compared based on CT before and after injection (78 Gy prescription dose). In contrast to the PTV and bladder, significant advantages (p<0.01) resulted in respect of all analysed rectal dose values comparing pre spacer with post spacer plans for both techniques. Rectal NTCP (normal tissue complication probability) reached the lowest percentage after spacer injection irrespective of the technique, with a mean reduction of >50% for both IMRT and 3D CRT. Significantly (p<0.01) higher D(mean), and V(78) for the PTV were reached with IMRT vs. 3D CRT plans, with a smaller rectum V(76) but larger rectum V(50). The injection of a spacer gel between the prostate and anterior rectal wall is associated with considerably lower doses to the rectum and consequentially lower NTCP values irrespective of the radiotherapy technique.


A pathway for biosynthesis of divinyl ether fatty acids in green leaves.
[1-14C]alpha-Linolenic acid was incubated with a particulate fraction of homogenate of leaves of the meadow buttercup (Ranunculus acris L.). The main product was a divinyl ether fatty acid, which was identified as 12-[1'(Z),3'(Z)-hexadienyloxy]-9(Z),11(E)-dodecadienoic acid. Addition of glutathione peroxidase and reduced glutathione to incubations of alpha-linolenic acid almost completely suppressed formation of the divinyl ether acid and resulted in the appearance of 13(S)-hydroxy-9(Z), 11(E),15(Z)-octadecatrienoic acid as the main product. This result, together with the finding that 13(S)-hydroperoxy-9(Z), 11(E),15(Z)-octadecatrienoic acid served as an efficient precursor of the divinyl ether fatty acid, indicated that divinyl ether biosynthesis in leaves of R. acris occurred by a two-step pathway involving an omega6-lipoxygenase and a divinyl ether synthase. Incubations of isomeric hydroperoxides derived from alpha-linolenic and linoleic acids with the enzyme preparation from R. acris showed that 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid was transformed into the divinyl ether 12-[1'(Z)-hexenyloxy]-9(Z), 11(E)-dodecadienoic acid. In contrast, neither the 9(S)-hydroperoxides of linoleic or alpha-linolenic acids nor the 13(R)-hydroperoxide of alpha-linolenic acid served as precursors of divinyl ethers.


Risk of catheter-associated bloodstream infection by catheter type in a neonatal intensive care unit: a large cohort study of more than 1100 intravascular catheters.
The aim of this study was to evaluate the risk of catheter-associated bloodstream infection (CABSI) among different catheter types using a large prospective database in the neonatal intensive care unit (NICU) of a tertiary care centre in Switzerland. We included all neonates admitted to the NICU with at least one central intravascular catheter inserted between January 2017 and December 2020. We used marginal Cox model to determine the risk of CABSI among different catheter types. A total of 574 neonates and 1103 intravascular catheters were included in the study: 581 venous umbilical catheters, 198 arterial umbilical catheters and 324 peripherally inserted central catheters (PICCs). We identified 17, four and four CABSIs in neonates with venous umbilical catheters, arterial umbilical catheters and PICCs, respectively. The risk of CABSI increased after two days of umbilical catheter maintenance. Using univariable Cox models, and adjusting for sex and gestational age, we observed a similar CABSI risk between venous and arterial umbilical catheters (HR 0.57; 95% CI 0.16e2.08). Birth weight was associated with CABSI, with higher weight being protective (HR 0.37, 95% CI 0.16e0.81). Strategies aimed at reducing umbilical catheter dwell time, particularly in low and very low birth weight neonates, may be effective in decreasing the incidence of CABSI in this population.


EUS-FNA Biopsies to Guide Precision Medicine in Pancreatic Cancer: Results of a Pilot Study to Identify KRAS Wild-Type Tumours for Targeted Therapy.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death and lacks effective treatment options. Diagnostic endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies represent an appealing source of material for molecular analysis to inform targeted therapy, as they are often the only available tissue for patients presenting with PDAC irrespective of disease stage. However, EUS-FNA biopsies are typically not used to screen for precision medicine studies due to concerns about low tissue yield and quality. Epidermal growth factor receptor (EGFR) inhibition has shown promise in clinical trials of unselected patients with advanced pancreatic cancer, but has not been prospectively tested in KRAS wild-type patients. Here, we examine the clinical utility of EUS-FNA biopsies for molecular screening of KRAS wild-type PDAC patients for targeted anti-EGFR therapy to assess the feasibility of this approach. Fresh frozen EUS-FNA or surgical biopsies from PDAC patient tumours were used to screen for KRAS mutations. Eligible patients with recurrent, locally advanced, or metastatic KRAS wild-type status who had received at least one prior line of chemotherapy were enrolled in a pilot study (ACTRN12617000540314) and treated with panitumumab at 6mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS). 275 patient biopsies were screened for KRAS mutations, which were detected in 88.3% of patient samples. 8 eligible KRAS wild-type patients were enrolled onto the interventional study between November 2017 and December 2020 and treated with panitumumab. 4-month PFS was 14.3% with no objective tumour responses observed. The only grade 3/4 treatment related toxicity observed was hypomagnesaemia. This study demonstrates proof-of-principle feasibility to molecularly screen patients with pancreatic cancer for targeted therapies, and confirms diagnostic EUS-FNA biopsies as a reliable source of tumour material for molecular analysis. Single agent panitumumab was safe and tolerable but led to no objective tumour responses in this population.


Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.
To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. NCT01827904. This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.


Design and interpretation of bioassays for carcinogenicity.
A description is presented of the difficulties often met in developing meaningful scientific discussions regarding regulatory policy, with examples. In particular, the design and interpretation of rodent bioassays evoke strong emotional responses in many areas. It is suggested that interested parties engage in a scientific debate on some of the more important issues in the appropriate journals, with the purpose of seeking consensus whenever that may be found.


Beetroot juice ingestion does not improve neuromuscular performance and match-play demands in elite female hockey players: a randomized, double-blind, placebo-controlled study.
Beetroot juice is a dietary supplement that contains high levels of inorganic nitrate (NO3-) and that its intake has proven effective at increasing blood nitric oxide (NO) concentrations improving endurance performance. However, the effect of this supplement in team sport performance, especially in female athletes, has been barely studied. This study aimed to compare the acute effects of beetroot juice supplementation on neuromuscular performance and match-play demands in elite female field hockey players. Eleven elite female hockey players (22.8 ± 5.1 years) belonging to a bronze team medal in Eurohockey Club Champions Cup participated in this study. Participants were randomly divided into two groups undergoing a test battery with beetroot juice (70 mL, 6.4 mmol NO3-) or placebo (70 mL, 0.04 mmol NO3-) in two different days with one week between protocols. The neuromuscular test battery consisted of a countermovement jump, isometric handgrip strength (i.e., dominant hand), 20 m-sprint and repeated sprint ability test (RSA). Afterward, a simulated hockey match play (2 × 12.5 min) was performed and recorded by Global Positioning System (GPS). No statistically significant improvements were observed in any physical parameters analysed comparing beetroot juice compared to placebo ingestion, countermovement jump (p = 0.776, ES = 0.16), isometric handgrip strength (p = 0.829; ES = - 0.08), 20 m sprint test (p = 0.227; ES = - 0.23), mean repeated sprint ability (p = 0.955, ES = 0.03) and in any physical match demands measured by GPS (p = 0.243-1.000; ES = 0.02-0.47). Acute beetroot juice supplementation did not produce any statistically significant improvement in neuromuscular performance or match-play demands in elite female field hockey players. The study was registered in ClinicalTrials.gov with the following ID: NCT05209139. The study was retrospectively registered by 26 January 2022.


Effect of dissolved organic matter on copper bioavailability to a coastal dinoflagellate at environmentally relevant concentrations.
The speciation and bioavailability of copper (Cu) in the marine environment are affected by the presence of dissolved organic matter (DOM). Previous studies conducted at dissolved Cu concentrations >100 nM confirmed that Cu bioavailability depends on the concentration of labile Cu, as measured by anodic stripping voltammetry (ASV), which aligns with the expectations of the biotic ligand model (BLM). However, ambient Cu concentrations in coastal waters are generally lower, ranging between 1 and 80 nM, and the effect of DOM on the bioavailability of Cu to marine organisms has not been tested within that range of Cu concentrations. The present study aims to assess the impact of two types of DOM, a commercially available fulvic acid, and marine DOM extracted by ultrafiltration, on Cu bioavailability to phytoplankton using short-term 65Cu internalisation by the marine dinoflagellate Prorocentrum micans. Results showed that Cu internalisation decreases with DOM additions as expected according to the BLM and in agreement with ASV measurements of labile Cu, at the highest tested Cu concentration (100 nM). On the contrary, at a lower Cu concentration (20 nM), organic complexes appear to be partially bioavailable, thereby challenging the general applicability of the BLM model at environmentally relevant concentrations in coastal areas.


High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats.
Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes. Earlier we had demonstrated differential effects of high-fat diet-induced obesity (DIO) and genetically inherited obesity (GIO) on metabolic, hormonal profile, male fertility, and spermatogenesis using two rat models. The present study aimed to understand the effect of DIO and GIO on DNA methylation in male germline, and its subsequent effects on the resorbed (post-implantation embryo loss) and normal embryos. First, we assessed the DNA methylation enzymatic machinery in the testis by Real-Time PCR, followed global DNA methylation levels in spermatozoa and testicular cells by ELISA and flow cytometry, respectively. Further, we performed Methylation Sequencing in spermatozoa for both the groups. Sequencing data in spermatozoa from both the groups were validated using Pyrosequencing. Expression of the differentially methylated genes was assessed in the resorbed and normal embryos sired by the DIO group using Real-Time PCR for functional validation. We noted a significant decrease in Dnmt transcript and global DNA methylation levels in the DIO group and an increase in the GIO group. Sequencing analysis showed 16,966 and 9113 differentially methylated regions in the spermatozoa of the DIO and GIO groups, respectively. Upon pathway analysis, we observed genes enriched in pathways involved in embryo growth and development namely Wnt, Hedgehog, TGF-beta, and Notch in spermatozoa for both the groups, the methylation status of which partially correlated with the gene expression pattern in resorbed and normal embryos sired by the DIO group. Our study reports the mechanism by which diet-induced and genetically inherited obesity causes differential effects on the DNA methylation in the male germline that could be due to a difference in the white adipose tissue accumulation. These differences could either lead to embryo loss or transmit obesity-related traits to the offspring in adult life.


Clinician perspectives on reasons for, implications and management of unplanned patient returns to the Emergency Department: A descriptive study.
Unplanned return visits to the emergency department (ED) have been associated with adverse outcomes and may reflect the quality of care delivered. Several studies speculate the reasons for return and suggest clinician behaviour as potentially influencing a patient's decision to return to the ED. There is little research about this issue from the clinician's perspective, which is necessary to inform future practice improvement. A descriptive cross sectional design was employed to ascertain perspectives on identification and management of return visits occurring within 48 hours of discharge. An electronic survey was distributed to all medical, nursing, and clerical staff at one ED. Descriptive statistics were used for quantitative data and content analysis was performed on textual data. Results were categorised as barriers or facilitators, then mapped to the Theoretical Domains Framework. A response rate of 59.7% (n=86/144) was achieved. Staff reported increased levels of concern for this patient group but not all staff were aware of the policy for managing return patients (40.7%). Five barriers and three facilitators were identified that mapped to eight influencers of behaviour including knowledge, memory and environmental factors. Overall, staff were aware of return patients but lacked familiarity with policy and processes to identify and commence relevant protocols. Further review of current practice as well as the patient perspective is required before any intervention to improve practice is developed.


Novel cross-link breaker based on zwitterion structure: synthesis, structure and druggability studies.
It has been universally acknowledged that the increase in cardiac and vascular stiffness is due to the formation of advanced glycosylation end-products (AGEs). Research on the stable form of 3-(carboxymethyl)-4-methylthiazol bromide sodium salt (C6H7BrNNaO2S) showed that it had a notable effect on breaking the AGEs. Two compounds with novel structures, zwitterionic 3-(carboxymethyl)-4-methylthiazol (C6H7O2NS) and a dipolymer (C12H15O4N2S2Br) complex, were obtained. When compared with the forms of sodium salt and dipolymer, zwitterion had an obvious advantage in stability, solubility, synthesis and pH, which made the zwitterion a promising drug. The structure of sodium salt, dipolymer and zwitterion was comparatively analyzed by such methods as single crystal X-ray diffraction, ESI-MS, 1H NMR, FT-IR and in situ IR.


Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking.
TMEM127 is a poorly known tumor suppressor gene associated with pheochromocytomas, paragangliomas, and renal carcinomas. Our incomplete understanding of TMEM127 function has limited our ability to predict variant pathogenicity. To better understand the function of the transmembrane protein TMEM127 we undertook cellular and molecular evaluation of patient-derived germline variants. Subcellular localization and steady-state levels of tumor-associated, transiently expressed TMEM127 variants were compared to the wild-type protein using immunofluorescence and immunoblot analysis, respectively, in cells genetically modified to lack endogenous TMEM127. Membrane topology and endocytic mechanisms were also assessed. We identified 3 subgroups of mutations and determined that 71% of the variants studied are pathogenic or likely pathogenic through loss of membrane-binding ability, stability, and/or internalization capability. Investigation into an N-terminal cluster of missense variants uncovered a previously unrecognized transmembrane domain, indicating that TMEM127 is a 4- transmembrane, not a 3-transmembrane domain-containing protein. Additionally, a C-terminal variant with predominant plasma membrane localization revealed an atypical, extended acidic, dileucine-based motif required for TMEM127 internalization through clathrin-mediated endocytosis. We characterized the functional deficits of several germline TMEM127 variants and identified novel structure-function features of TMEM127. These findings will assist in determining pathogenicity of TMEM127 variants and will help guide future studies investigating the cellular role of TMEM127.


Utilizing nanozymes for combating COVID-19: advancements in diagnostics, treatments, and preventative measures.
The emergence of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses significant challenges to global public health. Despite the extensive efforts of researchers worldwide, there remains considerable opportunities for improvement in timely diagnosis, specific treatment, and effective vaccines for SARS-CoV-2. This is due, in part, to the large number of asymptomatic carriers, rapid virus mutations, inconsistent confinement policies, untimely diagnosis and limited clear treatment plans. The emerging of nanozymes offers a promising approach for combating SARS-CoV-2 due to their stable physicochemical properties and high surface areas, which enable easier and multiple nano-bio interactions in vivo. Nanozymes inspire the development of sensitive and economic nanosensors for rapid detection, facilitate the development of specific medicines with minimal side effects for targeted therapy, trigger defensive mechanisms in the form of vaccines, and eliminate SARS-CoV-2 in the environment for prevention. In this review, we briefly present the limitations of existing countermeasures against coronavirus disease 2019 (COVID-19). We then reviewed the applications of nanozyme-based platforms in the fields of diagnostics, therapeutics and the prevention in COVID-19. Finally, we propose opportunities and challenges for the further development of nanozyme-based platforms for COVID-19. We expect that our review will provide valuable insights into the new emerging and re-emerging infectious pandemic from the perspective of nanozymes.


Antiproliferative activity, cell-cycle dysregulation, and cellular differentiation: salicyl- and catechol-derived acyclic 5-fluorouracil O,N-acetals against breast cancer cells.
Herein we report the preparation and biological activity of three compounds with the general formula 1-[2-(5-substituted-2-hydroxybenzyloxy)-1-methoxyethyl]-5-fluorouracil. A catechol-derived compound such as 1-[3-(2-hydroxyphenoxy)-1-methoxypropyl]-5-fluorouracil and two salicyl-derived compounds such as (Z)-1-[4-(2-hydroxyphenyl)-1-methoxybut-3-enyl]-5-fluorouracil [(Z)-11] and its dihydrogenated derivative 1-[4-(2-hydroxyphenyl)-1-methoxybutyl]-5-fluorouracil were prepared to complete the set of six O,N-acetals. The most active compound against the MCF-7 breast cancer cell line was (Z)-11: IC(50)=9.40+/-0.64 microM. Differentiated breast cancer cells generate fat deposits in the cytoplasm. MCF-7 cells treated with (Z)-11 underwent an increase in lipid content relative to control cells after three days of treatment. Our results suggest that there may be significant potential advantages in the use of this new differentiating agent for the treatment of breast cancer.


Hormone production by the postmenopausal ovary in cases of benign ovarian neoplasia.
The objective of this study was to determine whether hormone production by postmenopausal ovaries containing benign ovarian tumors differed from that of normal postmenopausal ovaries. The sera of 32 postmenopausal patients were assayed before and after bilateral oophorectomy for estrone, 17 beta-estradiol, androstenedione, testosterone, and dehydroepiandrosterone sulfate. The data from all patients as a group were analyzed, followed by analysis of the data from 15 patients with normal ovaries separately from the remaining 17 patients who had nonfunctioning, benign ovarian tumors. For patients with benign ovarian tumors there was a statistically significant drop in estrone (from a presurgical level of 55.8 +/- 46.3 pg/ml to a postoperative level of 29.9 +/- 10.2 pg/ml, p < 0.03) and 17 beta-estradiol (from 18.6 +/- 14.1 pg/ml preoperatively to 9.8 +/- 3.8 pg/ml postoperatively, p < 0.02). For postmenopausal woman with normal ovaries there was no significant drop in estrone or 17 beta-estradiol after bilateral oophorectomy. There was a statistically significant drop in testosterone and androstenedione after bilateral oophorectomy both for women with normal ovaries and for those with benign tumors. No significant differences in dehydroepiandrosterone sulfate were noted in either group. These data suggest that, although normal postmenopausal ovaries have not been demonstrated to secrete clinically significant amounts of estrogen, those that contain benign ovarian tumors do secrete small but significant amounts of estrone and 17 beta-estradiol. Both tumor-containing and normal ovaries secrete the androgens androstenedione and testosterone, this secretion not being significantly influenced by the presence of a tumor.


(2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands.
Within the constantly growing number of histamine H4 (H4R) receptor ligands there is a large group of azine derivatives. A series of novel compounds in the group of 4-methylpiperazine-1,3,5-triazine-2-amines were designed and obtained. Considered structures were modified at the triazine 6-position by introduction of variously substituted arylethenyl moieties. Their affinities to histamine H4 receptors were evaluated in radioligand binding assays with use of Sf9 cells, transiently expressing human H4R. Pharmacological studies results allowed to identify 4-[(E)-2-(3-chlorophenyl)ethenyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (Ki = 253 nM) as the most potent compound in the present series.


A review on current trends in the treatment of human infection with H7N9-avian influenza A.
The H7N9 subtype of avian influenza is an enzootic and airborne virus which caused an influenza outbreak in China. Infected individuals mostly worked with poultry, suggesting H7N9 virus-infected poultry as the primary source of human infection. Significantly increased levels of proinflammatory mediators (chemokines, cytokines) during virus infection could hamper the immune system and aggravate the infection. Severe cases are marked by fulminant pneumonia, acute respiratory distress syndrome (ARDS) and encephalopathy. Left untreated, the condition may rapidly progress to multi-organ failure and death. Reverse transcription polymerase chain reaction (rRT-PCR) is the gold standard diagnostic test for H7N9 avian influenza. Use of neurominidase inhibitor antivirals remain the main treatment. New antivirals are developed to counteract neurominidase inhibitor resistance H7N9 viral strains. Corticosteroid use in viral pneumonia may provoke mortality and longer viral shedding time. Subjects at high risk of contracting avian influenza H7N9 infection are recommended to receive annual seasonal influenza vaccination.


Cooperative group clinical trials in general thoracic surgery: report from the 2012 Robert Ginsberg Clinical Trials Meeting of the General Thoracic Surgical Club.
At the 25th Annual General Thoracic Surgical Club meeting in March 2012, the major cooperative groups presented updates on clinical trials at the Robert Ginsberg Clinical Trials Meeting. There were 57 members in attendance. Representatives from the Radiation Treatment Oncology Group (RTOG), American College of Surgeons Oncology Group (ACOSOG), Cancer and Leukemia Group B (CALGB), Southwest Oncology Group (SWOG), National Cancer Institute of Canada Clinical Trials Group (NCIC), and the Eastern Cooperative Oncology Group (ECOG) presented an overview of trials currently accruing or in development. These include oncologic trials that thoracic surgeons are currently accruing patients to in North America. The purpose of this review is to centralize the information to assist surgeons enrolling patients into oncologic clinical trials in thoracic surgery.


Phorbol myristate acetate activates protein kinase C, stimulates the phosphorylation of endogenous proteins and inhibits phosphate transport in mouse renal tubules.
Calcium-activated, phospholipid-dependent protein kinase (protein kinase C) has been implicated in the regulation of transport processes in a variety of tissues and cell lines. To establish whether protein kinase C participates in the regulation of renal phosphate transport, we examined the effect of phorbol myristate acetate (PMA), a potent activator of protein kinase C, on phosphate uptake in fresh preparations of mouse renal tubules, and we correlated the changes in transport activity with protein kinase C activation and phosphorylation of endogenous proteins. PMA inhibited Na+-dependent phosphate transport, elicited a rapid translocation of protein kinase C from the cytosolic to the particulate fraction and stimulated the phosphorylation of endogenous substrates in the cytosolic and brush border membrane fractions. Effects of PMA were maximal after a 10 min incubation of the tubules with the activator. 4 alpha-Phorbol, an inert analogue of PMA, did not elicit any of these effects. The present results demonstrate a temporal correlation between inhibition of Na+-dependent phosphate transport, translocation and activation of protein kinase C, and phosphorylation of endogenous proteins in mouse renal tubules. These data suggest that protein kinase C may play a regulatory role in phosphate transport in mammalian kidney.


Hepatocellular protection by nitric oxide or nitrite in ischemia and reperfusion injury.
Ischemia and reperfusion (I/R)-induced liver injury occurs in several pathophysiological disorders including hemorrhagic shock and burn as well as resectional and transplantation surgery. One of the earliest events associated with reperfusion of ischemic liver is endothelial dysfunction characterized by the decreased production of endothelial cell-derived nitric oxide (NO). This rapid post-ischemic decrease in NO bioavailability appears to be due to decreased synthesis of NO, enhanced inactivation of NO by the overproduction of superoxide or both. This review presents the most current evidence supporting the concept that decreased bioavailability of NO concomitant with enhanced production of reactive oxygen species initiates hepatocellular injury and that endogenous NO or exogenous NO produced from nitrite play important roles in limiting post-ischemic tissue injury.


Erythrocyte glutathione peroxidase activity and serum lipid pattern: A comparison between Indian immigrants and Danes.
A comparative data on erythrocyte glutathione peroxidase (GSH-Px) activity, serum cholesterol and serum fatty acid pattern between Indian immigrants and Danes have been presented. The erythrocyte GSH-Px activity in the Indian immigrants has been found to be significantly increased as compared to that in the Danish group when t-buthylhydroperoxide was used as a substrate. Also a significant correlation (R less than or equal to 0.09) was found in the GSH-Px activities in the Indian group with the three peroxides, viz., hydrogen peroxide, cumene hydroperoxide and t-butylhydroperoxide, used. This correlation was, however, missing in the Danish group. Serum cholesterol was found to be significantly lower in the Indian group as compared to the Danes. Also total serum fatty acid patterns between the two groups differed considerably.


In vitro adhesion of mouse fetal germ cells to extracellular matrix components.
Mouse primordial germ cells (PGCs) isolated from the dorsal mesentery and gonadal ridges of 10.5-12.5 days post coitum (dpc) embryos showed a progressively increasing adhesiveness to laminin and fibronectin coated substrates, whereas type I collagen and various glycosaminoglycans (hyaluronic acid, heparin and chondroitin-sulphates) were poor adhesive substrates. At later stages germ cells appeared to lose their adhesiveness to fibronectin and laminin substrates; the ability to adhere to laminin decreased very rapidly in male and slowly in female germ cells. Oocytes and prospermatogonia from 15.5 dpc fetal gonads showed poor adhesiveness to all substrates tested. PGC adhesion to laminin and fibronectin substrates did not require calcium but was markedly trypsin sensitive. Antibodies against the fibronectin receptor of CHO fibroblasts and short peptides containing the Arg-Gly-Asp sequence greatly reduced PGC adhesion to fibronectin. Following adhesion to laminin or fibronectin, most PGCs did not exhibit a morphology typical of motile cells, but remained spherical. A significant proportion (about 30%) of oocytes from 13.5-14.5 dpc embryos appeared, however, able to spread and elongate following attachment to laminin. The results support the hypothesis that mouse PGCs may utilize laminin and/or fibronectin as adhesive substrates during migration and gonad colonization, but indicate that additional factors are probably required to promote PGC motility. In addition, our data provide indirect evidence that binding sites for specific components of extracellular matrix are present in PGCs, and that their expression may be developmentally regulated.


How to measure the QT interval--what is normal?
The QT interval extends from the beginning of the QRS complex to the end of the T wave. Since the report of Jervell and Lange-Nielsen in 1957, it has been difficult to determine whether to measure a QT or a QU interval. U waves are more prominent in the left chest leads and less prominent in lead II, with the end of the T wave in lead II corresponding to the end of significant repolarization in any other lead. Therefore, by convention, lead II has been chosen to measure the QT interval. Numerous attempts at correction have been made, but Bazett's correction (QT/square root of RR) remains the current standard. In stable sinus rhythm, a QT interval corrected for heart rate (QTc) of > 0.44 sec is considered abnormal. In this study, in the presence of sinus arrhythmia, the QT interval following the shortest RR interval was > 0.46 sec in 98.4% of patients with the congenital long QT syndrome, but in only 3.8% of control subjects (p < 0.0001). Likewise, in the presence of sinus arrhythmia, the uncorrected QT interval varied by > 0.03 seconds in a 10-sec rhythm strip of lead II in 33% of long QT syndrome patients but in 0% of controls (p < 0.01). The QT interval varied depending on autonomic tone and state of wakefulness, being approximately 19 msec longer in sleeping patients with a heart rate of 60 beats/min than in awake patients with the same heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)


A "bridging" (safety/tolerance) study of besipirdine hydrochloride in patients with Alzheimer's disease.
Besipirdine hydrochloride is a novel compound with cholinergic and adrenergic activity being investigated as a treatment for Alzheimer's disease (AD). The pharmacodynamics of some anti-dementia drugs are known to differ in patients with AD as compared with elderly normals. The present study was designed to determine the maximum tolerated dose (MTD) of multiple oral doses of besipirdine in AD patients. Twelve AD patients (NINCDS/ADRDA criteria; 7M, 5F, ages 58-75, mean age 65) were randomized to besipirdine (n = 9) or placebo (n = 3) in a double-blind, parallel-group, rising-dose design. Doses were 10, 20, 30, and 40 mg bid for 2 days each, followed by 50 and 60 mg bid for 5 days each. The most common adverse events were asymptomatic postural hypotension and asymptomatic bradycardia. Two patients on active drug developed severe adverse events: 1 after 3 days at 50 mg bid (nausea and vomiting); 1 after 3 days at 60 mg bid (angina). Due to the anginal episode, the study was terminated on Day 17. Plasma concentrations increased linearly with dose for besipirdine and its major metabolite. The two patients who developed severe adverse events had the highest plasma concentrations measured. Besipirdine 50 mg bid was considered the maximum tolerated dose (MTD).


Covalent decoration of graphene oxide with dendrimer-encapsulated nanoparticles for universal attachment of multiple nanoparticles on chemically converted graphene.
We report a method for universal assembly of multiple nanoparticles with different sizes and compositions on a single chemically converted graphene sheet with good control over particle sizes in the range of 1 to 2 nm through the covalent immobilization of dendrimer-encapsulated nanoparticles.


Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment.
It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca2+, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl2, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca2+, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.


Presence of angina pectoris before acute myocardial infarction and degree of residual stenosis after coronary thrombolysis.
This study tested the hypothesis that the degree of residual stenosis after coronary thrombolysis reflected that of original stenosis presented by symptom of angina before acute myocardial infarction (AMI). The relation between the presence of angina before AMI and the degree of residual stenosis after coronary thrombolysis was observed in 57 patients with successful coronary thrombolysis for AMI. Patients with significant coronary artery stenoses other than the artery responsible for AMI were excluded from this study. In 22 patients with chronic angina for 2 weeks or longer before AMI, 14 patients had a residual stenosis of 75% or more and 8 patients had a residual stenosis of less than 75%. In 35 patients with angina for less than 2 weeks or not at all before AMI, 9 patients had a residual stenosis of 75% or more, and 26 patients had a residual stenosis of less than 75% (p less than 0.01). In the course of progression of coronary artery disease, some patients had AMI without severe underlying stenosis and others with severe underlying stenosis. Patients with chronic angina before AMI might tend to have AMI with acute occlusion superimposed on the severe organic stenosis. Patients without chronic angina before AMI would be more at risk for AMI caused by acute occlusion without underlying severe stenosis.


Anatrophic nephrolithotomy in the solitary kidney.
A retrospective analysis was conducted on 30 patients who had undergone anatrophic nephrolithotomy for staghorn calculus disease in a solitary kidney. No statistically significant difference (p greater than 0.1) was found between the average preoperative and postoperative renal function values. Of 27 patients who were infected preoperatively 19 were rendered free of further urinary tract infection and 24 of 30 patients (80 per cent) had no further recurrence of renal calculi. Because of the predictable morbidity and mortality associated with the non-operative management of staghorn calculus disease these patients are managed best by the complete surgical removal of all calculi and intensive antimicrobial therapy.


Gender differences and dose proportionality in the toxicokinetics of udenafil and its active metabolite following oral administration in rodents.
Udenafil is a long-acting oral phosphodiesterase type 5 inhibitor used to treat erectile dysfunction which may also have beneficial effects on cardiovascular diseases. Udenafil is mainly biotransformed to the active metabolite N-dealkylated udenafil via cytochrome P450 3A. The aim of this study was to investigate the gender differences and dose proportionality of the toxicokinetics of udenafil and its metabolite N-dealkylated udenafil in rodents. Udenafil was administered orally by gavage to male and female B6C3F1/N mice (100, 240, 350, and 500 mg/kg) and F344 rats (60, 120, and 240 mg/kg). Plasma concentrations of udenafil and N-dealkylated udenafil were simultaneous measured via liquid chromatography-tandem mass spectrometry. Female mice showed higher systemic exposure to udenafil than male mice, whereas female rats showed lower systemic exposure to udenafil than male rats after repeated administration at high dose. Systemic exposure to the metabolite, N-dealkylated udenafil, was lower in female than male mice and rats. A dose proportionality assessment by power model revealed a lack of dose proportionality in systemic exposure (Cmax, AUC24h and AUCinf) after administration of 100-500 mg/kg of udenafil in mice and 60-240 mg/kg in rats. This study thus demonstrates gender and species differences with regard to the toxicokinetic profiles of udenafil and its active metabolite N-dealkylated udenafil after oral administration of udenafil to mice and rats of both sexes. Our findings suggest the possibility of gender differences in the toxicokinetics of udenafil in humans and suggests that further study is needed in this cohort.


Cell cycle-driven neuronal apoptosis specifically linked to amyloid peptide Abeta1-42 exposure is not exacerbated in a mouse model of presenilin-1 familial Alzheimer's disease.
We have shown previously that beta-catenin and cyclin D1 are up-regulated in cortical neurons from homozygous mice carrying the familial Alzheimer's disease (FAD) presenilin-1 M146V mutation in a knock-in model (PS1 KI(M146V) mice), leading to cell cycle-associated apoptosis. Here, we have aimed to determine (i) whether this phenotype is present in heterozygous PS1 KI(M146V) mice, which reflects more accurately the PS1 FAD condition in humans and (ii) whether Abeta(1-42), which is invariably present in the PS1 FAD brain and is thought to affect neuronal cell cycle kinetics, may contribute to the abnormal cell cycle/cell death phenotype seen in PS1 KI(M146V) mice. We demonstrate that cell cycle-linked apoptosis occurs in heterozygous PS1 KI(M146V) post-mitotic neurons. In addition, there is a significant Abeta-associated increase in cell cycle and cell death that is not further modified by the PS1 KI(M146V) mutation. Our results are consistent with a cell cycle-associated neurodegeneration model in the PS1 FAD brain in which the loss of PS1-dependent beta-catenin regulatory function is sufficient to commit susceptible neurons to an abortive cell cycle, and may act synergistically with the Abeta cytotoxic challenge present in the PS1 FAD brain to expand the neuronal population susceptible to cell cycle-driven apoptosis.


Duodenal ulcerogens cysteamine and propionitrile decrease duodenal neutralization of acid in the rat.
Neutralization of acid was evaluated in rat proximal duodenal segments isolated from biliary and pancreatic secretions. Duodenal ulcerogenic doses of cysteamine produced a significant decrease in acid disposal 0.5-2 hr after treatment. Oral or subcutaneous administration of the duodenal ulcerogen was effective. The potent ulcerogen cysteamine produced a more pronounced decrease than propionitrile (a weak duodenal ulcerogen). The failure of ethanolamine, a nonulcerogenic structural analog of cysteamine to significantly alter acid disposal suggests that the effect is not due to the toxic properties of the duodenal ulcerogen. The results reinforce the concept that the duodenum is able to dispose of significant quantities of acid. The decrease in acid-handling may contribute to duodenal susceptibility to acid after treatment with ulcerogens and possibly reflects pathophysiologic changes early in duodenal ulceration.


The role of community health centers in providing behavioral health care.
The prevalence of behavioral health problems is higher for low-income individuals, yet this population is less likely to receive behavioral health treatment. Community health centers have their advantages as behavioral health-care providers because they serve a majority low-income population and are located in medically underserved areas. Their role in providing behavioral health care is expected to expand under health reform as they are expected to double their patient capacity, and due to increased insurance coverage for individuals with behavioral health problems. However, the ability of community health centers to provide behavioral health care is compromised by provider shortages and funding shortfalls.


Time to exonerate eyewitness memory.
Understandably enough, most people are under the impression that eyewitness memory is unreliable. For example, research shows that memory is malleable, so much so that people can come to confidently remember traumatic events that never actually happened. In addition, eyewitness misidentifications made with high confidence in a court of law are known to have played a role in more than 70% of the 358 wrongful convictions that have been overturned based on DNA evidence since 1989. However, recent research demonstrates that eyewitness confidence is highly indicative of accuracy on an initial, uncontaminated, properly administered photo lineup. In other words, low confidence indicates that the test result (i.e., the ID) is inconclusive, whereas high confidence indicates that the test result is far more conclusive. Critically, for the DNA exonerees who were misidentified by an eyewitness in a court of law, in every case where their initial confidence can be determined, the eyewitness appropriately expressed low confidence. For any other kind of evidence (e.g., DNA, fingerprints), an inconclusive test result like that would have been the end of it. By contrast, in the case of eyewitness evidence, investigators repeatedly tested (and therefore unwittingly contaminated) memory until a seemingly conclusive high-confidence ID could be presented to the jury. Blaming eyewitness memory for the failure of the criminal justice system to accept the inconclusive nature of the initial (uncontaminated) eyewitness evidence seems misguided. In addition to exonerating the innocent defendants who were wrongfully convicted, the time has come to exonerate eyewitness memory too.


An electrophoretic mobility shift assay for methionine sulfoxide in proteins.
Study of the posttranslational modification of methionine to its sulfoxide has been receiving increasing attention because of its implication in regulation of protein activity, but techniques for the detection of this modification remain limited. In particular, there has been no method to detect the oxidation of methionine on polyacrylamide gels. Here we demonstrate that alkylation of methionine introduces a charge change that shifts the mobility of the protein on an acidic gel relative to the alkylation-resistant sulfoxide form.


Long term effects of ritodrine on blood pressure and heart rate of adolescents exposed during the prenatal stage.
To determine the long term cardiovascular effects in adolescents exposed to ritodrine during prenatal stage. Twenty-seven ritodrine-exposed subjects and 19 controls, of both sexes, clinically healthy, and born at normal term, were evaluated for systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) each during 48 hours, with a Colin Ambulatory monitor. Data analysis were performed by individual Cosinor method, and non-parametric Mann Whitney's test and Lamotte procedures. Adolescents who were exposed to ritodrine showed losses in the HR rhythm and rising middle pulse values. Although SBP and DBP rhythm remains constant, the increase of maximum and minimum values for SBP as well as a rise of maximal rates of DBP suggest a possible hypertensive effect mediated by beta mimetic exposure. This study suggests a hypertensive effect mediated by beta mimetic exposure.


Photosynthetic pathways, distribution, and ecological characteristics of grass species in egypt.
This study is based both on our own results, especially δ13C analyses, and on data in the literature. Of the 225 species of Poaceae reported from Egypt, 105 species show the C3 and 120 the C4 type of photosynthetic CO2 fixation. Winter annual and perennial grasses active in winter are mainly C3 species, while summer annuals and the other perennials are mainly C4 species. The percentage of C3 species decreases with decreasing latitude. This seems to be mainly related to increasing temperatures. The C3 grass species are found preferentially in the Mediterranean, Irano-Turanian, Mediterranean/Irano-Turanian, and Saharo-Arabian chorotypes, while the C4 species are mainly found in the Sudanian, Saharo-Arabian/Sudanian and Tropical chorotypes. In Egypt, the NADP+-ME and NAD+-ME subtypes of C4 photosynthesis are found in about equal numbers of C4 species, while the PCK subtype is relatively rare.


Pediatric day-care surgery: a 30-year hospital experience.
Over a 30-year period (may 1955 to December 1985), day care surgery was performed on 39,654 patients at the Winnipeg Children's Hospital (WCH). Up to 51% of all pediatric surgical cases and 59% of elective pediatric cases, involving more than 50 different procedures, were performed annually on a day-care basis. The overall incidence of postoperative problems and admission to hospital was 1.5% and 1.1%, respectively. A unique preoperative home visiting program by nurses was demonstrably effective in reducing late cancellations by 75%. The WCH experience adds further evidence that day-care surgery in a pediatric hospital is safe and effective for a large proportion of infants and children requiring operation.


Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia.
The purpose of this study was to assess if simvastatin has an anti-inflammatory activity in patients with hypercholesterolemia. Simvastatin, an inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, reduced cardiovascular events in patients with myocardial infarction and hypercholesterolemia. Sixteen patients with polygenic hypercholesterolemia were randomly allocated to diet (n = 8) or diet plus 20 mg/day simvastatin (n = 8) for eight weeks. Before and at the end of treatment period, lipid profile and monocyte expression of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) were measured. At baseline no difference in lipid profile and monocyte expression of TNF and IL-1beta were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1beta was seen. In patients with diet plus simvastatin, significant decreases of total cholesterol (-27%, p<0.02), low density lipoprotein-cholesterol (-33%, p<0.02), and monocyte expression of TNF (-49%, p<0.02) and IL-1beta (-35%, p<0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1beta than did patients assigned to diet alone. This study suggests that simvastatin possesses anti-inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL-1beta expressed by monocytes.


A rapid method for detection and identification of flaviviruses by polymerase chain reaction and nucleic acid hybridization.
A polymerase chain reaction (PCR) technique was developed and evaluated for the detection of flaviviruses. A set of sense and antisense oligomeric DNA primers were constructed from nucleotide sequences of the conserved region of the genome of several different flaviviruses. Virus specific complementary DNA (cDNA) was prepared by reverse transcription of total RNA extracted from infected cell cultures. Amplified cDNA was identified by nucleic acid hybridization with specific oligomeric internal probes. Various conditions, such as number of cycles and annealing temperature were examined to optimize the detection of viral RNAs from infected cell cultures. Slot blot hybridization with a radioactive probe was used to evaluate the sensitivity of PCR amplification. The PCR amplified RNA sequences of dengue 2 (DEN-2), West Nile (WN), St. Louis encephalitis (SLE) and Kunjin (KUN) virus and detected 0.1 to 1 pg of viral RNA. Japanese encephalitis (JE), Yellow Fever virus (YF), DEN-1, 3, and 4 viruses were not amplified. The more frequent occurrence of mismatches in the 3' primer binding site may explain the failure to amplify cDNA of these viruses.


Reliability of the amplitude of low-frequency fluctuations in resting state fMRI in chronic schizophrenia.
The resting state amplitude of low frequency fluctuations (ALFF) in functional magnetic resonance imaging has been shown to be reliable in healthy subjects, and to correlate with antipsychotic treatment response in antipsychotic-naïve schizophrenia patients. We found moderate to high test-retest stability of ALFF in chronically treated schizophrenia patients assessed twice over a median interval of 2.5 months.


Protracted vomiting following abrupt cessation of psychotropics: a case report.
The case of a 23-year-old patient treated with haloperidol, imipramine, and benztropine mesylate is presented to illustrate an unusually severe reaction to the abrupt cessation of neuroleptic medication. In addition to the description of the withdrawal reaction, a possible explanation of the clinical phenomenon is offered.


On the phase-field modelling of a miscible liquid/liquid boundary.
Mixing of miscible liquids is essential for numerous processes in industry and nature. Mixing, i.e. interpenetration of molecules through the liquid/liquid boundary, occurs via interfacial diffusion. Mixing can also involve externally or internally driven hydrodynamic flows, and can lead to deformation or disintegration of the liquid/liquid boundary. At the moment, the mixing dynamics remains poorly understood. The classical Fick's law, generally accepted for description of the diffusion process, does not explain the experimental observations, in particular, the recent experiments with dissolution of a liquid solute by a liquid solvent within a horizontal capillary (Stevar and Vorobev, 2012). We present the results of the numerical study aimed at development of an advanced model for the dissolution dynamics of liquid/liquid binary mixtures. The model is based on the phase-field (Cahn-Hilliard) approach that is used as a physics-based model for the thermo- and hydrodynamic evolution of binary mixtures. Within this approach, the diffusion flux is defined through the gradient of chemical potential, and, in particular, includes the effect of barodiffusion. The dynamic interfacial stresses at the miscible interface are also taken into account. The simulations showed that such an approach can accurately reproduce the shape of the solute/solvent boundary, and some aspects of the diffusion dynamics. Nevertheless, all experimentally-observed features of the diffusion motion of the solute/solvent boundary, were not reproduced.


[The theory-practice problem of blood pressure assessment].
The theoretical basis for assessment of blood pressure described in the guidelines of the ISH-ESC and in JNC 7 ignores the variability of blood pressure and is therefore not applicable in general practice. Although the guidelines do not meet the daily requirements, they are not questioned by the physician, and are therefore confusing both physicians and millions of patients taking self-recordings. The unsolved problems are: The confidence interval for the single readings and the mean values are ignored. For this reason, the assignment of the patient to the different categories of hypertension is variable and dependent on pure chance. The effects of therapy cannot be detected in a reliable way. Judging the quality of self-recorded data, the blood pressure variability is interpreted as an error of measurement. The problem can be avoided if, instead of single values, mean values out of a sufficient number of measurements and their confidence intervals are assessed.


The ratio of QRS/RV6-V1: a new electrocardiographic predictor of short- and long-term adverse clinical outcomes in patients with acute myocardial infarction combined with new-onset right bundle branch block.
A few studies have focused on electrocardiography (ECG) parameters correlating with clinical prognosis in patients with acute myocardial infarction (AMI) combined with new-onset right bundle branch block (RBBB). To assess the prognostic value of a new ECG parameter, namely, the ratio of QRS duration/RV6-V1 interval (QRS/RV6-V1), in patients with AMI combined with new-onset RBBB. A total of 272 AMI patients combined with new-onset RBBB who received primary percutaneous coronary intervention (P-PCI) were retrospectively enrolled in the study. First, the patients were divided into survival group and non-survival group. Demographic, angiographic, and ECG characteristics were compared between the two groups. Receiver operating characteristic (ROC) curve was used to screen the best ECG parameter for predicting 1-year mortality. Second, the ratio of QRS/RV6-V1, a continuous variable, was converted to the high ratio group and low ratio group according to the optimal cutoff value point determined by the X-tile software. We compared the patient's demographic, angiographic, and ECG characteristics, in-hospital major adverse cardiovascular events (MACE), and 1-year mortality between the two groups. Multivariate logistic and Cox regressions were used to evaluate whether the ratio of QRS/RV6-V1 was an independent prognostic factor of in-hospital MACE and 1-year mortality. The ROC curve showed that the ratio of QRS/RV6-V1 had a higher value for predicting in-hospital MACE and 1-year mortality than the QRS duration, RV6-V1 interval, and RV1 interval. The patients in the high ratio group had significantly higher CK-MB peak and Killip class, lower ejection fraction (EF%), higher ratio of the left anterior (LAD) descending artery as infarct-related artery (IRA), and longer total ischemia time (TIT) than those in the low ratio group. The QRS duration was wider in the high ratio group than that in the low ratio group, whereas RV6-V1 was narrower in the high ratio group compared with that in the low ratio group. The in-hospital MACE rate (93.3% vs. 31.0%, p < 0.001) and 1-year mortality rate (86.7% vs. 13.2%, p < 0.001) in the high ratio group were higher than those in the low ratio group. The higher ratio of QRS/RV6-V1 was an independent predictor of in-hospital MACE (odds ratio, 8.55; 95% CI, 1.40-52.37; p = 0.02) after adjusting other confounders. Cox regression showed that the higher ratio of QRS/RV6-V1 predicted higher 1-year mortality of the patients with AMI combined with new-onset RBBB [hazard ratios (HR), 12.4; 95% CI, 7.26-21.22); p < 0.001] than the lower ratio of QRS/RV6-V1, and the HR still stayed at 2.21 even after a multivariable adjustment (HR, 2.21; 95% CI, 1.05-4.64); p = 0.037). According to the results of our study, the high ratio of QRS/RV6-V1 (>3.0) was a valuable predictor of short- and long-term adverse clinical outcomes in AMI patients combined with new-onset RBBB. The implications of the high ratio of QRS/RV6-V1 were severe ischemia and pseudo synchronization between bi-ventricle.


Comparison of ureteral and cervical descents during vaginal hysterectomy for uterine prolapse.
The study measured ureteral and cervical locations during vaginal hysterectomy for prolapse and the extent of parametrial ligament shortening possible. Cervical and ureteral position were measured in 26 women undergoing uterine prolapse correction. Parametrial clamp tip location was also measured. The cervix lay between 0 and -14.5 cm (below) the hymen (mean +/- SD -5.35 +/- 3.96 cm) and the ureters lay +5.0 to -4.0 cm (mean +/- SD +1.89 +/- 1.99 cm). Correlation of ureteral with cervical position was 0.69 (P <.01) and correlation with ipsilateral uterosacral ligament clamp positions was 0.80 (P <.01). Regression line slope relating cervical descent and cervix to ureter distance was 0.65, indicating that for every 3 cm of cervical descent there was 2 cm widening of the gap between the cervix and ureters and 1 cm descent of the ureter. For every 3 cm of cervical descent the ureters descend 1 cm, thereby widening the ureterocervical gap and permitting ligament shortening during vaginal hysterectomy.


What Patients Say: Large-Scale Analyses of Replies to the Parkinson's Disease Patient Report of Problems (PD-PROP).
Free-text, verbatim replies in the words of people with Parkinson's disease (PD) have the potential to provide unvarnished information about their feelings and experiences. Challenges of processing such data on a large scale are a barrier to analyzing verbatim data collection in large cohorts. To develop a method for curating responses from the Parkinson's Disease Patient Report of Problems (PD-PROP), open-ended questions that asks people with PD to report their most bothersome problems and associated functional consequences. Human curation, natural language processing, and machine learning were used to develop an algorithm to convert verbatim responses to classified symptoms. Nine curators including clinicians, people with PD, and a non-clinician PD expert classified a sample of responses as reporting each symptom or not. Responses to the PD-PROP were collected within the Fox Insight cohort study. Approximately 3,500 PD-PROP responses were curated by a human team. Subsequently, approximately 1,500 responses were used in the validation phase; median age of respondents was 67 years, 55% were men and median years since PD diagnosis was 3 years. 168,260 verbatim responses were classified by machine. Accuracy of machine classification was 95% on a held-out test set. 65 symptoms were grouped into 14 domains. The most frequently reported symptoms at first report were tremor (by 46% of respondents), gait and balance problems (>39%), and pain/discomfort (33%). A human-in-the-loop method of curation provides both accuracy and efficiency, permitting a clinically useful analysis of large datasets of verbatim reports about the problems that bother PD patients.


Overhead electricity power lines and childhood leukemia: a registry-based, case-control study.
To evaluate the role of exposure to low-frequency electromagnetic fields generated by overhead power lines on the risk of childhood leukemia, we carried out a case-control study in the area (Varese province) covered by the Lombardy Cancer Registry. Exposure to magnetic fields was estimated using line load data and the distance between subjects' homes and the nearest power line. A total of 101 cases and 412 controls were investigated. Twenty subjects (9 cases and 11 controls) were considered exposed. A significant fourfold increase in risk for leukemia in exposed subjects and a dose-response relationship were found. The risk was higher than that reported by other studies. Potential biases related to the representativity of controls and validity of exposure assessment do not seem to have influenced the risk estimates. We suggest that measures to remedy residential exposure should be taken wherever practicable.


Pathologic evidence of pseudoexfoliation in cases of in-the-bag intraocular lens subluxation or dislocation.
To provide complete histopathologic evaluation of explanted capsular bags that spontaneously dislocated in the late postoperative period, with the main objective being to assess the presence of pseudoexfoliation (PXF) material. Goethe-University Frankfurt, Frankfurt, Germany, and John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Retrospective case series. Standard gross and light microscopy and complete histopathology were performed on explanted subluxated and dislocated capsular bags containing an intraocular lens (IOL) or a capsular tension ring (CTR) and an IOL. Questionnaires were sent to explanting surgeons, and a patient chart review was performed, when available. The specimens were represented by capsular bags containing an IOL (n = 37) or an IOL-CTR (n = 3). The IOLs included 3-piece hydrophobic acrylic (n = 13), 1-piece hydrophobic acrylic (n = 7), 3-piece silicone (n = 6), 1-piece hydrophilic acrylic (n = 6), 3-piece hydrophilic acrylic (n = 2), and 1-piece poly(methyl methacrylate) (PMMA) (n = 6) designs; all CTRs were PMMA. Soemmering ring formation was mild in 8 specimens, moderate in 18 specimens, and severe in 14 specimens. Excessive contraction of the capsular bag with capsulorhexis phimosis was observed in 24 specimens. Twenty-six specimens had histopathologic evidence of PXF; 13 had a clinical history or evidence of PXF. Pseudoexfoliation might be implicated in a larger proportion of late in-the-bag IOL subluxations and dislocations than previously thought as a result of significant clinical underdiagnosis. This might indicate a need for new considerations during the preoperative and postoperative cataract surgery assessments and follow-up.


Can a single composite resin serve all purposes?
The consensus view less than a decade ago was that direct posterior composites should be restricted to small restorations, preferably in premolar teeth with little, if any, occlusal function. Major advances in adhesive systems, materials and restorative techniques have combined to allow us to question this view and our increased clinical evidence base makes it appropriate to reconsider this viewpoint.


Gender incidence of intracytoplasmic morphologically selected sperm injection-derived embryos: a prospective randomized study.
The aim of this prospective randomized study was to determine if the use of intracytoplasmic morphologically selected sperm injection (IMSI) is associated with gender incidence. Couples who underwent IVF-preimplantation genetic screening (PGS) cycles, as a result of advanced maternal age, were randomly allocated into two groups: intracytoplasmic sperm injection (ICSI; n=80) or intracytoplasmic morphologically selected sperm injection (IMSI; n=80). The incidences of genders were compared between ICSI- and IMSI-derived embryos. Considering all the biopsied embryos were characterized as normal for sex chromosome, the results showed that IMSI results in a significantly higher incidence of female embryos as compared with ICSI (65.1% versus 54.0%, respectively, P=0.0277). After analysing only euploid embryos for the eight selected chromosomes, a significantly higher incidence of XX embryos derived from IMSI was also observed compared with ICSI cycles (66.9% versus 52.5%, respectively, P=0.0322). This result was confirmed by logistic regression, which demonstrated a nearly 2-fold increase in euploid XX embryos derived from spermatozoa selected by high magnification (OR 1.83, 95% CI 1.05-3.35, P=0.032). A higher proportion of morphologically normal spermatozoa analysed under high magnification seem to carry the X chromosome. The aim of this study was to determine if the use of intracytoplasmic morphologically selected sperm injection (IMSI) is associated with gender incidence. Couples who underwent IVF with preimplantation genetic screening, as a result of advanced maternal age, were randomly allocated into two groups: intracytoplasmic sperm injection (ICSI; n=80) or intracytoplasmic morphologically selected sperm injection (IMSI; n=80). The incidences of genders were compared between ICSI- and IMSI-derived embryos. Our results showed that a significantly higher incidence of female embryos derived from IMSI compared with ICSI cycles (66.9% versus 52.5%, respectively, P=0.0322). This result was confirmed by logistic regression, which demonstrated a nearly 2-fold increase in female embryos derived from sperm selected by high magnification (OR 1.83, 95% CI 1.05-3.35, P=0.032). A higher proportion of morphologically normal spermatozoa analysed under high magnification seem to carry the X chromosome.


An in situ assessment of the routes and extents of colonisation of the mouse embryo by embryonic stem cells and their descendants.
An embryonic stem (ES) cell line stably expressing lacZ under the control of an endogenous promoter has been isolated and used as a marker to follow the fate of ES cells injected into blastocysts and morulae, before midgestation. The results show a multisite pattern of blastocyst colonization by ES cells deposited into the blastocoel cavity and a low degree of mingling between ES cells and ICM cells. Furthermore, analysis of dispersal of ES cell descendants in postimplantation chimaeric embryos showed that colonization can be highly variable from one region of the embryo to another. In contrast, a high and reproducible degree of chimaerism was obtained when the ES cells were injected at the morula stage prior to ICM formation.


Ex vivo drug sensitivity testing as a means for drug repurposing in esophageal adenocarcinoma.
Esophageal cancer remains one of the hardest cancers to treat with rising incidence rates, low overall survival and high levels of treatment resistance. The lack of clinically available biomarkers hinder diagnosis and treatment stratification. While large scale sequencing approaches have uncovered a number of molecular makers, little has translated in the routine treatment of esophageal cancer patients. We evaluate the treatment response towards a panel of 215 FDA-approved and 163 epigenetic compounds of 4 established and 2 patient-derived esophageal cancer cell lines. Cell viability was evaluated after 72h of treatment using cell titer glow. The drug sensitivity testing results for gemcitabine and cisplatin were validated using clonogenic assays. The tested cell lines display different drug sensitivity profiles, although we found compounds that display efficacy in all of the tested established or patient-derived cell lines. Clonogenic assays confirmed the validity of the drug sensitivity testing results. Using the epigenetic library, we observed high sensitivity towards a number of epigenetic modifiers. Ex vivo drug sensitivity testing may present a viable option for the treatment stratification of esophageal cancer patients and holds the potential to greatly improve patient outcome while reducing treatment toxicity.


Complex carbohydrates at the ocular surface of the mouse: an ultrastructural and cytochemical analysis.
Scanning electron microscopy (SEM) of mouse cornea and conjunctiva fixed with picric acid-paraformaldehyde-glutaraldehyde (PA-P-G) mixture revealed a thin layer of amorphous material covering the microvilli of the corneal surface cells. At the transmission electron microscopic (TEM) level, this layer of material stained positively with dialyzed iron, alcian blue and cationized ferritin, all of which are markers for anionic sulfate or carboxyl groups. The corneal surface was negative for high iron diamine, which specifically stains sulfate groups. These results indicate that the murine ocular surface is rich in carboxyl groups. Treatment with neuraminidase prior to fixation significantly reduced (P less than 0.005) cationic ferritin binding, suggesting that most of the carboxyl groups at the ocular surface are associated with sialic acid residues. The corneal surface also stained positively at the TEM level when a periodic acid-thiocarbohydrazide-silver protein sequence (PA-T-SP) was applied. This result indicated the presence of periodic acid-Schiff (PAS)-positive glycoprotein and glycolipid at the ocular surface.


Synthesis of heterocycles via Pd-ligand controlled cyclization of 2-chloro-N-(2-vinyl)aniline: preparation of carbazoles, indoles, dibenzazepines, and acridines.
The Pd-catalyzed condensation of 2-bromostyrene and 2-chloroaniline derivatives yields stable diphenylamine intermediates, which are selectively converted to five-, six-, or seven-membered heteroaromatics (indoles, carbazoles, acridines, and dibenzazepines). The selectivity of these intramolecular transformations is uniquely ligand-controlled and offers efficient routes to four important classes of heterocycles from a common precursor.


Physiologic responses to a staircase lung volume optimization maneuver in pediatric high-frequency oscillatory ventilation.
Titration of the continuous distending pressure during a staircase incremental-decremental pressure lung volume optimization maneuver in children on high-frequency oscillatory ventilation is traditionally driven by oxygenation and hemodynamic responses, although validity of these metrics has not been confirmed. Respiratory inductance plethysmography values were used construct pressure-volume loops during the lung volume optimization maneuver. The maneuver outcome was evaluated by three independent investigators and labeled positive if there was an increase in respiratory inductance plethysmography values at the end of the incremental phase. Metrics for oxygenation (SpO2, FiO2), proximal pressure amplitude, tidal volume and transcutaneous measured pCO2 (ptcCO2) obtained during the incremental phase were compared between outcome maneuvers labeled positive and negative to calculate sensitivity, specificity, and the area under the receiver operating characteristic curve. Ventilation efficacy was assessed during and after the maneuver by measuring arterial pH and PaCO2. Hemodynamic responses during and after the maneuver were quantified by analyzing heart rate, mean arterial blood pressure and arterial lactate. 41/54 patients (75.9%) had a positive maneuver albeit that changes in respiratory inductance plethysmography values were very heterogeneous. During the incremental phase of the maneuver, metrics for oxygenation and tidal volume showed good sensitivity (> 80%) but poor sensitivity. The sensitivity of the SpO2/FiO2 ratio increased to 92.7% one hour after the maneuver. The proximal pressure amplitude showed poor sensitivity during the maneuver, whereas tidal volume showed good sensitivity but poor specificity. PaCO2 decreased and pH increased in patients with a positive and negative maneuver outcome. No new barotrauma or hemodynamic instability (increase in age-adjusted heart rate, decrease in age-adjusted mean arterial blood pressure or lactate > 2.0 mmol/L) occurred as a result of the maneuver. Absence of improvements in oxygenation during a lung volume optimization maneuver did not indicate that there were no increases in lung volume quantified using respiratory inductance plethysmography. Increases in SpO2/FiO2 one hour after the maneuver may suggest ongoing lung volume recruitment. Ventilation was not impaired and there was no new barotrauma or hemodynamic instability. The heterogeneous responses in lung volume changes underscore the need for monitoring tools during high-frequency oscillatory ventilation.


Erythrophagocytosis by dysplastic neutrophils in chronic myelomonocytic leukemia and subsequent transformation to acute myeloid leukemia.
Erythrophagocytosis by neutrophils is a rare phenomenon in myeloid malignancies, and its clinicopathologic significance is not fully understood. We report a unique case of erythrophagocytosis by dysplastic neutrophils in chronic myelomonocytic leukemia (CMML) and subsequent transformation to acute myeloid leukemia (AML). Review of multiple marrow samples, both pretreatment and post-treatment, demonstrated a correlation between percentage of dysplastic neutrophils and degree of erythrophagocytosis. Erythrophagocytosis was observed only in dysplastic forms of neutrophils. Post-transplant marrows with engraftment of donor cells showed no neutrophilic dysplasia or erythrophagocytosis. Possible mechanisms of neutrophilic erythrophagocytosis in myeloid malignancies are discussed.


Transverse maxillary distraction with a bone-anchored appliance: dento-periodontal effects and clinical and radiological results.
In 29 adult patients presenting with maxillary deficiency, a bone-anchored palatal distractor (Surgi-Tec NV, Brugge, Belgium) was applied after osteotomy of the anterolateral walls of the maxillary sinuses, midpalatal suture, and, eventually, separation of the pterygomaxillary sutures. Expansion proceeded at a rate of 0.33-0.66 mm per day and the device was retained for 4-6 months for consolidation. Active orthodontic therapy was started after 8-10 weeks. The increment of arch width and the perimeter were evaluated using dental casts. Tooth thermal sensitivity and the periodontal side effects of treatment were monitored clinically after distraction, at device removal, and after 1 year. Bone healing was also investigated during the procedure using conventional radiological techniques. This experience confirms that transverse maxillary distraction is an effective technique in adult patients, leading to the formation of new bone. There were no noticeable intraoperative complications, but postsurgical periodontal side effects were documented. The procedure offers advantages over traditional teeth-borne appliances in terms of rapidity of treatment and the absence of mechanical forces acting on the teeth. Further evaluation is required to assess the long-term stability and periodontal consequences of this technique.


Functional requirement of the Arabidopsis importin-α nuclear transport receptor family in autoimmunity mediated by the NLR protein SNC1.
IMPORTIN-α3/MOS6 (MODIFIER OF SNC1, 6) is one of nine importin-α isoforms in Arabidopsis that recruit nuclear localization signal-containing cargo proteins to the nuclear import machinery. IMP-α3/MOS6 is required genetically for full autoimmunity of the nucleotide-binding leucine-rich repeat immune receptor mutant snc1 (suppressor of npr1-1, constitutive 1) and MOS6 also contributes to basal disease resistance. Here, we investigated the contribution of the other importin-α genes to both types of immune responses, and we analyzed potential interactions of all importin-α isoforms with SNC1. By using reverse-genetic analyses in Arabidopsis and protein-protein interaction assays in Nicotiana benthamiana, we provide evidence that among the nine α-importins in Arabidopsis, IMP-α3/MOS6 is the main nuclear transport receptor of SNC1, and that IMP-α3/MOS6 is required selectively for autoimmunity of snc1 and basal resistance to mildly virulent Pseudomonas syringae in Arabidopsis.


Postmortem diagnosis of sudden unexpected death from Streptococcus suis type 2 infection: a case report.
Streptococcus suis causes meningitis, septicemia, arthritis, endocarditis and death in both pigs and humans. Sudden death is rarely documented in the forensic field and almost all cases were diagnosed pre-mortem. Here we report a 49-year-old man who died from S. suis type 2 infection. S. suis was identified as the causative pathogen using bacterial culture, standard biochemical and coagglutination tests, specific DNA amplification by polymerase chain reaction, and histopathologic examination. We discuss the postmortem investigation of a suspected S. suis infection.


Global population genomic signature of Spodoptera frugiperda (fall armyworm) supports complex introduction events across the Old World.
Native to the Americas, the invasive Spodoptera frugiperda (fall armyworm; FAW) was reported in West Africa in 2016, followed by its chronological detection across the Old World and the hypothesis of an eastward Asia expansion. We explored population genomic signatures of American and Old World FAW and identified 12 maternal mitochondrial DNA genome lineages across the invasive range. 870 high-quality nuclear single nucleotide polymorphic DNA markers identified five distinct New World population clusters, broadly reflecting FAW native geographical ranges and the absence of host-plant preferences. We identified unique admixed Old World populations, and admixed and non-admixed Asian FAW individuals, all of which suggested multiple introductions underpinning the pest's global spread. Directional gene flow from the East into eastern Africa was also detected, in contrast to the west-to-east spread hypothesis. Our study demonstrated the potential of population genomic approaches via international partnership to address global emerging pest threats and biosecurity challenges.


Forest leaf litter nutrient discharge patterns in snowmelt surface runoff and watershed scale remote sensed simulation.
The leaf litter decomposition is the important chain for the nutrient cycle in forest ecosystem, but its degradation dynamics and pulse discharge patterns in freeze-thawing watershed needed complete understanding. By integrating field observations and MODIS data, the temporal-spatial distributions of snow coverage and forest leaf litter biomass were analyzed. The critical period for snowmelt runoff under warming temperature and the relatively slow degradation patterns were identified. The on-site observations snowmelt runoff showed discharge concentration and fraction dynamics of typical forest leaf litter nutrients (carbon, nitrogen, and phosphorus) in thawing period. The snowmelt runoff flow and nutrient flux observed the linear regressions with the increased temperature from -8 °C to 6 °C (r2 = 0.443-0.987). The concentration of TOC, TN, and TP reached summit value around 50.0, 6.0, and 0.5 mg L-1 in the snowmelt runoff, respectively. The fraction analysis proved that the much high composition of dissolved organic fraction and the biggest organic phosphorus percentage was 94%. The comparison experiments of forest soil with or without leaf litter cover demonstrated that the leaf litter caused a lower discharge load in the snowmelt flow, and the leaf litter cover can decease the potential transport capability of the snowmelt runoff. Coupled with remote sensing data, the watershed leaf litter nutrient discharge model was developed with snowmelt hydrological process mode. The watershed averaged discharge of TOC, TN, and TP from deciduous broad-leaved forest leaf litter was around 851.99, 75.05, and 9.78 mg·m-2, respectively. The yearly simulation showed the spatial distribution variance of the nutrient discharge loads were held by different forest types, elevations, and slopes. The critical loss area identification provided new mitigations solution. The findings suggested that seasonal discharge of forest leaf litter nutrient in thawing period acted as a key contributor to watershed water pollution.


Perinatal outcome of congenital heart disease in a population with high consanguinity.
To report the perinatal pattern and outcome of fetuses with congenital heart disease (CHD) in consanguineous marriages. Retrospective chart review was performed for fetuses undergoing fetal echocardiography (FE) in our institution. The primary outcome was survival at 28 days after birth. Between 1 January 2005 and 31 December 2010, 1950 pregnant women carrying 2151 fetuses underwent a total of 2828 FEs. CHD was diagnosed in 152 fetuses (7.1%), and perinatal outcome was available in 120, among which 78 (65%) had consanguineous parents. Thirteen fetuses died in utero, while 86 (71.7%) survived. The most prevalent lesions included left heart obstruction (25.8%), conotruncal malformations (21.7%), septal defects (18.3%), and cardiomyopathy (15.8%). Correct diagnosis was achieved in 92.2% of the cases. Extracardiac malformations occurred in 48.3% of the fetuses and were associated with increased mortality regardless of the type of CHD (P<0.001, odds ratio 6.8, 95% confidence interval 2.7-17.5). Joint FE clinics detect most CHD with high accuracy. Consanguinity contributes to a higher prevalence of fetal cardiac and non-cardiac malformations. The presence of extracardiac anomalies is associated with an increase in perinatal mortality.


Acute dapsone poisoning: clinical features and pharmacokinetic studies.
A case of acute dapsone poisoning in a 57 year old man is reported. Peak plasma dapsone concentrations of 18.8 mg/l were observed 20 hours after ingestion, and methaemoglobin concentrations fell in parallel with dapsone. Plasma dapsone concentrations declined mono-exponentially with time, and the half-life (29.7 hours) was similar to that described in subjects receiving conventional doses. Moreover, the ratio of monoacetyl-dapsone (MADDS) to dapsone remained constant as plasma concentrations fell. These observations suggest that N-acetylation of dapsone was not saturated even at the toxic concentrations observed.


In vivo immunogold labeling confirms large-scale chromatin folding motifs.
The difficulty in localizing specific cellular proteins by immuno-electron microscopy techniques limits applications of electron microscopy to cell biology. We found that in vivo immunogold labeling improves epitope accessibility, ultrastructural preservation and three-dimensional visualization, and allows correlated light and electron microscopy. We detected large-scale chromatin folding motifs within intact interphase nuclei of CHO cells and visualized the ultrastructure of DNA replication 'factories' labeled with GFP-proliferating cell nuclear antigen (PCNA).


Suicide ideation and a post-disaster assessment of risk and protective factors among Hurricane Harvey survivors.
Previous studies have documented evidence of increased suicidality after natural disasters. While there is some disagreement about when and how long mental health consequences are sustained in the post-disaster setting, it is nevertheless an important outcome requiring further examination. In the present study, a sample of Hurricane Harvey survivors (n=316) were interviewed over a three-month period beginning in October 2017, two months after a Category 4 hurricane devastated the Texas Gulf Coast. Using logistic regression, the analysis examines sociodemographic vulnerabilities, as well as individual risks that potentially exacerbate and protections that mitigate the odds of suicide ideation among survivors. Approximately 10 percent of the sampled survivors reported suicide ideation post-Hurricane Harvey. Females, persons with elevated symptoms of post-traumatic stress symptoms, persons reporting moderate to high levels of food insecurity, and those with previous mental health issues were related to higher odds in reported suicide ideation. We examined a number of protective factors and religious social capital and optimism were both negative and statistically significant (p < 0.05) and related to lower odds of suicide ideation. To our knowledge, these findings are the first to come out of the Hurricane Harvey disaster zone, specifically focusing on suicide ideation. Mental health professionals need to continue to be sensitive to the nuance of disaster impact on the psychological functioning of survivors, with potential negative mental health symptoms persisting 6 to 12 months after a natural disaster event.


Anaerobic induction of the maize GapC4 promoter in poplar leaves requires light and high CO2.
The maize (Zea mays L.) glyceraldehyde-3-phosphate dehydrogenase gene 4 ( GapC4) promoter confers anaerobic gene expression in tobacco (Nicotiana tabacum L.), potato (Solanum tuberosum L.) and Arabidopsis thaliana (L.) Heynh. Here we have investigated its expression in hybrid poplar (Populus tremula x P. alba). Our results show that the promoter is not expressed in leaves and stems under normoxic conditions while anaerobiosis induces reporter gene expression in leaves up to a level observed for the STLS-1 promoter from potato that is shown to confer leaf-specific gene expression in transgenic poplar. Anaerobic induction is cell autonomous and requires a CO2 atmosphere and light. As in tobacco, the GapC4 promoter in poplar is wound inducible. The induction by CO2 and light may reflect a natural situation because flooding, a natural cause of anaerobiosis, is often accompanied by high CO2 concentrations in the floodwater. Our results show that the GapC4 promoter is suitable as an anaerobic reporter and as an inducible gene expression system in poplar.


Increasing resourcefulness: the key to declining resources.
Nurse executives face many daily issues related to balancing scarce resources with an ever-increasing demand for high quality services and programs. Never before have nursing organizations been faced with such relentless pressure to conserve resources and control costs in the process to meet organizational missions.


Formation of fluorine-18 labeled diaryl ureas--labeled VEGFR-2/PDGFR dual inhibitors as molecular imaging agents for angiogenesis.
Urea subunits are common components of various pharmaceuticals' core structure. Since in most cases the design and development of PET biomarkers is based on approved or potential drugs, there is a growing need for a general labeling methodology of urea-containing pharmacophores. As a part of research in the field of molecular imaging of angiogenic processes, we synthesized several highly potent VEGFR-2/PDGFR dual inhibitors as potential PET biomarkers. The structure of these inhibitors is based on the N-phenyl-N'-{4-(4-quinolyloxy)phenyl}urea skeleton. A representative inhibitor was successfully labeled with fluorine-18 by a three-step process. Initially, a two-step radiosynthesis of 4-[(18)F]fluoro-aniline from 1,4-dinitrobenzene (60min, EOB decay corrected yield: 63%) was performed. At the third and final step, the 4-[(18)F]fluoro-aniline synthon reacted for 30min at room temperature with 4-(2-fluoro-4-isocyanato-phenoxy)-6,7-dimethoxy-quinoline to give complete conversion of the labeled synthon to 1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-3-(4-[(18)F]fluoro-phenyl)-urea. The desired labeled product was obtained after total radiosynthesis time of 3h including HPLC purification with 46+/-1% EOB decay corrected radiochemical yield, 99% radiochemical purity, 99% chemical purity, and a specific activity of 400+/-37GBq/mmol (n=5).


The stress response and adolescents' adjustment: the impact of child maltreatment.
Experience with and management of stress has implications for adolescents' behavioral and socioemotional development. This study examined the relationship between adolescents' physiological response to an acute laboratory stressor (i.e., Trier Social Stress Test; TSST) and anger regulation and interpersonal competence in a sample of 175 low-income urban adolescents (51.8% girls). Findings suggested that heightened reactivity as indicated by cortisol, heart rate, and blood pressure was associated with increased interpersonal competence and anger regulation. However, these findings were context dependent such that, for youth high in self-reported child maltreatment, heightened reactivity was associated with decreased interpersonal competence and anger regulation. Results highlight the importance of considering how context may condition the effect of stress reactivity on functioning during adolescence.


Comparison of avian cell substrates for propagating subtype C avian metapneumovirus.
Avian metapneumovirus (AMPV) is a respiratory viral pathogen that causes turkey rhinotracheitis (TRT) or swollen head syndrome (SHS) in chickens. AMPV was first isolated in South Africa during the early 1970s and has subsequently spread worldwide during the 1980s to include Europe, Asia, and South America. In 1996, a genetically distinct AMPV subgroup C was isolated in the US following an outbreak of TRT. Vero cells are currently the best available substrate for AMPV propagation but are of non-avian origin. A number of different avian cell substrates have been compared to determine which is the most suitable for the propagation of AMPV to sufficiently high titers. Of the cell substrates tested, primary turkey turbinate and kidney and chicken kidney cells produced titers equal to or greater than Vero cells. Turkey turbinate and kidney epithelial cells that were life-span extended by the ectopic expression of human telomerase catalytic subunit (HTERT) initially displayed AMPV titers comparable to Vero cell controls, but declined in virus production with increased passage in culture. Interestingly, plaques emanating from Vero propagated virus were relatively small and dispersed, when analyzed by immunofluorescent assays (IFA), while both turkey turbinate and kidney cell propagated AMPV produced larger plaques. Even with these differences, there were no changes in the predicted amino acid sequences of the nucleocapsid (N) and phosphoprotein (P) genes of AMPV propagated in either turkey turbinate or Vero host cells. However, the fusion (F) gene showed 11 amino acid differences (98.7% identity) between the two host cell types. These results suggest that AMPV propagated in homologous avian cellular substrates may produce more infectious virus with possibly more effective fusion activity, compared to Vero cell propagation.


A Smartphone App to Assist Scalp Localization of Superficial Supratentorial Lesions--Technical Note.
Neuronavigation is an established technology in neurosurgery. In parts of the world and certain circumstances in which neuronavigation is not easily available or affordable, alternative techniques may be considered. An app to assist scalp localization of superficial supratentorial lesions has been introduced, and its accuracy has been compared with established neuronavigation systems. Sina is a simple smartphone app that overlaps the transparent patients' computed tomography/magnetic resonance images on the background camera. How to use Sina intraoperatively is described. The app was used for scalp localization of the center of the lesions in 11 patients with supratentorial pathologies <3 cm in longest diameter and <2 cm from the cortex. After localization of the lesion using Sina, the center of the lesion was marked on the scalp using standard neuronavigation systems and the deviations were measured. Implementation of Sina for intraoperative scalp localization is simple and practical. The center of the lesions localized by Sina was 10.2 ± 2 mm different from localization done by standard neuronavigation systems. When neuronavigation is not easily available or affordable, Sina can be helpful for scalp localization and preoperative planning of the incision for selected supratentorial pathologies.


Sex difference in effect of ankle landing biomechanics in sagittal plane on knee valgus moment during single-leg landing.
Ankle landing strategies affects the biomechanical characteristics of the knee joint, especially knee frontal plane loading. However, no studies have investigated whether the association between ankle landing biomechanics in sagittal plane and the knee frontal plane loading differs between sexes. The purpose of this study was to examine whether there is a sex difference in the effect of ankle plantar flexion at the contact angle, ankle range of motion (ROM), and ankle plantar flexion moment on knee valgus loading during single-leg landing. Twenty-five females and twenty-four males performed a single-leg landing. Joint kinematics and kinetics of the lower extremities were measured. The relationship between ankle biomechanics in the sagittal plane (ankle plantar flexion angle at contact, ROM, and peak ankle plantar flexion moment) and peak knee valgus moment were analyzed. In males, the larger ankle plantarflexion angle at contact and ROM were significantly associated with lower peak knee valgus moment. In addition, in males only, a greater peak ankle plantar flexion moment was significantly associated with a lower peak knee valgus moment and greater peak ankle inversion moment. Altering ankle landing strategies in the sagittal plane during single-leg landing may reduce the knee valgus moment, which is one of risk factors for anterior cruciate ligament injury, in males only.


Association between an indel polymorphism within CTH and the risk of sudden cardiac death in a Chinese population.
Individuals harbouring specific genetic variations might trend towards suffering sudden cardiac death. Cystathionine-γ-lyase is one of the key enzymes of endogenous hydrogen sulfide production, and a key factor on the expression regulation of hydrogen sulfide in human heart. Compelling studies have suggested the cardioprotective effects of hydrogen sulfide, while it remains controversial whether cystathionine-γ-lyase and hydrogen sulfide are beneficial to cardiovascular diseases. In this study, we performed a candidate-gene-based study to evaluate the association of the Indel polymorphism rs113044851 within the 3' untranslated region of Cystathionine-γ-lyase gene and risk of sudden cardiac death in a Chinese Han population. Logistic regression analysis showed that the insertion allele of rs113044851 significantly decreased the risk of sudden cardiac death [odds ratio = 0.58; 95% confidence interval:0.38-0.88; P = 0.0076]. Further genotype-phenotype association analysis indicated that the insertion allele was significantly associated with lower expression of cystathionine-γ-lyase in myocardium tissues. The subsequently in-silico predication revealed that compared with the deletion allele, the binding of the insertion allele with miR-1324 matched better. Finally, dual-luciferase activity assay validated the prediction that the gene transcriptional activity indicated by firefly luciferase activity with ins/ins genotype was lower than that with del/del genotype. In summary, our data suggested that rs113044851 might contribute to susceptibility of sudden cardiac death via regulating gene expression at post-transcriptional level. This indel has the potential to become a molecular diagnosis marker and genetic counseling of sudden cardiac death.


Risk reconsidered: targets of violence in the social networks of people with serious psychiatric disorders.
Risk Reconsidered: Targets of violence in the Social Networks of People with Serious Mental illness. This exploratory analysis addresses the questions: 1) Who among the members of the social network of a person diagnosed with a major psychiatric disorder is likely to become a target of violence? 2) What kind of relationships do targets have with respondents in terms of the quality and quantity of interactions?, and 3) What are the risk factors that contribute to being a target of violence for people who are in the social networks of persons with serious mental disorders? The samples of 169 people with serious mental disorders were followed for 30 months. A logistic regression model of the risk for being a target of violence among the members of the cohort's social network reveals that both target and respondent characteristics are salient, and that mothers who live with adult children who have schizophrenia and co-occurring substance abuse bear a substantially elevated risk of becoming a target of violence, compared to other social network members. Other factors that elevate the risk for being a target of violence are being an immediate family members of the respondent, more time in residence with the respondent, and whether the respondent is financially dependent on the family. Respondents with the most mental health center visits had lower odds of committing an act or threat of violence against a social network member.