Inhibition of the enzyme purine nucleoside phosphorylase (PNP) reduces refractoriness to transfused platelets in a dog model.
To better define the role of T-cells in alloimmunization, we induced purine nucleoside phosphorylase (PNP) deficiency in a dog platelet transfusion model. Short-term administration of eight different drug schedules using several combinations of the PNP inhibitor 8-aminoguanosine and/or deoxyguanosine did not induce significant toxicity in four treated animals as demonstrated by blood chemistries, cell counts, and autologous platelet recovery and survival measurements. However, continuous long-term daily administration of these agents produced significant renal and/or hepatic toxicity leading to death in five of six animals. Modification of the drug schedule to early short-term administration of both deoxyguanosine and 8-aminoguanosine, followed by long-term intermittent doses of only 8-aminoguanosine, was not only well tolerated by all the animals but also resulted in significant immunosuppression. Overall, six of nine evaluable dogs (67%) treated with some combination of PNP inhibitors did not become refractory to eight weekly transfusions of platelets from a single random donor dog, P less than 0.005, compared to untreated controls, only 3/21 (14%) not immunized. Furthermore, in four evaluable recipients, discontinuation of the 8-aminoguanosine while continuing platelet transfusions from their original donors did not result in refractoriness. In addition, these four recipients were also unable to recognize platelets from two other random donors. This suggests that both specific and non-specific tolerance to foreign platelet antigens had been induced by PNP-inhibitor therapy. Other evidence for the efficacy of this immunosuppressive treatment was the almost normal post-transfusion recovery and survival of donor platelets, both during and after treatment. This suggests failure to form even low levels of platelet alloantibodies in the immunosuppressed recipients. In contrast, B-cell immunity to soluble antigens was intact as demonstrated by a normal antibody response to keyhole limpet haemocyanin (KLH) antigen.


Peroneal neuropathy misdiagnosed as L5 radiculopathy: a case report.
The purpose of this case report is to describe a patient who presented with a case of peroneal neuropathy that was originally diagnosed and treated as a L5 radiculopathy. A 53-year old female registered nurse presented to a private chiropractic practice with complaints of left lateral leg pain. Three months earlier she underwent elective left L5 decompression surgery without relief of symptoms. Lumbar spine MRI seven months prior to lumbar decompression surgery revealed left neural foraminal stenosis at L5-S1. The patient symptoms resolved after she stopped crossing her legs. This report discusses a case of undiagnosed peroneal neuropathy that underwent lumbar decompression surgery for a L5 radiculopathy. This case study demonstrates the importance of a thorough clinical examination and decision making that ensures proper patient diagnosis and management.


Effects of Pretreatments on Patulin Removal from Apple Juices Using Lactobacilli: Binding Stability in Simulated Gastrointestinal Condition and Modeling.
Recently, researchers have reported the presence of patulin as a mycotoxin in commercial apple products, especially apple juices. The aim of this study was to assess adsorption of patulin from artificially contaminated apple juice using two lactic acid bacteria (LAB) strains of Lactobacillus acidophilus ATCC 4356 and Lactobacillus plantarum ATCC 8014. Furthermore, effects of five physical and chemical pretreatments on the patulin adsorption were investigated. Results demonstrated that patulin adsorption abilities of both strains increased with NaOH pretreatment but decreased after autoclaving. The NaOH-treated L. plantarum ATCC 8014 showed the best removal rate (59.74%) after 48 h of refrigerated storage, compared with the NaOH-treated L. acidophilus ATCC 4356 (52.36%). Moreover, stability of the LAB-patulin complex was assessed in simulated gastrointestinal tract conditions and a low quantity of patulin was released into the solution. The patulin adsorption process by NaOH-treated L. plantarum ATCC 8014 followed Freundlich isotherm model and pseudo-second-order kinetic model. Fourier transform infrared spectroscopy showed that polysaccharide and protein components of the L. plantarum ATCC 8014 cell wall played key roles in patulin adsorption. The major functional groups of the cell wall that were involved in adsorbing patulin included -OH/-NH, -CH2, C=O, and C-O groups. The current results suggest that NaOH-treated L. plantarum ATCC 8014 cells include the potential to detoxify patulin-contaminated apple juices.


Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells.
AP-1, the polypeptide product of c-jun, recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation. Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells, increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA. Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells. Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation. Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation, increased c-jun expression. TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts. Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells, and that exposure to TPA increases this rate 3.3-fold. Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription. The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min. In contrast, the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h. These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms.


Plasma PAF-AH (PLA2G7): Biochemical Properties, Association with LDLs and HDLs, and Regulation of Expression.
This chapter is focused on the plasma form of PAF-acetylhydrolase (PAF-AH), a lipoprotein-bound, calcium-independent phospholipase A2 activity also referred to as lipoprotein-associated phospholipase A2 and PLA2G7. PAF-AH catalyzes the removal of the acyl group at the sn-2 position of PAF and truncated phospholipids generated in settings of inflammation and oxidant stress. Here, I discuss current knowledge related to the structural features of this enzyme, including the molecular basis for association with lipoproteins and susceptibility to oxidative inactivation. The circulating form of PAF-AH is constitutively active and its expression is upregulated by mediators of inflammation at the transcriptional level. Several new mechanisms of regulation have been identified in recent years, including effects mediated by PPARs, VEGFR, and the state of cellular differentiation. Moreover, I discuss recent studies describing significant variations in the structure and regulation of PAF-AH from diverse species, which is likely to have important implications for the function of this enzyme in vivo.


Are US results for assisted reproduction better than the rest? Is it a question of competence or policies?
A comparison of nationally published 2006 data from the USA, UK and Australia and New Zealand (ANZ) was performed. Although live births/cycle was higher in USA, live birth/embryo transferred was significantly higher in ANZ (18.2%) compared with both USA and UK (13.8%) (P<0.001). The multiple rates were significantly lower in ANZ (12.0%) compared with USA (30.7%) and UK (25.2%) (P<0.001). The incidence of oocyte donation was significantly higher in the USA (11.1%) than in ANZ (2.8%) and UK (3.9%) (P<0.001). There was significantly higher cycle cancellation in USA (11.5%) compared with the UK (6.8%) and ANZ (9.5%) (P<0.001). The incidence of frozen embryo transfer cycles was significantly higher in ANZ (59%) compared with both UK (24%) and USA (22%) (P<0.001). The total live birth rate from fresh and frozen cycles for the same year was significantly higher in ANZ at 32.0% compared with the UK at 28.8% (P<0.001) with half the multiple rate. It is argued that the USA's higher success rates are explained by policy (transferring higher number of embryos) and selection issues (cancelling or avoiding poor responders) rather than being a matter of clinical competence.


Enzymatic deacylations of esterified saccharides--III. Comparison of de-esterifications by serum esterases from different sources.
1. 14C-labelled methyl 2,6-di-O-pivaloyl-alpha-D-glucopyranoside (1) was used as a substrate for esterases from rabbit, guinea pig, mouse, donkey, pig, horse, sheep and human sera. 2. Stepwise de-esterification of the diester substrate 1 occurred with rabbit, guinea pig and mouse serum. Data on time-course experiments and kinetic data are reported. 3. The use of donkey, pig, horse, sheep and human serum led to the migration of the 2-O-pivaloyl group in substrate 1 to the position 4- in the sugar molecule, followed by stepwise de-esterifications of both 1 and the newly formed methyl 4,6-di-O-pivaloyl-alpha-D-glucopyranoside (4). A report is given on the time-course experiments.


A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays.
For decades, epineurial electrodes have been used in clinical therapies involving the stimulation of peripheral nerves. However, next generation peripheral nerve interfaces for applications such as neuroprosthetics would benefit from an increased ability to selectively stimulate and record from nerve tissue. This increased selectivity may require the use of more invasive devices, such as the Utah Slanted Electrode Array (USEA). Previous research with USEAs has described the histological response to the implantation of these devices in cats and rats; however, no such data has been presented in humans. Therefore, we describe here the degree of penetration and foreign body reaction to USEAs after a four-week implantation period in human median and ulnar nerves. We found that current array designs penetrate a relatively small percentage of the available endoneurial tissue in these large nerves. When electrode tips were located within the endoneurial tissue, labels for axons and myelin were found in close proximity to electrodes. Consistent with other reports, we found activated macrophages attached to explanted devices, as well as within the tissue surrounding the implantation site. Despite this inflammatory response, devices were able to successfully record single- or multi-unit action potentials and elicit sensory percepts. However, modifying device design to allow for greater nerve penetration, as well as mitigating the inflammatory response to such devices, would likely increase device performance and should be investigated in future research.


Comparison of nifedipine and metoprolol on collateral coronary blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia.
This study compared the effects of nifedipine and metoprolol on collateral-dependent myocardial blood flow in a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia. Collateral coronary circulation was induced in 15 three-week-old piglets by banding of the proximal left anterior descending coronary artery (LAD). After 8-10 wk, the distal LAD was ligated and the open-chest pigs were randomized to receive infusions of either saline, nifedipine (5 micrograms.kg-1.min-1) or metoprolol (10 micrograms.kg-1.min-1) for 30 min during isoflurane anaesthesia (2%). Transient ischaemia was induced by 30 sec occlusion of the left circumflex artery. Arterial blood pressures, heart rate and regional myocardial blood flow (radiolabelled microspheres technique) were measured at the end of drug infusion (baseline) and one minute after transient ischaemia. No differences in the blood flow to the collateral-dependent (CD) myocardium or haemodynamic variables were observed at baseline among the three groups. Following transient ischaemia, in the nifedipine but not in the metoprolol group, blood flow to the CD myocardium was reduced by 28 +/- 24% in the epicardium (P < 0.05) and 56 +/- 20% in the endocardium (P < 0.01), resulting from intercoronary and transmural steal. This was associated with a moderate increase (10%, P < 0.05) in the heart rate in the nifedipine group. In a swine model of chronic coronary obstruction and acute ischaemia during isoflurane anaesthesia, the collateral coronary blood flow was maintained in the presence of metoprolol, but reduced in the presence of nifedipine following transient ischaemia due to intercoronary and transmural steal.


Regulation of plasma lecithin:cholesterol acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal.
Plasma lecithin:cholesterol acyltransferase (LCAT) activity is increased during the clearance phase of alimentary lipemia induced by a high-fat test meal in normal subjects. Ultracentrifugal fractionation of high density lipoproteins (HDL) into HDL(2), HDL(3), and very high density (VHD) subfractions followed by analyses of lipid and protein components has been accomplished at intervals during alimentary lipemia to seek associations with enzyme changes. HDL(2) lipids and protein increased substantially, characterized primarily by enrichment with lecithin. HDL(3), which contain the main LCAT substrates, revealed increased triglycerides and generally reduced cholesteryl esters which were reciprocally correlated, demonstrating a phenomenon previously observed in vitro by others. Both changes correlated with LCAT activation, but partial correlation analysis indicated that ester content is primarily related to triglycerides rather than LCAT activity. The VHD cholesteryl esters and lysolecithin were also reduced. Plasma incubation experiments with inactivated LCAT showed that alimentary lipemic very low density lipoproteins (VLDL) could reduce levels of cholesteryl esters in HDL by a nonenzymatic mechanism. In vitro substitution of lipemic VLDL for postabsorptive VLDL resulted in enhanced reduction of cholesteryl esters in HDL(3) and VDH, but not in HDL(2), during incubation. Nevertheless, augmentation of LCAT activity did not result, indicating that cholesteryl ester removal from substrate lipoproteins is an unlikely explanation for activation. Since VHD and HDL(3), which contain the most active LCAT substrates, were also most clearly involved in transfers of esters to VLDL and low density lipoproteins, the suggestion that LCAT product lipoproteins are preferentially involved in nonenzymatic transfer and exchange is made. The main determinant of ester transfer, however, appears to be the level of VLDL, both in vitro and in vivo. Rose, H. G., and J. Juliano. Regulation of plasma lecithin: cholesteryl acyltransferase in man. III. Role of high density lipoprotein cholesteryl esters in the activating effect of a high-fat test meal.


Electromagnetic Shielding Effectiveness of Woven Fabrics with High Electrical Conductivity: Complete Derivation and Verification of Analytical Model.
In this paper, electromagnetic shielding effectiveness of woven fabrics with high electrical conductivity is investigated. Electromagnetic interference-shielding woven-textile composite materials were developed from a highly electrically conductive blend of polyester and the coated yarns of Au on a polyamide base. A complete analytical model of the electromagnetic shielding effectiveness of the materials with apertures is derived in detail, including foil, material with one aperture, and material with multiple apertures (fabrics). The derived analytical model is compared for fabrics with measurement of real samples. The key finding of the research is that the presented analytical model expands the shielding theory and is valid for woven fabrics manufactured from mixed and coated yarns with a value of electrical conductivity equal to and/or higher than σ = 244 S/m and an excellent electromagnetic shielding effectiveness value of 25⁻50 dB at 0.03⁻1.5 GHz, which makes it a promising candidate for application in electromagnetic interference (EMI) shielding.


Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan.
The roles of the hepatitis B virus (HBV), cigarette smoking and alcohol consumption in the etiology of hepatocellular carcinoma (HCC) were examined in a case-control study involving 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. Information on smoking and drinking habits was obtained by a detailed interview survey, and the results were analyzed in conjunction with serum hepatitis B surface antigen (HBsAg) status after adjustment for sex, age and other possible confounding factors. Individuals positive for serum HBsAg showed a relative risk (RR) for HCC of 13.8 (95% confidence interval, Cl 5.9 to 32.5), whereas heavy drinkers experienced about a 2-fold risk increase compared with non-drinkers. Light or moderate drinkers, however, demonstrated RRs near the unity. Some risk excess was observed among ex-smokers (RR = 1.5, 95% CI 0.8 to 2.8) and current smokers (RR = 1.5, 0.8 to 2.7) compared with non-smokers, but without evidence for a dose-response relationship in terms of pack-years. Analysis among HBsAg-negative subjects revealed similar non-significant association with smoking, and there was no clear interaction between alcohol and cigarette consumption on HCC risk. Other significant risk factors included positive histories of blood transfusion (RR = 3.7, 2.2 to 6.3) and familiar liver disease (RR = 2.6, 1.6 to 4.2). Attributable risk calculations suggest that chronic HBV infection and heavy drinking may account for 17% and 13% of HCC occurrence, respectively, in this high risk area. The association of cigarette smoking with HCC was not evident in our study.


Selenium supplementation of lung epithelial cells enhances nuclear factor E2-related factor 2 (Nrf2) activation following thioredoxin reductase inhibition.
The trace element selenium (Se) contributes to redox signaling, antioxidant defense, and immune responses in critically ill neonatal and adult patients. Se is required for the synthesis and function of selenoenzymes including thioredoxin (Trx) reductase-1 (TXNRD1) and glutathione peroxidases (GPx). We have previously identified TXNRD1, primarily expressed by airway epithelia, as a promising therapeutic target to prevent lung injury, likely via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms. The present studies utilized the TXNRD1 inhibitor auranofin (AFN) to test the hypothesis that Se positively influences Nrf2 activation and selenoenzyme responses in lung epithelial cells. Murine transformed Club cells (mtCCs) were supplemented with 0, 10, 25, or 100 nM Na2SeO3 to create a range of Se conditions and were cultured in the presence or absence of 0.5 μM AFN. TXNRD1 and GPX2 protein expression and enzymatic activity were significantly greater upon Se supplementation (p < 0.05). AFN treatment (0.5 μM AFN for 1 h) significantly inhibited TXNRD1 but not GPx activity (p < 0.001). Recovery of TXNRD1 activity following AFN treatment was significantly enhanced by Se supplementation (p < 0.041). Finally, AFN-induced Nrf2 transcriptional activation was significantly greater in mtCCs supplemented in 25 or 100 nM Na2SeO3 when compared to non-supplemented controls (p < 0.05). Our novel studies indicate that Se levels positively influence Nrf2 activation and selenoenzyme responses following TXNRD1 inhibition. These data suggest that Se status significantly influences physiologic responses to TXNRD1 inhibitors. In conclusion, correction of clinical Se deficiency, if present, will be necessary for optimal therapeutic effectiveness of TXNRD1 inhibitors in the prevention of lung disease.


Solitary lymph node metastasis without local recurrence of primary chordoma.
Chordoma is a malignant neoplasm believed to arise from notochord remnants. Its incidence is highest in the sixth decade and is generally regarded as a locally aggressive tumor with slow progression growth rate. Its metastatic incidence ranges from 5 to 40%, and it is generally believed that metastases without local recurrence of primary neoplasm are extremely rare. We report a case of a 38-year-old male patient with solitary inguinal lymph node metastasis without local recurrence of a previously surgically treated primary sacrococcygeal chordoma.


Growth curves for intracranial volume in normal Asian children fortify management of craniosynostosis.
Although the charting of normal intracranial volume (ICV) is fundamental for managing craniosynostosis, Asian norms in this regard are unknown. The purpose of this study was to establish a growth curve for ICVs in a large series of normal Asian children, providing reference values to guide corrective surgery. A total of 124 normal children (male, 63; female, 61) and 41 children diagnosed with craniosynostoses were analyzed. Patients aged 0-8 years presenting to the emergency room and subjected to computed tomography (CT) for head trauma served as the reference cohort. Axial CT head scan data were obtained from radiographic archives at Jichi Medical University. Imaging was done on a Siemens CT scanner (5-mm slice thickness), using a DICOM viewer to measure ICVs. ICVs were plotted against age, and best-fit logarithmic curves for normal subjects were generated, without and with gender stratification. Male and female growth curves were similar in shape but diverged past the age of 1 year (male > female). ICVs of patients with craniosynostoses were plotted to male and female growth curves by disease subset, revealing the following: sagittal synostosis, near normal (or marginally larger); metopic synostosis, below normal; other non-syndromic synostoses (unilateral, bilateral, and lambdoidal) and Crouzon syndrome, near normal; Apert syndrome, above normal; and Pfeiffer syndrome, variable. ICVs of early childhood were investigated in Asian subjects, creating growth curves that set criteria for timing, planning and goalsetting in surgical correction of craniosynostosis.


Does the relative silicone content of different syringes affect the stability of foam in sclerotherapy?
Sclerotherapy has become the gold standard in the treatment of varicose veins. Foam sclerosing solution with sodium tetradecyl sulfate (STS) is one of the most popular agents used. This study examined the possibility that relative silicone content of different syringes may affect the overall foam stability. A double-syringe system (DSS) technique to make sclerosing foam (STS 0.5% and air) was applied. Four different brands of syringes were tested. The time required for half of the original volume of sclerosing solution to settle was recorded. The time for the sclerosing solution to settle to half of its initial volume varied with each brand of syringes. The type of syringe used in the DSS technique to produce foam for sclerotherapy is a determinant of foam stability. Whether this will affect the result of sclerotherapy requires further investigation.


Crystal structure of the copper-containing quercetin 2,3-dioxygenase from Aspergillus japonicus.
Quercetin 2,3-dioxygenase is a copper-containing enzyme that catalyzes the insertion of molecular oxygen into polyphenolic flavonols. Dioxygenation catalyzed by iron-containing enzymes has been studied extensively, but dioxygenases employing other metal cofactors are poorly understood. We determined the crystal structure of quercetin 2,3-dioxygenase at 1.6 A resolution. The enzyme forms homodimers, which are stabilized by an N-linked heptasaccharide at the dimer interface. The mononuclear type 2 copper center displays two distinct geometries: a distorted tetrahedral coordination, formed by His66, His68, His112, and a water molecule, and a distorted trigonal bipyramidal environment, which additionally comprises Glu73. Manual docking of the substrate quercetin into the active site showed that the different geometries of the copper site might be of catalytic importance.


Treatment of advanced malignant melanoma with coumarin and cimetidine: a pilot study.
Based on previous results demonstrating that coumarin and cimetidine render objective tumor regressions in renal cell carcinoma, we conducted a pilot study to determine whether these drugs possess activity against malignant melanoma. A total of 22 patients with advanced melanoma received 100 mg coumarin p.o. daily for 14 days; on day 15, cimetidine was added at an oral dose of 300 mg four times daily. Both drugs were continued until progression of disease. In all, 12 patients had previously been treated, but all patients had a favorable performance status. No response was observed in 19 patients. Two patients with a low tumor burden achieved a partial response and a third showed a minor response. There was no toxicity from this regimen. Although coumarin and cimetidine at this dose and schedule did not display significant activity in this study population, further studies are warranted to explore higher doses and focus on patients with relatively low tumor burdens.


Coping with predator stress: interclonal differences in induction of heat-shock proteins in the water flea Daphnia magna.
Although predation is a strong selection pressure, little is known about the molecular mechanisms to cope with predator stress. This is crucial to understanding of the mechanisms and constraints involved in the evolution of antipredator traits. We quantified the expression of heat-shock protein 60 (Hsp60), a potential marker for predator stress, in four clones of the water flea Daphnia magna, when exposed to fish kairomones. Expression of Hsp60 induction increased after 6 h and returned to base levels after 24 h of predator stress. This suggests that it is a costly transient mechanism to temporarily cope with novel predator stress, before other defences are induced. We found genetic variation in the fixed levels and in the fish-induced levels of Hsp60, which seemed to be linked to each clone's history of fish predation. Our data suggest that Hsp60 can be considered part of a multiple-trait antipredator defence strategy of Daphnia clones to cope with predator stress.


Clinical application of Web Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo): Patterns of blood sampling and patient characteristics among clinician users.
Use of population pharmacokinetics (PopPK) to facilitate PK-informed prophylaxis in clinical practice has gained momentum among haemophilia providers due to the accessibility of tools such as the Web Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) and availability of extended half-life (EHL) factor concentrates. It is unknown how clinicians implement PopPK. To investigate the evolution of PopPK use in clinical practice by comparing blood sampling strategies, patient features, and factor group between initial and recent periods of WAPPS-Hemo availability. PK data for haemophilia A and haemophilia B patients from two time periods were extracted from the WAPPS-Hemo database: early availability (10/2015-09/2016) and recent use (10/2017-09/2018). We compared patient characteristics (age, body weight, haemophilia type), product type and dose, and blood sampling times between the time frames. Over 1900 eligible infusions were submitted to WAPPS-Hemo during the periods studied, with 85% representing FVIII concentrates. In the recent cohort, PK profiles were requested for younger patients (median age 18 vs 26 years), with increased proportional EHL FVIII use (29% vs 14% of infusions). High-use centres generally submitted fewer blood samples per infusion than non-high-use centres, although the number of samples collected by non-high-use centres decreased significantly over time. During both periods, blood sample timing was generally consistent with ISTH recommended windows. The use of WAPPS-Hemo by haemophilia providers grew by over threefold between the time periods investigated. While sampling times have included key time points proposed first by Björkman since early WAPPS-Hemo usage, a trend towards minimizing sampling was observed.


Inducible high resistance to colistin in Proteus strains.
Wild-type Proteus strains are usually resistant to colistin. We have observed an increase in the level of colistin resistance in four clinical isolates of P. vulgaris, P. morganii, and P. rettgeri by prior treatment with subinhibitory concentrations of the drug. The enhanced resistance in these strains was lost after cultivating them in colistin-free medium, indicating that the enhanced resistance in the Proteus group is inducible.


New tigliane and daphnane derivatives from Pimelea prostrata and Pimelea simplex.
From the methanol extract of Pimelea prostrata, prostratin (I) and 2 autoxidation products have been isolated. They are tigliane derivatives and relatively nonirritant on the mouse ear. The irritant pimelea factor P5 (IIa) also with a tigliane skeleton and related to mancinellin (IIb), as well as the irritant diterpene ester pimelea factor P1 (IIa, simplexin) with daphnane skeleton, were found to be present in both P. prostrata and P. simplex. Further the irritant homologue of simplexin, pimela factor IIIb was detected in P. prostrata. Some biogenetic consequences of these findings are discussed.


Episodic deluges in simulated hothouse climates.
Earth's distant past and potentially its future include extremely warm 'hothouse'1 climate states, but little is known about how the atmosphere behaves in such states. One distinguishing characteristic of hothouse climates is that they feature lower-tropospheric radiative heating, rather than cooling, due to the closing of the water vapour infrared window regions2. Previous work has suggested that this could lead to temperature inversions and substantial changes in cloud cover3-6, but no previous modelling of the hothouse regime has resolved convective-scale turbulent air motions and cloud cover directly, thus leaving many questions about hothouse radiative heating unanswered. Here we conduct simulations that explicitly resolve convection and find that lower-tropospheric radiative heating in hothouse climates causes the hydrologic cycle to shift from a quasi-steady regime to a 'relaxation oscillator' regime, in which precipitation occurs in short and intense outbursts separated by multi-day dry spells. The transition to the oscillatory regime is accompanied by strongly enhanced local precipitation fluxes, a substantial increase in cloud cover, and a transiently positive (unstable) climate feedback parameter. Our results indicate that hothouse climates may feature a novel form of 'temporal' convective self-organization, with implications for both cloud coverage and erosion processes.


[Clinical and managerial autonomy. Perception of the coordinators of the health centers in Mallorca, Spain].
The self-management has been linked with increased efficiency and job satisfaction. Before any changes aimed at a more autonomous management is important to know the position of professionals and managers. objective: To assess the importance attached by the coordinators of the health centers (HC) to the clinical and managerial autonomy, knowing their decision making capacity and their expectations about the feasibility of implementing a project of self-management. cross-sectional study, application questionnaire. Primary Care, 2009. All the coordinators of the HC of Mallorca (N = 47). 27 questions that explore the coordinator's opinion about the importance of the components of the self-management, its ability to present intervention, the propensity / aversion to risk, leadership, and the feasibility of a self-management. response rate: 42/47 (89,4%). 42 (100%) attaches the highest importance to the management of human resources, 41 (97,6%) to demand management and 40 (95,2%) to the management of waiting lists. 15 (35,7%) would take a financial risk, 14 (33,3%) were considered trained and 18 (42,9%) were willing to lead a process of self-management. 14 (33,3%) thought that the professionals in your team would not be interested in a process of self-management and 29 (69%) believed that others could develop HC of Mallorca. The respondents were coordinators have a limited ability to decide on the components of the self-management, being risk averse and make a little leadership ability and willingness to self-management projects.


Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders.
Partial Retraction of: The EMBO Journal (2010) 29: 3607-3620. DOI: 10.1038/emboj.2010.237 | Published online 24 September 2010 Journal statement The journal contacted the authors in February 2022 about potential image insertions and duplications in Fig 4A and 4E. In the absence of source data, the authors are retracting Fig 4A, the lower panel of Fig 4E (LAMP1 immunoblot), and the following statements in the text that rely on these data: "Quantitative analysis showed that the percentage of Flotillin-1 associated with DRMs was increased in LSD endolysosomal membranes (Figure 4A), indicating an increased amount of cholesterol-enriched regions in these membrane samples." "LAMP1 also displayed a similar distribution profile in WT and LSD cells (Figure 4E)". Author statement The authors could not verify the aberrations in panel A of Fig 4 and the lower immunoblot (LAMP1) of 4E because the original source data are no longer available (12 years after publication, which is beyond the institute's 10-year data retention policy). The authors wish to clarify that the main conclusions of the paper are not affected by the retraction of Figure panels 4A and 4E for the following reasons: Figure panel 4A supports the observation that there are increased cholesterol-enhanced regions in LSD samples. This finding is also supported by data provided in figs 4B, 4C and 4D. Figure panel 4E: The LAMP1 blot in Fig 4E shows that the distribution of protein normally excluded from DRMs is not altered between Wt and LSD samples. This result is also supported by the upper blot in this panel (Transferrin receptor). The authors apologize for these errors and agree with this corrigendum; no response could be obtained from AL.


The role of body weight in oral contraceptive failure: results from the 1995 national survey of family growth.
Many unintended pregnancies occur in women who use contraception. We conducted this study to determine if increasing body weight is associated with oral contraceptive (OC) failure. This retrospective cohort study consists of the 1916 women who reported using OCs in January 1993 and provided complete covariate information on the 1993 National Health Interview Survey and 1995 National Survey of Family Growth. Body weight and body mass index (BMI) were self-reported in 1993. The outcome was defined to be any conception occurring in women reporting OC use during the month of conception. Cox proportional hazards models were used to model the body weight/BMI-OC failure association. Women with a BMI >/= 30 had a statistically significant increased risk of having an OC failure as compared to women with BMIs of 20 to 24.9 (HR=1.80, 95% CI, 1.01, 3.20). However, after adjustment for age, marital status, education, poverty, race/ethnicity, parity, and dual method use, this increased risk was attenuated and no longer statistically significant (HR=1.51, 95% CI, 0.81, 2.82). Increasing body weight was not associated with an increased risk of OC failure in the unadjusted or adjusted models. We did not find a strong or statistically significant association between increasing body weight/BMI and OC failure among this population of women. Prospective studies specifically designed to examine this association are needed to determine if heavier women should be advised to use a contraceptive method other than OCs to prevent pregnancy.


Protein kinase C stimulates human B cell activating factor gene expression through reactive oxygen species-dependent c-Fos in THP-1 pro-monocytic cells.
BAFF is associated with various immunological diseases. Previously, we have reported that mouse B cell activating factor (mBAFF) expression was dependent on nuclear localization of co-activator, p300 and the activation of transcription factors including NF-κB and CREB. Here, we investigated whether transcription factor, c-Fos, regulates human (h) BAFF expression through promoter activation by PMA-induced reactive oxygen species (ROS) production. We cloned hBAFF promoter into luciferase-expressing pGL3-basic vector. The activity of 1.0 kb hBAFF promoter was higher than that in 0.75, 0.5 or 0.25 kb hBAFF promoter. The existence of three AP-1 binding motifs was computer-analyzed in hBAFF promoter. The stimulation with PMA and ionomycin (IOM) increased 1.0 kb hBAFF promoter activity, time-dependently. PMA/IOM-stimulation rapidly enhanced c-Fos expression in THP-1 human pro-monocytic cells. Binding of c-Fos to hBAFF promoter was detected by chromatin immunoprecipitation (ChIP) assay. hBAFF expression and its promoter activity were decreased by the transfection with small interference (si) RNA of c-Fos. ROS production in THP-1 cells was increased by PMA/IOM-stimulation. In addition, hBAFF activity stimulated by PMA/IOM was reduced by N-acetyl-cysteine (NAC), a well-known ROS scavenger. Serum starvation (0.5% FBS) producing ROS and the exogenous H(2)O(2) treatment also enhanced hBAFF promoter activity. c-Fos expression and AP-1 binding to oligonucleotide were reduced by the treatment with NAC. H(2)O(2) was not able to induce hBAFF expression in the presence of staurosporine, PKC inhibitor. Data suggest that hBAFF expression could be regulated by promoter activation through c-Fos association, which might be dependent on PMA-induced ROS production.


Intra-arterial infusion catheters with implantable injection chambers in maxillo-facial oncology.
An intra-arterial chemotherapy procedure in patients with malignant tumours in the oral and maxillo-facial region which, from the vascular point of view, can be dependent on the external carotid artery and/or its branches is presented. Particularly for the prevention of catheter infection, obstruction, etc., a subcutaneous pouch, connected to the infusion catheter, is implanted subcutaneously in the submastoid region.


The role of systemic inflammation linking maternal BMI to neurodevelopment in children.
Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations.


Prospective cohort study of Cryptosporidium infection and shedding in infants and their households.
Cryptosporidium spp are responsible for significant diarrheal morbidity and mortality in under-five children. There is no vaccine, thus a focus on prevention is paramount. Prior studies suggest that person-to-person spread may be an important pathway for transmission to young children. Here we describe a longitudinal cohort study of 100 families with infants to determine rates of cryptosporidiosis within households during the COVID-19 pandemic. Families living in Mirpur, Bangladesh with one infant age 6-8 months were enrolled and followed with weekly illness survey and stool testing for Cryptosporidium for 8 months. From December 2020 to August 2021, 100 families were enrolled. Forty-four percent of index children, and 35% of siblings had at least one Cryptosporidium infection. Shedding of Cryptosporidium occurred for a mean of 19 days (sd 8.3 days) in index infants, 16.1 days (sd 11.6) in children 1-5 years, and 16.2 days (sd 12.8) in adults. A longer duration of Cryptosporidium shedding was associated with growth faltering in infants. There was a spike in Cryptosporidium cases in May 2021, which coincided with a spike in SARS-CoV-2 cases in the region. In this intensive, longitudinal study of Cryptosporidium infection in families we found high rates of cryptosporidiosis in infants and children, and prolonged parasite shedding, especially among malnourished children. These data support that transmission within the household is an important route of exposure for young infants, and that treatment of non-diarrheal infection to interrupt person-to-person transmission within the home may be essential for preventing cryptosporidiosis in infants. Cryptosporidiosis is a leading cause of morbidity and mortality among children. We followed 100 families with infants living in Bangladesh and studied the incidence of Cryptosporidium infection. We found prolonged Cryptosporidium shedding in stool was common among infants and adults.


Surface chemistry of rare-earth oxide surfaces at ambient conditions: reactions with water and hydrocarbons.
Rare-earth (RE) oxide surfaces are of significant importance for catalysis and were recently reported to possess intrinsic hydrophobicity. The surface chemistry of these oxides in the low temperature regime, however, remains to a large extent unexplored. The reactions occurring at RE surfaces at room temperature (RT) in real air environment, in particular, in presence of polycyclic aromatic hydrocarbons (PAHs), were not addressed until now. Discovering these reactions would shed light onto intermediate steps occurring in automotive exhaust catalysts before reaching the final high operational temperature and full conversion of organics. Here we first address physical properties of the RE oxide, nitride and fluoride surfaces modified by exposure to ambient air and then we report a room temperature reaction between PAH and RE oxide surfaces, exemplified by tetracene (C18H12) on a Gd2O3. Our study evidences a novel effect - oxidation of higher hydrocarbons at significantly lower temperatures (~300 K) than previously reported (>500 K). The evolution of the surface chemical composition of RE compounds in ambient air is investigated and correlated with the surface wetting. Our surprising results reveal the complex behavior of RE surfaces and motivate follow-up studies of reactions between PAH and catalytic surfaces at the single molecule level.


DNA repair, cell cycle progression and cell death following camptothecin treatment in two murine lymphoma L5178Y sublines.
The processes involved in cell response to camptothecin (CPT) were investigated in two sublines of L5178Y (LY) murine lymphoma; LY-R, resistant and LY-S, sensitive to X-irradiation, which are inversely cross-sensitive to the drug. The cells were pulse-treated with 2 microM CPT for 1 h; this resulted in equal numbers of replication-related DNA double-strand breaks (DSBs) in both sublines. After drug removal, at different time points up to 24 h, the levels of DSBs were measured by using field inversion gel electrophoresis (FIGE) and comet assay at neutral pH. Both methods revealed faster DSBs repair in LY-S than in LY-R cells, in contrast with X-ray-induced DSBs. This however, was followed by the appearance of secondary breaks in the former subline. The cell cycle arrest was at S/G2 phase and comprised equal numbers of cells in LY-S and LY-R populations. In both sublines formation of giant cells took place, as well as delayed apoptosis starting about 20 h post-CPT incubation and proceeding with similar intensity. At the same time, the total number of necrotic cells appearing during post-exposure incubation in the LY-R subline exceeded that in the LY-S subline. We suggest that, beside previously documented higher susceptibility of topoisomerase I (Topo I) from LY-R cells to CPT, a higher initial rate of replication-related DSBs repair, but not lower propensity to apoptosis, may contribute to the relative CPT resistance of LY-S versus LY-R cells.


Brain stem cheiro-oral syndrome: neurological signs for brain stem lesions.
Cheiro-oral syndrome (COS) is characterized by a sensory disturbance in one hand and the ipsilateral oral corner. It is usually due to a lesion in the parietal cortex, thalamocortical projections or thalamus. Brain stem lesions may rarely produce COS. We present two COS patients with midbrain infarction and pontine hemorrhage, respectively. In our patients, unilateral oculomotor nerve palsy or medial longitudinal fasciculus syndrome concurred with sensory disturbances of cheiro-oral distribution. COS produced by cortical/thalamic lesion is not accompanied with such oculomotor signs. Thus, oculomotor deficits are decisive in differentiating brain stem from cortical or thalamic COS.


Molecular characterization and gene functional analysis of Dicer-2 gene from Nilaparvata lugens (Hemiptera: Geometroidea).
Nilaparvata lugens (Stål) (Hemiptera: Geometroidea), a serious rice pest in many countries of Asia, causes a great loss in rice production every year. RNA interference (RNAi) is a powerful technology for gene function study in insects and a potential tool for pest control. As a core component of RNAi pathway, Dicer-2 (Dcr-2) protein determines the production of small interfering RNA (siRNA) and is crucial for the efficiency of RNAi. In this study, the full-length complementary DNA (cDNA) of N. lugens Dcr-2 (NlDcr-2) was first cloned and analyzed, and then the RNAi experiment was conducted to explore the function of NlDcr-2 gene. The complete Dcr-2 cDNA of N. lugens was 4 971 bp in length with an open reading frame (ORF) of 1,656 amino acids. Phylogenetic and protein domain analysis showed that the predicted NlDcr-2 protein was similar to Tribolium castaneum. In the RNAi experiment, the messenger RNA level of NlDcr-2 was significantly reduced by NlDcr-2 double-stranded RNA (dsRNA) (dsDcr-2). Fifty-five per cent decrease of NlDcr-2 was found after 4 days of unremitting feeding. No significant effect was observed on the development of N. lugens after dsRNA ingestion.


A developmental-psychodynamic model for diabetic control.
This paper elaborates a psychodynamic-developmental model as a framework for understanding the wide range of adaptive and maladaptive responses to the self-care requirements of diabetes. Early life experience participates with other factors in influencing the ease with which diabetics implement diabetic control. This model emphasizes the importance of the mother-child interaction during the second phase of development, the toddler phase, at which time the child begins to establish a sense of autonomy and control over his own body and its functions, with bowel training viewed as a paradigm for body control. It is postulated that certain types of mothers such as controlling-intrusive mothers, overprotective mothers, or guilty, indifferent, or rejecting mothers create problems for the child related to the development of autonomy and the sense of comfortable and pleasurable control over his bodily functions. Conflicts generated during this period are reactivated with the onset of diabetes and lead to difficulty in implementing control. In some situations where conflicts with the caretaker figure were predominantly limited to aspects of control, trusting relations acted as a substrate for change and improvement in control in a supportive medical environment. Specific management recommendations based upon this model are presented.


Managing the solvent water polarization to obtain improved NMR spectra of large molecular structures.
In large molecular structures, the magnetization of all hydrogen atoms in the solute is strongly coupled to the water magnetization through chemical exchange between solvent water and labile protons of macromolecular components, and through dipole-dipole interactions and the associated "spin diffusion" due to slow molecular tumbling. In NMR experiments with such systems, the extent of the water polarization is thus of utmost importance. This paper presents a formalism that describes the propagation of the water polarization during the course of different NMR experiments, and then compares the results of model calculations for optimized water polarization with experimental data. It thus demonstrates that NMR spectra of large molecular structures can be improved with the use of paramagnetic spin relaxation agents which selectively enhance the relaxation of water protons, so that a substantial gain in signal-to-noise can be achieved. The presently proposed use of a relaxation agent can also replace the water flip-back pulses when working with structures larger than about 30 kDa. This may be a valid alternative in situations where flip-back pulses are difficult to introduce into the overall experimental scheme, or where they would interfere with other requirements of the NMR experiment.


Stereoselective analysis of the enantiomers of mexiletine by high-performance liquid chromatography using fluorescence detection and study of their stereoselective disposition in man.
A sensitive, stereoselective high-performance liquid chromatographic assay was developed for the resolution of the enantiomers of mexiletine as their 2-naphthoyl derivatives on a Pirkle type 1A chiral phase column. Detection of the derivatives was accomplished with a fluorescent detector. Maximum recovery of the enantiomers from plasma was 83% and was observed when plasma proteins were precipitated with a mixture of barium hydroxide-zinc sulphate. The calibration curve in plasma was linear over the concentration range 5-750 ng/ml for each enantiomer (r2 = 0.999) and in urine the linear range was 0.25-7.5 micrograms/ml (r2 = 0.999) for each enantiomer. The minimum detectable quantity of each enantiomer in plasma was 5 ng/ml at a signal-to-noise ratio of 5:1, representing 100 pg injected. A preliminary pharmacokinetic study was undertaken in one healthy male volunteer following an oral dose of 300 mg of racemic mexiletine hydrochloride. The apparent elimination half-lives determined from the plasma data were 12.1 and 14.1 h for the R(-) and S(+) enantiomers, respectively. The cumulative urinary excretion amounts of R(-)- and S(+)-mexiletine were found to be 8.01 and 10.46 mg, respectively. The plasma data indicated that a cross-over of the enantiomer ratios occurred at approximately 8 h. The urinary excretion of the enantiomers was consistent with the pattern found in plasma.


The effect of urapidil, an alpha-1 adrenoceptor antagonist and a 5-HT1A agonist, on the vascular tone of the porcine coronary and pulmonary arteries, the rat aorta and the human pulmonary artery.
Urapidil (Eupressyl(®)) an antihypertensive drug acting as an α1 antagonist and a 5-HT1A agonist, may be of special interest in the treatment of hypertension associated with preeclamptic toxaemia and hypoxia-induced pulmonary arterial vasoconstriction. However, the effect of urapidil on vascular tone has been poorly investigated. Vascular reactivity was evaluated using pulmonary and coronary arteries from 36 pigs, aortae from 22 rats and 9 human pulmonary artery samples suspended in organ chambers. Concentration-relaxation curves either to urapidil, 5-HT, or the 5-HT1A receptor agonist 8-OH-DPAT were constructed after pre-contraction of rings. Pig pulmonary and coronary artery rings were contracted with U46619, a thromboxane mimetic, rat aortic rings with either endothelin-1 or phenylephrine, and human pulmonary artery rings with U46619 or phenylephrine. Urapidil markedly inhibited phenylephrine-induced contractions in rat aortic rings with and without endothelium with a more pronounced effect observed in rings without endothelium. Both 5-HT and 8-OH-DPAT failed to induce relaxation in rat aortic rings with an intact endothelium. 5-HT, but not urapidil and 8-OH-DPAT, induced a concentration-dependent relaxation in the porcine coronary and pulmonary artery rings with an intact endothelium (P<0.05). 5-HT and phenylephrine but not urapidil caused concentration-dependent contractions in human pulmonary artery rings. The present findings, while confirming that urapidil is a potent inhibitor of α1-adrenoceptor-induced contraction, do not support the role of 5-HT1A receptor activation in the control of the vascular tone of the different types of arteries tested in response to urapidil. In addition, they indicate that urapidil seems to preferentially target arteries with endothelial dysfunction.


Vascular permeability in HPV+ oropharyngeal cancers aids in fluorescent image-guided transoral robotic surgery using indocyanine green.
Indocyanine green (ICG) fluorescent image (FI)-guided surgery has demonstrated success in improving intraoperative visualization and tumor resections. The objectives were to evaluate the use of IGC in FI-guided transoral robotic surgery (TORS) and the underlying molecular mechanism. HPV+ oropharyngeal squamous cell carcinoma (OPSCCa) patient (n = 10) undergoing TORS were enrolled in this prospective study. Participants received intravenous ICG. Excised tissues were evaluated for ICG accumulation, tumor demarcation, and pathological characteristics using In-vivo imaging system (IVIS), histology, and RNA sequencing. ICG accumulation was significantly increased in primary tumor and pathological lymph nodes compared with normal tissues (p < 0.001). IVIS was 91.3% accurate in identifying OPSCCa in excised tissues; the correlation between IVIS- and histologically determined tumor tissues was significant (R2 = 0.8301; p = 0.001). Genes associated with vascular and angiogenic signaling pathways were significantly upregulated in OPSCCa tissues. ICG effectively demarcates tumor margins in OPSCCa, due to the increased upregulation of genes associated with vascular permeability.


Siderophore production by Bacillus subtilis MF497446 and Pseudomonas koreensis MG209738 and their efficacy in controlling Cephalosporium maydis in maize plant.
Late wilt disease, caused by Cephalosporium maydis in maize plant, is one of the main economical diseases in Egypt. Therefore, to cope with this problem, we investigated the potentiality of plant growth promoting rhizobacteria in controlling this disease. Six strains (Bacillus subtilis, B. circulance, B. coagulanse, B. licheniformis, Pseudomonas fluroscence and P. koreensis) were screened for siderophore production, and using dual plate culture method and greenhouse experiment, antagonistic activity against C. maydis was studied. Using two superior strains, single and dual inoculation treatments in maize were applied in field experiment during the 2018 and 2019 seasons. Results indicated that B. subtilis and P. koreensis strains had shown the most qualitative and quantitative assays for siderophore production and antagonistic activities. In greenhouse, the most effective treatments on the pre- and post-emergence damping off as well as growth promotion of maize were T3 treatment (inoculated with B. subtilis), and T8 treatment (inoculated with P. koreensis). In field experiment, T5 treatment (inoculated with a mixture of B. subtilis and P. koreensis) showed significant increases in catalase (CAT), peroxidase (POX) and polyphenol oxidase (PPO) activities, as well as total chlorophyll and carotenoids than control treatments during the two growing seasons. In the same way, the highest effect in reducing infection and increasing the thickness of the sclerenchymatous sheath layer surrounding the vascular bundles in maize stem was observed and these results were a reflection of the increase in yield and yield parameters.


Applications and outcomes of periodic epidemiological surveys for schistosomiasis and related economic evaluation in the People's Republic of China.
The great success in schistosomiasis control in China is attributable to a range of factors. Periodic epidemiological surveys (PES) used for monitoring and adapting control interventions over time are an integral feature of the national schistosomiasis control programme. PES have enabled the dynamic trends of schistosomiasis epidemics to be closely pursued and have assisted in analysing subtle changes in endemicity. The results can be summarised mathematically allowing the variation in efficacy of control measures to be readily determined and enabling control strategies to be adjusted and updated. PES have been used in both cross-sectional and longitudinal pilot studies selected by appropriate sampling methods. In the early 1990s, when the World Bank Loan Project for schistosomiasis control commenced, economic evaluations were initiated in parallel. Cost-effectiveness analysis became a necessary tool to identify the most financially feasible yet effective options among a range of alternative control strategies. There was, however, a lack of standardised approaches rendering study comparisons across sites difficult. The global burden of disease study established the disability adjusted life year (DALY) as a measure of population health, combining in a single indicator years lost from premature death and years of life lived with disability. However, a recent meta-analysis reveals that the burden of schistosomiasis is underestimated, and hence, needs to be revised. It is envisaged that after the revision of DALYs lost due to schistosomiasis japonica, they will become an essential measure in future schistosomiasis control assessments in China and in other schistosome-endemic areas of the world.


Management of mild fetal pyelectasis: a comparative analysis.
The purpose of this study was to compare 2 protocols for the antenatal management of isolated mild fetal pyelectasis and perform a cost analysis. A retrospective analysis of unilateral and bilateral mild fetal pyelectasis followed at our institution from 2003 to 2006 was conducted. Fetuses with additional congenital anomalies or aneuploidy were excluded. Chi(2) analysis was used, and P < .05 was considered significant. Two hundred forty-four cases were identified, of which the majority were male (75.4% versus 24.6%). Eighty-eight patients were reevaluated every 4 weeks (protocol 1). The remaining 156 patients were reevaluated once in the third trimester (protocol 2). The mean number of ultrasound examinations in protocol 1 was 3.24, at a cost of $1187, compared with protocol 2, at $798. Resolution occurred in 59%, stabilization in 29%, and progression in 12%. There were no cases of progression to severe pyelectasis or a need for in utero intervention in either group. Mild fetal pyelectasis can be managed with 1 additional third-trimester ultrasound examination without a compromise in patient care. Average cost savings were $389 per patient for protocol 2, suggesting a benefit from this protocol over protocol 1.


Single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection at Bugando Medical Centre in Mwanza, Tanzania: a randomized, equivalence, controlled trial.
Caesarean section(C/S) has been found to increase rates of maternal infectious morbidities five times more than vaginal delivery. The provision of intravenous prophylactic antibiotics 30 to 60 minutes prior to C/S has been found to substantially reduce post-caesarean infection. At Bugando Medical Centre, there is no consistent protocol for the administration of antibiotic prophylaxis to patients who are undergoing emergency C/S. Providing repeated dosages of antibiotic prophylaxis after C/S is the common practice. This study aimed to determine the comparative efficacy of a single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection. From October 2011 to May 2012, a randomized, equivalence, non-blinding clinical trial was conducted at Bugando Medical Centre in Mwanza, Tanzania. A total of 500 eligible participants were enrolled in the study and were randomly allocated into two study arms -- "A" and "B". Participants in "A" received a single dose of gentamicin in combination with metronidazole 30 to 60 minutes prior to the operation, and participants in "B" received the same drugs prior to the operation but continued with for 24 hours. Both groups had 30 days of follow-up and were assessed for signs and symptoms of surgical-site infection as the primary outcome. The equivalence margin was set at 5%. The two-tailed equivalence was analyzed based on intention- to-treat analysis. The randomization was proper, as the distribution of various demographic and other baseline characteristics had a p-value of > 0.05. All 500 participants were included in our analysis; of these, no participants were lost to follow-up. Surgical-site infection occurred in 12 out of the 250 (4.8%) receiving single dose compared to 16 out of the 250 (6.4%) receiving multiple doses. There is an absolute proportion difference of 1.6% (95% Confidence interval: -2.4 - 5.6%) which lies outside the pre-specified 5% equivalence margin. We recommend the administration of pre-operative single dose antibiotic prophylaxis for emergency caesarean as this intervention proved to be not equivalent to multiple doses antibiotic prophylaxis in reducing surgical site infection. Single dose therapy also reduces staff workload along with medication costs.


Immediate effect of a meditation technique on blood glucose, state anxiety and relaxation in patients with type 2 diabetes: a pilot randomized crossover study.
Type 2 diabetes mellitus (T2DM) is a major burden on global health and economy. Various Yogic techniques are found to be beneficial in the management of T2DM. Mind Sound Resonance Technique (MSRT) is one of the yoga-based meditation techniques observed to be effective in clinical settings. Thirty-two patients with T2DM were randomized to either MSRT or supine rest (SR) sessions on two separate days separated by a washout period of one day. Fasting blood glucose levels were measured before and immediately after the sessions. State anxiety and subjective feeling of relaxation were assessed using Spielberg's state anxiety inventory (STAI) and Visual Analogue Scale (VAS) respectively. There were significant differences between MSRT and SR groups in fasting blood glucose (p=0.019), STAI scores (p<0.001) and subjective relaxation (p<0.001). Within group analyses revealed significant reductions (p<0.001) in fasting blood glucose and STAI scores, along with an increase in subjective relaxation following the practice of MSRT, whereas, non-significant changes were found following the SR session. A single session of MSRT was found to reduce blood glucose levels and state anxiety along with enhanced relaxation when compared to SR.


Tolerance to cold and glucose homeostasis in adrenal demedullated dogs.
The rise in O2 consumption and in glucose turnover, induced by acute cold exposure is not suppressed by adrenal demedullation in dogs. However, both at neutral and cold ambient temperature, the mean plasma glucose concentrations are higher in normal (N) than in adrenal-demedullated dogs (ADMX). In the cold, the fall in rectal temperature is larger in ADMX than in N dogs.


Extreme cold sensitivity of Salmonella typhimurium umu clones, effects of the umu region and flanking sequences.
The umuDC operons of both Salmonella typhimurium and Escherichia coli encode proteins which are essential for mutagenesis following exposure to ultraviolet radiation or a variety of chemicals. However S. typhimurium is less mutable and its umu operon appears to be less active for reasons that are unknown. This study shows that pBR322-based plasmids carrying cloned umuDC operons of either species confer cold sensitivity on both an E. coli umuC strain and a S. typhimurium pSLT- strain. Both S. typhimurium and E. coli umu clones make these lexA+ strains moderately cold-sensitive, but sensitivity produced by the cloned S. typhimurium umuDC operon is extreme when flanking regions of the chromosome are also present. Such instability might be significant in terms of explaining the polymorphisms seen in the regions of the chromosomes of Enterobacteriaceae surrounding the umuDC operon. In S. typhimurium this extreme cold sensitivity was almost certainly responsible for the delayed recognition of a chromosomal umuDC operon.


Application of principal component analysis for characterizing convergence patterns of inputs in interneurones of the cat forelimb segments.
We attempted to quantitatively describe a variety of convergence patterns of inputs from peripheral nerves and descending tracts (13 sources) onto interneurones of the cat forelimb segments (C6-C8). To this end we applied principal component analysis using the latency of firing as the parameter of each input. The first 3 principal components thus obtained explained 65% of the total variance of convergence patterns and characterized the input pattern of each cell. The first principal component correlated mainly with inputs from pads and the median nerve, the second with the cortico- and rubro-spinal tracts and the third with the superficial radial nerve.


'Normal' hearing thresholds and fundamental auditory grouping processes predict difficulties with speech-in-noise perception.
Understanding speech when background noise is present is a critical everyday task that varies widely among people. A key challenge is to understand why some people struggle with speech-in-noise perception, despite having clinically normal hearing. Here, we developed new figure-ground tests that require participants to extract a coherent tone pattern from a stochastic background of tones. These tests dissociated variability in speech-in-noise perception related to mechanisms for detecting static (same-frequency) patterns and those for tracking patterns that change frequency over time. In addition, elevated hearing thresholds that are widely considered to be 'normal' explained significant variance in speech-in-noise perception, independent of figure-ground perception. Overall, our results demonstrate that successful speech-in-noise perception is related to audiometric thresholds, fundamental grouping of static acoustic patterns, and tracking of acoustic sources that change in frequency. Crucially, speech-in-noise deficits are better assessed by measuring central (grouping) processes alongside audiometric thresholds.


Identification of possible candidate biomarkers for local or whole body radiation exposure in C57BL/6 mice.
Specific genes expressed as a result of whole body exposure to gamma-radiation have been previously identified. In this study, we examined the genes further as possible biomarkers for the blood lymphocytes of C57BL/6 mice after whole body or local irradiation of the thorax, abdomen, and left subphrenic area. We performed reverse transcriptase-polymerase chain reaction and real-time reverse transcriptase-polymerase chain reaction analysis of genes encoding platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD in blood lymphocytes, lung tissue, spleen, and intestines. The protein expression in blood lymphocytes was confirmed by Western blot analysis. The expression of platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD was significantly greater after 3 days as a result of 1 Gy of whole body irradiation. Moreover, local irradiation to the thorax, abdomen, or left subphrenic area, which are frequently exposed to therapeutic radiation doses, showed a tendency toward radiation-induced increased expression of these genes in both the blood and the locally irradiated organs. Western blot analysis also corroborated these results. Platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD might be candidates for biomarkers of radiation exposure. However, additional experiments are required to reveal the relationship between the expression levels and the prognostic effects after irradiation.


Complications arising from transfemoral, percutaneous implantation of an indwelling port-catheter system for hepatic infusion chemotherapy: Case series of the management and salvage of the system.
Regional hepatic arterial infusion of chemotherapy is performed for unresectable liver tumors via percutaneously implanted port-catheter systems; while these port-catheter systems are effective administration routes, they are associated with various complications. Withdrawal of the system is considered if the complications occur, but repeated hepatic arterial infusion of chemotherapy (HAIC) via an implanted port-catheter system is a last-resort treatment for unresectable advanced liver cancer, and the treatment must be continued. We discuss various cases with complications arising in the indwelling port area in hepatic arterial infusion of chemotherapy and report whether the system was salvaged. Between August 2013 and October 2017, eight patients (six males and two females) aged 61-80 years (mean age 76.6 years) with complications arising in a transfemoral indwelling port site for HAIC were referred to our department. All patients requested preservation of the system, especially the catheter. Each patient was assessed for the presence of "gross infection" based on a comprehensive evaluation of clinical findings and blood test results. In cases of "no gross infection," we performed catheter salvage procedures. If there was no clinical improvement following the catheter salvage procedure, the port-catheter system was withdrawn. This research work has been reported in line with the PROCESS criteria. The port-catheter systems were withdrawn in two patients: one due to lasting infection and the other due to ulcer recurrence. Three cases were treated by removal of hematoma through an incision and ointment. The system was withdrawn in one of these cases due to exacerbation of ulcer; thus, the catheters were salvaged in five patients. None of these five patients experienced a relapse from 3 months to over 1 year after the procedure. The success of subcutaneous HAIC significantly impacts a patient's prognosis, especially for unresectable tumors and residual tumor recurrences. Initially, we chose to preserve the devices without removal, particularly if there was no infection. However, this approach led to a delay in chemotherapy, prolongation of healing time, and additional complications. These cases demonstrate the importance of a thorough consultation with the patient's oncologist to discuss whether or not the device should be conserved.


Deep polyp image enhancement using region of interest with paired supervision.
Endoscopic medical imaging in complex curved intestinal structures are prone to uneven illumination, low contrast and lack of texture information. These problems may lead to diagnostic challenges. This paper described the first supervised deep learning based image fusion framework to enable the polyp region highlight through a global image enhancement and a local region of interest (ROI) with paired supervision. Firstly, we conducted a dual attention based network in global image enhancement. The Detail Attention Maps was used to preserve more image details and the Luminance Attention Maps was used to adjust the global illumination of the image. Secondly, we adopted the advanced polyp segmentation network ACSNet to obtain the accurate mask image of lesion region in local ROI acquisition. Finally, a new image fusion strategy was proposed to realize the local enhancement effect of polyp image. Experimental results show that our method can highlight the local details of the lesion area better and reach the optimal comprehensive performance with comparing with 16 traditional and state-of-the-art enhancement algorithms. And 8 doctors and 12 medical students were asked to evaluate our method for assisting clinical diagnosis and treatment effectively. Furthermore, the first paired image dataset LHI was constructed, which will be made available as an open source to research communities.


The acquisition of inorganic carbon by four red macroalgae.
Photosynthesis was studied in four species of red marine macroalgae: Palmaria palmata, Laurencia pinnatifida, Lomentaria articulata and Delesseria sanguinea. The rate of O2 evolution for submersed photosynthesis was measured as a function of incident photon flux density at normal pH and inorganic carbon concentration (pH 8.0, 2 mol m-3), and as a function of inorganic carbon concentration at pH 8.0 at saturating and at limiting photon flux density. The rate of CO2 uptake was measured for emersed photosynthesis as a function of CO2 partial pressure at saturating photon flux density. Previous pH-drift results suggest that Palmaria and Laurencia are able to use HCO inf3sup- as well as CO2 whereas Lomentaria and Delesseria are restricted to CO2. None of the algae are saturated by 2 mol m-3 inorganic carbon at high light (400 μmol m-2 s-1) but are saturated at low light (35 μmol m-2 s-1). The inorganic C concentration at which half the light-saturated rate of O2 evolution is achieved is higher for Palmaria and Laurencia (1.51 and 1.85 mol m-3) than for Lomentaria and Delesseria (0.772 and 0.841 mol m-3). The lower values for the latter two species could reflect their putative restriction to CO2. If expressed in terms of CO2, the half-saturation values yield 7.2 and 7.8 mmol m-3 respectively, which are very similar to values obtained previously during pH-drift experiments but at lower concentrations of HCO inf3sup- , consistent with restriction to CO2. The photosynthetic conductance (m s-1), calculated from the initial slope for photosynthesis at low concentrations of inorganic carbon, correlates with the suggested ability to extract inorganic carbon based on pH-drift results. Calculations made assuming that CO2 is the only species diffusing across the boundary layer are consistent with boundary layer thicknesses of 20 and 19 μm for Lomentaria and Delesseria respectively, which is feasible given the rapid water movement in the experiments. For Laurencia however, an unreasonably small boundary layer thickness of 6 μm is necessary to explain the flux, which indicates co-diffusion by HCO inf3sup- . In the apparent absence of external carbonic anhydrase, direct uptake of HCO inf3sup- , rather than external conversion to CO2 is indicated in this species. In air, the CO2 concentration at which photosynthesis is half-maximal increases in the same order as the ability to raise pH in drift experiments. At 21 kPa the CO2 compensation partial pressures for Palmaria and Laurencia at 0.56 and 1.3 Pa are low enough to suggest a carbon-concentrating mechanism is operating, while those of Lomentaria at 1.8 Pa and particularly that of Delesseria at 4.5 Pa could be explained without a carbon-concentrating mechanism. The algae tested (all except Delesseria) showed more O2 evolution than could be accounted for with a photosynthetic quotient of 1.0 and uncatalysed conversion of HCO inf3sup- to CO2 outside the cell in high light at pH 8.0 when high algal fresh weight per unit medium was used. These results are concordant with other data suggesting use of HCO inf3sup- by Palmaria and Laurencia, but discordant with the rest of the available information in indicating use of HCO inf3sup- by Lomentaria. The reason for this is unclear. The lightsaturated rate of O2 evolution on an algal area basis and the photon flux density needed to saturate photosynthesis were related partly to the habitat from which the seaweeds were collected, but more strongly to the ability to use HCO inf3sup- . Values for the two users of HCO inf3sup- , Palmaria (population used was intertidal; also occurs subtidally) and Laurencia (intertidal/shaded intertidal), were greater than for Lomentaria (shaded intertidal), which was greater than Delesseria (subtidal), both of which are believed to be restricted to CO2. In accordance with earlier δ13C data and, for Delesseria, estimates of the achieved growth rates in situ, carbon is likely to be saturating and use of HCO inf3sup- is unlikely to occur in the normal low-light habitats of Lomentaria and Delesseria. Analysis of N-use efficiencies show that they are closer to the low-CO2-affinity Laminariales than the high-CO2-affinity Fucaceae.


Continuous-flow mechanical circulatory support is not associated with early graft failure: An analysis of the International Society for Heart and Lung Transplantation registry.
Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF. Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n = 11 748), pulsatile (P)-MCS (n = 718), and CF-MCS (n = 3818). EGF was defined as death/retransplantation due to graft failure within 30 days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression. The incidence of EGF within 30 days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P = .10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P = .24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P = .16). CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30 days after transplant.


Circular orientation fluorescence emitter imaging (COFEI) of rotational motion of motor proteins.
Single-molecule fluorescence polarization technique has been utilized to detect structural changes in biomolecules and intermolecular interactions. Here we developed a single-molecule fluorescence polarization measurement system, named circular orientation fluorescence emitter imaging (COFEI), in which a ring pattern of an acquired fluorescent image (COFEI image) represents an orientation of a polarization and a polarization factor. Rotation and pattern change of the COFEI image allow us to find changes in the polarization by eye and further values of the parameters of a polarization are determined by simple image analysis with high accuracy. We validated its potential applications of COFEI by three assays: 1) Detection of stepwise rotation of F1-ATPase via single quantum nanorod attached to the rotary shaft γ; 2) Visualization of binding of fluorescent ATP analog to the catalytic subunit in F1-ATPase; and 3) Association and dissociation of one head of dimeric kinesin-1 on the microtubule during its processive movement through single bifunctional fluorescent probes attached to the head. These results indicate that the COFEI provides us the advantages of the user-friendly measurement system and persuasive data presentations.


Examination of the Novel National Institutes of Health-Supported Relative Citation Ratio, a Measure of Research Productivity, Among Academic Plastic Surgeons.
Considerable interest has been devoted to quantifying research productivity for the purposes of academic appointment and promotion in plastic surgery. A novel bibliometric, the relative citation ratio (RCR), integrates features unavailable in prior metrics, such as the h-index, including the ability to compare researchers in distinct fields. This investigation examines the RCR in relation to established measures of academic productivity and provides the benchmark data in plastic surgery. Online sources were queried to identify the characteristics of 955 academic plastic surgeons from 94 programs, ie, academic rank, gender, degrees, and fellowships. Bibliometric data were acquired using the iCite and Scopus databases. Comparative and correlational analyses of variables were performed. Academic plastic surgeons were exceptionally productive, with a mean RCR of 1.20 (interquartile range, 0.79-1.67) and a weighted RCR of 17.68 (interquartile range, 5.14-52.48). Increased mean RCR was significantly associated with advanced academic rank and fellowship training. Increased weighted RCR was significantly associated with advanced academic rank, male gender, PhD acquisition, publication experience, and fellowship training. The h-index was weakly correlated with mean RCR but strongly correlated with weighted RCR and publication experience. The RCR was associated with established markers of academic productivity, indicating its validity as a reliable field-normalized measure for the evaluation of plastic surgery faculty. Because scholarly output is a potential factor with respect to decisions of hiring, promotion, and allocation of funding, this modality of standardized comparison is paramount for plastic surgeons who exist within a larger general surgery department.


Accent on communication: the impact of regional and foreign accent on comprehension in adults with aphasia.
This study explored whether an unfamiliar non-native accent, differing in both segmental and prosodic features was more difficult for individuals with aphasia to understand than an unfamiliar native accent, which differed in segmental features only. Comprehension, which was determined by accuracy judgments on true/false sentences, and speed of response were assessed in the following three conditions: a familiar Southern Standard British English (SSBE) accent, an unfamiliar native Grimsby accent, and an unfamiliar non-native Chinese accent. Thirty-four English speaking adults (17 people with and 17 people without aphasia) served as listeners for this study. All listeners made significantly more errors in the unfamiliar non-native accent, although this difficulty was more marked for those with aphasia. While there was no affect of speaker accent on the response times of listeners with aphasia, listeners without aphasia were significantly slower with the unfamiliar non-native accent. The results indicate that non-native accented speech affects comprehension even on simple tasks in ideal listening conditions. The findings suggest that speaker accent, especially accents varying in both segmental and prosodic features, can be a barrier to successful interactions between non-native accented speakers and native listeners, particularly those with aphasia.


Perceived Needs of Veterans Transitioning from the Military to Civilian Life.
Despite existing separation services provided by the military, many transitioning to civilian life report continued or even worsening issues, including anger outbursts, PTSD, sustained substance use, and strained family relationships. Further, only 61% of the 1,906,754 veterans separated since 2002 participate in the VA health care system after separation, indicating that at least three quarters of a million veterans are not captured by research conducted in VA systems. The current study (N = 90) examined the perceived needs of veterans transitioning from the military to civilian life, assessed issues that prevent these individuals from participating in VA health care upon separation, and captured veteran recommendations to improve existing separation services, either prior to or after the transition to civilian life. Veterans identified several needs, including improved access to care, mental health and substance use counseling, and preparedness for adjustment and economical/financial issues. Implications for both care and policy are discussed.


Outcome measurement in Australian rehabilitation environments.
To determine the frequency and pattern of methods of outcome assessment used in Australian physical rehabilitation environments. Postal survey. A questionnaire on service type, staffing, numbers of adults treated and outcome measures used for 7 conditions related to injury and road trauma as well as stroke and neuromuscular disorders was sent to 973 services providing adult physical rehabilitation treatment. Questionnaires were completed by 440 service providers for a response rate of 45%, similar to that reported in a recent European survey reported in this journal. A small number of measures were reported as in use by most respondents, while a large number of measures were used by a few respondents. Measures of physical changes were used more frequently than those of generic well-being or quality of life. Ease of use and reporting to other professionals were cited as the most important reasons in selection of outcome measures. This Australian-wide survey detected considerable heterogeneity in outcome measurement procedures used in rehabilitation environments. While the goal of measurement may vary between providers and differ between conditions, the results highlight opportunities for harmonization, bench-marking and measurement of health-related quality of life.


The supraoptic nucleus: afferents from areas involved in control of body fluid homeostasis.
Physiological evidence indicates that the supraoptic nucleus may be an important integrating region for information relating to body fluid homeostasis. It is known that the supraoptic nucleus receives neural influences from brain receptive zones for plasma osmolality and angiotensin II, as well as from relay centers for blood pressure and blood volume. It is also known that these influences interact to modulate vasopressin release from the supraoptic nucleus. Therefore, a detailed investigation of the neurochemical afferents to the supraoptic nucleus from regions of the lamina terminalis and the brainstem was undertaken. Injection of a fluorescent retrograde tracer, doxorubicin, into the supraoptic nucleus was combined with histochemistry of angiotensin II and catecholamines. Following supraoptic nucleus injection, retrograde label was found in forebrain neurons of the subfornical organ, median preoptic nucleus, and organum vasculosum of the lamina terminals. Some labeled cells in the subfornical organ and organum vasculosum of the lamina terminalis were also found to contain angiotensin II immunoreactivity. In the brainstem, retrograde label was found in neurons of the A1, A2 and A6 cell groups. Many of these cells were also found to contain catecholamine fluorescence or tyrosine hydroxylase immunoreactivity. Corroboration of the A2 projection was obtained by lesions of this nucleus, which reduced catecholamine fluorescence in the supraoptic nucleus. These findings provide an anatomical basis for the functional observations that the supraoptic nucleus plays a key integrative role in the maintenance of body fluid homeostasis.


Rrp6: Integrated roles in nuclear RNA metabolism and transcription termination.
The yeast RNA exosome is a eukaryotic ribonuclease complex essential for RNA processing, surveillance, and turnover. It is comprised of a barrel-shaped core and cap as well as a 3'-5' ribonuclease known as Dis3 that contains both endo- and exonuclease domains. A second exonuclease, Rrp6, is added in the nucleus. Dis3 and Rrp6 have both shared and distinct roles in RNA metabolism, and this review will focus primarily on Rrp6 and the roles of the RNA exosome in the nucleus. The functions of the nuclear exosome are modulated by cofactors and interacting partners specific to each type of substrate. Generally, the cofactor TRAMP (Trf4/5-Air2/1-Mtr4 polyadenylation) complex helps unwind unstable RNAs, RNAs requiring processing such as rRNAs, tRNAs, or snRNAs or improperly processed RNAs and direct it toward the exosome. In yeast, Rrp6 interacts with Nrd1, the cap-binding complex, and RNA polymerase II to aid in nascent RNA processing, termination, and polyA tail length regulation. Recent studies have shown that proper termination and processing of short, noncoding RNAs by Rrp6 is particularly important for transcription regulation across the genome and has important implications for regulation of diverse processes at the cellular level. Loss of proper Rrp6 and exosome activity may contribute to various pathologies such as autoimmune disease, neurological disorders, and cancer. WIREs RNA 2016, 7:91-104. doi: 10.1002/wrna.1317 For further resources related to this article, please visit the WIREs website.


Pulsed Doppler echocardiography: principles and applications.
A new recording and display system is described for use with pulsed Doppler blood flow velocity detectors in the diagnosis of valvular and septal defects. The principles of the pulsed Doppler device are described along with the methods used to analyze and display the Doppler shifted signal from flow jets resulting from various valve defects. An M-mode display is combined with blood flow display to provide a convenient record of the clinical procedure. Examples of aortic stenosis, aortic insufficiency, mitral stenosis and regurgitation are presented along with signals from other valves.


Azygos catheter placement as a cause of failure of dialysis.
Common complications of venous dialysis catheters include sepsis and accidental removal. Angiographic demonstration of dialysis lines is only rarely requested usually to confirm the presence of clot or stenosis as a cause for poor dialysis flow. Poor flow can also be due to inadvertent placement of the catheter in the azygos system. The use of dialysis catheters with a long venous limb which extends beyond the arterial port may predispose to such placement as their lumen is lateral to the central axis of the catheter. In those patients with poor venous access catheter placement under angiographic control may be helpful.


Recombinant plasmid constructs expressing gene for antimicrobial peptide melittin for the therapy of Mycoplasma and chlamydia infections.
In view of growing number of pathogenic microbial strain resistant to routine antibiotics, antimicrobial peptides become promising agents for the therapy of infectious diseases. We studied in vivo effects of melittin, an antimicrobial peptide expressed in a recombinant plasmid vector, on infection with urogenital pathogens Chlamydia trachomatis, Mycoplasma hominis, and Mycoplasma gallisepticum. We obtained recombinant plasmid constructs, where melittin gene is under the control of tetracycline-dependent human cytomegalovirus promoter. Inhibition of experimental C. trachomatis, M. hominis, and M. gallisepticum infection after administration of recombinant plasmid vectors expressing melittin gene to BALB/c mice was demonstrated.


An assessment of the physicochemical properties and toxicity potential of carwash effluents from professional carwash outlets in Gauteng Province, South Africa.
The assessment of the quality of carwash effluents has received scant attention as a potential source of public and environmental health hazard in South Africa as demonstrated by the lack of literature in this subject. The physicochemical quality and potential ramifications of carwash effluents on receiving waterbodies were investigated in this study. Grab effluent samples were collected from six carwash outlets in Gauteng Province of South Africa and analysed for selected physicochemical qualities including biological oxygen demand (BOD), oil and grease, total petroleum hydrocarbons-gasoline range organics (TPH-GRO), pH, dissolved oxygen (DO), total solids (TS) and total dissolved solids (TDS), electrical conductivity (EC), nutrients (nitrates, nitrites and phosphates), anionic surfactants and heavy metals (zinc [Zn], copper [Cu], lead [Pb] and chromium [Cr]). Further, the toxicity potential of the effluent samples was assessed using organisms from four trophic levels ranging from Selenastrum capricornutum (primary producer), Daphnia magna (primary consumer), Poecilia reticulata (secondary-tertiary consumer) and Vibrio fischeri (decomposer). High pollutant levels were observed in all effluents with BOD ranging from 27 ± 2.1 to 650 ± 4.9 mg/l, TDS from 362 ± 8.5 to 686 ± 8.5 mg/l, GRO-TPH from 0.01 ± 0.0 to 7.6 ± 0.2 mg/l, DO from 0.0 to 0.1 mg/l, Zn from 0.79 ± 0.08 to 20 ± 2.12 mg/l, Cu from 0.77 ± 0.03 to 13 ± 0.71 mg/l and oil and grease from 12 ± 2.8 to 43 ± 2.1 mg/l. Ammonium concentrations ranged from 0.4 ± 0.1 to 75 ± 6.4 mg/l; turbidity from 109 ± 0.7 to 4000 ± 29.7 mg/l, anionic surfactants from 1.4 ± 0.1 to 5.8 ± 0.3 mg/l and TPH from <0.01 to 7.6 mg/l. Toxicity assessment assays resulted in 100 % mortality for fish and Daphnia after 96 and 24 h, respectively, and significant bioluminescence and growth reduction in V. fischeri and algae after 15 min and 72 h, respectively. Most of the measured physicochemical parameters were in concentrations above the Environmental Management Agency (EPA) stipulated guidelines. Additionally, the effluents demonstrated acute toxicity against all four test species.


Cardiac arrest cerebral ischemia model in mice failed to cause delayed neuronal death in the hippocampus.
Global cerebral ischemia models for genetically engineered mice are of particular importance for the study of delayed neuronal death, but have been complicated by variability of vascular anatomy. Here we developed a 5-min cardiac arrest model that was not affected by vascular anatomy, and evaluated the hippocampal neuronal injury in BL/6 and SV129 mice. Despite prolonged anoxic depolarization for approximately 7 min, however, no consistent ischemic neuronal injury was noted in the CA1 sector of the hippocampus in both strains. Thus, our observations suggested that murine hippocampal neurons are relatively resistant to ischemia compared with those in other rodents.


Balo's concentric sclerosis followed by MRI and positron emission tomography.
We report a case of Balo's concentric sclerosis diagnosed in vivo by characteristic MRI changes and stereotactic biopsy. Follow-up after 6 months of immunosuppressive treatment demonstrated virtually complete clinical remission, reduction of the white matter lesions on MRI and normalisation of regional cerebral glucose metabolism as assessed by positron emission tomography not only in white matter but also in the cerebral grey matter structures with input from the affected regions.


Neural Correlates of Sensory Eye Dominance in Human Visual White Matter Tracts.
A significant proportion of the human neurotypical population exhibits some degree of sensory eye dominance (SED), referring to the brain's preferential processing of one eye's input versus another. The neural substrates underlying this functional imbalance are not well known. Here, we investigated the relationship between visual white matter tract properties and SED in the human neurotypical population. Observers' performance on two commonly used dichoptic tasks were used to index SED, along with performance on a third task to address a functional implication of binocular imbalance: stereovision. We show that diffusivity metrics of the optic radiations (ORs) well predict behavioral SED metrics. We found no relationship between SED and stereosensitivity. Our data suggest that SED is not simply reflected by gray matter structural and functional alterations, as often suggested, but relates, at least in part to the microstructural properties of thalamocortical white matter.


Tool-Driven Advances in Neuropeptide Research from a Nematode Parasite Perspective.
Expanding 'omics' datasets for parasitic nematodes have accelerated the identification of putative drug targets derived from the nematode nervous system. However, novel drug target validation is hampered by the absence of adequate localisation, functional characterisation, and receptor deorphanisation tools in key nematode pathogens. Reverse genetics techniques have advanced to encompass transgenic, targeted mutagenesis, gene silencing (RNA interference), and genome editing (CRISPR/Cas9) approaches in Caenorhabditis elegans. Unfortunately the translation to nematode pathogens has been slow, such that parasite-focused toolbox development and optimisation is critical. Here we review the discovery, localisation, and functional characterisation toolkit available for parasitic nematode neuropeptide research, and assess the scope and limitations of the tools and techniques for novel nematicide discovery.


Enhanced drug delivery via hyperthermal membrane disruption using targeted gold nanoparticles with PEGylated Protein-G as a cofactor.
Gold nanoparticles (GNPs) with near infrared (NIR) plasmon resonance have been promisingly used in photothermal cancer therapy as a less invasive treatment. Recombinant Protein-G (ProG) was PEGylated to act as a cofactor to immobilize immunoglobulins (IgGs) on GNPs by the Fc region, resulting in optimal orientation of IgGs for efficient cancer targeting. In-vitro studies showed that HER-2 overexpressing breast cancer cells, SK-BR-3, were efficiently targeted and ablated at a laser power of 900 J/cm(2) (5 W/cm(2) for 3 min). However, as a means of enhancing treatment efficacy by increasing cellular sensitivity to chemotherapeutic agents, we showed that GNP exposure to lower power laser resulted in small disruptions of cell membrane due to localized hyperthermia. This did not lead to cell death but provided a mechanism for killing cancer cells by providing enhanced uptake of drug molecules thus leading to a new avenue for hyperthermia-anticancer drug combined cancer therapeutics. PEGylated recombinant Protein-G was used as a cofactor to optimize the orientation of IgGs providing "target seeking" properties to gold nanoparticles used in photothermal cancer therapy. The system demonstrated excellent properties in cancer therapy, with the hope and expectation of future clinical translation.


Ethics dilemmas of early detection of obesity.
To discuss the ethics dilemmas of the early detection of overweight and obesity. Analysis of the ethical aspects of early detection. The early detection of overweight and obesity entails a number of ethical dilemmas because it may both be helpful and harmful. It may help people to lead a healthier life and non-detection could be considered neglectful. It may, however, cause anxiety, interfere with people's integrity, focus only on individual causes and responsibilities, cause stigmatization and have adverse effects by inducing weight gain. CONCLUSIONS DOCUMENTATION OF MORE POSITIVE THAN NEGATIVE EFFECTS IS REQUIRED BEFORE EARLY DETECTION IS INTRODUCED.