Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning.
The field of HIV-1 vaccine research has seen a renaissance with the identification of antibodies that neutralize most circulating HIV-1 strains. An understanding of the structural mode of target recognition that these antibodies use and the immune pathways that lead to their development is emerging. This knowledge has provided fundamental insights into the pathways that elicit broadly neutralizing antibodies and provides a foundation for active and passive immunization strategies to prevent HIV-1 infection.


Personality factors and cognitive functioning in patients with somatic symptom and related disorders.
Somatic symptom and related disorders (SSRD) are often complicated by cognitive symptoms, including reduced information processing speed, memory, and planning. Depression has been related to poor cognitive functioning in SSRD, but the role of underlying personality factors is poorly understood. This study investigates the association between personality factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness) with cognitive functioning in patients with SSRD. Data from 366 patients with SSRD from a tertiary care expert center (mean age = 42.1 years (SD = 13.4), 59.6% women) were analyzed using a cross-sectional design. Neuropsychological assessments included measures of information processing speed, memory, attention, and executive function. Personality factors were assessed using the NEO-FFI and depressive symptoms using the PHQ-9. Regression analyses showed associations between neuroticism with poorer performance on visual memory (B = -0.09, SE = 0.04, β = -0.14, p = .019), and planning (B = -0.09. SE = 0.02, β = -0.23, p < .001). Extraversion was also inversely associated with visual memory (B = -0.13, SE = 0.05, β = -0.18, p = .011) and planning (B = -0.07, SE = 0.03, β = -0.17, p = .021) and openness was associated with better visual memory (B = 0.17, SE = 0.05, β = 0.19, p = .002). These associations were attenuated but remained significant after adjusting for depressive symptoms. Neuroticism, extraversion, and low openness were associated with lower cognitive functioning (particularly planning and visual memory) in patients with SSRD, which remained significant after taking depressive symptoms into account.


Chemical constituents from the flowers of Anomianthus dulcis (Dunal) J. Sinclair.
Phytochemical investigation of the flowers of Anomianthus dulcis led to the isolation of eleven known compounds. The isolated compounds were identified by analysis of physical and spectroscopic (IR, 1 D and 2 D NMR) data. We report five flavonoids (1-4 and 10), two chalcone-sesquiterpenoids (5 and 6), one indole alkaloid (7), one triterpenoid (8), and a mixture of two phenolic compounds (9 and 11). Remarkably, it is the second isolation of sumadain A (5) and sumadain B (6) from a natural source. Compounds 5 and 6 were evaluated against several cancer cell lines, as the previous report lacked biological activity studies. Compound 6 showed strong cytotoxicity against Hela, HT-29, HCT-116, and A549 cell lines, with IC50 values in the range of 5.43-14.64 µg/mL.


Specific and non-specific binding of long-chain fatty acids to firefly luciferase: cutoff at octanoate.
Firefly luciferase emits a burst of light when the substrates luciferin and ATP are mixed in the presence of oxygen. We (I. Ueda, A. Suzuki, Biophys. J. 75 (1998) 1052-1057) reported that long-chain fatty acids are specific inhibitors of firefly luciferase in competition with luciferin in microM ranges. They increased the thermal transition temperature. In contrast, 1-alkanols of the same carbon chain length inhibited the enzyme non-competitively in mM ranges and decreased the transition temperature. The present study showed that the action of fatty acids switched from specific to non-specific when the carbon chain length was reduced below C8 (octanoate). The fatty acids longer than C10 inhibited the enzyme in microM ranges whereas those shorter than C8 required mM ranges to inhibit it. The longer fatty acids increased whereas shorter fatty acids decreased the transition temperature. The Hill coefficients of longer chain bindings were less than one whereas those of shorter chain were more than one. The shorter fatty acids interacted with the enzyme cooperatively at multiple sites. Binding of the longer fatty acids is limited. Fatty acids longer than C10 are high-affinity specific binders and followed Koshland's induced-fit model. Those shorter than C8 are low-affinity non-specific denaturants and followed Eyring's rate process model. These results contradict the general consensus that the size of the receptor cavity discriminates specific binders.


Structure of the archaebacterial 7S RNA molecule.
The genes encoding the 7S RNAs of the archaebacteria Archaeoglobus fulgidus, Methanosarcina acetivorans, Sulfolobus, solfataricus, and Thermococcus celer have been isolated. All four genes occur as single genomic copies and are flanked by sequences containing potential signals for transcriptional promotion and termination. The genes encode RNA molecules approximately 300 nucleotides in length which conform strictly to a model of secondary structure common to all described archaebacterial 7S RNAs. Archaebacterial 7S RNAs exhibit a strong similarity to eukaryotic 7S RNAs in terms of overall secondary structure, while primary sequence conservation is limited to a specific structural domain of the molecule. This domain displays strong primary and secondary structural similarity to features of small eubacterial RNAs, including the small cytoplasmic (sc) RNA of Bacillus subtilis and the 4.5S RNA of Escherichia coli. Conservation of this structural domain among divergent RNA molecules across three kingdoms suggests that these RNAs are the descendants of a unique subcellular structure present before the divergence of the archaebacterial, eubacterial and eukaryotic kingdoms.


Serological evidence of exposure of Bornean wild carnivores to feline-related viruses at the domestic animal-wildlife interface.
We conducted an exploratory serological survey to evaluate the exposure of Bornean wild carnivores to several viruses common to domestic felids, at interface areas between protected forest and industrial agriculture in the Kinabatangan floodplain (Sabah, Malaysia). Blood samples, collected from wild carnivores (n = 21) and domestic cats (n = 27), were tested for antibodies against feline coronavirus (FCoV), feline panleukopenia virus (FPLV), feline herpesvirus (FHV) and feline calicivirus (FCV), using commercial enzyme-linked immunosorbent assay (ELISA) test kits. Anti-FCoV antibodies were detected in most species, including one flat-headed cat (Prionailurus planiceps, [1/2]), leopard cats (Prionailurus bengalensis, [2/5]), Malay civets (Viverra tangalunga, [2/11]) and domestic cats (Felis catus, [2/27]). Anti-FCV antibodies were present in all domestic cats and one flat-headed cat, while anti-FPLV antibodies were identified in Sunda clouded leopards (Neofelis diardi, [2/2]), domestic cats [12/27] and Malay civets [2/11]. Anti-FHV antibodies were only detected in domestic cats [2/27]. Our findings indicate pathogen transmission risk between domestic and wild carnivore populations at the domestic animal-wildlife interface, emphasizing the concern for wildlife conservation for several endangered wild carnivores living in the area. Special consideration should be given to species that benefit from their association with humans and have the potential to carry pathogens between forest and plantations (e.g., Malay civets and leopard cats). Risk reduction strategies should be incorporated and supported as part of conservation actions in human-dominated landscapes.


HIV-related/AIDS cholangiopathy: pictorial review with emphasis on MRCP findings and differential diagnosis.
Magnetic resonance cholangiopancreatography provides accurate, noninvasive diagnosis of HIV/AIDS cholangiopathy through the identification of characteristic ductal abnormalities including multiple intrahepatic strictures, papillary stenosis, and long segmental extrahepatic strictures. Endoscopic retrograde cholangiopancreatography should be reserved for cytological or bioptic investigation in doubtful cases and for operative treatment when appropriate. Furthermore, cross-sectional imaging allows differentiation from other causes of biliary dilatation in HIV-positive patients, including infectious (bacterial) cholangitis, portal biliopathy, pancreatic or duodenal lymphoma, and mycobacterial lymphadenopathies.


Activation of Cl- channels by avermectin in rat cultured hippocampal neurons.
The actions of the insecticide avermectin (AVM) were studied in rat cultured hippocampal neurons with patch-clamp techniques. Application of micromolar concentrations of AVM to voltage-clamped cells gave rise to whole-cell currents, which showed a slow time-course of activation in the order of 10 s, and wash-out periods of typically 20 min. Dose-response curves revealed a half-maximally activating AVM concentration (EC50) of 2.0 +/- 0.6 microM and a Hill coefficient of 1.5 +/- 0.9. The current activated by AVM was carried predominantly by Cl- ions, as demonstrated by ion-substitution experiments. The Cl- channel blocker picrotoxinin (100 microM) substantially but transiently reduced the AVM response. Outside-out patch recording showed that AVM opened Cl- channels with a conductance of 40 +/- 12 pS. The open-time distribution was characterized by two time constants of 11 ms and 259 ms. It is suggested that AVM directly activates Cl- channels in mammalian central neurons, which resemble the channels activated by the physiological transmitters GABA and glycine.


Glycerol for acute stroke: a Cochrane systematic review.
Brain oedema is a major cause of early death after stroke. Glycerol is a hyperosmolar agent that is claimed to reduce brain oedema. We sought to determine whether I. V. glycerol treatment in acute stroke, either ischaemic or haemorrhagic, influences death rates and functional outcome in the short or long term and whether the treatment is safe. The Cochrane Stroke Group Trials Register was searched, conference proceedings were screened and some trialists were personally contacted. We considered all completed, controlled, published and unpublished comparisons, evaluating clinical outcome, in which intravenous glycerol treatment was initiated within the first days after stroke onset. Death from all causes, functional outcome and adverse effects were analysed. Analysis of short term death for acute ischaemic and/or haemorrhagic stroke was possible in ten trials where 482 glycerol treated patients were compared with 463 control patients. Glycerol was associated with a non-significant reduction in the odds of death within the scheduled treatment period (OR 0.78, 95 % Confidence Intervals 0.58-1.06). Among patients with definite or probable ischaemic stroke, glycerol was associated with a significant reduction in the odds of death during the scheduled treatment period (odds ratio 0.65, 95 % CI 0.44-0.97). However, at the end of the scheduled follow up period there was no significant difference in the odds of death (odds ratio 0.98, 95 % CI 0.73-1.31). Functional outcome was reported in only two studies and there was a non-significant positive effect on outcome at the end of scheduled follow up (odds ratio 0.73, 95 % CI 0.37-1.42). Haemolysis seems to be the only relevant adverse effect of glycerol treatment. This systematic review suggests a favourable effect of glycerol treatment on short term survival in probable or definite ischaemic stroke, but the magnitude of the treatment effect may be minimal (as low as a 3 % reduction in odds). Because of the relatively small number of patients and because the trials have been performed in the pre-CT era, the results must be interpreted cautiously. The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke.


Management of Benign Phyllodes Tumors: A Dutch Population-Based Retrospective Cohort Between 1989 and 2022.
Phyllodes tumors (PTs) are rare tumors of the breast. The current National Comprehensive Cancer Network (NCCN) guidelines recommend excision of benign PTs, accepting close or positive margins. Controversy about the optimal treatment for benign PTs remains, especially regarding the preferred margin width after surgical excision and the need for follow-up evaluation. A nationwide retrospective study analyzed the Dutch population from 1989 to 2022. All patients with a diagnosis of benign PT were identified through a search in the Dutch nationwide pathology databank (Palga). Information on age, year of diagnosis, size of the primary tumor, surgical treatment, surgical margin status, and local recurrence was collected. The study enrolled 1908 patients with benign PT. The median age at diagnosis was 43 years (interquartile range [IQR], 34-52 years), and the median tumor size was 30 mm (IQR, 19-40 mm). Most of the patients (95%) were treated with breast-conserving surgery (BCS). The overall local recurrence rate was 6.2%, and the median time to local recurrence was 31 months (IQR, 15-61 months). Local recurrence was associated with bilaterality of the tumor (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.95-28.30) and positive margin status (OR, 2.51; 95% CI 1.36-4.63). The local recurrence rate was 8.9% for the patients with positive excision margins and 4.0% for the patients with negative excision margins. Notably, for 27 patients (22.6%) who experienced a local recurrence, histologic upgrading of the recurrent tumor was reported, 7 (5.9%) of whom had recurrence as malignant lesions. This nationwide series of 1908 patients showed a low local recurrence rate of 6.2% for benign PT, with higher recurrence rates following positive margins.


Effects of dietary cyclopropene fatty acids on the mixed function oxidase system of the rainbow trout (Salmo gairdneri).
Dietary cyclopropene fatty acids (CPFA) in rainbow trout (Salmo gairdneri) decreased cytochrome P-450 and b5 content and NADPH-cytochrome c reductase activity 67.8 percent, 22.0 percent, and 38.4 percent respectively compared to control-fed trout after 22 days. Dietary CPFA induced benzo(alpha)pyrene aryl hydrocarbon hydroxylase 37.5 percent over controls for the same time period. Microsomal protein levels were consistently lower in CPFA-fed trout. This pattern remained established in CPFA-fed trout for the duration of the experiment (74 days). The data suggest a possible mechanism by which dietary CPFA act as co-carcinogens.


Clones from two different genomic regions complement the cdc25 start mutation of Saccharomyces cerevisiae.
We have cloned the CDC25 gene of Saccharomyces cerevisiae whose product is required for traversing the Go phase of the cell cycle. A preliminary physical characterization of the CDC25 gene region is presented. In addition, we show that another gene, when cloned in a high-copy number plasmid, is able to partially suppress growth thermosensitivity of a strain carrying the cdc25 mutation. We briefly discuss the possible interaction of these gene products with adenylate cyclase encoded by the CDC35 gene.


Only sociodemographic variables predict quality of life after radiography in patients with head-and-neck cancer.
Psychosocial factors influence patient compliance and have an effect on survival. Identifying patients at risk of decreased quality of life (QOL) with no extra expenditure in terms of hospital staff time or resources is mandatory to plan psychosocial support. Between 1997 and 2000, 242 patients with head-and-neck cancer (30% pharyngeal, 29% oropharyngeal, and 13% laryngeal cancer) were screened. Of these, 28.5% refused to participate and 19.0% were excluded (Karnofsky performance score <50, language and cognitive deficits, death, or noncompliance). A total of 124 patients were assessed with the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at ti1 (beginning of radiotherapy [RT]). Eighty-three patients from this group were examined, with complete data from ti1 to ti3 (6 weeks after RT). The QOL did not change during RT. In logistic regression analysis, medical information, in contrast to sociodemographic variables, turned out to have no influence on the ability to predict low QOL (sensitivity 80% vs. 32%). Four sociodemographic variables were entered in the regression model (children, currently employment, ethanol abuse, level of secondary education) and accounted for 26% of variance in QOL at ti3. By routinely obtaining clinical information from the patient's history, patients at risk of low QOL after RT can be identified and could benefit from early psychosocial support.


The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling.
The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC's tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation-based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function.


Allies or enemies? The effect of regulatory T cells and related T lymphocytes on the profibrotic environment in bleomycin-injured lung mouse models.
Idiopathic pulmonary fibrosis (IPF) is characterized by permanent scarring of lung tissue and declining lung function, and is an incurable disease with increase in prevalence over the past decade. The current consensus is that aberrant wound healing following repeated injuries to the pulmonary epithelium is the most probable cause of IPF, with various immune inflammatory pathways having been reported to impact disease pathogenesis. While the role of immune cells, specifically T lymphocytes and regulatory T cells (Treg), in IPF pathogenesis has been reported and discussed recently, the pathogenic or beneficial roles of these cells in inducing or preventing lung fibrosis is still debated. This lack of understanding could be due in part to the difficulty in obtaining diseased human lung tissue for research purposes. For this reason, many animal models have been developed over the years to attempt to mimic the main clinical hallmarks of IPF: among these, inducing lung injury in rodents with the anti-cancer agent bleomycin has now become the most commonly studied animal model of IPF. Pulmonary fibrosis is the major side effect when bleomycin is administered for cancer treatment in human patients, and a similar effect can be observed after intra-tracheal administration of bleomycin to rodents. Despite many pathophysiological pathways of lung fibrosis having been investigated in bleomycin-injured animal models, one central facet still remains controversial, namely the involvement of specific T lymphocyte subsets, and in particular Treg, in disease pathogenesis. This review aims to summarize the major findings and conclusions regarding the involvement of immune cells and their receptors in the pathogenesis of IPF, and to elaborate on important parallels between animal models and the human disease. A more detailed understanding of the role of Treg and other immune cell subsets in lung injury and fibrosis derived from animal models is a critical basis for translating this knowledge to the development of new immune-based therapies for the treatment of human IPF.


Cocoa polyphenols and fiber modify colonic gene expression in rats.
Cocoa intake has been associated with health benefits, improving cardiovascular function and metabolism, as well as modulating intestinal immune function. The aim of this study was to take an in-depth look into the mechanisms affected by the cocoa intake by evaluating the colonic gene expression after nutritional intervention, and to ascertain the role of the fiber of cocoa in these effects. To achieve this, Wistar rats were fed for 3 weeks with either a reference diet, a diet containing 10 % cocoa (C10), a diet based on cocoa fiber (CF) or a diet containing inulin (I). At the end of the study, colon was excised to obtain the RNA to evaluate the differential gene expression by microarray. Results were validated by RT-PCR. The C10 group was the group with most changes in colonic gene expression, most of them down-regulated but a few in common with the CF diet. The C10 diet significantly up-regulated the expression of Scgb1a1 and Scnn1 g and down-regulated Tac4, Mcpt2, Fcer1a and Fabp1 by twofold, most of them related to lipid metabolism and immune function. The CF and I diets down-regulated the expression of Serpina10 and Apoa4 by twofold. Similar patterns of expression were found by PCR. Most of the effects attributed to cocoa consumption on genes related to the immune system (B cell and mast cell functionality) and lipid metabolism in the colon tissue were due not only to its fiber content, but also to the possible contribution of polyphenols and other compounds.


Transition of a liquid crystalline phosphatidylcholine bilayer to the gel phase in a vesicle reduces the internal aqueous volume.
The liquid crystalline to gel phase transition in phospholipid bilayers is associated with a marked reduction in the area per phospholipid molecule. Geometric considerations based on published data suggest that this decrease in molecular area is accompanied by a reduction in the internal aqueous volume trapped within a unilamellar bilayer vesicle. This volume reduction, which depends upon the shape of the vesicle, is shown to be between 23 and 60 percent. We have observed a 25 to 30 percent reduction in the internal aqueous volume of unilamellar vesicles about 700 A in diameter formed from dipalmitoylphosphatidylcholine using the self-quenching of 6-carboxyfluorescein trapped within this compartment.


Regional distribution of methionine-enkephalin- and beta-endorphin-like immunoreactivity in human brain and pituitary.
Concentrations of methionine-enkephalin- (Met-enkephalin) and beta-endorphin-like immunoreactivities were determined in 33 areas of human brain and pituitary using highly sensitive radioimmunoassays in combination with affinity chromatography for the purification of beta-endorphin. It was found that they have quite different distribution patterns, suggesting the existence of both endorphins in independent systems in the central nervous system. Determination of Met-enkephalin and beta-endorphin immunoreactivities in chronic alcoholics and opiate-dependent subjects revealed no gross changes in comparison to the normal subjects.


Continuous Positive Airway Pressure Does Not Improve Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea. A Randomized Clinical Trial.
Rationale: Obstructive sleep apnea (OSA) is associated with development of nonalcoholic fatty liver disease (NAFLD). The effects of continuous positive airway pressure (CPAP) on NAFLD in patients with concomitant OSA are unknown.Objectives: To investigate the effects of autoadjusting CPAP versus subtherapeutic CPAP treatment over 6 months on NAFLD activities.Methods: Patients with NAFLD and OSA, as defined by respiratory event index ≥5/h diagnosed by a validated level 3 Embletta device, were randomized into group A) autoadjusting CPAP (4-20 cm H2O) or group B) subtherapeutic CPAP (pressure fixed at 4 cm H2O). The primary endpoint was the difference in changes in intrahepatic triglyceride as measured by proton magnetic resonance spectroscopy after 6 months of therapy. Key secondary endpoints included changes in controlled attenuation parameter (CAP) and liver stiffness measurement measured with transient elastography, and serum cytokeratin-18 fragment.Measurements and Main Results: A total of 120 patients were randomized equally into two groups. There were significant correlations between CAP and respiratory event index (r = 0.203, P = 0.026), percentage of total recording time with SaO2 < 90% (r = 0.265, P = 0.003), and oxygen desaturation index (r = 0.214, P = 0.019). After 6 months of treatment, there were no significant differences of changes in primary and secondary endpoints between the two treatment groups. Regression analysis showed that weight change over 6 months correlated with changes in both intrahepatic triglyceride and CAP (P < 0.001).Conclusions: Despite significant correlations between hepatic steatosis and markers of severity of OSA, CPAP alone did not improve hepatic steatosis and fibrosis. However, the additional role of weight reduction through lifestyle modification deserves further investigation.


Progesterone-induced hyperventilation in the guinea pig.
Progesterone-induced hyperventilation has thus far not been reported in animals other than humans. Accordingly we investigated the effects of chronic progesterone treatment on ventilation in guinea pigs. Virgin female guinea pigs were divided into those treated with cholesterol as controls (C), progesterone (P), or estrogen plus progesterone (E&P). All hormones were administered in silastic capsules placed subcutaneously for 28 days. On day 28 arterial blood gases and respiratory rates were determined. Arterial pH was elevated in P- and E&P-treated animals compared with controls (7.43 +/- 0.04 and 7.43 +/- 0.03 vs 7.39 +/- 0.05, respectively, P less than 0.05). Arterial PCO2 was reduced in both progesterone-treated groups compared to controls (33.9 +/- 5.8 (P), 33.1 +/- 2.8 (E&P), 38.0 +/- 4.3 (C)), and was correlated with systemic progesterone concentrations in animals receiving E&P (r = -0.85, P less than 0.01) but not in animals receiving P alone (r = -0.07, P = N.S.). Arterial [HCO-3], PO2 and respiratory rates were not different between groups. We conclude that chronic progesterone administration produces hyperventilation in guinea pigs, and that estrogen facilitates this action of progesterone.


Combined-modality treatment of localized soft tissue sarcomas of the extremities.
Over the past 20 years, considerable progress has been made in the treatment of patients with extremity soft tissue sarcomas. There has been a migration away from amputation toward treatment by excision plus radiation for most patients with localized tumors. Decisions about the optimal use and sequencing of surgery and radiation remain complex. Whereas it is clear that local control is probably not impacted significantly by the treatment sequence, rates of wound complication, fibrosis, and edema are affected by the treatment sequence. In addition, recent single-institution reports indicate that some carefully selected patients can be treated by surgery alone. The recent data evaluating treatment by surgery alone and treatment sequencing variables do not lead to a situation in which clear, uniform recommendations for treatment can be made for many patients with extremity soft tissue sarcomas. Indeed, treatment planning for patients with extremity soft tissue sarcoma in the new millennium is infinitely more complex than it was in the era when amputation was the primary treatment for these patients. Considerable clinical experience and multidisciplinary input are required for optimal treatment planning for these patients. Future research should be directed at refining the indications for specific therapies, reducing the toxicities of local therapies, and developing more effective systemic therapies.


Dual regulation of the synthesis of the arginine pathway carbamoylphosphate synthase of Saccharomyces cerevisiae by specific and general controls of amino acid biosynthesis.
The synthesis of the arginine pathway carbamoylphosphate synthase (CPSase A) of Saccharomyces cerevisiae is subject to two control mechanisms. One mechanism is specific for CPSase A and is exerted by arginine; it probably involves a repressor-operator type of interaction. This "specific" mechanism regulates the expression of gene cpaI coding for the small "glutaminase" subunit of CPSase A but has little influence on the production of the large subunit of the enzyme, a product of gene cpaII. This large component, which alone has no biological significance, accumulates freely under conditions of arginine repression. The second mechanism is general: it controls enzyme synthesis in a number of amino acid biosynthetic pathways in addition to the arginine sequence. Two types of evidence that this "general" mechanism participates in the control of CPSase A synthesis are presented: (1) Derepression upon starvation for any amino acid of which the synthesis is subject to this general control; and (2) repression during growth in amino acid-rich medium. In contrast to the specific mechanism, the "general" mechanism regulates the expression of both the cpaI and cpaII genes.


A randomized comparison of defibrillation thresholds in the right ventricular outflow tract versus right ventricular apex.
To determine whether the placement of an implantable cardioverter-defibrillator (ICD) lead in the right ventricular outflow tract (RVOT) has the same defibrillation threshold (DFT) as the right ventricular apex (RVA). Right ventricular ICD leads have usually been placed in the RVA. Development of active fixation technology has allowed the placement of these leads in alternate locations such as the RVOT. At time of device implantation, 26 patients with either ischemic or dilated cardiomyopathy underwent DFT testing in both the RVA and RVOT using a binary search algorithm. Placement of the lead in the RVA had a mean DFT of 7.6 +/- 2.8 J while the placement of the lead in the RVOT had a mean DFT of 10.3 +/- 3.0 J. The median (25th and 75th percentiles) DFTs in the RVA and RVOT were 7.5 J (6 and 11 J) and 11 J (9 and 14 J), respectively (p = 0.0002). Placement of the right ventricular lead in the RVA has a significantly lower DFT than placement of the lead in the RVOT.


Instruments for assessment of impairments and activity limitations in patients with hand conditions: A European Delphi study.
To reach multidisciplinary European consensus on the assessment tools for impairments and activity limitations in patients with hand conditions. Electronic Delphi method. Thirty experts from European societies for hand therapy, hand surgery, and physical and rehabilitation medicine. In 3 rounds, participants were asked which of 13 preselected categories of the Brief International Classification of Functioning, Disability and Health (ICF) Core Set for Hand Conditions should be assessed. In addition, they were asked to choose which of 55 preselected instruments they preferred for each category by confirming or rejecting instrument-specific statements. All 13 preselected ICF categories were considered relevant. Consensus was based on ≥ 75% agreement. After 3 rounds, 9 instruments were selected: Shape Texture Identification Test, Semmes Weinstein Monofilament Test, Visual Analogue Scale for pain, goniometer, Jamar Dynamometer, Pinch Gauge Device, Cold Intolerance Symptom Severity questionnaire, Canadian Occupational Performance Measure, and Disabilities of the Arm, Shoulder and Hand Questionnaire. It remained undecided whether to use the Nine-Hole Pegboard Test or the Purdue Pegboard Test. In this European Delphi study, multidisciplinary consensus was reached on 9 assessment tools for impairments and activity limitations in patients with hand conditions addressing 13 categories of the Brief ICF Core Set for Hand Conditions.


Production and standing crop patterns of giant cutgrass (Zizaniopsis miliacea) in a freshwater tidal marsh.
Growth cycles and production of aboveground and belowground giant cutgrass (Zizaniopsis miliacea (Michx.) Doell and Asch.) were studied in a freshwater tidal marsh along the lower Savannah River near Savannah, Georgia, USA. Minimum aboveground live standing crop (142 g/m2) occurred in March with a steady increase thereafter to an October maximum (1,039 g/m2) followed by a rapid decline. Giant cutgrass aboveground net primary production was approximately 1,530 g/m2/yr. Rhizomes (358 g/m2/yr) and roots (160 g/m2/yr) yielded an annual belowground production of 518 g/m2/yr. Total above and belowground annual net production was estimated at 2,048 g/m2/yr.


Beyond Kolbe and Hofer-Moest: Electrochemical Synthesis of Carboxylic Anhydrides from Carboxylic Acids.
Herein we report a conceptually new non-decarboxylative electrolysis of carboxylic acids to obtain their corresponding anhydrides as highly valuable reagents in organic synthesis. All carbon atoms of the starting material are preserved in the product in an overall redox-neutral reaction. In a broad substrate scope of carboxylic acids the anhydrides are generated with high selectivity, which demonstrates the versatility of the developed method. Beneficially, no dehydrating reagents are required in comparison to conventional methods and the synthesis is based on uncritical starting materials using graphite and stainless steel as very inexpensive and eco-friendly electrode materials.


Oscillatory discharges in the auditory midbrain of the big brown bat contribute to coding of echo delay.
Subsequent to his breakthrough discovery of delay-tuned neurons in the bat's auditory midbrain and cortex, Albert Feng proposed that neural computations for echo delay involve intrinsic oscillatory discharges generated in the inferior colliculus (IC). To explore further the presence of these neural oscillations, we recorded multiple unit activity with a novel annular low impedance electrode from the IC of anesthetized big brown bats and Seba's short-tailed fruit bats. In both species, responses to tones, noise bursts, and FM sweeps contain long latency components, extending up to 60 ms post-stimulus onset, organized in periodic, oscillatory-like patterns at frequencies of 360-740 Hz. Latencies of this oscillatory activity resemble the wide distributions of single neuron response latencies in the IC. In big brown bats, oscillations lasting up to 30 ms after pulse onset emerge in response to single FM pulse-echo pairs, at particular pulse-echo delays. Oscillatory responses to pulses and evoked responses to echoes overlap extensively at short echo delays (5-7 ms), creating interference-like patterns. At longer echo delays, responses are separately evident to both pulses and echoes, with less overlap. These results extend Feng's reports of IC oscillations, and point to different processing mechanisms underlying perception of short vs long echo delays.


A cautionary tale of pyridoxine toxicity in cystathionine beta-synthase deficiency detected by two-tier newborn screening highlights the need for clear pyridoxine dosing guidelines.
Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.


Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children.
Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes.


Home monitoring of penile tumescence for erectile dysfunction. Initial experience.
A technique using nocturnal penile tumescence monitoring has been developed to gather objective data on an outpatient basis. Patients have readily accepted the procedure and have easily learned to operate the monitor. Data from this group of controls and subjects are consistent with previously published reports by others. Suggestions are made from possible further refinements in technique.


Acute Outflow Graft Occlusion-A Novel Predictable Complication of Lysis Therapy for the Treatment of Left Ventricular Assist Device Intra-Pump Thrombosis.
Lysis therapy is an established treatment option for intra-pump thrombosis of left ventricular assist devices (LVADs). In clinical routine, we observed repeated cases of acute outflow graft occlusions (OGO) associated with lysis therapy with need for urgent intervention. The aim of this investigation was to gain understanding of this observation. We screened data of 962 HeartWare ventricular assist device (HVAD) patients. One hundred twenty (13.8%) had intra-pump thromboses; 58 were treated with recombinant tissue-type plasminogen activator (rtPA). Mean age was 53.0 ± 11.1 years; 84.9% were male. In 13 (24.5%) patients, OGO occurred following rtPA-lysis. These patients showed an increase in left ventricular function (18.45% ± 12.62% to 27.73% ± 10.57%; p = 0.056), more frequent 1:1 aortic valve opening (OGO+: +36.4%; OGO-: +7.4%; p = 0.026), a decrease in LVAD pulsatility within 12 months prior intra-pump thrombosis (OGO+: -0.8 L/min [interquartile range {IQR}, -1.4 to -0.4 L/min]; OGO-: -0.3 L/min [IQR, -0.9 to 0.1 L/min]; p = 0.038) and lower HVAD flows at admission (OGO+: 6.7 L/min [IQR, 6.1-7.4 L/min]; OGO-: 8.3 L/min [IQR, 6.9-9.3 L/min]; p = 0.013), indicating a subclinical OGO prior intra-pump thrombosis. There were no differences in implantation techniques, blood parameters, and lysis strategy. Subclinical OGO represented a major risk factor for acute OGO following rtPA lysis therapy. We here propose an algorithm for risk stratification and dealing with patients presenting this first-described complication. Further research is required to confirm our results and decipher the underlying pathomechanism. http://links.lww.com/ASAIO/B97.


Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells.
The intestinal microbiota has a critical role in immune system and metabolic homeostasis, but it must be tolerated by the host to avoid inflammatory responses that can damage the epithelial barrier separating the host from the luminal contents. Breakdown of this regulation and the resulting inappropriate immune response to commensals are thought to lead to the development of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. We proposed that the intestinal immune system is instructed by the microbiota to limit responses to luminal antigens. Here we demonstrate in mice that, at steady state, the microbiota inhibits the transport of both commensal and pathogenic bacteria from the lumen to a key immune inductive site, the mesenteric lymph nodes (MLNs). However, in the absence of Myd88 or under conditions of antibiotic-induced dysbiosis, non-invasive bacteria were trafficked to the MLNs in a CCR7-dependent manner, and induced both T-cell responses and IgA production. Trafficking was carried out by CX(3)CR1(hi) mononuclear phagocytes, an intestinal-cell population previously reported to be non-migratory. These findings define a central role for commensals in regulating the migration to the MLNs of CX(3)CR1(hi) mononuclear phagocytes endowed with the ability to capture luminal bacteria, thereby compartmentalizing the intestinal immune response to avoid inflammation.


Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse.
C57 black mice given a single injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 40 mg/kg, developed marked reduction of striatal dopamine content and loss of dopaminergic neurons in the zona compacta of the substantia nigra. However, pretreatment with any one of four different antioxidants, alpha-tocopherol, beta-carotene, ascorbic acid or N-acetylcysteine, significantly decreased MPTP-induced striatal dopamine loss, and alpha-tocopherol prevented neuronal loss in the substantia nigra. Four chemical analogues of MPTP (cinnamaldehyde, N,N-dimethylcinnamylamine, arecoline and 2-methyl-1,2,3,4-tetrahydro-6,7-isoquinolinediol) were all found to lack dopaminergic nigrostriatal neurotoxicity in the mouse.


A Multisystem Mitochondrial Disease Caused by a Novel MT-TL1 mtDNA Variant: A Case Report.
Mitochondrial tRNA (MTT) genes are hotspot for mitochondrial DNA mutation and are responsible of half mitochondrial disease. MTT mutations are associated with a broad spectrum of phenotype often with complex multisystem involvement and complex genotype-phenotype correlations. MT-TL1 mutations, among which the m.3243A>G mutation is the most frequent, are associated with myopathy, maternal inherited diabetes and deafness, MELAS, cardiomyopathy, and focal segmental glomerulosclerosis. Here we report the case of an Italian 49-years old female presenting with encephalomyopathy, chronic proteinuric kidney disease and a new heteroplasmic m.3274_3275delAC MT-TL1 gene mutation. Our case demonstrates a systemic mitochondrial disease caused by the heteroplasmic m.3274_3275delAC MT-TL1 gene mutation, not yet described in the literature. A mitochondrial disease should be suspected in case of complex multisystem phenotypes, including steroid-resistant nephrotic syndrome with multisystemic involvement.


Deltoid contracture: a case with multiple muscle contractures.
Deltoid contracture is relatively uncommon. The literature consists primarily of case reports and few articles on large case series. The pathogenesis has been well studied. Muscle contractures can occur in the deltoid, biceps, triceps, gluteus and quadriceps muscles; however, cases of multiple muscle contractures are rare. We reported a patient with multiple contractures of the bilateral deltoid, bilateral gluteus, and bilateral quadriceps muscles, who had received repeated intramuscular injections during childhood and adulthood. The radiographic, including magnetic resonance imaging (MRI), features of the bone and joint abnormalities are presented. Some literatures reported that damage to the structures of the body due to intramuscular injection is related to the site of injection, age of the patient, and the volume, pH, chemical composition, and diffusional capacity of the injectate. Our patient had muscular contracture induced by needle injection regardless of her age, medication and injection site.


Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.
Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.


PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells.
G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments.


The effect of the DLTIDDSYWYRI motif of the human laminin α2 chain on implant osseointegration.
Considerable effort has been directed towards replacing lost teeth using tissue-engineering methods such as titanium implants. A number of studies have tried to modify bioinert titanium surfaces by coating them with functionally bioactive molecules for faster and stronger osseointegration than pure titanium surfaces. Recently, peptides have been recognized as valuable scientific tools in the field of tissue-engineering. The DLTIDDSYWYRI motif of the human laminin-2 α2 chain has been previously reported to promote the attachment of various cell types; however, the in vivo effects of the DLTIDDSYWYRI motif on new bone formation have not yet been studied. To examine whether a laminin-2-derived peptide can promote osseointegration by accelerating new bone formation in vivo, we applied titanium implants coated with the DLTIDDSYWYRI motif in a rabbit tibia model. The application of the DLTIDDSYWYRI motif-treated implant to tibia wounds enhanced collagen deposition and alkaline phosphatase expression. It significantly promoted implant osseointegration compared with treatment with scrambled peptide-treated implants by increasing the bone-to-implant contact ratio and bone area. These findings support the hypothesis that the DLTIDDSYWYRI motif acts as an effective osseointegration accelerator by enhancing new bone formation.


Isolation and Characterization of T Lymphocyte-Exosomes Using Mass Spectrometry.
Exosomes are cell-derived vesicles that have been implicated in the pathogenesis of many inflammatory diseases. In the immune system, it has been shown that T lymphocyte-derived exosomes are able to induce diverse cellular responses. There are several methods to isolate and to characterize exosomes, each with their own advantages and disadvantages. Here, we describe a centrifugation approach, combined with mass spectrometry characterization, as a means to study exosomes derived from primary human T lymphocytes. This method is sensitive and therefore can be applied when a limited amount of sample is available.


Near-infrared optical topography to assess activation of the parietal cortex during a visuo-spatial task.
Multi-channel near-infrared spectroscopy (NIRS) is a relatively new method to investigate the brain activation, based on changes in oxygenated haemoglobin (O2Hb) and deoxygenated haemoglobin (HHb). Recently, it has been shown that NIRS seems to be able to detect even small changes in O2Hb and HHb concentration due to cognitive demands. This study aimed at investigating the changes in O2Hb and HHb concentrations of the parietal cortex during a spatial task, a modified version of the Benton Line Orientation Task [Gur, R. C., Alsop, D., Glahn, D., Petty, R., Swanson, C. L., Maldjian, J. A., et al. (2000). An fMRI study of sex differences in regional activation to a verbal and a spatial task. Brain & Language, 74(2), 157-170.]. Twenty-four subjects were measured with NIRS while they had to estimate the orientation of a given line or to name the colour of the line in the control condition. Both conditions consisted of three activation phases each lasting 30 s, with a 10 s baseline and a 20 s post resting period. For assessing the changes in O2Hb and HHb concentrations, we measured with 24 NIRS channels over the parietal cortex using the NIRS apparatus ETG-100 (Hitachi Medical Ltd.). O2Hb concentration significantly increased during the active phase compared to the baseline for both conditions, but was significantly higher in the active phase for the line orientation condition compared to the colour naming condition bilaterally parieto-occipital. For the HHb concentrations, we only found significant decreases for both conditions but no differences between the conditions. The results of our study underscore the value of multi-channel NIRS for assessing cortical activation during cognitive tasks.


Development of macrophage and granulocyte colonies from human peripheral blood.
The presence of macrophage and granulocyte progenitor cells in the human peripheral blood enabled the establishment of colonies from this accessible tissue and obviated the need for bone marrow to achieve this task. We have developed a method of obtaining reproducible growth of macrophage/granulocyte colonies from human peripheral blood. Colonies of macrophages and granulocytes were obtained by plating peripheral blood mononuclear cells (PBM) in methylcellulose containing medium in the presence of medium conditioned by nonstimulated PBM (CM). At early stages of colony growth both macrophage and granulocyte colonies were detected while following 20-25 days in culture all colonies tested revealed monocyte-macrophage morphology. To obtain higher numbers of colonies, we tested different cell sources, different CM preparations and the effect of steroid hormones on colony development. We found that the mononuclear cells obtained from cord blood (CB) or from some patients with inflammatory bowel disease yielded much higher numbers of colonies than PBM from normal individuals. Colony development from these two sources did not depend on an external source of colony stimulating factor (CSF) but was augmented as a result of CSF supplementation. CM obtained from CB mononuclear cells as well as supernatants from some human monoblastic cell lines were similar in their CSF activity to CM from normal PBM and made possible the development of macrophage/granulocyte colonies. Higher numbers of colonies were induced by including physiological concentrations of estradiol in the culture medium, in the absence of external sources of CSF. The system described above enabled the analysis of cloned macrophages and their circulating progenitor cells as well as the assay of different preparations of CSF.


Organization and nucleotide sequence of ribosomal RNA genes on a circular 73 kbp DNA from the colourless flagellate Astasia longa.
Three tandemly arranged repeats (A, B, C) of 16S and 23S rDNA, and one supplementary (S) 16S rDNA adjacent to the 16S rDNA of repeat A, are present within an 18 kbp segment of a circular 73 kbp DNA from the colourless flagellate Astasia longa. The repeat units are separated by a short region containing a 5S rRNA gene and a gene for tRNA-Val (UAC). Sequence comparisons reveal 78%, 81%, and 67% identical nucleotides of the 23S rDNA (A), the 16S rDNA (B), and the 5S rDNA (A), respectively, with the corresponding genes of the Euglena gracilis chloroplast genome. As in Euglena chloroplasts, the 3'-terminal portion of the 23S rDNA is homologous to the 4.5S rRNA gene of higher plant chloroplast genomes. These results are supportive of a common evolutionary origin for the Astasia 73 kbp DNA and the Euglena 145 kbp chloroplast DNA.


[Unusual sequelae of a cranial injury].
A 13 year old child who had an apparently mild head injury presented with psychiatric sequelae. The main feature was a variable level of consciousness. The only explanation for the symptoms lay within the family environment. A hysterical converion symptom was possible but the start of a psychosis could not be excluded.


Aflatoxin residues in eggs of laying Japanese quail after long-term administration of rations containing low levels of aflatoxin B1.
The aim was to evaluate the excretion of residues of aflatoxin B(1) (AFB(1)), aflatoxin M(1) (AFM(1)), aflatoxin B(2a) (AFB(2a)) and aflatoxicol (AFL) in eggs of laying Japanese quail fed rations with low levels of aflatoxin B(1) for 90 days. The quail were randomly assigned into four experimental groups and given prepared rations containing either 0 (controls), 25, 50 or 100 microg AFB(1) kg(-1) feed. Thirty-two eggs per treatment were collected on days 1-7, 10, 20, 30, 60 and 90 of the aflatoxin treatment period, and submitted to aflatoxin analysis by high-performance liquid chromatography. Average egg production and feed consumption were not affected ( p > 0.05) by AFB(1). Egg weight was significantly lower ( p<0.05) only for groups exposed to 100 microg AFB(1) kg(-1). Residues of aflatoxins were detected in eggs at levels that ranged from 0.01 to 0.08 microg kg(-1) (AFB(1)), 0.03-0.37 microg kg(-1) (AFM(1)), 0.01-1.03 microg kg(-1)(AFB(2a)) and 0.01-0.03 microg kg(-1) (AFL). Results indicate that the excretion of aflatoxin residues in quail eggs might occur at relatively low concentrations under conditions of long-term exposure of quail to low levels of AFB(1).


Closed- or open-glottis pushing for vaginal delivery: a planned secondary analysis of the TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery study.
The effect on obstetrical outcomes of closed- or open-glottis pushing is uncertain among both nulliparous and parous women. This study aimed to assess the association between open- or closed-glottis pushing and mode of delivery after an attempted singleton vaginal birth at or near term. This was an ancillary planned cohort study of the TRAAP (TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery) randomized controlled trial, conducted in 15 French maternity units from 2015 to 2016 that enrolled women with an attempted singleton vaginal delivery after 35 weeks' gestation. After randomization, characteristics of labor and delivery were prospectively collected, with special attention to active second-stage pushing and a specific planned questionnaire completed immediately after birth by the attending care provider. The exposure was the mode of pushing, classified into 2 groups: closed- or open-glottis. The main endpoint was operative vaginal delivery. Secondary endpoints were items of maternal morbidity, including severe perineal laceration, episiotomy, postpartum hemorrhage, duration of the second stage of labor, and a composite severe neonatal morbidity outcome. We also assessed immediate maternal satisfaction, experience of delivery, and psychological status 2 months after delivery. The associations between mode of pushing and outcome were analyzed by multivariate logistic regression to control for confounding bias, with multilevel mixed-effects analysis, and a random intercept for center. Among 3041 women included in our main analysis, 2463 (81.0%) used closed-glottis pushing and 578 (19.0%) open-glottis pushing; their respective operative vaginal delivery rates were 19.1% (n=471; 95% confidence interval, 17.6-20.7) and 12.5% (n=72; 95% confidence interval, 9.9-15.4; P<.001). In an analysis stratified according to parity and after controlling for available confounders, the rate of operative vaginal delivery did not differ between the groups among nulliparous women: 28.7% (n=399) for the closed-glottis and 27.5% (n=64) for the open-glottis group (adjusted odds ratio, 0.93; 95% confidence interval, 0.65-1.33; P=.7). The operative vaginal delivery rate was significantly lower for women using open- compared with closed-glottis pushing in the parous population: 2.3% (n=8) for the open- and 6.7% (n=72) for the closed-glottis groups (adjusted odds ratio, 0.43; 95% confidence interval, 0.19-0.90; P=.03). Other maternal and neonatal outcomes did not differ between the 2 modes of pushing among either the nulliparous or parous groups. Among nulliparous women with singleton pregnancies at term, the risk of operative vaginal birth did not differ according to mode of pushing. These results will inform shared decision-making about the mode of pushing during the second stage of labor.


Blood flow in the tibialis anterior muscle by photoplethysmography during foot-transmitted vibration.
Photoplethysmography (PPG) was used to detect changes in the anterior tibial muscle blood flow (MBF) during foot-transmitted vibration in six healthy subjects. A filter was developed for reducing the vibration-induced artefacts in the PPG signal. The vibration applied was random with constant acceleration power density in the range 5-2000 Hz with an acceleration of 16-46 m s(-2) (rms). The application of the filter technique showed a dramatic reduction in the vibration-induced artefacts and distortion of the PPG signal was negligible. The mean ratio and correlation coefficient of MBF originating from filtered and non-filtered PPG signals was [mean (SD)] 0.89 (0.04) and 0.99, respectively. This made it possible to detect a relative increase in MBF of 20% during an acute vibration exposure. The results suggest that the use of the filter enables MBF to be measured by PPG during vibration, thus extending the range of applications of the PPG technique to include ergonomic conditions.


The finite-dimensional Freeman thesis.
I suggest a modification--and mathematization--of Freeman's thesis on the relations among "perception", "the finite brain", and "the world", based on my recent proposal that the theory of finite topological spaces is both an adequate and a natural mathematical foundation for human psychology.


The role of IL-17 in lung cancer growth.
Interleukin 17 (IL-17) is an inflammatory cytokine with multiple roles in immune protection, immunopathology, and inflammation-related tumors. Lung cancer is inflammation-related cancer, and a large number of studies have shown that IL-17 contributes to the metastasis and progression of lung cancer. However, some studies have shown that IL17 inhibits the occurrence of lung cancer. At present, there is still some controversy about the role of IL17 in the occurrence and development of lung cancer. This review introduces the basic characteristics of IL-17 and focuses on its role in lung cancer, in order to provide a certain theoretical basis for the prevention, diagnosis, and treatment of lung cancer.


Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex.
In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20-80min) and then by a late decrease in c-Fos and GAD65 expression (160min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability.


Assessment of health-related quality of life: Swedish version of polycystic ovary syndrome questionnaire.
Polycystic ovary syndrome questionnaire (PCOSQ) was developed in USA to ascertain specific health-related quality of life (HRQL) in polycystic ovary syndrome (PCOS). The Swedish version of PCOSQ should be tested prior to its use in research and clinical practice and the aims of the study were as follows: (a) determine the test-retest reliability and (b) confirm the domain structure of the Swedish version of PCOSQ; a 26-item questionnaire, divided into the five domains: emotions, body hair, weight concerns, infertility concerns and menstrual irregularities. PCOSQ translation from English to Swedish was followed by a test-retest and a factor analysis of obtained PCOSQ completed twice by 69 women with PCOS. The median age was 30 (21-37) years. The Kappa (kappa) statistic for the five domains ranged from 0.29 to 0.69 demonstrating fair to good agreement among items. The Intra-class Correlation Coefficient (ICC) for the five domains was high to excellent ranging from 0.79 to 0.96. The factor analysis presented six domains and the original domain structure was partly confirmed. The Swedish version of PCOSQ is reliable and can be used to measure HRQL in PCOS. Researchers and clinicians should be aware of the benefits of PCOSQ.


Structural polymorphism of human DR antigens.
DR ANTIGENS are polymorphic cell surface molecules whose expression is controlled by a locus closely linked or identical to the D locus of the major histocompatibility complex (MHC) of man (for reviews see refs 1, 2). They are functionally and structurally homologous to the murine la antigens determined by the I-E subregion of the MHC, a region which has been implicated in the genetic control of immune responses(3,4). Both sets of antigens are mainly expressed on cells associated with immune function (for reviews see refs 1, 2, 5), and are involved in mediating T-cell, B-cell and macrophage interactions required for the generation of immune responses(6-9). In addition, both consist of two non-covalently associated polypeptides, designated alpha and beta, with molecular weights of 34,000 and 28,000, respectively(10). The association of some DR antigens with increased susceptibility to certain diseases (for review see ref. 1) and the genetic restrictions imposed on cellular interactions by the HLA-D region(9,11) may represent the effects of structural variability among DR antigens. The aim of the studies reported here was to examine the nature and degree of structural variation among DR antigens isolated from cultured lymphoid B cells with different DR phenotypes. Such information may provide an understanding of the molecular mechanisms by which DR antigens mediate their function.


Flow cytometric quantification of HIV-1 Tat protein in tat-transfected Jurkat T cell lines.
The transactivator Tat protein represents a pivotal factor for the replication of human immunodeficiency virus type 1 (HIV-1). In this report, we describe a flow cytometry procedure designed to quantify the intracellular content of Tat protein in Jurkat CD4+ T lymphoblastoid cell lines, stably transfected with plasmids expressing full-length Tat protein. Various expression vectors were compared for their effectiveness to yield Tat protein in Jurkat cells, and several technical parameters were analyzed to optimize the assay. This method offers a quick and efficient approach to select stably transfected cell lines expressing different levels of specific protein.


Adenotonsillectomy in Arnold Chiari Malformation: Navigating Surgical Complexities.
Navigating Surgical Complexities associated with a case of Adenotonsillectomy in Arnold Chiari Malformation type 2. Arnold-Chiari or Chiari malformations (ACM) describe a group of deformities of the posterior fossa and hindbrain, which includes the cerebellum, pons, and medulla oblongata. Sleep-disordered breathing is a known but poorly evaluated comorbidity in patients with ACM. Obstructive sleep apnoea (OSA) in children is mainly caused by tonsillar and adenoid hypertrophy, and surgical resection of the palatine tonsils and adenoids is indicated depending on OSA severity. A 4-year-old male child suffering from Arnold Chiari type 2 malformation presented to us in OPD with Severe OSA. Clinical and endoscopic examination revealed presence of Grade 4 adenoids tissue and Grade 4 tonsillar hypertrophy. Patient was planned to undergo Coblation adenoidectomy and Tonsillectomy with Uvulopalatoplasty for the management of OSA. Patient tolerated the procedure well and extubating was un-eventful. Patient was kept in PICU for overnight observation and was discharged on next day without any major complications. Patient of Arnold Chiari malformation type 2 presenting with severe OSA due to peripheral cause like Chronic adenoid and tonsillar hypertrophy present an operative challenge due to nil neck extension and minimal oral cavity space. The key is that ACM 2 along with its complications, such as difficult airway, increased intracranial pressure, and autonomic dysfunction, makes it very challenging and requires well-structured and disciplined management by combined anaesthesiology, neurology, and operative team which emphasize on preoperative, intraoperative, and postoperative complications and its timely management.


Nitrogen mustards derived from alpha-hydroxymethyleneketones.
alpha-[Bis-(2-chloroethyl)]aminomethyleneketones were prepared starting from alpha-hydroxymethyleneketones and N-(2-chloroethyl)-2-chloroethanamine. Also 3-[2-(2-chloroethylthio)ethyl]aminomethylene-2-bornanone was synthesized from 2-(2-chloroethylthio)ethanamine and 3-hydroxymethylene-2-bornanone. This compound and 3-[bis-(2-chloroethyl]aminoemthylene-2-norbornanone were active against P388 lymphocytic leukemia in mice.


Effects of hypertonic saline versus mannitol in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings: a systematic review and meta-analysis.
Intracranial pressure control has long been recognized as an important requirement for patients with severe traumatic brain injury. Hypertonic saline has drawn attention as an alternative to mannitol in this setting. The aim of this study was to assess the effects of hypertonic saline versus mannitol on clinical outcomes in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings by systematically reviewing the literature and synthesizing the evidence from randomized controlled trials. We searched the MEDLINE database, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi (ICHUSHI) Web database with no date restrictions. We selected randomized controlled trials in which the clinical outcomes of adult patients with traumatic brain injury were compared between hypertonic saline and mannitol strategies. Two investigators independently screened the search results and conducted the data extraction. The primary outcome was all-cause mortality. The secondary outcomes were 90-day and 180-day mortality, good neurological outcomes, reduction in intracranial pressure, and serum sodium level. Random effects estimators with weights calculated by the inverse variance method were used to determine the pooled risk ratios. A total of 125 patients from four randomized trials were included, and all the studies were conducted in the intensive care unit. Among 105 patients from three trials that evaluated the primary outcome, 50 patients were assigned to the hypertonic saline group and 55 patients were assigned to the mannitol group. During the observation period, death was observed for 16 patients in the hypertonic saline group (32.0%) and 21 patients in the mannitol group (38.2%). The risks were not significant between the two infusion strategies (pooled risk ratio, 0.82; 95% confidence interval, 0.49-1.37). There were also no significant differences between the two groups in the other secondary outcomes. However, the certainty of the evidence was rated very low for all outcomes. Our findings revealed no significant difference in the all-cause mortality rates between patients receiving hypertonic saline or mannitol to control intracranial pressure. Further investigation is warranted because we only included a limited number of studies.


Artificial Intelligence Detection of Diabetic Retinopathy: Subgroup Comparison of the EyeArt System with Ophthalmologists' Dilated Examinations.
To compare general ophthalmologists, retina specialists, and the EyeArt Artificial Intelligence (AI) system to the clinical reference standard for detecting more than mild diabetic retinopathy (mtmDR). Prospective, pivotal, multicenter trial conducted from April 2017 to May 2018. Participants were aged ≥ 18 years who had diabetes mellitus and underwent dilated ophthalmoscopy. A total of 521 of 893 participants met these criteria and completed the study protocol. Participants underwent 2-field fundus photography (macula centered, disc centered) for the EyeArt system, dilated ophthalmoscopy, and 4-widefield stereoscopic dilated fundus photography for reference standard grading. For mtmDR detection, sensitivity and specificity of EyeArt gradings of 2-field, fundus photographs and ophthalmoscopy grading versus a rigorous clinical reference standard comprising Reading Center grading of 4-widefield stereoscopic dilated fundus photographs using the ETDRS severity scale. The AI system provided automatic eye-level results regarding mtmDR. Overall, 521 participants (999 eyes) at 10 centers underwent dilated ophthalmoscopy: 406 by nonretina and 115 by retina specialists. Reading Center graded 207 positive and 792 eyes negative for mtmDR. Of these 999 eyes, 26 eyes were ungradable by the EyeArt system, leaving 973 eyes with both EyeArt and Reading Center gradings. Retina specialists correctly identified 22 of 37 eyes as positive (sensitivity 59.5%) and 182 of 184 eyes as negative (specificity 98.9%) for mtmDR versus the EyeArt AI system that identified 36 of 37 as positive (sensitivity 97%) and 162 of 184 eyes as negative (specificity of 88%) for mtmDR. General ophthalmologists correctly identified 35 of 170 eyes as positive (sensitivity 20.6%) and 607 of 608 eyes as negative (specificity 99.8%) for mtmDR compared with the EyeArt AI system that identified 164 of 170 as positive (sensitivity 96.5%) and 525 of 608 eyes as negative (specificity 86%) for mtmDR. The AI system had a higher sensitivity for detecting mtmDR than either general ophthalmologists or retina specialists compared with the clinical reference standard. It can potentially serve as a low-cost point-of-care diabetic retinopathy detection tool and help address the diabetic eye screening burden.


Swallowing outcomes over time after total pharyngolaryngectomy and free flap reconstruction.
One of the challenges after total pharyngolaryngectomy (TPL) is to restore the swallowing function. The aim of this study was to compare swallowing outcomes between patients who underwent reconstruction with jejunum free flap (JFF) and other free flaps (OFFs). This retrospective study included patients who underwent TPL and free flap reconstruction. The endpoints were the evolution of swallowing outcomes during the first five years after treatment assessed by the Functional Oral Intake Scale (FOIS), and outcomes associated with complications. One hundred and eleven patients were included, 84 patients in the JFF group and 27 in the OFF group. The patients in the OFF group experienced more chronic pharyngostoma (p = 0.001) and pharyngoesophageal stricture (p = 0.008). During the first year, a lower FOIS score tended to be associated with OFF (p = 0.137), and this result remained stable over time. This study suggests that JFF reconstruction provides better swallowing outcomes than OFF reconstruction, stable over time.


Different affinities of native alpha1B-adrenoceptors for ketanserin between intact tissue segments and membrane preparations.
The pharmacological profiles of alpha1-adrenoceptors for ketanserin, prazosin, silodosin, and BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione dihydrochloride) were examined under different assay conditions. Among the tested antagonists and alpha1-adrenoceptors subtypes, ketanserin showed significantly lower affinity for the alpha1B-adrenoceptor subtype in intact tissue sampled from the rat tail artery, thoracic aorta, and cerebral cortex (functional pKB and binding pKi were approximately 6), than in cerebral cortex membrane preparations or whole cell and membrane preparations of alpha1B-adrenoceptor transfected human embryonic kidney 293T (HEK 293T) cells (pKi was approximately 8). In these tissues and cells, however, ketanserin showed a similar affinity (pKi = approximately 8) for alpha1A- and alpha1D-adrenoceptors even though the assays were conducted under different conditions. In contrast, the affinities of alpha1A-, alpha1B-, and alpha1D-adrenoceptors for prazosin, silodosin, and BMY 7378 did not significantly change under different assay conditions and in different tissues. The present study reveals that the pharmacological profiles of native alpha 1B-adrenoceptors for ketanserin is strongly influenced by the assay conditions and suggest that antagonist affinity is not necessarily constant.


Objective and subjective outcomes in comparing three different aspheric intraocular lens implants with their spherical counterparts.
To look for objective and subjective differences between three types of aspheric intraocular lens implants and their spherical counterparts. Thirty patients were randomised to receive one of six lens implants including three aspheric lenses and their spherical counterparts. Pre and postoperative testing was carried out including visual acuity, contrast sensitivity and wavefront analysis. All patients were asked to fill in a visual function questionnaire (modification of cataract TyPE) to assess subjective differences in visual quality. There was no significant difference between groups for best-corrected visual acuity. Contrast sensitivity testing showed the Tecnis lens to perform better than the Cee-on Edge in all lighting conditions with significant differences at 3 and/or 6 cycles/degree in three out of four lighting conditions. No significant differences in contrast sensitivity were seen between the other lens pairs. All aspheric lenses showed less spherical aberration than their spherical pairs with statistical significance reached in two out of three pairs (the Ceeon Edge vs Tecnis, and Acrysof Natural vs IQ). The questionnaire revealed no evidence of improved subjective vision with the aspheric lenses compared to the spherical lenses. This pilot study concurs with previously published trials in showing decreased spherical aberration and improved contrast sensitivity with aspheric lenses compared to spherical lenses. There was no evidence that the patients implanted with aspheric lenses rate their quality of vision higher than those implanted with spherical lenses. Study numbers were small and larger numbers may be required to demonstrate statistical differences in subjective data.


Vesiculobullous systemic lupus erythematosus. A report of four cases.
A vesiculobullous eruption is now recognized as a specific but rare cutaneous complication of systemic lupus erythematosus. Four additional cases are reported in whom the five previously proposed criteria were met. Increased activity of systemic lupus erythematosus affecting other organ systems was documented in three of four cases. All four patients demonstrated a positive lupus band, and three of four showed granular deposits of IgA along the basement membrane zone (BMZ). Evidence of glomerulonephritis was obtained in three of four cases, which resulted in death in one. The higher than expected incidence of IgA deposits in skin and renal disease in patients with vesiculobullous eruption of systemic lupus erythematosus is again confirmed. The eruption cleared in all four cases with either dapsone, 50 mg daily, or high doses of corticosteroids and immunosuppressive agents.


Polyglycolic acid sheets decrease post-endoscopic submucosal dissection bleeding in early gastric cancer: A systematic review and meta-analysis.
Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer (EGC). However, post-ESD bleeding remains a serious issue, particularly in patients treated with an antithrombotic agent or those have had a large mucosal resection (≥4 cm). Whether covering the ulcer bed induced by ESD with polyglycolic acid (PGA) sheets can prevent post-ESD bleeding remains to be questioned. Therefore, we performed a systematic review and meta-analysis to evaluate the effectiveness of PGA sheets on preventing post-ESD bleeding in patients with early gastric cancer (EGC) at a high risk of post-ESD bleeding. PubMed, Cochrane Library and EMBASE databases were searched for studies on the effect of PGA sheets shielding on inpatients with EGC and at a high risk of bleeding using post-ESD bleeding rate as the primary outcome. Among the four included studies (212 lesions in the PGA sheet group and 208 in the control group), post-ESD bleeding rate was significantly lower in the PGA sheet group than in the control group (4.9% vs 13.7%, risk ratio [RR] 0.33, 95% confidence interval [CI] 0.18-0.72, P = 0.004). A subgroup analysis showed that the application of PGA sheets effectively reduced the post-ESD bleeding rate in patients receiving antithrombotic agents (5.5% vs 15.2%; RR 0.37, 95% CI 0.17-0.79, P = 0.01). Although the application of PGA sheets tended to decrease the post-ESD bleeding rate in patients who had undergone large mucosal resections, the difference was not significant (4.5% vs 9.6%; RR 0.52, 95% CI 0.15-1.78, P = 0.29). PGA sheets can effectively prevent post-ESD bleeding in patients receiving antithrombotic agents. Further studies are needed to confirm whether PGA sheets can decrease post-ESD bleeding in patients underwent large mucosal resection.


Effects of d- and l-amphetamine on food intake: evidence for a dopaminergic substrate.
The present experiment examined the effects of d- and l-amphetamine on the intake of sugar, sweetened rat chow and unsweetened rat chow in free feeding rats. Rats were injected IP with 4 doses of d- or l-amphetamine (0.0, 0.125, 0.50 and 2.00 mg/kg). Regardless of drug condition, animals were found to prefer sugar over sweetened or unsweetened chow. d-Amphetamine significantly increased food intake at 0.125 and 0.50 mg/kg doses but not at 2.00 mg/kg. l-Amphetamine had no significant effects at any dose. Further, d-amphetamine significantly increased sugar intake but not sweetened or unsweetened chow. Since d- and l-amphetamine are equipotent at releasing noradrenaline, while d-amphetamine is 2 to 5 times more potent at releasing dopamine, the results suggest that d-amphetamine-induced feeding is associated with activation of a dopaminergic substrate.


Quantifying song bout production during zebra finch sensory-motor learning suggests a sensitive period for vocal practice.
Using an event-triggered recording system, the quantity of daily song bout production was measured weekly in male zebra finches (Taeniopygia guttata) during sensory-motor learning and at one year of age. Our aim was to ask whether the development of a stereotyped vocal pattern involves a practice-driven component. If so, we hypothesized that juvenile males learning song should sing more often than adults reciting a vocal pattern they had already learned, and that greater levels of juvenile singing should be associated with improvement in the quality of the adult song. Across the period measured (36-365 days of age), subjects showed an inverted U-shaped pattern of daily song bout production. Song bout production was lowest during subsong, with increased production associated with plastic song and song crystallization, although individual differences were large. Daily song bout production decreased in adulthood. Higher levels of song bout production during plastic song correlated with fewer sequencing errors in adult song patterns (r(2)=0.77). In contrast, quantity of singing during song crystallization showed no relationship to vocal stereotypy (r(2)=0.002). Our data suggest a sensitive period for vocal practice during zebra finch sensory-motor learning with consequences for the note-sequence fidelity of the adult vocal pattern.


[Present and future of echography in spondyloarthritis].
Today ultrasound in spondyloarthritis is being developed in three main areas. Joint ultrasound is similar to that described in rheumatoid arthritis and other synovitis, with extensive literature on the matter. Enthesis ultrasound has a growing number of publications that describe the main elementary lesions. Several ultrasound enthesis scores have been developed that provide an overall view of the patient status and this information is useful both in the field of diagnosis and in assessing disease activity. The sacroiliac joints have also received attention and the published sensitivity and specificity could be useful in clinical practice. The future is unknown, but ultrasound has many possibilities that include improving the reliability, the incorporation of enthesis ultrasound assessment to the diagnostic classification criteria as well as the likelyhood developing simplified scores.


Real-time MR imaging of myocardial regional function using strain-encoding (SENC) with tissue through-plane motion tracking.
To implement real-time myocardial strain-encoding (SENC) imaging in combination with tracking the tissue displacement in the through-plane direction. SENC imaging was combined with the slice-following technique by implementing three-dimensional (3D) selective excitation. Certain adjustments were implemented to reduce scan time to one heartbeat. A total of 10 volunteers and five pigs were scanned on a 3T MRI scanner. Spatial modulation of magnetization (SPAMM)-tagged images were acquired on planes orthogonal to the SENC planes for comparison. Myocardial infarction (MI) was induced in two pigs and the resulting SENC images were compared to standard delayed-enhancement (DE) images. The strain values computed from SENC imaging with slice-following showed significant difference from those acquired without slice-following, especially during systole (P < 0.01). The strain curves computed from the SENC images with and without slice-following were similar to those computed from the orthogonal SPAMM images, with and without, respectively, tracking the tag line displacement in the strain direction. The resulting SENC images showed good agreement with the DE images in identifying MI in infarcted pigs. Correction of through-plane motion in real-time cardiac functional imaging is feasible using slice-following. The strain measurements are more accurate than conventional SENC measurements in humans and animals, as validated with conventional MRI tagging.


Fluid dynamics characterization and thrombogenicity assessment of a levitating centrifugal pump with different impeller designs.
Technical guidelines nowadays recommend and regulate the use Computational Fluid Dynamics (CFD) to assess the performance of medical devices. CFD coupled to blood damage models has emerged as a powerful tool to evaluate the hemocompatibility of blood recirculating devices. The present study is aimed at evaluating the hydrodynamic performance and the thrombogenic potential of two prototypes of magnetically levitating centrifugal pumps. The two devices differ in the impeller configuration - 6-blades vs. 12-blades - and have been designed to be used in Cardiopulmonary Bypass (CPB) circuits during open heart surgery and in Extracorporeal Membrane Oxygenation (ECMO) to support patients with severe cardiac or respiratory failure. The pumps have been modelled using Direct Numerical Simulation coupled to Lagrangian analysis to predict platelet activation due to abnormal shear stress histories. Numerical results have been compared with experimental data in terms of head generation for different working points. Results show that the 6-blades pump has i) smaller stagnation areas, ii) lower stress levels and iii) higher strain rate, resulting in a lower thrombogenic potential, whereas the 12-blade impeller guarantees a more stable performance at high flow rates, suggesting its preferential use for more demanding applications, such as CPB.


Generating diagnostic report for medical image by high-middle-level visual information incorporation on double deep learning models.
Writing diagnostic reports for medical images is a heavy and tedious work. The automatic generation of medical image diagnostic reports can assist doctors to reduce their workload and improve diagnosis efficiency. It is of great significance to introduce image caption algorithm into medical image processing. Existing approaches attempt to generate medical image diagnostic reports using image caption algorithms but without taking the accuracy of pathological information in generated diagnostic reports into account. To solve the mentioned problem, we propose a Semantic Fusion Network (SFNet) including a lesion area detection model and a diagnostic generation model. The lesion area detection model can extract visual and pathological information from medical image, and the diagnostic report generation model can learn to fuse the two kinds of information to generate reports. Thus, the pathological information in the generated diagnostic reports can be more accurate. Experimental results have verified the performance of our model (Accuracy increases 1.2% on the Ultrasound Image Dataset and 2.4% on the Open-i X-ray Image Dataset), compared with the model only using visual feature to generate diagnostic reports. This work utilizes computer algorithms to generate the more accurate diagnostic reports for medical images automatically, which expands the application of computer-aided diagnosis and promotes the implementation of deep learning in the medical image analysis field.


Identification of metal-binding to proteins in seed samples using RF-HPLC-UV, GFAAS and MALDI-TOF-MS.
An extraction procedure using Tris-HCl buffer solution was employed in order to extract water-soluble proteins from seed samples of oat, wheat and soybean. Initially, the total protein concentration was determined by the Bradford method in each solution, after the extraction procedure. The soybean sample showed a higher concentration of total protein compared to the others. The protein extracts obtained were separated by reverse-phase chromatography (RP-HPLC-UV). The protein fractions were collected and analyzed by graphite furnace atomic absorption spectrometry (GFAAS) and matrix-assisted laser desorption/ionization (MALDI-TOF-MS) for determination of Cu, Fe, Mn and Zn and identification of proteins, respectively. The combination of techniques such as RP-HPLC-UV, GFAAS and MALDI-TOF-MS allowed the identification of several proteins bound to metals present in the seed samples.


Fate of toxic metals during estuarine mixing of fresh water with saline water.
Metals are among the most common environmental pollutants, and their presence in high concentration in waters and biota have devastating effects on flora, fauna, and human health. Flocculation process of metals during estuarine mixing can reduce the environmental hazards of metals and also can provide micronutrients to the aquatic system. The present investigation provides a thorough study of eliminating colloidal elements of copper, manganese, nickel, lead, and zinc during estuarine mixing of Shalmanrood River water with Caspian Sea water in Iran. The processes of flocculation were carried out in six different salinity regimes (0.45-2.4 ppt). The obtained result is indicative of non-conservative behavior of the studied metals. Higher flocculation resulted in a lower salinity regime. The obtained results indicated that most of the metals were eliminated during the initial mixing of fresh water with sea water at 0.45-0.9 ppt salinity interval. The trend of flocculation rates of elements is as follows: Zn (59.3%) > Pb (47.6%) > Mn (37.5%) > Cu (29.2%) > Ni (27%).The annual average load of copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) from Shalmanrood River to Caspian Sea decreases as a result of flocculation process from 9.9, 7.7, 8.9, 5.1, and 23.2 tons per year to 7, 4.8, 6.5, 2.7, and 9.4 tons per year, respectively. According to the cluster analysis, parameters such as temperature, pH, and Eh do not have any impact on flocculation of elements expect for Pb. The only parameter that influences the flocculation of Mn is the salinity. Metal speciation studies that are carried out by Eh-pH software show that the studied metals are present as oxides (Zn, Cu, and Ni) and hydroxides (Mn and Pb).


Chromogenic detection of Sarin by discolouring decomplexation of a metal coordination complex.
An innovative chromogenic sensing concept based on decomplexation of a tris-(bipyridine)iron(II) coordination complex has been developed for the detection of organophosphorus nerve agents. It was evaluated both on a simulant and real Sarin in vapour and liquid phases.


Epithelial to mesenchymal transformation in tubular epithelial cells undergoing anoxia.
Epithelial-mesenchymal transformation (EMT) has been proved to be a critical event in fibrogenesis of renal allografts. This study sought to determine whether anoxia could induce EMT from tubular epithelial cells (TEC). Rat TEC-line (NRK-52E) was cultured in Dulbelco's modified Eagle's medium (DMEM) without glucose under 100% N2 for 4 hours. After 6, 12, 24, 48, and 72 hours, the expressions of connective tissue growth factor (CTGF) mRNA and protein were measured by real-time RT-PCR and Western blot, respectively. Morphologic changes and cytoskeleton remodeling were observed in NRK-52E cells under laser confocal microscopy. Immunohistochemistry and flow cytometry were used to detect expression changes of E-cadherin, alpha-smooth muscle actin (SMA), types I and IV collagen, all of which are involved in TEC, EMT. After stimulation by anoxia, NRK-52E cells became round and enlarged with a remodeled cytoskeleton. The expressions of CTGF mRNA and protein were upregulated after 6 hours, reaching their peak at 48 hours. The expressions of types I and IV collagen, and alpha-SMA were all upregulated except for E-cadherin. Anoxia upregulated the expression of CTGF and other EMT-associated genes in NRK-52E cells.


S-adenosyl-L-methionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism.
The final urinary excretion product of selenium detoxification is trimethylselenonium ion. An assay has been developed for the enzyme, S-adenosylmethionine:thioether S-methyltransferase, responsible for this final methylation reaction. This assay employed high pressure liquid chromatography separation and quantitation of the trimethylselenonium ion produced by thioether methyltransferase acting on S-adenosylmethionine and dimethyl selenide. The enzyme was shown to reside primarily in the cytosol of mouse lung (30 pmol/mg protein/min) and liver (7 pmol/mg protein/min). Purification from mouse lung to a preparation that exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was achieved by DEAE, gel filtration, and chromatofocusing chromatographies. Thioether methyltransferase is monomeric with a molecular weight of 28,000 and has a pI of 5.3. The pH optimum was 6.3, and Km values for dimethyl selenide and S-adenosylmethionine were 0.4 and 1.0 microM, respectively. The enzyme was inhibited 50% by 25 microM sinefungin, an analog of S-adenosylmethionine, or 40 microM S-adenosylhomocysteine, the reaction product. Pure thioether methyltransferase methylated selenium in dimethyl selenide, tellurium in dimethyl telluride, and S in dimethyl sulfide and many other thioethers. These data suggest a general role for this novel enzyme in the synthesis of onium compounds with increased aqueous solubility helpful in their excretion.


Winging it--actin on the fly.
How actin dynamics might be regulated to generate specific cellular structures during development remains something of a mystery. New insights may be gained from the recent identification of a conserved cofilin phosphatase, Slingshot, which modulates actin dynamics to help control Drosophila wing hair morphogenesis.


Escherichia coli bactofection using Lipofectamine.
Successful gene delivery into mammalian cells using bactofection requires entry of the bacterial vector via cell surface integrin receptors followed by release of plasmid DNA into the cellular environment. We show, for the first time, that addition of the DNA transfection reagent Lipofectamine improves entry of invasive Escherichia coli into HeLa cells and enhances up to 2.8-fold green fluorescent protein (GFP) expression from a reporter plasmid. The addition of Lipofectamine may be applicable to other bacterial vectors to increase their DNA delivery efficiency into mammalian cells.


Pharmacokinetics and antihypertensive effects of low dose clonidine during chronic therapy.
Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml were achieved after 3.6 +/- 1.2 hours. After 5 days of repetitive dosing the maximal concentration was significantly higher, 0.66 +/- 0.06 ng/ml and remained so throughout chronic therapy (P = 0.018). The AUC, Tmax and T1/2 did not differ significantly between the acute dose and the chronic dosing pharmacokinetic studies. Clonidine also produced a significant fall in blood pressure. Supine diastolic blood pressure fell from 106 +/- 5 mmHg predose to 99 +/- 6 mmHg 2 hours after the first dose (P less than 0.05). The corresponding values after cyclopenthiazide alone were 108 +/- 8 and 105 +/- 8 mmHg (P = 0.13). Similar falls in blood pressure were produced during chronic therapy.


Blockade of hoarding in rats by diazepam: an analysis of the anxiety and object value hypotheses of hoarding.
The "security hypothesis" suggests food hoarding by rats serves to preempt attack and therefore might be motivated by "anxiety". The "object value" hypothesis suggests rats hoard objects that they perceive as valuable as related to some state or need. These hypotheses were evaluated with the anxiolytic drug diazepam, which is purported to both decrease anxiety and increase motivation to eat, and which accordingly either may decrease or increase hoarding. Using a new hoarding paradigm, diazepam (Valium: 0.25-5 mg/kg), was found to produce a dose-related reduction in hoarding that was dependent upon food pellet size and that was reversed by flumazenil (Ro 15-1788), a benzodiazepine receptor antagonist. Diazepam also slowed eating speed, blocked "dodging", a movement used to initiate hoarding, and impaired spatial navigation in a learning-set swimming pool task. The results fail to support the object value hypothesis of hoarding. Since perception of food size, motivation, motor ability and spatial abilities all probably contribute to successful food hoarding, the results provide several explanations other than, or in addition to, anxiety reduction for the drug's effects on hoarding. Nevertheless, the study provides a number of new sensitive measures of the effects of anxiolytic drugs and new insights into their behavioral effects.


MR contrast enhancement of intracranial lesions with Gd-DTPA.
Gd-DTPA is a paramagnetic contrast agent for MR that produces enhancement of lesions on T1-weighted images. Since it does not cross the intact blood-brain barrier (BBB), Gd-DTPA enhances only those pathologic processes that are associated with breakdown of the BBB and structures or lesions that are devoid of a BBB. Gd-DTPA improves conspicuity, helps characterize and delineate the extent of lesions, and increases the sensitivity for detection of cerebral abnormalities.