Purification Effect of PES-C Ultrafiltration Membrane Incorporated with Emodin on Acanthopanax Senticosus Injection.
A new PES-C/emodin ultrafiltration membrane was prepared by blending natural emodin with phenolphthalein polyethersulfone (PES-C) and was used to purify an acanthopanax senticosus injection in this study. Regarding the purified acanthopanax senticosus injection, its color became lighter, and its clarity increased. On the contrary, for an acanthopanax senticosus injection containing macromolecules, its color deepened, and its turbidity increased. Thermal stability of the purified acanthopanax senticosus injection was the best, followed by the original solution of the acanthopanax senticosus injection, and the acanthopanax senticosus injection containing macromolecules was the worst. The fingerprint spectrum of the purified acanthopanax senticosus injection was similar to the original solution of the acanthopanax senticosus injection, the relative peak area of each single peak was greater than 0.95, and the relative peak area of the total peak was greater than 0.96. Compared with the original solution of the acanthopanax senticosus injection, the histamine release amount and cell degranulation rate of the acanthopanax senticosus injection containing macromolecules increased, while those of the purified acanthopanax senticosus injection decreased, which reduced the risk of allergic reaction to a certain extent. "Inverse proof" confirmed that the acanthopanax senticosus injection containing macromolecules had certain liver and kidney toxicity, which indirectly proved that the liver and kidney toxicity of the purified acanthopanax senticosus injection was effectively reduced.


Associations of empirical dietary inflammatory index with heart failure in adults from the United States.
Recent evidence has shown associations between cardiovascular disease and a proinflammatory diet. We hypothesized that a proinflammatory diet, assessed using the Empirical Dietary Inflammatory Index (EDII), is associated with increased risk of prevalent heart failure (HF). This analysis included 13,687 participants (44.8 ± 19.4 years; 45.7% male, 67.8% whites) from the Third National Health and Nutrition Examination Survey. EDII score was calculated from the Food Frequency Questionnaire. Prevalent HF was determined by physician-diagnosed self-report. Multivariable logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between EDII score and prevalent HF across tertiles (reference group first tertile) and per 1-unit standard deviation (1-SD) increase. About 1.4% (n = 190) of the participants reported a history of HF. Each 1-SD increase in EDII score (0.276) conferred 25% increased odds of prevalent HF (OR (95% CI): 1.25 (1.07-1.46); p value = 0.006). Odds of HF increased as EDII tertile increased, indicating a dose-response relationship (OR (95% CI) for 2nd and 3rd tertiles compared to 1st tertile: 1.42 (0.99-2.04), 1.68 (1.15-2.46), respectively). These results were consistent in subgroups of the participants stratified by demographics and comorbidities. Proinflammatory dietary patterns are associated with an increased risk of HF. The risk of HF could potentially be reduced by avoiding proinflammatory dietary patterns.


Different ways of modeling spatial-frequency uncertainty in visual signal detection.
Inferior human signal-detection behavior compared with that of ideal observers has been explained by intrinsic uncertainty of the human observer with respect to certain signal parameters. One way to model this uncertainty is to assume that the observer simultaneously monitors multiple channels, corresponding to possible parameters. However, it is also conceivable to assume that an observer, uncertain about which channel to monitor, chooses a suboptimally tuned single filter. Finally, uncertainty may also cause the filter underlying a single channel to broaden. In this paper these different models are investigated with respect to spatial-frequency uncertainty for matched filters detecting Gabor signals. All three mechanisms predict a decrease in detection performance. However, it is shown that the resulting psychometric functions are different. While the slopes increase with uncertainty for the multiple-channel models, they decrease for a randomly chosen single channel. Broadening a single filter leads to parallel psychometric functions.


Importance of ozone precursors information in modelling urban surface ozone variability using machine learning algorithm.
Surface ozone (O[Formula: see text]) is primarily formed through complex photo-chemical reactions in the atmosphere, which are non-linearly dependent on precursors. Even though, there have been many recent studies exploring the potential of machine learning (ML) in modeling surface ozone, the inclusion of limited available ozone precursors information has received little attention. The ML algorithm with in-situ NO information and meteorology explains 87% (R[Formula: see text] = 0.87) of the ozone variability over Munich, a German metropolitan area, which is 15% higher than a ML algorithm that considers only meteorology. The ML algorithm trained for the urban measurement station in Munich can also explain the ozone variability of the other three stations in the same city, with R[Formula: see text] = 0.88, 0.91, 0.63. While the same model robustly explains the ozone variability of two other German cities' (Berlin and Hamburg) measurement stations, with R[Formula: see text] ranges from 0.72 to 0.84, giving confidence to use the ML algorithm trained for one location to other locations with sparse ozone measurements. The inclusion of satellite O[Formula: see text] precursors information has little effect on the ML model's performance.


Evaluation of GPs diagnostic knowledge and treatment practice in detection and treatment of early schizophrenia: a French postal survey in Brittany.
Evaluating French general practitioners (GPs) diagnostic knowledge and practice in the detection and treatment of early schizophrenia as well as needs and preferences with specialist services. A postal survey comprising 27 questions was conducted among 2,039 GPs from three counties of Western France. Composite scores were calculated to determine a level of diagnostic knowledge. A total of 515 GPs (25.3%) responded to the survey. The mean score to determine a level of knowledge on the most important aspects in detecting early stages of schizophrenia was 5.3 ± 2.50 [median = 6 (range 0-10)]. The mean score to determine the overall knowledge of schizophrenia was 8.1 ± 2.98 [median = 8 (range 1-16)]. The majority of surveyed GPs (76.1%) would treat early schizophrenia pharmacologically. A majority of GPs (53.9%) advise an insufficient duration of anti-psychotic treatment for first episode psychosis. The vast majority (90.8%) were in favour of a specialized outpatient service. French GPs tend to have a deficit in diagnostic knowledge and practice in detection and treatment of early schizophrenia. It seems important to provide GPs with continuing medical education (CME) on detection and management of early schizophrenia and to set up relevant specialized outpatient services.


Egg load is a cue for offspring sex ratio adjustment in a fig-pollinating wasp with male-eggs-first sex allocation.
Fig-pollinating wasps (Agaonidae) only reproduce within fig tree inflorescences (figs). Agaonid offspring sex ratios are usually female-biased and often concur with local mate competition theory (LMC). LMC predicts less female-bias when several foundresses reproduce in a fig due to reduced relatedness among intra-sexually competing male offspring. Clutch size, the offspring produced by each foundress, is a strong predictor of agaonid sex ratios and correlates negatively with foundress number. However, clutch size variation can result from several processes including egg load (eggs within a foundress), competition among foundresses and oviposition site limitation, each of which can be used as a sex allocation cue. We introduced into individual Ficus racemosa figs single Ceratosolen fusciceps foundresses and allowed each to oviposit from zero to five hours thus variably reducing their eggs-loads and then introduced each wasp individually into a second fig. Offspring sex ratio (proportion males) in second figs correlated negatively with clutch size, with males produced even in very small clutches. Ceratosolen fusciceps lay mainly male eggs first and then female eggs. Our results demonstrate that foundresses do not generally lay or attempt to lay a 'fixed' number of males, but do 'reset to zero' their sex allocation strategy on entering a second fig. With decreasing clutch size, gall failure increased, probably due to reduced pollen. We conclude that C. fusciceps foundresses can use their own egg loads as a cue to facultatively adjust their offspring sex ratios and that foundresses may also produce more 'insurance' males when they can predict increasing rates of offspring mortality.


Retrograde fixation of distal femoral fractures: results using a new nail system.
To investigate the management and outcome of distal femur fractures treated with retrograde nailing. Prospective. Unfallkrankenhaus Berlin, level I trauma center. A consecutive series of 47 patients with 48 fractures of the distal femur (37 fractures AO type A and 11 fractures type C) operated on between May 1999 and June 2000. Outcome was assessed by using standard radiographic criteria of time to union, incidence of infection, malunion, and knee function (Leung score). After an average time of 33 months (range 12-37 months), 44 patients were reexamined. Three patients were lost to follow-up. The average age was 44 years (range 17-92 years). Of patients, 19 sustained polytrauma, and 10 had associated soft tissue damage. A total of 34 patients underwent primary definitive osteosynthesis within 12 hours after trauma. All fractures healed after an average of 12.6 weeks (range 9-17 weeks). Seven complications were noted-three related to severity of injury (one deep venous thrombosis, two leg length shortenings of 1.5 cm and 2.5 cm) and four related to the operation (insufficient counterboring of the nail in two patients, one malreduction, one iatrogenic fracture of femur shaft). There was no relevant difference between type A and type C fractures in functional, clinical, or radiographic outcomes. Retrograde nailing is recommended as an alternative method to plate osteosynthesis in stabilizing distal femoral fractures, particularly in type C fractures.


Tuberculosis of the sacroiliac joint: clinical features, outcome, and evaluation of closed needle biopsy in 11 consecutive cases.
Sacroiliac joint (SIJ) involvement has been reported in up to 9.7 percent of patients with skeletal tuberculosis. Lack of awareness of this now uncommon form of infection often leads to diagnostic delay and increased morbidity. Eleven consecutive cases of SIJ tuberculosis are reported; clinical and radiologic features, diagnosis, treatment, and outcome are discussed. Buttock pain was the presenting complaint in all patients. However, radicular pain in the lower back (seven patients) or lower limb (10 patients) was common and in one patient precipitated an unnecessary surgical intervention. SIJ tuberculosis is frequently an isolated phenomenon. Therefore, direct sampling of the SIJ is necessary to establish the diagnosis. The recently described technique of closed needle biopsy of the SIJ was employed in all 11 patients and established the diagnosis in nine of the 11.


Short-term outcomes and mortality after interhospital intensive care transportation: an observational prospective cohort study of 368 consecutive transports with a mobile intensive care unit.
To evaluate short-term outcomes and mortality after interhospital transportation of intensive care patients performed by a mobile intensive care unit (MICU). This study was performed in the tertiary care process of interhospital transportation using the local MICU system in the South East of the Netherlands. Between March 2009 and December 2011, all transports of adult patients being performed by the local MICU centre have been documented; data on 42 variables, including a 24 h follow-up Sequential Organ Failure Assessment (SOFA) score of 368 consecutive interhospital transports of intensive care patients, were recorded. In 24 cases, the follow-up SOFA score was missing, so 344 data sets were included. No interventions have been done. Primary outcome measures were the mean SOFA score before and 24 h after transport, and the 24 h post-transport mortality. Moreover, the differences between the groups of 24 h post-transport survivors and non-survivors have been analysed. The mean SOFA score before transport was 8.8 for the whole population and 8.6 for those patients who were alive 24 h after transport, with a mean SOFA score of 8.4 after transport. The adverse events rate was 6.4%. Fourteen patients (4.1%) died within 24 h after transport. Patients in this group had a higher SOFA score, lower pH, higher age and more additional medical support devices than those patients in the survivor group. The non-significant decrease in the post-transport SOFA score and the lack of an association between transport and 24 h post-transport mortality indicates that in the study setting, interhospital transportation of intensive care patients performed by a MICU system was not associated with a clinically relevant deterioration of the patient.


Rapid and sensitive method for determination of haloperidol in human samples using nitrogen-phosphorus selective detection.
A sensitive gas-chromatographic method for quantitative analysis of haloperidol in human plasma is described. The use of nitrogen-phosphorus selective detection reduces the time required for analysis. Azaperone is used as the internal reference standard. The method is suitable for the determination of haloperidol plasma levels in patients treated with doses ranging from 1.2 to 200 mg/day. No interference from drugs needed in the associated antipsychotic therapy has been found. The simplicity, specificity and sensitivity of the method make it suitable for routine analysis of haloperidol plasma levels in psychotic patients undergoing chronic treatment.


Laparoscopic Major Hepatectomy-Technique and Outcomes.
With technological innovations especially newer parenchymal transection devices, improved understanding of hepatic anatomy facilitated by better imaging, and reconstructions along with experiences gained from advanced minimal invasive procedures, laparoscopic liver surgery is gaining momentum with more than 5300 reported cases worldwide. Most of the published literature comprises nonanatomical and segmental resections with only few case series having major hepatic resections performed by minimally invasive approach. Aim of this article is to share our technique and experience of total laparoscopic major hepatectomy. It is a retrospective analysis of prospectively maintained database of 56 patients, who underwent laparoscopic major hepatectomy for various indications during 2001 to 2013. Of 56 patients operated, 37 had malignant disease and 19 had benign lesions with mean size of 6.0 ± 2.8 cm. Thirty-four patients underwent right hepatectomy and 22 left with mean age of 54.8 ± 15.3 years. Mean operating time was 227.4 ± 51.8 min with mean blood loss 265.5 ± 143.4 ml and transfusion needed in 10.7 %. Pringle's maneuver was used in 19.6 % with mean occlusion time of 34.0 ± 11.4 min. Liver-specific complications were observed in 12.5 % and overall complications in 19.6 %. Mean resection margin length in malignant lesions was 2.1 ± 0.9 cm, with <1 cm margin noted in 5.4 %. Median hospital stay was 8 days (6-29) with readmission rate of 8.9 %, re-intervention rate of 5.3 % and 90 days mortality of 1.7 %. Laparoscopic major liver resection is a formidable task. It requires considerable expertise in both, advanced laparoscopy, and liver surgery. It can be feasible, safe, and oncologically adequate in well-selected cases in experience hands.


XIAP regulates caspase activity in degenerating axons.
Our knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase-6, and caspase-9 are present in axons and are cleaved upon nerve growth factor (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn axons and that CASP3(-/-) axons are protected from degeneration. XIAP(-/-) DRG sensory neurons degenerate more rapidly and contain more active caspase-3 than their wild-type counterparts, indicating that axonal caspases are normally regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3 activation and axonal degeneration are suppressed. Finally, we show that XIAP(-/-) embryos have stunted dermal innervation. We propose that XIAP-mediated caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development.


The role of TGF-β-activated kinase 1 in db/db mice and high glucose-induced macrophage.
Accumulating evidence reveals that inflammation plays a vital part in the development of diabetic nephropathy (DN), little information is available about the TGF-β-activated kinase 1 (TAK1) signal pathway activating inflammatory response in DN. We used bone marrow-derived macrophages (BMMs) and db/db mice to investigate the potential protective effects and mechanisms of TAK1 inhibitor (5Z-7-oxozeaenol) on diabetic kidney disease. The study showed that pretreatment with 5Z-7-oxozeaenol not only remarkably decreased high glucose (HG) stimulated excessive release of MCP-1 and TNF-α, but also significantly down-regulated ERK1/2, p38MAPK phosphorylation, and NF-κB activation in macrophages. In consistent, 5Z-7-oxozeaenol markedly reduced diabetes-induced albuminuria, histological changes, macrophage infiltration, and renal inflammatory cytokines expression and exerted its function through down-regulating ERK1/2, p38MAPK, NF-κB activation in the kidneys of db/db mice. Our findings may provide a novel direction to study the molecular mechanism and a perspective intervention to halt the progression of DN.


Augmenting Prediction of Intracranial Aneurysms' Risk Status Using Velocity-Informatics: Initial Experience.
Our primary goal here is to demonstrate that innovative analytics of aneurismal velocities, named velocity-informatics, enhances intracranial aneurysm (IA) rupture status prediction. 3D computer models were generated using imaging data from 112 subjects harboring anterior IAs (4-25 mm; 44 ruptured and 68 unruptured). Computational fluid dynamics simulations and geometrical analyses were performed. Then, computed 3D velocity vector fields within the IA dome were processed for velocity-informatics. Four machine learning methods (support vector machine, random forest, generalized linear model, and GLM with Lasso or elastic net regularization) were employed to assess the merits of the proposed velocity-informatics. All 4 ML methods consistently showed that, with velocity-informatics metrics, the area under the curve and prediction accuracy both improved by approximately 0.03. Overall, with velocity-informatics, the support vector machine's prediction was most promising: an AUC of 0.86 and total accuracy of 77%, with 60% and 88% of ruptured and unruptured IAs being correctly identified, respectively.


The Hsp40 Mas5 Connects Protein Quality Control and the General Stress Response through the Thermo-sensitive Pyp1.
Upon heat shock, the fission yeast Hsp40 chaperone Mas5 drives temperature-sensitive proteins toward protein aggregate centers (PACs) to avoid their degradation until lower temperatures favor their refolding. We show here that cells lacking Mas5 are resistant to oxidative stress. Components of the general stress pathways, the MAP kinase Sty1 and the transcription factor Atf1, are suppressors of this phenotype. Strain Δmas5 expresses higher levels of Sty1- and Atf1-dependent stress genes than wild-type cells. Pyp1, the main tyrosine phosphatase maintaining Sty1 inactive in the absence of stress, is a temperature-sensitive protein that aggregates upon temperature up-shifts in a Mas5-dependent manner. In strain Δmas5, Pyp1 is sent to proteasomal degradation even in the absence of stress. We propose that Pyp1 is a thermo-sensitive phosphatase, which during heat stress coalescences into PACs in a Mas5-dependent manner, to promote full activation of the anti-stress Sty1-Atf1 cascade.


Myasthenia gravis in South Africans: racial differences in clinical manifestations.
We present data on the phenotypic variation in myasthenia gravis of 205 subjects from a multi-racial South African cohort. Consecutive subjects seen more than twice from 1996 to 2006, were included. Documented observational data included a myasthenia gravis and extra-ocular eye muscle score. Results showed Black subjects were more likely than Whites to develop treatment-resistant complete ophthalmoplegia and ptosis (18% vs. 2%; p=0.041). Of the 14 patients with this phenotype, 13 had generalised disease and positive AChR antibodies. Despite similar sized cohorts, White subjects were more likely than Blacks to develop generalised myasthenia poorly responsive to therapy (p=0.005). There were no significant racial differences in the time between diagnosis to initiation of therapy, or the performance and timing of thymectomy. The racial variation in some phenotypic features of myasthenia gravis and outcome to therapy, highlights the need to study biological factors in different subgroups to develop a more rational approach to immuno-suppressive therapy.


Localized approximation for gaussian beams in elliptical cylinder coordinates.
We establish a localized approximation to evaluate the beam-shape coefficients of a Gaussian beam in elliptical cylinder coordinates. As for the case of spherical coordinates and of circular cylinder coordinates, this approximation provides an efficient way to speed up computations within the framework of a generalized Lorenz-Mie theory for elliptical cylinders.


Differential diagnosis of depression and Alzheimer's disease with the Addenbrooke's Cognitive Examination-Revised (ACE-R).
One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer's disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer's Disease (AD). This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer's disease (AD), and 94 age, gender and education matched participants of control group. The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74). ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.


Siliceous pneumoconiosis in two dogs.
A siliceous pneumoconiosis was detected in two dogs by light microscopical, transmission electron microscopical and elemental analysis methods. Aluminium and silicon were the predominant elements and were present in macrophages associated with airways and vessels. The significance and origin of the deposits are discussed.


TOB-STOP-COP (TOBacco STOP in COPd trial): study protocol-a randomized open-label, superiority, multicenter, two-arm intervention study of the effect of "high-intensity" vs. "low-intensity" smoking cessation intervention in active smokers with chronic obstructive pulmonary disease.
Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.


Carbon black nanoparticles induce pulmonary fibrosis through NLRP3 inflammasome pathway modulated by miR-96 targeted FOXO3a.
Carbon black nanoparticle (CBNP) is a core constituent of air pollutants like fine particulate matter (PM2.5) as well as a common manufactural material. It was proved to pose adverse effects on lung function and even provoke pulmonary fibrosis. However, the underlying mechanisms of CBNPs-induced pulmonary fibrosis remain unclear. The present study aimed to investigate the mechanism of fibrotic effects caused by CBNPs in rat lung and human bronchial epithelial (16HBE) cells. Forty-nine male rats were randomly subjected to 7 groups, means the 14-day exposure group (30 mg/m3), the 28-day exposure groups (5 mg/m3 and 30 mg/m3), the 90-day exposure group (30 mg/m3) and their respective controls. Rats were nose-only-inhaled CBNPs. 16HBE cells were treated with 0, 50, 100 and 200 μg/mL CBNPs respectively for 24 h. Besides, Forkhead transcription factor class O (FOXO)3a and miR-96 overexpression or suppression 16HBE cells were established to reveal relative mechanisms. Our results suggested CBNPs induced pulmonary fibrosis in time- and dose-dependent manners. CBNPs induced persisting inflammation in rat lung as observed by histopathology and cytology analyses in whole lung lavage fluid (WLL). Both in vivo and in vitro, CBNPs exposure significantly increased the expression of NLRP3 inflammasome, accompanied by the increased reactive oxygen species (ROS), decreased miR-96 and increased FOXO3a expressions dose -and time-dependently. MiR-96 overexpression or FOXO3a suppression could partially rescue the fibrotic effects through inhibiting NLRP3 inflammasome. Conclusively, our research show that CBNPs-induced pulmonary fibrosis was at least partially depended on activation of NLRP3 inflammasome which modulated by miR-96 targeting FOXO3a.


THINKING THE DREAM: DREAM AND DREAM THINKING IN SIGMUND FREUD, HANNA SEGAL, AND WILFRED BION.
In the dream and its interpretation, psychoanalysis, in its founding period around 1900, identified the "royal road to a knowledge of the unconscious in the psychic life." But already in the development of Freud's work itself, the dream lost its central position: As early as in the 1920s, psychoanalysis ceased to be a theory and practice defined by dream interpretation-a caesura in a process which completed itself in 1950. Two further developments proved, up to the present day, particularly momentous for the conception of the dream: Melanie Klein's development of the concept of "unconscious phantasy" and the extension of psychoanalytic treatment to psychosis, originally declared inaccessible to psychoanalytic therapy by Freud. This article draws an itinerary of this path and the subsequent fundamental changes in the psychoanalytic reflection on the dream affecting the whole of psychoanalysis until today, by casting spotlights on essential stations: conceptions of the dream developed by Hanna Segal and Wilfred Bion, the latter's theory perpetuating Freud's dream theory as well as it conceptualizes dreams, dreaming, and thinking in a fundamentally new way.


Estrogen receptor alpha augments changes in hemostatic gene expression in HepG2 cells treated with estradiol and phytoestrogens.
Phytoestrogens are popular alternatives to estrogen therapy however their effects on hemostasis in post-menopausal women are unknown. The aim of this study was to determine the effect of the phytoestrogens, genistein, daidzein and equol on the expression of key genes from the hemostatic system in human hepatocyte cell models and to determine the role of estrogen receptors in mediating any response seen. HepG2 cells and Hep89 cells (expressing estrogen receptor alpha (ERα)) were incubated for 24 h with 50 nM 17β-estradiol, genistein, daidzein or equol. Tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), Factor VII, fibrinogen γ, protein C and protein S mRNA expression were determined using TaqMan PCR. Genistein and equol increased tPA and PAI-1 expression in Hep89 cells with fold changes greater than those observed for estradiol. In HepG2 cells (which do not express ERα), PAI-1 and tPA expression were unchanged. Increased expression of Factor VII was observed in phytoestrogen treated Hep89 cells but not in similarly treated HepG2s. Prothrombin gene expression was increased in equol and daidzein treated HepG2 cells in the absence of the classical estrogen receptors. These data suggest that phytoestrogens can regulate the expression of coagulation and fibrinolytic genes in a human hepatocyte cell line; an effect which is augmented by ERα.


Human locomotion analysis: determination of muscular forces and nervous orders.
This study gives a modelization of gait which connects the kinematic and mechanical parameters of the motion with the characteristic ones of the muscular contraction (F, l, i, y). The problem, formulated from the equations of the motion related to a standard human being, is solved in terms of a minimization problem, taking into account the anatomical, physiological and energetic constraints of this motion by means of numerical calculations on a computer I.B.M. 360. This first approach allows us to determine the periods of activity of the different muscles, the exerted forces and the associated nervous orders during a stance phase. The model can be applied to the study of the effect of fatigue on motion.


Bonding and debonding brackets to porcelain and gold.
Today's orthodontic practice includes a larger proportion of adults. Because many of these adults have crown and bridge restorations fabricated from porcelain or gold, the orthodontist must use methods that permit the attachment of orthodontic brackets to porcelain and nonprecious metal or gold. A bracket may be placed on single-unit crowns of porcelain or gold, but banding becomes difficult. Thus bonding the orthodontic bracket to the restoration provides a satisfactory alternative. This clinical report describes several techniques for bonding orthodontic brackets to porcelain or gold surfaces, and some suggestions for removal of bonded brackets.


Predictive value of the composition of the vaginal microbiota in bacterial vaginosis, a dynamic study to identify recurrence-related flora.
Bacterial vaginosis (BV) is a highly prevalent disease in women, and increases the risk of pelvic inflammatory disease. It has been given wide attention because of the high recurrence rate. Traditional diagnostic methods based on microscope providing limited information on the vaginal microbiota increase the difficulty in tracing the development of the disease in bacteria resistance condition. In this study, we used deep-sequencing technology to observe dynamic variation of the vaginal microbiota at three major time points during treatment, at D0 (before treatment), D7 (stop using the antibiotics) and D30 (the 30-day follow-up visit). Sixty-five patients with BV were enrolled (48 were cured and 17 were not cured), and their bacterial composition of the vaginal microbiota was compared. Interestingly, we identified 9 patients might be recurrence. We also introduced a new measurement point of D7, although its microbiota were significantly inhabited by antibiotic and hard to be observed by traditional method. The vaginal microbiota in deep-sequencing-view present a strong correlation to the final outcome. Thus, coupled with detailed individual bioinformatics analysis and deep-sequencing technology, we may illustrate a more accurate map of vaginal microbial to BV patients, which provide a new opportunity to reduce the rate of recurrence of BV.


Plant Immune Mechanisms: From Reductionistic to Holistic Points of View.
After three decades of the amazing progress made on molecular studies of plant-microbe interactions (MPMI), we have begun to ask ourselves "what are the major questions still remaining?" as if the puzzle has only a few pieces missing. Such an exercise has ultimately led to the realization that we still have many more questions than answers. Therefore, it would be an impossible task for us to project a coherent "big picture" of the MPMI field in a single review. Instead, we provide our opinions on where we would like to go in our research as an invitation to the community to join us in this exploration of new MPMI frontiers.


Exposure effects of inhaled nickel nanoparticles on the male reproductive system via mitochondria damage.
Nickel nanoparticles (Ni NPs) have a wide range of application prospects, however there is still a lack of their safety evaluation for the reproductive system. Nowadays, male reproductive health has been widely concerned for the increasing incidence of male infertility. To investigate the male reproductive toxicity induced by Ni NPs and its relation with the mitochondrial fission and mitophagy, male mice were administered with or without 5, 15, and 45 mg/kg of Ni NPs by intratracheal instillation. At the end of intervention, sex hormone level, sperm abnormality rate, pathological morphology of testis, cell apoptosis and the expression levels of Drp1, Pink1 and Parkin proteins in testis tissues were detected. The results indicated that the rate of sperm deformity and serum levels of reproductive hormones increased obviously with the increasing concentrations of Ni NPs. Testicular spermatogenic cells were damaged and the number of apoptotic cells increased significantly. Furthermore, the expressions of key proteins (Drp1, Pink1 and Parkin) related to mitochondrial fission/autophagy in testis tissues also increased after exposure to Ni NPs. Collectively, mitochondria damage may play an important role in male mice reproductive toxicity induced by the intratracheal instillation of Ni NPs.


Occurrence of the Plant Growth Regulator Chlormequat in Food May Be Due to Natural Formation: A Preliminary Mechanistic Study.
The study reports the role of choline and compounds thereof in the formation of chlormequat under thermal conditions, with emphasis on the molecular mechanism involved in the transformation. The data show the decomposition of choline to chlormequat at 200 °C in presence of chloride ions, likely by nucleophilic substitution. Furthermore, the results suggest that phosphatidylcholine, glycerophosphocholine, and phosphocholine are the effective precursors of chlormequat under sufficient thermal conditions due to their capability to degrade to choline and/or the ability of the phosphate moiety to behave as a good leaving group with respect to nucleophilic attacks. Thermal treatments (120 and 200 °C) applied to egg powder, rich in phosphatidylcholine, and wheat flour, with choline at a substantial level, suggest that less energy is required for obtaining chlormequat from phosphatidylcholine than from choline. This observation is consistent with the postulated mechanism of a nucleophilic substitution with phosphate moieties acting as better leaving groups than the hydroxyl group.


Lectin binding to cells of Schistosoma mansoni sporocysts and surrounding Biomphalaria glabrata tissue.
The binding of different lectins to the surface of mother and daughter sporocysts of Schistosoma mansoni (Trematoda) and to cells of its intermediate host Biomphalaria glabrata (Gastropoda) was investigated. The test system consisted of several biotin-labeled lectins, an avidin-biotin-peroxidase complex and 3,3'-diaminobenzidine. The fixatives used were Formalin, Bouin's and Zenker's solutions; unfixed material was also studied. Most lectins reacted equally with host tissue and parasite tissue. However, receptors for Ulex europaeus I (most probably fucose) were only demonstrated on daughter sporocysts. Thus, a method was found to specifically mark Schistosoma mansoni daughter sporocysts in the digestive gland tissue of its intermediate host. Mother sporocysts and surrounding host tissue differed in their distribution of galactosyl groups. Both lack fucose and N-acetyl-galactosamine. The differences in lectin binding of galactosyl determinants were also observed during the in vitro development of mother to daughter sporocysts.


[Relevance of the clinical-pathological predictive factors in force in chromophobe renal cell cancer].
The identification of new subtypes of renal cell carcinoma (RCC) has made it necessary to re-evaluate the current clinical and pathological predictive factors (stage, Fuhrman nuclear grade, necrosis, lymphovascular invasion [LVI] and sarcomatoid component) in these new subtypes. The chromophobe renal cell carcinoma (CRCC) is considered a less aggressive subtype of RCC. The purpose of this article is to evaluate the usefulness of current clinicopathologic predictors of RCC in our series of CRCC. We retrospectively reviewed the clinicopathologic features of 63 patients with CRCC treated with radical nephrectomy. The parameters analyzed were tumor extension with the TNM, grade according to Fuhrman classification, LVI, tumor necrosis, tumor thrombus, surgical margin status, and involvement of the collecting system. The results (disease recurrence) were evaluated by Cox regression model with univariate and multivariate analysis. With a median follow up of 60.2 months (0.37-160.2), 8 (11%) patients had recurrence, with median time to recurrence of 31.7 months (5.37-124.33). In the univariate analysis, TNM extension (p=0.0001), Fuhrman grade III or IV (p=0.031), LVI (p=0.0001) and the presence of positive surgical margins (p=0.0001) were statistically significant variables for recurrence. In the multivariate analysis, only tumor stage was confirmed as an independent predictor of recurrence, pT1 versus pT2 (p=0.02, OR 0.27 95% CI 0.03-0.258) and pT2 versus higher stage (p=0.037, OR 0.173 95% CI 0.033-0.896). The tumor stage predicts aggressiveness in the CCRC. The classification of Fuhrman nuclear grade is not useful for this histological subtype.


Attenuation of the development of hypertension in spontaneously hypertensive rats by the thromboxane synthetase inhibitor, 4'-(imidazol-1-yl) acetophenone.
The compound 4'-(imidazol-1-yl) acetophenone was demonstrated to be a selective thromboxane (Tx) synthetase inhibitor in spontaneously hypertensive rats (SHR). Serum TxB2 concentrations (from clotted blood) were suppressed by 89.1% (p less than 0.001) and 41.2% (p less than 0.01) at 3 and 24 hours, respectively, following a single subcutaneous injection of 100 mg/kg of 4'-(Imidazol-1-yl) acetophenone suspended in olive oil. In contrast, plasma 6-keto-PGF1 alpha levels were not significantly altered at 3 hours following injection - a time when suppression of TXB2 was maximal. From 4 to 10 weeks of age, SHR were treated with daily injections of either 4'-(Imidazol-1-yl) acetophenone (100 mg/kg) in olive oil or olive oil alone. By 8 weeks of age systolic blood pressures in the treated group were 140.6 +/- 3.2 vs 156.6 +/- 4.5 mmHg in the control group (p less than 0.01). At ten weeks of age the separation was even more pronounced: 155.3 +/- 3.7 vs. 184.8 +/- 4.6 mmHg for treated vs. control animals (p less than 0.001). This data supports the hypothesis that thromboxanes may be involved in the development of SHR hypertension; however, alternative mechanisms are discussed.


Current treatment of metastatic renal cell carcinoma with xenogeneic immune ribonucleic acid.
In 1979 we reported a phase I trial involving 6 patients treated with immune ribonucleic acid for renal cell carcinoma. Since that report 27 patients with stage III or IV renal cell carcinoma have been assessed in a phase II trial. All patients have undergone excision of the primary tumor or superficial metastases, injection of tumor into guinea pigs and harvesting of immune ribonucleic acid. Autologous lymphocytes, obtained by plasmapheresis on an outpatient basis, have been incubated with immune ribonucleic acid and reinfused into the host. Results indicate complete response in 1 patient for more than 61 months, partial response in 5 patients for 6 to 10 months and stabilization in 10 patients for 2 to 8 months, all of whom had progressive disease before the institution of therapy. Six patients with continued progressive disease died at a median of 2 months after therapy. Of 5 patients treated in an adjuvant fashion only 1 has had a relapse from 9 to 18 months after therapy. Patients with pulmonary metastases seem to represent the most favorable group for this passive form of immunotherapy. This therapy would seem to offer reasonable alternatives in selected patients with advanced disease.


Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China.
To characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China. In total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed. Among the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65%) referred neurological symptoms. Anterior chamber activity was negative in most eyes within an onset of 7 days, which increased slightly with onset beyond 1 week. Exudative retinal detachment (366 eyes, 98%) and optic disc hyperaemia (314 eyes, 84%) were commonly observed at presentation. A typical ancillary examination helped with the diagnosis of VKH. Systemic corticosteroid therapy was prescribed. The logMAR best-corrected visual acuity improved significantly from 0.74 ± 0.54 at baseline to 0.12 ± 0.24 at the 1-year follow-up visit. The recurrence rate was 18% in the follow-up visits. Erythrocyte sedimentation rate and C-reactive protein were significantly correlated to VKH recurrences. Posterior uveitis, followed by mild anterior uveitis, is the typical initial manifestation in the acute phase of Chinese VKH patients. Visual outcome improvement is promising in most patients receiving systemic corticosteroid therapy in the acute phase. Detection of the clinical features at the initial onset of VKH could facilitate early treatment and better vision improvement.


Phase I trial of sorafenib in combination with 5-fluorouracil/leucovorin in advanced solid tumors.
This dose escalation, uncontrolled phase I study evaluated the tolerability, pharmacokinetics (PK), and antitumor activity of oral sorafenib 100, 200, or 400 mg twice daily (bid, continuous regimen) in combination with 5-fluorouracil/leucovorin (5-FU/LCV, intravenous infusion or bolus) in patients with advanced, solid tumors. A total of 47 patients (median age 57 years; colon cancer, 55%; pancreatic cancer, 21%; prior systemic therapy, 96%) received treatment; 24 were included in the PK analyses, and 38 were evaluable for tumor response. Treatment-emergent adverse events were observed in 98% of patients (≥grade 3, 55%); the most frequently reported were fatigue (51%), stomatitis/pharyngitis (47%), and hand-foot skin reaction (45%). Concomitant 5-FU/LCV resulted in no clinically relevant changes in the area under the plasma concentration-time curve in the dosing interval (AUC(0-12)) and maximum plasma concentration (C(max)) of sorafenib (100-400 mg bid) at steady state. Although the start of infusion until the last quantifiable plasma concentration (AUC(0-tn)) and C(max) of 5-FU were increased by concomitant sorafenib 100 to 200 mg, no consistent effect was observed with 400 mg sorafenib. Two (5%) patients with colon cancer achieved partial response; 16 (42%) patients (the majority with colon and pancreatic cancer) had stable disease. Sorafenib plus 5-FU/LCV was generally well tolerated with encouraging antitumor activity and no clinically relevant drug-drug interactions in patients with advanced solid tumors.


Effectiveness and Safety of Lumen-Apposing Metal Stents in Endoscopic Interventions for Off-Label Indications.
Although released only for drainage of pseudocyst and walled-off necrosis (WON) with ≤ 30% solid debris, the utilization of lumen-apposing metal stent (LAMS) in "real-world" practice has deviated from approved indications. We evaluated the contemporary use of LAMS and associated clinical, procedural outcomes in the setting of a tertiary referral center in the USA. Data from 303 consecutive patients who underwent LAMS placement were analyzed. Outcomes included technical and clinical success rates and adverse events. Of 303 patients, 190 (62.7%) received LAMS for off-label indications. The latter included gallbladder drainage (n = 56, 18.5%), gastroenterostomy (n = 52, 17.2%), treatment of gastrointestinal strictures (n = 37, 12.2%), biliary drainage (n = 20, 6.6%), temporary gastric access for endoscopy (n = 13, 4.3%), symptomatic WON with > 30% solid debris (n = 8, 2.6%), and miscellaneous (n = 4, 1.3%). Technical success rates in the on- and off-label arm were 98.2% and 95.8%, respectively (P = .331; 95% CI 0.08 to 1.96). Clinical success rates in the on- and off-label arm were 89.4% and 83.2%, respectively (P = .137; 95% CI 0.28 to 1.19). The rate of adverse events was 20.5% (n = 39) in the off-label arm and 16.8% (n = 19) in the on-label arm (P = .242; 95% CI 0.69 to 2.34). Off-label use of LAMS out-numbered on-label use in our practice. The safety profile between the groups was similar and with the exception of refractory stricture treatment, efficacy was comparable.


Comparative metabolism of benfuracarb in in vitro mammalian hepatic microsomes model and its implications for chemical risk assessment.
In vitro metabolism of benfuracarb in liver microsomes from seven species was studied in order to quantitate species-specific metabolic profiles and enhance benfuracarb risk assessment by interspecies comparisons. Using LC-MS/MS, a total of seven phase-I-metabolites were detected from the extracted chromatograms and six of them were unequivocally identified. Benfuracarb was metabolized via two metabolic pathways, the sulfur oxidation pathway and nitrogen sulfur bond cleavage, yielding carbofuran, which metabolized further. Analysis of the metabolic profiles showed that benfuracarb was extensively metabolized with roughly similar profiles in different species in vitro. In vitro intrinsic clearance rates as well as calculated in vivo hepatic clearances indicated that all seven species metabolize benfuracarb via the carbofuran metabolic pathway more rapidly than the sulfoxidation pathway. The highest interspecies differences in hepatic clearance rate values were for mouse and rat liver microsomes compared to human, i.e. 4.8 and 4.1-fold higher, as illustrated by in vivo hepatic clearance of carbofuran. Overall, there are quantitative interspecies differences in the metabolic profiles and kinetics of benfuracarb biotransformation. These findings illustrate that in vitro studies of benfuracarb metabolite profiles and toxicokinetics are helpful for the proper selection and interpretation of animal models for toxicological evaluation and chemical risk assessment.


The agency problem and medical acting: an example of applying economic theory to medical ethics.
In this article, the authors attempt to build a bridge between economic theory and medical ethics to offer a new perspective to tackle ethical challenges in the physician-patient encounter. They apply elements of new institutional economics to the ethically relevant dimensions of the physician-patient relationship in a descriptive heuristic sense. The principal-agent theory can be used to analytically grasp existing action problems in the physician-patient relationship and as a basis for shaping recommendations at the institutional level. Furthermore, the patients' increased self-determination and modern opportunities for the medical laity to inform themselves lead to a less asymmetrical distribution of information between physician and patient and therefore require new interaction models. Based on the analysis presented here, the authors recommend that, apart from the physician's necessary individual ethics, greater consideration should be given to approaches of institutional ethics and hence to incentive systems within medical ethics.


Enhancer methylation dynamics drive core transcriptional regulatory circuitry in pan-cancer.
Accumulating evidence has demonstrated that enhancer methylation has strong and dynamic regulatory effects on gene expression. Some transcription factors (TFs) can auto- and cross-regulate in a feed-forward manner, and cooperate with their enhancers to form core transcriptional regulatory circuitries (CRCs). However, the elaborated regulatory mechanism between enhancer methylation and CRC remains the tip of the iceberg. Here, we revealed that DNA methylation could drive the tissue-specific enhancer basal transcription and target gene expression in human cancers. By integrating methylome, transcriptome, and 3D genomic data, we identified enhancer methylation triplets (enhancer methylation-enhancer transcription-target gene expression) and dissected potential regulatory patterns within them. Moreover, we observed that cancer-specific core TFs regulated by enhancers were able to shape their enhancer methylation forming the enhancer methylation-driven CRCs (emCRCs). Further parsing of clinical implications showed rewired emCRCs could serve as druggable targets and prognostic risk markers. In summary, the integrative analysis of enhancer methylation regulome would facilitate portraying the cancer epigenomics landscape and developing the epigenetic anti-cancer approaches.


Modelling pollution dispersal around Solomon Islands and Vanuatu.
To assess potential dispersion of pollutants around Honiara, Solomon Islands, and Port Vila, Vanuatu, 3D ocean circulation models were developed using Telemac-3D. A series of scenarios then explore the vulnerability of the system and test potential control measures. Results show that high coastal concentrations are most likely during the wet season, with increased volumes of discharge as well as favourable wind speed and direction. Buoyant plumes flow along the coastline, and high concentrations build up in enclosed bays. Control measures tested focus on consolidating existing outflows at depth off-shore. This results in an overall reduction of surface concentrations along the coastline. However, the reduction is dependent on the depth, off-shore positioning, and volume of outflow. With increased concentrations then found at depth, the subsequent impact on off-shore and benthic ecosystems would also need to be considered.


Prognostic values of pathologic findings and hypoxia markers in 21 patients with salivary duct carcinoma.
Salivary duct carcinoma (SDC) is associated with aggressive clinical behavior. We examined the prognostic values of clinicopathologic variables and hypoxia biomarker expression in 21 patients with SDC treated by resection with/without neck dissection and radiotherapy. Tissue microarrays constructed from tumor blocks were stained with monoclonal antibodies to hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase-9, glucose transporter-1, and erythropoietin receptor. Locoregional control and survival rates were calculated by the Kaplan-Meier method and prognostic factors were calculated from uni- and multivariate analyses. The cervical nodal metastasis rate was 67% at initial diagnosis and the distant metastasis rate was 71% during follow-up. The only significant predictor of distant metastasis was nodal metastasis (P = 0.006). Actuarial 5-year locoregional control, distant metastasis-free survival, and overall survival rates were 57%, 40%, and 44%. Multivariate analysis showed that lymphovascular and perineural invasion and radiotherapy were independent predictors of overall survival (P < 0.025). None of the hypoxia biomarkers, however, was a significant predictor of locoregional control, distant metastasis, or survival. Lymphovascular and perineural invasion, but not hypoxia biomarkers, were significant prognostic factors for patients with SDC.


Targeting chemotherapy for hepatoma: arterial administration of anticancer drugs dissolved in Lipiodol.
In targeted cancer chemotherapy, Lipiodol Ultrafluid (Lipiodol) was used as a carrier of anticancer drugs, these drugs were termed as "oily anticancer agents". This arterial injection therapy with oily anticancer agents was performed for 323 patients with hepatoma. Serum alpha-fetoprotein (AFP) levels decreased in 165 (93%) of 177 AFP-positive patients. Reduced tumour size was observed in 210 (regression over 50% in 96 and less than 50% in 114) of 222 evaluable patients with unresectable hepatoma. In patients who preoperatively received a dose of styrene maleic acid neocarzinostatin (SMANCS)/Lipiodol of more than 0.7 mg/cm2 of maximal cut surface area of the tumour, complete necrosis or necrosis of almost the entire area of tumour was found, and non-cancerous liver tissue and the gallbladder remained unaffected. The survival period of 277 patients with unresectable hepatoma who were treated with oily anticancer agents is thought to be prolonged, especially of 147 patients, excluding those with Child C liver cirrhosis, with tumour occupying all segments of the liver, or with extrahepatic spread. The 1-, 2-, 3-, and 5-year survival rates were 84, 47, 37, and 34%, respectively.


Immunization to a syngeneic sarcoma by a monoclonal auto-anti-idiotypic antibody.
Idiotypic networks regulate the immune response to a variety of antigens. Antibodies generated against other antibodies, called anti-idiotypic antibodies, can themselves mimic antigen and elicit a specific immune response. They have been shown to induce delayed-type hypersensitivity (DTH) to model antigens in the mouse. As anti-idiotypic antibodies are thought to be involved in the response to tumour-associated antigens we tested whether injection of monoclonal antibodies derived from mice hyperimmunized to a syngeneic, chemically induced sarcoma could mimic antigen and induce DTH to the sarcoma in naive mice. One of the monoclonal antibodies, 4.72, primed BALB/c mice for DTH to the sarcoma but not for DTH to another sarcoma or to sheep erythrocytes. Antibody 4.72 did not induce DTH in mice of immunoglobulin allotype congeneic strains nor did it bind to the sarcoma cells. As antibodies specific for this sarcoma have not been detected, we do not know whether idiotype on immunoglobulin molecules is recognized by antibody 4.72. However, as the response induced by antibody 4.72 was both antigen-specific and allotype-restricted, analogous to those induced by anti-idiotypic antibodies in other systems, we propose that antibody 4.72 is an anti-idiotypic antibody.


Hyponatremic hypertensive syndrome.
Hyponatremic hypertensive syndrome is a manifestation of severe hypertension related to renal ischemia. The most common underlying cause of hyponatremic hypertensive syndrome in adults is severe atherosclerotic reno-vascular disorder while in children the most common cause of hyponatremic hypertensive syndrome is unilateral congenital renal artery stenosis due to some form of arterial dysplasia. An excessively stimulated renin-angiotensin-aldosterone system is mainly responsible for heavy polyuria, renal electrolyte loss and proteinuria. The neurological manifestations of hyponatremia and/or hypertensive encephalopathy are the main presenting symptoms, and they are not always in linear correlation with the degree of hyponatremia and/or hypertension. The cornerstone of management is the treatment of underlying hypertensive disease, but the correction of hyponatremic dehydration and safe decrease of blood pressure are essential in the emergency phase of hyponatremic hypertensive syndrome. The optimal antihypertensive therapy depends on the underlying condition. Revascularization, either surgical or by percutaneous transluminal angioplasty, is recommended for children with renal artery stenosis. Pharmacological treatment based on ACEI and/or ARB is the most efficient antihypertensive therapy for those with ischemic reno-parenchymal disorder. Nephrectomy is required if an affected kidney contributes less than 10% of the global renal function, if percutaneous transluminal angioplasty fails and the operative risk is too high, or in the case of extensive tumorous lesions.


Neuropathic agents in the management of pruritus in burn injuries: a systematic review and meta-analysis.
Pruritus is a common and often distressing complication after a burn injury. The purpose of this review is to explore the efficacy of drugs classically used to treat neuropathic pain in the management of pruritus after burn injury. A systematic literature search of medical databases was conducted to find studies investigating drugs listed in the National Institute for Health and Care Excellence (NICE) guideline (CG173, "neuropathic pain in adults") for the management of pruritus after burn injury in patients of any age. Controlled studies were stratified by the drug class studied and their risk of bias before conducting meta-analysis. A narrative review of case series or observational studies was presented. Severity of pruritus at any time point, with all quantitative and qualitative measures, was included. Fifteen studies were included in the final analysis, 10 investigated the use of gabapentinoids, 4 studied doxepin, and 1 local anesthetic agents. Meta-analysis of three randomized controlled trials (RCTs) demonstrated that the use of gabapentinoids was associated with an improvement in mean VAS (Visual Analog Scale) 0-10 scores of 2.96 (95% confidence interval (95% CI) 1.20 to 4.73, p<0.001) when compared with placebo or antihistamine. A meta-analysis of four RCTs investigating topical doxepin showed an improvement in mean VAS scores of 1.82 (95% CI 0.55 to 3.09, p<0.001). However, when excluding two studies found to be at high risk of bias, no such improvement was found (-0.32, 95% CI -1.64 to -0.99, p=0.83). This study suggests that gabapentinoids are beneficial in the management of burn-related pruritus. There is a lack of evidence to suggest that doxepin is an effective treatment. Topical local anesthetic agents may be safe and beneficial, but studies are scarce. Systematic review, level II.


The effect of chronic ACTH treatment on blood pressure and urinary excretion of steroids in the rat.
The effects of subcutaneous injections of synthetic ACTH during 14 subsequent days has been studied in the rat. ACTH caused a loss in body weight which was related to a negative water balance. Blood pressure rose rapidly and reached values higher than 180 mm Hg in all rats after 10 days of ACTH administration. During this period, urinary excretion of corticosterone and 18-hydroxy-deoxycorticosterone (18-OH-DOC) was increased more than ten times, while aldosterone excretion was increased only during the first two days. After withdrawal of ACTH, excretion of steroids normalized, or in some cases was even suppressed and water balance and body weight gain returned to normal values. However, blood pressure remained slightly higher than in controls after ten days. The effects of ACTH on water balance and blood pressure resemble those of corticosterone in the rat. The rapidly induced and sustained changes in blood pressure by ACTH administration suggest that this may be an useful model of experimental hypertension.


TGF-β induced reprogramming and drug resistance in triple-negative breast cells.
The development of drug resistance remains to be a major cause of therapeutic failure in breast cancer patients. How drug-sensitive cells first evade drug inhibition to proliferate remains to be fully investigated. Here we characterized the early transcriptional evolution in response to TGF-β in the human triple-negative breast cells through bioinformatical analysis using a published RNA-seq dataset, for which MCF10A cells were treated with 5 ng/ml TGF-β1 for 0 h, 24 h, 48 h and 72 h, and the RNA-seq were performed in biological duplicates. The protein-protein interaction networks of the differentially expressed genes were constructed. KEGG enrichment analysis, cis-regulatory sequence analysis and Kaplan-Meier analysis were also performed to analyze the cellular reprograming induced by TGF-β and its contribution to the survival probability decline of breast cancer patients. Transcriptomic analysis revealed that cell growth was severely suppressed by TGF-β in the first 24 h but this anti-proliferate impact attenuated between 48 h and 72 h. The oncogenic actions of TGF-β happened within the same time frame with its anti-proliferative effects. In addition, sustained high expression of several drug resistance markers was observed after TGF-β treatment. We also identified 17 TGF-β induced genes that were highly correlated with the survival probability decline of breast cancer patients. Together, TGF-β plays an important role in tumorigenesis and the development of drug resistance, which implies potential therapeutic strategies targeting the early-stage TGF-β signaling activities.


An implication of the mitochondrial carrier SLC25A3 as an oxidative stress modulator in NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is a type of steatosis not associated with excessive alcohol intake and includes nonalcoholic steatohepatitis (NASH), which can progress to advanced fibrosis and hepatocellular carcinoma. Mitochondrial dysfunction causes oxidative stress, triggering hepatocyte death and inflammation; therefore, the present study aimed to explore relationship between mitochondrial carriers and oxidative stress. Firstly, we established a high fat diet (HFD)-fed ICR mouse NAFLD model characterized by obesity with insulin resistance and found transcriptional upregulation of Slc25a17 and downregulation of Slc25a3 (isoform B) and Slc25a13 in their fatty liver. A mitochondrial phosphate and Cu carrier, SLC25A3, was further studied in wild-type (wt) and SLC25A3-defective HepG2 cells (C1 and C3). SLC25A3 deficiency had insignificant effect on mitochondrial membrane potential (MtMP) and oxygen consumption rate (OCR) in untreated cells but suppressed them when cells were exposed to oleic acid. C1 and C3 cells were prone to produce reactive oxygen species (ROS), and increased ROS was associated with reduced mRNA expression of glutathione peroxidase (GPX) 1 and glutathione disulfide reductase (GSX) in these cell lines. Interestingly, cytoplasmic and mitochondrial Cu accumulation significantly reduced in C1 cells, demonstrating a predominant contribution of SLC25A3 to Cu transport into mitochondrial matrix. Cytotoxicity of free fatty acids was unchanged between wt and SLC25A3-deficient cells. These results indicate that reduced expression of SLC25A3 in fatty liver contributes to electron leak from mitochondria by limiting Cu availability, rendering hepatocytes more susceptible to oxidative stress. This study provides evidence that SLC25A3 is a novel risk factor for developing NASH.


Development and validation of an instrument to measure collaborative goal setting in the care of patients with diabetes.
Despite known benefits of patient-perceived collaborative goal setting, we have a limited ability to monitor this process in practice. We developed the Patient Measure of Collaborative Goal Setting (PM-CGS) to evaluate the use of collaborative goal setting from the patient's perspective. A random sample of 400 patients aged 40 years or older, receiving diabetes care from the Virginia Commonwealth University Health System between 8/2012 and 8/2013, were mailed a survey containing potential PM-CGS items (n=44) as well as measures of patient demographics, perceived self-management competence, trust in their physician, and self-management behaviors. Confirmatory factor analysis was used to evaluate construct validity. External validity was evaluated via a structural equation model (SEM) that tested the association of the PM-CGS with self-management behaviors. The direct and two mediated (via trust and self-efficacy) pathways were tested. A total of 259 patients responded to the survey (64% response rate), of which 192 were eligible for inclusion. Results from the factor analysis supported a 37-item measure of patient-perceived CGS spanning five domains: listen and learn; share ideas; caring relationship; measurable objective; and goal achievement support (χ=4366.13, p<0.001; RMSEA=0.08). Results from the SEM supported the external validity of the PM-CGS. The relationship between CGS and self-management was partially mediated by perceived competence (p<0.05). The direct effect between the PM-CGS and self-management was significant (p<0.001). CGS can be validly measured by the 37-item PM-CGS. Use of the PM-CGS can help illustrate actionable deficits in goal-setting discussions.


Elevated intracellular concentrations of cyclic AMP inhibited serum-stimulated, density-arrested BALB/c-3T3 cells in mid G1.
The stimulation of DNA synthesis in quiescent, density-arrested BALB/c-3T3 cells by platelet-derived growth factor in plasma-supplemented medium was inhibited by the presence of isobutylmethylxanthine (IBMX) and cholera toxin, although neither IBMX or cholera toxin when used alone inhibited the stimulation of DNA synthesis. The cells were reversibly inhibited in mid G1 at a point 6 hr prior to the initiation of DNA synthesis. The inhibition of cell cycle traverse was associated with a 10-15 fold increase in cellular cyclic AMP concentration over basal levels. The reversal of this inhibition by removal of IBMX was correlated with a dramatic decrease in cyclic AMP levels. The traverse of G1 and the initiation of DNA synthesis after release from the cholera toxin and IBMX inhibition was dependent on the presence of plasma in the medium. Either somatomedin C (10-20 ng/ml) or insulin (10(-6)-10(-5) M) completely replaced the plasma requirement for late G1 progression and entry into S phase. Once the inhibited cells were released from the IBMX and cholera toxin block a subsequent increase in cyclic AMP did not prevent entry into S phase. The presence of cholera toxin alone inhibited the stimulation of human dermal fibroblasts. The elevation of intracellular cyclic AMP levels in the human dermal fibroblasts by cholera toxin was two to three fold greater than that found in the BALB/c-3T3 cells in the presence of cholera toxin and the IBMX.


Bilateral borderzone brain infarctions in association with heroin abuse.
A 25-year-old drug abuser who developed an unusual pattern of cerebral ischemic lesions is presented. Cerebral magnetic resonance imaging revealed bilateral borderzone infarctions which were attributed to a heroin-associated vasculitis of the basal cerebral arteries. Under probatory corticosteroid medication the mild neurological deficits completely disappeared.


NiO/graphene nanocomposite for determination of H2O2 with a low detection limit.
In this study, we have reported the preparation of NiO/graphene (NiO/GR) nanocomposite for determination of H2O2 via a convenient solid reaction. The electrocatalytic behaviors towards H2O2 are investigated by cyclic voltammetry and chronoamperometry in alkaline aqueous solution. Electrochemical results indicate that the NiO/GR nanocomposite exhibits a high peak current towards the oxidation of H2O2. Moreover, high electrocatalytic activity toward the oxidation of H2O2 is observed with a low detection limit of 0.7664 μM, high sensitivity of 591 μA mM(-1) cm(-2), a wide linear range of 0.25-4.75 mM (R(2)=0.9971). Besides, the sensor presents many attractive features such as high stability and reproducibility.


Effects of analogues of adenosine and methyl xanthines on insulin sensitivity in soleus muscle of the rat.
The concentration of insulin that produces half-maximal stimulation of glycolysis by stripped soleus muscle preparations is markedly increased by the adenosine analogues, 2-chloroadenosine and N6-phenylisopropyladenosine, but is markedly decreased by the methyl xanthine analogue, 8-phenyltheophylline. 2-Chloroadenosine increases the concentration of insulin required to stimulate glycolysis half maximally, from about 100 to 2000 mu units/ml. 8-Phenyltheophylline decreases this concentration of insulin from about 100 to 10 mu units/ml, an effect which is similar to that produced either by addition of adenosine deaminase to the medium or to exercise-training of the donor animals for 4 weeks.


1-(10-Bromo-anthracen-9-yl)-1H-imidazole.
In the title mol-ecule, C17H11BrN2, the planes of the anthracene ring system [maximum deviation from the mean plane = 0.036 (3) Å] and the imidazole ring form a dihedral angle of 85.14 (14)°. In the crystal, weak C-H⋯N and C-H⋯Br hydrogen bonds link the mol-ecules into double chains propagating along [01-1]. In addition, π-π stacking inter-actions between pairs of benzene rings are observed, with centroid-centroid distances of 3.7968 (17) and 3.8496 (16) Å.


Acetyl-CoA deficit in brain mitochondria in experimental thiamine deficiency encephalopathy.
Several pathologic conditions are known to cause thiamine deficiency, which induce energy shortages in all tissues, due to impairment of pyruvate decarboxylation. Brain is particularly susceptible to these conditions due to its high rate of glucose to pyruvate-driven energy metabolism. However, cellular compartmentalization of a key energy metabolite, acetyl-CoA, in this pathology remains unknown. Pyrithiamine-evoked thiamine deficiency caused no significant alteration in pyruvate dehydrogenase and 30% inhibition of α-ketoglutarate dehydrogenase activities in rat whole forebrain mitochondria. It also caused 50% reduction of the metabolic flux of pyruvate through pyruvate dehydrogenase, 78% inhibition of its flux through α-ketoglutarate dehydrogenase steps, and nearly 60% decrease of intramitochondrial acetyl-CoA content, irrespective of the metabolic state. State 3 caused a decrease in citrate and an increase in α-ketoglutarate accumulation. These alterations were more evident in thiamine-deficient mitochondria. Simultaneously thiamine deficiency caused no alteration of relative, state 3-induced increases in metabolic fluxes through pyruvate and α-ketoglutarate dehydrogenase steps. These data indicate that a shortage of acetyl-CoA in the mitochondrial compartment may be a primary signal inducing impairment of neuronal and glial cell functions and viability in the thiamine-deficient brain.


Causal relationships among self-management behaviors, symptom control, health-related quality of life and the influencing factors among Thai adolescents with asthma.
To examine causal relationships among asthma self-management behaviors, asthma symptom control, health-related quality of life and the influencing factors among Thai adolescents. A cross-sectional study was conducted using convenience sampling. A total of 240 adolescent-caregiver dyads from three tertiary hospitals in Bangkok, Thailand was ultimately included. Interviews and self-administered questionnaires assessing health-related quality of life, asthma symptom control, asthma self-management behaviors, health literacy, depression, comorbidities, family support, peer support, home environmental management, and relationships with health care providers were administered between November 2020 and July 2021. A hypothesized model based on the revised self- and family-management framework was proposed. Data were analyzed using descriptive statistics and path analysis. It was shown that the proposed model was a good fit for the empirical data and accounted for 67.2% of the variance in health-related quality of life. Depression and asthma symptom control directly affected quality of life (β = -0.132, P < 0.05; and β = 0.740, P < 0.05, respectively), while asthma self-management behaviors did not. Both depression and asthma self-management behaviors had indirect effects on the quality of life through asthma symptom control (β = -0.382, P < 0.05; and β = 0.225, P < 0.05, respectively). Health literacy (β = 0.343, P < 0.05), family support (β = 0.167, P < 0.05), peer support (β = 0.163, P < 0.05), and relationships with health care providers (β = 0.181, P < 0.05) also showed direct effects on asthma self-management behaviors. The findings confirmed the causal relationships among asthma symptom control, self-management behaviors, depression and health-related quality of life. Health literacy, support from family and peers, and relationships with health care providers were also found to influence asthma self-management behaviors. To achieve effective asthma control and good quality of life, a nursing intervention promoting asthma self-management for Thai adolescents should be developed. Early detection and intervention of depressive symptoms are also suggested.


Improved suppression of plaque-mimicking artifacts in black-blood carotid atherosclerosis imaging using a multislice motion-sensitized driven-equilibrium (MSDE) turbo spin-echo (TSE) sequence.
In this study, a turbo spin-echo (TSE) based motion-sensitized driven-equilibrium (MSDE) sequence was used as an alternative black-blood (BB) carotid MRI imaging scheme. The MSDE sequence was first optimized for more efficient residual blood signal suppression in the carotid bulb of healthy volunteers. Effective contrast-to-noise ratio (CNR(eff)) and residual signal-to-noise ratio (SNR) in the lumen measured from MSDE images were then compared to those measured from inflow saturation (IS) and double inversion-recovery (DIR) images. Statistically significant higher CNR(eff) and lower lumen SNR were obtained from MSDE images. To assess MSDE sequence in a clinical carotid protocol, 42 locations from six subjects with 50% to 79% carotid stenosis by duplex ultrasound were scanned with both MSDE and multislice DIR. The comparison showed that MSDE images present significantly higher CNR and lower lumen SNR compared to corresponding multislice DIR images. The vessel wall area and mean wall thickness measurements in MSDE images were slightly but significantly lower than those obtained with other blood suppression techniques. In conclusion, in vivo comparisons demonstrated that MSDE sequence can achieve better blood suppression and provide a more accurate depiction of the lumen boundaries by eliminating plaque mimicking artifacts in carotid artery (CA) imaging.


Papillomaviruses: different genes have different histories.
Papillomaviruses (PVs) infect stratified squamous epithelia in vertebrates. Some PVs are associated with different types of cancer and with certain benign lesions. It has been assumed that PVs coevolved with their hosts. However, recently it has been shown that different regions of the genome have different evolutionary histories. The PV genome has a modular nature and appeared after the addition of pre-existent blocks. This order of appearance in the PV genome is evident today in the different evolutionary rates of the different genes, with new genes--E5, E6 and E7--diverging faster than old genes--E1, E2, L2 and L1. Here, we propose an evolutionary framework aiming to integrate genome evolution, PV biology and epidemiology of PV infections.


The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex.
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. The GABA signaling system in the brain is comprised of GABA synthesizing enzymes, transporters, GABAA and GABAB receptors (GABAAR and GABABR). Alterations in the expression of these signaling components have been observed in several brain regions throughout aging and between sexes in various animal models. The hippocampus is the memory centre of the brain and is impaired in several age-related disorders. It is composed of two main regions: the Cornu Ammonis (CA1-4) and the Dentate Gyrus (DG), which are interconnected with the Entorhinal Cortex (ECx). The age- and sex-specific changes of GABA signaling components in these regions of the human brain have not been examined. This study is the first to determine the effect of age and sex on the expression of GABA signaling components-GABAAR α1,2,3,5, β1-3, γ2, GABABR R1 and R2 subunits and the GABA synthesizing enzymes GAD 65/67-in the ECx, and the CA1 and DG regions of the human hippocampus using Western blotting. No significant differences were found in GABAAR α1,2,3,5, β1-3, γ2, GABABR R1 and R2 subunit and GAD65/76 expression levels in the ECx, CA1 and DG regions between the younger and older age groups for both sexes. However, we observed a significant negative correlation between age and GABAAR α1subunit level in the CA1 region for females; significant negative correlation between age and GABAAR β1, β3 and γ2 subunit expression in the DG region for males. In females a significant positive correlation was found between age and GABAAR γ2 subunit expression in the ECx and GABABR R2 subunit expression in the CA1 region. The results indicate that age and sex do not affect the expression of GAD 65/67. In conclusion, our results show age- and sex-related GABAA/BR subunit alterations in the ECx and hippocampus that might significantly influence GABAergic neurotransmission and underlie disease susceptibility and progression.


Microprocessor assisted handling of oestrogen receptor assays.
The use of an Apple II microcomputer equipped with a light-pen for interactive analysis of steroid receptor data is described. Processing times have been reduced to less than 5 minutes per patient from around 45-60 minutes by the manual method. Graphical outputs using full and part data sets with derived results are printed for subsequent verification by the Consultant Medical Biochemist. Data processing backlogs have been completely eliminated by this system. The program has, of course, general applicability to any analyses producing a linear correlation between the x and y parameters, and its use in oestrogen receptor analysis is detailed principally because of a considerable and increasing demand for such assays in our department.


Vector methylation inhibits transcription from the SV40 early promoter.
Methylation of a plasmid containing the SV40 promoter linked to the chloramphenicol acetyl transferase (CAT) gene, with either murine DNA methylase or methylase SssI results in inhibition of the expression of the reporter gene after transfection into cultured cells. Methylation of the plasmid with the methylases HhaI and HpaII has no effect on the expression of this gene. Protein-DNA interactions in the SV40 promoter are not affected by the presence of methylcytosine suggesting that inactivation results from the formation of an inactive chromatin structure that is dependent on the high CG content of the plasmid.


Identification of potent anti-immunogenic agents through virtual screening, 3D-QSAR studies, and in vitro experiments.
A wealth of literature has highlighted the discovery of various immune modulators, frequently used in clinical practice, yet associated with numerous drawbacks. In light of this pharmacological deficiency, medical scientists are motivated to develop new immune modulators with minimized adverse effects yet retaining the improved therapeutic potential. T-cell differentiation and growth are central to human defense and are regulated by interleukin-2 (IL-2), an immune-modulatory cytokine. However, scientific investigation is hindered due to its flat binding site and widespread hotspot residues. In this regard, a prompt and logical investigation guided by integrated computational techniques was undertaken to unravel new and potential leads against IL-2. In particular, the combination of score-based and pharmacophore-based virtual screening approaches were employed, reducing the data from millions of small molecules to a manageable number. Subsequent docking and 3D-QSAR prediction via CoMFA further helped remove false positives from the data. The reliability of the model was assessed via standard metrics, which explain the model's fitness and the robustness of the model in predicting the activity of new compounds. The extensive virtual screening herein led to the identification of a total of 24 leads with potential anti-IL-2 activity. Furthermore, the theoretical findings were corroborated with in vitro testing, further endorsing the anti-inflammatory potential of the identified leads.


Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats.
We examined whether central somatostatin prevents an inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic secretion in conscious male Wistar rats (330-330 g). Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 days after the operation without anesthesia. An injection of CGRP (0.1, 1.0 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion dose-dependently. To confirm the inhibitory effect of CGRP (i.c.v.) was mediated via sympathetic nerves, phentolamine was injected intravenously (i.v.) bolus (0.5 mg kg(-1)) 0.5-h before CGRP (i.c.v.), followed by continuous infusion of 0.2 mg kg(-1) h(-1). Phentolamine (i.v.) reversed the inhibition produced by CGRP (i.c.v.). An injection of 4 nmol/10 microl somatostatin (i.c.v.) 5 min prior to CGRP injection diminished the inhibitory effect of CGRP (i.c.v.). It is concluded that centrally administered somatostatin diminished the inhibitory action of CGRP (i.c.v.) on pancreatic secretion, probably via inhibiting autonomic (sympathetic) nerve excitation at the central site.


Color-tunable photoluminescence and energy transfer of (Tb1-x Mn x )3Al2(Al1-x Si x )3O12:Ce3+ solid solutions for white light emitting diodes.
(Tb1-x Mn x )3Al2(Al1-x Si x )3O12:Ce3+ solid solution phosphors were synthesized by introducing the isostructural Mn3Al2(SiO4)3 (MAS) into Tb3Al5O12:Ce3+ (TbAG). Under 456 nm excitation, (Tb1-x Mn x )3Al2(Al1-x Si x )3O12:Ce3+ shows energy transfers (ET) in the host, which can be obtained from the red emission components to enhance color rendering. Moreover, (Tb1-x Mn x )3Al2(Al1-x Si x )3O12:Ce3+ (x = 0-0.2) exhibits substantial spectral broadening (68 → 86 nm) due to the 5d → 4f transition of Ce3+ and the 4T1 → 6A1 transition of Mn2+. The efficiency of energy transfer (η T, Ce3+ → Mn2+) gradually increases with increasing Mn2+ content, and the value reach approximately 32% at x = 0.2. Namely, the different characteristics of luminescence evolution based on the effect of structural variation by substituting the (MnSi)6+ pair for the larger (TbAl)6+ pair. Therefore, with structural evolution, the luminescence of the solid solution phosphors could be tuned from yellow to orange-red, tunable by increasing the content of MAS for the applications of white light emitting diodes (wLED).


Bacterial strains diversity in contaminated soils and their potential for bioremediation of total petroleum hydrocarbons in south west of Iran.
The main purpose of this research was investigating of bioremediation potential oily contaminated soils using native bacterial strains in an oil field. In this research, total bacterial consortium were identified in oily soils with sandy loam texture as case and non-contaminated soils as controls during six months. The dominant strains present on contaminated soil were identified by DNA extraction using 16S rDNA gene sequencing via NGS technique and compared with bacteria present in non-contaminated soil as control samples. Furthermore, quantitative variations of bacterial count along with total petroleum hydrocarbons (TPH) removal was performed in oily (case) samples to investigate the relation between TPH removal and changes in bacterial density. The TPH values were determined with gas chromatography equipped with a flame ionization detector (GC-FID). The dominant identified bacteria in oily soil were as follows: Halomonas, Moraxellaceae, Thalassobacillus, Zhihengliuella and Enterobacteriaceae which varied significantly from those identified in control soil. The bacterial diversity was higher in contaminated soil and a TPH removal of 50.9% was observed over a period of six months monitoring. Indigenous bacteria in oil-contaminated soils of an oilfield in south west of Iran were found to be able to degrade Total Petroleum Hydrocarbons. Our results showed that bioremediation of oil-contaminated soils can be implemented without need to amplification of heterogeneous bacteria. Considering sandy loam texture of soil samples, the identified strains of bacteria could be introduced as sufficient consortium for biodegradation of this soils with similar texture.


Kin4 kinase delays mitotic exit in response to spindle alignment defects.
For many polarized cells, it is critical that the mitotic spindle becomes positioned relative to the polarity axis. This is especially important in yeast, where the site of cytokinesis is predetermined. The spindle position checkpoint (SPOC) therefore delays mitotic exit of cells with a mispositioned spindle. One component of the SPOC is the Bub2-Bfa1 complex, an inhibitor of the mitotic exit network (MEN). Here, we show that the Kin4 kinase is a component of the SPOC and as such is essential to delay cell cycle progression of cells with a misaligned spindle. When spindles are correctly oriented, Kin4 and Bub2-Bfa1 are asymmetrically localized to opposite spindle pole bodies (SPBs). Bub2-Bfa1 then becomes inhibited by Cdc5 polo kinase with anaphase onset, a prerequisite for mitotic exit. In response to spindle misalignment, Kin4 and Bub2-Bfa1 are brought together at both SPBs. Kin4 now maintains Bub2-Bfa1 activity by counteracting Cdc5, thereby inhibiting mitotic exit.


Synthesis of β-Ca2P2O7:Tb3+ to gamma radiation detection by thermoluminescence.
In this work, luminescent emissions of beta-calcium pyrophosphate doped with terbium ions (β-Ca2P2O7:Tb3+) were studied. The Ca2P2O7:Tb3+ powders were prepared by precipitation and annealed at 900°C for 2h was applied on the powders to observe the beta phase. Radioluminescence measurements showed emission bands related with 5D3 (5D4)→7FJ transitions of Tb3+ ions. Three overlapped peaks at 126, 165 and 220°C were observed in thermoluminescence response. A linear TL dose-response in the range of 0.2-10Gy and an acceptable TL reproducibility were showed by the β-Ca2P2O7:Tb3+ samples exposed to 60Co gamma radiation. The TL glow curves were analyzed by Initial Rise method and Computational Glow-Curve Deconvolution assuming a General Order Kinetic model to evaluate the kinetic parameters related with the TL peaks.


FFT approximation in Alzheimer's disease.
The electroencephalographic modifications that occur during the course of Alzheimer's disease are characterised by an increase in the potential of low frequency bands, a diminution in the potential of alpha activity, and a change in the topographical distribution of the potential of all band frequencies. In this study, the fast Fourier transform (FFT) approximation was used to characterise modifications in the electroencephalogram location or orientation of the source of the dipole equivalent of the delta, theta, alpha1, alpha2, beta1 and beta2 frequencies in 20 with patients with Alzheimer's disease and in a control group of 20 age-matched subjects. A statistical (t-test) comparison of the two groups revealed a significant change in the location of the dipolar source along the vertical axis in 18 (90%) of the patients; this change involved all the frequency bands. There was also a significant movement of the dipolar source of the alpha1 band towards the anterior regions. In addition, the control group showed that there was a significant correlation between age and a more surface expression of the source of the delta, theta, alpha1 and beta1 bands.


Effect of acyl chain composition on salt-induced lamellar to inverted hexagonal phase transitions in cardiolipin.
Salt-induced fluid lamellar (L alpha) to inverted hexagonal (HII) phase transitions have been studied in diphosphatidylglycerols (cardiolipins) with different acyl chain compositions, using 31P nuclear magnetic resonance (NMR) spectroscopy. Cardiolipins with four myristoyl chains, tetramyristoyl cardiolipin (TMCL), and with four oleoyl chains, tetraoleoyl cardiolipin (TOCL), were synthesized chemically. TMCL was found to undergo a thermotropic lamellar gel to lamellar liquid-crystalline phase transition at 33-35 degrees C. This lipid exhibited an axially symmetric 31P-NMR spectrum corresponding to a lamellar phase at all NaCl concentrations between 0 and 6 M. In the case of TOCL, formation of an HII phase was induced by salt concentrations of 3.5 M NaCl or greater. These observations, taken together with earlier findings that bovine heart cardiolipin aqueous dispersions adopt an HII phase at salt concentrations of 1.5 M NaCl or greater, indicate that increasing unsaturation and length of the acyl chains favour formation of the HII phase in diphosphatidylglycerols.


Chemotherapy-induced irreversible alopecia in early breast cancer patients.
The purpose of this work is to determine the prevalence of chemotherapy-induced irreversible alopecia (CIIA), which is defined as an alopecia that exists at least 6 months after completion of chemotherapy and factors affecting CIIA in early breast cancer patients. We performed a cross-sectional study. We retrospectively identified breast cancer patients who had received AC (Adriamycin, Cyclophosphamide) or AC-T (AC followed by Taxane) as neoadjuvant or adjuvant chemotherapy. We conducted questionnaire survey regarding alopecia and measured hair density using phototrichogram. From February 2015 to May 2015, among 265 patients who responded properly to the questionnaire, the women who answered they had severe alopecia (alopecia > 50% of scalp) were 19 patients (7.2%). AC-only and AC-T treated patients reported severe alopecia in 2.7% and 10.5%, respectively, which were significantly different (p < 0.001). Mean hair density was 75 hair/cm2 (range 42-112) and 75.2/cm2 (range 48.3-102) on occipital area and vertex area, respectively. Hair loss was the most frequent in parietal area (42.6%). Half of total patients (46%) and 73% of CIIA patients regarded that their hair became thinner after chemotherapy CONCLUSIONS: We found that significant proportion of early breast cancer patients were suffering from severe CIIA, especially when they had been treated with AC followed by taxane regimen.


Right ventricular involvement in myocardial infarction and cardiogenic shock.
Right ventricular involvement in acute myocardial infarction and cardiogenic shock has received little attention by clinicians and researchers, although its pathophysiology, clinical presentation, and natural history are distinctly different from those of left ventricular infarction and associated cardiogenic shock. Right ventricular shock has important therapeutic implications for the management of patients, which need to be recognised. Investigators at the SHOCK Registry (Alice Jacobs and colleagues, J Am Coll Cardiol 2003; 341: 1273-79) evaluated 49 patients with cardiogenic shock predominantly due to right ventricular infarction and compared them with 884 patients with cardiogenic shock and predominantly left ventricular failure. Perhaps surprisingly, these investigators found that the in-hospital mortality of patients with right ventricular shock was not significantly lower than that of patients with left ventricular shock (53% vs 61%, p=0.296), despite the fact that patients with right ventricular shock were younger, with a lower prevalence of previous infarctions, fewer anterior infarct locations, and less multivessel disease. There was a shorter median time between index infarction and diagnosis of shock in patients with right ventricular shock. In multivariate analysis, right ventricular shock was not an independent predictor of lower in-hospital mortality. WHERE NEXT? The unexpectedly high mortality of patients with cardiogenic shock due to predominantly right ventricular infarction challenges the general notion that right ventricular involvement in myocardial infarction has only little relevance for patient's outcome. Therefore, more attention should be given to the detection of right ventricular involvement in acute myocardial infarction and particularly in cardiogenic shock. If right ventricular shock is diagnosed, urgent reperfusion of the infarct related artery and appropriate circulatory support are required.


Envelope modulation spectral (EMS) analyses of solo reading and choral reading conditions suggest changes in speech rhythm in adults who stutter.
A longstanding finding in persons who stutter is that stuttering frequency significantly reduces during choral reading when compared to the solo reading condition. Here, we tested the hypothesis that this decrease in stuttering frequency may be because speech of the normal speaker dictates the speech rhythm of a person who stutters. We used an automated, sensitive acoustic technique-Envelope Modulation Spectral (EMS) analysis- that allowed us to document speech rhythm. Seventeen adults who stutter (AWS) read sentences under two conditions: solo reading and choral reading. Percentage of syllables stuttered (%SS), the rate of speech, and speech rhythm were calculated from the recorded sentences from AWS. Further, AWS speech rhythm during solo reading was compared with typical adults. EMS was extracted for the full signal and seven-octave bands. From the extracted envelope six predictor variables (peak frequency, peak amplitude, energy in the spectrum 3-6 Hz, energy in the spectrum from 0 to 4 Hz, energy in the spectrum from 4 to 10 Hz, and the ratio of energy below4 Hz/above 4 Hz) were computed. Significant decrease in stuttering frequency and rate of speech was noticed in choral reading when compared to the solo reading condition. Further, analysis of EMS results suggested the statistically significant difference between two reading conditions (for peak frequency and peak amplitude), and between two groups for all predictor variables. Overall, current results highlight that decreases in stuttering during the choral reading is characterized by a decrease in rate and changes in some aspects of speech rhythm in Kannada speaking AWS.


Hypercrosslinked strong cation-exchange polymers for selective extraction of serum purine metabolites associated with gout.
In this study, hypercrosslinked strong cation-exchange polymer resins (HXLPP-SCX) were synthesized and employed as selective sorbents for the solid-phase extraction (SPE) of basic purine metabolites associated with gout. The HXLPP-SCX material was prepared based on hypercrosslinking reactions and sulfonated with concentrated H2SO4. This synthetic procedure is facile and efficient without using highly toxic reagent. The resulting resins were characterized in the form of monodisperse microspheres (mean diameters of 3‒5μm) with narrow pore size (2.1nm) and relatively high specific surface areas (801m(2)/g). The polymers also possess high ion-exchange capacity (IEC, 2.22mmol/g) and good adsorption and selectivity performances for basic compounds. The resins used as SPE sorbents permit the selective enrichment of three pivotal purine metabolites (hypoxanthine, xanthine and inosine) in human serum followed by HPLC analysis. Method validation including linearity range, sensitivity, accuracy and reproducibility were evaluated. This method was exemplarily applied in the analysis of serum purines in gout patients and healthy controls. The present results demonstrate a promising potential of this HXLPP-SCX material for the clinical sample pretreatment.