Asymptomatic bacteriuria: review and discussion of the IDSA guidelines.
Asymptomatic bacteriuria is a common finding, but is usually benign. Screening and treatment of asymptomatic bacteriuria is only recommended for pregnant women, or for patients prior to selected invasive genitourinary procedures. Healthy women identified with asymptomatic bacteriuria on population screening subsequently experience more frequent episodes of symptomatic infection, but antimicrobial treatment of asymptomatic bacteriuria does not decrease the occurrence of these episodes. Clinical trials in spinal-cord injury patients, diabetic women, patients with indwelling urethral catheters, and elderly nursing home residents have consistently found no benefits with treatment of asymptomatic bacteriuria. Negative outcomes with antimicrobial treatment do occur, including adverse drug effects and re-infection with organisms of increasing resistance. Optimal management of asymptomatic bacteriuria requires appropriate implementation of screening strategies to promote timely identification of the selected patients for whom treatment is beneficial, and avoidance of antimicrobial therapy where no benefit has been shown.


Immunobiological properties of a carboxy-terminal 53-amino acid peptide of the beta subunit of human chorionic gonadotropin.
Lengthening of the carboxy terminus unique region of beta-hCG from 30 to 45 amino acids was found in previous studies to improve immunogenicity and hormone neutralization capacity. The present study was carried out to determine whether further elongation of the peptide to 53 amino acids enhances to hormone neutralization capacity without loss of specificity characteristics. The peptide 93--145 of beta-hCG with substitution of cysteines at 93, 100 and 110 by alpha-aminobutyric acid was synthesized by solid phase and conjugated to tetanus toxoid by an active ester method. Rabbit antibodies against this conjugate reacted with CTP-53 and CTP-45 with a parallel slope in anti-CTP-53-[125I]Tyr-CTP--53 radioimmunoassay system. Other CTPs, e.g. CTP-26, CTP-31 and CTP-35 competed with lower efficiency; 50% inhibition of binding was obtained with 10-100 pmol/tube with these peptides instead of 0.5 pmol/tube for the homologous CTP-53. Anti-CTP-53 reacted with both beta-hCG and hCG but around twenty times greater amount of hCG was required to give 50% inhibition of binding as compared to CTP-53. The antigen binding capacity of anti-CTP-53 was around 4000 ng/ml for CTP-53 and 25 ng/ml for hCG. The anti-CTP-53 sera retained non-cross-reactivity with hLH as determined by direct binding with [125I]hLH and by competitive inhibition of CTP-53 binding with anti-CTP-53. Anti-CTP-53 neutralized the bioactivity of hCG in the Leydig cell bioassay and in the mouse uterine weight gain assay. Anti-CTP-53 antibodies were about three times more effective than anti-CTP-45 in their capacity to neutralize the bioactivity of hCG, though still substantially poorer than anti-beta-hCG sera in this respect.


The structure of Klebsiella serotype II capsular polysaccharide.
Using periodate oxidation, methylation analysis, the characterization of oligosaccharides obtained by partial acid hydrolysis, p.m.r. spectroscopy, and analytical ultracentrifugation, the structure of the (mildly alkali-treated) Klebsiella serotype 11 capusular polysaccharide has been elucidated. The tetrasaccharide repeating-unit comprises the sequence yields 3)-beta-D-Glcp-(1 yields 3)-beta-D-GlcUAp-(1 yields 3)-alpha-D-Galp-(1 yields with a 4,6-O-(1-carboxyethylidene)-alpha-D-galactosyl residue linked to O-4 of the glucuronic acid residue. The structural basis for some serological cross-reactions of the Klebseilla K11 antigen is discussed, and it is shown that rabbit antisera against the Klebsiella K11 test-strain predominantly contain K agglutinins specific for branch-terminal 4,6-O-(1-carboxyethylidene)-D-galactose.


[Characteristics of the functional organization of the kidney medullary substance in desert birds].
The contents of sodium, potassium, magnesium and urea equally increases from the renal cortex to medulla in desert birds. This process is due, mainly, to the countercurrent multiplior of the medulla and, under natural conditions, depends on the length of medullar cone and the number of Henle's loops.


There are things that we know that we know, and there are things that we do not know we do not know: Confidence in decision-making.
Metacognition, the ability to think about our own thoughts, is a fundamental component of our mental life and is involved in memory, learning, planning and decision-making. Here we focus on one aspect of metacognition, namely confidence in perceptual decisions. We review the literature in psychophysics, neuropsychology and neuroscience. Although still a very new field, several recent studies suggest there are specific brain circuits devoted to monitoring and reporting confidence, whereas others suggest that confidence information is encoded within decision-making circuits. We provide suggestions, based on interdisciplinary research, to disentangle these disparate results.


Dysfunctional synaptic pruning by microglia correlates with cognitive impairment in sleep-deprived mice: Involvement of CX3CR1 signaling.
Microglia are involved in sleep/wake cycles and the response to sleep loss. Synaptic pruning by microglia is necessary for central nervous system circuit refinement and contributes to cognitive function. Here, we investigated whether and how microglia-mediated synaptic pruning may be involved in cognitive deficits induced by sleep deprivation in mice. Mice were deprived of sleep by leaving them in a spontaneously rotating rod for 72 h, after which their cognitive function was assessed using an object location test, Y maze, and novel object recognition test. Sleep deprivation lowered the discrimination index for familiar locations in the object location test and Y maze. Microglial morphology was assessed using immunostaining Iba1, while microglia-mediated synaptic pruning was examined based on immunostaining PSD95, CD68, and Iba1. Sleep deprivation also activated microglial cells in the hippocampus, as reflected in bigger soma as well as fewer and shorter branches than normal sleep. Sleep deprivation downregulated phagocytic markers and internalization of postsynaptic protein 95 (PSD95), suggesting impaired synaptic pruning. CX3C motif chemokine receptor 1 (CX3CR1) signaling was detected in in vitro experiments. Sleep deprivation also downregulated CX3CR1. Activation of CX3CR1 signaling increased phagocytosis activity of BV2 microglia in vitro. Sleep deprivation dysregulates microglial CX3CR1 signaling and inhibits synaptic pruning, contributing to associated cognitive deficits. These findings identify CX3CR1-dependent synaptic pruning as a potential therapeutic target in which sleep deprivation causes recognition impairments.


Retinal microvascular network attenuation in Alzheimer's disease.
Cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. Retinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. Retinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62-0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63-0.97]) were more likely to have AD after appropriate adjustment. Patients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD.


Activation of human ribosomal genes by 5-azacytidine.
Cultured human fibroblasts were exposed to 5-azacytidine which inhibits methylation of newly synthesized DNA. A significant increase in the mean number of Ag-stained active nucleolus organizers has been observed in treated cells. This suggests that DNA methylation is involved in modulation of human rRNA synthesis.


Assessment of differential item functioning of the PHQ-9, HADS-D and PROMIS-depression scales in persons with and without multiple sclerosis.
We tested for the presence of differential item functioning (DIF) in commonly used measures of depressive symptoms, in people with multiple sclerosis (MS) versus people with a psychiatric disorder without MS. Participants included individuals with MS, or with a lifetime history of a depressive or anxiety disorder (Dep/Anx) but no immune-mediated inflammatory disease. Participants completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), and the Patient Reported Outcome Measurement Information System (PROMIS)-Depression. We assessed unidimensionality of the measures using factor analysis. We evaluated DIF using logistic regression, with and without adjustment for age, gender and body mass index (BMI). We included 555 participants (MS: 252, Dep/Anx: 303). Factor analysis showed that each depression symptom measure had acceptable evidence of unidimensionality. In unadjusted analyses comparing the MS versus Dep/Anx groups we identified multiple items with evidence of DIF, but few items showed DIF effects that were large enough to be clinically meaningful. We observed non-uniform DIF for one PHQ-9 item, and three HADS-D items. We also observed DIF with respect to gender (one HADS-D item), and BMI (one PHQ-9 item). For the MS versus Dep/Anx groups, we no longer observed DIF post-adjustment for age, gender and BMI. On unadjusted and adjusted analyses, we did not observe DIF for any PROMIS-D item. Our findings suggest that DIF exists for the PHQ-9 and HADS-D with respect to gender and BMI in clinical samples that include people with MS whereas DIF was not observed for the PROMIS-Depression scale.


Incorporation of 3H-thymidine in the nephron of Gasterosteus aculeatus L. and its stimulation by methyltestosterone. A high-speed scintillation autoradiographic study.
The rate of 3H-thymidine incorporation into different parts of the renal proximal tubule of female sticklebacks treated with methyltestosterone was investigated using high-speed scintillation autoradiography. The results are compared with those from normal males before or after mucous transformation of the kidney. Labelled cells are observed in all parts of the proximal tubule, with marked variations from one segment to another. They are numerous in part 2 of the proximal tubule, particularly in the distal region. Male sex hormones affect the labelling rate in all parts of the nephron, especially in the distal region of part 2 of the proximal tubule. In that particular area, new tubule formation by budding is observed in some individuals, but this process does not appear to be a general one. Correlation between the frequency of these figures and the time of treatment could not be established. Comparing the action of sex hormones in females with that in males reveals a difference in reactivity in the proximal zone of part 2 of the proximal tubule, where methyltestosterone has a strong action in females; in contrast, in "mature" and "immature" males, only a few labelled cells are present in this region. It is concluded that kidney enlargement during the breeding season does not result only from a swelling of cells belonging to part 2 of the proximal tubule, as was generally believed, but also from a lengthening or even a proliferation of the proximal tubules, induced by an increase in mitotic activity controlled by male sex hormones.


High performance liquid chromatographic enantioseparation development and analytical method characterization of the carboxylate ester of evacetrapib using an immobilized chiral stationary phase with a non-conventional eluent system.
Using multiple HPLC chromatographic modes and various chiral columns in the context of an automated screening system, a potential separation was initially identified for the methyl ester of evacetrapib and its stereoisomers using an immobilized polysaccharide-based HPLC column. The bonded nature of this column, the Chiralpak(®) IC, allows for enhanced separation development with a diverse solvent range not amenable to standard coated chiral stationary phases. The ternary eluent system ultimately identified provided isomer resolutions not obtainable via the more established hexane/alcohol or polar organic chromatographic modes. A systematic separation development process is described, first for the resolution of the isomers, and later incorporating five potential impurities. A robust separation system was eventually developed that effectively resolves all compounds within a reasonable analysis time.


Neuropeptide Y-like immunoreactivity of plasma during hypoglycaemia in man.
Previous studies have demonstrated that plasma Neuropeptide Y-like immunoreactivity (NPY-LI) increases after activation of sympathetic nerves. To test the hypothesis that the adrenal medulla may also be a significant source of circulating plasma NPY-LI and to determine if NPY is co-released with adrenal catecholamines, we have measured the peripheral venous concentrations of NPY-LI, adrenaline and noradrenaline in six patients, before and after induction of hypoglycaemia as part of pituitary function tests that also tested gonadotrophin and thyroid stimulating hormone release. The plasma adrenaline concentration was increased approximately 15 times (p less than 0.05) relative to baseline at 30 mins and remained elevated for the 90 minutes of the study. The plasma concentration of both noradrenaline and NPY-LI remained unchanged. These results failed to demonstrate an increase in the amount of NPY-LI released into the plasma during stimulation of the adrenal medulla with hypoglycaemic stress in man. They do not support significant co-release of NPY with adrenaline from the adrenal medulla in man, nor a physiological role for NPY as an adrenal hormone in human subjects in this situation.


Clinical and laboratory evaluation of 8-methoxypsoralen toxicity.
Twenty-seven patients with vitiligo took (Meladinine 8-methoxypsoralen) for 2 to 12 years. They were selected from those patients who, in an attempt to get a more rapid repigmentary response, exceeded the advised doses by ingesting from 7-16 tablets (equivalent to 70-160 mg) per day. These regimens were well tolerated. Hepatic and renal function were not affected.


Prognostic value of elevated preoperative serum CA125 in ovarian tumors of low malignant potential: a multinational collaborative study (ANZGOG0801).
Previous studies on prognostic factors in ovarian tumors of low malignant potential (LMP) were too small for robust conclusions. We examined the prognostic impact of preoperative serum CA125 ≥ 50 U/ml levels in patients diagnosed with ovarian LMP tumors in a large multinational cohort. This retrospective study included 940 patients with ovarian LMP tumors diagnosed between 1985 and 2008 at six gynecologic cancer centers. Patients either had radical treatment (bilateral salpingo-oophorectomy with or without hysterectomy) or conservative, fertility-sparing treatment. Multivariate Cox proportional hazard models were used to determine independent prognostic factors for disease-free (DFS) and overall survival (OS). Based on receiver operating characteristic curve (ROC), a preoperative serum CA125 level ≥ 50 U/ml was considered "elevated". CA125 was more often elevated in serous than in mucinous tumors and in advanced FIGO stages (2 to 4) compared to stage 1. DFS at 5 years was 89% and 95% in patients with elevated and normal CA125 levels (p<0.05). Similarly, the 5-year OS was 90% among patients with elevated CA125 compared to 95% among patients with normal levels (p<0.05). For both DFS and OS elevated CA125 levels and advanced stages of the disease were independent prognostic factors. Analysis of subgroups revealed that CA125 was only prognostic in serous LMP tumors. In the context of serous ovarian LMP tumors, elevated preoperative serum CA125 represents a biomarker independently associated with impaired disease-free and overall survival. CA125 is available in most centers and could inform surgeons about the risk of treatment failure.


It's not just an ileus: disparities associated with ileus following ventral hernia repair.
We sought to identify risk factors associated with postoperative ileus following ventral hernia repair. Utilizing the Nationwide Inpatient Sample (NIS) from 2008 to 2012, we identified adult patients that underwent either open or laparoscopic hernia repair for umbilical and ventral hernias with a diagnosis of umbilical/ventral hernia. We excluded cases with diagnosis of obstruction and bowel gangrene that underwent bowel resection, or with missing data. Risk variables of interest were age, sex, race, income status, insurance status, elective admission, comorbidity status (using the validated van Walraven Score), complications (mechanical, respiratory, postoperative infection, cardiovascular, intraoperative), morbid obesity, procedure type, conversion to open, mesh use, hospital type (rural, urban non-teaching, urban teaching), bed size, and region (northeast, midwest, south, west). Univariate analysis comparing patients with ileus vs control was performed. We then performed multivariable analysis using logistic regression, adjusting for all the risk variables, with ileus as the dependent variable. 30,912 patients were identified that met criteria. Of these, 2660 (8.61%) had postoperative ileus during their stay at the hospital. Univariate analysis showed all risk variables were associated with development of ileus with the exception of income status (p = 0.2903), elective admission (p = 0.7989), mesh use (p = 0.3620), and hospital bed size (p = 0.08351). Median length of stay was 7 days in the ileus cohort vs 3 days in control (p < 0.0001). Median total charges (adjusted to 2012 dollars) was $54,819 vs $35,058 (p < 0.0001). We then performed logistic regression adjusting for all risk variables and found that age (OR 1.66, p < 0.0001), male sex (OR 1.51, p < 0.0001), Black race (OR 1.49, p < 0.0001), comorbidity status (OR 1.12, p < 0.0001), laparoscopic cases converted to open (OR 1.55, p < 0.0001), postoperative complications (mechanical: OR 2.32, p < 0.0001, respiratory: OR 1.54, p < 0.0001, postoperative infection: OR 2.12, p < 0.0001, cardiovascular: OR 1.57, p = 0.0006, intraoperative: OR 1.29, p = 0.0200) were independently associated with increased risk of ileus. However, laparoscopic vs open (OR 0.76, p < 0.0001), elective admission (OR 0.91, p = 0.0378), and northeast vs south hospital region (OR 0.74, p < 0.0001) were independently associated with decreased risk of ileus. We performed a large observational study looking for risk factors associated with ileus following ventral hernia repair. Race and region of treatment are independent risk factors associated with ileus following ventral hernia repair, and a potential source of disparities in care and increased admission length and higher cost of care. Further prospective studies are warranted.


Anchoring visual subjective experience in a neural model: the coarse vividness hypothesis.
Subjective experience often accompanies perception and cognition. This elusive feeling is difficult to characterize, both theoretically and experimentally. Perceptual subjective experience is at the heart of a theoretical debate in consciousness research: does it correspond to a genuine psychological and biological process independent from cognitive abilities, or is it a cognitive illusion, a post-hoc construct, implying that perceptual consciousness can be reduced to a sum of cognitive functions? We reconsider this debate in the light of known properties of the visual system, derived from studies on visual object and scene recognition but not specifically targeting consciousness issues. We propose here that initial visual subjective experience is characterized by two key properties, coarseness and vividness: initial subjective experience is integrated, meaningful, but does not contain detailed information. Subjective experience is likely to arise first in high-level visual areas, in which information is encoded in a coarse and integrated manner. We propose that initial subjective experience is related to the concept of "vision at a glance", thought to result from a fast, implicit feed-forward sweep of activity in the visual system progressing from low-level areas to high-level areas (Hochstein and Ahissar (2002)Neuron, 36, 791-804). The details needed to overtly guide behavior would be retrieved in a secondary processing step of "vision with scrutiny", proceeding in a feed-back manner, from high-level to low-level areas. This secondary and optional descending process could thus later enrich conscious visual percepts with details. Our hypothesis provides parsimonious explanations for two intriguing findings: the double dissociation between attention and consciousness, and the mismatch between objective measures and subjective reports, that is sometimes used to argue that subjective experience is an illusion. We argue here that because visual subjective experience is initially coarse, it should not be probed by asking subjects to specify details. The coarse vividness hypothesis therefore offers a framework that accounts for the existence of an initial genuine subjective experience, defined by its coarseness and vividness, optionally followed by more refined and detailed processing that could underlie finer perceptual and cognitive abilities.


Comment on "Long-lived giant number fluctuations in a swarming granular nematic".
Narayan et al. (Reports, 6 July 2007, p. 105) reported giant number fluctuations attributed to curvature-driven active currents specific for nonequilibrium nematic systems. We present data demonstrating that similar results can be found in systems of spherical particles due either to inelastic clustering or persistent density inhomogeneity, suggesting two alternative explanations for their results.


Determination of the Hypnotic Potency in Rats of the Novel Ketamine Ester Analogue SN 35210.
Ketamine is a rapidly acting dissociative anaesthetic drug with additional sympathomimetic, analgesic, and antidepressant properties. Despite these advantages, clinical use is curtailed by prolonged psychomimetic effects apparent over the entire dose spectrum. In this study, we report on the hypnotic potency of SN 35210, the first ketamine ester-analogue designed for rapid offset via esterase-mediated hydrolysis. Thirty-three adult Sprague Dawley rats received intravenous racemic ketamine (n = 14), racemic SN 35210 (n = 19), S-enantiomer SN 35210 (n = 17), or R-enantiomer SN 35210 (n = 15), in crossover design. The ability to induce loss of righting reflex (LORR) at a given dose, the duration of righting reflex loss, and the time to return of normal behaviours were recorded. The ED50 for LORR was determined for all agents. The ED50 for righting reflex loss was racemic ketamine 9.6 (95% CI 8.5-10.9) mg/kg, racemic SN 35210 10.4 (95% CI 9.5-11.5) mg/kg, S-enantiomer SN 35210 10.6 (95% CI 9.1-11.8), and R-enantiomer SN 35210 10.3 (95% CI 9.1-11.4) mg/kg. The duration of righting reflex loss and time to return to normal behaviours were approximately 5 times greater for racemic ketamine than all 3 SN 35210 ester analogues. Racemic, and R and S-enantiomer SN 35210, produced LORR in rats at similar doses to the parent compound ketamine. The duration of righting reflex loss, and duration of behavioural aberration, was significantly reduced for all SN 35210 analogues.


Detection of compatibility between baclofen and excipients with aid of infrared spectroscopy and chemometry.
In the paper infrared (IR) spectroscopy and multivariate exploration techniques: principal component analysis (PCA) and cluster analysis (CA) were applied as supportive methods for the detection of physicochemical incompatibilities between baclofen and excipients. In the course of research, the most useful rotational strategy in PCA proved to be varimax normalized, while in CA Ward's hierarchical agglomeration with Euclidean distance measure enabled to yield the most interpretable results. Chemometrical calculations confirmed the suitability of PCA and CA as the auxiliary methods for interpretation of infrared spectra in order to recognize whether compatibilities or incompatibilities between active substance and excipients occur. On the basis of IR spectra and the results of PCA and CA it was possible to demonstrate that the presence of lactose, β-cyclodextrin and meglumine in binary mixtures produce interactions with baclofen. The results were verified using differential scanning calorimetry, differential thermal analysis, thermogravimetry/differential thermogravimetry and X-ray powder diffraction analyses.


A high-efficient and salt-rejecting 2D film for photothermal evaporation.
The solar-driven desalination is seen as a sustainable way to combat water scarcity. However, the solar steam generation efficiency has long been restricted by the high vaporization enthalpy of water and low energy density of natural sunlight. We introduced graphene oxide (GO) cross-linked with polyethyleneimine (PEI) as the photothermal material, with the enriched ammonic functional groups in modified GO membrane (GPM) activating water molecules to evaporate with much lower energy consumption. The vaporization enthalpy at the air-film interface is reduced up to 42% in GPM film by tuning the thermodynamic states of water. Consequently, GPM film enables a high evaporation rate of 2.48 kg m-2 h-1 with 95.7% energy conversion efficiency under 1 sun. With the aid of positive charges introduced by hydrolysis of PEI, the GPM exhibits excellent salt resistance and delivers an evaporation rate around 1.8 kg m-2 h-1 when treating 20 wt % NaCl solution.


Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis.
It has been recently demonstrated that NKG2D is an activating costimulatory receptor on natural killer (NK) cells, natural killer T (NKT) cells, activated CD8(+) T cells, and gammadelta T cells, which respond to cellular stress, such as inflammation, transformation, and infection. Here we show that intestinal inflammation in colitic SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells is characterized by significant increase of CD4(+)NKG2D(+) T cells and constitutive expression of NKG2D ligands, such as H60, Mult-1, and Rae-1, by lamina propria CD11c(+) dendritic cells. Furthermore, treatment with nondepleting and neutralizing anti-NKG2D MAb after transfer of CD4(+)CD45RB(high) T cells into SCID mice significantly suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of IFN-gamma by lamina propria CD4(+) T cells. These findings demonstrate that NKG2D signaling pathway is critically involved in CD4(+) T cell-mediated disease progression and suggest a new therapeutic target for inflammatory bowel diseases.


Effect of dorsal periaqueductal gray lesion on cardiovascular and behavioural responses to contextual conditioned fear in rats.
Contextual conditioned fear in the rat is characterized by a freezing immobility associated with a marked increase in blood pressure, a slow increase in heart rate, and ultrasonic vocalizations. A previous Fos study also revealed a marked activation of the ventrolateral part of the periaqueductal gray (VLPAG) and a much smaller activation of its dorsal part (DPAG). Recent chemical blockade experiments indicate that the main role of the VLPAG in the response is to impose the immobility necessary for the expression of the freezing component. We now test the role of the DPAG to see if its small activation (as revealed by Fos) is of any functional significance in the contextual fear response. Large N-methyl-D-aspartate (NMDA) excitotoxic lesions that destroyed most of the DPAG were made in 10 rats. Another group of 10 rats had sham lesions with saline. The animals were then implanted with blood pressure telemetric probes, fear conditioned, and finally tested. There was no significant difference in the amount of freezing and in the blood pressure response between the two groups. However, there was a complete abolition of ultrasonic vocalizations and a significantly greater increase in heart rate in the DPAG-lesioned group. The effect on vocalization and heart rate may be explained by lesion of adjacent structures: the lateral PAG and the superior colliculus (baroreflex alteration), respectively. Thus, most of DPAG appears to play little role in the expression of the contextual fear response.


Central histaminergic neurons regulate rabbit tracheal tension through the cervical sympathetic nerve.
We previously showed that stimulation of the posterior hypothalamus decreases tracheal tension and involves central histaminergic neurons. In the present study, we reveal that central histaminergic neurons project to the rostral ventrolateral medulla and affect cervical sympathetic nervous activity in rabbits. Administration of histamine into the fourth ventricle increased cervical sympathetic nervous activity and decreased tracheal tension. These effects were inhibited by administration of a histamine H receptor antagonist, pyrilamine, into the fourth ventricle. Unilateral injection of DL-homocysteic acid into the tuberomammillary nucleus increased cervical sympathetic nervous activity, an effect was antagonized by bilateral injection of pyrilamine into the rostral ventrolateral medulla. The pulse correlogram between the stimulation pulse applied to the tuberomammillary nucleus and the cervical sympathetic nerve activity showed a mode at 150 to 200 ms, which was reduced by pyrilamine administration into the fourth ventricle. Fibers anterogradely labeled by Phaseolus vulgaris leucoagglutinin (PHA-L) injected into the tuberomammillary nucleus were distributed in the A1, A2, C1, and C2 areas which are determined by tyrosine hydroxylase-immunohistochemistry. PHA-L positive neurons were in close contact with tyrosine hydroxylase-immunoreactive neurons in these four areas. Cell bodies in the tuberomammillary nucleus retrogradely labeled with fluorogold from the rostral ventrolateral medulla were immunoreactive with histamine. These results suggest that an excitatory efferent pathway projects from the tuberomammillary nucleus to the cervical sympathetic nerve and that the histaminergic neurons of this pathway influence tracheal tension through the rostral ventrolateral medulla.


Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding.
The aim of this study was to investigate a potential therapy for left ventricular assist device (LVAD)-associated bleeding. Nonsurgical bleeding is the most frequent complication of LVAD support. Recent evidence has demonstrated that supraphysiological shear stress from continuous-flow LVADs accelerates von Willebrand factor (vWF) metabolism by the action of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) (the vWF protease). An acquired vWF deficiency causes bleeding. This suggests that ADAMTS-13 is a clinical target to reduce vWF degradation. We tested the hypothesis that inhibition of ADAMTS-13 with doxycycline, an inexpensive, clinically approved drug, reduces vWF degradation during shear stress. Whole blood was collected from human donors (n = 15), and purified, recombinant ADAMTS-13 protein was obtained. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the dose relationship between doxycycline and ADAMTS-13 activity prior to shear stress (n = 10). To determine the effect of shear stress, plasma and recombinant ADAMTS-13 were exposed to LVAD-like supraphysiological shear stress (approximately 175 dyne/cm(2)). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting (n = 10). Förster resonance energy transfer was used to quantify plasma ADAMTS-13 activity (n = 10). An ELISA was used to quantify vWF:collagen binding activity. Platelet aggregometry was performed with adenosine 5'-diphosphate, collagen, and ristocetin (vWF-platelet pathway) agonism (n = 10). Doxycycline significantly decreased plasma ADAMTS-13 activity (p = 0.01) and the activity of recombinant human ADAMTS-13 protein by 21%. After plasma was exposed to shear stress, the same pattern of vWF degradation was observed as previously reported for LVAD patients, and vWF:collagen binding activity decreased significantly (p = 0.002). Doxycycline significantly decreased ADAMTS-13 activity (p = 0.04) and the activity of recombinant ADAMTS-13 by 18%, protected large vWF multimers from degradation, and significantly decreased the levels of the 5 smallest vWF fragments by 12 ± 2% (p < 0.05). As a result, vWF:collagen binding activity was significantly restored (p = 0.004). ADAMTS-13 inhibition with doxycycline did not hyperactivate platelets. Inhibition of ADAMTS-13 by doxycycline decreased vWF degradation and improved vWF function during supraphysiological shear stress without hyperactivating platelets. ADAMTS-13 is a clinical target to reduce vWF degradation, improve vWF function, and potentially reduce bleeding during LVAD support.


Hematologic and Oncologic Emergencies in the Pediatric Intensive Care Unit: What Nurses Should Know.
Most children admitted to the pediatric intensive care unit with a new or reoccurring hematology or oncology diagnosis are at high risk for developing a hematologic or oncologic emergency. Although these children represent a low percentage of pediatric critical care admissions, their acuity is high, and their care is complicated and challenging. Nurses are an essential part of the interprofessional team of providers who care for these critically ill patients. Experience recognizing acute decompensation and excellent assessment and communication skills significantly improve patient outcomes.


Composite lymphoma of concurrent T zone lymphoma and large cell B cell lymphoma in a dog.
Evolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes. An 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL. The occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately "composite lymphoma".


Synthesis and root growth-inhibitory activity of 2- and 3-(haloacetylamino)-3-(2-furyl)propanoic acids.
A convenient synthesis of 2- and 3-(chloroacetylamino)-3-(2-furyl)propanoic acids (6a, 7a) and their fluoro analogs were developed. Both 6a and 7a showed 51-55% root growth-inhibitory activity towards rape seedlings at the concentration of 1.0x10(-4) M.


Dominant negative knockout of p53 abolishes ErbB2-dependent apoptosis and permits growth acceleration in human breast cancer cells.
We previously reported that the ErbB2 oncoprotein prolongs and amplifies growth factor signalling by impairing ligand-dependent downregulation of hetero-oligomerised epidermal growth factor receptors. Here we show that treatment of A431 cells with different epidermal growth factor receptor ligands can cause growth inhibition to an extent paralleling ErbB2 tyrosine phosphorylation. To determine whether such growth inhibition signifies an interaction between the cell cycle machinery and ErbB2-dependent alterations of cell signalling kinetics, we used MCF7 breast cancer cells (which express wild-type p53) to create transient and stable ErbB2 transfectants (MCF7-B2). Compared with parental cells, MCF7-B2 cells are characterised by upregulation of p53, p21(WAF) and Myc, downregulation of Bcl2, and apoptosis. In contrast, MCF7-B2 cells co-transfected with dominant negative p53 (MCF7-B2/Delta p53) exhibit reduced apoptosis and enhanced growth relative to both parental MCF7-B2 and control cells. These data imply that wild-type p53 limits survival of ErbB2-overexpressing breast cancer cells, and suggest that signals of varying length and/or intensity may evoke different cell outcomes depending upon the integrity of cell cycle control genes. We submit that acquisition of cell cycle control defects may play a permissive role in ErbB2 upregulation, and that the ErbB2 overexpression phenotype may in turn select for the survival of cells with p53 mutations or other tumour suppressor gene defects.


In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells.
Increasing evidence from small animal models shows that myeloid-derived suppressor cells (MDSCs) can play a crucial role in inhibiting allograft rejection and promoting transplant tolerance. We identified CD3(-)CD20(-)HLA-DR(-)CD14(+)CD33(+)CD11b(+) cells in peripheral blood of healthy rhesus macaques. These putative monocytic MDSCs constituted 2.1% ± 1.7% of lin(-)HLA-DR(-) peripheral blood mononuclear cells. Administration of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF increased their incidence to 5.3% ± 3.4%. The total number of MDSCs that could be flow sorted from a single whole rhesus leukapheresis product was 38 ± 13 × 10(6) (n = 10 monkeys). Freshly isolated or cryopreserved MDSCs from mobilized monkeys incorporated in cultures of anti-CD3- and anti-CD28-stimulated autologous T cells markedly suppressed CD4(+) and CD8(+) T cell proliferation and cytokine secretion (interferon γ, IL-17A). Moreover, these MDSCs enhanced CD4(+)CD25(hi)Foxp3(+) regulatory T cell (Treg) expansion while inhibiting proliferation of activated memory T cells and increasing Treg relative to effector and terminally differentiated memory T cells. Inhibition of arginase-1, but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect of the MDSCs on CD8(+) T cell proliferation. Consequently, functional MDSCs can be isolated from nonhuman primates for prospective use as therapeutic cellular vaccines in transplantation.


Musculoskeletal Tissue Engineering Using Fibrous Biomaterials.
In tissue engineering, scaffolds should provide the topological and physical cues as native tissues to guide cell adhesion, growth, migration, and differentiation. Fibrous structure is commonly present in human musculoskeletal tissues, including muscles, tendons, ligaments, and cartilage. Biomimetic fibrous scaffolds are thus critical for musculoskeletal tissue engineering. Electrospinning is a versatile technique for fabricating nanofibers from a variety of biomaterials. However, conventional electrospinning can only generate 2D nanofiber mats. Postprocessing methods are often needed to create 3D electrospun nanofiber scaffolds. In this chapter, we present two novel electrospinning-based scaffold fabrication techniques, which can generate 3D nanofiber scaffolds in one-station process: divergence electrospinning and hybrid 3D printing with parallel electrospinning. These techniques can be applied for engineering tissues with aligned fiber structures.


Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia.
It is concluded from a review of the literature and a pilot survey that schizophrenic patients more frequently have a history of obstetric complications (OCs) than do other psychiatric patients and normal subjects. OCs are associated with increased cerebral ventricular size in both infancy and adulthood, and are more common among non-familial schizophrenic patients. Neonatal cerebrovascular events consequent upon OCs provide a mechanism to explain the increased risk of neurodevelopmental deviance and later schizophrenia.


The significance of CT scan or MRI in the evaluation of salivary gland tumors.
Imaging modalities such as CT scan or MRI are frequently employed for the diagnosis of neoplastic lesions in the salivary glands. To evaluate the efficacy of the CT scan and the MRI in differentiating malignant neoplasm from benign lesions, 120 CT scans and 31 MRIs were retrospectively analyzed from 147 patients with salivary gland masses. All images were analyzed focusing on the presence of several relevant features. The pathologic results were matched with radiological features and also tabulated with radiological assessment. For the CT scans, the contour and margin of the lesion and tissue plane obliteration were found to be statistically significant indicators for malignant neoplasms. Among 69 CT scans interpreted as 'benign' by a radiologist, five cases (7%) were histologically diagnosed as 'malignant'. On the other hand, 20 out of 51 CT scans (39%) were misinterpreted as 'malignant'. For MRI, two out of 14 cases (14%) were radiologically misdiagnosed as 'benign' and six out of 17 patients (35%) as 'malignant'. In conclusion, whereas both the CT and MRI showed a similar level of accuracy in evaluation of salivary gland tumors, they showed a considerable tendency of misdiagnosis, especially by interpreting benign tumors as 'malignant'.


Manipulation of host plant cells and tissues by gall-inducing insects and adaptive strategies used by different feeding guilds.
Biologists who study insect-induced plant galls are faced with the overwhelming diversity of plant forms and insect species. A challenge is to find common themes amidst this diversity. We discuss common themes that have emerged from our cytological and histochemical studies of diverse neotropical insect-induced galls. Gall initiation begins with recognition of reactive plant tissues by gall inducers, with subsequent feeding and/or oviposition triggering a cascade of events. Besides, to induce the gall structure insects have to synchronize their life cycle with plant host phenology. We predict that reactive oxygen species (ROS) play a role in gall induction, development and histochemical gradient formation. Controlled levels of ROS mediate the accumulation of (poly)phenols, and phytohormones (such as auxin) at gall sites, which contributes to the new cell developmental pathways and biochemical alterations that lead to gall formation. The classical idea of an insect-induced gall is a chamber lined with a nutritive tissue that is occupied by an insect that directly harvests nutrients from nutritive cells via its mouthparts, which function mechanically and/or as a delivery system for salivary secretions. By studying diverse gall-inducing insects we have discovered that insects with needle-like sucking mouthparts may also induce a nutritive tissue, whose nutrients are indirectly harvested as the gall-inducing insects feeds on adjacent vascular tissues. Activity of carbohydrate-related enzymes across diverse galls corroborates this hypothesis. Our research points to the importance of cytological and histochemical studies for elucidating mechanisms of induced susceptibility and induced resistance.


Congenital lung abnormality quantification by computed tomography: The CLAQ method.
To date, no consensus has been reached on the optimal management of congenital lung abnormalities, and factors predicting postnatal outcome have not been identified. We developed an objective quantitative computed tomography (CT) scoring method, and assessed its value for clinical decision-making. Volumetric CT-scans of all patients born with a congenital lung abnormality between January 1999 and 2018 were assessed. Lung disease was quantified using the newly-developed congenital lung abnormality quantification (CLAQ) scoring method. In 20 equidistant axial slices, cells of a square grid were scored according to the abnormality within. The scored CT parameters were used to predict development of symptoms, and SD scores for spirometry and exercise tolerance (Bruce treadmill test) at 8 years of age. CT-scans of 124 patients with a median age of 5 months were scored. Clinical diagnoses included congenital pulmonary airway malformation (49%), bronchopulmonary sequestration (27%), congenital lobar overinflation (22%), and bronchogenic cyst (1%). Forty-four patients (35%) developed symptoms requiring surgery of whom 28 (22%) patients became symptomatic before a CT-scan was scheduled. Lesional hyperdensity was found as an important predictor of symptom development and decreased exercise tolerance. Using receiver operating characteristic analysis, an optimal cut-off value for developing symptoms was found at 18% total disease. CT-quantification of congenital lung abnormalities using the CLAQ method is an objective and reproducible system to describe congenital lung abnormalities on chest CT. The risk for developing symptoms may increase when more than a single lung lobe is affected.


Phosphoenolpyruvate carboxylase of Thiobacillus thioparus. I. General properties.
Phosphoenolpyruvate (PEP) carboxylase (orthophosphate:oxalacetate carboxylase (phosphorylating), EC 22.214.171.124) was purified 19-fold from the obligate chemoautotroph, Thiobacillus thioparus. Michaelis constants for the substrates were found to be 0.44 mM for phosphoenolpyruvate, 0.89 mM for bicarbonate, and 0.37 mM for magnesium, using Tris-HC1, pH 7.3. 1-Aspartate, 1-malate, and orthophosphate were found to be inhibitors of enzyme activity, while acetyl CoA, FDP, GTP, and CDP had no effect. Dioxane greatly stimulated enzyme activity.


Anserine (beta-alanyl-3-methyl-L-histidine) improves neurovascular-unit dysfunction and spatial memory in aged AβPPswe/PSEN1dE9 Alzheimer's-model mice.
Anserine/carnosine supplementation improves cerebral blood flow and verbal episodic memory in elderly people, as we previously reported. Anserine's buffering activity is superior to that of carnosine at neutral pH. In human sera, carnosine but not anserine is rapidly cleaved by carnosinase, limiting its effectiveness. This study examined the effects of anserine on AβPPswe/PSEN1dE9 Alzheimer's disease (AD) model mice over 18-months old, an age at which these mice exhibit detectable memory deficits. We found that 8 weeks of anserine treatment completely recovered the memory deficits, improved pericyte coverage on endothelial cells in the brain, and diminished chronic glial neuroinflammatory reactions in these mice. These results suggest that anserine (beta-alanyl-3-methyl-L-histidine) supplementation improved memory functions in AD-model mice by exerting a protective effect on the neurovascular units, which are composed of endothelial cells, pericytes, and supporting glial cells.


A label-free colorimetric aptasensor for simple, sensitive and selective detection of Pt (II) based on platinum (II)-oligonucleotide coordination induced gold nanoparticles aggregation.
Herein, a gold nanoparticles (AuNPs) based label-free colorimetric aptasensor for simple, sensitive and selective detection of Pt (II) was constructed for the first time. Four bases (G-G mismatch) mismatched streptavidin aptamer (MSAA) was used to protect AuNPs from salt-induced aggregation and recognize Pt (II) specifically. Only in the presence of Pt (II), coordination occurs between G-G bases and Pt (II), leading to the activation of streptavidin aptamer. Streptavidin coated magnetic beads (MBs) were used as separation agent to separate Pt (II)-coordinated MSAA. The residual less amount of MSAA could not efficiently protect AuNPs anymore and aggregation of AuNPs will produce a colorimetric product. With the addition of Pt (II), a pale purple-to-blue color variation could be observed by the naked eye. A detection limit of 150nM and a linear range from 0.6μM to 12.5μM for Pt (II) could be achieved without any amplification.


Successful treatment with plasma exchange in adult-onset Still's disease with hyper-IL-18-naemia and hyperallergic state.
Adult-onset Still's disease (AOSD) is a rheumatoid disorder characterized by high fever, polyarthritis, leukocytosis, hyperferritinaemia, and mild liver involvement. We describe the case of a patient with AOSD with severe liver dysfunction. His serum levels of interleukin-10 and 18 showed a similar trend to his disease activity. Drug lymphocyte stimulation tests were positive for three drugs in the patient. Hypercytokinaemia was controlled by plasma exchange therapy.


Characteristics of frequent users of the emergency department in the general adult population: A systematic review of international healthcare systems.
The objectives of this study were to synthesize and compare population characteristics associated with frequent emergency department (ED) use within and across healthcare systems. A systematic review of literature published between 1950 and 2015 was conducted. Healthcare systems of included studies were categorized using the Rothgang-Wendt typology. Demographic, clinical and health service utilization characteristics of frequent ED users in the general adult population were identified within each healthcare system. Pooled estimates, stratified by healthcare system, were calculated to compare the association of each characteristic with frequent, compared to non-frequent, emergency room use. Twenty moderate to high quality comparative cohort studies were included. Among these, five healthcare systems were identified: National Health Insurance; Private Healthcare; National Health Service; Social Health Insurance and Etatist Social Health Insurance. Many similar characteristics were observed: in most healthcare systems, frequent ED users were more likely to be older, female, and have a mental health diagnosis. Previous hospitalizations and high primary care use (>3 visits/year) were associated with future frequent ED use in the NHIS and NHS systems. Observed similarities suggest that frequent ED use may not differ from one healthcare system to the next. With increasing need to develop solutions for high ED utilization world-wide, targeted efforts must be made to bolster dissemination and uptake of effective interventions across healthcare contexts.


Second malignancies and Hodgkin's disease--the Royal Marsden Hospital experience.
The frequency of secondary malignant neoplasms occurring in patients treated for Hodgkin's disease at the Royal Marsden Hospital between 1963 and 1978 is reported and the literature is reviewed. 730 patients were reviewed and 583 patients permanently resident in the United Kingdom were included in the analysis. The frequency of leukaemia and solid tumors was determined from age- and sex-corrected data from the South Thames Cancer Registry. Thirty-seven malignancies were recorded in 36 patients including 9 leukaemias, 10 lung cancers, 6 skin cancers and 2 non-Hodgkin's lymphoma, all of which were observed in significant excess. When all remaining sites are combined, there was a slight excess but no one site is individually significant.


Doxorubicin-loaded polypeptide nanorods based on electrostatic interactions for cancer therapy.
An amphiphilic anionic polypeptide, methoxypolyethylene glycol-poly (glutamic acid) (mPEG-PGA), was synthesized, characterized and evaluated as a nanocarrier for the cationic anticancer drug doxorubicin hydrochloride (DOX·HCl). The complex self-assembled into nanorods in aqueous solutions via electrostatic interactions and exhibited a superior drug loading content (50.8%) and drug loading efficiency (90.2%). The average major axis of the drug-loaded nanorods was approximately 300nm, as determined by transmission electron microscopy. An in vitro release assay showed that drug-loaded nanorods exhibited pH-sensitivity and sustained release. Haemolysis assays demonstrated that the polypeptide was haemocompatible, and the polypeptide drug carrier significantly reduced the haemolysis ratio of DOX·HCl. The pharmacokinetics study showed that DOX-loaded nanorods significantly prolonged the resident time in blood. An in vitro cytotoxicity study and cellular uptake assays demonstrated that the DOX-loaded nanorods resulted in higher cell proliferation inhibition and a higher level of tumour cell uptake in A549 cells than with free DOX·HCl. The prolonged circulation and enhanced antitumor efficacy of DOX-loaded nanorods shows promise for efficient cancer chemotherapy.


Quantitation of macromolecular binding using size exclusion filters: application to a fucosyltransferase assay.
A method to quantify the covalent attachment of small radiolabeled substrates to macromolecules on the basis of molecular weight using size exclusion filters in an Amicon Centrifree micropartition system is described. GDP-[14C]-L-fucose was covalently attached to asialofetuin in a fucosyltransferase reaction catalyzed by mouse spermatogenic cell extracts. Radiolabeled product was separated from unreacted substrate by centrifuging 200-400 microliter of cell extract through a 10-kDa size exclusion filter at 1000 g for 10 to 20 min. After 10 washes with an appropriate buffer, no detectable radioactivity was found in the eluant and the membrane-bound radiolabeled product was counted in a scintillation vial. Using this method the fucosyltransferase activity of mouse spermatogenic cells was approximately 17 pmol/mg protein/min which is essentially identical to values obtained using size exclusion chromatography. This technique provides a rapid, efficient, and inexpensive alternative for the isolation and detection of acceptor-substrate complexes.


Potentiating role of cyclic AMP in pancreatic enzyme secretion, demonstrated by means of forskolin.
The role of cyclic AMP in the regulation of enzyme secretion by the rabbit pancreas has been investigated by means of forskolin, an activator of the catalytic subunit of adenylate cyclase. Forskolin increases the cyclic AMP level in isolated pancreatic acini in a dose-dependent way. Basal amylase release, however, remains unchanged. Forskolin potentiates the increase in amylase release induced by the C-terminal octapeptide of cholecystokinin (CCK-8). Potentiation is already apparent at hormone concentrations which are only marginally effective in stimulating amylase secretion. CCK-8 alone does not raise the cellular cAMP level, but it potentiates the forskolin-induced increase. In relative terms, potentiation is higher with decreasing concentration of forskolin. These results indicate that cAMP alone does not play a direct role in CCK-stimulated pancreatic enzyme secretion in the rabbit, but it potentiates enzyme secretion already stimulated through a cAMP-independent process.


Antioxidant activities of seabuckthorn (Hippophae rhamnoides) during hypoxia induced oxidative stress in glial cells.
The present study reports the cytoprotective and antioxidant properties of alcoholic leaf extract of seabuckthorn (SBT) against hypoxia induced oxidative stress in C-6 glioma cells. Exposure of cells to hypoxia for 12 h resulted in a significant increase in cytotoxicity and decrease in mitochondrial transmembrane potential compared to the controls. Further an appreciable increase in nitric oxide and reactive oxygen species (ROS) production was noted which in turn was responsible for fall in intracellular antioxidant levels and GSH/GSSG ratio. There was a significant increase in DNA damage during hypoxia as revealed by comet assay. Pretreatment of cells with alcoholic leaf extract of SBT at 200 mug/ml significantly inhibited cytotoxicity, ROS production and maintained antioxidant levels similar to that of control cells. Further, the leaf extract restored the mitochondrial integrity and prevented the DNA damage induced by hypoxia. These results indicate that the leaf extract of SBT has strong antioxidant and cytoprotective activity against hypoxia induced oxidative injury.


Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma.
Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population.


IVRT'/IVRT index is a useful tool for detection of elevated left ventricular filling pressure in patients with preserved ejection fraction.
Deterioration of active relaxation results in prolongation of isovolumteric relaxation time (IVRT), however, when left ventricular filling pressure elevates, mitral valve opens earlier and IVRT shortens. This shortening is not seen when IVRT is measured with tissue Doppler imaging (IVRT'). Then, IVRT' prolongs with the deceleration of active relaxation independent of left ventricular filling pressure. We hypothesized that IVRT' reflects the relaxation rate, thus, the ratio of IVRT' to IVRT may possibly detect left ventricular filling pressure elevation. The group of 39 subjects (aged 64 +/- 5 years) with preserved ejection fraction (EF > 50%) underwent combined echocardiographic and hemodynamic examinations. Echocardiographic parameters of mitral inflow and mitral annular motion were correlated with invasive indices of left ventricular relaxation and filling pressure. Time constant of isovolumetric pressure decline (tau) correlated closely with IVRT' (r = 0.73, P < 0.001) but not with early diastolic velocity of mitral annulus (E') (r =-0.207, P = 0.206). The best parameter correlating with M-LVDP was IVRT'/IVRT (r = 0.694, P < 0.001, M-LVDP = 7.7 x IVRT'/IVRT + 5.1). A weaker relation was also noted between the ratio of early mitral peak inflow velocity to early diastolic velocity of mitral annulus (E/E') and M-LVDP (r = 0.469, P < 0.001). The relationships between standard Doppler parameters and left ventricular diastolic pressures were uniformly poor. The study demonstrated that IVRT' may serve as a surrogate of left ventricular active relaxation. IVRT'/IVRT index may be applied to estimate left ventricular filling pressure.


The role of ultrasound and magnetic resonance cholangiopancreatography for the diagnosis of biliary stricture after liver transplantation.
To identify the diagnostic value of ultrasound (US) and magnetic resonance cholangiopancreatography (MRCP) in diagnosing biliary strictures after liver transplantation. Sixty patients with clinically suspected biliary strictures after liver transplantation were retrospectively evaluated. All patients underwent US and MRCP before the standard of reference (SOR) procedure: endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography. Radiological images were analyzed for biliary dilatation and strictures. By SOR, biliary dilatation was present in 55 patients, stricture in 53 (44 anastomotic, 4 intrahepatic, 5 both), and dilatation and/or stricture in 58. Dilatation was diagnosed by US and MRCP in 39 and 45, respectively (sensitivity 71% vs. 82%, p=0.18). Stricture was diagnosed by US and MRCP in 0 and 42, respectively (sensitivity 0% vs. 79%, p<0.0001). False positive stricture was diagnosed by MRCP in 2. Dilatation and/or stricture was diagnosed by US in 39 and MRCP in 50 (sensitivity 67% vs. 86%, p=0.01); however, using both techniques, sensitivity increased to 95%. MRCP is superior to US for diagnosing biliary strictures after liver transplantation primarily because MRCP can detect stricture. The combination of US and MRCP seems superior to either method alone. Our data suggest that in patients with normal US and MRCP, direct cholangiography could be avoided.


Knowledge and attitude of Lebanese women about cosmetics: a cross-sectional survey.
The Middle East and North Africa region, including Lebanon, is well known for its excessive cosmetics expenditure. While the use of beauty products is increasing, it is unclear if customers are aware of the products' safety and proper use. To explore Lebanese women's knowledge and attitudes toward cosmetics use. A cross-sectional study was conducted from January to May 2021 among a sample of adult Lebanese women. Data were collected using an electronic questionnaire divided into 3 sections (sociodemographic characteristics, cosmetics knowledge, and attitude) and shared via social media platforms. Knowledge and attitude scores were then calculated. Descriptive and regression analysis was performed using Statistical Package for the Social Sciences. P value < .05 was considered statistically significant. A total of 1,051 females completed the survey, and the age range of the majority 744 (70.8%) was between 18 and 20 years. The mean score of participants' knowledge was 7.54 ± 2.7 (range 0-14) with 658 (62.6%) of the respondents being knowledgeable about cosmetics. The study sample exhibited an overall positive attitude toward cosmetics. A significant association was observed between the area of residency and monthly income of respondents and their knowledge toward cosmetic products (P < .001). The self-administered questionnaire may have resulted in information bias and it targeted only those having internet access, and the age group 18 to 20 years was overrepresented. The study sample demonstrated a good level of knowledge as well as a positive attitude toward cosmetics. However, raising awareness on the acute and chronic side effects of cosmetics is warranted.


Magic angles and fibre stretch in arterial tissue: Insights from the linear theory.
This work is motivated by the current widespread interest in modelling the mechanical response of arterial tissue. A widely used approach within the context of anisotropic nonlinear elasticity is to use an orthotropic incompressible hyperelasticity model which, in general, involves a strain-energy density that depends on seven independent invariants. The complexity of such an approach in its full generality is daunting and so a number of simplifications have been introduced in the literature to facilitate analytical tractability. An extremely popular model of this type is where the strain energy involves only three invariants. While such models and their generalisations have been remarkably successful in capturing the main features of the mechanical response of arterial tissue, it is generally acknowledged that such simplified models must also have some drawbacks. In particular, it is intuitively clear that the correlation of such models with experiment will suffer limitations due to the restricted number of invariants considered. Our purpose here is to use the linearised theory for infinitesimal deformations to provide some guidelines for the development of a more robust nonlinear theory. The linearised theory for incompressible orthotropic materials is developed and involves six independent elastic constants. The general stress-strain law is inverted to provide an expression for the fibre stretch in terms of the stress. We examine the linearised response for simple tension in two mutually perpendicular directions corresponding to the axial and circumferential directions in the artery, obtaining an explicit expression for the fibre stretch in terms of the applied tension, fibre angle and linear elastic constants. The focus is then on determining the range of fibre orientation angles that ensure that the fibres are in tension in these simple tension tests. It is shown that the fibre stretch is positive for both simple tension tests if and only if the fibre angle is restricted to lie between two special angles called generalised magic angles. For the special case where the strain-energy function for the nonlinear model depends only on the three invariants I1,I4,I6, it is shown that the corresponding linearised model, called the standard linear model (SLM), depends on three elastic constants and the fibre stretch is positive only in the small range of fibre angles between the classic magic angles 35.26° and 54.74°. However, when the two additional invariants I5,I7 are included in the nonlinear strain energy so that the corresponding linear model involves four elastic constants, it is shown that the domain of fibre angle for which the stretch is positive is much larger and that the fibre stretch is monotonic with respect to the fibre angle in this range.


[Immunohistochemical analysis of epidermal growth factor receptors expression in malignant ovarian tumors].
To study the frequency of EGFR expression in patients having malignant and benign ovarian tumors and to analyze its relation to some clinico-pathological factors. In a prospective study 71 patients with malignant and 19 with benign ovarian tumors were included for the period 1999-2004. We utilized immunohistochemical analysis with monoclonal mouse antihuman EGFR antibody and EGFR pharm Dx kit (DAKO). The frequency of EGFR expression for the malignant ovarian tumours was 62.9% compared to 36.8% for the benign ones (p = 0.042). The patients with peritoneal washing positive for tumour cells and those with progressing cancer express EGFR significantly more frequently, 77% and 75%, respectively (p = 0.05). Malignant ovarian tumours have significantly greater frequency of EGFR expression compared to benign ovarian tumours.


Periimplant bone changes in different abutment heights and insertion timing in posterior mandibular areas: Three-year results from a randomized prospective clinical trial.
To compare the influence of the abutment height and its insertion timing on the marginal bone change (MBC) variation of implants placed at posterior mandibular partial edentulous areas in a medium follow-up period. This randomized clinical trial (RCT) comprised a sample of patients with posterior mandibular edentulous areas, treated with at least two implants and distributed into three groups: implants connected to a 2 mm height abutment during the surgical stage (Group A); implants connected to a 1 mm height abutment during the surgical stage (Group B); and implants connected to a 2 mm height abutment after 2 months (Group C). Clinical and radiographic measurements were performed during a 36-month period (T4). The MBC was set as the main variable in study. Statistical significance was set at 0.05. A total of 29 subjects and 59 implants were enrolled in this study. A mean MBC of 0.35 ± 0.46 mm, 0.60 ± 0.81 mm, and 0.71 ± 0.90 mm was computed for groups A, B and C, respectively, at T4. Significant differences were found between groups A and C in terms of MBC variation after 3 years of treatment (p = .048). Multiple linear regression analysis showed a significant influence of the first-year MBC and the abutment insertion timing has independent predictor variables for the MBC assessed at T4. The installation of 2-mm prosthetic abutments, at the time of implant placement, in areas with limited keratinized mucosa presents as a favorable treatment option in terms of periimplant marginal bone maintenance.


Absorption and urinary excretion of the coffee diterpenes cafestol and kahweol in healthy ileostomy volunteers.
To determine the absorption and urinary excretion of the cholesterol-raising coffee diterpenes cafestol and kahweol in humans. Nine healthy ileostomists consumed a dose of one, two or three cups of French-press coffee together with a standardized breakfast on three separate days in random order. Subsequently, ileostomy effluent was collected for 14 h and urine for 24 h. Stability of cafestol and kahweol was also assessed under simulated gastrointestinal tract conditions. Absorption of diterpenes, stability of diterpenes during incubation with gastrointestinal fluids, and urinary excretion of diterpenes. Corrected mean absorptions expressed as percentages of the amount consumed and the amount entering the duodenum were 67 and 88%, respectively, for cafestol, and 72 and 93%, respectively, for kahweol. We found losses of diterpenes during incubation in vitro with gastric juice (cafestol, 24%; kahweol, 32%), during storage with ileostomy effluent (cafestol, 18%; kahweol, 12%), and during freeze-drying (cafestol, 26%; kahweol, 32%). Mean excretion of glucuronidated plus sulphated conjugates in urine was 1.2% of the ingested amount for cafestol and 0.4% of the ingested amount for kahweol. About 70% of the ingested cafestol and kahweol is absorbed in ileostomy volunteers. Possibly, undetected metabolites are present in ileostomy effluent, resulting in lower absorption percentages. Only a small part of the diterpenes is excreted as a conjugate of glucuronic acid or sulphate in urine. Therefore, these compounds are extensively metabolized in the human body.


Perceived value of the clinical dual-degree program to DPM/MHA alumni.
This article provides an analysis of the perceived value to doctor of podiatric medicine/master of health-care administration (DPM/MHA) alumni of the clinical dual-degree program at Des Moines University, Des Moines, Iowa, and a review of the literature on physician leaders. An in-depth review of the current literature and an evaluation of survey results from 21 of 33 alumni of the DPM/MHA dual-degree program at Des Moines University was completed. There was an overwhelming positive response from alumni toward the DPM/MHA dual-degree program. It was also found that there is a need for physician leaders who obtain knowledge and understanding of the business aspects of medicine in the current health-care industry. These survey results provide justification that the DPM/MHA dual-degree program at Des Moines University is fulfilling its goal of providing an educational background in the administrative and clinical aspects of medicine that prepares students for the complex and ever-changing health-care industry. The dual-degree program is a great opportunity for the podiatric medicine profession and podiatric medical schools to increase their collaboration with MHA programs to offer dual-degree programs to help fill the void and prepare future physician leaders.


[Total hip arthroplasty in children and adolescents].
Arthritis Arthritis of the hip in children and adolescent can induce lesions of the articular cartilage and severe handicap. When conservative surgical methods are without benefit, total hip arthroplasty should be an alternative solution. Chronic pain, abnormal social life and scolarity, stiffness and impossibility for osteotomies are the main criteria to decide and to choose for an arthroplasty.Two main groups of etiology are as follow * group I concerns rhumatologie arthritis. Arthroplasty is decided with pediatricians, physiotherapists… Other joints are often involved and post-operative cares need intensive physiotherapy. Femoral head necrosis of renal disease and sickle cell disease belong to this group.* group II concerns sequelae of previous femoral osteotomy: septic osteoarthritis, severe stiffness, sequelae of hip dislocation, necrosis of slipped capital epiphysiolysis…Since 1990, Dr J.L. Jouve has operated on 11 hips in patients aged for 14 to 20. Prosthesis used were custom made, Symbios, Switzerland.Results group I: The custom made in this group is interesting because it is obvious to maintain the largest bony pool and to avoid to ream the metaphysis and diaphysis. It is also necessary to thinck in advance for further procedure because these patients are young. Technical surgical approach is without any particularity, no case of fracture was noticed. Post-operative weight-bearing was delayed for 45 days. With a short follow-up of 2 years, results are excellent.Results group II: The custom made is necessery in these cases with an abnormal morphology of the proximal femur and narrow canal following earlier femoral osteotomies. Immediate results are also excellent. Hip arthroplasty with custom made is a nice procedure when other surgical treatments are not possible. But further studies are necessary with a larger follow-up.Tumors Osteosarcoma and Ewing's sarcoma needs sometimes wide resections of the proximal femur and reconstruction of the hip joint. In our experience and ISOLS' series, it seems that following data are favourable: - cemented complete prosthesis of the femur resected and no allograft, - excellent reconstruction of the muscles of the hip: extensors, abductors and fascia lata, without to try a fixation of these muscles on the prosthesis - use of an acetabular mobile cup to preserve further surgery with, for exemple, an acetabular arthroplasty. Two cases of Ewing's sarcoma are presented, girls aged 15 and 12.Length of the resection was 23 and 19 cm. Post-operative results are good.


Enhancing the carotenoid content of atherosclerotic plaque: implications for laser therapy.
Selective laser ablation of human atherosclerotic plaque is possible because endogenous carotenoid pigments found in atherosclerotic plaque confer a twofold preferential absorption of laser radiation at 450 to 500 nm. In this study, patients with carotid endarterectomy were pretreated with oral beta carotene to determine if the carotenoid content and therefore laser selectivity of plaque could be increased in vivo. Beta carotene-treated patients had a significant, nearly twofold increase in their plaque carotenoid concentration, which increased from 0.22 to 0.40 microgram beta carotene/mg cholesterol. These results suggest that selective ablation of atherosclerotic plaque may be enhanced by pretreating patients with doses of oral beta carotene for short periods of time.


Free flap reconstruction of tumors involving the cranial base.
The authors describe their experience in treating 24 patients who underwent resection of tumors involving anterior, middle or posterior cranial fossa with immediate reconstruction. All were reconstructed with free flaps, 15 rectus abdominis, 4 radial forearm, 3 latissimus dorsi, 2 great omentum, and one scapular flap. There was one latissimus dorsi flap loss due to arterial thrombosis in a heavily irradiated patient. Three patients presented with a temporary cerebrospinal fluid leak, one of them with meningitis which resolved after intravenous antibiotics and continuous lumbar drainage. Fifteen patients were followed (mean 2 years). Five died of recurrence. Four presented local recurrence. Six patients are alive with no signs of recurrence. Free flaps, especially the rectus abdominis flap and the latissimus dorsi, are versatile flaps and may be easily positioned to cover several structures or anatomical surfaces.


[Principles of radical surgery of gastric carcinoma (author's transl)].
For over a decade, therapeutic results in cases of macrocarcinoma have remained almost constant. The absolute 5-year survival rate is 10-15%. However, in cases of early detection, the 5-year survival rate is over 90%. Systematic screening to detect the cancers early has resulted. The practical results is the systematic observation of high-risk groups. The therapy of choice for macrocarcinoma and cancer that is detected early is subtotal resection. Resection of the cardia should be replaced by gastrectomy, which should also be performed only when defined diagnostic criteria are met.


Long-term digital mobile phone use and cognitive decline in the elderly.
Research on long-term exposure to electromagnetic fields on cognition is lacking. We investigated the associations between frequent digital mobile phone use and global and domain-specific cognitive changes in older persons, a vulnerable group experiencing age-associated cognitive decline. We assessed 871 non-demented Chinese participants in the Singapore Longitudinal Ageing Studies cohort on the frequency of digital mobile phone use, neurocognitive performance and confounding variables at baseline, and neurocognitive performance at the 4-year follow-up. Findings showed that digital mobile phone users were typically self-selected to possess characteristics favoring better cognitive functioning and concomitantly demonstrate better performance on cognitive tasks. There was evidently no significant deleterious effect of digital mobile phone use on cognitive functioning in older people. Findings suggest, however, that digital mobile phone use may have an independent facilitating effect on global and executive functioning.


Ultrasound and Point Shear Wave Elastography in Livers of Patients with Primary Sclerosing Cholangitis.
Point shear wave elastography (pSWE) is an ultrasound-based method for non-invasive quantification of liver fibrosis. The objective of this study was to explore liver pSWE in patients with primary sclerosing cholangitis (PSC) for assessment of fibrosis. Fifty-five non-transplant patients with PSC (38 males, 17 females; mean age: 46.4 y) were included and compared with 24 matched controls. Median (range) PSC duration was 8.1 (0-33) y. Ultrasonographic scanning followed by liver stiffness measurement by pSWE was performed using a conventional ultrasound system (Philips iU22). Signs of liver fibrosis on B-mode were identified in 21 patients (38%). Splenomegaly was found in 19 patients (35%) and ascites in two patients (4%). Successful pSWE measurements were achieved in the right liver lobe of all individuals and in the left liver lobe of 36 patients (65.5%). PSC patients had significantly higher median shear wave velocity (SWV) than controls in the right liver (median [range] SWV 1.26 [0.73-2.57] m/s vs. 1.09 [0.88-1.25] m/s, p < 0.001). SWV measured in the left liver lobe and spleen did not differ between PSC patients and controls. Our findings indicate that PSC patients have increased median SWV, indicating more fibrosis compared with controls; however, a wide range of SWV values were obtained among PSC patients, possibly reflecting the various stages in disease development.


Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma.
Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety. Two trials of wGC and 3 trials of GC were identified. Because the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), for response rates and grade ≥ 3 toxicities were calculated. The 95% CI overlapped, suggesting agreement between wGC and GC. No clear difference in response rates and grade ≥ 3 toxicities between GC and wGC were observed. Gemcitabine combined with day 1 cisplatin and wGC yielded similar responses and grade ≥ 3 toxicities in advanced UC in a hypothesis-generating pooled analysis of phase II trials. Considering the probable lower nephrotoxicity of fractionated cisplatin, prospective evaluation of wGC might be warranted across cisplatin-eligible and -ineligible patients to develop a single chemotherapy template for the development of combinations with biological agents in a broad population of patients.


Surface Modification of Halogenated Polymers. 7. Local Reduction of Poly(tetrafluoroethylene) and Poly(chlorotrifluoroethylene) by a Scanning Electrochemical Microscope in the Feedback Mode.
Fluoropolymers have been reduced locally by the radical anion of a redox mediator electrogenerated at a microelectrode operating in the configuration of a scanning electrochemical microscope. Approach curves with different redox mediators were used to investigate the reduction mechanism of the fluoropolymer. Different factors are discussed, such as the monomer reduction mechanism, the kinetic control by the surface modification growth, and the conductivity of the modified surface. The fluoropolymers' reduction parallels the trends observed in organic electrochemistry in solution within the haloalkane series.


EVI1 protein interaction dynamics: Targetable for therapeutic intervention?
High expression of the transcriptional regulator EVI1 encoded at the MECOM locus at 3q26 is one of the most aggressive oncogenic drivers in acute myeloid leukemia (AML) and carries a very poor prognosis. How EVI1 confers leukemic transformation and chemotherapy resistance in AML is subject to important ongoing clinical and experimental studies. Recent discoveries have revealed critical details on genetic mechanisms of the activation of EVI1 overexpression and downstream events of aberrantly high EVI1 expression. Here we review and discuss aspects concerning the protein interactions of EVI1 and the related proteins MDS-EVI1 and ΔEVI1 from the perspective of their potential for therapeutic intervention.


Corticotropin-releasing factor (CRF) receptor subtypes in mediating neuronal activation of brain areas involved in responses to intracerebroventricular CRF and stress in rats.
Corticotropin-releasing factor (CRF) plays an important role in stress responses through activation of its receptor subtypes, CRF1 receptor (CRF(1)) and CRF2 receptor (CRF(2)). The parvocellular paraventricular nucleus of the hypothalamus (PVNp), the central nucleus of the amygdala (CeA), and the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), which are rich in CRF neurons with equivocal expression of CRF(1) and CRF(2), are involved in stress-related responses. In these areas, Fos expression is induced by various stimuli, although the functions of CRF receptor subtypes in stimuli-induced Fos expression are unknown. To elucidate this issue and to examine whether Fos is expressed in CRF or non-CRF neurons in these areas, the effects of antalarmin and antisauvagine-30 (AS-30), CRF(1)- and CRF(2)-specific antagonists, respectively, on intracerebroventricular (ICV) CRF- or 60min-restraint-induced Fos expression were examined in rats. ICV CRF increased the number of Fos-positive CRF and non-CRF neurons in the PVNp, with the increases being inhibited by antalarmin in CRF and non-CRF neurons and by AS-30 in CRF neurons. Restraint also increased Fos-positive CRF and non-CRF neurons in the PVNp, with the increases being inhibited by antalarmin in the CRF neurons. ICV CRF also increased Fos-positive non-CRF neurons in the CeA and the BNSTov, which was inhibited by AS-30 in both areas, and inhibited by antalarmin in the BNSTov only. Restraint increased Fos-positive non-CRF neurons in the CeA and BNSTov, with the increases being almost completely inhibited by either antagonist. These results indicate that both ICV CRF and restraint activate both CRF and non-CRF neurons in the PVNp and non-CRF neurons in the CeA and BNSTov, and that the activation is mediated by CRF(1) and/or CRF(2). However, the manner of involvement for CRF(1) and CRF(2) in ICV CRF- and restraint-induced activation of neurons differs with respect to the stimuli and brain areas; being roughly equivalent in the CeA and BNSTov, but different in the PVNp. Furthermore, the non-CRF(1&2)-mediated signals seem to primarily play a role in restraint-induced activation of non-CRF neurons in the PVNp since the activation was not inhibited by CRF receptor antagonists.


A review of biocontrol agents in controlling late blight of potatoes and tomatoes caused by Phytophthora infestans and the underlying mechanisms.
Phytophthora infestans causes late blight on potatoes and tomatoes, which has a significant economic impact on agriculture. The management of late blight has been largely dependent on the application of synthetic fungicides, which is not an ultimate solution for sustainable agriculture and environmental safety. Biocontrol strategies are expected to be alternative methods to the conventional chemicals in controlling plant diseases in the integrated pest management (IPM) programs. Well-studied biocontrol agents against Phytophthora infestans include fungi, oomycetes, bacteria, and compounds produced by these antagonists, in addition to certain bioactive metabolites produced by plants. Laboratory and glasshouse experiments suggest a potential for using biocontrol in practical late blight disease management. However, the transition of biocontrol to field applications is problematic for the moment, due to low and variable efficacies. In this review, we provide a comprehensive summary on these biocontrol strategies and the underlying corresponding mechanisms. To give a more intuitive understanding of the promising biocontrol agents against Phytophthora infestans in agricultural systems, we discuss the utilizations, modes of action and future potentials of these antagonists based on their taxonomic classifications. To achieve a goal of best possible results produced by biocontrol agents, it is suggested to work on field trials, strain modifications, formulations, regulations, and optimizations of application. Combined biocontrol agents having different modes of action or biological adaptation traits may be used to strengthen the biocontrol efficacy. More importantly, biological control agents should be applied in the coordination of other existing and forthcoming methods in the IPM programs. © 2023 Society of Chemical Industry.


A controlled trial of fixed versus tailored calorie intake in patients receiving intravenous feeding after abdominal surgery.
Excessive intravenous calorie intakes have been shown to increase fat deposition and CO2 production with deleterious results. A controlled trial has therefore been performed to determine whether there is clinical benefit from tailoring calorie intake of intravenously fed patients to the patient's metabolic expenditure. Twenty patients requiring intravenous feeding after abdominal surgery were randomly allocated to receive either (i) a constant regimen containing 2 600 calories and 15.55 g nitrogen or (ii) a varied regimen with a fixed calorie: N2 ratio of 167:1 but with the calorie intake adjusted according to the previous day's metabolic expenditure. Only one patient had a requirement of greater than 2 600 calories; there was no difference in mean RQ during intravenous feeding between the constant regimen (0.90 +/- 0.10 s.d.) and the varied regimen (0.90 +/- 0.09 s.d.) and no significant difference in peak CO2 production. Excess calorie intake over expenditure did not correlate with increased positive nitrogen balance but on the varied regimen patients receiving a higher nitrogen intake tended to be in more positive nitrogen balance. This study suggests that a fixed calorie intake of 2 600 calories per day is suitable for adult patients requiring intravenous feeding after abdominal surgery but currently prescribed nitrogen intakes may be suboptimal.


[Intratumor injection of recombinant attenuated salmonella carrying Mycobacterium tuberculosis heat shock protein 70 and herpes simplex virus thymidine kinase genes to suppress murine melanoma growth].
To study the effection of suppression murine melanoma growth by Intratumor injection of recombinant attenuated salmonella carrying heat shock protein 70 and herpes simplex virus thymidine kinase genes. Plasmids PCMV-mtHSP70-IRES-TK were electro-transferred into salmonella typhimurium SL7207 to construct recombinant salmonella typhimurium. In vivo, Recombinant bacteria were injected into the mouse melanoma and the antitumor effection was observed. The survival period was recorded and safety analysis for this vaccine in each group. In vivo, the mtHSP70/HSV-tk recombinant bacteria can suppress tumor growth significantly and extend survival. After recombinant Salmonella, 10(9) CFU/mL, was administered as an intratumoral injection, No diarrhea were observed. During therapy, body weight did not change markedly. Results of the animal experiment suggests intratumor injection of recombinant attenuated salmonella typhimurium containing mtHSP70 and HSV-tk genes, has targeting ability against B16 tumor cell and could significantly inhibit tumor growth .


Psychosocial and cognitive function in children with nephrotic syndrome: association with disease and treatment variables.
To investigate possible differences in emotional/behavioral problems and cognitive function in children with nephrotic syndrome compared to healthy controls and to examine the effect of disease-specific and steroid treatment-specific characteristics on the abovementioned variables. Forty-one patients with nephrotic syndrome (23 boys, age range: 4.4-15.2 years) and 42 sex- and age-matched healthy control subjects (20 boys, age range: 4.1-13.4 years) were enrolled in the study. Disease (severity, age of diagnosis, duration) and steroid treatment (total duration, present methylprednisolone dose and duration of present dose) data were collected. In order to assess children's emotional/behavioral problems, the Child Behavior Checklist was administered. The Wechsler Intelligence Scale for Children - Third Edition was administered to assess Full-Scale, Verbal, and Performance intelligence quotient (IQ) scores. The patients presented with more internalizing problems (P = 0.015), including withdrawal (P = 0.012) and somatic complaints (P = 0 .011), but not more anxiety/depression or externalizing problems. A significant association was found between severity of disease and somatic complaints (P = 0.017) as well as externalizing problems (P = 0.030). Years of illness were significantly more in those presenting with abnormal anxiety/depression (P = 0.011). Duration of steroid medication was significantly higher among those presenting with abnormal anxiety/depression (P = 0.011) and externalizing problems (P = 0.039). IQ was not associated significantly with disease or steroid treatment variables. Psychosocial factors and outcomes may be important correlates of children's nephrotic syndrome and potential targets of thorough assessment and treatment.


Nucleostemin: a multiplex regulator of cell-cycle progression.
Nucleostemin (NS) is a protein concentrated in the nucleolus of most stem cells and also in many tumor cells, which has been implicated in cell-cycle progression owing to its ability to modulate p53. Depletion of NS causes G(1) cell-cycle arrest, but its overexpression does so as well. Recently, this paradox has been clarified. NS overexpression causes a sequestration of murine double minute 2 (MDM2), preventing the destruction of p53. A recent study has demonstrated that loss of NS promotes the interaction of L5 and L11 ribosomal proteins with MDM2 and, thus, also prevents p53 degradation. This new finding expands our understanding of the multiple modes of NS action and reinforces the concept that the nucleolus has key roles in cell-cycle progression.


Endothelium-mediated negative dromotropic effects of intravascular acetylcholine.
Acetylcholine acting through specific muscarinic membrane receptors causes a negative dromotropic effect and, in blood vessels, causes a vasodilation which results from its action on the endothelial cells via release of nitric oxide (NO). We decided to study this effect in isolated Krebs-Henseleit retrogradely perfused guinea pig hearts. A pair of stimulating electrodes was placed in the right atrium and to record the auricular-ventricular interval (A-V delay) one recording electrode was placed on the left atrium and the other on the tip of the ventricle. Hearts were paced at a rate of 3.8+/-0.1 Hz and perfused at a coronary flow rate of 9+/-0.25 ml/min. To obtain dose-response curves, single doses (as boluses) of acetylcholine were infused and the maximal A-V delay induced by each dose was determined. Perfusion of agents that inhibit NO accumulation (L-Arginine methyl ester (L-NAME) (0.5 mM)) or oxyhemoglobin (6 microM) caused displacement of the acetylcholine dose-response curve downward and to the right. Perfusion of NO-sparing agents like superoxide dismutase and dithiothreitol caused an upward and leftward displacement. Infusion of NO solutions or a NO donor (diethylamine-nitric oxide [DEA-NO]) caused a dose-dependent negative dromotropic effect. In contrast, inhibition of the prostaglandin metabolic pathway by Indomethacin (0.01 mM) caused potentiation of acetylcholine effects which were reversed when it was co-perfused with L-NAME. When endothelial intravascular muscarinic receptors were selectively blocked by perfusion of a non-permeable macromolecule: dextran ( > 2000 kDa) covalently complexed to the receptor blocker (3-(2'-aminobenzhydryloxy) tropane)), the negative dromotropic effect of intravascular acetylcholine was diminished in a concentration-dependent manner up to complete blockade. Our data indicate that the dromotropic effect caused by intracoronary administration of acetylcholine is the result solely of activation of intravascular endothelial muscarinic receptors, that nitric oxide and prostaglandins are non-synergistic endothelial mediators of this effect and that there may be an interaction between NO and prostaglandin metabolic pathways.


Risks associated with arsenic exposure resulting from the consumption of California wines sold in the United States.
Concerns have recently been raised about the presence of arsenic (As) in wine. In this analysis, 101 different California wines were evaluated for organic and inorganic As concentration. The average concentrations of total inorganic As in red, blush and white wines were 6.12μg/L (range: 0.40-20.5μg/L), 21.6μg/L (range: 0.92-41.2μg/L) and 9.5μg/L (0.57-30.4μg/L). The average concentrations of total organic As in red, blush and white wines were 0.64μg/L (0.10-2.74μg/L), 0.99μg/L (0.50-2.28μg/L), and 0.51μg/L (0.10-1.78μg/L). A screening level risk assessment was conducted to assess the potential non-carcinogenic risk resulting from wine consumption. The hazard quotient (HQ) for the inorganic As RfD and the As content of red, blush and white wines was each less than one; indicating that the non-cancer health risk was insignificant. Results indicate that ingestion of California wine does not pose a hazard due to inorganic As content.


The Association between Chronic Hemodialysis and Toe Pinch Force in Japanese Patients: Cross-Sectional Study.
The purpose of this cross-sectional study was to investigate the effect of chronic hemodialysis on toe pinch force (TPF). A total of 37 chronic hemodialysis patients without type 2 diabetes mellitus (T2DM) (age: 69.4 ± 11.8 years, duration of hemodialysis: 3.5 ± 3.4 years) were enrolled in this study. The TPF in chronic hemodialysis patients without T2DM was compared with that in 34 apparently healthy participants and 37 chronic hemodialysis patients with T2DM. There was no significant difference in clinical profiles between healthy participants and chronic hemodialysis patients with and without T2DM. The TPF in chronic hemodialysis patients without T2DM was lower compared with that in healthy participants (2.70 ± 1.05 kg vs. 3.34 ± 0.99 kg, p = 0.025). In addition, the TPF in patients with T2DM was even lower compared with that in patients without T2DM (2.12 ± 1.01 kg vs. 2.70 ± 1.05 kg, p = 0.042). This study showed a dramatic reduction in TPF in chronic hemodialysis patients, especially in those with T2DM.


Production of the antiviral proteins 2'5'oligoadenylate synthetase, PKR and Mx in interstitial cells and spermatogonia.
We report an in vitro analysis of the spatial pattern of production of three antiviral proteins (2'5'oligoadenylate synthetase, 2'5'AS; double-stranded RNA-activated protein kinase, PKR; and Mx protein, Mx) in the rat testis, in basal conditions and following stimulation with interferon (IFN) or Sendai virus. The two major constituents of interstitial tissue--Leydig cells and macrophages--constitutively produce 2'5' oligoadenylate synthetase (2'5'AS), PKR and Mx. Production of an isoform of 2'5'AS was induced following Leydig cells stimulation by the Sendai virus. The most immature germ cells, spermatogonia, were devoid of 2'5'AS whatever the type of stimulation, whereas IFN treatment induced Mx production and increased PKR production in this cell type. IFN stimulation strongly increased PKR production in all three cell types. This new set of data extends our previous investigations and demonstrates that the testis possesses an anti-viral defense system involving IFNs and IFN-induced anti-viral proteins.