Search

Nature 606(7915), 678 - 682 (2022). doi:10.1038/s41586-022-04827-6, Published by Nature Publ. Group, London [u.a.]

Background: Ductal carcinoma in situ (DCIS) is a risk factor for the development of invasive ductal carcinoma. Previous work has shown that an increased presence of T cells corresponds to high-risk DCIS features: age 5 cm, high-grade, palpable mass, hormone receptor negativity, and HER2 positivity. The presence of T cells colocalized with tumor is emerging as a predictor of response to checkpoint inhibition in invasive cancer. We previously have demonstrated that intratumoral injections of a checkpoint inhibitor (pembrolizumab) in DCIS resulted in an increased number of T cells, but without tumor cell killing. We hypothesized that the addition of an agent that could potentiate both innate and adaptive immune responses might increase the efficacy of checkpoint inhibition. Methods/Materials: We administered intralesional injections of immunotherapy (4-8 mg pembrolizumab + 2-4mg mRNA 2752) to patients with “high-risk” DCIS in an attempt to modulate the immune system and protect from disease progression and recurrence. Two patients have been enrolled and completed therapy and 4 more are being treated. Immune infiltrates were characterized by multiplex immunofluorescence (mIF) staining of pre- and post-treatment tissue samples using two 6-plex panels. Staining was performed on a Leica Bond autostainer and images were acquired on a Vectra Polaris imaging system. Image analysis was performed utilizing inForm and QuPath software packages, as well as R scripts. Results: The first patient treated, a 41-year-old woman with ER+/PR+, HER2- disease, with low T cells in her pre-treatment biopsy, received one dose of pembrolizumab (8mg) with mRNA 2752 (4mg). While she experienced fatigue, sustained fever, and muscle aches for 3-5 days, draining node enlargement and redness and swelling at the breast a week after treatment, there was no change on her post-treatment MRI, and no significant change in the number of T cells in her post-treatment tissue. The second patient, a 74-year-old woman with ER-/PR-, HER2+ disease had high numbers of T cells in the pre-treatment biopsy. She received one injection of pembrolizumab (4mg) with mRNA 2752 (2mg), followed 3 weeks later by an injection of pembrolizumab (4mg) alone. She declined the second dose of mRNA 2752 due to side effects from the first injection. Her post-treatment MRI showed some reduction in tumor volume and her post-treatment biopsy showed no evidence of DCIS, as well as an increase in T cells. Conclusions: The presence of T cells prior to therapy is likely to be important for eliciting a strong anti-tumor response. The addition of an agent that enhances both innate and adaptive immune responses may increase the efficacy of immune checkpoint blockade. Four additional patients will have completed their therapy by the end of August and we await results. It will be important to understand if pre-existing T cells within the DCIS lesion are a predictor for response to therapy as we continue to screen and enroll patients. Citation Format: Nicole F. Schindler, Alexa Glencer, Phoebe Miller, Christopher Schwartz, Gillian Hirst, Alexander Borowsky, Michael Campbell, Laura Esserman. Intralesional injections with checkpoint inhibitors and cytokines can modify DCIS lesions with infiltrating T cells [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B005.

Background/Aim: Testing for human epidermal growth factor receptor 2 (HER2) positivity in women diagnosed with ductal carcinoma in situ (DCIS) is not performed routinely, although the frequency of HER2+ DCIS is at least 30%. HER2+ DCIS lesions may be at higher risk of progression to invasive carcinoma, and specific isoforms of HER2 may lead to different malignant potential. Loss of the HER2 extracellular domain engineered in mouse models demonstrates rapid progression to invasive behavior. Evaluating isoforms of HER2 may aid in classifying DCIS lesions as higher or lower risk, and may provide insight for novel treatment and prevention approaches. Methods: A cohort of high risk DCIS cases were assembled, enriched for the presence of high risk features, including large size (>5 cm) and palpable. Immunohistochemistry (IHC) and FISH were used to identify cases that were HER2 positive. MultiplexIHC was used to detect extracellular and intracellular domains of HER2, with imaging analysis performed to identify HER2 isoforms of HER2+ specimens. Isoforms were characterized as 1) full-length/extracellular domain (ECD) intact, 2) pure/complete loss of ECD (p95 isoform), 3) subclonal populations of both full-length ECD and p95 and 4) gradient/representing partial loss of ECD per cell (reflecting post-translational cleavage). Results: Out of 51 cases, 34 (67%) cases were HER2+. In multiplexIHC analysis for HER2, 51% displayed gradient (partial) or focal (subclonal) loss of the extracellular domain. 33% displayed pure p95 isoform (complete loss of ECD). Only 16% of the cohort displayed full-length HER2 extracellular domain. Conclusions: HER2 expression is much more common in large in situ lesions than in invasive lesions. This suggests that HER2 positivity may play a role in protecting against invasion. Investigation of HER2 Isoform testing using multiplex staining reveals heterogeneity with partial or complete loss of the HER2 extracellular domain being most common. Loss of the extracellular domain of human epidermal growth factor receptor 2 (HER2) p95 isoform is predominant among patients diagnosed with HER2 positive ductal carcinoma in situ (DCIS). Citation Format: Nicole F. Schindler, Alexa Glencer, Hidetoshi Mori, Gillian Hirst, Cristian Maldonado Rodas, Michael Campbell, Laura Esserman, Alexander Borowsky. Loss of the extracellular domain of human epidermal growth factor receptor 2 (HER2) p95 isoform is common in large DCIS lesions [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B013.

The tetraneutron has attracted the attention of nuclear physicists during the past decades, but there is still no unambiguous confirmation of its existence or non-existence. A new experiment based on $$^{8}$$ He(p, 2p) $$^{7}$$ H{t+ $$^{4}n$$ } reaction, with direct detection of the four neutrons, has been carried out at RIBF, which can hopefully help to draw a definite conclusion on the tetraneutron system.

Nuclear instruments & methods in physics research / A 1014, 165701 (2021). doi:10.1016/j.nima.2021.165701, Published by North-Holland Publ. Co., Amsterdam

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear—particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome. Mouse models of NF1-associated optic pathway glioma show that tumour initiation and growth are driven by aberrantly high levels of NLGN3 shedding in the optic nerve in response to retinal neuron activity.

The isospin characters of low-energy dipole excitations in neutron-rich unstable nucleus 20O were investigated, for the first time in unstable nuclei. Two spectra obtained from a dominant isovector probe (View the MathML sourceO20+Au) and a dominant isoscalar probe (View the MathML sourceO20+α) were compared and analyzed by the distorted-wave Born approximation to extract independently the isovector and isoscalar dipole strengths. Two known 1−1− states with large isovector dipole strengths at energies of 5.36(5) MeV (View the MathML source11−) and 6.84(7) MeV (View the MathML source12−) were also excited by the isoscalar probe. These two states were found to have different isoscalar dipole strengths, 2.70(32)% (View the MathML source11−) and 0.67(12)% (View the MathML source12−), respectively, in exhaustion of the isoscalar dipole-energy-weighted sum rule. The difference in isoscalar strength indicated that they have different underlying structures. ispartof: Physics Letters B vol:768 pages:387-392 status: published

7 pags., 3 figs. -- 27th International Nuclear Physics Conference (INPC2019), The tetraneutron has attracted the attention of nuclear physicists during the past decades, but there is still no unambiguous confirmation of its existence or nonexistence. A new experiment based on 8 He(p,2p)7H{t+4n} reaction, with direct detection of the four neutrons, has been carried out at RIBF, which can hopefully help to draw a definite conclusion on the tetraneutron system., We acknowledge the support of the RIBF accelerator staff and the BigRIPS team for providing the high-quality beam. Z. H. Yang acknowledges the financial support from the Foreign Postdoctoral Researcher program of RIKEN. T. Aumann acknowledges the support by DFG via SFB 1245. P. Koseoglou acknowledges the support from BMBF (NUSTAR.DA grant No.05P 15RDFN1).

Distilled water plus 0.1% surfactant suspensions of spores of Aspergillus flavus and Aspergillus parasiticus were exposed to several radiation levels of cobalt-60 gamma rays. Spores of A. flavus isolate M-141 were exposed to radiation levels of approximately 16, 90 and 475 Krads and inoculated onto a sterile rice substrate which was then monitored for aflatoxin production. In this initial trial with A. flavus M-141, aflatoxins B1 and M production on rice increased as radiation dose increased. At the highest dose, this increase was more than 50 times higher than the non-irradiated controls. Spores of an aflatoxin G1-producing A. parasiticus isolate, M-1094, were exposed to 90, 215 and 430 Krads and resulted in increased production of aflatoxins G1, B1, and M. Aflatoxin production by M-1094 was highest at the low and medium dose levels. Irradiation of spores of this isolate with 430 Krads produced no observable spore germination or growth on rice and no detectable aflatoxin after 1 week of incubation at 27 ...

Neurons have recently emerged as essential cellular constituents of the tumor microenvironment, where their activity increases the growth of a diverse number of solid tumors. While the role of neurons in tumor progression has been previously demonstrated, the importance of neuronal activity to tumor initiation is less clear, particularly in the setting of cancer predisposition syndromes. In the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome, in which tumors arise in close association with nerves, 15% of individuals develop low-grade neoplasms of the optic pathway (optic gliomas) during early childhood, raising the intriguing possibility that postnatal light-induced optic nerve activity drives tumor initiation. Here, we employ an authenticated murine model of Nf1 optic glioma to demonstrate that stimulation of optic nerve activity increases optic glioma growth, while decreasing optic nerve activity via light deprivation prevents tumor formation and maintenance. By manipulating environmental light to modulate optic pathway (retinal) neuron activity, we show that Nf1 optic glioma initiation depends on neuronal activity during a developmental period susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly high optic nerve neuroligin-3 (Nlgn3) shedding in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacologic inhibition of Nlgn3 shedding blocks murine Nf1 optic gliomagenesis and progression. Collectively, these studies establish an obligate role for neuronal activity in the development of certain brain tumors, elucidate a therapeutic strategy to reduce optic glioma incidence or mitigate tumor progression, and underscore the role of Nf1 mutation-mediated dysregulation of neuronal signaling pathways in the NF1 cancer predisposition syndrome.

The tetraneutron has been drawing the attention of the nuclear physics community for decades, but a firm conclusion on its existence and properties is still far from being reached despite many experimental and theoretical efforts. New measurements have recently been performed at RIBF with the SAMURAI spectrometer by applying complementary reaction probes, which will help to pin down the properties of this four-neutron system., Comment: 5 pages, 2 figures, conference proceedings of XXII International Conference on Few-Body Problems in Physics (FB22), Caen, France, July 2018

Insulin-degrading enzyme (IDE, insulysin) is the best characterized catabolic enzyme implicated in proteolysis of insulin. Recently, a peptide inhibitor of IDE has been shown to affect levels of insulin, amylin, and glucagon in vivo. However, IDE(-/-) mice display variable phenotypes relating to fasting plasma insulin levels, glucose tolerance, and insulin sensitivity depending on the cohort and age of animals. Here, we interrogated the importance of IDE-mediated catabolism on insulin clearance in vivo. Using a structure-based design, we linked two newly identified ligands binding at unique IDE exosites together to construct a potent series of novel inhibitors. These compounds do not interact with the catalytic zinc of the protease. Because one of these inhibitors (NTE-1) was determined to have pharmacokinetic properties sufficient to sustain plasma levels >50 times its IDE IC50 value, studies in rodents were conducted. In oral glucose tolerance tests with diet-induced obese mice, NTE-1 treatment improved the glucose excursion. Yet in insulin tolerance tests and euglycemic clamp experiments, NTE-1 did not enhance insulin action or increase plasma insulin levels. Importantly, IDE inhibition with NTE-1 did result in elevated plasma amylin levels, suggesting the in vivo role of IDE action on amylin may be more significant than an effect on insulin. Furthermore, using the inhibitors described in this report, we demonstrate that in HEK cells IDE has little impact on insulin clearance. In total, evidence from our studies supports a minimal role for IDE in insulin metabolism in vivo and suggests IDE may be more important in helping regulate amylin clearance.

The species of the family Goodeidae have evolved reproductive strategies involving intraovarian gestation, early evacuation of nearly yolk-exhausted embryos from the ovigerous tissue into the ovarian cavity, placental matrotrophy during intraluminal gestation, and the birth of highly developed fry. The inner ovarian lining becomes hypervascularized during gestational periods and functions as the maternal component of the placental association. Embryotrophic liquid is secreted by the inner ovarian epithelium into the ovarian cavity. Comparative electrophoretic analyses of embryotrophe and maternal blood serum provide evidence for the transfer of maternal serum proteins into the embryotrophe. Trophotaeniae, proctodaeal processes of the embryos, provide a surface for nutrient absorption. Endocytic activity was demonstrated by ingestion of unspecific tracer proteins in various species. Moreover, the trophotaenial absorptive cells (TACs) in Ameca splendens ingest various proteins or random copolymers conjugated to colloidal gold as well as radioiodinated proteins in a way that satisfies the criteria of receptor-mediated endocytosis. Several aminopeptidases (APs) on the surface of TACs were identified as protein binding sites as evidenced by inhibition of binding and uptake of marker proteins in the presence of AP substrates or AP inhibitors. Morphological adaptations of the embryonic circulatory system pertaining to nutrient and gas exchange were characterized. The embryonic epidermis comprises two layers of squamous cells closely underlain by a dense capillary net. Efficient gas exchange is facilitated by a thin embryotrophe-blood barrier of both the embryonic skin and the intraovarian lining.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-dependent enzyme that catalyzes the initial and rate-limiting step of tryptophan catabolism resulting in the local depletion of tryptophan and the concomitant production of kynurenine, both of which are immunosuppressive. Targeting IDO1 in combination with PD-1/PD-L1-targeted antibodies has shown promise in early phase clinical trials in several cancers and strongly suggests that, in some patients, IDO1 expression restrains PD-1/PD-L1-targeted checkpoint therapies. While some cancers extrinsically express IDO1 in response to IFN-γ produced from an ongoing, yet ineffective immune response, others select for the intrinsic expression of IDO1, independent of an immune response. We identified several cancer cell lines that intrinsically expressed either IDO1 or the related isozyme TDO2. Using these cell lines, we discovered LY3381916, a potent and selective inhibitor of cell-based IDO1 activity (IDO1 7 nM; TDO2 >20 µM). Using a variety of techniques, we demonstrated that LY3381916 binds to newly synthesized apo-IDO1 lacking heme, but does not inhibit mature heme-bound IDO1. Protein x-ray crystallography confirmed that LY3381916 binds to apo-IDO1 where it occupies the heme-binding pocket of IDO1. As a result of this novel mechanism of action, substantial inhibition of IDO1 in tumors requires the turn-over of mature heme-bound IDO1. Modeling of the pre-clinical PK/PD relationship suggests QD dosing of LY3381916 will maintain greater than 90% inhibition over 24 hours. In addition, due to the favorable properties of the drug, significant central nervous system (CNS) penetration has been measured for LY3381916 (rodent kp,uu 0.26). Kynurenine-mediated agonism of the aryl hydrocarbon receptor (AHR) is immunosuppressive in the tumor microenvironment. Inhibition of IDO1 and the subsequent reduction of kynurenine can relieve this immunosuppression. However, several heme-binding IDO1 inhibitors have been shown to replace kynurenine as an AHR agonist potentially limiting their ability to relieve this IDO1-dependent immunosuppressive mechanism. LY3381916 shows no confounding agonism of AHR up to 100 µM. Additionally, we characterized LY3381916 in pre-clinical tumor models and demonstrated that it was able to enhance LY3300054, anti-PD-L1 antibody (LY3300054) activity, which was associated with an enhanced T cell response. Based on these characteristics, LY3381916 is currently being investigated in a Phase I clinical trial. These data suggest further development of LY3381916 may be warranted. Citation Format: Frank C. Dorsey, Karim A. Benhadji, Lillian L. Sams, Debra A. Young, John F. Schindler, Karen L. Huss, Alexander Nikolayev, Carmine Carpenito, David Clawson, Bonita Jones, Andrew L. Faber, James E. Thomas, Steven A. Haney, Gaiying Zhao, William T. McMillen, Tod Smeal, Daniel J. Sall, Michael D. Kalos, Sandaruwan Geeganage, James R. Henry. Identification and characterization of the IDO1 inhibitor LY3381916 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5245.

The grain boundary (GB) network in biaxially textured YBa/sub 2/Cu/sub 3/O/sub x/ (Y123) coated conductors is the key to their transport properties and determines the upper limit for the critical current density. In this contribution we report on detailed EBSD (electron backscattering diffraction) investigations of the formation of these GB networks in Y123 films deposited on highly biaxially textured metallic substrates and the comparison of the measured critical current density with simulations based on the exact knowledge of the underlying GB network. Highly cube textured Ni-tapes were prepared by rolling and recrystallization and detailed texture maps were determined by EBSD before and after the deposition of Y123 films by thermal evaporation or pulsed laser deposition. This allowed the quantitative evaluation of both the Y123-growth on different oriented Ni-grains and the GB misorientation network which determines the critical current density. This exact texture information was also used to calculate the critical current density based on the well known exponential j/sub c/-dependence across Y123 tilt GBs and is compared to the measured transport j/sub c/ across the same substrate area.

The Popeye domain containing (Popdc) gene family displays preferential expression in skeletal muscle and heart. Only recently a significant gain in the understanding of the function of Popdc genes in the heart has been obtained. The Popdc genes encode membrane proteins harboring an evolutionary conserved Popeye domain, which functions as a binding domain for cyclic adenosine monophosphate (cAMP). Popdc proteins interact with the two-pore channel TREK-1 and enhance its current. This protein interaction is modulated by cAMP. Null mutations of members of the Popdc gene family in zebrafish and mouse are associated with severe cardiac arrhythmia phenotypes. While in zebrafish an atrioventricular block was prevalent, in mouse a stress-induced sinus bradycardia was observed, which was due to the presence of sinus pauses. Moreover, the phenotype develops in an age-dependent manner, being absent in the young animal and becoming increasingly severe, as the animals grow older. This phenotype is reminiscent of the sick sinus syndrome (SSS), which affects mostly the elderly and is characterized by the poor ability of the cardiac pacemaker to adapt the heart rate to the physiological demand. While being a prevalent disease, which is responsible for a large fraction of pacemaker implantations in Western countries, SSS is poorly understood at the molecular level. It is therefore expected that the study of the molecular basis of the stress-induced bradycardia in Popdc mice will shed new light on the etiology of pacemaker disease.

The potential importance of several functional amino acids in the activity of L-aspartase from Escherichia coli has been examined by site-directed mutagenesis. Amino acids whose importance in enzyme activity was suggested by chemical modification and pH dependence studies were chosen as candidates for investigation. The selection of the particular amino acid targets was guided by homology comparisons among the other sequenced bacterial L-aspartases and by the broader comparison among the fumarase-aspartase enzyme family. Substitution of the most highly conserved cysteine with either serine or alanine, or the most highly conserved histidine with leucine, had no significant effect on the activity of L-aspartase or on the sensitivity of these mutated L-aspartases to cysteine and histidine specific modifying reagents. However, alteration of each of the two conserved lysines to arginine did cause dramatic changes in the catalytic properties of the enzyme. Modification of lysine 54 results in the complete loss of enzyme activity. However, this activity loss appears to be related to changes in the subunit association properties of the arginine 54 mutant. Lysine 326 appears to be involved in substrate binding. Modification of this residue causes a 5-fold increase in the Km for aspartic acid, a drastic decrease in kcat/Km, and a change in the divalent metal ion requirements of the enzyme.

Objective: To compare the results for homocysteine concentration using chemiluminescence and HPLC methods in samples from school-age children. In addition, to determine the reference values for patients of this age group and assess the real prognostic value of homocysteine in healthy children. Methods: A prospective observational study was undertaken to determine plasma levels of homocysteine using two different assays, HPLC and chemiluminescence, in 185 samples from school-age children living in Santo Andre, with no chronic or inflammatory diseases, and absence of pubertal development. Results: The results were presented in percentiles and reference values were determined within this age group (7-9 years old). Homocysteine concentration ranged from 2.0 to 9.9 µmol/l (r = 0.821 and p < 0.001). Conclusions: It was verified that chemiluminescence is comparable to HPLC when both techniques are used to detect homocysteine in school-age children. There is an important correlation between both methods, which allows investigation of this amino acid as a risk factor for heart diseases.

The classical nuclear factor kappaB (NF-kappaB) signaling pathway is under the control of the IkappaB kinase (IKK) complex, which consists of IKK-1, IKK-2, and NF-kappaB essential modulator (NEMO). This complex is responsible for the regulation of cell proliferation, survival, and differentiation. Dysregulation of this pathway is associated with several human diseases, and as such, its inhibition offers an exciting opportunity for therapeutic intervention. NEMO binding domain (NBD) peptides inhibit the binding of recombinant NEMO to IKK-2 in vitro. However, direct evidence of disruption of this binding by NBD peptides in biological systems has not been provided. Using a cell system, we expanded on previous observations to show that NBD peptides inhibit inflammation-induced but not basal cytokine production. We report that these peptides cause the release of IKK-2 from an IKK complex and disrupt NEMO-IKK-2 interactions in cells. We demonstrate that by interfering with NEMO-IKK-2 interactions, NBD peptides inhibit IKK-2 phosphorylation, without affecting signaling intermediates upstream of the IKK complex of the NF-kappaB pathway. Furthermore, in a cell-free system of IKK complex activation by TRAF6 (TNF receptor-associated factor 6), we show that these peptides inhibit the ability of this complex to phosphorylate downstream substrates, such as p65 and inhibitor of kappaB alpha (IkappaB alpha). Thus, consistent with the notion that NEMO regulates IKK-2 catalytic activity by serving as a scaffold, appropriately positioning IKK-2 for activation by upstream kinase(s), our findings provide novel insights into the molecular mechanisms by which NBD peptides exert their anti-inflammatory effects in cells.

International audience; Study design:Retrospective study.Objectives:To determine the potential impact of rehabilitation care on associated symptoms and functional improvements of paraplegic patients with metastatic spinal cord compression.Setting:CMN Propara, Montpellier (France).Measures:Demographics, Functional Independence Measure (FIM), Frankel Modified Score and Visual Analog Scale (VAS) for pain, intercurrent adverse medical events and neurological outcome, duration of stay, survival time, rehospitalization in a non-Spinal Cord Injury unit, number of contracts defining the patients rehabilitation goals, number of contracts defining the patients duration of stay within the rehabilitation center.Results:We reviewed the charts of 26 patients. The initial neurological profile was paraplegia or paraparesis for 24 patients and quadriparesis for 2 patients. Regarding functional improvements: four patients demonstrated a poor functional evolution, five patients showed no functional improvements or very slight improvements and all the other patients showed an increase in their overall functional aptitudes. At the end of the stay, 14 patients were urinary independent. Our study reports 52 rehospitalizations in an another unit and 101 outpatient visits during their rehabilitation stay in a physical medicine and rehabilitation (PM&R) center. For the 14 patients who were deceased at the time of data collection, the median survival rate post-paraplegia was 12.7 months. A total of 12 of the 14 patients spent more than a third of their remaining survival time in a rehabilitation center.Discussion:Compared to the patients' life expectancy, their stay in a rehabilitation center is too long and prevents them from spending time with family and loved ones. The occurrence rate of the associated symptoms is high because of both cancer-related disorders and neurological disorders caused by the spinal cord lesion. PM&R professionals are faced with patients affected by chronic pain and fatigue as well as frequent rehospitalizations, short stays and outpatient stays, in the primary oncology unit. This study focuses on the need to privilege the patients' comfort over their functional rehabilitation.Spinal Cord advance online publication, 10 June 2008; doi:10.1038/sc.2008.75.

Photocurrent spectroscopy is used to investigate the quantum-confined Stark shift of In0.5Ga0.5As/GaAs self-assembled quantum dots grown on (100) and (311)B planes. By comparing the Stark shift for dots grown on (100) and (311)B planes, we find that in the (311)B dots, the electron and hole wave functions are displaced by a strain-induced piezoelectric field directed from the apex to the base of the dots.

The isolated vascular effects of intravenous administration of the angiotensin converting enzyme (ACE) inhibitor enalaprilat were investigated. Thirty male patients undergoing cardiopulmonary bypass (CPB) were studied. According to a randomized sequence, 0.04 mg kg-1 enalaprilat (low-dose, n = 10), 0.08 mg kg-1 (high-dose, n = 10) enalaprilat or saline solution as placebo (control group, n = 10) was given as an i.v. bolus during CPB. Changes in mean arterial pressure (MAP) and venous reservoir (RV) of the extracorporeal circulation were studied as indices of arterial resistance and venous capacitance. Mean arterial blood pressure (MAP) and peripheral vascular resistance (SVR) were significantly more reduced in the high-dose enalaprilat group (MAP: -36 mm Hg after 9 min; SVR: -836 dyn s cm-5) than in the low-dose group (MAP: -13 mm Hg after 10 min). Volume of the reservoir (RV) decreased in both enalaprilat treated groups indicating additional (dose-dependent) venous pooling effects of the substance (low-dose: -300 ml; high-dose: -520 ml; control group: -100 ml). Skin capillary blood flow measured by laser Doppler flowmetry (LDF) increased after injection of 0.04 mg kg-1 enalaprilat, whereas it decreased significantly when MAP fell markedly in patients treated with high-dose enalaprilat. I.v. enalaprilat had dose-dependent vasodilating properties in the arterial and venous vessel system indicating reduction in pre- and afterload. Microcirculation in both enalaprilat treated groups improved as long as reduction in blood pressure was not limited.

There are reports of globulin abnormalities in various types of tumors during chemotherapy. Recently, even IgE levels seem to play an important role in the tumor's immune response. Trace elements, like Selenium (Se), act as basic components of essential system which play roles in immunology. Chemotherapy has been associated with decrease concentration of Se and this fact has been correlated with immunodepression states.

[Co(CO) 2 (R 2 PCH 2 ) 3 CCH 3 ][Co(CO) 4 ] (R  C 6 H 5 ) reacts with NaBH 4 , depending on the reaction conditions, to give CoH(CO) 2 (R 2 PCH 2 ) 2 C(CH 3 )CH 2 PR 2 · BH 3 and CoH(CO)(R 2 PCH 2 ) 3 CCH 3 . The hydride CoH(CO)(R 2 PCH 2 ) 3 CCH 3 is also formed by the reaction of [Co(CO) 2 (R 2 PCH 2 ) 3 CCH 3 ][Co(CO) 4 ] with LiOH, NaOH and NaNH 2 . The reaction with LiOH primarily gives (acetone) 3 -LiCo(CO)(R 2 PCH 2 ) 3 CCH 3 , which is also formed by reduction of [Co(CO) 2 (R 2 PCH 2 ) 2 C(CH 3 )CH 2 PR 2 ] 2 with lithium in THF/acetone solution. In liquid ammonia [Co(CO) 2 (R 2 PCH 2 ) 3 CCH 3 ][Co(CO) 4 ] at 20°C yields Co(CONH 2 )(CO)(R 2 PCH 2 ) 3 CCH 3 . This compound reacts in the same solvent at 60°C to yield the hydride CoH(CO)(R 2 PCH 2 ) 3 CCH 3 . CH 3 I and HClO 4 react with CoH(CO)(R 2 PCH 2 ) 3 CCH 3 yielding CoI(R 2 PCH 2 ) 3 CCH 3 and the unstable [Co(H) 2 (CO)(R 2 PCH 2 ) 3 CCH 3 ]ClO 4 , respectively. The deutero complex CoD(CO)(R 2 PCH 2 ) 3 CCH 3 was also synthesized. The new compounds were characterized, as much as possible, by their IR, 1 H NMR and 31 P NMR data.

Octacarbonyldicobalt reacts with the tritertiary phosphine 1,1,1-tris(diphenylphosphinomethyl)ethane (TDPME) to give the ionic complex [Co(CO)2TDPME][Co(CO)4]. Treatment of [Co(CO)2TDPME][Co(CO)4] with Na[B(C6H5)4], HClO4 and CH3J yields the cobalt(I)-salts [Co(CO)2TDPME]X [X == B(C6H5)4, ClO4, J]. With CH3J, [Co(CO)2TDPME]J can also be converted to Co(CO)2(J)(R2PCH2)2C(CH3)[CH2PR2CH3 +]J-in which TDPME is acting as a bidentate ligand. [Co(CO)2TDPME]ClO4 forms with KCN the non ionic compound Co(CN)(CO)(TPDME). The IR spectra of all compounds between 2100 and 400 cm-1 are reported. Based on Raman polarization data a tetragonal pyramid has been proposed for the five-coordinated cobalt(I) in the cation [Co(CO)2TDPME]+.

Carp erythrocytes were fractionated by angle-head centrifugation which yielded fractions with a linear increase in density. Haematological examinations revealed that the heavier red blood cells of carp had greater volumes (MCV), more haemoglobin (MCH) and higher haemoglobin concentrations (MCHC) than light ones. The same experiments with human red cell fractions yielded a decrease in MCV, constant MCH and an increase in MCHC. Haemoglobin content in individual erythrocytes was also determined by scanning stage absorbance cytophotometry to establish the frequency distribution of the cellular haemoglobin contents. In carp, the distribution was symmetrical with the means increasing with density. No such change with cell density was found in human erythrocytes. Both carp and human erythrocytes incorporated [2-14C]glycine in vitro. After gel filtration, radioactivity was detected in carp, but not in human, haemoglobin fractions. 14C was found in all three haemoglobin fractions, obtained by isoelectric focusing, and was present in the haem and in the globin. [2-14C]glycine-labelled erythrocytes were reinjected into chronically cannulated carp and followed in vivo for several months. With time, the main peak of scintillation counts shifted from red cell fractions of low to high density. This is considered as evidence that density and age of red cells in carp are positively correlated and that erythrocytes can synthesize haemoglobin while circulating in the peripheral blood.

Two aflatoxin-producing isolates of Aspergillus flavus were grown for 5 days on Wort media at 2, 7, 13, 18, 24, 29, 35, 41, 46, and 52 C. Maximal production of aflatoxins occurred at 24 C. Maximal growth of A. flavus isolates occurred at 29 and 35 C. The ratio of the production of aflatoxin B 1 to aflatoxin G 1 varied with temperature. Aflatoxin production was not related to growth rate of A. flavus ; one isolate at 41 C, at almost maximal growth of A. flavus , produced no aflatoxins. At 5 days, no aflatoxins were produced at temperatures lower than 18 C or higher than 35 C. Color of CHCl 3 extracts appeared to be directly correlated with aflatoxin concentrations. A. flavus isolates grown at 2, 7, and 41 C for 12 weeks produced no aflatoxins. At 13 C, both isolates produced aflatoxins in 3 weeks, and one isolate produced increasing amounts with time. The second isolate produced increasing amounts through 6 weeks, but at 12 weeks smaller amounts of aflatoxins were recovered than at 6 weeks.

Experiments were conducted to determine the culture requirements that would insure a probability of high ochratoxin production with a given isolate. Experiments at ambient temperatures (72 ± 2°F) determined the levels of the two most readily controlled variables, time and moisture content, during the growth of a high toxin-producing isolate (M298) of Aspergillus ochraceus. Tests were conducted in 2.8 L - Fernbach flasks containing 100 g shredded wheat and inoculated with spores on a transfer needle. Amounts of ochratoxin A/flask were determined by comparison against standards on TLC after chloroform extraction. Statistical analysis showed a relation between ochratoxin yield, water levels, and incubation periods. A water level of 40–70 ml/flask with an incubation period of 19-21 days at ambient temperatures should give a near to maximum yield of ochratoxin A.

n/a

Aflatoxicogenic isolates of Aspergillus were tested for their aflatoxin production after 8 weeks of growth on wort agar medium at high (41, 46 ± 1 C) and low (2, 7 ± 0.5 C) temperatures. Controls were grown at approximately 22 C, a temperature known to be favorable for aflatoxin production. There were two replications of each treatment. All replicate cultures of the 25 isolates grown at 22 C were positive for aflatoxin. Aflatoxins were not detected in wort agar when cultures were incubated at other test temperatures. It appears that both Aspergillus flavus and Aspergillus parasiticus will not produce aflatoxins when grown at ⩽ 7.5 C or at ⩾ 40 C.

Aspergillus flavus grew on a substrate of crushed and fresh red pepper (Capsicum frutescens) and produced anatoxins B1 and G1. In addition, there was a shift in the ratio of aflatoxins B1 to G1 as compared to the ratio of these aflatoxins when grown on a Wort agar substrate. The increase in the proportionate amount of aflatoxin G1 to aflatoxin B1 extracted from the crushed red pepper was statistically significant at the 0.1% level.

The effect of Vitamin E on the incidence and severity of RLF and BPD remains unclear. A prospective randomized controlled trial to further assess the role of Vit E in infants of 750-1500 gm to date includes 79 surviving infants (total n=105) of 29.5 wk (26-33 wk) gest., and birth weight 1130 gm (760-1500 gm). Randomization into groups was performed according to birth weight, (250 gm increments) initial Fi02 and need for intubation. Parenteral Vit E was administered on a fixed schedule within 12 hr of birth to 30 of the infants for 4 wk for a total dosage of 430 units followed by oral administration if tolerating feeds, or continued parenteral administration until 6 wk of age. There was no clinically significant difference between the two groups. Vit E levels were not significantly different at birth but were significantly higher in the Vit E group through-out the first 6 wk (33.8 vs. 6.9 mg/l, p

We report on the time resolved polarized emission from individual conjugated polymer chains as a function of temperature. Besides observing intrachain energy transfer in real time, we can also infer dephasing times from homogeneous linewidths.