Modelling umbilical vein blood flow normograms at 14-40 weeks of gestation by quantile regression analysis.
To construct reference limits for gestation of umbilical vein blood flow (UVBF) in normal singleton pregnancies between 14 and 40 weeks of gestation using quantile regression. We ultrasonographycally examined 852 fetuses from low-risk pregnancies between 16 and 40 weeks of gestation in a prospective cross-sectional study. UV diameter and time-averaged maximum velocity (TAMXV) were measured in UV intra-abdominal portion by real time and Doppler ultrasonography. A semi-automatic measurement software was used to obtain UV diameter values. UVBF was then calculated from UV diameter and TAMXV measurements and expressed both as absolute value and as value normalized for fetal abdominal circumference (UVBF/AC). Individual centile values of the variables investigated were established by quantile regression in the gestational interval considered. In 50 cases UVBF was measured twice by the same investigator or by a second investigator and the intra- and inter-observer agreement were calculated. A significant increase in UV diameter, TAMXV, UVBF absolute value and UVBF/AC was evidenced in the gestational period considered. Growth charts were established based on these measurements. The intra- and inter-observer intraclass correlation coefficients resulted as 0.92 (0.87-0.96) and 0.89 (0.84-0.97), respectively, for UBVF. In this study we constructed UVBF charts using quantile regression in a large cohort of low-risk pregnancies. These charts offer the advantage of specific estimated regression parameters for each percentile, better defining the normal range of UVBF. This promises to be useful in the diagnosis and management of fetuses with abnormal fetal growth.


Sleep disturbances and circadian CLOCK genes in borderline personality disorder.
Borderline personality disorder (BPD) is characterised by a deep-reaching pattern of affective instability, incoherent identity, self-injury, suicide attempts, and disturbed interpersonal relations and lifestyle. The daily activities of BPD patients are often chaotic and disorganized, with patients often staying up late while sleeping during the day. These behavioural patterns suggest that altered circadian rhythms may be associated with BPD. Furthermore, BPD patients frequently report suffering from sleep disturbances. In this review, we overview the evidence that circadian rhythms and sleep are disturbed in BPD, and we explore the possibility that personality traits that are pertinent for BPD may be associated with circadian typology, and perhaps to circadian genotypes. With regards to sleep architecture, we review the evidence that BPD patients display altered non-REM and REM sleep. A possible cue to a deeper understanding of this temporal dysregulation might be an analysis of the circadian clock at the molecular and cellular level, as well as behavioural studies using actigraphy and we suggest avenues for further exploration of these factors.


Effects of pituitary adenylate cyclase activating polypeptide on the survival and signal transduction pathways in human choriocarcinoma cells.
The pituitary adenylate cyclase activating polypeptide (PACAP) has several effects in endocrine and reproductive organs, including the placenta. PACAP is generally known as a survival-promoting peptide acting on divergent signal transduction pathways. However, its effects on the survival and signaling mechanisms of trophoblast cells are not known. In the present study we found that 1-h pretreatment with PACAP38 did not significantly influence the survival of JAR cytotrophoblast cells. However, the survival rate of cells exposed to oxidative stress or CoCl(2)-induced in vitro hypoxia showed a significant further decrease in PACAP-treated cells, implying that PACAP sensitizes the cells to these stressors. This was not observed in the case of lipopolysaccharide or ethanol treatment. Western blot data revealed that, in cells exposed to oxidative stress, PACAP treatment decreased phosphorylation of all extracellular signal-regulated kinase (ERK), phospho-jun N-terminal kinase (JNK), protein kinase B, p38 mitogen-activated protein kinase (MAPK), and phospho-glycogen synthase kinase (GSK) and the expression of bax. The overall effect seems to be a sensitizing effect in almost all examined pathways when oxidative stress was applied, which may explain the enhancing effect of PACAP on cell death in contrast to most other cell types examined so far. Our data show that the signaling mechanism of PACAP may be different in trophoblast cells to that observed in other cell lines.


A case report of an uncommon phaeoid fungal infection in nasal polyposis and review of literature.
Nasal polyposis is an inflammatory condition of mucous membrane of the nose and paranasal sinuses with unknown aetiology. Massive nasal polyps can obstruct the nasal cavity causing discomfort and lowered quality of life. Thus, aetiological diagnosis is important for treatment, especially in recurrent nasal polyposis. We present a rare case of pansinusitis with bilateral ethmoidal polyps caused by an unusual phaeoid fungus Fonsecaea pedrosoi in a 65-year-old immunocompetent male from a rural background. The diagnosis was made by endoscopic nasal examination; high resolution computed tomography of the paranasal sinuses, detection of fungal hyphae in 10% potassium hydroxide wet mount and culture.


Peripheral MR angiography.
Peripheral MR Angiography is rapidly developing and becoming the standard method for evaluating peripheral vascular disease. MRA allows accurate and detailed assessment of peripheral vasculature without requiring arterial catheterization, nephrotoxic contrast, or ionizing radiation. Latest improvements in this area include time-resolved MR angiography, stepping table bolus chase 3D MR angiography, fluoro-triggering, sub-systolic thigh compression to eliminate venous contamination, and parallel imaging. This article reviews these advances, describes how to use them effectively and how to avoid common pitfalls.


Morphologic aspects of airways of patients with pulmonary emphysema followed by bronchial asthma-like attack.
Morphometric analysis of airways was performed in autopsied lungs from four patients with pulmonary emphysema (PE) followed by bronchial-asthma (BA)-like attacks (Group PE+BA) (four males, 72 +/- 9 yr). The results were compared with those from five pulmonary emphysema patients (Group PE) (five males, age 71 +/- 4 hr), three patients with bronchial asthma (Group BA) (one female and two males, age 65 +/- 7 yr), and four control subjects with no pulmonary diseases (Group Cont) (one female, three males, age 64 +/- 4 yr). The proportion of gland area to bronchial wall (gland%), ratio of goblet-cell occupancy to the total epithelial layer (goblet%), thickness of the basement membrane, amount of intraluminal mucus (mucus occupying ratio; MOR%), and number of various cell types per square millimeter in airway walls in a section 4 microns thick were measured in central (3 to 8 mm diameter) and peripheral airways (2 mm or less diameter). Gland% for the PE+BA group was significantly greater than that for the Cont group, whereas it did not differ significantly from that of the PE or BA groups. Goblet% and thickness of the basement membrane in central and/or peripheral airways in Group PE+BA were significantly greater than those in Group Cont, whereas those in Group PE were similar to those in Group Cont. Although not statistically significant, MOR% in central and peripheral airways from Group PE+BA showed a similar value to that in Group BA, whereas MOR% in Group PE was the same as that in Group Cont. The eosinophil number in peripheral airways walls in Group PE+BA showed a similar value to that in Group BA, which was significantly greater than in Group Cont. Other cells (macrophages, lymphocytes, and neutrophils) showed similar values among Groups PE+BA, PE, and BA. The number of eosinophils in central and/or peripheral airways correlated significantly with both goblet% and BMT, whereas other cells did not. These findings indicate that the airways of Group PE+BA are morphologically similar to those of Group BA, suggesting a combination of pulmonary emphysema with bronchial asthma.


Glucose phosphate isomerase deficiency: biochemical and molecular genetic studies on the enzyme variants of two patients with severe haemolytic anaemia.
Biochemical and molecular genetic studies were performed on the enzyme variants of two patients compound heterozygous for glucose phosphate isomerase (GPI) deficiency, both suffering from severe haemolytic anaemia. The enzymes of case 1 (GPI 'Zwickau') and case 2 (GPI 'Nordhorn' [25]), revealed reduced GPI activity and remarkable thermolability. Glucose-6-phosphate (Gluc-6-P) concentration was elevated 2.3 times in case 1 and 3.8 times in case 2. Sequencing the patients' GPI genes showed four different point mutations, two of them involving highly conserved amino acids. The c1039 C-->T substitution, found in the gene of GPI 'Zwickau', has been described recently [30] and causes an Arg 347-->Cys substitution close to the putative catalytic site. The second mutation in this case is a novel c1538 G-->A substitution causing a Trp-->stop mutation at position 513 apparently resulting in premature RNA degradation thus resulting either in a complete lack of protein or a protein which does not show GPI activity. In the gene of GPI 'Nordhorn' a c1028 A-->G mutation was discovered, also previously described [1, 9] causing a Gln 343-->Trp substitution. The second mutation was a novel splice site mutation at the border of intron 15 to exon 16: IVS15-(-2) A-->C which leads to an aberrant splicing of exon 16, thus resulting either in a truncated and most likely inactive enzyme or in no protein at all. Biochemical and molecular genetic studies performed with the enzyme variants GPI 'Zwickau' and GPI 'Nordhorn' showed that in both cases the simultaneous occurrence of a single amino acid substitution affecting the active site, together with a nonsense mutation leading to the loss of major parts of the enzyme probably explains the severe clinical course of the disease.


Variable Message Signs for road tunnel emergency evacuations.
This paper investigates the design of Variable Message Signs (VMS) as a way-finding aid for road tunnel emergency evacuations. The use of the Theory of Affordances is suggested to provide recommendations on the design of VMS. A preliminary evaluation of 11 selected VMS systems was performed and 6 of them were further evaluated using an affordance-based within subject stated-preference questionnaire administered to a sample of 62 participants. Results are used to provide recommendations on the characteristics of the VMS systems, such as (1) size of the sign (large or small); (2) use of flashing lights; (3) colour scheme; (4) message coding (i.e., text, pictograms or a combination of them). The best performing VMS features for road tunnel emergency evacuation included the use of larger signs, flashing lights, the combination of emergency exit pictorial symbol in green in one panel and text in amber in the other panel.


Anti-inflammatory stent coatings: dexamethasone and related compounds.
The dexamethasone-eluting stent was a well-tolerated and effective means of providing sustained site-specific drug delivery to the porcine coronary artery wall for 28 days, although longer-term biocompatibility of the polymer coating was not assessed. Dexamethasone did not reduce the neointimal hyperplastic response to injury, despite sustained tissue levels of drug.


Urinary diversion: tailored solutions for individual patients.
Various urinary diversions are at disposition for reconstructive surgery after cystectomy. The chosen diversion has a strong impact on patients' life regarding complications and quality of life. The purpose of this review is to summarize the current tendency to adapt surgical solutions to individual needs of the patient. Tailored surgery requires that the surgeon has been trained in the handling of all gut segments. Only in this case can he react to anatomical variants, patient comorbidities and oncological circumstances, as well as to the prognosis and the social circumstances of the patient with a tailored diversion. Changing demography and ageing populations with increasing incidence of muscle invasive bladder cancer request new, less invasive methods of urinary diversions. There is little evidence as to which is the best urinary diversion due to a lack of well designed studies. The ileum conduit is still the most used urinary diversion worldwide. However, there are multiple techniques available to us, which guarantee the safest solution in combination with the highest quality of life for the construction of tailored urinary diversion.


An NMR study of the interaction of 15N-labelled bradykinin with an antibody mimic of the bradykinin B2 receptor.
An isotope-edited NMR study of the peptide hormone bradykinin (RPPGFSPFR) bound to the Fab fragment of a monoclonal antibody against bradykinin (MBK3) is reported. MBK3 was previously shown to provide a binding site model of the B2 bradykinin receptor [Haasemann, M., Buschko, J., Faussner, A., Roscher, A. A., Hoebeke, J., Burch, R. M. & Muller-Esterl, W. (1991) Anti-idiotypic antibodies bearing the internal image of a bradykinin epitope, J. Immunol. 147, 3882-3892]. Bradykinin was obtained in a uniformly 15N-labelled form using recombinant expression of a fusion protein consisting of the glutathione-binding domain of glutathione S-transferase fused to residues 354-375 of the high-molecular-mass kininogen from which bradykinin was released by proteolytic digestion with its natural protease plasma kallikrein. Bradykinin forms a complex with the Fab fragment of MBK3 which exchanges slowly on the NMR time scale. The 15N and 1H resonances of the tightly bound residues of bradykinin show appreciable changes in chemical shift with respect to the free form, while the 15N and 1H linewidths indicate that the hydrodynamic behaviour of bound bradykinin is dominated by the high-molecular-mass Fab fragment. The NMR data indicate that essentially the entire nonapeptide is involved in binding. The kinetics of the ligand-exchange process, together with resonance assignments obtained via exchange spectroscopy. indicate that bradykinin binds to MBK3 only in the all-trans conformation at all three Xaa-Pro amide bonds. NH-NH NOE connectivities suggest that bradykinin is bound in an extended conformation. The spectroscopic data obtained from this study are compared to recently proposed computational models of the conformation of bradykinin bound to the B2 receptor.


Correction to: Sex estimation of infants through geometric morphometric analysis of the ilium.
After publication of the original article, it was brought to authors' attention two errors that were included in the final publication.


An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while Remodeling Mature Amyloid Fibrils.
Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. It has been shown that lysine residues play a key role in the formation of these aggregates. Thus, the ability to disrupt aggregate formation by covalently modifying lysine residues could lead to the discovery of therapeutically relevant antiamyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aβ1-40 as model amyloidogenic proteins, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation. We also observed that IQ reacted with free amines within the amyloid fibrils preventing their dissociation and seeding capacity.


A new generation somatostatin-dopamine analogue exerts potent antitumoral actions on pituitary neuroendocrine tumor cells.
Background: Pituitary neuroendocrine tumors (PitNETs) represent approximately 15% of all intracranial tumors and usually are associated with severe comorbidities. Unfortunately, a relevant number of patients do not respond to currently available pharmacological treatments, that is, somatostatin analogs (SSAs) or dopamine-agonists (DA). Thus, novel, chimeric somatostatin/dopamine compounds (dopastatins) that could improve medical treatment of PitNETs have been designed. Objective: This study aims to determine the direct therapeutic effects of a new-generation dopastatin, BIM-065, on primary cell cultures from different PitNETs subtypes. Methods: Thirty-one PitNET-derived cell cultures (9 corticotropinomas, 9 somatotropinomas, 11 nonfunctioning pituitary adenomas [NFPAs], and 2 prolactinomas), were treated with BIM-065, and key functional endpoints were assessed (cell viability, apoptosis, hormone secretion, expression levels of key genes, free cytosolic [Ca2+]i dynamics, etc.). AtT-20 cell line was used to evaluate signaling pathways in response to BIM-065. Results: This chimeric compound decreased cell viability in all corticotropinomas and somatotropinomas tested, but not in NFPAs. BIM-065 reduced ACTH, GH, chromogranin-A and PRL secretion, and increased apoptosis in corticotropinomas, somatotropinomas, and NFPAs. These effects were possibly mediated through modulation of pivotal signaling cascades like [Ca2+]i kinetic and Akt- or ERK1/2-phosphorylation. Conclusions: Our results unveil a robust antitumoral effect in vitro of the novel chimeric compound BIM-065 on the main PitNET subtypes, inform on the mechanisms involved, and suggest that BIM-065 could be an efficacious therapeutic option to be considered in the treatment of PitNETs.


A monoclonal antibody recognizing the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) trisaccharide alphaKdo(2-->4)alphaKdo(2-->4)alphaKdo of Chlamydophila psittaci 6BC lipopolysaccharide.
A monoclonal antibody (mAb) S45-18 was generated against a synthetic neoglycoconjugate containing the trisaccharide alphaKdo(2-->4)alphaKdo(2-->4)alphaKdo (Kdo, 3-deoxy-D-manno-oct-2-ulopyranosonic acid) which represents a structure of the lipopolysaccharide (LPS) from Chlamydophila psittaci 6BC. The antibody was characterized by binding and inhibition assays in ELISA using: (i) the immunizing antigen and chemically synthesized derivatives thereof; (ii) chlamydial elementary bodies (EB); and (iii) LPS of Chl. psittaci 6BC and Chlamydia trachomatis L2. The specificity was determined in comparison to that of mAb S25-23 recognizing the alphaKdo(2-->8)alphaKdo(2-->4)alphaKdo trisaccharide which represents an epitope shared by all species of the family. MAb S45-18 bound to an epitope of the structure alphaKdo(2-->4)alphaKdo(2-->4)alphaKdo, with lower reactivity with the (2-->8)-(2-->4)-linked analog. Using chlamydial EB or LPS, mAb S45-18 bound preferentially to LPS and EB of Chl. psittaci. Therefore, Chl. psittaci LPS contains, in addition to the known genus-specific epitope, a species-specific epitope.


Lactate disposal in resting trained and untrained forearm skeletal muscle during high intensity leg exercise.
At a given oxygen uptake (VO2) and exercise intensity blood lactate concentrations are lower following endurance training. While decreased production of lactate by trained skeletal muscle is the commonly accepted cause, the contribution from increased lactate removal, comprising both uptake and metabolic disposal, has been less frequently examined. In the present study the role of resting skeletal muscle in the removal of an arterial lactate load (approximately 11 mmol.l-1) generated during high intensity supine leg exercise (20 min at approximately 83% maximal oxygen uptake) was compared in the untrained (UT) and trained (T) forearms of five male squash players. Forearm blood flow and the venoarterial lactate concentration gradient were measured and a modified form of the Fick equation used to determine the relative contributions to lactate removal of passive uptake and metabolic disposal. Significant lactate uptake and disposal were observed in both forearms without any change in forearm VO2. Neither the quantity of lactate taken up [UT, 344.2 (SEM 118.8) mumol.100 ml-1; T, 330.3 (SEM 85.3) mumol.100 ml-1] nor the quantity disposed of [UT, 284.0 (SEM 123.3) mumol.100 ml-1, approximately 83% of lactate uptake; T, 300.8 (SEM 77.7) mumol.100 ml-1, approximately 91% of lactate uptake] differed between the two forearms. It is concluded that while significant lactate disposal occurs in resting skeletal muscle during high intensity exercise the lower blood lactate concentrations following endurance training are unlikely to result from an increase in lactate removal by resting trained skeletal muscle.


Intracellular lipid particles of eukaryotic cells.
In this review article we describe characterization of intracellular lipid particles of three different eukaryotic species, namely mammalian cells, plants and yeast. Lipid particles of all types of cells share a general structure. A hydrophobic core of neutral lipids is surrounded by a membrane monolayer of phospholipids which contains a minor amount of proteins. Whereas lipid particles from mammalian cells and plants harbor specific classes of polypeptides, mainly perilipins and oleosins, respectively, yeast lipid particles contain a more complex set of enzymes which are involved in lipid biosynthesis. Function of lipid particles as storage compartment and metabolic organelle, and their interaction with other subcellular fractions are discussed. Furthermore, models for the biogenesis of lipid particles are presented and compared among the different species.


Spontaneous intracerebral hemorrhage: to operate or not to operate, that's the question.
The occurrence of a spontaneous intracerebral hemorrhage in Israel's Prime Minister attracted the scrutiny of local and international media on neurosurgeons as they made therapeutic decisions. In the ensuing public debate, it was suggested that extraordinary measures (surgical treatment) were undertaken only because of the celebrity of the patient. To evaluate the criteria used to select surgical versus medical management for SICH. We retrospectively reviewed the files of 149 consecutive patients with SICH admitted to our medical center from January 2004 through January 2006. Their mean age was 66 (range 3-92 years), and 62% were male. SICH localization was lobar in 50% of patients, thalamus in 23%, basal ganglia in 15%, cerebellum in 13%, intraventricular in 6%, and pontine in 1%. Mean admission Glasgow Coma Score was 9 (range 3-15). Risk factors included hypertension (74%), diabetes mellitus (34%), smoking (14%) and amyloid angiopathy (4%). Fifty percent of patients were on anticoagulant/antiplatelet therapy, including enoxaparin (3%), warfarin (7%), warfarin and aspirin (9%), or aspirin alone (34%). Craniotomy was performed in 30% of patients, and ventriculostomy alone in 3%. Rebleed occurred in 9% of patients. Six months after treatment 36% of operated patients were independent, 42% dependent, and 13% had died. At 6 months, 37% of non-operated patients were independent, 15% dependent, and 47% had died. One-third of the SICH patients, notably those who were experiencing ongoing neurologic deterioration and had accessible hemorrhage, underwent craniotomy. The results are good, considering the inherent mortality and morbidity of SICH.


Idelalisib-associated Colitis: Histologic Findings in 14 Patients.
Idelalisib is an inhibitor of the PI3Kδ isoform approved for treatment of patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Many patients develop gastrointestinal symptoms during idelalisib therapy; however, the pathologic effects of this drug have not been characterized. We identified 50 patients who received at least 3 months of idelalisib therapy. Clinical findings and symptoms were noted for each patient, and endoscopic findings were recorded for those who underwent colonoscopic examination. Hematoxylin and eosin-stained sections from colonic biopsy samples were evaluated for histologic patterns of injury. Twenty-three (46%) patients experienced diarrhea during treatment with idelalisib, including 8 with severe symptoms (≥7 stools/d above baseline and/or requiring hospitalization). Fourteen patients underwent colonoscopic examination with mucosal biopsy. Twelve (86%) of these had colitis characterized by intraepithelial lymphocytosis, crypt cell apoptosis, and neutrophilic infiltration of crypt epithelium. Eleven patients had symptoms severe enough to warrant drug withdrawal, including 9 who were also treated with corticosteroids. Idelalisib commonly causes diarrheal symptoms in patients undergoing therapy for B-cell neoplasia, which may be severe in nearly 20% of patients. Characteristic histologic features include the combination of intraepithelial lymphocytosis and crypt cell apoptosis, often accompanied by neutrophils. Discontinuation of the drug results in symptomatic improvement and resolution of histologic changes.


Direct Three-Dimensional Shape Measurement by Digital Light-in-Flight Holography.
A method for direct shape measurement with short laser light pulses and digital holography with a CCD array is proposed. An in-line holographic setup is used in which the reference beam is reflected from a blazed reflection grating, i.e., a Littrow setup. By this method a relatively large optical delay is created between the reference and the object beams even with a small object-reference angle, which is necessary because of the limited resolution of the CCD. The delay varies continuously across one axis of the CCD array. In this way different object sections are reconstructed from different parts of the CCD, which in turn correspond to a certain path length from the object. By putting the sections together, one can evaluate the three-dimensional shape. Theoretical as well as experimental results are presented.


Prevention of glucocorticoid induced osteoporosis with alendronate or alfacalcidol: relations of change in bone mineral density, bone markers, and calcium homeostasis.
To explore the relation of changes in measures of bone turnover and changes in bone mineral density (BMD) of the lumbar spine and total hip over 18 months in a double-blinded, randomized trial, comparing the effect of alfacalcidol (101 patients) versus alendronate (100 patients) on BMD in patients who recently started treatment with glucocorticoids for various rheumatic diseases. Associations between changes in serum procollagen type I C-propeptide (P1CP), fasting urine N-terminal telopeptide of type I collagen (NTx), serum calcium, parathyroid hormone (PTH), osteocalcin, and change from baseline in BMD over 18 months were explored with regression and correlation analyses. In both treatment groups, there was a statistically significant decrease in NTx. In the alfacalcidol group there was also a significant increase in P1CP and osteocalcin, in contrast to the alendronate group, but BMD in the alfacalcidol decreased versus an increase in the alendronate group (p < 0.001). In neither treatment group were changes in biochemical measures correlated with the change in BMD, with the exception of a negative correlation in the alendronate group between changes in total hip BMD and NTx. Use of alendronate resulted in an increased PTH in 27 patients, but the increase in BMD of these patients was not statistically significantly different compared to patients taking alendronate with normal PTH levels. Changes in BMD were not associated with changes in bone measures, with the exception of NTx in the alendronate group. For the patient taking glucocorticoids in clinical practice, the value of serial assessment of bone markers is low; changes in markers are no substitute for changes in BMD. ClinicalTrials.gov number: NCT00138983.


Activated B cells mediate efficient expansion of rare antigen-specific T cells.
Potent professional antigen-presenting cells (APC) are essential tools to activate and expand antigen-specific T cells in vitro for use in adoptive immunotherapy. CD40-activated B cells can be easily generated and propagated from human donors and have been successfully used to generate antigen-specific T-cell cultures. Here we show that CD40-activated B cells strongly and specifically expand rare populations of antigen-specific CD8 T cells, with frequencies of less than 1 in 20,000 CD8 T cells in peripheral blood. We focused on T cells recognizing an epitope from the human papillomavirus 16 (HPV-16) E7 protein. In 6 of 6 healthy donors, epitope-specific CD8+ T cells were found to be "rare" by this criterion, as shown by staining with human leukocyte antigen (HLA)/peptide multimers. Using peptide-loaded CD40-activated B cells, epitope-specific T cells could be selectively expanded in all donors up to 10(6) fold, and the resulting T-cell cultures contained up to 88% specific T cells. These results strongly encourage the use of CD40-stimulated B cells as APCs in immunotherapy.


Microextraction with polyethersulfone for bisphenol-A, alkylphenols and hormones determination in water samples by means of gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry analysis.
In the present work, the suitability of polyethersulfone (PES) tube was assessed for the simultaneous sorptive microextraction of commonly found endocrine disrupting compounds in natural waters such as bisphenol-A (BPA), nonylphenol technical mixture (NP mix), 4-tert-octylphenol (4tOP), 4-n-octylphenol (4-nOP), 17β-estradiol (E2) and 17α-ethynilestradiol (EE2). After the concentration of target compounds in the PES polymer, the analytes were recovered soaking the polymer with a suitable solvent (ethyl acetate or methanol), derivatized using N,O-bis(trimethylsilyl)trifluoroacetamide with 1% of trimethylchlorosilane (BSTFA+1% TMCS) and determined by gas chromatography-mass spectrometry (GC-MS). The analysis was also performed without derivatization step by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Extraction parameters (addition of MeOH, ionic strength, extraction speed and time and desorption time) were evaluated and the optimum conditions were fixed as follows: 150 mL water samples containing a 10% (w/v) of sodium chloride and using 5 tubular PES sorbent fibers (1.5 cm length×0.7 mm o.d.). Equilibrium conditions were achieved after 9 h, with absolute extraction efficiencies ranging from 27 to 56%. On the whole, good apparent recoveries were achieved (68-103% and 81-122% for GC-MS and LC-MS/MS, respectively) using deuterated analogues as surrogates. Achieved quantification limits (LOQs) varied between 2-154 ng/L and 2-63 ng/L for all the compounds using GC-MS and LC-MS/MS, respectively. The effect of organic matter was evaluated previous to apply the final method to the analysis of estuarine and wastewater real samples. The comparison of both methods showed that overall, PES-LC-MS/MS provided shorter sample preparation time and better LODs, but PES-silylation-GC-MS allowed the simultaneous determination of all the studied compounds with adequate repeatability and accuracy.


In vitro and in vivo availability of commercial prednisone tablets.
A three-way crossover bioavailability study was performed using nine adult male volunteers with three different commercial prednisone tablets. Plasma samples were assayed for prednisolone, the active metabolite of prednisone, by a radioimmunoassay method. Statistical analysis showed significant differences in the rate of appearance of prednisolone in plasma but not in the amount converted to prednisolone. The results suggest that differences in in vivo rates of appearance of prednisolone in plasma correlate with in vitro rates of dissolution.


Two-colour generation in a chirped seeded free-electron laser: a close look.
We present the experimental demonstration of a method for generating two spectrally and temporally separated pulses by an externally seeded, single-pass free-electron laser operating in the extreme-ultraviolet spectral range. Our results, collected on the FERMI@Elettra facility and confirmed by numerical simulations, demonstrate the possibility of controlling both the spectral and temporal features of the generated pulses. A free-electron laser operated in this mode becomes a suitable light source for jitter-free, two-colour pump-probe experiments.


A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase.
The structure of calcium-bound calmodulin (Ca2+/CaM) complexed with a 26-residue peptide, corresponding to the CaM-binding domain of rat Ca2+/CaM-dependent protein kinase kinase (CaMKK), has been determined by NMR spectroscopy. In this complex, the CaMKK peptide forms a fold comprising an alpha-helix and a hairpin-like loop whose C-terminus folds back on itself. The binding orientation of this CaMKK peptide by the two CaM domains is opposite to that observed in all other CaM-target complexes determined so far. The N- and C-terminal hydrophobic pockets of Ca2+/CaM anchor Trp 444 and Phe 459 of the CaMKK peptide, respectively. This 14-residue separation between two key hydrophobic groups is also unique among previously determined CaM complexes. The present structure represents a new and distinct class of Ca2+/CaM target recognition that may be shared by other Ca2+/CaM-stimulated proteins.


Loktanella litorea sp. nov., isolated from seawater.
A Gram-negative, non-motile, rod-shaped bacterial strain, designated DPG-5(T), was isolated from seawater of the South Sea, Korea and subjected to a study using a polyphasic taxonomic approach. Strain DPG-5(T) grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2 % (w/v) NaCl. Neighbour-joining phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DPG-5(T) fell within the clade comprising members of the genus Loktanella, and formed a cluster with the type strains of Loktanella rosea, Loktanella maricola, Loktanella koreensis and Loktanella tamlensis, with which it exhibited highest 16S rRNA gene sequence similarity values of 96.7, 96.5, 96.2 and 96.7 %, respectively. The 16S rRNA gene sequence similarity values between strain DPG-5(T) and the type strains of the other species of the genus Loktanella were in the range of 94.4-96.0 %. The DNA G+C content of strain DPG-5(T) was 57.6 mol%. Strain DPG-5(T) contained Q-10 as the predominant ubiquinone and C(18 : 1)ω7c and 11-methyl C(18 : 1)ω7c as the major fatty acids. The major polar lipids found in strain DPG-5(T) were phosphatidylcholine and phosphatidylglycerol. Differential phenotypic properties, together with the phylogenetic distinctiveness, showed that strain DPG-5(T) is differentiated from other species of the genus Loktanella. On the basis of the data presented, strain DPG-5(T) is considered to represent a novel species of the genus Loktanella, for which the name Loktanella litorea sp. nov. is proposed. The type strain is DPG-5(T) (= KCTC 23883(T) = CCUG 62113(T)).


[Measurement of "flow-volume" curves and "closing volume" in occupational medicine. Normal findings in healthy subjects (author's transl)].
A method is described for measuring, by a single test, some functional respiratory indexes, such as lung volumes, dynamic tests (flow-volume curve included), rapid He and CO2 curves, "closing volume". The normal values of "closing volume" and of forced expiratory flows obtained in 114 healthy subjects (65 men and 49 women) are then reported. Such values are comparable to those obtained by other authors. An equipment is used by the authors which is easily transportable to the workplace; their method can therefore be used for surveys of workers exposed to occupational respiratory risk during a working shift. The described respiratory index should be able to detect in a pre-clinical stage the early functional changes in chronic bronchitis.


Neuroimaging predictors of AED resistance in new-onset epilepsies.
The best prognostic factors in early-onset epilepsies are the response to the first antiepileptic drug (AED) trial, age at seizure onset, number of seizures prior to treatment, and the presence of a lesion or abnormal neurologic examination. However, early and adequate response to AED is most likely an epiphenomenon reflecting the nature of underlying epileptogenicity, which may be defined as a complex interaction of underlying pathology, genetics, and environment. Patients with the same type of epileptogenic lesion, for example, hippocampal sclerosis, may have a varying response to AED. Modern neuroimaging, in particular quantitative magnetic resonance imaging (MRI) techniques may be helpful to better understand this complex interaction of factors leading to refractoriness. Patients who respond well to AEDs have no or minor MRI abnormalities, and among those with underlying lesions there is an inverse correlation between outcome and the extent of MRI-defined neuronal damage outside the main lesion, which may be undetectable by visual analyses of routine MRI. The extent of neuronal damage appears to be related to the severity of initial precipitating injuries, probably interacts with genetic factors, and may progress over time when seizures are uncontrolled. The presence and extent of abnormalities detected by quantitative MRI may also be helpful to guide AED withdrawal in those patients who are seizure free for >2 years. Combined MRI measures may have potential clinical value for predicting AED response in near future.


Incidence of bisphosphonate-related osteonecrosis of the jaw in high-risk patients undergoing surgical tooth extraction.
As the most suitable approach for preventing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing surgical tooth extraction is still under discussion, the present study evaluates the incidence of BRONJ after surgical tooth extraction using a standardized surgical protocol in combination with an adjuvant perioperative treatment setting in patients who are at high-risk for developing BRONJ. High-risk patients were defined as patients who received intravenous bisphosphonate (BP) due to a malignant disease. All teeth were removed using a standardized surgical protocol. The perioperative adjuvant treatment included intravenous antibiotic prophylaxis starting at least 24 h before surgery, a gastric feeding tube and mouth rinses with chlorhexidine (0.12%) three times a day. In the follow-up period patients were examined every 4 weeks for the development of BRONJ. Minimum follow-up was 12 weeks. In 61 patients a total number of 184 teeth were removed from 102 separate extraction sites. In eight patients (13.1%) BRONJ developed during the follow-up. A higher risk for developing BRONJ was found in patients where an additional osteotomy was necessary (21.4% vs. 8.0%; p = 0.0577), especially for an osteotomy of the mandible (33.3% vs. 7.3%; p = 0.0268). Parameters including duration of intravenous antibiotic prophylaxis, the use of a gastric feeding tube and the duration of intravenous BP therapy showed no statistical impact on the development of BRONJ. Furthermore, patients currently undergoing intravenous BP therapy showed no higher risk for BRONJ compared with patients who have paused or completed their intravenous BP therapy (p = 0.4232). This study presents a protocol for surgical tooth extraction in high-risk BP patients in combination with a perioperative adjuvant treatment setting, which reduced the risk for postoperative BRONJ to a minimum. However, the risk for BRONJ increases significantly if an additional osteotomy is necessary, especially in the mandible.


Providing care and sharing expertise: reflections of nurse-specialists in palliative home care.
This study explored the experiences, perspectives, and reflections of five nurse-specialists in palliative home care, whose dual role includes caring for patients in their daily practice as well as sharing their knowledge, skills, expertise, and experiences with other home care nurses in the community. A qualitative research design, incorporating face-to-face semistructured interviews, was used. Interviews were based on open-ended questions such as: "What is your experience in providing palliative home care to patients and their families? How do you feel about sharing your expertise and experiences with home care nurses?" Data were content analyzed using the constant comparative method. Three major themes and a number of subthemes emerged: (1) acknowledging one's own limitations and humanness: (a) calling for backup, (b) learning as we go along, (c) coping with emotional demands, and (d) interacting with family members; (2) building a collaborative partnership: (a) working collaboratively, (b) sharing information, (c) guiding home care nurses, and (d) being nonjudgmental; and (3) teamwork and implementing palliative home care teams. Nurse-specialists play a key role in palliative home care as both carers and as resources of expert knowledge for other home care nurses caring for palliative patients. As the population ages, the health care system will be faced with increasing requests for high-quality palliative home care. The results of this study demonstrate that, from the perspective of the nurse-specialists of NOVA-Montréal (a nonprofit social and health service organization), nurse-specialists can work collaboratively with home care nurses to improve patients' quality of care and their quality of life. Moreover, patients and their families would benefit from the more widespread establishment of palliative care teams within community health organizations.


Stem cells and the vasculature.
Unraveling the contribution of stem and progenitor cells to blood vessel formation and, reciprocally, the importance of blood vessels to the production and function of stem and progenitor cells, has been a major focus of vascular research over the last decade, but has spawned many controversies. Here I review how vascular stem and progenitor cells contribute both vascular and nonvascular cells during development and in disease, and how nonvascular stem and progenitor cells might contribute to vascular lineages. I also discuss the role of the vasculature in forming stem and progenitor cell niches. Finally, I highlight the potential relevance of these relationships to disease etiology and treatment.


[Induction of left ventricular remodeling and dysfunction in the recipient heart following donor heart myocardial infarction: new insights into the pathological role of tumor necrosis factor-alpha from a novel heterotopic transplant-coronary ligation model].
Neurohormonal and cytokine activation after acute myocardial infarction contribute to cardiac remodeling. This study aimed to examine the effects of tumor necrotic factor (TNF)-alpha and angiotensin II on cardiac remodeling and dysfunction after acute myocardial infarction. We performed isogenic heterotopic cardiac transplantation and simultaneous coronary ligation to produce myocardial infarction in the donor heart, and to evaluate the hearts of both donors and recipients in Lewis rats. The recipients in the ligation group showed significant body-weight loss, hyperthermia, tachycardia, hypotension and leukocytosis at day 7. A significant decrease in left ventricular fractional shortening and + dP/dt, and a significant increase in left ventricular enddiastolic dimension/body weight and left ventricular enddiastolic pressure were also observed in the recipient hearts in the ligation group at day 7. With the exception of the increased perivascular fibrosis, these recipient responses were no longer seen at day 21. TNF-alpha was significantly elevated not only in the plasma but also in the recipient hearts in the ligation group at day 7. In contrast, angiotensin II was significantly increased only in the infarct region of the donor hearts, but not in the plasma. Further, the recipients' transient left ventricular remodeling and dysfunction were completely abolished by the intravenous administration of chimeric TNF-alpha soluble receptor. We developed a novel heterotopic cardiac transplantation-coronary ligation model capable of inducing myocardial infarction in the absence of downstream hemodynamic effects, and allowing differential quantification of indexes of cardiac remodeling in vivo, such as the local and remote effects of angiotensin II and TNF-alpha on cardiac remodeling. Modification of activated cytokines, such as TNF-alpha induced by cardiac ischemic stress, might be a beneficial strategy for the treatment of cardiac dysfunction and subsequent cardiac remodeling after acute myocardial infarction.


Characterization of the nucleic acid binding region of the intermediate filament protein vimentin by fluorescence polarization.
Employing deletion mutant proteins and fluorescein-labeled oligodeoxyribonucleotides in a fluorescence polarization assay, the nucleic acid binding site of the intermediate filament (IF) subunit protein vimentin was localized to the middle of the arginine-rich, non-alpha-helical, N-terminal head domain. While deletion of the first few N-terminal residues (up to amino acid 17) had almost no effect, deletions of residues 25-64 or 25-68 essentially abolished the binding of nucleic acids by the respective proteins. Proteins with smaller deletions, of residues 25-39 or 43-68, were still able to bind nucleic acids quite well at low ionic strength, but only the proteins containing the first DNA-binding wing (residues 27-39) retained the ability to stably bind nucleic acids at physiological ionic strength. These results were confirmed by data obtained with two synthetic peptides whose sequences correspond to the smaller deletions. Nitration experiments showed that one or more of the tyrosines in the head domain are responsible for the stable binding by intercalation. Interestingly, the residues responsible for binding nucleic acids can be deleted without major influence on the in vivo polymerization properties of the mutant proteins. Only the protein with the largest internal deletion, of residues 25-68, failed to form filaments in vivo. Since the N-terminal head domains of IF proteins are largely exposed on the filament surface, but nevertheless essential for filament assembly, these results support the model that the middle of the head domain of vimentin may loop out from the filament surface and thus be available for interactions with other cellular structures or molecules.


The incidence and prevalence of amblyopia detected in childhood.
We present incidence estimates for amblyopia using data from a study of a cohort of 364 children from a single English county who were referred during 1983 for occlusion therapy. Using a criterion of a visual acuity of 6/12 or worse to define amblyopia, we estimate that 3.0% of the county's children develop the condition. Successful treatment of some of these children means that 1.9% will remain amblyopic as adults.


Reread-adapt and answer-comprehend intervention with Deaf and hard of hearing readers: effect on fluency and reading achievement.
The researchers investigated the effect of the Reread-Adapt and Answer-Comprehend intervention (Therrien, Gormley, & Kubina, 2006) on the reading fluency and achievement of d/Deaf and hard of hearing elementary-level students. Children in the third, fifth, and sixth grades at a state school for d/Deaf and hard of hearing students received a fluency intervention that was supplemental to their regular reading instruction. Significant improvement was found on a generalized measure of reading fluency after intervention. Though the researchers found no significant improvement in performance on a generalized measure of comprehension after intervention, the students demonstrated consistently good comprehension on both literal and inferential questions during the intervention sessions. The findings support the importance of incorporating a comprehension monitoring strategy in fluency instruction.


Readmission to intensive care unit after initial recovery from major thoracic oncology surgery.
Little has been published regarding outcomes subsequent to complications after thoracic surgery. The present study investigated outcomes and risk factors associated with mortality in patients admitted to an intensive care unit (ICU) after initial recovery from thoracic oncology surgery. From March 2001 to August 2005, 1,087 patients underwent major resection for lung or esophageal cancer. Ninety-four (8.6%) of those patients required ICU care after initial recovery, and were the subject of the present retrospective review. The patient group included 85 males (90.4%), of mean age 66 years. Patients were classified as either survivors (n = 63, 67%) or nonsurvivors (n = 31, 33%). The most common reason for ICU readmission was pulmonary complication (n = 73, 77.7%). Sixty-four patients (68.1%) required mechanical ventilation and 42 (43.3%) required renal support. Multivariate analysis showed that the initial acute physiological assessment and chronic health evaluation (APACHE) III score at readmission to ICU, duration of mechanical ventilation, and renal support were risk factors for in-hospital mortality. The overall three-year survival was 50.6%. Cox analysis showed that survivors who underwent tracheostomy had a poor prognosis (p = 0.011). Of 12 late mortalities in survivors who underwent tracheostomy, 9 (75%) were due to cancer-unrelated causes. The ICU readmission after thoracic oncology surgery was associated with high in-hospital mortality. Identification of patients with a high APACHE score and (or) prolonged ventilation at readmission may help predict the risk of mortality. Preemptive strategies designed to optimize treatment of such high-risk patients may improve outcomes. Survivors from ICU readmission after thoracic oncology surgery require meticulous and frequent follow-up due to a high risk of deterioration after discharge.


Disaffiliation, substance use, and exiting homelessness.
This study tested whether social affiliation was associated with exits from homelessness for a county-wide probability sample of 397 homeless adults who were followed over a 15-month period culminating in 1992. For the total sample, support from family or friends and service use were related to an increased likelihood of exiting from homelessness. Surprisingly, exits from homelessness were associated with social affiliation (i.e., support from family/friends and services use) only among homeless adults who did not have current substance-use disorders. This relationship did not hold for those with current substance-use disorders. Findings suggest that homeless adults without current substance-use disorders may be better able to engage services and support from family/friends to exit homelessness than homeless adults who have current substance-use disorders. Perhaps service providers who are targeting homeless adults with substance-use disorders and want to help them exit homelessness need to emphasize initiating substance-use treatment before addressing other issues.


RNA synthesis in alpha-amanitin-poisoned rats: prevention of recovery by inhibition of protein synthesis.
The treatment with cycloheximide of rats previously poisoned with alpha-amanitin hinders the recovery of RNA synthesis observed in the liver of rats treated with alpha-amanitin alone. The recovery of RNA synthesis can be ascribed to the capability of poisoned rats to synthesize new RNA-polymerase II.


Nasal-secretion leukocyte populations determined by flow cytometry during acute rhinovirus infection.
Leukocyte populations in the secretions of volunteers challenged by intranasal inoculation with rhinovirus serotype 25 were evaluated by means of flow cytometry. With the light-scatter properties of peripheral blood leukocytes as the standard of reference, significant increases (P less than .05) of both lymphocytes and phagocytes (polymorphonuclear leukocytes plus monocytes) were detected in the nasal secretions of persons infected by the viral challenge. There was a direct correlation of nasopharyngeal symptom severity with both the percentage of lymphocytes (P less than .05) and the percentage of phagocytes (P less than .001). Monoclonal antibodies for specific cell-membrane antigens identified the lymphocytes and phagocytes as leukocytes and also demonstrated the presence of a population of monocytic cells during the phase of maximal symptoms. The panel of monoclonals chosen did not unequivocally identify a lymphocyte population except in the presence of nosebleed. However, the results show that flow cytometry can be used to investigate nasal-secretion cell populations during the rhinovirus common cold.


Handling ovarian cancer FIGO III-IV : evolution over the last 30 years.
The treatment of ovarian cancer FIGO III-IV has undergone substantial changes in the last 30 years. As I was involved as an oncological surgeon in the treatment of these patients since 1979 and made my PhD thesis on this subject, I consider myself a privileged witness of this evolution. In the late 1970's two major changes took place: the introduction of combination chemotherapy containing cisplatin and the concept of debulking surgery. In 1980 we embarked on an ambitious treatment plan combining maximal cytoreductive surgery, 6 cycles of chemotherapy, second look laparotomy and panabdominal irradiation. The results were analyzed in 1991 and gave rise to the following changes. Surgical cytoreduction could only be considered optimal if no residual tumor was left and residual tumor correlated with median survival. Upfront surgery was abandoned in FIGO IV and FIGO III with a very high tumor load. Panabdominal irradiation was too toxic. A recent randomized study has established equivalency of survival in FIGO IIIc between interval debulking after 3 cycles and upfront surgery. Initial tumor load remains a determinant of long- term cure and optimal upfront surgery is critical in patients with a metastatic tumor load of less than 100 gram. Retroperitoneal node dissection becomes important when complete resection of peritoneal metastases can be obtained. In experienced hands selection for primary debulking or for interval debulking seems possible at laparoscopic exploration.


Influence of local tumour stage and grade on reliability of serum prostate-specific antigen in predicting skeletal metastases in patients with adenocarcinoma of the prostate.
To determine whether serum prostate-specific antigen (PSA) can be reliably used to predict the absence or presence of skeletal metastases on the bone scan in patients with adenocarcinoma of the prostate. We studied 450 consecutive men presenting with adenocarcinoma of the prostate between 1991 and 1995. Serum PSA was measured by the Hybritech Tandem-R monoclonal immunoradiometric assay and bone scanning was performed with 99m-technetium-labelled methylene diphosphonate. In total, 46 patients were excluded for one or more of the following reasons: serum PSA not available; radionuclide bone scan inconclusive; histology of the prostate other than adenocarcinoma; hormonal or other therapy given prior to obtaining the serum PSA and/or bone scan. Of the 404 patients included, 43% had poorly differentiated (grade 3), 74% had locally advanced (stages T3-4) tumours and 50% had skeletal metastases. The mean and median serum PSA were 348 and 52 ng/ml, respectively, and 77% of the patients had a serum PSA >20 ng/ml. The negative predictive value (for the absence of metastases on bone scan) of a serum PSA <20 ng/ml was 87% for the whole group of patients, 92, 94 and 70% for grade 1, 2 and 3 tumours, and 95, 83 and 50% for stage T1-2, T3 and T4 tumours, respectively. The positive predictive value (for the presence of metastases on bone scan) of a serum PSA >100 ng/ml was 80% for the whole group of patients. In patients presenting with adenocarcinoma of the prostate, serum PSA alone is not sufficiently reliable to predict the absence or presence of metastases on the radionuclide bone scan. In patients with grade 3 and clinical stage T3-4 tumours, a bone scan should be obtained for accurate staging, regardless of the serum PSA value.


[Observation of clinical and electrophysiological features in patients with distal myasthenia gravis].
Objective: To explore the clinical and electrophysiological features and prognosis of distal myasthenia gravis (MG). Methods: Data of MG patients in Beijing Tiantan Hospital from October 2016 to March 2017 were reviewed, including thorough neurological examinations, nerve conduction studies, repetitive nerve stimulations (RNS) and needle electromyographies. Distal MG patients were included and were analyzed as to their clinical and electrophysiological features and response to treatments. Results: Four patients (7.7%) could be classified as distal type among 52 definitely diagnosed MG patients. They had initial symptoms at age 36 to 64 and developed distal limb muscle weakness in the first month to 6 years after the onset of this disease. Hand muscles were preferentially involved in a non-uniform way. And one patient also had leg weakness on his tibialis anterior muscles. RNS showed a more significant decrement at slow rates in distal muscles, compared with proximal muscles. The baseline compound muscle action potentials (CMAP) of the distal affected muscles presented with slightly decreased or fluctuating amplitudes. Their weakness of ocular, bulbar, proximal and distal limb muscles improved generally after administration of acetylcholinesterase inhibitors or steroids plus acetylcholinesterase inhibitors. Electrophysiological reexaminations revealed increased baseline CMAPs, reduced decrement on RNS, and relief of myogenic changes on needle electromyography. Conclusions: Relatively prominent distal limb muscle weakness can be found in a minority of MG patients. Besides profound decrement on slow rate RNS, the involved distal muscles may have a characteristic decreased baseline CMAP, sometimes with a diurnal fluctuation. Distal MG responds well to regular treatments. Its short-term prognosis seems similar to that of common MG with proximal predominance.


Photophysiology and primary production of phytoplankton in freshwater.
In the last 10 years enormous progress has been made in developing new instruments to collect physiological data from natural phytoplankton. In this review we summarize the motivation which has powered this engagement and focus on new technologies used to measure fluorescence, absorption and biochemical compositions of natural phytoplankton cells from nature. Combining the knowledge of phytoplankton structure along with taxon-specific measurements of photosynthetic activity and biochemical cell composition, can lead to new models which increase the reliability of water quality prediction. Furthermore, recent progress in the analysis of photophysiological fitness of phytoplankton cells has revealed new knowledge about the phylogenetic diversity of metabolic strategies to cope with light and nutrient stress. Future progress in single cell analysing systems will be discussed.


Use of the SF-36 in the evaluation of a drug detoxification program.
The aim of this study was to analyse whether the SF-36 questionnaire is a useful tool to evaluate the treatment outcome of a drug detoxification program. A pre post assessment of consecutive referrals to a drug detoxification program of a psychiatric state hospital in north-western Germany was conducted. Seventy-nine males and twenty-one females with a diagnosis of multiple substance use were included. MOS short form 36 (SF-36) was used upon admission and discharge to assess changes in self-perceived health status. Severity scales from the addiction severity interview (ASI) were used to rate severity of illness by a physician at program entry. Patients with severe comorbidity (hepatitis B, depression, attempted suicide) reported significant worse health states, compared to those without. Positive correlations between physician rated addiction severity and patients' self-perceived health status were observed, most strongly for mental health status. For the 48 patients with 2 assessments significant improvements during the treatment period were observed on SF-36 subscales 'general health' and 'physical functioning'. Patients with severe physical and/or mental problems upon admission had more benefits from treatment than patients without. SF-36 questionnaire is a useful instrument to monitor the health status and to evaluate treatment effects in drug addicts.


Controlling comonomer distribution in random copolymers by chemical coloring of surface-tethered homopolymers: an insight from discontinuous molecular dynamics simulation.
Postpolymerization chemical modification ("coloring") of homopolymer brushes made of A units using B chemical moieties produces surface-anchored random copolymers (RCPs) A(1-x)B(x), where x is the degree of "coloring". We employ discontinuous molecular dynamics to study the "coloring" process in macromolecular tethers made of various lengths grafted at low and high densities on flat impenetrable surfaces. We demonstrate that the comonomer distribution in the A(1-x)B(x) RCPs depends on the interplay among (1) the length and the grafting density of the A-based homopolymer anchors, (2) the solubility of the parent homopolymer, and (3) the solubility of the B coloring units. Chemical modification of sparsely spaced chains on the surface leads to nearly random comonomer distribution in the A(1-x)B(x) RCPs regardless of the solubility of A and B. In contrast, the distribution of A and B units in A(1-x)B(x) RCPs prepared from homopolymers tethered at high grafting densities depends on the solubility of the parent homopolymer. Chemical modification of well-solvated A homopolymer grafts results in comonomer distributions that resemble those of diblock copolymers, comprising lightly modified blocks near the surface and heavily "colored" blocks at the top of the grafts. The relative lengths of the two blocks can be tuned by varying the solubility of B. Under poor solvent conditions, the distribution of A and B in the A(1-x)B(x) RCP is more complex; it is governed by the conformation of the parent A macromolecular anchors that form collapsed clusters before the coloring reaction.


Diketoacid HIV-1 integrase inhibitors: An ab initio study.
The stable tautomeric forms of two representative arene-substituted diketoacid HIV-1 integrase inhibitors, 5-ClTEP and L-731,988, were investigated by B3LYP with 6-31G*, 6-31G(d,p), and 6-31+G(d,p) basis sets. Optimization with MP2/6-31G* was also performed for 5-ClTEP. The solvation effect was considered using a conductor-like screening model. With the density functional theory method, the trans diketo conformations are more stable than the cis conformers. The difference is 14 kJ mol(-1) for 5-ClTEP and 33 kJ mol(-1) for L-731,988. Two trans diketo structures were obtained. The difference between these two trans diketo structures is less than 4 kJ mol(-1) calculated at the B3LYP/6-311+G(3df,2p) level. Two enol forms prevail over the diketo tautomers and are calculated to have the same free energy. Because there is no barrier observed between these two enol forms, they can interchange easily such that a delocalized transition state is suggested to be the observed form. Contradictory to the results of the MP2 method that predicts a preference for the trans diketo forms, the B3LYP method predicts a preference for the enol tautomers, which is in agreement with the experimental results.


Ureteropelvic junction obstruction in children: 10 years' experience in one institution.
We reviewed our experience over 10 years with pyeloplasty for ureteropelvic junction obstruction. Preoperative and postoperative isotope renal scans were performed to assess the surgical outcome, with particular emphasis on the postoperative change in renal function (RF). We retrospectively reviewed the medical records of 137 consecutive children with ureteropelvic obstruction operated between January 1994 and December 2003. A total of 109 kidneys in 102 patients were evaluated with renal echo and (99m)Tc-diethylenetriaminepentaacetic renography both before and after Anderson-Hynes dismembered pyeloplasty. The improvement of RF >5% was noted in 67 kidneys (61.5%), the function remained stable in 30 kidneys (27.5%), and it deteriorated (>5%) in 12 kidneys (11.0%). Five patients (4.6%) required repeat pyeloplasty for either prolonged urine leakage or reobstruction with deterioration in RF. Dismembered pyeloplasty in children with ureteropelvic junction obstruction is safe. The renal functional improvement can be expected in the majority of kidneys that have impaired function at presentation.


Observation of an Anomalous Line Shape of the η^{'}π^{+}π^{-} Mass Spectrum near the pp[over ¯] Mass Threshold in J/ψ→γη^{'}π^{+}π^{-}.
Using 1.09×10^{9} J/ψ events collected by the BESIII experiment in 2012, we study the J/ψ→γη^{'}π^{+}π^{-} process and observe a significant abrupt change in the slope of the η^{'}π^{+}π^{-} invariant mass distribution at the proton-antiproton (pp[over ¯]) mass threshold. We use two models to characterize the η^{'}π^{+}π^{-} line shape around 1.85 GeV/c^{2}: one that explicitly incorporates the opening of a decay threshold in the mass spectrum (Flatté formula), and another that is the coherent sum of two resonant amplitudes. Both fits show almost equally good agreement with data, and suggest the existence of either a broad state around 1.85 GeV/c^{2} with strong couplings to the pp[over ¯] final states or a narrow state just below the pp[over ¯] mass threshold. Although we cannot distinguish between the fits, either one supports the existence of a pp[over ¯] moleculelike state or bound state with greater than 7σ significance.


The Protein Neddylation Inhibitor MLN4924 Suppresses Patient-Derived Glioblastoma Cells via Inhibition of ERK and AKT Signaling.
Glioblastoma is a highly aggressive and lethal brain tumor, with limited treatment options. Abnormal activation of the neddylation pathway is observed in glioblastoma, and the NEDD8-activating enzyme (NAE) inhibitor, MLN4924, was previously shown to be effective in glioblastoma cell line models. However, its effect has not been tested in patient-derived glioblastoma stem cells. We first analyzed public data to determine whether NEDD8 pathway proteins are important in glioblastoma development and patient survival. NAE1 and UBA3 levels increased in glioblastoma patients; high NEDD8 levels were associated with poor clinical outcomes. Immunohistochemistry results also supported this result. The effects of MLN4924 were evaluated in 4 glioblastoma cell lines and 15 patient-derived glioblastoma stem cells using high content analysis. Glioblastoma cell lines and patient-derived stem cells were highly susceptible to MLN4924, while normal human astrocytes were resistant. In addition, there were various responses in 15 patient-derived glioblastoma stem cells upon MLN4924 treatment. Genomic analyses indicated that MLN4924 sensitive cells exhibited enrichment of Extracellular Signal Regulated Kinase (ERK) and Protein kinase B (AKT, also known as PKB) signaling. We verified that MLN4924 inhibits ERK and AKT phosphorylation in MLN4924 sensitive cells. Our findings suggest that patient-derived glioblastoma stem cells in the context of ERK and AKT activation are sensitive and highly regulated by neddylation inhibition.


Using γ-Ray Polymerization-Induced Assemblies to Synthesize Polydopamine Nanocapsules.
This work reports a simple and robust strategy for synthesis of polydopamine nanocapsules (PDA NCs). First, polymer assemblies were synthesized by a γ-ray-induced liquid-liquid (H2O-acrylate) interface polymerization strategy, in the absence of any surfactants. 1H nuclear magnetic resonance analysis and molecular dynamics simulation reveal that the generation of polymer assemblies largely depends on the hydrophilicity of acrylate and gravity of the oligomers at the interface. By virtue of the spherical structure and mechanic stability of the polymer assemblies, PDA NCs are next prepared by the interfacial polymerization of dopamine onto the assemblies, followed by the removal of templates by using ethanol. The polydopamine nanocapsules are shown to load and release ciprofloxacin (CIP, a model drug), such that the CIP-loaded PDA NCs are able to inhibit the growth of Escherichia coli.


Testosterone delivery systems for women: present status and future promise.
In women, testosterone (T) is increasingly recognized as a steroid with multiple non-reproductive effects. Testosterone deficiency in menopausal women is more common than appreciated, particularly in patients on hormone replacement or with surgical menopause. Replacement of T is an established therapy for male hypogonadism, and as a result innovative new delivery systems have evolved to optimize physiologic delivery. However, in women, modalities of T replacement remain underdeveloped and at present provide artificial and/or supraphysiologic androgen levels. This review discusses the androgen replacement modalities presently available for women, and those being developed for future use.


Sexual dimorphism and growth hormone induction of murine pheromone-binding proteins.
A number of structurally very similar pheromone-binding proteins (major urinary proteins; MUPs) are synthesized in mouse liver and rapidly excreted in the urine. Male and female inbred mice display different characteristic patterns of MUP expression. Here we present a detailed study of the RNA and protein products corresponding to specific MUP genes previously isolated from genomic DNA of the Balb/c strain. By in vitro transcription of equivalent cDNA clones, translation of the resulting RNA in the reticulocyte lysate system and isoelectric focusing, the protein products of genes BL1, BS1 and BS6 were shown to be MUP 2a, MUP 2b and MUP 4 respectively. MUPs 2a and 2b were shown to be abundant both in Balb/c male urine and among the translation products of total Balb/c male liver mRNA. Two oligodeoxynucleotide probes, oBL1A and oBS1, selective for BL1 and BS1 mRNA respectively, were chemically synthesized. mRNA that hybridized with these probes (oBL1A mRNA and oBS1 mRNA) was present at different characteristic levels in the Balb/c and C57BL/6 inbred strains. In both strains the level of expression was much higher in males than females and the male/female expression ratio of oBS1 RNA was higher than that of oBL1A RNA. Comparison of these mRNA levels with the amounts of different MUP proteins present in urine and the translation products of liver mRNA indicated that proteins other than MUP 2a and MUP 2b are coded for by the C57BL/6 oBL1A and oBS1 mRNAs. C57BL/6 mice homozygous for the lit mutation are GH deficient and transcribe MUP genes at a level much lower than that obtaining in normal mice of either sex, indicating that transcription is induced by GH in both males and females. When lit/lit mice were treated with GH under two different regimes, MUP gene transcription was partially induced to different degrees and the level of oBL1A mRNA was induced more highly than that of oBS1 mRNA. Thus there exists a correlation between the inducibility of these mRNAs and their level of expression in females relative to males; oBL1A mRNA is both more highly expressed in females and more readily induced by GH than oBS1 mRNA. This suggests that the male and female expression patterns are due to differential inducibility of different MUP genes together with a stronger inducing stimulus in males. GH administered continuously by infusion repressed MUP gene expression.(ABSTRACT TRUNCATED AT 400 WORDS)


[Characteristics of the damage to immunocompetent organs in experimental slow influenza infection].
Morphological changes in immunocompetent organs were studied in 30 mice with slow influenza infection. Histological, histochemical, and electron microscopy studies revealed destructive changes in different cell populations of the thymus and spleen. The changes were more pronounced in the reticuloendothelial cells of the thymus and endothelium of thymic capillaries. Complex examination helps to outline the general pathological patterns in interpreting the pathogenesis of experimental slow influenza infection.


[Persistence of left superior vena cava associated to esophageal atresia: presentation of 5 cases].
Esophageal atresia is known to be associated with a variety of additional congenital anomalies in multiple organ systems. Persistent left superior vena cava is one of the most common venous thoracic anomaly, occurring in about 0,3% of the population. The aim of this study was to characterize persistent left superior vena cava in infants treated in Hospital Dona Estefânia with esophageal atresia. A retrospective review of all children treated for esophageal atresia from January 2002 to December 2013 was undertaken. Charts were reviewed for gestational age, weight, type of atresia, preoperative echocardiogram, associated anomalies, surgical approach, eventual postoperative echocardiogram and angioresonance for the study of congenital venous anomaly. Of 107 children, five had persistent left superior vena cava. Of the five cases, one had prenatal diagnosis. Further investigation showed duodenal atresia in one, urologic malformation, coloboma and bilateral ear deformities in other. All five patients were operated on through right thoracotomy and primary anastomosis was performed after ligation of the trachea-esophageal fistula and underwent angioresonance to characterize the vascular anomaly. No operative or post-operative complications were registered. Inspite of the preoperative workup, the anomaly was only identified in one of the patients. Generally, diagnosis of PLSVC is incidentally found during routine left-sided central venous catheterizations. It is essential to characterize the pattern of cardiac venous return that places those patients at a risk for paradoxical embolic complications to the arterial system.


N3-alkylation during formation of quinazolin-4-ones from condensation of anthranilamides and orthoamides.
Dimethylformamide dimethylacetal (DMFDMA) is widely used as a source of electrophilic one-carbon units at the formate oxidation level; however, electrophilic methylation with this reagent is previously unreported. Reaction of anthranilamide with DMFDMA at 150 °C for short periods gives mainly quinazolin-4-one. However, prolonged reaction with dimethylformamide di(primary-alkyl)acetals leads to subsequent alkylation at N(3). 3-Substituted anthranilamides give 8-substituted 3-alkylquinazolin-4-ones. Condensation of anthranilamides with dimethylacetamide dimethylacetal provides 2,3-dimethylquinazolin-4-ones. In these reactions, the source of the N(3)-alkyl group is the O-alkyl group of the orthoamides. By contrast, reaction with the more sterically crowded dimethylformamide di(isopropyl)acetal diverts the alkylation to the oxygen, giving 4-isopropoxyquinazolines, along with N(3)-methylquinazolin-4-ones where the methyl is derived from N-Me of the orthoamides. Reaction of anthranilamide with the highly sterically demanding dimethylformamide di(t-butyl)acetal gives largely quinazolin-4-one, whereas dimethylformamide di(neopentyl)acetal forms a mixture of quinazolin-4-one and N(3)-methylquinazolin-4-one. The observations are rationalised in terms of formation of intermediate cationic electrophiles (alkoxymethylidene-N,N-dimethylammonium) by thermal elimination of the corresponding alkoxide from the orthoamides. These are the first observations of orthoamides as direct alkylating agents.


[Relationship between levels of sex hormones and response to cardiac resynchronisation therapy in men].
To study the relationship between levels of sex hormones and eﬀectiveness of cardiac resynchronisation therapy (CRT) in men with chronic heart failure (CHF). The best response to CRT (mean time, 38 [19,0;53,7] months) was identifed by a maximum decrease in left ventricular end-systolic volume (LVESV) in 58 men (mean age, 54.8±9.6) with CHF (61% IHD). Based on testosterone (TES) level, patients were divided into group 1 (n=28; 48%) - TES < median value (13.8 nmol/l) and group 2 (n=30; 52%) - TES > median value. Exercise tolerance (ET), echocardiography (EchoCG) parameters, plasma levels of NTproBNP, interleukin (IL) - 1β, IL-6, IL-10, tumor necrosis factor α (TNF-α), С-reactive peptide (CRP), galectin-3 (Gal-3), matrix metalloprotease-9 (ММР-9), tissue inhibitors of metalloproteinases TIMP-1, TIMP-4, and the indexes MMP-9/TIMP-1 and MMP-9/TIMP-4 were evaluated in dynamics. Levels of TES, progesterone (PGN), dehydroepiandrosterone sulphate (DHEAS), and estradiol (Е2) were measured at baseline. Based on LVESV changes, non-responders (LVESV decrease by 15% but 30%) were identifed. In group 2, atrial fibrillation (р=0.064) and radiofrequency ablation of atrioventricular connection (р=0.014) were observed more frequently; incidence of diabetes mellitus was lower (р=0.017); QRS was smaller (р=0.001); ET was higher both at baseline (р=0.022) and in dynamics (р=0.018); numbers of responders and super-responders were greater (р=0.007); levels of PGN (р=0.028), Il-1β (р=0.020), IL-10 (р=0.013), TNF- α (р=0.006) were higher; and Е2/TES was lower (р=0.004). While EchoCG parameters did not diﬀer at baseline, group 2 showed a tendency towards greater changes in LVESV (р=0.069) and LV end systolic dimension (р=0.087), and a greater increase in LV ejection fraction (р=0.007). In dynamics: In group 1, a decrease in NT-proBNP was observed (р=0.015); in group 2, decreases in IL-1β (р=0.001), IL-6 (р=0.015), IL-10 (р=0.001), TNF-α (р=0.001), TIMP-1 (р=0.046), and Gal-3 (р=0.051) were observed. Levels of sex hormones were correlated with EchoCG parameters, biomarkers of immune inﬂammation, fibrosis, and NTproBNP. The ROC analysis showed that a TES level not lower than 13.8 nmol/l was a predictor for a positive response to CRT with a sensitivity of 63.4% and specifcity of 76.5% (AUC=0.687; р=0.026). High levels of TES and PGN were associated with beter eﬀectivity of CRT, higher ET, greater proportions of responders and super-responders, and reduced immune inﬂammation activity and fibrosis. A level of TES not lower than 13.8 nmol/l was a predictor for a positive response to CRT.


Orientation Perception in Real and Virtual Environments.
Spatial perception in virtual environments has been a topic of intense research. Arguably, the majority of this work has focused on distance perception. However, orientation perception is also an important factor. In this paper, we systematically investigate allocentric orientation judgments in both real and virtual contexts over the course of four experiments. A pattern of sinusoidal judgment errors known to exist in 2D perspective displays is found to persist in immersive virtual environments. This pattern also manifests itself in a real world setting using two differing judgment methods. The findings suggest the presence of a radial anisotropy that persists across viewing contexts. Additionally, there is some evidence to suggest that observers have multiple strategies for processing orientations but further investigation is needed to fully describe this phenomenon. We also offer design suggestions for 3D user interfaces where users may perform orientation judgments.


DNA strandness changes during in situ hybridization conditions.
DNA strandness changes occurring during in situ hybridization were monitored using monoclonal antibodies. Our results show that: 1) RNase induces formation of single stranded DNA, 2) after denaturation-renaturation, single stranded DNA is found principally in centromeric areas, and 3) double stranded DNA is still observed after each step.


Heart Transplant and Mechanical Circulatory Support in Patients With Advanced Heart Failure.
Patients with advanced heart failure have a poor prognosis and heart transplant is still the best treatment option. However, the scarcity of donors, long waiting times, and an increasing number of unstable patients have favored the development of mechanical circulatory support. This review summarizes the indications for heart transplant, candidate evaluation, current immunosuppression strategies, the evaluation and treatment of rejection, infectious prophylaxis, and short and long-term outcomes. Regarding mechanical circulatory support, we distinguish between short- and long-term support and the distinct strategies that can be used: bridge to decision, recovery, candidacy, transplant, and destination therapy. We then discuss indications, risk assessment, management of complications, especially with long-term support, and outcomes. Finally, we discuss future challenges and how the widespread use of long-term support for patients with advanced heart failure will only be viable if their complications and costs are reduced.


[Not Available].
Objetivo: mediante la técnica de consenso Delphi, conocer la opinión de un grupo de expertos en nutrición, educación y gastronomía para buscar consenso sobre metodologías educativas en alimentación saludable, alumnos de tercero a quinto año básico, sus familias y profesores.Métodos: con los resultados de encuestas y grupos focales realizados previamente a niños, padres y profesores, se elaboró un cuestionario que fue enviado a 51 expertos en nutrición, educación y gastronomía en una primera ronda. Los resultados fueron analizados y reenviados en una segunda ronda con las preguntas no consensuadas, obteniendo 38 respuestas.Resultados: hubo consenso en que se pueden cambiar hábitos en escuelas mediante talleres de cocina con chefs o monitores, educación activo-participativa y huertos escolares. Padres y profesores deben tener habilidades culinarias saludables para educar a los niños. Estos deben hacer uso racional del dinero en la escuela. Para ello es necesario cambiar la oferta del kiosko hacia alimentos saludables, o suprimirlo si no es saludable. Los profesores deben capacitarse con talleres de autocuidado y vida sana para educar en alimentación saludable a los niños en horarios de clase con material educativo, talleres de cocina con recetas y aprovechar horarios de desayuno y almuerzo para actividades educativas. Los padres deben participar en talleres para escoger alimentos saludables en lugares de venta y preparar menús saludables. Los niños deben aprender habilidades culinarias simples, preparando y degustando alimentos saludables. Conclusiones: estos resultados son fundamentales para diseñar materiales educativos en alimentación saludable que cambien los malos hábitos alimentarios actuales.


Peri-marketing surveillance of lamotrigine in The Netherlands: doctors' and patients' viewpoints.
Evaluation of daily clinical practice in prescribing lamotrigine in refractory epilepsy patients. A collaborative, retrospective, peri-marketing study was performed in in- and out-patients attending one of the three Dutch epilepsy centres. Analysis of both patients' and doctors' information was performed in 520 patients using questionnaires and medical files. After one year of treatment 76% of patients maintained LTG treatment, an intention-to-treat analysis showed > = 50% seizure reduction in 23% of patients; 20-50% seizure reduction in 23% of patients. Six percent of patients became at least three months seizure free. In about 20% of patients seizures became less severe and shorter of duration, while in 6% an increase was found. After three months a significant decrease in number of concomitant antiepileptic drugs was found (change from mean 1.8 to 1.5 AEDs) (p = < 0.01). After twelve months the mean number of AEDs was 1.4 per patient. Overall percentage of side effects appeared to be significantly higher if patients' questionnaire data were used. Epilepsy patients considered side effects as an important factor in the choice of medication and in withdrawal of medication. Future developments of new AEDs should take this into account. This perimarketing study gives insight information about long-term daily use of lamotrigine, with emphasis on effectiveness. Patients complained in the questionnaires much more about side-effects, than was known according to the medical file. Therefore, it seems necessary to perform perimarketing studies more systematically.


Control of methicillin-resistant Staphylococcus aureus in a burn unit: role of nurse staffing.
We investigated retrospectively the spread of methicillin-resistant Staphylococcus aureus (MRS) in a burn unit. During 8 months, 34% of the patients acquired MRS, and transmission continued despite barrier isolation precautions and treatment of colonized personnel with topical intranasal antibiotics. Several findings suggested MRS was spread primarily by contact transmission involving personnel: case-control comparison showed burn size to be the major host risk factor for colonization; correlation analysis of environmental factors revealed a significant (p = 0.001) association of new cases with increased patient load and with staffing by overtime or temporary nurses; and environmental sampling yielded few colonies of MRS. The outbreak halted following implementation of control measures, among which assignment of separate nurses to colonized patients appeared to be essential. The association of different nurse staffing variables with persistence then eradication of MRS suggests nurse staffing may have been an important factor in staphylococcal transmission.


Occupational skin disease among Australian healthcare workers: a retrospective analysis from an occupational dermatology clinic, 1993-2014.
Healthcare workers (HCWs) are at risk of developing occupational skin disease (OSD). To ascertain the causes of OSD in Australian HCWs in a tertiary referral clinic. A retrospective review was performed of patients assessed at the Occupational Dermatology Clinic in Melbourne from 1993 to 2014. Of 685 HCWs assessed in the clinic over a period of 22 years, 555 (81.0%) were diagnosed with OSD. The most common diagnosis was irritant contact dermatitis (ICD) (79.1%), followed by allergic contact dermatitis (ACD) (49.7%). Natural rubber latex allergy was also relatively frequent (13.0%). The major substances causing ACD were rubber glove chemicals (thiuram mix and tetraethylthiuram disulfide), preservatives (formaldehyde, formaldehyde releasers, and isothiazolinones), excipients in hand cleansers, which are hard-to-avoid weak allergens, and antiseptics. ACD caused by commercial hand cleansers occurred more frequently than ACD caused by alcohol-based hand rubs (ABHRs). Occupational ICD was mostly caused by water/wet work and hand cleansers, and environmental irritants such as heat and sweating. Understanding the causes of OSD in HCWs is important in order to develop strategies for prevention. We suggest that skin care advice should be incorporated into hand hygiene education. The use of ABHRs should be encouraged, weak allergens in skin cleansers should be substituted, and accelerator-free gloves should be recommended for HCWs with OSD.


Acute multiple arterial thrombosis after cisplatin in base of tongue carcinoma: case report.
Arterial thromboses following cisplatin-based chemotherapy in head and neck cancers are extremely rare and devastating complication. A 54-year-old male smoker had an acute history of left lower limb pain and calf claudication 3 days following the first cycle of cisplatin-based chemotherapy given concurrently with radiotherapy for squamous cell carcinoma of the base of tongue. CT angiography showed extensive abdominal aortic thrombus along with involvement of left common iliac, saphenopopliteal, and tibeal arteries as well as moderate stenosis in the proximal segments of left anterior descending and right coronary artery. We suggest that endothelial damage and hypercoaguable state secondary to cisplatin may have induced severe arterial and coronary thrombosis. This is the first reported case of acute multiple arterial thrombosis following cisplatin in head and neck cancer. It is a dreaded complication and has a dismal prognosis if not promptly recognized and treated.


Differentiating presacral masses in anorectal malformations and isolated sacrococcygeal teratomas.
Presacral masses associated with anorectal malformations (ARM) are most frequently dermoid or teratomas. Sacrococcygeal teratoma (SCT), in isolation, is a different condition. There are limited data comparing the two. The aim of this study was to compare presacral masses associated with ARM and isolated SCTs. A retrospective review was performed from 1979 to 2018. Patients with presacral masses and associated ARM (n = 39) were identified and compared to patients with isolated SCTs (n = 32). Those with presacral mass and ARM had a lower proportion of immature and mixed teratomas by pathology and a longer time to mass resection. They had higher percentages of sacral anomalies (76% versus 9%), tethered cord (50% versus 6%), and other anomalies (51% versus 9%). For long-term bowel function, patients with presacral mass and ARM were more likely to be fecally incontinent and require enemas (59% versus 11%). Regarding isolated SCTs, 4% recurred with a time to recurrence of 7 months. Compared to patients with isolated SCT, patients with presacral mass and ARM had lower grade tumors. In addition, they had a higher proportion of sacral defects and other congenital defects, as well as worse bowel function outcomes.


Eel parasite diversity and intermediate host abundance in the River Rhine, Germany.
European eels (Anguilla anguilla) from 2 sampling sites on the Rhine river (near Karlsruhe and near Worms) were investigated with respect to their parasite communities. Nine different metazoan species were found to live in and on the eels. The highest number of species was recorded from the intestine, which contained up to 6 different helminths. Among these, acanthocephalans were the most prevalent worms with the eel-specific parasite Paratenuisentis ambiguus as the dominant species of the intestinal component communities at both sites. Comparing the intestinal parasites from eels caught near Karlsruhe with those from Worms, the acanthocephalans showed a significantly lower abundance at Worms. A significantly lower mean number of intestinal helminth species as well as a significantly lower Brillouin's Index was found at Worms compared with Karlsruhe. This difference could be related to the abundance of the respective intermediate crustacean hosts. At the sampling site Worms the amphipod Corophium curvispinum was the dominant crustacean. Additionally, only the isopod Jaera istri and the amphipod Dikerogammarus villosus were found. All these crustacean species have only recently colonized the Rhine river system via the Main-Danube canal, built in the early 1990s. They are not known to act as intermediate hosts for any of the acanthocephalans found in the eels. The site near Karlsruhe exhibited a higher crustacean diversity, including Asellus aquaticus and different species of the genus Gammarus, which are all known intermediate hosts for the acanthocephalans found. Therefore, changes of eel parasite diversity can be correlated with the appearance of invading crustacean species (neozoans).


Transient elevation of intrasynaptosomal free calcium by putrescine.
The role of polyamines in the regulation of free intrasynaptosomal Ca2+, [Ca2+]i was studied. After preincubation of rat brain synaptosomes with 5 mM difluormethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, the K+-induced increase of [Ca2+]i was 33% less than that in non-treated synaptosomes. Putrescine (1 mM) added together with DFMO negated the effect of DFMO suggesting that abnormally low polyamine concentrations were the reason for the diminished K+-response. Putrescine alone did not alter the K+-response to [Ca2+]i. Instead putrescine (0.5 mM) caused a rapid (less than 10 s) transient increase in [Ca2+]i but did not simultaneously increase 45Ca2+ uptake into polarized synaptosomes. Neither spermidine nor spermine (0.5 mM) significantly altered [Ca2+]i. The results suggest that polyamines play a role in the regulation of free intrasynaptosomal Ca2+.


Effectiveness of Mulligan's mobilization with movement techniques on pain and disability of peripheral joints: a systematic review with meta-analysis between 2008-2017.
The Mulligan method of manual therapy advocates the use of 'mobilization with movement (MWM)' techniques to effectively manage peripheral joint 'positional fault' dysfunctions. To provide an updated evidence-based systematic review and meta-analysis regarding the effectiveness of MWM techniques. PubMed, EBSCOhost, PEDro, Cochrane Library and Google Scholar between 1st August 2008-31st August 2017. Two reviewers applied the population intervention comparison outcome (PICO) question to screen the studies for this review. Only RCTs/CCTs were included. Information on study design, subjects, intervention, outcome measures and efficacy results were extracted. Methodological quality was independently assessed by two reviewers using the PEDro Scale. Sixteen studies with 576 participants were included in four separate meta-analyses for pain and disability. The I2 index assessed the heterogeneity between studies. MWMs have demonstrated statistically signiﬁcant improvements against sham treatment, passive and control intervention techniques for pain [mean difference (95%CI):-16.12 (-19.77, -12.48) & I=72%] and disability [mean difference (95%CI):-17.51 (-22.84, -12.19) 2 2 2 2 & I=88%] or against another manual therapy treatment [pain mean difference (95%CI): -10.43 (-11.38, -9.48) & I=0%], however not against another manual therapy treatment for disability. The clinical signiﬁcance of the pooled differences was compared against Minimal Clinically Important Difference values. No long-term effectiveness data were identified in any of the included studies. The overall post-intervention short-term statistical and clinical significance of MWM techniques has been verified, although the high heterogeneity identified may require further validation of those methods. Systematic review registration number: PROSPERO 2016:CRD42017071595.


The activation energy of stabilised/solidified contaminated soils.
Developing an understanding of the time-related performance of cement-treated materials is essential in understanding their durability and long-term effectiveness. A number of models have been developed to predict this time-related performance. One such model is the maturity concept which involves use of the 'global' activation energy which derives from the Arrhenius equation. The accurate assessment of the activation energy is essential in the realistic modelling of the accelerated ageing of cement-treated soils. Experimentally, this model is applied to a series of tests performed at different elevated temperatures. Experimental work, related to the results of a time-related performance on a contaminated site in the UK treated with in situ stabilisation/solidification was carried out. Three different cement-based grouts were used on two model site soils which were both contaminated with a number of heavy metals and a hydrocarbon. Uncontaminated soils were also tested. Elevated temperatures up to 60 degrees C and curing periods up to 90 days were used. The resulting global activation energies for the uncontaminated and contaminated soils were compared. Lower values were obtained for the contaminated soils reflecting the effect of the contaminants. The resulting equivalent ages for the uncontaminated and contaminated mixes tested were 5.1-7.4 and 0.8-4.1 years, respectively. This work shows how a specific set of contaminants affect the E(a) values for particular cementitious systems and how the maturity concept can be applied to cement-treated contaminated soils.


Atmospheric oxygen accelerates the induction of a post-mitotic phenotype in human dermal fibroblasts: the key protective role of glutathione.
It has been proposed that ageing of human dermal fibroblasts occurs as a multi-stage process during which cells progress from a mitotic to a post-mitotic state. We describe the development of a simple and novel cell-cloning model for identifying and quantifying the different fibroblast morphotypes associated with the induction of post mitotic behaviour. We have found that under atmospheric (20%) oxygen tension a significant proportion of human dermal fibroblasts are rapidly induced to switch from a mitotic to a post-mitotic phenotype. In contrast, under more physiological (4%) oxygen conditions, the induction of a post-mitotic phenotype is largely prevented. Increasing oxidative stress by addition of hydrogen peroxide or depletion of glutathione also induced a switch from a mitotic to a post-mitotic phenotype in these cells, whereas addition of the anti-oxidant N-acetylcysteine under atmospheric (20%) oxygen tension potently inhibited this process. In addition, a statistically significant correlation was observed between the magnitude of intracellular glutathione depletion and the reduction in the population of mitotic cells in this model. We propose that the switch from a mitotic to a post-mitotic phenotype represents a process of cellular ageing and that standard atmospheric oxygen tension imposes a substantial oxidative stress on dermal fibroblasts which accelerates this process in culture. The data also suggest that intracellular glutathione levels strongly influence the induction of a post-mitotic phenotype and that, by implication, depletion of glutathione may play a significant role in the progression of cellular ageing in human skin.