Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion.
Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers.


Rapidly eroding piñon-juniper woodlands in New Mexico: response to slash treatment.
The piñon (Pinus edulis Engelm.)-juniper [Juniperus monosperma (Engelm.) Sarg.] woodlands of Bandelier National Monument are experiencing accelerated erosion. Earlier studies suggest that causes of these rapidly eroding woodlands are related to an unprecedented rapid transition of ponderosa pine (Pinus ponderosa C. Lawson) savanna to piñon-juniper woodlands as a result of cumulative historical effects of overgrazing, fire suppression, and severe drought. To study the effectiveness of slash treatment in reducing accelerated erosion, we used sediment check dams to quantify sediment yield from twelve paired microwatersheds (300-1100 m2) within an existing paired water-shed study. Six of the twelve microwatersheds were located in a 41-ha (treatment) watershed with scattered slash treatment, whereas six microwatersheds were located in an adjacent 35-ha untreated (control) watershed. The primary purpose of our research was to quantify the rates of sediment yield between the treated and control microwatersheds. Sediment yield was measured from 15 individual storms during the months of June-September (2000 and 2001). In response to slash treatment, mean seasonal sediment yield for 2000 equaled 2.99 Mg/ha in the control vs. 0.03 Mg/ha in the treatment and 2.07 Mg/ha in the control vs. 0.07 Mg/ha in the treatment in 2001. The practice of slash treatment demonstrates efficacy in reducing erosion in degraded piñon-juniper woodlands by encouraging herbaceous recovery. Our data show that slash treatment increases total ground cover (slash and herbaceous growth) beyond a potential erosion threshold. Restored piñon-juniper woodlands, as the result of slash treatment, provide a forest structure similar to pre-grazing and pre-fire suppression conditions and decrease catastrophic fire hazard.


The modENCODE Data Coordination Center: lessons in harvesting comprehensive experimental details.
The model organism Encyclopedia of DNA Elements (modENCODE) project is a National Human Genome Research Institute (NHGRI) initiative designed to characterize the genomes of Drosophila melanogaster and Caenorhabditis elegans. A Data Coordination Center (DCC) was created to collect, store and catalog modENCODE data. An effective DCC must gather, organize and provide all primary, interpreted and analyzed data, and ensure the community is supplied with the knowledge of the experimental conditions, protocols and verification checks used to generate each primary data set. We present here the design principles of the modENCODE DCC, and describe the ramifications of collecting thorough and deep metadata for describing experiments, including the use of a wiki for capturing protocol and reagent information, and the BIR-TAB specification for linking biological samples to experimental results. modENCODE data can be found at http://www.modencode.org.


Effects of continuous positive airway pressure therapy on right ventricular function assessment by tissue Doppler imaging in patients with obstructive sleep apnea syndrome.
The effects of continuous positive airway pressure (CPAP) therapy on right ventricular (RV) function in patients with obstructive sleep apnea syndrome (OSAS) has not been previously studied by tissue Doppler imaging (TDI). The aim of this study was to assess RV function using TDI in patients with OSAS before and after CPAP therapy. Twenty-eight patients with newly diagnosed OSAS in the absence of any confounding factors and 18 controls were included in this study. The peak systolic velocity (S'm), early (E'm) and late (A'm) diastolic myocardial peak velocities at tricuspid lateral annulus, isovolumic acceleration (IVA), myocardial precontraction time (PCT'm), myocardial contraction time (CT'm), and myocardial relaxation time (RT'm) were measured. All echocardiographic parameters were calculated 6 months after CPAP therapy. The RV diastolic parameters such as E'm velocity and E'm-to-A'm ratio were significantly lower, RT'm was significantly prolonged, A'm velocity was similar in patients with OSAS compared to controls; and the RV systolic parameters such as IVA and CT'm were significantly lower and S'm was similar in patients with OSAS compared to controls. At the end of the treatment, 20 of 28 patients were compliant with CPAP therapy. E'm velocity, E'm-to-A'm ratio, IVA, and CT'm increased, PCT'm, PCT'm-to-CT'm ratio, and RT'm decreased significantly after therapy, whereas S'm velocity and A'm velocity did not change after CPAP treatment in the compliant patients. OSAS is associated with RV systolic and diastolic dysfunction, and 6 months of CPAP therapy improves the RV systolic and diastolic dysfunction.


Action-Self Quenching: Dimer-Induced Fluorescence Quenching of Chromophores as a Probe for Biomolecular Structure.
To obtain a more detailed understanding of how structure influences the function and interaction of biomolecules, it is important to develop structure sensitive techniques to probe these relationships. Alongside in vivo and in vitro techniques, it is instructive to consider in vacuo methodologies: for example native mass spectrometry, ion mobility mass spectrometry, and FRET. Here, we propose a novel technique for probing biomolecular structure based on the changes in photophysics of a chromophore upon dimer formation. Comparison of solution and gas phase measurements on a doubly tagged tripeptide shows that dimer-induced fluorescence quenching is accompanied by an increase in photofragmentation yield. The 12-28 fragment of amyloid beta was used to show that as the charge state was increased-previously shown to cause a conformational change from compact random coil to extended helical structure-the disappearance of a band at 495 nm could be correlated with the level of self-quenching. The presence of features in the action spectrum of the +3 charge state of both quenched and unquenched chromophores allowed inference of multiple conformations. Single wavelength measurements on doubly tagged ubiquitin cations were performed to show that the technique is feasible on a small protein. These results demonstrate that self-quenching is a sensitive and fast gas-phase probe of biomolecular structure that can be directly linked to solution phase measurements. Further, it is capable of probing very small changes in conformation, making it complementary to FRET based techniques, which are insensitive at very short chromophore separations.


Biological Networks for Cancer Candidate Biomarkers Discovery.
Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field.


Complete Locked-in and Locked-in Patients: Command Following Assessment and Communication with Vibro-Tactile P300 and Motor Imagery Brain-Computer Interface Tools.
Many patients with locked-in syndrome (LIS) or complete locked-in syndrome (CLIS) also need brain-computer interface (BCI) platforms that do not rely on visual stimuli and are easy to use. We investigate command following and communication functions of mindBEAGLE with 9 LIS, 3 CLIS patients and three healthy controls. This tests were done with vibro-tactile stimulation with 2 or 3 stimulators (VT2 and VT3 mode) and with motor imagery (MI) paradigms. In VT2 the stimulators are fixed on the left and right wrist and the participant has the task to count the stimuli on the target hand in order to elicit a P300 response. In VT3 mode an additional stimulator is placed as a distractor on the shoulder and the participant is counting stimuli either on the right or left hand. In motor imagery mode the participant is instructed to imagine left or right hand movement. VT3 and MI also allow the participant to answer yes and no questions. Healthy controls achieved a mean assessment accuracy of 100% in VT2, 93% in VT3, and 73% in MI modes. They were able to communicate with VT3 (86.7%) and MI (83.3%) after 2 training runs. The patients achieved a mean accuracy of 76.6% in VT2, 63.1% in VT3, and 58.2% in MI modes after 1-2 training runs. 9 out of 12 LIS patients could communicate by using the vibro-tactile P300 paradigms (answered on average 8 out of 10 questions correctly) and 3 out of 12 could communicate with the motor imagery paradigm (answered correctly 4,7 out of 5 questions). 2 out of the 3 CLIS patients could use the system to communicate with VT3 (90 and 70% accuracy). The results show that paradigms based on non-visual evoked potentials and motor imagery can be effective for these users. It is also the first study that showed EEG-based BCI communication with CLIS patients and was able to bring 9 out of 12 patients to communicate with higher accuracies than reported before. More importantly this was achieved within less than 15-20 min.


Metabolic engineering for plant natural products biosynthesis: new procedures, concrete achievements and remaining limits.
Microorganisms and plants represent major sources of natural compounds with a plethora of bioactive properties. Among these, plant natural products (PNPs) remain indispensable to human health. With few exceptions, PNP-based pharmaceuticals come from plant specialized metabolisms and display a structure far too complex for a profitable production by total chemical synthesis. Accordingly, their industrial processes of supply are still mostly based on the extraction of final products or precursors directly from plant materials. This implies that particular contexts (e.g. pandemics, climate changes) and natural resource overexploitation are main drivers for the high production cost and recurrent supply shortages. Recently, biotechnological manufacturing alternatives gave rise to a multitude of benchmark studies implementing the production of important PNPs in various heterologous hosts. Here, we spotlight unprecedented advancements in the field of metabolic engineering dedicated to the heterologous production of a prominent series of PNPs that were achieved during the year 2020. We also discuss how the knowledge accumulated in recent years could pave the way for a broader manufacturing palette of natural products from a wide range of natural resources.


Kidney 11 beta-HSD2 is inhibited by glycyrrhetinic acid-like factors in human urine.
We have previously shown that human urine contains substances that, like glycyrrhetinic acid, inhibit 11 beta-HSD1. We have named these substances "glycyrrhetinic acid-like factors" or GALFs. We now have found that human urine contains measurable quantities of both 11 beta(HSD1)- and 11 beta(HSD2)-GALF inhibitory substances. Both are markedly elevated in pregnancy. Their chemical and high-performance liquid chromatography (HPLC) characteristics suggest that several of the GALFs are steroidal. Large quantities of neutral 11 beta(HSD1)- and 11 beta(HSD2)-GALFs can be extracted directly from urine into ethyl acetate, yielding fraction EA1. Hydrolysis of the GALFs remaining in the aqueous phase by beta-glucuronidase markedly increases the total amounts of GALFs, with the majority now being ethyl acetate extractable (fraction EA2). These EA2 post-hydrolysis GALFs can be separated by HPLC resulting in at least six components with inhibitory activity against each isoenzyme. Only two GALF peaks are active against both 11 beta-HSD1 and 11 beta-HSD2. The others are peaks with specific 11 beta(HSD1)- and 11 beta(HSD2)-GALF inhibitory activity. The GALFs in the same posthydrolysis EA2 extract are also inhibitory toward the 11 beta-HSD1 that is present in vascular smooth muscle where they may play a role in the mechanisms controlling blood pressure. We have also found that 11 beta-HSD2 is selectively inhibited by 5 alpha- (but not by 5 beta-) reduced steroids. GC-MS analysis of the 11 beta(HSD2)-GALFs in EA2 is now being performed to determine whether this group includes 3 alpha,5 alpha-ring A-tetrahydro-reduced derivatives of steroids.


Rosai-Dorfman Disease of Nasal Soft Tissue: A Case Report.
Rosai-Dorfman disease (RDD) is characterized by sinus histiocytosis with massive lymphadenopathy, and the tissue exhibits positive results for S100 and CD68. This lesion typically affects the lymph nodes and rarely involves the nasal soft tissues. This report aims to present a case of RDD involving the nasal soft tissues, presenting with nasal congestion and rhinorrhea as the primary complaints. The patient underwent surgery navigated by nasal endoscope did not report recurrence after operation.


Electroacupuncture ameliorates learning and memory deficits via hippocampal 5-HT1A receptors and the PKA signaling pathway in rats with ischemic stroke.
Hippocampal 5-HT1A receptors and the PKA signaling pathway have been implicated in learning and memory. This study aimed to investigate whether PKA signaling mediated by 5-HT1A receptors was involved in the electroacupuncture (EA)-mediated learning and memory in a rat model of middle cerebral artery occlusion-induced cognitive deficit (MICD). Compared to no treatment or non-acupoint EA treatment, EA at DU20 and DU24 acupoints improved the neurological deficit of scores, shortened escape latency and increased the frequency of crossing the platform in the Morris water maze test. T2-weighted imaging demonstrated that the MICD rat brain lesions were mainly located in the cortex and hippocampus, and injured volumes were reduced after EA. Furthermore, we found that these behavioral changes were concomitant with the deficit of the 5HT1A and PKA signaling pathways in the hippocampus, as the activation of the 5-HT1A receptor, the reduction of PKA kinase activity, and AMPA and NMDA receptor phosphorylation occurred in the injured hippocampus at Day 14 after MICD. Additionally, EA dramatically elevated the activation of PKA. Moreover, EA significantly increased intracellular calcium concentrations regulated by the activation of NMDA receptors. Therefore, PKA kinase and NMDA receptors mediated by 5-HT1A receptors in the hippocampus might contribute to improving learning and memory during the recovery process following ischemic stroke with an EA intervention.


Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxygen in bleomycin-mediated DNA chain breakage.
Bleomycin-dependent DNA chain breakage catalyzed by rat lung microsomes and NADPH was significantly inhibited by the reactive oxygen scavengers superoxide dismutase and dimethylurea and by the metal chelator EDTA. Cytochrome c and nitro blue tetrazolium, compounds which interfere with microsomal electron transport, also inhibited bleomycin-mediated DNA chain breakage. In contrast to these agents, ascorbic acid significantly enhanced this bleomycin-mediated reaction. In addition to ascorbic acid, the redox cycling compounds paraquat, nitrofurantoin and mitomycin C also significantly increased the DNA damage by bleomycin. The stimulatory action of these redox cycling compounds was significantly inhibited by superoxide dismutase, demonstrating that reactive oxygen generated by the redox cycling of these compounds was diverted to the bleomycin-DNA complex. These collective observations support the concept that oxidation/reduction of adventitious iron bound by bleomycin and accompanying reactive oxygen generation participate in the microsome-catalyzed DNA damage mediated by bleomycin.


Associations of Personality Traits with Internet Addiction: A Cross-Cultural Meta-Analysis with a Multilingual Approach.
With a novel multilingual approach, this cross-cultural meta-analysis study investigated the associations between personality traits and Internet addiction. Articles were identified and retrieved by searching through general and language-specific databases, and thereafter reviewed for inclusion based on the selection criteria. Random effects models with the Hartung-Knapp-Sidik-Jonkman method were used to examine the associations of Internet addiction with seven personality traits: Openness, Conscientiousness, Extraversion, Agreeableness, Neuroticism, Psychoticism, and Lie (OCEAN-PL). Forest plots with summary statistics were produced to inspect the between-study heterogeneity. Subgroup analysis was performed to further determine the contributions of moderators (geographic region, population subgroup, scales for assessing personality traits and Internet addiction, and language of publication) to the observed between-study heterogeneity. Funnel plots and Egger's test were used to detect possible small-study effects. A sample of 34,438 participants from 37 studies (24 from Asia) were included for data analysis. The major languages of publications of the selected articles were English and Asian languages. According to the pooled results, Internet addiction was associated positively with Neuroticism and Psychoticism, but negatively with Conscientiousness, Extraversion, Agreeableness, and Lie. Geographic region and language of publication significantly moderated the associations of Internet addiction with Agreeableness and Neuroticism, and Openness and Extraversion, respectively. No significant small-study effect was present for all OCEAN-PL personality traits, except Neuroticism. In conclusion, the Internet addiction group is relatively more neurotic and psychotic, and less conscientious, extraverted, agreeable, and untruthful than the nonaddiction group. A multilingual approach is useful for improving the search strategies for systematic reviews, cross-cultural meta-analyses in particular.


A field test for host fruit odour discrimination and avoidance behaviour for Rhagoletis pomonella flies in the western United States.
Prezygotic isolation due to habitat choice is important to many models of speciation-with-gene-flow. Habitat choice is usually thought to occur through positive preferences of organisms for particular environments. However, avoidance of non-natal environments may also play a role in choice and have repercussions for post-zygotic isolation that preference does not. The recent host shift of Rhagoletis pomonella (Diptera: Tephritidae) from downy hawthorn, Crataegus mollis, to introduced apple, Malus domestica, in the eastern United States is a model for speciation-with-gene-flow. However, the fly is also present in the western United States where it was likely introduced via infested apples ≤ 60 years ago. R. pomonella now attacks two additional hawthorns in the west, the native C. douglasii (black hawthorn) and the introduced C. monogyna (English ornamental hawthorn). Flight tunnel tests have shown that western apple-, C. douglasii- and C. monogyna-origin flies all positively orient to fruit volatile blends of their respective natal hosts in flight tunnel assays. Here, we show that these laboratory differences translate to nature through field-trapping studies of flies in the state of Washington. Moreover, western R. pomonella display both positive orientation to their respective natal fruit volatiles and avoidance behaviour (negative orientation) to non-natal volatiles. Our results are consistent with the existence of behaviourally differentiated host races of R. pomonella in the west. In addition, the rapid evolution of avoidance behaviour appears to be a general phenomenon for R. pomonella during host shifts, as the eastern apple and downy hawthorn host races also are antagonized by non-natal fruit volatiles.


Pancreatic microvascular permeability in caerulein-induced acute pancreatitis.
Microvascular permeability was studied in the isolated perfused rat pancreas using a rapid multiple indicator-dilution technique. Capillary extractions, permeability-surface area products (PS), and extravascular volumes of distribution (EVV) were determined for 22Na+, 51Cr-labeled EDTA, [57Co]-cyanocobalamin (B12), and 125I-labeled insulin at various perfusion flows. Permeability to albumin was negligible. PS for Na+ and EDTA increased with increasing flow, whereas PS for cyanocobalamin and insulin approached diffusion-limited exchange at flows greater than 3 ml.min-1.g-1. Permeability coefficients for Na+, EDTA, B12, and insulin were 36, 22, 11, and 3.48 x 10(-5) cm/s, respectively, and the permeability ratio for B12/insulin (3.16) indicated restricted diffusion to insulin. In the presence of unlabeled B12 and insulin EVV (0.15-0.19 ml/g) for EDTA, B12 and insulin approximated the interstitial volume. Caerulein-induced pancreatitis or treatment with the synthetic protease inhibitor camostate had no significant effects on permeability. In caerulein-treated rats, EVV for B12 was elevated (0.17 +/- 0.01 vs. 0.28 +/- 0.06; P less than 0.01), reflecting the interstitial edema associated with this model of pancreatitis. Permeability of the rat pancreatic microvasculature is similar to that of other fenestrated tissues, but it is 10- to 20-fold greater than that of continuous capillaries. Contrary to previous assumptions, permeability does not appear to be increased after induction of acute interstitial pancreatitis.


Dynamics of bubble oscillation in constrained media and mechanisms of vessel rupture in SWL.
Rupture of small blood vessels is a primary feature of the vascular injury associated with shock-wave lithotripsy (SWL) and cavitation has been implicated as a potential mechanism. To understand more precisely the underlying mechanical cause of the injury, the dynamics of SWL-induced bubble dynamics in constrained media were investigated. Silicone tubing and regenerated cellulose hollow fibers of various inner diameters (0.2 to 1.5 mm) were used to fabricate vessel phantoms, which were placed in a test chamber filled with castor oil so that cavitation outside the phantom could be suppressed. Degassed water seeded with 0.2% Albunex contrast agent was circulated inside the vessel phantom, and intraluminal bubble dynamics during SWL were examined by high-speed shadowgraph imaging and passive cavitation detection via a 20-MHz focused transducer. It was observed that, in contrast to the typical large and prolonged expansion and violent inertial collapse of SWL-induced bubbles in a free field, the expansion of the bubbles inside the vessel phantom was significantly constrained, leading to asymmetric elongation of the bubbles along the vessel axis and, presumably, much weakened collapse. The severity of the constraint is vessel-size dependent, and increases dramatically when the inner diameter of the vessel becomes smaller than 300 microm. Conversely, the rapid, large intraluminal expansion of the bubbles causes a significant dilation of the vessel wall, leading to consistent rupture of the hollow fibers (i.d. = 200 microm) after less than 20 pulses of shock wave exposure in a XL-1 lithotripter. The rupture is dose-dependent, and varies with the spatial location of the vessel phantom in the lithotripter field. Further, when the large intraluminal bubble expansion was suppressed by inversion of the lithotripter pressure waveform, rupture of the hollow fiber could be avoided even after 100 shocks. Theoretical calculation of SWL-induced bubble dynamics in blood confirms that the propensity of vascular injury due to intraluminal bubble expansion increases with the tensile pressure of the lithotripter shock wave, and with the reduction of the inner diameter of the vessel. It is suggested that selective truncation of the tensile pressure of the shock wave may reduce tissue injury without compromising the fragmentation capability of the lithotripter pulse.


Allergenic Activity of Individual Cat Allergen Molecules.
More than 10% of the world's population suffers from an immunoglobulin E (IgE)-mediated allergy to cats which is accompanied mainly by respiratory symptoms such as rhinitis and asthma. Several cat allergen molecules have been identified, but their allergenic activity has not been investigated in depth. Purified cat allergen molecules (Fel d 1, Fel d 2, Fel d 3, Fel d 4, Fel d 6, Fel d 7 and Fel d 8) were characterized via mass spectrometry and circular dichroism spectroscopy regarding their molecular mass and fold, respectively. Cat-allergen-specific IgE levels were quantified via ImmunoCAP measurements in IgE-sensitized subjects with (n = 37) and without (n = 20) respiratory symptoms related to cat exposure. The allergenic activity of the cat allergens was investigated by loading patients' IgE onto rat basophils expressing the human FcεRI receptor and studying the ability of different allergen concentrations to induce β-hexosaminidase release. Purified and folded cat allergens with correct masses were obtained. Cat-allergen-specific IgE levels were much higher in patients with a respiratory allergy than in patients without a respiratory allergy. Fel d 1, Fel d 2, Fel d 4 and Fel d 7 bound the highest levels of specific IgE and already-induced basophil degranulation at hundred-fold-lower concentrations than the other allergens. Fel d 1, Fel d 4 and Fel d 7 were recognized by more than 65% of patients with a respiratory allergy, whereas Fel d 2 was recognized by only 30%. Therefore, in addition to the major cat allergen Fel d 1, Fel d 4 and Fel d 7 should also be considered to be important allergens for the diagnosis and specific immunotherapy of cat allergy.


Structural studies on heparan sulphate from human lung fibroblasts. Characterization of oligosaccharides obtained by selective periodate oxidation of D-glucuronic acid residues followed by scission in alkali.
1. (3)H- and (35)S-labelled heparan sulphate was isolated from monolayers of human lung fibroblasts and subjected to degradations by (a) deaminative cleavage and (b) periodate oxidation/alkaline elimination. Fragments were resolved by gel- and ion-exchange-chromatography. 2. Deaminative cleavage of the radioactive glycan afforded mainly disaccharides with a low content of ester-sulphate and free sulphate, indicating that a large part (approx. 80%) of the repeating units consisted of uronosyl-glucosamine-N-sulphate. Blocks of non-sulphated [glucuronosyl-N-acetyl glucosamine] repeats (3-4 consecutive units) accounted for the remainder of the chains. 3. By selective oxidation of glucuronic acid residues associated with N-acetylglucosamine, followed by scission in alkali, the radioactive glycan was degraded into a series of fragments. The glucuronosyl-N-acetylglucosamine-containing block regions yielded a compound N-acetylglucosamine-R, where R is the remnant of an oxidized and degraded glucuronic acid. Periodate-insensitive uronic acid residues were recovered in saccharides of the general structure glucosamine-(uronic acid-glucosamine)(n)-R. 4. Further degradations of these saccharides via deaminative cleavage and re-oxidations with periodate revealed that iduronic acid may be located in sequences such as glucosamine-N-sulphate-->iduronic acid-->N-acetylglucosamine. Occasionally the iduronic acid was sulphated. Blocks of iduronic acid-containing repeats may contain up to five consecutive units. Alternating arrangements of iduronic acid- and glucuronic acid-containing repeats were also observed. 5. (3)H- and (35)S-labelled heparan sulphates from sequential extracts of fibroblasts (medium, EDTA, trypsin digest, dithiothreitol extract, cell-soluble and cell-insoluble material) afforded similar profiles after both periodate oxidation/alkaline elimination and deaminative cleavage.


catena-Poly[silver(I)-μ-acridine-9-carboxyl-ato-κN:O,O'].
In the title coordination polymer, [Ag(C(14)H(8)NO(2))](n), the Ag(I) cation is coordinated by two O atoms and one N atom from two symmetry-related acridine-9-carboxyl-ate ligands in a distorted trigonal-planar geometry. The metal atoms are connected by the ligands to form chains running parallel to the b axis. π-π stacking inter-actions [centroid-to-centroid distances 3.757 (2)-3.820 (2) Å] and weak Ag⋯O inter-actions further link the chains to form a layer network parallel to the ab plane. The Ag(I) cation is disordered over two positions, with refined site-occupancy factors of 0.73 (3):0.27 (3).


Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schoenlein patients. Italian Group of Renal Immunopathology.
The influence of angiotensin converting enzyme (ACE) gene polymorphism on the progression of primary IgA nephropathy (pIgAN) is still debated. Even though the allele frequency was reported to be similar to controls, in some studies D/D patients had a faster decline of renal function and need of dialysis. Since Henoch-Schoenlein purpura (HSP) nephritis is considered a systemic vasculitis with renal lesions indistinguishable from pIgAN, we investigated the effect of the ACE polymorphism on presentation and progression of HSP IgAN. We examined the insertion (I) and deletion (D) polymorphism in intron 16 of ACE gene by PCR amplification of genomic DNA of 82 patients (37 children), with biopsy-proven IgAN associated with HSP enrolled in a collaborative study. No significant association with clinical presentation at onset or with final outcome was found (functional impairment at outcome in 31.8%, D/D, 27.4%, I/D and 44% I/I, heavy proteinuria in 36.3% D/D, 21.6% I/D, and 11.1% I/I). Patients homozygous for the D allele had a greater number of extrarenal relapses (P=0.0028). No association was found between the ACE genotype and the presence of hypertension at onset and at the end of the follow-up. No difference was found between adults and children. In this cohort of HSP IgAN, no ACE I/D polymorphisms were found to be associated with progressive deterioration of renal function. Different genes possibly involved in vasculitis might more strictly modulate expression and evolution of HSP IgAN.


Efficacy and tolerability of oral propafenone versus quinidine in the treatment of recent onset atrial fibrillation: A randomized, prospective study.
A prospective, randomized study was conducted to evaluate the efficacy and tolerability of oral propafenone and quinidine for the conversion of paroxysmal atrial fibrillation (AF). Eighty one consecutive patients (female/male 46/35; mean age 64.0 +/- 11.6), admitted to hospital with AF lasting no longer than 48 hours, were randomized in terms of their pharmacological therapy. Forty three patients (55%) were randomly assigned to Group I and received propafenone 600 mg orally as the initial therapy, with an additional dose of 300 mg after eight hours, if the sinus rhythm had not been restored by then. Thirty eight patients (45%) (Group II) received 1 mg digoxin IV followed by an oral loading of quinidine (400 mg followed by 200 mg every two hours). The conversion rate assessed after 24 hours was the same in both groups (Gr. I vs. Gr. II: 90.7 vs. 91.4%), with the same number of mild side effects (Gr. I vs. Gr. II: 37.2% vs. 45.7%). No life-threatening adverse events were reported. Propafenone achieved a higher efficacy rate during the first eight hours (83.3 vs. 54.3%; p = 0.01), with a significantly shorter time required to sinus rhythm recovery throughout the study period, with a median time of 165 min (95% confidence interval 120-278) vs. 360 min (95% confidence interval 298-650; p < 0.05). There was some indication of greater effectiveness of propafenone than quinidine in early sinus rhythm restoration in patients with: no structural heart disease, in those with an AF duration shorter than 12 hours, and in patients with an ejection fraction > 55%. Although both drugs revealed the same effectiveness, the conversion to sinus rhythm in the group treated with propafenone was observed more quickly despite the longer paroxysmal AF episode duration.


Progress and potential in organoid research.
Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.


Post-tuberculosis lung disease and inflammatory role players: can we characterise the myriad inflammatory pathways involved to gain a better understanding?
Tuberculosis (TB) remains a global health threat, and even after successful TB treatment, a subset of patients develops serious long-term lung impairments, recently termed post-tuberculosis lung disease (PTLD). Much remains to be discovered, as PTLD as a post-TB disease is a developing field, still in its infancy. The pathogenesis of PTLD is not fully elucidated but has been linked to elevated inflammatory pathways. The complexity of PTLD makes it challenging to pinpoint the specific inflammatory pathways involved in its pathophysiology. Therefore, this paper provides a comprehensive review of inflammatory cytokines and their potential roles in PLTD, with a specific focus on interleukin 6 (IL-6), IL-1, IL-8, tumour necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-β) and C-Reactive Protein (CRP). We delve into PTLD pathology, discuss its impact on lung function and review risk factors for PTLD. In addition, we summarise the current gaps in knowledge, provide recommendations for measuring inflammatory biomarkers and propose potential directions for future studies. We propose that future studies measure a wide range of inflammatory markers in TB populations with and without PTLD. In addition, studies could isolate peripheral blood mononuclear cells from patient blood to try and identify possible impairments that could be correlated with a PTLD diagnosis. Given that the PTLD field is still in an early stage of development, a comprehensive inflammatory analysis may help to know which pathways are key in PTLD development, and this may ultimately help to predict patients who are at risk. More research is warranted.


The effects of stance configuration and target distance on reaching. I. Movement preparation.
The aim of the present study was to investigate the relationship between the focal and postural components of a functional movement during the preparatory phase of a task. The contribution of the arms, trunk, and legs were varied by having subjects reach for two targets within and two beyond arm's length. In addition, the degree of postural stability was manipulated by varying the size of the base of support (BoS). Nine subjects reached and grasped a dowel placed at four locations while standing on a force plate with their feet in a parallel or step stance (right foot forward) under simple reaction-time (RT) conditions. Anticipatory postural adjustments (APAs) occurring prior to arm movement and RTs were analyzed. APAs varied depending on the demands of the task. For movements within arm's length, subjects selected different strategies to initiate the movement. However, for movements beyond arm's length, all subjects used the same strategy: the center of pressure (CoP) was shifted posteriorly, which resulted in the center of mass (CoM) moving towards the target. Target distance and BoS had no effect on the onset of APAs. In contrast, amplitude and duration of APAs increased linearly with target distance, and amplitude was always greater during the more posturally stable BoS configuration. Although wrist RT increased linearly with movement amplitude for both stance configurations, the rate of change was less under the more stable BoS. These results suggest that, during the performance of a functional task, dynamic changes that occur in the trunk and lower extremities prior to initiation of arm movement serve not only to stabilize the body, but are also used to initiate and assist whole-body reaching.


An ionic liquid process for mercury removal from natural gas.
Efficient scrubbing of mercury vapour from natural gas streams has been demonstrated both in the laboratory and on an industrial scale, using chlorocuprate(II) ionic liquids impregnated on high surface area porous solid supports, resulting in the effective removal of mercury vapour from natural gas streams. This material has been commercialised for use within the petroleum gas production industry, and has currently been running continuously for three years on a natural gas plant in Malaysia. Here we report on the chemistry underlying this process, and demonstrate the transfer of this technology from gram to ton scale.


Electronic connectivity between hospital pairs: impact on emergency department-related utilization.
To use more precise measures of which hospitals are electronically connected to determine whether health information exchange (HIE) is associated with lower emergency department (ED)-related utilization. We combined 2018 Medicare fee-for-service claims to identify beneficiaries with 2 ED encounters within 30 days, and Definitive Healthcare and AHA IT Supplement data to identify hospital participation in HIE networks (HIOs and EHR vendor networks). We determined whether the 2 encounters for the same beneficiary occurred at: the same organization, different organizations connected by HIE, or different organizations not connected by HIE. Outcomes were: (1) whether any repeat imaging occurred during the second ED visit; (2) for beneficiaries with a treat-and-release ED visit followed by a second ED visit, whether they were admitted to the hospital after the second visit; (3) for beneficiaries discharged from the hospital followed by an ED visit, whether they were admitted to the hospital. In adjusted mixed effects models, for all outcomes, beneficiaries returning to the same organization had significantly lower utilization compared to those going to different organizations. Comparing only those going to different organizations, HIE was not associated with lower levels of repeat imaging. HIE was associated with lower likelihood of hospital admission following a treat-and-release ED visit (1.83 percentage points [-3.44 to -0.21]) but higher likelihood of admission following hospital discharge (2.78 percentage points [0.48-5.08]). Lower utilization for beneficiaries returning to the same organization could reflect better access to information or other factors such as aligned incentives. HIE is not consistently associated with utilization outcomes reflecting more coordinated care in the ED setting.


Postural Responses to a Suddenly Released Pulling Force in Older Adults with Chronic Low Back Pain: An Experimental Study.
Chronic low back pain (CLBP), one of the most common musculoskeletal conditions in older adults, might affect balance and functional independence. The purpose of this study was to investigate the postural responses to a suddenly released pulling force in older adults with and without CLBP. Thirty community-dwelling older adults with CLBP and 26 voluntary controls without CLBP were enrolled. Participants were required to stand on a force platform while, with one hand, they pulled a string that was fastened at the other end to a 2-kg or to a 4-kg force in the opposite direction at a random order. The number of times the participants lost their balance and motions of center of pressure (COP) when the string was suddenly released were recorded. The results demonstrated that although the loss of balance rates for each pulling force condition did not differ between groups, older adults with CLBP had poorer postural responses: delayed reaction, larger displacement, higher velocity, longer path length, and greater COP sway area compared to the older controls. Furthermore, both groups showed larger postural responses in the 4-kg pulling force condition. Although aging is generally believed to be associated with declining balance and postural control, these findings highlight the effect of CLBP on reactive balance when responding to an externally generated force in an older population. This study also suggests that, for older adults with CLBP, in addition to treating them for pain and disability, reactive balance evaluation and training, such as reaction and movement strategy training should be included in their interventions. Clinicians and older patients with CLBP need to be made aware of the significance of impaired reactive balance and the increased risk of falls when encountering unexpected perturbations.


Colour contrast sensitivity with different intraocular lens materials in the right and left eyes in same day surgery.
To study possible differences in colour contrast sensitivity between different intraocular lens (IOL) materials with consecutive same day cataract surgery performed in the right and left eyes. Central colour contrast sensitivity was measured with a computer graphics system along the protan, deutan and tritan axes. Thirty-four patients with cataract were studied. The patients were randomized to one of three groups: group 1 received a Clariflex (silicone) lens in one eye and an Akreos Fit (hydrophilic acrylic) lens in the other; group 2 received an Akreos lens in one eye and a Sensar AR40e (hydrophobic acrylic) lens in the other, and group 3 received a Clariflex lens in one eye and an AR40e lens in the other. Surgery was performed in both eyes on the same day. A postoperative questionnaire was distributed, asking the patients to describe any differences experienced between their two eyes. There were no significant differences between the three different IOLs in any colour axis. There were no complications of importance during surgery. Thirty-two of the 34 patients answered the questionnaire. Twenty-one patients experienced some difference between their two eyes in distance vision and 23 noticed differences in near vision. For distance vision, nine reported better vision in the eye with the Akreos IOL, eight in the eye with the Clariflex IOL lens and four in the eye with the AR40e IOL. For near vision, 12 preferred the Akreos lens, eight the Clariflex lens and three the AR40e lens. There were no significant differences between the three different IOLs in any colour axis.


The retinal oxygen profile in cats.
This study records for the first time the retinal tissue oxygen partial pressure as a function of location within the retina of the domestic cat. Tissue pO2 was recorded with oxygen sensitive microelectrodes that use the polarographic principle. The mean vitreal pO2 close to the internal limiting membrane was 20.2 +/- 2.3 mmHg. The internal limiting membrane does not act as a diffusion barrier for oxygen. As the electrode was advanced into the inner retina, the tissue pO2 rose gradually to a value of 24.6 +/- 2.3 mmHg and then fell to a minimum of 12.0 +/- 5.5 mmHg before rising again to a value of 29.2 +/- 2.5 mmHg. Further insertion resulted in a sudden steep rise of tissue pO2 values to 72.0 +/- 5.1 mmHg, after which there was no further alteration in measured values. Although the exact location within the retina of the recording electrode was not known, it is probable that the tissue pO2 minimum occurs at about the level of the inner nuclear layer. Therefore, it is probable that the retinal avascular layers receive their oxygen supply primarily from the choroidal circulation in the cat.


Papillary neoplasias of the biliary tract.
The authors conducted a revisional study of intraepithelial papillary lesions of the bile ducts, characterized by being a kind of rare, intraductal growing cholangiocarcinoma. Articles published in the last 10 years were reviewed. The authors considered that the adenoma-carcinoma development is an important feature to warrant prophylactic measures through excisions. The histological type and biomolecular behavior may have relevance in the postoperative course of such lesions, which have a better prognosis when compared with other histological types.


Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells.
The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.


Hypotensive anaesthesia with remifentanil combined with desflurane or isoflurane in tympanoplasty or endoscopic sinus surgery: a randomised, controlled trial.
To compare the effect of remifentanil combined with desflurane or isoflurane on the quality of the operative field and surgical conditions, blood loss, and recovery during tympanoplasty or endoscopic sinus surgery. Randomised, double-blinded clinical study. Sixty-four patients were scheduled for elective tympanoplasty or endoscopic sinus surgery. The patients were randomly divided into two groups: desflurane or isoflurane. After anaesthesia induction, all patients received a continuous remifentanil infusion of 0.2-0.5 microg/kg/min until a mean arterial pressure of 65-75 mmHg was achieved. Heart rate and mean arterial pressure were recorded throughout anaesthesia. Blood loss was measured at the end of surgery. Achievement of a bloodless operative field was rated on a 100 mm visual analogue scale. Following completion of surgery, the time to extubation and to achievement of an Aldrete score of nine or more was recorded. Sixty-three patients were evaluated. The total dose of remifentanil and the total blood loss were similar in both groups (p > 0.05). Time to extubation and to an Aldrete score of nine or more for the desflurane group was significantly less than for the isoflurane group (p 0.05). Although desflurane and isoflurane both enabled good surgical conditions (in terms of quality of operative field) and convenient induction of hypotension for tympanoplasty and endoscopic sinus surgery, the recovery characteristics of desflurane were better than those of isoflurane. Therefore, desflurane may be preferable to isoflurane in such circumstances.


Expression of CYP3A4, CYP3A5 and CYP3A7 in human duodenal tissue.
The essential role of cytochrome P450 3A4 (CYP3A4) in human small intestine is well established, and CYP3A5 seems also to be present in most subjects. However, the role of CYP3A7 in the small intestine remains poorly characterized. We have therefore studied the expression of these CYP3A enzymes in the duodenal tissue from 19 patients, using a specific RT-PCR (reverse transcriptase-polymerase chain reaction) method. CYP3A4 and CYP3A5 were present at the mRNA level in the duodenum of 18 and 19 of the 19 patients studied, respectively. In contrast, mRNA for CYP3A7 was not found in the duodenum in any of the patients. These findings strongly suggest that, unlike CYP3A4 and CYP3A5, CYP3A7 is not expressed in human duodenum.


Stent thrombosis: a poor man's disease?
Stent thrombosis is a rare but devastating complication of coronary stent implantation. The incidence and potential predictors were assessed in a "real world" single center. To examine whether socioeconomic status indeed affects the occurrence of stent thrombosis. We searched our database for cases of "definite" stent thrombosis (according to the ARC Dublin definitions). Each case was matched by procedure date, age and gender with three cases of stenting that did not result in stent thrombosis. Demographic and clinical parameters were compared and socioeconomic status was determined according to a standardized polling and market survey database. A total of 3401 patients underwent stent implantation in our hospital during the period 2004-2006. Their mean age was 63 +/- 11 years, and 80% were males. Twenty-nine cases (0.85%) of "definite" sub-acute/late stent thrombosis were recorded. Mortality at 30 days was recorded in 1 patient (3.5%). Thrombosis occurred 2 days to 3 years after stent implantation. All patients presented with acute myocardial infarction. Premature clopidogrel discontinuation was reported in 60%. Patients with stent thrombosis had significantly higher rates of AMI at the time of the initial procedure (76 vs. 32%, P < 0.001) and were cigarette smokers (60 vs. 28%, P < 0.001). Drug-eluting stents were used less in the stent thrombosis group. There was no difference in stent diameter or length between the two groups. Socioeconomic status was significantly lower in the stent thrombosis group, 3.4 +/- 2.4 vs. 5.4 +/- 2.6 (mean +/- SD, scale 1-10, P < 0.01). The incidence rate of stent thrombosis is at least 0.85% in our population. It appears in patients with significantly lower socioeconomic status and with certain clinical predictors. These results warrant stricter follow-up and support the policy of healthcare providers regarding patients at risk for stent thrombosis.


p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models.
Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress, apoptosis, and inflammatory response. Previously, we proved that p-coumaric acid prevents ethanol induced reproductive toxicity; however, p-coumaric acid (PCA) on ethanol mediated hepatotoxicity has not been examined yet. In our work, we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs, apoptosis, oxidative stress, and Nrf2 signaling. Foremost, we found that PCA could protect ethanol induced both L-02 and HepG2 hepatic cells by inhibiting cytotoxicity, ROS production, mitochondrial depolarization, and nuclear fragmentation. Also, in vivo experiments showed that the ethanol increasing the lipid markers (TBARS, CD) and depletes the antioxidants thereby increased phosphorylation of JNK, ERK, and p38 in rat liver tissues. Interestingly, PCA treatments inhibit ethanol exposed lipid markers and depletion of antioxidants, which directs the inhibition of MAPKs activation in rat liver tissues. We also noticed that the PCA protected ethanol induced apoptosis and liver markers by inhibiting the expression of Bax, caspases; AST, ALT, ALS, and LDH in liver tissue. Overall, the ameliorative consequence of PCA on ethanol induced oxidative stress and apoptosis was achieved by suppressing the expression of CYP2E1 and overexpressing Nrf2 and its target protein HO-1 in rat liver tissue. As a result, PCA was marked to be an effective antioxidant with notable hepatoprotection by inhibiting MAPKs and apoptosis signaling via enhancing Nrf2 signaling.


Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation.
Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals. A case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) using a (11)C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling. Twenty-four aHCV cases completed NCT and (1)H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent (1)H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on (1)H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in (11)C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations. Poorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher (11)C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.


The characterisation of flavone-DNA isoform interactions as a basis for anticancer drug development.
The interactions of small molecules with nucleic acids are of considerable interest for the design of novel anticancer compounds. The physical properties and sequence specificity observed in the interactions between a group of flavonoids with proven antitumour activity and various nucleic acid structures are summarised. UV and fluorescence spectroscopy, together with competition dialysis, were used to assess the affinity of the drugs for the nucleic acid structures in the presence or absence of different metal ions. The effect of these compounds on breast and leukaemia cancer cell lines was evaluated using MTS and COMET assays and flow cytometry. The flavonoids studied are weak duplex DNA-binding ligands and the binding of flavonoids to DNA is affected by metal ions. Baicalein and quercetin display stronger affinity for triplex and quadruplex than for double-stranded DNA and offer interesting scaffolds for the design of novel, high order DNA-binding agents.


An explanation of eye movements seen in internuclear ophthalmoplegia.
Recent findings in experiments on monkeys show that a horizontal saccade is made by a pulse-step of neural activity, part of which rises to medial rectus (MR) motoneurons on the fibers of the medial longitudinal fasciculus (MLF). If inhibitory as well as excitatory fibers run in the MLF, then the data show that each MLF must carry both the excitatory and inhibitory activity required for contralateral, horizontal saccades. Therefore, interruption of these fibers removes not only excitation from the ipsilateral MR but inhibition from the contralateral MR. Such a lesion also disturbs the correct relationship between the pulse and the step and creates abnormal saccades. These facts make it possible to explain why, in internuclear ophthalmoplegia, the eye on the side of the lesion adducts slowly and inadequately, while the opposite eye has nystagmus in abduction.


Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models.
The optimization of the dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-one R(2) and R(12) positions led to the identification of the first MLK1 and MLK3 subtype-selective inhibitors within the MLK family. Compounds 14 (CEP-5104) and 16 (CEP-6331) displayed good potency for MLK1 and MLK3 inhibition with a greater than 30- to 100-fold selectivity for related family members MLK2 and DLK. Compounds 14 and 16 were orally active in vivo in a mouse MPTP biochemical efficacy model that was comparable to the first-generation pan-MLK inhibitor 1 (CEP-1347). The MLK1 structure-activity relationships were supported by the first-reported X-ray crystal structure of MLK1 bound with 16.


Trace metal behaviour in estuarine and riverine floodplain soils and sediments: a review.
This paper reviews the factors affecting trace metal behaviour in estuarine and riverine floodplain soils and sediments. Spatial occurrence of processes affecting metal mobility and availability in floodplains are largely determined by the topography. At the oxic-anoxic interface and in the anoxic layers of floodplain soils, especially redox-sensitive processes occur, which mainly result in the inclusion of metals in precipitates or the dissolution of metal-containing precipitates. Kinetics of these processes are of great importance for these soils as the location of the oxic-anoxic interface is subject to change due to fluctuating water table levels. Other important processes and factors affecting metal mobility in floodplain soils are adsorption/desorption processes, salinity, the presence of organic matter, sulphur and carbonates, pH and plant growth. Many authors report highly significant correlations between cation exchange capacity, clay or organic matter contents and metal contents in floodplain soils. Iron and manganese (hydr)oxides were found to be the main carriers for Cd, Zn and Ni under oxic conditions, whereas the organic fraction was most important for Cu. The mobility and availability of metals in a floodplain soil can be significantly reduced by the formation of metal sulphide precipitates under anoxic conditions. Ascending salinity in the flood water promotes metal desorption from the floodplain soil in the absence of sulphides, hence increases total metal concentrations in the water column. The net effect of the presence of organic matter can either be a decrease or an increase in metal mobility, whereas the presence of carbonates in calcareous floodplain soils or sediments constitutes an effective buffer against a pH decrease. Moreover, carbonates may also directly precipitate metals. Plants can affect the metal mobility in floodplain soils by oxidising their rhizosphere, taking up metals, excreting exudates and stimulating the activity of microbial symbionts in the rhizosphere.


Clinical experience with sensitive thyrotropin measurements: diagnostic and therapeutic implications.
A two-site immunoradiometric assay for serum thyrotropin (TSH) was modified to improve the analytical sensitivity. The sensitivity achieved (detection limit, approximately 0.1 microU/ml; lower limit of quantitative measurement, approximately 0.4 microU/ml) was comparable to that of the best competitive binding research assays, yet this assay can be performed routinely. Serum TSH was 1.82 +/- 0.69 (mean +/- s.d.) (range 0.4-3.4 microU/ml) in healthy individuals and 1.83 +/- 0.90 microU/ml (range 0.7-3.7 microU/ml) in patients with nonthyroidal disorders. By contrast, 97% of clinically hyperthyroid patients (Graves' disease, toxic nodular goiter) with high serum free T4 (FT4) and T3 had suppressed serum TSH values, i.e., less than 0.3 microU/ml. Among patients with euthyroid Graves' ophthalmopathy or nontoxic goiter those clinically suspected of mild hyperthyroidism had TSH values less than 0.3 microU/ml, while those judged euthyroid had normal values. A large proportion of thyroid patients on antithyroid drugs (poorly to well-controlled) had suppressed TSH. Of Graves' patients in remission (normal FT4 and T3), 75% had normal TSH, but individual levels changed significantly over time, suggesting that a progressive decline in TSH may be useful in predicting recurrences. In hypothyroid patients taking L-T4, serum TSH was subnormal in patients with elevated FT4, but TSH was also low in six patients clinically suspected to be thyrotoxic despite normal FT4 and T3 and in 32% of asymptomatic patients with normal thyroid hormone levels. Conversely, 23% of thyroid cancer patients who had undergone thyroidectomy were taking insufficient L-T4 to completely suppress TSH secretion. In 25 individuals who underwent thyrotropin releasing hormone (TRH) stimulation tests, the baseline serum TSH value correlated well with the peak serum TSH value post-TRH (r = 0.85). We conclude that sensitive TSH measurements could establish or confirm the diagnosis of hyperthyroidism in equivocal cases, replace most TRH-stimulation tests and be of value in optimizing L-T4 suppression therapy for thyroid cancer patients post-thyroidectomy.


Cryptococcus neoformans isolates from Yaoundé human immunodeficiency virus-infected patients exhibited intra-individual genetic diversity and variation in antifungal susceptibility profiles between isolates from the same patient.
Cryptococcal meningitis is a dreadful opportunistic fungal infection amongst human immunodeficiency virus (HIV)-infected patients. One complication in the management of the disease is the possible infection of a patient by two or more different strains of Cryptococcus neoformans. This study investigated the intra-individual genetic diversity and antifungal susceptibility of C. neoformans isolates from Yaoundé (Cameroon) HIV-infected patients with cryptococcal meningitis. Twenty-five clinical isolates were obtained during a prospective study. Five colonies were randomly collected from each initial sample. The 150 isolates obtained (125 colonies and 25 initial samples) were submitted to serotyping by multiplex PCR. Genotyping analyses were achieved using RFLP, and minisatellite- and microsatellite-length polymorphism. The antifungal susceptibility testing was carried out using a Sensititre YeastOne kit. Seven antifungals were tested: itraconazole, fluconazole, amphotericin B, ketoconazole, 5-fluorocytosine, posaconazole and voriconazole. The 150 isolates were identified as C. neoformans serotype A and genotype VNI. The microsatellite and minisatellite sequence analyses generated 15 genotypes. Six out of 25 (24 %) patients were found to be infected by two different genotypes. Antifungal susceptibility showed several profiles: posaconazole (0.015-0.25 µg ml-1), amphotericin B (0.06-1 µg ml-1), fluconazole (0.5-16 µg ml-1), itraconazole (0.008-0.12 µg ml-1), ketoconazole (0.008-0.12 µg ml-1), 5-fluorocytosine (0.25-16 µg ml-1) and voriconazole (0.008-0.12 µg ml-1). It was noted that isolates from the same patient might present different susceptibility profiles to an antifungal drug with differences of more than four dilutions. The results achieved highlighted the possible presence of isolates with different genotypes in a patient with dissimilar antifungal susceptibility profiles during a single episode of cryptococcal meningitis.


Recent advances in tissue engineering scaffolds based on polyurethane and modified polyurethane.
Organ repair, regeneration, and transplantation are constantly in demand due to various acute, chronic, congenital, and infectious diseases. Apart from traditional remedies, tissue engineering (TE) is among the most effective methods for the repair of damaged tissues via merging the cells, growth factors, and scaffolds. With regards to TE scaffold fabrication technology, polyurethane (PU), a high-performance medical grade synthetic polymer and bioactive material has gained significant attention. PU possesses exclusive biocompatibility, biodegradability, and modifiable chemical, mechanical and thermal properties, owing to its unique structure-properties relationship. During the past few decades, PU TE scaffold bioactive properties have been incorporated or enhanced with biodegradable, electroactive, surface-functionalised, ayurvedic products, ceramics, glass, growth factors, metals, and natural polymers, resulting in the formation of modified polyurethanes (MPUs). This review focuses on the recent advances of PU/MPU scaffolds, especially on the biomedical applications in soft and hard tissue engineering and regenerative medicine. The scientific issues with regards to the PU/MPU scaffolds, such as biodegradation, electroactivity, surface functionalisation, and incorporation of active moieties are also highlighted along with some suggestions for future work.


Evidence for differences in regioselective and stereoselective glucuronidation of silybin diastereomers from milk thistle (Silybum marianum) by human UDP-glucuronosyltransferases.
The flavonolignan silybin, the main component of silymarin, extract from the seeds of Silybum marianum, is used mostly as a hepatoprotectant. Silybin is almost 1:1 mixture of two diastereomers A and B. The individual UDP-glucuronosyltransferases (UGTs) contributing to the metabolism of silybin diastereomers have not been identified yet. In this study, the contribution of UGTs to silybin metabolism was examined. The potential silybin metabolites were formed in vitro by incubating silybin (i) with the human liver microsomal fraction, (ii) with human hepatocytes and finally (iii) with 12 recombinant UGTs (UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15 and 2B17). High-performance liquid chromatographic (HPLC) techniques with UV detection and additionally MS detection were used for metabolite identification. Hepatocytes and microsomes formed silybin A-7-O-β-D-glucuronides, B-7-O-β-D-glucuronides, A-20-O-β-D-glucuronides and B-20-O-β-D-glucuronides. With recombinant UGTs, the major role of the UGT1A1, 1A3, 1A8 and 1A10 enzymes but also of the UGT1A6, 1A7, 1A9, 2B7 and 2B15 in the stereoselective reactions leading to the respective silybin glucuronides was confirmed. UGT1A4, UGT2B4 and UGT2B17 did not participate in silybin glucuronidation. The predominant formation of 7-O-β-D-glucuronides and the preferential glucuronidation of silybin B diastereomer in vitro by human UGTs were confirmed.


p27 deficiency is associated with migration defects in PDGF-expressing gliomas in vivo.
p27(Kip1) is a cyclin dependent kinase inhibitor that functions as a tumor suppressor in a variety of different cancers. While p27 has a well established role in regulating the cell cycle, it has also been shown to regulate cellular migration by influencing the activation state of the small GTPase RhoA. We recently demonstrated that loss of p27 enhances tumor progression and leads to a dramatic decrease in survival in PDGF-induced oligodendrogliomas. Here we show that p27 deficient PDGF-expressing glial cells contained elevated levels of Rho-GTP and were less migratory than wild type cells. Migration defects in p27 deficient cells were rescued by either Rho kinase inhibition or expression of p27 or CK(-), a mutant of p27 that cannot bind cyclins/cdks. The RCAS/tv-a retroviral system was used to specifically induce PDGF-expressing gliomas in mice. Many of the p27 deficient mice died earlier than wild type mice and displayed hydrocephalus which was associated with periventricular tumors that failed to invade the normal brain parenchyma. Invasion failure was reversed by co-expression of PDGF with either the GAP domain of p190(RhoGAP), a negative regulator of Rho, or p27, or CK(-). These results suggest that p27 mediated regulation of the Rho pathway is cell cycle independent and demonstrate for the first time a migration defect in cancer cells that is associated with p27 deficiency in vivo in a mouse tumor model.


Cellular and Molecular Mechanisms of Vestibular Ageing.
While age-related auditory deficits and cochlear alterations are well described, those affecting the vestibular sensory organs and more broadly the central vestibular pathways are much less documented. Although there is inter-individual heterogeneity in the phenomenon of vestibular ageing, common tissue alterations, such as losses of sensory hair cells or primary and secondary neurons during the ageing process, can be noted. In this review, we document the cellular and molecular processes that occur during ageing in the peripheral and central vestibular system and relate them to the impact of age-related vestibular deficits based on current knowledge.


Monitoring of end tidal carbon dioxide and transcutaneous carbon dioxide during neonatal transport.
To assess the accuracy of measurements of end tidal carbon dioxide (CO2) during neonatal transport compared with arterial and transcutaneous measurements. Paired end tidal and transcutaneous CO2 recordings were taken frequently during road transport of 21 ventilated neonates. The first paired CO2 values were compared with an arterial blood gas. The differences between arterial CO2 (Paco2), transcutaneous CO2 (TcPco2), and end tidal CO2 (Petco2) were analysed. The Bland-Altman method was used to assess bias and repeatability. Petco2 correlated strongly with Paco2 and TcPco2. However, Petco2 underestimated Paco2 at a clinically unacceptable level (mean (SD) 1.1 (0.70) kPa) and did not trend reliably over time within individual subjects. The Petco2 bias was independent of Paco2 and severity of lung disease. Petco2 had an unacceptable under-recording bias. TcPco2 should currently be considered the preferred method of non-invasive CO2 monitoring for neonatal transport.


[Oral contraceptive drugs, hyperhomocysteinaemia and cerebral ischaemic events in a 31-year-old woman--a case report].
We present a case of a 31-year-old female who was admitted to the hospital due to recurrent syncope. Transoesophageal echocardiography revealed the presence of an interventricular septum defect with insignificant left-to-right shunt and excluded intracardiac thrombi. Magnetic resonance of brain showed several ischaemic areas of vascular origin. Tests for arrhythmias or vaso-vagal reflex as the causes of syncope were negative. Further examinations revealed hyperhomocysteinaemia which, together with prolonged oral contraceptive treatment, might have caused cerebral arterial thrombosis.


Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial.
Age-related losses of muscle mass, strength, and function (sarcopenia) pose significant threats to physical performance, independence, and quality of life. Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia. A multicenter, randomized, controlled, double-blind, 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index. The active group (n = 184) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks. The control group (n = 196) received an iso-caloric control product to consume twice daily for 13 weeks. Primary outcomes of handgrip strength and SPPB score, and secondary outcomes of chair-stand test, gait speed, balance score, and appendicular muscle mass (by DXA) were measured at baseline, week 7, and week 13 of the intervention. Handgrip strength and SPPB improved in both groups without significant between-group differences. The active group improved more in the chair-stand test compared with the control group, between-group effect (95% confidence interval): -1.01 seconds (-1.77 to -0.19), P = .018. The active group gained more appendicular muscle mass than the control group, between-group effect: 0.17 kg (0.004-0.338), P = .045. This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement resulted in improvements in muscle mass and lower-extremity function among sarcopenic older adults. This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability.


Classification and therapeutic approaches in autoimmune hemolytic anemia: an update.
Autoimmune hemolytic anemia (AIHA) is an uncommon autoantibody-mediated immune disorder that affects both children and adults. The diagnosis of AIHA relies mainly on the direct antiglobulin test, which is a highly sensitive and relatively specific test. The classification of AIHA is based on the pattern of the direct antiglobulin test and on the immunochemical properties of the autoantibody (warm or cold type), but also on the presence or absence of an underlying condition or disease (secondary vs primary AIHAs) that may have an impact on treatment and outcome. The distinction between AIHAs due to warm antibody (wAIHA) and AIHAs due to cold antibody is a crucial step of the diagnostic procedure as it influences the therapeutic strategy. Whereas corticosteroids are the cornerstone of treatment in wAIHA, they have no or little efficacy in cold AIHA. In wAIHA that is refractory or dependent to corticosteroids, splenectomy and rituximab are both good alternatives and the benefit?risk ratio of each option must be discussed on an individual basis. In chronic agglutinin disease, the most common variety of cold AIHA in adults, beyond supportive measures, rituximab given either alone or in combination with chemotherapy may be helpful. In this article, the classification of AIHA and the recent progress in therapeutics are discussed.


Development and validation of a risk score to identify patients at high risk for opioid-related adverse drug events.
Opioid-related adverse drug events (ORADEs) are common causes of hospitalization and increased health care costs. To (a) estimate rates of specific adverse drug events (ADEs) among gastrointestinal (GI) surgery patients receiving postoperative opioids; (b) examine the utility of a risk-scoring model in categorizing patients at high risk of experiencing ORADEs; and (c) quantify potential clinical/economic benefits of targeting high-risk GI surgical patients for opioid-sparing regimens in terms of hospitalization cost, length of stay (LOS), and 30-day readmission rates. Using a retrospective design based on an administrative database, patients with an inpatient surgical procedure between January 1, 2010, and December 31, 2010, were included. GI surgical patients aged greater than 18 years followed from admission through 30 days postdischarge were characterized as high or low risk using clinical/demographic characteristics and were evaluated for several outcomes. Using multivariate logistic regression, the ORADE incidence, total hospitalization cost, LOS, and 30-day readmissions were compared for high-risk and low-risk patients. In 87.8% (n = 3,235) of the surgical population, there was a strong concordance between risk assignment and ORADE incidence. Among the remaining 12.2% (n = 449) of patients, 5.5% (n = 202) were low risk with an ORADE, and 6.7% (n = 247) were high risk without an ORADE. Overall, 20.6% (n = 344) of high-risk patients experienced ≥1 ORADE (mean cost: $31,988; LOS: 12.1 days) compared with only 5.3% (n = 107) of low-risk patients (mean cost: $25,216; LOS: 8.0 days). High-risk patients had higher hospitalization costs and longer LOS than low-risk patients, respectively (mean cost: $19,234 vs. $13,036; mean LOS: 6.8 days vs. 3.3 days). These differences correspond to 47.0% higher costs for high-risk patients and an LOS approximately twice as long compared with low-risk patients. Patient clinical/demographic characteristics influence the risk of developing ORADEs. Risk assessment tools can effectively identify high-risk patients, thereby enabling interventions that can reduce ORADEs, decrease hospital costs, and improve postsurgical experiences for patients.


Pre-dialysis patients' perceived autonomy, self-esteem and labor participation: associations with illness perceptions and treatment perceptions. A cross-sectional study.
Compared to healthy people, patients with chronic kidney disease (CKD) participate less in paid jobs and social activities. The aim of the study was to examine a) the perceived autonomy, self-esteem and labor participation of patients in the pre-dialysis phase, b) pre-dialysis patients' illness perceptions and treatment perceptions, and c) the association of these perceptions with autonomy, self-esteem and labor participation. Patients (N = 109) completed questionnaires at home. Data were analysed using bivariate and multivariate analyses. The results showed that the average autonomy levels were not very high, but the average level of self-esteem was rather high, and that drop out of the labor market already occurs during the pre-dialysis phase. Positive illness and treatment beliefs were associated with higher autonomy and self-esteem levels, but not with employment. Multiple regression analyses revealed that illness and treatment perceptions explained a substantial amount of variance in autonomy (17%) and self-esteem (26%). The perception of less treatment disruption was an important predictor. Patient education on possibilities to combine CKD and its treatment with activities, including paid work, might stimulate positive (realistic) beliefs and prevent or challenge negative beliefs. Interventions focusing on these aspects may assist patients to adjust to CKD, and ultimately prevent unnecessary drop out of the labor market.


[Regional prospective study of psychiatric sequelae of legal abortion].
117 (45%) of the 263 women of German nationality who underwent socially indicated abortions in the postal-code area 2300 (Kiel) in the first quarter of 1982 were investigated before the abortion as well as one year later. As far as age, marital status and number of children were concerned, these women did not differ significantly from the other 55%. One year later information was collected on the women's emotional adjustment by means of a questionnaire concerning feelings of guilt and loss, personal reports of adjustment process and the investigator's judgement. According to the findings, 79% of the women had adjusted without any problems, 14% were still in a state of emotional imbalance, 7% were clearly impaired emotionally and in their everydays functioning. 21% of the women, who had adjustment problems, had already been more depressive before the abortion. One year later, they were also more depressive than the other women, more dissatisfied with their lives in general and with their sex lives. They were in greater doubt as to whether they had made the right decision, showed less inclination to consider a further abortion and reported stronger post-abortive feelings of guilt. Significantly connected with later emotional difficulties were low social class, a difficult financial situation, lack of intrapsychic differentiation between sex and reproduction, no partner or negative relation with partner and partner disagreements, particularly in the case where the male partner was more in favour of abortion than the woman. Statistically insignificant, although tendencially noticeable were social isolation, non-employment and pre-pregnancy psychical problems. Age, marital status, number of children, simultaneous abortion/sterilisation, previous abortions, a broken home in the patient's youth had no effect on the emotional adjustment after the abortion. The common factor of all variables predicting post-abortive emotional problems seems to be an external motivation for abortion together with a greater ambivalence towards the pregnancy.


K252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr virus (EBV)--associated nasopharyngeal carcinoma cells.
Recent studies revealed an unexpected role of the neurotrophin receptor pathway, BDNF/TrkB signaling, in cancer metastasis and anoikis (i.e. detachment-induced cell death). Survival of cancer cells in detached state (known as anoikis-resistance) is known to be pre-requisite for metastasis. Nasopharyngeal carcinoma (NPC), an endemic head and neck cancer in Southeast Asia, is highly invasive, metastatic, and etiologically associated with Epstein-Barr virus (EBV, an oncovirus) infection. Mechanistic studies on the invasive/metastatic nature of NPC can facilitate the development of anti-metastatic therapy in NPC. Thus far, the role of BDNF/TrkB signaling in virus-associated human cancer is unclear. Here, using multiple cell line models of NPC with EBV-association (HONE-1-EBV, HK1-LMP1 and C666-1), we investigated the potential involvement of BDNF/TrkB signaling in cellular migration and anoikis-resistant characteristics of NPC. We found that all three EBV-associated NPC cell lines tested were intrinsically anoikis-resistant (i.e. survived in detached state) and expressed both BDNF and TrkB. BDNF stimulation induced cellular migration, but not proliferation of these cells. Further, we examined if pharmacologic targeting of anoikis-resistance of NPC cells can be achievable by a proof-of-concept Trk inhibitor, K252a, in these EBV-associated NPC models. Our results demonstrated that K252a, was able to attenuate BDNF-induced migration and proliferation of NPC cells. More importantly, we demonstrated for the first time that K252a harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against EBV-associated human cancer cells, namely NPC cells. This proof-of-concept study demonstrated that K252a, a Trk inhibitor, can potentially be used as an anoikis-sensitizing agent in NPC.


Delayed Diagnosis in Army Ranger Postdeployment Primaquine-Induced Methemoglobinemia.
Presumptive antirelapse therapy (PART) with primaquine for Plasmodium vivax malaria postdeployment is an important component of the US military Force Health Protection plan. While primaquine is well tolerated in the majority of cases, we present a unique case of an active duty Army Ranger without glucose-6-phosphatase dehydrogenase or cytochrome b5 reductase (b5R) deficiencies who developed symptomatic methemoglobinemia while taking PART following a deployment to Afghanistan.


Hydrogel Microchambers Integrated with Organic Electrodes for Efficient Electrical Stimulation of Human iPSC-Derived Cardiomyocytes.
A hydrogel-based microchamber with organic electrodes for efficient electrical stimulations of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is described. The microchamber is made from molecularly permeable, optically transparent, and electrically conductive polyvinyl alcohol (PVA) hydrogel and highly capacitive carbon electrode modified with poly(3,4-ethylenedioxythiophene) (PEDOT). Spheroids of hiPSC-CMs are cultured in microchambers, and electrically stimulated by the electrode for maturation. The large interfacial capacitance of the electrodes enables several days of electrical stimulation without generation of cytotoxic bubbles even when the electrodes are placed near the spheroids. The spheroids can be cultivated in the closed microchambers because of the permeated nutrients through the hydrogel, thus the spheroids are stably addressable and the culture medium around the sealed microchambers can be simply exchanged. Synchronized beating of the spheroids can be optically analyzed in situ, which makes it possible to selectively collect electrically responsive cells for further use. As the hydrogel is electrically conductive, the amount of electrical charge needed for maturing the spheroids can be reduced by configuring electrodes on the top and the bottom of the microchamber. The bioreactor will be useful for efficient production of matured hiPSC-CMs for regenerative medicine and drug screening.


ZmHAK5 and ZmHAK1 function in K+ uptake and distribution in maize under low K+ conditions.
Potassium (K+ ) is an essential macronutrient for plant growth and development. Transporters from the KT/HAK/KUP family play crucial roles in K+ homeostasis and cell growth in various plant species. However, their physiological roles in maize are still unknown. In this study, we cloned ZmHAK5 and ZmHAK1 and investigated their functions in maize (Zea mays L.). In situ hybridization showed that ZmHAK5 was mainly expressed in roots, especially in the epidermis, cortex, and vascular bundle. ZmHAK5 was characterized as a high-affinity K+ transporter. Loss of function of ZmHAK5 led to defective K+ uptake in maize, under low K+ conditions, whereas ZmHAK5-overexpressing plants showed increased K+ uptake activity and improved growth. ZmHAK1 was upregulated under low K+ stress, as revealed by RT-qPCR. ZmHAK1 mediated K+ uptake when heterologously expressed in yeast, but its transport activity was weaker than that of ZmHAK5. Overexpression of ZmHAK1 in maize significantly affected K+ distribution in shoots, leading to chlorosis in older leaves. These findings indicate that ZmHAK5 and ZmHAK1 play distinct roles in K+ homeostasis in maize, functioning in K+ uptake and K+ distribution, respectively. Genetic manipulation of ZmHAK5 may represent a feasible way to improve K+ utilization efficiency in maize.


Enantioselective synthesis of 5,7-bicyclic ring systems from axially chiral allenes using a Rh(I)-catalyzed cyclocarbonylation reaction.
A transfer of chirality in an intramolecular Rh(I)-catalyzed allenic Pauson-Khand reaction (APKR) to access tetrahydroazulenones, tetrahydrocyclopenta[c]azepinones and dihydrocyclopenta[c]oxepinones enantioselectively (22-99% ee) is described. The substitution pattern of the allene affected the transfer of chiral information. Complete transfer of chirality was obtained for all trisubstituted allenes, but loss of chiral information was observed for disubstituted allenes. This work constitutes the first demonstration of a transfer of chiral information from an allene to the 5-position of a cyclopentenone using a cyclocarbonylation reaction. The absolute configuration of the corresponding cyclocarbonylation product was also established, something that is rarely done.


Visual field defects for vergence eye movements and for stereomotion perception.
An objective visual field can be mapped in terms of stimulus-induced eye movement. The authors used the scleral coil technique to record vergence and conjugate eye movements while stimulating different visual field locations with a 3 X 3 deg target whose image vergence was oscillated. For each of three subjects tested there was a visual field location where vergence eye movements were much weaker than in a control location of equal retinal eccentricity. On the other hand, conjugate eye movements driven from these two locations by lateral motion were similar. Field defects for ocular vergence coincided with regions in which oscillating retinal disparity failed to produce a sensation of motion in depth, although visual responses to static disparity were normal, and psychophysical thresholds for lateral motion showed no defect with either binocular or monocular viewing. It was concluded, therefore, that the perceptual stereomotion scotomata were not due to a monocular loss, but to a defective binocular interaction between motion signals from the left and right eyes, and that this defective interaction was specific for opposed rather than parallel motion in the two eyes. Furthermore, the visual loss was specific for motion rather than for position. The correlation between the field defects for ocular vergence and stereomotion perception leads the authors to suggest that the same defect in binocular interaction is responsible for both the eye movement and sensory abnormalities. Two candidate hypotheses are proposed: one is framed in terms of a single population, and the other in terms of two populations of cortical neurons.


Synthesis and (spectro)electrochemistry of mixed-valent diferrocenyl-dihydrothiopyran derivatives.
Three novel diferrocenyl complexes were prepared and characterised. 2,2-Diferrocenyl-4,5-dimethyl-3,6-dihydro-2H-thiopyran (1, sulphide) was accessible by the hetero-Diels-Alder reaction of diferrocenyl thioketone with 2,3-dimethyl-1,3-butadiene. Stepwise oxidation of 1 gave the respective oxides 2,2-diferrocenyl-4,5-dimethyl-3,6-dihydro-2H-thiopyran-1-oxide (2, sulfoxide) and 2,2-diferrocenyl-4,5-dimethyl-3,6-dihydro-2H-thiopyran-1,1-dioxide (3, sulfone), respectively. The molecular structures of 1 and 3 in the solid state were determined by single crystal X-ray crystallography. The oxidation of sulphide 1 to sulfone 3, plays only a minor role on the overall structure of the two compounds. Electrochemical (cyclic voltammetry (= CV), square wave voltammetry (= SWV)) and spectroelectrochemical (in situ UV-Vis/NIR spectroscopy) studies were carried out. The CV and SWV measurements showed that an increase of the sulphur atom oxidation from -2 in 1 to +2 in 3 causes an anodic shift of the ferrocenyl-based oxidation potentials of about 100 mV. The electrochemical oxidation of 1-3 generates mixed-valent cations 1(+)-3(+). These monooxidised species display low-energy electronic absorption bands between 1000 and 3000 nm assigned to IVCT (= Inter-Valence Charge Transfer) electronic transitions. Accordingly, the mixed-valent cations 1(+)-3(+) are classified as weakly coupled class II systems according to Robin and Day.


[Femoral nerve lesion in heparin therapy].
Two case reports on femoral nerve lesion due to hematoma in the iliopsoas muscle or as the case may be in the iliacus muscles on both sides are presented with review of the literature. Synopsis of the reported cases--certainly a minority of anticoagulant therapy complications nevertheless increasingly mentioned in the literature--suggests that there might be a higher risk of bleeding for women within the first week of so-called high-dose heparin therapy. Coagulation studies do not contribute essentially in preventing retroperitoneal haematoma since they are within therapeutic limits in many cases. So clinical observation is crucial in the diagnosis of this complication of heparin therapy, which might occur more frequently under concomitant administration of acetacylic acid. Early surgical decompression of the femoral nerve seems to provide better results seen on follow-up than conservative treatment, especially in patients with rapid onset of severe limb weakness.


Corticospinal tract abnormalities are associated with weakness in multiple sclerosis.
The association of MR imaging abnormalities with clinical disability in multiple sclerosis (MS) has been disappointing. This association might be improved by imaging specific functional systems in the central nervous system-for example, the motor system in a patient with weakness. Our aim was to assess the relationship between muscle strength in MS and corticospinal tract (CST) abnormalities detected with multimodality MR imaging of the brain. In 47 individuals with MS, diffusion tensor imaging (DTI) at 3T was used to reconstruct the intracranial CSTs. Tract profiles depicted the variation in T2 relaxation time, magnetization transfer ratio (MTR), and DTI-derived indices (fractional anisotropy and diffusivity) as a function of normalized position along the tract. Brain parenchymal fraction was calculated as a normalized measure of brain volume. Stepwise linear regression modeling was used to determine the MR imaging indices most closely related to ankle dorsiflexion and hip flexion strength assessed with quantitative dynamometry. Individuals with MS were significantly weak: Average ankle strength fell 1.7 SDs below the age-, handedness-, and sex-corrected healthy mean. Brain parenchymal fraction was not associated with weakness. A parsimonious model that includes MTR in the brain stem and MS clinical subtype explained 30%-45% of the variance in ankle and hip strength. The model was successfully applied to scans and strength data from the same individuals at an earlier time point. MR imaging abnormalities specific to the motor tract are associated with clinical dysfunction related to that tract. The relevant abnormalities are found in the brain stem, distant from the periventricular inflammatory lesions that are common in MS. This suggests that neurodegeneration, rather than primary inflammation, at least partially explains the findings.


Reduced dielectric loss in new colossal permittivity (Pr, Nb)TiO2 ceramics by suppressing adverse effects of secondary phases.
Here, we develop new colossal permittivity (CP) (Pr0.5Nb0.5)xTi1-xO2 ceramics by controlling the secondary phases, and then both colossal permittivity (εr = 6-8 × 104, 1 kHz) and low dielectric loss (tan δ = 3.7-7.5%, 1 kHz) can be realized in a composition range (x = 0.5-2.5%). The ceramics with x = 1% possess a high dielectric constant (εr = 74 533), and importantly a low dielectric loss (tan δ = 3.7%) can be found, which is lower than most of the typical CP materials and chemically modified TiO2 ceramics. In addition, the εr changing rates of 143 per degree Celsius and 35 per kiloHertz indicate an excellent temperature and frequency stability of the dielectric behaviors. XRD, FE-SEM and element mapping are conducted to probe the secondary phases, and element line scanning is used to explore the elemental composition of the secondary phases. The test results indicate that optimized dopants can enhance the dielectric properties, while secondary phases induced by x > 5% dopants can cause adverse effects on the dielectric properties. XPS results further demonstrate that the defect-dipole theory may be suitable to explain the significant improvement of dielectric properties. We believe that (Pr, Nb)TiO2 ceramics are one of the most competitive candidates in the field of electronic and energy-storage devices.


Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment.
The World Health Organization (WHO) HIV drug resistance (HIVDR) threshold survey method was developed for surveillance of transmitted HIVDR in resource-limited countries. The method is being implemented with minimal resources as a routine public health activity to produce comparable results in multiple countries and areas within countries. Transmitted drug resistant HIV strains will be seen first in cities or health districts where antiretroviral treatment (ART) has been widely available for years. WHO recommends countries begin surveillance in these areas. Each survey requires < or =47 specimens from individuals consecutively diagnosed with HIV to categorize resistance to each relevant drug class as <5%, 5-15% or >15%. Use of routinely collected information and remnant specimens is recommended to minimize costs. Site and individual eligibility criteria are designed to minimize inclusion of ARV-experienced individuals and individuals infected before ART was available. Surveys have been implemented in 21 countries. In this supplement, seven countries report results of <5% transmitted HIVDR in areas where ART has been available for the longest time period. The main challenges in implementation are acquiring sufficient numbers of eligible specimens and optimizing specimen handling. The WHO HIVDR threshold survey method is feasible in resource-limited countries and produces information relevant to ART and drug resistance prevention planning.


[A profile of the medical conduct preceding child death at a tertiary hospital].
To study the profile of care provided to pediatric patients suffering fatal outcomes at a university hospital, including: description of models, comparisons between units, associated factors, participants involved and records of decisions made. Cross-sectional study. One of the investigators reviewed the medical and nursing records of deceased patients. Interviews were held and questionnaires filled out with the care team members over a period of 12 months (May 1, 2002 to April 30, 2003). The study included 106 cases. The most frequent treatment patterns at the hospital were: withholding advanced life support (51.9%) and unsuccessful cardiopulmonary resuscitation (44.3%). The decision to make a do-not-resuscitate order occurred later in the intensive care unit (p < 0.05). The restricted care category was more prevalent in the neonatal unit and among patients with chronic diseases that limit survival (p < 0.05). The professionals that most often participated in the decision-making process were the unit s treating physician and resident (52.8%) and the medical team (31.1%). Parents or guardians were observed to have been involved in 20.8% of cases. For the entire hospital, seven cases (6.6%) of ambiguous or discordant cardiopulmonary resuscitation procedures were found. Procedures involving limitation of therapy are frequent, especially in the neonatal unit. Diagnosis of brain death and withdrawal of advanced life support are, nevertheless, rare. Decisions to grant do-not-resuscitate orders are generally mate late, especially in the intensive care unit. In this sample procedures for full participation in decisions and for recording decisions were imperfect.