A cobalt adduct of an N-hydroxy-piperidinium cation.
Cooperativity between organic ligands and transition metals in H-atom (proton/electron) transfer catalysis has been an important recent area of investigation. Tetramethylpiperidine-N-oxyl (TEMPO) radicals feature prominently in this area, prompting us to examine cooperativity between its hydrogenated congener, TEMPOH, and Co centers ligated by dihydrazonopyrrole ligands which have previously been shown to also store H-atom equivalents. Addition of TEMPOH to ( tBu,TolDHP)CoOTf results in formation of an unusual Co-adduct of 1-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium (TEMPOH2 +) which has been characterized with IR spectroscopy and single crystal X-ray diffraction. This adduct is thermally unstable, and decomposes, putatively via N-O homolysis, to generate 2,2,6,6-tetramethylpiperidine and the Co-hydroxide complex [( tBu,TolDHP)CoOH][OTf]. Computational investigations suggest a proton-coupled electron transfer step to generate the TEMPOH2 + adduct where the Co center serves as an electron acceptor. Despite the prevalence of aminoxyl reagents in catalysis, particularly in aerobic transformations, metal complexes of differently hydrogenated congeners of TEMPO are rare. The isolation of a TEMPOH2 + adduct and investigations into its formation shed light on related transformations that may occur during metal-aminoxyl cooperative catalysis.


[Hemolytic uremic syndrome with severe neurological involvement: how should it be managed?].
The management of diarrhea-associated hemolytic and uremic syndrome (D(+) HUS) with severe acute neurological involvement continues to be debated. We report on 2 cases and discuss the treatment. CASE REPORT 1: A 2.5-year-old girl presented with generalized seizures during gastroenteritis. Blood tests revealed features of HUS and a pyramidal syndrome was found on physical examination. Brain MRI, 24h after admission, showed lesions in the periventricular and subcortical area. She was started on peritoneal dialysis (PD) and daily plasma exchanges (PE) for 10 days. Her neurological condition improved quickly as well as the findings of the second brain MRI performed after PE. One year later she had no apparent neurological or renal sequelae. CASE REPORT 2: A 2.5-year-old boy presented with generalized seizures during gastroenteritis for 3 days, leading to a diagnosis of HUS. He also had a severe pyramidal syndrome with spastic tetraparesis and aphasia. Brain MRI, 48 h after admission, revealed severe bilateral and symmetric lesions involving the thalami, internal and external capsules, lenticular nuclei, and brainstem. He was started on PD and daily PE for 10 days. Brain MRI performed after PE was unchanged. Clinically, his neurological condition improved slowly with regression of spastic tetraparesis and progressive recovery of motor skills. Nine months later, his renal function is normal but he is still having intensive physiotherapy. Both children have received similar management including 10 PEs started within 48 h after the diagnosis of D(+) HUS with severe neurological involvement, but their neurological outcome appeared to be significantly different. There is no clear proof in the literature concerning the effects of PE in such patients, even when performed very early. Eculizumab, an antibody that inhibits complement factor 5a and the formation of the membrane attack complex, has recently been used in such cases and seems to provide a more specific therapeutic action. Control studies are needed to specify its use in this disease.


Value of visual inspection, bimanual palpation, and intraoperative ultrasonography during hepatic resection for liver metastases of colorectal carcinoma.
Intraoperative detection of new nodules is common in patients undergoing hepatectomy for colorectal liver metastases, although the value of intraoperative diagnosis is not well assessed. A prospectively collected and recorded database was retrospectively analyzed. Helical computed tomography (CT) results were correlated with those of the intraoperative diagnosis in 183 consecutive patients undergoing 254 consecutive hepatectomies, including repeated resection for colorectal liver metastases. In total, 270 nodules were newly detected during 65 hepatectomies. The sensitivity of CT to detect metastatic nodules was 72.8% (722/992), but it decreased to 34.6% (125/361) for small (≤ 1 cm diameter) tumors. Intraoperative visual inspection and/or palpation detected 207 of 270 nodules. Intraoperative ultrasonography (IOUS) played an important role in identifying deep (≥ 1 cm from the surface) and comparatively small (≤ 1 cm diameter) nodules (4/9 vs. 16/18, respectively, for those >1 cm vs. ≤ 1 cm diameter). The likelihood of intraoperative detection of new nodules increased from 10 in 112 to 6 in 9 when the preoperative tumor number increased from solitary to ≥ 10, resulting in an overall likelihood of 65 in 254 (25.6%). Of 65 patients with new nodules, 21 had at least one nodule that was detected only by IOUS. Preoperatively scheduled hepatectomy was altered in 47 (72%) patients, although additional limited resection(s) were sufficient to remove these nodules in 43 (91%) of them. Visual inspection, palpation, and IOUS had equally indispensable roles in detecting new nodules during hepatectomy. Detection was common and usually necessitated alteration, albeit moderately, of the surgical plan.


No longer endemic to Africa: Kribiodosis Kieffer, 1921 (Diptera, Chironomidae) new to Oriental China with a phylogeny and expanded adult generic diagnoses.
Kribiodosis Kieffer, 1921, an African genus of Chironomini (Diptera: Chironomidae), is newly recorded from the Oriental region through a new species K. cantonensis sp. n. Detailed descriptions of the male, female and a DNA barcode are provided. With the inclusion of the new species bearing scutal tubercle and fused tibial comb, the generic diagnosis needs revision and expansion. The phylogenetic position of Kribiodosis within the tribe Chironomini is explored based on five concatenated genetic makers (18S, 28S, CAD1, CAD4 and COI-3P) using both mixed-model Bayesian inference and maximum likelihood methods. Kribiodosis is placed as a core member of the Microtendipes group but its precise sister group remains unclear. Inclusion of the analysis of Nilodosis Kieffer, another Chironomini genus with an African-Oriental distribution, reveals an unexpected robust position as sister to a large and diverse inclusive group of many Chironomini.


Takayasu's arteritis: a challenging diagnosis.
The practices of medicine and surgery are inherently and irrevocably entwined. This case report highlights the need for an integrated, multi-disciplinary approach to care of the modern patient. Our patient fulfils the traditional Ishikawa's criteria and the modified Ishikawa's criteria for the clinical diagnosis of Takayasu's disease. Her case underpins the need for co-ordinated care and careful periodic review of the symptomatology and signs of the multiple clinic attendees.


(E)-3,3'-(Diazene-1,2-di-yl)bis-(1-methyl-1,4,5,6-tetra-hydro-pyrrolo-[3,4-c]pyrazol-5-ium) dinitrate dihydrate.
The title compound, C(12)H(18)N(8) (2+)·2NO(3) (-)·2H(2)O, was synthesized unexpectedly from 3-amino-1-methyl-1,4,5,6-tetra-hydro-pyrrolo-[3,4-c]pyrazol-5-ium chloride and cerium(IV) ammonium nitrate. The cation has a crystallographically imposed centre of symmetry. In the crystal, the ions and water mol-ecules are linked via O-H⋯N, N-H⋯O and O-H⋯O hydrogen bonds into a three-dimensional network.


Cerebral blood flow and carbon dioxide reactivity in children with bacterial meningitis.
We examined total and regional cerebral blood flow (CBF) by stable xenon computed tomography in 20 seriously ill children with acute bacterial meningitis to determine whether CBF was reduced and to examine the changes in CBF during hyperventilation. In 13 children, total CBF was normal (62 +/- 20 ml/min/100 gm) but marked local variability of flow was seen. In five other children, total CBF was significantly reduced (26 +/- 10 ml/min/100 gm; p less than 0.05), with flow reduced more in white matter (8 +/- 5 ml/min/100 gm) than in gray matter (30 +/- 15 ml/min/100 gm). Autoregulation of CBF appeared to be present in these 18 children within a range of mean arterial blood pressure from 56 to 102 mm Hg. In the remaining two infants, brain dead within the first 24 hours, total flow was uniformly absent, averaging 3 +/- 3 ml/min/100 gm. In seven children, CBF was determined at two carbon dioxide tension (PCO2) levels: 40 (+/- 3) mm Hg and 29 (+/- 3) mm Hg. In six children, total CBF decreased 33%, from 52 (+/- 25) to 35 (+/- 15) ml/min/100 gm; the mean percentage of change in CBF per millimeter of mercury of PCO2 was 3.0%. Regional variability of perfusion to changes in PCO2 was marked in all six children. The percentage of change in CBF per millimeter of mercury of PCO2 was similar in frontal gray matter (3.1%) but higher in white matter (4.5%). In the seventh patient a paradoxical response was observed; total and regional CBF increased 25% after hyperventilation. Our findings demonstrate that (1) CBF in children with bacterial meningitis may be substantially decreased globally, with even more variability noted regionally, (2) autoregulation of CBF is preserved, (3) CBF/CO2 responsitivity varies among patients and in different regions of the brain in the same patient, and (4) hyperventilation can reduce CBF below ischemic thresholds.


Design, synthesis, and biological evaluation of 4-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives as potent antitubercular agents.
Based on stereoelectronic feature analysis using density functional theory (DFT) at B3LYP/3-21∗G level, a series of 4-(5-nitrofuran-2-yl)prop-2-en-1-one derivatives with low LUMO energies (<-0.10eV); concentrated over the nitro group, furan moiety and α,β-unsaturated carbonyl bridge were envisaged as potential antitubercular agents. The target compounds were prepared by condensation of 5-nitro-2-furaldehyde with various ketones under acidic condition. The compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis H37Rv and their cytotoxicity in VERO cell line. Several synthesized compounds showed good antitubercular activity of <5μM along with low cytotoxicity. In particular, compound ((E)-3-(5-nitrofuran-2-yl)-1-(4-(piperidin-1-yl)phenyl)prop-2-en-1-one) (3v) was found to be very potent (MIC: 0.19μM) with good selectivity index (MIC(90)/CC(50): >1800). Thus, this study shows the potential of stereoelectronic property analysis in developing improved nitroaromatics as antitubercular agents.


Colchicine treatment differently affects releasable thyrotropin-releasing hormone (TRH) pools in the hypothalamic paraventricular nucleus (PVN) and the median eminence (ME).
1. Hypophysiotropic thyrotropin-releasing hormone (TRH) is synthesized in the hypothalamic paraventricular nucleus (PVN) and transported to the median eminence (ME) where it enters the hypophyseal portal blood. TRH in the ME is situated exclusively in nerve terminals, whereas TRH in the PVN and septum is of extrinsic (nerve terminals) as well as intrinsic (perikarya) origin. 2. To determine the source and possible differential regulation of TRH release from these structures, we blocked TRH axonal delivery by i.c.v. administration of colchicine into the lateral cerebral ventricle of euthyroid or hypothyroid rats in doses of 7.5 mug or 7.5, 75 and 100 microg, respectively, two days prior to the evaluation of the TRH secretion from the PVN, ME and the septum in vitro. 3. In euthyroid rats a low dose of colchicine did not significantly affect plasma TSH. The secretory response to both ethanol in an isosmolar medium and a high K+ in the ME as well as the PVN explants was well preserved. However, colchicine treatment resulted in the significant increase of basal secretion of TRH from the PVN. 4. Hypothyroidism induced by 200 mg/l methimazole in drinking water for two weeks resulted in growth arrest, elevated plasma thyrotropin and decreased TRH content in the PVN and the ME. Colchicine partially decreased elevated plasma thyrotropin and increased the TRH content in the PVN and its basal release in vitro which was independent of extracellular Ca2+. Interestingly, a TRH release from the PVN could not be further stimulated either by K+ membrane depolarization or by ethanol. TRH responsiveness to the stimulation remained unaffected in the ME. The effect of colchicine on the septal TRH secretion was intermediate between the effect observed in the PVN and the ME. 5. In conclusion, the absence of a TRH secretory response to stimuli in the PVN after colchicine disruption of the microtubules and Golgi system suggests that stimulated TRH release observed from the PVN explants in vitro occurs from nerve terminals projecting to the PVN from other brain regions. The independence from extracellular calcium implies that TRH released under the non-stimulating conditions occurs most likely via the constitutive secretory pathway from dendrites and/or perikarya. Regulation of septal TRH is markedly different from the hypophysiotropic one.


Production, purification and characterization of an extracellular keratinase from Lysobacter NCIMB 9497.
The aim of this study was to determine the keratinolytic ability of a range of bacteria and subsequently, to characterize the keratinase showing the greatest biotechnological potential. Nine bacteria, reported to produce extracellular proteases, were screened for production of keratinases. Of these, Lysobacter NCIMB 9497 exhibited the highest keratinolytic activity. The keratinase from this strain (Mr 148 kDa) was purified and characterized. Optimum activity occurred at 50 degrees C; no inhibition was demonstrated by phenylmethylsulphonyl fluoride (PMSF), but inhibition by EDTA was demonstrated. This study indicates that keratinase is a metalloprotease with a high degree of keratinolytic activity and stability. This is the first detailed report of a metalloprotease with keratinolytic activity. The novel reaction mechanism, degree of keratinolytic activity and stability indicate considerable biotechnological potential in the leather industry, and in the processing of poultry waste.


On the representation of task information in task switching: evidence from task and dimension switching.
Task switching research has revealed that task changes lead to a performance switch cost. The present study focuses on the organization of task components in the task set. Three different views of task set organization have been distinguished and evidence in favor of each of these has been reported in the literature. In four experiments, we orthogonally varied the categorization task (magnitude and parity) and the stimulus dimension on which the categorization was to be made. Experiments 1, 2, and 4 used Stroop-like number stimuli, whereas Experiment 3 used global-local stimuli to define the stimulus dimension. In Experiments 2-4, the cue-stimulus interval was also varied. The findings showed that a change of any component resulted in a cost, without any reliable difference in the size of these costs. These results are consistent with the flat view on task-set organization, which assumes that the task set binds all elements in an unstructured representation, which is completely reconfigured each time a change to the task set is required. The implications of these findings are discussed in relation to other findings and the different views on task-set organization.


Structure-activity relationships of Erwinia carotovora quorum sensing signaling molecules.
Production of virulence factors and secondary metabolites is regulated in the phytopathogen Erwinia carotovora by quorum sensing involving N-acylated homoserine lactone (AHL) signaling molecules. Non-hydrolyzable AHL analogues were synthesized and screened in vivo. The biological activity of each compound was correlated with its ability to bind Erwinia AHL receptor proteins (LuxR homologues) in vitro. There is an excellent correlation between carbapenem production in vivo and in vitro binding to CarR. However, no such correlation could be found between exoprotease production and analogue binding to EccR. Our data are consistent with the involvement of a third, as yet uncharacterized LuxR homologue.


Effect of denervation on endothelium-derived relaxing factor-dependent relaxation in the rat cremaster muscle.
Endothelium-derived relaxation mediated primarily by endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is essential in the maintenance of vascular tone. However, little is known about the effects of denervation on EDRF-mediated relaxation in the microcirculation after reimplantation. Using intravital videomicroscopy in the rat cremaster model, this study assessed the effect of acute and chronic denervation of the muscle, produced by severing the genitofemoral nerve, on EDRF-mediated vasorelaxation. The results demonstrated that acetylcholine-induced EDRF relaxation (10(-6)M) significantly relieved norepinephrine-induced vasoconstriction in small arteries (40-80 microns diameter) in both the acute and chronic denervated muscles. There was no significant difference in the relaxant response between the denervated or innervated controls in each group or between the acute or chronic groups. This relaxation was prevented by methylene blue (10(-4) M). These findings suggest that EDRF-mediated relaxation in the microcirculation is not dependent on tissue innervation. Thus the use of potent endothelial dependent agonists may be of use in cases of vasospasm postreimplantation.


Altered juvenile hormone metabolism, reproduction and stress response in Drosophila adults with genetic ablation of the corpus allatum cells.
Juvenile hormone (JH), which controls many developmental and physiological processes in Drosophila melanogaster, is synthesized de novo in the specialized endocrine glands, corpus allatum (CA). The present study concerns JH metabolism, reproduction and stress resistance in Drosophila with genetic ablation of a part of CA cells. The correlated regulation of JH biosynthesis and degradation in Drosophila adults has been found: ablation of CA cells led to (1) a dramatic decrease in activity of the key regulatory enzyme of JH biosynthesis, juvenile hormone acid methyl transferase and (2) a considerable increase in JH-hydrolyzing activity. It has been also shown that ablation of CA cells caused three significant physiological changes: (1) an increase in the intensity of response of JH degradation system to heat stress; (2) a disturbance of reproduction; (3) a decrease in stress resistance. Pharmacological rise of JH level rescued JH-hydrolyzing activity, fecundity and stress resistance in CA-ablated females. Pronouncedly, all the physiological effects caused by CA ablation were significant in females but not in males indicating a sexual dimorphism of JH physiological roles in Drosophila adults.


Detection of overdosage of sedation in a patient with renal failure by the absence of lower oesophageal motility.
We report an accidental overdosage of morphine and midazolam in a patient with renal failure receiving haemofiltration detected by the absence of oesophageal motility. This situation demonstrates the difficulties of assessing the level of sedation as well as the dosage requirements in this type of patient.


A drug repositioning algorithm based on a deep autoencoder and adaptive fusion.
Drug repositioning has caught the attention of scholars at home and abroad due to its effective reduction of the development cost and time of new drugs. However, existing drug repositioning methods that are based on computational analysis are limited by sparse data and classic fusion methods; thus, we use autoencoders and adaptive fusion methods to calculate drug repositioning. In this study, a drug repositioning algorithm based on a deep autoencoder and adaptive fusion was proposed to mitigate the problems of decreased precision and low-efficiency multisource data fusion caused by data sparseness. Specifically, a drug is repositioned by fusing drug-disease associations, drug target proteins, drug chemical structures and drug side effects. First, drug feature data integrated by drug target proteins and chemical structures were processed with dimension reduction via a deep autoencoder to characterize feature representations more densely and abstractly. Then, disease similarity was computed using drug-disease association data, while drug similarity was calculated with drug feature and drug-side effect data. Predictions of drug-disease associations were also calculated using a top-k neighbor method that is commonly used in predictive drug repositioning studies. Finally, a predicted matrix for drug-disease associations was acquired after fusing a wide variety of data via adaptive fusion. Based on experimental results, the proposed algorithm achieves a higher precision and recall rate than the DRCFFS, SLAMS and BADR algorithms with the same dataset. The proposed algorithm contributes to investigating the novel uses of drugs, as shown in a case study of Alzheimer's disease. Therefore, the proposed algorithm can provide an auxiliary effect for clinical trials of drug repositioning.


The Role of Macroautophagy and Chaperone-Mediated Autophagy in the Pathogenesis and Management of Hepatocellular Carcinoma.
Hepatocarcinogenesis is a long process with a complex pathophysiology. The current therapeutic options for HCC management, during the advanced stage, provide short-term survival ranging from 10-14 months. Autophagy acts as a double-edged sword during this process. Recently, two main autophagic pathways have emerged to play critical roles during hepatic oncogenesis, macroautophagy and chaperone-mediated autophagy. Mounting evidence suggests that upregulation of macroautophagy plays a crucial role during the early stages of carcinogenesis as a tumor suppressor mechanism; however, it has been also implicated in later stages promoting survival of cancer cells. Nonetheless, chaperone-mediated autophagy has been elucidated as a tumor-promoting mechanism contributing to cancer cell survival. Moreover, the autophagy pathway seems to have a complex role during the metastatic stage, while induction of autophagy has been implicated as a potential mechanism of chemoresistance of HCC cells. The present review provides an update on the role of autophagy pathways in the development of HCC and data on how the modulation of the autophagic pathway could contribute to the most effective management of HCC.


Synchronous anal canal carcinoma in a heterosexual couple.
Sexually transmitted Human Papilloma Virus (HPV) infection is a known risk factor for cancer of the anal canal in both men and women. We describe a report of synchronous carcinoma of the anal canal in a heterosexual couple. High risk type 16 HPV DNA was detected in both tumors. Longstanding sexual partners may share risk of HPV-associated anal canal cancer.


Estimation of biogas produced by the landfill of Palermo, applying a Gaussian model.
In this work, a procedure is suggested to assess the rate of biogas emitted by the Bellolampo landfill (Palermo, Italy), starting from the data acquired by two of the stations for monitoring meteorological parameters and polluting gases. The data used refer to the period November 2005-July 2006. The methane concentration, measured in the CEP suburb of Palermo, has been analysed together with the meteorological data collected by the station situated inside the landfill area. In the present study, the methane has been chosen as a tracer of the atmospheric pollutants produced by the dump. The data used for assessing the biogas emission refer to night time periods characterized by weak wind blowing from the hill toward the city. The methane rate emitted by the Bellolampo dump has been evaluated using a Gaussian model and considering the landfill both as a single point source and as a multiple point one. The comparison of the results shows that for a first approximation it is sufficient to consider the landfill of Palermo as a single point source. Starting from the monthly percentage composition of the biogas, estimated for the study period, the rate of biogas produced by the dump was evaluated. The total biogas produced by the landfill, obtained as the sum of the emitted component and the recovered one, ranged from 7519.97 to 10,153.7m3/h. For the study period the average monthly estimations of biogas emissions into the atmosphere amount to about 60% of the total biogas produced by the landfill, a little higher than the one estimated by the company responsible for the biogas recovery plant at the landfill.


Fitness-related patterns of genetic variation in rhesus macaques.
The patterning of quantitative genetic descriptions of genetic and residual variation for 15 skeletal and six life history traits was explored in a semi-free-ranging group of rhesus macaques (Macaca mulatta Zimmerman 1780). I tested theoretical predictions that explain the magnitude of genetic and residual variation as a result of 1. strength of a trait's association with evolutionary fitness, or 2. developmental and physiological relationships among traits. I found skeletal traits had higher heritabilities and lower coefficients of residual variation than more developmentally and physiologically dependent life history traits. Total lifetime fertility had a modest heritability (0.336) in this population, and traits with stronger correlations to fitness had larger amounts of residual variance. Censoring records of poorly-performing individuals on lifetime fertility and lifespan substantially reduced their heritabilities. These results support models for the fitness-related patterning of genetic variation based on developmental and physiological relationships among traits rather than the action of selection eroding variation.


Emotional eating and its effect on eating behaviour after a natural disaster.
Emotional eaters are hypothesised to overeat in response to negative emotions or stress. However, the empirical evidence for such a moderating role is mixed. This study examined the effect of emotional eating on eating behaviour before and after the occurrence of a natural disaster (an earthquake) in a sample of predominantly middle-aged and older women. As expected, women who scored high on emotional eating reported an increase in overeating after the earthquake. This effect was qualified by an interaction: emotional eaters who reported high levels of post-earthquake distress reported an increase in overeating, whereas non-stressed emotional eaters and non-emotional eaters did not.


Determination of metabolites of cytochrome P-450 model systems using high-performance liquid chromatography.
High-performance liquid chromatographic techniques were developed for the simultaneous detection of metabolites in a cytochrome P-450 model system composed of NADH, haemoglobin and methylene blue. Monohydroxylated metabolites were determined following aniline, acetanilide and phenol hydroxylations. 4-Aminoantipyrine, 7-hydroxycoumarin and p-nitrophenol were determined after dealkylation of 4-N,N-dimethylamino-antipyrine, 7-ethoxycoumarin and p-nitroanisole. These substrates are commonly used for measuring cytochrome P-450 activities. Treatment of the samples was minimal, consisting of a simple deproteinization, and did not involve any organic extraction. Separations were carried out on reversed-phase columns and the products were detected by UV adsorption. Separations were completed in less than 15 min and the detection limits were between 0.5 and 4 microM.


Mapping divided households and residency changes: the effect of couple separation on sexual behavior and risk of HIV infection.
Using census data we identify geographic patterns in residency changes in Lesotho over a decade. Using kriging to spatially interpolate data from 8,510 households we identify regions where households have members temporarily living away from home (divided households). Further, using a multivariate analysis and data from 2,026 couples we determine whether a partners' absence increases the likelihood of having extramarital partners and/or risk of HIV infection. Approximately 40% of individuals moved between 2001 and 2011; mainly to, and within, urbanized regions. Many households are divided: ~40% have members elsewhere in Lesotho, ~30% in South Africa (SA). Geographic patterns are apparent; they differ based on where the household member is living. Many couples were temporarily separated: ~50% of wives, ~20% of husbands. Separation was not a risk factor for HIV. Only men were more likely to have extramarital partners if their spouse was away: ~1.5 times if in Lesotho, ~3 times if in SA. The high degree of geographic mixing necessitates synchronizing interventions within Lesotho, and with SA, to successfully reduce transmission. It will be challenging to reduce concurrency in men with wives away from home. Our results are generalizable to other sub-Saharan countries where residency changes are common.


Protective efficiacy of taurine against pulmonary edema progression: experimental study.
Re-expansion pulmonary edema (RPE) is an acute, rare and potentially lethal complication. Its beginning is sudden and dramatic. The mechanism is not yet fully understood. Some authors suggest that it may occur after rapid re-inflation of a collapsed lung. It was reported by other authors that it may relate to surfactant depletion or may result from hypoxic capillary damage, leading to increased capillary permeability. In RPE, unilateral lung injury is initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils. These toxic oxygen products are the results of re-oxygenation of a collapsed lung. Treatment of re-expansion pulmonary edema is basically preventive.


The Chlamydia trachomatis type III-secreted effector protein CteG induces centrosome amplification through interactions with centrin-2.
The centrosome is the main microtubule organizing center of the cell and is crucial for mitotic spindle assembly, chromosome segregation, and cell division. Centrosome duplication is tightly controlled, yet several pathogens, most notably oncogenic viruses, perturb this process leading to increased centrosome numbers. Infection by the obligate intracellular bacterium Chlamydia trachomatis (C.t.) correlates with blocked cytokinesis, supernumerary centrosomes, and multipolar spindles; however, the mechanisms behind how C.t. induces these cellular abnormalities remain largely unknown. Here we show that the secreted effector protein, CteG, binds to centrin-2 (CETN2), a key structural component of centrosomes and regulator of centriole duplication. Our data indicate that both CteG and CETN2 are necessary for infection-induced centrosome amplification, in a manner that requires the C-terminus of CteG. Strikingly, CteG is important for in vivo infection and growth in primary cervical cells but is dispensable for growth in immortalized cells, highlighting the importance of this effector protein to chlamydial infection. These findings begin to provide mechanistic insight into how C.t. induces cellular abnormalities during infection, but also indicate that obligate intracellular bacteria may contribute to cellular transformation events. Centrosome amplification mediated by CteG-CETN2 interactions may explain why chlamydial infection leads to an increased risk of cervical or ovarian cancer.


Mesenchymal stem cells differentiate to retinal ganglion-like cells in rat glaucoma model induced by polystyrene microspheres.
The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.


The copper metallome in prokaryotic cells.
As a trace element copper has an important role in cellular function like many other transition metals. Its ability to undergo redox changes [Cu(I) ↔ Cu(II)] makes copper an ideal cofactor in enzymes catalyzing electron transfers. However, this redox change makes copper dangerous for a cell since it is able to be involved in Fenton-like reactions creating reactive oxygen species (ROS). Cu(I) also is a strong soft metal and can attack and destroy iron-sulfur clusters thereby releasing iron which can in turn cause oxidative stress. Therefore, copper homeostasis has to be highly balanced to ensure proper cellular function while avoiding cell damage.Throughout evolution bacteria and archaea have developed a highly regulated balance in copper metabolism. While for many prokaryotes copper uptake seems to be unspecific, others have developed highly sophisticated uptake mechanisms to ensure the availability of sufficient amounts of copper. Within the cytoplasm copper is sequestered by various proteins and molecules, including specific copper chaperones, to prevent cellular damage. Copper-containing proteins are usually located in the cytoplasmic membrane with the catalytic domain facing the periplasm, in the periplasm of Gram-negative bacteria, or they are secreted, limiting the necessity of copper to accumulate in the cytoplasm. To prevent cellular damage due to excess copper, bacteria and archaea have developed various copper detoxification strategies. In this chapter we attempt to give an overview of the mechanisms employed by bacteria and archaea to handle copper and the importance of the metal for cellular function as well as in the global nutrient cycle.


Aspergillus myositis in a patient with a myelodysplastic syndrome.
We present the case of an elderly man who, while being treated with corticosteroids for a myelodysplastic syndrome, developed myositis of the calf due to Aspergillus fumigatus. Despite therapy with amphotericin B the myositis failed to resolve and he died. At autopsy, a localized necrotizing myositis of the right calf was found with no evidence of disseminated Aspergillus infection. Myositis in the setting of disseminated candidiasis or cryptococcosis has been previously reported. This case is unique in that it is the first reported case of localized fungal myositis and of myositis caused by Aspergillus.


Sex pheromone of Poecilocerus pictus (Fabricus) (acridoidea: pyrogomorphidae): I. Experimental identification and external morphology of the female sex pheromone gland.
Bioassay experiments showed the presence of sex pheromone in females of Poecilocerus pictus. It was further confirmed experimentally that the sex pheromone substances are secreted in the metathoracic and first two abdominal segments. Dissections of the females revealed the presence of a thin sac-like gland in the metathoracic segment. Ethernal extract of this gland was tested in a bioassaying apparatus to confirm its identity as a sex pheromone producing organ.


Variability in prescribing for musculoskeletal pain in Finnish primary health care.
To assess primary care physicians' prescribing patterns for musculoskeletal pain in different diagnostic categories. The data were collected in 25 randomly selected health centres, in which a total of 28 physicians took part in the four-week study. Physicians recorded all the medicines they prescribed for patients visiting due to pain. Visits resulting in a diagnosis of musculoskeletal disease or injury were included in this study. Analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), were prescribed for 61% of the patients. NSAIDs were prescribed for 46%, topical analgesics for 15% and opioids for 4% of the patients. In general, ibuprofen was the most frequently prescribed drug but back and neck pains were most commonly treated with naproxen. No difference between patients' genders was observed in analgesic prescriptions. Prescribing was associated with patient's age, physician's view on priority of visit, diagnosis and intensity of pain. There was a large variation in prescribing patterns between individual physicians and between different areas of the country. NSAIDs are the prevailing treatment for musculoskeletal pain in Finnish primary health care. Different drugs are favoured according to the diagnosis. The large variability in prescribing patterns cannot be explained solely by the characteristics of pain or patients.


Use of patellar allograft to reconstruct a patellar tendon-deficient knee after total joint arthroplasty.
A catastrophic complication after total knee arthroplasty (TKA) is rupture of the patellar tendon. Several techniques for treatment have been described, including cast immobilization with or without operative repair, the use of a semitendinosus, fascia lata, or hamstring tendon autogenous graft, the use of a Dacron 4-mm vascular graft (U.S. Catheter and Instrument, Glen Falls, NY), the use of bovine xenograft and even transplantation of an entire allograft extensor mechanism. Treatment results of patellar tendon rupture after TKA can be discouraging. Altered tissue quality secondary to connective tissue diseases, diabetes, rheumatoid arthritis, lupus erythematosus, secondary hyperparathyroidism, or concurrent steroid medications contributes to poor results. Additionally, no one treatment has provided consistent clinical success. Successful treatment of a patient with a ruptured patellar tendon after TKA using the bone-patellar tendon-bone allograft commonly used for anterior cruciate ligament reconstruction is reported.


Experimental infection of juvenile domestic and Canada geese with two different clades of H5N1 high pathogenicity avian influenza virus.
Eighteen-day-old domestic geese (Anser anser f. domestica) and 3-week-old Canada geese (Branta canadensis) were experimentally infected with 10(6) EID50/bird of H5N1 high pathogenicity avian influenza (HPAI) virus isolates belonging to clades 1 and 2.2. Clinical signs were observed in all of the groups and included listlessness, inappetence, marked incoordination, torticollis, paralysis and lethargy. Mortality reached 100% (Canada geese) and 40-50% (domestic geese). During necropsy, congestion and hemorrhagic lesions were most often observed. Histopathological lesions were located in multiple organs and included inflammatory and hemorrhagic changes and, in later stages, occurrences of necrosis. All of the tested organ samples collected between 3 and 8 days PI were found positive in rRT-PCR, but the highest concentration of RNA was found in the brain. The observed delayed onset of mortality and prolonged duration of the disease in young domestic geese may be related to numerous host and virus factors.


Clones of MRC-C cells may be superior to the parent line for the culture of 229E-like strains of human respiratory coronavirus.
A clone was selected from the MRC-C continuous heteroploid cell line which was significantly better than MRC-C for the culture of human respiratory coronavirus (HCV) 229E, strain LP. Such clones could prove generally useful for the isolation of HCV-229E from clinical specimens, and for the propagation and assay of laboratory adapted strains.


Toward the synthesis of spirastrellolide A: construction of two C1-C25 diastereomers containing the BC-spiroacetal.
[reaction: see text] Stereo-controlled syntheses of two possible C1-C25 diastereomers of spirastrellolide A containing the cis-disubstituted tetrahydropyran and [6,6]-spiroacetal are reported, exploiting boron-mediated asymmetric aldol and allylation methodology.


A Mobile Phone App for the Provision of Personalized Food-Based Information in an Eating-Out Situation: Development and Initial Evaluation.
Increasing pressure from governments, public health bodies, and consumers is driving a need for increased food-based information provision in eating-out situations. Meals eaten outside the home are known to be less healthy than meals eaten at home, and consumers can complain of poor information on the health impact and allergen content of meals eaten out. This paper aimed to describe the development and early assessment of a mobile phone app that allows the provision of accurate personalized food-based information while considering individual characteristics (allergies, diet type, and preferences) to enable informed consumer choice when eating out. An app was designed and developed to address these requirements using an agile approach. The developed app was then evaluated at 8 public engagement events using the System Usability Scale (SUS) questionnaire and qualitative feedback. Consideration of the literature and consultation with consumers revealed a need for information provision for consumers in the eating-out situation, including the ability to limit the information provided to that which was personally relevant or interesting. The app was designed to provide information to consumers on the dishes available in a workplace canteen and to allow consumers the freedom to personalize the app and choose the information that they received. Evaluation using the SUS questionnaire revealed positive responses to the app from a range of potential users, and qualitative comments demonstrated broad interest in its use. This paper details the successful development and early assessment of a novel mobile phone app designed to provide food-based information in an eating-out situation in a personalized manner.


Probathylepadidae, a new family of Scalpelliformes (Thoracica: Cirripedia: Crustacea), for Probathylepas faxian gen. nov., sp. nov., from a hydrothermal vent in the Okinawa Trough.
A new pedunculate barnacle, Probathylepas faxian gen. and sp. nov., is described from a hydrothermal vent in the Okinawa Trough. A new scalpelliform family, Probathylepadidae, is also proposed for the new genus and species. Probathylepadidae differs from all other five families of the order Scalpelliformes by the capitulum bearing eight primal plates and two whorls of imbricating supplementary plates, and the peduncle being without scales. The relationships between the species of the new family and sessile barnacles are also discussed.


A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.
Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type. During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy. In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.


Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.
Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes.


[Validation of the Brazilian version of mini-test CASI-S].
To determine CASI-S accuracy in the diagnosis of dementia. The Cognitive Abilities Screening Instrument - Short Form (CASI-S) was applied in 43 Alzheimer's disease (AD) patients and 74 normal controls. AD diagnosis was based on DSM-IV, NINCDS-ADRDA, and CAMDEX. CASI-S includes: registration, temporal orientation, verbal fluency (4-legged animals in 30s), and recall (3 words). Its maximum score is 33 points. A copy of 2 pentagons was added. ROC curve showed an accuracy of 0.87, with standard error of 0.032, and 95% confidence intervall between 0.795 and 0.925. The cut-off score for cognitive deficit was 23, with sensitivity of 76.7%, specificity 86.5%, positive likelihood ratio (LR) 5.68, and negative LR 0.27. The cut-off score for subjects 70 years or older was 20, with sensitivity of 71.4% and specificity 97.1%. CASI-S is a practical test, with high specificity, particularly in individuals above 70 years of age. The adding of the drawing test did not improve its accuracy.


Differential distribution of apolipoprotein E isoforms in human plasma lipoproteins.
The polymorphism of apolipoprotein E (apo E) accounts for a substantial amount of the genetic variance of cholesterol levels in man. The epsilon-2 allele and the epsilon-4 allele raises plasma and low density lipoprotein cholesterol levels as compared to the epsilon-3 allele. Whereas the lower cholesterol levels in carriers of the epsilon-2 allele can, at least in part, be attributed to the grossly deficient binding of apo E-2 to the apo B,E receptor, apo E-3 and E-4 bind to the same degree. We used gel filtration and ultracentrifugation to separate lipoproteins and subsequent immunoblotting analysis to study the apo E isoform distribution. We always found lipoproteins of lower density relatively enriched in apo E-4 and high density lipoproteins relatively depleted of apo E-4 as compared to apo E-3. This was also seen in plasma of heterozygous subjects that simultaneously express two apo E isoforms. Also, the apo E-A-II complex was directly shown by immunoblotting. Furthermore, when purified iodinated apo E was incubated with plasma in vitro, apo E-4 also reassociated more with lipoproteins of lower density than apo E-3. We conclude that apo E-3 and apo E-4 have a different lipoprotein particle distribution in vivo. This differential lipoprotein distribution may account for differences in the metabolism between apo E-3 and E-4.


Dopamine-induced neurogenic vasodilatation in isolated perfused muscle preparation of the dog.
Dopamine, injected into the lumbar aorta of the dog in doses which produce a reversible inhibition of synaptic transmission in the lumbar paravertebral ganglia (0.5-64x10-8 moles), produces a neurogenic vasodilatation in the isolated perfused hindleg or gracilis muscle. This was abolished by acute preganglionic decentralization and by administration into the perfused preparation of alpha-adrenoceptor blocking agents, but not of atropine or diphenhydramine. After decentralization, preganglionic electrical stimulation restored the dopamine-induced indirect vasodilatation. The neurogenic vasodilatation was also seen with intra-aortic injections of epinine (2-32x10-8 moles) and apomorphine (1.2-19.2x10-8 moles) and was preferentially blocked by haloperidol (0.26x10-6 moles). (-)-Noradrenaline, injected into the lumbar aorta in baroreceptor-denervated dogs, was found to be equipotent with dopamine in eliciting the neurogenic vasodilatation; this (-)-noradrenaline-induced effect was preferentially blocked by phentolamine (8x10-6 moles). The possibility that the neurogenic vasodilatation, which occurs upon intra-aortic injection of dopamine in the dog, is due to its gnaglionic-inhibitory effect is discussed.


REDV/Rapamycin-loaded polymer combinations as a coordinated strategy to enhance endothelial cells selectivity for a stent system.
A major challenge in the development of drug eluting stent platform is the sustained inhibition of smooth muscle cell (SMC) proliferation while endothelial cell (EC) coverage is promoted. We demonstrated in this study that the combination of rapamycin-loaded polymer base layer and Arg-Glu-Asp-Val (REDV) peptide tethered top layer is a coordinated strategy to enhance EC-specific selectivity. A 2-methacryloyloxyethyl phosphorylcholine(MPC)-co-n-stearyl methacrylate (SMA) [PMS] film was prepared as a base coating to load rapamycin. MPC-co-SMA-co-p-nitrophenyloxycarbonyl polyethyleneglycol methacrylate (MEONP) [PMSN] was synthesized to form the top layer, which conjugated the EC-specific ligand REDV peptide that promotes EC attachment. The top layer functioned as a diffusion barrier, and the polymer film can sustain the rapamycin release of for over 120 days. The In vitro cell behavior of EC and SMC indicated that the rapamycin loaded polymer film inhibited cell growth in the first few days of drug release. After 8 days of drug release, the composite coating consistently resisted the nonspecific adsorption of SMC, whereas REDV enhanced EC attachment specifically. A rabbit iliac injury model was used to evaluate the in vivo of the application of this kind of surface-modified stainless steel stent. The composite polymer coating approach could significantly promote re-endothelialization without causing neointimal hyperplasia. The combination of an EC-specific ligand with rapamycin-loaded polymeric coating may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.


Cephalometric Norms in an Omani Adult Population of Arab Descent.
This study aimed to establish cephalometric norms for an Omani population of Arab descent and to compare these with established cephalometric values for Caucasians. This cross-sectional study was conducted at the Military Dental Centre and Oman Dental College in Muscat, Oman, between May 2014 and October 2016. A total of 150 Omani patients between 20-29 years old seeking orthodontic treatment were included. All participants had a symmetrical face, class I molar and canine relationships, proper intercuspation, a normal overjet/overbite (<3 mm) and mild spacing/crowding of the teeth (≤3 mm). Lateral cephalography was performed in centric occlusion with the lips relaxed and the head in a natural position. Cephalometric measurements were then compared with Eastman Standard norms. The Omani subjects were found to have a slightly retrusive maxilla, an increased angle between the maxillary and mandibular planes and shorter facial heights in comparison to the Eastman Standard norms. Furthermore, incisor relations were edge-to-edge in nature and the interincisal angle was reduced, suggesting that the Omani subjects had more proclined incisors. In addition, the lips were more protrusive and the nasolabial angle was more obtuse. In the Omani sample, increased proclination of the incisors was observed in comparison to Eastman Standard norms. As such, slightly more proclined incisors should be considered acceptable and natural among Omani patients of Arab descent. The cephalometric findings of this study may be helpful in the diagnosis and treatment planning of orthodontic problems among Omanis of Arab descent.


Millettia speciosa Champ cellulose-based hydrogel as a novel delivery system for Lactobacillus paracasei: Its relationship to structure, encapsulation and controlled release.
We report for the first time the usage of Millettia speciosa Champ cellulose (MSCC) and carboxymethylcellulose (MSCCMC) for the fabrication of 3D-network hydrogel as delivery system for probiotics. The structural features, swelling behavior and pH-responsiveness of MSCC-MSCCMC hydrogels and their encapsulation and controlled-release behavior for Lactobacillus paracasei BY2 (L. paracasei BY2) were mainly studied. Structural analyses demonstrated that MSCC-MSCCMC hydrogels with porous and network structures were successfully synthesized through the crosslinking of -OH groups between MSCC and MSCCMC molecules. An increasing concentration of MSCCMC significantly improved the pH-responsiveness and swelling ability of the MSCC-MSCCMC hydrogel toward neutral solvent. Besides, the encapsulation efficiency (50.38-88.91 %) and release (42.88-92.86 %) of L. paracasei BY2 were positively correlated with the concentration of MSCCMC. The higher the encapsulation efficiency was, the higher the release in the target intestine. However, due to the existence of bile salts, controlled-release behavior decreased the survivor rate and physiological state (degrading cholesterol) of encapsulating L. paracasei BY2. Even so, the number of viable cells encapsulated by hydrogels still reached the minimum effective concentration in the target intestine. This study provides an available reference for the practical application of hydrogels fabricated from the cellulose of the Millettia speciosa Champ plant for probiotic delivery.


Dopamine receptor D3 agonist (Pramipexole) reduces morphine-induced cardiac fibrosis.
Morphine is routinely used for pain management in heart failure patients. However, extended morphine exposure associates with major adverse cardiovascular events. Reports link the dopamine receptor D2-family with morphine-induced nociception modulation. This study first assessed whether morphine induces cardiac remodeling in healthy mice, then whether DRD3 agonist (DRD3ag, D2-family member) adjunct therapy prevents morphine-induced cardiac remodeling. Mice received morphine (2 mg/kg/day i. p.) for 7 days (D7) and were either euthanized at D7 or kept 7 more days without morphine (i.e. withdrawal period, D8-D14): G1, morphine; G2, morphine/DRD3ag; G3, morphine + withdrawal; G4, morphine/DRD3ag + withdrawal; G5, morphine + withdrawal/DRD3ag. A separate cohort of animals were used as naïve tissues. We evaluated functional and molecular parameters of cardiac remodeling. Although we did not observe significant differences in systolic function, morphine induced both interstitial fibrosis and cardiomyocyte hypertrophy. Interestingly, DRD3ag abolished these effects. Compared to naïve tissues, collagen 1 increased after withdrawal in G3 and G4 and collagen 3 increased in G1-G4 but at higher levels in G1 and G2. Only G5 did not show collagen differences compared to naïve, suggesting DRD3ag treatment during withdrawal may be beneficial and prevent morphine-induced fibrosis. Smad2/3 phosphorylation increased during withdrawal, indicating a likely upstream pathway for the observed morphine-induced fibrosis. Overall, our data suggest that DRD3ag adjunct therapy decreases morphine-induced adverse cardiac remodeling.


Risk-Mitigating Policies and Adversarial Behavior: Case of Backlash.
A probabilistic game-theoretic model is developed within both a static and a dynamic framework to capture adversary-defender conflict in the presence of backlash. I find that not accounting for backlash in counteradversary policies may be costly to the target government. But to minimize adversarial backlash requires understanding how backlash emerges and if, and how, adversaries strategize to goad target governments into policies that induce backlash. The dynamic version of the model shows that when backlash occurs with a time lag, an escalation of the conflict is likely to occur.


The influence of bioactive glyoxylate bearing Schiff base on antifungal and antioxidant activities to chitosan quaternary ammonium salts.
In this study, to investigate the influence of glyoxylate bearing Schiff base on bioactivity to chitosan quaternary ammonium salts, different chitosan derivatives were synthesized by ion exchange of glyoxylate bearing Schiff base with chitosan quaternary ammonium salts (TMCI and HACC). For this purpose, glyoxylate was prepared by Schiff base reaction of glyoxylic acid and amino heterocycles and it was further ionization to substitute iodide ions and chloride ions. After structural characterization by FTIR and 1H NMR, the antifungal and antioxidant activities were measured. Results indicated that glyoxylate bearing Schiff base could improve the bioactivity of TMCI and HACC obviously. Specifically, anionic TMCI with Schiff base of amino pyridines possessed best antioxidant activity >92.40% at 1.6 mg/mL against DPPH radicals. Meanwhile, they showed antifungal activity >84.88% at 1.0 mg/mL against G. cingulate. Furthermore, the cytotoxicity was evaluated, and all samples showed good cell viability >80.14% at 1000 μg/mL.


Bio-ethanol production from non-food parts of cassava (Manihot esculenta Crantz).
Global climate issues and a looming energy crisis put agriculture under pressure in Sub-Saharan Africa. Climate adaptation measures must entail sustainable development benefits, and growing crops for food as well as energy may be a solution, removing people from hunger and poverty without compromising the environment. The present study investigated the feasibility of using non-food parts of cassava for energy production and the promising results revealed that at least 28% of peels and stems comprise dry matter, and 10 g feedstock yields >8.5 g sugar, which in turn produced >60% ethanol, with pH ≈ 2.85, 74-84% light transmittance and a conductivity of 368 mV, indicating a potential use of cassava feedstock for ethanol production. Thus, harnessing cassava for food as well as ethanol production is deemed feasible. Such a system would, however, require supportive policies to acquire a balance between food security and fuel.


Determination of the absolute configuration of the sugar residues of complex polysaccharides by circular dichroism spectroscopy.
Circular dichroism spectroscopy is used to determine the absolute configuration of the constituent sugar residues of bacterial polysaccharides from two strains of Streptococcus sanguis which are important receptors in bacterial coaggregation in the formation of dental plaque. A high-pressure liquid chromatographic method for carbohydrate analysis of glycoproteins, glycolipids, and polysaccharides has been extended to sugar chirality determination by collection of the eluted HPLC fractions and subsequent measurement of their circular dichroism spectra. The method involves methanolysis of the polysaccharide followed by formation of O-benzoyl derivatives and HPLC on reverse-phase columns. Circular dichroism spectra of the collected derivatives in acetonitrile solution in the region 230 nm show large ellipticity bands resulting from "chiral exciton" interaction among the O-benzoyl chromophores which are sensitive to the orientation of hydroxyl groups in the parent sugars. The sensitivity of the method is in the submicrogram range for the absolute configuration of single sugar residues. The circular dichroism of the intact polysaccharide in aqueous solution shows CD bands from the amide chromophore in the region 180 to 220 nm which are sensitive to the chirality of 2-acetamido sugar residues.


Divergent structures and functions of the Cupin proteins in plants.
Cupin superfamily proteins have extensive functions. Their members are not only involved in the development of plants but also responded to various stresses. Whereas, the research on the Cupin members has not attracted enough attention. In this article, we summarized the research progress on these family genes in recent years and explored their evolution, structural characteristics, and biological functions. The significance of members of the Cupin family in the development of plant cell walls, roots, leaves, flowers, fruits, and seeds and their role in stress response are highlighted. Simultaneously, the prospective application of Cupin protein in crop enhancement was introduced. Some members can enhance plant growth, development, and resistance to adversity, thereby increasing crop yield. It will be as a foundation for future effective crop research and breeding.


Implantable extra-aortic balloon assist powered by transformed fatigue-resistant skeletal muscle.
The hypothesis tested in this study was whether a skeletal muscle could be transformed to be fatigue resistant, to be used to power an implantable extra-aortic balloon assist device, and therefore to provide dynamically significant cardiac assistance. Eight dogs underwent implantation of an Itrel pacemaker to stimulate the thoracodorsal nerve over 8 to 18 weeks and transform the latissimus dorsi muscle. Biopsies of these muscles confirmed near complete (up to 98%) transformation into fatigue-resistance type I muscle fibers, identified by the adenosinetriphosphatase histochemical stains. Biochemical assays showed conversion of myosin isoforms to that of myocardial V3 phenotype, decreased activity of anaerobic glycolytic marker, and increased activity of aerobic enzyme marker, which indicated greater resemblance of such muscle to the myocardial fibers. In four dogs, the optimal stimulation parameters of such muscles in response to a burst stimulator, which synchronizes and summates the muscle contraction, were studied and compared with the contralateral, nontransformed muscle. Fatigue tests confirmed the marked fatigue resistance of the transformed muscle. In four dogs, a 100 ml balloon was placed beneath the transformed latissimus dorsi muscle and connected to the thoracic aorta with a Dacron graft. By means of the optimal burst-stimulating parameters identified above, the latissimus dorsi muscle was stimulated to contract during diastole, compressing the balloon to achieve diastolic augmentation while allowing the balloon to fill during systole. A 39% increase (p less than 0.001) in the "subendocardial viability index" (diastolic pressure-time index/tension-time index) was obtained as calculated from the left ventricular and ascending aortic pressure tracings. We conclude that the skeletal muscle can be transformed to resemble myocardium, which can generate sufficient force to provide hemodynamically significant and clinically relevant counterpulsation.


Predictors of Prolonged Length of Stay After Pituitary Adenoma Resection: A Large Cohort Analysis Using the National Inpatient Sample (2016-2019).
In this nationwide retrospective study, the authors aimed to identify demographic, clinical, and baseline health risk factors predictive of a prolonged length of stay (PLOS) for patients with pituitary adenomas (PAs). The National Inpatient Sample dataset from 2016 to 2019 was utilized to identify all included hospitalizations for PA resection as identified by the appropriate diagnosis-related group code. Comorbidities were classified based on the Charlson Comorbidity Index mapping of ICD-10 codes, and PLOS was identified as any stay longer than 3 days. Univariable and multivariable logistic regression models, accounting for the sample design, were built to determine factors associated with PLOS and emergent surgery. Overall, 30 945 patients were included in this study with 10 535 patients having PLOS. Female patients experienced an increased odds of PLOS (odds ratio [OR]: 1.29; P < .001). Black patients (OR: 1.49; P < .001) and Hispanic patients (OR: 1.30; P = .003) had 1.49 times and 1.30 times the odds of PLOS compared to White patients, respectively. Compared to patients insured by Medicare, patients insured by Medicaid had an increased odds of PLOS (OR: 1.36; P = .007) as well as emergent surgery (OR: 5.40; P < .001). When stratified by emergent surgeries, Black patients (OR: 1.89; P < .001), Hispanic patients, (OR: 2.14; P < .001), and patients on Medicaid insurance (OR: 1.71; P < .001) were at an increased risk of emergent procedures. However, female sex (OR: 0.65; P < .001), upper third quartile (OR: 0.73; P = .017), and fourth quartile (OR: 0.69; P = .014) of patients categorized by zip code income were at decreased odds of an emergent procedure. Black and Hispanic patients, patients with Medicaid insurance, and patients of low socioeconomic status patients are at significantly higher risk of emergent PA resection and PLOS. Efforts to prevent emergent surgeries and shorten hospitalization after pituitary surgery may need to primarily focus on patient groups with select sociodemographic characteristics.


[Arteriovenous malformations: clinical and neuroradiologic study].
We report our experience in clinical and neuroradiological findings on the vascular malformation in our department from January 1988 to March 1990. We have discussed the actual diagnostic modalities and have reviewed the literature.


Altered Sleep Duration and Poor Quality of Sleep Among Pharmacy Students Amidst COVID-19 Lockdown: A South-Indian Study.
The nationwide lockdown enforced due to the spread of coronavirus disease-2019 had a definite impact on sleep. To observe any changes in the duration, pattern and quality of sleep among pharmacy students due to the lockdown. A google form-based cross-sectional and descriptive study was carried out after approval was obtained from the ethical committee in the month of July 2021 among 310 pharmacy students. The validated form was electronically administered after obtaining the informed consent. All the data pertaining to duration, pattern and quality of sleep before and during the lockdown was collected and analyzed using STATA version 16.0. Out of 310 participants, the study revealed an increase in the time needed to fall asleep (p value < 0.001) and in the total duration of sleep (p value < 0.001). A delay in the time of sleep in the morning (p value < 0.001) and at night (p value < 0.001) was also one among the many significant results. The incidences of jerky leg movements (p value < 0.001), snoring (p value < 0.001), frequent nightmares (p value < 0.001) and anxiety (p value < 0.001) were also increased as a direct effect of the lockdown. The study has confirmed the detrimental impact of the lockdown on sleep among pharmacy students. All attributes of sleep duration and sleep quality have achieved statistical significance signifying the need to develop cognitive behavioral interventions and prevent the worsening of mental health amidst the COVID-19 era.


Soft X-ray spectro-ptychography of boron nitride nanobamboos, carbon nanotubes and permalloy nanorods.
Spectro-ptychography offers improved spatial resolution and additional phase spectral information relative to that provided by scanning transmission X-ray microscopes. However, carrying out ptychography at the lower range of soft X-ray energies (e.g. below 200 eV to 600 eV) on samples with weakly scattering signals can be challenging. Here, results of soft X-ray spectro-ptychography at energies as low as 180 eV are presented, and its capabilities are illustrated with results from permalloy nanorods (Fe 2p), carbon nanotubes (C 1s) and boron nitride bamboo nanostructures (B 1s, N 1s). The optimization of low-energy X-ray spectro-ptychography is described and important challenges associated with measurement approaches, reconstruction algorithms and their effects on the reconstructed images are discussed. A method for evaluating the increase in radiation dose when using overlapping sampling is presented.


Amphetamine induces excess release of striatal acetylcholine in vivo that is independent of nigrostriatal dopamine.
The effect of amphetamine on striatal acetylcholine (ACh) release was studied by an in vivo intrastriatal microdialysis technique. Although we expected systemic amphetamine to inhibit baseline striatal ACh release, the opposite was found. In addition, we found that the amphetamine-induced striatal ACh release did not depend on nigrostriatal DA since 6-hydroxydopamine (6-OHDA) lesions had no effect on amphetamine-induced ACh release. Local intrastriatal injection of amphetamine via the microdialysis probe had no effect on striatal ACh release even when the probe was located more laterally in striatum to take advantage of the medial to lateral gradient of striatal ACh and D2 receptors. The hypothesis that amphetamine increased extracellular striatal ACh by increasing the release of biogenic amines besides dopamine was tested by pharmacological manipulations designed to specifically increase local striatal norepinephrine or serotonin levels. The serotonergic and noradrenergic manipulations had no effect on striatal ACh levels. These results indicate that amphetamine-induced release of ACh in striatum is mediated via distal brain regions that are functionally connected with the striatum.


Beware frontotemporal dermoids - they may have intracranial extension: a case of a middle cranial fossa cyst.
Congenital orbitofacial dermoid cysts are epithelial lined structures of ectodermal origin that may be associated with sinus tracts and variable deep extension. Midline lesions may extend intracranially, while lateral lesions are thought never to do so. Consequently only midline lesions are usually imaged prior to surgery. We describe a lateral dermoid sinus communicating with an intracerebral dermoid cyst within the middle cranial fossa in a 3 year-old with recurrent periorbital cellulitis and intermittent discharge from a small pimple in the temporal region. This case demonstrates that some lateral "dermoids" need to be treated with more caution if there are unusual features such as dimpling, discharge of material or recurrent wider infection, and preoperative imaging should be carried out to exclude intracranial extension.


Does dietary fat cause a dose dependent glycemic response in youth with type 1 diabetes?
To determine the glycemic impact of dietary fat alone consumed without prandial insulin in individuals with T1D. Thirty participants with T1D (aged 8-18 years) consumed a test drink with either 20 g glucose or 1, 13, 26, 39, 51 g of fat with negligible carbohydrate/protein on 6 consecutive evenings, in a randomized order without insulin. Continuous glucose monitoring was used to measure glucose levels for 8 h postprandially. Primary outcome was mean glycemic excursion at each 30 min interval for each test condition. Generalized linear mixed models with a random effect for people with diabetes were used to test for an increase in blood glucose excursion with increasing quantity of fat. Glycemic excursions after 20 g glucose were higher than after fat drinks over the first 2 h (p < 0.05). Glycemic excursion for the fat drinks demonstrated a dose response, statistically significant from 4 h (p = 0.026), such that increasing loads of fat caused a proportionally larger increase in glycemic excursion, remaining statistically significant until 8 h (p < 0.05). Overall, for every 10 g fat added to the drink, glucose concentrations rose by a mean of 0.28 mmol L-1 from 330 min (95% CI 0.15 to 0.39, p < 0.001). Fat ingested without other macronutrients increases glucose excursions from 4 to 8 h after ingestion, in a dose dependent manner. These observations may impact on insulin dosing for high-fat foods in individuals with T1D.


Mucolytics: when dispensable, when necessary?
Many patients with chest disease have difficulty in clearing their chests of sputum. A variety of substances have been used in an attempt to help them. Mucolytic drugs can alter the rheological properties of mucus by acting directly on the secretions or by modifying the metabolic activity of the mucus secreting cells. Many physicians and patients are certain to reap a benefit. This paper will discuss the effectiveness of mucolytic therapy.


Single-agent Smac-mimetic compounds induce apoptosis in B chronic lymphocytic leukaemia (B-CLL).
Defective apoptosis is a hallmark of the progression of B chronic lymphocytic leukaemia (B-CLL). Smac-mimetics have been shown to induce apoptosis in several tumours. We describe the in vitro pro-apoptotic activity and regulation of the molecular pathway induced by new Smac-mimetics in B-CLL. The cytotoxic effect was significantly higher in B-CLL samples than in healthy controls. No significant synergistic effect was observed in combined treatment. In conclusion one of our compounds (Smac66), used as monotherapy and not in combination, is highly active against B-CLL cells thus suggesting a promising therapeutic potential as a new class of antileukemic drugs in haematology.


Advancing Roles of Healthcare Professionals in Palliative Radiotherapy.
New methods of working in relation to the management of patients requiring palliative radiotherapy are being embraced in hospital departments around the world. Team members are expanding on their previously assigned scope of practice to take on duties that had previously only been assigned to a consultant clinical oncologist. Career frameworks such as the four-tier model have been built upon to identify the skills held by other healthcare professionals and show how they may be best placed to take on additional roles within a patient pathway. Experiences of four departments in different countries report their local experiences in using both therapeutic radiographers and nursing staff to undertake advanced and consultant-level practice in relation to the management of both palliative radiotherapy patients and their research work streams. Involvement of other healthcare professionals within the clinical or research pathway for the management of palliative radiotherapy patients can be achieved. Their involvement can support clinicians and help to ensure the safe and efficient management of patients requiring palliative radiotherapy.


A baseline study of medication error rates at Baylor University Medical Center in preparation for implementation of a computerized physician order entry system.
To determine baseline levels of medication errors and their root causes so as to highlight areas of potential process improvements and serve as a ruler against which to measure future improvements. A prospective pharmacist intervention study determining errors in 1014 medication orders at Baylor University Medical Center. Only errors in the process of medication ordering were documented; errors in drug administration were not considered. Root causes of errors were examined. The baseline medication error rate was 111.4 per 1000 orders (n = 1014). Most common were dosing errors (43.4 per 1000 orders), followed by frequency errors (19.7 per 1000 orders) and unavailable drug errors (12.8 per 1000 orders). Of the 113 total errors found, 52 (46%) had a transcription-based cause, i.e., an error in inputting the handwritten physician order into a computer system. System- or process-related root causes (such as duplicate orders or lack of crossover from one information system to another) accounted for 35.4% of the errors, and prescribing based causes (such as wrong dosage or nonformulary drugs) accounted for 18.6% of errors. Implementing a computerized physician order entry (CPOE) system would eliminate order-entry transcription-based errors. Its ability to resolve system/process-based and prescribing-based root causes of error is not as clear. Furthermore, the modification of processes due to implementation of CPOE could lead to new types of errors. Present processes must be redesigned according to evidence-based medicine, and future processes must be anticipated as technological changes occur. Such efforts-rather than outright reliance on technology--are more likely to lead to an error-free environment after CPOE is implemented.


[Differences in the gene structure of the matrix protein and hemagglutinin in remantadine-resistant and -sensitive variants of the influenza virus type A FPV].
The oligonucleotide mapping technique and RNA-RNA hybridization revealed structural differences between the HA- and M-protein genes of two variants of influenza A FPV, remantadine-sensitive and remantadine-resistant ones. A quantitative estimation of the structural divergence of the two influenza FPV pairs of genes was carried out. The possible functional role of the differences in the structure of the HA- and M-protein genes of the two FPV variants is discussed.


Direct measurements of the dextran-dependent calcium uptake by rat peritoneal mast cells.
The metallochromic indicator murexide has been used to monitor calcium concentration changes during the dextran-induced, phosphatidylserine-dependent degranulation of rat peritoneal mast cells. The dextran-induced Ca2+-uptake showed an absolute dependence on the presence of phosphatidylserine. The extent of Ca2+-uptake increased with phosphatidylserine in a concentration-dependent manner. At 25 degrees C the half-life of the uptake process equalled 35 +/- 5 s. Exposure of the mast cells to dextran in the presence of Ca2+, but in the absence of phosphatidylserine, desensitized the cells. The subsequent addition of phosphatidylserine failed to restore the Ca2+-uptake activity. However, the Ca2+-ionophore A23187 did promote Ca2+ uptake by the cells without PS.


Acute Elemental Mercury Poisoning Masquerading as Fever and Rash.
This is a case series of 3 children from a single family who developed symptomatic elemental mercury poisoning requiring hospitalization and chelation. The mercury exposure primarily occurred in the home but the mercury was also tracked to one of their schools requiring environmental cleanup at both the home and school. The clinical assessment and management, as well as public health investigation and response, are discussed. There are many lessons learned in this difficult, often delayed, diagnosis. Early recognition of this environmental toxic exposure is essential. Communication between the clinicians and public health officials played a critical role. Public education prevented panic. Proper environmental sampling, and assessment and management of those exposed, were a few of the many challenges faced in this complicated case series.


Effectiveness research in oncology with electronic health record data: A retrospective cohort study emulating the PALOMA-2 trial.
Oncology electronic health record (EHR) databases have increased in quality and availability over the past decade, yet it remains unclear whether these clinical practice data can be used to conduct reliable comparative effectiveness studies. We sought to emulate a clinical trial with EHR data in the advanced breast cancer population and compare our results against the trial. This cohort study used EHR data from US oncology practices. All elements of the study were defined to mimic the PALOMA-2 trial as closely as possible. Patients with hormone-positive, HER-2 negative metastatic breast cancer with no prior treatment for metastatic disease were included. Patients initiating palbociclib and letrozole on the same day following the earliest record of metastasis were compared to those initiating letrozole only. The primary associational measure was the conditional hazard ratio for time-to-next treatment (TTNT). TTNT is well-measured in our data source and amenable for calibration against the randomized study results of the PALOMA-2 trial. We used multiple imputation for several patient characteristics with missing values. There were 3836 study-eligible women with advanced breast cancer. The hazard ratio for TTNT in the observational study (HR: 0.62; 95% CI: 0.56-0.68) was closely aligned with that of the randomized trial (HR: 0.64; 95% CI: 0.52-0.78). Under our assumptions on missing data and comparability of the two study populations, results from our non-randomized study closely matched that of the randomized trial. Further studies are needed to determine whether EHR data can yield reliable conclusions on treatment effects in oncology.


Sensitive periods in development and risk for psychiatric disorders and related endpoints: a systematic review of child maltreatment findings.
Variation in the mental health of people who have experienced childhood maltreatment is substantial. One hypothesis is that this variation is attributable, in part, to the timing of maltreatment-specifically, whether maltreatment occurs during sensitive periods in development when the brain is maximally sensitive to particular types of environmental input. To determine whether there is scientific consensus around when periods of peak sensitivity occur, we did a systematic review of human observational studies. Although 89 (75%) of the 118 unique cross-sectional or longitudinal cohort studies we identified reported timing effects, no consistent sensitive periods were identified for any of the most studied outcomes. Thus, observational research on childhood maltreatment has yet to converge on a single period (or set of periods) of increased vulnerability. We identified study characteristics that might contribute to these between-study differences and used observations from our Review to suggest a comprehensive set of recommendations for future research.


Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.
Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.


Ochratoxin A and citrinin induced nephrosis in Beagle dogs. II. Pathology.
Beagle dogs were given ochratoxin A (0.1 and 0.2 mg/kg) and citrinin (5 and 10 mg/kg) alone and in two dose combinations for 14 days. The gross lesions included focal peritonitis and intestinal intussusceptions in dogs given citrinin. Changes in the kidneys of dogs given ochratoxin A were degeneration and necrosis with desquamation of tubular epithelial cells, primarily in the straight segment of the proximal tubules. Dogs given 10 mg/kg citrin had similar changes in the distal tubules and collecting ducts. Dogs given combined doses of citrinin and ochratoxin A had degeneration and necrosis in proximal and distal tubules, and in thin segments and the collecting ducts; there were desquamated cells and granular casts in the lumina. Dogs given ochratoxin A had necrosis of lymphoid tissues in the spleen, tonsil, thymus, peripheral lymph nodes and lymph nodules of the ileum, colon and rectum. There was ulceration of the mucosa of the intestine in dogs given large combined doses of ochratoxin A and citrinin.


Feasibility of total thyroidectomy in the treatment of thyroid carcinoma: postoperative radioactive iodine evaluation of 140 cases.
The objective of this study was to evaluate our experience with so-called total thyroidectomy. Fifty cases (the retrospective group) had been operated on before the start of the study and had been on thyroid replacement therapy; this was discontinued, thyroid-stimulating hormone was administered, and iodine-131 studies were performed. Ninety cases (the prospective group) were evaluated 3 or more weeks postoperatively with no thyroid hormone having been administered. All patients were given 50 microcuries of iodine-131 and uptake studies were performed 24 hours later. All the patients were evaluated at a time when it was believed that practically all circulating hormone secreted by the thyroid gland before its removal had been metabolized or excreted from the body. If the patients with iodine-131 uptakes only in the region of the pyramidal lobe are considered to have had total thyroidectomy, we find that 85.7% of the patients studied had an uptake of less than 1.5%, and 96.4% had an uptake of less than 2.5%. There is increasing evidence to indicate that total thyroidectomy is the procedure of choice in the treatment of differentiated thyroid carcinoma. The present study indicates that with proper technique, total resection of the thyroid gland is feasible in nearly all cases of thyroid carcinoma.


Synthesis and photocatalytic activity of TiO2 nanowires in the degradation of p-aminobenzoic acid: A comparative study with a commercial catalyst.
The photocatalytic degradation of p-aminobenzoic acid was studied using TiO2 nanowires as the catalyst synthesized through a hydrothermal procedure. The as-synthesized TiO2 nanowires were fully characterized by SEM, TEM, XRD and Raman with a very high surface area of 512 m(2) g(-1). The photocatalytic degradation of p-aminobenzoic acid was carried out under 180 min of constant radiation and the results were compared with P25 as commercial catalyst. Optimal experimental conditions were determined for TiO2 nanowires with a catalyst dosage of 1.0 g L(-1) under acidic conditions with a 20 μM p-aminobenzoic acid solution obtaining 95% of degradation. Under similar experimental conditions comparative studies were performed obtaining 98% of degradation when P25 is employed. In both systems, a pseudo first order reaction was found to provide the best correlations, with constant rates of 2.0 × 10(-2) min(-1) and 2.4 × 10(-2) min(-1) for TiO2 nanowires and P25, respectively.


[Immunological tolerance of intraocular eyelashes after penetrating corneal injury].
Penetrating eye injuries often lead to serious symptoms, such as severe inflammation and pain, especially if residual intraocular foreign bodies are present. This case report describes a patient who suffered a penetrating corneal injury resulting in eyelashes being displaced into the anterior chamber. Although no treatment was given the anterior chamber of the eye did not show any inflammatory reactions 2 weeks after the trauma. In addition to the accident mechanism the material of which the foreign body is composed plays a decisive role. While iron, copper and wooden foreign bodies lead to severe intraocular inflammation, keratin is immunologically well-tolerated.


Cue-elicited drug craving represses ERK activation in mice prefrontal association cortex.
Morphine addiction is characterized by compulsive drug-taking behavior and high rates of relapse that reflect reward-controlled learning, consolidation and reconsolidation of drug cues. Extracellular signal-regulated protein kinase (ERK) is one of the cellular molecules that have been highly implicated in the synaptic plasticity processes of learning and memory in cocaine addiction. However, the roles of ERK in the morphine-paired conditioned place preference (CPP) are not clear. In the present study, we found that compared to the morphine-unpaired and saline-paired and saline-unpaired groups, morphine-paired mice showed depressed ERK2 activity in the Frontal Association Cortex (FrA), whereas ERK1 activity was not changed in the same region. In the Accumbens Nucleus (Acb) and Caudate Putamen (CPu) that are associated with cocaine addiction, the activities of ERK1 and ERK2 among four groups showed no difference. These results suggest that the FrA plays an important role in morphine craving and that ERK2 is involved in eliciting the environment-related morphine craving, which is totally different from those induced by morphine itself.


Efficiency of beta-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters.
Densities of beta-adrenoceptor subtypes and their contributions to stimulation of adenylyl cyclase were studied in heart ventricles from cardiomyopathic (BIO 8262) and control Syrian hamsters (CLAC) at 4 different ages: 30, 100, 200, and 300 days. In BIO ventricles neither total beta-adrenoceptor density nor that of the beta 1-adrenoceptor subtype differed from the controls, whereas the density of beta 2-adrenoceptors was significantly higher in myocardium from 200- and 300-day-old BIO compared to that from age-matched CLAC hamsters. Stimulation of adenylyl cyclase by the non-selective beta-adrenoceptor agonist isoprenaline did not differ between strains, but the beta 1-adrenoceptor mediated component was significantly reduced in cardiomyopathic hamsters of all age groups. In 300-day-old animals beta 1-adrenoceptors accounted for 83% (CLAC) and 68% (BIO) of total beta-adrenoceptor binding sites, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via beta 1-adrenoceptors. Thus, the present study shows a lower coupling efficiency of beta 1-adrenoceptors compared to the beta 2-adrenoceptor subtype in ventricles from healthy Syrian hamsters and a progressive, further reduction in beta 1-adrenergic function in cardiomyopathic animals.


Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment.
Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment.


Experience with Gleason histopathologic grading of prostatic cancer in Japan.
Histologic characteristics of prostate cancer in Japan were evaluated in a retrospective analysis of 267 cases. These specimens were graded by the Gleason histopathologic grading system, and the proportional distribution of histologic features and the death rate were compared with those of Gleason's results in the literature. The system demonstrates significant correlation with mortality rates for each grade group in our cases, and it was also found that the death rates as obtained by our figures were comparable to those of Gleason in each category. The results help to provide the basis for future comparative multinational trials of prostate cancer.


Effects of carotid sinus nerve stimulation at different times in the respiratory and cardiac cycles on variability of heart rate and blood pressure of normotensive and renal hypertensive dogs.
It was the purpose of the present study to determine (1) whether or not there exists a common respiratory and cardiac cycle time effect of the baroreceptor control of heart rate (HR) and blood pressure (BP) in spontaneously breathing anaesthetized dogs and (2) whether this effect, if present, is abnormal in dogs with renal hypertension. The baroreflex responses were evoked by brief low-intensity electrical carotid sinus nerve stimulation (CSNS) triggered by the R-wave in the electrocardiogram with an adjustable delay (0-210 ms) and positioned in either inspiration or expiration. All baroreceptor afferent nerves were intact. Brief CSNS had no noticeable effect on breathing. The responses of means of HR, respiratory sinus arrhythmia (RSA), and systolic and diastolic respiratory blood pressure waves (RBPWsyst, RBPWdiast) to CSNS were not different for normotensive and hypertensive dogs. No cardiac, but a small respiratory cycle time effect on means of HR, BPsyst and BPdiast was observed. The magnitude of RSA and RBPWdiast was markedly enhanced for expiratory CSNS at each delay after the R-wave. Inspiratory CSNS diminished the magnitude of RSA and RBPW only if applied during systole, and become ineffective for delays greater than 200 ms after the R-wave. During both respiratory phases, CSNS was elevated at times of central presentation of the natural sinoaortal baroreceptor discharges (120 ms and 70 ms, respectively). The magnitudes of RSA and RBPW were influenced simultaneously and in the same way by CSNS throughout. It is concluded that, under the present experimental conditions, RSA and RBPW have a common central origin.


STAT3 regulates SRGN and promotes metastasis of nasopharyngeal carcinoma through the FoxO1-miR-148a-5p-CREB1 axis.
Nasopharyngeal carcinoma (NPC), which is marked by a distinct distribution, is a common subtype of epithelial carcinoma arising from the nasopharyngeal mucosal lining. SRGN acts as an important and poor prognostic factor of NPC through multiple different mechanisms. However, the biological role and mechanism of SRGN in NPC remain unknown. Expression levels of miR-148a-5p, CREB1, FoxO1, and SRGN in NPC tissues and cell lines were tested by qRT-PCR or/and Western blot. The impacts of miR-148a-5p, CREB1, FoxO1, and SRGN on NPC cell viability, proliferation, migration, and invasion were estimated in vitro by CCK-8, colony formation, wound healing and Transwell experiments, and in vivo by a xenograft tumor model. JASPAR analysis was used to predict the binding activity of Foxo1 (CREB1) with the miR-148a-5p (SRGN) promoter, and the interaction was validated by EMSA and ChIP assays. The miR-148a-5p-CREB1 interaction was validated by a dual-luciferase reporter and RIP assays. CREB1 and SRGN were increased while miR-148a-5p was decreased in NPC. Silencing of SRGN and CREB1, as well as miR-148a-5p overexpression, repressed NPC tumor progression in vitro and in vivo. CREB1 promoted SRGN expression in NPC by targeting the promoter area of SRGN. Silencing of FoxO1 facilitated NPC tumor progression, while silencing of STAT3 repressed NPC tumor progression. FoxO1 bound to and regulated miR-148a-5p in NPC, and miR-148a-5p targeted CREB1. Additionally, FoxO1 knockdown abolished the downregulation of CREB1 and SRGN induced by STAT3 silencing. Our results suggest that STAT3 regulates SRGN and promotes the growth and metastasis of NPC through the FoxO1-miR-148a-5p-CREB1 axis.


Estimation of household health cost and climate adaptation cost with its health related determinants: empirical evidences from western Nepal.
Limited evidence is available concerning the household-level costs of prevailing diseases and the potential cost of climate adaptation in Nepal. This study estimates these costs and assesses the relationships between prevalent diseases and climate adaptation at the household level using survey data from 420 households. An ingredients-based approach was used to estimate the cost of health and adaptation, and a Probit regression model was used to analyze the relationship between prevalent diseases and climate adaptation costs. Household direct curative costs are the highest among health cost components. Two-thirds of total health costs are direct costs for households. On average, 15.90% of household income is used for direct cost of health care. The climate hazard cost among afflicted households is estimated to be high. In addition, diseases like malaria, typhoid and jaundice, their costs, climate awareness program, droughts, family size and loss of per capita income are more likely to raise the cost of climate adaptation. The occurrence of gastritis, prevalence of diarrhea and cold waves are less likely to affect the cost. Policymakers should implement health financing schemes and adaptation strategies to prevent the loss of human health in western Nepal.