Effect of paced breathing on ventilatory and cardiovascular variability parameters during short-term investigations of autonomic function.
Paced breathing (PB) around 0.25 Hz has been advocated as a means to avoid confounding and to standardize measurements in short-term investigations of autonomic cardiovascular regulation. Controversy remains, however, as to whether it causes any alteration in autonomic control. We addressed this issue in 40 supine, middle-aged, healthy volunteers by assessing the changes induced by PB (0.25 Hz for 8 min) on 1) ventilatory parameters, 2) the indexes of autonomic control of cardiovascular function, and 3) the spectral indexes of cardiovascular variability. Subjects were grouped into group 1 (n = 31), if spontaneous breathing was regular and within the high-frequency (HF) band (0.15-0.45 Hz), or group 2 (n = 9), if it was irregular or slow (< 0.15 Hz). In both groups, PB was accompanied by an increase in minute ventilation (both groups, P < 0.01), whereas tidal volume increased only in group 1 (P = 0.0003). End-tidal CO2 decreased by [median (lower quartile, upper quartile)] -0.2 (-0.5, -0.1)% (group 1, P < 0.0001) and -0.6 (-0.8, -0.5)% (group 2, P = 0.008). Mean R-R interval and systolic and diastolic pressure remained remarkably stable (all P > or = 0.13, both groups). No significant changes were observed in spectral indexes of R-R and pressure variability (all P > or = 0.12, measured only in group 1 to avoid confounding), except in the HF power of pressure signals, which significantly increased (all P < 0.05) in association with increased tidal volume. In conclusion, PB at 0.25 Hz causes a slight hyperventilation and does not affect traditional indexes of autonomic control or, in subjects with spontaneous breathing in the HF band, most relevant spectral indexes of cardiovascular variability. These findings support the notion that PB does not alter cardiovascular autonomic regulation compared with spontaneous breathing.


Assessing the quality of offshore Binomial sampling biosecurity inspections using onshore inspections.
Introduction of pests and diseases through trade is one of the main socio-ecological challenges worldwide. Although Binomial sampling inspection at the border can reduce pest entry risk, it is common for consignments to fail inspection, wasting resources for both exporter and importer. Outsourcing the inspection to the exporting country could reduce the cost of inspection for both parties. However, there is then a need to assess the quality of the offshore inspection. In this paper, we develop an inverse method combining past inspection data on the pathway, an onshore inspection sample, and the Beta-Binomial model to infer the sample size of the offshore inspection. We illustrate the method on two case studies: the importation of live plants through germplasm into Australia and the importation of pelleted seeds in New Zealand. In these case studies, we found that detecting four to five infested units in a single onshore inspection was typically sufficient to significantly doubt the presence of a compliant offshore inspection. We also ran a simulation experiment to quantify the statistical power to reject or accept the presence of compliant offshore inspection in practice: In highly infested pathways, we could detect the absence of offshore inspections after inspecting five consignments onshore. Less infested pathways required inspecting 20 to 60 consignments onshore. Our study demonstrates that Binomial sampling onshore can be used to assess the quality of offshore inspections.


Animal personality and state-behaviour feedbacks: a review and guide for empiricists.
An exciting area in behavioural ecology focuses on understanding why animals exhibit consistent among-individual differences in behaviour (animal personalities). Animal personality has been proposed to emerge as an adaptation to individual differences in state variables, leading to the question of why individuals differ consistently in state. Recent theory emphasizes the role that positive feedbacks between state and behaviour can play in producing consistent among-individual covariance between state and behaviour, hence state-dependent personality. We review the role of feedbacks in recent models of adaptive personalities, and provide guidelines for empirical testing of model assumptions and predictions. We discuss the importance of the mediating effects of ecology on these feedbacks, and provide a roadmap for including state-behaviour feedbacks in behavioural ecology research.


[Does sonographic kidney morphology and morphometry provide evidence of pediatric kidney function?].
Compared with conventional X-ray investigation, ultrasound examination has a variety of advantages in the evaluation of urinary tract disorders in infancy and childhood. It does not involve exposure to contrast medium and radiation; low costs, minimal stress to the young patients, high diagnostic accuracy and easy reproducibility are further benefits. Postoperative follow-up of obstructive disorders can be easily performed and the results quantified by means of ultrasound. Morphometric data correlate well with renal function. As urologists become more familiar with ultrasonic morphologic and morphometric data, X-ray examinations in childhood will be confined to a few specific indications.


Measuring Subjective Cognitive Decline in Older Adults: Harmonization Between the Cognitive Change Index and the Measurement of Everyday Cognition Instruments.
Self and informant (proxy or study partner) reports of everyday cognitive functioning have been shown to be associated with incipient neurodegenerative disease. The 20-item Cognitive Change Index (CCI) and the 39-item Measurement of Everyday Cognition (ECog) were each developed to characterize early subjective changes in cognitive function. We examined the relationship between CCI and ECog self and informant-based evaluations to determine content overlap and provide a co-calibration for converting between these widely used instruments. 950 participants (57.1% female, mean age = 71.2 years) from ADNI and the Indiana ADRC with self-based evaluations and 279 participants (60.9% female, mean age = 71.8 years) with informant-based evaluations (Indiana ADRC) were included. Analyzed variables for the CCI and ECog included domain mean scores, memory domain total scores, and total scores for all items. Spearman correlations, regression analyses, and frequency distributions were used to assess the relationship between CCI and ECog. Sex, age, years of education, race/ethnicity, APOE ɛ4 carrier status, and baseline diagnosis were also analyzed as potentially relevant covariates. CCI and ECog total scores were highly correlated for the self (r = 0.795, p < 0.001) and informant-based (r = 0.840, p < 0.001) versions, as expected. Frequency distributions of self and informant total scores were generated and plotted separately. Quadratic regressions for self (r2 = 0.626) and informant (r2 = 0.741) scores were used to create a translation table between the CCI and ECog total scores. Self and informant total scores can be harmonized and translated between the CCI and ECog to facilitate cross-study and longitudinal assessment of perceived cognitive change, an important patient-reported outcome.


A visual screen of protein localization during sporulation identifies new components of prospore membrane-associated complexes in budding yeast.
During ascospore formation in Saccharomyces cerevisiae, the secretory pathway is reorganized to create new intracellular compartments, termed prospore membranes. Prospore membranes engulf the nuclei produced by the meiotic divisions, giving rise to individual spores. The shape and growth of prospore membranes are constrained by cytoskeletal structures, such as septin proteins, that associate with the membranes. Green fluorescent protein (GFP) fusions to various proteins that associate with septins at the bud neck during vegetative growth as well as to proteins encoded by genes that are transcriptionally induced during sporulation were examined for their cellular localization during prospore membrane growth. We report localizations for over 100 different GFP fusions, including over 30 proteins localized to the prospore membrane compartment. In particular, the screen identified IRC10 as a new component of the leading-edge protein complex (LEP), a ring structure localized to the lip of the prospore membrane. Localization of Irc10 to the leading edge is dependent on SSP1, but not ADY3. Loss of IRC10 caused no obvious phenotype, but an ady3 irc10 mutant was completely defective in sporulation and displayed prospore membrane morphologies similar to those of an ssp1 strain. These results reveal the architecture of the LEP and provide insight into the evolution of this membrane-organizing complex.


Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine and parasite resistance: cross-sectional surveys from antenatal care visit and delivery in rural Ghana.
Despite decades of prevention efforts, the burden of malaria in pregnancy (MiP) remains a great public health concern. Sulfadoxine-pyrimethamine (SP), used as intermittent preventive treatment in pregnancy (IPTp-SP) is an important component of the malaria prevention strategy implemented in Africa. However, IPTp-SP is under constant threat from parasite resistance, thus requires regular evaluation to inform decision-making bodies. In two malaria endemic communities in the Volta region (Adidome and Battor), a cross-sectional hospital-based study was conducted in pregnant women recruited at their first antenatal care (ANC) visit and at delivery. Basic clinical and demographic information were documented and their antenatal records were reviewed to confirm IPTp-SP adherence. Peripheral and placental blood were assayed for the presence of Plasmodium falciparum parasites by quantitative polymerase chain reaction (qPCR). One hundred and twenty (120) positive samples were genotyped for mutations associated with SP resistance. At first ANC visit, P. falciparum prevalence was 28.8% in Adidome and 18.2% in Battor. At delivery, this decreased to 14.2% and 8.2%, respectively. At delivery, 66.2% of the women had taken at least the recommended 3 or more doses of IPTp-SP and there was no difference between the two communities. Taking at least 3 IPTp-SP doses was associated with an average birth weight increase of more than 360 g at both study sites compared to women who did not take treatment (p = 0.003). The Pfdhfr/Pfdhps quintuple mutant IRNI-A/FGKAA was the most prevalent (46.7%) haplotype found and the nonsynonymous Pfdhps mutation at codon A581G was higher at delivery among post-SP treatment isolates (40.6%) compared to those of first ANC (10.22%). There was also an increase in the A581G mutation in isolates from women who took 3 or more IPTp-SP. This study confirms a positive impact following the implementation of the new IPTp-SP policy in Ghana in increasing the birth weight of newborns. However, the selection pressure exerted by the recommended 3 or more doses of IPTp-SP results in the emergence of parasites carrying the non-synonymous mutation on codon A581G. This constant selective pressure calls into question the time remaining for the clinical utility of IPTp-SP treatment during pregnancy in Africa.


Soy protein isolate does not affect ellagitannin bioavailability and urolithin formation when mixed with pomegranate juice in humans.
We investigated the effect of mixing soy protein isolate and pomegranate juice (PJ) on the bioavailability and metabolism of ellagitannins (ETs) in healthy volunteers. Eighteen healthy volunteers consumed PJ alone or PJ premixed with soy protein isolate (PJSP). The concentration of plasma ellagic acid (EA) and urine urolithins was measured. There was no significant difference in plasma EA over a 6-h period between the two interventions. While the maximum concentration of plasma EA after PJSP consumption was slightly but significantly lower than after PJ consumption, EA remained in the plasma longer with an elimination half-life t1/2E at 1.36±0.59 versus 1.06±0.47h for PJSP and PJ consumption, respectively. Urinary urolithin A, B and C was not significantly different between the two interventions. In conclusion, premixing soy protein isolate and PJ did not affect the bioavailability or the metabolism of pomegranate ETs in healthy volunteers.


Melliferous flora and pollen characterization of honey samples of Apis mellifera L., 1758 in apiaries in the counties of Ubiratã and Nova Aurora, PR.
The aim of this study was to carry out a survey of the flora with potential for beekeeping in the counties of Ubiratã and Nova Aurora-PR through the collection of plants and pollen analyses in honey samples collected monthly. 208 species of plants were recorded, distributed in 66 families. The families that showed the major richness of pollen types were: Asteraceae, Myrtaceae and Solanaceae. Approximately 80 pollen types were found in honey samples, most of them were characterized as heterofloral. Cultivated plants, such as Glycine max (soybean) and Eucalyptus spp., were representative in some months of the year. Exotic species, such as Ricinus communis and Melia azedarach, were also frequent. However, over than 50% of the pollen types belong to native species of the region, such as Schinus terebinthifolius, Baccharis spp. Alchornea triplinervia, Parapiptadenia rigida, Hexaclamys edulis, Zanthoxylum sp. and Serjania spp., indicating the importance of the native vegetation for the survival of the colonies.


lncRNA LEF1-AS1 Acts as a Novel Biomarker and Promotes Hypopharyngeal Squamous Cell Carcinoma Progression and Metastasis by Targeting the miR-221-5p/GJA1 Axis.
Hypopharyngeal squamous cell carcinoma (HSCC) is highly malignant and extremely aggressive, making it one of the worst prognoses among all kinds of head and neck squamous cell carcinoma (HNSCC); therefore, gaining insight into molecular mechanisms of HSCC is of profound significance. In the current manuscript, we revealed the elevated expression of long noncoding RNA (lncRNA) LEF1-AS1 in HNSCC which was associated with the poor prognosis by bioinformatic analysis. Moreover, we noticed that LEF1-AS1 dramatically accelerated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in HSCC cell line FaDu. Most importantly, we illustrated that LEF1-AS1 played as a competitive endogenous RNA (ceRNA) via sponging miR-221-5p and thereby positively regulated gap junction protein alpha 1 (GJA1) expression, thus aggravated tumor progression and EMT. In conclusion, for the first time, we demonstrated lncRNA LEF1-AS1 as a novel biomarker for HNSCC and suggested LEF1-AS1/miR-221-5p/GJA1 axis as promising diagnostic and therapeutic target for HSCC treatment.


A comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of anthranilamide derivatives that are multidrug resistance modulators.
In a continuing effort to develop potent and selective modulators of P-glycoprotein (P-gp) activity overcoming the chemoresistance acquired by tumor cells during cancer chemotherapy, we developed 3D quantitative structure-activity relationship (3D QSAR) models using CoMFA and CoMSIA analyses. This study correlates the P-glycoprotein inhibitory activities of 49 structurally related anthranilamide derivatives to several physicochemical parameters representing steric, electrostatic, acceptor, donor, and hydrophobic fields. Both CoMFA and CoMSIA models using three different alignment conformations gave good internal predictions, and their cross-validated r2 values are between 0.503 and 0.644. These most comprehensive CoMFA and CoMSIA models are useful in understanding the structure-activity relationships of anthranilamide derivatives as well as aid in the design of novel derivatives with enhanced modulation of P-gp activity.


Analgesic effects of preinjection low-level laser/light therapy (LLLT) before third molar surgery: a double-blind randomized controlled trial.
The aim of this study was to evaluate the analgesic effects of low-level laser therapy (LLLT) on preinjection sites in patients scheduled for third molar removal. This double-blind randomized controlled trial included 163 healthy patients undergoing third molar extractions. The study participants were randomly divided into an LLLT and a placebo group. Objective and subjective data sets were obtained from physiologic feedback (heart rate and sweat response) and a questionnaire, respectively. In the LLLT group, each targeted injection site was irradiated twice with 198 mW continuous wave for 30 seconds with a 0.088 cm2 focal spot at an applied energy of 5.94 J and fluence of 67.50 J/cm2. Measurements were recorded from 4 time-points during data acquisition. There was no significant difference between the LLLT and placebo groups in pain experience scores associated with the injected sites for maxillary or mandibular third molar extractions. Mean heart rates before and during injection were lower in the LLLT group than in the placebo group for both maxillary and mandibular regions. No statistically significant differences were observed for any remaining parameters. The present data indicated that preinjection LLLT did not effectively decrease the pain felt during local anesthetic injections before third molar surgery.


Role of prostaglandins in controlling plasma fibronectin levels.
Fibronectin is a normal glycoprotein component of plasma, interstitial fluid, and extracellular matrix which has binding sites for collagen, gelatin, actin, glycosaminoglycans, fibrin, Staphylococcus aureus, and some cells. Since it is a dimer, it can crosslink these substances to each other or to extracellular components of basement membrane, thereby affecting many physiological processes. The level of circulating fibronectin is markedly reduced following even moderate blunt or operative trauma, thermal injury, starvation, advanced cancers, hemorrhage, etc. Replacement therapy has been tried with some success in patients who become septic following multiple injuries. The reduction in plasma fibronectin has been attributed to several causes including consumption by binding to cell debris at the site of injury, binding to circulating cell debris and its subsequent removal by elements of the phagocytic system, and degradation by proteolytic cleavage. However, the amount of fibronectin removed from circulation raises some question about this. In this paper, we used indomethacin, ibuprofen, imidazole, and essential fatty acid deprivation to inhibit the synthesis of prostaglandins in young adult rats. Thirty minutes after ip administration of one of the inhibitors, the rats were subjected to a midline laparotomy and mild intestinal manipulation. Blood samples were taken at intervals following closure of the incision and analyzed for fibronectin. In all cases, the normal decline in plasma fibronectin seen in untreated rats was abrogated by inhibiting prostaglandin synthesis. Since imidazole specifically inhibits thromboxane A synthesis, this strongly suggests that thromboxanes directly or indirectly control the trauma-induced reduction in circulating fibronectin. This was confirmed by ip injection of thromboxane into the rats which resulted in a decline in plasma fibronectin levels.


The effect of exercise combined with a cognitive-enhancement group training program on cognition and depression in the community-dwelling elderly.
[Purpose] In this study, we investigated the effects of combining exercise with a cognitive-enhancement group program on cognition and depression in a group of community-dwelling elderly people. [Subjects and Methods] The study's subjects consisted of 30 community-dwelling elderly people of both genders, whose average age was 78 years. They participated in a program of physical exercise combined with a cognitive-enhancement group training program. This consisted of sessions lasting 60 minutes that took place once a week over 3 months. To assess the participants' levels of cognition and depression, we conducted batteries of tests using, respectively, the Korean versions of the Consortium to Establish a Registry for Alzheimer's Disease assessment packet (CERAD-K) and the Geriatric Depression Scale-Short Form (GDS-SF). [Results] The Verbal Fluency test, Word List Memory test, Modified Boston Naming test, Mini Mental Status Examination (Korean Version) (MMSE-KC), Constructional Praxis task and Constructional Recall task showed significant improvement, but improvement in the Word List Recall and Word List Recognition tests did not achieve significant levels. Meanwhile, the symptoms of depression were shown to decrease significantly. [Conclusion] Physical exercise combined with a cognitive-enhancement group training program was effective in improving, some of the components of cognition, as well as alleviating depression. This program should be used for the prevention of dementia in community-dwelling elderly, through the intervention should be complemented in order to improve more of the components of cognition.


Genetic, physical, and phenotypic characterization of the Del(13)Svea36H mouse.
The Del(13)Svea36H deletion was recovered from a radiation mutagenesis experiment and represents a valuable resource for investigating gene content and function at this region of mouse Chromosome (Chr) 13 and human Chr 6p21.3-23 and 6p25. In this paper we examine the physical extent of chromosome loss and construct an integrated genetic and radiation hybrid map of the deleted segment. We show that embryos which are homozygous for the deletion die at or before implantation and that heterozygotes are subviable, with a substantial proportion of carriers dying after mid-gestation but before weaning. The majority of viable carriers exhibit a variety of phenotypes including decreased size, eyes open at birth, corneal opacity, tail kinks, and craniofacial abnormalities. Both the heterozygous viability and the penetrance of the visible phenotypes vary with genetic background.


Sequential growth of zinc oxide nanorod arrays at room temperature via a corrosion process: application in visible light photocatalysis.
Many photocatalyst systems catalyze chemical reactions under ultraviolet (UV) illumination, because of its high photon energies. Activating inexpensive, widely available materials as photocatalyst using the intense visible part of the solar spectrum is more challenging. Here, nanorod arrays of the wide-band-gap semiconductor zinc oxide have been shown to act as photocatalysts for the aerobic photo-oxidation of organic dye Methyl Orange under illumination with red light, which is normally accessible only to narrow-band semiconductors. The homogeneous, 800-1000-nm-thick ZnO nanorod arrays show substantial light absorption (absorbances >1) throughout the visible spectral range. This absorption is caused by defect levels inside the band gap. Multiple scattering processes by the rods make the nanorods appear black. The dominantly crystalline ZnO nanorod structures grow in the (0001) direction, i.e., with the c-axis perpendicular to the surface of polycrystalline zinc. The room-temperature preparation route relies on controlled cathodic delamination of a weakly bound polymer coating from metallic zinc, an industrially produced and cheaply available substrate. Cathodic delamination is a sequential synthesis process, because it involves the propagation of a delamination front over the base material. Consequently, arbitrarily large sample surfaces can be nanostructured using this approach.


Acute canine ehrlichiosis: platelet survival and factor 3 assay.
Ten dogs experimentally inoculated with Ehrlichia canis were thrombocytopenic 14 days after inoculation. Circulating platelet concentrations had declined rapidly by postinoculation day 10, but remained at or slightly below the 14-day concentration during the remainder of the 42-day experimental period. The percentage of circulating megathrombocytes also increased to 8.7 times preinoculation concentrations indicating the existence of accelerated thrombocytopoiesis. The release of platelet factor 3 (PF-3) from normal canine platelets was delayed after incubation of the platelets in globulin fractions from infected dogs. Inhibition of PF-3 release was attributed to the effect of an unidentified substance present only in the dialyzed globulin fraction of infected canine serums. The presence of antiplatelet antibody in these dogs was not evident. Survival of 51Cr-labeled platelets was decreased in infected dogs, but was most abbreviated in infected dogs that were thrombocytopenic when injected with labeled platelets. Thus, accelerated nonantibody-mediated destruction of platelets contributes markedly to the development of thrombocytopenia in dogs with acute ehrlichiosis.


Pancreatic islet cell reaggregation systems: efficiency of cell reassociation and endocrine cell topography of rat islet-like aggregates.
Single cells isolated from rat islets of Langerhans were cultured under conditions that support reassociation into islet-like aggregates. Comparisons were made of enzymatic methods of islet dissociation, rotational or static culture conditions, and culture at basal or stimulatory glucose concentrations. Over a period of 4 days the aggregates progressed through three stages of organization: cell coalescence to cellular chains, rearrangement of chains into small spheroids, and growth of spheroids. The numerical yield of aggregates was optimum after islets were dissociated with dispase. Culture under rotation resulted in the production of more aggregates of significantly larger diameter than under static conditions. Medium glucose concentrations of 4 and 11 mM supported cell reassociation under rotator culture, but no aggregation occurred under static culture at the basal (4 mM) glucose level. Aggregates resulting from 4-day rotator culture exhibited endocrine cell distributions similar to intact islets. Islet aggregates released insulin in response to glucose, but nonaggregated cells, maintained in culture, did not. The present comparisons reveal significant variability in the cellular composition, rate of formation, and yield of aggregates, and suggest that the methodology for producing aggregates should be carefully considered in experimental design.


Scalable pumping approach for extracting the maximum TEM(00) solar laser power.
A scalable TEM(00) solar laser pumping approach is composed of four pairs of first-stage Fresnel lens-folding mirror collectors, four fused-silica secondary concentrators with light guides of rectangular cross-section for radiation homogenization, four hollow two-dimensional compound parabolic concentrators for further concentration of uniform radiations from the light guides to a 3 mm diameter, 76 mm length Nd:YAG rod within four V-shaped pumping cavities. An asymmetric resonator ensures an efficient large-mode matching between pump light and oscillating laser light. Laser power of 59.1 W TEM(00) is calculated by ZEMAX and LASCAD numerical analysis, revealing 20 times improvement in brightness figure of merit.


Mummified Thyroid Nodules: Conventional and Contrast-Enhanced Ultrasound Features.
The purpose of our study was to highlight the conventional and contrast-enhanced ultrasound (US) features of mummified thyroid nodules, which should help differentiate them from histologically proven papillary thyroid carcinomas (PTCs). Thirty-one patients with 33 mummified thyroid nodules, which showed suspicious US findings that were suggestive of malignancy, as well as 33 patients with 38 surgically confirmed PTCs were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of shadowing and halo, presence of punctate echogenic foci, vascularity, and contrast enhancement parameters for each nodule. The final diagnosis of mummified thyroid nodules was confirmed via fine-needle aspiration (FNA) or surgery. Of the 33 mummified thyroid nodules, 9 (27.3%) were confirmed by surgery to be benign, and 24 (72.7%) were proven by FNA to be benign. A univariate analysis indicated that the mummified thyroid nodules more frequently showed wider-than-tall shapes, marked hypoechogenicity, the presence of posterior shadowing, the absence of nodular vascularity, hypoenhancement or no enhancement, and peak index and area under the curve indices of less than 1 in the findings of preoperative US and contrast-enhanced US compared to PTCs. A multivariate analysis showed that marked hypoechogenicity and an area under the curve index of less than 1 were independent characteristics related to mummified nodules for discriminating from PTCs (all P < .05). Benign thyroid nodules may display shrinkage over time and may reveal malignant US features. Awareness of these findings and their connection with initial and follow-up US examinations should help identify mummified thyroid nodules and to avoid surgical excision or unnecessary FNA.


Tryptase: a clinical indicator of mast cell-dependent events.
Mast cells and basophils are implicated as major effector cells in allergic disease. However, both mast cell and basophil involvement in clinical events have been difficult to assess heretofore because of localization of mast cells in tissues and the small numbers of basophils in the circulatory system. Tryptase has been found to be a discriminating marker for the participation of human mast cells in immediate allergic responses, and therefore provides precise assessment of mast cell activation. High tryptase levels in serum, plasma, and other biologic fluids are consistent with mast cell activation in systemic anaphylaxis and other immediate hypersensitivity allergic reactions. Although basophil activation has been implicated in late phase response to allergen challenge, sensitive specific indicators of basophil activation are still under investigation.


Identification of the nucleolar targeting signal of human angiogenin.
Angiogenin is endocytosed by subconfluent endothelial cells, translocated to the nucleus and accumulates in the nucleolus. It also localizes into the nucleolus of digitonin-permeabilized endothelial cells. The peptide RRRGL corresponding to residues 31-35 of human angiogenin specifically targets non-nuclear carrier proteins such as albumin, an anti-human nucleolus monoclonal antibody and R33A angiogenin to the nucleolus of permeabilized endothelial cells. Proteins conjugated with a "mutant" peptide, RRAGL, are not imported. Fluorescein isothiocyanate-conjugated RRRGL is also rapidly imported into the nucleus and localized to the nucleolus, whereas the "mutant" peptide is not. Residue R33 is essential for nuclear translocation and R31 and R32 appear to modulate this process. Thus, 31RRRGL35 is a nuclear localization signal responsible for the nucleolar targeting of human angiogenin.


Optical properties and energy transfer processes in Tb3+-doped ZnSe quantum dots.
Tb3+-Doped ZnSe quantum dots (QDs) with a Tb content in the range of 0.5-7% were successfully synthesized by a wet chemical method. X-Ray diffraction (XRD) and transmission electron microscopy (TEM) analyses revealed that the as-synthesized QDs had a zinc blende (ZB) structure with a particle size of approximately 4 nm. The effect of Tb-doping on the structure and optical properties of the ZnSe QDs was studied. The emission spectra and photoluminescence (PL) decay kinetics data confirmed the successful incorporation of Tb3+ ions into the ZnSe host. The PL spectra also revealed that the intensity of dopant emission was significantly enhanced owing to the energy transfer (ET) from the host emission. The efficiency of the ET process from the ZnSe host to Tb3+ ions and between Tb3+ ions and the nature of these interaction mechanisms were determined by applying the Inokuti-Hirayama and Reisfeld models. The features of the ligand field and the optical properties of Tb3+ ions in the ZnSe QDs were studied using Judd-Ofelt theory. The dependence of the chromaticity features of ZnSe:Tb3+ QDs on the Tb concentration was estimated by the chromaticity coordinates and correlated color temperature (CCT). The Tb3+-doped ZnSe QDs with visible, tunable, and very long lifetime emission have potential for practical applications such as biological labeling, photocatalysis, and white-LED devices.


Sequential addition of platelet factor and plasma to BALB/c 3T3 fibroblast cultures stimulates somatomedin-C binding early in cell cycle.
Recent studies have shown that confluent cultured fibroblasts must be rendered competent by a factor contained in platelets before they can respond to plasma components and progress from G0 to S phase of the cell cycle. Somatomedin-C is one of the components of platelet-poor plasma necessary for cell cycle progression, but other factors present in somatomedin-C-deficient plasma are also required. Because both competence and progression factors contained in somatomedin-C-deficient serum modulate somatomedin-C action in fibroblasts, this study was undertaken to examine their possible influence on the binding of 125I-labeled somatomedin-C. Exposure of BALB/c 3T3 fibroblasts to high concentrations of platelet-derived growth factor alone prevented the time-dependent decrease in somatomedin-C binding which occurs in serum-free medium. Lower concentrations of the growth factor or 5% (vol/vol) platelet-poor plasma reduced but did not abolish this decrease. In contrast, sequential addition of platelet-derived growth factor followed by platelet-poor plasma resulted in a 75% increase in 125I-labeled somatomedin-C binding over basal levels during the first 2 hr. Binding increased by 125% when somatomedin-C-deficient platelet-poor plasma was substituted for normal platelet-poor plasma. The hormonal induction of somatomedin-C receptors appears to be a mechanism whereby peptide growth factors such as platelet-derived growth factor may condition the cell to respond optimally to somatomedin-C.


Sub-site specific time trends of carcinoma stomach in North Kerala--a retrospective analysis.
The time trends in the incidence of carcinoma stomach in the various sub-sites in stomach have been documented in the western population. The incidence of carcinoma of gastric cardia is found to be increasing, while that of the antrum is seen to be decreasing. Data from tropics is lacking on this aspect. This retrospective study was performed to look into the site-specific time trends of carcinoma stomach. Endoscopy registers maintained in the Department of Gastroenterology, Medical College, Kozhikode, Kerala in South India were screened over the period of 20 years from 1982 to 2001. Histopathologically confirmed cases of adenocarcinoma were included in the study. The cases were categorized according to different areas of stomach--cardia, fundus, body and antrum as per International classification of diseases 0-9 (zero-nine) codes. Time trend for each sub site was calculated using one-way ANOVA and Chi-square for trend. Of the 26,886 upper GI endoscopies done over 20 years, 1771 were found to be gastric adenocarcinomas. Gastric antrum was the most common site of cancer over the years (47.8%). There was a significant rising trend for gastric cancer of the cardia without a similar trend for the cancer of the body and antrum during the study period. The sub site-specific time trends of carcinoma stomach are not similar to the pattern seen in western countries. There is a rising trend for the cancer of the cardia with a stable trend for distal cancers over 20 years.


Multiple intra-renal artery aneurysms causing renal obstruction managed with radical nephrectomy.
A 46-year-old male with a history of hypertension presented with symptoms of persistent abdominal fullness and a non-pulsatile abdominal mass. Subsequent computed tomographic angiography studies revealed the presence multiple large renal aneurysms from the segmental branches of the renal artery and an enlarged hydronephrotic kidney with minimal parenchyma. The renal deterioration appeared to be as a result of an obstruction caused by the large intra-renal aneurysms at the level of the renal calyces. Since the right kidney had no function, an open radical nephrectomy was subsequently performed without complications at 3 months follow up.


Uranyl complexation by chloride ions. Formation of a tetrachlorouranium(VI) complex in room temperature ionic liquids [Bmim][Tf2N] and [MeBu3N][Tf2N].
The tetrachlorouranium(VI) complex is formed in [Bmim][Tf2N] and [MeBu3N][Tf2N] from a uranium(VI) solution in the presence of a stoichiometric quantity of chloride ions. The [UVIO2Cl4]2- absorption and emission spectra show bands splitting in comparison with the [UVIO2]2+ spectra, as observed in the solid state, organic solvents, and chloroaluminate-based ionic liquids. The fluorescence lifetime of [UO2Cl4]2- in [MeBu3N][Tf2N] is 0.7 +/- 0.1 mus. The reduction potential of this complex is -1.44 and -1.8 V vs Ag/Ag+ respectively in [Bmim][Tf2N] and [MeBu3N][Tf2N] and does not depend on the chloride concentration. The mechanism proposed for the redox process is a monoelectronic reduction to form [UVO2Cl4]3-, followed by a chemical reaction. The tetrachlorouranium(V) complex seems more stable in [Bmim][Tf2N] than in [MeBu3N][Tf2N]. The electrochemical analysis put in evidence specific interactions of the ionic liquid cation with the uranium anionic species.


Humidity Sensitive Structural Dynamics and Solvatomagnetic Effects in a 3D Co(II)-Based Coordination Polymer.
A chiral Co(II)-based coordination polymer, [Co3(pimda)2(H2O)5] (1, H3pimda = 2-propyl-1H-imidazole-4,5-dicarboxylic acid) with 3D hyperkagomé topology is reported. Upon heating/cooling, the water molecules which are coordinated to a pair of crystallographically symmetric Co(II) ions are removed/recovered discretely in two steps, giving [Co3(pimda)2(H2O)4] (2) and [Co3(pimda)2(H2O)3] (3), which is evidenced by the reversible single-crystal-to-single-crystal (SCSC) structural transformations. As the coordination geometry of the two Co(II) ions changes from octahedron to trigonal bipyramid, obvious color change from pink for 1 to dark violet for 2 and 3 is observed. Further magnetic measurements demonstrate the presence of a solvatomagnetic effect from paramagnets for 1 and 2 to weak ferromagnet for 3. Moreover, as revealed by the variable-temperature crystallographic measurements, the first and second dehydration temperatures could be controlled from 298 K (25 °C) and 383 K (110 °C) sealed in a capillary (high humidity) to 255 K (-18 °C) and 307 K (34 °C) in dry N2 (low humidity), indicating the strong humidity sensitivity of the structural dynamics.


Visual impairment and its associated factors among medical and health sciences students at the University of Gondar, Northwest Ethiopia.
Visual impairment (VI) is a decreased ability to see things which is critical problem for health professionals and students to whom normal vision is essential for their daily activity. If it is not timely managed, visual impairment leads to physical, psychological, and socio-economic malfunctions to the victims and nation. Despite the above impacts, currently there is no study in Ethiopia on this topic. Therefore, this study aimed to determine the prevalence of visual impairment and its associated factors among Medical and Health Science students at the University of Gondar. A cross-sectional study was conducted from January to March 2020 among Medical and Health Science students. After recruiting study participants using systematic random sampling technique, we applied pre-tested self-administered questionnaire for sociodemographic variables and also visual acuity measurement was performed using Snellen chart placed at a distance of 6 meters. Visual acuity tested separately for each eye and for both eyes in a well- illuminated area. Pinhole was used for those participants with a visual acuity of < 6/9. Participants with a presenting visual acuity of < 6/12 in the better eye were diagnosed as having visual impairment. Epi data version 3.1 and stata version 14 were used for data entry and statistical analysis, respectively. Binary logistic regression was used, and the Adjusted Odds Ratio (AOR) with the 95% Confidence Interval (CI) was reported to declare the statistical significance and strength of association between VI and independent variables. A total of 654 students were screened for visual acuity. The prevalence of visual impairment was 12.5% (95% CI: 10.21, 15.31). Age above 25 years (AOR = 1.8; 95% CI: 1.02, 3.26) and current alcohol drinking (AOR = 2.9; 95% CI: 1.7, 5.00), were statistically significant factors of visual impairment. The prevalence of visual impairment among medical and health science students was high. Age of study participant and current alcohol consumption were statically significant factors. This study warrants the routine screening of Medical and Health science students for visual impairment.


Restraint stress on female mice diminishes the developmental potential of oocytes: roles of chromatin configuration and histone modification in germinal vesicle stage oocytes.
The mechanisms by which restraint stress impairs oocyte developmental potential are unclear. Factors causing differences between the developmental potential of oocytes with surrounded nucleolus (SN) and that of oocytes with nonsurrounded nucleolus (NSN) are not fully characterized. Furthermore, the relationship between increased histone acetylation and methylation and the increased developmental competence in SN oocytes is particularly worth exploring using a system where the SN configuration can be uncoupled (dissociated) from increased histone modifications. In this study, female mice were subjected to restraint for 24 or 48 h or for 23 days before being examined for oocyte chromatin configuration, histone modification, and development in vitro and in vivo. Results showed that restraint for 48 h or 23 days impaired NSN-to-SN transition, histone acetylation and methylation in SN oocytes, and oocyte developmental potential. However, whereas the percentage of stressed SN oocytes returned to normal after a 48-h postrestraint recovery, neither histone acetylation/methylation in SN oocytes nor developmental competence recovered following postrestraint recovery with equine chorionic gonadotropin (eCG) injection. Priming unstressed mice with eCG expedited oocyte histone modification to an early completion. Contrary to the levels of acetylated and methylated histones, the level of phosphorylated H3S10 increased significantly in the stressed SN oocytes. Together, the results suggest that 1) restraint stress impaired oocyte potential with disturbed histone modifications; 2) SN configuration was uncoupled from increased histone acetylation/methylation in the restraint-stressed oocytes; and 3) the developmental potential of SN oocytes is more closely correlated with epigenetic histone modification than with chromatin configuration.


Role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis in decompensated cirrhosis.
Objective: To assess the role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis (SBP) in decompensated cirrhosis.Methods: Ascites samples, as well as demographic and laboratory data, were collected at admission from patients with decompensated cirrhosis. Ascitic endocan, tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by ELISA. The influencing factors of SBP, the correlation of ascitic endocan with other inflammatory indicators, and the diagnostic value of ascitic endocan for SBP were analyzed.Results: A total of 167 patients were enrolled, 39 with the SBP group and 128 in the non-SBP group. Ascitic endocan, TNF-α, and IL-6 levels were significantly higher in the SBP group than in the non-SBP group (p < 0.001). Multivariate analysis demonstrated that ascitic endocan was an independent risk factor for SBP [OR = 1.006 (95% CI: 1.002-1.011); p < 0.001]. Endocan was positively correlated with ascites polymorphonuclear leukocytes, TNF-α, and IL-6. ROC curve analysis showed that ascitic endocan had an AUC of 0.805 for the diagnosis of SBP (p < 0.001) and had a sensitivity of 82.1% and specificity of 73.4% when the cut-off value was 295.011 pg/ml.Conclusions: Ascitic endocan level is an independent risk factor and a valuable diagnostic indicator for SBP in decompensated cirrhosis.


Characterization of a human colorectal carcinoma cell line with acquired resistance to flavopiridol.
Flavopiridol is a broad-spectrum inhibitor of cyclin-dependent kinases (cdks) and represents the first in this anticancer class to enter clinical trials. In anticipation of the likelihood that, as with other cancer drugs, acquired resistance may limit the drug's efficacy, an acquired resistance model has been established by in vitro drug exposure of the human colon carcinoma cell line HCT116. This stably resistant line, possessing 8-fold resistance to flavopiridol, showed a lack of cross-resistance to the anticancer agents etoposide, doxorubicin, paclitaxel, topotecan, and cisplatin, and notably to other chemical classes of cdk inhibitors: the aminopurines roscovitine and purvalanol A, 9-nitropaullone, and hymenialdisine. Resistance did not seem to be related to differences in the levels of multidrug resistance drug efflux proteins, P-glycoprotein, and MRP1. Moreover, there were no changes in overall drug accumulation between the resistant and sensitive cell lines. Flavopiridol induced cell cycle arrest, apoptosis, and inhibition of retinoblastoma gene product phosphorylation on serine 780 in both parental and resistant lines, but the latter required 8-fold higher concentrations to achieve these effects. Cyclin E protein levels and cyclin E-associated kinase activity were increased in the resistant line, suggesting that overexpression of cyclin E may be the mechanism of resistance to flavopiridol. However, transfection of cyclin E to increase expression of this protein did not result in an increase in resistance to flavopiridol. Thus, up-regulation of cyclin E alone does not seem to cause resistance to this cdk inhibitor.


Fine-needle aspiration cytology of prostate: experience in a nonacademic practice.
Fine-needle aspiration cytology of the prostate is becoming increasingly accepted and used in the United States. This is a report of the experience of a nonacademic practice in which the aspirations were performed by a number of urologists, usually in the office, and were interpreted by a number of pathologists with varying degrees of experience in cytopathology. Of 187 patients, 159 had smears adequate for evaluation, and 99 had histologic/substantiating clinical follow-up for comparison. The resulting specificity was 97%, sensitivity was 91%, and the false-negative rate was 9%. These figures compare favorably with those reported in studies from academic university-based practices.


Fodinicola feengrottensis gen. nov., sp. nov., an actinomycete isolated from a medieval mine.
A filamentous, Gram-positive actinobacterium was isolated from acidic rocks in a medieval alum slate mine and was investigated by means of a polyphasic taxonomic approach. A 16S rRNA gene sequence similarity study indicated that strain HKI 0501(T) forms an individual line of descent and is related to certain members of the suborder Frankineae, order Actinomycetales (<95 % sequence similarity). Distance-matrix and neighbour-joining analyses set the branching point of the novel isolate between two clades, one being represented by members of the genus Cryptosporangium (family 'Kineosporiaceae') and the other by members of the genera Frankia and Acidothermus (family Frankiaceae and family Acidothermaceae, respectively). The organism had meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan and xylose as the characteristic cell-wall sugar. The muramic acid in the peptidoglycan was found to be N-acetylated. The major menaquinones were MK-9(H(4)), MK-9(H(6)) and MK-9(H(8)) and the fatty acid profile was characterized by the predominance of iso-C(16 : 0), 10-methyl C(17 : 0), C(17 : 1) cis9 and 10-methyl iso-C(18 : 0). The polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol and several unknown phospholipids and glycolipids. Mycolic acids were absent. The DNA G+C content was 65 mol%. The distinct phylogenetic position and the phenotypic markers that clearly separate the novel organism from all other members of the suborder Frankineae indicate that strain HKI 0501(T) represents a novel genus and species, for which the name Fodinicola feengrottensis gen. nov., sp. nov. is proposed. The type strain of Fodinicola feengrottensis is HKI 0501(T) (=DSM 19247(T) =JCM 14718(T)).


[Effects of epigallocatechin-3-gallate modification on the bonding stability of an etch-and-rinse adhesive to intraradicular dentin].
Objective: To evaluate the effects of epigallocatechin-3-gallate (EGCG) modification on the bonding stability of an etch-and-rinse adhesive to intraradicular dentin, and to find a new strategy to improve the stability of bonding interface. Methods: EGCG was incorporated into Single Bond 2 (SB2) with the concentration of 200 mg/L and 400 mg/L respectively to fabricated experimental adhesives group A and group B, while Single Bond 2 without EGCG was used as control group. Laser scanning confocal microscope (LSCM) and scanning electron microscope (SEM) were used to observe the bacterial biofilm adherent to the surface of the cured adhesive. Micro-Raman spectrum was used to test the degree of conversion (DC) of adhesives. The push-out bond strength of instant testing and aging with thermocycling for 5 000 times were also tested. Results: Group A and group B showed inhibiting effect on the biofilm formation of Enterococcus faecalis and performed better with higher concentration. No significant differences were detected in DC among group A ([69.73±0.68]%), group B ([69.03±1.65]%) and control group ([70.06±1.62]%) (P>0.05), and the immediate push-out bond strength of control group ([10.45±2.00] MPa) was not compromised compared to group A ([10.02±2.03] MPa) and group B ([9.95±3.03] MPa) (P>0.05). After thermocycling for 5 000 times, group A ([7.01±1.39] MPa) and group B ([7.62±1.88] MPa) showed significantly higher push-out bond strength than control group did ([5.08±1.56] MPa) (P<0.05). Conclusions: EGCG modified etch-and-rinse adhesives showed anti-bacterial effect and enhanced bonding stability of intraradicular dentin-adhesive interfaces.


[Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in 2 patients with symptoms of Reye syndrome].
Two patients are described, who were submitted to our clinic with signs of the Reye syndrome. In both cases a medium-chain acylcoënzyme A dehydrogenase (MCAD) deficiency was diagnosed. This is an inborn error of the mitochondrial beta-oxidation of fatty acids. Stimulation of the fatty acid oxidation in case of this enzyme deficiency might result in a metabolic crisis presenting clinically as the Reye syndrome. The structure of a fatty acid molecule and the process of beta-oxidation of fatty acids are discussed shortly in this article. The most important clinical, diagnostic and therapeutic aspects of MCAD deficiency are presented next. A MCAD deficiency seems not to be rare in cases presenting as a Reye-like syndrome. Accurate distinction between MCAD deficiency and Reye syndrome can be made by gas chromatographic together with mass spectrometric analysis of urine. Investigation of so called crisis urine is of utmost importance. Confirmation of the diagnosis needs measuring of MCAD enzyme activity in cultured fibroblasts or in leucocytes of the patient.


[Not Available].
The cultural history of alcoholic fermentation goes back to very early periods of human being. But only in the 19th century the nature of the biological production of alcohol was discovered. In that time chemistry and botany had a different, complementary view to alcoholic fermentation. While the positions of chemists are well-known and much discussed in the historiography of science the contribution of botanists to fermentation research is almost entirely forgotten nowadays. The work of the mycologist Oscar Brefeld, who studied yeast fermentation from 1873 to 1876, illustrates the special botanical view to the ontogenetical side of alcoholic fermentation, to morphlogical and physiological differences between growing and dying, fermenting and fermented yeast cells, and to the energetic and ecological role of fermentation as well as its universality in vegetable kingdom.


Nano-approaches and Recent Advancements in Strategies to Combat Challenges Associated with Thyroid Cancer Therapies.
The prevalence of thyroid cancer (TC) is more common in women and is up to 43% in patients aged between 45-65 years. The battle against TC is hampered by the lack of effective diagnostic and therapeutic approaches. The effectiveness of surgical procedures, such as thyroidectomy and nutraceutical treatments, are accompanied by several difficulties and still require further research. Alternatively, the DNA-damaging traditional model of chemotherapy is linked to poor solubility, untoward systemic effects, and associated cytotoxicity, instituting an urgent need to establish a specialized, factual, and reliable delivery tool. In order to overcome the limitations of conventional delivery systems, nanotechnology-based delivery tools have shown the potential of articulating endless inherent implementations. The probable benefits of emerging nanotechnology-based diagnostic techniques include rapid screening and early illness diagnosis, which draws investigators to investigate and assess the possibility of this treatment for TC. Subsequently, organic (e.g., liposomes, polymer-based, and dendrimers) and inorganic (e.g., gold, carbon-based, mesoporous silica, magnetic, and quantum dots) NPs and hybrids thereof (liposome-silica, chitosan-carbon, and cell membrane-coated) have been projected for TC biomarker screening, therapy, and detection, providing better outcomes than traditional diagnostic and treatment techniques. Therefore, this review aims to offer a broad perspective on nanoplatform in TC, accompanied by present and potential future treatment options and screening techniques. The goal of cancer therapy has traditionally been to "search a thorn in a hayloft"; therefore, this article raises the possibility of treating TC using nano-oncotherapeutics, which might be useful clinically and will encourage future researchers to explore this tool's potential and drawbacks.


Identification of novel genes in testicular cancer microenvironment based on ESTIMATE algorithm-derived immune scores.
Testicular cancer is the most common solid malignancy among young men. We downloaded data of testicular cancer patients from The Cancer Genome Atlas database to find novel genes in the testicular cancer microenviroment based on ESTIMATE algorithm-derived immune scores. A total of 156 cases of testicular cancer were included in this study and 165 cases of normal testicular tissues were used. We divided the testicular cancer patients into high- and low-score groups based on their immune scores. We identified 1,226 differentially expressed genes (fold change > 2, false discovery rate < 0.05), including 688 downregulated genes and 538 upregulated genes, between these two groups. The top Gene Ontology terms were involved in the immune response-regulating cell surface receptor signaling pathway, immune response-activating cell surface receptor signaling pathway, external side of the plasma membrane, and receptor ligand activity. By performing the Kyoto Encyclopedia of Genes and Genomes analysis, we demonstrated that cAMP signaling pathway was highly enriched among these differentially expressed genes. High expression of LINC01564, LINC02208, ODAM, RNA5SP111, and RNU6-196P were found to be associated with poor overall survival. The expression of genes was further validated by the Human Protein Atlas and only ALB and IFNG were demonstrated to be differentially expressed between testis tissue and testicular cancer tissue.


Two subgingival plaque-sampling strategies used with RNA probes.
The purpose of this study was to compare the results of microbiological RNA-probe analysis after subgingival plaque sampling applying two different strategies. In 220 patients, clinical examinations were obtained prior to commencement of therapy for aggressive or generalized severe chronic periodontitis (n = 113), after combined mechanical and antibiotic anti-infective periodontal therapy (n = 43), or because of periodontal pockets despite adequate therapy (n = 64). Subgingival plaque samples were obtained from the three pockets with the deepest probing depths. Two sterile paper points were inserted simultaneously into the periodontal pockets. One paper point from each pocket was put into a separate transport vial; the second paper point was pooled (multiple site test [MT3]) with paper points from each of the two other sampling sites from the respective patient into a transport vial. The content of each vial was analyzed separately for Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Porphyromonas gingivalis, and Treponema denticola (Td) with a commercially available RNA-probe test. For all tested pathogens, log-transformed numbers of bacteria were higher in pooled samples compared to the mean values for the separate samples (P < or =0.01). However, for Td only, statistically significant differences in frequency were seen between the separate samples and MT3. These findings were observed over all samples as well as after evaluation of subgroups separately. Pooling of plaque samples increased the bacterial counts per analysis compared to separate samples and thus may increase the probability of detecting existing pathogens. However, this observation only was statistically significant for the frequency of Td.


Obliteration of the tympanomastoid cavity: long term results of the Rambo operation.
Radical mastoidectomy and tympanomastoid obliteration with fat tissue, also called the Rambo operation, is proposed to those patients suffering chronic middle-ear disease, with or without cholesteatoma, who have no useful hearing in an ear which cannot be kept dry despite all conservative treatment. We analysed retrospectively a series of 46 patients operated upon in our department. Information recorded included the surgical indications, surgical observations, post-operative care and complications. All patients were invited to comment on their long term anatomical and functional results and to express their degree of satisfaction with the procedure. Recurrent infectious episodes were observed in seven cases. Residual cholesteatoma were observed in three cases. After treatment, these patients did not present with further complications. One case presented with multiple episodes of infection with recurrences of cholesteatoma and finally had the obliterated cavity transformed into an open cavity again. For most of the patients, in the long term (i.e. one to 23 years post-operatively (mean eight years)), the operation resulted in a dry ear, ending the need for frequent consultations to clean and disinfect diseased ears or open cavities. Obliteration of the tympanomastoid cavity, as proposed by Tom Rambo, shortens considerably the post-operative care period, in comparison with canal wall down mastoidectomy, and is therefore indicated if no serviceable hearing can be expected. In the long term, the rate of complications is low and patients are satisfied.


Relationships Among Cognitive Function, Frailty, and Health Outcome in Community-Dwelling Older Adults.
Frailty and cognitive impairment are significant problems faced by older adults, which have a significant impact on their activities of daily living, social activities, and quality of life. Cross-sectional study. A total of 252 older adults in two communities in Yangzhou were randomly selected. The cognitive function of the elderly was assessed using the Memory and Executive Screening (MES). The frailty phenotype was used to evaluate the frail situation of older adults. The activity of daily living (ADL), functional activities questionnaire (FAQ), and European quality of 5-dimensions (EQ-5D) were used to evaluate health outcomes in the elderly. SEM was used to explore the direct and indirect relationship among cognitive function, frailty and health outcomes. There was a significant direct correlation between cognitive function and frailty; the direct effect was -0.521. The influence path of cognitive function on health outcomes included direct and indirect effects; the total effect was -0.759. The effect of frailty on health outcomes included direct and indirect effects; the total effect was 0.440. According to SEM, cognitive function interacts with frailty and may reduce the quality of life, the ADL, and social activities among older adults directly and indirectly, so future assessments of older adults should consider both cognitive function and frailty, so as to further improve the health outcome of the elderly. When formulating relevant intervention measures in the future, we need to consider that it cannot only improve the cognitive function, but also improve the frail situation, so as to jointly improve the health outcomes of older adults.


Bullying investigation reveals shocking levels of harassment.
AFTER CARE Quality Commission (CQC) inspectors recorded allegations last January of bullying among staff at Barts Health NHS Trust, London, the organisation took the unusual step of commissioning an independent investigation to find out exactly what was going on.


Production of polymalic acid and malic acid by Aureobasidium pullulans fermentation and acid hydrolysis.
Malic acid is a dicarboxylic acid widely used in the food industry and also a potential C4 platform chemical that can be produced from biomass. However, microbial fermentation for direct malic acid production is limited by low product yield, titer, and productivity due to end-product inhibition. In this work, a novel process for malic acid production from polymalic acid (PMA) fermentation followed by acid hydrolysis was developed. First, a PMA-producing Aureobasidium pullulans strain ZX-10 was screened and isolated. This microbe produced PMA as the major fermentation product at a high-titer equivalent to 87.6 g/L of malic acid and high-productivity of 0.61 g/L h in free-cell fermentation in a stirred-tank bioreactor. Fed-batch fermentations with cells immobilized in a fibrous-bed bioreactor (FBB) achieved the highest product titer of 144.2 g/L and productivity of 0.74 g/L h. The fermentation produced PMA was purified by adsorption with IRA-900 anion-exchange resins, achieving a ∼100% purity and a high recovery rate of 84%. Pure malic acid was then produced from PMA by hydrolysis with 2 M sulfuric acid at 85°C, which followed the first-order reaction kinetics. This process provides an efficient and economical way for PMA and malic acid production, and is promising for industrial application.


Early archives of genetically-restricted proviral DNA in the female genital tract after heterosexual transmission of HIV-1.
In order to characterize human immunodeficiency virus type 1 (HIV-1) variants that are transmitted in women via heterosexual intercourse, the env V1-V3 sequences of HIV-1 provirus (DNA) and free virus (RNA) in paired samples of blood and cervicovaginal secretions of untreated chronically and primary infected African women were compared. Env RNA sequences retrieved from plasma and genital compartments formed a single cluster in primary infection. In contrast, env RNA sequences from these two compartments were distinct in chronically infected women. Analysis of proviral DNA of primary infected women showed that most HIV-1 sequences derived from the genital epithelia form independent clusters from HIV-1 sequences of DNA from peripheral blood mononuclear cells and RNA recovered from plasma and genital secretions. Similarly, the analysis of proviral DNA in the genital compartment of chronically infected women showed the persistence of genetically-restricted cluster of HIV-1. These observations indicate that a viral subpopulation is archived as proviral DNA in the female genital tract early in primary infection, and suggest that HIV-1 variants from the male donor are selected in the female mucosal site during male to female transmission of HIV-1.


Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes.
Parasitic infection with Plasmodium falciparum is responsible for the most severe form of human malaria in which patients suffer from periodic fever. It is well established that during intra-erythrocytic maturation of the parasite in the red blood cell (RBC), the RBC becomes significantly more cytoadhesive and less deformable; these and other biochemical factors together with human host factors such as compromised immune status are important contributors to the disease pathology. There is currently substantial interest in understanding the loss of RBC deformability due to P. falciparum infection, but few results are available concerning effects of febrile conditions or parasitization on RBC membrane rheology. Here, for the first time, we report rheology of the single, isolated RBC with and without P. falciparum merozoite invasion, spanning a range from room temperature to febrile conditions (41 degrees C), over all the stages of parasite maturation. As expected, stiffness increased with parasite maturation. Surprisingly, however, stiffness increased acutely with temperature on a scale of minutes, particularly in late trophozoite and schizont stages. This acute stiffening in late falciparum stages may contribute to fever-dependent pathological consequences in the microcirculation.


Addendum to Killeen's (2019) Bidding for Delayed Rewards.
Killeen (2019) portrayed an intimate relation between diverse economic indices, in particular compensation functions, discount functions, and demand functions. The article bemused some experts, however, by its counterintuitive prediction of an increase in the amount bid as the delay increased. Furthermore, the article failed to provide an explicit treatment of the small-soon versus large-late choice paradigm, to cite several papers that provided precedent for the current work, and to demonstrate the adequacy of his expenditure functions for data on purchasing decisions. These shortcomings are remedied in the current note, and some additional extensions offered.


Coil embolization of ruptured middle cerebral artery aneurysms in the first 2 months of life. Report of two cases.
Intracranial artery aneurysms are very rare in infants. There have been no previous reports of coil embolization to branches of the middle cerebral artery (MCA) in infants. The authors describe successful embolization of ruptured aneurysms of the right frontoopercular MCA branch in a 31-day-old infant, and of the left sylvian MCA branch in a 54-day-old infant. One of the cases involves a dissection flap. The authors also review cases in which coil embolization was used for intracranial aneurysms in the first 2 months of life.


Transmitter interactions in the central cholinergic control of blood pressure regulation.
There are at least five mechanisms by which the central nervous system regulates neural and humoral systems that control the blood pressure (BP). Particular attention has been paid to central cholinergic-adrenergic interactions in the regulation of BP. Physostigmine and other anticholinesterases which penetrate the blood-brain barrier, both carbamates and organophosphates, produce an increase of BP. This effect can be abolished by atropine, but not by methylatropine. The available evidence indicates that physostigmine and other AChE inhibitors initially produce an activation of central muscarinic receptors, which subsequently leads to an increase of the peripheral adrenergic activity. The hypertensive response to physostigmine is possible only if a functionally competent ChE is present in the brain. This effect of physostigmine is regularly associated with a dose-related increase in the neural activity in the preganglionic fibers of the cervical sympathetic nerve. BP rise after physostigmine is significantly less in immunosympathectomized animals and almost completely abolished after chemical sympathectomy. Physostigmine significantly increased the plasma concentration of catecholamines. After electrocoagulation of the locus coeruleus, not only did a significant decrease occur in the basic level of noradrenaline in plasma, but there was also a strong depression of the noradrenaline plasma response to physostigmine and immobilization. Physostigmine increased lipolysis and glycogenolysis, whereas neostigmine did not produce any change. Several directly acting cholinergic agonists alter the functions of the cardiovascular system when injected directly into the cerebral ventricular system, or directly into various brain regions. The most probable sites of action of AChE inhibitors and directly acting cholinergic agonists are the locus coeruleus, the nucleus tractus solitarii and the rostral ventrolateral medulla (RVLM). The primary activation of the cholinergic synapse is believed to take place in RVLM. Met-enkephalin, Leu-enkephalin and beta-endorphin, when applied exogenously, depress or even abolish the hypertensive effect of physostigmine. The same type of response was obtained after application of substances which inhibit the enkephalin-degrading enzymes (bestatin, phosphoramidon). Thus, the exogenous or endogenous enkephalins activate the opioid receptors in the brain and at the same time produce a depression of the cholinergic-adrenergic interaction in the central nervous system, which is a prerequisite for the hypertensive response to physostigmine. The functional role of the central cholinergic mechanisms in BP control under physiological conditions has not been established with certainty. These mechanisms might have a more significant role under pathological or homeostatic disturbances. For example, physostigmine showed a life-saving effect in acute hypovolemic shock in rabbits.


Effect of altered environmental temperature on established infection.
An alteration of ten degrees Celsius in environmental temperature significantly alters the mortality from severe established Escherichia coli and Staphylococcus aureus infection in mice. Many patients with severe infection are nursed in wards without air conditioning. It is suggested that even modest levels of environmental stress may influence their recovery.


Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission.
The terminal step in cytokinesis, called abscission, requires resolution of the membrane connection between two prospective daughter cells. Our previous studies demonstrated that the coiled-coil protein centriolin localized to the midbody during cytokinesis and was required for abscission. Here we show that centriolin interacts with proteins of vesicle-targeting exocyst complexes and vesicle-fusion SNARE complexes. These complexes require centriolin for localization to a unique midbody-ring structure, and disruption of either complex inhibits abscission. Exocyst disruption induces accumulation of v-SNARE-containing vesicles at the midbody ring. In control cells, these v-SNARE vesicles colocalize with a GFP-tagged secreted polypeptide. The vesicles move to the midbody ring asymmetrically from one prospective daughter cell; the GFP signal is rapidly lost, suggesting membrane fusion; and subsequently the cell cleaves at the site of vesicle delivery/fusion. We propose that centriolin anchors protein complexes required for vesicle targeting and fusion and integrates membrane-vesicle fusion with abscission.


Multiplex Surface Plasmon Resonance Imaging-Based Biosensor for Human Pancreatic Islets Hormones Quantification.
Diabetes arises from secretory defects in vascularized micro-organs known as the islets of Langerhans. Recent studies indicated that furthering our understanding of the paracrine effect of somatostatin on glucose-induced insulin secretion could represent a novel therapeutic avenue for diabetes. While many research groups are interested in insulin and glucagon secretion, few are particularly focused on studying the paracrine interaction in islets' cells, and none on monitoring a secretory fingerprint that contemplates more than two hormones. Surface plasmon resonance imaging can achieve high-throughput and multiplexed biomolecule quantification, making it an ideal candidate for detection of multiple islet's secretion products if arrays of hormones can be properly implemented on the sensing surface. In this study, we introduced a multiplex surface plasmon resonance imaging-based biosensor for simultaneous quantification of insulin, glucagon, and somatostatin. Performing this multiplex biosensing of hormones was mainly the result of the design of an antifouling sensing surface comprised by a mixed self-assembly monolayer of CH3O-PEG-SH and 16-mercaptohexadecanoic acid, which allowed it to operate in a complex matrix such as an islet secretome. The limit of detection in multiplex mode was 1 nM for insulin, 4 nM for glucagon, and 246 nM for somatostatin with a total analysis time of 21 min per point, making our approach the first reporting a label-free and multiplex measurement of such a combination of human hormones. This biosensor holds the promise of providing us with a mean for the further understanding of the paracrine effect of somatostatin on glucose-induced insulin secretion and consequently help develop novel therapeutic agents for diabetes.


Superhydrophilic In-Situ-Cross-Linked Zwitterionic Polyelectrolyte/PVDF-Blend Membrane for Highly Efficient Oil/Water Emulsion Separation.
Because of weak hydrophilicity, membranes always experience fouling problems during separations. This phenomenon seriously impedes the development of membrane technologies for practical industrial-oil wastewater treatment. In this work, we successfully fabricated a superhydrophilic zwitterionic poly(vinylidene fluoride) (PVDF) membrane using a two-part process with an in situ cross-linking reaction during nonsolvent-induced phase separation and a subsequent sulfonation reaction. To prepare this zwitterionic PVDF membrane, a copolymer poly(dimethylaminoethyl methacrylate-co-2-hydroxyethyl methacrylate) (PDH) was synthesized as a zwitterionic polymer precursor and used as an additive in membrane preparation. This zwitterionic additive is well-immobilized in the membrane using in situ cross-linking to ensure the long-term stability of the membrane, and subsequent sulfonation transforms the precursor to a zwitterionic polymer to produce a superhydrophilic membrane. This superhydrophilic zwitterionic PVDF membrane exhibits high water permeation flux and good antifouling properties for separating oil-in-water emulsions with high separation efficiency.


MR imaging features of breast lymphoma.
Mammographic, ultrasonographic and MR imaging features in a patient with non-Hodgkin's lymphoma are reported in this paper. Mammography and ultrasonography revealed ill-defined, round masses with skin thickening. Precontrast T1W images demonstrated multiple well-defined, hypointense masses, which showed rapid rim enhancement in dynamic postcontrast sequence. The enhancement rate indicated malignant pathology. MR imaging demonstrated the extent of involvement more apparently than conventional imaging. Although, not pathognomonic for lymphoma, MR imaging may be helpful in evaluation and follow-up of breast masses in patients with previous lymphoma.


Prevalence and Correlates of Diabetes Prevention Program Referral and Participation.
As the burden of type 2 diabetes rises, there is increasing focus on improving the reach of evidence-based lifestyle interventions. Using nationally representative data, this study identifies how frequently at-risk adults are being referred to and participating in diabetes prevention programming, and explores correlates of referral, participation, and interest. Data from the 2016 National Health Interview Survey, a cross-sectional survey of U.S. households, were analyzed in 2017. The study population consisted of adults (aged ≥18 years) without a self-reported diabetes diagnosis, who were likely eligible for diabetes prevention programming based on (1) self-reported diagnosis of prediabetes or gestational diabetes, and (2) meeting BMI criteria. Prevalence of self-reported referral and participation was determined, and sociodemographic correlates of referral, participation, and interest were characterized through multivariable logistic regression analyses. The study population consisted of 2,341 adults. The majority were female (63%), white (74.6%), non-Hispanic (83.4%), and aged ≥45 years (68.2%). A total of 4.2% reported ever being referred to a 12-month prevention program and only 2.4% reported ever participating. In multivariable logistic regression, race was correlated with referral (black and Asian adults more likely to report referral) and age was positively correlated with participation. More than 25% of adults who were never referred or participated reported an interest in engaging in programming. Although more than one quarter of adults likely eligible for diabetes prevention programming express interest in participating, few are being referred and fewer still have participated. This underscores the need for efforts to enhance program referral and access.


Solution and solid-state spin-crossover behavior in a pseudotetrahedral d7 ion.
This Communication describes a pseudotetrahedral d7 complex, [PhBP3]Co(OSiPh3), that exhibits thermally induced spin-crossover both in solution and in the solid state. Magnetic crossover behavior is achieved by confluence of the X-type ligand and the tripodal auxiliary employed. Four-coordinate platforms of the present geometry type may offer a new approach to magnetic spin-crossover behavior distinct from their electronically related pseudooctahedral counterparts.


Accelerometer-Measured Physical Activity Data Sets (Global Physical Activity Data Set Catalogue) That Include Markers of Cardiometabolic Health: Systematic Scoping Review.
Cardiovascular disease accounts for 17.9 million deaths globally each year. Many research study data sets have been collected to answer questions regarding the relationship between cardiometabolic health and accelerometer-measured physical activity. This scoping review aimed to map the available data sets that have collected accelerometer-measured physical activity and cardiometabolic health markers. These data were then used to inform the development of a publicly available resource, the Global Physical Activity Data set (GPAD) catalogue. This review aimed to systematically identify data sets that have measured physical activity using accelerometers and cardiometabolic health markers using either an observational or interventional study design. Databases, trial registries, and gray literature (inception until February 2021; updated search from February 2021 to September 2022) were systematically searched to identify studies that analyzed data sets of physical activity and cardiometabolic health outcomes. To be eligible for inclusion, data sets must have measured physical activity using an accelerometric device in adults aged ≥18 years; a sample size >400 participants (unless recruited participants in a low- and middle-income country where a sample size threshold was reduced to 100); used an observational, longitudinal, or trial-based study design; and collected at least 1 cardiometabolic health marker (unless only body mass was measured). Two reviewers screened the search results to identify eligible studies, and from these, the unique names of each data set were recorded, and characteristics about each data set were extracted from several sources. A total of 17,391 study reports were identified, and after screening, 319 were eligible, with 122 unique data sets in these study reports meeting the review inclusion criteria. Data sets were found in 49 countries across 5 continents, with the most developed in Europe (n=53) and the least in Africa and Oceania (n=4 and n=3, respectively). The most common accelerometric brand and device wear location was Actigraph and the waist, respectively. Height and body mass were the most frequently measured cardiometabolic health markers in the data sets (119/122, 97.5% data sets), followed by blood pressure (82/122, 67.2% data sets). The number of participants in the included data sets ranged from 103,712 to 120. Once the review processes had been completed, the GPAD catalogue was developed to house all the identified data sets. This review identified and mapped the contents of data sets from around the world that have collected potentially harmonizable accelerometer-measured physical activity and cardiometabolic health markers. The GPAD catalogue is a web-based open-source resource developed from the results of this review, which aims to facilitate the harmonization of data sets to produce evidence that will reduce the burden of disease from physical inactivity.


[Immunochemical properties of short recombinant polypeptides of proteine of, the West Nile virus bearing epitopes of domains I and II].
Fragments cDNA (nt 935-1475, 1091-1310, 935-1193) encoding N-terminal part of protein E of West Nile virus (WNV), strain LEIV-Vlg99-27889-human were obtained and cloned. Recombinant polypeptides of glycoprotein E (E1-86, E53-126, E1-180) of the WNV with corresponding amino acid sequence to the cloned fragments of cDNA and modeling the epitopes of domains I and II of surface glycoprotein E were purified by affinity chromatography. Twelve types of monoclonal antibodies (MAbs) created in our laboratory against recombinant polypeptide E1-180 interact with glycoprotein E of the WNV as results of Western blot and ELISA that is demonstrating an similarity of chemical structure of short recombinant polypeptides and corresponding amino acid sequence regions of WNV protein E. Analysis of interactions of MAbs with short recombinant polypeptides and protein E of tick-borne encephalitis virus let us reveal no less than six epitopes within domains I and II of glycoprotein E of the WNV. No less than seven types of MAbs to 86-126 aa region of the domain II were found where located peptide providing fusion of virus--cell membranes (98-110 aa). The epitope for anti-receptor MAbs 10H10 within 53-86 aa region of domain II of protein E of the WNV was mapped and it shows that the fusion peptide and co-receptor of protein E for cellular laminin-binding protein (LBP) are spatial nearness. X-ray model of protein E let us suppose that bc-loop (73-89 aa) of domain II interacts with LBP and together with cd-loop (fusion peptide) determines an initial stages of penetration virions into cell.


Integrating Genetic, Environmental, and Social Networks to Reveal Transmission Pathways of a Dolphin Foraging Innovation.
Cultural behavior, which is transmitted among conspecifics through social learning [1], is found across various taxa [2-6]. Vertical social transmission from parent to offspring [7] is thought to be adaptive because of the parental generation being more skilled than maturing individuals. It is found throughout the animal kingdom, particularly in species with prolonged parental care, e.g., [8, 9]. Social learning can also occur among members of the same generation [4, 10, 11] or between older, non-parental individuals and younger generations [7] via horizontal or oblique transmission, respectively. Extensive work on primate culture has shown that horizontal transmission of foraging behavior is biased toward species with broad cultural repertoires [12] and those with increased levels of social tolerance [13, 14], such as great apes. Vertical social transmission has been established as the primary transmission mechanism of foraging behaviors in the Indo-Pacific bottlenose dolphin (Tursiops aduncus) population of Shark Bay, Western Australia [6, 9, 15, 16]. Here, we investigated the spread of another foraging strategy, "shelling" [17], whereby some dolphins in this population feed on prey trapped inside large marine gastropod shells. Using a multi-network version of "network-based diffusion analysis" (NBDA), we show that shelling behavior spreads primarily through non-vertical social transmission. By statistically accounting for both environmental and genetic influences, our findings thus represent the first evidence of non-vertical transmission of a foraging tactic in toothed whales. This research suggests there are multiple transmission pathways of foraging behaviors in dolphins, highlighting the similarities between cetaceans and great apes in the nature of the transmission of cultural behaviors. VIDEO ABSTRACT.


Latex hypersensitivity among allergic Egyptian children: relation to parental/self reports.
Latex allergy is one of the major health concerns and allergic reactions to latex may be serious and fatal. In this study, we sought to determine the frequency of latex hypersensitivity in a group of allergic Egyptian infants and children and its relation to the history provided by the patients or caregivers. We consecutively enrolled 400 patients with physician diagnosed allergic diseases. The study measurements included clinical evaluation for the site and duration of allergy, history suggestive of latex allergy, family history of allergy, and skin prick testing (SPT) using a commercial latex extract. The study revealed that 16/400 (4%) patients had positive SPT; 11 of them only had positive history of sensitivity to latex. Positive latex SPT was reported in 3.4% (11/326) of patients with bronchial asthma, 5.9% (7/118) of patients with skin allergy, and 4.5% (2/44) of patients with allergic rhinitis. SPT was positive in 7.4% (4/54) of patients with concomitant respiratory and skin allergy. Latex SPT was more specific than sensitive (97.69% and 77.77%, resp.) with a negative predictive value of 99.47%. Although underrecognized, latex is an important allergen in the pediatric age group with a sensitization frequency of 4% among allergic children. It was observed to be especially associated with multiple allergic diseases coexisting in the same patient. Pediatric allergologists should educate their patients on latex allergy and encourage the use of latex-free products.


Radiographic and computed tomographic appearance of tracheal collapse with axial rotation in four dogs.
Tracheal collapse with axial rotation was diagnosed in four dogs. Radiographs showed increased tracheal dorsoventral height at the caudal cervical and thoracic inlet with and apparent intraluminal soft tissue opacity, mimicking an intraluminal tracheal foreign body. Computed tomography confirmed dorsoventral tracheal collapse with axial rotation in all dogs. Short-term outcome with medical treatment of all dogs was excellent.


Nicotine Increases Alcohol Intake in Adolescent Male Rats.
Background: Use of alcohol and tobacco, the two most concurrently abused drugs, typically first occurs during adolescence. Yet, there have been no systematic analyses of ethanol (EtOH) and nicotine (Nic) interactions during adolescence. Recent animal studies report that kappa-opioid (KOR) receptor activation mediates age differences in drug reinforcement. Our hypothesis is that concurrent self-administration of EtOH and Nic will be greater in adolescent rats because of age differences in KOR function. Furthermore, exposure to alcohol and nicotine during adolescence has been reported to increase EtOH intake in adulthood. We performed a longitudinal animal study and hypothesized adolescent rats allowed to self-administer nicotine would drink more alcohol as adults. Methods: Adolescent, postnatal day (P)32, and adult (P90) male and female Sprague-Dawley rats were allowed to self-administer EtOH, Nic, or a combination of both, EtOH+Nic, in an intravenous self-administration paradigm. The role of KOR was pharmacologically evaluated with the KOR antagonist, norbinaltorphamine (norBNI) and with the KOR agonist, U50,488H. Alcohol drinking was subsequently evaluated with male rats in a drinking in the dark (DID), 2-bottle choice test. Results: Concurrent Nic increased EtOH intake in adolescent males, but not in adults or females. Pharmacological blockade of KOR with norBNI robustly increased EtOH+Nic self-administration in adult male rats, but had no effect with female rats. Lastly, in our longitudinal study with male rats, we found prior self-administration of Nic or EtOH+Nic during adolescence increased subsequent oral EtOH intake, whereas prior self-administration of EtOH alone in adults increased subsequent EtOH drinking. Conclusions: There are major age- and sex-differences in the reinforcing effects of EtOH+Nic. Adolescent males are sensitive to the reinforcing interactions of the two drugs, whereas this effect is inhibited by KOR activation in male adults. Nicotine self-administration in adolescent males also increased subsequent oral EtOH intake. These findings suggest that brain mechanisms underlying the reinforcing effects of EtOH and nicotine are both age- and sex-dependent, and that tobacco or e-cigarette use may increase the vulnerability of teenage boys to alcohol abuse.


[Multidisciplinary approach to the treatment of musculo-skeletal tumors].
Tumors of the musculoskeletal system are relatively rare. They occur mostly in the young, while in older age groups metastases and myeloma are more prevalent. Treatment has undergone major change in the past 20 years with the introduction of neoadjuvant treatment protocols. According to recent reports 5-year survival rates have increased from 20% to 60-70%. These new protocols involve the use of modern imaging modalities, immunohistochemical pathological analysis and improved surgical technics. This has required establishment of multidisciplinary teams of experts to escort the patient through all the steps of current treatment.


The N-terminal extension of UBE2E ubiquitin-conjugating enzymes limits chain assembly.
Protein ubiquitylation depends upon the concerted action of ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). All E2s have a conserved ubiquitin-conjugating (UBC) domain but many have variable extensions N- and C-terminal to the UBC domain. For many E2s, the function of the extension is not well understood. Here, we show that the N-terminal extension of the UBE2E proteins regulates formation of polyubiquitin chains by the processive UBC domain. Target proteins are therefore monoubiquitylated by full-length UBE2E, whereas the UBC domain alone polyubiquitylates proteins. Although the N-terminal extension of UBE2E1 is largely disordered in solution, these residues have a critical role in limiting chain building, and when fused to the highly processive E2, UBE2D2, ubiquitylation is limited. For some E2s, interaction of ubiquitin with the 'backside' of the UBC domain promotes polyubiquitylation. However, interaction of ubiquitin with the backside of the UBC domain of UBE2E1 does not appear to be important for processivity. This study underscores the importance of studying full-length E2 proteins and not just the highly conserved core domain.


Effects of adding remifentanil to propofol anesthesia on systemic hemodynamics, cardiac output, and middle cerebral artery flow velocity during electroconvulsive therapy: a pilot study.
The purpose of this study was to examine the effects of adding remifentanil to propofol anesthesia on systemic hemodynamics, cardiac output, and middle cerebral artery (MCA) blood flow velocity during electroconvulsive therapy (ECT). Twelve patients undergoing ECT were enrolled in this study. The patients received anesthesia by one of the following 2 methods: either propofol alone at a dose of 1.0 mg/kg, or propofol 0.75 mg/kg with remifentanil 1.0 μg/kg in turn during successive ECT sessions, immediately before the administration of succinylcholine. All patients were monitored for blood pressure, heart rate, cardiac output, and MCA flow velocity by transcranial Doppler sonography. Middle cerebral artery flow velocity increased after ECT in both anesthesia method groups and lasted for 2 minutes after ECT. No difference in MCA flow velocity was observed between the 2 methods at any time point. Seizure duration was longer under propofol with remifentanil than under propofol alone [propofol with remifentanil, 32 (3) seconds; propofol alone, 24 (4) seconds; P < 0.01]. In contrast, no difference in time to awakening (time from the ECT stimulus to the patient's ability to open eyes) was observed between the 2 groups [propofol with remifentanil, 183 (19) seconds; propofol alone, 185 (21) seconds]. The addition of remifentanil (1 μg/kg) is suitable for reduction of the propofol dose during ECT, without any adverse hemodynamic effects, including on cerebral blood flow.


Volumetric analysis of bilateral spinal canal decompression via hemilaminectomy versus laminoplasty in cervical spondylotic myelopathy.
Cervical spondylotic myelopathy (CSM) is a degenerative process of the cervical spine requiring surgical decompression to prevent neurological deterioration. While both anterior and posterior approaches yield satisfactory results, posterior decompression is preferred in cases of the multilevel disease. In 2015, we described a muscle-sparing, novel technique of bilateral osteoligamentous decompression via hemilaminectomy (OLD) for CSM. In this study, we investigate whether this technique offers comparable volumetric results to laminoplasty in terms of spinal canal enlargement and whether this technique can yield significant clinical improvement. Patients undergoing OLD due to CSM were prospectively enrolled in this study and then matched to and compared with a historic cohort of patients with CSM treated by laminoplasty. An independent sample t test was performed to analyze whether the volumetric gain in the two separate groups was statistically significant. Patients in the OLD cohort were clinically evaluated with the mJOA score preoperatively and 3 months postoperatively. To assess clinical improvement, a paired sample t test was performed. A total of 38 patients were included in the analysis: 19 underwent OLD and 19 underwent laminoplasty. Both groups were well matched in terms of sex, age, preoperative spinal canal volume, and involved levels. Both surgical methods yielded statistically significant volumetric gain in the cervical spinal canal, but a trend towards a greater volume gain was seen in the OLD group. In the OLD group, a statistically significant clinical improvement was also demonstrated. Our study reveals that OLD can yield a comparable extent of decompression to laminoplasty in CSM while also delivering statistically significant clinical improvement.


Novel non-local effects in three-terminal hybrid devices with quantum dot.
We predict non-local effect in the three-terminal hybrid device consisting of the quantum dot (QD) tunnel coupled to two normal and one superconducting reservoirs. It manifests itself as the negative non-local resistance and results from the competition between the ballistic electron transfer (ET) and the crossed Andreev scattering (CAR). The effect is robust both in the linear and non-linear regimes. In the latter case the screening of charges and the long-range interactions play significant role. We show that sign change of the non-local conductance depends on the subgap Shiba/Andreev states, and it takes place even in absence of the Coulomb interactions. The effect is large and can be experimentally verified using the four probe setup. Since the induced non-local voltage changes sign and magnitude upon varying the gate potential and/or coupling of the quantum dot to the superconducting lead, such measurement could hence provide a controlled and precise method to determine the positions of the Shiba/Andreev states. Our predictions ought to be contrasted with non-local effects observed hitherto in the three-terminal planar junctions where the residual negative non-local conductance has been observed at large voltages, related to the Thouless energy of quasiparticles tunneling through the superconducting slab.


Excited states of chlorophyll a and b in solution by time-dependent density functional theory.
The ground state and excited state electronic properties of chlorophyll (Chl) a and Chl b in diethyl ether, acetone, and ethanol solutions are investigated using quantum mechanical and molecular mechanical calculations with density functional theory (DFT) and time-dependent DFT (TDDFT). Although the DFT/TDDFT methods are widely used, the electronic structures of molecules, especially large molecules, calculated with these methods are known to be strongly dependent on the functionals and the parameters used in the functionals. Here, we optimize the range-separated parameter, μ, of the CAM-B3LYP functional of Chl a and Chl b to reproduce the experimental excitation energy differences of these Chl molecules in solution. The optimal values of μ for Chl a and Chl b are smaller than the default value of μ and that for bacteriochlorophyll a, indicating the change in the electronic distribution, i.e., an increase in electron delocalization, within the molecule. We find that the electronic distribution of Chl b with an extra formyl group is different from that of Chl a. We also find that the polarity of the solution and hydrogen bond cause the decrease in the excitation energies and the increase in the widths of excitation energy distributions of Chl a and Chl b. The present results are expected to be useful for understanding the electronic properties of each pigment molecule in a local heterogeneous environment, which will play an important role in the excitation energy transfer in light-harvesting complex II.