[Pericardioversion and catheter ablation use of rivaroxaban in light of X-VERT and VENTURE-AF trials].
Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia and causes mortality in the community. Cardioversion and catheter ablation are frequently used methods for rhythm control. Oral anticoagulants have been used for many years in the prevention of thromboembolic complications in patients with AF. Both cardioversion and catheter ablation have been associated with certain complication risks especially thromboembolism, which can be significantly reduced by adequate anticoagulation. In this review, we discuss the efficacy and safety parameters of continuous rivaroxaban treatmentn compared with dose-adjusted vitamin K antagonist therapy in patients who were planned to undergo cardioversion and catheter ablation according to the data of X-VERT and VENTUREAF trials.


Understanding clinical reasoning: A phenomenographic study with entry-level physiotherapy students.
Entry-level students' conceptualizations of clinical reasoning can provide a starting point for program planning related to clinical reasoning development with a focus on patient-centered care. The aim of the study is to explore how physiotherapy students understand clinical reasoning midway through their education. Nine physiotherapy students were interviewed at the end of their third semester. Semi-structured individual interviews were conducted, recorded and transcribed verbatim. A phenomenographic approach to qualitative data analysis, seeking to explore variations in students' conceptions was applied. The students' ways of understanding clinical reasoning could be described as: 1) the cognitive process of the physiotherapist; and 2) the relational process of the collaborative partnership between the physiotherapist and the patient. A contrastive analysis shows how the cognitive and relational perspectives are developed through the relationships among three dimensions of clinical reasoning: 1) problem-solving; 2) context of working; and 3) own learning. By identifying the critical variation in students' conceptions of clinical reasoning, focus can be placed on pedagogical arrangements to facilitate students' progression toward a person-centered approach.


Overexpression of sirt7 exhibits oncogenic property and serves as a prognostic factor in colorectal cancer.
Sirtuins play an important role in cancer development. Sirt7, as a member of this family, is frequently overexpressed in certain carcinomas, but the oncogenic mechanism is seldom reported. In this study, Sirt7 was characterized for its role in colorectal cancer aggressiveness and underlying molecular mechanisms. Quantitative PCR, Western blotting, and immunohistochemistry were performed to study Sirt7 expression in a cohort of colorectal cancer tissues and non-tumor tissues and cells. A series of in vitro and in vivo assays was performed to elucidate the function of Sirt7 in colorectal cancer and its underlying mechanisms. Association between the Sirt7 signature and survival was examined using Kaplan-Meier analysis and log-rank tests. The Sirt7 protein level significantly correlated with tumor stage (P = 0.029), lymph node metastasis (P = 0.046), and poor patient survival (P < 0.05). Sirt7 knockdown significantly inhibited colorectal cancer cell proliferation, colony formation, and motility. Ectopic Sirt7 expression promoted colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Moreover, Sirt7 enhanced MAPK pathway activity concomitantly with p-ERK and p-MEK upregulation. In Sirt7-overexpressing cells, the mesenchymal markers vimentin and fibronectin were upregulated, and the epithelial markers E-cadherin and β-catenin were downregulated, which was linked to enhanced invasion by colorectal cancer cells. Our findings suggest that Sirt7 plays an important role in the development and progression of human colorectal cancer and functions as a valuable marker of colorectal cancer prognosis.


Retinoic acid-induced expression of tissue transglutaminase in human promyelocytic leukemia (HL-60) cells.
Addition of retinoic acid to human promyelocytic leukemia cells results in a dramatic increase in cellular transglutaminase activity. This increase is due to the induction of a specific intracellular transglutaminase, tissue transglutaminase. Retinoic acid-induced expression of tissue transglutaminase is potentiated by analogues of cyclic AMP. The induction of the enzyme can be detected within 6 h of the addition of the retinoid to the cell and results in increases of the enzyme of at least 50-fold. The induction of HL-60 transglutaminase is a specific response of the cells to retinoic acid and is not seen with other agents that induce HL-60 differentiation. We believe that the induction of tissue transglutaminase is a useful index of the early events in retinoid-regulated gene expression in both normal and transformed cells.


Histo-functional effects of Peganum harmala on male rat's spermatogenesis and fertility.
The Peganum harmala is currently used by the Jordanian populations systemically for its antispasmodic, diuretic, sedative and analgesic effects and externally for its antirheumatic effect. To study effects of Peganum harmala on the reproductive system and fertility using adult male albino rats. A total of 20 rats were involved in this study and were divided into two groups. Group (A) a vehicle-treated control and group (B) a treated group with aqueous extract of Peganum harmala at a dose of 300 mg/kg body weight for 60 days. This dose induces a significant decrease in the weight of reproductive organs (p<0.01) when compared to controls. The sperm motility and density in cauda epidydimides and testicular ducts were significantly decreased (p<0.01). Furthermore treatments have remarkably altered the histoarchitecture of testes. Spermatogenesis was inhibited at both primary and secondary spermatocyte stages. Epididymides showed reduced number of spermatozoa. Lumen of vas deferentia were devoid of sperms. The secretary activities of seminal vesicle and ventricular prostate were also reduced. Spermatocytes parameters were altered which included a significant decrease count (p<0.001). In addition counts of developing spermatocytes in treated rats showed a decrease in number of spermatocytes and spermatids (p<0.001) when compared to controls. Serum hormonal assay indicated a decrease in Testosterone and Follicular Stimulating Hormone (FSH) levels in treated rats. A decreased in number female rats impregnated by males receiving treatment was observed and demonstrated by a decrease in the implantation sites and viable fetuses number (p<0.01). The aqueous extracts of Peganum harmala might have adverse effects on the processes of spermatogenesis due to direct or indirect effects on somniferous tubules and or the pituitary testicular axis.


Detailed mechanism and kinetics of the reaction of Criegee intermediate CH2OO with HCOOH investigated via infrared identification of conformers of hydroperoxymethyl formate and formic acid anhydride.
The reaction of Criegee intermediate CH2OO with HCOOH is important in atmospheric chemistry, but its mechanism and kinetics are little investigated. We recorded time-resolved infrared absorption spectra of transient species produced upon irradiation at 308 nm of a flowing mixture of CH2I2/O2/N2/HCOOH at 298 K. Bands of CH2OO were observed initially upon irradiation; their decrease was accompanied with the appearance of several bands near 887, 925, 1052, 1115, 1170, 1342, 1391, and 1760 cm-1, assigned to the absorption of hydroperoxymethyl formate [HC(O)OCH2OOH, HPMF], that decreased in intensity at a later period with the appearance of absorption bands of the anti-conformer of formic acid anhydride [anti-(HCO)2O, FAN] near 998, 1101, 1767, and 1821 cm-1. The main contributions of the infrared absorption of HPMF are from an open-form conformer, but small contributions from the intramolecular hydrogen-bonded conformer that absorbs near 1070, 1170, and 1732 cm-1 were identified. Observed infrared spectra of both conformers of HPMF and anti-FAN agree satisfactorily with the anharmonic vibrational wavenumbers and IR intensities predicted with the B3LYP/aug-cc-pVTZ method. We derived a rate coefficient for CH2OO + HCOOH to be k = (1.4 ± 0.3) × 10-10 cm3 molecule-1 s-1 from formation of HPMF. We found also that anti-FAN was produced mainly from the open-form conformer with rate coefficient k = (1460 ± 30) s-1; the intramolecular hydrogen-bonded conformer of HPMF is stable.


Meningitis in preterm neonates: importance of cerebrospinal fluid parameters.
Cerebrospinal fluid parameters are of great importance in diagnosing meningitis, but normal values for preterm neonates are based on small, single-center studies. We sought to determine current values for preterm neonate cerebrospinal fluid parameters and assess the association of cerebrospinal fluid parameters with culture proven meningitis. We performed a cohort study of the first lumbar puncture from 4632 neonates < 34 weeks' gestation performed in the years 1997 to 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical Group. We identified 95 cases of meningitis from the 4632 lumbar punctures. The area under the receiver operating characteristic curves for white blood cell count, glucose, and protein were 0.80, 0.63, and 0.72, respectively, for prediction of culture-proven meningitis. Cerebrospinal fluid parameters used to diagnose meningitis in the absence of dependable cerebrospinal fluid cultures are unreliable. Caution should be employed when interpreting cerebrospinal fluid parameters in the premature neonate.


Use of corneas for transplant after self-inflicted eyeballs enucleation in the Italian law.
The authors analyze from an ethical and legal point of view the case of a 37 year old man, hospitalized for four days because of a 'dissociative syndrome', who had introduced in both his orbits a portable radio antenna. Most likely, he completed the self-enuclation using his own hands. He was brought to the Ophtalmic Hospital by nurses who handed the two eyeballs to the physicians who ascertained that the corneas were intact. Then, they performed the conservative extraction. In the following days those corneas were transplanted (keratoplasty) on two subjects on the waiting list at that hospital. The case raises the question of whether it is lawful and ethically acceptable to take, for transplant use, the corneas of a mentally incapable patient who has excised his own eyeballs. The authors analyze the case from the angle of the Italian law and Oviedo Convention. Neither of them has a specific regulation on this topic. It is therefore necessary to apply general principles that holdvalidfor Italy and a variety of countries worldwide. Particularly, the choice to use the corneas for transplant did not prejudice the physical integrity of the patient, who could no longer utilize his own eyeballs. His self-determination has not been affected; in fact, he was not in the position to make a conscious decision. Additionally, the so-called "implied consent" could be applied. Therefore, the principle of human solidarity, which is the moral duty to benefit others, seems to prevail in the case at hand.


Photocatalytic activity of graphene oxide-TiO2 thin films sensitized by natural dyes extracted from Bactris guineensis.
This study synthesized and characterized composites of graphene oxide and TiO2 (GO-TiO2). GO-TiO2 thin films were deposited using the doctor blade technique. Subsequently, the thin films were sensitized with a natural dye extracted from a Colombian source (Bactris guineensis). Thermogravimetric analysis, X-ray diffraction, Raman spectroscopy, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and diffuse reflectance measurements were used for physico-chemical characterization. All the samples were polycrystalline in nature, and the diffraction signals corresponded to the TiO2 anatase crystalline phase. Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR) verified the synthesis of composite thin films, and the SEM analysis confirmed the TiO2 films morphological modification after the process of GO incorporation and sensitization. XPS results suggested a possibility of appearance of titanium (III) through the formation of oxygen vacancies (Ov). Furthermore, the optical results indicated that the presence of the natural sensitizer and GO improved the optical properties of TiO2 in the visible range. Finally, the photocatalytic degradation of methylene blue was studied under visible irradiation in aqueous solution, and pseudo-first-order model was used to obtain kinetic information about photocatalytic degradation. These results indicated that the presence of GO has an important synergistic effect in conjunction with the natural sensitizer, reaching a photocatalytic yield of 33%.


Stream Algal Biofilm Community Diversity Along An Acid Mine Drainage Recovery Gradient Using Multimarker Metabarcoding.
In southeastern Ohio, active remediation of streams affected by Acid Mine Drainage (AMD) has proven to be successful for some streams, while others have not recovered based on macroinvertebrate assessment. In this study, biofilms were collected from three Moderately Impaired, three Recovered, and two Unimpaired streams. The biodiversity was characterized by metabarcoding using two universal barcode markers (16S and 18S) along with two algal specific markers (UPA and rbcL) and high-throughput amplicon sequencing. For each marker, the ordination of Bray-Curtis Index calculated from the total Amplicon Sequence Variants (ASVs) present in each stream showed the Unimpaired and Recovered streams clustered, while Moderately Impaired streams were more distant. Focusing on the algal ASVs, the Shannon index for the rbcL, and UPA markers showed significantly lower alpha diversity in Moderately Impaired streams compared to Unimpaired streams, but the Recovered streams were not significantly different from the other two stream categories. The two universal markers together captured all algal phyla providing an outline of the diversity, but the two algal specific markers produced a greater number of ASVs and taxonomic depth for algal taxa. Further examination of the UPA marker revealed a drastic decrease in relative abundance of diatoms in Moderately Impaired streams compared to Recovered and Unimpaired streams. Likewise, diatom genera identified in the rbcL data and indicative of stream water quality showed marked differences in relative abundance among stream categories. Although all markers were useful, the algal-specific UPA and rbcL contributed more insights into algal community differences among stream categories.


Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in choledocho-venous fistula rats.
We have previously demonstrated that after bile duct ligation hepatocytes express Bcl-2, although the mechanisms regulating Bcl-2 expression were not identified. Our aim was to determine if biliary constituents induce hepatocellular expression of Bcl-2 by a cyclooxygenase-2 (COX-2)-dependent mechanism. We used the choledocho-venous fistula (CVF) rat model for these studies and inhibited COX-2 by feeding the animals nimesulide, a selective inhibitor of COX-2 activity. Serum bile acids were 70-fold greater in CVF animals compared with controls, although liver histology and serum alanine aminotransferase values remained normal for the duration of the study. Neither Bcl-2 nor COX-2 was detected in sham-operated animals. However, Bcl-2 was expressed in hepatocytes but not in other liver cells in the CVF animals. In contrast, COX-2 protein was identified in Kupffer cells but not in hepatocytes of CVF animals. Hepatic Bcl-2 protein expression was fourfold lower in the livers from nimesulide-treated CVF rats. In conclusion, high circulating concentrations of biliary constituents are associated with stimulation of de novo hepatocyte expression of Bcl-2 and Kupffer cell expression of COX-2. These data suggest Kupffer cell-derived prostanoids may regulate Bcl-2 expression in the hepatocyte.


Dysregulation of Parvalbumin Expression in the Cntnap2-/- Mouse Model of Autism Spectrum Disorder.
Due to the complex and heterogeneous etiology of autism spectrum disorder (ASD), identification of convergent pathways and/or common molecular endpoints in the pathophysiological processes of ASD development are highly needed in order to facilitate treatment approaches targeted at the core symptoms. We recently reported on decreased expression of the Ca2+-binding protein parvalbumin (PV) in three well-characterized ASD mouse models, Shank1-/-, Shank3B-/- and in utero VPA-exposed mice. Moreover, PV-deficient mice (PV+/- and PV-/-) were found to show behavioral impairments and neuroanatomical changes closely resembling those frequently found in human ASD individuals. Here, we combined a stereology-based approach with molecular biology methods to assess changes in the subpopulation of PV-expressing (Pvalb) interneurons in the recently characterized contactin-associated protein-like 2 (Cntnap2-/-) knockout mouse model of ASD. The CNTNAP2 gene codes for a synaptic cell adhesion molecule involved in neurodevelopmental processes; mutations affecting the human CNTNAP2 locus are associated with human ASD core symptoms, in particular speech and language problems. We demonstrate that in Cntnap2-/- mice, no loss of Pvalb neurons is evident in ASD-associated brain regions including the striatum, somatosensory cortex (SSC) and medial prefrontal cortex (mPFC), shown by the unaltered number of Pvalb neurons ensheathed by VVA-positive perineuronal nets. However, the number of PV-immunoreactive (PV+) neurons and also PV protein levels were decreased in the striatum of Cntnap2-/- mice indicating that PV expression levels in some striatal Pvalb neurons dropped below the detection limit, yet without a loss of Pvalb neurons. No changes in PV+ neuron numbers were detected in the cortical regions investigated and also cortical PV expression levels were unaltered. Considering that Cntnap2 shows high expression levels in the striatum during human and mouse embryonic development and that the cortico-striato-thalamic circuitry is important for speech and language development, alterations in striatal PV expression and associated (homeostatic) adaptations are likely to play an important role in Cntnap2-/- mice and, assumingly, in human ASD patients with known Cntnap2 mutations.


Inverse leidenfrost drop manipulation using menisci.
Drops deposited on an evaporating liquid bath can be maintained in an inverse Leidenfrost state by the vapor emanating from the bath, making them levitate and hover without effective friction. These perfectly non-wetting droplets create a depression in the liquid interface that sustains their weight, which generates repellent forces when they approach a meniscus rising against a wall. Here, we study this reflection in detail, and show that frictionless Leidenfrost drops are a simple and efficient tool to probe the shape of an unknown interface. We then use the menisci to control the motion of the otherwise elusive drops. We create waveguides to direct and accelerate them and use parabolic walls to reflect and focus them. This could be particularly beneficial in the scale up of droplet cryopreservation processes: capillary interactions can be used to transport, gather and collect vitrified biological samples in absence of contact and contamination.


Association of inflammatory gene polymorphisms and conventional risk factors with arterial stiffness by age.
Inflammatory gene polymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory gene polymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. We recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene polymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP-1, ICAM-1, and TNF-α. Associations of CAVI with genetic and conventional risk factors were estimated by sex and age group (34-49, 50-59, and 60-69 years) using a general linear model. The association with 5-year change in CAVI was examined longitudinally. Glucose intolerance was associated with high CAVI among women in all age groups, while hypertension was associated with high CAVI among participants in all age groups, except younger women. Mean CAVI for the CD14 CC genotype was lower than those for the TT and CT genotypes (P for trend = 0.005), while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49 years (P = 0.006). No association of the other 6 polymorphisms with CAVI was observed. No association with 5-year change in CAVI was apparent. Inflammatory gene polymorphisms were not associated with arterial stiffness. To confirm these results, further large-scale prospective studies are warranted.


Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort.
Prostate cancer tends to affect older men and to progress relatively slowly. Since the prevalence of comorbidity increases with advancing age, competing causes of death are important contributors to death rates among prostate cancer patients. Accurate determination of the underlying causes of death in older men dying with prostate cancer may thus also be more difficult. We compared the distribution of underlying causes of death in decedents from a population-based cohort of elderly prostate cancer patients to that from a population-based comparison cohort of elderly men without prostate cancer. Among decedents from the prostate cancer patient cohort, we examined associations of patient demographics, disease stage, and initial treatment, with assignment of a prostate cancer underlying cause of death (versus any other cause) by use of multivariable logistic regression. In the subgroup of prostate cancer patient decedents having underlying causes of death other than prostate cancer, the underlying cause distribution was compared with that in nonprostate cancer cohort decedents. Prostate cancer was the underlying cause for 39% (95% confidence interval [CI] = 36.3-41.9) of the decedents in the prostate cancer cohort. Causes of death among prostate cancer patients not dying of prostate cancer were similar to those among the nonprostate cancer cohort decedents. However, in those who were aggressively treated, the adjusted odds of other cancer causes of death were 51% higher (odds ratio [OR] = 1.51; 95% CI = 1.08-2.10) than that in nonprostate cancer patient decedents, while in those treated with watchful waiting the adjusted odds were 34% lower (OR = 0.66; 95% CI = 0.47-0.93). Initial treatment may influence the underlying cause of death reported in vital statistics for prostate cancer patients.


Two-Dimensional Intrinsic Half-Metals With Large Spin Gaps.
Through a systematic search of all layered bulk compounds combined with density functional calculations employing hybrid exchange-correlation functionals, we predict a family of three magnetic two-dimensional (2D) materials with half-metallic band structures. The 2D materials, FeCl2, FeBr2, and FeI2, are all sufficiently stable to be exfoliated from bulk layered compounds. The Fe2+ ions in these materials are in a high-spin octahedral d6 configuration leading to a large magnetic moment of 4 μB. Calculations of the magnetic anisotropy show an easy-plane for the magnetic moment. A classical XY model with nearest neighbor coupling estimates critical temperatures, Tc, for the Berezinskii-Kosterlitz-Thouless transition ranging from 122 K for FeI2 to 210 K for FeBr2. The quantum confinement of these 2D materials results in unusually large spin gaps, ranging from 4.0 eV for FeI2 to 6.4 eV for FeCl2, which should defend against spin current leakage even at small device length scales. Their purely spin-polarized currents and dispersive interlayer interactions should make these materials useful for 2D spin valves and other spintronic applications.


Features of recent codon evolution: a comparative polymorphism-fixation study.
Features of amino-acid and codon changes can provide us important insights on protein evolution. So far, investigators have often examined mutation patterns at either interspecies fixed substitution or intraspecies nucleotide polymorphism level, but not both. Here, we performed a unique analysis of a combined set of intra-species polymorphisms and inter-species substitutions in human codons. Strong difference in mutational pattern was found at codon positions 1, 2, and 3 between the polymorphism and fixation data. Fixation had strong bias towards increasing the rarest codons but decreasing the most frequently used codons, suggesting that codon equilibrium has not been reached yet. We detected strong CpG effect on CG-containing codons and subsequent suppression by fixation. Finally, we detected the signature of purifying selection against Amid R:U dinucleotides at synonymous dicodon boundaries. Overall, fixation process could effectively and quickly correct the volatile changes introduced by polymorphisms so that codon changes could be gradual and directional and that codon composition could be kept relatively stable during evolution.


Inhibition drives configural superiority of illusory Gestalt: Combined behavioral and drift-diffusion model evidence.
Illusory Kanizsa figures demonstrate that a perceptually completed whole is more than the sum of its composite parts. In the current study, we explored part/whole relationships in object completion using the configural superiority effect (CSE) with illusory figures (Pomerantz & Portillo, 2011). In particular, we investigated to which extent the CSE is modulated by closure in target and distractor configurations. Our results demonstrated a typical CSE, with detection of a configural whole being more efficient than the detection of a corresponding part-level target. Moreover, the CSE was more pronounced when grouped objects were presented in distractors rather than in the target. A follow-up experiment systematically manipulated closure in whole target or, respectively, distractor configurations. The results revealed the effect of closure to be again stronger in distractor, rather than in target configurations, suggesting that closure primarily affects the inhibition of distractors, and to a lesser extent the selection of the target. In addition, a drift-diffusion model analysis of our data revealed that efficient distractor inhibition expedites the rate of evidence accumulation, with closure in distractors particularly speeding the drift toward the decision boundary. In sum, our findings demonstrate that the CSE in Kanizsa figures derives primarily from the inhibition of closed distractor objects, rather than being driven by a conspicuous target configuration. Altogether, these results support a fundamental role of inhibition in driving configural superiority effects in visual search.


[Prevalence of patent foramen ovale in young patients with cerebral ischemic accident of unknown origin].
Patent foramen ovale has been associated with stroke in young patients with cryptogenic stroke. The purpose of this study is to examine the prevalence of patent foramen ovale in this group of patients, as well as their anatomical and functional characteristics by contrast echocardiography, trying to determine ictus risk markers in young patients with acute ischemic stroke. Prospective study of 90 patients under the age of 50 who were hospitalised consecutively due to a clinical presentation suggestive of stroke. No cause was found in 55 out of 90 (group I) and the rest, in which an stroke was finally disregarded, were used as the control group (group II). A transthoracic and transesophageal echocardiography examination with 2 types of contrast agents was performed in all patients to determine the presence of a patent foramen ovale and its anatomical and functional characteristics. Patent foramen ovale was observed more frequently in group I than in group II (43 versus 21%; p < 0.05). Among patients with a patent foramen ovale those with an ischemic stroke showed greater mobility of the oval membrane, more frequent large shunts of contrast in a single frame in the left heart, and more frequent shunts at rest. Transesophageal echocardiography without contrast showed a high sensitivity (90%) and specificity (93%) for detecting anatomically permeable foramen ovale whereas contrast transthoracic echocardiography showed a low sensitivity (13%). There were no differences between the two contrasts used. Near half of young patients with ischemic stroke of an unknown origin have a patent foramen ovale. A bigger mobility of the membrane of the oval cavity and a large degree of shunt contrast as well as shunt at rest detected by contrast transesophageal echocardiography, seem to identify patent foramen ovale patients with ischemic stroke. In these patients, transthoracic echocardiography has low sensibility for detecting permeability of the foramen ovale.


Detection of deleterious genotypes in multigenerational studies. II. Theoretical and experimental dynamics with selfing and selection.
A mathematical model was developed to help interpret genotype and allele frequency dynamics in selfing populations, with or without apomixis. Our analysis provided explicit time-dependent solutions for the frequencies at diallelic loci in diploid populations under any combination of fertility, viability, and gametic selection through meiotic drive. With no outcrossing, allelic variation is always maintained under gametic selection alone, but with any fertility or viability differences, variation will ordinarily be maintained if and only if the net fitness (fertility x viability) of heterozygotes exceeds that of both homozygotes by a substantial margin. Under pure selfing and Mendelian segregation, heterozygotes must have a twofold fitness advantage; the level of overdominance necessary to preserve genetic diversity declines with apomixis, and increases with segregation distortion if this occurs equally and independently in male and female gametes. A case study was made of the Arabidopsis act2-1 actin mutant over multiple generations initiated from a heterozygous plant. The observed genotypic frequency dynamics were consistent with those predicted by our model for a deleterious, incompletely recessive mutant in either fertility or viability. The theoretical framework developed here should be very useful in dissecting the form(s) and strength of selection on diploid genotypes in populations with negligible levels of outcrossing.


COMPARATIVE ANALYSIS OF SURGICAL HEMOSTATIC SPONGES IN LIVER INJURY: STUDY IN RATS.
Obtaining effective hemostasis either in the traumatic or surgical lesions of parenchymal viscera, especially the liver, has always been a challenge. Comparative study between the use of different hemostatic sponges in hepatic wound and their capacity of integration to cells in a short period. Fifteen Wistar rats were divided into three groups. Through laparotomy a standardized wound in hepatic right lobe was made. The animals were treated with three sponges, being gelatin in group I, equine collagen in group II, and oxidized cellulose in group III. The hemostatic capacity was analysed. On the 7º day after surgery samples for histology analysis (H&E and picrosirius) were collected for inflammatory evaluation and collagen quantification (types I and III) with polarized microscopy. All materials used had similar haemostatic effects, with no significant difference in hemostasis time. In the assessment of tissue repair and adhesions provoked, as well as analysis of the inflammatory process, the gelatin sponge presented greater inflammation and adhesions to the contiguous structures to the procedure in relation to the other groups. Animals which had their wounds treated with collagen and regenerated cellulose sponges presented better results in relationship to the ones treated with gelatin sponge.


[The course and treatment of chronic hepatitis B in HIV-infected patients].
The paper reviews the data available in the literature on patients with mixed hepatitis B virus (HBV) and HIV infection, its course and outcomes. The unity of the mechanisms of contamination with HBV and HIV increases the likelihood of these infections in patients. About 70% of HIV-infected patients are carriers of the markers, the presence of which is indicative of current or previous HBV infection. An average of 7.6% of HIV-infected patients were diagnosed as having chronic hepatitis B (CHB) in West Europe and North America. The notification rate of CHB in adult HIV-infected patients was 5-7% in the Russian Federation. Most specialists report that HIV-infected patients have a severer course of HBV. Mixed HBV and HIV infection, and low CD4+ lymphocyte count in particular, increase the risk for death from hepatic diseases and there is evident hepatotoxicity during antiretroviral therapy. The management of patients with mixed HBV and HIV infection is determined by indications for therapy for both HIV infection and CHV infection, by the availability of double-action antiviral drugs (that suppress either HIV or HBV replication), by the development of their resistance in one or both viruses. Indications and preferable variants of using various treatment regimens are given.


Macronuclear genetics of Tetrahymena. II. Macronuclear location of somatic mutations to cycloheximide resistance.
Somatic cycloheximide-resistant mutants of syngen 1 of Tetrahymena pyriformis were isolated and genetically characterized. Two properties of the mutants were independently examined: (a) The transmission of the mutant phenotype during conjugation and (b) the kinetics of phenotypic assortment during vegetative propagation. The results of both studies strongly support the idea that these somatic mutations have a macronuclear location. The kinetics of assortment are consistent with the idea that the syngen 1 macronucleus contains about 45 assorting genetic units. The sib-selection method employed here, used in conjunction with the analysis of assortment kinetics and a previously described test for randomness of distribution, provides a probe of macronuclear genetics applicable to many ciliates, including those in which conjugation is not known to occur or is not under experimental control.


Immune reconstitution after T-cell replete HLA haploidentical hematopoietic stem cell transplantation using high-dose post-transplant cyclophosphamide.
As HLA haploidentical related donors are quickly available, HLA haploidentical hematopoietic stem cell transplantation (haploHSCT) using high-dose post-transplant cyclophosphamide (PTCy) is now widely used. Recent basic and clinical studies revealed the details of immune reconstitution after T-cell replete haploHSCT using PTCy. T cells and NK cells in the graft proliferate abundantly at day 3 post-haploHSCT, and the PTCy eliminates these proliferating cells. After ablation of proliferating mature cells, donor-derived NK cell reconstitution occurs after the second week; however, recovering NK cells remain functionally impaired for at least several months after haploHSCT. PTCy depletes proliferating cells, resulting in the preferential accumulation of Treg and CD4+ T cells, especially the memory stem T cell (TSCM) phenotype. TSCM capable of both self-renewal and differentiation into effector T cells may play an important role in the first month of immune reconstitution. Subsequently, de novo T cells progressively recover but their levels remain well below those of donor CD4+ T cells at the first year after haploHSCT. The phenotype of recovering T cells after HSCT is predominantly effector memory, whereas B cells are predominantly phenotypically naive throughout the first year after haploHSCT. B cell recovery depends on de novo generation and they are not detected until week 4 after haploHSCT. At week 5, recovering B cells mostly exhibit an unconventional transitional cell phenotype and the cell subset undergoes maturation. Recent advances in immune reconstitution have improved our understanding of the relationship between haploHSCT with PTCy and the clinical outcome.


Predicting Mood Changes in Bipolar Disorder through Heartbeat Nonlinear Dynamics.
Bipolar Disorder (BD) is characterized by an alternation of mood states from depression to (hypo)mania. Mixed states, i.e., a combination of depression and mania symptoms at the same time, can also be present. The diagnosis of this disorder in the current clinical practice is based only on subjective interviews and questionnaires, while no reliable objective psychophysiological markers are available. Furthermore, there are no biological markers predicting BD outcomes, or providing information about the future clinical course of the phenomenon. To overcome this limitation, here we propose a methodology predicting mood changes in BD using heartbeat nonlinear dynamics exclusively, derived from the ECG. Mood changes are here intended as transitioning between two mental states: euthymic state (EUT), i.e., the good affective balance, and non-euthymic (non-EUT) states. Heart Rate Variability (HRV) series from 14 bipolar spectrum patients (age: 33.439.76, age range: 23-54; 6 females) involved in the European project PSYCHE, undergoing whole night ECG monitoring were analyzed. Data were gathered from a wearable system comprised of a comfortable t-shirt with integrated fabric electrodes and sensors able to acquire ECGs. Each patient was monitored twice a week, for 14 weeks, being able to perform normal (unstructured) activities. From each acquisition, the longest artifact-free segment of heartbeat dynamics was selected for further analyses. Sub-segments of 5 minutes of this segment were used to estimate trends of HRV linear and nonlinear dynamics. Considering data from a current observation at day t0, and past observations at days (t􀀀1, t􀀀2,...,), personalized prediction accuracies in forecasting a mood state (EUT/non-EUT) at day t+1 were 69% on average, reaching values as high as 83.3%. This approach opens to the possibility of predicting mood states in bipolar patients through heartbeat nonlinear dynamics exclusively.


Fe(II)-Catalyzed Ligand-Controlled Dissolution of Iron(hydr)oxides.
Dissolution of iron(III)phases is a key process in soils, surface waters, and the ocean. Previous studies found that traces of Fe(II) can greatly increase ligand controlled dissolution rates at acidic pH, but the extent that this also occurs at circumneutral pH and what mechanisms are involved are not known. We addressed these questions with infrared spectroscopy and 57Fe isotope exchange experiments with lepidocrocite (Lp) and 50 μM ethylenediaminetetraacetate (EDTA) at pH 6 and 7. Addition of 0.2-10 μM Fe(II) led to an acceleration of the dissolution rates by factors of 7-31. Similar effects were observed after irradiation with 365 nm UV light. The catalytic effect persisted under anoxic conditions, but decreased as soon as air or phenanthroline was introduced. Isotope exchange experiments showed that added 57Fe remained in solution, or quickly reappeared in solution when EDTA was added after 57Fe(II), suggesting that catalyzed dissolution occurred at or near the site of 57Fe incorporation at the mineral surface. Infrared spectra indicated no change in the bulk, but changes in the spectra of adsorbed EDTA after addition of Fe(II) were observed. A kinetic model shows that the catalytic effect can be explained by electron transfer to surface Fe(III) sites and rapid detachment of Fe(III)EDTA due to the weaker bonds to reduced sites. We conclude that the catalytic effect of Fe(II) on dissolution of Fe(III)(hydr)oxides is likely important under circumneutral anoxic conditions and in sunlit environments.


Lack of correlation between cardiac mass and arteriolar structural changes in mild-to-moderate hypertension.
A morphological restructuring of cardiac and arteriolar tissue is common in hypertension. The parallel evolution of these two processes as a compensatory response to pressure overload is a frequently assumed but unsubstantiated hypothesis. To evaluate this possibility, we have concomitantly measured left ventricular mass (LVM; two-dimensional echo) and minimal forearm vascular resistance (FVR; derived from the ratio of intra-arterial blood pressure: forearm blood flow by venous plethysmography) at maximal postischemic (13 min ischemia + 1 min hand exercise) reactive hyperemia. The study was performed on 29 essential hypertensive patients (15 males, 14 females, aged 50 +/- 10 years) who had not been undergoing treatment for hypertension for at least 15 days at the time of study. Minimum FVR was taken as a hemodynamic index of the integrated arteriolar lumen at the forearm level. LVM index and minimum FVR ranged from normal to clearly altered values. In spite of a wide spread of values, no correlation existed between the individual values of the two variables. Systemic mean blood pressure correlated with minimum FVR and tended to correlate with LVMI. Thus, morphological restructing of cardiac and arteriolar tissue does not seem to evolve in parallel in human hypertension. Pressure overload may contribute to cardiovascular hypertrophy, but other unrelated mechanisms may also underlie the development of cardiac and arteriolar abnormalities of human hypertension.


Representations of grapho-motor patterns unique to Chinese character writing: evidence from a patient with mirror writing.
This study investigated the grapho-motor patterns used in writing Chinese characters. A Chinese patient, CSC, who demonstrated post-brain-injury mirror writing, was recruited. In Experiment 1, non-mirrored writing responses were obtained when CSC was instructed to copy asymmetrical non-verbal symbols and pictures. Resembling the patterns observed in a patient's writing reported in a previous study, it was hypothesized that CSC's mirror writing was a result of untransformed preserved grapho-motor patterns. In Experiments 2 and 3, CSC was further instructed to copy real Chinese characters, pseudo-characters with authentic radicals and logographemes (i.e., stroke clusters that frequently occur in radicals), and Hangul characters with stroke clusters resembling the shapes of authentic logographemes. The results showed that CSC demonstrated mirror writing only when authentic Chinese orthographic units were involved. Non-mirrored writing responses were obtained from stimuli without authentic Chinese orthographic units. In sum, CSC's performance supported the existence of grapho-motor patterns of Chinese orthographic units represented in the brain. Theoretical implications were discussed.


Overexpression of alternatively spliced tissue factor induces the pro-angiogenic properties of murine cardiomyocytic HL-1 cells.
Tissue factor (TF) is expressed in 2 isoforms: membrane-bound "full length" (fl)TF and soluble alternatively spliced (as)TF. flTF is the major thrombogenic form of TF. Although the function of asTF is poorly understood, it was suggested that asTF contributes to tumor-associated growth and angiogenesis. In the heart of a developing embryo, asTF is expressed much later compared to flTF, but in adult heart, asTF exhibits a distribution pattern similar to that of flTF. Thus, it is possible that asTF may play a role in heart development via pro-angiogenic signaling. The purpose of the present study was to examine the effects of murine asTF overexpression in murine cardiomyocyte-like HL-1 cells on their pro-angiogenic potential, the chemotaxis of monocytic cells, and the expression of fibroblast growth factor-2 (FGF2), cysteine-rich 61 (Cyr61), and vascular endothelial growth factor (VEGF). Expression of FGF2, Cyr61 and VEGF was assessed on reverse transcription-polymerase chain reaction and western blot. Cell migration, proliferation, and endothelial tube formation assays were carried out. It was found that overexpression of murine asTF in HL-1 cells increases their proliferation and pro-angiogenic properties. The supernatant of murine asTF-overexpressing HL-1 cells induces the chemotaxis of monocytic cells. Overexpression of murine asTF in murine cardiomyocytic cells increases their proliferation, monocyte migration, and pro-angiogenic properties -possibly- mediated by the induction of the pro-migratory and pro-angiogenic factors FGF2, Cyr61 and VEGF. Thus, we propose that murine asTF may serve as a migration- and angiogenesis-promoting factor.


High-Performance Ultraviolet-to-Infrared Broadband Perovskite Photodetectors Achieved via Inter-/Intraband Transitions.
A high-performance vertically injected broadband UV-to-IR photodetector based on Gd-doped ZnO nanorods (NRs)/CH3NH3PbI3 perovskite heterojunction was fabricated on metal substrates. Our perovskite-based photodetector is sensitive to a broad spectral range, from ultraviolet to infrared light region (λ = 250-1357 nm). Such structure leads to a high photoresponsivity of 28 and 0.22 A/W, for white light and IR illumination, respectively, with high detectivity values of 1.1 × 1012 and 9.3 × 109 Jones. Optical characterizations demonstrate that the IR detection is due to intraband transition in the perovskite material. Metal substrate boosts carrier injection, resulting in higher responsivity compared to the conventional devices grown on glass, whereas the presence of Gd increases the ZnO NRs performance. For the first time, the perovskite-based photodetector is demonstrated to extend its detection capability to IR (>1000 nm) with high room temperature responsivity across the detected spectrum, leading to a high-performance ingenious cost-effective UV-to-IR broadband photodetector design for large-scale applications.


Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle.
In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism. Six hundred fifty-two of all genes identified to be differentially regulated on SREBP overexpression had a sterol regulatory element (SRE) motif in their promoter sequences. Among these, 429 were specifically regulated by SREBP-1a, 69 by SREBP-1c, and 154 by both 1a and 1c. Because both isoforms recognize the same binding motif, we determined whether some of these functional differences could depend on the environment of the SRE motifs in the promoters. Results from promoter analysis showed that different combinations of transcription factor binding sites around the SRE binding motifs may determine regulatory networks of transcription that could explain the superposition of lipid and cholesterol metabolism with various other pathways involved in adaptive responses to stress like hypoxia and heat shock, or involvement in the immune response.


Metal complexes containing natural and and artificial radioactive elements and their applications.
Recent advances (during the 2007-2014 period) in the coordination and organometallic chemistry of compounds containing natural and artificially prepared radionuclides (actinides and technetium), are reviewed. Radioactive isotopes of naturally stable elements are not included for discussion in this work. Actinide and technetium complexes with O-, N-, N,O, N,S-, P-containing ligands, as well π-organometallics are discussed from the view point of their synthesis, properties, and main applications. On the basis of their properties, several mono-, bi-, tri-, tetra- or polydentate ligands have been designed for specific recognition of some particular radionuclides, and can be used in the processes of nuclear waste remediation, i.e., recycling of nuclear fuel and the separation of actinides and fission products from waste solutions or for analytical determination of actinides in solutions; actinide metal complexes are also usefulas catalysts forcoupling gaseous carbon monoxide,as well as antimicrobial and anti-fungi agents due to their biological activity. Radioactive labeling based on the short-lived metastable nuclide technetium-99m ((99m)Tc) for biomedical use as heart, lung, kidney, bone, brain, liver or cancer imaging agents is also discussed. Finally, the promising applications of technetium labeling of nanomaterials, with potential applications as drug transport and delivery vehicles, radiotherapeutic agents or radiotracers for monitoring metabolic pathways, are also described.


Deciphering the Novel Target Genes Involved in the Epigenetics of Hepatocellular Carcinoma Using Graph Theory Approach.
Even after decades of research, cancer, by and large, remains a challenge and is one of the major causes of death worldwide. For a very long time, it was believed that cancer is simply an outcome of changes at the genetic level but today, it has become a well-established fact that both genetics and epigenetics work together resulting in the transformation of normal cells to cancerous cells. In the present scenario, researchers are focusing on targeting epigenetic machinery. The main advantage of targeting epigenetic mechanisms is their reversibility. Thus, cells can be reprogrammed to their normal state. Graph theory is a powerful gift of mathematics which allows us to understand complex networks. In this study, graph theory was utilized for quantitative analysis of the epigenetic network of hepato-cellular carcinoma (HCC) and subsequently finding out the important vertices in the network thus obtained. Secondly, this network was utilized to locate novel targets for hepato-cellular carcinoma epigenetic therapy. The vertices represent the genes involved in the epigenetic mechanism of HCC. Topological parameters like clustering coefficient, eccentricity, degree, etc. have been evaluated for the assessment of the essentiality of the node in the epigenetic network. The top ten novel epigenetic target genes involved in HCC reported in this study are cdk6, cdk4, cdkn2a, smad7, smad3, ccnd1, e2f1, sf3b1, ctnnb1, and tgfb1.


[Detection of bovine leukaemia virus (BLV) in tissue samples of naturally and experimentally infected cattle].
Enzootic bovine leukaemia (EBL) which is caused by the bovine leukaemia virus (BLV) still plays a remarkable role despite a significant success in sanitation programmes. In the Federal Republic of Germany it was not possible to eradicate the disease until today. Sporadically during slaughter or necropsy of cattle neoplastic lesions of the lymphatic tissues are observed that need to be clarified with regard to BLV as etiological agent. Due to the fact that in most instances no serological data are available from the respective animals and blood drawings from the original holdings are not easy to obtain the polymerase chain reaction (PCR) opens new avenues as supplementary diagnostic tool to test unfixed lymphatic tissues for the presence of BLV proviral DNA. Lymph node tissues from 10 naturally or experimentally BLV-infected cattle, which have been monitored virologically and serologically, and tissues from 4 negative animals were processed, DNA was extracted and subjected to PCR to amplify BLV env gene specific sequences. The results show that in cattle with BLV-induced leukosis as well as in cattle, which were clinically healthy and unsuspicious at slaughter or at post-mortem, either with persistent lymphocytosis (PL) or without, BLV proviral DNA could be detected easily in samples of lymphatic tissues and in high concordance with serological data. In this article data from the National and OIE reference laboratory for EBL at the Friedrich-Loeffler-Institut (FLI, Germany) are presented. Elaborated laboratory protocols for processing of tissue samples and performing of BLV-PCR are recommended.


Immigration of susceptible hosts triggers the evolution of alternative parasite defence strategies.
Migration of hosts and parasites can have a profound impact on host-parasite ecological and evolutionary interactions. Using the bacterium Pseudomonas aeruginosa UCBPP-PA14 and its phage DMS3vir, we here show that immigration of naive hosts into coevolving populations of hosts and parasites can influence the mechanistic basis underlying host defence evolution. Specifically, we found that at high levels of bacterial immigration, bacteria switched from clustered regularly interspaced short palindromic repeats (CRISPR-Cas) to surface modification-mediated defence. This effect emerges from an increase in the force of infection, which tips the balance from CRISPR to surface modification-based defence owing to the induced and fixed fitness costs associated with these mechanisms, respectively.


Recommendations for cancer prevention trials using potentially ototoxic test agents.
Preventive oncology applies pharmacologic agents to reverse, retard, or halt progression of neoplastic cells to invasive malignancy, a process that may require administration of agents over long periods of time. Although ototoxicity may be a tolerable side effect of anticancer or antimicrobial therapy, even modest ototoxicity may not be acceptable in agents developed for preventive oncology that are routinely administered to subjects who neither are, nor necessarily will become, clinically ill. Age-related shifts in hearing may occur over the course of longterm or open-ended therapy; consequently, age-adjusted norms enable researchers to better distinguish hearing loss caused by drugs from that caused by aging. Norms for hearing sensitivity are derived from the Baltimore Longitudinal Study of Aging and are the basis for the proposed audiologic monitoring recommendations. Audiologic monitoring recommendations are presented that standardize patient selection, adverse event reporting, posttreatment follow-up, and audiologic testing for potentially ototoxic investigational agents. These recommendations are applicable to trials of investigational agents as well as various classes of drugs used in routine clinical care.


Epidermoid tumor of the cerebellopontine angle: diagnostic value of computed tomographic metrizamide cisternography.
The extent of spread of an epidermoid tumor in the posterior fossa may be difficult to discern preoperatively. Conventional computed tomographic (CT) studies may not outline the tumor capsule, and the low attenuation of the tumor itself may not allow a distinction from cerebrospinal fluid. CT metrizamide cisternography was helpful in delineating the inferior pole of an epidermoid tumor, which could then be delivered through a transtentorial approach.


Isolated secretion granules from parotid glands of chronically stimulated rats possess an alkaline internal pH and inward-directed H+ pump activity.
Secretion granules have been isolated from the parotid glands of rats that have been chronically stimulated with the beta-adrenergic agonist, isoproterenol. These granules are of interest because they package a quantitatively different set of secretory proteins in comparison with granules from the normal gland. Polypeptides enriched in proline, glycine, and glutamine, which are known to have pI's greater than 10, replace alpha-amylase (pI's = 6.8) as the principal content species. The internal pH of granules from the treated rats ranges from 7.8 in a potassium sulfate medium to 6.9 in a choline chloride medium. The increased pH over that of normal parotid granules (approximately 6.8) appears to reflect the change in composition of the secretory content. Whereas normal mature parotid granules have practically negligible levels of H+ pumping ATPase activity (Arvan, P., G. Rudnick, and J. D. Castle, 1985, J. Biol. Chem., 260, 14945-14952) the isolated granules from isoproterenol-treated rats undergo a time-dependent internal acidification (approximately 0.2 pH unit) that requires the presence of ATP and is abolished by an H+ ionophore. Additionally, an inside-positive granule transmembrane potential develops after ATP addition that depends upon ATP hydrolysis. Two independent methods have been used that exclude the possibility that contaminating organelles are the source of the H+-ATPase activity. Together these data provide clear evidence for the presence of an H+ pump in the membranes of parotid granules from chronically stimulated rats. However, despite the presence of H+-pump activity, fluorescence microscopy with the weak base, acridine orange, reveals that the intragranular pH in live cells is greater than that of the cytoplasm.


Refractory Acute Respiratory Distress Syndrome Secondary to COVID-19 Successfully Extubated to Average Volume-assured Pressure Support Non-invasive Ventilator.
Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the highly infectious novel SARS-CoV-2 coronavirus spread by droplet transmission. Consequently, the use of respiratory devices that may potentially promote aerosolization like non-invasive positive pressure ventilation (NIPPV) for diseases such as obstructive sleep apnea (OSA), advanced chronic obstructive lung disease, pulmonary hypertension (PH), and neuromuscular respiratory disease has been called into question. We present a case of a patient with history of OSA and PH convalescing from refractory acute respiratory distress syndrome (ARDS) secondary to COVID-19 who was successfully extubated to average volume-assured pressure support (AVAPS). A 74-year-old male with medical history notable for OSA on NIPPV, PH, and hypertension presented with respiratory failure secondary to COVID-19 confirmed on polymerase chain reaction (PCR) test. His respiratory status worsened leading to ARDS requiring intubation. He was initially extubated to high flow nasal cannula (HFNC) due to hospital policy to avoid NIPPV due to concerns of viral dissemination. He did not tolerate HFNC and required re-intubation for prolonged period. He was then medically optimized for a second attempt and extubated two days later to AVAPS with an anti-viral filter and negative pressure room with a goal of optimizing his critical illness myopathy and pre-existing OSA and PH. He tolerated extubation well, and over the next five days was weaned from alternating AVAPS/HFNC to eventually requiring two liters nasal cannula in the day and AVAPS mode at night. This case highlights a potential therapeutic option for patients with severe respiratory failure secondary to COVID-19. This patient's pre-existing comorbidities of OSA and PH markedly increased his risk for extubation failure on HFNC. The use of AVAPS after his second extubation attempt helped ensure ventilation and oxygenation non-invasively. COVID-19 can lead to prolonged dependence on mechanical ventilation. This pandemic has the potential to create medical resource scarcities, especially in rural areas where ventilators and trained personnel are already in short supply. By using AVAPS mode, this patient was able to rehabilitate his myopathy and participate in intermittent weaning of HFNC to ultimately simple nasal cannula. AVAPS is useful tool to facilitate extubation, as it allows non-invasive support of respiratory dynamics, particularly in those with co-morbidities such as OSA and PH. Further, larger scale studies are needed to determine its exact role during the COVID-19 pandemic.


Antioxidant and cytotoxic activities of Aphanes arvensis extracts.
The objectives of this study were to examine the free radical scavenging activity and the protective effects against macromolecular oxidation as well as the cytotoxic activity of Aphanes arvensis aqueous and methanolic extracts. Free radical scavenging activity was determined by DPPH method. The methanolic extract showed a scavenging activity nearly equivalent to Trolox and Vitamin C and has an IC(50) value of 4.54 microg/mL. Total antioxidant capacity was determined by CUPRAC method. The antioxidant capacity of aqueous and methanolic extract was 0.792 and 1.550 mmol TE/g DWE, respectively. The protective effect of A. arvensis extracts against lipid peroxidation was evaluated using a liposome oxidation system. The methanolic extract was more active than the aqueous extract. The aqueous extract possessed protective effect against protein oxidation in a dose dependent manner. Both extracts showed inhibitory effect on DNA oxidation as measured by plasmid relaxation assay. Results presented here indicate that A. arvensis possess strong antioxidant activity and protective effects with very little cytotoxic effect, and they can therefore be used as a natural additive in food, cosmetic and pharmaceutical industries.


Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma.
Interim (18)F-FDG PET performed early during the course of therapy in diffuse large B-cell lymphoma (DLBCL) is a good predictor of outcome. However, interpretation criteria for interim PET for the evaluation of tumour response are still not clearly defined. The study aim was to assess whether interim PET can predict overall survival (OS) and progression-free survival (PFS) in DLBCL patients following three different sets of parameters, two qualitative (visual) methods and one semiquantitative. A total of 50 newly diagnosed DLBCL patients were prospectively enrolled in this study. All patients had a PET/CT scan at diagnosis and an interim PET/CT scan after the second or third cycle of chemotherapy. Three methods of evaluation for the interim PET/CT were used: a qualitative three-point scoring (3-PS) method, a qualitative 5-PS method and a semiquantitative method (ΔSUVmax). The degree of correlation between therapy response seen on FDG PET and PFS and OS was determined. The analysis of the visual 3-PS method showed no statistically significant difference in PFS and OS. The estimated 5-year PFS and OS were 79 % and 92 %, respectively, in patients with an interim PET scan showing uptake not greater than in the liver versus 50 % in patients with uptake greater than in the liver, and this difference was statistically significant. The optimal cut-off value of ΔSUVmax that could predict the PFS and OS difference in patients with DLBCL was 76 % (95 % CI 62.7-89.2 %) and 75 % (95 % CI, 54.6-95.4 %), respectively. Our results support the use of liver uptake as an indicator in the qualitative evaluation of interim PET, or a ΔSUVmax greater than 75 % in semiquantitative analysis. Interim PET may predict PFS and OS and could be considered in the prognostic evaluation of DLBCL.


Camouflaging scars in the head and neck area.
Any break in the continiuty of healthy skin results in the formation of a scar. The way the scar is formed and the factors affecting the final appearance are discussed. Basic surgical principles as they relate to the revision of scars and the different surgical techniques used for revising scars are presented. Surgical adjuncts used following scar revision and hypertrophic scars and keloids and their treatment are also discussed.


Prevalence and correlates of mental disorders in a school-survey sample.
Most of the adult mental disorders have their origins early in life. As the epidemiology of childhood psychiatric disorder in Italy has not been extensively investigated, we have evaluated the prevalence of mental disorders and their association with socio-familiar variables in a representative sample of children aged 6 to 11. The study was conducted on a school- sample of 1028 children, aged 6 to 11, attending 12 primary schools in Florence (Italy). The diagnoses were made according to DSM IV diagnostic criteria, integrated by the description of each symptom, using specially trained teachers as lay-interviewers. Odds ratios with 95% C.I. chi squares and a stepwise binary logistic analysis have been performed. Nine hundred ninety nine children (506 males; 493 females) were studied. Of them, 10.5% received a psychiatric diagnosis, with a higher prevalence in males (66.7% vs.33.3, p<0.01). The most prevalent groups of mental disorders were the behavioural/impulse control (7.2%) and anxiety (6.4%) disorders. Attention Deficit with Hyperactivity Disorder was the most represented diagnosis (5.6% of the children). All the other mental disorders were relatively rare, with only separation anxiety and overanxious disorder exceeding 1% prevalence. Male gender, organic disease, having mother divorced, not present or dead, attending school full-time, cohabitation in the family were associated with an increased risk for any childhood mental disorder. About one in ten children aged 6-11 suffers from a mental disorder. Male gender, loss of mother and lower socio-economic status are associated with mental disorders in children. Further long-term prospective studies are needed, in order to clarify the epidemiological and psychopathological relationships between childhood and adult mental disorders.


Serological comparison of type Asia 1 foot and mouth disease virus isolates from Thailand.
Antigenic variation of type Asia 1 foot and mouth disease (FMD) virus in Thailand was examined using a total of 50 field viruses isolated between 1986 and 1992. A two-dimensional serum neutralisation test was used to calculate r values for comparison of these isolates with a reference vaccine strain, Asia 1 Bangkok 1960 (BKK/60). Viruses were also compared to two field isolates, Asia 1 36-2/88 and Asia 1 45/88, and some were compared to another vaccine strain, Asia 1 Nakhon Pathom 1984 (NPT/84). In 80% of cases, field isolates were deemed to be significantly different from the vaccine virus Asia 1 BKK/60, and the distribution of r values indicated that there would be some advantage in selecting a new vaccine strain more closely related to contemporary field strains.


The rapid response system and end-of-life care.
To review the recent observational studies reporting the role of the rapid response team (RRT) in end-of-life care (EOLC) planning for hospitalized patients. Initial RRT studies focussed on its role in detecting and preventing avoidable morbidity. However, patients who are in the process of dying will also trigger RRT activation criteria. Single-centre studies from several countries reveal that up to 25% of RRT calls involve patients with a pre-existing limitation of medical therapy (LOMT) and 10% result in new implementation of a new LOMT. A recent seven hospital study revealed that such EOLC RRT calls occur in significantly older patients, who are less likely to be from home and more likely to be admitted with a nonsurgical condition. Importantly, almost 50% of patients subject to EOLC RRT call die in hospital, and in many cases the last RRT call occurs on the day of death. Up to one-third of RRT calls involve patients at the end of their life. Better understanding of the features of these patients may guide improved advance care and EOLC planning for hospitalized patients.


Phase transition in random walks with long-range correlations.
Motivated by recent results in the theory of correlated sequences, we analyze the dynamics of random walks with long-term memory (binary chains with long-range correlations). In our model, the probability for a unit bit in a binary string depends on the fraction of unities preceding it. We show that the system undergoes a dynamical phase transition from normal diffusion, in which the variance D(L) scales as the string's length L, into a superdiffusion phase ( D(L) approximately Lalpha,alpha>1), when the correlation strength exceeds a critical value. We demonstrate the generality of our results with respect to alternative models, and discuss their applicability to various data, such as coarse-grained DNA sequences, written texts, and financial data.


The evolutionarily related beta-barrel polypeptide transporters from Pisum sativum and Nostoc PCC7120 contain two distinct functional domains.
Several beta-barrel-type channels are involved in the translocation or assembly of outer membrane proteins of bacteria or endosymbiotically derived organelles. Here we analyzed the functional units of the beta-barrel polypeptide transporter Toc75 (translocon in outer envelope of chloroplasts) of the outer envelope of chloroplasts and of a protein, alr2269, from Nostoc PCC7120 with homology to Toc75, both proteins having a similar domain organization. We demonstrated that the N-terminal region functions as a recognition and complex assembly unit, whereas the C terminus forms the beta-barrel-type pore. The pore region is, in turn, modulated by the N terminus of the proteins. The protein from Nostoc PCC7120, which shares a common ancestor with Toc75, is able to recognize precursor proteins destined for chloroplasts. In contrast, the recognition of peripheral translocon subunits by Toc75 is a novel feature acquired through evolution.


Damned if you do, damned if you don't: potassium binding resins in hyperkalemia.
Sodium polystyrene sulfonate (SPS) potassium binding resins increase colonic potassium excretion and are approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperkalemia. In 2009, the FDA recommended that sorbitol, a cathartic often given with SPS to prevent obstipation, not be added to SPS powder because of associated colonic necrosis. A premixed oral suspension of SPS in 33% sorbitol was not included in this warning. SPS resins increase stool potassium excretion in normokalemic subjects, but proportionately more potassium is excreted due to cathartics when the two are combined. In hyperkalemic patients, oral SPS mixed in water significantly decreases serum potassium within 24 hours. SPS/sorbitol-associated colonic necrosis is most commonly seen in patients who have received enemas in the setting of recent abdominal surgery, bowel injury, or intestinal dysfunction. It is a rare event, on the order of 0.2 to 0.3%, almost exclusively present in patients at risk. The agent most likely associated with colonic necrosis is 70% sorbitol, and animal data support that etiology. There is very little data to suggest that oral SPS given with 33% sorbitol (in the premixed form) or SPS powder in water orally or as an enema causes colonic necrosis. SPS ion-exchange resins are the only agents, other than dialysis and diuretics, available to increase potassium excretion in hyperkalemia, and when used appropriately, they appear to be clinically effective and reasonably safe.


Photobiomodulation therapy by NIR laser in persistent pain: an analytical study in the rat.
Over the past three decades, physicians have used laser sources for the management of different pain conditions obtaining controversial results that call for further investigations. In order to evaluate the pain relieving possibilities of photobiomodulation therapy (PBMT), we tested two near infrared (NIR) laser systems, with different power, against various kinds of persistent hyperalgesia animal models. In rats, articular pain was reproduced by the intra-articular injection of sodium monoiodoacetate (MIA) and complete Freund's adjuvant (CFA), while compressive neuropathy was modelled by the chronic constriction injury of the sciatic nerve (CCI). In MIA and CFA models, (NIR) laser (MLS-Mphi, ASA S.r.l., Vicenza, Italy) application was started 14 days after injury and was performed once a day for a total of 13 applications. In MIA-treated animals, the anti-hyperalgesic effect of laser began 5 min after treatment and vanished after 60 min. The subsequent applications evoked similar effects. In CFA-treated rats, laser efficacy started 5 min after treatment and disappeared after 180 min. In rats that underwent CCI, two treatment protocols with similar fluence but different power output were tested using a new experimental device called Multiwave Locked System laser (MLS-HPP). Treatments began 7 days after injury and were performed during 3 weeks for a total of 10 applications. Both protocols reduced mechanical hyperalgesia and hindlimb weight bearing alterations until 60 min after treatment with a higher efficacy recorded for the animals treated using the higher power output. In conclusion, this study supports laser therapy as a potential treatment for immediate relief of chronic articular or neuropathic pain.


[Treatment of gastrointestinal stromal tumor (GIST)--review of the literature and a case report].
Gastrointestinal stromal tumors (GIST) are rare mesenchimal tumors that are characterized by constitutive overexpression of the tyrosin-kinase receptor KIT (CD117). The authors analyse the basis of the treatment of gastric GIS, starting form the study of a recent observed case. Report of one case treated with endoscopic resection. Evaluation of treatment and 2-years follow-up. The treatment of gastric GIST must be modulated on prognostic, genetic and molecular factors. These factors are the basis of the formation and growth of GIST. Complete surgical extirpation without rupture remains the only curative treatment of localized favourable prognosis. Endoscopic treatment, as in our case, reflect the modulation of therapy on prognostic factors. Selective targeted therapy of metastatic disease yields encouraging clinical responses.


Sensory Substitution and Augmentation Using 3-Degree-of-Freedom Skin Deformation Feedback.
During tool-mediated interaction with everyday objects, we experience kinesthetic forces and tactile sensations in the form of vibration and skin deformation at the fingerpad. Fingerpad skin deformation is caused by forces applied tangentially and normally to the fingerpad skin, resulting in tangential and normal skin displacement. We designed a device to convey 3-degree-of-freedom (DoF) force information to the user via skin deformation, and conducted two experiments to determine the devices effectiveness for force-feedback substitution and augmentation. For sensory substitution, participants used 1-DoF and 3-DoF skin deformation feedback to locate a feature in a 3-DoF virtual environment. Participants showed improved precision and shorter completion time when using 3-DoF compared to 1-DoF skin deformation feedback. For sensory augmentation, participants traced a path in space from an initial to a target location, while under guidance from force and/or skin deformation feedback. When force feedback was augmented with skin deformation, participants reduced their path-following error over the cases when force or skin deformation feedback are used separately. We conclude that 3-DoF skin deformation feedback is effective in substituting or augmenting force feedback. Such substitution or augmentation could be used when force feedback is unattainable or attenuated due to device limitations or system instability.


Deodorants, value, and performance.
For the health-care market, like the deodorant market, the message is clear: Add value or your product will not be competitive. For physicians of all specialties, the best way to add value is to measure and improve performance. Performance measurement is critical to improvement in health care. Without measurement, there can be no improvement in quality. Without improvement in quality, there is no added value. Oncologists can take at least two actions to add value for their health plans: (1) measure practice performance and demonstrate a quality improvement; and (2) become the personal-care physician for cancer patients.


The initiation of gait in lower limb amputees: some related data.
The initiation of gait, from balanced standing position to the toe-off of the stance leg, was analyzed in 8 unilateral above-knee (AK) and 10 unilateral below-knee (BK) males amputees. Thirty-one parameters were measured, including ground-foot forces and the movements and timing of hip, knee, and ankle joints. The significant changes from the normal pattern of initiation of gait found in the AK and BK amputees, as well as significant changes between the two amputees groups themselves, are described. The amputees were divided into two subgroups: those who start walking with their prosthesis and those starting with their normal leg. The two groups were compared statistically for each amputation level and all were compared to a normal subjects group. Differences relating to the choice of the swing leg were found. The findings are reported as part of a future databank.


Palladium-catalyzed dicarbonylative synthesis of tetracycle quinazolinones.
An interesting procedure for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-ones has been developed. Starting from commercially available 2-bromoanilines and 2-bromobenzyl amines, with the assistance of a palladium catalyst, the desired products were isolated in good yields. Notably, this procedure proceeded in a highly selective manner; two molecules of CO were incorporated into the substrates selectively.


Solid-state NMR correlation experiments and distance measurements in paramagnetic metalorganics exemplified by Cu-cyclam.
We show how to record and analyze solid-state NMR spectra of organic paramagnetic complexes with moderate hyperfine interactions using the Cu-cyclam complex as an example. Assignment of the (13)C signals was performed with the help of density functional theory (DFT) calculations. An initial assignment of the (1)H signals was done by means of (1)H-(13)C correlation spectra. The possibility of recording a dipolar HSQC spectrum with the advantage of direct (1)H acquisition is discussed. Owing to the paramagnetic shifting the resolution of such paramagnetic (1)H spectra is generally better than for diamagnetic solid samples, and we exploit this advantage by recording (1)H-(1)H correlation spectra with a simple and short pulse sequence. This experiment, along with a Karplus relation, allowed for the completion of the (1)H signal assignment. On the basis of these data, we measured the distances of the carbon atoms to the copper center in Cu-cyclam by means of (13)CR2 relaxation experiments combined with the electronic relaxation determined by EPR.


Plant-pollinator network structural properties differentially affect pollen transfer dynamics and pollination success.
Plant-pollinator network studies have uncovered important generalities in the structure of these communities, rapidly advancing our understanding of the underlying drivers of such a structure. In spite of this, however, it is still unclear how changes in structural network properties influence overall plant pollination success. One key limitation is the lack of information on the relationship between network structural properties and aspects of pollination and plant reproductive success. Here, we estimate four plant species network structural metrics (interaction strength, weighted degree, closeness centrality, and specialization level), commonly used to describe their importance within plant-pollinator networks, at two different sites, and evaluate their effects on pollen deposition and pollen tube success. We found a positive effect of plant-pollinator specialization and a negative effect of closeness centrality on heterospecific pollen load size. We also found a marginal negative effect of closeness centrality on pollen tube success. Our results suggest that increasing plant-pollinator specialization within nested communities (pollinated by one or very few generalist insect species) may result in high levels of heterospecific pollen transfer. Furthermore, the differential effects of plant-pollinator network metrics on pollination success (pollen receipt and pollen tube success), highlight the need to integrate quantity (e.g. visitation rate) and quality (e.g. pollen delivery) aspects of pollination to achieve a more mechanistic understanding of the relationship between plant-pollinator network structure and function. Such knowledge is key to evaluate the resilience and stability of plant-pollinator communities and the services they provide in the face of increasing human disturbances.


Prostate cancer genomics, biology, and risk assessment through genome-wide association studies.
Prostate cancer (PC) is the most common malignancy observed in men. It is evident that genetic factors play some important roles in PC etiology. Recently, genome-wide association studies in diverse ethnic groups have identified more than 40 germline variants of various genes or chromosomal loci that are significantly associated with PC susceptibility, including multiple 8q24 loci, prostate-specific genes, metabolic and hormone-related genes, and many regions where no coding gene is annotated. However, there are only a few variants or genes for which biological significance or functions have been elucidated so far. The greatest challenge related to genome-wide association studies loci in prostate genomics is to understand the functional consequences of these PC-associated loci and their involvement in PC biology and carcinogenesis. There have been attempts to determine PC risk estimations by combining multiple PC-associated variants for clinical tests, and these can identify a very minor population with high risk of PC. However, they cannot distinguish risk of aggressive PC from that of non-aggressive PC. Further identification of PC-susceptibility loci in larger genome-wide association studies cohorts and biological insights gained from such functional analyses have the potential to translate into clinical benefits, including the development of reliable biomarkers, risk estimation, and effective strategies for screening and prevention of PC.


Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications.
Melanoma is one of the most dangerous forms of skin cancer, characterized by early metastasis and rapid development. In search for effective treatment options, much attention is given to triterpenoids of plant origin, which are considered promising drug candidates due to their well described anticancer properties and relatively low toxicity. This paper comprehensively summarizes the antimelanoma potential of natural triterpenoids, that are also used as scaffolds for the development of more effective derivatives. These include betulin, betulinic acid, ursolic acid, maslinic acid, oleanolic acid, celastrol and lupeol. Some lesser-known triterpenoids that deserve attention in this context are 22β-hydroxytingenone, cucurbitacins, geoditin A and ganoderic acids. Recently described mechanisms of action are presented, together with the results of preclinical in vitro and in vivo studies, as well as the use of drug delivery systems and pharmaceutical technologies to improve the bioavailability of triterpenoids. This paper also reviews the most promising structural modifications, based on structure-activity observations. In conclusion, triterpenoids of plant origin and some of their semi-synthetic derivatives exert significant cytotoxic, antiproliferative and chemopreventive effects that can be beneficial for melanoma treatment. Recent data indicate that their poor solubility in water, and thus low bioavailability, can be overcome by complexing with cyclodextrins, or the use of nanoparticles and ethosomes, thus making these compounds promising antimelanoma drug candidates for further development.


Hidden Markov models for wavelet-based blind source separation.
In this paper, we consider the problem of blind source separation in the wavelet domain. We propose a Bayesian estimation framework for the problem where different models of the wavelet coefficients are considered: the independent Gaussian mixture model, the hidden Markov tree model, and the contextual hidden Markov field model. For each of the three models, we give expressions of the posterior laws and propose appropriate Markov chain Monte Carlo algorithms in order to perform unsupervised joint blind separation of the sources and estimation of the mixing matrix and hyper parameters of the problem. Indeed, in order to achieve an efficient joint separation and denoising procedures in the case of high noise level in the data, a slight modification of the exposed models is presented: the Bernoulli-Gaussian mixture model, which is equivalent to a hard thresholding rule in denoising problems. A number of simulations are presented in order to highlight the performances of the aforementioned approach: 1) in both high and low signal-to-noise ratios and 2) comparing the results with respect to the choice of the wavelet basis decomposition.


Protection of tissue physicochemical properties using polyfunctional crosslinkers.
Understanding complex biological systems requires the system-wide characterization of both molecular and cellular features. Existing methods for spatial mapping of biomolecules in intact tissues suffer from information loss caused by degradation and tissue damage. We report a tissue transformation strategy named stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD), which uses a flexible polyepoxide to form controlled intra- and intermolecular cross-link with biomolecules. SHIELD preserves protein fluorescence and antigenicity, transcripts and tissue architecture under a wide range of harsh conditions. We applied SHIELD to interrogate system-level wiring, synaptic architecture, and molecular features of virally labeled neurons and their targets in mouse at single-cell resolution. We also demonstrated rapid three-dimensional phenotyping of core needle biopsies and human brain cells. SHIELD enables rapid, multiscale, integrated molecular phenotyping of both animal and clinical tissues.


Cytokinin-binding proteins from tobacco callus share homology with osmotin-like protein and an endochitinase.
To study the signal transduction of cytokinins, we characterized cytokinin-binding proteins (CBPs) isolated from tobacco callus Nicotiana tabacum. Two high-affinity CBPs, CBP1 and CBP2, were isolated from the soluble fraction of tobacco callus BY-2 cells by anion exchange chromatography on a DEAE-cellulose column and affinity chromatography on a benzyladenine (BA)-linked Sepharose 4B column. Cytokinin-binding activity was determined by the equilibrium dialysis method. The degree of purification of CBP1 and CBP2 was 270 and 600-fold, respectively. These proteins had molecular masses of 34 kDa and 26 kDa, and to bind benzyladenine (BA) with dissociation constants (Kd) of 8.9 x 10(-6) M and 1.1 x 10(-6) M, respectively. Binding of BA to CBP2 was inhibited by zeatin and kinetin but not by adenine, adenosine, ATP or IAA. The optimum pH for binding of BA to CBP1 and CBP2 was approximately pH 6.5 and 7.5, respectively. CBP1 showed significant homology (90%) with endochitinase and CBP2 with osmotin-like protein (OLP). These findings and the results of immunoblotting analysis and cytokinin-binding assay of recombinant OLP indicated that CBP2 is OLP, a stress protein.


Pharmacological activation of heme oxygenase (HO)-1/carbon monoxide pathway prevents the development of peripheral neuropathic pain in Wistar rats.
Recent studies have emphasized the contribution of neuroinflammation and oxido-nitrosative stress to neuropathic pain. Both, heme oxygenase (HO)-1 and carbon monoxide (CO) play an important role in regulating free radical generation and inflammation. Herein, we investigated the role of HO-1/CO pathway, by using hemin, a selective HO activator, and CO-releasing molecule (CORM)-2, a CO-releasing agent, in rat sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain. CCI rats exhibited full development of behavioral hypersensitivity symptoms, including cold allodynia, mechanical and thermal hyperalgesia and also exhibit of a significant increase in spinal cord pro-inflammatory cytokines (TNF-α and IL-1β) and oxido-nitrosative stress markers, both in spinal cord and ipsilateral sciatic nerve homogenate. Spinal (10 and 30 μg/rat, intrathecal (i.t.)), but not systemic (5 and 10 mg/kg, subcutaneous (s.c.)), administration of hemin for 14 days significantly prevented the development of behavioral hypersensitivity. Further, simultaneous administration of hemin via spinal (10 μg/rat, i.t.) and systemic (5 mg/kg, s.c.) routes led to a more pronounced inhibition of the development of behavioral hypersensitivity. Further, administration of CORM-2 (1 and 5 mg/kg, s.c.), dose-dependently and most effectively, prevented the development of behavioral hypersensitivity. Both hemin and CORM-2 produced ameliorative beneficial effects that paralleled with the extent of reduction of oxido-nitrosative stress and pro-inflammatory cytokines. Also, hemin and CORM-2 significantly improved the levels of HO-1 and activity of anti-oxidant enzymes such as superoxide dismutase and catalase. Thus, it may be concluded that chronic pharmacological activation of HO-1/CO pathway may prevent the development of behavioral symptoms of neuropathic pain, through an activation of anti-inflammatory and anti-oxidant mechanisms.


Coexistence of adenosine deaminase, histidine decarboxylase, and glutamate decarboxylase in hypothalamic neurons of the rat.
Neurons immunoreactive for the enzyme adenosine deaminase (ADA) in the posterior basal hypothalamus of the rat have a distribution pattern similar to those immunoreactive for histidine decarboxylase (HDC) and are particularly numerous in the tuberal (TM), caudal (CM) and postmammillary caudal (PCM) hypothalamic magnocellular nuclei which harbor neurons containing glutamic acid decarboxylase (GAD). The extent to which these enzymes coexist within neurons of these hypothalamic regions was examined using either serial sections or simultaneous immunostaining for ADA and HDC or GAD in the same section. Analysis of serial sections revealed neuronal coexistence of ADA with HDC or GAD in both TM and CM. In addition some neurons in CM, the only area examined for triple coexistence, were found to contain all three enzymes. In sections processed for ADA simultaneously with HDC or GAD, nearly all ADA-immunoreactive neurons in TM, CM, and PCM as well as those scattered between these nuclei were found to contain HDC, and nearly all contained GAD. Exceptions to this, however, were small cells located lateral to the posterior arcuate nucleus, which appeared to contain ADA but not HDC, and large neurons located at the anterior extreme of TM, which appeared to contain ADA but not GAD. The relatively few ADA- compared with GAD-containing neural systems in brain, together with the presence of ADA in GAD-containing hypothalamic magnocellular neurons, which appear to have widespread projections throughout the brain, indicate that ADA may be a convenient immunohistochemical marker for anatomical investigations of these projections.(ABSTRACT TRUNCATED AT 250 WORDS)


A transient bond model for dynamic constraints in meso-scale coarse-grained systems.
The dynamical properties of entangled polymers originate from the dynamic constraints due to the uncrossability between polymer chains. We propose a highly coarse-grained simulation model with transient bonds for such dynamically constrained systems. Based on the ideas of the responsive particle dynamics (RaPiD) model [P. Kindt and W. J. Briels, J. Chem. Phys. 127, 134901 (2007)] and the multi-chain slip-spring model [T. Uneyama and Y. Masubuchi, J. Chem. Phys. 137, 154902 (2012)], we construct the RaPiD type transient bond model as a coarse-grained slip-spring model. In our model, a polymer chain is expressed as a single particle, and particles are connected by transient bonds. The transient bonds modulate the dynamics of particles, but they do not affect static properties in equilibrium. We show the relation between parameters for the entangled polymer systems and those for the transient bond model. By performing simulations based on the transient bond model, we show how model parameters affect the linear viscoelastic behavior and the diffusion behavior. We also show that the viscoelastic behavior of entangled polymer systems can be well reproduced by the transient bond model.


Virtual reality, disability and rehabilitation.
Virtual reality, or virtual environment computer technology, generates simulated objects and events with which people can interact. Existing and potential applications for this technology in the field of disability and rehabilitation are discussed. The main benefits identified for disabled people are that they can engage in a range of activities in a simulator relatively free from the limitations imposed by their disability, and they can do so in safety. Evidence that the knowledge and skills acquired by disabled individuals in simulated environments can transfer to the real world is presented. In particular, spatial information and life skills learned in a virtual environment have been shown to transfer to the real world. Applications for visually impaired people are discussed, and the potential for medical interventions and the assessment and treatment of neurological damage are considered. Finally some current limitations of the technology, and ethical concerns in relation to disability, are discussed.


Review of the Amphibian Immune Response to Chytridiomycosis, and Future Directions.
The fungal skin disease, chytridiomycosis (caused by Batrachochytrium dendrobatidis and B. salamandrivorans), has caused amphibian declines and extinctions globally since its emergence. Characterizing the host immune response to chytridiomycosis has been a focus of study with the aim of disease mitigation. However, many aspects of the innate and adaptive arms of this response are still poorly understood, likely due to the wide range of species' responses to infection. In this paper we provide an overview of expected immunological responses (with inference based on amphibian and mammalian immunology), together with a synthesis of current knowledge about these responses for the amphibian-chytridiomycosis system. We structure our review around four key immune stages: (1) the naïve immunocompetent state, (2) immune defenses that are always present (constitutive defenses), (3) mechanisms for recognition of a pathogen threat and innate immune defenses, and (4) adaptive immune responses. We also evaluate the current hot topics of immunosuppression and immunopathology in chytridiomycosis, and discuss their respective roles in pathogenesis. Our synthesis reveals that susceptibility to chytridiomycosis is likely to be multifactorial. Susceptible amphibians appear to have ineffective constitutive and innate defenses, and a late-stage response characterized by immunopathology and Bd-induced suppression of lymphocyte responses. Overall, we identify substantial gaps in current knowledge, particularly concerning the entire innate immune response (mechanisms of initial pathogen detection and possible immunoevasion by Bd, degree of activation and efficacy of the innate immune response, the unexpected absence of innate leukocyte infiltration, and the cause and role of late-stage immunopathology in pathogenesis). There are also gaps concerning most of the adaptive immune system (the relative importance of B and T cell responses for pathogen clearance, the capacity and extent of immunological memory, and specific mechanisms of pathogen-induced immunosuppression). Improving our capacity for amphibian immunological research will require selection of an appropriate Bd-susceptible model species, the development of taxon-specific affinity reagents and cell lines for functional assays, and the application of a suite of conventional and emerging immunological methods. Despite current knowledge gaps, immunological research remains a promising avenue for amphibian conservation management.


Cutaneous vascular and sudomotor responses in human skin grafts.
Each year millions of individuals sustain burns. Within the US 40,000-70,000 individuals are hospitalized for burn-related injuries, some of which are quite severe, requiring skin grafting. The grafting procedure disrupts neural and vascular connections between the host site and the graft, both of which are necessary for that region of skin to contribute to temperature regulation. With the use of relatively modern techniques such as laser-Doppler flowmetry and intradermal microdialysis, a wealth of information has become available regarding the consequences of skin grafting on heat dissipation and heat conservation mechanisms. The prevailing data suggest that cutaneous vasodilator capacity to an indirect heat stress (i.e., heating the individual but not the evaluated graft area) and a local heating stimulus (i.e., directly heating the graft area) is impaired in grafted skin. These impairments persist for ≥4 yr following the grafting procedures and are perhaps permanent. The capacity for grafted skin to vasodilate to an endothelial-dependent vasodilator is likewise impaired, whereas its capacity to vasodilate to an endothelial-independent vasodilator is generally preserved. Sweating responsiveness is minimal to nonexistent in grafted skin to both a whole body heat stress and local administration of the primary neurotransmitter responsible for stimulating sweat glands (i.e., acetylcholine). Likewise, there is no evidence that this absence of sweat gland responsiveness improves as the graft matures. In contrast to the heating stimuli, cutaneous vasoconstrictor responses to both indirect whole body cooling (i.e., exposing the individual to a cold stress but not at the evaluated graft area) and direct local cooling (i.e., directly cooling the graft area) are preserved in grafted skin as early as 5-9 mo postgrafting. If uninjured skin does not compensate for impaired heat dissipation of grafted skin, individuals having skin grafts encompassing significant fractions of their body surface area will be at a greater risk for a hyperthermic-related injury. Conversely, the prevailing data suggest that such individuals will not be at a greater risk of hypothermia upon exposure to cold environmental conditions.