Insights on the Interaction between Transthyretin and Aβ in Solution. A Saturation Transfer Difference (STD) NMR Analysis of the Role of Iododiflunisal.
Several strategies against Alzheimer disease (AD) are directed to target Aβ-peptides. The ability of transthyretin (TTR) to bind Aβ-peptides and the positive effect exerted by some TTR stabilizers for modulating the TTR-Aβ interaction have been previously studied. Herein, key structural features of the interaction between TTR and the Aβ(12-28) peptide (3), the essential recognition element of Aβ, have been unravelled by STD-NMR spectroscopy methods in solution. Molecular aspects related to the role of the TTR stabilizer iododiflunisal (IDIF, 5) on the TTR-Aβ complex have been also examined. The NMR results, assisted by molecular modeling protocols, have provided a structural model for the TTR-Aβ interaction, as well as for the ternary complex formed in the presence of IDIF. This basic structural information could be relevant for providing light on the mechanisms involved in the ameliorating effects of AD symptoms observed in AD/TTR± animal models after IDIF treatment and eventually for designing new molecules toward AD therapeutic drugs.


Effects of local biotic neighbors and habitat heterogeneity on seedling survival in a spruce-fir valley forest, northeastern China.
Seedlings are vulnerable to many biotic and abiotic agents, and studying seedling dynamics helps understand mechanisms of species coexistence. In this study, the relative importance of biotic neighbors and habitat heterogeneity to seedling survival was examined by generalized linear mixed models for 33 species in a spruce-fir valley forest in northeastern China. The results showed that the relative importance of these factors varied with species and functional groups. Conspecific negative density dependence (CNDD) was important to the survival of Abies nephrolepis and Picea koraiensis seedling, whereas phylogenetic negative density dependence (PNDD) was critical to Pinus koraiensis and Betula platyphylla, as well as functional groups of tree, deciduous, and shade-intolerant seedlings. For shrubs and Acer ukurunduense, habitat heterogeneity was significant. Despite of the significance of CNDD, PNDD, and habitat heterogeneity on seedling survival, large proportions of the total variance were not accounted for by the studied variables, suggesting the needs to examine the influences of other factors such as pests, diseases, herbivores, forest structure, species functional traits, and microclimatic conditions on seedling survival in the future.


Sympathectomy or doxazosin, but not propranolol, blunt myocardial interstitial fibrosis in pressure-overload hypertrophy.
The adaptive changes that develop in the pressure-overloaded left ventricular (LV) myocardium include cardiomyocyte hypertrophy and interstitial fibrosis. Although the former is known to depend to a sizeable extent on sympathetic (over)activity, little information exists whether the same applies to the latter, ie, whether excess catecholamine exposure contributes to the imbalance between collagen deposition by fibroblasts and degradation by matrix metalloproteases (MMPs), eventually leading to LV collagen accumulation. Sprague-Dawley rats were subjected to abdominal aortic banding (B) or sham operation (S) and treated with beta-blockade (Bb, oral propranolol, 40 mg/kg per day), chemical sympathectomy (Sx, 6-hydroxydopamine, 150 mg/kg intraperitoneal twice per week) or vehicle (Vh). Ten weeks later, systolic blood pressure, LV weight, collagen abundance (computer-aided histology), zymographic matrix metalloproteinase (MMP)-2 activity and its specific tissue inhibitor concentration (TIMP-2) were measured. Both sympathectomy and beta-blockade failed to attenuate the banding-induced blood pressure elevation but significantly attenuated the attendant LV hypertrophy. As expected, pressure-overload hypertrophy was associated with interstitial fibrosis (collagen: 4.37+/-1.23% BVh versus 1.23+/-0.44% SVh, P<0.05), which was abolished by sympathectomy (2.55+/-1.31%, P=not significant versus SSx) but left unchanged by beta-blockade (4.11+/-1.23%, P<0.05 versus both SBb and BSx). beta-blockade, but not sympathectomy, was also associated with an increased TIMP-2/MMP-2 ratio (P<0.05), indicating reduced interstitial collagenolytic activity. In separate groups of banded and sham-operated rats, treatment with the alpha-receptor blocker doxazosin (10 mg/kg per day) displayed similar antifibrotic and biochemical effects as sympathectomy. Thus in the course of experimental pressure overload, the sympathetic nervous system plays a major pro-fibrotic role, which is mediated via alpha-adrenergic but not beta-adrenergic receptors.


Improvement in bioavailability of transdermally applied flurbiprofen using tulsi (Ocimum sanctum) and turpentine oil.
Penetration enhancing potential of tulsi and turpentine oil on transdermal delivery of flurbiprofen, a potent non-steroidal anti-inflammatory agent, was investigated. The transdermal permeation rate of flurbiprofen across the rat abdominal skin from binary solvent mixture composition of propylene glycol (PG):isopropyl alcohol (IPA) (30:70%, v/v) was 98.88 microg/cm(2)/h, significantly higher than other binary solvent mixtures. The corresponding steady state plasma concentration, 0.71 microg/ml, was much lower than required steady state plasma concentration of 3-5 microg/ml. Hence influence of tulsi and turpentine oil in the optimized binary solvent mixture along with the increased drug load on the flurbiprofen permeation was evaluated. The magnitude of the flux enhancement factor with turpentine oil and tulsi oil was 2.4 and 2.0 respectively at 5% (v/v) concentration beyond which there was no significant increase in the flux. Addition of 2% (w/v) hydroxypropyl methylcellulose (HPMC), as a thickening agent, resulted in desired consistency for the fabrication of patch with insignificant effect on permeation rate of flurbiprofen. The reservoir type of transdermal patch formulation, fabricated by encapsulating the flurbiprofen reservoir solution within a shallow compartment moulded from polyester backing film and microporous ethyl vinyl acetate membrane, did not modulate the skin permeation of flurbiprofen through rat skin in case of turpentine formulations whereas flux of formulations with tulsi oil was significantly altered. The influence of penetration enhancer and solvents on the anatomical structure of the rat skin was studied. Enhancement properties exhibited by turpentine oil and tulsi oil in optimized binary solvent mixture were superior as compared to solvent treated and normal control groups with negligible skin irritation. The fabricated transdermal patches were found to be stable. The bioavailability of flurbiprofen with reference to orally administered flurbiprofen in albino rats was found to increase by 2.97, 3.80 and 5.56 times with transdermal patch formulation without enhancer, tulsi and turpentine oil formulations, respectively. The results were confirmed by pharmacodynamic studies in rat edema inflammation model.


Low physical activity and mortality in women: baseline lifestyle and health as alternative explanations.
The aim of this study was to investigate the association between physical activity and mortality in post-menopausal women. In addition, the authors wanted to investigate to what extent this association could be attributed to confounding from other lifestyle factors, and to reverse causation due to a number of common health problems that may inhibit the ability to exercise. A total of 27,734 women aged 51-83 years from the Swedish Mammography Cohort were investigated. In 1997 they responded to a detailed questionnaire including questions on physical activity, diet, alcohol intake, smoking, and medical problems. During follow-up in 1999-2004, 1,232 deaths were identified by linkage to the National Population Register. Women with low physical activity (35 MET*h/day) had a 3.22 times increased mortality (95% confidence interval (CI) = 2.35-4.43) compared with the most active women (>50 MET*h/day). No increased risk was seen in women with moderate compared with high physical activity. Sedentary women tended to have a less healthy lifestyle and more health problems at baseline, e.g. almost 30% of them reported high blood pressure compared with less than 20% of active women. Baseline medical problems and lifestyle factors such as smoking, diet, and education accounted for 30% of the excess risk seen in sedentary women (24% and 6% respectively). This study indicates that even fairly small amounts of activity will reduce mortality in older women. However, sedentary women seemed to be a selected group with more medical problems and a less healthy lifestyle. The findings indicate that the association between physical inactivity and mortality will be overestimated if this is not taken into account.


Diffusion Tensor Imaging Studies on Recovery of Injured Optic Radiation: A Minireview.
The optic radiation (OR) is a visual neural fiber pathway for the transfer of visual information from the lateral geniculate body of the thalamus to the primary visual cortex. To demonstrate the recovery of an OR injury, quantification and visualization of changes to the injured OR are necessary. Diffusion tensor imaging (DTI) allows determination of the state of an OR by assessing the obtained DTI parameters. In particular, diffusion tensor tractography (DTT), which is derived from DTI data, allows three-dimensional visualization of the OR. Thus, recovery of an injured OR can be demonstrated by examining changes in DTI parameters and/or configuration on follow-up DTI scans or via DTT of the injured OR. Herein, we review nine DTI-based studies that demonstrated recovery of OR injuries. The results reported in these studies suggest that an OR injury has a potential for recovery. Moreover, the results of these studies can form a basis for elucidating the recovery mechanisms of injured OR. These studies have suggested two recovery mechanisms for OR injury: recovery via the original OR pathway or via the transcallosal fibers of the corpus callosum. However, only nine studies on this topic have been conducted to date and six of those nine studies were case reports. Therefore, further studies involving larger numbers of subjects and reporting precise evaluations of changes in OR injury during recovery are warranted.


Zeta potential determination with a microchannel fabricated in solidified solvents.
This paper proposes a simple and versatile method for the determination of the zeta potential of a channel wall and discusses the values measured for the surface of frozen solvents, which are not only of scientific interest but also of potential use for microfluidic platforms. The zeta potential of the solid surface is an important parameter for discussing its electrokinetic properties, the distribution and reaction of ions in an electric double layer, and the fluidic behavior in the space surrounded by the surface. While the zeta potential of colloidal matters can be determined from their electrophoretic mobility, it is often difficult to determine that of a bulk material. In this paper, the zeta potential of a microchannel fabricated in a frozen solvent is determined by measuring the apparent mobility of microparticles as the probe. The electrophoretic mobility of the microparticles has been measured in advance using microchip electrophoresis under various conditions. This approach allows us to determine the zeta potential of water-ice and frozen cyclohexane. We discuss the pH dependence of the zeta potential of ice and also effects of the NaCl concentration on that of ice and frozen cyclohexane.


[Hematopoietic cell differentiation orchestrated by transcription factor network and its related pathogenesis].
It has long been considered that hematopoietic system development is based on hematopoietic stem cell differentiation with a gradual loss of multipotency. However, recent studies have indicated that hematopoietic stem cells are composed of subsets that exhibit lineage skewing, thereby comprising a heterogeneous population. Therefore, the present hierarchical development model of the hematopoietic system may be reconsidered. Appropriate transcription regulators and epigenetic influences are required for cell differentiation. To this end, transcription factors, such as GATA1 for erythropoiesis and PU.1 for myelopoiesis, have been believed to play key roles at the initiation of hematopoietic cell differentiation. However, the mechanisms controlling the expression of these transcription factors are controlled, and the points at which the lineage commitments occur from hematopoietic stem cells through to progenitor cells are not fully elucidated. As per the findings of this study, we propose that the regulation of transcription and epigenetic factors are central events in hematopoietic cell differentiation.


Simulations of the absorption and fluorescence of indole in aqueous solution and at a nonpolar/polar interface.
Theoretical results are presented on the absorption and fluorescence of indole in aqueous solution as well as at the air/water surface. We use a combined quantum chemical statistical mechanical model with explicit solvent. An approximate ab initio complete active space self-consistent field description of the indole molecule is used, coupled to a discrete polarizable water medium. From the bulk simulations, strong support is found for the interchange mechanism, which explains the unusual solvent shift of the fluorescence of indole or tryptophan in a polar surrounding by a solvent induced switch of the fluorescing state. Two mechanisms are given to explain the different shifts for indole at the interface. First, a dielectric depletion effect, which is expected from the reduction of the amount of polar media. Second, an interface-specific effect, which derives from the stronger hydrogen bond formation at the surface. The latter effect acts to increase the shift for both absorption and emission at the surface as compared to the bulk. From these results, the intrinsic probe photophysics of tryptophan in proteins is discussed in terms of the properties of the protein/solvent interface and the orientation of the amino acid.


Transgenic mice expressing a truncated Peromyscus leucopus TNF-alpha gene manifest an arthritis resembling ankylosing spondylitis.
Several studies have implicated tumor necrosis factor-alpha (TNF-alpha) in autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the role of TNF-alpha in inflammatory arthritis, we generated transgenic mice harboring a truncated Peromyscus leucopus TNF-alpha (Pe-TNF) gene. An arthritic phenotype closely resembling human ankylosing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic phenotype in detail by radiographic and histologic techniques. It consisted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus TNF-alpha gene, in contrast to the RA-like phenotype described in transgenic mice expressing a truncated human TNF-alpha gene. The Pe-TNF transgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-alpha may initiate an autoimmune arthritis resembling ankylosing spondylitis.


Exoskeleton versus end-effector robot-assisted therapy for finger-hand motor recovery in stroke survivors: systematic review and meta-analysis.
The growing number of stroke survivors with residual hand disabilities requires the development of efficient recovery therapy, and robotic rehabilitation can play an important role. The study aims to compare the relative effects of end-effector (EE) and exoskeleton (EXO) hand devices in motor recovery of patients with finger-hand motor impairment stroke. We identified randomized controlled trials (RCTs) through search in database on PubMed, Embase, MEDLINE, Cochrane library until October 2020. We included as outcomes: motricity index (MI), quick version of disabilities of the arm, shoulder, and hand (QuickDASH) questionnaire, and Fugl-Meyer assessment for upper extremity (FMAUE). We performed a systematic review, a meta-analysis, and a surface under the cumulative ranking analysis (SUCRA). We included five RTCs and 149 subjects. MI showed a signifìcant improvement (p < .05) in robotic intervention group compared to control group (effect size, ES: 9.47; confidence interval, CI: 3.91, 15.03). QuickDASH reported a significant reduction (p < .05) in EXO group (ES: -6.71; CI: -9.17, -4.25). FMAUE showed a significant improvement (p < .05) in the EE group (ES:3; CI:1.97, 4.04). SUCRA analysis of MI demonstrated that robotic interventions are more likely to be the best option for motor recovery (97.3% of probability EXO; 48.3% EE; 4.4% control). Despite the limited number of studies included, exoskeleton robotic devices might be a better option than end-effector devices in the treatment of fingers motor impairment in stroke patients. Further studies are still needed to confirm the findings and should focus on a direct comparison of the two devices.


Immunohistochemical localization of kallikrein in human pancreas and salivary glands.
The localization of kallikrein in human exocrine organs was studied with a direct immunofluorescence method. In the submandibular and parotid salivary glands, kallikrein was found apically in the striated duct cells whereas it was absent from the main excretory ducts or present only as a weak luminal rim. Kallikrein was not found in the acinar cells or in cells of the intercalated ducts. In the pancreas, kallikrein-specific fluorescence was seen in the granular portion of the acinar cells, whereas the islets of Langerhans and ductal cells were unstained.


[Visual evoked potentials in patients with refraction amblyopia in the presence of high myopia].
The informative value of a method for assessing the degree of amblyopia, developed by the author, was assessed in examinations of 16 children (29 eyes) with ametropic amblyopia caused by high myopia and 41 healthy controls. The method consists in recording the pattern-reversal visual evoked potentials (VEP) evoked by 4 patterns of different checksize and contrast. A relationship has been revealed between the VEP types detected by the proposed method and the degree of amblyopia (degree of vision acuity loss). The author came to a conclusion that in ametropic amblyopia, similarly as in stimulus deprivation amblyopia, changes of VEP develop that reflect the deterioration of contrast sensitivity function in low spatial frequencies. The developed VEP method with the modifications described in this paper may be useful in the diagnosis and objective evaluation of the degree of amblyopia.


Strategies for combating bacterial biofilm infections.
Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.


Regulation of CO2 fixation gene expression in Acidithiobacillus ferrooxidans ATCC 23270 by Lix984n shock.
Acidithiobacillus ferrooxidans ATCC 23270 is an important model organism for bioleaching and bioremediation studies owing to its diverse metabolic capabilities, whereas lix984n is a widely used extractant. Little is known about the response of cbb genes in A. ferrooxidans to lix984n shock. Thus, to elucidate the response of the CO2 fixation genes in A. ferrooxidans ATCC 23270 to the addition of lix984n, the gene expression of cbb genes was examined using a real-time PCR. Although a natural increase or decrease in the expression of most cbb genes was observed after 5 min of shock with 3% (v/v) lix984n, sdhC and cbbR exhibited quick responses to the shock. Ten min of shock had a greater effect on the cbb gene expression, yet 15 min of shock had a significant effect on the Calvin cycle in A. ferrooxidans ATCC 23270, as the expression of all the cbb genes reached a very high level. Therefore, after a short lix984n shock, a solution of A. ferrooxidans can be re-used for bioleaching.


Theory of a reconstructive structural transformation in capsids of icosahedral viruses.
A theory of a reconstructive structural transformation in icosahedral capsid shells is developed for a whole family of virulent human viruses. It is shown that the reversible rearrangement of proteins during the virus maturation transformation is driven by the variation in the wave number l associated with the protein density distribution function. The collective displacement field of protein centers from their positions in the initial (procapsid) and the final (capsid) two-dimensional icosahderal structures is derived. The amplitude of the displacement field is shown to be small and it minimizes the calculated free energy of the transformation. The theory allows us to propose a continuous thermodynamical mechanism of the reconstructive procapsid-to-capsid transformation. In the frame of the density-wave approach, we also propose to take an equivalent plane-wave vector as a common structural feature for different icosahedral capsid shells formed by the same proteins. Using these characteristics, we explain the relation between the radii of the procapsid and capsid shells and generalize it to the case of the viral capsid polymorphism.


Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: profiling and comparison of two drug compendia.
Use of oral anticancer agents is gaining wide acceptance in the treatment of cancer. However, patients receiving oral therapy are at high risk for drug-drug interactions (DDIs). To create a drug profile for each clinically significant DDI involving selected oral anticancer agents and evaluate the agreement between 2 commonly used DDI compendia: Drug Interaction Facts (DIF) 2008 and Micromedex DRUGDEX. DDI profiles were developed based on primary and tertiary literature reviews. DIF 2008 and Micromedex DRUGDEX were compared to assess the consistency of listings, severity, and scientific evidence ratings of DDIs involving the oral anticancer agents that were selected. The Spearman correlation test was used to assess the correlation of the severity ratings between the 2 compendia. A total of 184 DDIs were identified. A DDI profile was created for 40 of these that met the predetermined criteria for clinically significant interactions. The comparative assessment showed inconsistency in DDI listings (15.2% of those identified were listed in DIF only and 46.7% were listed in Micromedex only), severity ratings (Spearman correlation coefficient 0.49), and scientific evidence ratings (disagreement 25.8%). The discrepancies in DDI listing and rating systems between the compendia evaluated here reflect the need for more studies to standardize the definitions and classifications of DDIs.


Different effects of metformin and insulin on primary and secondary chemoprevention of colorectal adenoma in diabetes type 2: Traditional and Bayesian meta-analysis.
Metformin and insulin differently affect the risk of colon cancer in type 2 diabetic patients, however their effects on colon adenoma is not clear. PubMed, ISI, Scopus and Cochrane databases were searched for studies reporting. The outcomes were total adenoma; advanced adenoma and recurrent adenoma. Traditional and Bayesian meta-analysis were conducted via random-effects models. Odds ratios (OR) with 95 % confidence intervals (CIs) / or credible intervals (CrI) were used to describe the ratio of different events. A random-effects model described by DerSimonian and Laird was performed, when significant between-study heterogeneity existed. Alternatively, an inverse variance fixed effects model was used, when there was no significant heterogeneity across studies. The potential publication bias was assessed with funnel plot, Egger and Begg's regression asymmetry tests. Moreover, "trim and fill" procedure was used to assess the possible effect of publication bias. For metformin intake, 11 studies (51991 patients) were included. The results showed that metformin significantly decreased the risk of advance adenoma (OR= 0.51, p< 0.001). The risk of total adenoma was not associated with metformin use (OR= 0.86, p=0.274), and metformin did not affect the risk of adenoma recurrence (OR= 0.89, p=0.137). Five studies (2678 patients) were included in the analysis to determine the effect of insulin therapy. Insulin significantly increased the risk of colorectal adenoma (OR= 1.43, p=0.002). These findings indicate that metformin has no protective effect on total and recurrent adenoma, whilst it significantly reduces the risk of advanced adenoma, but insulin increases the risk of total adenoma.


Method for increasing coupling efficiency between helical-core and standard single-mode fibers.
Helical core fibers (HCFs) suffer from low coupling efficiency and unavoidable excitation of higher order modes below the cutoff wavelength because of a core tilt with respect to the symmetry axis of the cladding. We propose an effective way of increasing the coupling efficiency to a HCF by untwisting its beginning section in a hydrogen flame. The proposed solution provides also a control over the excitation of higher order modes in HCFs and can be applied in splicing as well as in a free-space launching configuration. We experimentally demonstrate that by using the proposed method, the coupling efficiency between a SMF-28 and HCF can be increased to the level reachable for straight fibers, which is limited only by a modal fields mismatch. We also present detailed numerical and analytical studies of the coupling efficiency between a HCF and SMF versus the pitch distance in the partially untwisted input section of the HCF, which takes into account fundamental and higher-order modes.


Single frequency 1645 nm Er:YAG nonplanar ring oscillator resonantly pumped by a 1470 nm laser diode.
A 1645 nm Er:YAG nonplanar ring oscillator, resonantly pumped by a 1470 nm laser diode, is reported. By using a 0.5%-doped Er:YAG nonplanar ring resonator, a 0.284 W single-frequency laser output at 1645 nm was obtained with a slope efficiency of 42.1%. The beam quality in x and y directions were 1.064 and 1.039, respectively.


[Buprenorphine and pentazocine in acute myocardial infarct. Study for a differential use].
Morphine is known as the best analgesic for patients with acute myocardial infarction complicated by heart failure. In patients with uncomplicated acute myocardial infarction, buprenorphine has recently been indicated as an alternative to the widely used pentazocine. In order to verify if the haemodynamic effects of the two drugs differed, a randomized double-blind controlled trial was performed on 20 patients with uncomplicated acute myocardial infarction: 10 patients were treated with i.v. pentazocine 30 mg. and 10 patients with buprenorphine 0.30 mg. (equianalgesic doses). Right atrial, ventricular and pulmonary artery and capillary pressure, cardiac index, total pulmonary and total systemic resistance were measured before testing and 15', 30', 60', 180' and 240' after drug injection. PO2 was measured before drug injection and 30' and 60' later. Data were analyzed using the Wilcoxon test. All patients in each group showed uniform results: pentazocine increased total systemic resistance (mean increase 17%) while buprenorphine lowered it (mean reduction 12%) (P less than 0.05). Pentazocine lowered cardiac index (mean reduction 5.9%) while buprenorphine increased it (mean increase 9.3%) (P less than 0.05). Maximum changes occurred within 60' after the administration of both drugs. The other parameters did not change significantly from basal values. These results suggest that in patients with acute myocardial infarction uncomplicated by heart failure pentazocine and buprenorphine may be used in different haemodynamic situations. In the cases in which a reduction in total systemic resistance is desired, buprenorphine seems most suitable. However, in the presence of vagal reaction for instance, pentazocine may be administered.


Cardiac transplantation: patient selection in the current era.
Heart transplantation is a treatment option available to patients with end-stage heart failure who meet standardized selection criteria for transplant. Through a rigorous evaluation process, professionals set out to establish the patient's severity of heart failure, screen for comorbidities that may negatively affect survival, and assess psychosocial variables necessary for successful outcomes following transplantation. Because of a limited donor organ supply, each of these factors must be examined carefully to assure that this scarce resource is used to its greatest potential benefit.


Electrostatic lateral interactions drive ESCRT-III heteropolymer assembly.
Self-assembly of ESCRT-III complex is a critical step in all ESCRT-dependent events. ESCRT-III hetero-polymers adopt variable architectures, but the mechanisms of inter-subunit recognition in these hetero-polymers to create flexible architectures remain unclear. We demonstrate in vivo and in vitro that the Saccharomyces cerevisiae ESCRT-III subunit Snf7 uses a conserved acidic helix to recruit its partner Vps24. Charge-inversion mutations in this helix inhibit Snf7-Vps24 lateral interactions in the polymer, while rebalancing the charges rescues the functional defects. These data suggest that Snf7-Vps24 assembly occurs through electrostatic interactions on one surface, rather than through residue-to-residue specificity. We propose a model in which these cooperative electrostatic interactions in the polymer propagate to allow for specific inter-subunit recognition, while sliding of laterally interacting polymers enable changes in architecture at distinct stages of vesicle biogenesis. Our data suggest a mechanism by which interaction specificity and polymer flexibility can be coupled in membrane-remodeling heteropolymeric assemblies.


Citizens' views on the practices of zero-grazing and cow-calf separation in the dairy industry: Does providing information increase acceptability?
The primary aim of this study was to assess the influence of provision of information on lay citizens' opinions regarding 2 common management practices, zero-grazing and cow-calf separation. To aid in the interpretation of the findings, our secondary aim was to explore the awareness and opinions of Brazilian citizens about these practices. We surveyed a convenience sample of Brazilian citizens (192 men and 208 women), recruited in a public place, with the majority stating that they were largely unfamiliar with animal production and lived in urban environments. Participants were presented short scenarios with information on the primary production factors and welfare concerns for and against zero-grazing (n = 200) or cow-calf separation (n = 200). Participants were then asked to state their position (reject, indifferent, or support), and to provide the reason(s) justifying their position. Immediately following, participants were provided a short statement describing either zero-grazing or cow-calf separation, depending on what question they responded to in the first part. Two closed questions (Q) followed each of these statements: (Q1) "Are you aware of this practice?" with choices yes, somewhat, or no, and (Q2) "What is your position regarding this practice?" with choices reject, indifferent, or support. Only 31 and 33% of the respondents were aware of zero-grazing and cow-calf separation, respectively. Previous awareness of existence of practice did not influence levels of support. Provision of information resulted in more people rejecting the practices of zero-grazing and cow-calf separation. Participants' main justifications to reject zero-grazing and cow-calf separation focused on perceived negative effects of practices on farm animal welfare and product quality, and loss of naturalness. Survey participants, Brazilians living in urban environments, with little or no association with dairy production, were generally unaware that many cows do not have access to pasture and that cows are separated from their calf at birth. Independent of provision of additional information, most participants did not support these practices. Provision of brief explanatory information played a minor role in influencing people's views, but failed to result in general acceptance.


How to image the gallbladder in suspected cholecystitis.
As a result of important advances in medical imaging, the oral cholecystogram is no longer the primary test of gallbladder function and anatomy. Real-time ultrasonography and cholescintigraphy, both highly sensitive and specific tests, are the two major methods for assessing gallbladder pathology. Oral cholecystography, endoscopic retrograde pancreatography, and percutaneous gallbladder puncture serve as supplementary tests. Decisions about which test to use depend on the kind of gallbladder disease that is suspected as well as the estimated likelihood of the disease before the information is obtained from the procedure. Thus, ultrasonography is the test of choice for chronic cholecystitis, with oral cholecystography reserved for situations in which the diagnosis is uncertain after ultrasonography. When acute cholecystitis is suspected, ultrasonography is also the test of choice in most patients, and cholescintigraphy is used to resolve uncertainty.


Descemet's Membrane Biomimetic Microtopography Differentiates Human Mesenchymal Stem Cells Into Corneal Endothelial-Like Cells.
Loss of corneal endothelial cells (CECs) bears disastrous consequences for the patient, including corneal clouding and blindness. Corneal transplantation is currently the only therapy for severe corneal disorders. However, the worldwide shortages of corneal donor material generate a strong demand for personalized stem cell-based alternative therapies. Because human mesenchymal stem cells are known to be sensitive to their mechanical environments, we investigated the mechanotransductive potential of Descemet membrane-like microtopography (DLT) to differentiate human mesenchymal stem cells into CEC-like cells. Master molds with inverted DLT were produced by 2-photon lithography (2-PL). To measure the mechanotransductive potential of DLT, mesenchymal stem cells were cultivated on silicone or collagen imprints with DLT. Changes in morphology were imaged, and changes in gene expression of CEC typical genes such as zonula occludens (ZO-1), sodium/potassium (Na/K)-ATPase, paired-like homeodomain 2 (PITX2), and collagen 8 (COL-8) were measured with real-time polymerase chain reaction. At least immunofluorescence analysis has been conducted to confirm gene data on the protein level. Adhesion of MSCs to DLT molded in silicone and particularly in collagen initiates polygonal morphology and monolayer formation and enhances not only transcription of CEC typical genes such as ZO-1, Na/K-ATPase, PITX2, and COL-8 but also expression of the corresponding proteins. Artificial reproduction of Descemet membrane with respect to topography and similar stiffness offers a potential innovative way to bioengineer a functional CEC monolayer from autologous stem cells.


Effect of substrate and phosphate ions on the quaternary structure symmetry of glyceraldehyde-3-phosphate dehydrogenases of mung beans and rabbit muscle.
Effects of glyceraldehyde-3-phosphate (G-3-P) and phosphate ions on thermal inactivation of glyceraldehyde-3-phosphate dehydrogenases (GPDHs) of mung beans and rabbit muscle have been studied at different pH. In the absence of any ligand, the two enzymes show a striking similarity in the pH-dependence of the kinetics of thermal inactivation. At lower pH values both the enzymes biphasic kinetics with each phase accounting for about half of the starting activity (a C2 symmetry of the homotetrameric enzyme molecule). The kinetics change to a single exponential decay at higher pH values, a D2 symmetry [Malhotra & Srinivasan (1985) Arch. Biochem. Biphys. 236, 775-781; Malhotra & Tikoo (1991) Indian, J. Biochem. Biophys. 28, 16-21]. With each enzyme, phosphate ions are found to have no effect on the kinetic pattern at lower pH, but G-3-P brings about a change from biphasic to a single exponential decay. At higher pH values, G-3-P has no effect on the single exponential decay kinetic pattern, but phosphate ions change the same to a biphasic loss of activity with each phase accounting for about half of the starting activity. It has been concluded that with both the enzymes, G-3-P and phosphate ions have higher affinity and stabilise the D2- and C2-symmetry conformation, respectively. Binding isotherms of the two substrates for these enzymes have been described based on the ligand concentration-dependence of the changes in the rate constants and kinetic pattern of thermal inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel Function of Lysine Methyltransferase G9a in the Regulation of Sox2 Protein Stability.
G9a is a lysine methyltransferase (KMTase) for histone H3 lysine 9 that plays critical roles in a number of biological processes. Emerging evidence suggests that aberrant expression of G9a contributes to tumor metastasis and maintenance of a malignant phenotype in cancer by inducing epigenetic silencing of tumor suppressor genes. Here, we show that G9a regulates Sox2 protein stability in breast cancer cells. When G9a lysine methyltransferase activity was chemically inhibited in the ER(+) breast cancer cell line MCF7, Sox2 protein levels were decreased. In addition, ectopic overexpression of G9a induced accumulation of Sox2. Changes in cell migration, invasion, and mammosphere formation by MCF7 cells were correlated with the activity or expression level of G9a. Ectopic expression of G9a also increased Sox2 protein levels in another ER(+) breast cancer cell line, ZR-75-1, whereas it did not affect Sox2 expression in MDA-MB-231 cells, an ER(-) breast cancer cell line, or in glioblastoma cell lines. Furthermore, treatment of mouse embryonic stem cells with a KMT inhibitor, BIX-01294, resulted in a rapid reduction in Sox2 protein expression despite increased Sox2 transcript levels. This finding suggests that G9a has a novel function in the regulation of Sox2 protein stability in a cell type-dependent manner.


Congenital skeletal abnormalities in a tawny owl chick (Strix aluco).
In this case report, we describe a tawny owl chick (Strix aluco) coming from a Wild Fauna Recovery Center with multiple congenital malformations in the limbs. The animal was unable to fly and showed marked malnutrition and poor general appearance. Physical, radiologic, and anatomic examinations showed osseous malformations including dislocation of radius and carpometacarpus with abnormal nonfunctional fixation of ligamentum propatagialis, absence of most parts of the bones of the manus in both wings, and twisted nonfused left tarsometatarsus with marked griphosis of digits. Routine toxicologic and pathologic examinations did not reveal a specific etiology.


Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways.
Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5-20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose >250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-β1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-α, IL-6, and NF-κB expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.


Molecular cloning of two alternatively spliced forms of human phosphatidic acid phosphatase cDNAs that are differentially expressed in normal and tumor cells.
Phosphatidic acid (PA) and diacylglycerol (DG) are lipids involved in signal transduction and in structural membrane-lipid biosynthesis in cells. Phosphatidic acid phosphatase (PAP) catalyzes the conversion of PA to DG. This enzyme exists in at least two isoforms, one of which (PAP1) is presumed to be cytosolic and membrane associated and the other (PAP2) to be an integral membrane protein. Homology search of the GenBank database using a murine sequence probe enabled the cloning of several putative human isoenzymes. Two isoforms, presumed to be alternative splice variants from a single gene, designated as PAP2-alpha1 and PAP2-alpha2, have been cloned and expressed. The PAP2-alpha1 and PAP2-alpha2 have a 84% and a 72% overall match, respectively, with the published mouse PAP amino acid sequence. The area of alternative exon usage was confined to the coding region at amino acids 20 to 70. Ectopic expression of PAP2-alpha1 and PAP2-alpha2 cDNAs in ECV304 endothelial cells led to a 6- to 8-fold and a 2-fold increase in PAP activity, respectively, in cell-free extracts using an in vitro assay that measured the conversion of [14C]PA to [14C]DG. The increase in PAP activity in PAP2-alpha-transfected cells correlated with a >50% decrease in the steady-state PA level. Northern analysis showed that PAP2-alpha mRNA expression was suppressed in several tumor tissues, notably those derived from the lower alimentary tract. Subsequent analysis of colon tumor tissue derived from four donors confirmed lower expression of PAP2-alpha than in matching normal colon tissue. Considering these data and previous demonstrations that certain transformed cell lines have lower PAP activity, we suggest that human PAP cDNAs may be candidates for gene therapy for certain tumors.


Beta-thromboglobulin in mesangial IgA nephritis.
Plasma beta-thromboglobulin (beta-TG) concentration were determined in 28 patients with mesangial IgA nephritis (17 with focal glomerular sclerosis and 11 without any glomerular sclerosis) and compared with those from 52 normal subjects and 24 patients controls with no evidence of renal disease. The mean beta-TG concentration in the patients with IgA nephritis [159 +/- 63 ng/ml (SD)] significantly different from the patients controls [32 +/- 25 ng/ml (SD)] (p less than 0.001) as well as the group of normal subjects [23 +/- 17 ng/ml (SD)] (p less than 0.001). In another group of 12 patients with diffuse mesangial proliferative glomerulonephritis with no IgA deposits (non IgA nephritis) the mean beta-TG concentration [126 +/- 86 ng/ml (SD)] though different from that of the normal as well as patient controls (p less than 0.001) was not significantly different from the IgA nephritis patients. The elevated beta-TG levels in the nephritic patients showed no correlation with serum creatinine, creatinine clearance or proteinuria but was significantly correlated with the degree of glomerular sclerosis (r = 0.44) (p less than 0.05). In vivo activation of the platelets is suggested by these findings of elevated beta-TG in patients with diffuse proliferative mesangial glomerulonephritis (IgA and non IgA).


Octapeptide segments from the amino terminus of glycophorin A contain the antigenic determinants of the M and N blood groups systems.
Human red blood cells with phenotype N/N and M/M were tested in an agglutination assay with anti-N and anti-M antibodies, respectively. After incubation of the synthesized octapeptide (Leu-Ser-Thr-Thr-Glu-Val-Ala-Met) from the N-amino terminus of glycophorin A, with anti-N antibody, there was significant inhibition of the agglutination of the N-positive cells. There was also inhibition of the agglutination of the M-positive cells with anti-M antibody by the synthesized octapeptide (Ser-Ser-Thr-Thr-Gly-Val-Ala-Met) from the M-amino terminus of glycophorin A. There was no inhibition, however, of the agglutination of M-positive cells with anti-M antibodies by the N-amino terminal octapeptide. Likewise, the M-amino terminal octapeptide did not inhibit agglutination of N-positive cells with anti-N. Because the synthesized octapeptides contained no carbohydrate, the anti-N and anti-M specificity appears to be determined principally by the peptides themselves. Further studies with the use of chimeric peptides indicate that the amino terminal amino acid leucine of N-glycophorin A is a primary determinant of the N antigen, whereas the amino terminal serine of M-glycophorin A is a primary determinant for the M antigen.


Finite size effects on locating conformational transitions for macromolecules.
It has been shown from simulation and experiment that locations of peaks in structural and thermodynamic quantities accompanying "phase" transitions of a single macromolecule (collapse or crystallization/melting) do not coincide. Thus, for chains with finite lengths these different measures yield apparently different results for transition temperatures. To resolve this issue we use scaling, verified by computer simulations, to conclusively show that these different locations for peak positions are simply a consequence of the finite chain length, as has been conjectured previously.


Epidemiological patterns of tuberculosis in Croatia in the period 1996-2005.
The last comprehensive publication on tuberculosis in Croatia and the earliest impact of war, besides the yearly routine reports, was done in 1996 in Croatian. We were, therefore, interested to explore incidence trends and to highlight the early post-war tuberculosis epidemiological patterns in the next ten years period (1996-2005). A retrospective analysis of epidemiological data on all registered tuberculosis cases in Croatia searching the databases of 21 Croatian Public Health Institutes and the National Tuberculosis Registry was made. During the study period, the total tuberculosis incidence rates in Croatia dropped from 45 to 25.8/100 000 inhabitants. The average highest age-specific rates were recorded in the age group > or = 65 years being in decrease in all age groups. Paediatric cases (0-14 years) represented 4.5% of all cases. Tuberculosis cases among males were recorded in 64% cases, and 83.6% were indigenous population. Tuberculosis was bacteriologically confirmed in 67.7% cases. A low proportion of drug resistance (3.3%) was recorded. During 1985-2005, 56 tuberculosis cases among 242 AIDS cases were reported. Tuberculosis mortality showed a decreasing trend (p < 0.001). However, tuberculosis has still had the highest mortality rates among infectious diseases in Croatia. Despite the War chain of events and tuberculosis programmatic changes, tuberculosis incidence rates in Croatia have been decreasing but they are still far away from national target, incidence rate of 10/100 000 declared in 1998 and much higher than in European Union and Western Europe. Tuberculosis among children, resistance to tuberculosis drugs and HIV prevalence, significant problems in many European countries, have not caused problems in tuberculosis control in Croatia. This favourable epidemiological situation must be kept and improved through strengthened tuberculosis control measures.


Graphene Hollow Micropatterns via Capillarity-Driven Assembly for Drug Storage and Neural Cell Alignment.
Electrical conductivity, cell-guided surface topology, and drug storage capacity of biomaterials are attractive properties for the repair and regeneration of anisotropic tissues with electrical sensitivity, such as nerves. However, designing and fabricating implantable biomaterials with all these functions remain challenging. Herein, we developed a freestanding graphene substrate with micropatterned surfaces by a simple templating method. Importantly, the raised surface micropatterns had an internal hollow structure. The morphology results showed that the template microgroove width and the graphene nanosheet size were important indicators of the formation of the hollow structures. Through real-time monitoring and theoretical analysis of the formation process, it was found that the main formation mechanism was the delamination and interlayer movement of the graphene nanosheets triggered by the evaporation-induced capillary force. Finally, we achieved the controlled release of loaded microparticles and promoted the orientation of rat dorsal root ganglion neurons by applying an electric field to the hollow micropatterns. This capillarity-induced self-assembly strategy paves the way for the development of high-performance graphene micropatterned films with a hollow structure that have potential for clinical application in the repair of nerve injury.


Profile of systemic sclerosis in a tertiary care center in North India.
To study the clinical and immunological profile in patients of systemic sclerosis from North India and compare it with other ethnic groups. Patients presenting to us between the years 2001 and 2004 and fulfilling the American Rheumatism Association (ARA) criteria for systemic sclerosis were included. There were 84 females and 16 males with the mean age of 32.5 +/-11.62 years and a mean duration of 6.49 +/- 4.34 years. All patients were admitted to the dermatology ward for detailed history and examination including Rodnan score. Investigations including hemogram, hepatic and renal functions, serum electrolytes, urine for albumin, sugar, microscopy and 24h urinary protein estimation, antinuclear antibody, chest X-ray, barium swallow, pulmonary function test, electrocardiogram and skin biopsy were done. The most common presenting symptoms were skin binding-down (98.5%), Raynaud's phenomenon 92.9%, pigmentary changes 91%, contracture of fingers 64.6%, fingertip ulcer 58.6%, restriction of mouth opening 55.5%, dyspnea 51.1%, joint complaints 36.7% and dysphagia in 35.2%. The mean Rodnan score was 25.81 +/- 10.04 and the mean mouth opening was 24.6 +/- 19.01 mm. The laboratory abnormalities included raised ESR in 87.8%, ANA positive in 89.1%, proteinuria in 6.0%, abnormal chest X-ray in 65.3%, abnormal barium swallow in 70.2% and reduced pulmonary function test in 85.8%. The clinical and immunological profile of systemic sclerosis in North India is similar to that of other ethnic groups except that pigmentary changes are commoner and renal involvement is relatively uncommon.


Dendritic cells in cancer immunotherapy.
Antigen presentation is a critical regulatory element for the induction of cellular immune responses. Thus, one of the principal current goals of tumor immunotherapy is to control and enhance tumor antigen presentation. In this respect, dendritic cells (DC) are now being widely investigated as immunotherapeutic agents for the treatment of disseminated malignancies. At present, numerous ways to employ DCs for tumor immunotherapy are being tested, ranging from direct in situ expansion and activation of DCs to adoptive transfer of ex vivo generated DCs, and numerous techniques have been designed to optimize DC activation, tumor antigen delivery to DCs, and induction of tumor-specific, as well as helper immune responses, in vivo. However, the results of recent preclinical studies and the diversity of the clinical phase I trials that are currently underway indicate that little is still known about the exact mechanisms by which DCs modulate tumor immunity and pose the concern that premature clinical trials might not yield the desired results and might be harmful to, rather than promote, the concept of DC-based tumor immunotherapy. This review summarizes some of the current approaches to induce tumor immunity by DC-based vaccination and discusses their advantages and concerns.


Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology.
Nanoparticles are of great importance in development and research because of their application in industries and biomedicine. The development of nanoparticles requires proper knowledge of their fabrication, interaction, release, distribution, target, compatibility, and functions. This review presents a comprehensive update on nanoparticles' toxic effects, the factors underlying their toxicity, and the mechanisms by which toxicity is induced. Recent studies have found that nanoparticles may cause serious health effects when exposed to the body through ingestion, inhalation, and skin contact without caution. The extent to which toxicity is induced depends on some properties, including the nature and size of the nanoparticle, the surface area, shape, aspect ratio, surface coating, crystallinity, dissolution, and agglomeration. In all, the general mechanisms by which it causes toxicity lie on its capability to initiate the formation of reactive species, cytotoxicity, genotoxicity, and neurotoxicity, among others.


An FPGA Based Energy-Efficient Read Mapper With Parallel Filtering and In-Situ Verification.
In the assembly pipeline of Whole Genome Sequencing (WGS), read mapping is a widely used method to re-assemble the genome. It employs approximate string matching and dynamic programming-based algorithms on a large volume of data and associated structures, making it a computationally intensive process. Currently, the state-of-the-art data centers for genome sequencing incur substantial setup and energy costs for maintaining hardware, data storage and cooling systems. To enable low-cost genomics, we propose an energy-efficient architectural methodology for read mapping using a single system-on-chip (SoC) platform. The proposed methodology is based on the q-gram lemma and designed using a novel architecture for filtering and verification. The filtering algorithm is designed using a parallel sorted q-gram lemma based method for the first time, and it is complemented by an in-situ verification routine using parallel Myers bit-vector algorithm. We have implemented our design on the Zynq Ultrascale+ XCZU9EG MPSoC platform. It is then extensively validated using real genomic data to demonstrate up to 7.8× energy reduction and up to 13.3× less resource utilization when compared with the state-of-the-art software and hardware approaches.


[Correlated activity of neurons in the sensorimotor cortices of the left and right hemispheres of rabbit brain during immobilization catatony].
Spike trains of individual neurons in the sensorimotor cortex detected in simultaneous multiunit records from the left and right rabbit brain hemispheres were analyzed in the baseline state, during immobilization ("animal hypnosis"), and after the termination of this state. The crosscorrelation analysis of pulse series revealed a relationship between the moments of spike generation by neurons of the left and right hemispheres. A significant correlation between the spike trains was considered as an interaction between the neurons (i.e., mutual influence of the cells on each other). It was shown that the strength of the effects of left-hemispheric neurons on cells of the right hemisphere could significantly vary (as compared to baseline) at any stage of the experiment and in any of the time periods analyzed. The strength of the effects activity by neurons of the right-hemispheres on cells of the left-hemispheres significantly changed only after the termination of the immobilization state and in substantially lower time limits.


Hirschsprung's disease genes and the development of the enteric nervous system.
Hirschsprung's disease or aganglionic megacolon causes chronic, congenital obstipation at an incidence of 1 per 5000 live births. Two approaches have been vital to the present understanding of the pathogenesis and genetic background of the disease: disease linkage analyses and mouse models of aganglionic megacolon. Because the increasing number of transgenic or natural mouse strains with congenital megacolon has led to mutation screening in Hirschsprung's disease patients, almost every second patient could now receive a genetic explanation for his/her disease. The known disease genes include tyrosine kinase receptor Ret, endothelin receptor B and its ligand endothelin 3. In addition, mutations have been found in the gene encoding the glial cell line-derived neurotrophic factor, the ligand for Ret, but these may only have a modifier effect. The mouse models have also provided insight into the developmental mechanisms of the normal intestinal innervation. We combine here the present clinical data on the gene mutations in Hirschsprung's disease with the experimental molecular biology data, and formulate a hypothesis on the pathogenesis of this multigenic-multifactorial disease.


[Analysis of structure and causes of mortality of HIV-infected in Volga Federal District in 2005 - 2010].
Among with morbidity and affection, mortality is an objective indicator of HIV-infection epidemic process intensity. Dynamics of mortality of HIV-infected in Volga Federal District (VFD) in 2005 - 2010, distribution of deceased by disease stage, period of start and coverage by antiretroviral therapy were studied based on approved statistical forms and additional collected data, the leading causes of death were revealed, comparative analysis with population of HIV-infected in penitentiary system institutions was performed. All-cause mortality was established to have dynamics of growth in HIV-infected population in VFD in 2005 - 2010, at the same time HIV-infection mortality has a certain tendency of stabilization after 2007 with subsequent decline in 2010, that apparently is related to wide use of combined antiretroviral therapy. HIV-infection mortality among HIV-infected in penitentiary system of the district is significantly higher than mortality in the general population of HIV-infected in VFD. The leading cause of death in HIV-infection is tuberculosis.


A Preliminary Model of Motivation for Pornography Consumption Among Men Participating in Zoophilic Virtual Environments.
Although zoophilic blogs and websites attract the attention of zoophiles and others who are curious about this sexual activity, the motivations for consuming this type of pornography are not clear. This study aimed to confirm the factorial validity of the Pornography Consumption Inventory in an online sample of men with sexual interest in animals, and to construct an association model between motivations for pornography consumption and the following psychological variables: depression, sexual impulsiveness, and strength of sexual interest in animals. In this cross-sectional study, we located a website that catered to a network of people with a sexual interest in animals. Subsequently, a questionnaire was made available online to members of this network. Results support the 4-factor model of the Pornography Consumption Inventory. Depression and strength of sexual interest in animals were negatively and positively correlated with the sexual curiosity factor, respectively. Sexual impulsiveness was positively associated with the emotional avoidance, excitement seeking, and sexual pleasure factors. Depression and sexual impulsiveness were positively correlated. Psychological factors can differently motivate the consumption of pornography among men who visit zoophilic blogs and websites. With these preliminary data, we can identify some characteristics of this population.


Fluoxetine protects against big endothelin-1 induced anti-apoptosis by rescuing Kv1.5 channels in human pulmonary arterial smooth muscle cells.
Pulmonary Kv channels are thought to play a crucial role in the regulation of cell proliferation and apoptosis. Previous studies have shown that fluoxetine upregulated the expression of Kv1.5 and prevented pulmonary arterial hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The current study was designed to test how fluoxetine regulates Kv1.5 channels, subsequently promoting apoptosis in human PASMCs cultured in vitro. Human PASMCs were incubated with low-serum DMEM, ET-1, and fluoxetine with and without ET-1 separately for 72 h. Then the proliferation, apoptosis, and expression of TRPC1 and Kv1.5 were detected. In the ET-1 induced group, the upregulation of TRPC1 and down regulation of Kv1.5 enhanced proliferation and anti-apoptosis, which was reversed when treated with fluoxetine. The decreased expression of TRPC1 increased the expression of Kv1.5, subsequently inhibiting proliferation while promoting apoptosis. The results from the present study suggested that fluoxetine protects against big endothelin-1 induced anti-apoptosis and rescues Kv1.5 channels in human pulmonary arterial smooth muscle cells, potentially by decreasing intracellular concentrations of Ca²⁺.


Cardiac tamponade in diarrhoea-positive haemolytic uraemic syndrome.
The spectrum of extra-renal involvement secondary to diarrhoeal (D+) haemolytic uraemic syndrome (HUS) includes neurological, gastrointestinal, hepatic, pancreatic and cardiac complications. Among the cardiac complications, myocardial injury has been more commonly reported with HUS. Literature is scarce on HUS-associated pericardial involvement. We report a HUS-induced significant pericardial effusion that resulted in a cardiac tamponade. We also discuss the diagnostic and therapeutic implications of this complication.


Five shades of gray: Conceptual and methodological issues around multivariate models of performance validity.
This study was designed to empirically investigate the signal detection profile of various multivariate models of performance validity tests (MV-PVTs) and explore several contested assumptions underlying validity assessment in general and MV-PVTs specifically. Archival data were collected from 167 patients (52.4%male; MAge = 39.7) clinicially evaluated subsequent to a TBI. Performance validity was psychometrically defined using two free-standing PVTs and five composite measures, each based on five embedded PVTs. MV-PVTs had superior classification accuracy compared to univariate cutoffs. The similarity between predictor and criterion PVTs influenced signal detection profiles. False positive rates (FPR) in MV-PVTs can be effectively controlled using more stringent multivariate cutoffs. In addition to Pass and Fail, Borderline is a legitimate third outcome of performance validity assessment. Failing memory-based PVTs was associated with elevated self-reported psychiatric symptoms. Concerns about elevated FPR in MV-PVTs are unsubstantiated. In fact, MV-PVTs are psychometrically superior to individual components. Instrumentation artifacts are endemic to PVTs, and represent both a threat and an opportunity during the interpretation of a given neurocognitive profile. There is no such thing as too much information in performance validity assessment. Psychometric issues should be evaluated based on empirical, not theoretical models. As the number/severity of embedded PVT failures accumulates, assessors must consider the possibility of non-credible presentation and its clinical implications to neurorehabilitation.


Successful Treatment of Community-Acquired Methicillin-Resistant Staphylococcus Aureus Necrotizing Pneumonia in the Setting of Chronic Graft-Versus-Host Disease.
Necrotizing pneumonia (NP) is a rare complication of community-acquired pneumonia that results in tissue necrosis and permanent destruction of the lung parenchyma. This study presents a case of a 21-year old male patient with T-cell acute lymphoblastic lymphoma who was treated with chemotherapy and matched-unrelated donor stem cell transplantation. His post-transplant course included chronic graft-versus-host disease (GVHD) and subsequent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) necrotizing pneumonia. In addition to antibiotics, steroids were used to help blunt the proinflammatory response following CA-MRSA pneumonia and this led to a rapid improvement in our patient's clinical course. CA-MRSA pneumonia is often treated with vancomycin. Given the nature of necrotizing pneumonia, the use of a toxin reducing agent like linezolid and adjunct therapy with corticosteroids was beneficial in the management of this disease process in our patient with chronic GVHD. Further prospective studies are needed to evaluate this regimen as a therapeutic alternative.


Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM patients.
Platelets participate in the atherothrombotic complications of diabetes. Recent data demonstrate that platelet reactivity can be modulated via cell-cell interactions with erythrocytes and neutrophils. In this study, platelet reactivity was evaluated in 30 IDDM patients. We used an analytical procedure that permits an independent evaluation of platelet activation (granule release, eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell-free releasates) after platelet stimulation with collagen in the presence or absence of other blood cells. The interaction between platelets and erythrocytes (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT, betaTG, TXA2 release) and recruitment in both patients and control subjects. The erythrocyte enhancement of platelet TXA2 synthesis and recruitment was significantly higher in the patients, while no differences were detected in platelet granule release. The elevated platelet recruitment in the IDDM patients was found to be due to 1) increased susceptibility of diabetic platelets to the prothrombotic effect of erythrocytes and 2) the greater response of diabetic platelets to their own cell-free releasate. Patients with poor metabolic control (elevated HbA1c) or longer evolution time had an even greater platelet recruitment. The presence of microalbuminuria is not related to the platelet recruitment. Since platelet recruitment is an essential step in thrombus growth, its enhancement may favor thrombotic complications in IDDM.


An ethical issue in the psychotherapy of pain and other symptoms.
Pain presents an ethical problem in psychotherapy which it shares with other symptoms. It presents this problem because initially it does not give rise to the same expectations as overt psychological complaints such as depression or anxiety. At first glance pain appears to represent an obvious example of the traditional doctor/patient relationship...I hope to demonstrate that what began as a transaction in the medicine of organic disease, may become, before the patient recognizes it, a process of personal change of which the consequences may often not be foreseen. Such a development poses a problem in bioethics. If the development can be foreseen, the problem may be forestalled. If not, the proceedings may reflect paternalism and we need to consider if that is acceptable. The problem is not unique to pain but tends to be masked by the initial context of somatic treatment.


Dinuclear rhenium complexes as redox-active pendants in a novel electrodeposited polycyclopentadithiophene material.
The novel [Re2(μ-H)(μ-OOC-CPDT)(CO)6(μ-3-Me-pydz)] complex (1; OOC-CPDT = 4H-cyclopenta[2,1-b:3,4-b']dithiophene-4-carboxylate, 3-Me-pydz = 3-methylpyridazine) has been prepared and characterized by single-crystal X-ray diffraction, density functional theory (DFT), and time-dependent DFT computations, UV-vis absorption and emission spectroscopy, and cyclic voltammetry (CV). The measured properties indicate the lack of electronic communication in the ground state between the CPDT and the rhenium diazine moieties. Oxidative electropolymerization of 1, achieved by repeated potential cycling (-0.4 to +1.0 V vs Fc(+)/Fc, in acetonitrile) with different supporting electrolytes, on different electrodes, afforded an electroactive and stable metallopolymer (poly-1). In situ measurements of the mass of the growing film (on a gold electrode, with an electrochemical quartz microbalance) confirmed the regularity of the polymerization process. The polymer exhibits two reversible oxidation peaks of the thiophene chain and a broad irreversible reduction peak (-1.4 V, quite close to that observed for the reduction of monomer 1), associated with a remarkably delayed sharp return peak, of comparable associated charge, appearing in close proximity (+0.3 V) to the first oxidation peak of the neutral polythiophene chain. This charge-trapping effect can be observed upon repeated cycles of p and n doping, and the negative charge is maintained even if the charged electrode is removed from the solution for many hours. Electrochemical impedance spectroscopy showed that the main CV oxidation peak corresponds to facile charge transfer, combined with very fast diffusion of both electrons and ions within the polymer. In summary, poly-1 provides a new example of a metallopolymer, in which the conductive properties of the π-conjugated system are added to the redox behavior of the pendant-isolated complexes.


An Overview of Signal Processing Techniques for Remote Health Monitoring Using Impulse Radio UWB Transceiver.
Non-invasive remote health monitoring plays a vital role in epidemiological situations such as SARS outbreak (2003), MERS (2015) and the recently ongoing outbreak of COVID-19 because it is extremely risky to get close to the patient due to the spread of contagious infections. Non-invasive monitoring is also extremely necessary in situations where it is difficult to use complicated wired connections, such as ECG monitoring for infants, burn victims or during rescue missions when people are buried during building collapses/earthquakes. Due to the unique characteristics such as higher penetration capabilities, extremely precise ranging, low power requirement, low cost, simple hardware and robustness to multipath interferences, Impulse Radio Ultra Wideband (IR-UWB) technology is appropriate for non-invasive medical applications. IR-UWB sensors detect the macro as well as micro movement inside the human body due to its fine range resolution. The two vital signs, i.e., respiration rate and heart rate, can be measured by IR-UWB radar by measuring the change in the magnitude of signal due to displacement caused by human lungs, heart during respiration and heart beating. This paper reviews recent advances in IR- UWB radar sensor design for healthcare, such as vital signs measurements of a stationary human, vitals of a non-stationary human, vital signs of people in a vehicle, through the wall vitals measurement, neonate's health monitoring, fall detection, sleep monitoring and medical imaging. Although we have covered many topics related to health monitoring using IR-UWB, this paper is mainly focused on signal processing techniques for measurement of vital signs, i.e., respiration and heart rate monitoring.


Gray-scale and color Doppler ultrasound imaging findings of an ovarian inguinal hernia and torsion of the herniated ovary: a case report.
Inguinal hernia is extremely rare among girls. The hernia sac may sometimes involve intestinal structures, but ovaries in the sac are uncommon. Early diagnosis of a possible ovarian torsion is essential because potential amenable benefits can be achieved with surgery. A baby girl was admitted to our pediatric emergency unit with the complaints of swelling and erythema of the left groin. Then gray-scale ultrasonography and color Doppler ultrasonography was performed immediately at the emergency radiology room. In our case, ovarian torsion was diagnosed by gray-scale ultrasonography and color Doppler ultrasonography. After the diagnosis of ovarian torsion, the patient underwent surgery. It is possible to diagnose inguinal emergencies by high-resolution ultrasonography and color Doppler ultrasonography.


Anti-F(ab')2 antibody in HIV type 1 infection: relationship to hypergammaglobulinemia and to antibody specific to the V3 loop region of glycoprotein 120.
As HIV infection and autoimmune disease share certain similarities, it has been suggested that HIV may disrupt control of humoral immunity by the antiidiotype network, and that this may be evident as increased IgG antibody to F(ab')2. When anti-F(ab')2 was quantified by ELISA in sera of randomly chosen HIV-infected versus uninfected donors, some HIV-infected sera did contain increased anti-F(ab')2, resulting in a median amount twofold higher than in uninfected sera. Moreover, when data were grouped by blood CD4 lymphocyte count, anti-F(ab')2 in HIV+ groups appeared to rise as CD4 lymphocytes declined. However, increased anti-F(ab')2 mirrored the elevation in serum IgG closely, and normalization of anti-F(ab')2 to serum IgG concentration equalized the groups so that no relationship to CD4 lymphocytes remained. Hypergammaglobulinemia is therefore strongly implicated as a cause of variation in anti-F(ab')2. After dissociation of immune complexes, anti-F(ab')2 activity per microgram of monomeric IgG was slightly increased over normal only in the HIV-infected group with fewest CD4 lymphocytes, without statistical significance. In contrast, the proportion of IgG antibody to the V3-neutralizing determinant in HIV-1 decreased significantly as disease advanced. The same was true for 12 HIV+ individuals studied longitudinally for 500-1300 days. The data suggest that measuring serum anti-F(ab')2 is misleading when immune complexes are present: apparent increases as disease progresses are due to increased IgG and, possibly, to related technical artifacts. During HIV infection, the proportion of antiidiotypic IgG in fact remains unaltered or falls, making this an unlikely cause of suppressed humoral immunity to HIV-1.


Subclinical exposure to low-dose endotoxin impairs EEG maturation in preterm fetal sheep.
Exposure to chorioamnionitis is strongly associated with neurodevelopmental disability after premature birth; however, it remains unclear whether subclinical infection affects functional EEG maturation. Chronically instrumented 103-104-day-old (0.7 gestational age: term 147 days) fetal sheep in utero were randomized to receive either gram-negative LPS by continuous low-dose infusion (100 ng iv over 24 h, followed by 250 ng/24 h for 4 days; n = 6) or the same volume of normal saline (n = 9). Arterial plasma cortisol, ACTH, and IL-6 were measured. The delta (0-3.9 Hz), theta (4-7.9 Hz), alpha (8-12.9 Hz), and beta (13-22 Hz) components of the EEG were determined by power spectral analysis. Brains were taken after 10 days for histopathology. There were no changes in blood gases, cardiovascular variables, or EEG power during LPS infusion, but a transient rise in plasma cortisol and IL-6 (P < 0.05). LPS infusion was associated with loss of the maturational increase to higher frequency activity, with reduced alpha and beta power, and greater delta power than saline controls from 6 to 10 days (P < 0.05). Histologically, LPS was associated with increased numbers of microglia and TNF-α-positive cells in the periventricular white matter and frontoparietal cortex, increased caspase-3-positive cells in white matter, but no loss of CNPase-positive oligodendrocytes, Nurr-1 subplate cells, or gyral complexity. These data suggest that low-dose endotoxin exposure can impair EEG maturation in preterm fetal sheep in association with neural inflammation but without hemodynamic disturbances or cortical injury.


Building Spiritual Care in Nursing: An Overview of Ku's Spiritual Studies in Taiwan.
This paper describes the overview of Ku's spiritual literature on nursing through five stages in Taiwan: the development of a spiritual framework, a scale of spiritual distress, a spiritual care model, a spiritual nursing course, and a spiritual care book in nursing. The article demonstrates the process of building spiritual care in nursing from constructing theoretical frameworks, measurements, and applying to education. The integrative overview of Ku's spiritual studies developed in this article could be an example in clinical and education fields for nurse administrators to develop spiritual capabilities.


Visualization and simulated surgery of the left ventricle in the virtual pathological heart of the Virtual Physiological Human.
Ischaemic heart failure remains a significant health and economic problem worldwide. This paper presents a user-friendly software system that will form a part of the virtual pathological heart of the Virtual Physiological Human (VPH2) project, currently being developed under the European Commission Virtual Physiological Human (VPH) programme. VPH2 is an integrated medicine project, which will create a suite of modelling, simulation and visualization tools for patient-specific prediction and planning in cases of post-ischaemic left ventricular dysfunction. The work presented here describes a three-dimensional interactive visualization for simulating left ventricle restoration surgery, comprising the operations of cutting, stitching and patching, and for simulating the elastic deformation of the ventricle to its post-operative shape. This will supply the quantitative measurements required for the post-operative prediction tools being developed in parallel in the same project.


Alcohol biomarkers in applied settings: recent advances and future research opportunities.
During the past decade, advances have been made in the identification, development, and application of alcohol biomarkers. This is important because of the unique functions that alcohol biomarkers can serve in various applied settings. To carry out these functions, biomarkers must display several features including validity, reliability, adequacy of temporal window of assessment, reasonable cost, and transportability. During the past two decades, several traditional alcohol biomarkers have been studied in multiple human studies. Meanwhile, several new, promising biomarkers, including various alcohol metabolites and alcohol biosensors, are being explored in human studies. In addition, researchers have explored using biomarkers in combination and using biomarkers in combination with self-reports, resulting in increased sensitivity with little sacrifice in specificity. Despite these advances, more research is needed to validate biomarkers, especially the new ones, in humans. Moreover, recent advances in high-throughput technologies for genomics, proteomics, and metabolomics offer unique opportunities to discover novel biomarkers, while additional research is needed to perfect newly developed alcohol sensors. Development of more accurate biomarkers will help practicing clinicians to more effectively screen and monitor individuals who suffer from alcohol use disorders.


Converting enzyme inhibitors in heart failure.
The renin-angiotensin system is activated in heart failure in proportion to the severity of the haemodynamic derangement and to diuretic dose. Angiotensin converting enzyme (ACE) inhibitors reduce circulating levels of angiotensin II and aldosterone and, in some patients, plasma noradrenaline, vasopressin and cortisol. Typically there is potassium retention and a minor increase in plasma potassium, but cumulative sodium balance may increase or decrease depending on pretreatment fluid and haemodynamic status and on policy regarding diuretic dose. Circulatory dynamics usually improve and blood flow to the brain, myocardium and kidneys is preserved. Changes in glomerular filtration rate are dictated by haemodynamic characteristics and, again, by diuretic dose and dietary sodium. There are potential hazards with ACE inhibitor therapy but most problems can be anticipated and avoided. Future trends may include the introduction of ACE inhibitors with or without concomitant diuretic therapy in early cardiac failure, and intravenous ACE inhibition immediately after acute myocardial infartion. Whether the ACE inhibitors will prove more successful than alternative antihypertensive agents in preventing cardiac complications (including heart failure) of hypertension, is an intriguing question.


Protein-Protein Interaction Interface Residue Pair Prediction Based on Deep Learning Architecture.
Proteins usually fulfill their biological functions by interacting with other proteins. Although some methods have been developed to predict the binding sites of a monomer protein, these are not sufficient for prediction of the interaction between two monomer proteins. The correct prediction of interface residue pairs from two monomer proteins is still an open question and has great significance for practical experimental applications in the life sciences. We hope to build a method for the prediction of interface residue pairs that is suitable for those applications. Here, we developed a novel deep network architecture called the multi-layered Long-Short Term Memory networks (LSTMs) approach for the prediction of protein interface residue pairs. First, we created three new descriptions and used other six worked characterizations to describe an amino acid, then we employed these features to discriminate between interface residue pairs and non-interface residue pairs. Second, we used two thresholds to select residue pairs that are more likely to be interface residue pairs. Furthermore, this step increases the proportion of interface residue pairs and reduces the influence of imbalanced data. Third, we built deep network architectures based on Long-Short Term Memory networks algorithm to organize and refine the prediction of interface residue pairs by employing features mentioned above. We trained the deep networks on dimers in the unbound state in the international Protein-protein Docking Benchmark version 3.0. The updated data sets in the versions 4.0 and 5.0 were used as the validation set and test set respectively. For our best model, the accuracy rate was over 62 percent when we chose the top 0.2 percent pairs of every dimer in the test set as predictions, which will be very helpful for the understanding of protein-protein interaction mechanisms and for guidance in biological experiments.


Amphetamine use and sexual risk among men who have sex with men: results from the National HIV Behavioral Surveillance study--New York City.
A 2004-2005 survey among 503 men who have sex with men who attend public venues in New York City was used to examine the relationship of amphetamine use with sexual risk behaviors. Among the men recruited, 51.1% were under 30 years of age, 27.4% were Latino, and 23.3% were African American. Most identified as either gay (78.9%) or bisexual (18.1%). A standardized questionnaire collected data on demographics, sexual risk behaviors, drug and alcohol use, history of HIV testing, and occurrences of sexually transmitted infections. Amphetamine use in the past year was reported by 13.8%. Of those, 71.0% used amphetamines with sex. Amphetamine use was associated with unprotected receptive anal intercourse with non-main partners. In event-specific analysis, amphetamine use was higher with unprotected encounters compared with protected encounters. This study confirms the association between amphetamine use and sexual risk furthers our understanding of risky circumstances and lays the groundwork for the design of interventions.


Stabilized lithium-ion battery anode performance by calcium-bridging of two dimensional siloxene layers.
A Ca-bridged siloxene (Ca-siloxene) composed of two-dimensional siloxene planes with Ca bridging was synthesized via a solid state metathesis reaction using TaCl5 to extract Ca from CaSi2. Three different Ca-siloxenes synthesized at Cl2/Ca molar ratios of 0.25, 1.25 and 2.5 (CS0.25, CS1.25 and CS2.5, respectively) were fabricated and investigated as anode active materials for lithium-ion batteries. Both secondary and primary Ca-siloxene particles, which serve to increase the contact interfaces with conductive materials and to generate accessible sites for lithium ions, respectively, were found to become smaller and to have increased pore volumes as the Cl2/Ca molar ratio was increased. These Ca-siloxenes exhibited stable charge/discharge performance as anode materials, with 69-99% capacity retention after 50 charge/discharge cycles (compared with 36% retention for a conventional Kautsky-type siloxene). The charge capacity also increased with increases in the Cl2/Ca molar ratio, such that the CS2.5 showed the highest capacity after 50 charge/discharge cycles. This may reflect the formation of Si6Li6 rather than SiLi4.4 and suggests the maintenance of layered Si planes for large capacity retention after charge/discharge cycling. The increase of contact interfaces between acetylene black (as a conductive material) and Ca-siloxenes was found to effectively increase the lithium-ion capacity of Ca-siloxene during high rate charge/discharge cycling.


Graduation Day: Healthcare Transition From Pediatric to Adult.
Because more patients with pediatric-onset chronic conditions are surviving into adulthood, they are graduating from pediatric healthcare to self-management and adult healthcare. This transfer of care needs to be a process of transitioning medical and nutrition care. Despite having position statements from professional organizations and several proposed models, issues in the transition process have been well described, and gaps in transition care persist. Healthcare providers need to be aware of special needs of emerging adults related to education on chronic condition and self-management skills, emotional support before and after transition, and legal rights for both the patient and the parent if the emerging adult is not developmentally appropriate to make his or her own healthcare decisions. Both pediatric and adult providers need to be in active communication with each other and the patient to develop trusting relationships and actively support the transition of care. This review of literature describes several models for transitioning, measureable outcomes, insurance provider issues, and legal issues pertaining to healthcare transition.


Synthesis of 2,3-dihydroselenophene and selenophene derivatives by electrophilic cyclization of homopropargyl selenides.
The synthesis of several highly functionalized 2,3-dihydroselenophenes from homopropargyl selenides via electrophilic cyclization is described. Electrophiles such as I(2), ICl, and PhSeBr were used in a simple process employing CH(2)Cl(2) as solvent at room temperature, which gave the cyclized products in high yields. 4-Iodo-2,3-dihydroselenophenes obtained by this methodology were submitted to a dehydrogenation reaction using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to give 3-iodoselenophenes. 4-Iodo-5-phenyl-2,3-dihydroselenophene was also submitted to the thiol copper-catalyzed and Heck-type reactions giving the desired products under mild reaction conditions.


Optimal timing of simethicone administration prior to upper endoscopy: A multicenter, single-blind, randomized controlled trial.
Background and study aims Simethicone is useful as premedication for upper endoscopy because of its antifoaming effects. We aimed to evaluate the effect of timing of simethicone administration on mucosal visibility. Patients and methods In this multicenter, randomized, endoscopist-blinded study, patients scheduled for upper endoscopy were randomized to receive 40 mg simethicone at the following time points prior to the procedure: 20 to 30 minutes (early group), 0 to 10 minutes (late group) or 20 mg simethicone at both time points (split-dose group). Images were taken from nine predefined locations in the esophagus, stomach, and duodenum before endoscopic flushing. Each image was scored on mucosal visibility by three independent endoscopists on a 4-point scale (lower scores indicating better visibility), with adequate mucosal visibility defined as a score ≤ 2. Primary outcome was the percentage of patients with adequate total mucosal visibility (TMV), reached if all median subscores for each location were ≤ 2. Results A total of 386 patients were included (early group: 132; late group: 128; split-dose group: 126). Percentages of adequate TMV were 55%, 42%, and 61% in the early, late, and split-dose group, respectively ( P < 0.01). Adequate TMV was significantly higher in the split-dose group compared to the late group ( P < 0.01), but not compared to the early group ( P = 0.29). Differences between groups were largest in the stomach, where percentages of adequate mucosal visibility were higher in the early (68% vs 53%, P = 0.03) and split-dose group (69% vs 53%, P = 0.02) compared to the late group. Conclusions Mucosal visibility can be optimized with early simethicone administration, either as a single administration or in a split-dose regimen.


[Adjuvant BCG immunotherapy in the management of superficial bladder tumors].
The net benefit of BCG immunotherapeutic prophylactic effect on recurrence of superficial bladder tumours was investigated. The BCG treatment group consisted of 121 stage Ta, T1 patients, while the control group, 49 patients, was treated only with transurethral resection. During 3-year follow-up recurrence rate in the control group was 55.1%, while in the BCG group in the two-and-a-half-year follow-up it was 23.9%. The yearly repeated 6-week cycles resulted in decrease of recurrence rate to 11.8%. The recurrence indexes were 2.2 and 0.6 in the control group and in the repeated treatment group respectively. A progression rate of 18.8% was recorded in the control group and 4.1% in the treatment group. Finally both clinical and investigative results were summarised and the necessity of repeated immunotherapeutic BCG courses were emphasized.


Effect of root canal filling materials on dimensions of cone-beam computed tomography images.
To evaluate the discrepancy of root canal filling (RCF) measurements obtained from original root specimens and cone-beam computed tomography (CBCT) images. Seventy-two human maxillary anterior teeth were prepared up to an ISO #50 K-File 1 mm short of the apical foramen. Thus, the teeth were randomly divided into 8 groups, according to the root canal filling material: Sealapex®, Sealapex®+gutta-percha points, Sealer 26®, Sealer 26®+gutta-percha points, AH PlusTM, AH PlusTM+gutta-percha points, Grossman Sealer, and Grossman Sealer+gutta-percha points. After root canal preparation and RCF, CBCT scans were acquired and the specimens were sectioned in axial, sagittal and coronal planes. The RCF measurements were obtained in different planes and thicknesses to determine the discrepancy between the original root specimens (using a digital caliper) and the CBCT images (using the scanner's proprietary software). One-way analysis of variance and Tukey tests were used for statistical analyses. The significance level was set at α=5%. Measurements of the different endodontic filling materials were 9% to 100% greater on the CBCT images than on the original root specimens. Greater RCF dimensions were found when only sealers were used, with statistically significant difference among the groups. RCF dimensions were greater on CBCT images than on the original root specimens, especially when only sealer was used.


Synthesis of reduced graphene oxide/ZnO nanocomposites using grape fruit extract and Eichhornia crassipes leaf extract and a comparative study of their photocatalytic property in degrading Rhodamine B dye.
In the present work, we report the comparative study of photocatalytic degradation of Rhodamine B (RhB) dye in aqueous solution by using ZnO-graphene nanaocomposites obtained using two different natural reducing agents namely Grape and Eichhornia crassipes. Graphene oxide (GO) was synthesized by Hummer's method followed by reduction of the graphene oxide using natural reducing agents Grape and Eichhornia crassipes. The two samples of graphene oxide (Gr-rGO and Ei-rGO) were treated with ZnO to form a rGO-ZnO nanocomposites. The dye degradation was observed by the decrease in the absorption and decolorization in the presence of visible light. The degradation efficiency was found to be dependent on the concentration of rGO-ZnO nanocomposites added to the dye solution. The Ei-rGO has a higher adsorbing capacity due to its large surface area. A degradation efficiency of 67% was achieved by ZnO alone, whereas with the rGO-ZnO nanocomposite, the photocatalytic degradation efficiency for removal of RhB dye was found to be enhanced. The degradation efficiency was 70.0% and 97.5% with Gr-rGO-ZnO and Ei-rGO-ZnO nanocomposites respectively. The enhanced photocatalytic activity of Ei-rGO-ZnO composites could be attributed to the strong interaction with the ZnO and the defect sites available in Ei-rGO. Graphical abstractGraphical abstract of the carried work.


Mechanistic Studies on a Cu-Catalyzed Asymmetric Allylic Alkylation with Cyclic Racemic Starting Materials.
Mechanistic studies on Cu-catalyzed asymmetric additions of alkylzirconocene nucleophiles to racemic allylic halide electrophiles were conducted using a combination of isotopic labeling, NMR spectroscopy, kinetic modeling, structure-activity relationships, and new reaction development. Kinetic and dynamic NMR spectroscopic studies provided insight into the oligomeric Cu-ligand complexes, which evolve during the course of the reaction to become faster and more highly enantioselective. The Cu-counterions play a role in both selecting different pathways and in racemizing the starting material via formation of an allyl iodide intermediate. We quantify the rate of Cu-catalyzed allyl iodide isomerization and identify a series of conditions under which the formation and racemization of the allyl iodide occurs. We developed reaction conditions where racemic allylic phosphates are suitable substrates using new phosphoramidite ligand D. D also allows highly enantioselective addition to racemic seven-membered-ring allyl chlorides for the first time. 1H and 2H NMR spectroscopy experiments on reactions using allylic phosphates showed the importance of allyl chloride intermediates, which form either by the action of TMSCl or from an adventitious chloride source. Overall these studies support a mechanism where complex oligomeric catalysts both racemize the starting material and select one enantiomer for a highly enantioselective reaction. It is anticipated that this work will enable extension of copper-catalyzed asymmetric reactions and provide understanding on how to develop dynamic kinetic asymmetric transformations more broadly.


Electron attachment to tetrazoles: The influence of molecular structure on ring opening reactivity.
The electron-induced reactivity of 5-(4-chlorophenyl)-1H-tetrazole and 5-chloro-1-phenyl-1H-tetrazole was studied using a trochoidal electron monochromator quadrupole mass spectrometer experimental setup. 5-(4-chlorophenyl)-1H-tetrazole underwent dissociative electron attachment to form Cl-, [M-HCl]-, and [M-H]-. 5-chloro-1-phenyl-1H-tetrazole underwent associative electron attachment to form the parent anion and dissociative electron attachment to form Cl-, CN2Cl-, [M-N2-Cl]-, and [M-HCl]-. For each anion product, the ion yield was measured as a function of incident electron energy. Density functional theory calculations were performed to support the experimental results with estimates of the energetic thresholds for the different reaction pathways. While the tetrazole group is susceptible to electron-induced ring opening in both molecules, this process was only observed for 5-chloro-1-phenyl-1H-tetrazole, indicating that this process is influenced by the structure of the molecule.


The Bentall procedure without the use of a prepared valved-conduit: a step backwards?
A repeat Bentall procedure or a Bentall procedure in an immobile aortic root such as a prior homograft that has calcified can be problematic. Separating the valve from the conduit and with a modified elephant trunk concept we have simplified the proximal graft anastomosis using a running suture technique. This is followed by coronary ostia implantation and then by lowering the aortic valve onto the aortic annulus using a running suture technique.