Trends but not individual values of central venous oxygen saturation agree with mixed venous oxygen saturation during varying hemodynamic conditions.
Previous studies found contradictory results regarding the question whether mixed venous oxygen saturation (Svo2) and central venous oxygen saturation (Scvo2) are equivalent. The inconsistency of study results may result from different study designs and different, partly questionable, statistical approaches. The authors performed a prospective clinical trial comparing individual oxygen saturation values as well as the trend of values in blood from the superior vena cava (Scvo2), the right atrium (Srao2), and the pulmonary artery (Svo2) during varying hemodynamic situations. The subjects were 70 patients scheduled to undergo elective neurosurgical operations in the sitting position. Oxygen saturation was measured photospectrometrically in blood samples simultaneously taken at four different time points during supine and sitting positions. Statistical analysis was performed following the recommendations of Bland and Altman. Five hundred two comparative sets of measurements were obtained. Ninety-five percent limits of agreement ranging from +/-6.83 to +/-9.30% for single values were interpreted as clinically unacceptable. In contrast, correlations between changes of Svo2 and Scvo2 as well as of Svo2 and Srao2 were interpreted as clinically acceptable (R > or = 0.755, Pearson correlation coefficient; P < or = 0.0001). In this sample of patients, exact numerical values of Scvo2 and Srao2 are not equivalent to those of Svo2 in varying hemodynamic conditions. However, for clinical purposes, the trend of Scvo2 may be substituted for the trend of Svo2. In addition, previous studies investigating the agreement between Svo2 and Scvo2 were found to be lacking in their chosen statistical approaches.


Abandoned, lost or otherwise discarded fishing gear (ALDFG) as part of marine litter at the seafloor of the Baltic Sea - Characterization, quantification, polymer composition and possible impact.
As an important part of marine litter at the seafloor "Abandoned, lost, discarded or otherwise lost fishing gear" (ALDFG) is gaining increasing attention in environmental assessments. Within this study marine litter at the seafloor of the Baltic Sea was quantified and characterized with special regard to fishery as source. Litter items (LI) were collected within fishery catches by bottom trawling during three cruises in 2020 and 2021. The resulting mean litter abundance was 9.2 LI/km2. Approximately 56 % of all LI were plastic, with PE as the most frequently identified polymer. ALDFG was present in considerable amounts with a mean value of 2.2 LI/km2 (22.2 %). However, the absolute counts of fishery nets were low (0.4 LI/km2; 4.2 %). Regarding weight, fishery nets are the dominant part of litter at the Baltic seafloor. Threshold values for marine litter at the seafloor are missing and might be developed using quantitative data on ALDFG.


The effect of propranolol on salivary gland function and dental caries development in young and aged rats.
Medications commonly used in elderly people cause hyposalivation and are associated with an enhanced prevalence of dental caries. Propranolol (a beta-adrenergic antagonist) is a commonly used antihypertensive agent that is prescribed for long-term use. The purpose of this investigation was to compare the effects of this drug on salivary composition and flow rate, and on caries, in young and aged rats. Forty young (28-day) and 36 aged (20-month) female Sprague-Dawley rats were infected with Streptococcus sobrinus 6715 and fed a cariogenic diet for 28 days. Propranolol was given in high (20 mg/kg/day) and low (10 mg/kg/day) doses via osmotic pumps. Unoperated and desalivated animals served as controls. Smooth-surface caries scores in the young animals receiving propranolol at 20 mg/kg/day were statistically higher than in the young intact rats (p < or = 0.05). Increased smooth-surface and sulcal caries scores were recorded in the aged propranolol-treated animals, but the differences were not statistically significant when compared with those in intact aged animals. Propranolol in aged animals did not affect the amount of alveolar bone loss but increased the risk of development of root caries. Young animals harboured greater populations of Strep. sobrinus and total cultivable flora than did all aged groups except the desalivated group. Salivary flow rates, induced by pilocarpine, were not decreased by the chronic administration of propranolol. Although the total protein concentration in parotid and submandibular saliva from drug-treated animals was reduced, differences were not observed in their SDS-PAGE profile when compared with unoperated animals. The findings demonstrate that chronic use of propranolol reduced the total protein concentration in saliva of all animals, increased caries susceptibility, but did not reduce the stimulated salivary flow rate.


[The role of health promoting schools for increasing health equity].
Socioeconomic health inequalities are a major field of action in public health and tackling them is one of its main goals. However, there has been little success in reducing these health inequalities. This points to a large research deficit. Inequalities in health are already evident in childhood and adolescence, showing that those with a low socioeconomic background have more risk factors and at the same time fewer resources than their socially more privileged peers. Although health promotion aims at achieving equity in health, interventions rarely consider the socioeconomic status and can therefore provide only little evidence regarding socioeconomically differentiated intervention effects. How can we ensure that all children and young people have equal chances to grow up healthy?In order to come closer to answering this question, it is the aim of this article to give an overview of health inequalities in childhood and adolescence and to highlight the contribution of school and school-based health promotion interventions for tackling health inequalities and increasing equity in health. School is not only a place where adolescents can always be reached, regardless of their socioeconomic background, it has the potential to both exacerbate and reduce health inequalities.


Quantitative plasma D-dimer levels among patients undergoing pulmonary angiography for suspected pulmonary embolism.
To test the hypothesis that a low D-dimer level has a high negative predictive value for acute pulmonary embolism (PE) among patients undergoing diagnostic pulmonary angiography. Blinded comparison of quantitative plasma D-dimer levels, measured using a monoclonal antibody assay, with pulmonary angiographic results from 173 patients with suspected acute PE. Tertiary care setting at fur participating institutions. Plasma samples were analyzed in 173 patients who underwent diagnostic pulmonary arteriography for suspected acute PE. Sensitivity, specificity, and predictive values of quantitative plasma D-dimer levels for the diagnosis of PE, using pulmonary angiographic data as the criterion standard test. Of 35 patients with D-dimer values less than 500 ng/mL, only three had abnormal pulmonary angiograms. The negative predictive value of a plasma D-dimer level less than 500 ng/mL for acute PE was 91.4% (95% confidence interval [CI], 76.9% to 98.2%). D-dimer levels were greater than 500 ng/mL in 42 of 45 patients with PE and in 96 of 128 patients without PE (P = .016). Sensitivity, specificity, and positive predictive value of a plasma D-dimer level greater than 500 ng/mL for acute PE were 93.3% (95% CI, 81.7% to 98.6%), 25.0% (95% CI, 17.5% to 32.5%), and 30.4% (95% CI, 22.8% to 38.1%), respectively. The results of our study indicate that quantitative plasma D-dimer levels can be useful in screening patients with suspected PE who require pulmonary angiography. Plasma D-dimer values less than 500 ng/mL may obviate the need for pulmonary angiography, particularly among medical patients for whom the clinical suspicion of PE is low. The plasma D-dimer value, assayed using a commercially available enzyme-linked immunosorbent assay kit, is a sensitive but nonspecific test for the presence of acute PE.


An Exploratory Study of Allied Health Students' Experiences of Electronic Medical Records During Placements.
Allowing students to access and document in electronic medical records (eMRs) during clinical placements is viewed as critical for ensuring that graduates have a high level of digital proficiency prior to entering the workforce. Limited studies have explored student access to eMRs in health disciplines outside of medicine and nursing. Our main objective was to examine allied health students' experiences and perceptions of the opportunity to develop eMR competencies during their placement, across a range of allied health disciplines and placement settings. An explanatory sequential design was used, comprising a quantitative survey (n = 102) followed by qualitative semi-structured interviews (n = 6) with senior allied health students to explore their experiences and perceptions of eMR access during placements. Of the 93 students who responded to the question about their placement eMR, nine (10%) reported their placement site did not use an eMR and four students reported that they were not allowed to access the eMR during their placement. Most students (64%, 54 out of 84) accessed the system using their own credentials, but 31% (26 out of 84) used someone else's log-in and password. Students were satisfied with the eMR training and support received while on placement, but there was significant variability across sites on the level of training and support provided. All students believed that eMR access was beneficial for learning and preparation for work, improved delivery of care, taking ownership of work, and feeling responsible for patient care. Providing students with access to eMRs during placements is fundamental to the development of a student's professional identity and to recognizing their role in the delivery of interprofessional patient care. For graduates to be equipped to effectively contribute to multi-disciplinary care in a digital health environment, universities need to work with practice partners to standardize and formalize eMR access, registration, training, and support, and to provide students with early exposure and training on eMRs in university courses.


Serial evaluation of left ventricular contraction and relaxation in Takotsubo cardiomyopathy by 2D speckle tracking echocardiography.
A 78-year-old woman was referred to our hospital because of general fatigue. The electrocardiogram showed ST elevation in the I, II, aVL, and V2-V6 leads. Echocardiography showed left ventricular apical akinesis. On emergent cardiac catheterization, left ventricular basal hyperkinesis and apical akinesis without coronary artery stenosis were found. The patient was diagnosed with Takotsubo cardiomyopathy. Two-dimensional myocardial speckle tracking echocardiography was performed on admission, the 8th hospital day, and the 15th hospital day. Gradual improvement in wall motion abnormality and longitudinal peak systolic strain, peak systolic strain rate, and early diastolic strain rate from the basal to apical region of the left ventricle were observed objectively, and she achieved remission. We herein report a case of Takotsubo cardiomyopathy in which objective improvement in left ventricular contraction and relaxation was observed by 2D speckle tracking imaging and bull's eye mapping.


New Raman spectrometer using a digital micromirror device and a photomultiplier tube detector for rapid on-line industrial analysis. Part II: Choice of analytical methods.
In this paper, the performances of four improved analytical methods (backward stepwise selection of peak intensities, sum of characteristic peaks of a component, moving window partial least squares, and genetic algorithms) using wavelength selection for the analysis of xylene mixtures by Raman spectroscopy are tested for further use on the new "digital micromirror device associated with a photomultiplier tube" Raman spectrometer. It is shown that the errors of prediction using only a few selected points (from 4 to 49 depending on the method) are almost the same as when using the whole spectral range (1050 points). Compared to the last two methods, the "backward stepwise selection of peak intensities" and "sum of characteristic peaks of a component" methods are robust under industrial conditions and appear to be well suited for chemical quantitative analysis with the new Raman spectrometer, which allows the measurements of the total intensity to be made simultaneously for a number of pre-selected frequencies. Results show that the errors of prediction can be near to or even lower than 2%.


The relative importance of biological and environmental factors on the trophodynamics of a pelagic marine predator, the blue shark (Prionace glauca).
Marine ecosystems have been significantly altered by the cumulative impacts of human activities. Pelagic sharks have become vulnerable to increases in mortality rates caused by fishing. The decrease in number of these top predators could have substantial cascading effects on wider marine communities. Concerns about these potential impacts, and the critical need for effective management, have led to an increased interest in assessing the trophic ecology of sharks. While stable isotope analyses have been used to provide relevant insights about the trophic ecology of sharks, the causal factors leading to trophic variation between individuals has been largely overlooked. Here, we investigated the relative effect of biological factors, geographic location, and environmental factors on the spatial trophodynamics of the blue shark (Prionace glauca). Specifically, stable isotope values of δ15N and δ13C, and the estimated trophic position (TP) were analysed for 180 blue sharks collected from south of the Canary Islands in the Atlantic Ocean, to the north-western Mediterranean Sea. The results showed that models which included combined variables explained the variation in δ15N, TP and δ13C values better than models which considered only stand-alone predictors. The independent contributions of environmental variables and biological factors seemed to be more important than geographic location for δ15N and TP. δ15N and TP increased in a curvilinear fashion with body size, and TP was higher for females. In the case of δ13C values, only an effect from sex was observed. Among environmental variables, chlorophyll-a, pelagic productivity, and sea-surface temperature proved to be reliable predictors, particularly for δ15N and TP, most likely due to their relationship with productivity and prey availability. This study provides new information on ranking the factors that influence the trophodynamics of the blue shark, namely the environment, the geographic location, and the biological factors of the species.


Density and reproductive success in wild populations of Diplotaxis erucoides (Brassicaceae).
One possible consequence of low population density, particularly in self-incompatible plants, is reproductive failure. I surveyed seed set per flower in two populations of the self-incompatible annual Diplotaxis erucoides (Brassicaceae) in Jerusalem, Israel. Widely spaced plants had lower fruit set and fewer seeds per filled silique than did plants growing close to conspecific neighbors. Such density-dependent reproductive success could help explain the maintanence of spatial patchiness in plant populations, and could also have implications for population dynamics of rare species.


Biochemical analysis of the replication initiator protein of staphylococcal plasmid pC194.
The staphylococcal plasmid pC194 is replicated through the rolling-circle mechanism. Its replication protein RepA has been proposed to initiate replication by making a bond between Y214 and DNA phosphate via transesterification and to terminate it by hydrolyzing DNA with E210 and carrying out strand transfer. We tested this model by examining the catalytic functions of the protein with purified RepA proteins and single-stranded DNA oligomers. The wild-type RepA formed a covalent bond with the DNA phosphate at the predicted initiation site. It hydrolyzed the phosphodiester bond at the site, which activity was found to depend on the presence of a large pseudopalindrome contained in the replication origin. The protein carried out a strand-transfer reaction which mimicked the termination step of replication. A Y214F and an E210A mutant respectively lacked the transesterification and the hydrolytic activity. These results are consistent with the previously proposed model, which was based solely on molecular genetics results. In addition, an E142A mutant was found to lack both activities, suggesting that the residue may coordinate the divalent cation necessary for them. A possible role of the pseudopalindrome in controlling the two activities of RepA during a replication cycle is also discussed.


Coat protein stimulates replication complexes of alfalfa mosaic virus to produce virion RNAs in vitro.
Viral replication complexes (RCs) were gradient-purified from cowpea mesophyll protoplasts 21 h after inoculation with alfalfa mosaic virus. These membranous structures incorporate [32P]UMP into double- and single-stranded RNAs in the absence of added template. When coat protein is added prior to the reaction the incorporation in both RNA fractions is stimulated several times. Part of the single-stranded product RNAs are released from the RCs. The stimulation of incorporation in high molecular mass RNAs by coat protein can be mimicked only to a certain extent by addition of a ribonuclease inhibitor or of an excess of viral RNA prior to the reaction. This shows that the coat protein is not only protecting the product of the RCs against degradation by ribonuclease, but that it is stimulating the synthesis and release of viral RNAs from RCs as well. This leads to the hypothesis that with alfalfa mosaic virus some coat protein is necessary for the release of messenger RNA from the RC. The hypothesis explains why the viral genome RNAs, although they are of messenger polarity, cannot start a replication cycle in the absence of coat protein: RCs containing the parental RNAs could be formed but no amplification of them could take place since no messenger RNAs needed for the production of viral polymerase proteins would be released into the cytoplasm.


Removal of chlorophenols from aqueous solution by fly ash.
Fly ash from coal-fired thermal power plants can be used for the removal of 2-chlorophenol (2-CP) and 2,4-dichlorophenol (2,4-DCP) with enthalpy changes of about -3 kcal/mol. The amounts of 2-CP and 2,4-DCP removed are affected by the pH value of the solution. The efficiency of removal improves when the pH value is less than the pK(a) values of 2-CP and 2,4-DCP, respectively. The adsorbed amount of chlorophenol by fly ash is also affected by particle diameter, carbon content, and the specific surface area of the ash used in this study. As expected, more adsorption takes place with fly ash of higher carbon content and larger specific surface area. Moreover, the adsorbed amount of chlorophenol is not influenced by the matrix in the wastewater, as shown by studying the removal of 2-CP and 2, 4-DCP in wastewater from a synthetic fiber plant. Chlorophenols in the wastewater were also removed efficiently through a fly ash column, with breakthrough times being inversely proportional to flow rates.


The ecotoxicology of vegetable versus mineral based lubricating oils: 3. Coral fertilization and adult corals.
Biodegradable vegetable-derived lubricants (VDL) might be less toxic to marine organisms than mineral-derived oils (MDL) due to the absence of high molecular weight aromatics, but this remains largely untested. In this laboratory study, adult corals and coral gametes were exposed to various concentrations of a two-stroke VDL-1A and a corresponding MDL to determine which lubricant type was more toxic to each life stage. In the fertilization experiment, gametes from the scleractinian coral Acropora microphthalma were exposed to water-accommodated fractions (WAF) of VDL-1A and MDL for four hours. The MDL and VDL-1A WAFs inhibited normal fertilization of the corals at 200 microg l(-1) total hydrocarbon content (THC) and 150 microg l(-1) THC respectively. Disturbance of a stable coral-dinoflagellate symbiosis is regarded as a valid measure of sub-lethal stress in adult corals. The state of the symbiosis in branchlets of adult colonies of Acropora formosa was monitored using indicators such as dinoflagellate expulsion and dark-adapted photosystem II yields of dinoflagellate (using pulse amplitude modulation fluorescence). An effect on symbiosis was measurable following 48 h exposure to the lubricants at concentrations of 190 microg l(-1) and 37 microg l(-1) THC for the MDL and VDL-1A respectively. GC/MS revealed that the main constituent of the VDL-1A WAF was the compound coumarin, added by the manufacturer to improve odour. The fragrance containing coumarin was removed from the lubricant formulation and the toxicity towards adult corals re-examined. The coumarin-free VDL-2 exhibited significantly less toxicity towards the adult corals than all of the other oil types tested, with the only measurable effect being a slight but significant drop in photosynthetic efficiency at 280 microg l(-1).


Perinatal outcomes associated with subsequent pregnancy among adolescent mothers in Peru.
To assess the perinatal outcomes of a subsequent pregnancy among adolescent mothers living in Peru. A large hospital-based retrospective cohort study was conducted to evaluate singleton births during a 9-year period (2001-2009). The study population was divided into 3 groups: adolescents aged 15-19 years who had 1 previous parturition (n=2074), nulliparous adolescents (n=20721), and multiparous adults aged 20-29 years (n=23 129). No significant differences were found between multiparous adolescents and the 2 control groups with regard to preterm delivery, perinatal death, and 5-minute Apgar score below 7. Logistic regression analysis showed no significant differences in the rates of cesarean delivery or preterm birth before 34 or 37 weeks. After adjusting for confounding factors, low birth weight (LBW) and small for gestational age (SGA) were more likely to occur during a subsequent pregnancy among adolescent mothers than during the 1st pregnancy among nulliparous adolescents. The odds ratios were 1.38 (95% CI, 1.14-1.67) and 1.27 (95% CI, 1.02-1.56), respectively. Multiparous adolescents are more likely to experience LBW or SGA than are nulliparous adolescents. No significant differences in other perinatal outcomes were found among the 3 study groups.


Editorial for the Special Issue on Recent Advances in Reactive Ion Etching and Applications of High-Aspect-Ratio Microfabrication.
Reactive ion etching (RIE) is the dominating technology for micromachining semiconductors with a high aspect ratio (HAR) [...].


The impact of facial expression and communicative gaze of a humanoid robot on individual Sense of Agency.
Sense of Agency (SoA) is the feeling of control over one's actions and their outcomes. A well-established implicit measure of SoA is the temporal interval estimation paradigm, in which participants estimate the time interval between a voluntary action and its sensory consequence. In the present study, we aimed to investigate whether the valence of action outcome modulated implicit SoA. The valence was manipulated through interaction partner's (i) positive/negative facial expression, or (ii) type of gaze (gaze contact or averted gaze). The interaction partner was the humanoid robot iCub. In Experiment 1, participants estimated the time interval between the onset of their action (head movement towards the robot), and the robot's facial expression (happy vs. sad face). Experiment 2 was identical, but the outcome of participants' action was the type of robot's gaze (gaze contact vs. averted). In Experiment 3, we assessed-in a within-subject design-the combined effect of robot's type of facial expression and type of gaze. Results showed that, while the robot's facial expression did not affect participants' SoA (Experiment 1), the type of gaze affected SoA in both Experiment 2 and Experiment 3. Overall, our findings showed that the robot's gaze is a more potent factor than facial expression in modulating participants' implicit SoA.


Mechanical fatigue testing in silico: Dynamic evolution of material properties of nanoscale biological particles.
Biological particles have evolved to possess mechanical characteristics necessary to carry out their functions. We developed a computational approach to "fatigue testing in silico", in which constant-amplitude cyclic loading is applied to a particle to explore its mechanobiology. We used this approach to describe dynamic evolution of nanomaterial properties and low-cycle fatigue in the thin spherical encapsulin shell, thick spherical Cowpea Chlorotic Mottle Virus (CCMV) capsid, and thick cylindrical microtubule (MT) fragment over 20 cycles of deformation. Changing structures and force-deformation curves enabled us to describe their damage-dependent biomechanics (strength, deformability, stiffness), thermodynamics (released and dissipated energies, enthalpy, and entropy) and material properties (toughness). Thick CCMV and MT particles experience material fatigue due to slow recovery and damage accumulation over 3-5 loading cycles; thin encapsulin shells show little fatigue due to rapid remodeling and limited damage. The results obtained challenge the existing paradigm: damage in biological particles is partially reversible owing to particle's partial recovery; fatigue crack may or may not grow with each loading cycle and may heal; and particles adapt to deformation amplitude and frequency to minimize the energy dissipated. Using crack size to quantitate damage is problematic as several cracks might form simultaneously in a particle. Dynamic evolution of strength, deformability, and stiffness, can be predicted by analyzing the cycle number (N) dependent damage, [Formula: see text] , where α is a power law and Nf is fatigue life. Fatigue testing in silico can now be used to explore damage-induced changes in the material properties of other biological particles. STATEMENT OF SIGNIFICANCE: Biological particles possess mechanical characteristics necessary to perform their functions. We developed "fatigue testing in silico" approach, which employes Langevin Dynamics simulations of constant-amplitude cyclic loading of nanoscale biological particles, to explore dynamic evolution of the mechanical, energetic, and material properties of the thin and thick spherical particles of encapsulin and Cowpea Chlorotic Mottle Virus, and the microtubule filament fragment. Our study of damage growth and fatigue development challenge the existing paradigm. Damage in biological particles is partially reversible as fatigue crack might heal with each loading cycle. Particles adapt to deformation amplitude and frequency to minimize energy dissipation. The evolution of strength, deformability, and stiffness, can be accurately predicted by analyzing the damage growth in particle structure.


A mathematical model of proximal tubule absorption.
A previous model of the mechanisms of flow through epithelia was modified and extended to include hydrostatic and osmotic pressures in the cells and in the peritubular capillaries. The differential equations for flow and concentration in each region of the proximal tubule were derived. The equations were solved numerically by a finite difference method. The principal conclusions are: (i) Cell NaCl concentration remains essentially isotonic over the pressure variations considered; (ii) channel NaCl concentration varies only a few mosmol from isotonicity, and the hydrostatic and osmotic pressure differences across the cell wall are of the same order of magnitude; (iii) both reabsorbate osmolality and pressure-induced flow are relatively insensitive to the geometry of the system; (iv) a strong equilibrating mechanism exists in the sensitivity of the reabsorbate osmolality to luminal osmolality; this mechanism is far more significant than any other parameter change.


Issues in organ procurement, allocation, and transplantation.
Organ transplantation extends lives and improves health but presents complex ethical dilemmas for nurses caring for donors, recipients, and their families. This article overviews organ procurement and allocation, discusses ethical dilemmas in transplantation, and offers strategies from professional and biblical perspectives for coping with moral distress and maintaining compassionate care.


Cultural differences in the development of cognitive shifting: East-West comparison.
Prior research has documented that Japanese children's performance on the Dimensional Change Card Sorting (DCCS) task can be influenced by their observation of another person completing the task, which is referred to as social transmission of disinhibition. The current study explored whether Canadian children would also show a social transmission of disinhibition and whether their performance would be comparable to that of Japanese children. In this study, 3- and 4-year-olds in Canada and Japan were given both the standard version and social version of the DCCS. Results indicated that Canadian children displayed the social transmission of disinhibition, but their effects were significantly weaker than those with Japanese children. On the other hand, performance on the standard DCCS was comparable between children in the two countries. We discuss the results in terms of cultural differences in the relationship between self and other.


Epigenetic regulation in the pathogenesis of non-melanoma skin cancer.
Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.


Killer-cell immunoglobulin-like receptors and cytomegalovirus reactivation during late pregnancy.
Human cytomegalovirus (CMV) represents an important public health concern as it is associated with severe morbidity and mortality in transplant recipients, HIV-infected individuals and pregnant women given the risk of congenital infection. Congenital CMV is a leading cause of neurological sequelae, developmental delay and birth defects worldwide. Cytomegalovirus can be transmitted to the foetus following maternal infection or reactivation. NK cells expressing killer-cell immunoglobulin-like receptors (KIR) are part of the innate immune system and the first line of defence against viral incursions. Previous reports have shown that KIR genes are associated with CMV infections in the post-transplant setting. In this study, we set out to determine whether a protective effect of KIR genes over CMV infection is seen in Mexican pregnant women. Cytomegalovirus infection was assessed through nucleic acid testing in 200 pregnant women and 600 healthy blood donors comprising the Mexican mestizo reference population. Killer-cell immunoglobulin-like receptors and HLA-C genotypes were obtained from 200 pregnant women and 300 reference samples using a comprehensive PCR-SSP approach. We observed statistically lower carrier frequencies of cB03|tA01 gene-content haplotype, of cB03 haplotype motif, of the KIR2DL5 + 2DS3/2DS5 gene pair and of KIR2DL5 amongst CMV-positive pregnant women in comparison with those CMV negative. None of these were associated with CMV status in the reference population. Logistic regression analysis revealed that the most important factor determining CMV status during third-trimester pregnancies was the KIR2DL5 + 2DS3/2DS5 gene pair (OR 0.376 (95%CI 0.174, 0.811, P = 0.013). Our results indicate that CMV-protective KIR gene associations described in Caucasoid populations are also present in the genetically distinct Mexican mestizo population. Our results suggest that certain KIR gene combinations provide protection against CMV infections occurring during late-term pregnancies, a finding of utmost epidemiological importance given its implication with congenital CMV infections.


A model for improving medication use in home health care patients.
(1) To develop a model for the identification and resolution of problems associated with suboptimal medication use in elderly patients receiving home health care; (2) To select the most important identifiable problems and develop structured procedures for their resolution. Expert panel review, problem selection, and development of a problem resolution model and guidelines. Home health care. A panel with expertise in home health nursing, pharmacy, clinical pharmacology, gerontology, pharmacoepidemiology, and health services research. A list of potential problems associated with the most frequently used classes of drugs was compiled for review by the panel. Problems that were controversial or that could not be identified in the home care setting were excluded. Panel members individually ranked the remainder. Detailed procedures for identification and resolution of the 15 top-ranking problems were developed. Not applicable. Potential medication problems were defined by both drug use and symptoms or clinical signs associated with specific adverse effects, to ensure that clinically relevant problems would be identified. The model developed for problem assessment and resolution was centered on the drug utilization review (DUR) coordinator and the attending home health nurse. Following guidelines developed by the panel, the DUR coordinator advises the home health nurse about identified problems and how to resolve them. One of these practitioners, usually the nurse, then contacts the attending physician to explain their concerns, offer potential solutions, and request instructions. A potentially useful model for the identification and resolution of medication problems in the home health care setting was developed. This model is currently being evaluated in a randomized controlled trial.


The Recognition of the Distribution Features of Corticospinal Neurons by a Retrograde Trans-synaptic Tracing to Elucidate the Clinical Application of Contralateral Middle Trunk Transfer.
Corticospinal neurons (CSNs) undertake direct cortical outputs to the spinal cord and innervate the upper limb through the brachial plexus. Our previous study has shown that the contralateral middle trunk transfer to the paralyzed upper extremity due to cerebral injury can reconstruct the functional cerebral cortex and improve the function of the paralyzed upper extremity. To interpret the cortical reconstruction and the motor improvement after the middle trunk transfer, we explored the distribution of CSNs connecting to the middle, upper, and lower trunk of the brachial plexus by retrograde trans-neuronal tracing using pseudorabies virus (PRV-EGFP or PRV-mRFP). We show that, rather than an individual specific area, these CSNs labelled by each trunk of the brachial plexus were widespread and mainly assembled within the primary motor cortex (M1), secondary motor cortex (M2), primary somatosensory cortex (S1), and slightly within the secondary somatosensory cortex (S2). The three trunk-labelled CSNs were intermingled in these cortices, and mostly connected to more than two trunks, especially the middle trunk-labelled CSNs with higher proportion of co-labelled neurons. Our findings revealed the distribution features of CSNs connecting to the adjacent spinal nerves that innervate the upper limb, which can improve our understanding of the corticospinal circuits associated with motor improvement and the functional cortical reconstruction after the middle trunk transfer.


Doppler echocardiographic assessment of the valve area in patients with atrioventricular valve stenosis by application of the continuity equation.
The orifice area was non-invasively assessed in 19 patients with mitral or mitral and tricuspid stenosis by combined cross-sectional and Doppler echocardiography. Stroke volume was calculated as the product of aortic or pulmonic cross-sectional area and the time velocity integral of the flow across that valve, and the stenotic valve area was obtained as the stroke volume divided by the time velocity integral of the stenotic valve. In addition, the mitral valve area was estimated by the pressure half-time method of Hatle et al. The non-invasive determinations were compared with those calculated by the Gorlin formula at cardiac catheterization. The valve area obtained by combined cross-sectional and Doppler echocardiography showed a close correlation with the Gorlin area, r = 0.90, SEE = 0.13 cm2, n = 20. In contrast, the valve area estimated by the pressure half-time method showed only a moderate correlation with the Gorlin area, r = 0.68, SEE = 0.38 cm2, n = 18, and estimates by this method tended to significantly overestimate the Gorlin area. In conclusion, non-invasive valve area determinations based on combined cross-sectional and Doppler echocardiography can be used to accurately quantify the severity of the lesion in patients with atrioventricular valve stenosis, while determinations by the pressure half-time method may show errors of a magnitude that limits its clinical applicability.


Self-report adherence measures in chronic illness: retest reliability and predictive validity.
Patient self-report is a practical method for measuring adherence, but little is known about its optimal use. To examine the retest reliability and predictive validity of 3 different types of self-report adherence measures among patients with common chronic illnesses. Correlation and regression analyses of data from an ongoing randomized controlled trial. Patients (N = 415) aged >or=40 years recruited from a primary care network with arthritis, asthma, chronic lung disease, congestive heart failure, depression, and/or diabetes mellitus, plus impairment in >or=1 basic activity and/or a score of >or=4 on the 10-item Center for Epidemiologic Studies Depression Scale. : Self-report adherence (administered variously at baseline, 2, 4, and 6 weeks, and 6 months): number of pills taken/number of pills prescribed (PT/PP), using 1-7 days recall, and global reports of medication adherence and overall adherence tendencies. Six-month functional outcomes: Health Assessment Questionnaire (HAQ) and Short Form-36 (SF-36). Correlation coefficients among contemporaneously administered 1-7 days PT/PP measures were >or=0.78. Correlations among PT/PP measures and global adherence measures, and among PT/PP measures at 2 and 4 weeks, ranged from 0.11 to 0.54. PT/PP measures using >or=3-4 days recall significantly predicted adjusted 6-month HAQ but not SF-36 score. Self-report PT/PP and general medication adherence measures tap different behavioral constructs. Self-reported PT/PP at a given point in time is not necessarily representative of medication adherence over time. Among chronically ill patients, 3-4 days recall of PT/PP yield adherence estimates, which are practically as reliable and valid as longer intervals and which predict functional outcomes.


Photoparoxysmal response in late infantile neuronal ceroid-lipofuscinosis.
A patient presented with rapid developmental regression whose MRI findings suggested a leukodystrophy, but nerve, muscle, skin, and bone marrow biopsies were unrevealing. A characteristic photoparoxysmal response on electroencephalogram provided an important clue for the correct diagnosis of late infantile neuronal ceroid-lipofuscinosis, which was confirmed later with electron microscope examination of a brain biopsy. In patients with rapid neurologic deterioration, diagnosis of neuronal ceroid-lipofuscinosis should be considered and an electroencephalogram should be performed using photic stimulation to look for characteristic findings.


A strategy for characterizing the mixing state of immiscible aerosol components and the formation of multiphase aerosol particles through coagulation.
We demonstrate that the coagulation of two aerosol droplets of different chemical composition can be studied directly through the unique combination of optical tweezers and Raman spectroscopy. Multiple optical traps can be established, allowing the manipulation of multiple aerosol droplets. Spontaneous Raman scattering allows the characterization of droplet composition and mixing state, permitting the phase segregation of immiscible components in multiphase aerosol to be investigated with spatial resolution. Stimulated Raman scattering allows the integrity of the droplet and uniformity of refractive index to be probed. The combination of these spectroscopic probes with optical tweezers is shown to yield unprecedented detail in studies of the coagulation of decane and water droplets.


Contact probe voltammetry for in situ monitoring of the reactivity of phenolic tomato (Solanum lycopersicum L.) compounds with ROS.
The application of an in situ electrochemical contact probe methodology for monitoring reactivity of antioxidant polyphenolic compounds in tomato fruits is described. Upon electrochemical generation of reactive oxygen species (ROS), characteristic voltammetric responses were recorded for compounds resulting from the reaction of such species with tomato compounds. This suggests that new electrochemically oxidizable compounds are generated from the oxidation of highly reactive polyphenolic compounds with ROS. Therefore, an evaluation of the antioxidant capacity of such species could be made from voltammetric data for different tomato varieties.


Modulating the Biofunctionality of Metal-Organic-Framework-Encapsulated Enzymes through Controllable Embedding Patterns.
Embedding an enzyme within a MOF as exoskeleton (enzyme@MOF) offers new opportunities to improve the inherent fragile nature of the enzyme, but also to impart novel biofunctionality to the MOF. Despite the remarkable stability achieved for MOF-embedded enzymes, embedding patterns and conversion of the enzymatic biofunctionality after entrapment by a MOF have only received limited attention. Herein, we reveal how embedding patterns affect the bioactivity of an enzyme encapsulated in ZIF-8. The enzyme@MOF can maintain high activity when the encapsulation process is driven by rapid enzyme-triggered nucleation of ZIF-8. When the encapsulation is driven by slow coprecipitation and the enzymes are not involved in the nucleation of ZIF-8, enzyme@MOF tends to be inactive owing to unfolding and competing coordination caused by the ligand, 2-methyl imidazole. These two embedding patterns can easily be controlled by chemical modification of the amino acids of the enzymes, modulating their biofunctionality.


Differentiation resistance through altered retinoblastoma protein function in acute lymphoblastic leukemia: in silico modeling of the deregulations in the G1/S restriction point pathway.
As in many cancer types, the G1/S restriction point (RP) is deregulated in Acute Lymphoblastic Leukemia (ALL). Hyper-phosphorylated retinoblastoma protein (hyper-pRb) is found in high levels in ALL cells. Nevertheless, the ALL lymphocyte proliferation rate for the average patient is surprisingly low compared to its normal counterpart of the same maturation level. Additionally, as stated in literature, ALL cells possibly reside at or beyond the RP which is located in the late-G1 phase. This state may favor their differentiation resistant phenotype. A major phenomenon contributing to this fact is thought to be the observed limited redundancy in the phosphorylation of retinoblastoma protein (pRb) by the various Cyclin Dependent Kinases (Cdks). The latter may result in partial loss of pRb functions despite hyper-phosphorylation. To test this hypothesis, an in silico model aiming at simulating the biochemical regulation of the RP in ALL is introduced. By exploiting experimental findings derived from leukemic cells and following a semi-quantitative calibration procedure, the model has been shown to satisfactorily reproduce such a behavior for the RP pathway. At the same time, the calibrated model has been proved to be in agreement with the observed variation in the ALL cell cycle duration. The proposed model aims to contribute to a better understanding of the complex phenomena governing the leukemic cell cycle. At the same time it constitutes a significant first step in the creation of a personalized proliferation rate predictor that can be used in the context of multiscale cancer modeling. Such an approach is expected to play an important role in the refinement and the advancement of mechanistic modeling of ALL in the context of the emergent and promising scientific domains of In Silico Oncology and more generally In Silico Medicine.


Regulatory interactions in the dimeric cytochrome bc(1) complex: the advantages of being a twin.
The dimeric cytochrome bc(1) complex catalyzes the oxidation-reduction of quinol and quinone at sites located in opposite sides of the membrane in which it resides. We review the kinetics of electron transfer and inhibitor binding that reveal functional interactions between the quinol oxidation site at center P and quinone reduction site at center N in opposite monomers in conjunction with electron equilibration between the cytochrome b subunits of the dimer. A model for the mechanism of the bc(1) complex has emerged from these studies in which binding of ligands that mimic semiquinone at center N regulates half-of-the-sites reactivity at center P and binding of ligands that mimic catalytically competent binding of ubiquinol at center P regulates half-of-the-sites reactivity at center N. An additional feature of this model is that inhibition of quinol oxidation at the quinone reduction site is avoided by allowing catalysis in only one monomer at a time, which maximizes the number of redox acceptor centers available in cytochrome b for electrons coming from quinol oxidation reactions at center P and minimizes the leakage of electrons that would result in the generation of damaging oxygen radicals.


Arterial blood-gas analyses during electroconvulsive therapy in a parturient.
Arterial blood gases and vital signs were monitored in a patient receiving electroconvulsive therapy (ECT) during the third trimester of pregnancy. Alterations in blood pressure and heart rate were similar to those noted in prior studies. Pretreating with 100 percent oxygen (02) and assisting ventilation until return of adequate spontaneous respirations, prevented hypoxemia, significant hypercarbia, and cardiovascular changes. The administration of succinylcholine prevented the systemic manifestations of the electrically-induced seizure. One fetal arrhythmia occurred, apparently unrelated to changes in maternal Pa02, and resolved spontaneously. This technic of anesthesia would appear to be acceptable for ECT in the parturient.


Autophagy in the intestinal epithelium is not involved in the pathogenesis of intestinal tumors.
Autophagy has been demonstrated to be associated with the pathogenesis of cancer, but no consensus has been reached about its precise role. Therefore, we investigated whether autophagy in the intestinal epithelium is involved in the pathogenesis of intestinal tumors. To evaluate the relationship between autophagy and intestinal tumors, GFP-LC3-APC(min/+) mice were generated by mating GFP-LC3 transgenic mice with APC(min/+) mice. Autophagy was weakly induced in the intestinal polyp regions of the mice in comparison to their non-polyp regions. Under starved conditions, autophagy was not induced in the polyp regions, whereas it was observed in the non-polyp regions. Then, to examine whether a lack of autophagy in the intestinal epithelium enhances the induction of intestinal tumor, Atg7flox/flox:vil-cre-APC(min/+) mice, in which Atg7 had been conditionally deleted in the intestinal epithelium, were generated by mating Atg7flox/flox:vil-cre mice with APC(min/+) mice. However, there was no significant difference in the number of intestinal polyps between the Atg7flox/flox:vil-cre-APC(min/+) and the corresponding control Atg7flox/flox-APC(min/+) mice. These results indicate that autophagy in the intestinal epithelium is not involved in the pathogenesis of intestinal tumors, and future research should focus on regulating autophagy as a form of cancer therapy.


Incorporation of single dinitrophenyl-modified proteins into the 30 S subunit of Escherichia coli ribosomes by total reconstitution.
In this first of two consecutive papers, the main objective of which is to present a new approach to the systematic localization of individual proteins located in the Escherichia coli ribosome by immunoelectron microscopy, we describe the derivatization of several purified 30 S proteins (S12, S21, S14, S19, S18, S17) with 2,4-[3,5-3H]dinitrofluorobenzene at pH 7.4 and 8.4 and the uptake of each dinitrophenylated protein in place of the corresponding unmodified protein into totally reconstituted 30 S subunits. Reverse-phase high performance liquid chromatography is used to purify the proteins, to separate and characterize the products of 2,4-[3,5-3H]dinitrofluorobenzene modification, and to analyze the protein composition of the reconstituted subunits. The extent of dinitrophenyl (DNP) modification is estimated by both radioactivity and integrated peak areas, using dual wavelength monitoring at 214 and 360 nm. DNP derivatives of each of the six proteins are efficiently incorporated into reconstituting 30 S subunits. Incorporation of any of the six DNP-modified proteins does not interfere with binding of Phe-tRNA(Phe) in a poly(U)-dependent manner. This result, as well as data showing that unmodified protein competes with DNP-protein for uptake during reconstitution, provide evidence that each DNP-protein occupies the same position in 30 S subunit as does unmodified protein. In general, for a given protein, unmodified and/or less modified forms are incorporated in preference to more modified forms. Modification of protein S19 at pH 7.4 proceeds with selective formation of one derivative in high yield. Reverse-phase high performance liquid chromatography analysis of acid hydrolysates of a purified sample of this derivative, as well as of peptides derived from it by digestion with Staphylococcus aureus protease, show the N-terminal proline to be the predominant site of DNP-derivatization.


Accessibility and distribution of intraerythrocytic antigens of Plasmodium-infected erythrocytes following mild glutaraldehyde fixation and detergent extraction.
Malarial antigens on the surface of infected erythrocytes have been described by many investigators. However, few of these antigens have been unambiguously demonstrated to be exposed on the surface of erythrocytes. This study demonstrates that mild glutaraldehyde fixation results in the cytoplasmic face of the host membrane becoming accessible to antibody under conditions that normally do not expose the cytoplasmic face of uninfected erythrocytes. These results indicate that caution should be used in interpreting data on the membrane disposition of malarial antigens. Detergent extraction of the glutaraldehyde-fixed erythrocytes results in an increased permeabilization such that malarial antigens on the parasite surface and within the cytoplasm of the infected erythrocyte are accessible to antibody. The accessibility of these antigens was demonstrated by both immunofluorescence and two-color flow cytometry. The antigens within the host cytoplasm were not diffuse but associated with patchy aggregates. Analysis of the antigens associated with the cytoplasmic aggregates by immunoelectron microscopy indicated that they were not associated with membrane-bound compartments. The fixation and permeabilization protocol described herein will have useful applications for the characterization and analysis of malarial antigens.


miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit.
Brown adipocytes are a primary site of energy expenditure and reside not only in classical brown adipose tissue but can also be found in white adipose tissue. Here we show that microRNA 155 is enriched in brown adipose tissue and is highly expressed in proliferating brown preadipocytes but declines after induction of differentiation. Interestingly, microRNA 155 and its target, the adipogenic transcription factor CCAAT/enhancer-binding protein β, form a bistable feedback loop integrating hormonal signals that regulate proliferation or differentiation. Inhibition of microRNA 155 enhances brown adipocyte differentiation and induces a brown adipocyte-like phenotype ('browning') in white adipocytes. Consequently, microRNA 155-deficient mice exhibit increased brown adipose tissue function and 'browning' of white fat tissue. In contrast, transgenic overexpression of microRNA 155 in mice causes a reduction of brown adipose tissue mass and impairment of brown adipose tissue function. These data demonstrate that the bistable loop involving microRNA 155 and CCAAT/enhancer-binding protein β regulates brown lineage commitment, thereby, controlling the development of brown and beige fat cells.


Selective tissue distribution and long circulation endowed by paclitaxel loaded PEGylated poly(ε-caprolactone-co-L-lactide) micelles leading to improved anti-tumor effects and low systematic toxicity.
High tumor targeting and sustained drug concentration are key points for successful anti-tumor therapy, however, it is a challenging task. In this work, a novel micelle formulation of paclitaxel (PTX) has been prepared for the purpose of prolonging the blood circulation time as well as improving the accumulation of the drug within the tumor tissue. PEGylated P(CL-co-LLA) (poly(ε-caprolactone-co-L-lactide)) micelles containing PTX were prepared by solid dispersion-sonication method with a higher drug-loading efficiency and encapsulation ratio (28.4% and 94.7%, respectively). Pharmacokinetic study revealed that the drug-loading micelles exhibited a higher AUC values and a prolonged residence time of drug in the blood circulation than those of PTX injection. As demonstrated by tissue distribution and anti-tumor study in S180 tumor-bearing mice, the PEG-P(CL-co-LLA)/PTX micelles displayed modified tissue distribution of PTX and increased accumulation of PTX in tumor, therefore, resulted in anti-tumor effects enhancement and drug concentration in the normal tissues reduction. Furthermore, the preliminary safety tests were performed by measuring the body weight, histopathology, blood cell counts and clinical chemistry parameters, and the results showed no subacute toxicity to hematological system, major organs or tissues in mice. Taken together, our valuation shows that PEG-P(CL-co-LLA) micelles is a potential drug delivery system of PTX for the effective treatment of the tumor and systematic toxicity reduction, thus, the micellar formulation can provide a useful alternative dosage form for i.v. administration of PTX.


Thermal response of two sexually dimorphic Calopteryx (Odonata) over an ambient temperature range.
Organisms may internally or behaviorally regulate their body temperatures or conform to the ambient air temperatures. Previous evidence is mixed on whether wing pigmentation influences thermoregulation in various odonates.We investigated the thermal response of sympatric North American Calopteryx aequabilis and Calopteryx maculata with a thermal imaging study across a 25°C ambient temperature range.We found that regressions of thorax temperature on ambient temperature standardized by species had similar slopes for male and female C. maculata, but females were consistently 1.5°C warmer than males. In contrast, the sexes of C. aequabilis differed in slope, with C. aequabilis females having a slope less than 1.0 and males having a slope greater than 1.0.We found that regressions of thorax temperature on ambient temperature standardized by sex had similar slopes for males and females of both species, but C. maculata females were consistently 2.1°C warmer than C. aequabilis females.Given that C. aequabilis is strongly sexually dimorphic in pigment, but C. maculata is not, our findings suggest that wing pigmentation may influence thermal response rate in sympatric populations of both species.


A Response Prediction Scheme Was Created Using Data from the I-SPY2 Trial.
The developed RPS-5 response prediction scheme was more predictive of pathologic complete response.


Net-building behaviour, tolerance and development of two caddisfly species from the river Rhine (Hydropsyche contubernalis and H. pellucidula) in relation to the oxygen content.
Tolerance, growth and development of H. contubernalis and H. pellucidula were analyzed at different O2-concentrations to determine the species specific potency amplitude in relation to O2-concentration. In addition netbouilding behaviour was compared at different O2-concentrations and current velocities. Under anaerobic conditions slightly greater tolerance was observed in H. contubernalis than in H. pellucidula. But at a higher O2-concentration H. contubernalis showed a distinctly higher O2-deficiency tolerance than H. pellucidula in relation to net-building activity, growth and development. In addition, more than 50% of H. contubernalis instars built capture nets with regular meshes at an O2-saturation of only 30% (15°C). High growth rates were also found at 50% O2-saturation and more than half the larvae developed into imagos. In addition to diminished net-spinning activity the mean growth rate started to decrease at an O2-saturation of 70% to 38% and the development into an imago was not possible in H. pellucidula. Because H. contubernalis corresponds to a regulative type, being able to maintain a high level of netbuilding activity, growth rate and development over a wide range (50% to 100% O2-saturation). On the other hand H. pellucidula corresponds to a conform type, because physiological efficiency decreases rapidly with falling O2-concentration, so that development into an imago is no longer possible below 85% O2-saturation. Positive correlation between net-spinning activity and tested current velocity between 10 cm/s and 25 cm/s (15°C) was found in H. pellucidula. H. contubernalis showed no change in net-building activity, over this range of current velocity. H. contubernalis can be classified as an euryoecious species with a great potency amplitude in relation to O2-concentration and current velocity. The high tolerance to O2-deficiency conditions probably allowed the early recolonization of the Mittel-and Niederrhein when a distinct O2-deficit (mean 29%, max 56%) could still be measured. H. contubernalis can be considered a bioindicator of O2-deficiency situations. Undisturbed development of H. pellucidula in this section of the river requires a further improvement in O2-content.


Clinical heterogeneity in the tricho-dento-osseous syndrome.
The tricho-dento-osseous syndrome (TDO syndrome) involves morphologic abnormalities of hair, teeth, and skeleton. Clinical findings of the TDO syndrome are excessively curly (fuzzy) hair, enamel hypoplasia, and skeletal findings of a generalized pattern of osseous sclerosis. We report an autosomal dominant syndrome with similar hair and teeth morphology, but with a skeletal dysplasia consisting of sclerosis and thickening of the calvarium with long bones that show subtle undertubulation but no sclerosis.


A comparison of three sampling techniques to estimate the population size of caterpillars in trees.
Three sampling techniques commonly used to estimate the population size of caterpillars and sawfly larvae in trees (branch samples, frass production, water basins), were compared with respect to sampling error and economic costs. At the level of tree populations (e.g. forests), on an arbitrary date, the mean caterpillar intensity per tree (expressed in numbers of larvae or their biomass per 100 shoots) was predicted from the mean frass production per tree (expressed in mg frass per m2 forest floor per day). At the level of the single tree, the frass production on an arbitrary date was related to the population intensity, but, due to the large sampling error, did not provide an accurate prediction. Summing the frass produced over the whole season reduced this error and predicted the seasonal abundance of larvae in single trees, estimated as their maximum intensity or their density (numbers of larvae or their biomass per m2 forest floor). The maximum population intensity was not related to the population density. The sampling techniques suffer from large errors unrelated to larval abundance. The main sources of error (i.e. weather or predation of the larvae) usually cause an underestimation of population size. Labour, the main cause of high costs, was low in the basin technique and high in the frass production technique. Possible ways of reducing errors and applications of the three techniques are discussed.


Development of CuAg/Cu2O nanoparticles on carbon nitride surface for methanol oxidation and selective conversion of carbon dioxide into formate.
Herein we report a catalyst consisting of CuAg/Cu2O nanoparticles (NPs), synthesized on the two-dimensional carbon nitride (CN) surface via galvanic exchange route for electrocatalytic methanol oxidation and carbon dioxide reduction. The lower reduction potential of copper ([Cu+(aq) + e- → Cu(s)], + 0.52 eV) compared to Ag ([Ag+(aq) + e- → Ag(s)], +0.80 eV) makes Cu(0) easily exchangeable by Ag+ ions via galvanic exchange without applying any external bias. In a two-step process, the Cu NPs are synthesized first on CN surface by adsorbing Cu2+ precursors and reducing them by NaBH4. Due to unstable nature of Cu2+ in aqueous medium some Cu2O NPs (a mixed phase of Cu/CuO) were also formed. Thereafter in the second step, Ag+ precursors are brought in contact with the already synthesized Cu and Cu2O nanoparticles (NPs). The Cu and Cu2O NPs present on the surface of CN are partially exchanged by Ag atoms to generate bimetallic CuAg/Cu2O NPs. Two atoms of Ag are expected to be deposited for every Cu atom replaced. As galvanic replacement occurs on the solid surface of carbon nitride, there is only a partial replacement of Cu and Cu2O atoms. The catalysts CN/Cu/Cu2O and CN/CuAg/Cu2O were evaluated for their performance towards methanol oxidation and carbon dioxide reduction. CN/CuAg/Cu2O showed twice the current density for methanol oxidation than CN/Cu/Cu2O in a 0.5 M methanol solution. Probably the reason for high activity of Ag than Cu is related to the weak bond of oxygen on silver substrate for oxidation reactions and strong binding affinity on copper substrate. In case of carbon dioxide reduction (CO2 reduction) the product was identified to be formate by oxidizing the product (formate) on a Pt ring electrode. The results revealed CN/CuAg/Cu2O shows a better selectivity towards formic acid formation than CN/Cu/Cu2O using the rotating ring disc electrode (RRDE). A probable reason may be the strain induced by alloy formation which could favor a reduced coverage of adsorbed hydrogen and a decrease in oxophilicity of the compressively strained copper.


Actin remodeling to facilitate membrane fusion.
Actin and its associated proteins participate in several intracellular trafficking mechanisms. This review assesses recent work that shows how actin participates in the terminal trafficking event of membrane bilayer fusion. A recent flurry of reports defines a role for Rho proteins in membrane fusion and also demonstrates that this role is distinct from any vesicle transport mechanism. Rho proteins are well known to govern actin remodeling, which implicates this process as a condition of membrane fusion. A small but significant body of work examines actin-regulated events of intracellular membrane fusion, exocytosis and endocytosis. In general, actin has been shown to act as a negative regulator of exocytosis. Cortical actin filaments act as a barrier that requires transient removal to allow vesicles to undergo docking at the plasma membrane. However, once docked, F-actin synthesis may act as a positive regulator to give the final stimulus to drive membrane fusion. F-actin synthesis is clearly needed for endocytosis and intracellular membrane fusion events. What may seem like dissimilar results are perhaps snapshots of a single mechanism of membranous actin remodeling (i.e. dynamic disassembly and reassembly) that is universally needed for all membrane fusion events.


Identification of Lactobacillus curvatus TMW 1.624 dextransucrase and comparative characterization with Lactobacillus reuteri TMW 1.106 and Lactobacillus animalis TMW 1.971 dextransucrases.
Recently, it was affirmed that the exopolysaccharides (EPSs) of Lactobacillus curvatus TMW 1.624, Lactobacillus reuteri TMW 1.106 and Lactobacillus animalis TMW 1.971 improve the quality of gluten-free breads and that they can be produced in situ to levels enabling baking applications. In this study we provide insight into the molecular and biochemical background of EPS production of these three strains. EPS formation strongly correlated with growth and took place during the exponential phase. Gtf genes were heterologously expressed, purified and their enzymatic properties as well as the structures of the EPSs formed were compared. Structural comparison of EPS formed by heterologously expressed glucosyltransferases (Gtfs) and of those formed by the wildtype lactobacilli confirmed that the respective genes/enzymes were identified and examined. The glucan formed by L. animalis Gtf was identified as a linear low molecular weight dextran. Optimal enzymatic conditions were pH 4.4 and 45 °C for the L. reuteri Gtf and pH 4.4 and 31 °C for L. curvatus Gtf. The Gtf from L. animalis had an optimal pH of 5.8 and displayed more than 50% of activity over a broad temperature profile (22-59 °C). The three Gtfs were stimulated by various mono- and divalent metal ions, dextran, as well as levan to different extents.


Functional nuclear pores reconstituted with beta 1-4 galactose-modified O-linked N-acetylglucosamine glycoproteins.
Nuclear pore proteins bearing O-linked N-acetylglucosamine (GlcNAc) are involved in nuclear transport, although a role for their glycosylation is not established. Xenopus egg extracts capable of reforming functional nuclei in vitro yielded nuclei with impaired transport and reduced nuclear pore density when depleted of wheat germ agglutinin-binding proteins. Many of the nuclear pores remaining in wheat germ agglutinin-depleted nuclei showed a striking loss of internal structure. Nuclear transport and normal nuclear pore structure were restored by the addition of nuclear pore glycoproteins from rat liver or Xenopus eggs. Glycoproteins modified by the addition of galactose to O-linked GlcNAc were also competent for assembling normal nuclear pores and restoring nuclear transport. Aphidicolin-sensitive DNA synthesis was unaffected by the removal or modification of O-linked GlcNAc glycoproteins. These data argue against a requirement for a lectin-like recognition of O-linked GlcNAc glycoproteins in nuclear pore assembly, nuclear transport, or DNA synthesis.


TIR-domain enzymatic activities at the heart of plant immunity.
Toll/interleukin-1/resistance (TIR) domain proteins contribute to innate immunity in all cellular kingdoms. TIR modules are activated by self-association and in plants, mammals and bacteria, some TIRs have enzymatic functions that are crucial for disease resistance and/or cell death. Many plant TIR-only proteins and pathogen effector-activated TIR-domain NLR receptors are NAD+ hydrolysing enzymes. Biochemical, structural and functional studies established that for both plant TIR-protein types, and certain bacterial TIRs, NADase activity generates bioactive signalling intermediates which promote resistance. A set of plant TIR-catalysed nucleotide isomers was discovered which bind to and activate EDS1 complexes, promoting their interactions with co-functioning helper NLRs. Analysis of TIR enzymes across kingdoms fills an important gap in understanding how pathogen disturbance induces TIR-regulated immune responses.


A Canonical Correlation Analysis Study on the Association Between Neighborhood Green Space and Residents' Mental Health.
Based on survey data conducted in Guangzhou in 2021, this study employs canonical correlation analysis (CCA) to evaluate the relationship between neighborhood green space, residents' green space use behavior, and their mental health. The results show that compared with the objectively measured accessibility, residents' subjective perceived accessibility of neighborhood green space plays a greater role in promoting green space use behavior and mental health. Meanwhile, the plant diversity, safety, and the number of recreational facilities in a green space can promote the frequency of green space use, improve residents' mental health status and reduce their perceived stress. Although perceived accessibility is more related to green space use behavior than green space quality indicators, green space safety and recreational facilities have many more benefits on mental health than perceived accessibility. In addition, residents' green space use behavior, especially green space visit frequency, can promote mental health and reduce perceived stress.


Influence of age on the pharmacokinetics of ceftazidime in acutely ill, adult patients.
The single and multiple i.v. dose pharmacokinetics of ceftazidime were investigated in 37 acutely ill patients with normal age-related glomerular function. Distribution was rapid with similar t1/2 alpha at all ages. Compared to the younger patients, elderly subjects had lower total and renal clearances and reduced urinary recovery. Ceftazidime clearance was closely correlated with glomerular function. The t1/2 beta was approximately 2 h in young and middle-aged patients, 2.73 h in patients aged 60-79 years, and 3.54 h in those above 80 years. The AUC was more than doubled in the oldest patients compared to individuals younger than 40 years. Vss did not change with advancing age, but was larger than previously reported in healthy volunteers. Elimination variables were not altered during multiple dosing, but a small but significant increase in AUC was detected in the elderly. Dose reduction by 50% in patients more than 70 years old is suggested.


[Contribution of the biceps brachii and pronator teres muscles to the efforts of pronation or supination. I. Statistical work (author's transl)].
The electrical activity of the biceps brachii and pronator teres muscles is studied through the prono-supination of the forearm in some isometrical conditions (static work) with different loads and joint positions. If the pronator teres is always being active in pronation, this activity is a function of the load and of the wrist and elbow positions. The same phenomena can be observed for the biceps brachii but when in supination. From the curvilinear relationships between the integrated electrical activity and the load--observed on both muscles--some torque-angle relationships can be established for the biceps brachii which show that a bifunctional muscle seems to be characterized by a very and unique force-length relationship.


One-pot tandem decarboxylative allylation-Heck cyclization of allyl diphenylglycinate imines: rapid access to polyfunctionalized 1-aminoindanes.
1-Aminoindanes are generated from allyl diphenylglycinate imines employing a "one-pot" palladium-catalyzed decarboxylative allylation-Heck cyclization cascade. Variation of both the aryl and allyl moieties leads to a diverse range of polycyclic imines, amenable to the synthesis of natural products and other biologically relevant small molecules.


Separation and molecular weight estimation of phosphatases in psoriatic scales by disc-electrophoresis.
Disc-electrophoretic investigations of psoriatic scale homogenates (15000 x g supernatant) revealed several different phosphatase activities. At pH 5 either five different phosphatase active bands (substrates: p-nitrophenylphosphate, naphthylphosphate) or three different bands (substrate: glycerophosphate) could be obtained. At pH 7 only one band (substrate: p-nitrophenylphosphate) showed phosphatase activity. At pH 9.9 either two bands (substrate: p-nitrophenylphosphate) or three bands (substrate: glycerophosphate) could be demonstrated. the acid p-nitrophenylphosphatase activity of the psoriatic specific bands "9" and "10" could be distinguished by their different fluoride and tartrate susceptibility. Also the alkaline glycerophosphatase activities could be differentiated by distinct Ca and Mg susceptibility.


Interferon-beta therapy for malignant melanoma: the dose is crucial for inhibition of proliferation and induction of apoptosis of melanoma cells.
We investigated the anti-tumor effect of human interferon-beta (HuIFN-beta) against malignant melanoma. In vitro study revealed that HuIFN-beta not only inhibited proliferation of melanoma cells (seven cell lines: MM-AN, MM-BP, MM-LH, MM-RU, PM-WK, RPM-EP, RPM-MC) but also induced apoptosis in a dose dependent fashion, though the sensitivity to HuIFN-beta was different among cell lines. In addition, we administered HuIFN-beta into cutaneous metastatic lesions of melanoma and evaluated clinical and histopathological effects. Although the size of the metastatic cutaneous lesion did not change by the intralesional injection of HuIFN-beta, histopathological examination revealed apoptotic changes of melanoma cells along with dense lymphohistiocytic infiltration. The present study confirmed direct and indirect inhibitory effects of HuIFN-beta on human melanoma cells and suggests that local higher concentration of HuIFN-beta is needed to eradicate melanoma lesions.


Triplex micron-resolution acoustic, photoacoustic, and optical transmission microscopy via photoacoustic radiometry.
We present a new sensing technique, termed photoacoustic radiometry (PAR), for mapping the optical attenuation properties of a sample. In PAR, laser pulses attenuated via transmission through the sample impinge on the ultrasound transducer and generate a photoacoustic (PA) signal within it. Spatial variation of the optical attenuation properties of the sample influences the amplitude of the PAR signal, providing image contrast. Performed simultaneously with pulse-echo ultrasound and PA imaging, this triplex imaging technique enables rapid characterization of samples with micrometer-resolution in a single scan. In this work, we demonstrate that the PAR technique can be easily integrated into existing PA microscopy systems, with applications in imaging biological samples and non-destructive evaluation of optically opaque materials such as silicon wafers.


2-Methoxy-5((3,4,5-trimethosyphenyl) seleninyl) phenol causes G2/M cell cycle arrest and apoptosis in NSCLC cells through mitochondrial apoptotic pathway and MDM2 inhibition.
Nonsmall cell lung cancer (NSCLC) is one of the most common malignancies and needs novel and effective chemotherapy. In this study, our purpose is to explore the anticancer effects of 2-methoxy-5((3,4,5-trimethosyphenyl) seleninyl) phenol (SQ) on human NSCLC (A549 and H460) cells. We found that SQ suppressed the proliferation of NSCLC cells in time- and dose-dependent manners, and blocked the cells at G2/M phase, which was relevant to microtubule depolymerization. Additionally, SQ induced A549 and H460 cell apoptosis by activating the mitochondrial apoptotic pathway. Further, we demonstrated that SQ enhanced the generation of reactive oxygen species (ROS), and pretreatment with N-acetyl- L-cysteine (NAC) attenuated SQ-induced cell apoptosis. Meanwhile, SQ mediated-ROS generation caused DNA damage in A549 and H460 cells. Our data also revealed that SQ-induced apoptosis was correlated with the inhibition of mouse double minute 2 (MDM2) in A549 and H460 cells. In summary, our research indicates that the novel compound SQ has great potential for therapeutic treatment of NSCLC in future.


Implementing an electronic medical record in a family medicine practice: communication, decision making, and conflict.
Electronic medical record (EMR) systems offer substantial opportunities to organize and manage clinical data in ways that can potentially improve preventive health care, the management of chronic illness, and the financial health of primary care practices. The functionality of EMRs as implemented, however, can vary substantially from that envisaged by their designers and even from those who purchase the programs. The purpose of this study was to explore how unique aspects of a family medicine office culture affect the initial implementation of an EMR. As part of a larger study, we conducted a qualitative case study of a private family medicine practice that had recently purchased and implemented an EMR. We collected data using participant observation, in-depth interviews, and key informant interviews. After the initial data collection, we shared our observations with practice members and returned 1 year later to collect additional data. Dysfunctional communication patterns, the distribution of formal and informal decision-making power, and internal conflicts limited the effective implementation and use of the EMR. The implementation and use of the EMR made tracking and monitoring of preventive health and chronic illness unwieldy and offered little or no improvement when compared with paper charts. Implementing an EMR without an understanding of the systemic effects and communication and the decision-making processes within an office practice and without methods for bringing to the surface and addressing conflicts limits the opportunities for improved care offered by EMRs. Understanding how these common issues manifest within unique practice settings can enhance the effective implementation and use of EMRs.


Reactivity of phosphonodithioato-dppt Ni(II) mixed ligand complexes with halogens: first example of a metal-coordinating tribromide anion.
The first example of a metal complex containing a tribromide anion is presented and characterised by X-ray diffraction. Hybrid DFT calculations were used to investigate the nature of the bond in coordinating trihalides and the differences with the corresponding mono-halide complexes.


Planning for the HPV vaccine and its impact on cervical cancer prevention.
Genital human papilloma virus (HPV), the most common sexually transmitted disease in the United States, is associated with cervical cancer in women, and penile cancers in men. The infection is asymptomatic until a malignancy develops. Of the more than 90 subtypes, only a small number are associated with malignancies. Vaccines made with recombinant HPV proteins have been shown effective in preventing infection with the more virulent strains of the virus.


Off-label use of misoprostol for labor induction: a nation-wide survey in Switzerland.
Off-label use of drugs is frequent in obstetrical practice. No data however are available about nation-wide off-label use in obstetrics regarding frequency and patient information. The objective of our study was to assess the clinical practice of off-label use of misoprostol for labor induction. We performed a prospective nation-wide survey study by means of a validated questionnaire in three languages in Switzerland. All registered obstetricians/gynaecologists in Switzerland were included. Of 1100 subjects, 725 (66%) answered the questionnaire; 69 subjects were excluded because they were not actively practicing OB/GYN, resulting in a total of 656 questionnaires included in the analysis. A total of 512 out of 656 obstetricians/gynaecologists (78%) use misoprostol for labor induction. The most frequent administration route of misoprostol is intravaginal (86%), in a single dose of 50μg (94%), at a dose interval range from 4 to 6h (85%). Among the users of misoprostol, 314 (61%) answered that they do not inform their patients about the off-label use of the medication. Among the non-users of misoprostol, the main reason for non-use is absent license for obstetric indications (48%) and non-availability (14%). If misoprostol were to be licensed for this indication, and commercially available, 69% of current non-users would use it. Non-users of misoprotol use prostaglandin E2 vaginal gel, ovules or slow-release vaginal insert, and oxytocin for labor induction. Misoprostol is the single most commonly used drug for labor induction in Switzerland, although it is not licensed and although there are effective, licensed alternative drugs available. A minority of practitioners inform the patients about the off-label use.


Direct fluorimetric determination of ascorbic acid by the supramolecular system of AA with beta-cyclodextrin derivative.
We established a simple and selective fluorimetric method for the determination of ascorbic acid (AA) with the novel mono-[6-N(4-carboxy-phenyl)]-beta-cyclodextrin (ACD). The method is based on the fluorescence intensity of ACD decreases as the ACD-AA supramolecular complexes form. The fluorescence intensity is measured at excitation and emission wavelengths of 270 and 352 nm, respectively. Under optimum condition, a linear relationship is obtained between the fluorescence intensity and the concentration of AA in the range of 0.05-8.0 microgml(-1). The detection limit is 0.012 microgml(-1). The method has been applied to the direct analysis of AA in real samples with satisfactory results.


Medicine as business, learned profession, and moral enterprise: an evolution of emphasis, 1905-2005.
Despite criticisms of the medical profession from certain quarters, organized medicine has in many ways been a positive force for advancing physicians' ethics and professionalism. Review of articles published in The Journal of the South Carolina Medical Association through the past century suggests sustained concern and increasing sophistication in how we deal with these topics.


Analysis of independent variables affecting survival after recurrence of prostate cancer.
Two hundred and sixty-six patients developed recurrence after external beam radiation therapy for Stage B or C prostate cancer. The median survival from the time of recurrence was 30 months, the 5-year actuarial survival was 22% and the 8-year actuarial survival was 13%. The original stage influences survival after recurrence. Median survival is 35 months for Stage B and 27 months for Stage C. Five-year actuarial survivals are 31% for Stage B and 16% for Stage C. The site of recurrence (infield or metastatic) influences survival after recurrence. Median survival is 33 months for infield and 25 months for metastatic. Five-year actuarial survival is 30% for infield and 17% for metastatic. The time of recurrence influences survival after recurrence, comparing survival in patients recurring in the first year after treatment, to patients recurring in the second or later years after treatment. Median survival after recurrence is 14 months for those who recur in the first year, 32 months for those who recur later. Histologic grade influences survival after recurrence. Median survivals are 49 months for well differentiated, 31 months for moderately differentiated, and 23 months for poorly differentiated. Cox regression analysis indicates that original stage, site of recurrence (local vs. metastatic), time of recurrence after therapy, and histologic grade are all independent variables influencing survival after recurrence (p = less than .01). This study supports the aggressive treatment of prostate cancer to prevent recurrence and provides a means of estimating prognosis for patients who suffer a recurrence of their prostate cancer after treatment.


Mutation in AIDS restriction gene affecting HIV infection and disease progression in a high risk group from Northeastern India.
HIV estimates for 2009 released by National AIDS Control Organization (NACO) reveals that 2.4 million people in India were living with HIV, 39% being female, 4.4% children and 82.4% adult males between the age group of 15 and 49 years. Persons with host genetic polymorphism CCR5Δ32 mutation are known to be partially or fully resistant to HIV infection. Persons with mutation affecting both the alleles (homozygous) are resistant to HIV infection whereas single allele (heterozygous) polymorphism leads to slower progression to AIDS. CCR5Δ32 mutation is commoner in Caucasians but less prevalent amongst Africans and Asians thereby rendering them susceptible to HIV infection. 571 HIV serologically naive subjects from a young and homogenous male population hailing from the seven northeastern states; West Bengal and Gorkha people were selected. All the subjects belonged to a special high risk group, sexually active and typically working in difficult and uncongenial terrain involved in frequent moves including overseas missions. Their family lives are severely disrupted. 181 HIV seropositive cases of which 92 cases that were admitted in a large tertiary care hospital were also included. The distribution of CCR5Δ32 polymorphism amongst both HIV seronegative (HSN) and HIV seropositive study cohorts (HSP) using molecular methods was studied. There was failure to detect any CCR5Δ32 amongst this study group suggesting that this population from the northeastern India, West Bengal and Gorkha people are not protected by this specific host polymorphism in respect of acquisition of HIV infection as well as progression to AIDS.


Bullous pemphigoid following radiotherapy.
We report the case of a 57-year-old woman who developed bullous pemphigoid 3 weeks after electron beam radiotherapy. The bullae were confined to the area of the radiation field and responded to topical clobetasol propionate 0.05% cream (Dermovate). This is the second case of bullous pemphigoid confined to an area of previous radiotherapy. Radiotherapy may be a rare trigger for the development of bullous pemphigoid.


A case of steroid-resistant cystitis as an immune-related adverse event during treatment with nivolumab for lung cancer, which was successfully treated with infliximab.
Immune checkpoint inhibitors are widely used in various cancers as a standard treatment. However, while various immune-related adverse events related to immune checkpoint inhibitors have been reported, there are few reports of lower urinary tract symptoms. The patient was a 60-year-old man with primary lung cancer who was receiving long-term nivolumab therapy. He was referred to our department due to the sudden onset of glans penile pain and micturition pain. We suspected non-bacterial cystitis as an immune-related adverse event caused by nivolumab and were able to treat it by administering prednisolone. While his symptoms and findings on cystoscopy recurred during prednisolone therapy, we were able to treat him again by administering an additional dose of infliximab. A few reports have described cases of immune checkpoint inhibitor-induced cystitis for which prednisolone was effective. This report is the first to describe cystitis as a steroid-resistant immune-related adverse event.


Comparative effectiveness of financing models in development assistance for health and the role of results-based funding approaches: a scoping review.
Over the past three decades, there has been an unprecedented growth in development assistance for health through different financing models, ranging from donations to results-based approaches, to improve health in low- and middle-income countries. Since then, the global burden of disease has started to shift. However, it is still not entirely clear what the comparative effect of the different financing models is. To assess the effect of these financing models on various healthcare targets, we systematically reviewed the peer-reviewed and gray literature. We identified 19 studies and found that results-based financing approaches have an overall positive impact on institutional delivery rates and numbers of healthcare facility visits, though this impact varies greatly by context.Donors might be better served by providing a results-based financing scheme combining demand and supply side health-related schemes. It is essential to include rigorous monitoring and evaluation strategies when designing financing models.


Dendrimer-mediated synthesis of supported rhodium nanoparticles with controlled size: effect of pH and dialysis.
Rh-dendrimer nanocomposites were synthesized in solution under different conditions and were subsequently used as precursors for the preparation of ZrO2-supported Rh nanoparticles. Elemental analysis, UV-vis, XPS, and STEM measurements were used to estimate the extent of the Rh-dendrimer interactions and to illustrate how the solution pH and dialysis affect the number of Rh atoms complexed with each dendrimer molecule, as well as the final size of the ZrO2-supported Rh particles. When the solution acidity was not controlled and the solution was not purified by dialysis, Rh particles with sizes in the 1-6 nm range were formed on the ZrO2 support. In contrast, the formation of nearly uniform Rh particles was observed when the synthesis was performed under controlled pH and dialysis conditions. Furthermore, the size of these Rh particles can be regulated by controlling the Rh/dendrimer ratio in the original solution.


Arnica montana L. extract containing 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin accelerates growth and differentiation of human subcutaneous preadipocytes and leads volumizing of skin.
An important factor in the aging of the face is a reduction in the volume of adipose tissue. This reduction in adipose tissue contributes to decreased skin elasticity, which is also part of the aging process. Overall, these lead to wrinkle formation. Fat injection is a common means of addressing this issue and is used to reduce the effects of aging on the face and to increase the fullness of the lips and breasts. However, fat injection is an invasive surgical procedure. This study aimed to discover novel cosmetic ingredients that increase the volume of subcutaneous (pre)adipocytes to create the appearance of more youthful skin. We focused on the number of subcutaneous preadipocytes and the accumulation of lipid droplets. To discover natural ingredients that increase both of these, extracts of 380 natural products were prepared and screened for their effects on both growth and differentiation (i.e., lipid droplet accumulation) of human subcutaneous preadipocytes. One extract was found to have the desired effects, and this was further studied to determine the active compounds. We then evaluated its efficacy in a human clinical study. We found that Arnica montana L. flower extract (AFE) accelerates both the growth and the differentiation of human subcutaneous preadipocytes. AFE was found to significantly increase the volume of adipocyte spheroids. The active compounds 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin were found to be responsible for the effects of AFE on preadipocytes. In a human clinical study, gels containing 1% AFE successfully enhanced the volume of the lips and face with reduction of wrinkles with no adverse reactions. This is the first report to demonstrate that AFE and the included compounds, 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin, act on preadipocytes. AFE would be ideal for use in products that plump the face to reduce wrinkles and create a more youthful appearance.


Induction of acute phase proteins by dexamethasone in rat hepatocyte primary cultures.
The effect of dexamethasone on the synthesis of acute phase proteins has been studied in primary cultures of rat hepatocytes. In the absence of dexamethasone no detectable amounts of alpha 2-macroglobulin were synthesized by hepatocytes cultured for 1 day. alpha 2-Macroglobulin synthesis was induced by dexamethasone concentrations of 10(-8) M or higher with a maximum at a concentration of 10(-7) M. alpha 1-Acid glycoprotein was synthesized in the absence of dexamethasone; however, its synthesis was also greatly stimulated by dexamethasone concentrations of 10(-8)-10(-6) M. Synthesis of alpha 1-proteinase inhibitor was stimulated only 1.4-fold at a dexamethasone concentration of 10(-7) M. The kinetics of induction of alpha 2-macroglobulin and alpha 1-acid glycoprotein were studied at a dexamethasone concentration of 10(-7) M. After an initial lag phase of 3 h the synthesis of both proteins showed a steady increase during 2 days. Synthesis of albumin remained unchanged under these experimental conditions. Unlike alpha 2-macroglobulin and alpha 1-acid glycoprotein tyrosine aminotransferase activity increased already during the first 3 h of induction by dexamethasone with a maximum at 12 h followed by a slight decrease.


Recurrence Rates and Pharmacological Treatment for Hemorrhoidal Disease: A Systematic Review.
Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD. Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews. The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5% following surgery or phlebotonics, with most (n = 19) reporting rates of 20% or less. In addition to time since treatment, risk factors for recurring disease were similar to those for HD in general. With respect to treatment, micronized purified flavonoid fractions significantly improved the main symptoms of HD compared to other pharmacological treatments. The SLRs did not identify any RWE studies reporting recurrence in patients receiving systemic or topical treatments, highlighting the need for future research in this area. Further, more studies are needed to understand the optimum duration of medical treatment to prevent recurrence.


Pollution shapes the microbial communities in river water and sediments from the Olifants River catchment, South Africa.
Human activities such as agriculture and mining are leading causes of water pollution worldwide. Individual contaminants are known to negatively affect microbial communities. However, the effect of multifaceted pollution on these communities is less well understood. We investigated, using next-generation sequencing of the 16S rRNA genes, the effects of multisource (i.e., fertilizer industry and mining) chronic pollution on bacterial and archaeal communities in water and sediments from the Olifants River catchment, South Africa. Water samples showed less microbial species diversity than sediments and both habitats displayed different microbial communities. Within each of these habitats, pollution had no effect on alpha diversity but shaped the microbial composition and taxonomy-based predicted functions. Certain prokaryotic taxa and functional groups were indicative of different degrees of pollution. Heterotrophic taxa (e.g., Flavobacterium sp.) and sulphur-oxidizing bacteria (i.e., Thiobacillus sp.) were indicators of pollution in water and sediments, respectively. Ultimately, this information could be used to develop microbial indicators of water quality degradation.


Elective Mechanical Circulatory Support in the Percutaneous Treatment of Patients With Combined Complex Coronary Artery Disease and Severe Aortic Valve Stenosis.
One of the procedural concerns during percutaneous treatment of patients with concomitant coronary artery disease (CAD) and aortic valve stenosis (AS) is the risk of hemodynamic instability. In the present study, we assessed the safety and effectiveness of elective hemodynamic support with the Impella 2.5 system (Abiomed, Inc) in patients undergoing combined high-risk percutaneous coronary intervention (PCI) and balloon aortic valvuloplasty (BAV), as a bridge to transcatheter aortic valve replacement. Ten patients suffering from acute coronary syndrome (ACS) and severe AS were included. In all patients, we first performed PCI with the hemodynamic support of the Impella 2.5 system, and then BAV. The Impella catheter was successfully positioned in the left ventricle in all instances. All cases were successful, without any intraprocedural complications. All patients were discharged without any major clinical events. These preliminary results suggest that elective use of the Impella 2.5 system is safe and effective when performing PCI and BAV in high-risk ACS patients suffering from concomitant severe CAD and AS.