Nutrigonometry IV: Thales' theorem to measure the rules of dietary compromise in animals.
Diet specialists and generalists face a common challenge: they must regulate the intake and balance of nutrients to achieve a target diet for optimum nutrition. When optimum nutrition is unattainable, organisms must cope with dietary imbalances and trade-off surplus and deficits of nutrients that ensue. Animals achieve this through compensatory rules that dictate how to cope with nutrient imbalances, known as 'rules of compromise'. Understanding the patterns of the rules of compromise can provide invaluable insights into animal physiology and behaviour, and shed light into the evolution of diet specialisation. However, we lack an analytical method for quantitative comparisons of the rules of compromise within and between species. Here, I present a new analytical method that uses Thales' theorem as foundation, and that enables fast comparisons of the rules of compromise within and between species. I then apply the method on three landmark datasets to show how the method enables us to gain insights into how animals with different diet specialisation cope with nutrient imbalances. The method opens new avenues of research to understand how animals cope with nutrient imbalances in comparative nutrition.


Farnesol abrogates epithelial to mesenchymal transition process through regulating Akt/mTOR pathway.
Epithelial mesenchymal transition (EMT) refers to a phenomenon through which epithelial cells develop the metastatic and invasive potential, which are closely related to carcinogenesis. Farnesol (FOH) obtained from the oils of diverse plants can exhibit significant therapeutic actions against obesity, diabetes, inflammatory conditions and cancers. Here, we evaluated the potential effects of FOH on growth and metastasis and it was observed that FOH significantly abrogated cell proliferation in lung cancer cells. Moreover, FOH inhibited cell repair movement by wound healing assay and reduced cell adhesion. It suppressed the expression of mesenchymal genes such as fibronectin, vimentin, N-cadherin, twist, and snail, and increased expression of epithelial genes such as occludin and E-cadherin. It also attenuated the migration and invasion through the inhibition of the PI3K/Akt/mTOR signaling pathway. Furthermore, FOH inhibited the tumor growth of xenograft mouse lung cancer model, and modulated the expression of mesenchymal and epithelial markers. The results suggest that FOH may block the PI3K/Akt/mTOR signaling pathway and thus exhibit anti-proliferative and anti-metastatic activity against lung cancer cells.


Third order harmonic imaging for biological tissues using three phase-coded pulses.
Compared to the fundamental and the second harmonic imaging, the third harmonic imaging shows significant improvements in image quality due to the better resolution, but it is degraded by the lower sound pressure and signal-to-noise ratio (SNR). In this study, a phase-coded pulse technique is proposed to selectively enhance the sound pressure of the third harmonic by 9.5 dB whereas the fundamental and the second harmonic components are efficiently suppressed and SNR is also increased by 4.7 dB. Based on the solution of the KZK nonlinear equation, the axial and lateral beam profiles of harmonics radiated from a planar piston transducer were theoretically simulated and experimentally examined. Finally, the third harmonic images using this technique were performed for several biological tissues and compared with the images obtained by the fundamental and the second harmonic imaging. Results demonstrate that the phase-coded pulse technique yields a dramatically cleaner and sharper contrast image.


Norms for the Spanish version of the Eating Disorders Examination Questionnaire (S-EDE-Q).
This study presents normative data on the Spanish Version of the Eating Disorders Examination Questionnaire (S-EDE-Q) for adolescents and young adults in Spain. A sample of 1,543 men and women, aged 12 - 21 years, completed the S-EDE-Q as part of a larger assessment battery. Means, standard deviations, clinical significance and percentile ranks for the raw Restraint, Eating Concern, Shape Concern, and Weight Concern subscales and the Global Score by age group and gender are presented. Data on any and regular occurrences of dieting, bingeing and compensatory behaviors by age group and gender are reported. Compared with men, women scored higher on all the subscales and reported more key eating disorders (ED) and compensatory behavior. Compared with adolescents, young adults scored higher on the Restraint and Shape Concern subscales and reported more dietary restraint (DR), objective binge episodes (OBE) and diuretic misuse (DIUR). These results can help researchers and clinicians interpret the S-EDE-Q scores of adolescents and young adults in Spanish-speaking countries.


Long-term impact of pulses crop rotation on soil fungal diversity in aerobic and wetland rice cultivation.
Pulse crop rotation in rice cultivation is a widely accepted agronomic practice. Depending upon the water regime, rice cultivation has been classified into wetland and aerobic practices. However, no studies have been conducted so far to understand the impact of pulse crop rotation and rice mono-cropping on fungal diversity, particularly in aerobic soil. A targeted metagenomic study was conducted to compare the effects of crop rotations (rice-rice and rice-pulse) on fungal diversity in wetland and aerobic rice soils. Out of 445 OTUs, 41.80% was unknown and 58.20% were assigned to six phyla, namely Ascomycota (56.57%), Basidiomycota (1.32%), Zygomycota (0.22%), Chytridiomycota (0.04%), Glomeromycota (0.03%), and Blastocladiomycota (0.02%). Functional trait analysis found wetland rice-pulse rotation increased symbiotrophs (36.7%) and saprotrophs (62.1%) population, whereas higher pathotrophs were found in aerobic rice-rice (62.8%) and rice-pulse (61.4%) cropping system. Certain soil nutrients played a major role in shaping the fungal community; Ca had significant (p < 0.05) positive impact on saprotroph, symbiotroph and endophytes, whereas Cu had significant (p < 0.05) negative impact on pathotrophs. This study showed that rice-pulse crop rotation could enhance the saprophytic and symbiotic fungal diversity in wetland and reduce the population of pathogens in aerobic rice cultivation.


New insights into the hepatitis E virus genotype 3 phylodynamics and evolutionary history.
Hepatitis E virus (HEV) is an emergent hepatotropic virus endemic mainly in Asia and other developing areas. However, in the last decade it has been increasingly reported in high-income countries. Human infecting HEV strains are currently classified into four genotypes (1-4). Genotype 3 (HEV-3) is the prevalent virus genotype and the mostly associated with autochthonous and sporadic cases of HEV in developed areas. The evolutionary history of HEV worldwide remains largely unknown. In this study we reconstructed the spatiotemporal and population dynamics of HEV-3 at global scale, but with particular emphasis in South America, where case reports have increased dramatically in the last years. To achieve this, we applied a Bayesian coalescent-based approach to a comprehensive data set comprising 97 GenBank HEV-3 sequences for which the location and sampling date was documented. Our phylogenetic analyses suggest that the worldwide genetic diversity of HEV-3 can be grouped into two main Clades (I and II) with a Ƭmrca dated in approximately 320years ago (95% HPD: 420-236years) and that a unique independent introduction of HEV-3 seems to have occurred in Uruguay, where most of the human HEV cases in South America have been described. The phylodynamic inference indicates that the population size of this virus suffered substantial temporal variations after the second half of the 20th century. In this sense and conversely to what is postulated to date, we suggest that the worldwide effective population size of HEV-3 is not decreasing and that frequently sources of error in its estimates stem from assumptions that the analyzed sequences are derived from a single panmictic population. Novel insights on the global population dynamics of HEV are given. Additionally, this work constitutes an attempt to further describe in a Bayesian coalescent framework, the phylodynamics and evolutionary history of HEV-3 in the South American region.


Cloning and expression of draTG genes from Azospirillum lipoferum.
A genomic library of Azospirillum lipoferum was constructed with phage lambda EMBL4 as vector. From this library, the genes encoding dinitrogenase reductase ADP-ribosyltransferase (DRAT), draT, and dinitrogenase reductase-activating glycohydrolase (DRAG), draG, were cloned by hybridization with the heterologous probes of Rhodospirillum rubrum. As in R. rubrum, draT is located between draG and nifH, the gene encoding dinitrogenase reductase (a substrate for the DRAG/DRAT system). In the crude extract of Escherichia coli harboring the expression vector for this region, DRAT and DRAG enzyme activities were detected, confirming the identity of the cloned genes. Southern hybridization with genomic DNA from different Azospirillum spp., demonstrated a correlation between observable draTG hybridization and the biochemical demonstration of this covalent modification system.


The changing incidence of caesarean section in the health district of Central Manchester.
The caesarean section rate in England and Wales has practically doubled from 5.6% in 1974 to 10.6% in 1982. Because most statistical reports are based on the practice of individual hospitals and do not reflect what is occurring in a particular community, a retrospective study of the incidence of, and reasons for, caesarean section performed in residents of the geographically defined Health District of Central Manchester was carried out for 1974 and 1982. The caesarean section rate in this community increased from 7% in 1974 to 16% in 1982. Caesarean sections performed for failure to progress in labour, previous caesarean section and preterm fetal compromise before labour accounted for three quarters of the increase. Breech presentation was not a significant contributor to the increase. The reasons for the increase in caesarean sections performed for failure to progress in the first stage of labour were not clarified in the records, and is the subject of prospective investigation.


Electrophoretic identification of the brain isoenzyme of creatine kinase following treatment with anti-BB antisera.
A procedure is described for accurately determining the presence of true creatine kinase isoenzyme BB by fluorescent staining following electrophoresis on either cellulose acetate or agarose. Treatment of sera with anti-BB inhibiting antibody prior to electrophoresis and subsequent enzymatic staining allows clear identification of creatine kinase BB in presence of interfering artifacts. The utilization of an immunological means of identifying BB following electrophoresis avoids the pitfall of associating an artifactual BB isoenzyme with a disease state. Using this technique, presence of creatine kinase BB in patients with carcinoma, cardiac disease and renal failure has been verified.


Insight into Iron Leaching from an Ascorbate-Oxidase-like Fe-N-C Nanozyme and Oxygen Reduction Selectivity.
Ascorbate (H2 A) is a well-known antioxidant to protect cellular components from free radical damage and has also emerged as a pro-oxidant in cancer therapies. However, such "contradictory" mechanisms underlying H2 A oxidation are not well understood. Herein, we report Fe leaching during catalytic H2 A oxidation using an Fe-N-C nanozyme as a ferritin mimic and its influence on the selectivity of the oxygen reduction reaction (ORR). Owing to the heterogeneity, the Fe-Nx sites in Fe-N-C primarily catalyzed H2 A oxidation and 4 e- ORR via an iron-oxo intermediate. Nonetheless, trace O2 ⋅- produced by marginal N-C sites through 2 e- ORR accumulated and attacked Fe-Nx sites, leading to the linear leakage of unstable Fe ions up to 420 ppb when the H2 A concentration increased to 2 mM. As a result, a substantial fraction (ca. 40 %) of the N-C sites on Fe-N-C were activated, and a new 2+2 e- ORR path was finally enabled, along with Fenton-type H2 A oxidation. Consequently, after Fe ions diffused into the bulk solution, the ORR at the N-C sites stopped at H2 O2 production, which was the origin of the pro-oxidant effect of H2 A.


Cancer care and cancer survivorship care in the United States: will we be able to care for these patients in the future?
The combination of a shortfall in oncologists and primary care physicians and an increased number of patients using more health care resources raises concerns about our health care system's ability to accommodate future patients with cancer and cancer survivors.


Self-healable printed magnetic field sensors using alternating magnetic fields.
We employ alternating magnetic fields (AMF) to drive magnetic fillers actively and guide the formation and self-healing of percolation networks. Relying on AMF, we fabricate printable magnetoresistive sensors revealing an enhancement in sensitivity and figure of merit of more than one and two orders of magnitude relative to previous reports. These sensors display low noise, high resolution, and are readily processable using various printing techniques that can be applied to different substrates. The AMF-mediated self-healing has six characteristics: 100% performance recovery; repeatable healing over multiple cycles; room-temperature operation; healing in seconds; no need for manual reassembly; humidity insensitivity. It is found that the above advantages arise from the AMF-induced attraction of magnetic microparticles and the determinative oscillation that work synergistically to improve the quantity and quality of filler contacts. By virtue of these advantages, the AMF-mediated sensors are used in safety application, medical therapy, and human-machine interfaces for augmented reality.


A rare case of tympanostomy tube otorrhea: Pigmentiphaga.
Tympanostomy tube otorrhea (TTO) is a common complication of tympanostomy tubes. The most common bacteria associated with TTO include Haemophalis influenza, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. We present the first case of a 9 year-old female with a history of 22q11 syndrome, hemifacial microsomia, Tetralogy of Fallot, and hearing aid dependence with left-sided profound sensorineural and right-sided moderate conductive hearing loss who presented with TTO caused by the bacteria Pigmentiphaga daeguenesis/kulla, a gram-negative bacteria often found in soil. This patient's otorrhea did not respond to typical otic antibiotic formulations, but was ultimately treated successfully with intramuscular ceftriaxone. We describe the natural history, presentation and management for a case of TTO caused by a rare bacteria from the genus Pigmentiphaga.


The Zurich Study. V. Anxiety and phobia in young adults.
From data collected within the frame of a longitudinal epidemiologic study of a representative sample population of young adults (the Zurich Study), anxiety disorders--anxiety and phobic states--were analyzed. The current prevalence rate was found to be 2.9% for anxiety states and 4.3% for phobic states, totaling 7.2%. Because of their anxiety disorders, one-fifth of the cases had undergone treatment during the preceding 12 months. Substantial difficulties arose, from the point of view of classification. The currently used categories, such as anxiety states, panic attacks, agoraphobia, simple phobia, social phobia, have more in common than differing symptoms. On a syndromal level, numerous overlapping configurations resulted which can only be artificially forced into the aforementioned diagnostic classes of anxiety disorders. On the symptom level, merely a few operationalized items defined these categories. In this way, most of a broad identical 'nonspecific' symptomatology was not taken into account. This was exemplified by a comparison of anxiety states and agoraphobia. In fact, these two groups did not differ significantly in many symptoms or in SCL-90 profiles, but did show a highly significant difference from control samples. Both groups suffered to the same great degree from depressive, cardiovascular, and gastrointestinal symptoms. We doubt whether any forced categorical diagnostic differentiation of anxiety and phobic states is at all reasonable.


Thromsbospondin-1 binds to the heavy chain of elastase activated coagulation factor V (FVaHNE) and enhances thrombin generation on the surface of a promyelocytic cell line.
Thrombospondin 1 (TSP1) has the ability to bind to HL-60 cells and to reversibly inhibit human neutrophil elastase (HNE). Human factor V (FV) can be cleaved by HNE thereby providing FV with cofactor activity (FVa(HNE)). Experiments were performed to evaluate the ability of HNE expressed on the surface of HL-60 cells to generate FVa(HNE) to support thrombin generation, and to determine the effect of TSP1 on this reaction. Western blot analysis showed TSP1 forming a complex with FVa(HNE) within a region corresponding to the heavy chain of FV. Enzymatic reactions were performed to determine the role of TSP1-HNE-FVa(HNE) on the surface of HL-60 cells, namely the assembly of the prothrombinase complex. Thrombin generation was measured by the chromogenic substrate S2238. Exposure of factor V to HL-60 cells prior to the addition of prothrombin and activated factor X provided FV with cofactor activity. HL-60 cells were found capable of synthesizing factor V with cofactor activity, but HL-60 cells failed to synthesize and/or to provide factor X with enzymatic activity. The ability of HL-60 cells to synthesize FV and TSP1 was demonstrated. The addition of exogenous TSP1 enhanced both the rate and amount of thrombin generated on the HL-60 cell surface. Despite the ability of TSP1 to reversibly inhibit HNE in a purified system, TSP1 expression favors the reactions leading to thrombin generation on the HL-60 cell surface. These observations are relevant to clinical conditions where there is a prothrombotic state such as malignant tumors.


Improved estimation of total oxygen uptake in exercise by evaluation of aerobic fitness.
The purpose of the present study was to contrive a new practical method for estimating total O2 uptake during exercise from total heart beats after individual evaluation of aerobic fitness levels. Twenty healthy male subjects participated in cycle ergometer tests, maximal O2 uptake (VO2max) tests and various simple tests including simple endurance tests. From the cycle ergometer results, the following formula for estimating total O2 uptake in exercise was determined: TVO2 (ml X kg-1) = SR125 X (45.8 X mean HR + 4268) X THB X 10(-4) where TVO2, THB, and mean HR are total O2 uptake, total heart beats, and mean heart rate (beats X min-1) in exercise, respectively, and SR125 is the slope of the regression line between accumulated heart beats and accumulated O2 uptake during exercise at 125 beats X min-1 of mean HR. SR125 had a significant correlation not only with VO2max but also with each score (X) in any simple endurance tests such as, for example, a step test for 2 min. In this case, accordingly, SR125 can be found as; SR125 = -0.00118X + 0.3478. These formulae indicate that the total O2 uptake of any exercising subject can be estimated from his total heart beats regardless of intensities of exercise when his aerobic fitness level is evaluated by the simple endurance test. The total O2 uptake estimated by our method was compared to that measured by the Douglas bag method, and the discrepancy between the two results was less than the errors of values estimated by traditional methods.


Application of anaerobic ammonium-oxidizing consortium to achieve completely autotrophic ammonium and sulfate removal.
The simultaneous ammonium and sulfate removal was detected in an anammox reactor, consisted of ammonium oxidization with sulfate deoxidization, and subsequently traditional anammox process, in via of middle medium nitrite with solid sulfur and N2 as the terminal products. The pure anammox bacteria offered a great biotechnological potential for the completely autotrophic reaction indicated by batch tests. Denaturing gradient gel electrophoresis (DGGE) analysis further revealed that a new organism belonging to Planctomycetales was strongly enriched in the defined niche: the redox of ammonium and sulfate. The new species "Anammoxoglobussulfate" was so considered as holding a critical role in the ammonium oxidization with sulfate deoxidization to nitrite. Afterwards, the Planctomyces existing in the bacteria community performed the anammox process together to achieve the complete nitrogen and sulfate removal. The potential use of sulfate as electron acceptor for ammonium oxidizing widens the usage of anammox bacteria.


Trace identification of cysteine enantiomers based on an electrochemical sensor assembled from CuxS@SOD zeolite.
The nonchiral sensor concept based on a sodalite (SOD) zeolite loaded CuxS (CuxS@SOD) catalyst is proposed as a sensing platform for chiral cysteine (Cys) determination. Chiral Cys is analyzed by the difference of binding capacity between CuxS catalysts. The observed current in amperometric i-t curve (A i-t C) is always positive for the L-cysteine (L-Cys), while it is negative for the D-cysteine (D-Cys). Under differential pulse voltammetry (DPV) method, the characteristic current peak for the CuxS@SOD moves to right (positive potential position) with the addition of L-Cys while it moves to left (negative potential direction) with the addition of D-Cys, respectively. Cyclic voltammetry (CV) is consistent with DPV and discusses the diffusion control mechanism. In this work, the ultra-trace determination of cysteine enantiomers reaches the limit of detection (LOD) of 0.70 fM and 0.60 fM by the highly efficient CuxS catalyst restrained in the nanosized SOD zeolite cages of the opening window pores, respectively. The sensor opens up a novel potential prospect for achiral composite in the field of chiral recognition through electrochemical methods with extra-low concentration.


Contact area, contact pressure, and pressure patterns of the tendon-bone interface after rotator cuff repair.
The contact pressure and contact area at the tendon-bone interface after the most commonly used rotator cuff repair methods have not been investigated. There are no significant differences among the transosseous, the single-row suture anchor, and the double-row suture anchor techniques in terms of contact pressure, contact area, and pressure patterns at the tendon-bone interface. Controlled laboratory study. After creating a full-thickness supraspinatus tendon tear in 10 cadaveric shoulder specimens, we inserted pressure-sensitive film between the tendon stump and the bone, and we repaired the tear by (1) transosseous, (2) single-row suture anchor, and (3) double-row suture anchor techniques. The contact area of the double-row technique was 42% greater than that of the transosseous technique (P < .0001) and 60% greater than that of the single-row technique. The contact area of the transosseous technique was 31% greater than that of the single-row technique (P = .0015). The average pressures of the single-row and double-row techniques were 18% (P = .014) and 16% (P = .03) greater, respectively, than that of the transosseous technique, but there was no significant difference between the single-row and double-row techniques (P = .915). The double-row technique produced the greatest contact area and the second-highest contact pressure, whereas the single-row technique created the highest contact pressure and the least contact area. The transosseous technique produced the second-greatest contact area and the least contact pressure. The double-row suture anchor technique and the transosseous technique may provide a better environment for tendon healing.


TCR CDR3-antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens?
Ovarian cancer continues to present significant challenges for early detection and treatment, indicating a need for novel approaches to improve disease outcomes. In this report, we applied a previously described algorithm for detecting chemical complementarity between candidate cancer antigens and complementarity determining region-3 (CDR3) amino acid sequences from tumor resident T-cell receptors. Current literature indicates an association between high CDR3-cancer antigen complementarity and improved survival outcomes. For example, high CDR3-BRAF electrostatic complementarity is associated with a better melanoma outcome. However, such CDR3-cancer antigen chemical complementarity in ovarian cancer was largely associated with worse outcomes. Specifically, high CDR3-MAGEB4 and CDR3-TDRD1 electrostatic complementarity was associated with lower ovarian cancer disease free survival (DFS). Additionally, high CDR3-MAGEB4 and CDR3-TDRD1 electrostatic complementarity was associated with decreased MAGEB4/TDRD1 gene expression and gene copy numbers, consistent with a selection against ovarian cancer cells expressing these antigens. However, when TDRD1 was split into fragments, high CDR3-TDRD1 hydrophobicity complementarity, for a specific TDRD1 fragment, was associated with increased DFS and higher immune marker expression levels. This dichotomy highlights the myriad of opportunities to establish risk stratifications and to identify potential, actionable cancer antigens using immunogenomic parameters.


Daily Exposure to Sucrose Impairs Subsequent Learning About Food Cues: A Role for Alterations in Ghrelin Signaling and Dopamine D2 Receptors.
The prevalence of hedonic foods and associated advertising slogans has contributed to the rise of the obesity epidemic in the modern world. Research has shown that intake of these foods disrupt dopaminergic systems. It may be that a disruption of these circuits produces aberrant learning about food-cue relationships. We found that rodents given 28 days of intermittent access to sucrose exhibited a deficit in the ability to block learning about a stimulus when it is paired in compound with food and another stimulus that has already been established as predictive of the food outcome. This deficit was characterized by an approach to a cue signaling food delivery that is usually blocked by prior learning, an effect dependent on dopaminergic prediction-error signaling in the midbrain. Administering the D2 agonist quinpirole during learning restored blocking in animals with a prior history of sucrose exposure. Further, repeated central infusions of ghrelin produced a deficit in blocking in the same manner as sucrose exposure. We argue that changes in dopaminergic systems resulting from sucrose exposure are mediated by a disruption of ghrelin signaling as rodents come to anticipate delivery of the highly palatable sucrose outside of normal feeding schedules. This suggestion is supported by our finding that both sucrose and ghrelin treatments resulted in increases in amphetamine-induced locomotor responding. Thus, for the first time, we have provided evidence of a potential link between alterations in D2 receptors caused by the intake of hedonic foods and aberrant learning about cue-food relationships capable of promoting inappropriate feeding habits. In addition, we have found preliminary evidence to suggest that this is mediated by changes in ghrelin signaling, a finding that should stimulate further research into modulation of ghrelin activity to treat obesity.


Secretory carcinoma of salivary gland - A systematic review of pediatric case reports and case series.
Mammary analog secretory carcinoma (MASC) is a new pathological entity of salivary gland origin recognized as Secretory Carcinoma (SC) in the WHO 2017 classification. Pediatric cases of MASC were reviewed systematically from 2010 to 2019. Databases were searched from 2010 to 2019 for pediatric case reports and case series, excluding retrospective studies. A total of 12 manuscripts were reviewed for clinical, histological and immunohistochemical findings. A total of 13 pediatric cases (11 case reports and 1 case series of 2 cases) of MASC in pediatric patients were found. The youngest reported age was 5 years. The common site was parotid gland usually presenting as a slowly growing firm, painless mass. MASC should be considered in the differential diagnosis of salivary gland tumors in pediatric population, especially from parotid gland. Extended research on such recent entities with more inputs from new cases reported in literature may outstretch the possibilities of therapeutic fusion inhibition in future.


Characteristics of paediatric home care provision: the two dominant models in England.
To describe characteristics of paediatric home care teams Home care provision is increasing and recent government initiatives such as support for Princess Diana Memorial Fund nursing teams will provide additional impetus to universal provision. However, little is known about the characteristics of paediatric home care teams. A postal survey of all services in England (n = 137) listed in the 13th edition of RCN 1996 Directory of Community Children's Nursing Services was undertaken. A response rate of 85.5% was achieved. More than half (54.6%) of the teams had been founded after 1990. Most (72.2%) were managed through paediatric or child health directorates and most (77.8%) were based in hospitals. The size of teams varied enormously (range 1-22; median 3). Only a small (5.6%) minority of teams provided care at night although over a third (37%) reported making special arrangements for terminally ill children. The survey revealed two dominant models of paediatric home care: the community model with strong links to primary health care and other local provisions and the hospital outreach model with strong links to the hospital service. A number of weaknesses in current provision are identified: variability in geographical coverage; undesirably low core staffing numbers; poor 24-h coverage; and potentially compromised staff skills and knowledge. The need for research to clarify the strengths of the different models and their effectiveness is highlighted.


Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization.
To determine the subgroup of patients in whom office hysteroscopy should be routinely performed before an in vitro fertilization (IVF) program. Retrospective cohort analysis. Tertiary education and research hospital. Two hundred twenty-three patients who underwent a uterine evaluation by office hysteroscopy before the IVF and embryo transfer cycle. The office hysteroscopy was performed in the follicular phase of the menstrual cycle before the IVF cycle. The office findings: number of polyps, number of multiple polyps, and polyp size. Patients with polycystic ovary syndrome (PCOS) had a higher number of endometrial polyps, but the difference was not statistically significant (28.9% vs. 18.3%). When comparing the patients according to BMI, patients with BMI >or=30 had a statistically significantly higher number of endometrial polyps versus BMI <30 (52% vs. 15%). On the other hand, obesity was positively correlated with the occurrence of polyps, size of the polyps, and occurrence of multiple number of polyps in the correlation analysis. In addition, logistic regression analysis using age, obesity, duration of infertility, and estradiol levels revealed that obesity was an independent prognostic factor for the development of endometrial polyps. Office hysteroscopy should be performed in patients with BMI >or=30 because obesity may act as an initiator for the pathogenesis of endometrial polyps.


Mitochondrial transfer between cell crosstalk - An emerging role in mitochondrial quality control.
Intercellular signaling and component conduction are essential for multicellular organisms' homeostasis, and mitochondrial transcellular transport is a key example of such cellular component exchange. In physiological situations, mitochondrial transfer is linked with biological development, energy coordination, and clearance of harmful components, remarkably playing important roles in maintaining mitochondrial quality. Mitochondria are engaged in many critical biological activities, like oxidative metabolism and biomolecular synthesis, and are exclusively prone to malfunction in pathological processes. Importantly, severe mitochondrial damage will further amplify the defects in the mitochondrial quality control system, which will mobilize more active mitochondrial transfer, replenish exogenous healthy mitochondria, and remove endogenous damaged mitochondria to facilitate disease outcomes. This review explores intercellular mitochondrial transport in cells, its role in cellular mitochondrial quality control, and the linking mechanisms in cellular crosstalk. We also describe advances in therapeutic strategies for diseases that target mitochondrial transfer.


Mechanical properties, fracture resistance, and fatigue limits of short fiber reinforced dental composite resin.
Cycling masticatory loads decrease the strength of particulate filler composites (PFCs) and initiate the failure process by fatigue. The life expectancy of a composite resin restoration under stress remains difficult to predict. The purpose of this study was to determine the fracture resistance and the compressive fatigue limits (CFL) of anterior crown restorations made of a short-fiber reinforced composite resin (SFC), to investigate selected mechanical properties of the material following standard test methods, and to observe their correlation with the CFL. Specimens (n=10) were fabricated either from SFC (everX Posterior, GC Corp) or PFC (G-ænial anterior, GC Corp). The properties investigated were flexural strength (FS), compression strength (CS), diametral-tensile strength (DTS), and single-edge-notched-bend fracture toughness (FT) following ISO standards. Fracture resistance was determined by static load (n=10) and the CFL at 10000 cycles was determined using a staircase approach (n=20), both on anterior composite resin crowns. The results were analyzed with 1-way ANOVA (α=.05) or 2-way ANOVA (α=.05) followed by a Tukey B post hoc test and the Pearson-correlation analysis. The SFC crowns had higher fracture resistance (954 ±121 N) than the PFC crowns (415 ±75 N) (P<.001) and higher CFL (267 ±23 N) than the PFC crowns (135 ±64 N) (P<.001). SFC revealed also higher FT (2.6 ±0.6 MPa·m(1/2)) than the PFC (1.0 ±0.2 MPa·m(1/2)) (F=69.313, P<.001). A significant correlation was observed only between the FT and the CFL (r(2)=0.899; P<.001). SFC crowns showed good performance under static and fatigue loading. FT was the only in vitro test method that filtered as a clinically relevant parameter.


Steroidal modulation of steroid secretion in vitro: an experimental approach to intra-follicular regulatory mechanisms.
Studies in vitro and in vivo indicate that steroid secretion by granulosa cells of the developing follicle is modulated in part by steroid hormones themselves. Androgens stimulate progestin synthesis in vitro by granulosa cells of all developmental stages independently of their role as an estrogen precursor; generally, the action of estradiol results in suppression of progesterone secretion. The nature of the relationship between steroid secretion by granulosa cells and the physiological processes of follicular development or atresia remains to be investigated in greater detail. The cellular mechanism(s) of steroidal modulation of steroid secretion is unknown but apparently does not involve changes in the number of granulosa cell LH receptors per se.


Neoadjuvant HIFU treatment for malignant fibrous histiocytoma: report of a case.
High-intensity focused ultrasound (HIFU) is an innovative, noninvasive, extracorporeal technique that induces coagulative necrosis of tumor tissue by thermal effects and cavitation. In published studies, HIFU has usually been used as an alternative to surgery, with or without other treatment modalities, to achieve curative tumor ablation or palliative tumor cytoreduction. Neoadjuvant HIFU treatment for primary inoperable malignant fibrous histiocytoma has never been reported, and neoadjuvant radiotherapy, chemoradiation, or chemotherapy is routinely under consideration. This is the first case in which HIFU ablation contributed as a neoadjuvant therapy to facilitate function-sparing resection, not as a replacement for surgery. It suggests that HIFU ablation may have some unique major advantages for treating inoperable huge soft-tissue sarcomas as a neoadjuvant local treatment modality, especially for patients for whom neoadjuvant chemotherapy or radiotherapy is not indicated.


Towards a coherent European approach for taxation of combustible waste.
Although intra-European trade of combustible waste has grown strongly in the last decade, incineration and landfill taxes remain disparate within Europe. The paper proposes a more coherent taxation approach for Europe that is based on the principle of Pigovian taxation, i.e. the internalization of environmental damage costs. The approach aims to create a level playing field between European regions while reinforcing incentives for sustainable management of combustible waste. Three important policy recommendations emerge. First, integrating waste incineration into the European Emissions Trading System for greenhouse gases (EU ETS) reduces the risk of tax competition between regions. Second, because taxation of every single air pollutant from waste incineration is cumbersome, a differentiated waste incineration tax based on NO(x) emissions can serve as a second-best instrument. Finally, in order to strengthen incentives for ash treatment, a landfill tax should apply for landfilled incineration residues. An example illustrates the coherence of the policy recommendations for incineration technologies with diverse environmental effects.


Conventional Transarterial Chemo embolization Using Streptozocin in Patients with Unresectable Neuroendocrine Liver Metastases.
The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. A total of 52 patients with predominant liver disease were treated with cTACE using an emulsion of streptozocin, Lipiodol and embolization particles. A sequential approach was favored in patients with high liver tumor burden. Clinical, biological and radiological responses were evaluated using carcinoid symptoms, biomarkers and mRecist criteria, respectively. A total of 127 procedures were performed with a sequential approach in 65% of patients. All patients received streptozocin and Lipiodol. Carcinoid syndrome was improved in 69% of patients after treatment (p = 0.01). Post-embolization syndrome was reported in 78% of patients. At the end of all cTACE, objective response and non-progressive disease were 32% and 70%, respectively. Progression-free survival was 18.3 ± 13.3 months (median 14.9) and median overall survival (OS) from start of treatment was 74 months. The OS at 1 year, 2 years, 3 years and 5 years was 91% (IC = 84-99%), 84% (CI = 72-95%), 69% (CI = 53-84%) and 63% (C = 46-81%), respectively. cTACE using streptozocin is an effective and well-tolerated palliative option for patients with neuroendocrine liver metastases, associated with prolonged survival and delayed time to progression.


Endoscopic sphincterotomy for suspected dysfunction of the sphincter of Oddi.
Fifty-one patients who underwent endoscopic sphincterotomy for suspected dysfunction of the sphincter of Oddi were evaluated retrospectively. The procedure resulted in complete abolition of pain allowing discontinuation of analgesics in 31 of the 46 patients available for follow-up. Patients with a dilated bile duct and delayed drainage of contrast material as demonstrated at endoscopic retrograde cholangiopancreatography (ERCP) had a more favorable response to sphincterotomy than those with normal ductal findings (p = 0.01). There was a higher complication rate in those without ductal dilation and delayed drainage compared to those with these ERCP abnormalities (p = 0.03). Sphincter of Oddi manometry was obtained in 29 patients prior to sphincterotomy; 24 were available for follow-up. A favorable outcome for sphincterotomy did not correlate with manometric assessment, particularly in patients with an abnormal ductal system.


Nano-opto-electro-mechanical switches operated at CMOS-level voltages.
Combining reprogrammable optical networks with complementary metal-oxide semiconductor (CMOS) electronics is expected to provide a platform for technological developments in on-chip integrated optoelectronics. We demonstrate how opto-electro-mechanical effects in micrometer-scale hybrid photonic-plasmonic structures enable light switching under CMOS voltages and low optical losses (0.1 decibel). Rapid (for example, tens of nanoseconds) switching is achieved by an electrostatic, nanometer-scale perturbation of a thin, and thus low-mass, gold membrane that forms an air-gap hybrid photonic-plasmonic waveguide. Confinement of the plasmonic portion of the light to the variable-height air gap yields a strong opto-electro-mechanical effect, while photonic confinement of the rest of the light minimizes optical losses. The demonstrated hybrid architecture provides a route to develop applications for CMOS-integrated, reprogrammable optical systems such as optical neural networks for deep learning.


On the reduced retention of extravesicular noradrenaline in rabbit atria produced by potassium.
The effects of KC1 on the retention of extravesicular (--)-[3H]noradrenaline were investigated. Atria, from reserpine-pretreated rabbits, were exposed to tropolone and pargyline before incubation with (--)-[3H]noradrenaline. After efflux for 50-60 min, exposure of tissues to media containing 65 mM KC1 resulted in increased efflux of (--)-[3H]noradrenaline. This effect was not Ca2+-dependent and was not altered by oxymetazoline, phentolamine, indomethacin or methacholine. The KC1-induced reduction in retention of (-)-[3H]noradrenaline was, however inhibited by cocaine and desipramine, but not by lidocaine. Efflux was not increased by RbCl and CsCl. It is suggested that KCl may have accelerated the efflux of extravesicular (--)-[3H]noradrenaline by increasing a cocaine- and desipramine-sensitive carrier-mediated efflux process.


Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome.
To investigate associations between gene expression pattern of apoptotic biomarkers in cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of oocytes and embryos. 40 intracytoplasmic sperm injection patients, of whom 20 were PCOS and 20 were healthy women, were included in this study. Serum hormone levels were measured using Radioimmunoassay for each patient. The expression of survivin, caspase-3, and caspase-7 in 200 cumulus complexes surrounding mature oocytes (100 in PCOS versus 100 in control groups) collected individually at pick up was examined by real-time polymerase chain reaction (real-time PCR). The expression levels of survivin were significantly lower in PCOS patients than those of normal women while caspase-3 and caspase-7 expression levels were higher in PCOS patients (p < 0.05). There was a statistically significant correlation between the levels of these genes and embryo quality. This study reveals that the measurement of survivin, caspase-3, caspase-7 levels in cumulus cells of PCOS patients could be used as genetic biomarkers for oocyte and embryo selection under an ART program. However, further prospective studies are required to elucidate this issue.


Increased expression of pro-inflammatory cytokines and lack of up-regulation of anti-inflammatory cytokines in early distemper CNS lesions.
To investigate the pathogenesis of early lesions in canine distemper virus (CDV) leukoencephalomyelitis, the expressions of pro- and anti-inflammatory cytokines such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and transforming growth factor (TGF)-beta and the housekeeping genes beta-actin and GAPDH were studied using semi-quantitative RT-PCR. Relative cytokine values were related to the degree of CDV infection, MHC class II expression and infiltration of CD4-, CD8- and CD3epsilon-positive lymphocytes. Actin up-regulation, in contrast to GAPDH, was influenced by CDV infection and therefore could not be used as an internal standard to study cytokine expression. In early CDV infection of the cerebellum, either no detectable lesions or mild infiltration of CD8 positive cells or demyelination and up-regulation of MHC class II antigen were observed. IL-6, -8, -12 and TNF-alpha transcripts were found in 94%, 94%, 78% and 56% of distemper dogs, respectively, compared to 17%, 33%, 0% and 0% in controls, whereas IL-1beta, -2 and IFN-gamma were not detectable in any of the studied cerebella. Conversely, IL-10 and TGF-beta transcripts were present in 83% and 100% of the investigated cerebella of distemper dogs and controls. Relative RT-PCR results, expressed as %GAPDH, revealed a significant up-regulation of IL-6, -8, -12 and TNF-alpha mRNA in distemper dogs; whereas IL-10 and TGF-beta showed only a weak and not significantly increased expression following infection. Relative pro-inflammatory cytokine expression values were highest following CDV infection, indicating that the virus itself directly triggered the up-regulation of the pro-inflammatory cytokines. Succeeding changes, such as lymphocyte infiltration, MHC class II up-regulation and demyelination resulted only in a minor additional increase in cytokine expression, implying a secondary or by-stander mechanism of cytokine activation by these changes. Disease initiation and progression in early distemper leukoencephalomyelitis seemed to be due to a lacking or inappropriate response of the anti-inflammatory cytokines in the presence of a vigorous up-regulation of pro-inflammatory cytokines.


Early consumption of ultra-processed foods among children under 2 years old in Brazil.
To evaluate the complementary food consumption according to the extent and purpose of food processing based on NOVA classification among children aged 6-24 months of Federal District, Brazil. We performed a cross-sectional study using a 24-h recall to estimate the daily energy intake and nutrients according to NOVA classification. We conducted a linear regression to assess the association between the processed and ultra-processed foods (UPF) energy intake and the daily energy intake from saturated fat, daily energy intake from total sugars and daily intake of sodium. Federal District, Brazil. Five hundred and thirty-eight children aged between 6 and 24 months attended at Primary Health Care Units from March 2017 to March 2018. On average, children aged from 6 to 12 and from 12 to 24 months consumed 2393 and 4054 kJ/d, respectively, and processed and UPF represented one-third of dietary energy intake. Group 2 (processed and UPF) was higher carbohydrate contributors, and lower protein, fibre and most micronutrient contributors, when compared with Group 1 (unprocessed, minimally processed foods and processed culinary ingredients). In addition, the higher the energy intake from processed and UPF, the higher was the daily energy intake from saturated fat, daily energy intake from total sugar and daily intake of sodium. Children are being exposed early to processed and UPF and their share affect the diet's nutritional quality.


Iron, intracellular calcium ion, lipid peroxidation and carcino-genesis.
The evaluation of the accumulated experimental results on the action of complexed iron on cells indicates that the provoked cell injury is rather the consequence of an inhibition of the cytosolic Ca2+ concentration regulatory system than an effect of iron-induced lipid peroxidation. The role of the consequent intracellular ionic environment change in the preneoplastic and neoplastic transformation of the cell is discussed.


The effect of different doses of nonylphenol on the blood-testicular barrier integrity, hormone level, and DNA damage in the testes of rats.
Determining the molecular characteristics of the damage caused by NP exposure in the testis is very important for understanding the source of the damage and developing treatment methods accordingly. Therefore, in this study, it is aimed to evaluate the toxic effects that different doses of NP may cause in the testis, including blood-testicular barrier integrity and sperm DNA damage. For this purpose, 50 adult male Wistar albino rats were used in the study. Low, medium, and high-dose NP groups and the corn oil group were formed. After NP administration at determined doses for 15 days, the testis tissue taken under anesthesia was fixed in formaldehyde. Paraffin blocks were embedded using the routine histological tissue follow-up method. Histopathological and immunohistochemical analyses were performed by taking 5 μm thick sections from paraffin blocks. The other testicular tissue was taken for the Western blot, Elisa, and comet methods, and the findings of sperm DNA analysis and the blood-testicular barrier were examined. NP caused the seminiferous epithelium to be disorganized and have significantly fewer cells in the testes of rats in different dose NP-induced groups. Compared with the control group, mTOR, Cx43, SCF, and HSP70 protein levels were decreased, while the expression of MMP-9 levels was increased in the different NP dose groups. Furthermore, tissue testosterone and inhibin B levels and SF-1 immunoreactivity intensity gradually decreased depending on the dose increase of NP. DNA damage of testicular tissues were increased in NP groups depending on NP dose. These results suggest that it is evident that NP, a commonly used industrial chemical, is an endocrine disrupting chemical (EDC) with estrogenic activity exerting adverse effects on health and that urgent measures are needed regarding the use.


Effects of contact time on the sequestration and bioavailability of different classes of hydrophobic organic chemicals to benthic oligochaetes (Tubificidae).
Differences in bioavailability of hydrophobic organic compounds (HOC) to benthic deposit feeders have been related to differences in sediment-HOC contact time and sequestration (formation of slowly desorbing fractions) status. As a consequence, it was postulated that contact time and/or sequestration should be incorporated into risk assessment. In the present study, we investigated the effect of contact time on the bioavailability and sequestration of different classes of HOC. For this purpose, we simultaneously measured the steady-state accumulation into benthic oligochaetes (Tubificidae) and the distribution over rapidly and slowly desorbing fractions in laboratory-contaminated sediment at different contact times. The decrease in rapidly desorbing fractions (Frap) of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and 2,2-bis (4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) after a contact time of 959 d did not exceed a factor of 1.2. Similarly, the reduction in bioavailability was a factor of 2.3 at maximum, indicating that long contact times do not necessarily result in pronounced bioavailability reduction. For chlorobenzenes, the bioavailability was reduced with a factor of 5 to 18. This decrease corresponded with a pronounced reduction in Frap, which was attributed to losses of rapidly desorbing compounds. Over 75% of the variation in biota-to-sediment accumulation factors (BSAFs) of the PAHs and chlorobenzenes at the three contact times could be explained by differences in Frap. The present study provides evidence of a relationship between sequestration status and bioavailability of HOC to benthic deposit feeders.


[Surgery during pregnancy].
The decision for surgical intervention during pregnancy should be interdisciplinary and include all aspects of prenatal care. The risk of surgery to mother and fetus must be calculated and weighed against the disadvantages of other, nonradical methods. If there is no danger to the mother, the highest priority in all therapeutic considerations is the fetus and its development. The greatest threat to the fetus exists during the first trimester. In case surgery cannot be postponed till after birth, they should be done if possible during the 4th to 6th months of pregnancy, not the first trimester. In case of danger to the mother, necessary surgery must be performed any time during the pregnancy. Once extrauterine fetal survival is possible (the 24th or 25th week of pregnancy), danger to the mother and the child's mortality and morbidity of the various options must be carefully weighed for both premature delivery and continued pregnancy. Due to the problems of prematurity, any surgery during pregnancy should be carried out only in perinatal clinics outfitted with neonatologic intensive care units.


Efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis.
To systematically evaluate the curative efficacy and safety of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA), comparing with platelet-rich plasma alone. Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI) and Embase were searched for randomized controlled trials (RCTs) and cohort studies regarding the efficacy and safety of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA) comparing with platelet-rich plasma alone before January 15, 2022. The methodological quality of the ultimately included studies was assessed comprehensively, and meta-analysis was implemented using RevMan 5.3 software. Thirteen articles (9 RCTs, 4 cohort studies), including 1118 patients, were covered. There was no significant difference between the PRP + HA therapy and PRP-alone therapy in VAS scores at 3 months, 6 months and 12 months, WOMAC total scores at 3 months and KOOS at 1 month and 6 months. Compared with PRP-alone therapy, PRP + HA therapy was associated with significantly better improvement in VAS scores at 1 month, WOMAC total scores at 6 months, KOOS at 3 months, IKDC scores at 6 months and Lequesne index scores at 3 and 6 months. However, the smallest treatment effect of VAS scores, WOMAC total scores, KOOS and IKDC scores did not exceed the minimum clinically important difference (MCID). However, PRP + HA therapy got a greater reduction in the rate of adverse events, compared with PRP-alone therapy. The results of this meta-analysis indicated that PRP + HA therapy was not found to be superior to PRP-alone therapy in pain relief and function improvement for patients with KOA. However, combined PRP with HA injections was generally safer than PRP injections alone, by assessing the incidence of adverse events.


Potential medicinal plants involved in inhibiting 3CLpro activity: A practical alternate approach to combating COVID-19.
At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for the development of anti-SARS drugs. Online search engines, such as Web of Science, Google Scholar, Scopus and PubMed, were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CLpro. Various pure compounds, including polyphenols, terpenoids, chalcones, alkaloids, biflavonoids, flavanones, anthraquinones and glycosides, have shown potent inhibition of SARS-CoV-2 3CLpro activity with 50% inhibitory concentration (IC50) values ranging from 2-44 µg/mL. Interestingly, most of these active compounds, including xanthoangelol E (isolated from Angelica keiskei), dieckol 1 (isolated from Ecklonia cava), amentoflavone (isolated from Torreya nucifera), celastrol, pristimerin, tingenone and iguesterin (isolated from Tripterygium regelii), tannic acid (isolated from Camellia sinensis), and theaflavin-3,3'-digallate, 3-isotheaflav1in-3 gallate and dihydrotanshinone I (isolated from Salvia miltiorrhiza), had IC50 values of less than 15 µg/mL. Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive, with Ki values ranging from 2.4-43.8 μmol/L. Given the significance of plant-based compounds and the many promising results obtained, there is still need to explore the phytochemical and mechanistic potentials of plants and their products. These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.


Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies.
Intraoperative evaluation of specimens during radical prostatectomy using frozen sections can be time and labor intensive. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can rapidly generate images that closely resemble H&E histology in freshly excised tissue, without requiring freezing or microtome sectioning. Specimens are stained with nuclear and cytoplasmic/stromal fluorophores, and NLM evaluation can begin within 3 min of grossing. Fluorescence signals can be displayed using an H&E color scale, facilitating pathologist interpretation. This study evaluates the accuracy of prostate cancer detection in a blinded reading of NLM images compared with the gold standard of formalin-fixed, paraffin-embedded H&E histology. A total of 122 freshly excised prostate specimens were obtained from 40 patients undergoing radical prostatectomy. The prostates were grossed, dissected into specimens of ~10 × 10 mm with 1-4 mm thickness, stained for 2 min for nuclear and cytoplasmic/stromal contrast, and then rinsed with saline for 30 s. NLM images were acquired and multiple images were stitched together to generate large field of view, centimeter-scale digital images suitable for reading. Specimens were then processed for standard paraffin H&E. The study protocol consisted of training, pretesting, and blinded reading phases. After a washout period, pathologists read corresponding paraffin H&E slides. Three pathologists achieved a 95% or greater sensitivity with 100% specificity for detecting cancer on NLM compared with paraffin H&E. Pooled sensitivity and specificity was 97.3% (93.7-99.1%; 95% confidence interval) and 100.0% (97.0-100.0%), respectively. Interobserver agreement for NLM reading had a Fleiss κ = 0.95. The high cancer detection accuracy and rapid specimen preparation suggest that NLM may be useful for intraoperative evaluation in radical prostatectomy.


Properties of Pseudomonas AM1 primary-amine dehydrogenase immobilized on agarose.
1. The primary-amine dehydrogenase of Pseudomonas AM1 (primary amine:(acceptor) oxidoreductase (deaminating), EC 1.4.99.-) was purified by an improved method and covalently attached to cyanogen bromide-activated Sepharose 4B. The immobilized enzyme showed very little change in its sensitivity to heat and to inhibition by semicarbazide as compared with the soluble enzyme, but had enhanced stability at 0 degrees C. The pH optimum of the immobilized enzyme remained unchanged at pH 7.4. 2. A new type of spectrophotometric assay is described in which sedimentation of the immobilized enzyme in the cuvette is prevented by increasing the viscosity by the presence of 10% (w/w) polyethylene glycol (M1 20 000). Detailed kinetic analysis using this assay showed only insignificant differences in the Km values for n-butylamine and phenazine methosulphate between the soluble and Agarose-bound enzymes. The results are compared with those for other oxidoreductase enzymes immobilized on Sepharose.


Proton radiotherapy in management of pediatric base of skull tumors.
Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma (n = 10), chondrosarcoma (n = 3), rhabdomyosarcoma (n = 4), and other sarcomas (n = 3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors (n = 6), angiofibromas (n = 2), and chondroblastoma (n = 1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival of the males was significantly superior to that of the female patients (p = 0.002). Of the patients with benign tumors, 1 patient (giant cell tumor) had local failure at 10 months. The other 8 patients continued to have local tumor control; all 9 patients were alive at last follow-up (actuarial 5-year local control and overall survival rate of 89% and 100%, respectively). Severe late effects (motor weakness and sensory deficits) were observed in 2 (7%) of 29 patients. Proton RT for children with aggressively recurring tumors after major skull base surgery can offer a considerable prospect of tumor control and survival. Longer follow-up is necessary to assess the real value of protons, in particular with regard to bone growth and cosmetic outcome.


Hyperplastic gastric polyp with foci of ossification.
Stromal ossification has been reported in relation with gastrointestinal (GI) cancers. Heterotopic ossification of benign gastric polyps with bone formation is rarely documented and sometimes associated with calcification. Thus, the presence of foci of metaplastic bone (FMB) does not always imply GI cancer.


Characteristics of successful natural enemies in models of biological control of insect pests.
Biological control of insect pests is characterised by a persistent, strong reduction in the pest population following the introduction of a natural enemy. Analysis of mathematical models suggests that differential exploitation of patches of the pest in a spatially heterogeneous environment provides the most likely mechanism to account for known successes.


Right ventricular systolic and diastolic function assessed by two-dimensional speckle tracking echocardiography in dogs with myxomatous mitral valve disease.
Pulmonary hypertension (PH) is a common comorbidity in dogs with myxomatous mitral valve disease (MMVD), and can induce various changes in the right heart, such as right ventricular (RV) hypertrophy, dilatation, and dysfunction. We hypothesized that RV function, not only systolic function but also diastolic function, could be worsened with PH progression. We aimed to compare RV systolic and diastolic function in dogs with MMVD. Twenty healthy dogs and sixty-eight dogs with MMVD were enrolled. Dogs with MMVD were classified into the probability of PH. Two-dimensional and Doppler echocardiographic indices for right heart and two-dimensional speckle tracking echocardiography indices were measured. The morphological indicators of the right heart were significantly higher only in the high probability of PH group. The RV strain, early-diastolic and systolic strain rates were significantly lower in the high probability of PH group than those in the low and intermediate probability of PH groups. Multivariate analysis showed that increased RV internal dimension normalized by body weight and RV myocardial performance index were significantly associated with the presence of right-sided congestive heart failure. Speckle tracking echocardiography-derived RV systolic and diastolic function were activated in the low and intermediate probability of PH groups. However, dogs with high probability of PH showed RV myocardial dysfunction and dilatation. Increased RV myocardial performance index and end-diastolic RV internal dimension normalized by body weight were significantly associated with the presence of right-sided congestive heart failure in dogs with MMVD.


Immunomodulatory zinc-based materials for tissue regeneration.
Zinc(Zn)-based materials have contributed greatly to the rapid advancements in tissue engineering. The qualities they possess that make them so beneficial include their excellent biodegradability, biocompatibility, anti-bacterial activity, among and several others. Biomedical materials that act as a foreign body, will inevitably cause host immune response when introduced to the human body. As the osteoimmunology develops, the immunomodulatory characteristics of biomaterials have become an appealing concept to improve implant-tissue interaction and tissue restoration. Recently, Zn-based materials have also displayed immunomodulatory functions, especially macrophage polarization states. It can promote the transformation of M1 macrophages into M2 macrophages to enhance the tissue regeneration and reconstruction. This review covers mainly Zn-based materials and their characteristics, including metallic Zn alloys and Zn ceramics. We highlight the current advancements in the type of immune responses, as well as the mechanisms, that are induced by Zn-based biomaterials, most importantly the regulation of innate immunity and the mechanism of promoting tissue regeneration. To this end, we discuss their applications in biomedicine, and conclude with an outlook on future research challenges.


Osteoarticular Infections: Younger Children With Septic Arthritis and Low Inflammatory Patterns Have a Better Prognosis in a European Cohort.
Osteoarticular infections (OAI) are associated with complications and sequelae in children, whose prediction are of great importance in improving outcomes. We aimed to design risk prediction models to identify early complications and sequelae in children with OAI. This observational study included children (>3 months-17 years old) with acute OAI admitted to a tertiary-care pediatric hospital between 2008 and 2018. Clinical treatment, complications and sequelae were recorded. We developed a multivariable logistic predictive model for an acute complicated course (ACC) and another for sequelae. A total of 240 children were identified, 17.5% with ACC and 6.0% and 3.6% with sequelae at 6 and 12 months of follow-up, respectively. In the multivariable logistic predictive model for ACC, predictors were fever at admission [adjusted odds ratio (aOR): 2.98; 95% confidence interval (CI): 1.10-8.12], C-reactive protein ≥100 mg/L (aOR: 2.37; 95% CI: 1.05-5.35), osteomyelitis (aOR: 4.39; 95% CI: 2.04-9.46) and Staphylococcus aureus infection (aOR: 3.50; 95% CI: 1.39-8.77), with an area under the ROC curve of 0.831 (95% CI: 0.767-0.895). For sequelae at 6 months, predictors were age ≥4 years (aOR: 4.08; 95% CI: 1.00-16.53), C-reactive protein ≥110 mg/L (aOR: 4.59; 95% CI: 1.25-16.90), disseminated disease (aOR: 9.21; 95% CI: 1.82-46.73) and bone abscess (OR: 5.46; 95% CI: 1.23-24.21), with an area under the ROC curve of 0.887 (95% CI: 0.815-0.959). In our model we could identify patients at low risk for complications and sequelae, probably requiring a less aggressive approach.


Pre-procedural estimate of individualized bleeding risk impacts physicians' utilization of bivalirudin during percutaneous coronary intervention.
This study sought to assess whether incorporation of routine bleeding risk estimates affected the utilization of bivalirudin during percutaneous coronary intervention (PCI). Bivalirudin use during PCI has been shown to reduce bleeding complications. However, a risk-treatment paradox exists, in which patients at highest risk for bleeding are least likely to receive bivalirudin. Whether routine estimation of individualized bleeding risk can affect physicians' use of bivalirudin is unknown. PCI data from a single health system between 2007 and 2011 were analyzed. Beginning in July 2009, individualized bleeding risk estimates were provided immediately preceding PCI. Using a pre-post design, we compared bivalirudin use before and after this implementation, for patients across 3 strata of bleeding risk (<1%, 1% to 3%, and >3%). Data from 6,491 PCI procedures were analyzed. Overall, bivalirudin use increased in the post-implementation period (26.9% vs. 34.2%, p < 0.001). Bivalirudin use increased in intermediate (27% to 35%, p < 0.001) and high bleeding risk patients (25% to 43%, p < 0.001), and decreased in low-risk patients (30% to 25%, p = 0.014). During the same period, bleeding complications decreased in intermediate-risk (3.4% to 1.8%, p = 0.009) and high-risk (6.9% to 3.7%, p = 0.005) patients and remained unchanged in low-risk patients (1.1% to 1.0%, p = 0.976). There was an increase in bivalirudin use and a lower incidence of bleeding after the incorporation of individualized bleeding risk estimates into clinical practice. This implementation led to a reversal of the risk-treatment paradox, through a rational increase in bivalirudin use in patients at intermediate and high bleeding risk and decreased use in lower-risk patients.


Why have mutagenesis studies not located the general base in ras p21.
Ras p21 plays a major role in the control of cell growth, and oncogenic mutations of this protein have been found in human cancers. Unfortunately, the detailed mode of action of Ras p21 is still unclear, in spite of the great interest in this protein and the availability of its X-ray crystal structure. In particular, mutagenesis studies of different active site residues could not identify the general base for GTP hydrolysis. Here we tackle this question using a computer simulation approach with clear and reliable energy considerations and conclude that the most likely general base is the bound GTP itself. Obviously, the identification of such a general base cannot be easily accomplished by mutagenesis experiments.


PET-CT imaging and reality.
The spectrum of human diseases caused by members of the Aspergillus genus is extensive. It ranges from allergic reactions to colonization of preexisting pulmonary cavities to invasion and destruction of lung parenchyma with pyemic spread to brain, skin, and other organs, causing rapid death. The immune status of the host is a crucial factor in determining the phenotype and severity of the disease. In this case report Chronic Necrotizing Pulmonary Aspergillosis (CNPA), a rare, locally- or semi-invasive variant of pulmonary Aspergillosis, mimicking lung metastasis is presented. The 60-year-old male patient had earlier received multiple cycles of systemic chemotherapy due to colorectal carcinoma. Our case report focuses on the benefits and the possible disadvantages of PET-CT imaging in CNPA.


Evaluation of saliva flow rates, Candida colonization and susceptibility of Candida strains after head and neck radiation.
Hyposalivation is a long-term effect in patients receiving head and neck radiation. Radiotherapy can predispose oral colonization by Candida species of the mucosa. This study aims to evaluate the correlation between hyposalivation, measured by unstimulated saliva flow rates (SFR) and fungal colonization of the oral cavity, and also the resistance of isolated Candida strains to antimicrobial therapy. Fifty-three consecutive patients with radiotherapy were examined for late radiation damage on dental hard tissue and the salivary glands (SFR over a period of 5 min). The SFR were divided into three different values of hyposalivation: grade I (SFR 0.1-0.25 ml/min), grade II (SFR ≤0.1 ml/min), and grade III (SFR = 0.0 ml/min). Candidal colonization was defined using Sabouraud agar and identified using API 20C AUX (biomerieux) in the patients' rinsing water. Susceptibility was tested with Etest (amphotericin B, ketoconacole, voriconacole, and fluconacole). Hyposalivation grade I was detected in 23% (9.1 × 10(1) colony forming units (cfu); range, 200-5,900 cfu), hyposalivation grade II in 26% (4.3 × 10(1) cfu; range, 110-3,300 cfu), and hyposalivation grade III in 51% (2.0 × 10(3) cfu; range, 300-19,475 cfu) of patients. A significant correlation between the SFR and candidal colonization and clinical presentation (European Organization for Research and Treatment of Cancer (EORTC) score) was detected (Mann-Whitney test, p = 0.031). Twenty Candida albicans and 27 non-albicans species were identified. The resistance of C. albicans was higher than that of non-albicans strains against antimicrobial agents. By comparison, amphotericin B showed the greatest and fluconazole the least effect. A higher value of hyposalivation correlates with a higher risk of candidal colonization in patients who have received radiotherapy and also with a higher EORTC score. The spectrum of Candida is wide and susceptibility against antifungal therapy differs. In long-term examinations of patients with xerostomia after radiotherapy, the EORTC score can be used to measure hyposalivation. Reduced susceptibility of C. albicans might introduce complications to therapy. Findings of more non-albicans strains show a change in colonization which should be examined in further studies.


Conversions during laparoscopic cholecystectomy: risk factors and effects on patient outcome.
In view of the substantial, at times conflicting, literature on conversion to open surgery during laparoscopic cholecystectomy (LC), we have considered it timely to review the subject to identify the risk factors for conversion and its consequences. The review is based on a complete literature search covering the period 1990 to 2005. The search identified 109 publications on the subject: 68 retrospective series, 16 prospective nonrandomized studies, 8 prospective randomized clinical trials, 5 prospective case-controlled studies, 5 reviews and 7 others (3 observational, 2 population-based studies, 1 national survey, and 1 editorial). As the majority of reported studies are retrospective, firm conclusions cannot be reached. Single factors that appear to be important include male gender, extreme old age, morbid obesity, cirrhosis, previous upper abdominal surgery, severe/advanced acute and chronic disease, and emergency LC. The combination of patient- and disease-related risk factors increases the conversion risk. In the training of residents, the number of cases needed for reaching proficiency exceeds 200 cases. The value of predictive scoring systems is important in the selection of cases for resident training. Conversion exerts adverse effects on operating time, postoperative morbidity, and hospital costs, especially when it is enforced. There appears to be no absolute contraindication to LC that is agreed upon by all. There is consensus on certain individual risk factors and their additive effect on the likelihood of conversion. Predictive systems based on these factors appear to be useful in selection of cases for resident training.


Polypunctosides E-K: seven new steroidal saponins from Polygonatum punctatum Royle ex Kunth and their nitric oxide production inhibitory activities.
Polygonatum punctatum Royle ex Kunth is a high-value medicinal plant found in old natural forests. A phytochemical study on the roots of this plant led to the isolation of seven new steroidal saponins including four furostans (1-4) and three furospirostans (5-7). Their structures were elucidated as (25R)-26-O-(β-D-glucopyranosyl)-furost-5-ene-3β,17α,22α,26-tetraol 3-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (1), (25R)-26-O-(β-D-glucopyranosyl)-furost-5-ene-3β,14α,17α,22α,26-pentaol 3-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (2), (25R)-26-O-(β-D-glucopyranosyl)-furost-5-ene-22α-methoxy-3β,17α,26-triol 3-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (3), (25R)-26-O-(β-D-glucopyranosyl)-furost-5-ene-22α-methoxy-3β,17α,26-triol 3-O-[α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)]-[acetoxy-(→ 6)]-β-D-galactopyranoside (4), 26-O-(β-D-glucopyranosyl)-14α,17α-dihydroxynuatigenin 3-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (5), 26-O-(β-D-glucopyranosyl)-17α-hydroxynuatigenin 3-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (6), and 26-O-(β-D-glucopyranosyl)-14α-hydroxynuatigenin 3-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (7) by extensive spectroscopic analyses, including infrared, high-resolution electrospray ionization mass spectrometry, and one- and two-dimensional nuclear magnetic resonance spectroscopy. Compounds 1-7 inhibited nitric oxide production in lipopolysaccharide activated RAW264.7 cells with IC50 values ranging from 41.5 ± 3.2 to 62.2 ± 3.7 µM, compared to 33.8 ± 2.6 µM for the positive control compound L-NMMA.


Ischemic heart disease as copper deficiency.
Atherosclerosis is a complex process beginning early in life and often leading to death from ischemic heart disease in middle age. Hundreds of factors are said to contribute to this risk. More than 50 similarities between animals deficient in copper and people with ischemic heart disease have been identified. Some of the more important characteristics of this illness have been produced in experiments in which men and women were fed diets low in copper. Diets with similarly low amounts of copper are readily available to the population at large. More aspects of the anatomy, biochemistry, chemistry, epidemiology, pathogenesis and pathophysiology of ischemic heart disease can be explained by considering this illness to be a problem of copper deficiency than by considering any of several other explanations that have been offered.


Biosynthesis of reovirus-specified polypeptides. Molecular cDNA cloning and nucleotide sequence of the reovirus serotype 1 Lang strain s2 mRNA which encodes the virion core polypeptide sigma 2.
Human reovirus serotype 1 Lang strain s2 mRNA, which encodes the virion inner capsid core polypeptide sigma 2, was cloned as a cDNA:mRNA heteroduplex in Escherichia coli using phage M13. A complete consensus nucleotide sequence was determined. The Lang strain s2 mRNA is 1331 nucleotides in length and possesses an open reading frame with a coding capacity of 335 amino acids, sufficient to account for a sigma 2 polypeptide of 37,682 daltons. Comparison of the serotype 1 Lang s2 sequence derived from cDNA clones of s2 mRNA with the serotype 3 Dearing S2 sequence derived from cDNA clones of the S2 dsRNA genome segment reveals 86 percent homology at the nucleotide level. The predicted sigma 2 polypeptides of the Lang and Dearing strains display 98 percent homology at the amino acid level. Of 147 silent nt differences in the translated region, 136 were in the third base position of codons.


Progress in the genetics of uveitis.
Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.


Dependence of smooth muscle tone upon pulsatility in the iliac artery of the anaesthetised pig.
The aim of the study was to examine features of the myogenic response of a conduit artery to the presence and absence of pulsatile pressure. The iliac arteries of 16 anaesthetised pigs (10 in control conditions, 6 under sympathetic blockade) were instrumented with flowmeter, sonomicrometry crystals for diameter measurement, a micro-tip manometer for pressure measurement and snares placed proximally and distally to the crystals to isolate a test segment from the remainder of the arterial system. When the snares were tightened to occlude the test segment, systemic arterial pressure remained constant. There was a large shift in the pressure-diameter relationship, in that there was a rapid decline in test segment pressure for the same diameter. This indicated arterial wall smooth muscle relaxation in response to removal of pulsatility of arterial pressure. The difference in mean pressure between pulsatility present and absent was significant (p < 0.0001, paired t test, n = 10). Before proximal and distal occlusion, test segment pressure was (mean ± SD) 92.26 ± 12.39 mmHg, whereas after distal and proximal occlusion at the same diameter, it was 42.34 ± 10.87 mmHg. We conclude that in the presence of pulsatile pressure, there is a large proportion of arterial wall smooth muscle tone related to stretch of the arterial wall during the cardiac cycle, indicating that, under normal pulsatile pressure conditions, much of the normal tone can be attributed to the pulsatile component of the arterial myogenic response.


Predictive Factors for Two-Year Survival in Dogs with Hepatobiliary Diseases: Importance of Clinical and Laboratory Monitoring.
Long-term outcomes and survival predictors for different clinicopathologies (idiopathic chronic hepatitis, liver fibrosis, vacuolar hepatopathy) in dogs with hepatobiliary diseases are poorly described. In this study, ninety dogs were followed up for up to five years to investigate clinical factors that predict two-year survival in canine patients after liver biopsy. Univariate and multivariate analyses were performed based on clinical and laboratory data to determine the association between clinical and laboratory data and mortality rates. Overall, the one-, two-, and five-year mortality rates were 28.9%, 45.6%, and 78.9%, respectively. Univariate analysis indicated that male gender, ascites, elevated serum gamma-glutamyl transpeptidase (GGT), hypercholesterolemia, hypoalbuminemia, prolonged activated partial thromboplastin clotting time (aPTT), and prolonged thrombin clotting time (TT) were associated with an increased two-year mortality rate. Results from multivariate analysis demonstrated a significant association between male gender (p = 0.022), elevated serum GGT (p < 0.001), hypoalbuminemia (p < 0.001), and prolonged aPTT (p < 0.001) and an increased two-year mortality rate, regardless of the specific type of liver pathology. Elevated GGT was associated with the highest risk for increased two-year mortality (95% CI: hazard ratio 6.02-41.21). In conclusion, various clinical factors in dogs with liver diseases are useful for prognosis prediction.


Brain macrophages synthesize interleukin-1 and interleukin-1 mRNAs in vitro.
Amoeboid microglial cells (brain macrophages) were purified from early post-natal mouse brain cultures. The percentage of cells stained with an anti-Mac-1 antibody was greater than 95%. Stimulation of these brain macrophages by lipopolysaccharides induced the synthesis of interleukin-1 (IL-1), which, in part, remained associated with the cell surface and, in part, was released into the culture medium. In contrast, pure primary astrocyte cultures and cell lines of transformed or immortalised astrocytes did not synthesise significant amounts of IL-1, demonstrating that amoeboid microglia and not astrocytes synthesise IL-1 in vitro. These physiological data were confirmed by RNA hybridisation studies showing that, on LPS treatment, brain macrophages synthesise significant amounts of IL-1 alpha and IL-1 beta mRNAs.


Four butyrolactones and diverse bioactive secondary metabolites from terrestrial Aspergillus flavipes MM2: isolation and structure determination.
The chemical constituents and biological activities of the terrestrial Aspergillus flavipes MM2 isolated from Egyptian rice hulls are reported. Seven bioactive compounds were obtained, of which one sterol: ergosterol (1), four butyrolactones: butyrolactone I (2), aspulvinone H (3), butyrolactone-V (6) and 4,4'-diydroxypulvinone (7), along with 6-methylsalicylic acid (4) and the cyclopentenone analogue; terrien (5). Structures of the isolated compounds were deduced by intensive studies of their 1D & 2D NMR, MS data and comparison with related structures. The strain extract and the isolated compounds (1-7) were biologically studied against number of microbial strains, and brine shrimp for cytotoxicity. In this article, the taxonomical characterization of A. flavipes MM2 along with its upscale fermentation, isolation and structural assignment of the obtained bioactive metabolites, and evaluate their antimicrobial and cytotoxic activities were described.


Now or future? Analyzing the effects of message frame and format in motivating Chinese females to get HPV vaccines for their children.
This study aims to examine the impacts of gain vs. loss-framed messages and narrative messages on Chinese women's intentions to get HPV vaccines for their children. A survey experiment was conducted among Chinese females (N = 453) assessing their responses to 3 types of messages (i.e. gain-framed, loss-framed and narrative) designed to promote HPV vaccination. No main effect was found for message types, but loss-framed message slightly increased vaccination intention. Time orientation moderated the relationship between message framing and vaccination intention. Narrative message works better among present-minded individuals, whereas gain-framed message was more persuasive for future-minded individuals. Integration of message frames (gain vs. loss) and message type (narrative vs. non-narrative) is recommended for future research. Narrative persuasion could be an effective tool in promoting health behaviors especially among present-minded individuals, or when the consequences of health decisions are temporally distant.


Left-right coding of past and future in language: the mental timeline during sentence processing.
The metaphoric mapping theory suggests that abstract concepts, like time, are represented in terms of concrete dimensions such as space. This theory receives support from several lines of research ranging from psychophysics to linguistics and cultural studies; especially strong support comes from recent response time studies. These studies have reported congruency effects between the dimensions of time and space indicating that time evokes spatial representations that may facilitate or impede responses to words with a temporal connotation. The present paper reports the results of three linguistic experiments that examined this congruency effect when participants processed past- and future-related sentences. Response time was shorter when past-related sentences required a left-hand response and future-related sentences a right-hand response than when this mapping of time onto response hand was reversed (Experiment 1). This result suggests that participants can form time-space associations during the processing of sentences and thus this result is consistent with the view that time is mentally represented from left to right. The activation of these time-space associations, however, appears to be non-automatic as shown by the results of Experiments 2 and 3 when participants were asked to perform a non-temporal meaning discrimination task.


Report of a successful ongoing pregnancy as a result of IMSI with assisted oocyte activation.
We report a successful ongoing pregnancy obtained in a case of total globozoospermia after intracytoplasmic morphologically selected sperm injection (IMSI) with oocyte activation. The first semen analysis on investigation showed partial globozoospermia. However, under high magnification assessment at oocyte retrieval only round headed sperm were observed. Considering the high risk of a complete failure to fertilize from IMSI the couple gave written informed consent to the use of oocyte activation media post IMSI. One embryo fertilized, developed to a hatching blastocyst and was transferred resulting in an ongoing pregnancy. This successful outcome shows the use of IMSI is useful in the evaluation of total globozooozpermia and therefore aids in the justification of the use of oocyte activation media.


Cu and Co nanoparticles co-doped MIL-101 as a novel adsorbent for efficient removal of tetracycline from aqueous solutions.
Chromium metal-organic framework (MIL-101(Cr)) has been widely studied for removing organic contaminants from aqueous solutions due to its excellent water stability and giant pore size, but its low adsorption capacity limits the application. In this study, a new adsorbent MIL-101 loaded with CuCo bimetallic nanoparticles (CuCo/MIL-101) was successfully fabricated and applied in removal of tetracycline (TC) from aqueous solutions. The adsorption capacity of CuCo/MIL-101 for TC increased by 140% compared with that of pure MIL-101, which may be attributed to the chemical bonding between Cu and Co BNPs in MIL-101 and TC molecules. The effects of pH, ionic strength, humic acid and contact time on the adsorption were also discussed in detail. The results showed that the removal efficiency of TC solution with high concentration (100 mg L-1) by CuCo/MIL-101 was still as high as 82.9%. The data of adsorption kinetics and isotherms could be well fitted by Elovich model and Freundlich model, respectively. According to the fitting parameters, the maximum adsorption capacity of CuCo/MIL-101 reached up to 225.179 mg g-1. Additionally, the adsorption process of TC onto CuCo/MIL-101 was spontaneous and endothermic. Electrostatic interactions could play an important role in the adsorption process. The enhanced adsorption capacity, excellent reusability and water stability demonstrated the potential of CuCo/MIL-101 composite as a novel adsorbent for the removal of TC from aqueous solutions.


HER2, a human epidermal growth factor, being activated by amplification, is a negative prognostic factor in breast cancer. HER2 is the target of anti-HER2 antibodies (Trastuzumab, Pertuzumab…). For more than 10 years, breast cancers have been classified into HER2 positive and HER2 negative. However, the advent of new cytotoxic drugs combined with anti-HER2 antibodies, such as TDM1 or trastuzumab déruxtécan, have shown very promising therapeutic activity in patients with low HER2 expression breast cancer. These new therapeutic perspectives encourage a better identification of low HER2 tumours in order to identify patients who could benefit from them. Thus, the classification of breast tumours evolves to individualize HER2-negative tumours (score 0), HER2-positive tumours (score 3+ and 2+ amplified) and HER2-low tumours (scores 1+ and 2+ not-amplified). HER2-low tumours are common and represent more than half of all breast cancers. To identify these HER2-low tumours, pathology laboratories should not change their usual technique calibrated according to ASCO/CAP and GEFPICS recommendations. Until more clinical data about response to these new treatment strategies are available, GEFPICS does not require pathologists to identify this HER2-low category. Nevertheless, this designation will allow clinicians to identify patients whose tumours fall into this category in the very short term and offer them new treatment options.


Rubella IgG total antibody avidity and IgG subclass-specific antibody avidity assay and their role in the differentiation between primary rubella and rubella reinfection.
The total rubella IgG antibody avidity ELISA, as described by Hedmann for differentiation between acute primary rubella and reinfection, persisting or non-specific IgM antibodies were evaluated in 212 sera of four categories of patients with known history (n = 149) and in one group (n = 39) of patients with a history of unclear nature. The development of the IgG ratio (avidity) from low (less than 30%) to higher levels (greater than 30%) was determined in 146 sera from 96 cases with acute primary rubella between days 1 to 256 after onset of exanthem, with a borderline between low (less than 30%) and high (greater than 30%) avidity after four weeks after onset of exanthem. From seven days to 14 years following vaccination, the IgG ratio increased more slowly following vaccination, with a useful borderline at 2 1/2 months. In 80 sera from 13 women with reinfection during pregnancy, six infants with rubella embryopathy, and 19 pregnant women with rubella IgM antibodies detected during antenatal screening, the total IgG ratio ranged between 48% and 100%, indicating a previous infection. The diagnostic value of the IgG subclass-specific antibody avidity assay was investigated in 40 of the 251 sera. The results confirmed those of the total IgG avidity assay. Both tests are of additional help for differentiating serologically primary rubella from reinfection or recent from previous vaccination.


Interrelationship between the kallikrein-kinin system and hypertension: a review.
The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.


[Regional anesthesia today--possibilities and limits: introduction (author's transl)].
The various procedures of regional anesthesia were widely used before the introduction of intratracheal anesthesia; thereafter, it was replaced by the today commonly used general anesthesia. Regional anesthesia nonetheless plays an important role, primarily in outpatient treatment, because a large number of surgical departments still have no anesthesiologist on the staff. Often the surgeon is responsible for both the operation and the anesthesia. Indications, risks, and complications including legal problems related to regional anesthesia are discussed.


[Ventricular assist device as alternative to heart transplant in a hospitalized patient in an intensive care unit: clinical case].
To present and analyze a clinical case that addresses the care plan for a patient with permanent ventricular assist in an intensive care unit (ICU). CLINICAL CASE PRESENTATION: A 65-year-old man admitted to an ICU in a tertiary teaching hospital in September 2011 after receiving an implant of a permanent ventricular assist device (Heartmate II). The case analysis has been structured into 3 categories identified in the review of the literature: prevention of risks and complications, management of the device and health education. This study shows the importance of establishing a protocolized care plan for the patients who are carriers of permanent ventricular assist in the ICU. This would avoid postoperative complications, reduce costs and hospitalization time.