Description of a novel IncP plasmid harboring blaKPC-2 recovered from a SPM-1-producing Pseudomonas aeruginosa from ST277.
The high rates of carbapenem resistance among Brazilian Pseudomonas aeruginosa isolates are mainly associated with the clone ST277 producing the carbapenemase SPM-1. Here, the complete genetic composition of a IncP plasmid harboring blaKPC-2 in isolates of this endemic clone carrying chromosomal blaSPM-1 was described using whole genome sequencing. These results confirm the association of these two carbapenemases in ST277 and also describe the genetic composition of a novel blaKPC-2-plasmid. Considering the fact that this association occurs in a high-risk clone, monitoring the dissemination of this plasmid should be a public health concern.


Delayed elimination of digoxin antidotum determined by radioimmunoassay.
An observation of a treatment with digitalis antibodies (Fab-fragments) in a young child is presented. The elimination of this antidotum proved to be much slower than normally expected. In the patient's history, the disappearance of the Fab-fragments out of the blood lasted 142 days with a half-life of 15.6 days, whereas an elimination with a T1/2 of 28 hours is accepted. Probably there has been intracellular penetration of the antibodies into the liver, caused by concomitant diseases (Hepatitis A and B infections). An "in vitro" experiment is reported. It demonstrates the equimolar binding of the Fab-fragments for digoxin and shows that the elimination of the Fab-fragments can be established by a routine radioimmunoassay of digoxin, in an indirect way.


What can we learn from past and recent Bavarian knowledge for the future development of European veterinary herbal medicine? An ethnoveterinary study.
While the interest in finding medical solutions for the worldwide antibiotics crisis is rising, the legal possibility of simplified authorization of herbal veterinary medicinal products is dwindling. An important basis for both the preservation and development of knowledge in veterinary herbal medicine are pharmacological and clinical studies on the performance of herbal remedies, based on historical written sources on the treatment of farm animals with medicinal plants, as well as current ethnoveterinary research. Nevertheless, there is only limited systematic ethnoveterinary research in Europe, with the exceptions of the Mediterranean region, Switzerland and Austria. We conducted a survey on the ethnoveterinary knowledge of farmers in Bavaria, and analyzed two regional historical textbooks. We documented the local veterinary knowledge about livestock in Bavaria based upon local historical textbooks and upon ethnoveterinary interviews to discover opportunities for the future development of European veterinary herbal medicine. In 2018/2019 we conducted 77 semi-structured interviews with 101 farmers from different types of farms. Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process, source of knowledge) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers' satisfaction) were collected. To compare our data with the literature, the use reports of two local historical textbooks were analyzed and compared with the data from the interviews. 716 homemade remedy reports (HRs) for altogether 884 use reports (URs) were documented in this study. We picked the 363 HRs that consisted of a single plant species with or without other natural products (HSHRs) for a deeper analysis. These HSHRs were prepared from 108 plant species that belonged to 57 botanical families. The most URs were documented for the families of: Asteraceae, Linaceae and Urticaceae. Calendula officinalis L. (Asteraceae), Linum usitatissimum L. (Linaceae) and Urtica dioica L. (Urticaceae) were the most often documented single species. A total of 448 URs were gathered for the 363 HSHRs. The largest number of URs was for treatments of gastrointestinal disorders and metabolic dysfunctions, followed by skin alterations and sores. For nearly half of the URs the source of knowledge was family and friends. For 80 URs the source of knowledge was different from that of the corresponding HSHRs. For 68% of the URs farmers mentioned at least one use during the last 5 years. Half of the plant species that were mentioned in the historical literature were also mentioned in URs by the interviewees. In Bavaria, medicinal plants are actively used by farmers to treat their livestock with a high level of satisfaction. The knowledge is not passed on from generation to generation in a purely static way, but is dynamically developed by the users in almost one fifth of the URs. Ethnoveterinary research combined with data from regional historical textbooks may facilitate pharmacological and clinical studies in veterinary medicine, and the discussion about a simplified registration for traditional herbal veterinary medicinal products.


Study design I.
This is the first of a series of articles that will describe the different types of study design; considerations when choosing a study design; and the advantages and disadvantages of each type of study. This first article explains the importance of choosing an appropriate design and the decisions to be made when doing so.


Assessment and comparison of fecal continence in children following primary posterior sagittal anorectoplasty and abdominoperineal pull through for anorectal anomaly using clinical scoring and MRI.
We aimed to compare and contrast these main surgical procedures for ARM in terms of structural outcome through pelvic MRI & functional outcome through Kelly's scoring. A prospective study was conducted from August 2011 to July 2013 including all the cases of ARM managed in single stage (operated by one surgeon, first author) since 1995 that came for follow up at age of 3 years or more. Patients were divided in three groups: Group 8.A, PSARP (60 patients); Group B, Abdomino-PSARP (40 patients); and Group C, APPT (40 patients). The functional assessment of anal continence was carried out at the age of 3years or more using Kelly's method. Structural assessment was done by 1.5-T Magnetic Resonance Imaging (MRI). In 24 patients with rectobulbar fistula, 71.5% of Group A patients had good continence. In 50 patients with rectoprostatic fistula, 73.7% of Group A, 70% of group B and only 36% of Group C had good outcomes. Better development of each muscle was associated with better outcomes in terms of anal continence (P=0.001). There is better outcome with PSARP and Abdomino-PSARP in patients with rectobulbar and rectoprostatic fistula. MRI is a valuable modality for postoperative structural analysis of patients with ARM and is also useful for predicting the long term functional outcome of these cases.


Synthesis and characterization of konjac glucomannan-graft-polyacrylamide via gamma-irradiation.
The synthesis of konjac glucomannan-graft-polyacrylamide (KGM-g-PAM) was carried out at 25 degrees C by gamma-irradiation under a N2 atmosphere. The effects of absorbed radiation dosage and monomer concentration on grafting yield and water absorbency were studied. The grafted copolymers were characterized using Fourier Transform Infrared(FTIR) spectroscopy, nuclear magnetic resonance (NMR), x-ray diffraction (XRD),thermogravimetric analysis (TGA) and gel permeation chromatography (GPC). The grafting yield was observed to increase with increasing absorbed dosage and monomer concentration. Compared with the original KGM, the grafted copolymers exhibited better thermal stability and water absorbency. The results suggest that gamma-irradiation is convenient and efficient for inducing graft copolymerization of KGM and acrylamide (AM).


Stroke rate is markedly reduced after carotid endarterectomy by avoidance of protamine.
Postoperative neurologic injury remains a significant risk of carotid endarterectomy. Mechanisms include embolization of debris and formation of thrombus on the newly endarterectomized surface. We hypothesized that the risk of postoperative neurologic injury would be lower in those patients who did not receive protamine for reversal of heparin anticoagulation. We reviewed 348 consecutive primary carotid endarterectomies performed since January 1, 1986, to determine the relationship between surgical outcomes and reversal of heparin anticoagulation. Patients undergoing additional simultaneous cardiovascular procedures were excluded. One hundred ninety-three patients received protamine after completion of the endarterectomy. The remaining 155 patients did not receive any protamine. All patients in both groups survived to discharge. There were no strokes in those patients who did not receive any protamine; however, the stroke rate in the protamine group was 2.6% (5 of 193), p < 0.045. The incidence of hematoma requiring reexploration was 1.0% (2 of 193) and 1.9% (3 of 155) in the protamine and no-protamine groups, respectively (p = NS). Intraoperative shunting was used more frequently in the no-protamine group (84% vs 67%, p < 0.001), and patch angioplasty was performed more frequently in the protamine group (35% vs 15%, p < 0.001). However, neither shunting nor patching significantly influenced stroke rates. We conclude that carotid endarterectomy without reversal of heparin anticoagulation is associated with a reduced postoperative stroke rate without a significant increase in morbidity rates.


Physical and chemical characteristics of apolipoprotein A-I-lipid complexes produced by Chinese hamster ovary cells transfected with the human apolipoprotein A-I gene.
Chinese hamster ovary cells transfected with the human apolipoprotein A-I gene linked to the human metallothionein gene promoter region secrete large quantities of apolipoprotein A-I (7.1 +/- 0.4% total secreted protein) in the presence of zinc. Approx. 16% of the secreted apolipoprotein A-I is complexed with lipid and can be isolated ultracentrifugally at d less than or equal to 1.21 g/ml. The latter complexes are composed of discs and vesicles as judged by electron microscopy and can be further separated by column chromatography into three fractions: fraction I, mostly vesicles (60-260 nm) and large discs (18-20 nm diameter); fraction II, discs 14.2 +/- 2.6 nm diameter; and fraction III, nonresolvable by electron microscopy. The latter fraction is extremely lipid-poor (94% protein, 6% phospholipid); in contrast, the protein, phospholipid and unesterified cholesterol content for the other fractions are 43, 33 and 24%, respectively, for fraction I and 53, 33 and 14%, respectively, for fraction II. Fraction II particles contain three and four apolipoprotein A-Is per particle as determined by protein crosslinking while large structures in fraction I contain primarily six to seven apolipoprotein A-Is per particle. Following incubation with purified lecithin: cholesterol acyltransferase, discoidal particles were transformed into apparent spherical particles 12.9 +/- 3.4 nm diameter; this transformation coincided with 19-21% conversion of unesterified cholesterol to esterified cholesterol. The apolipoprotein A-I-lipid complexes isolated from Chinese hamster ovary cell media are similar to nascent HDL found in plasma of lecithin:cholesterol acyltransferase-deficient patients and those secreted by the human hepatoma line, Hep G2. The ability of the Chinese hamster ovary cell nascent HDL-like particles to undergo transformation in the presence of purified lecithin:cholesterol acyltransferase indicates that they are functional particles.


The diagnosis of neoplasia in patients with asymptomatic microscopic hematuria: a decision analysis.
Clinical decision analysis and a computer model were used to evaluate the performance of alternative strategies for the diagnosis of neoplasia in adults with asymptomatic microscopic hematuria. Strategies consisted of sequences of diagnostic tests, including ultrasound, excretory urography, angiography, computerized tomography and cystoscopy. The strategies have a sensitivity of 98 to 100 per cent for bladder cancer and 90 to 94 per cent for renal carcinoma, and a specificity of 99 per cent. The cost per carcinoma diagnosed is $75,000 to $86,000 at 1 per cent prevalence and $5,000 to $5,800 at 15 per cent prevalence. Strategies using cystoscopy or ultrasound as the initial diagnostic test minimized cost and morbidity while maintaining diagnostic accuracy. Excretory urography does not add significantly to diagnostic accuracy but it does add to cost and morbidity.


A new model for measuring breeding genetic distance. II. Polygenic traits.
The breeding genetic distance measure of a single locus (Carlson & Welch, 1977) is extended to polygenic traits. For two populations with means -x and approximately x, theta(-x, approximately x) is defined as the size of the largest subpopulation with mean approximately x which can be (artificially) selected from a population with mean -x. The distance is defined as 1--theta(-x, approximately x). It is shown that theta(-x, approximately x) can be calculated from truncation selection and formulas (two loci) and tables (three and four loci) are given. Values for theta(-x, approximately x) based on a normal approximation are seen to be adequate for most cases. The measure is applied to a data example (human skin colour) and to a discussion of the idea of 'genetic inertia'.


Effect of thermal and non-thermal techniques for microbial safety in food powder: Recent advances.
Food powders are appreciated worldwide, as it enables food to be preserved for an extended period without significant loss of quality, even under the ambient storage condition. However, it is evidenced that the development of resistant microbial spore and viable microbial cells is a matter of concern even in low moisture foods like food powders. For microbial inactivation, the strategy generally applied is the implication of conventional preservation methods, such as heat treatment which is greatly accompanied by degradation of nutritional organoleptic properties. To overcome the shortcomings of conventional thermal processing, a set of advanced or emerging technologies are being developed which can inactivate the microbial spores and viable microbial cells capable of surviving with maximum retention in the nutritional or organoleptic profile. The examples include infrared heating, microwave heating, radiofrequency heating, instant control pressure drop technology, high-pressure processing, pulsed electric field, pulsed light, ozone processing, and cold plasma. In this review, the potential of different advanced thermal and non-thermal technologies towards the inactivation of spores and viable cells of microorganisms in food powders has been highlighted precisely along with their mechanism of action. The summary of the literature encompassing the use of different processing techniques will help the readers to understand the underlying mechanism of microbial inactivation associated with each processing techniques applied to powders. Eventually, this information will help them to select the suitable technique (individual or in combination with another counterpart) to inactivate spores and viable cells in a specific food powder.


Two novel prehabilitation apps to help patients stop smoking and risky drinking prior to hip and knee arthroplasty.
Daily smoking or risky drinking increases the risk of complications after surgery by ~50%. Intensive prehabilitation aimed at complete cessation reduces the complication rate but is time-consuming. The purpose of this study was to carry out preoperative pilot tests (randomized design) of the feasibility (1A) and validation (1B) of two novel prehabilitation apps, habeat® (Ha-app) or rehaviour® (Re-app). Patients scheduled for hip or knee arthroplasty with daily smoking, risky drinking, or both were randomised to one of the two apps. In part 1A, eight patients and their staff measured feasibility on a visual analog scale (VAS) and were interviewed about what worked well and the challenges requiring improvement. In part 1B, seven patients and their staff tested the improved apps for up to two weeks before validating the understanding, usability, coverage, and empowerment on a VAS and being interviewed. In 1A, all patients and staff returned scores of ≥5 for understanding the apps and mostly suggested technical improvements. In 1B, the scores varied widely for both apps, with no consensus achieved. Two of four patients (Ha-app) and one-third of the patients (Re-app) found the apps helpful for reducing smoking, but without successful quitting. The staff experienced low app competencies among patients and high time consumption. Specifically, patients most often needed help for the Ha-app, and the staff most often for Re-app; however, the staff reported the Re-app dashboard was more user-friendly. Support and follow-up from an addiction specialist staff member were suggested to complement the apps, thereby increasing the time consumption for staff. This pilot study to test prototype apps generated helpful feedback for the app developers. Based on the patient and staff comments, multiple improvements in functionality seem required before scaling up the evaluation for effect on prehabilitation and postoperative complications.


Effect of PET microplastics on the growth, digestive enzymes, and intestinal flora of the sea cucumber Apostichopus japonicus.
Marine microplastic (MP) pollution is becoming a serious problem and their potentially toxic effects on marine organisms have attracted much attention. Sea cucumber is very important for the safety and health of marine ecosystems. However, there have been relatively few studies on the effects of microplastic pollution on sea cucumbers at environmentally-related concentrations and under controlled conditions. Therefore, this study evaluated the effects of polyethylene terephthalate (PET) microplastics (particle sizes: 0.5-45 μm, 2-200 μm, and 20-300 μm; and three concentration levels for each particle size, approximately 103, 104, and 105 particles/kg) on the basic biological indicators, intestinal digestive enzymes, and intestinal flora of Apostichopus japonicus after a 28-day feeding experiment. This study showed that environmentally-related and high concentrations of microplastics had little effect on A. japonicus. This study provides valuable reference information about the effects of marine microplastic pollution on sea cucumbers.


A nano-delivery system for bioactive ingredients using supercritical carbon dioxide and its release behaviors.
For the purpose of ensuring the bioavailability of bioactive ingredients, a nano-delivery system with low toxicity was developed using supercritical carbon dioxide (SC-CO2). Compared to thin-film hydration (TFH), obtaining nano-scale liposomes is easier using SC-CO2. The characteristic of these liposomes was also demonstrated by the analysis of particle size and morphology. An in vitro release study showed that liposomes produced using SC-CO2 were resistant to low pH in simulated gastric conditions. In a simulated intestinal environment, enteric solubility of these liposomes was enhanced, which are important properties for controlled releasing bioactive ingredient. Furthermore, SC-CO2-produced liposomes had a higher storage stability than those produced using TFH. Analysis of the organic solvent residue in the liposomes by gas chromatography-mass spectrometry (GC-MS) indicated that SC-CO2-produced liposomes had lower toxicity than those produced by TFH. A chemical free nano-delivery system using SC-CO2 has been revealed for storage and controlled release of bioactive ingredients.


Dynamic internalization and recycling of a metal ion transporter: Cu homeostasis and CTR1, the human Cu⁺ uptake system.
Cu ion (Cu) entry into human cells is mediated by CTR1 (also known as SLC31A1), the high-affinity Cu transporter. When extracellular Cu is raised, the cell is protected against excess accumulation by rapid internalization of the transporter. When Cu is lowered, the transporter returns to the membrane. We show in HEK293 cells overexpressing CTR1 that expression of either the C-terminal domain of AP180 (also known as SNAP91), a clathrin-coat assembly protein that sequesters clathrin, or a dominant-negative mutant of dynamin, decreases Cu-induced endocytosis of CTR1, as does a dynamin inhibitor and clathrin knockdown using siRNA. Utilizing imaging, siRNA techniques and a new high-throughput assay for endocytosis employing CLIP-tag methodology, we show that internalized CTR1 accumulates in early sorting endosomes and recycling compartments (containing Rab5 and EEA1), but not in late endosomes or lysosomal pathways. Using live cell fluorescence, we find that upon extracellular Cu removal CTR1 recycles to the cell surface through the slower-recycling Rab11-mediated pathway. These processes enable cells to dynamically alter transporter levels at the plasma membrane and acutely modulate entry as a safeguard against excess cellular Cu.


GITR subverts Foxp3(+) Tregs to boost Th9 immunity through regulation of histone acetylation.
Glucocorticoid-induced TNFR-related protein (GITR) is a costimulatory molecule with diverse effects on effector T cells and regulatory T cells (Tregs), but the underlying mechanism remains poorly defined. Here we demonstrate that GITR ligation subverts the induction of Foxp3(+) Tregs and directs the activated CD4(+) T cells to Th9 cells. Such GITR-mediated iTreg to Th9 induction enhances anti-tumour immunity in vivo. Mechanistically, GITR upregulates the NF-κB family member p50, which recruits histone deacetylases to the Foxp3 locus to produce a 'closed' chromatin structure. Furthermore, GITR ligation also activates STAT6, and STAT6 renders Il9 locus accessible via recruitment of histone acetyltransferase p300, and together with inhibition of Foxp3, GITR induces strong Th9 responses. Thus, Th9 cells and iTregs are developmentally linked and GITR can subvert tolerogenic conditions to boost Th9 immunity.


A quasi-one-dimensional model for ion-aerosol interactions and aerosol charge state downwind of corona-producing alternating current (AC) HVPL under stable atmospheric conditions.
Corona ions produced by high voltage power lines (HVPL) can alter the local atmospheric electrical environment downwind, potentially increasing electrostatic charge on airborne particulates via ion-aerosol attachment. However, previous epidemiological assessments attempting to assess this 'corona ion hypothesis' have used proxies e.g. ion concentration or distance from HVPL, rather than aerosol charge state directly, due to difficulties in modeling this quantity. We present a quasi-1D model incorporating both Gaussian plume dynamics and ion-aerosol and ion-ion interaction microphysics which could be applied to future studies of charged aerosol near HVPL. The response of the model to changes in a range of input parameters is characterized, and validation is attempted by means of comparison with previous work where ion- and aerosol concentrations and properties (including electrical mobility and electric charge states) upwind and downwind of HVPL are measured.


Mould spoilage of cereals during transportation by sea from Latin America to Europe mechanisms, impact and management.
Safe water contents of consignments of cereals to be shipped overseas can be calculated from the relation between mould-free storage time and storage conditions (temperature of the environment, aw of the cereal), corrected for heterogeneity of water distribution, content of damaged kernels and degree of infestation by insects. The validity of this model was substantiated by the inspection of shipments and theoretical data from the literature. This predictive model can usefully be substituted for previously used, ill-defined criteria like average or any portion's water content and should prompt the trade to sell consignments of cereals on the basis of dry substance.


The intricacies of cardiac sarcoidosis: a case report involving the coronary arteries and a review of the literature.
Primary cardiac sarcoidosis (CS) is rare, and concomitant involvement of the coronary arteries is rarer still. Successful diagnosis of this disease is difficult due to its nonspecific symptoms which mimic those of idiopathic dilated cardiomyopathy (IDCM). We describe a 47-year-old Caucasian male who underwent orthotopic heart transplant for presumed IDCM. Examination of the explanted heart revealed numerous nonnecrotizing granulomata throughout, similar granulomata in the walls of the large coronary arteries, and large areas of fibrosis. In cases of IDCM with symptoms of angina or acute coronary syndrome, the possibility of CS should be considered. Herein, we present this case and a review of the relevant literature.


Increased CTGF expression in alveolar epithelial cells by cyclic mechanical stretch: Its mechanism and the therapeutic effect of pirfenidone.
The mechanisms of fibrosis onset and development remain to be elucidated. However, it has been reported that mechanical stretch promotes fibrosis in various organs and cells, and may be involved in the pathogenesis of pulmonary fibrosis. We demonstrated that ventilator-induced lung hyperextension stimulation in mice increased the expression of connective tissue growth factor (CTGF), a profibrotic cytokine, in lung tissue. Increased CTGF expression induced by cyclic mechanical stretch (CMS) was also observed in vitro using A549 human alveolar epithelial cells. Pathway analysis revealed that the induction of CTGF expression by CMS involved MEK phosphorylation. Furthermore, early growth response 1 (Egr-1) was identified as a transcription factor associated with CTGF expression. Finally, the antifibrotic drug pirfenidone significantly reduced CTGF expression, MEK phosphorylation, and Egr-1 levels induced by CMS. Thus, our results demonstrated that profibrotic cytokine CTGF induced by CMS may be a therapeutic target of pirfenidone.


Corticosteroid-binding globulin and estrogens in maternal and cord blood.
Corticosteroid-binding globulin (CBG) is produced by the liver in small concentrations and binds steroids with high affinity. Its concentration in the blood is sensitive to endogenous or exogenous estrogens in a dose-response manner and serves as a biological assay for estrogens. CBG concentrations were measured in sera collected from maternal and umbilical vein blood during labor and delivery and at elective cesarean section and correlated with endogenous estradiol and estriol concentrations. CBG and estradiol concentrations of maternal blood were significantly exceeded those of maternal serum. A highly significant increase in cord blood estriol concentration was found following vaginal delivery compared to elective cesarean section, indicating an increase in adrenal activity due to the stress of labor. CBG levels correlated directly with maternal estradiol but not estriol cencentrations. Cord blood CBG concentration varied little despite a wide range of estrogen concentrations. The physiologic significance of CBG concentrations in maternal and fetal blood is discussed.


Grease, anthraxgate, and kennel cough: a revisionist history of early veterinary vaccines.
In conclusion, it is remarkable just how farsighted many of the early vaccine investigators were. Jenner was apparently very comfortable with contagion and even recognized that infectious agents could gradually change and adapt to a new species. Pasteur, long before his fowl cholera experiment, dreamed that attenuation could yield safe vaccines and it took him no time at all therefore to recognize the significance of that serendipitous experiment. The fact that two other investigators were also developing anthrax vaccines simultaneously is yet another example of how the times favor certain discoveries. Finally Ferry, while constrained by the fact that he had no idea that distemper was caused by a virus, recognized well the concept of secondary infection and rationalized, not unreasonably, that his vaccine might assist in controlling this. It is also clear that we must look skeptically at the accepted historical record. Thus, it is clear that Jenner used horse-derived material as a source of vaccine material and that vaccinia may in fact be the long-lost agent of horsepox. Certainly this would not be news to many nineteenth-century investigators and veterinarians. Individuals planning to use live vaccinia in recombinant vaccines may wish to keep this in mind. Who discovered anthrax vaccine? Burdon-Sanderson clearly recognized that he could attenuate the organism. Greenfield showed that this could protect against disease although he was far from developing an effective vaccine. Poor Henri Toussaint was probably the first to develop an effective product but did not publicize his results widely. It was left to Louis Pasteur to take the risks inherent in a high-profile public experiment and win. I believe that he richly deserves the prize. Finally, who deserves the credit for distemper vaccine? First, Carré deserves much more credit than hitherto for discovering that distemper was caused by a virus. Second, Ferry, although misled by his identification of B. bronchiseptica deserves credit for realizing that his vaccine could play a role in controlling secondary infections. The true discoverer of an effective distemper vaccine was the Italian, Puntoni, but once again the publicity went to others, Laidlaw and Dunkin. Thus a pattern emerges that prior discovery matters little in the face of aggressive publicity. If nobody knows you did the experiment you might as well have never done it in the first place. Publish or perish is by no means a new phenomenon.


Effect of obesity on insulin resistance in normal subjects and patients with NIDDM.
Insulin resistance (IR) is a characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) as well as obesity, and a majority of NIDDM patients are obese. To assess the effect of obesity independent of NIDDM on IR, we studied the relationship between IR and obesity in 65 normal and 58 NIDDM subjects; we used body mass index (BMI) as a measure of obesity and glucose infusion rate (GINF) during a euglycemic hyperinsulinemic (120 mU.m-2.min-1) glucose clamp as a measure of IR. In lean normal subjects, GINF was 57.7 +/- 2.2 mumol.kg-1.min-1 (10.4 +/- 0.4 mg.kg-1.min-1) and the lean NIDDM subjects were markedly insulin-resistant, with a GINF of 34.4 +/- 2.8 mumol.kg-1.min-1 (6.2 +/- 0.5 mg.kg-1.min-1). Obese normal subjects were also insulin-resistant compared with lean normal subjects, with a GINF of 36.1 +/- 2.2 mumol.kg-1.min-1 (6.5 +/- 0.4 mg.kg-1.min-1), and obesity caused an increase in IR in NIDDM, with a GINF of 21.1 +/- 1.4 mumol.kg-1.min-1 (3.8 +/- 0.25 mg.kg-1.min-1) in the obese NIDDM subjects. Therefore, approximately 61% of the IR in obese NIDDM subjects is due to NIDDM, with 39% due to obesity, demonstrating a greater impact of NIDDM than of obesity in causing IR. The correlation between GINF and BMI was much better in normal subjects (r = -0.75) than in NIDDM subjects (r = -0.50) as was the relationship between fasting insulin level and BMI (r = -0.59 in normal subjects, r = -0.48 in NIDDM subjects). As expected, the fasting insulin level was also strongly correlated to GINF in normal subjects (r = -0.61); however, this relationship was weaker in NIDDM subjects ( r = -0.46). In conclusion, 1) obesity has a major impact to cause insulin resistance in nondiabetic subjects, but the effect of obesity on IR in NIDDM is less; 2) NIDDM per se is the major contributor to IR in NIDDM; and 3) the fasting insulin level is a better surrogate marker of IR in nondiabetic subjects than in NIDDM patients.


[Giant cell tumours in a pyramidal bone: a clinical case and a review of the literature].
Giant cell tumours (GCT) of the bone are benign, but locally invasive tumours. We present a new case of carpus GCT, involving the triquetrum. The diagnosis required a prior biopsy before doing the block resection. This treatment is the best option to avoid recurrences. We review the literature on this particular lesion in the carpus bone.


The risk of eating disorders following the August 4th, 2020 explosion in Beirut and its relationship with trauma exposure and PTSD symptoms.
To date, no study has demonstrated the link between the diagnosis of provisional PTSD and ED in people exposed to the explosion of August 4th, 2020. Online participants were classified into 4 categories according to the degree of exposure to the explosion (unexposed, slightly exposed, moderately exposed, and severely exposed). The screening for ED was done using the standardized SCOFF questionnaire and the screening for provisional PTSD using the standardized IES-R questionnaire. Our sample included 703 participants. In the bivariate analysis, there was a trend for an association between degree of exposure to the explosion and the risk of development of an ED (p = 0.055). The independent variables included in the multivariate analysis that were statistically associated with a risk of developing eating disorders are secondary school as the highest level of education (p = 0.029; OR = 2.15) and the risk of PTSD (p = 0.041; OR = 2.05) according to IES-R, specifically hyperarousal (p = 0.028; OR = 1.07) as a symptom cluster. Provisional PTSD played a mediating role, creating a partial and indirect relationship between the degree of exposure to the explosion and the risk of developing ED with a β coefficient of 0.075 (p < 0.001) CONCLUSION: The risk of PTSD according to IES-R was found to be a determinant of a higher risk of developing ED among participants exposed to the explosion in addition to mediating between the effect of exposure severity and the risk of ED. It is essential to fully assess and manage PTSD symptoms and ED patients exposed to such a psychological trauma.


Time-domain optical imaging: discrimination between scattering and absorption.
A technique for discriminating between scattering and absorbing inclusions located in the center of a scattering slab is presented. The technique is based on an empirical model that provides a simple mathematical expression to describe the change in the time-resolved transmission resulting from the presence of an inclusion. Experimental results from various configurations show that the technique allows for proper recognition of the type of an inclusion whether it is scattering or absorbing. This technique is a significant step toward tissue differentiation.


The influence of 2020 coronavirus lockdown on presentation of oral and maxillofacial trauma to a central London hospital.
The novel coronavirus COVID-19 was first identified in China in December 2019. Its spread resulted in a pandemic, with the United Kingdom entering a period of national lockdown on 23 March 2020 to reduce disease burden on the National Health Service (NHS). King's College Hospital is a Major Trauma Centre serving an inner-city population of 700,000 with 120,000 patients attending the emergency department (ED) annually. We aimed to determine the effect of lockdown on OMFS trauma presentations and lessons learned from emergency service provision during a pandemic. All referrals to the oral and maxillofacial surgical (OMFS) team from ED during the first six weeks of the lockdown period - 23 March 2020 - 3 May 2020 - were compared with the same six-week period in 2019. A total of 111 referrals were made to OMFS during the first six weeks of the lockdown period in 2020 compared with 380 referrals in 2019. Of these, 50.5%, (n=192) were related to facial trauma in 2019 vs (63.1%, n=70) in 2020. Fewer patients were admitted under OMFS: 17.4% (n=35) in 2019 vs 2.9% (n=2) in 2020, and a greater number of patients were discharged from OMFS care directly from the ED: 63.2% (n=127) in 2019 vs 82.9% (n=58) in 2020. There was profound effect of the lockdown on referrals to OMFS from the ED, in number and type of diagnosis. This is potentially reflective of the increased availability of acute/emergency dental services in South-East London during the lockdown period. This gives us valuable insight for service planning in the event of further restrictions.


Protective effect of tannins from Ficus racemosa in hypercholesterolemia and diabetes induced vascular tissue damage in rats.
To evaluate the protective effect of tannins from Ficus racemosa (F. racemosa) on the lipid profile and antioxidant parameters in high fat meal and streptozotocin induced hypercholesteremia associated diabetes model in rats. The crude tannin fraction was separated from the acetone (70% v/v) bark extract of F. racemosa. Oral administration of tannin fraction (TF) (100 & 200 mg/kg body weight) to rats fed with high fat meal for 30 days (4% cholesterol, 1% cholic acid, 0.5% egg albumin) and injected with streptozotocin (35 mg/kg i.p. in citrate buffer on 14th day). The administration of TF significantly reverse the increased blood glucose, total cholesterol, triglycerides, low density lipoprotein and also significantly restored the insulin and high density lipoprotein in the serum. In addition tannins significantly restored the activity of antioxidant enzymes such as superoxide dismutase, catalase and decreased the, glutathione peroxidase, and glutathione, thereby restoring the antioxidant status of the organs to almost normal levels. The results of this study show that two different doses of tannin supplementation had a favorable effect on plasma glucose and lipid profile concentrations. It also had an influence on attenuating oxidative stress in diabetic tats.


Inhibition of adenylate cyclase of rat hepatic membranes by glycosaminoglycans.
Glycosaminoglycans are long non-branched polysaccharides composed of repeating disaccharide units. In a previous in vitro study we have shown that such molecules are able to modulate substrate phosphorylation catalyzed by cAMP-dependent protein kinase. Here, we investigate the impact of glycosaminoglycans, such as heparan sulfate, dermatan sulfate, chondroitin 4- and 6-sulfate, keratan sulfate and hyaluronic acid upon adenylate cyclase, which directly regulates cAMP-dependent protein kinase activity via cAMP synthesis. In rat liver plasma membrane preparation we have determined forskolin- and guanosine-5'-beta, gamma-imidotriphosphate-induced cAMP formation catalyzed by adenylate cyclase in the presence of increasing concentrations of glycosaminoglycans. The results indicate that glycosaminoglycans strongly influence enzymic conversion of ATP into cAMP. The highest reduction of adenylate cyclase activity is observed in the presence of dermatan sulfate and heparan sulfate. Moreover, the inhibitory effect of these two glycosaminoglycans is higher when guanosine-5'-beta, gamma-imidotriphosphate, instead of forskolin, is used as stimulator of adenylate cyclase. Further characterization of enzyme inhibition mediated by dermatan sulfate shows that this molecule exerts an inhibitory effect of mixed type.


Cascaded and nonlinear DNA assembly amplification for sensitive and aptamer-based detection of kanamycin.
Simple, selective and sensitive monitoring of antibiotic residues in food is essential for food safety and human health because of its side effects upon inappropriate usage. Here, with a new label- and enzyme-free significant signal enhancement approach by the coupling of catalytic hairpin assembly (CHA) with nonlinear hybridization chain reaction (nHCR), we developed a fluorescence aptamer sensor for the detection of trace kanamycin in milk samples with high selectivity and sensitivity. The binding of the target kanamycin to the aptamer probe could initiate the CHA between two hairpins for the formation of partial DNA duplexes, which further triggered the nHCR of other three hairpins to yield branched DNA complexes with a multitude of active G-quadruplex structures. The subsequent intercalation of the organic dye, thioflavin T, into G-quadruplex structures resulted in significantly enhanced fluorescence responses for realizing sensitive sensing of kanamycin in the dynamic range of 0.1-300 nM with a detection limit of 46.1 pM. Besides, this strategy could also achieve the monitoring of kanamycin selectively in spiked milk samples. With features of high sensitivity and simplicity in a non-enzyme/label fashion, our signal amplification strategy has high potentials for establishing sensitive and convenient means to monitor various antibiotics.


Topographical differences in the physiological response of canine airway smooth muscle.
The resting membrane potential (Em), electrical and contractile response were studied in three anatomically separate areas of trachealis muscle and also in bronchial muscle (2nd generation) isolated from mongrel dogs. These responses were studied before and after administration of a single dose of histamine, serotonin, carbachol and prostaglandin F2 alpha. A cross-sectional area of airway smooth muscle in each preparation was directly assessed from the histological sections. These values were used to evaluate isometric tension (in g/mm2). It was found that (1) cross-sectional area of airway smooth muscle varies with location; (2) resting membrane potential of airway smooth muscle from upper, middle and lower portions of dog trachea was similar, i.e., -60.4 +/- 0.8, -60.2 +/- 0.4 and -60.8 +/- 0.9 mV, respectively; (3) resting membrane potential of bronchial airway smooth muscle (2nd generation) was -63.4 +/- 0.5 significantly higher (P less than 0.01) than the membrane potential observed in the trachealis muscle; (4) both contractile and electrical changes after single doses of histamine and serotonin administration showed a vertical gradient response. The largest contractile and electrical responses to these two agents were found in preparations from the lower portion of trachea and the smallest response was observed in upper tracheal preparations; (5) contractile responses after a single dose of carbachol and PGF2 alpha, when expressed as isometric tension also showed vertical gradient. In contrast, membrane potential changes after carbachol and prostaglandin F2 alpha were similar in all three types of tracheal segments. Airway smooth muscle of the 2nd generation of bronchi showed large responses after single doses of histamine, carbachol and prostaglandin F2 alpha but the response after serotonin was smaller than that seen in the lower trachea.


Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes.
Deregulation of calcium has been implicated in neurodegenerative diseases, including Alzheimer's disease (AD). Previously, we showed that saturated free-fatty acid, palmitate, causes AD-like changes in primary cortical neurons mediated by astrocytes. However, the molecular mechanisms by which conditioned medium from astrocytes cultured in palmitate induce AD-like changes in neurons are unknown. This study demonstrates that this condition medium from astrocytes elevates calcium level in the neurons, which subsequently increases calpain activity, a calcium-dependent protease, leading to enhance p25/Cdk5 activity and phosphorylation and activation of the STAT3 (signal transducer and activator of transcription) transcription factor. Inhibiting calpain or Cdk5 significantly reduces the upregulation in nuclear level of pSTAT3, which we found to transcriptionally regulate both BACE1 and presenilin-1, the latter is a catalytic subunit of γ-secretase. Decreasing pSTAT3 levels reduced the mRNA levels of both BACE1 and presenilin-1 to near control levels. These data demonstrate a signal pathway leading to the activation of STAT3, and the generation of the amyloid peptide. Thus, our results suggest that STAT3 is an important potential therapeutic target of AD pathogenesis.


Single Cell Technologies to Dissect Heterogenous Immune Cell Therapy Products.
Single cell tools have dramatically transformed the life sciences; concurrently, autologous and allogeneic immune cell therapies have recently entered the clinic. Here we discuss methods, applications, and considerations for single cell technologies in the context of immune cell manufacturing. Molecular heterogeneity can be profiled at the level of the genome, epigenome, transcriptome, proteome, metabolome, and antigen receptor repertoire, in isolation or in tandem through multi-omic approaches. Such data inform heterogeneity within cell products and can be linked to potency readouts and clinical data, with the ultimate goal of identifying Critical Quality Attributes to predict patient outcomes. Non-destructive approaches hold promise for monitoring cell state and analyzing the impacts of gene edits within engineered products. Destructive omics approaches could be combined with non-destructive technologies to predict therapeutic potency. These technologies are poised to redefine cell manufacturing toward rapid, cost-effective, and high-throughput methods to detect and respond to dynamic cell states.


Spontaneous closure of uncomplicated ventricular septal defect.
The charts of 222 patients with a diagnosis of ventricular septal defect (VSD) were reviewed to determine the overall incidence, the prevalence of membranous and muscular defects and the rates of spontaneous VSD closure. VSD diagnosis and location were determined primarily from reports of 2-dimensional and pulsed Doppler echocardiograms. In a 5-year period, VSDs occurred in 3.85/1,000 live full-term births and 7.06/1,000 live premature births. The VSD closed spontaneously in 20 of 44 patients (45%) followed from birth (University Hospital group) during a mean follow-up of 12 months. Of 165 patients not followed from birth (referred group), the VSD closed spontaneously in 37 (22%). Overall, VSD location was determined in 101 of 209 patients (48%) and was distributed as follows: membranous 66 (65%), muscular 32 (32%) and subpulmonic 3 (3%). Rates of spontaneous closure for membranous and muscular VSDs were 37% and 50%, respectively, for the University Hospital group and 9% and 9%, respectively, for the referred group (no significant difference in either case). Surgical closure was required in 30 of 165 referred patients (18%) and only 1 of 44 University Hospital patients (2%). There was no significant difference in rate of closure for premature vs full-term infants or small vs larger defects. Data for patients followed from birth more likely reflect the true natural history of VSD.


Inverse planning simulated annealing for magnetic resonance imaging-based intracavitary high-dose-rate brachytherapy for cervical cancer.
To develop a technique using exclusively magnetic resonance imaging (MRI) to perform dwell position identification, targets and organs at risk delineation, and to apply inverse planning dose optimization to high-dose-rate brachytherapy for cervical cancer. We included 15 consecutive women treated with high-dose-rate (HDR) brachytherapy for cervical cancer. All patients underwent MRI after placement of tandem and ring applicator containing a gadodiamide-filled dummy marker. This technique allowed direct visualization of the source pathway and precise definition of the intra-applicator source positions. For each patient, we delineated gross target volume (GTV), high-risk clinical target volume (HR-CTV), and organs at risk on MRI, according to the European Gynecological GEC-ESTRO Working Group definitions. We performed inverse planning simulated annealing (IPSA) and analyzed the dose-volume histograms with the following endpoints: D(90), D(100), and V(100) for GTV and HR-CTV; D0.1 cc, D1 cc, D2 cc for bladder, rectum, and bowel; and dose at Point A. The intra-applicator source pathway was easily visualized on MRI using the gadodiamide-filled marker. IPSA provided excellent target coverage. The mean D(90) and V(100) for HR-CTV were 103+/-5% and 92+/-3%, respectively. IPSA provided excellent bladder sparing. D1 cc and D2 cc of bladder were 73+/-10% and 67+/-10%, respectively. We developed a novel technique that allows direct visualization of the intra-applicator source pathway on MRI. Using this technique, we successfully performed inverse planning directly from MRI.


Effects of copper-aspirin complex on platelet aggregation and thrombosis in rabbits and mice.
The effects of intragastric and intraduodenal copper-aspirin complex on rabbit platelet aggregation were observed by Born's method. Myers's method was used to evaluate the antithrombotic effect of copper-aspirin complex in mice. In-vitro copper-aspirin complex selectively inhibited arachidonic acid-induced platelet aggregation with an IC50 value (concentration resulting in 50% inhibition) of 13.2 microM (95% confidence limits 9.1-16.8 microM). Copper-aspirin complex (10 mg kg(-1) given intragastrically or intraduodenally) was more potent than aspirin in inhibiting arachidonic acid-induced platelet aggregation. Copper-aspirin complex (10 mg kg(-1)) had a stronger inhibitory effect and a longer duration of action when given intragastrically than when given intraduodenally. It was shown by radioimmunoassay that copper-aspirin complex significantly reduced the level of thromboxane B2 in plasma while markedly increasing that of 6-ketoprostaglandin F1alpha (6keto-PGF1alpha). Copper-aspirin complex (10 mg kg(-1) given intragastrically for 7 days) significantly reduced mouse mortality caused by intravenous injection of arachidonic acid. The results suggest that both in-vitro and in-vivo copper-aspirin complex is more potent in selectively inhibiting arachidonic acid-induced platelet aggregation than aspirin. When given intragastrically the complex has a more potent antiplatelet effect and a longer duration of action than when given intraduodenally. The antithrombotic effect of the complex was more potent than that of aspirin.


Acute effects of a single neurodynamic mobilization session on range of motion and H-reflex in asymptomatic young subjects: A controlled study.
Neurodynamic techniques have yielded good clinical results in the treatment of various pathologies. The objective of this study is to examine the short-term effects of neurodynamic techniques of the sciatic nerve on hip ROM (range of motion) and on the amplitude and latency of the soleus H-reflex and M-waves, in young asymptomatic subjects. In a double-blind controlled trial design, 60 young asymptomatic participants were randomly assigned into six groups with different levels of manipulation of the sciatic nerve. The passive straight leg raise test was used to evaluate the hip ROM amplitude. All evaluations were performed before, 1 min after, and 30 min after intervention. For each time-point, spinal and muscle excitability were also tested. ROM increased in all groups, but none of the treatment groups had superior effects than the group with no treatment. This means that ROM testing maneuvers increased ROM amplitude, with no add-on effect of the proposed neurodynamic techniques. Neurophysiological responses changed similarly in all groups, showing that the aftereffects were not intervention-specific. We observed a significant negative association between the change in limb temperature and the change in latencies of all potentials. ROM-testing procedures performed repeatedly increase ROM amplitude. This observation should be considered when evaluating the aftereffects of therapeutic interventions on ROM amplitude. None of the explored neurodynamic techniques produced acute aftereffects on hip ROM amplitude, spinal or muscle excitability different to the induced by the ROM testing maneuver.


TGF-β-induced fibrotic stress increases G-quadruplex formation in human fibroblasts.
Scar formation after wound healing is a major medical problem. A better understanding of the dynamic nuclear architecture of the genome during wound healing could provide insights into the underlying pathophysiology and enable novel therapeutic strategies. Here, we demonstrate that TGF-β-induced fibrotic stress increases formation of the dynamic secondary DNA structures called G-quadruplexes in skin fibroblasts, which is coincident with increased expression of collagen 1. This G-quadruplex formation is attenuated by a small molecule inhibitor of intracellular Ca2+ influx and an anti-fibrotic compound. In addition, we identify G-quadruplex-forming sequences in the promoter region of COL1A1, which encodes collagen 1, and confirm their ability to form G-quadruplex structures under physiologically relevant conditions. Our findings reveal a link between G-quadruplexes and scar formation that may lead to novel therapeutic interventions.


Incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation.
The incidence of positive C4d deposition in peritubular capillaries (PTC) in long-term survival cases remains controversial. Some incidences of positive C4d deposition in PTC in cases of long-term survival less than 10 yr have been reported. We retrospectively examined the incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation and the histological and clinical characteristics of the positive C4d staining cases. We examined 14 protocol biopsy cases performed at Osaka University Hospital between March 2004 and March 2005. The average interval between the operation and the day of biopsy was 15.4 yr. Histological diagnosis was made in accordance with the Banff 97 classification. Paraffin-embedded tissue was stained with polyclonal anti-C4d antibody. Detection of donor-specific antibody (DSA) was determined by flow cytometric assay. The cases were divided according to C4d positivity. Three of 14 cases (21.4%) were C4d positive and belonged to the C4d+/DSA+ group, while 11 cases were of the C4d-/DSA- group. There were no significant differences between the two groups in serum creatinine (sCr) or proteinuria at the time of biopsy. A trend towards decreasing rate of the inverse of sCr (1/sCr) in the C4d+/DSA+ group was noted. In the C4d+/DSA+ group, three transplant glomerulopathy (TGP) were identified. On the other hand, TGP were identified in six of 11 cases of the C4d-/DSA- group. We investigated the relevance of typical chronic rejection (CR) features and the positivity of C4d. No significant differences were observed between the CR features and C4d depositions in PTC (p = 0.26). In long-term survival cases with positive C4d, a trend towards decreasing rate of 1/sCr was revealed, but their histological characteristic features was not recognized.


Inducing Curvature to Pyracylene upon π-Expansion.
We disclose a successive π-expansion of pyracylene towards boat-shaped polycyclic scaffolds. The unique structural features of the resulting compounds were revealed by X-ray crystallographic analysis. Depending on the extent of π-expansion the compounds display intense bathochromically shifted absorption bands in their UV/Vis spectra and are prone to several redox events as documented by cyclic voltammetry. The experimental observations are in line with the computational studies based on density functional theory, suggesting progressive narrowing of the HOMO-LUMO gap and distinct evolution of the electronic structure and aromaticity.


Rapunzel syndrome due to ingested hair extensions: Surgical and psychiatric considerations.
Rapunzel syndrome is a unique clinical manifestation of trichotillomania and trichophagia. The resulting gastric trichobezoar can be massive and necessitate surgical extraction. We present a case involving a 15 year-old female with a known history of trichotillomania. The patient possessed symptoms of nausea and early satiety, and admitted that she had recently consumed a large number of hair extensions. Computed tomography imaging revealed a massive gastric bezoar not amenable to endoscopic extraction. The patient underwent surgical laparotomy, and a large gastric trichobezoar was removed through an anterior gastrotomy. The trichobezoar extended past the pylorus into the duodenum, thus confirming a diagnosis of Rapunzel syndrome. Trichobezoars formed from the consumption of hair extensions is a rare cause of Rapunzel syndrome. Surgical extraction is often necessitated due to the sheer size of the gastric bezoar that results from consuming hair extensions. If not previously established, psychiatric consultation should be pursued in the immediate post-operative course as these patients may require pharmacologic management along with behavioral therapy to avoid further episodes of trichotillomania. This case presents a unique and modern manifestation of Rapunzel syndrome. Surgical treatment most often is required when a patient presents with a massive gastric trichobezoar. Regular post-operative psychiatric follow-up is necessary to prevent recurrent episodes.


Bacterial biofilm in adenoids of children with chronic otitis media. Part I: a case control study of prevalence of biofilms in adenoids, risk factors and middle ear biofilms.
Biofilms are communities of bacteria embedded in a self-produced glycocalyx matrix. Adenoids have been shown to harbor bacterial biofilms. Aim/objectives: To compare the prevalence of biofilms in adenoid of children with chronic otitis media (COM) (group1) versus a control group without any COM (group 2) having adenoids removed because of hypertrophy. One hundred and three children were prospectively enrolled in this case-control study, group 1 (n = 52) and group 2 (n = 51). The main outcome measurement was the prevalence of biofilm in adenoidectomy specimens analyzed using confocal laser scanning microscopy. Children in group 1 who had middle ear (ME) effusion and requiring the insertion of a tympanostomy tube underwent biopsy of the ME mucosa and effusion sampling. Biofilms were found in adenoids' specimens of both groups and in the ME biopsy and effusion. The biofilm prevalence in adenoids was 63.5% (33/52) in group 1 and 47.1% (24/51) in group 2. Day nursery and previous antibiotics intake were significantly more frequent in group 1 than in group 2. This case-control study demonstrates that adenoid tissue in children with COM contains more mucosal biofilms than adenoid tissue removed for hypertrophy. Biofilm was seen in ME biopsies and effusion.


Characteristics of the influence of auxins on physicochemical properties of membrane phospholipids in monolayers at the air/aqueous solution interface.
Interactions between representatives of plant hormones and selected membrane lipids have been studied in monolayers at the air/aqueous solutions interface with π-A isotherm analysis, microscopic visualization and grazing incidence X-ray diffraction technique (GIXD). Four phytohormones: indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), 2-naphthoxyacetic acid (BNOA) and 2,4-dichlorophenoxyacetic acid (2,4-D), belonging to the class of auxins differ as regards the chemical structure of the aromatic molecular fragment. The studied phospholipids have been chosen since they are omnipresent in the biological membranes of plant and animal kingdom. Our results revealed that both natural (IAA and IBA) and synthetic (2,4-D and BNOA) phytohormones modify the physicochemical characteristics of the investigated lipid monolayers. Auxins caused strong diminishing of the monolayer condensation, especially for DPPC and SOPE, which may be attributed to the phase transition in these monolayers. In the performed experiments the key step of auxins action occurs when the molecules interact with monolayers in the expanded state-when the space in the lipid head-group region is large enough to accommodate the molecules of water soluble auxins. The application of GIXD technique confirmed that auxin molecules are also present at the interface at higher surface pressure (30 mN/m). The obtained results showed that among the investigated auxins, the largest influence on the lipid monolayers occurred in the case of BNOA, which molecule possesses the largest aromatic fragment. In contrast, 2,4-D, having the smallest aryl group affects the studied lipid systems to the smallest extent.


Default mode network abnormalities in idiopathic generalized epilepsy.
Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.


Ion mobility spectrometry and high resolution mass-spectrometry as methodologies for rapid identification of the last generation of new psychoactive substances.
A new drug trafficking trend has been observed in the last years by the introduction in the black market of new psychoactive substances (NPS) in order to difficult competent authority controls. In this study, ion mobility spectrometry (IMS) and high-resolution mass-spectrometry (HRMS) were proposed as vanguard and rearguard methodologies for the rapid identification of the last generation of NPS in seizures. The combined use of IMS and HRMS has been evaluated through the analysis of 24 NPS seized from 2016 to 2018 in Valencia (Spain) to demonstrate the utility of this approach. The characteristic reduced mobility (K0) values for seized NPS were determined and mass-mobility relationships were proposed and evaluated for the main NPS families: amphetamine and cathinone derivatives, and synthetic cannabinoids. IMS did not allow a unequivocal identification by itself; so, HRMS analysis was employed as rearguard confirmation methodology for the right identification of NPS. Thus, the combined use of IMS and HRMS can be considered as promising alternative for the rapid screening and identification of NPS in seizures.


Deep learning empowered volume delineation of whole-body organs-at-risk for accelerated radiotherapy.
In radiotherapy for cancer patients, an indispensable process is to delineate organs-at-risk (OARs) and tumors. However, it is the most time-consuming step as manual delineation is always required from radiation oncologists. Herein, we propose a lightweight deep learning framework for radiotherapy treatment planning (RTP), named RTP-Net, to promote an automatic, rapid, and precise initialization of whole-body OARs and tumors. Briefly, the framework implements a cascade coarse-to-fine segmentation, with adaptive module for both small and large organs, and attention mechanisms for organs and boundaries. Our experiments show three merits: 1) Extensively evaluates on 67 delineation tasks on a large-scale dataset of 28,581 cases; 2) Demonstrates comparable or superior accuracy with an average Dice of 0.95; 3) Achieves near real-time delineation in most tasks with <2 s. This framework could be utilized to accelerate the contouring process in the All-in-One radiotherapy scheme, and thus greatly shorten the turnaround time of patients.


Programming generality into a performance feedback writing intervention: A randomized controlled trial.
Substantial numbers of students in the United States are performing below grade-level expectations in core academic areas, and these deficits are most pronounced in the area of writing. Although performance feedback procedures have been shown to produce promising short-term improvements in elementary-aged students' writing skills, evidence of maintenance and generalization of these intervention effects is limited. The purpose of this study was to examine the immediate, generalized, and sustained effects of incorporating multiple exemplar training into the performance feedback procedures of a writing intervention using a randomized controlled trial (RCT). Results indicated that although the addition of multiple exemplar training did not improve students' writing performance on measures of stimulus and response generalization, it did result in greater maintenance of intervention effects in comparison to students who received performance feedback without generality programming and students who engaged in weekly writing practice alone.


Treatment of aqueous wastes by means of Thermophilic Aerobic Membrane Reactor (TAMR) and nanofiltration (NF): process auditing of a full-scale plant.
This work focuses on the Thermophilic Aerobic Membrane Reactor (TAMR) process. The research was carried out on a full-scale facility where, all along a 12-year period, daily monitoring and process audit tests were conducted for the process analysis and optimization. The plant treated -light and high-strength aqueous wastes and two different configurations were adopted: (1) thermophilic biological reactor + ultrafiltration (TAMR) and (2) TAMR + nanofiltration (TAMR + NF). In the latter case, the average chemical oxygen demand removal yield was equal to 89% and an effective denitrification (nitrogen oxides removal equal to 96%) was achieved by reducing the dissolved oxygen concentration in the bioreactor. Low specific sludge production was observed. Poor sludge settling properties were measured by a lab-scale settling test; respirometric tests (nitrogen uptake rate and ammonia uptake rate) showed the presence of denitrification and the inhibition of nitrification. Hydrodynamic tests revealed the presence of a significant dead space, thus showing room for improving the overall process performance. Finally, the rheological properties of the sludge were measured as a function of the biomass concentration, pH, temperature, and aeration scheme.


Clinical efficacy of transcrestal sinus floor augmentation, in comparison with lateral approach, in sites with residual bone height ≤6 mm: A systematic review and meta-analysis.
This paper addressed two focused questions: Focused question 1 (Q1) "what is the clinical efficacy of transcrestal sinus floor augmentation (TSFA), as compared to lateral sinus floor augmentation (LSFA) in sites with residual bone height (RBH) ≤6 mm, in randomized clinical trials (RCTs) and controlled clinical trials (CCTs)?"; Focused question 2 (Q2) "what is the estimated effectiveness of TSFA for outcomes in Q1, in RCTs, CCTs or cohort studies?" An electronic search (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials) and hand search were conducted from January 1986 until December 2022. All eligible clinical studies expressly reporting TSFA in sites with RBH ≤6 mm were included. The data were extracted, and the risk of bias in individual studies was evaluated. Meta-analysis was performed whenever possible. Seven RCTs were included for Q1 and 25 studies (9 RCTs, 2 CCTs, 14 single arm cohort studies) for Q2. Q1: Meta-analysis did not show significant difference in the implant survival, sinus membrane perforation and marginal bone loss between TSFA and LSFA groups. Q2: Meta-analysis showed TSFA had a high implant survival rate (96.5%, 95% CI: 93.2%-98.9%) at least 1 year after surgery, and limited sinus membrane perforation (5.4%, 95% CI: 2.7%-8.8%). The results also presented higher patient satisfaction for TSFA. With the limitations of the present study (high risk of bias in individual studies), it can be concluded that there was no significant difference in implant survival, Schneiderian membrane perforation and MBL between two approaches in sites with RBH ≤6 mm.


Exposure to sexual content and problematic sexual behaviors in children and adolescents: A systematic review and meta-analysis.
Exposure to sexual content, such as online pornography or live sexual content, has been posited in the literature as a risk factor for problematic sexual behaviors (PSBs) in children and adolescents, and has been identified as an important avenue for research and intervention, particularly given the ubiquitous access to technology among children. To examine the association between live/violent and non-violent sexual content exposure and PSB among children and adolescents. Objectives also include informing future research on sexual content exposure as a risk factor for PSB, and providing clinical recommendations related to prevention and intervention. Results are based on 16,200 participants (28.65 % female; Mage = 14.26; range = 4.74-17.92) and 27 studies conducted in North America, Europe, Asia, and Africa. A systematic review was conducted of available literature published up to September 2021. Abstract and full-text review were conducted to assess whether studies met inclusion criteria. Random-effects meta-analyses were conducted on included studies. Significant associations were found between exposure to non-violent sexual content and likelihood of engaging in PSB (OR = 1.82; p < .001; 95 % CI: 1.50-2.21), and between exposure to violent/live sexual content and PSB (OR = 2.52; p < .001; 95 % CI: 1.75-3.61). Sex emerged as a moderator of the association between exposure to non-violent sexual content and PSB, such that the association was stronger in studies with a greater proportion of females. Results support the need for future research on risk factors and mechanisms implicated in PSB. Prevention and intervention programs for children with PSB and their families could benefit from incorporating education on sexual content exposure.


Premature senescence of human endothelial cells induced by inhibition of glutaminase.
Cellular senescence is now recognized as an important mechanism of tumor suppression, and the accumulation of senescent cells may contribute to the aging of various human tissues. Alterations of the cellular energy metabolism are considered key events in tumorigenesis and are also known to play an important role for aging processes in lower eukaryotic model systems. In this study, we addressed senescence-associated changes in the energy metabolism of human endothelial cells, using the HUVEC model of in vitro senescence. We observed a drastic reduction in cellular ATP levels in senescent endothelial cells. Although consumption of glucose and production of lactate significantly increased in senescent cells, no correlation was found between both metabolite conversion rates, neither in young endothelial cells nor in the senescent cells, which indicates that glycolysis is not the main energy source in HUVEC. On the other hand, glutamine consumption was increased in senescent HUVEC and inhibition of glutaminolysis by DON, a specific inhibitor of glutaminase, led to a significant reduction in the proliferative capacity of both early passage and late passage cells. Moreover, inhibition of glutaminase activity induced a senescent-like phenotype in young HUVEC within two passages. Together, the data indicate that glutaminolysis is an important energy source in endothelial cells and that alterations in this pathway play a role in endothelial cell senescence.


Investigating the conservatism-disgust paradox in reactions to the COVID-19 pandemic: A reexamination of the interrelations among political ideology, disgust sensitivity, and pandemic response.
Research has documented robust associations between greater disgust sensitivity and (1) concerns about disease, and (2) political conservatism. However, the COVID-19 disease pandemic raised challenging questions about these associations. In particular, why have conservatives-despite their greater disgust sensitivity-exhibited less concern about the pandemic? Here, we investigate this "conservatism-disgust paradox" and address several outstanding theoretical questions regarding the interrelations among disgust sensitivity, ideology, and pandemic response. In four studies (N = 1,764), we identify several methodological and conceptual factors-in particular, an overreliance on self-report measures-that may have inflated the apparent associations among these constructs. Using non-self-report measures, we find evidence that disgust sensitivity may be a less potent predictor of disease avoidance than is typically assumed, and that ideological differences in disgust sensitivity may be amplified by self-report measures. These findings suggest that the true pattern of interrelations among these factors may be less "paradoxical" than is typically believed.


Experimentally induced pulmonary arterial occlusion with detachable balloon in pigs: thin-section CT findings.
The authors evaluated changes of lung attenuation in pigs, with special attention to the mosaic pattern of low attenuation, at thin-section computed tomography (CT) after obstruction of the proximal pulmonary artery with a detachable balloon. In seven pigs, nine sites of the descending pulmonary artery were obstructed with detachable balloons. This-section CT scans of the lungs were obtained immediately (n = 9) and at 1 week (n = 5), 2 weeks (n = 1), 3 weeks (n = 2), 4 weeks (n = 1), 6 weeks (n = 1), 8 weeks (n = 1), and 12 weeks (n = 1) after pulmonary artery obstruction. No statistically significant difference was found between the measured lung attenuation of the normal lung and that of the lung distal to the obstruction. Of the nine sites of pulmonary artery obstruction, five (56%) showed an irregular area of increased lung attenuation without lobular architecture. The diameter of the pulmonary artery after obstruction, compared with the diameter before obstruction, decreased by a range of 13%-57% (mean, 35%) and by 0-67% (mean, 44%) at levels 1 cm and 2 cm distal to the obstruction, respectively. This experimental study reveals that regional low-attenuation areas do not develop for up to 12 weeks after the obstruction of proximal pulmonary artery, despite a marked decrease in the diameter of the pulmonary artery distal to the obstruction.


Plasma protein profiles and prognosis in gastric cancer.
In 104 patients with gastric cancer the serum proteins carcinoembryonic antigen (CEA), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP) (orosomucoid) and alpha 1-antichymotrypsin (ACT) were measured pre-operatively. The estimated median survival of patients with both raised CEA and ACT was only 5 weeks in contrast to 64 weeks for those with both proteins normal. An intermediary group with one of these proteins raised and the other normal had an estimated median survival of 15 weeks. Similar results were obtained by considering a combination of CEA with either AGP or CRP. For these data the results were not explicable in terms of associations between survival time and patient's age, stage, operative procedure, histological classification or site of primary tumour.


Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women.
To estimate the efficacy of isotretinoin for prevention of progression of low-grade squamous intraepithelial lesions (SIL) of the cervix to high-grade lesions or invasive cervical cancer; to estimate the regression rate of low-grade SIL with isotretinoin and the toxicity of isotretinoin in this setting; and to correlate serum CD4 levels with progression of low-grade SIL. A randomized, phase III, observation-controlled, multicenter trial was performed in which 117 human immunodeficiency virus (HIV)-positive women with low-grade SIL of the cervix received either oral isotretinoin at 0.5 mg/kg per day for 6 months or observation. Papanicolaou smears and colposcopy/biopsy were done at regular intervals during follow-up. The primary endpoint was progression to high-grade SIL or cervical cancer. Twenty-one of 102 women (20.6%) completing follow-up experienced progression to high-grade SIL, 13 in the observation group and eight in the isotretinoin group. This difference was not significant (P =.29). No cases of invasive cancer were seen. Baseline CD4 levels were lower than anticipated (median 329 cells/mm(3)), but not associated with time to progression (P =.36). Most subjects (63 of 102, 61.7%) used highly active antiretroviral therapy. Subjects under age 30 were more likely to progress than those older than 30 (P =.046). Isotretinoin was not associated with longer time to progression of low-grade SIL. This appears to be a chronic condition in HIV-positive women, with a low risk of progression and significant rate of resolution. As in the general population, observation without excisional therapy may be appropriate for HIV-positive women with low-grade SIL.


[State of the art of oral and maxillofacial surgery in the 13th century].
A report is given on the level of knowledge achieved in the treatment of oral and maxillofacial diseases in the 13th century under the influence of arab medicine.


The FDA nozzle benchmark: "In theory there is no difference between theory and practice, but in practice there is".
The utility of flow simulations relies on the robustness of computational fluid dynamics (CFD) solvers and reproducibility of results. The aim of this study was to validate the Oasis CFD solver against in vitro experimental measurements of jet breakdown location from the FDA nozzle benchmark at Reynolds number 3500, which is in the particularly challenging transitional regime. Simulations were performed on meshes consisting of 5, 10, 17, and 28 million (M) tetrahedra, with Δt = 10-5 seconds. The 5M and 10M simulation jets broke down in reasonable agreement with the experiments. However, the 17M and 28M simulation jets broke down further downstream. But which of our simulations are "correct"? From a theoretical point of view, they are all wrong because the jet should not break down in the absence of disturbances. The geometry is axisymmetric with no geometrical features that can generate angular velocities. A stable flow was supported by linear stability analysis. From a physical point of view, a finite amount of "noise" will always be present in experiments, which lowers transition point. To replicate noise numerically, we prescribed minor random angular velocities (approximately 0.31%), much smaller than the reported flow asymmetry (approximately 3%) and model accuracy (approximately 1%), at the inlet of the 17M simulation, which shifted the jet breakdown location closer to the measurements. Hence, the high-resolution simulations and "noise" experiment can potentially explain discrepancies in transition between sometimes "sterile" CFD and inherently noisy "ground truth" experiments. Thus, we have shown that numerical simulations can agree with experiments, but for the wrong reasons.


Cavitation Suppression of Bileaflet Mechanical Heart Valves.
Mechanical heart valves (MHVs) are widely used to replace diseased heart valves, but it may suffer from cavitation due to the rapid closing velocity of the leaflets, resulting in the damage of red blood cells and platelets. The aim of this study is to apply computational fluid dynamics (CFD) method to investigate the cavitation in bileaflets mechanical heart valves (BMHVs) and discuss the effects of the conduit and leaflet geometries on cavitation intensity. Firstly, CFD method together with moving-grid technology were applied and validated by comparing with experimental results obtained from other literature. Then the leaflets movement and the flow rate of BMHVs with different conduit geometries and leaflet geometries are compared. At last, the duration time of the saturated vapor pressure and the closing velocity of leaflets at the instant of valve closure were used to represent the cavitation intensity. Larger closing velocity of leaflets at the instant of valve closure means higher cavitation intensity. For BMHVs with different conduit geometries, the conduit with Valsalva sinuses has the maximum cavitation intensity and the straight conduit has the minimum cavitation intensity, but the leaflets cannot reach the fully opened state in a straight conduit. For BMHVs with different leaflet geometries, in order to minimize the cavitation intensity, the leaflets are better to have a large thickness and a small rotational radius. CFD method is a promising method to deal with cavitation in BMHVs, and the closing velocity of leaflets has the same trend with the cavitation intensity. By using CFD method, the effects of the conduit geometry and the leaflet geometry on cavitaion in BMHVs are found out.


ACTH-like neurotropic peptides: possible regulators of rat brain cyclic AMP.
The influence of behaviorally active, N-terminal fragments of ACTH on the accumulation of cAMP in rat brain investigated in broken cell preparations of subcortical tissue, in slices of neostriatum and in vivo. ACTH1--24 has a biphasic effect on the activity of adenylate cyclase in broken cell preparations of rat brain subcortical tissue: concentrations below 25 micrometer stimulated, whereas concentrations of 0.1 mM and higher inhibited adenylate cyclase activity. The magnitude of the stimulation was dependent on the concentrations of ATP and Mg2+ in the incubation medium. Structure activity studies revealed that at a concentration of 10(-4) M ACTH1--16-NH2 and ACTH4--7 also inhibited the activity of adenylate cyclase, whereas ACTH11--24, ACTH1--10, ACTH4--10, [D-Phe7]ACTH1--10 and [D-Phe7]ACTH4--10 were inactive in this respect. Addition of 0.8 mM EGTA but not of 0.25 mM Ca2+ prevented the inhibition by 10(-4) M ACTH1--24. GMP-N-P (10(-5) M), naltrexone (10(-3) M) and ergometrine (10(-3) M) did not influence the inhibitory effect. ACTH1--24 enhanced the accumulation of cAMP in slices from rat brain neostriatum in a dose-dependent manner. This effect was already maximal 7.5 min after the addition of the peptide and was potentiated by isobutylmethylxanthine, a potent inhibitor or phosphodiesterase. Intraventricular injection of 1 microgram ACTH1--16-NH2 in rats significantly elevated (+ 27%) the concentration of cAMP in the septal region 60 min after the injection of the peptide. The results are discussed in terms of a possible involvement of cAMP as a second messenger in the central nervous system for N-terminal fragments of ACTH.


Successful extracorporeal lung assistance for overwhelming pneumonia in a patient with undiagnosed full blown aids--a controversial therapy in HIV-patients.
A case is described of overwhelming pneumonia in a patient with a history of coughing since three months. Because of hypoxia and hypercapnia that could not be managed by optimal mechanical ventilation, the patient required urgent extracorporeal lung assistance (ECLA, also known as ECMO). Afterwards the diagnosis of full blown AIDS was made. Appropriate antiviral, antibiotic and antimycotic therapy was successfully established. The patient was weaned from ECLA 4 days later, and discharged from hospital after two months.


Determination of volatile fatty acids in urine by gas chromatography on a new stationary phase.
A rapid gas chromatographic method for determination of volatile fatty acids in urine is described. Acids up to five carbon atoms, including their isomers can be separated in less than six minutes on the new stationary phase Fluorad FC430. Good separation and sensitivity is obtained with isothermal conditions.


In vitro surgical and non-surgical air-polishing efficacy for implant surface decontamination in three different defect configurations.
Evaluation of surgical and non-surgical air-polishing in vitro efficacy for implant surface decontamination. One hundred eighty implants were distributed to three differently angulated bone defect models (30°, 60°, 90°). Biofilm was imitated using indelible red color. Sixty implants were used for each defect, 20 of which were air-polished with three different types of glycine air powder abrasion (GAPA1-3) combinations. Within 20 equally air-polished implants, a surgical and non-surgical (with/without mucosa mask) procedure were simulated. All implants were photographed to determine the uncleaned surface. Changes in surface morphology were assessed using scanning electron micrographs (SEM). Cleaning efficacy did not show any significant differences between GAPA1-3 for surgical and non-surgical application. Within a cleaning method significant (p < 0.001) differences for GAPA2 between 30° (11.77 ± 2.73%) and 90° (7.25 ± 1.42%) in the non-surgical and 30° (8.26 ± 1.02%) and 60° (5.02 ± 0.84%) in the surgical simulation occurred. The surgical use of air-polishing (6.68 ± 1.66%) was significantly superior (p < 0.001) to the non-surgical (10.13 ± 2.75%). SEM micrographs showed no surface damages after use of GAPA. Air-polishing is an efficient, surface protective method for surgical and non-surgical implant surface decontamination in this in vitro model. No method resulted in a complete cleaning of the implant surface. Air-polishing appears to be promising for implant surface decontamination regardless of the device.


Reversible Bevacizumab Induced Vocal Fold Necrosis.
As the use of anti-angiogenic treatments is gaining scope in the treatment of various malignancies, there are increasing reports of laryngeal side effects. We report two cases of laryngeal necrosis and dysphonia. Two patients with gynecological malignancies presented with severe dysphonia 11-24 months after initiation of bevacizumab therapy. Videostroboscopic examination of the larynx revealed bilateral ulcerations and eschar of the superior surface with absent mucosal waves. Patients were treated with discontinuation of the bevacizumab, vocal rest, and proton pump inhibitors. Both had improvement in voice and resolution of the eschar and ulceration. Shallow sulci and mild breathiness persisted in one patient. With increasing use of potent systemic anti-angiogenic compounds, clinicians should be vigilant of this important complication of therapy. Time to onset of symptoms and reversibility of symptoms vary by patient and require further study. There may be long-term voice sequelae.


Immuno-deficiency in Schwartz-Jampel syndrome.
Two sisters born in a consanguineous marriage and affected by Schwartz-Jampel syndrome had a complex immunodeficiency, involving not only the humoral but also the cellular immune response.


A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer.
The study objective was to compare endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with mediastinoscopy for mediastinal lymph node staging of potentially resectable non-small cell lung cancer. Patients with confirmed or suspected non-small cell lung cancer who required mediastinoscopy to determine suitability for lung cancer resection were entered into the trial. All patients underwent EBUS-TBNA followed by mediastinoscopy under general anesthesia. If both were negative for N2 or N3 disease, the patient underwent pulmonary resection and mediastinal lymphadenectomy. Between July 2006 and August 2010, 190 patients were registered in the study, 159 enrolled, and 153 were eligible for analysis. EBUS-TBNA and mediastinoscopy sampled an average of 3 and 4 lymph node stations per patient, respectively. The mean short axis of the lymph node biopsied by EBUS-TBNA was 6.9 ± 2.9 mm. The prevalence of N2/N3 disease was 35% (53/153). There was excellent agreement between EBUS-TBNA and mediastinoscopy for mediastinal staging in 136 patients (91%; Kappa, 0.8; 95% confidence interval, 0.7-0.9). Specificity and positive predictive value for both techniques were 100%. The sensitivity, negative predictive value, and diagnostic accuracy for mediastinal lymph node staging for EBUS-TBNA and mediastinoscopy were 81%, 91%, 93%, and 79%, 90%, 93%, respectively. No significant differences were found between EBUS-TBNA and mediastinoscopy in determining the true pathologic N stage (McNemar's test, P = .78). There were no complications from EBUS-TBNA. Minor complications from mediastinoscopy were observed in 4 patients (2.6%). EBUS-TBNA and mediastinoscopy achieve similar results for the mediastinal staging of lung cancer. As performed in this study, EBUS-TBNA can replace mediastinoscopy in patients with potentially resectable non-small cell lung cancer.


Volatile methylsiloxanes through wastewater treatment plants - A review of levels and implications.
The use of siloxanes has been increasing due to physicochemical properties that are appropriate to be included in the formulations of a large variety of consumer products. This implies a considerable release of these chemicals into the environment, which caught the attention of the scientific community in view of some reports of potential hazardous effects. However, the studies related to the presence and partition of volatile methylsiloxanes (VMSs) in wastewater treatment plants (WWTPs) are still scarce. The aim of this review is to provide a comprehensive assessment of the current state of the knowledge concerning the presence of VMSs in WWTPs and also a discussion of the efficiency of the removal technologies available. Levels, fate and behaviour of VMSs in WWTPs were reviewed, covering not only the water and sludge lines during the treatment processes, but also in the surrounding air. Several approaches for the analysis of VMSs within the WWTPs have been developed to cope with the complexity of the mentioned matrices, which led to sometimes challenging protocols. Hence, an overview of methodologies normally used was also included in the present review. Regarding the wastewater samples, VMSs have been detected in influents in concentrations ranging from a few nanograms to a hundred micrograms per litre, in which linear VMSs were usually detected in lower levels than cyclic siloxanes. The levels of VMSs in effluents were lower than those found in influents, suggesting an effective removal from the water line. However, they are commonly accumulating in the sludge, instead of suffering degradation during the treatment process. Therefore, due to the volatile character of VMSs it can be expected that a fraction may be removed in WWTPs by volatilization, thus completing the mass balances to the whole treatment facilities.


Hormones and neurotransmitters control cyclic AMP metabolism in choroid plexus epithelial cells.
The choroid plexus is a major site of CSF production. When primary cultures of bovine choroid plexus epithelial cells were exposed to 1 micrograms/ml cholera toxin, a 50-fold increase of intracellular cyclic AMP was found 1 h later. Exposure of cells to 10(-5) M isoproterenol, 10(-4) M prostaglandin E1, 10(-5) M histamine, and 10(-5) M serotonin caused increases of intracellular cyclic concentrations of 100-, 50-, 20-, and 4-fold, respectively. From 5 to 15 min were required for these maximal responses to occur. Many other molecules including prolactin, vasopressin, and corticotropin did not alter cellular cyclic AMP levels. The accumulation of cyclic AMP could be inhibited by specific antagonists: propranolol inhibited the isoproterenol-mediated stimulation while diphenhydramine and metiamide inhibited the histamine response. In addition, diphenhydramine inhibited serotonin-dependent cyclic AMP accumulation. Combinations of isoproterenol, prostaglandin E1, histamine, and serotonin elicited additive responses as measured by cyclic AMP accumulation with one exception, i.e., serotonin inhibited the histamine response. Our findings suggest that distinct receptor sites on choroid plexus epithelia exist for isoproterenol, prostaglandin E1, and histamine. Efflux of cyclic AMP into the extracellular medium was found to be a function of the intracellular cyclic AMP levels over a wide range of concentrations. Our studies provide direct evidence for hormonal regulation of cyclic AMP metabolism in epithelial cells of the choroid plexus.


Serum Biomarkers for Autoimmune Hepatitis Type 1: the Case for CD48 and a Review of the Literature.
In autoimmune hepatitis (AIH), the persisting inflammation contributes to fibrosis progression, for which conventional biochemical markers manifest relatively unsatisfactory prediction. Herein, we assessed the value of serum CD48 (sCD48) as an indicator for inflammation and fibrosis in AIH type 1. The levels of sCD48 were detected first in an exploratory cohort using ELISA. In this cohort, compared with healthy controls (4.90 ng/mL, P < 0.0001), primary biliary cholangitis (7.32 ng/mL, P < 0.0001), and non-alcoholic fatty liver disease (7.76 ng/mL, P < 0.0001), sCD48 levels were elevated in AIH (12.81 ng/mL) and correlated with histological inflammation and fibrosis. Further using multivariate logistic regression analysis, sCD48 was identified as an independent predictor for both significant inflammation (G3-4) and advanced fibrosis (S3-4). Two predictive scores, based on sCD48, were constructed for diagnosing significant inflammation and advanced fibrosis (sCD48-AIH-SI and sCD48-AIH-AF, respectively). Using these data as a premise, predictive abilities were subsequently evaluated and verified in a validation cohort. In the exploratory cohort, the area under the receiver operating characteristic curve of sCD48 and sCD48-AIH-SI, for significant inflammation, were 0.748 and 0.813, respectively. Besides, during treatment follow-up, sCD48 levels gradually decreased from immunosuppression initiation to re-evaluation biopsy, in parallel with aspartate transaminase, total sera IgG, and fibrosis-4 score. For AIH patients in a re-evaluation biopsy cohort, sCD48 could predict significant fibrosis (S2-4). Further using immunohistochemistry, hepatic CD48 expression was elevated in AIH patients and decreased after treatment. In conclusion, sCD48 and sCD48-based predictive scores predict histological inflammation and fibrosis in AIH-1. Detecting sCD48 might help in the clinical management of AIH.


Sulfication-induced non-radiative electron-hole recombination dynamics in graphene quantum dots for tuning photocatalytic performance.
GQDs, or graphene quantum dots, are promising materials for energy-related applications. Their optoelectronic properties can be modified by adding heteroatoms, making them good candidates for photocatalysts. However, the structure-property relationship of these materials still needs to be investigated to control their properties better. In particular, photocatalysis of GQDs is hindered by non-radiative electron-hole recombination. In this study, density functional theory (DFT) calculations were performed to investigate the electronic structures and optical properties of GQDs doped with three distinct sulfur functional groups, i.e., sulfur oxide (O3HS), sulfhydryl (SH), and thiophene (C4H4S), respectively. The results suggest that sulfur doping decreases the GQD bandgap. In particular, the asymmetric capping of the GQD edges with the C4H4S groups led to additional peaks at low excitation energies, whereas for GQDs functionalized with O3HS or SH groups, only a shift in the main absorption peak or a change in the absorption intensity was observed. SH functionalization drastically increased electronic coupling, while C4H4S functionalization induced more charge-relaxation channels in the GQDs. Thus, the results shed light on the mechanisms governing the photocatalytic efficiency of GQDs.


Protein N-glycosylation in trypanosomatids. A pathway with odd enzymes at both ends.
This review deals with the pathway leading to the synthesis of asparagine-linked oligosaccharides in trypanosomatid protozoa. Special emphasis is put on steps differing from those occurring in mammalian cells.


6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39.
Many (dietary) bitter compounds, e.g. flavonoids, activate bitter receptor hTAS2R39 in cell-based assays. Several flavonoids, amongst which some flavanones, are known not to activate this receptor. As certain flavanones are known to mask bitter taste sensorially, flavanones might act as bitter receptor antagonists. Fourteen flavanones were investigated for their potential to reduce activation of hTAS2R39 by epicatechin gallate (ECG), one of the main bitter compounds occurring in green tea. Three flavanones showed inhibitory behavior towards the activation of hTAS2R39 by ECG: 4'-fluoro-6-methoxyflavanone, 6,3'-dimethoxyflavanone, and 6-methoxyflavanone (in order of decreasing potency). The 6-methoxyflavanones also inhibited activation of hTAS2R14 (another bitter receptor activated by ECG), though to a lesser extent. Dose-response curves of ECG at various concentrations of the full antagonist 4'-fluoro-6-methoxyflavanone and wash-out experiments indicated reversible insurmountable antagonism. The same effect was observed for the structurally different agonist denatonium benzoate.


Electrophysiological and histological studies of chronically implanted intrapapillary microelectrodes in rabbit eyes.
To determine the safety and efficacy of transsclerally placed intrapapillary wire microelectrodes implanted chronically into the optic nerve head of rabbit eyes. Four platinum wire microelectrodes were passed through the sclera and implanted into the optic nerve head of five rabbit eyes for 4-6 months. Color fundus photography, fluorescein angiography, electroretinograms (ERGs), and visually evoked potentials (VEPs) were used to monitor the retina. Electrically evoked potentials (EEPs) were elicited by bipolar electrical stimulation of the optic nerve axons by different combinations of the four electrodes immediately after the implantation and at 1-month intervals thereafter. The effects of the chronic implantation of the electrodes on the morphology of the optic nerve were evaluated by histological and immunohistochemical examinations at 4 and 6 months after the implantation. All of the electrodes remained stable in the implanted sites throughout the post-implantation period, except for one electrode that had pulled out of the optic nerve head at 1 month after implantation. No intraocular infection, inflammation, or vitreoretinal proliferation was observed in any eye. EEPs could be elicited from each pair of electrodes at all testing times. The mean threshold currents (charge densities) to evoke EEPs increased from 19.3 +/- 9.2 microA (6.0 +/- 2.9 microC/cm2) on the implantation day to 78.8 +/- 31.9 microA (24.6 +/- 10.0 microC/cm2) at 1 month after implantation, but did not change significantly thereafter. The implicit time and amplitude of the a- and b-waves of the ERGs and of P1 of the VEPs did not change significantly throughout the post-implantation period. Histological evaluation of the optic nerve head revealed slight tissue encapsulations surrounding the electrode and increased expression of glial fibrillary acidic protein near the surface of the optic nerve. Implantation of transscleral intrapapillary microelectrodes appears to be safe and effective. These findings indicate that the implantation of microelectrodes in the optic nerve head should be considered for an optic nerve-based prosthesis.