[Management of primary central nervous system lymphoma].
Primary CNS lymphoma is the malignant brain tumor whose prognosis has improved the most the two past decades. The majority of the patients achieve a complete remission with treatment and a substantial minority may hope to be cured. The treatment includes high-dose methotrexate polychemotherapy combined or not with whole brain radiotherapy (WBRT). Elderly patients who are exposed to a high risk of treatment induced neurotoxicity need a specific management avoiding or defering WBRT. In young patients, the main questions concerning the treatment are the role of consolidation WBRT and intensive chemotherapy with peripheral blood stem cell rescue in the initial treatment of PCNSL. As recently shown, national and international collaborative efforts make now possible randomized trials for this rare disease, which would contribute to better define the treatment strategy. New insights in PCNSL tumorigenesis would help to better understand the heterogeneity of outcome and to develop efficient targeted therapies.


The effect of adenine nucleotides on the rate and fate of glutamine utilization by incubated mitochondria isolated from rat mesenteric lymph nodes.
The rate of glutamine utilization by isolated lymphocyte mitochondria is 21.4 nmol/min per mg protein, of which 72% is converted to glutamate. Addition of ATP, ADP or AMP increased the rate of glutamine utilization by 60%. Evidence is presented that this is due to a stimulation of oxoglutarate dehydrogenase activity by ADP: this may account for the stimulation of glutamine utilization by concanavalin A in lymphocyte.


Preoperative external rotation deficit does not predict poor outcomes or lack of improvement after reverse total shoulder arthroplasty.
The purpose was to compare postoperative outcomes and functional improvement between patients with preoperative aER deficits vs. preserved aER function. There were 115 patients in the <0° aER group and 314 in the ≥30° aER group. Preoperative patients in the <0° group were worse for all measures except subjective pain while post-operatively, they had significantly greater improvement for all measures of motion. Postoperatively, both groups achieved comparable scores for forward elevation, pain, SST and ASES. This study demonstrates that patients with a complete aER deficit can recover substantial and comparable function after RTSA.


Study on the interaction of artificial and natural food colorants with human serum albumin: A computational point of view.
Due to the high amount of artificial food colorants present in infants' diets, their adverse effects have been of major concern among the literature. Artificial food colorants have been suggested to affect children's behavior, being hyperactivity the most common disorder. In this study we compare binding affinities of a group of artificial colorants (sunset yellow, quinoline yellow, carmoisine, allura red and tartrazine) and their natural industrial equivalents (carminic acid, curcumin, peonidin-3-glucoside, cyanidin-3-glucoside) to human serum albumin (HSA) by a docking approach and further refinement through atomistic molecular dynamics simulations. Due to the protein-ligand conformational interface complexity, we used collective variable driven molecular dynamics to refine docking predictions and to score them according to a hydrogen-bond criterion. With this protocol, we were able to rank ligand affinities to HSA and to compare between the studied natural and artificial food additives. Our results show that the five artificial colorants studied bind better to HSA than their equivalent natural options, in terms of their H-bonding network, supporting the hypothesis of their potential risk to human health.


Mutational analysis of the apical region of domain II of the HCV IRES.
The hepatitis C virus internal ribosome entry site (IRES) binds directly to the 40S ribosomal subunit via domains III/IV while domain II induces conformational changes on the ribosome which have been implicated in the decoding process. Here, we performed an extensive mutational study within the apical portion of domain II in order to address the functional role of this region on translation. Our results showed that the conservation of most nucleotides in this region was only partially related to the IRES function. Notwithstanding, however, selected single point mutations within the apical loop had a deleterious effect on IRES activity.


Cellular mechanism of bile acid-accelerated hepatocyte polarity.
We recently discovered that the major mammalian bile acid, taurocholate, accelerated polarity in primary rat hepatocytes. Taurocholate increased cellular cAMP and signals through an Epac-Rap1-MEK-LKB1-AMPK pathway for its polarity effect. This review discusses possible mechanisms for how taurocholate affects different cell polarity factors, particularly AMPK, and thereby regulates events that generate polarity. These include tight junction formation, apical trafficking, recycling endosome dynamics, and cytoskeleton rearrangement. We also discuss whether the effects of taurocholate are mediated by other LKB1 downstream kinases, such as Par1 and NUAK1.


High-order harmonic generation from a thin film crystal perturbed by a quasi-static terahertz field.
Studies of laser-driven strong field processes subjected to a (quasi-)static field have been mainly confined to theory. Here we provide an experimental realization by introducing a bichromatic approach for high harmonic generation (HHG) in a dielectric that combines an intense 70 femtosecond duration mid-infrared driving field with a weak 2 picosecond period terahertz (THz) dressing field. We address the physics underlying the THz field induced static symmetry breaking and its consequences on the efficient production/suppression of even-/odd-order harmonics, and demonstrate the ability to probe the HHG dynamics via the modulation of the harmonic distribution. Moreover, we report a delay-dependent even-order harmonic frequency shift that is proportional to the time derivative of the THz field. This suggests a limitation of the static symmetry breaking interpretation and implies that the resultant attosecond bursts are aperiodic, thus providing a frequency domain probe of attosecond transients while opening opportunities in precise attosecond pulse shaping.


Efficacy and safety of osimertinib for leptomeningeal metastases from EGFR-mutant non-small cell lung cancer: a pooled analysis.
The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs). A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies. Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.


Functional maps of the junctions between interglobular contacts and active sites in glycolytic enzymes -- a comparative analysis of the biochemical and structural data.
Oligomers and separate subunits of the glycolytic enzymes often have different catalytic properties. However, spectral data show an apparent lack of significant conformational changes during oligomerization. Since the conformation of an enzyme determines its catalytic properties, the structural mechanism(s) influencing the activity is of considerable interest. Analysis of the spatial structures of the junctions between interglobular contacts and binding sites may give a clue to the mechanism(s) of the activation. In this work, the problem was studied using available structural and biochemical data for the oligomeric enzymes of glycolysis. Computational analysis of the structures of the junctions has identified three structurally distinct types of junctions: 1. interglobular binding site (2 of 8 enzymes); 2. domain-domain stabilization (5 of 8); and 3. 'sequence overlap' or a local conformational change (all enzymes). Thus the catalytic activity may be influenced through the shifts of the modules of protein structure (types 1, 2) and/or due to a slight change in the local structure (type 3). The more common junctions of types 2 and 3 are well conserved among eukaryotic enzymes, which suggests their biological importance. The results suggest that a profound and a complex change in conformation in subunits of an oligomeric enzyme may not be necessary for a significant change in the catalytic properties. The analysis maps the residues important for the junctions and thus for the link between the catalytic activity and the oligomeric state of the enzymes.


[Application of the Gail method of calculating risk in the population of Valencia].
The objective of this study was to verify whether the method defined by Gail is applicable and predictive in a population of women in Valencia (Spain). Of the 685 patients diagnosed with breast cancer and attended-to in 2000-2001, 186 incident cases were identified. The variables studied were obtained from a specific questionnaire which included characteristics of reproductive history, number of biopsies and contraceptive pill consumption prior to the diagnosis. Using the model of the National Surgical Adjuvant Breast and Bowel Project (NSABP), an adaptation of the Gail model, the risk of developing breast cancer at 5 years was estimated. Only 40% of those women diagnosed as having breast cancer would have been identified as a high-risk patient by the Gail method. With our population group, the method detected the elderly women with a medical history of breast cancer who developed advanced stage disease. The Gail method does not adapt well to the study population of Valencia. It would be necessary to add other risk-factors to the Gail method so as to identify more patients in our area.


Flexible integration of continuous sensory evidence in perceptual estimation tasks.
Temporal accumulation of evidence is crucial for making accurate judgments based on noisy or ambiguous sensory input. The integration process leading to categorical decisions is thought to rely on competition between neural populations, each encoding a discrete categorical choice. How recurrent neural circuits integrate evidence for continuous perceptual judgments is unknown. Here, we show that a continuous bump attractor network can integrate a circular feature, such as stimulus direction, nearly optimally. As required by optimal integration, the population activity of the network unfolds on a two-dimensional manifold, in which the position of the network's activity bump tracks the stimulus average, and, simultaneously, the bump amplitude tracks stimulus uncertainty. Moreover, the temporal weighting of sensory evidence by the network depends on the relative strength of the stimulus compared to the internally generated bump dynamics, yielding either early (primacy), uniform, or late (recency) weighting. The model can flexibly switch between these regimes by changing a single control parameter, the global excitatory drive. We show that this mechanism can quantitatively explain individual temporal weighting profiles of human observers, and we validate the model prediction that temporal weighting impacts reaction times. Our findings point to continuous attractor dynamics as a plausible neural mechanism underlying stimulus integration in perceptual estimation tasks.


Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model.
We explore the use of a clinical orthovoltage X-ray treatment unit as a small-animal radiation therapy system in a tumoral model of cervical cancer. Nude mice were subcutaneously inoculated with 5 x 106 HeLa cells in both lower limbs. When tumor volume approximated 200 mm3 treatment was initiated. Animals received four 2 mg/kg intraperitoneal cycles (1/week) of cisplatin and/or 6.25 mg/kg of gemcitabine, concomitant with radiotherapy. Tumors were exposed to 2.5 Gy/day nominal surface doses (20 days) of 150 kV X-rays. Lead collimators with circular apertures (0.5 to 1.5 cm diameter) were manufactured and mounted on the applicator cone to restrict the X-ray beam onto tumors. X-ray penetration and conformality were evaluated by measuring dose at the surface and behind the tumor lobe by using HS GafChromic film. Relative changes in tumor volume (RTV) and a clonogenic assay were used to evaluate the therapeutic response of the tumor, and relative weight loss was used to assess toxicity of the treatments. No measurable dose was delivered outside of the collimator apertures. The analysis suggests that dose inhomogeneities in the tumor reach up to +/- 11.5% around the mean tumor dose value, which was estimated as 2.2 Gy/day. Evaluation of the RTV showed a significant reduction of the tumor volume as consequence of the chemoradiotherapy treatment; results also show that toxicity was well tolerated by the animals. Results and procedures described in the present work have shown the usefulness and convenience of the orthovoltage X-ray system for animal model radiotherapy protocols.


Characterization and comparison of gasification and incineration fly ashes generated from municipal solid waste in Singapore.
Slagging-gasification has received increasing attention as a municipal solid waste treatment technology. Compared with incineration, slagging-gasification can produce valuable syngas and generates by-products that can be easier reusable in different applications in some cases. Among these by-products, the gasification fly ash (GFA) is the only hazardous solid residue to be landfilled. To explore its potential recycling methods and maximize its recycling efficiency, the detailed physicochemical properties of GFA are crucial. This study conducted a comprehensive characterization of six GFA samples and the results were compared with one incineration fly ash (IFA) sample and available data of IFA collected in Singapore in literature. X-ray fluorescence (XRF), and microwave acid digestion (MAD) followed by inductively coupled plasma optical emission spectroscopy (ICP-OES) and inductively coupled plasma mass spectroscopy (ICP-MS) were carried out to determine the physicochemical composition of ashes. X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were applied to identify their mineralogical composition. The hazard of the material was assessed through one-stage batch leaching tests. The results showed that the GFAs and IFA were both mainly composed of calcium compounds and chloride salts. However, GFA contained higher amounts of heavy metals especially lead (Pb) and zinc (Zn) than IFA. Zn contents in tested GFA samples were in a range of 1.4-3.0%, indicating the potential to recover Zn. The Ca(OH)2 content in GFA samples was up to 24.1%, which could be recovered as a low-grade lime. Based on the characteristics of GFA, a reusing method combining civil engineering utilization and resource recovery was suggested.


Epilepsy and pregnancy. New issues for an old disorder.
Clinicians and their women patients with epilepsy face difficult decisions. There is evidence to suggest that antiepileptic drugs increase the risk of major malformations, minor anomalies, neonatal hemorrhage, and delayed fetal growth and development. Maternal seizures also appear to be disadvantageous to the fetus, increasing the risk of miscarriage, premature labor, intracranial hemorrhage, and perhaps, developmental or learning difficulties. Both medications and seizures have the potential to cause difficulties. This article discusses change in antiepileptic drug metabolism, changes in seizure frequency, adverse pregnancy outcomes, and principles of management.


Outcomes of lower urinary and bowel function in meningomyelocele patients with augmentation enterocystoplasty.
We evaluated the outcomes of augmentation ileocystoplasty in video-urodynamics (V-UDS) and questionnaires related to bowel and urinary function. In 22 meningomyelocele (MMC) patients (11 male and 11 female, a mean age at surgery 14.4 years) who underwent augmentation ileocystoplasties, V-UDS was performed before and at a median of 15 months (6-120 months) after the surgery and the questionnaires were answered at a median of 7.1 years (1.1-14.5 years) after surgery. Concomitant procedures of urethral sling in four, cecostomy in four and ureteral reimplantation in two were performed at augmentation ileocystoplasty. V-UDS showed a significant improvement after the surgery in bladder capacity, bladder compliance and detrusor overactivity. Vesicoureteral reflux (VUR) disappeared after the surgery in 16 of 19 ureters with VUR. Although questionnaire for urinary condition using International Consultation on Incontinence Questionnaire-Short Form demonstrated that 80% of patients were completely free from urinary incontinence after surgery, more than a half of patients had persistent or deteriorated bowel function such as urgency of bowel movement and fecal incontinence in questionnaires for bowel function. Even with complaints in bowel function, more than 80% of MMC patients had a high level of satisfaction with augmentation enterocystoplasty in overall quality of life (QOL). Benefits of augmentation ileocystoplasty were maintained in urodynamic parameters as well as urinary continence. Although augmentation ileocystoplasty generally provides high QOL for MMC patients refractory to conservative therapies, an advance of fecal management can make MMC patients' QOL superior to a current state.


Retrospective review of Google Trends to gauge the popularity of global surgery worldwide: A cross-sectional study.
Global surgery is a growing movement worldwide, but its expansion has not been quantified. Google Search is the most popular search engine worldwide, and Google Trends analyzes its queries to determine popularity trends. We used Google Trends to analyze the regional and temporal popularity of global surgery (GS). Furthermore, we compared GS with global health (GH) to understand if the two were correlated. This is a retrospective cross-sectional study examining Google Trends of GS and GH. We searched the terms "global surgery" and "global health" on Google Trends (Google Inc., CA, USA) from January 2004 to May 2021. We identified time trends and compared the two search terms using SPSS v26 (IBM, WA, USA) to run summary descriptive analyses and Wilcoxon rank-sum tests. The ten countries most interested in GS were India (5.0%), the United Kingdom (5.0%), Ireland (4.0%), the United States (4.0%), Australia (3.0%), Canada (3.0%), New Zealand (3.0%), Germany (2.0%), South Africa (2.0%), and Nigeria (1.0%). GS became more popular after 2015 (2.3% vs. 1.3%, P < 0.001) and was consistently less popular than GH (1.6% vs. 45.3%, P = 0.04). The difference between GS and GH interest levels increased after 2015 (45.4% vs. 42.9%, P = 0.04). GS is less popular than GH, more popular in high-income countries, and has become more popular after 2015 when the Lancet Commission on Global Surgery published its seminal report. The World Health Organization passed resolution WHA 68.15. Future advocacy efforts should target low- and middle-income countries primarily.


Efficient synthesis of 8-oxo-dGTP: a mutagenic nucleotide.
An efficient synthesis of mutagenic and oxidative DNA damage product, 8-oxo-dGTP (4) has been achieved in high yield, along with a serendipitous generation of 8-dimsyl-dG (2). In combination with dPTP (5), 8-oxo-dGTP (4) can be formulated into a kit for investigating DNA random mutagenesis.


Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCepsilon signaling and cardioprotection.
Aldehydes are common reactive constituents of food, water and air. Several food aldehydes are potentially carcinogenic and toxic; however, the direct effects of dietary aldehydes on cardiac ischemia-reperfusion (IR) injury are unknown. We tested the hypothesis that dietary consumption of aldehydes modulates myocardial IR injury and preconditioning. Mice were gavage-fed the alpha, beta-unsaturated aldehyde acrolein (5mg/kg) or water (vehicle) 24h prior to a 30-min coronary artery occlusion and 24-hour reperfusion. Myocardial infarct size was significantly increased in acrolein-treated mice, demonstrating that acute acrolein exposure worsens cardiac IR injury. Furthermore, late cardioprotection afforded by the nitric oxide (NO) donor diethylenetriamine/NO (DETA/NO; dose: 0.1mg/kg x 4, i.v.) was abrogated by the administration of acrolein 2h prior to DETA/NO treatment, indicating that oral acrolein impairs NO donor-induced late preconditioning. To examine potential intracellular targets of aldehydes, we investigated the impact of acrolein on mitochondrial PKCepsilon signaling in the heart. Acrolein-protein adducts were formed in a dose-dependent manner in isolated cardiac mitochondria in vitro and specific acrolein-PKCepsilon adducts were present in cardiac mitochondrial fractions following acrolein exposure in vivo, demonstrating that mitochondria are major targets of aldehyde toxicity. Furthermore, DETA/NO preconditioning induced both PKCepsilon translocation and increased mitochondrial PKCepsilon localization. Both of these responses were blocked by acrolein pretreatment, providing evidence that aldehydes disrupt cardioprotective signaling events involving PKCepsilon. Consumption of an aldehyde-rich diet could exacerbate cardiac IR injury and block NO donor-induced cardioprotection via mechanisms that disrupt PKCepsilon signaling.


Increased concentrations of arachidonic acid lipoxygenase metabolites in amniotic fluid during parturition.
This study was undertaken to examine whether spontaneous labor at term is associated with changes in the amniotic fluid concentrations of arachidonate lipoxygenase metabolites. Amniotic fluid was obtained from 15 women at term in active labor (with cervical dilatation of at least 6 cm) and from 15 nonlaboring control women matched for maternal age, parity, and gestational age. Cultures of amniotic fluid for bacteria and mycoplasma were negative. Products of arachidonate lipoxygenase metabolism--12-hydroxyeicosatetraenoic acid (12-HETE), 15-hydroxyeicosatetraenoic acid (15-HETE), and leukotriene B4--were measured by radioimmunoassay. The median concentrations of 12-HETE, 15-HETE, and leukotriene B4 in the amniotic fluid of nonlaboring women were 11.50 ng/mL, 0.45 ng/mL, and 21 pg/mL, respectively, and in the amniotic fluid of laboring women, 24.63 ng/mL, 4.34 ng/mL, and 96 pg/mL, respectively. The differences between labor and nonlabor amniotic fluid concentrations of all three lipoxygenase products were significant (P less than .05, Wilcoxon test). These observations are consistent with involvement of products of the lipoxygenase pathway of arachidonic acid metabolism in the mechanism of human parturition.


Impact of dexamethasone intraocular suspension 9% on intraocular pressure after routine cataract surgery: post hoc analysis.
To characterize intraocular pressure (IOP) response after treatment with dexamethasone intraocular suspension 9% vs placebo (vehicle) injection or topical prednisolone acetate 1% and to identify factors associated with increased IOP after cataract surgery. Data were pooled from two multicenter phase 3 clinical trials of patients undergoing routine cataract surgery. Randomized, double-blind study and open-label study. Subjects were randomized to treatment with dexamethasone intraocular suspension or placebo in the double-blind study 1 and to dexamethasone intraocular suspension or topical prednisolone acetate in the open-label study 2. Subjects who experienced 10 mm Hg or greater, 15 mm Hg or greater, or 20 mm Hg or greater postoperative IOP increase from baseline were stratified by baseline IOP. Univariate and multivariate logistic regression models of patient variables were applied to identify independent risk factors predictive of IOP elevation of 10 mm Hg or greater or 15 mm Hg or greater. The study comprised 414 subjects. Dexamethasone intraocular suspension was associated with a slightly higher mean IOP at the first postoperative visit vs prednisolone (P < .05); however, mean IOP was not statistically different between the 2 groups by postoperative day 8 (P = .5006) or thereafter. Univariate analysis showed that both prednisolone and dexamethasone intraocular suspension increased risk for postoperative IOP elevation compared with placebo; however, there was no statistically significant increased risk with dexamethasone intraocular suspension vs prednisolone. Aside from antiinflammatory treatment, risk factors for postoperative IOP elevation by univariate and multivariate analyses were higher baseline IOP, high myopia, and, when defining IOP increase as 15 mm Hg or greater from baseline, male sex. Dexamethasone intraocular suspension was associated with IOP elevation patterns comparable with topical prednisolone. High myopia, higher baseline IOP, and male sex were significant predictors of postoperative IOP elevation in this cohort.


Tilla König and the birth of the Camphill movement: an appreciation.
The purpose of this paper is to bring to the foreground someone who, through her own choice, sought to remain the background in the development of the worldwide Camphill Movement - Tilla Konig.


Determination of occlusal vertical dimension: a literature review.
The vertical dimension of occlusion refers to the length of the face as determined by the amount of separation of the jaws. Its determination is important for fabrication of all restorations. Many techniques have been used for measurement of the vertical dimension of occlusion in dentulous and edentulous patients. These range from using preextraction records to the use of swallowing, functionally acquired jaw positions associated with phonetics, and cephalometric radiographs and evaluation of radiopaque paste in the vestibular fornix. There is no universally accepted or completely accurate method of determining the vertical dimension of occlusion in edentulous patients. There seem to be no significant advantages of one technique other than those of cost, time, and equipment requirements. It is the end result that matters. It should be satisfactory to the dentist and the patient from an esthetic point of view and not induce degenerative changes from a functional standpoint. Regardless of the technique, the vertical dimension of occlusion must be determined carefully by the dentist for a successful prosthesis.


Hepatic artery aneurysm erosion into the stomach: an unusual cause of gastrointestinal bleeding.
Hepatic artery aneurysms are the second most common visceral aneurysms. The natural history of hepatic artery aneurysms typically results in enlargement, rupture, and life-threatening hemorrhage. Atherosclerosis, traditionally, has been the most common cause of hepatic artery aneurysm. A case of a hepatic artery aneurysm invading the stomach is presented to draw attention to the clinical presentation of this potentially catastrophic entity. A 74-year-old man presented to the Emergency Department (ED) with hematemesis. He was hemodynamically stable with a hemoglobin of 10.5. Abdominal CT imaging revealed a hepatic artery aneurysm that eroded into the stomach. The erosion was successfully repaired operatively and the aneurysm was embolized. The most common symptom is epigastric pain. The clinical and radiological findings of a hepatic artery aneurysm eroding into the stomach with subsequent upper and lower gastrointestinal hemorrhage, as highlighted in the case reported, have received little prior attention in the medical literature.


Magnification characteristics of fundus imaging systems.
To compare the magnification properties of 11 different fundus cameras (including 1 stereo fundus camera), a Rodenstock (infrared) scanning laser ophthalmoscope (SLO), the Heidelberg Laser Tomographic Scanner (LTS), and the Heidelberg Retina Tomograph (HRT). A cross-sectional study of the relationship between the true size of a fundus feature and its photographic-computer image in 14 different fundus imaging devices. This relationship was evaluated for each instrument using a model eye adjusted for axial ametropia between +11 diopter (D) and -14 D. To simulate refractive ametropia, the "crystalline lens" was removed to render the model eye aphakic, and the axial length was adjusted to give aphakic ametropia from emmetropia to +20 D. A correction factor (p) was calculated for each instrument, which can be used in calculations for determining true retinal size. The following were found to be of telecentric construction, Zeiss Oberkochen (WS240 Heidelberg), Zeiss Oberkochen (UK), Zeiss Oberkochen (Cologne), Nikon NF505, Kowa RCXV, SLO prototype (UK), LTS, and the HRT, and each exhibited a constant relationship between p and degree of ametropia of the model eye. The Canon CF6OU, Canon CF6OS, Canon CR4-45NM, Nidek 3-DX, Olympus GRCW, and Carl Zeiss Jena Retinophot were found not to be telecentric and exhibited a linear relationship between p and degree of ametropia of the model eye. For all instruments, p remained unchanged for axial and refractive ametropias of the same degree. The study has shown that not all fundus imaging systems are telecentric, so the use of a single magnification correction value may not be appropriate. These findings have important implications for the way in which true retinal size calculations are performed. Examples are given to show how the tabulated values of correction factors can be used for both telecentric and nontelecentric cameras in image size calculations.


Beyond the physician's perspective: A review of patient-reported outcomes in dermatologic surgery and cosmetic dermatology.
Patient-reported outcome measures (PROMs) are utilized in health care to quantify the patient's perspective of a health condition or treatment on outcomes, such as health-related quality of life (HRQoL) and patient satisfaction. In dermatology, this is particularly relevant because the patient's perspective is critical in evaluating the outcome of cosmetic procedures as well as skin cancer treatment. We review seven validated PROMs that have been reported in the dermatologic surgery and cosmetic dermatology literature. For patients undergoing cosmetic procedures, the use of PROMs provides additional valuable outcome data beyond physician assessment. For patients with skin cancer, women experience a unique and often greater impact on HRQoL during treatment, which has been captured through PROMs. The recent development of multi-module instruments, such as the FACE-Q and FACE-Q Skin Cancer, have facilitated comprehensive assessments of treatment that impact multiple domains of HRQoL. The use of PROMs allows for dermatologists to reliably capture important disease- and treatment-related concerns, thus improving the patient experience.


Diagnostic Performance of Endoscopic Ultrasonography with Water-Filled Balloon Method for Superficial Esophageal Squamous Cell Carcinoma.
Endoscopic ultrasonography (EUS) is a commonly used tool for preoperative depth diagnosis of superficial esophageal squamous cell carcinoma (ESCC). Probing EUS using the water-filled balloon method is a simple and safe examination. The aim of this study was to clarify the diagnostic performance of EUS with the water-filled balloon method for superficial ESCC compared to magnifying narrow-band imaging (ME-NBI). We retrospectively examined 403 lesions in 393 consecutive patients diagnosed with ESCC and evaluated them with ME-NBI and EUS. Clinicopathological findings were collected, and the accuracy of the preoperative diagnosis was compared between ME-NBI and EUS-B. EUS examiners were not blinded to prior ME-NBI results, and EUS results may have been influenced by ME-NBI results. The pathological tumor depth of the EP/LPM in 152 lesions, MM/SM1 in 130 lesions, and deep submucosa (SM2/SM3) in 121 lesions was examined. The proportion of total lesions with an accurate diagnosis was significantly higher in EUS than in ME-NBI (67.7% versus 62.0%, P = 0.015). When analyzed by clinical depth diagnosis using ME-NBI, the proportion of lesions with an accurate diagnosis was significantly higher for EUS in MM/SM1 (55.7% versus 46.1%, P = 0.033). The sensitivity was significantly higher in EUS for SM2/SM3 lesions (76.0% versus 54.5%, P < 0.001). The accuracy and specificity of EUS, which differentiate MM/SM1 from EP/LPM or SM2/SM3, were significantly higher than those of ME-NBI. The median endoscopic ultrasonography procedure time was approximately 6.5 min. EUS with the water-filled balloon method is a safe and straightforward method that can be performed on lesions clinically diagnosed as MM/SM1 using ME-NBI. We retrospectively reviewed lesions in patients diagnosed with ESCC and evaluated them using magnifying endoscopy with narrow-band imaging (ME-NBI) and endoscopic ultrasound using the water-filled balloon method (EUS-B). We conclude that EUS-B can increase the diagnostic accuracy.


[Not Available].
Influence of storage time and moisture content on the development of ochratoxin A and citrinin in legumes kernel of ecological and conventional provenance Mould growth can cause the occurrence of mycotoxins in grain and legumes. Less information is known for legumes of ecological provenance. For this reason a storage trial was carried out with peas and horse beans, to examine the production of ochratoxin A (OTA) and citrinin (CT) in legumes kernel from ecological provenance. For that purpose kernels from legumes were remoistened to different moisture contents (MC, 14%/19%) and stored 24 weeks in a research granary (tower silo). This experiment should simulate the storage situation in farm scale from winter to summer. Every four weeks, the CO2-content was determined and samples taken for the analysis of moisture, OTA and CT. At week 24 and a MC of <18% 1.9 μg OTA/kg of beans and 0.7 μg OTA/kg of peas (conventionally produced) were found.


Increased serotonin release in mice frontal cortex and hippocampus induced by acute physiological stressors.
The effects of acute physiological stressors (5 s tail pinch, handling and forced swimming at +25 and +5 degrees C for 3 min each) on serotonin (5-HT) release in the mouse brain were investigated using in vivo microdialysis. The extracellular 5-HT levels were determined by a newly developed highly-sensitive and selective high-performance liquid chromatography method based on derivatization with benzylamine and fluorescence detection. The basal levels of 5-HT in 3 min microdialysates from the ventral hippocampus and frontal cortex were 0.68+/-0.21 and 0.75+/-0.28 fmol/6 microl (n=24), respectively. All three stressors caused an immediate, significant and reversible increase (handling: 150%; swimming: 240%) of extracellular 5-HT levels in both brain structures, suggesting a more dynamic role played by the serotonergic system in response to acute stress.


Cooperation in group-structured populations with two layers of interactions.
Recently there has been a growing interest in studying multiplex networks where individuals are structured in multiple network layers. Previous agent-based simulations of games on multiplex networks reveal rich dynamics arising from interdependency of interactions along each network layer, yet there is little known about analytical conditions for cooperation to evolve thereof. Here we aim to tackle this issue by calculating the evolutionary dynamics of cooperation in group-structured populations with two layers of interactions. In our model, an individual is engaged in two layers of group interactions simultaneously and uses unrelated strategies across layers. Evolutionary competition of individuals is determined by the total payoffs accrued from two layers of interactions. We also consider migration which allows individuals to move to a new group within each layer. An approach combining the coalescence theory with the theory of random walks is established to overcome the analytical difficulty upon local migration. We obtain the exact results for all "isotropic" migration patterns, particularly for migration tuned with varying ranges. When the two layers use one game, the optimal migration ranges are proved identical across layers and become smaller as the migration probability grows.


Assessment of the individual and mixture toxicity of cadmium, copper and oxytetracycline, on the embryo-larval development of the sea urchin Paracentrotus lividus.
Multiple pollutions by trace metals and pharmaceuticals have become one of the most important problems in marine coastal areas because of its excessive toxicity on organisms living in this area. This study aimed to assess the individual and mixture toxicity of Cu, Cd, and oxytetracycline frequently existing in the contaminated marine areas and the embryo-larval development of the sea urchin Paracentrotus lividus. The individual contamination of the spermatozoid for 1 h with the increasing concentrations of Cd, Cu, and OTC decreases the fertility rate and increases larvae anomalies in the order Cu > Cd > OTC. Moreover, the normal larva frequency and the length of spicules were more sensitive than the fertilization rate and normal gastrula frequency endpoints. The mixture toxicity assessed by multiple experimental designs showed clearly that concentrations of Cd, Cu, and OTC superior to 338 μg/L, 0.56 μg/L, and 0.83 mg/L, respectively, cause significant larva malformations.


Plasma exchange and rituximab in the management of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus.
To report a case of acute occlusive retinal vasculopathy secondary to systemic lupus erythematosus (SLE) successfully treated with plasma exchange and rituximab Case report. A 25-year-old female presenting acutely with lupus retinal vasculitis was treated urgently with plasma exchange after failure to respond to intravenous methylprednisolone. Following this, fluorescein angiography demonstrated reperfusion of occluded arterioles. Visual acuity improved from 6/60 to 6/6 bilaterally. Remission was maintained following rituximab (Rituxan) in combination with mycophenolatemofetil and oral prednisolone. Early treatment with plasma exchange achieved reperfusion of the occluded microvascular circulation with correspondingly good visual recovery and should be considered when patients present with corticosteroid refractory retinal vasculitis associated with SLE.


Chromatographic separation of vitamin D3 sulfate and vitamin D3.
This paper describes a simple chromatographic technique on Sephadex LH20 for the separation of vitamin D3 sulfate from free vitamin D3 and its metabolites. This technique has been used in the study of vitamin D3 sulfate metabolism in rats. Seven hours after injection of vitamin D3 sulfate (35S or 35S and 3H) only the peak of vitamin D sulfoconjugate was found in chromatographic elution of serum extracts.


In vivo diode dosimetry for total marrow irradiation.
To describe a method and evaluate the efficacy of using a p-type silicon diode as an alternative to thermoluminescent dosimeters for verifying the accuracy of total marrow irradiation setups and calculations. A calibration factor has been measured for a 6 MV photon beam incident horizontally onto a polystyrene phantom inside an in-house built total marrow irradiation stand. Signal responses due to positioning and orientation of the diode with respect to the source were compared to a 0.6 cc cylindrical ionization chamber inside a polystyrene phantom. Procedures for predicting the diode reading and taking entrance measurements have been developed and action levels established to determine causes for discrepancies when ratios between predicted and actual values fell outside a +/- 5% tolerance range. Measurements were taken at the skin surface over the umbilicus calculation point for alternating 1.5 Gy anterior and posterior fractions given bidaily over a 3-day period. A total of 137 measurements taken from January to September 1994 for 23 patients were analyzed using a frequency histogram. The histogram indicated a mean reading of 1.002 +/- 2.6, and that three of the measurements fell outside the 5% tolerance. Investigation into the cause of the discrepancies showed that the diode had been improperly placed one time and that further patient immobilization needs to be considered. It is possible to use a diode as an in vivo dosimeter for a total marrow irradiation technique. The ease of implementation and immediate readouts make a diode system preferable to a thermoluminescent system for identifying systematic errors and verifying treatment configurations and monitor unit calculations.


Hooded broadcast sprayer for particle drift reduction.
There is renewed interest amongst crop protection professionals and regulators in the adoption of spray hoods to further reduce pesticide off-target movement during applications. Although the benefits of sprayer hoods have been reported since the early 1950s, adoption has been relatively low among farmers and applicators. The objective of this study was to evaluate the effectiveness of spray hoods in reducing pesticide drift of spray solutions from nozzles typically used for herbicide applications in row crops with tolerance to dicamba or 2,4-D. Hooded applications substantially reduced spray drift potential across all treatment scenarios compared to conventional applications. Hooded applications using the AIXR nozzle without drift-reducing adjuvant (DRA) had a similar area under the drift curve (31.5) compared to conventional applications (open sprayer) using the TTI nozzle with DRA (27.7), despite the major droplet size differences between these treatments (DV50 = 447.5 and 985 μm, respectively). These results indicate that the adoption of spray hoods combined with proper nozzle selection, and the use of DRAs can substantially reduce spray drift potential during pesticide applications. The use of this technology can be complementary to other drift-reducing technologies. © 2021 Society of Chemical Industry.


Increased tacrolimus blood concentration by Beni-Madonna - a new hybrid citrus cultivar categorized as 'Tangor', in a liver transplant patient: likely furanocoumarin-mediated inhibition of CYP3A4 or P-glycoprotein.
A drug interaction leading to greater exposure to tacrolimus. Tacrolimus and Beni-Madonna (a new cultivar citrus categorized as 'Tangor'). A 9-month-old girl with biliary atresia (body weight, 7.5 kg) taking tacrolimus after liver transplantation. The time course was consistent with the appearance of the interaction, which was confirmed by an increase in the blood concentration of tacrolimus. Dihydroxybergamottin was detected in peel of Beni-Madonna and in peel and fruit pulp of grapefruit. Avoiding Beni-Madonna intake. Inhibition of activity of CYP3A4, P-glycoprotein, or both, by Beni-Madonna. Clinicians should be aware of this potential interaction, and patients taking drugs such as tacrolimus (the kinetics of which are affected by grapefruit juice) should avoid Beni-Madonna intake. Further study is required to determine if other Citrus species categorized as Tangor contain furanocoumarins.


Assessing the susceptibility and efficacy of traditional neurotoxic (pyrethroid) and new-generation insecticides (chlorfenapyr, clothianidin, and pyriproxyfen), on wild pyrethroid-resistant populations of Anopheles gambiae from southern Benin.
The objective of this study was to determine the susceptibility of wild Anopheles gambiae sensu lato (s.l.) from southern Benin to the new insecticides (chlorfenapyr (CFP), pyriproxyfen (PPF), and clothianidin (CTD)) and assess the efficacy of insecticide-treated bed nets (ITNs) that contain these new products. Wild An. gambiae from the Benin communes of Allada, Ifangni, Akpro-Missérété, and Porto-Novo were tested for their susceptibility to CFP and PPF using the WHO bottle tests, and pyrethroids (alpha-cypermethrin, deltamethrin, and permethrin) and CTD using WHO tube tests. WHO cone tests were used to evaluate the efficacy of Interceptor® (which contains alpha-cypermethrin (ACM) only), Interceptor® G2, (CFP + ACM), and Royal Guard® nets (PPF + ACM). The ovaries of blood-fed An. gambiae from Ifangni exposed to a new PPF net were dissected, and egg development status was examined using Christopher's stages to determine the fertility status of the mosquitoes. Using a standardized protocol, the oviposition rate and oviposition inhibition rate were calculated from live blood-fed An. gambiae placed in oviposition chambers after exposure to PPF. In all four mosquito populations, pyrethroid mortality ranged from 5 to 80%, while chlorfenapyr and clothianidin mortality ranged from 98 to 100%. At Ifangni, all mosquitoes exposed to Royal Guard® nets were infertile (100%) while the majority (74.9%) of mosquitoes exposed to Interceptor® nets had fully developed their eggs to Christopher's stage V. The oviposition inhibition rate after exposure of the mosquitoes to the PPF was 99% for the wild population of An. gambiae s.l. and the susceptible laboratory strain, An. gambiae sensu stricto (Kisumu). The results of this study suggest that pyrethroid-resistant An. gambiae from the selected communes in southern Benin are susceptible to chlorfenapyr, clothianidin, and pyriproxyfen. In addition, based on bioassay results, new and unused Interceptor® G2 and Royal Guard® nets were effective on Ifangni's mosquito populations. Despite the availability of new effective insecticides, continued vigilance is needed in Benin. Therefore, monitoring of resistance to these insecticides will continue to periodically update the Benin national insecticide resistance database and management plan.


Application of alkaloids in reversing multidrug resistance in human cancers.
Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.


Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction.
Eukaryotic protein degradation by the proteasome and the lysosome is a dynamic and complex process in which ubiquitin has a key regulatory role. The distinctive morphology of the postmitotic neuron creates unique challenges for protein degradation systems with respect to cell-surface protein turnover and substrate delivery to proteolytic machineries that are required for both synaptic plasticity and self-renewal. Moreover, the discovery of ubiquitin-positive protein aggregates in a wide spectrum of neurodegenerative diseases underlines the importance and vulnerability of the degradative system in neurons. In this article, we discuss the molecular mechanism of protein degradation in the neuron with respect to both its function and its dysfunction.


Surgical removal of an undifferentiated abdominal sarcoma from a koi carp (Cyprinus carpio).
An undifferentiated abdominal sarcoma was removed surgically from a koi carp. The diagnostic procedures, including radiography and computed tomography, and the procedures for general anaesthesia and the surgical approach for a celiotomy in a fish are described. The gross and microscopic appearance of the tumour is described and illustrated.


Chemotactic activity of lectins in vitro.
The effects of concanavalin A (Con A) and leucoagglutinin (LA) on the locomotor response of phagocytes have been studied in vitro. At concentrations of 1 to 4 microgram/mol, Con A and LA induced maximal chemokinesis and chemotaxis of monocytes, macrophages and, to a lesser degree, also of neutrophils. The lectin-induced locomotion was accompanied by membrane alterations and metabolic changes, as shown by an increase of the 3H-uridine uptake and a rise of the hexose monophosphate shunt activity. The chemotactic activity of Con A was inhibited by alpha-methyl mannoside (50 mM) or by pretreatment of the cells with trypsin. These data indicate that lectins such as Con A induce chemotaxis by a specific binding to receptors of the cell membrane. It is suggested that bivalent ligand binding is required as a signal to elicit chemotactic locomotion.


Rectal fold thickness as an indicator of disease.
Rectal folds are seen best in the lateral view. Normal values for the thickness of the folds have been established by measuring these in patients with a diagnosis of irritable bowel syndrome who had no evidence of rectal disease. In severe ulcerative colitis the valves disappear, but they are present earlier in the disease. The first barium enema examination in patients with ulcerative colitis was assessed. When the valve thickness could be measured in these patients it showed values significantly greater than normal. It is uncommon for this finding to be the sole indicator of disease. Patients with Crohn's disease of the rectum showed no increase in the fold thickness. This observation may be helpful in distinguishing between these two forms of colitis.


A new method for assaying rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and its application in a study of the effect of dietary cholesterol on this effect of dietary cholesterol on this enzyme.
A new method suitable for measuring rat liver 3-hydroxy-3-methylglutaryl-CoA reductase activity is described and its advantages over methods previously available are discussed. An accurate time course was measured for the inhibition of liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase activity by dietary cholesterol; this enzyme was affected 1 1/4 h after the rats began to consume a cholesterol-rich diet. In this experiment there was no correlation between concentrations of microsomal cholesterol ester and the activity of 3-hydroxy-3-methylglutary-CoA reductase.


Cardiac paraganglioma (chemodectoma): a case report and review of the literature.
A rare case of paraganglioma (chemodectoma) of the heart is reported. This is the fifth case reported in the world literature and only the second case discovered in a living person. A review of the historical background, embryology, anatomy, and pathology of the paraganglia is provided. The previously reported four cases are also discussed.


High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease.
Anderson-Fabry disease is a rare lysosomal storage disorder. It results from a deficiency of the lysosomal alpha-galactosidase A and leads to progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. Some of the typical clinical findings such as tiredness, dry skin, myalgia and arthralgia as well as vague gastrointestinal complaints are also symptoms of hypothyroidism. Therefore, we studied the thyroid function in patients with Anderson-Fabry disease. Thyroid function was studied in 11 patients (6 female, 5 male) with Anderson-Fabry disease by measuring thyroid-stimulating hormone (TSH) and free thyroxine serum levels. Nine patients had chronic kidney disease with stage 1 and two with stage 5. Subclinical hypothyroidism (normal serum free thyroxine concentrations along with elevated serum TSH levels) was found in 4 of 11 patients (36.4%). Subclinical hypothyroidism was observed in both male and female patients as well as in patients with stage 1 and stage 5 kidney disease. Subclinical hypothyroidism is a common finding in patients with Anderson-Fabry disease, showing an excess prevalence as compared to the normal population. The high frequency seems to be relevant regarding the potential consequences of a hypothyroid state.


The artificial urinary sphincter in the female: indications for use, surgical approach and results.
Female urinary incontinence is a common problem. Among the many treatment options a few patients may be suitable candidates for the artificial urinary sphincter (AUS). The indications for placement of an AUS are much more common in males: however, we review the indications, technique and potential complications of the AUS in the female population. Although few indications exist for the placement of an AUS in women, if proper patient selection is made, with strict adherence to proper surgical technique, it can be a suitable treatment option for those suffering from sphincteric incontinence.


What we have learned about conducting randomized controlled trials in the NICHD MFMU network.
The National Institute of Child Health and Human Development (NICHD) created the NICHD Maternal Fetal Medicine Units Network in 1986 to conduct randomized trials and observational studies in perinatal medicine to improve adverse pregnancy and infant outcomes. From 1986 to 2002, the Network has started 16 randomized trials. Five of the trials are described, with particular attention given to difficult issues that arose, such as feasibility, sample size estimation, randomization in very high risk pregnancies, changing clinical practice, importance of the study question to the investigators, and lack of recruitment. Changes that the Network group made to their organization and methodology as a result of these issues are described, together with their application to some of the other trials proposed and conducted by the group.


Bacterial redox protein azurin induce apoptosis in human osteosarcoma U2OS cells.
As a low molecular weight redox protein elaborated from the pathogenic bacteria Pseudomonas aeruginosa, azurin is one of representative bacterial products applied in the treatment of tumour. We found that the growth of U2OS cells was significantly inhibited by azurin in a dose-dependent manner with the IC(50) value of 114.54+/-7.65 mgl(-1). But the growth of MG63 cells or L02 cells was almost not inhibited by azurin (P<0.05). Moreover, when treated with azurin, U2OS cells showed typical apoptotic morphological features observed by fluorescent microscopy (AO and Hoechst 33258) and transmission electron microscopy. Typical DNA "ladder" bands were also observed. The apoptosis rate was 35.8% tested by fluorescence-activated cell sorter (Annexin-V-FITC(+)/PI(-)) and the cell-cycle arrested in G(1) phase. But no apoptotic features were observed in control cells. The down-regulation of Bcl-2 (an inhibitor of apoptosis) were detected in U2OS cells when azurin was added for 24h. In contrast, the level of Bax and caspase-3 were significantly up-regulated. So we concluded that azurin could selectively induce apoptosis of human osteosarcoma U2OS cells and the induction of apoptosis by azurin was closely associated with down-regulation of Bcl-2, up-regulation of Bax and activation of caspase-3.


Sudden quench of harmonically trapped mass-imbalanced fermions.
Dynamical properties of two-component mass-imbalanced few-fermion systems confined in a one-dimensional harmonic trap following a sudden quench of interactions are studied. It is assumed that initially the system is prepared in the non-interacting ground state and then, after a sudden quench of interactions, the unitary evolution is governed by interacting many-body Hamiltonian. By careful analysis of the evolution of the Loschmidt echo, density distributions of the components, and entanglement entropy between them, the role of mass imbalance and particle number imbalance on the system's evolution stability are investigated. All the quantities studied manifest a dramatic dependence on the number of heavy and lighter fermions in each component at a given quench strength. The results may have implications for upcoming experiments on fermionic mixtures with a well-defined and small number of particles.


Chlordiazepoxide and stress tolerance in rats.
Intraperitoneal injections of chlordiazepoxide in rats attenuated the severity of stomach ulcers induced by a single restraint session. However, when the drug was withheld during the last session of a series of repeated restraint treatments, stomach erosions developed in the animals. Vehicle-controls, on the other hand, had adapted to the chronic stress, as indexed by a decline in gastric pathology. The results were discussed in reference to stress adaptation and drug withdrawal effects.


A unique mRNA species for a regulatory subunit of cAMP-dependent protein kinase is specifically induced in haploid germ cells.
Cyclic AMP (cAMP) and its action by way of cAMP-dependent protein kinase is important for sperm motility. Previous studies on germ cells have demonstrated a selective decrease in the amount of type I cAMP-dependent protein kinase during spermatid development, and that type II was the major form present in elongating spermatids and in mature sperm. This would indicate activation of a gene in haploid germ cells, encoding a regulatory subunit of type II protein kinase. However, haploid expression of such a gene has so far not been shown. In the present study we demonstrate high-levelled expression of a unique mRNA species for a specific regulatory subunit of type II cAMP-dependent protein kinase at late stages of spermatogenesis, i.e. during spermatid elongation.


Nanotechnology application in food packaging: A plethora of opportunities versus pending risks assessment and public concerns.
Environmental factors, oxidation and microorganisms contamination, are the major causes for food spoilage, which leads to sensory features alteration, loss of quality, production of harmful chemicals and growth of foodborne pathogens capable to cause severe illness. Synthetic preservatives, traditional conserving methods and food packaging (FP), although effective in counteracting food spoilage, do not allow the real-time monitoring of food quality during storage and transportation and assent a relatively short shelf life. In addition, FP may protect food by the spoilage caused by external contaminations, but is ineffective against foodborne microorganisms. FP preservative functionalities could be improved adding edible natural antioxidants and antimicrobials, but such chemicals are easily degradable. Nowadays, thanks to nanotechnology techniques, it is possible to improve the FP performances, formulating and inserting more stable antioxidant/antimicrobial ingredients, improving mechanical properties and introducing intelligent functions. The state-of-the-art in the field of nanomaterial-based improved FP, the advantages that might derive from their extensive introduction on the market and the main concerns associated to the possible migration and toxicity of nanomaterials, frequently neglected in existing reviews, have been herein discussed.


Alterations in the maternal behavior of rats rearing malnourished offspring.
Investigations of maternal behavior of mothers fed a low-protein diet indicated deficits in retrieval and in the rate of nest-building. In addition, they indicated a concomitant increase in time spent with young when assessed during periods not associated with the retrieval/nest-building test session. The adrenalectomized mother, another case that produces growth-stunted progeny, was compared with both low-protein and control mothers for maternal behavior. Unlike the low-protein mother, the adrenalectomized mother did not exhibit retrieval or nest-building deficits; however, the adrenalectomized mother did display an increase in time spent with young. These data suggest that although deficits in retrieval and nest-building can be attributed to the nutritional condition of the mother, the stimulus characteristics of the malnourished pup are important in eliciting the increased time spent with the litter.


Synthesis of a new chiral N,N,N-tridentate pyridinebisimidazoline ligand library and its application in Ru-catalyzed asymmetric epoxidation.
A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (>99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins. [reaction: see text]


Promotion of granular activated carbon on methanogenesis of readily acidogenic carbohydrate-rich waste at low inoculation ratio.
Although granular activated carbon (GAC) supplementation into food waste anaerobic digestion system is an efficient means to enhance methane production. As yet, little is known whether GAC supplementation is suitable for the extreme condition of pH below 4.5, which occurs in the use of readily acidogenic carbohydrate-rich waste (RACW) as methanogenic substrate when at low inoculation/substrate (I/S) ratio. This study investigated the effects of GAC on RACW anaerobic digestion under different inoculation/substrate (I/S) ratios. It was found that the addition of GAC was a preferred alternative method to enhancing I/S ratio for promoting methane production from RACW. The additive dose of 20 g/L was recommended for the methanogenesis of RACW at low I/S of 1:2, and the methane yield was enhanced by 12 times (505 mL/g-VS) compared with that (42 mL/g-VS) from the control. This promotion resulted from the apparently solving the over-acidogenesis problem and the adjustment of pH to the desired range. Further investigation revealed that the added GAC enhanced the activities of acetate kinase and coenzyme F420, that engaged in the acidogenic and methanogenic reactions. Meanwhile, the decrease of hydrogenase and increase of c-Cyts implied that the metabolism of direct interspecies electron transfer (DIET) was probably stimulated by GAC. Microbial investigation inferred that the enriched hydrogenotrophic methanogens and DIET-mediated syntrophic partners of Geobacter/Syntrophomonas with Methanosarcina were responsible for the enhanced methane yield.


Selective partitioning of cholesterol and a model drug into liposomes of varying size.
The resistance of a lipid bilayer with respect to a bending deformation generally depends on the presence of membrane additives such as sterols, cosurfactants, peptides, and drugs. As a consequence, the partitioning of membrane additives into liposomes becomes selective with respect to liposome size; i.e., membrane rigidification depletes the membrane additives in the smaller (more strongly curved) liposomes. We have measured this liposome size-selective partitioning for two membrane additives - cholesterol and the porphyrin-based photosensitizer temoporfin - using asymmetrical flow field-flow fractionation (AF4) of liposomes and radioactive labeling of the membrane additive and lipid. The method yields either the molar cholesterol-to-lipid or the temoporfin-to-lipid ratio as a function of liposome size, from which we calculate the corresponding change of the membrane bending stiffness. For small unilamellar fluid-phase liposomes composed of palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylglycerol (POPG), we find that cholesterol rigidifies the host membrane in a manner consistent with previously reported measurements. In contrast, temoporfin softens this membrane. Partitioning results for gel-phase liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) are also curvature-sensitive but cannot be interpreted on the basis of the bending stiffness alone.


Neighborhood socioeconomic status is associated with low diversity gut microbiomes and multi-drug resistant microorganism colonization.
Social disparities continue to limit universal access to health care, directly impacting both lifespan and quality of life. Concomitantly, the gut microbiome has been associated with downstream health outcomes including the global rise in antibiotic resistance. However, limited evidence exists examining socioeconomic status (SES) associations with gut microbiome composition. To address this, we collected information on the community-level SES, gut microbiota, and other individual cofactors including colonization by multidrug-resistant organisms (MDROs) in an adult cohort from Wisconsin, USA. We found an association between SES and microbial composition that is mediated by food insecurity. Additionally, we observed a higher prevalence of MDROs isolated from individuals with low diversity microbiomes and low neighborhood SES. Our integrated population-based study considers how the interplay of several social and economic factors combine to influence gut microbial composition while providing a framework for developing future interventions to help mitigate the SES health gap.


Preparation modifications for damaged vital posterior teeth.
The preservation of a severely damaged tooth with a cast restoration requires that the preparation be modified to make use of remaining tooth structure. Preexisting preparation features, such as boxes and isthmuses, and new ones, such as boxes, grooves, and pin holes, are employed to provide adequate retention and resistance. When destruction of coronal tooth structure exceeds one-half of the clinical crown, a pin-retained amalgam or composite resin core should be used to build up the tooth to receive a cast restoration.


Long-term increase of CD4+ central memory cells in HIV-1-infected individuals by therapeutic HIV-1 rgp160 immunization.
To evaluate functional potential and phenotypic markers in HIV-1-infected patients immunized with HIV-1 rgp160. We assessed changes in T-cell phenotype and immune function in 12 HIV-1-infected individuals that were part of a therapeutic vaccine study from 1992 to 1995 [Sandstrom E, Wahren B. Therapeutic immunisation with recombinant gp160 in HIV-1 infection: a randomised double-blind placebo-controlled trial. Nordic VAC-04 Study Group. Lancet 1999;353(9166):1735-42]. The patients received 160 microg HIV-1 rgp160 or placebo i.m. at baseline (day 0), and months 1, 2, 3, 4, 6, and thereafter every 3 months. Frozen peripheral blood mononuclear cells (PBMC) were retrieved from time points 0, 9, 12 and 24 months for phenotypic analysis utilizing flow cytometry. Up-regulation of immune activation markers HLA-DR and CD38 was observed at baseline and throughout the monitoring period on both CD4+ and CD8+ T cells in all patients, reflecting immune activation due to persistent high viral load. Further enhanced expression of activation markers was observed over time in the vaccine group, but not the placebo group. We also observed a consistent long-term increase of the CD4+ central memory population (CD3+CD4+CD45RA-CCR7+) in the vaccinated group. Administration of eight doses of rgp160 in a year appeared to partially reverse some of the defects exerted by HIV-1 on the immune system. A combination of vaccination with effective antiretroviral therapy (ART) may thus represent an immunotherapeutic intervention for treatment of chronic HIV-1 infection. The improvement of a HIV-1-specific central memory population and HIV-1 antigen-specific CD4+ lymphoproliferative responses may have contributed to the short-term improved survival reported in the vaccinated group.


Influence of electrical isolation on the structure and reflectivity of multilayer coatings deposited on dielectric substrates.
Multilayers prepared with electrically isolated or grounded surfaces during deposition are shown to have dramatically different hard-x-ray, soft-x-ray, and neutron reflectivity characteristics. The effect has been observed for (100) silicon wafers, fused silica, and borate glass substrates of different sizes and with different surface roughness and flatness for multilayer structures prepared by rf and dc magnetron sputtering.


Patients' Experiences With the Removal of a Ureteral Stent: Insights From In-depth Interviews With Participants in the USDRN STENTS Qualitative Cohort Study.
To describe the experiences of patients undergoing stent removal in the USDRN Study to Enhance Understanding of Stent-Associated Symptoms (STENTS), a prospective, observational cohort study of patients with short-term ureteral stent placement post-ureteroscopy. We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) painful or bothersome aspects of stent removal, (2) symptoms immediately after removal, and (3) symptoms in the days following removal. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. The 38 participants interviewed were aged 13-77 years, 55% female, and 95% White. Interviews were conducted 7-30 days after stent removal. Almost all participants (n = 31) described that they experienced either pain or discomfort during stent removal, but for most (n = 25) pain was of short duration. Many participants (n = 21) described anticipatory anxiety related to the procedure, and several (n = 11) discussed discomfort arising from lack of privacy or feeling exposed. Interactions with medical providers often helped put participants at ease, but also increased discomfort for some. Following stent removal, several participants described lingering pain and/or urinary symptoms, but these largely resolved within 24 hours. A few participants described symptoms persisting for more than a day post stent removal. These findings on patients' experiences during and shortly after ureteral stent removal, particularly the psychological distress they experienced, identify opportunities for improvement in patient care. Clear communication from providers about what to expect with the removal procedure, and the possibility of delayed pain, may help patients adapt to discomfort.


Cryptosporidium parvumcompetes with the intestinal epithelial cells for glucose and impairs systemic glucose supply in neonatal calves.
Cryptosporidiosis is one of the main causes of diarrhea in children and young livestock. The interaction of the parasite with the intestinal host cells has not been characterized thoroughly yet but may be affected by the nutritional demand of the parasite. Hence, we aimed to investigate the impact of C. parvum infection on glucose metabolism in neonatal calves. Therefore, N = 5 neonatal calves were infected with C. parvum on the first day of life, whereas a control group was not (N = 5). The calves were monitored clinically for one week, and glucose absorption, turnover and oxidation were assessed using stable isotope labelled glucose. The transepithelial transport of glucose was measured using the Ussing chamber technique. Glucose transporters were quantified on gene and protein expression level using RT-qPCR and Western blot in the jejunum epithelium and brush border membrane preparations. Plasma glucose concentration and oral glucose absorption were decreased despite an increased electrogenic phlorizin sensitive transepithelial transport of glucose in infected calves. No difference in the gene or protein abundance of glucose transporters, but an enrichment of glucose transporter 2 in the brush border was observed in the infected calves. Furthermore, the mRNA for enzymes of the glycolysis pathway was increased indicating enhanced glucose oxidation in the infected gut. In summary, C. parvum infection modulates intestinal epithelial glucose absorption and metabolism. We assume that the metabolic competition of the parasite for glucose causes the host cells to upregulate their uptake mechanisms and metabolic machinery to compensate for the energy losses.


Management of superior oblique overaction in A-pattern deviations.
Surgical management of overaction of the superior oblique muscle is discussed with reference to such conditions as A-pattern, Brown's syndrome, torsional torticollis, and homolateral inferior oblique or contralateral inferior rectus paresis. The authors perform weakening of the superior oblique from the temporal side of the superior rectus for slight or moderate overaction. They prefer posterior tenectomy for mild overaction and scleral disinsertion of the tendon in moderate overaction causing A-pattern of no more than 25 pd. With 25-30 pd. they perform translation-recession of the muscle by the nasal approach.


[Comparative magnetic resonance imaging of renal space-occupying lesions with a high and low field MRI system].
A prospective study of the diagnostic accuracy and image quality of two MRI systems in the detection of renal tumors was investigated. 34 patients with the clinical suspicion of a space-occupying renal lesion were examined by MRI with a low field (0.2 Tesla magnet) and a high field (1.5 Tesla magnet) for comparison. An "informed" and a "blind" observer evaluated all of the MR images. In addition, the signal-to-noise and contrast-to-noise ratios were evaluated as second quality parameters. In 29 cases the results could be compared with a confirmed release diagnosis. Diagnostic accuracy was comparable with both systems (Sensitivity for both observer on LF apparatus: 83%, HF apparatus: 81%) although the signal-to-noise and contrast-to-noise ratios were significantly poorer at low field. The low field system in comparable to the high field MRI for detection and differentiation of renal space-occupying lesions.


Bullous acrodermatitis enteropathica: case report of a unique clinical presentation and review of the literature.
Acrodermatitis enteropathica is a rare autosomal recessive disease characterized by pink scaly plaques and erosions in the periorificial and acral regions. A mutation in a gene responsible for zinc transport results in significant zinc deficiency in individuals lacking oral supplementation. We present a female infant with acrodermatitis enteropathica with crusting of the periorificial regions along with perineal plaques. A delay in diagnosis and treatment led to the development of pronounced painful acral bullae. Although plaques and erosions in the periorificial and acral regions are most commonly observed, bullae should also be considered in the spectrum of clinical manifestations of acrodermatitis enteropathica. The rare bullous variant of acrodermatitis enteropathica can be distinguished histologically.


FAMSi: A Synthetic Biology Approach to the Fast Assembly of Multiplex siRNAs for Silencing Gene Expression in Mammalian Cells.
RNA interference (RNAi) is mediated by an ∼21-nt double-stranded small interfering RNA (siRNA) and shows great promise in delineating gene functions and in developing therapeutics for human diseases. However, effective gene silencing usually requires the delivery of multiple siRNAs for a given gene, which is often technically challenging and time-consuming. In this study, by exploiting the type IIS restriction endonuclease-based synthetic biology methodology, we developed the fast assembly of multiplex siRNAs (FAMSi) system. In our proof-of-concept experiments, we demonstrated that multiple fragments containing three, four, or five siRNA sites targeting common Smad4 and/or BMPR-specific Smad1, Smad5, and Smad8 required for BMP9 signaling could be assembled efficiently. The constructed multiplex siRNAs effectively knocked down the expression of Smad4 and/or Smad1, Smad5, and Smad8 in mesenchymal stem cells (MSCs), and they inhibited all aspects of BMP9-induced osteogenic differentiation in bone marrow MSCs (BMSCs), including decreased expression of osteogenic regulators/markers, reduced osteogenic marker alkaline phosphatase (ALP) activity, and diminished in vitro matrix mineralization and in vivo ectopic bone formation. Collectively, we demonstrate that the engineered FAMSi system provides a fast-track platform for assembling multiplexed siRNAs in a single vector, and thus it may be a valuable tool to study gene functions or to develop novel siRNA-based therapeutics.


[Substance P].
Substance P (SP) is a polypeptide formed by 11 amino acids of the tachykinin family. SP is found in the peripheral nervous system, particularly in small diameter myelinated and non myelinated afferent fibers. It is concentrated at both proximal and distal ends of sensory neurones to the skin, mucous membranes, viscera and vessels throughout the body. In the central nervous system SP is concentrated in the basal ganglia (striatonigral system), the habenulo-interpeduncular system, the brain stem (particularly in afferent spinal tract neurones) and the hypothalamus. Neurones containing SP may also contain other neurotransmitters. Criteria for identification of SP are similar to those applying to other neuromediators except for duration of action, which is comparatively greatly prolonged for SP. SP exerts complex synaptic effects, both pre- and post-synaptic, and usually acts as an activating factor. Its physiological role is unknown but it could intervene in peripheral nociceptive processes by its peripheral (oedema and plasma extravasation) and central (excitation of dorsal horn sensory neurones and facilitation of medullary reflexes by depolarization of motor neurones) effects; in central regulation of nociceptive impulses (analgesic effect); in regulation of some vegetative functions (glandular secretion, digestive and vasomotor motility, hypothalamic functions); in certain motor regulatory actions as suggested by the large amounts of SP in the striatonigral tract and the motor effects induced by injection of SP into the substantia nigra; in control of some learning processes; in control of growth of some central nerve fibers during development.


Intensity-Modulated Radiation Therapy for Early-Stage Squamous Cell Carcinoma of the Glottic Larynx: A Systematic Review and Meta-Analysis.
Early-stage squamous cell carcinoma of the glottic larynx is commonly treated with 2-dimensional or 3-dimensional conventional radiation therapy (CRT). Despite its use in other head and neck cancers, intensity-modulated radiation therapy (IMRT) remains controversial in this patient population. A systematic review was performed by querying 3 databases (Pubmed, Embase, Web of Science) for articles published between December 1, 2000 and September 2, 2022. Included studies reported outcomes in at least 10 patients treated with IMRT for early-stage glottic cancer. Data were extracted and reported following PRISMA standards. Pooled outcomes were estimated using random-effects models. Primary outcome was the rate of local failure (LF) following IMRT. Secondary outcomes included rates of regional failure (RF) following IMRT and rates of LF and RF following CRT. A total of 15 studies (14 retrospective, 1 prospective) consisting of 2083 patients were identified. IMRT was used in 873 patients (64% T1, 28% T2). Multiple treatment (partial larynx, single vocal cord carotid sparing) and image-guided radiation therapy techniques were used. The pooled crude rate of LF was 7.6% (95% confidence inverval [CI], 3.6%-11.5%) and actuarial LF rates at 3 and 5 years were 6.3% (95% CI, 2.2%-10.3%) and 9.0% (95% CI, 4.4%-13.5%), respectively. The pooled crude rate of RF after IMRT was 1.5% (95% CI, 0.5%-2.5%). On metaregression analysis, increased rate of LF was significantly associated with T2 disease (P < .001) and grade 2 to 3 histology (P < .001). Treatment with CRT was reported in 738 patients (76% T1, 22% T2). Among the studies reporting outcomes of both modalities, there was no significant difference in LF (log odds ratio; P = .12) or RF (log odds ratio; P = .58) between IMRT or CRT. In patients with early-stage glottic cancer, retrospective data suggests local and regional control are similar for patients treated with IMRT and CRT. Additional prospective studies with uniform methods of volume delineation and image guidance are needed to confirm the efficacy of IMRT.


Do silicone nasal septal splints with integral airway reduce postoperative eustachian tube dysfunction?
This study aims to compare the effects of Merocel nasal packs and silicone nasal septal splints with integral airway on the ventilation and pressure of the middle ear when applied intranasally after septoplasty for isolated septal deviation. A prospective, randomized trial. A tertiary referral center. Fifty-one patients who underwent septoplasty for nasal respiratory impairment caused by septal deviation were randomized into 2 groups. After septoplasty, bilateral anterior Merocel nasal packs were applied in one group, while silicone nasal septal splints with integral airway were applied in the other group. Middle ear pressures were compared using preoperative and post-operative tympanometry. Pathological decrease in the middle ear pressure in at least 1 ear was determined in 17 patients (73.9%) in the Merocel group compared with only 6 patients (21.4%) in the silicone nasal septal splint group at the 48th postoperative hour. In the first 24 hours following surgery, decreases in tympanometric pressures were seen in both groups, but more in the Merocel group. After 24 hours, middle ear pressures continued to decrease in the Merocel group but started to increase in the silicone nasal septal splint group. Because they allow inhalation through the nose and cause less Eustachian tube dysfunction than Merocel, using silicone nasal septal splints with integral airway instead of packing after septoplasty seems a more reasonable option.


The expression of phytohemagglutinin genes in Phaseolus vulgaris is associated with organ-specific DNA methylation patterns.
Using methylation sensitive restriction enzymes and DNA gel blot analyses, we have examined DNA methylation patterns at the chromosomal locus harboring the two phytohemagglutinin genes of Phaseolus vulgaris. In cotyledons, where the genes are highly expressed, several sites have become undermethylated, whereas the methylation status of other sites remains constant, both in cotyledons and in other organs. Taken together with measurements of mRNA levels, these studies provide evidence that organ-specific changes in DNA methylation patterns are associated with the organ-specific expression of nuclear genes in a dicotyledonous plant.


Corrigendum: Downregulation of TrkC Receptors Increases Dendritic Arborization of Purkinje Cells in the Developing Cerebellum of the Opossum, Monodelphis domestica.
[This corrects the article DOI: 10.3389/fnana.2020.00056.].


Support Vector Machine versus Multiple Logistic Regression for Prediction of Postherpetic Neuralgia in Outpatients with Herpes Zoster.
Postherpetic neuralgia (PHN), as the most common complication of herpes zoster (HZ), is very refractory to current therapies. Studies of HZ have indicated that early aggressive pain interventions can effectively prevent PHN; therefore, accurately predicting PHN in outpatients with HZ and treating HZ promptly, would be of great benefit to patients. Multiple logistic regression (MLR) has often been used to predict PHN. However, support vector machine (SVM) has been poorly studied in predicting PHN in outpatients with HZ. The aim of our retrospective study was to analyze the data of outpatients with HZ to evaluate the use of SVM for predicting PHN by comparing it with MLR. A retrospective study. Department of Anesthesiology in China. The data of 732 outpatients with HZ from January 1, 2015 to May 31, 2020 were reviewed. Risk factors for having PHN in outpatients with HZ were screened using least absolute shrinkage and selection operator (LASSO) algorithm. Then, SVM and MLR were used to predict PHN in outpatients with HZ based on screened risk factors. The data from 600 patients were used for training set and another 132 patients for test set. The receiver operating characteristic (ROC) curve was drawn from the 132 test set of patients. The prediction accuracy of the models was assessed using the area under curve (AUC). The incidence of having PHN in outpatients with HZ was 19.4%. The risk factors selected by LASSO algorithm were gender, age, VAS scores, skin lesion area, initial treatment time, anxiety, sites of HZ (multiple skin lesions), types of HZ (bullous) and types of pain (knife cutting). The AUC for the SVM and MLR in test set were 0.884 versus 0.853. According to the ROC curve, the specificity and the sensitivity were 0.879 and 0.840 for SVM, and 0.780 and 0.840 for MLR, respectively. Retrospective study and relatively small sample size. Both SVM and MLR had good discriminative power, but SVM has better performance in predicting PHN in outpatients with HZ, regarding the prediction accuracy and specificity.


Higher Baseline Serum Irisin Decreases Risk for Body Mass Index Increment in Chinese Populations: A 3.2-Year Cohort Study.
Irisin, a newly discovered myokine, exerts beneficial effects on energy metabolism. However, published results from studies examining the relationship between irisin concentration and obesity have been conflicting. The aim of our study was to investigate the association between serum irisin level and obese individuals with different body mass index (BMI) values and to explore the question of whether serum irisin can predict the risk of increases in the BMI. This study based on the data collected in the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION). The cross-sectional cohort study was carried out from May 2011 to August 2011, and a longitudinal cohort study was conducted from July 2014 to October 2014 to complete the first 3.2-year follow-up. We enrolled 93 low-weight subjects (BMI < 18.5 kg/m2), 94 normal-weight subjects (BMI 18.5-23.9 kg/m2), 98 overweight subjects (BMI 24.0-27.9 kg/m2) and 93 obese subjects (BMI ≥ 28 kg/m2). Subjects in the normal-weight, overweight and obese groups were selected to match low-weight subjects by age and sex. Serum samples were obtained from all subjects to determine the irisin level. Subjects with a higher serum irisin level tended to have significantly lower changes in BMI and body fat percentage and higher baseline high-density lipoprotein cholesterol level (p < 0.05). No significant correlation was observed between serum irisin level and the baseline obesity index. Serum irisin level was positively correlated to an active lifestyle (i.e. physical activity; β = 1.138, p = 0.032) and negatively correlated to fasting plasma glucose level (β = - 0.996, p = 0.023), changes in BMI (β = - 0.533, p = 0.002), waist circumference (β = - 0.102, p = 0.018), body fat percentage (β = - 0.457, p = 0.001) and Chinese visceral adiposity index (β = - 0.280, p = 0.028). After adjustment for cofactors, higher baseline serum irisin was an independent factor for a decreased BMI increment (baseline serum irisin: odds ratio 0.747, 95% confidence interval 0.652-0.949, p = 0.002). Higher serum irisin at baseline independently predicted a lower BMI increment in Chinese populations.


Dechlorination of polychlorinated dibenzo-p-dioxins catalyzed by noble metal catalysts under mild conditions.
Dechlorination of polychlorinated dibenzo-p-dioxins such as 2,7-dichlorodibenzo-p-dioxin (2,7-DCDD) and 1,2,6,7-tetrachlorodibenzo-p-dioxin (1,2,6,7-TCDD) was carried out in a solution of NaOH in 2-propanol in the presence of carbon-supported noble metal catalyst (Pd/C or Rh-Pt/C) at temperatures between 23 and 35 degrees C. At initial concentrations of 140-240 micrograms/ml, 2,7-DCDD and 1,2,6,7-TCDD were efficiently converted to a chlorine-free product, dibenzo-p-dioxin (DD), in high yield (60-80%). The conversion of 2,7-DCDD and 1,2,6,7-TCDD and the yield of DD were hardly affected by the atmosphere (N2 or air). We postulate that the displacement of aromatic chlorines by hydrogen selectively occurs on the catalyst, involving hydrogen-transfer from 2-propanol to the substrates.


Locating the rate-determining step(s) for three-step hydrolase-catalyzed reactions with DYNAFIT.
Hydrolytic reactions of oligopeptide 4-nitroanilides catalyzed by human-alpha-thrombin, human activated protein C and human factor Xa were studied at pH 8.0-8.4 and 25.0+/-0.1 degrees C by the progress curve method and individual rate constants were calculated mostly within 10% internal error using DYNAFITV. A systematic strategy has been developed for fitting a three-step consecutive mechanism to eighteen hundred to six thousand time-course data points polled from two to four independent kinetic experiments. Enzyme and substrate concentrations were also calculated. Individual rate constants well reproduce published values obtained under comparable conditions and the Michaelis-Menten kinetic parameters calculated from these elementary rate constants are also within reasonable limits of published values. For comparison, the integrated Michaelis-Menten equation was also fitted to data from twelve sets. Both the k(cat) and k(cat)/K(m) values are within 15% agreement with those calculated using the elementary rate constants obtained with DYNAFITV. Rate constants for the second and third consecutive steps are within 3-4 fold indicating that both determine the overall rate. The Factor Xa-catalyzed hydrolysis of N-alpha-Z-D-Arg-Gly-Arg-pNA.2HCl at pH 8.4 in a series of buffers containing increasing fractions of deuterium at 25.0+/-0.1 degrees C shows a very strong dependence of k(3) and a moderate dependence of k(2) on D content in the buffer: the fractionation factors are: 0.49+/-0.03 for K(1,) 0.70+/-0.05 for k(2), and (0.32+/-0.03)(2) for k(3).


Acute Ventilatory Support During Whole-Body Hybrid Rowing in Patients With High-Level Spinal Cord Injury: A Randomized Controlled Crossover Trial.
High-level spinal cord injury (SCI) results in profound spinal and supraspinal deficits, leading to substantial ventilatory limitations during whole-body hybrid functional electrical stimulation (FES)-rowing, a form of exercise that markedly increases the active muscle mass via electrically induced leg contractions. This study tested the effect of noninvasive ventilation (NIV) on ventilatory and aerobic capacities in SCI. This blinded, randomized crossover study enrolled 19 patients with SCI (level of injury ranging from C4 to T8). All patients were familiar with FES-rowing and had plateaued in their training-related increases in aerobic capacity. Patients performed two FES-rowing peak exercise tests with NIV or without NIV (sham). NIV increased exercise tidal volume (peak, 1.50 ± 0.31 L vs 1.36 ± 0.34 L; P < .05) and reduced breathing frequency (peak, 35 ± 7 beats/min vs 38 ± 6 beats/min; P < .05) compared with the sham test, leading to no change in alveolar ventilation but a trend toward increased oxygen uptake efficiency (P = .06). In those who reached peak oxygen consumption (Vo2peak) criteria (n = 13), NIV failed to significantly increase Vo2peak (1.73 ± 0.66 L/min vs 1.78 ± 0.59 L/min); however, the range of responses revealed a correlation between changes in peak alveolar ventilation and Vo2peak (r = 0.89; P < .05). Furthermore, those with higher level injuries and shorter time since injury exhibited the greatest increases in Vo2peak. Acute NIV can successfully improve ventilatory efficiency during FES exercise in SCI but may not improve Vo2peak in all patients. Those who benefit most seem to be patients with cervical SCI within a shorter time since injury. ClinicalTrials.gov; Nos.: NCT02865343 and NCT03267212; URL: www.clinicaltrials.gov.


Retracted: Design and Implementation of Dance Online Teaching System Based on Optimized Load Balancing Algorithm.
[This retracts the article DOI: 10.1155/2022/3829118.].


Where to Draw the LINE-Are Retrotransposable Elements Here to Stay?
The frequency of somatic retrotranspositions of Long Interspersed Nuclear Elements 1 (LINE1) over a lifetime in healthy colonic epithelium and colorectal tumors has recently been reported. Indicative of a cell type-specific effect, LINE1 sequences in colonic epithelium showed lower levels of DNA methylation compared to other cell types examined in the study. Consistent with a role for DNA methylation in transposon silencing, the decreases in DNA methylation observed at LINE1 elements in colonic epithelium were accompanied by increases in LINE1 mRNA levels. In human primary colorectal tumors, LINE1 retrotransposition frequency was tenfold higher than in normal colonic tissues, with insertions potentially altering genomic stability and cellular functions. Here, we discuss the discoveries made by Nam and colleagues, emphasizing the intestinal-specific methylation signature regulating the LINE1 lifecycle and how this new information could shape future drug discovery endeavors against colorectal cancer.


Challenges and opportunities of group therapy for adolescent substance abuse: a critical review.
Group intervention has been the most commonly employed treatment modality for adolescents with substance use disorders (SUD). Evidence has been accumulating in support for the efficacy of diverse forms of group therapy that have been utilized with adolescents. It has been argued however, that aggregation of youths who display problem behavior into group interventions may, under some conditions, produce iatrogenic effects on all participants. This assertion known also as "deviancy training" and its presumed effect on treatment outcomes has created a barrier to progress regardless of the fact that it has not been tested or empirically supported in heterogeneous groups of adolescents treated for SUD. It is imperative to optimize group intervention while considering how to prevent, reduce and control, potentially iatrogenic effects associated with the aggregation of antisocial youths in heterogeneous groups. The main objective of this review is to address the challenges and opportunities regarding group treatment of adolescent SUD.


Genetic variation in platelet integrin alphabeta (GPIIb/IIIa) and the metastatic potential of renal cell carcinoma.
To explore whether genetic polymorphisms in platelet receptors known to be associated with platelet activity have any association with haematogenous metastases in renal cell carcinoma (RCC), as platelets and their fibrinogen receptors may be central to haematogenous cancer spread, in addition to various adhesive proteins on both platelets and tumour cells on themselves. The glycoprotein alpha(IIb)beta3 (GPIIb/IIIa) is the main fibrinogen receptor on platelets, with GPIb-IX-V and GPIa/IIa being the von Willebrand Factor and collagen receptors, respectively. In a cross-sectional survey of 128 men treated for RCC (55 with disseminated disease and 73 with a local disease), they were genotyped using DNA extracted from freshly drawn blood, and central clinical data were recorded. The frequency of possessing the GPIIIaPl(A2) allele among patients with metastatic RCC was 43.6%, and with local disease was 24.7% (P = 0.024). The frequencies of the different alleles of the GIB-IX-V, C3550T and GPIa/IIa C807T polymorphisms did not differ between the groups. In a stepwise logistic regression (metastatic vs local RCC) the Pl(A2) allele remained a significant risk factor, with an odds ratio of 2.7 (95% confidence interval, 1.1-6.5; P = 0.02). The prothrombotic Pl(A2) allele of platelet fibrinogen receptor GPIIb/IIIa increased the risk of metastases in RCC in men.


Enhanced production of biomass and lipids by Euglena gracilis via co-culturing with a microalga growth-promoting bacterium, Emticicia sp. EG3.
Euglena gracilis, a unicellular flagellated microalga, is regarded as one of the most promising species as microalgal feedstock for biofuels. Its lipids (mainly wax esters) are suitable for biodiesel and jet fuel. Culture of E. gracilis using wastewater effluent will improve the economics of E. gracilis biofuel production. Enhancement of the productivity of E. gracilis biomass is critical to creating a highly efficient biofuels production system. Certain bacteria have been found to promote microalgal growth by creating a favorable microenvironment. These bacteria have been characterized as microalgae growth-promoting bacteria (MGPB). Co-culture of microalgae with MGPB might offer an effective strategy to enhance microalgal biomass production in wastewater effluent culture systems. However, no MGPB has been identified to enhance the growth of E. gracilis. The objectives of this study were, therefore, to isolate and characterize the MGPB effective for E. gracilis and to demonstrate that the isolated MGPB indeed enhances the production of biomass and lipids by E. gracilis in wastewater effluent culture system. A bacterium, Emticicia sp. EG3, which is capable of promoting the growth of microalga E. gracilis, was isolated from an E. gracilis-municipal wastewater effluent culture. Biomass production rate of E. gracilis was enhanced 3.5-fold and 3.1-fold by EG3 in the co-culture system using a medium of heat-sterilized and non-sterilized wastewater effluent, respectively, compared to growth in the same effluent culture but without EG3. Two-step culture system was examined as follows: E. gracilis was cultured with or without EG3 in wastewater effluent in the first step and was further grown in wastewater effluent in the second step. Production yields of biomass and lipids by E. gracilis were enhanced 3.2-fold and 2.9-fold, respectively, in the second step of the system in which E. gracilis was co-cultured with EG3 in the first step. Emticicia sp. EG3 is the first MGPB for E. gracilis. Growth-promoting bacteria such as EG3 will be promising agents for enhancing E. gracilis biomass/biofuel productivities.


Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer.
This corrects the article DOI: 10.1038/bjc.2016.363.