["Ear rage": misophonia : Review and current state of knowledge].
Misophonia is a devastating disorder. It is known as an affective sound-processing disorder characterized by the experience of strong negative emotions (e.g., anger, distress) in response to human sounds such as eating/swallowing/breathing. Other sounds produced by humans but not directly by human bodies can also be misophonic triggers (e.g. pen clicking) or environmental sounds (animal sounds/sounds of machines). The type of aversive triggers is individual. The reaction to trigger sounds can depend on many factors, such as assessment of the sound, personal experience, social context or psychological profile. However, there is currently no consensus in defining misophonia. Misophonia is also not yet classified by any official diagnostic system, although it seems to be a separate disorder. There are also associations with other disorders such as activity disorders, tinnitus, hyperacusis, and autism spectrum disorders. In 2013, the first definition criteria were published for the diagnosis of misophonia. Specifically, fMRI showed abnormal activation of the anterior insular cortex (AIC) and other brain areas responsible for the processing and regulation of emotions. To date, no randomized controlled trials evaluating treatments have been published. The use of cognitive and behavioral interventions have been reported as well as external sound systems and sound masking systems as known in the tinnitus retraining therapy. Sufferers try to minimize the trigger sounds by wearing ear plugs or music headphones. Otolaryngologists may also encounter patients with symptoms of misophonia, e.g., when hearing screening is requested or advice should be given on different therapeutic options. This report provides an overview of the current state of knowledge in misophonia and its diagnosis and treatment.


Cancer immunotherapy: T cells and neutrophils working together to attack cancers.
The discovery of immune checkpoint inhibitors that boost T cell activity has revolutionized cancer treatment. However, these therapies do not work in all patients, and the quest is on to understand why. Two new studies published in this issue of Cell reveal the surprising finding that activated T cells can recruit neutrophils to kill cancer cells.


Giant colonic mucocele following palliative surgery for metastatic adenocarcinoma.
We report an unusual case of a giant colonic mucocele following ileo-sigmoid bypass surgery in a patient with advanced adenocarcinoma of the splenic flexure. The formation of a giant colonic mucocele resulted from distal splenic flexure obstruction due to tumour relapse and proximal caecal obstruction due to peritoneal disease with subsequent accumulation of mucus in the closed loop.


Simultaneous Application of High-Intensity Focused Electromagnetic and Synchronized Radiofrequency for Fat Disruption: Histological and Electron Microscopy Porcine Model Study.
Radiofrequency (RF) and high-intensity focused electromagnetic (HIFEM) technologies are used for noninvasive body shaping as standalone modalities. To examine the effects of novel synchronized RF and HIFEM on subcutaneous adipose tissue in a porcine animal model. Seven large white pigs aged 6 months received 3 abdominal treatments of simultaneous application of synchronized RF and HIFEM (30 minutes, once per week). Punch biopsies of treated and control subcutaneous tissue were collected at the baseline, 4 days, 2 weeks, 1 month, and 2 months. Specimens were examined by light and scanning electron microscopy. Adipocyte volume was analyzed. Fat tissue temperature was measured in situ (fiber optic probes) and superficially (thermal imager). Fat layer was heated to temperatures of 42 to 45°C. Signs of fat apoptosis (shape alternations and pyknotic nuclei) appeared at day 4 and peaked between 2 weeks and 1 month. Adipocyte volume decreased significantly (p < .001) by 31.1% at 2 weeks, 1 month (-23.6%), and 2 months (-22.0%). Control samples showed healthy adipocytes. Scanning electron microscopy micrographs corroborated histology findings, showing flattened, volume-depleted and disrupted adipocytes. Synchronized RF with HIFEM procedure resulted in a significant and sustained fat reduction with no adverse events.


Prevalence of trochlear dysplasia in symptomatic isolated lateral patellofemoral osteoarthritis: Transverse study of 101 cases.
Patellofemoral osteoarthritis (PFOA) is usually associated with femorotibial osteoarthritis; isolated forms involve several specific risk factors. Trochlear dysplasia (TD) alters stress patterns in the patellofemoral joint, inducing PFOA. The association of TD and isolated PFOA was analyzed without distinguishing medial facet, global and lateral facet involvement. The study hypothesis was that TD prevalence is high in isolated lateral PFOA (ILPFOA). The aim of the study was to assess TD prevalence in a symptomatic ILPFOA population and identify risk factors. Eighty-four patients (101 knees) underwent lateral vertical patellectomy (LVP) for symptomatic ILPFOA between November 1998 and September 2019. Demographic, clinical and radiographic data were collected retrospectively from preoperative records. TD was analyzed by 2 blinded surgeons on lateral radiographs. TD prevalence was 88.1%. TD was significantly more advanced in patients under 45 years of age at surgery (64.5% stage 2 or 3; p=0.019). Non-TD cases showed significantly more frequent valgus deformity (83.3%; p=0.042) and overweight (BMI, 32±4.1; p<0.001). TD is a known risk factor for PFOA, present in almost 9 in 10 cases in the present series of ILPFOA. These findings reinforce the hypothesis that it plays a role in onset of ILPFOA. TD also induces early pain, leading to surgery. Overweight and valgus deformity are contributing factors for ILPFOA. IV; transverse study.


Predominant learning approaches of medical students in Saudi Arabia.
This study aims at identifying the predominant learning approaches by Saudi medical students across Saudi Arabia and assess its possible associations with sociodemographic and educational characteristics. A cross-sectional study design using the Approaches and Study Skills Inventory for Students questionnaire. The questionnaire gives rise to three possible learning approaches; deep, strategic and surface approaches. Bivariate analyses were performed through independent samples t-test and χ2 tests where appropriate. A multinominal regression analysis was performed to obtain risk estimates and 95% CIs. A total of 3767 students participated and were included in the analysis. The predominant learning approach was the deep approach, followed by the strategic and surface approaches (40.59%, 37.81% and 21.60%, respectively). Males and students belonging to private medical schools were more likely to adopt a strategic rather than a deep one (relative risk ratio (RRR) 1.22, 95% CI 1.06 to 1.42 and RRR 1.32, 95% CI 1.05 to 1.65, respectively). Students with an A grade point average (GPA) were less likely to adopt a surface approach, whereas those with a C GPA were more likely to adopt it (RRR=0.67, 95% CI 0.54 to 0.83 and RRR=1.29, 95% CI 1.02 to 1.61, respectively). The findings from this study show that medical students predominantly favour the deep learning approach. Results from this study encourage the continuous adaptation of clinical teaching in medical schools to optimise students' learning experiences.


Quantitative proteomic analysis of aberrant expressed lysine acetylation in gastrointestinal stromal tumors.
Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence. Currently, we understand the genome, transcriptome and proteome in GIST. However, posttranscriptional modification features in GIST remain unclear. In the present study, we aimed to construct a complete profile of acetylome in GIST. Five common protein modifications, including acetylation, succinylation, crotonylation, 2-hydroxyisobutyrylation, and malonylation were tested among GIST subgroups and significantly differentially- expressed lysine acetylation was found. The acetylated peptides labeled with Tandem Mass Tag (TMT)under high sensitive mass spectrometry, and some proteins with acetylation sites were identified. Subsequently, these proteins and peptides were classified into high/moderate (H/M) risk and low (L) risk groups according to the modified NIH classification standard. Furthermore, cell components, molecular function, biological processes, KEGG pathways and protein interaction networks were analyzed. A total of 2904 acetylation sites from 1319 proteins were identified, of which quantitative information of 2548 sites from 1169 proteins was obtained. Finally, the differentially-expressed lysine acetylation sites were assessed and we found that 42 acetylated sites of 38 proteins were upregulated in the H/M risk group compared with the L risk group, while 48 acetylated sites of 44 proteins were downregulated, of which Ki67 K1063Ac and FCHSD2 K24Ac were the two acetylated proteins that were most changed. Our novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.


Managing HIV. Part 2: Phases of disease. 2.1 Primary HIV infection.
The most important principle in managing primary HIV infection is not to miss the diagnosis. It presents an early opportunity for counselling and education aimed at maximising quality of life and minimising the risk of transmitting HIV (particularly high during the viraemia of primary infection).


Relative tolerance to upper- and lower-limb aerobic exercise in patients with peripheral arterial disease.
To investigate the effects of peripheral arterial disease (PAD) on relative tolerance to upper- and lower-limb aerobic exercise. Peak cardiorespiratory responses evoked by an incremental arm-cranking test (ACT) and an incremental leg-cranking test (LCT) were compared in patients with PAD (N=101; median age 69 year, range 50-85 years). Claudication distance (CD) and total distance before intolerable claudication pain (maximum walking distance: MWD) were also assessed during walking. Peak oxygen consumption (V O(2)) for the ACT was 94% of that measured for the LCT (1.01+/-0.03 versus 1.10+/-0.03lmin(-1), respectively; P<0.001), but in a significant proportion of patients (35%; P<0.001), exceeded that recorded for the LCT. The ratio of upper- to lower-limb peak V O(2) was higher (0.98+/-0.04 compared to 0.98+/-0.05lmin(-1) and 1.00+/-0.06 compared to 1.21+/-0.06lmin(-1); P<0.01), whereas walking performance (CD: 94+/-14 versus 187+/-25 m, P<0.01; MWD: 227+/-20 versus 394+/-33 m, P<0.01) was lower for patients in the lowest ankle to brachial pressure index quartile compared to patients in the highest quartile, respectively. Upper-limb aerobic conditioning could be a useful exercise stimulus for maintaining or improving cardiorespiratory function in patients with severe PAD as they have a greater relative upper-limb aerobic power.


Effect of dexmedetomidine on hemodynamic responses to tracheal intubation: A meta-analysis with meta-regression and trial sequential analysis.
An uncontrolled adrenergic response during tracheal intubation may lead to life-threatening complications. Dexmedetomidine binds to α2-receptors and may attenuate this response. The primary aim of our meta-analysis is to investigate dexmedetomidine efficacy in attenuating sympathetic response to tracheal intubation, compared with placebo or no dexmedetomidine, in terms of heart rate and blood pressure at intubation. Meta-analysis with meta-regression and trial sequential analysis. Systematic search from inception until December 1, 2020 in the following databases: Pubmed, Scopus, the Cochrane Central Register of Controlled Trials, EMBASE and Google Scholar. All randomized controlled trials investigating intravenous dexmedetomidine as premedication in adult patients undergoing tracheal intubation were included in our study. Studies were included without any language or publication date restriction. A trial sequential analysis and a post-hoc meta-regression were performed on the main outcomes. Hemodynamic parameters and heart rate at tracheal intubation, dose of anesthetic needed for induction of anesthesia, total anesthetic requirement throughout the operative procedure, postoperative pain and percentage of patients requiring analgesics at 24 postoperative hours, postoperative nausea and vomiting, intraoperative and postoperative bradycardia, hypotension, dizziness, shivering and/or respiratory depression. Ninety-nine included studies randomized 6833 patients. During laryngoscopy, all hemodynamic parameters were significantly greater in the no dexmedetomidine group. In particular, in the dexmedetomidine group, systolic blood pressure differed by -21.8 mm Hg (95% CI -26.6 to -17.1, p-value < 0.001, I2 97%), mean arterial pressure by -12.8 mm Hg (95% CI -15.6 to -10.0, p-value < 0.001, I2 98%), and heart rate by -16.9 bpm (95% CI -19.8 to -13.9, p-value < 0.001, I2 98%). Patients receiving premedication with dexmedetomidine for tracheal intubation, compared with no dexmedetomidine, have a lower blood pressure and heart rate, however, the risk of bradycardia and hypotension is relevant and its use during daily practice should be cautiously evaluated for each patient.


Analysis of omeprazole and 5-OH omeprazole in human plasma using hydrophilic interaction chromatography with tandem mass spectrometry (HILIC-MS/MS)--eliminating evaporation and reconstitution steps in 96-well liquid/liquid extraction.
Bioanalytical methods using liquid/liquid extraction (LLE) and liquid chromatography with electrospray tandem mass spectrometry (LC-MS/MS) are widely used. The organic extracts need to be evaporated and reconstituted, hampering further improvement of throughput and automation. In this study, we demonstrated a novel approach of eliminating these two steps in 96-well LLE by using hydrophilic interaction chromatography with MS/MS (HILIC-MS/MS) on silica column with high organic/low aqueous mobile phase. Omeprazole, its metabolite 5-OH omeprazole, and internal standard desoxyomeprazole, were extracted from 0.05 ml of human plasma using 0.5 ml of ethyl acetate in a 96-well plate. A portion (0.1 ml) of the ethyl acetate extract was diluted with 0.4 ml of acetonitrile and 10 microl was injected onto a Betasil silica column (50 mm x 3.0 mm, 5 microm) and detected by API 3000 and 4000 with (+) ESI. Mobile phase with linear gradient elution consists of acetonitrile, water, and formic acid (from 95:5:0.1 to 73.5:26.5:0.1 in 2 min). The flow rate was 1.5 ml/min with total run time of 2.75 min. The method was validated for a low limit of quantitation at 2.5 ng/ml for both analytes. The method was also validated for specificity, reproducibility, stability and recovery. Lack of adverse matrix effect and carry-over was also demonstrated. The inter-day precision and accuracy of the quality control samples at low, medium and high concentration levels were <4.4% relative standard deviation (R.S.D.) and 4.1% relative error (R.E.) for omeprazole, and 4.5% R.S.D. and 5.6% R.E. for 5-OH omeprazole, respectively.


Design, Synthesis, and In Vitro Antiproliferative Activity of Hydantoin and Purine Derivatives with the 4-Acetylphenylpiperazinylalkyl Moiety.
Cancer represents one of the most serious health problems and the second leading cause of death around the world. Heterocycles, due to their prevalence in nature as well as their structural and chemical diversity, play an immensely important role in anti-cancer drug discovery. In this paper, a series of hydantoin and purine derivatives containing a 4-acetylphenylpiperazinylalkyl moiety were designed, synthesized, and biologically evaluated for their anticancer activity on selected cancer cell lines (PC3, SW480, SW620). Compound 4, a derivative of 3',4'-dihydro-2'H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, was the most effective against SW480, SW620, and PC3 cancer cell lines. Moreover, 4 has high tumor-targeting selectivity. Based on docking studies, it was concluded that R isomers of 3',4'-dihydro-2'H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione could be further studied as promising scaffolds for the development of thymidine phosphorylase inhibitors.


Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric determination of anandamide and its analogs in rat brain and peripheral tissues.
A simple and selective method for the determination of anandamide (arachidonoylethanolamide), an endogenous cannabinoid receptor ligand, and its analogs with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) was developed. The calibration curve for standard anandamide was linear over the range 625 fmol-125 pmol per injection (r = 0.999) with a precision of 1.0% (C.V.) at 25 pmol. The detection limit attained was 200 fmol per injection at a signal-to-noise ratio of 2. Anandamide and its analogs were extracted from rat brain and peripheral tissues according to the method of Folch, and the recovery of anandamide from rat brain homogenates was 67.0-72.6%. The method was applied to their determination in rat brain and peripheral tissues.


Psyllium husk combined with hydroxycitrate reduces body weight gain and body fat in diet-induced obese rats.
The fortified physiological activities of psyllium with hydroxycitrate (HCA) will promote the use of this mixture in making nutraceutical foods. Male Sprague-Dawley rats were fed high-fat diets containing fiber-free (control), cellulose (F-control), psyllium husk (WF-1), and psyllium husk + HCA (WF-2) for 4 weeks. Weight gains in WF-2 were significantly lower than those of the control (P < .05). Relative weights of perirenal and epididymal fat in WF-2 were significantly lower than in the other groups (P < .05). The levels of feces bile acid and fat in WF-2 were significantly higher than in the other groups (P < .05). The levels of plasma triacylglycerol and HTR (high-density lipoprotein cholesterol/total cholesterol) in fiber-containing groups (F-control, WF-1 and WF-2) were significantly lower than in the control (P < .05). Especially, triacylglycerol was significantly lower in WF-2 than in WF-1 and F-control (P < .05). Dietary supplementation with psyllium increased the total short-chain fatty acid concentration (23.36 μmol/L in WF-1 and 26.97 μmol/L in WF-2), compared with F-control (18.97 μmol/L) and control (10.92 μmol/L) diets. The mixture of psyllium and HCA reduced both body weight gain and body fat in high fat-fed rats, suggesting efficacy as an antiobesity supplement.


Electron guiding in macroscopic borosilicate capillaries with large bending angles.
This work presents experiments about the transmission of electrons with an energy of around 15 keV with beam currents up to 20 µA through macroscopic glass capillaries. A systematic study was conducted to experimentally investigate the transmission of electrons through borosilicate glass capillaries with curve angles of 90°, 180°, 270° and 360° for the first time. The focus of the work was to identify the conditions under which the injected electron current is transmitted through the capillary. It was also shown that the transmission process in the macroscopic capillaries can be optically observed by cathodoluminescence-the interaction of electrons with the capillary surface causes locally a blue glow. Different distinctive "glow states" were observed and are found to correlate with different states of electron transmission.


Artificial intelligence in screening, diagnosis, and classification of diabetic macular edema: A systematic review.
We review the application of artificial intelligence (AI) techniques in the screening, diagnosis, and classification of diabetic macular edema (DME) by searching six databases- PubMed, Scopus, Web of Science, Science Direct, IEEE, and ACM- from January 1, 2005 to July 4, 2021. A total of 879 articles were extracted, and by applying inclusion and exclusion criteria, 38 articles were selected for more evaluation. The methodological quality of included studies was evaluated using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). We provide an overview of the current state of various AI techniques for DME screening, diagnosis, and classification using retinal imaging modalities such as optical coherence tomography (OCT) and color fundus photography (CFP). Based on our findings, deep learning models have an extraordinary capacity to provide an accurate and efficient system for DME screening and diagnosis. Using these in the processing of modalities leads to a significant increase in sensitivity and specificity values. The use of decision support systems and applications based on AI in processing retinal images provided by OCT and CFP increases the sensitivity and specificity in DME screening and detection.


Enhancement by nalidixic acid of the thermal susceptibility of the Ts-7 mutant of Escherichia coli TAU-bar.
Nadilidixic acid at 5 x 10(-6) M produced a substantial increase in thermal susceptibility of Ts-7, suggesting either that the thermal and nalidixic acid targets are identical or closely interdependent.


FBXO22, ubiquitination degradation of PHLPP1, ameliorates rotenone induced neurotoxicity by activating AKT pathway.
Parkinson's disease (PD) is a neurodegenerative disease caused by the lacking of dopaminergic neurons. Many reports have illustrated that rotenone is applied to establish the experimental model of PD, which simulates PD-like symptoms. FBXO22 is a poorly understood protein that may be involved in neurological disorders. However, little is known about FBXO22 in PD. In this study, first, SH-SY5Y cells were treated with rotenone to construct PD model in vitro. It was discovered that the FBXO22 expression was down-regulated following rotenone treatment. Additionally, overexpression of FBXO22 reduced rotenone treatment-mediated cell apoptosis in SH-SY5Y cells. In view of the ubiquitination effect of FBXO22, our study uncovered that FBXO22 bound with and degraded PHLPP1 by ubiquitination. Next, the effects of PHLPP1 on AKT pathway in PD were further explored. It was demonstrated that PHLPP1 inactivated AKT pathway through down-regulating the pAKT/AKT and pmTOR/mTOR levels. Through rescue assays, the results showed that PHLPP1 overexpression partially reversed the reduction of rotenone induced neurotoxicity caused by FBXO22 overexpression. Finally, we found that overexpression of FBXO22 alleviated rotenone-induced PD symptoms in rat model. Moreover, it was discovered that l-dopa treatment could not affect the FBXO22 expression in PD. In conclusion, findings from our work proved that FBXO22 degraded PHLPP1 by ubiquitination to ameliorate rotenone induced neurotoxicity, which attributed to activate AKT pathway. This work suggested that FBXO22 may be an effective biological marker for PD treatment.


Crystal structure of 2-[4-(4-chloro-phen-yl)-1-(4-meth-oxy-phen-yl)-2-oxoazetidin-3-yl]benzo[de]iso-quinoline-1,3-dione dimethyl sulfoxide monosolvate.
In the title solvated compound, C28H19N2O4·C2H6OS, the central β-lactam ring is almost planar (r.m.s. deviation = 0.002 Å). It makes dihedral angles of 1.92 (11), 83.23 (12) and 74.90 (10)° with the meth-oxy- and chloro-phenyl rings and the ring plane of the 1H-benzo[de]iso-quinoline-1,3(2H)-dione group [maximum deviation = 0.089 (1)], respectively. An intra-molecular C-H⋯O hydrogen bond closes an S(6) ring and helps to establish the near coplanarity of the β-lactam and meth-oxy-benzene rings. In the crystal, the components are linked by C-H⋯O hydrogen bonds, C-H⋯π inter-actions and aromatic π-π stacking inter-actions [centroid-to-centroid distances = 3.6166 (10) and 3.7159 (10) Å], resulting in a three-dimensional network, The dimethyl sulfoxide solvent mol-ecule is disordered over two sets of sites in a 0.847 (2):0.153 (2) ratio.


Estimating retrospective indoor radon concentrations with a new device.
From the (222)Rn mixed with air, the short-lived daughters (218)Po, (214)Pb, (214)Bi, and (214)Po attach to dust particles and are deposited on surfaces where finally (210)Pb and (210)Po are formed. The alpha particles from (210)Po can be measured on surfaces such as window glass or mirrors. The design and construction are presented of a new device using a silicon detector to measure this (210)Po. Some preliminary results are reported and estimates of retrospective radon concentrations are made from them.


Efficacy of the Neodymium-Doped Yttrium Aluminum Garnet Laser in the Treatment of Keloid and Hypertrophic Scars: A Systematic Review and Meta-analysis.
Keloid and hypertrophic scars are the most common types of pathological scars. They can cause itching, pain, erythema, and psychological stress due to cosmetic problems, decreasing the quality of life for affected individuals. The neodymium-doped yttrium aluminum garnet (Nd:YAG) multipurpose laser is used to treat pathological scars, and studies have shown that the Nd:YAG laser can markedly improve scarring. We performed a meta-analysis to evaluate the efficacy of the Nd:YAG laser in the treatment of keloid and hypertrophic scars. A literature search of PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang was performed between January 1st, 2010, and July 14th, 2021. The Vancouver Scar Scale (VSS) was used to evaluate treatment outcomes. We used the R version 4.0.0 software for statistical analysis. The Nd:YAG laser improved the condition of keloid and hypertrophic scars and reduced VSS score (mean difference [MD]: 2.96, 95% confidence interval [CI]: 2.08-3.84, p < 0.01). There was no obvious difference in the results between regions. A subgroup analysis by scar type revealed that the curative effect of the Nd:YAG laser on keloid scars (MD: 2.02, 95% CI: 0.58-4.63, p = 0.10) was less marked compared with that on hypertrophic scars (MD: 3.05, 95% CI: 1.58-4.52, p < 0.01). With the combined use of the Nd:YAG laser and other treatment methods, a more significant change in VSS score was noted (MD: 4.28, 95% CI: 2.07-6.49). This meta-analysis showed that the Nd:YAG laser can improve the condition of keloid and hypertrophic scars and effectively reduce VSS score. Moreover, the curative effect of this approach on keloid scars is less marked compared with that on hypertrophic scars. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


TRANSLATION AND VALIDATION OF ENGLISH VERSION OF EVIDENCE-BASED PRACTICE COMPETENCE QUESTIONNAIRE.
Background: Valid and reliable tools must be implemented to measure nursing students' evidence-based practice (EBP) knowledge and skills that transfer to their practice. Purpose: To-translate and validate the English version of the Evidence Based Practice Competence Questionnaire (EBP-COQ-E). Methods: The EBP-COQ developed by Ruzafa-Martinez in Spain was administered to a sample of 279 undergraduate nursing students. Results: The content validity index was 96.16%, indicating that all items were correlated with the measurement of EBP competence. The Cronbach's alpha was 0.83, indicating good internal consistency. In confirmatory factor analysis, a three-factor solution was extracted with an eigenvalue greater than one, indicating a good measure of what it purports to be measuring. Conclusion: EBP-COQ-E can be recommended for standard implementation in English-speaking students taking EBP courses.


The GATA factor Serpent cross-regulates lozenge and u-shaped expression during Drosophila blood cell development.
The Drosophila GATA factor Serpent interacts with the RUNX factor Lozenge to activate the crystal cell program, whereas SerpentNC binds the Friend of GATA protein U-shaped to limit crystal cell production. Here, we identified a lozenge minimal hematopoietic cis-regulatory module and showed that lozenge-lacZ reporter-gene expression was autoregulated by Serpent and Lozenge. We also showed that upregulation of u-shaped was delayed until after lozenge activation, consistent with our previous results that showed u-shaped expression in the crystal cell lineage is dependent on both Serpent and Lozenge. Together, these observations describe a feed forward regulatory motif, which controls the temporal expression of u-shaped. Finally, we showed that lozenge reporter-gene activity increased in a u-shaped mutant background and that forced expression of SerpentNC with U-shaped blocked lozenge- and u-shaped-lacZ reporter-gene activity. This is the first demonstration of GATA:FOG regulation of Runx and Fog gene expression. Moreover, these results identify components of a Serpent cross-regulatory sub-circuit that can modulate lozenge expression. Based on the sub-circuit design and the combinatorial control of crystal cell production, we present a model for the specification of a dynamic bi-potential regulatory state that contributes to the selection between a Lozenge-positive and Lozenge-negative state.


Gains in understanding of podocyte loss.
Podocyte loss is a key element underlying glomerulosclerosis. Various mechanisms have been proposed for cell loss. These include local hemodynamic effects and local stresses on cell and hemodynamic changes, which together may contribute to detachment of podocytes, leading to sclerosis. Elegant studies based on classic observations add state-of-the-art imaging, modeling, intravital microscopy, and ultrastructural geometry analyses and provide new insights into potential mechanisms for injury and loss of this key cell.


The role and mechanism of β-arrestin2 in signal transduction.
β-arrestin2 is a ubiquitously expressed scaffold protein localized on the cytoplasm and plasma membrane. It was originally found to bind to GPCRs, uncoupling G proteins and receptors' binding and inhibiting the signal transduction of the GPCRs. Further investigations have revealed that β-arrestin2 not only mediates the desensitization of GPCRs but also serves as a multifunctional scaffold to mediate receptor internalization, kinase activation, and regulation of various signaling pathways, such as TLR4/NF-κB, MAPK, Wnt, TGF-β, and AMPK/mTOR pathways. β-arrestin2 regulates cell invasion, migration, autophagy, angiogenesis, and anti-inflammatory effects by regulating various signaling pathways, which play a vital role in many physiological and pathological processes. This paper reviews the structure and function of β-arrestin2, the regulation of β-arrestin2 based signaling pathways. The role and mechanism of β-arrestin2 signaling have been delineated in sufficient detail. The prospect of regulating the expression and activity of β-arrestin2 in multisystem diseases holds substantial therapeutic promise.


Radiograph-based study of gender-specific vertebral area gain in healthy children and adolescents as a function of age, height, and weight.
This study reports gender-specific vertebral area gain data from children and adolescents. Vertebral area was measured on lateral and anteroposterior thoracic and lumbar spine radiographs from 100 female and 100 male subjects aged 7-28 yr. T9, T11, T12, L1, and L2 X-ray area calculation was based on calculation of the area of the geometric figure of a trapezoid whose 2 nonparallel sides were equal in length, taking account of the waisted shape of the vertebrae. Both the boys and girls of our study population showed statistically significant dependence (p<0.001) of vertebral area gain on chronologic age, height, and weight right through the end of puberty, and especially so up to age 15 yr. However, height and weight were clearly better predictors of lateral and anteroposterior vertebral area gain than was chronologic age. Once vertebral growth is complete by age 18 yr or so, the lateral vertebral areas of the male subjects-regardless of body weight and height-are, on average, 25% larger, and the anteroposterior areas up to 30% larger than those of their female counterparts. After adjusting for chronologic age, height, and weight however we did not find significant differences, between gender, in vertebral area of male and female subjects, neither among children younger than 11 yr nor adolescents ages of 12-14 yr and young adults older than 18 yr.


The Maudsley reactive and nonreactive strains of rats: a clarification.
The origin of the Maudsley reactive and nonreactive strains of rats and the construction of the survey of researches using them are briefly reviewed in the light of Archer's criticisms. The reasons for reasserting that they represent a valid dichotomy in emotionality are summarized.


The Efficacy of Music for Emotional Wellbeing During the COVID-19 Lockdown in Spain: An Analysis of Personal and Context-Related Variables.
The strict lockdown experienced in Spain during March-June 2020 as a consequence of the COVID-19 crisis has led to strong negative emotions. Music can contribute to enhancing wellbeing, but the extent of this effect may be modulated by both personal and context-related variables. This study aimed to analyze the impact of the two types of variables on the perceived efficacy of musical behaviors to fulfill adults' emotional wellbeing-related goals during the lockdown established in Spain. Personal variables included age, gender, musical training, personality, resilience, and perception of music's importance. Contextual variables referred to living in a region with a high COVID-19 impact, perception of belonging to a risk group, being alone, having caring responsibilities during confinement, and amount of time of music listening as compared to prior to the crisis. The study was conducted retrospectively during August-December 2020, when the strict lockdown was over in Spain. An online survey was disseminated among the general population and groups of musicians, and the answers of 507 adults (from 18 years on, 73.9% females, 51.3% musically trained adults) were analyzed. Only personal, but not COVID-19 context-related variables, showed an impact on music's efficacy. The youngest age group of adults and those with musical training reported the highest efficacy of music for wellbeing enhancement, and music's importance was found to be the main significant predictor of music's perceived efficacy. Our findings suggest that the people who have been reported to be emotionally more vulnerable during the lockdown, due to either a strong impact on their daily lives or their lower resilience, perceive a higher benefit from musical behaviors. Being musically trained, even for a small number of years, also leads to a perception of higher efficacy of music for the achievement of emotional wellbeing goals. However, this effect is explained by the musically trained individuals' higher perception of music's importance. Although musical behaviors can be generally considered as important for wellbeing enhancement, our study highlights who are the potential individuals who could benefit the most from music-related activities for obtaining better levels of wellbeing, at least within the current context of the COVID-19 crisis.


Neighborhood deprivation and risk of mortality among men with prostate cancer: Findings from a long-term follow-up study.
The overall survival rate of prostate cancer (PCa) has improved over the past decades. However, huge socioeconomic and racial disparities in overall and prostate cancer-specific mortality exist. The neighborhood-level factors including socioeconomic disadvantage and lack of access to care may contribute to disparities in cancer mortality. This study examines the impact of neighborhood deprivation on mortality among PCa survivors. North Carolina-Louisiana Prostate Cancer Project (PCaP) data were used. A total of 2113 men, 1046 AA and 1067 EA, with PCa were included in the analysis. Neighborhood deprivation was measured by the Area Deprivation Index (ADI) at the census block group level using data from the US Census Bureau. Quintiles of ADI were created. Cox proportional hazards and competing risk models with mixed effects were performed to estimate the effect of neighborhood deprivation on all-cause and PCa-specific mortality adjusted for age, race, study site, insurance status, and comorbidities. Participants living in the most deprived neighborhoods had an increased risk for all-cause mortality (quintiles 4 + 5: adjusted hazard ratio [aHR] = 1.51, 95% confidence interval [CI] = 1.16-1.96) compared to those in the least deprived (quintile 1) neighborhoods. The risk of prostate cancer-specific mortality was also higher among those living in the deprived neighborhoods (quintiles 4 + 5: aHR = 1.90, 95% CI = 1.10-3.50) than those in the least deprived neighborhood. The findings suggest neighborhood-level resources or health interventions are essential to improve survival among men with PCa. Additional research should focus on the mechanisms of how the neighborhood environment affects mortality.


Reverse Z-effect phenomenon in a basicervical femoral fracture using cephalomedullary nail with two superior antirotation screws: A case report and procedure evaluation.
We present a case of reverse Z-effect phenomenon in a basicervical femoral fracture using a cephalomedullary nail together with two superior antirotation screws and evaluate the procedure. An 86-year-old woman fell in her home and could not stand due to right hip joint pain. X-ray and CT imaging showed a right basicervical femoral fracture (AO/OTA classification; 31B3), and open reduction and internal fixation (OR/IF) was performed with a cephalomedullary nail and two superior antirotation screws (TES Nail, HOMS, Tokyo, Japan). Two months later, X-ray showed penetration of the femoral head by the inferior lag screw with lateral migration of the two superior antirotation screws; the so-called "reverse Z-effect"; without any trauma. We performed the exchange of a shorter inferior lag screw for the longer one, and replaced the sliding type end cap with one of rocking type. The reverse Z-effect has been reported in cases with two lag screws, i.e. one inferior and one superior, in the past; however, to our knowledge, there has been no case reported in the literature using two superior antirotation screws together with one inferior lag screw.


Treatment of osteoarthritis with tiaprofenic acid: biochemical and histological protection against cartilage breakdown in the Pond-Nuki canine model.
Experimental and cage matched control animals were sacrificed 12 weeks after production of ligamentous instability in the right knee, and biochemical studies were performed on eroded OA and normal articular cartilage. Significant protection was afforded by tiaprofenic acid administered orally at 15 mg/kg body weight. Chondroprotection was manifested by reduction of fast sedimenting proteoglycan aggregates, as well as retention of hyaluronate content, and favorable proteoglycan aggregate S value levels. This agent showed significant chondroprotective action under the conditions of these studies.


Quality improvement: Online resources to support nursing education and practice.
Quality improvement (QI) competence is included in the American Association of Colleges of Nursing Essentials for pre-licensure and graduate degrees and is invaluable to nurses at all levels of professional practice. Among barriers to integration of QI competency is insufficient QI knowledge and skills among faculty and practicing nurses. Many nurses completed their nursing education before the introduction of the QI competencies in nursing programs, and it is understandable if they lack QI knowledge, skills, and attitudes. The purpose of this review is to provide information about QI online resources to nursing faculty, nurse leaders, and nurses in clinical practice with educational and training tools and opportunities to broaden their QI competence. The authors completed a comprehensive review of online resources for learning and/or teaching QI in health care and explored the websites of eight organizations. Within eight selected websites, the authors chose over 20 online self-study resources to learn and/or teach QI in health care with content for beginner, intermediate, and advanced learners. The QI online resources are easily accessible and can enable learning and engagement in QI of nursing faculty, students, and practicing nurses with no or limited exposure to the discipline.


Molecular evidence of placental hypoxia in preeclampsia.
Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease. Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps. Our results highlight a striking global gene expression similarity between 3% O(2)-treated explants, high-altitude placentae, and importantly placentae from preeclamptic pregnancies. We demonstrate herein the utility of explant culture and high-altitude placenta as biologically relevant and powerful models for studying the oxygen-mediated events in preeclampsia. Our results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.


EASY score (Eloquent, Age and baseline SYmptoms score) for outcome prediction in patients with acute ischemic stroke.
A pragmatic tool for the early and reliable prediction of recovery in patients with acute ischemic stroke is needed. We aimed to test the addition of brain eloquent areas involvement in variables predicting poor outcome, using a simple scoring system. Retrospective study of patients with anterior circulation acute ischemic stroke treated with best medical treatment and/or endovascular reperfusion. Primary outcome measure was 3-months poor outcome (mRs 3-6). We developed a prognostic model based on clinical data and a quantitative scoring system of the main eloquent brain areas involved on early follow-up CT, and analyzed its accuracy to predict poor outcome comparatively to three other prognostic models. The final model was used to develop a score for outcome prediction based on the multivariable analysis. A total of 197 patients were included (poor outcome = 62; mean age 67 ± 15.1 years; 44% females). Independent predictors of poor outcome were increasing age (p < 0.001), baseline NIHSS (p = 0.03), and the involvement of two brain areas: posterior limb of internal capsule (p < 0.001) and postero-superior corona radiata (p < 0.001). This model showed to be the most accurate to predict poor outcome (Balance Accuracy = 77.74%; C-Statistic = 0.891). The derived risk score attributing points for each of these variables (EASY score) showed similar performances (Balance Accuracy = 82.11%; C-Statistic = 0.90). The EASY score is an easy-to-apply and accurate tool to predict the 3-months functional outcome after ischemic stroke, relying on simple clinical features and the assessment of two key eloquent brain areas on early follow-up CT.


Gold-nanoparticle-based fluorescent "turn-on" sensor for selective and sensitive detection of dimethoate.
A simple approach to fabricate a highly selective and sensitive dimethoate probe was developed based on Rhodamine B (RB)-functionalized gold nanoparticles (AuNPs). The quenching of RB fluorescence in the presence of AuNPs in the solution, mediated by fluorescence resonance energy transfer, was observed. In the presence of dimethoate, the fluorescence intensity of the RB-AuNP solution is gradually recovered when dimethoate molecules displace RB molecules on the surface of the AuNPs, which significantly increased the fluorescence intensity of RB. Fluorescence is proportional to the dimethoate concentration in the range of 0.005-1.0 ppm (R2 = 0.989), and the LOD was 0.004 ppm. The recoveries of dimethoate in water and fruit samples were 86-116% with a good RSD (< 9.3%). Because of its high sensitivity, excellent selectivity, and convenient fabrication process, this method is a promising candidate for dimethoate screening.


Energy-Based Therapies for Erectile Dysfunction: Current and Future Directions.
Energy-based therapies are novel treatments for erectile dysfunction that are thought to work by stimulation of tissue vasodilation, neoangiogenesis, and so forth. Low-intensity extracorporeal shock wave therapy (Li-ESWT) is the energy-based therapy with the most robust evidence basis demonstrating efficacy and safety. Among this evidence, randomized controlled trials (RCTs) evaluating Li-ESWT have largely been focused on responders to phosphodiesterase-5 inhibitors. Many of these RCTs have limitations including short follow-up durations, inconsistent protocols, and small sample sizes. Until more diverse patient populations are studied and these limitations are addressed, the use of Li-ESWT should remain limited to IRB-approved clinical research trials.


Cancer of the bladder in spinal cord injury patients.
Since 1963, 10 cases of bladder carcinoma have been detected in 1,052 new admissions to our center. A high percentage of these patients had squamous cell carcinoma and/or squamous elements. This relatively high incidence stimulated a prospective study of 81 spinal cord injury patients either maintained on intraurethral catheter drainage for 10 years or an external appliance for 15 years. There were changes of squamous metaplasia in 19 per cent of the cases but no cancer was detected. It remains undetermined if squamous metaplasia is a pre-malignant lesion. However, the incidence of squamous metaplasia and squamous cell carcinoma in paraplegics with chronically infected bladders is not uncommon. Any spinal cord injury patient with hematuria needs a complete bladder evaluation and any long-term paraplegic with chronic infection should undergo cystoscopy and Papanicolaou smears as part of the yearly checkup.


Evaluation of apical extrusion and cone-beam computed tomography assessment of irrigant penetration in oval-shaped canals, using XP Endo Finisher and EndoActivator.
Thorough cleaning of the pulp space is a challenging task. The mechanical instrumentation alone is usually not sufficient to completely debride the canals, and therefore, it requires the chemical action of irrigants also to disinfect the difficult to reach areas. The purpose of this study was to determine apical extrusion and assess irrigant penetration through cone-beam computed tomography (CBCT) for EndoActivator (EA) and XP Endo Finisher (XP). Sixty single-rooted mandibular premolars with oval-shaped canals were equally divided into three groups after instrumentation, based on the final irrigation: Group-1 syringe needle (30G Max-I-probe), Group-2 EA, and Group-3 XP. After the final irrigation, the weight of the extruded sodium hypochlorite was calculated. The prepared canals were then irrigated with a radiopaque contrast medium, which was activated according to the group of the sample (Group-1, 2, or 3). The volume of irrigant filled in the canal, especially in the apical third was determined through special tools in CBCT imaging. One-way ANOVA test was used to compare the different groups. Significantly more apical extrusion was seen in XP (P < 0.001). Both XP and EA have shown complete penetration of irrigant in the canal (100%).


Insulin sensitivity and secretion in healthy elderly human subjects with 'abnormal' glucose tolerance.
Glucose tolerance deteriorates dramatically with advancing age. It is not known whether the underlying pathophysiology is different in older subjects. We employed a two step hyperinsulinaemic euglycaemic glucose clamp with [6(14)C] glucose infusion to compare peripheral and hepatic insulin sensitivity in eight elderly (EAGT) with eight young (YAGT) subjects with abnormal (matched) glucose tolerance and nine elderly subjects with normal glucose tolerance (ENGT). There was no difference in basal HGO (EAGT 14.5 +/- 0.9, YAGT 15.3 +/- 1.1 mumol kg-1 min-1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 +/- 0.8, YAGT 13.4 +/- 0.8 mumol kg-1 min-1) and step 2 (EAGT 25.1 +/- 3.1, YAGT 27.2 +/- 2.7 mumol kg-1 min-1). HGO was lower in the EAGT subjects at step 1 (2.3 +/- 0.4 vs. 4.3 +/- 0.6 mumol kg-1 min-1 P = 0.01). Incremental serum insulin response to oral glucose was comparable (EAGT 66.8 +/- 11.6 YAGT 57.8 +/- 12.2 mU l-1.h). Compared to the ENGT group the EAGT group was insulin resistant with a lower MCR of glucose at step 1 (2.03 +/- 0.28 vs. 3.23 +/- 0.44 ml kg-1 min-1 P = 0.04) and at step 2 (6.18 +/- 0.83 vs. 9.64 +/- 0.38 ml kg-1 min-1 P = 0.004) and had a lower early insulin response (AUC 0-30 min 5.9 +/- 1.1 vs. 9.8 +/- 1.4 mU l-1.h P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)


Living-Donor Lung Transplantation for Dyskeratosis Congenita.
This report describes 2 cases of dyskeratosis congenita in patients with progressive pulmonary diseases who required urgent living-donor lung transplantations. In the first case, a 13-year-old boy underwent bone marrow transplantation for aplastic anemia at age of 6 years. Severe pulmonary right-to-left shunting and fibrosis developed, and his condition deteriorated with acute fibrosis exacerbation and increased intrapulmonary shunt. He underwent lung transplantation and recovered uneventfully. In the second case, a 3-year-old girl with Revesz syndrome underwent bone marrow transplantation for refractory cytopenia. At 6 years of age, she had progressive hypoxia and a brain abscess. Her respiratory condition worsened, and she recovered uneventfully after urgent lung transplantation.


Synthesis and properties of thermoplastic starch laurates.
Maize starch was allowed to react homogeneously in N,N-dimethylacetamide (DMAc)/LiCl with lauric acid activated with 4-toluenesulfonyl chloride, N,N'-dicyclohexylcarbodiimide/4-(1-pyrrolidinyl)pyridine, 1,1'-carbonyldiimidazole, and N,N-dimethylformamide (DMF) combined with oxalyl chloride. Characterization of the products by means of 13C NMR spectroscopy revealed different substitution patterns depending on the activation agent. The activation of lauric acid with DMF in combination with oxalyl chloride gave starch laurates of highest degree of substitution (DS), yield and reaction efficiency. The melting temperatures and the solubility of the thermoplastic starch laurates were found to depend on the DS, the substitution pattern, and on the molar mass of the starch esters.


Aptamer-mediated DNA concatemer functionalized magnetic nanoparticles for reversible capture and release of circulating tumor cells.
Effectively capturing, releasing, and reanalyzing circulating tumor cells (CTCs) are critical in cancer diagnosis and individualized treatment. Traditional immunomagnetic separation has disadvantages of low sensitivity and specificity, and is time-consuming and costly in CTCs capture. It is also easily disturbed by the microenvironment in releasing and analyzing CTCs. Here, we proposed an aptamer-mediated DNA concatemer functionalized magnetic nanoparticles (MNPs-AMDC) for the reversible capture and release of CTCs. In this study, aptamers were used both for efficiently capturing CTCs without complicated assembly steps and stimulus-response switch for releasing CTCs with little influence on cellular activity. The MNPs-AMDC was demonstrated to effectively capture (83%) and release CTCs with a good viability rate (92%). Moreover, this device was also tested in clinical blood samples, which would provide a universal tool for diagnosing cancer and treating individuals.


Automatic human identification from panoramic dental radiographs using the convolutional neural network.
Human identification is an important task in mass disaster and criminal investigations. Although several automatic dental identification systems have been proposed, accurate and fast identification from panoramic dental radiographs (PDRs) remains a challenging issue. In this study, an automatic human identification system (DENT-net) was developed using the customized convolutional neural network (CNN). The DENT-net was trained on 15,369 PDRs from 6300 individuals. The PDRs were preprocessed by affine transformation and histogram equalization. The DENT-net took 128 × 128 × 7 square patches as input, including the whole PDR and six details extracted from the PDR. Using the DENT-net, the feature extraction took around 10 milliseconds per image and the running time for retrieval was 33.03 milliseconds in a 2000-individual database, promising an application on larger databases. The visualization of CNN showed that the teeth, maxilla, and mandible all contributed to human identification. The DENT-net achieved Rank-1 accuracy of 85.16% and Rank-5 accuracy of 97.74% for human identification. The present results demonstrated that human identification can be achieved from PDRs by CNN with high accuracy and speed. The present system can be used without any special equipment or knowledge to generate the candidate images. While the final decision should be made by human specialists in practice. It is expected to aid human identification in mass disaster and criminal investigation.


Myxoid Adrenocortical Adenoma: A report of two cases and literature review.
Myxoid adrenocortical adenomas are uncommon. There were only 61 cases reports documented, and the tumors are tended to be misdiagnosed in virtue of being rare and distinctive histological features. Recently we encountered two myxoid adrenocortical adenoma cases of a 31-year-old Chinese woman and a 45-year-old Chinese man. The patients did not receive further treatment after surgery and were still alive after following up for 20 months. Myxoid adrenocortical adenomas is extremely rare. Recognition of this entity would be beneficial for pathologists to avoid msidiagnosis, and unnecessary treatment.


Correction: The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer.
[This corrects the article DOI: 10.1371/journal.pone.0225357.].


Extreme Energy Dissipation via Material Evolution in Carbon Nanotube Mats.
Thin layered mats comprised of an interconnected meandering network of multiwall carbon nanotubes (MWCNT) are subjected to a hypersonic micro-projectile impact test. The mat morphology is highly compliant and while this leads to rather modest quasi-static mechanical properties, at the extreme strain rates and large strains resulting from ballistic impact, the MWCNT structure has the ability to reconfigure resulting in extraordinary kinetic energy (KE) absorption. The KE of the projectile is dissipated via frictional interactions, adiabatic heating, tube stretching, and ultimately fracture of taut tubes and the newly formed fibrils. The energy absorbed per unit mass of the film can range from 7-12 MJ kg-1, much greater than any other material.


Variation of phlorotannins among three populations of Fucus vesiculosus as revealed by HPLC and colorimetric quantification.
In ecological studies, phlorotannins have conventionally been quantified as a group with similar functionality. Since this group consists of oligo- and polymers, the quantification of their pooled contents alone may not sufficiently describe the variation of these metabolites. Genetic variation, plastic responses to environment, and the ecological functions of separate phlorotannin oligo- and polymers may differ. Two analyses, i.e., the colorimetric Folin-Ciocalteu assay and a normal-phase high-performance liquid chromatographic (HPLC) method were used to study genetic and environmental variation in phlorotannins of the brown alga Fucus vesiculosus (L.). The colorimetric method provides the total phlorotannin content, the latter a profile of 14 separate traces from the phenolic extract that represent an individual or groups of phlorotannins. We reared the algae that originated from three separate populations in a common garden for 3 months under ambient and enriched-nutrient availability and found that they differed in both their total phlorotannin content and in phlorotannin profiles. Some individual traces of the profiles separated the populations more clearly than the colorimetric assay. Although nutrient enrichment decreased total phlorotannin content, it did not show a significant influence on the phlorotannin profile. This implies that plastic responses of compounds other than phlorotannins may interfere with the determination of total phlorotannins. However, the phlorotannin profile and the total content showed genetic variation among local populations of F. vesiculosus; therefore, phlorotannins may respond to natural selection and evolve both quantitatively and qualitatively.


Functional and early weight-bearing protocol for achilles tendon ruptures: a retrospective study.
Conservative treatment of achilles tendon rupture (ATR) might be favoured in centres with an early weight-bearing protocol, but no consensus exists on the clear definition of an early weight-bearing protocol. The aim of this study is to evaluate the introduction of an early weight-bearing conservative treatment protocol in patients with ATR compared to patients without this protocol. A single-centre retrospective study was performed. All patients presenting with an ATR during a 10-year period were included. Between January 1st 2008 and December 31st 2015, all patients were included for either operative or conservative treatment without an early weight-bearing protocol (non-EWB). Between January 1st 2016 and 30th June 2019, patients were, primarily, treated conservatively with early weight-bearing protocol (EWB). A primary-outcome parameter was re-rupture, and secondary-outcome parameters were treatment-related complications. In the period 2008-2015, 246 patients were treated with non-EWB. In the period 2016-2019, 58 patients were treated conservatively with EWB. No significant differences were found in re-rupture rates between non-EWB (5.3%) and conservative EWB (6.9%) (p = 0.536) or conservative non-EWB (9.4%) and conservative EWB (6.9%) (p = 0.283). Pulmonary embolism (1.0%) and deep venous thrombosis (1.0%) were observed in operative non-EWB patients. In conservative EWB patients, superficial pressure ulcers (5.2%) and treatment failure (5.2%) were observed. Conservative treatment of ATR with an early weight-bearing protocol showed similar re-rupture rates and complication rates compared to conservative and operative treatments without an early weight-bearing protocol.


How the EcoRI endonuclease recognizes and cleaves DNA.
One popular recombinant DNA tool is the EcoRI endonuclease, which cleaves DNA at GAATTC sites and serves as a paradigm for sequence specific DNA-enzyme interactions. The recently revised X-ray crystal structure of an EcoRI-DNA complex reveals EcoRI employs novel DNA recognition motifs, a four alpha-helix bundle and two extended chains, which project into the major groove to contact substrate purines and pyrimidines. Interestingly, pyrimidine contacts had been predicted based on genetic and biochemical studies. Current work focuses on the EcoRI active site structure, enzyme and substrate conformational changes during catalysis, and host-restriction system interactions.


Polycyclic aromatic hydrocarbons in sedimentary cores of Tibetan Plateau: Influence of global warming on cold trapping.
Cold condensation is an important pathway for polycyclic aromatic hydrocarbons (PAHs) depositing at remote alpine lakes after long-range atmospheric transportation. However, in the context of global warming, the obvious temperature rise in the Tibetan Plateau (TP) might have an impact on the air deposition of PAHs by controlling the extent of cold condensation. To investigate the influence of rising temperatures on the atmospheric deposition of PAHs, two dated sedimentary cores from Pumoyum Co Lake (PC) and Selin Co Lake (SC) were collected, respectively and concentrations of 16 individual PAHs were measured. In both PC and SC, the total concentration of 16 PAHs presented relatively lower levels in four historical periods of "hot anomaly" including 1973-1975, 1988-1989, 1998-1999, and 2006-2007. This indicated that the hot temperatures might restrict the atmospheric deposition of PAHs. Besides, the results of the principal component analysis did discriminate those "hot anomalies". As the temperature kept increasing in TP, for low molecular weight PAHs and high molecular weight PAHs, the influence of rising temperatures on the cold condensation was different. Therefore, it was identified that the effect of global warming on the environmental fate of POPs cannot be neglected, especially in alpine regions like TP.


Binding of galactosylsphingosine (psychosine) by albumin.
On applying [3H]galactosylsphingosine (psychosine) and albumin to a gel filtration column, either as a pre-incubated mixture or as separate solutions, the lipid and albumin co-eluted. When albumin and [3H]galactosylsphingosine were incubated with Sephadex G-50, the concentration of galactosylsphingosine outside the gel increased as the concentration of albumin increased. These observations indicate that albumin binds galactosylsphingosine. By using an equilibrium gel procedure, it was estimated that one molecule of albumin has 7.4 binding sites for galactosylsphingosine, and that the dissociation constant is 3.9 X 10(-6) M. These values appear compatible with the potency of albumin to suppress galactosylsphingosine-induced hemolysis.


Facile synthesis, metastable phase induced morphological evolution and crystal ripening, and structure-dependent photocatalytic properties of 3D hierarchical anatase superstructures.
Unique 3D hierarchical anatase TiO2 superstructures with evolvable morphologies and tunable sizes were successfully fabricated through a facile solvothermal route without using any structure-directing additives. A complex assembly process involving nucleation of nascent nanoparticles, agglomeration and ordered attachment of tiny nanocrystals, and regrowth induced by metastable crystal phase was put forward for the formation and morphology evolution of the anatase superstructures. It was revealed the crystalline phase experienced a ripening process from semicrystal to mesocrystal status accompanying the morphologies evolving from peony-like to chrysanthemum-like and eventually to spherical structures. The obtained 3D hierarchical anatase TiO2 superstructures exhibited superior photocatalytic activities for organic pollutant degradation, which could be largely attributed to the more efficient light-harvesting ability and the high specific surface area of the unique structures.


Immigration and earnings inequality in America's new small-town destinations.
Research on the relationship between immigrant population concentration and earnings inequality is divided between two perspectives. Supply-side arguments maintain that areas attracting large numbers of immigrants experience minimal wage growth at the bottom of the earnings distribution, which increases local levels of earnings inequality. Demand-side arguments contend that industrial restructuring reduces the pay of manual labor regardless of, and even prior to, the arrival of foreign-born workers. Adjudicating between these two perspectives is hindered by issues of potential endogeneity, which confound attempts to independently assess the effects of immigration on inequality or vice versa using OLS regression. We consider a third perspective called the reciprocal effects hypothesis which contends that immigrant concentration and earnings inequality emerge together through a mutually reinforcing feedback process. We explore this question in America's "new small-town destinations" using data from U.S. micropolitan statistical areas. We use three-stage least squares estimation to address the endogeneity problem and to test these three hypotheses. While we find support for both the supply- and demand-side perspectives, the results are best explained by the reciprocal effects hypothesis.


Mindlin solution on ground deformation caused by the trench excavation during installation of concrete diaphragm wall panels.
Concrete diaphragm walls (CDWs) are widely used as support of deep excavation in soft ground in urban areas. Ground deformation occurs during the excavation of trenches for the installation of the CDW panels due to ground stress release. This paper investigates the ground deformation during slurry trenching using Mindlin solution. The pressure of slurry used to protect the trench stability during excavation is simulated as a triangularly distributed load on the trench walls, the soil stress state is solved using Mindlin solution, and the horizontal and vertical ground displacement are obtained through integral transformation of ground strain. The rationality of the solution is verified through comparison between the analytical solution and field measurement. Sensitivity analyses are performed on soil elastic modulus, Poisson's ratio, trench excavation depth and panel length. Simplified formulation is proposed for the prediction of horizontal ground deformation. The impact of excavation stages and adjacent panels on the ground deformation is explored. The study finds that the Mindlin solution is able to provide an approximate solution on the ground deformation during slurry trenching, and the simplified formulation can be used to provide a fast estimate of the horizontal ground movement in engineering practice.


Role of sex steroids and prostaglandins during the luteal life cycle in domestic cats and lynxes.
Although lynxes and domestic cats are both felids, their luteal life cycles differ. As in many species, corpora lutea (CLs) of domestic cats regress after pregnancy or pseudopregnancy. By contrast, CLs of lynxes do not functionally regress following the cycle of their formation. They stay physiologically active and persist for several years. To obtain an improved understanding of the life cycle of both species, we comparatively studied the CLs of these species in detail. In this review, we summarize the similarities and differences of their CLs regarding sex steroid and prostaglandin generation and receptors. The most evident differences were visible in the CLs of lynxes, which persist from previous cycles, compared with CLs of lynxes and domestic cats from the recent luteal cycle. We assume that these differences could indicate processes ensuring long-term luteal survival and functionality, for example, by high estrogen production/metabolism or by antioxidative effects.


Cloning, expression, and characterization of a novel alkali-tolerant xylanase from alkaliphilic Bacillus sp. SN5.
A xylanase gene (xyn11A) was cloned from the genomic library of alkalophilic Bacillus sp. SN5. It encoded a polypeptide of 366 amino acids, consisting of a family 11 glycoside hydrolase, a short linker region, and a family 36 carbohydrate-binding module (CBM). The intact xylanase Xyn11A and the CBM-linker-truncated Xyn11A-LC were expressed in Escherichia coli BL21 (DE3). Both purified recombinant proteins exhibited the highest activity at 55 °C. The optimal pH for Xyn11A activity was 7.5, whereas Xyn11A-LC showed a broad pH profile (>80% activity at pH 5.5-8.5) with optimal activity at pH 5.5 and 7.5-8.0. They had high alkali tolerance, retaining over 80% residual activity after preincubation at pH 8.5-11.0 at 37 °C for 1 H. Xyn11A-LC showed better thermal stability, lower affinity, and lower catalytic activity to insoluble xylan than Xyn11A, whereas its specific activity for soluble beechwood xylan (4,511.9 U/mg) was greater than that of Xyn11A (3,136.4 U/mg). These results implied that the CBM of Xyn11A could change the enzymatic properties and play a role in degrading insoluble xylan. Xyn11A-LC is a family 11 alkali-tolerant cellulase-free xylanase with high specific activity, which qualifies it as a potential candidate for industrial applications, especially in the paper industry.


Clinical implications of mother-to-child transmission of HCV.
Testing for vertical transmission of hepatitis C virus (HCV) infection in infants and children will enable early identification of the majority of uninfected HCV-exposed infants and children, and will provide significant emotional relief for the parents. The small percentage of infected children should be offered enrollment in well-designed clinical trials of optimal medical management for prevention of the predicted long-term outcomes of chronic HCV infection: chronic hepatitis, cirrhosis and hepatocellular carcinoma.


Clinical outcomes of laminoplasty for patients with lysosomal storage disease including mucopolysaccharidosis and mucolipidoses: a retrospective cohort study.
Although the clinical efficacy of laminoplasty in adult cervical spondylotic myelopathy or ossification of posterior longitudinal ligament has been frequently reported, there are only few reports of laminoplasty for patients with lysosome storage diseases (LSDs). Therefore, this study aimed to report the midterm clinical and radiological outcomes of patients with LSDs after cervical laminoplasty. Six patients with LSD who underwent laminoplasty with/without C1 laminectomy for cervical myelopathy were enrolled. Clinical evaluations, including the cervical Japanese Orthopedic Association (cJOA) score and visual analog scale (VAS) scores for upper extremity numbness, and radiographic parameters, including C2-C7 lordotic angle, atlanto-dens interval (ADI), and ⊿ADI, were evaluated preoperatively, at 2 years postoperatively, and at the final follow-up. Five patients had mucopolysaccharidoses (type I: n = 1, II: n = 3, VII: n = 1) and one patient had mucolipidoses type III. The mean age of patients at surgery was 27.5 years, and the mean postoperative follow-up period was 61 months. All mucopolysaccharidoses cases required C1 posterior arch resection with C2-C7 laminoplasty. No critical complications were observed postoperatively. There were no significant differences in C2-C7 angle (p = 0.724) and ⊿ADI (p = 0.592) between the preoperative and final follow-ups. The cJOA score and VAS for numbness significantly improved at the final follow-up (p = 0.004 and p = 0.007, respectively). The cervical myelopathy in patients with LSD could be safely and effectively treated with laminoplasty with/without C1 posterior arch resection after excluding patients with atlantoaxial instability. Atlantoaxial stability and symptom improvement could be maintained at an average of 5 years postoperatively.


Clinical and pathological aspects of benign and malignant squamous epithelium of the corpus uteri; a report of two cases.
Two patients with primary squamous cell carcinoma of the uterus are described. In both patients, the disease was at an advanced stage when the diagnosis was made. Although endometrial malignancies with squamous elements account for 10-30% of endometrial carcinomas, primary squamous cell carcinoma of the uterus is extremely rare. Up to now fewer than 30 cases have been reported. The pathogenesis, morphogenesis and aetiology of squamous epithelium in the corpus uteri is discussed. Finally, some clinical aspects of the primary squamous cell carcinoma of the corpus uteri are reviewed.


[Nausea and dizziness in a patient with heart failure and cardiac resynchronization therapy].
A 77-year-old man with ischemic cardiomyopathy, severely reduced left ventricular function, and biventricular defibrillator for primary prevention received catheter ablation for multiple ventricular tachycardia despite amiodarone treatment. A few weeks later, the patient presented with unspecific symptoms such as general malaise and nausea.


Tissue-specific expression of a plant turgor-responsive gene with amino acid sequence homology to transport-facilitating proteins.
We report the isolation of a turgor-responsive gene of pea, trg-31, whose transcription induced within 30 min after the loss of leaf turgor. Structure of the coding region and 1.4 kb of 5' untranslated region was determined by DNA sequencing. A 3 kb promoter fragment from trg-31 was fused to a beta-glucuronidase (GUS) reporter gene in pBI101, tobacco leaf disks and mature plants analyzed for turgor-responsive induction of GUS mRNA. Significant amino acid sequence homology exists between trg-31 and putative transport proteins of bovine, Phaseolus, soybean and Escherichia coli membranes.


Digital array scanned interferometer: sensors and results.
Digital array scanned interferometers (DASI) blend characteristics of a grating spectrometer and a two-beam interferometer for acquisition of hyperspectra. DASI's posses field-widened capabilities that permit very high throughput. Aspects of DASI design, hyperspectra, and data processing methods are presented. In particular, we provide data showing that photon-noise-limited hyperspectra are achievable for DASI data.


Diagnosis of penicillin allergy. An evaluation of the leucocyte aggregation test in man.
A study was made to establish the value of the leucocyte aggregation test (LAT) in drug allergy using penicillin antigen. The antigen-induced human peripheral blood leucocyte aggregation was measured quantitatively. The results obtained have been compared with the leucocyte migration inhibition test (LMIT) in patients with or without delayed penicillin allergy. Among forty-four penicillin-allergic subjects and thirty-six control subjects, LAT was found positive in respectively 70.5 and 30.5% (P less than 0.001) whereas LMIT was found positive in respectively 56.8 and 50% of the patients. These results were confirmed by multiple correspondence analysis (MCA), using a computer. Furthermore, this method, enables a more comprehensive and reliable interpretation of the tests, by the help of various quantitative and qualitative criteria. It is concluded that LAT shows more discrimination than the LMIT in distinguishing a penicillin-allergic population from a non-allergic one. In addition, LAT offers great technical advantages over the LMIT for the diagnosis of drug allergy.


15-Deoxy-Δ12,14-prostaglandin J2 enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPARγ pathways.
Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-γ (PPARγ), 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ(2) in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ(2), but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ(2) and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPARγ antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ(2)-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ(2) activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ(2) exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPARγ.


Role of GPRC6A in Regulating Hepatic Energy Metabolism in Mice.
GPRC6A is a widely expressed G-protein coupled receptor that regulates energy metabolism. Global deletion of Gprc6a in mice is reported to result in a metabolic syndrome-like phenotype and conditional deletion of Gprc6a in pancreatic β-cell and skeletal muscle respectively impair insulin secretion and glucose uptake. In the current study, we explore the hepatic functions of GPRC6A by conditionally deleting Gprc6a in hepatocytes by cross breeding Alb-Cre and Gprc6aflox/flox mice to obtain Gprc6aLiver-cko mice. Gprc6aLiver-cko mice on a normal diet showed excessive hepatic fat accumulation and glycogen depletion. These mice also exhibit impaired glucose and pyruvate tolerance, but normal insulin sensitivity. Decreased circulating FGF-21 levels and FGF-21 message expression in the liver were found in Gprc6aLiver-cko mice. Hepatic transcriptome analysis identified alterations in multiple pathways regulating glucose, fat and glycogen metabolism in Gprc6aLiver-cko mice. Taken together, our studies suggest that GPRC6A directly regulates hepatic metabolism as well as regulates the production and release of FGF-21 to control systemic energy homeostasis. GPRC6A's unique regulation of β-cell, skeletal muscle and hepatic function may represent a new therapeutic target for treating disordered energy metabolism metabolic syndrome and type 2 diabetes.


Feeding Malic Acid to Chickens at Slaughter Age Improves Microbial Safety with Regard to Campylobacter.
This study supplied malic acid-supplemented drinking water to flocks that were naturally Campylobacter-positive and assessed the effect of feeding malic acid to chickens on Campylobacter reduction and poultry production. In Experiment 1, chickens were provided with malic acid-supplemented drinking water for three weeks. The contamination loads of Campylobacter were decreased by 0.91-0.98 log after the first week of use (p < 0.05). However, this effect did not persist over time and significant decontamination could not be found in the second and third weeks of application. Thus, in Experiment 2 malic acid-supplemented drinking water was given to chickens for a period of five days at slaughter age. The Campylobacter carriage was found to be effectively decreased by 1.05-1.55 log (p < 0.05). Malic acid had no adverse effects on chicken body weight, weight gain, intestinal indices, or the microbiota. In addition, it could change the composition of chicken meat since the moisture content was increased by 5.12-5.92% (p < 0.05) and the fat content was decreased by 1.60% (p < 0.05). Our study provides an effective means for reducing the contamination of Campylobacter during the chicken rearing period and this method can be applied to promote the safe development of poultry farming and its products.


Use of microdialysis to study interstitial nitric oxide and other reactive oxygen and nitrogen species in skeletal muscle.
Microdialysis techniques can be used to sample the interstitial space of tissues such as skeletal muscle. Analytical developments have allowed adaptations of these techniques to permit continuous monitoring of nitric oxide and a number of other reactive oxygen and nitrogen species in skeletal muscle extracellular space. Methods are described for assessment of interstitial nitrate and nitrite content, superoxide anion content, hydroxyl radical activity, and the content of relatively stable lipid radicals detectable using spin trapping and electron spin resonance techniques in skeletal muscle of rodents at rest and during contractile activity.


Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.
Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection. We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years. This was a multicenter trial. Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge. Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy. Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention. This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p > 0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p > 0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34). The predetermined sample size to adequately reduce the risk of type II error was not achieved. Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560. ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p> 0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p> 0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).


[Peutz-Jeghers syndrome (mucocutaneous melanosis associated with gastrointestinal polyposis). Presentation of 5 cases presenting in the same family].
Five brothers suffering from Peutz-Jeghers syndrome with freckles in the skin of the face and mucous membrane of the oral cavity, and intestinal polyps are reported. These patients have not been traditionally considered of being at risk. The current opinion is that patients with this disorder can develop malignancies in the gastrointestinal tract, and tumors in other organs.


Management of Malignant Colon Polyps.
A 54-year-old otherwise healthy woman presented for screening colonoscopy, during which 4 pedunculated 5- to 12-mm polyps distributed throughout the colon were found (Fig. 1). The 12-mm sigmoid polyp was removed with hot snare polypectomy in a nonpiecemeal fashion. Pathology demonstrated 3 tubular adenomas and a poorly differentiated invasive carcinoma in a sigmoid polyp without tumor budding, invading 0.8 mm into the submucosa, with lymphovascular invasion and with a deep margin of 0.6 mm. The next week, she underwent repeat flexible sigmoidoscopy with tattooing of the polypectomy site. She had a normal staging CT chest/abdomen/pelvis as well as CEA level and later underwent uneventful laparoscopic sigmoid resection, which included the area of endoscopic tattoo. Final pathology confirmed the presence of the tattooed area and polypectomy scar and showed no residual primary tumor and 2/18 positive lymph nodes (Fig, 2). She was referred to medical oncology for adjuvant chemotherapy.


A non-lethal chemically based approach to investigate the quality of harbour sediments.
A non-lethal chemically based approach was used to investigate the quality of harbour sediments receiving combined road runoff and sewage effluents. A previous investigation of the behaviour of the amphipod Corophium volutator linked polycyclic aromatic hydrocarbons (PAH) in sediments corresponding to the probable effects levels listed in the sediment quality guidelines of the Canadian Council of the Marine Environment to a sediment avoidance response. Since the amphipods did not biotransform contaminants, bioaccumulation was the only fate pursued to examine the bioavailability of PAH. For five Halifax Harbour sediments, a relationship was established between the threshold effects level representing the amphipods' avoidance response and the bioaccumulation of PAH. A body burden of 0.3-1.1 mumol/kg (wet weight) was determined for the sum of abundant parental PAH in amphipods exposed to sediments that initiated the behavioural effect. PAH were much more available from spiked sediments than from field sediments, with biota-sediment accumulation factors of 2.2-7.8 compared to <0.01-0.3, respectively. Animals exposed to PAH-spiked sediments avoided contaminated sediments when their body burden was up to seven times higher than observed with field sediments. This latter result and two exposures to sediments collected further away from sewage discharges point to a role for unidentified chemicals in the body burden and behaviour relationship. Further research is warranted to develop this promising assessment tool.


A novel method of measuring gas phase nitric oxide concentration in cell cultures.
This is the first report on the measurement of nitric oxide (NO) concentrations in the gas phase in a squamous cell culture. The technique may permit the assessment of NO output under conditions that aim to mimic facets of pathology in relatively inaccessible tissues. The primary aim of this study was to devise a method to detect the NO concentration produced by cell cultures in the gas phase of a culture flask. A secondary aim was to determine whether the effect of hypoxia or radiation on NO production in a human squamous cell carcinoma cell culture would be detectable with this technique. The NO concentration was measured off-line using a rapid-response chemiluminescent analyzer. The gas samples were aspirated from cell culture flasks (i) under normal culture conditions, (ii) under conditions of hypoxia and (iii) following radiation of human head and neck squamous cell carcinoma cell line cultures. Elevated levels of the gas phase NO concentration were consistently obtained from the cell culture flasks using this experimental set-up. Hypoxia and radiation diminished NO production.


Cricket Meal (Gryllus bimaculatus) as a Protein Supplement on In Vitro Fermentation Characteristics and Methane Mitigation.
The aim of this work was to conduct the effects of cricket (Gryllus bimaculatus) meal (CM) as a protein supplement on in vitro gas production, rumen fermentation, and methane (CH4) mitigation. Dietary treatments were randomly assigned using a completely randomized design (CRD) with a 2 × 5 factorial arrangement. The first factor was two ratios of roughage to concentrate (R:C at 60:40 and 40:60), and the second factor was the level of CM to replace soybean meal (SBM) in a concentrate ratio at 100:0, 75:25, 50:50, 25:75, and 0:100, respectively. It was found that in vitro DM degradability and the concentration of propionic (C3) were significantly increased (p < 0.05), while the potential extent of gas production (a + b), acetate (C2), acetate and propionate (C2:C3) ratio, and protozoal population were reduced (p < 0.05) by lowering the R:C ratio and the replacement of SBM by CM. In addition, rumen CH4 production was mitigated (p < 0.05) with increasing levels of CM for SBM. In this study, CM has the potential to improve rumen fermentation by enhancing C3 concentration and DM degradability, reduced methane production, and C2:C3 ratio. The effects were more pronounced (p < 0.05) at low levels of roughage.


Aflatoxins are natural scavengers of reactive oxygen species.
The role of aflatoxins (AFs) in the biology of producing strains, Aspergillus sect. Flavi, is still a matter of debate. Over recent years, research has pointed to how environmental factors altering the redox balance in the fungal cell can switch on the synthesis of AF. Notably, it has been known for decades that oxidants promote AF synthesis. More recent evidence has indicated that AF synthesis is controlled at the transcriptional level: reactive species that accumulate in fungal cells in the stationary growth phase modulate the expression of aflR, the main regulator of AF synthesis-through the oxidative stress related transcription factor AP-1. Thus, AFs are largely synthesized and secreted when (i) the fungus has exploited most nutritional resources; (ii) the hyphal density is high; and (iii) reactive species are abundant in the environment. In this study, we show that AFs efficiently scavenge peroxides and extend the lifespan of E. coli grown under oxidative stress conditions. We hypothesize a novel role for AF as an antioxidant and suggest its biological purpose is to extend the lifespan of AFs-producing strains of Aspergillus sect. Flavi under highly oxidizing conditions such as when substrate resources are depleted, or within a host.


Comparison of motor strategies in sit-to-stand and back-to-sit motions between healthy and Alzheimer's disease elderly subjects.
We studied the kinematics of shoulder displacement during sit-to-stand and back-to-sit in 6 healthy elderly subjects and six elderly subjects with mild to moderate Alzheimer's disease in order to elucidate the impact of Alzheimer's disease on motor planning and control processes. During sit-to-stand, Alzheimer's disease subjects reduced their forward displacement and started their upward displacement earlier than healthy elderly subjects. Furthermore, shoulder path curvatures were more pronounced for upward compared with downward displacement in healthy elderly group, in contrast with Alzheimer's disease group. Temporal analysis found that: 1) for both groups, profiles of velocity of sit-to-stand and back-to-sit showed two peaks corresponding respectively to forward/upward and to downward/backward displacements, 2) peaks of velocity were almost comparable between the two groups, 3) duration of sit-to-stand was shorter than duration of back-to-sit in the two groups and 4) duration of sit-to-stand and back-to-sit was shorter in Alzheimer's disease group than in healthy elderly group. However, dissimilarities were observed for transition and deceleration phases during sit-to-stand, and for acceleration and transition phases during back-to-sit, between the two groups. Interestingly, while sit-to-stand and back-to-sit differed in healthy elderly subjects during transition and deceleration phases, such a difference was not observed for Alzheimer's disease subjects. So, our study showed that invariant spatio-temporal movement parameters in the two groups differed, while non-invariant parameters did not, and suggests that higher level motor process of whole body motions are affected by Alzheimer's disease, while lower level motor features remain intact.


Microevolution of the noble crayfish (Astacus astacus) in the Southern Balkan Peninsula.
The noble crayfish (Astacus astacus) displays a complex historical and contemporary genetic status in Europe. The species divergence has been shaped by geological events (i.e. Pleistocene glaciations) and humanly induced impacts (i.e. translocations, pollution, etc.) on its populations due to species commercial value and its niche degradation. Until now, limited genetic information has been procured for the Balkan area and especially for the southernmost distribution of this species (i.e. Greece). It is well known that the rich habitat diversity of the Balkan Peninsula offers suitable conditions for genetically diversified populations. Thus, the present manuscript revisits the phylogenetic relationships of the noble crayfish in Europe and identifies the genetic make-up and the biogeographical patterns of the species in its southern range limit. Mitochondrial markers (i.e. COI and 16S) were used in order to elucidate the genetic structure and diversity of the noble crayfish in Europe. Two of the six European haplotypic lineages, were found exclusively in Greece. These two lineages exhibited greater haplotypic richness when compared with the rest four (of "Central European" origin) while they showed high genetic diversity. Divergence time analysis identified that the majority of this divergence was captured through Pleistocene, suggesting a southern glacial refugium (Greece, southern Balkans). Furthermore, six microsatellite markers were used in order to define the factors affecting the genetic structure and demographic history of the species in Greece. The population structure analysis revealed six to nine genetic clusters and eight putative genetic barriers. Evidence of bottleneck effects in the last ~5000 years (due to climatic and geological events and human activities) is also afforded. Findings from several other research fields (e.g. life sciences, geology or even archaeology) have been utilized to perceive the genetic make-up of the noble crayfish. The southernmost part of Balkans has played a major role as a glacial refugium for A. astacus. Such refugia have served as centres of expansion to northern regions. Recent history of the noble crayfish in southern Balkans reveals the influence of environmental (climate, geology and/or topology) and anthropogenic factors.


Fetal Nasal Bone Length as a Novel Marker for Prediction of Adverse Perinatal Outcomes in the First-Trimester of Pregnancy.
Adverse outcomes of pregnancy are a challenging health-care problem. Prediction of adverse pregnancy outcomes is important to prevent the morbidities of the foetus and the mother. To study the clinical interest of fetal nasal bone length in predicting adverse pregnancy outcomes in the first trimester of pregnancy. A population-based retrospective cohort study. Data from 868 women with first-trimester fetal nasal bone length and birth records available were enrolled. Fetal nasal bone length percentiles were determined and evaluated for their ability to predict adverse pregnancy outcomes such as preterm birth, preterm labour, preterm premature rupture of membranes, early preterm birth, gestational diabetes mellitus, gestational hypertension-preeclampsia, small-for-gestational age foetuses, macrosomia, oligohydramnios, polyhydramnios and fetal distress. Fetal nasal bone length >95th percentile was significantly associated with preterm labor and preterm premature rupture of membranes (p=0.02, accuracy 0.91 and p=0.001, accuracy 0.94, respectively), whereas nasal bone length >99th percentile was significantly associated with preterm labor and oligohydramnios (p=0.006, accuracy 0.95 and p=0.014, accuracy 0.97). Fetal nasal bone length at high percentiles in the first trimester of pregnancy may aid in the prediction of adverse outcomes such as preterm labour, preterm premature rupture of membranes and oligohydramnios.


The effect of intraocular tetrodotoxin on the postnatal reduction in the numbers of optic nerve axons in the rat.
We have examined the effects of blocking retinal ganglion cell activity with the sodium channel blocker tetrodotoxin (TTX) on the postnatal reduction in the number of optic nerve axons (and, by interference, the degree of ganglion cell loss in the retina). TTX was injected every other day into the left eyes of a series of albino rats beginning on the day of birth, continuing through the 3rd, 7th, 12th or 14th days when the animals were killed and the optic nerves from both eyes were prepared for electron microscopy. The numbers of axons in the TTX treated and untreated optic nerves from the opposite side were determined from electron micrographs, and compared to the number seen in normal rats at the same ages. Both the magnitude and the time course of the reduction in the number of axons in the TTX-treated and untreated nerves were found to be similar to those seen in normal animals. However, there was a slight reduction in the loss of optic axons in the untreated nerves on the side opposite the TTX injections; this attenuation in axon loss could be mimicked by large systemic injections of TTX, and is probably attributable to a general systemic effect following repeated intraocular injections. These findings indicate that blocking ganglion cell activity with intraocular injections of TTX has little effect on the normal rate of axon loss from the optic nerve and on the numbers of ganglion cells that die during the first two weeks of postnatal life.