Injuries of the distal radioulnar joint.
Injuries of the distal radioulnar (DRU) joint are common. If the joint is unstable or discongruous, attempts should be made to restore anatomic alignment and stability. Although most acute injuries of the DRU joint are easily treated, they are often overlooked or misdiagnosed because they usually occur in association with other major injuries of the upper limb. Acute and chronic abnormalities are described briefly and the treatment for each is discussed. Appropriate diagnosis and management of the acute injury will yield a much higher success rate than reconstructive procedures to correct a chronic disorder. A differentiation should be made between DRU joint dysfunction and ulnar impingement against the carpus; ulnar shortening is the most commonly used technique to treat the latter condition. In an elderly patient, a Darrach procedure is the preferred treatment for a DRU joint dysfunction; in younger patients, the treatment of choice appears to be resection arthroplasty of the DRU joint with preservation of the ulnar length, the ulnar styloid, and the triangular fibrocartilage complex (TFCC). In cases of malunion of the distal radius with involvement of the DRU joint, the recommended treatment is corrective osteotomy and soft tissue reconstruction of the ligamentous support of the joint.


Long interspersed nuclear element-1 (LINE1)-mediated deletion of EVC, EVC2, C4orf6, and STK32B in Ellis-van Creveld syndrome with borderline intelligence.
Previous work has shown Ellis-van Creveld (EvC) patients with mutations either in both alleles of EVC or in both alleles of EVC2. We now report affected individuals with the two genes inactivated on each allele. In a consanguineous pedigree diagnosed with EvC and borderline intelligence, we detected a 520-kb homozygous deletion comprising EVC, EVC2, C4orf6, and STK32B, caused by recombination between long interspersed nuclear element-1 (LINE-1 or L1) elements. Patients homozygous for the deletion are deficient in EVC and EVC2 and have no increase in the severity of the EvC typical features. Similarly deletion carriers demonstrate absence of digenic inheritance in EvC. Further, the phenotype of these patients suggests that the EVC-STK32B deletion also leads to mild mental retardation and reveals that loss of the novel genes C4orf6 and STK32B causes at most mild mental deficit. In an EvC compound heterozygote of different ethnic origin we identified the same LINE-to-LINE rearrangement due to a different recombination event. These findings highlight the importance of L1 repetitive sequences in human genome architecture and disease.


Hepatoprotection by Ginsenoside Rg1 in alcoholic liver disease.
Alcoholic hepatitis (AH) has caused serious mortality to the world's population. Despite tremendous efforts to reduce disease burden, effective treatments for this disease are still lacking. Ginsenoside Rg1 (G-Rg1) has been reported to be hepatoprotective in several liver injury models. However, therapeutic potential of this drug in AH has not been tested. In this study, using a chronic ethanol-feeding model, we found that ethanol-fed mice presented clinical indicators of liver injury, such as elevated serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (Tbil), as well as development of hepatic steatosis. Upon treatment with G-Rg1, animals showed marked decreases in serum biochemical parameters, as well as improvement in liver histology. Mechanistically, G-Rg1 blocked the induction of cytochrome P4502E1 (CYP2E1), and prevented the generation of reactive oxygen species (ROS), mitochondria damage, as well as hepatocellular apoptosis. As a result, NLRP3 inflammasome activation was inhibited, which subsequently suppressed the production of active caspase-1 and inflammatory cytokines. Our data has demonstrated a hepatoprotective role for G-Rg1 in AH, and identified potential drugable pathways to improve disease outcomes. These findings may have significant implications for developing novel therapies for inflammatory liver diseases.


Effect of acute hepatic encephalopathy on [3H]dopamine release from rat cerebral cortex and striatum in vitro: role of Ca2+.
Hepatic encephalopathy (HE) is characterized by motor symptoms associated with disturbed functions of the dopaminergic systems, but the underlying mechanisms are not clear. A previous study from our laboratories revealed that HE, induced in rats by repeated treatment with thioacetamide, enhanced the 50 mM potassium (KCl)-stimulated release of newly loaded [3H]dopamine in both striatal and frontal cerebral cortical slices in the presence of Ca2+. In the present study we compared the effects of HE on dopamine release in striatal and frontal cerebral cortical slices and synaptosomes in the presence and absence of Ca2+. HE enhanced the KCl-stimulated [3H]dopamine release from striatal and frontal cortical synaptosomes in the presence of Ca2+ to the same extent as in slices prepared from the respective brain regions. In the absence of Ca2+ a slight reduction in dopamine release was observed in frontal cortical synaptosomes from HE rats when compared to control rats, while no effect of HE on the release was discernible in frontal cortical and striatal slices and striatal synaptosomes. We conclude that in both brain regions studied HE stimulates dopamine exocytosis triggered by Ca2+ influx without affecting the release mediated by means of plasma membrane transporters or exocytosis involving intraterminal Ca2+.


Formation of dielectric layers and charge regulation in protein adsorption at biomimetic interfaces.
Protein charge is an important parameter in the understanding of protein interactions and function. Proteins are subject to dynamic charge regulation, that is, the influence of the local environment (such as charged interfaces and biopolymers) on protein charge. Charge regulation is governed by differences in the dielectric and electrostatic environment between adsorbed protein and the free protein in bulk solution. In this work protein charge regulation is addressed experimentally by employing electrochemistry at interfaces between two immiscible electrolyte solutions (ITIES) as well as theoretically by developing a new protein adsorption model at ITIES. Electrochemistry at ITIES is shown to be particularly well suited to study protein charge regulation as the adsorbed protein experiences a different dielectric environment compared to the bulk phase and the external control of the water/oil potential difference allows systematic studies on how potential induced ion gradients affect protein charge. The theoretical model incorporates all the features of the experimental system and specifically takes into account protein charge regulation at ITIES as well as the impact of the formation of dielectric layers on the experimentally observed impedance. The model parameters include the protein charge-pH profile, bulk pH, and the overall potential difference. It is shown that the formation of a dielectric layer and the associated charge regulation are the main factors dictating the observed experimental behavior. Finally, the theoretical model is used to interpret literature results, and the consistency between the model and the relatively large data set suggests that the model may be used more generally for understanding and predicting protein adsorption.


Structural properties of legume lectins.
The above data provide immunochemical evidence that lectins isolated from different legume species may be structurally related proteins and are probably homologues. This generalization derives from the great overall similarities in physical, chemical and biological properties of these proteins. More specifically, these proteins appear to be immunologically closely related and possess a high degree of conservation in their primary structures. Acceptance of this generalization implies a common physiological function for these proteins. Hence, in the search for their function, serious consideration must be given to the group as a whole. A number of legume species were shown to be totally devoid of proteins with hemagglutinin activity. Without exception, however, these plants contained cross reacting material which was immunologically closely related to one or more of the classic lectins. These results suggest that independent of whether a legume seed extract can agglutinate red blood cells, it appears to contain a protein physiologically homologous to the well studied legume lectins. Further, these observations suggest that "hemagglutinin activity" may not be a required manifestation of the "normal" in vivo activity of this group of proteins. All legumes appear to contain a specific alpha-galactosidase, but only rarely does this enzyme possess hemagglutinin activity. We suspect the hemagglutinin activity associated with the alpha-galactosidase-hemagglutinin molecule may result from slow hydrolysis of cell surface carbohydrate receptors and may not be important with respect to the general functioning of this class of protein. It is clear that a great many questions about these interesting proteins remain to be answered.(ABSTRACT TRUNCATED AT 250 WORDS)


Polaromonas eurypsychrophila sp. nov., isolated from an ice core.
A Gram-stain-negative, aerobic, rod-shaped, beige bacterium, strain B717-2T, was isolated from an ice core drilled from Muztagh Glacier on the Tibetan Plateau, China. According to phylogenetic analyses based on 16S rRNA gene sequences, the novel strain was related most closely to Polaromonas vacuolataand shared 97.7 % similarity with the type strain of this species. It grew optimally at pH 7, at 15 °C and with 2 % (w/v) NaCl. Major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids were summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), summed feature 8 (C18 : 1ω7c, C18 : 1ω6c) and C16 : 0. The sole respiratory quinone was Q-8. The DNA G+C content was 63.4 mol %. In DNA-DNA hybridization tests, strain B717-2T shared 37.0±1.9, 30.0±1.7, 26.0±0.9, 23.4±0.5 and 18.4±1.9 % DNA-DNA relatedness with Polaromonas jejuensisJS12-13T, P. vacuolata 34-PT, Polaromonas aquatica CCUG 39402T, Polaromonas glacialisCr4-12T and Polaromonas cryoconitiCr4-35T, respectively. Based on the phenotypic, phylogenetic and genetic characteristics, strain B717-2T represents a novel species of the genus Polaromonas, for which the name Polaromonaseurypsychrophila sp. nov. is proposed. The type strain is B717-2T (=CGMCC 1.15322T=JCM 31171T).


Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: identification of an RGFRRR motif governing fungal cell entry.
MtDef4 is a 47-amino acid cysteine-rich evolutionary conserved defensin from a model legume Medicago truncatula. It is an apoplast-localized plant defense protein that inhibits the growth of the ascomycetous fungal pathogen Fusarium graminearum in vitro at micromolar concentrations. Little is known about the mechanisms by which MtDef4 mediates its antifungal activity. In this study, we show that MtDef4 rapidly permeabilizes fungal plasma membrane and is internalized by the fungal cells where it accumulates in the cytoplasm. Furthermore, analysis of the structure of MtDef4 reveals the presence of a positively charged γ-core motif composed of β2 and β3 strands connected by a positively charged RGFRRR loop. Replacement of the RGFRRR sequence with AAAARR or RGFRAA abolishes the ability of MtDef4 to enter fungal cells, suggesting that the RGFRRR loop is a translocation signal required for the internalization of the protein. MtDef4 binds to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Amino acid substitutions in the RGFRRR sequence which abolish the ability of MtDef4 to enter fungal cells also impair its ability to bind PA. These findings suggest that MtDef4 is a novel antifungal plant defensin capable of entering into fungal cells and affecting intracellular targets and that these processes are mediated by the highly conserved cationic RGFRRR loop via its interaction with PA.


Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.
Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or dose reduction of warfarin after coadministration of tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.


Retropharyngeal Hematoma as an Unusual Presentation of Myelodysplastic Syndrome: A Case Report.
BACKGROUND Retropharyngeal hematoma is a relatively rare diagnosis that requires a high clinical suspicion and stabilization of the airway to prevent rapid deterioration. We report a case of a spontaneous retropharyngeal hematoma in an elderly patient with myelodysplastic syndrome and associated thrombocytopenia. CASE REPORT A 90-year-old man with myelodysplastic syndrome was brought to the Emergency Department with complaints of difficulty swallowing and muffled voice for 24 hours. Upon arrival, his vital signs and physical exam were unremarkable, except that when he was asked to take a sip of water, he could not swallow it. Complete blood count was remarkable for leukocytosis of 14.3×10³/mcL, hemoglobin of 9.0 gm/dL, and platelet count of 26×10³/mcL. Chest X-ray and lateral soft-tissue neck X-rays were grossly unremarkable. The patient was admitted for further evaluation and was scheduled for esophagogastroduodenoscopy. During intubation for esophagogastroduodenoscopy, the patient was noted to have significant airway narrowing. A subsequent CT scan revealed a 3×2×2 cm supraglottic hypodensity, thought to represent a retropharyngeal hematoma. The patient was transferred to the Intensive Care Unit (ICU) and received platelet transfusions. The ICU course was complicated by anemia, which necessitated transfusion of packed red blood cells. On hospital day 7, the patient reported resolution of his symptoms and was discharged home. CONCLUSIONS This case adds to the growing body of literature on spontaneous retropharyngeal hematomas. High clinical suspicion is warranted in patients who present with acute dysphagia, odynophagia, and dysphonia. Prompt imaging and airway management are vital in managing patients with this condition.


Transdominant DeltaTAp73 isoforms are frequently up-regulated in ovarian cancer. Evidence for their role as epigenetic p53 inhibitors in vivo.
Despite strong homology, the roles of TP53 and TP73 in tumorigenesis seem to be fundamentally different. In contrast to TP53, tumor-associated overexpression of TP73 in many different cancers, combined with virtual absence of inactivating mutations and lack of a cancer phenotype in the TP73 null mouse are inconsistent with a suppressor function but instead support an oncogenic function. The discovery of NH(2)-terminally truncated p73 isoforms, collectively called DeltaTAp73, is now the focus of intense interest because they act as potent transdominant inihibitors of wild-type p53 and transactivation-competent TAp73. Therefore, establishing deregulated DeltaTAp73 expression in tumors could be the crucial link to decipher which of the two opposing roles of this bipolar gene is the biologically relevant one. This study is the largest to date and encompasses 100 ovarian carcinomas with complete expression profile of all NH(2)-terminal isoforms, discriminating between TAp73 and DeltaTAp73 (DeltaNp73, DeltaN'p73, Ex2p73, and Ex2/3p73) by isoform-specific real-time reverse transcription-PCR. We find that the set of NH(2)-terminal p73 isoforms distinguishes ovarian cancer patients from healthy controls and thus is a molecular marker for this diagnosis. Ovarian cancers strongly and almost universally overexpress DeltaN'p73 compared with normal tissues (95% of cancers). About one-third of tumors also exhibit concomitant up-regulation of the antagonistic TAp73, whereas only a small subgroup of tumors overexpress DeltaNp73. Thus, deregulation of the E2F1-responsive P1 promoter, rather than the alternate P2 promoter, is mainly responsible for the production of transdominant p53/TAp73 antagonists in ovarian cancer. Tumor stage, grade, presence of metastases, p53 status, and residual disease after resection are significant prognostic markers for overall and recurrence-free survival. A trend is found for better overall survival in patients with low expression of DeltaN'p73/DeltaNp73, compared with patients with high expression. A strong correlation between deregulated DeltaTAp73 and p53 status exists. p53 wild-type cancers exhibit significantly higher deregulation of DeltaN'p73, DeltaNp73, and Ex2/3p73 than p53 mutant cancers. This data strongly supports the hypothesis that overexpression of transdominant p73 isoforms can function as epigenetic inhibitors of p53 in vivo, thereby alleviating selection pressure for p53 mutations in tumors.


[The principal functional appliances. Characteristics and clinical indications].
The author present a review of the six most important functional appliances available now, showing the way of construction, his working and clinical applications. Appliances are extremely valid to rectify skeletric malocclusion of I, II, III class, with ipertonic perioral musculature and with a wrong position of the tongue in growing patient with the FMA under 25 degrees; must be done a correct diagnosis based on patient clinical exam, observation of the model of study and finally on the observation of radiographic exam.


Evaluation of Oral Pentoxifylline, Colchicine, and Penile Traction for the Management of Peyronie's Disease.
Currently, there are several treatment options for Peyronie disease (PD). Although surgical interventions have better reported outcomes than conservative therapy, surgery is not suitable for all patients with PD. Therefore, oral therapy for PD is still a frequently used treatment due to low cost, convenience and limited side effects. However, current literature on the efficacy of oral therapy in PD is inconclusive. Pentoxifylline and colchicine have both shown some promise though further studies are required to confirm their effectiveness. The aim of this study was to assess the efficacy of oral therapy for PD, including pentoxifylline and colchicine, coupled with the Andropenis penile traction therapy (PTT) extender on degree of penile curvature and plaque size. Between March 2015 and June 2018, a prospectively collected database for patients receiving oral therapy for PD (pentoxifylline and/or colchicine) was reviewed. Collected data variables were compared at baseline and after 6 months of treatment, including degree of curvature, plaque size, and penile Doppler ultrasound parameters (peak systolic velocity, minimum diastolic velocity, and pulsatility index). PTT was applied by the patient for a total of 1 hour per day for 6 months. A total of 46 patients were involved in this study. Mean age was 56 ± 10 years. There was a significant decrease in the degree of penile curvature after 6 months (55.8º ± 20º vs 41.4º ± 20.8º; P = .03). Likewise, the plaque size decreased significantly from 5.42 ± 2.7 to 2.42 ± 1.71 cm2; P = .0001. There was a significant increase in the peak systolic velocity from 29.8 ± 10.02 to 38.2 ± 11cm/sec; P = .02, whereas no statistically significant difference could be detected regarding end diastolic velocity (M = 0.56 ± 3.1 vs 1.59; P = .415) or pulsatility index (Mdiff = 0.03; CI = -0.06 to 0.12; P = .473). Furthermore, there was no statistically significant difference in medication type of pentoxifylline or colchicine (Mdiff = 17.23; CI = -3.31 to 37.77; P = .09). Altogether, pentoxifylline and colchicine, taken with concomitant PTT, present a potentially convenient, low cost, and effective treatment for penile curvature and plaque resulting from PD. Prospective randomized trials are still required for better evaluation of the course of PD with patients undergoing conservative management. Ibrahim A, Gazzard L, Alharbi M, et al. Evaluation of Oral Pentoxifylline, Colchicine, and Penile Traction for the Management of Peyronie's Disease. Sex Med 2019;7:459-463.


Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group.
Myocardial infarction, sudden cardiac death, cerebrovascular accidents, blood pressure control and treatment tolerability were studied in a randomized double-blind trial conducted in 6357 men and women aged 40-64 years with uncomplicated essential hypertension (diastolic blood pressures 100-125 mmHg). At the start of the trial 3185 patients received treatment based on a beta-blocker (oxprenolol), while in the remaining 3172 placebo replaced oxprenolol. Supplementary drugs, excluding beta-blockers, were used as necessary in both treatment groups, with the aim of reducing diastolic pressure to 95 mmHg or less. Patients were followed for 3-5 years, a total of 25 651 patient years at risk. In most respects the two groups fared equally well; sudden death (relative risk [RR] 1.08; 95% confidence interval [Cl] 0.68 and 1.72), myocardial infarction (RR 0.83; Cl 0.59 and 1.16) and cerebrovascular accident (RR 0.97; Cl 0.64 and 1.47) rates were similar. Beta-blocker based therapy was associated with significantly lower average blood pressures, earlier ECG normalization, less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension. Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability. In smokers the cardiac event rate was doubled. We propose that beta-blocker treatment effects depend on smoking status, with a significant interaction benefiting non-smoking men. Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events. Proportional hazards analysis also underlines the importance of other cardiovascular risk factors. The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients.


A polystyrene-supported 9-amino(9-deoxy)epi quinine derivative for continuous flow asymmetric Michael reactions.
A polystyrene (PS)-supported 9-amino(9-deoxy)epi quinine derivative catalyzes Michael reactions affording excellent levels of conversion and enantioselectivity using different nucleophiles and structurally diverse enones. The highly recyclable, immobilized catalyst has been used to implement a single-pass, continuous flow process (residence time: 40 min) that can be operated for 21 hours without significant decrease in conversion and with improved enantioselectivity with respect to batch operation. The flow process has also been used for the sequential preparation of a small library of enantioenriched Michael adducts.


CT Validation of Intraoperative Implant Position and Knee Alignment as Determined by the MAKO Total Knee Arthroplasty System.
Robotic-assisted technology in total knee arthroplasty (TKA) aims to increase implantation accuracy, with real-time data being used to estimate intraoperative component alignment. Postoperatively, Perth computed tomography (CT) protocol is a valid measurement technique in determining both femoral and tibial component alignments. The aim of this study was to evaluate the accuracy of intraoperative component alignment by robotic-assisted TKA through CT validation. A total of 33 patients underwent TKA using the MAKO robotic-assisted TKA system. Intraoperative measurements of both femoral and tibial component placements, as well as limb alignment as determined by the MAKO software were recorded. Independent postoperative Perth CT protocol was obtained (n = 29) and compared with intraoperative values. Mean absolute difference between intraoperative and postoperative measurements for the femoral component were 1.17 degrees (1.10) in the coronal plane, 1.79 degrees (1.12) in the sagittal plane, and 1.90 degrees (1.88) in the transverse plane. Mean absolute difference between intraoperative and postoperative measurements for the tibial component were 1.03 degrees (0.76) in the coronal plane and 1.78 degrees (1.20) in the sagittal plane. Mean absolute difference of limb alignment was 1.29 degrees (1.25), with 93.10% of measurements ≤3 degrees of postoperative CT measurements. Overall, intraoperatively measured component alignment as estimated by the MAKO robotic-assisted TKA system is comparable to CT-based measurements.


Applying the PRECISION approach in biopsy naïve and previously negative prostate biopsy patients.
The PRECISION trial provides level 1 evidence supporting prebiopsy multiparametric magnetic resonance imaging (mpMRI) followed by targeted biopsy only when mpMRI is abnormal [1]. This approach reduced over-detection of low-grade cancer while increasing detection of clinically significant cancer (CSC). Still, important questions remain regarding the reproducibility of these findings outside of a clinical trial and quantifying missed CSC diagnoses using this approach. To address these issues, we retrospectively applied the PRECISION strategy in men who each underwent prebiopsy mpMRI followed by systematic and targeted biopsy. Clinical, imaging, and pathology data were prospectively collected from 358 biopsy naïve men and 202 men with previous negative biopsies. To apply the PRECISION approach, a retrospective analysis was done comparing the cancer yield from 2 diagnostic strategies: (1) mpMRI followed by targeted biopsy alone for men with Prostate Imaging Reporting and Data System ≥ 3 lesions and (2) systematic biopsy alone for all men. Primary outcomes were biopsies avoided and the proportion of CSC cancer (Grade Group 2-5) and non-CSC (Grade Group 1). In biopsy naïve patients, the mpMRI diagnostic strategy would have avoided 19% of biopsies while detecting 2.5% more CSC (P= 0.480) and 12% less non-CSC (P< 0.001). Thirteen percent (n= 9) of men with normal mpMRI had CSC on systematic biopsy. For previous negative biopsy patients, the mpMRI diagnostic strategy avoided 21% of biopsies, while detecting 1.5% more CSC (P= 0.737) and 13% less non-CSC (P< 0.001). Seven percent (n= 3) of men with normal mpMRI had CSC on systematic biopsy. Our results provide external validation of the PRECISION finding that mpMRI followed by targeted biopsy of suspicious lesions reduces biopsies and over-diagnosis of low-grade cancer. Unlike PRECISION, we did not find increased diagnosis of CSC. This was true in both biopsy naïve and previously negative biopsy cohorts. We have incorporated this information into shared decision making, which has led some men to choose to avoid biopsy. However, we continue to recommend targeted and systematic biopsy in men with abnormal MRI.


Deep Slow Motion Video Reconstruction With Hybrid Imaging System.
Slow motion videos are becoming increasingly popular, but capturing high-resolution videos at extremely high frame rates requires professional high-speed cameras. To mitigate this problem, current techniques increase the frame rate of standard videos through frame interpolation by assuming linear object motion which is not valid in challenging cases. In this paper, we address this problem using two video streams as input; an auxiliary video with high frame rate and low spatial resolution, providing temporal information, in addition to the standard main video with low frame rate and high spatial resolution. We propose a two-stage deep learning system consisting of alignment and appearance estimation that reconstructs high resolution slow motion video from the hybrid video input. For alignment, we propose to compute flows between the missing frame and two existing frames of the main video by utilizing the content of the auxiliary video frames. For appearance estimation, we propose to combine the warped and auxiliary frames using a context and occlusion aware network. We train our model on synthetically generated hybrid videos and show high-quality results on a variety of test scenes. To demonstrate practicality, we show the performance of our system on two real dual camera setups with small baseline.


[A framework for assessing essential public health nursing skills and achievement levels required for students graduating from schools that provide education for obtaining a license as a public health nurse in Japan].
This study aimed to develop a framework for essential skills and the achievement levels necessary for students graduating from schools that provide education for obtaining a license as a public health nurse (PHN) in Japan. Two rounds of questionnaire-based investigations using the Delphi methodology were conducted. Subjects were 197 PHNs from municipalities or companies and 146 nurse educators from universities, colleges, junior colleges, or technical nursing schools. (1) The essential skills framework consisted of three (macro, intermediate and micro) levels. Macro-level items were based on the principle of justice, a primary pillar of health care: (A) community assessment to identify health problems; (B) solving and improving particular health problems in collaboration with people to enable them to promote their own health; (C) promoting equitable access and distribution of community resources for health and daily living. Micro-level items had four achievement levels: (I) independent; (II) instructor-guided; (III) laboratory exercise; (IV) theoretical understanding. Micro-level items for A and B had two domains for achievement: individual/family and group/community. (2) In the first round over 70% of respondents said "very important," "important" or "acceptable" for all micro-level items. In the second round, over 90% said all micro-level items fit within macro and intermediate-level items. (3) In the second round, micro-level items attained 70% consensus among PHNs and nurse educators were 71 of 93 (76.3%). Micro-level expression was used for adjustment and the final framework of essential skills yielded 3 macro, 8 intermediate and 59 micro-level items and 95 levels of achievement. (4) In the final framework, the level of achievement for "individual/family" (Macro-level A and B) was almost level I, and for "group/community" almost II or III. The number of micro-level items at level IV for C was 14 of 21 (66.7%). (5) Compared with PHNs, educators generally assigned a more advanced achievement level for the same skill. This framework offers more clarity to the content and competency of practice and thus should be useful for basic and continuing PHN education. The assumption driving this study was the necessity to improve the nursing educational system, and develop an appropriate curriculum for the PHN national licensure.


[Weight monitoring in parenteral nutrition: from theory to practice].
To assess the usefulness of establishing a routine gravimetric as quality assurance after the development of parenteral nutrition (PN) with a gravimetric error less than ± 5%. Prospective study in which 5 to 8 large volume PN were weighed daily during 2 months and for 4 months all small volume PN, considering this the real weight. The theoretical weight was calculated taking into account the densities, volumes of all products used in processing and the weight of the bags used. The gravimetric error was calculated as a percentage compared to the theoretical weight. 168 large volume PN and 42 small volume were weighed, gravimetric errors measures were 1.42% (SD=1.31) and 1.26% (SD=0.64), with a gravimetric error less than 5% in 98,8% and 100% respectively. Establishing a routine gravimetric control is an useful strategy that can help to guarantee the quality of the PN development.


Risk of Guillain-Barré syndrome after vaccination against human papillomavirus: a systematic review and meta-analysis, 1 January 2000 to 4 April 2020.
BackgroundGuillain-Barré syndrome (GBS) is a rare autoimmune disease that can follow viral infections and has in a few cases been linked to vaccinations. Pre-licensure clinical trials did not observe an association between human papillomavirus (HPV) vaccination and GBS, a post-marketing study from 2017 reported an increased relative risk.AimWe assessed the risk of GBS after HPV vaccination through a systematic literature review and meta-analysis.MethodsWe searched Embase, MEDLINE and Cochrane for studies reporting on the risk of GBS after HPV vaccination in individuals aged ≥ 9 years, published between 1 January 2000 and 4 April 2020, excluding studies without a comparator group. Seven studies reporting relative effect sizes were pooled using random-effects meta-analysis. We assessed quality of evidence using the GRADE approach. Study protocol was registered (PROSPERO No. #CRD42019123533).ResultsOf 602 identified records, we included 25 studies. Based on over 10 million reports, cases of GBS were rare. In 22 studies no increased risk was observed, while in three studies a signal of increased risk of GBS after HPV vaccination was identified. Meta-analysis yielded a pooled random-effects ratio of 1.21 (95% CI: 0.60-2.43); I2 = 72% (95% CI: 36-88). This translates to a number needed to harm of one million to be vaccinated to generate one GBS case. Quality of evidence was very low.ConclusionsThe absolute and relative risk of GBS after HPV vaccination is very low and lacks statistical significance. This is reassuring for the already implemented vaccination programmes and should be used in respective communication activities.


The Nature-Nurture Debates: 25 Years of Challenges in Understanding the Psychology of Gender.
Nature-nurture debates continue to be highly contentious in the psychology of gender despite the common recognition that both types of causal explanations are important. In this article, we provide a historical analysis of the vicissitudes of nature and nurture explanations of sex differences and similarities during the quarter century since the founding of the Association for Psychological Science. We consider how the increasing use of meta-analysis helped to clarify sex difference findings if not the causal explanations for these effects. To illustrate these developments, this article describes socialization and preferences for mates as two important areas of gender research. We also highlight developing research trends that address the interactive processes by which nature and nurture work together in producing sex differences and similarities. Such theorizing holds the promise of better science as well as a more coherent account of the psychology of women and men that should prove to be more influential with the broader public.


Tunicamycin-induced photoreceptor atrophy precedes degeneration of retinal capillaries with minimal effects on retinal ganglion and pigment epithelium cells.
Endoplasmic reticulum (ER) stress is recognized as a contributing factor to various ocular neurovascular pathologies including retinitis pigmentosa, glaucoma, and diabetic retinopathy (DR). ER stress in particular is implicated in the development of DR, which is significantly influenced by inflammation driven retinal vascular degeneration and dysfunction. Ultimately, loss of vision occurs if left untreated. However, the identity of the target cells and their temporal involvement in diabetes-mediated dysfunction need further investigation. Early diabetes-induced stress in photoreceptor cells is proposed as the driver of inflammatory mediated neurovascular changes during diabetes. Although tunicamycin induced ER stress results in photoreceptor loss, its consequences for retinal vascular degeneration and retinal ganglion (RGC) and pigment epithelium (RPE) cell loss remains unclear. Here we show intravitreal delivery of tunicamycin primarily induced ER stress in photoreceptor cells resulting in their loss by apoptosis. This was concomitant with induced expression of the unfolded protein response marker CHOP in these cells. We also demonstrated significant degeneration of retinal capillaries following the loss of photoreceptor cells with minimal impact on loss of RGC and RPE cells. However, activation of retinal microglial and Muller cells were noticeable. Thus, our data support the notion that ER stress mediated dysfunction and/or loss of photoreceptor cells in response to inflammation and oxidative stress could precede retinal vascular and neuronal dysfunction and degeneration.


Mucoadhesive nanostructured polyelectrolytes complexes modulate the intestinal permeability of methotrexate.
Nanostructured polyelectrolytes complexes (nano PECs) loaded with methotrexate (MTX) were obtained by the polyelectrolyte complexation of chitosan (CS) and hyaluronic acid (HA), further incorporating hypromellose phthalate (HP). The mean diameter of nano PECs ranged from 325 to 458nm, with a narrow size distribution. Zeta potential was close to +30mV, decreasing to +21mV after the incorporation of HP, a range of values that favour the physical stability of system as the interaction with cationic biological membranes. The electrostatic interactions between the different components were indicated by the FTIR data. The mucoadhesiveness of nano PECs was demonstrated and MTX and HP influenced this property. The cell viability assays showed the biosafety of the isolated polymers and nano PECs in intestinal HT29-MTX and Caco-2 cell lines at 4h of test. The permeability values of MTX loaded in CS/HA nano PECs were 7.6 and 4-fold higher than those of CS/HA/HP nano PECS and free drug, respectively, in the Caco-2 monoculture. In mucus secreting co-culture cell model these values were 3 and 6.5 fold, respectively. Such features indicate that nano PECs developed in this work can be promising carriers for MTX in the treatment of local or systemic diseases.


[Biological treatments for contaminated soils: hydrocarbon contamination. Fungal applications in bioremediation treatment].
Bioremediation is a spontaneous or controlled process in which biological, mainly microbiological, methods are used to degrade or transform contaminants to non or less toxic products, reducing the environmental pollution. The most important parameters to define a contaminated site are: biodegradability, contaminant distribution, lixiviation grade, chemical reactivity of the contaminants, soil type and properties, oxygen availability and occurrence of inhibitory substances. Biological treatments of organic contaminations are based on the degradative abilities of the microorganisms. Therefore the knowledge on the physiology and ecology of the biological species or consortia involved as well as the characteristics of the polluted sites are decisive factors to select an adequate biorremediation protocol. Basidiomycetes which cause white rot decay of wood are able to degrade lignin and a variety of environmentally persistent pollutants. Thus, white rot fungi and their enzymes are thought to be useful not only in some industrial process like biopulping and biobleaching but also in bioremediation. This paper provides a review of different aspects of bioremediation technologies and recent advances on ligninolytic metabolism research.


[Development of digital PCR molecular tests for clinical practice: principles, practical implementation and recommendations].
Digital PCR (dPCR) is a 3rd generation technology that complements traditional end-point PCR and real-time PCR. It was developed to overcome certain limitations of conventional amplification techniques, in particular for the detection of small amounts of nucleic acids and/or rare variants. This technology is in a full swing because of its high sensitivity and major applications in various domains such as oncology, transplantation or non-invasive prenatal testing. Consequently, PCRd also has great interest in many areas of medical biology, particularly for clinical applications aiming at detecting and quantifying specific genetic or epigenetic alterations of nucleic acids, even with specimens containing very low concentration of the nucleic acids of interest (e.g. liquid biopsies). However, this technique requires a good training of users and compliance with certain precautions. A lack in such a knowledge can lead to many errors in the conduct of the experiment and the interpretation of the results. In this review, we present the context in which this technology has emerged by describing in particular its principle and the main factors that can influence the quality of the analysis. Then, we propose a number of practical recommendations for the implementation of a test based on dPCR in clinical laboratories with an eye on quality requirements.


Clinical Characteristics and Outcomes among Patients with Covid-19 in Different Regions of the World.
The SARS-CoV-2 outbreak began in China in December 2019 and rapidly spread globally. Up to July 2020, the number of cases of coronavirus disease 2019 (COVID-19) had been increasing in the USA, Italy, England, Spain and numerous other countries. Patients with this disease in different countries present with different clinical manifestations and different prognosis. The present study aimed to analyse the clinical characteristics of patients infected with SARS-CoV-2 in different regions of the world and provide special advices for the different regions to prevent the spread and a second outbreak of COVID-19. Key Words: COVID-19, SARS-CoV-2, Characteristics, Worldwide.


Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma.
High morbidity and mortality of cancer, especially colorectal cancer (CRC), in diabetic patients have been reported. In this study, we investigated the relationship between the presence of diabetes mellitus (blood hemoglobin A1C was 6.5% or higher at the time of diagnosis of CRC) and the progression and liver metastasis of CRC. Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC (DM-CRC) and the liver metastasis, were also investigated. Of the 473 CRC patients who underwent curative surgical resection, 148 (31%) had diabetes. In DM-CRC cases, the stage was more advanced, with more cases in stage IV or postoperative disease recurrence. Histopathological findings correlated with liver metastasis in DM-CRC, including budding grade, perineural invasion, and myxomatous tumor stroma, and all were highly correlated with the stage. Additionally, myxomatous stroma showed the strongest correlation with liver metastasis in multivariate analysis. Myxomatous stroma in stage III cases correlated with liver recurrence. The myxomatous stroma was abundant in biglycan protein and contained numerous CD90-positive mesenchymal stem cells (MSCs). In human colon cancer cell line HT29, biglycan expression was induced by high sugar concentration, fatty acids, and insulin, and its contact co-culture with MSCs resulted in enhanced stemness and epithelial-mesenchymal transition phenotype. Thus, DM-CRC has higher malignant phenotypes compared to non-DM-CRC, and the involvement of diabetes-induced biglycan may act as a pathogenic factor.


Heterogeneity in Brain Microstructural Development Following Preterm Birth.
Preterm-born children are at increased risk of lifelong neurodevelopmental difficulties. Group-wise analyses of magnetic resonance imaging show many differences between preterm- and term-born infants but do not reliably predict neurocognitive prognosis for individual infants. This might be due to the unrecognized heterogeneity of cerebral injury within the preterm group. This study aimed to determine whether atypical brain microstructural development following preterm birth is significantly variable between infants. Using Gaussian process regression, a technique that allows a single-individual inference, we characterized typical variation of brain microstructure using maps of fractional anisotropy and mean diffusivity in a sample of 270 term-born neonates. Then, we compared 82 preterm infants to these normative values to identify brain regions with atypical microstructure and relate observed deviations to degree of prematurity and neurocognition at 18 months. Preterm infants showed strikingly heterogeneous deviations from typical development, with little spatial overlap between infants. Greater and more extensive deviations, captured by a whole brain atypicality index, were associated with more extreme prematurity and predicted poorer cognitive and language abilities at 18 months. Brain microstructural development after preterm birth is highly variable between individual infants. This poorly understood heterogeneity likely relates to both the etiology and prognosis of brain injury.


catena-Poly[[tetra-aqua-[μ(2)-1,4-bis-(1,2,4-triazol-1-yl)butane-κN:N]cadmium(II)] sulfate].
In the polymeric title compound, {[Cd(C(8)H(12)N(6))(H(2)O)(4)]SO(4)}(n), the Cd(II) atom is located on an inversion center and coordinated by four water mol-ecules and two 1,4-bis-(1,2,4-triazol-yl)butane ligands in a distorted CdO(4)N(2) octa-hedral geometry. The 1,4-bis-(1,2,4-triazol-yl)butane ligand is centrosymmetric, the mid-point of the central C-C bond being located on an inversion center. It links adjacent water-coordinated metal atoms into polymeric chains running along the c axis. Adjacent chains are linked by O-H⋯N hydrogen bonds. The S atom of the sulfate anion is located on a twofold rotation axis, thus the sulfate anion is equally disordered over two sites. The sulfate anion links with the polymeric chains via O-H⋯O hydrogen bonds, generating a three-dimensional supra-molecular network.


Anterior surgical treatment of cervical spondylotic myelopathy: review article.
Cervical spondylotic myelopathy (CSM) is a common indication for cervical spine surgery. Surgical options include anterior, posterior, or combined procedures each with specific advantages and disadvantages. This article will provide a description of the various anterior alternatives and discuss the available evidence used in guiding the surgical decision making process with the aim of answering the following questions: (1) What anatomical/disease related factors favor anterior over posterior surgeries? (2) What are the common anterior procedures and how safe and effective are they? (3) What are the most effective options for multilevel CSM? (4) Is there a role for motion preservation? An additional objective is to discuss technical advances that have improved success rates for anterior procedures. The PubMed database was searched. Keywords were CSM and anterior surgery. Three hundred eighty two articles were found one hundred three were reviewed. Articles describing anterior cervical techniques were selected along with studies describing the various anterior techniques or comparisons of anterior to posterior techniques. Anterior decompression and fusion procedures are more effective than posterior procedures for patients with primarily ventrally located compression especially in the presence of cervical kyphosis. ACDF, ACCF, and hybrid combinations are safe and effective treatment options for multilevel CSM. Anterior procedures may be more cost effective and result in significantly improved postoperative quality of life and health-related quality of life measures compared to posterior procedures. Anterior cervical decompression techniques are safe and effective in the treatment of CSM. Anterior surgeries may be preferable to posterior approaches, when considering health-related quality of life measures and cost effectiveness.


Resolving Binding Events on the Multifunctional Human Serum Albumin.
Physiological processes rely on initial recognition events between cellular components and other molecules or modalities. Biomolecules can have multiple sites or mode of interaction with other molecular entities, so that a resolution of the individual binding events in terms of spatial localization as well as association and dissociation kinetics is required for a meaningful description. Here we describe a trichromatic fluorescent binding- and displacement assay for simultaneous monitoring of three individual binding sites in the important transporter and binding protein human serum albumin. Independent investigations of binding events by X-ray crystallography and time-resolved dynamics measurements (switchSENSE technology) confirm the validity of the assay, the localization of binding sites and furthermore reveal conformational changes associated with ligand binding. The described assay system allows for the detailed characterization of albumin-binding drugs and is therefore well-suited for prediction of drug-drug and drug-food interactions. Moreover, conformational changes, usually associated with binding events, can also be analyzed.


Bluetongue virus serotype 26: infection kinetics and pathogenesis in Dorset Poll sheep.
Bluetongue virus serotype 26 (BTV-26) has recently been isolated from sheep in Kuwait. The aim of this study was to assess the pathogenicity and infection kinetics of BTV-26 in Dorset Poll sheep. Six sheep were experimentally infected with BTV-26 and samples taken throughout the study were used to determine the kinetics of infection using a pan specific BTV real time RT-PCR assay and two group specific ELISAs. Five of the six sheep showed mild clinical signs characteristic of bluetongue including conjunctivitis, reddening of the mouth mucosal membranes, slight oedema of the face and nasal discharge. Viral RNA was detected in 5 of the 6 sheep by real time RT-PCR, however the levels of viral RNA detected in the samples were lower and of shorter duration than seen with other field strains of BTV. Virus was isolated from the blood of infected animals at the peak of viraemia at around 9 dpi. Antibodies against BTV were first detected by 7 dpi using the early detection BTV ELISA and a little later (7-14 dpi) using a BTV specific competitive ELISA. Four of the five remaining sheep developed neutralising antibodies to BTV-26, measured by a serum neutralisation test (SNT), with titres (log(10)) ranging from 1.40 to 2.08.


Basal membrane localization of MRP1 in human placental trophoblast.
The placental trophoblast is considered to act as a barrier between mother and fetus, mediating the exchange of various materials across the placenta. ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) and multidrug-resistance protein (MRP) are expressed in the placenta and function as efflux transport systems for xenobiotics. In the present study, we aimed to determine the localization of MRP1 in the human placenta in comparison with that of P-gp. Western blotting analysis with human placental membrane vesicles indicated that P-gp and MRP1 are localized on the brush-border membranes and basal membranes, respectively. Immunohistochemical analysis with human normal full-term placenta showed that anti-P-gp monoclonal antibody F4 stained the brush-border side of the trophoblast cells, whereas anti-MRP1 monoclonal antibody MRPr1 stained the basal side. These results confirm that P-gp and MRP1 are located on the brush-border membranes and basal membranes, respectively, of human full-term placental trophoblast. MRP1 was also detected on the abluminal side of blood vessels in the villi. Accordingly, MRP1 may play a role distinct from that of P-gp, which is considered to restrict the influx of xenobiotics into the fetus.


Oxidative Stress Biomarkers in Predictive Multi-Class Modeling of Depression Severity with Diabetes Mellitus, Cardiovascular Disease and Hypertension Comorbidity.
In this study, depression severity was defined by the Patient Health Questionnaire (PHQ-9) and five machine learning algorithms were applied to classify depression severity in the presence of diabetes mellitus (DM), cardiovascular disease (CVD), and hypertension (HT) utilizing oxidative stress (OS) biomarkers (8-isoprostane, 8-hydroxydeoxyguanosine, reduced glutathione and oxidized glutathione), demographic details, and medication for eight hundred and thirty participants. The results show that the Random Forest (RF) outperformed other classifiers with the highest accuracy of 92% in a 4-class depression classification when considering all OS biomarkers along with DM, CVD and HT. RF also achieved the highest accuracy of 91% in 3-class classification when studying depression in presence of DM only and an accuracy of 88% and 87% in 5-class classification when investigating depression with CVD and HT, respectively. Moreover, RF performed best in the 3-class depression model with an accuracy of 85% when examining depression severity in the presence of OS biomarkers only. Our findings suggest that depression severity can be accurately identified with RF as a base classifier and that OS is a major contributor to depression severity in the presence of comorbidities. Biomarker analysis can supplement DSM-5-based diagnostics as part of personalized medicine and especially as point of care testing has become available for many of the given OS biomarkers.Clinical Relevance- Depression is the most common form of psychiatric disorder that has an oxidative stress etiology. Current diagnosis relies primarily on the Diagnostic and Statistical Manual for Mental Disorders (DSM-5), which may be too general and not informative for optimal multi-comorbidity diagnostics and treatment. Understanding the role of oxidative stress associated with depression can provide additional information for timely detection, comprehensive assessment, and appropriate intervention of depression illness.


Inhibition of intestinal ascorbic acid uptake by lipopolysaccharide is mediated via transcriptional mechanisms.
Ascorbic acid (AA) accumulation in intestinal epithelial cells is an active transport process mainly mediated by two sodium-dependent vitamin C transporters (SVCT-1 and SVCT-2). To date, little is known about the effect of gut microbiota generated lipopolysaccharide (LPS) on intestinal absorption of water-soluble vitamins. Therefore, the objective of this study was to investigate the effects of bacterially-derived LPS on AA homeostasis in enterocytes using Caco-2 cells, mouse intestine and intestinal enteroids models. Pre-treating Caco-2 cells and mice with LPS led to a significant decrease in carrier-mediated AA uptake. This inhibition was associated with a significant reduction in SVCT-1 and SVCT-2 protein, mRNA, and hnRNA expression. Furthermore, pre-treating enteroids with LPS also led to a marked decrease in SVCT-1 and SVCT-2 protein and mRNA expression. Inhibition of SVCT-1 and SVCT-2 occurred at least in part at the transcriptional level as promoter activity of SLC23A1 and SLC23A2 was attenuated following LPS treatment. Subsequently, we examined the protein and mRNA expression levels of HNF1α and Sp1 transcription factors, which are needed for basal SLC23A1 and SLC23A2 promoter activity, and found that they were significantly decreased in the LPS treated Caco-2 cells and mouse jejunum; this was reflected on level of the observed reduction in the interaction of these transcription factors with their respective promoters in Caco-2 cells treated with LPS. Our findings indicate that LPS inhibits intestinal carrier- mediated AA uptake by down regulating the expression of both vitamin C transporters and transcriptional regulation of SLC23A1 and SLC23A2 genes.


Immune dysregulation and osteosarcoma: Staphylococcus aureus downregulates TGF-β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma.
Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti-tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co-cultured with osteosarcoma and S. aureus exhibited increased IFN-γ, TNF-α and IL-12p70 cytokine secretion, decreased TGF-β cytokine secretion and increased mRNA expression of TNF-α when compared with macrophages co-cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN-γ and TNF-α cytokine secretion, decreased TGF-β cytokine secretion, increased mRNA expression of TNF-α and increased surface receptor expression of CD80 when co-cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma-induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti-osteosarcoma macrophage response.


Evolution of a Biomass-Fermenting Bacterium To Resist Lignin Phenolics.
Increasing the resistance of plant-fermenting bacteria to lignocellulosic inhibitors is useful to understand microbial adaptation and to develop candidate strains for consolidated bioprocessing. Here, we study and improve inhibitor resistance in Clostridium phytofermentans (also called Lachnoclostridium phytofermentans), a model anaerobe that ferments lignocellulosic biomass. We survey the resistance of this bacterium to a panel of biomass inhibitors and then evolve strains that grow in increasing concentrations of the lignin phenolic, ferulic acid, by automated, long-term growth selection in an anaerobic GM3 automat. Ultimately, strains resist multiple inhibitors and grow robustly at the solubility limit of ferulate while retaining the ability to ferment cellulose. We analyze genome-wide transcription patterns during ferulate stress and genomic variants that arose along the ferulate growth selection, revealing how cells adapt to inhibitors through changes in gene dosage and regulation, membrane fatty acid structure, and the surface layer. Collectively, this study demonstrates an automated framework for in vivo directed evolution of anaerobes and gives insight into the genetic mechanisms by which bacteria survive exposure to chemical inhibitors.IMPORTANCE Fermentation of plant biomass is a key part of carbon cycling in diverse ecosystems. Further, industrial biomass fermentation may provide a renewable alternative to fossil fuels. Plants are primarily composed of lignocellulose, a matrix of polysaccharides and polyphenolic lignin. Thus, when microorganisms degrade lignocellulose to access sugars, they also release phenolic and acidic inhibitors. Here, we study how the plant-fermenting bacterium Clostridium phytofermentans resists plant inhibitors using the lignin phenolic, ferulic acid. We examine how the cell responds to abrupt ferulate stress by measuring changes in gene expression. We evolve increasingly resistant strains by automated, long-term cultivation at progressively higher ferulate concentrations and sequence their genomes to identify mutations associated with acquired ferulate resistance. Our study develops an inhibitor-resistant bacterium that ferments cellulose and provides insights into genomic evolution to resist chemical inhibitors.


Exploring cardiovascular disease risk evaluation in patients with inflammatory joint diseases.
Cardiovascular disease (CVD) risk calculators developed for the general population have been shown to inaccurately predict CVD events in patients with inflammatory joint disease (IJD). European guidelines for CVD prevention recognize the presence of carotid plaques (CP) as a very high CVD risk factor, equivalent of coronary artery disease. Patients with IJD have a high prevalence of CP. We evaluated if CP resulted in reclassification of patients with IJD into a more appropriate CVD risk class and recommended lipid lowering treatment. CVD risk evaluation was performed in patients with IJD using SCORE and ACC/AHA risk calculators to predict CVD events. Of the 335 IJD patients evaluated (including rheumatoid arthritis n=201, ankylosing spondylitis n=85 and psoriatic arthritis n=49), 183 and 159 IJD patients had a calculated CVD risk by SCORE and ACC/AHA <5%, indicating no need of lipid lowering treatment (LLT). However, of patients with low to moderate risk calculated by SCORE and ACC/AHA, 67 (36.6%) and 48 (30.2%) had CP and should according to guidelines receive intensive LLT. For patients with high risk, in the LLT considered group, 54.9% and 58.1% were reclassified to correct treatment when adding information on the presence of CP. Our results reveal a considerable reclassification into correct CVD risk category when adding CP in female patients. The high frequency of asymptomatic atherosclerosis in patients with IJD has a notable impact on CVD risk stratification. Identification of CP will reclassify patients into recommended CVD preventive treatment group, which may be clinically important.


Postoperative urinary tract infection and surgical site infection in instrumented spinal surgery: is there a link?
A potential relationship between postoperative urinary tract infection (UTI) and surgical site infection (SSI) following posterior spinal fusion and instrumentation (PSFI) was investigated. A retrospective review was performed of prospectively collected demographic, clinical and microbiological data of 466 consecutive patients (median age, 53.7 years (interquartile range (IQR) 33.8-65.6); 58.6% women) undergoing PSFI to identify those with UTI in the first 4 weeks and SSI in the first 12 weeks after PSFI. Overall, 40.8% had an American Society of Anesthesiologists score of >2, and 49.8% had undergone fusion of more than three segments. Eighty-nine patients had UTI, 54 had SSI, and 22 had both conditions. In nine of the 22 (38%) cases, the two infections were caused by the same microorganism. The urinary tract was the probable source of SSI by Gram-negative bacteria in 38% (8/21) of cases. On multivariate analysis, UTI (OR 3.1, 95% CI 1.6-6.1; P 0.001) and instrumentation of more than three segments (OR 2.7, 95% CI 1.1-6.3; P 0.024) were statistically associated with SSI. Patients receiving ciprofloxacin for UTI had higher microbial resistance rates to fluoroquinolones at SSIs (46.13%) than those without ciprofloxacin (21.9%), although the difference did not reach statistical significance (p 0.1). In our series, UTI was significantly associated with SSI after PSFI. On the basis of our results, we conclude that further efforts to reduce the incidence of postoperative UTI and provide adequate empirical antibiotic therapy that avoids quinolones whenever possible may help to reduce SSI rates and potential microbial resistance.


The effect of protease, amylase, and nonstarch polysaccharide-degrading enzyme supplementation on nutrient utilization and growth performance of broiler chickens fed corn-soybean meal-based diets.
A study was conducted to determine if amylase and protease addition would improve nutrient digestion during the first 2 wk of growth. The experimental treatments included a control corn-soybean meal-based diet and diets supplemented with either amylase or amylase plus protease. No effect of enzyme supplementation was observed on BW gain and feed conversion ratio. This was corroborated by similar ileal starch and protein digestibility values, which averaged 96.8, 96.8, and 96.9% and 83.9, 80.1, and 79.6%, respectively, for the control and for the amylase or amylase plus protease supplemented diets. Total tract digestibility of starch averaged 97.8, 97.7 and 97.7% for the 3 diets and was followed by a similar diet with AMEn values of 3,129, 3,129, and 3,106 kcal/kg. In another study, a 2(3) factorial arrangement of 8 dietary treatments was used to evaluate the effect of corn particle size (conventional or coarse vs. fine) and the addition of a nonstarch polysaccharide enzyme, amylase, or both on growth performance and nutrient utilization of broiler chickens from 1 to 21 d of age. Chickens fed a diet containing a conventionally ground corn (geometric mean diameter of 736 µm) showed higher (P < 0.001) BW gain (808 vs. 750 g/bird) and lower feed conversion ratio (1.27 vs. 1.32) than those consuming a fine corn-containing diet (geometric mean diameter of 482 µm). This was further substantiated by a lower AMEn content (2,852 vs. 2,972 kcal/kg). Addition of amylase had no effect on growth performance of chickens fed a conventional corn-containing diet, but improved BW gain, feed conversion ratio, and diet AMEn in those fed the finely ground corn, possibly due to increased starch digestion in the upper gut. Addition of nonstarch polysaccharide enzymes was effective for both diets, with the most pronounced effects observed in feed conversion ratio for the conventional corn-containing diet (1.27 vs. 1.23) and BW gain (750 vs. 789 g/bird) for the fine corn-containing diet. This was followed by the same magnitude of difference in diet AMEn content, which increased from 2,972 to 3,042 and 2,852 to 3,009 kcal/kg following enzyme addition.


Are people successful at learning sequences of actions on a perceptual matching task?
We report the results of an experiment in which human subjects were trained to perform a perceptual matching task. Subjects were asked to manipulate comparison objects until they matched target objects using the fewest manipulations possible. An unusual feature of the experimental task is that efficient performance requires an understanding of the hidden or latent causal structure governing the relationships between actions and perceptual outcomes. We use two benchmarks to evaluate the quality of subjects' learning. One benchmark is based on optimal performance as calculated by a dynamic programming procedure. The other is based on an adaptive computational agent that uses a reinforcement-learning method known as Q-learning to learn to perform the task. Our analyses suggest that subjects were successful learners. In particular, they learned to perform the perceptual matching task in a near-optimal manner (i.e., using a small number of manipulations) at the end of training. Subjects were able to achieve near-optimal performance because they learned, at least partially, the causal structure underlying the task. In addition, subjects' performances were broadly consistent with those of model-based reinforcement-learning agents that built and used internal models of how their actions influenced the external environment. We hypothesize that people will achieve near-optimal performances on tasks requiring sequences of action-especially sensorimotor tasks with underlying latent causal structures-when they can detect the effects of their actions on the environment, and when they can represent and reason about these effects using an internal mental model.


[Reha Aftercare--One Size Fits All? Analyses of Rehab Patients which do not Benefit from Reha Aftercare].
In an own research project fund-ed by this program rehabilitation aftercare as part of a revised rehabilitation philosophy ("new credo") was tested and evaluated in a controlled longitudinal trial. Rehabilitation patients from the intervention group reported significantly better implementation of rehabilitation contents and objectives in everyday life during 12 months after their rehabilitation stay. Better long-term effects were also detectable. Anyway, not all rehabilitation patients seemed to benefit from the intervention. The present analysis focuses on this subgroup: How do rehabilitation patients that do not benefit from the "new credo" differ from rehabilitation patients that draw advantage from it? Data from a controlled study were used for secondary analysis. 3 clinics implemented the "new credo". Primary outcomes were: participation constraints (IMET) and functional disabilities in everyday life (FFbH-R). The intervention clinics recruited a total of 166 rehabilitation patients. Data from 163 cases could be analyzed using quantitative methods. In addition, interview data from 7 unsuccessful rehabilitation patients was analyzed qualitatively. 102 (63%) rehabilitation patients improved their values in FFbH-R or IMET by at least 0.3 effect sizes (successful group). Among the 61 unsuccessful rehabilitation patients, 17 (10%) started rehabilitation with initial values that high that they could not reach the fixed minimal improvement criteria ("low burdened" group). They were excluded from further analysis. The remain-ing 44 (27%) rehabilitation patients constitute the "unsuccessful" group.Both groups have comparable levels of impairment concerning somatic and psychosocial parameters.At the end of the rehabilitation stay the "unsuccessful" group reached improvements of moderate to large effect sizes concerning the recorded health parameters. One year after rehabilitation "unsuccessful" rehabilitation patients fall back to their baseline levels of impairment, while the successful maintain their achieved effects after rehabilita-tion. The 2 groups rated several aspects of the intervention differently and the "unsuccessful" group rated the preparation for the time after the rehabilitation worse.The number of perceived aftercare elements proves to be the strongest predictor of failure in multivariate evaluation; "clinic facilities" is the only other independent predictor.During the interviews, "unsuccessful" patients reported different individual barriers for implementation of physical activity in daily life. Rehabilitation patients, who did not benefit from the new rehabilitation and aftercare concept, did neither differ in sociodemographic nor in disease-specific characteristics from the successful rehabilitation patients. However, differences in the implementation of the new rehabilitation philosophy and its individual components in the rehabilitation clinics are significantly associated with the occurrence of success or failure. Ov-er-all, the results of our study indicate a need for more flexible design of rehabilitation and aftercare adjusted to individual needs.


The role of IL-6 in the radiation response of prostate cancer.
Hormone-resistant (HR) prostate cancers are highly aggressive and respond poorly to treatment. IL-6/STAT3 signaling has been identified to link with the transition of HR and aggressive tumor behavior. The role of IL-6 in the radiation response of prostate cancer was investigated in the present study. The murine prostate cancer cell line (TRAMP-C1) and the hormone-resistant cell sub-line, TRAMP-HR, were used to assess the radiation response using in vitro clonogenic assays and tumor growth delay in vivo. Biological changes following irradiation were investigated by means of experimental manipulation of IL-6 signaling. Correlations among IL-6 levels, tumor regrowth, angiogenesis and myeloid-derived suppressor cell (MDSC) recruitment were examined in an animal model. HR prostate cancer cells had a higher expression of IL-6 and more activated STAT3, compared to TRAMP-C1 cells. HR prostate cancer cells had a greater capacity to scavenge reactive oxygen species, suffered less apoptosis, and subsequently were more likely to survive after irradiation. Moreover, IL-6 expression was positively linked to irradiation and radiation resistance. IL-6 inhibition enhanced the radiation sensitivity of prostate cancer, which was associated with increased p53, RT-induced ROS and oxidative DNA damage. Furthermore, when mice were irradiated with a sub-lethal dose, inhibition of IL-6 protein expression attenuated angiogenesis, MDSC recruitment, and decreased tumor regrowth. These data demonstrate that IL-6 is important in the biological sequelae following irradiation. Therefore, treatment with concurrent IL-6 inhibition is a potential therapeutic strategy for increasing the radiation response of prostate cancer.


Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion.
Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.


Nationwide awareness-raising program for viral hepatitis in Japan: the "Shitte kan-en" project.
Chronic viral hepatitis is one of the most widespread infectious diseases in Japan. In the 2009 financial year, the Japanese government enacted the Basic Act on Hepatitis Measures, followed by the Basic Guidelines for Promotion of Control Measures for Hepatitis 2 years later. The guidelines emphasize the importance of provision and dissemination of accurate information on viral hepatitis and public awareness-raising. A subsidy program on hepatitis was therefore launched by the Ministry of Health, Labour and Welfare in 2011, called "Shitte kan-en" (in English, "Let's learn about hepatitis"), and involves popular Japanese actors and singers. The project started awareness-raising activities in the 2013 financial year, as the "National Campaign Project for Hepatitis Measures". It aims to communicate concise and accurate information about hepatitis and the necessity of testing for viral hepatitis. It also encourages citizens to take a positive approach to early detection and treatment. To date, the main initiatives of the project are as follows: i) celebrity visits to prefectural governors to draw attention to the condition, ii) educational events in cooperation with hepatologists in regional core hospitals, iii) support for partner companies' hepatitis awareness activities in workplaces, and iv) support for the activities of program promoters. Targeting approaches to particular groups is likely to be key to success for general awareness-raising. Evaluation of the effectiveness of this multifaceted approach is warranted to reduce the undiagnosed population and improve the link between testing and care for viral hepatitis in Japan.


Multifunctional Water Sensors for pH, ORP, and Conductivity Using Only Microfabricated Platinum Electrodes.
Monitoring of the pH, oxidation-reduction-potential (ORP), and conductivity of aqueous samples is typically performed using multiple sensors. To minimize the size and cost of these sensors for practical applications, we have investigated the use of a single sensor constructed with only bare platinum electrodes deposited on a glass substrate. The sensor can measure pH from 4 to 10 while simultaneously measuring ORP from 150 to 800 mV. The device can also measure conductivity up to 8000 μS/cm in the range of 10 °C to 50 °C, and all these measurements can be made even if the water samples contain common ions found in residential water. The sensor is inexpensive (i.e., ~$0.10/unit) and has a sensing area below 1 mm², suggesting that the unit is cost-efficient, robust, and widely applicable, including in microfluidic systems.


Emergency Physician-Performed Point-of-Care Ultrasound of a Renal Mass.
Emergency physicians (EPs) frequently integrate point-of-care ultrasound (POCUS) into the initial bedside evaluation of patients presenting to the emergency department with acute flank pain. A POCUS-first diagnostic approach can allow EPs to promptly assess for life-threatening pathologies of the aorta and gallbladder. POCUS is also a critical bedside tool to determine renal causes of acute flank pain, such as hydronephrosis in the setting of nephrolithiasis, subcapsular hematomas, renal abscesses, pyelonephritis, and renal masses. This report illustrates a case in which EP-performed POCUS led to the incidental diagnosis of a malignant renal mass in a patient presenting with flank pain. We review the specifics of the ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) Bosniak classification system used by radiologists for risk stratification of cystic renal masses (CRMs).


Diagnostic Accuracy of Contemporary Selection Criteria in Prostate Cancer Patients Eligible for Active Surveillance: A Bayesian Network Meta-Analysis.
Several active surveillance (AS) criteria have been established to screen insignificant prostate cancer (insigPCa, defined as organ confined, low grade and small volume tumors confirmed by postoperative pathology). However, their comparative diagnostic performance varies. The aim of this study was to compare the diagnostic accuracy of contemporary AS criteria and validate the absolute diagnostic odds ratio (DOR) of optimal AS criteria. First, we searched Pubmed and performed a Bayesian network meta-analysis (NMA) to compare the diagnostic accuracy of contemporary AS criteria and obtained a relative ranking. Then, we searched Pubmed again to perform another meta-analysis to validate the absolute DOR of the top-ranked AS criteria derived from the NMA with two endpoints: insigPCa and favorable disease (defined as organ confined, low grade tumors). Subgroup and meta-regression analyses were conducted to identify any potential heterogeneity in the results. Publication bias was evaluated. Seven eligible retrospective studies with 3,336 participants were identified for the NMA. The diagnostic accuracy of AS criteria ranked from best to worst, was as follows: Epstein Criteria (EC), Yonsei criteria, Prostate Cancer Research International: Active Surveillance (PRIAS), University of Miami (UM), University of California-San Francisco (UCSF), Memorial Sloan-Kettering Cancer Center (MSKCC), and University of Toronto (UT). I2 = 50.5%, and sensitivity analysis with different insigPCa definitions supported the robustness of the results. In the subsequent meta-analysis of DOR of EC, insigPCa and favorable disease were identified as endpoints in ten and twenty-two studies, respectively. The pooled DOR for insigPCa and favorable disease were 0.44 (95%CI, 0.31-0.58) and 0.66 (95%CI, 0.61-0.71), respectively. According to a subgroup analysis, the DOR for favorable disease was significantly higher in US institutions than that in other regions. No significant heterogeneity or evidence of publication bias was identified. Among the seven AS criteria evaluated in this study, EC was optimal for positively identifying insigPCa patients. The pooled diagnostic accuracy of EC was 0.44 for insigPCa and 0.66 when a more liberal endpoint, favorable disease, was used. [https://www.crd.york.ac.uk/prospero/], PROSPERO [CRD42020157048].


Visual regulation of manual aiming: a comparison of methods.
Visual regulation of upper limb movements occurs throughout the trajectory and is not confined to discrete control in the target area. Early control is based on the dynamic relationship between the limb, the target, and the environment. Despite robust outcome differences between protocols involving visual manipulations, it remains difficult to identify the kinematic events that characterize these differences. In this study, participants performed manual aiming movements with and without vision. We compared several traditional approaches to movement analysis with two new methods of quantifying online limb regulation. As expected, participants undershot the target and their movement endpoints were more variable when vision was not available. Although traditional measures such as reaction time, time after peak velocity, and the presence of discontinuities in acceleration were sensitive to the visual manipulation, measures quantifying the trial-to-trial spatial variability throughout the trajectory were the most effective in isolating the time course of online regulation.


Comparison of kinematic analysis by mapping tibiofemoral contact with movement of the femoral condylar centres in healthy and anterior cruciate ligament injured knees.
Two methods of analysis of knee kinematics from magnetic resonance images (MRI) in vivo have been developed independently: mapping the tibiofemoral contact, and tracking the femoral condylar centre. These two methods are compared for the assessment of kinematics in the healthy and the anterior cruciate ligament injured knee. Sagittal images of both knees of 20 subjects with unilateral anterior cruciate ligament injury were analysed. The subjects had performed a supine leg press against a 150 N load. Images were generated at 15 degrees intervals from 0 degrees to 90 degrees knee flexion. The tibiofemoral contact, and the centre of the femoral condyle (defined by the flexion facet centre (FFC)), were measured from the posterior tibial cortex. The pattern of contact in the healthy knee showed the femoral roll back from 0 degrees to 30 degrees, then from 30 degrees to 90 degrees the medial condyle rolled back little, while the lateral condyle continued to roll back on the tibial plateau. The contact pattern was more posterior in the injured knee (p=0.012), particularly in the lateral compartment. The medial FFC moved back very little during knee flexion, while the lateral FFC moved back throughout the flexion arc. The FFC was not significantly different in the injured knee (p=0.17). The contact and movement of the FFC both demonstrated kinematic events at the knee, such as longitudinal rotation. Both methods are relevant to design of total knee arthroplasty: movement of the FFC for consideration of axis alignment, and contact pattern for issues of interface wear and arthritic change in ligament injury.


Protein Acetylation and Butyrylation Regulate the Phenotype and Metabolic Shifts of the Endospore-forming Clostridium acetobutylicum.
Clostridium acetobutylicum is a strict anaerobic, endospore-forming bacterium, which is used for the production of the high energy biofuel butanol in metabolic engineering. The life cycle of C. acetobutylicum can be divided into two phases, with acetic and butyric acids being produced in the exponential phase (acidogenesis) and butanol formed in the stationary phase (solventogenesis). During the transitional phase from acidogenesis to solventogenesis and latter stationary phase, concentration peaks of the metabolic intermediates butyryl phosphate and acetyl phosphate are observed. As an acyl group donor, acyl-phosphate chemically acylates protein substrates. However, the regulatory mechanism of lysine acetylation and butyrylation involved in the phenotype and solventogenesis of C. acetobutylicum remains unknown. In our study, we conducted quantitative analysis of protein acetylome and butyrylome to explore the dynamic change of lysine acetylation and butyrylation in the exponential phase, transitional phase, and stationary phase of C. acetobutylicum Total 458 lysine acetylation sites and 1078 lysine butyrylation sites were identified in 254 and 373 substrates, respectively. Bioinformatics analysis uncovered the similarities and differences between the two acylation modifications in C. acetobutylicum Mutation analysis of butyrate kinase and the central transcriptional factor Spo0A was performed to characterize the unique role of lysine butyrylation in the metabolic pathway and sporulation process of C. acetobutylicum Moreover, quantitative proteomic assays were performed to reveal the relationship between protein features (e.g. gene expression level and lysine acylation level) and metabolites in the three growth stages. This study expanded our knowledge of lysine acetylation and butyrylation in Clostridia and constituted a resource for functional studies on lysine acylation in bacteria.


msechBari, a new MITE-like element in Drosophila sechellia related to the Bari transposon.
A few occurrences of miniature inverted-repeat transposable elements (MITEs) have been reported in species of the genus Drosophila. Here, we describe msechBari, a MITE-like element in Drosophila sechellia. The element is short, approximately 90 bp in length, AT-rich and occurs in association with, or close to, genes, characteristics that are typical for MITEs. The identification was performed in silico using the sequenced genome of D. sechellia and confirmed in a laboratory strain. This short element is related to the Bari_DM transposon of Drosophila melanogaster, having terminal inverted repeats (TIRs) of a similar length and a high identity with the full-length Bari_DM element. The estimated recent origin of the element and the homogeneity observed between copies found in the genome suggests that msechBari could be active in D. sechellia.


Transfer of nitrogen fixation genes from a bacterium with the characteristics of both Rhizobium and Agrobacterium.
Strain T1K, reported to be Rhizobium trifolii strain T1 carrying the drug resistance plasmid RU-1drd, was able to transfer a cluster of nif+ genes to Escherichia coli K-12. Additional genetic material, resembling the gal-chlA region of E. coli, was also transferred from strain T1K. The segregation pattern of these transferred genes suggested that they were on a plasmid. Although strain TIK was able to nodulate red and white clover, it also formed very slow-growing galls on tomato stems and shared many physiological properties with Agrobacterium tumefaciens, to which it seemed more closely related than to R. trifolii. The R. trifolii hybrid T1 (R1-19drd), constructed by conjugation, did not share any of these properties of both A. tumefaciens. Thus, strain T1K appears to be a bacterium with properties of both A. tumefaciens and R. trifolii and with the capacity to transfer nif+ genes and other functions which it may have "cloned" from another bacterium such as Klebsiella.


Informed Consent at Gunpoint: When Psychiatry Affects Gun Ownership.
As states take more steps to connect patients' gun ownership to their mental health, psychiatrists are being asked to provide mental health information after clinical interviews as well as after confiscation. This move into the patient-physician relationship raises new questions about how psychiatrists should obtain informed consent when interviews may result in reports to legal authorities. Consent warnings are already practiced more in the breach than in the observance and informed consent is imperfect at its best. In communities torn by controversies surrounding gun control, vehement political views will further influence these established themes to result in unprecedented pressures on patient confidentiality. This analysis draws on new movements in ethical theory and behavioral medicine that go beyond balancing principles to question the use of psychiatry in firearm reporting, and support a vigorous practice of informed consent to protect both individuals and the communities they live in.


A revised definition for cure of childhood acute lymphoblastic leukemia.
With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse).


Interhemispheric interaction affected by identification of Chinese characters.
One aspect of interhemispheric processing that has recently received attention is whether it increases or decreases the processing power of the brain. The present study investigated whether dividing information between the hemispheres becomes more advantageous to task performance as computational complexity increases. A Chinese character matching task was given to subjects involving three levels of computational complexity (the pairs of characters being divided into three types, visually similar, homonymous, and synonymous). The result showed no difference in performance between within-field and across-field presentation for visually similar characters. Performance was significantly better for across field than within field with homophones and synonyms. However, the error rates of within field for phonetic matching was significantly higher than those for semantic matching. These results suggest that both the computational difficulty of materials and the intrinsic function of each hemisphere play a role in interhemispheric processing.


Safety assessment of Maillard reaction products of chicken bone hydrolysate using Sprague-Dawley rats.
The Maillard reaction products of chicken bone hydrolysate (MRPB) containing 38% protein, which is a derived product from chicken bone, is usually used as a flavor enhancer or food ingredient. In the face of a paucity of reported data regarding the safety profile of controversial Maillard reaction products, the potential health effects of MRPB were evaluated in a subchronic rodent feeding study. Sprague-Dawley rats (SD, 5/sex/group) were administered diets containing 9, 3, 1, or 0% of MRPB derived from chicken bone for 13 weeks. During the 13-week treatment period, no mortality occurred, and no remarkable changes in general condition and behavior were observed. The consumption of MRPB did not have any effect on body weight or feed and water consumption. At the same time, there was no significant increase in the weights of the heart, liver, lung, kidney, spleen, small intestine, and thymus in groups for both sexes. Serological examination showed serum alanine aminotransferase in both sexes was decreased significantly, indicating liver cell protection. No treatment-related histopathological differences were observed between the control and test groups. Based on the results of this study, the addition of 9% MRPB in the diet had no adverse effect on both male and female SD rats during the 90-day observation. Those results would provide useful information on the safety of a meaty flavor enhancer from bone residue as a byproduct of meat industry.


The emerging role of targeted therapies for advanced well-differentiated gastroenteropancreatic neuroendocrine tumors.
Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are unique and complex neoplasms, exhibiting a wide spectrum of diverse clinical behaviors. The contemporary management of well-differentiated GEP-NETs is marked by the availability of a wide range of targeted therapies. Areas Covered: For patients with localized or oligometastatic disease, surgical resection remains the preferred approach and is associated with excellent long-term outcomes. For patients with unresectable but isolated liver metastases, multiple liver-directed therapies, including hepatic arterial based therapies and ablative techniques, exist. For patients with metastatic and progressive disease, a number of systemic therapies exist: molecular targeted agents, peptide receptor radionuclide therapy (PRRT), and systemic chemotherapy. Furthermore, somatostatin analogs (SSA) are an important component of therapy, both effectively controlling symptoms of hormonal overproduction and contributing to slowing tumor progression. Expert Opinion: In the near future, advances in our understanding of tumor biology, genetics, immunology, nanotechnology, and radiation pharmacology should only continue to expand the availability of targeted therapies, improving the outcomes of patients with GEP-NETs. We herein review the management of advanced well-differentiated GEP-NETS with a particular emphasis on the role of targeted therapies.


Real, potentially real, and hypothetical monetary rewards in probability discounting.
Although hypothetical rewards have been used almost exclusively in human discounting studies, investigations of their validity are limited. The present experiment compared the discounting of monetary reward value by probability across conditions in which the rewards were real, potentially real, and hypothetical. Twenty-four undergraduates choose between an uncertain large reward and a certain small reward 60 times (trials). In the real and hypothetical reward conditions, the participants made choices with real and hypothetical money, respectively, in every trial. In the potentially real condition, they did so with real money in randomly selected three of the 60 trials and with hypothetical money in the remainder. The log10 -transformed h values of a hyperbolic probability-discount function and the values of the area under the curve with an ordinal transformation of odds against were higher and lower, respectively, in the potentially real and in the hypothetical reward conditions than in the real reward condition, demonstrating that the probability discounting of hypothetical monetary rewards was larger than that of real rewards. These results suggest that future studies are required to identify why the hypothetical reward procedure overestimates the discounting rates of real rewards.


Interfacial melting mechanism of nanocrystals determined by interfacial energy and interfacial stress.
To clarify the interface melting mechanism, a unified analytical expression was developed to describe the depression and superheating of Tm(D) functions for metallic nanoparticles, nanostructures, and nanoparticles embedded in a coherent or incoherent interface. Tm(D) functions are determined by the sign of γss, fss (or γsl and fsl), and D0 as caused by the change of interface environments. We found that there is TCIm(D) > TNSm(D) > TIIm(D) > TNPsm(D) for Ag nanocrystals within different interfaces. Moreover, for a given size, Tm(D)/Tm(∞) decreases with the reduction of γss/fss for nanoparticles, nanostructures and nanoparticles embedded in incoherent interfaces, while an opposite trend occurs for the coherent interfaces. In addition, we also found that there is TNPsm(D)/Tm(∞) < TIIm(D)/Tm(∞) < TNSm(D)/Tm(∞), which is in agreement with the relation of γNPssl/fNPssl < γIIss/fIIss < γNSss/fNSss. By analyzing the γss(D) (or γsl(D)), fss(D) (or fsl(D)) and γss(D)/fss(D) (or γsl(D)/fsl(D)) functions of Ag nanocrystals and comparing with their Tm(D) functions, it is found that there is a high consistency between the variation of γss(D)/fss(D) (γsl(D)/fsl(D)) and Tm(D)/Tm, which reveals that the size dependence of Tm(D)/Tm is determined by γss(D)/fss(D) (or γsl(D)/fsl(D)). Our predictions show a good agreement with the available theoretical and experimental results.


Properties of strains of Escherichia coli isolated from a variety of sources.
Strains of Escherichia coli causing urinary-tract infections were found to be more commonly haemolytic than were faecal strains. Strains from the introitus that subsequently gave rise to urinary-tract infections resembled urinary strains and those that did not give rise to infections resembled faecal strains. alpha-Haemolysin production was closely associated, in strains from a variety of different sources, with the production of a haemolysin detectable in liquid medium and with cytotoxicity in tissue culture.