Nonorganellar acyl carrier protein from oleaginous yeast is a homologue of ribosomal protein P2.
Acyl carrier protein (ACP) is responsible for carrying the growing fatty acid chain from one enzyme active site to the next during fatty acid biosynthesis. Here we report the identification, purification, immunocytochemical localization, and cloning of ACP from the oleaginous yeast, Rhodotorula glutinis. The soluble fraction of this organism can synthesize triacylglycerol and is able to accept the acyl group from acyl-ACP for the synthesis. The ACP, cloned from the system, showed a significant similarity with ribosomal protein P2. Expression and characterization of the recombinant protein showed that the ACP was acylated in vitro. The recombinant protein was post-translationally modified, since it was observed in [14C]beta-alanine labeling and matrix-assisted laser desorption mass spectroscopic analysis. Site-directed mutants were generated to identify a serine residue responsible for phosphopantetheinylation and found that mutation of serine 59 to alanine abrogated the fatty acylation ability of the protein. These results demonstrate that a novel modification of ribosomal protein P2 allows it to act as an acyl carrier protein and participate in acylation reactions.


Determinants of chronic pain 3 years after moderate or serious injury.
Patients with pain 3 years after injury are at risk of lifetime pain. It is not known if the predictors of chronic pain at 3 years are the same as those for earlier time points or whether other factors become important. Clarifying these factors will aid our understanding of the development of long-term pain and further inform the development of models for screening and early intervention for pain in the aftermath of injury. Patients admitted to two trauma centers underwent a comprehensive physical and psychological assessment of known and potential risk factors for chronic pain during their index admission. Three years after injury, these patients were assessed for the presence of chronic pain (score was ≥5 on an 11-point numerical rating scale during the last episode of pain, and present in the last month and at least two times in the past week) and pain-related disability. Logistic regression was used to identify independent risk factors for the presence of chronic pain and disability. Two hundred and twenty patients (75.9% of the original cohort) were assessed at 3 years. Of these, 146 (66.7%) reported some pain and 52 (23.7%) reported chronic pain. Factors (present at the time of injury) that predicted chronic pain were lower socioeconomic status, pain severity, and injury severity. The predictive power of these combined factors was modest. Three years after serious injury, almost a quarter of patients report chronic pain, and more than a third report at least moderate pain-related disability. The predicative power of measures taken in the acute setting is not enough to support discharge screening alone as a method of triaging high-risk patients to early intervention.


Prostaglandin I2 is responsible for ameliorating prostaglandin E2 stress in stimulating the expression of tumor necrosis factor α in a β-amyloid protein -dependent mechanism.
Cyclooxygenase-2 (COX-2) has been found to be induced during the early stage of Alzheimer's disease (AD). Using mouse-derived astrocyte and APP/PS1 transgenic (Tg) mice as model systems, we firstly elucidated the mechanisms underlying COX-2 metabolic production including prostaglandin (PG)E2- and PGI2-mediated tumor necrosis factor α (TNF-α) regulation. Specifically, PGE2 accumulation in astrocyte activated the p38 and JNK/c-Jun signaling pathways via phosphorylation, resulting in TNF-α expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 in stimulating the production of TNF-α by inhibiting the activity of TNF-α promoter and the binding activity of AP1 on the promoter of TNF-α. Moreover, our data also showed that not only Aβ1-42 oligomers but also Aβ1-42 fibrils have the ability to involve in mediating the antagonistic effects of PGE2 and PGI2 on regulating the expression of TNF-α via a p38- and JNK/c-Jun-dependent, AP1-transactivating mechanism. Reciprocally, the production of TNF-α finally accelerated the deposition of β-amyloid protein (Aβ)1-42 in β-amyloid plaques (APs), which contribute to the cognitive decline of AD.


Maintenance of normothermia at operation room temperature of 24 degrees C in adult and pediatric patients undergoing liver transplantation.
Hypothermia is common during surgery in regular operating room (OR) temperature. The effect of increasing the OR temperature to 24 degrees C coupled with simple warming measures to maintain normothermia in both pediatric and adult patients during living donor liver transplantation (LDLT) was evaluated. One hundred patients undergoing LDLT were separated into pediatric (GI) and adult (GII) groups. Nasopharyngeal temperature (NT) at each hour for the first 6 h, at the time of anhepatic phase, 5 and 30 min after reperfusion, and each hour for the last 2 h of the operation was recorded, compared and analyzed. A significant difference in core temperature variation was noted between the two groups. GI tended to be hyperthermic, while GII remained mildly hypothermic throughout the procedure. A sudden decrease of NT was observed in both groups during the anhepatic and reperfusion phases. Correlation between liver graft weight over recipient body weight ratio rather than the graft weight itself was found in GI, but no such correlation was found in GII. OR temperature of 24 degrees C, together with simple active and passive warming measures are more effective in maintaining normothermia during liver transplantation in pediatric patients than in adults.


Rhizobial infection does not require cortical expression of upstream common symbiosis genes responsible for the induction of Ca(2+) spiking.
For the establishment of an effective root nodule symbiosis, a coordinated regulation of the infection processes between the epidermis and cortex is required. However, it remains unclear whether the symbiotic genes identified so far are involved in epidermal and/or cortical infection, e.g. epidermal and cortical infection thread formation or cortical cell division. To analyze the symbiotic gene requirements of the infection process, we have developed an epidermis-specific expression system (pEpi expression system) and examined the symbiotic genes NFR1, NFR5, NUP85, NUP133, CASTOR, POLLUX, CCaMK, CYCLOPS, NSP1 and NSP2 for involvement in the infection process in the epidermis and cortex. Our study shows that expression of the upstream common symbiosis genes CASTOR, POLLUX, NUP85 and NUP133 in the epidermis is sufficient to induce formation of infection threads and cortical cell division, leading to the development of fully effective nodules. Our system also shows a requirement of CCaMK, CYCLOPS, NSP1 and NSP2 for the entire nodulation process, and the different contributions of NFR1 and NFR5 to cortical infection thread formation. Based on these analyses using the pEpi expression system, we propose a functional model of symbiotic genes for epidermal and cortical infection.


Electrokinetic Torque Generation by DNA Nanorobotic Arms Studied via Single-Molecule Fluctuation Analysis.
DNA nanotechnology has enabled the creation of supramolecular machines, whose shape and function are inspired from traditional mechanical engineering as well as from biological examples. As DNA inherently is a highly charged biopolymer, the external application of electric fields provides a versatile, computer-programmable way to control the movement of DNA-based machines. However, the details of the electrohydrodynamic interactions underlying the electrical manipulation of these machines are complex, as the influence of their intrinsic charge, the surrounding cloud of counterions, and the effect of electrokinetic fluid flow have to be taken into account. In this work, we identify the relevant effects involved in this actuation mechanism by determining the electric response of an established DNA-based nanorobotic arm to varying design and operation parameters. Borrowing an approach from single-molecule biophysics, we determined the electrical torque exerted on the nanorobotic arms by analyzing their thermal fluctuations when oriented in an electric field. We analyze the influence of various experimental and design parameters on the "actuatability" of the nanostructures and optimize the generated torque according to these parameters. Our findings give insight into the physical processes involved in the actuation mechanism and provide general guidelines that aid in designing and efficiently operating electrically driven nanorobotic devices made from DNA.


Eif3ba regulates cranial neural crest development by modulating p53 in zebrafish.
Congenital diseases caused by abnormal development of the cranial neural crest usually present craniofacial malformations and heart defects while the precise mechanism is not fully understood. Here, we show that the zebrafish eif3ba mutant caused by pseudo-typed retrovirus insertion exhibited a similar phenotype due to the hypogenesis of cranial neural crest cells (NCCs). The derivatives of cranial NCCs, including the NCC-derived cell population of pharyngeal arches, craniofacial cartilage, pigment cells and the myocardium derived from cardiac NCCs, were affected in this mutant. The expression of several neural crest marker genes, including crestin, dlx2a and nrp2b, was specifically reduced in the cranial regions of the eif3ba mutant. Through fluorescence-tracing of the cranial NCC migration marker nrp2b, we observed reduced intensity of NCC-derived cells in the heart. In addition, p53 was markedly up-regulated in the eif3ba mutant embryos, which correlated with pronounced apoptosis in the cranial area as shown by TUNEL staining. These findings suggest a novel function of eif3ba during embryonic development and a novel level of regulation in the process of cranial NCC development, in addition to providing a potential animal model to mimic congenital diseases due to cranial NCC defects. Furthermore, we report the identification of a novel transgenic fish line Et(gata2a:EGFP)pku418 to trace the migration of cranial NCCs (including cardiac NCCs); this may serve as an invaluable tool for investigating the development and dynamics of cranial NCCs during zebrafish embryogenesis.


Bacterial persistence as a phenotypic switch.
A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from such persistent bacteria remain sensitive to the antibiotic. We investigated the persistence of single cells of Escherichia coli with the use of microfluidic devices. Persistence was linked to preexisting heterogeneity in bacterial populations because phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates. Quantitative measurements led to a simple mathematical description of the persistence switch. Inherent heterogeneity of bacterial populations may be important in adaptation to fluctuating environments and in the persistence of bacterial infections.


[Comparative evaluation of the effectiveness of various narcotic analgesics after intravenous autoanalgesia].
The article is devoted to an investigation of intravenous analgesia with different narcotic analgetic drugs (phentanyl, morphine, dipidolor). A comparative assessment of the influence upon central hemodynamics, lung ventilation, acid-base metabolism and blood gases was performed, as well as the degree of analgesia in using these drugs. A conclusion is made that morphine and phentanyl are preferable for the intravenous postoperative autoanalgesia.


Injected anti-sense RNAs specifically block messenger RNA translation in vivo.
As a test for a method to analyze gene function in embryogenesis, the translation of a specific mRNA has been blocked in vivo by microinjection of complementary (anti-sense) RNA. RNA complementary to globin mRNA was synthesized in vitro by transcription of an inverted globin cDNA clone. After injection into frog oocyte cytoplasm, the anti-sense globin RNA forms a hybrid with globin mRNA and selectively prevents its translation. Deletion mapping of the anti-sense RNA shows that the 5' region of the globin mRNA must be covered in order to block translation. This method may allow one to study the function of many genes for which DNA clones are available by preventing the expression of the endogenous gene as protein.


Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets.
The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA(3)) and NA (sNA(4)) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-microg doses of these antigens elicited strong antibody responses, which were adjuvant dependent. Interestingly, coadministration of both antigens strongly enhanced the HA-specific but not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA(3) dramatically reduced virus replication (e.g., by lowering pulmonary titers by about 5 log(10) units), immunization with sNA(4) markedly decreased the clinical effects of infection, such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly, and safely produced in high quantities. In particular, our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.


Streamlining cardiovascular clinical trials to improve efficiency and generalisability.
Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease.


Romedi: An Open Data Source About French Drugs on the Semantic Web.
The W3C project, "Linking Open Drug Data" (LODD), linked several publicly available sources of drug data together. So far, French data, like marketed drugs and their summary of product characteristics, were not integrated and remained difficult to query. In this paper, we present Romedi (Référentiel Ouvert du Médicament), an open dataset that links French data on drugs to international resources. The principles and standard recommendations created by the W3C for sharing information were adopted. Romedi was connected to the Unified Medical Language System and DrugBank, two central resources of the LODD project. A SPARQL endpoint is available to query Romedi and services are provided to annotate textual content with Romedi terms. This paper describes its content, its services, its links to external resources, and expected future developments.


Universal depression prevention: An umbrella review of meta-analyses.
Depression is a disabling, highly prevalent, frequently chronic, and difficult-to-treat disorder with an immense cognitive, social, and economic burden. Given that many of the advances in other non-communicable disorders like cancer have been in prevention rather than treatment, the prevention of depression is currently an unmet public health priority. We sought to provide an overview of the meta-analytic literature through conducting a systematic umbrella review of universally delivered preventive interventions for depression. The search was conducted on March 18, 2021 utilising the following databases (all accessed through EBSCOHost); Allied and Complementary Medicine Database, CINAHL Complete, Global Health, Health Source: Nursing/Academic Edition, MEDLINE Complete and APA PsychArticles. The following search terms related to depression, prevention, and trial study design. Two authors independently screened articles and a third resolved discrepancies. Eligibility criteria sought to identify meta-analyses that investigated the prevention of depression (i.e., reduced incidence) through intervention studies that were universal, in that they were designed to be delivered to entire populations Six meta-analyses on psychological interventions, two school-based meta-analyses, and one eHealth meta-analysis were included in this umbrella review. Findings indicated that all identified studies were of good quality and one was of fair quality. One previous meta-review that examined physical activity to prevent depression was included in results, comprising eight meta-analyses. Preventive interventions have primarily and successfully utilized psychological therapeutic components, delivered at the school, community, and workplace settings. Both school- and eHealth-based interventions hold some utility for depression prevention. There is meta-analytic evidence that physical activity is efficacious for depression prevention. However, universal prevention is inconsistently defined. There is a pressing need for well-designed randomized controlled preventative interventions for depression before recommendations can be universally accepted with convincing level of evidence.


Effect of white wine on esophageal peristalsis and acid clearance.
In a previous study it was demonstrated that white wine reduces the lower esophageal sphincter pressure and induces gastroesophageal reflux characterized by reflux episodes of long duration. In the present study, it was evaluated whether wine disturbs esophageal peristalsis and acid clearance. Twelve healthy volunteers (7F, 23-37 years) received 300 ml white wine (8% vol/vol; WW), an ethanol solution (8% vol/vol; ET) or tap water (WA) together with a standardized meal in a random order. Acid clearance was tested by instillation of 15 ml 0.1 N HCI into the distal esophagus. The number of swallows (dry swallow every 30 sec) were counted until pH rose again above 5. Five wet swallows (5 ml) were applied to test primary peristalsis and five insufflations of 20 ml of air were performed to test secondary peristalsis. Each test was done immediately after and 60 min after ingestion of the beverages. A significantly higher number of swallows were needed to clear the esophagus immediately after ingestion of wine (P < 0.01; median number: WW 12; ET 8; WA 7) due to an increase in the frequency of failed, simultaneous, and low-amplitude contractions. The frequency of triggered secondary contractions was decreased (P < 0.02; WW 70%; ET 100%; WA 100%) and the latency between air injection and onset of secondary peristalsis was prolonged (P < 0.05; WW 9 sec; ET 7 sec; WA 6 sec) immediately after ingestion of white wine. Wet swallow induced primary peristalsis was not influenced by wine. No significant differences in the measured parameters were seen 60 min after ingestion of the three beverages. White wine disturbs temporarily esophageal clearance due to a disturbance of triggering secondary peristalsis and due to an increase in ineffective contractions. The ethanol content alone is not responsible for the effects of white wine on esophageal peristalsis and acid clearance.


Gas chromatographic determination of pesticides in vegetable samples by sequential positive and negative chemical ionization and tandem mass spectrometric fragmentation using an ion trap analyser.
A selective and sensitive chromatographic method is described for the determination of nine organochlorine and organophosphorus pesticides in vegetable samples by gas chromatography-mass spectrometry. The proposed method combines the use of positive and negative chemical ionisation and tandem mass spectrometric fragmentation, resulting in a significant increase in selectivity and allowing the simultaneous confirmation and quantification of trace levels of pesticides in complex vegetable matrices. Parameters relative to ionisation and fragmentation processes were optimised to obtain maximum sensitivity. Repeatability and reproducibility studies yielded relative standard deviations lower than 25% in all cases. Identification criteria, such as retention time and relative abundance of characteristic product ions, were also evaluated in order to guarantee the correct identification of the target compounds. The method was applied to real vegetable samples to demonstrate its use in routine analysis.


Machine Learning-Based Software Defect Prediction for Mobile Applications: A Systematic Literature Review.
Software defect prediction studies aim to predict defect-prone components before the testing stage of the software development process. The main benefit of these prediction models is that more testing resources can be allocated to fault-prone modules effectively. While a few software defect prediction models have been developed for mobile applications, a systematic overview of these studies is still missing. Therefore, we carried out a Systematic Literature Review (SLR) study to evaluate how machine learning has been applied to predict faults in mobile applications. This study defined nine research questions, and 47 relevant studies were selected from scientific databases to respond to these research questions. Results show that most studies focused on Android applications (i.e., 48%), supervised machine learning has been applied in most studies (i.e., 92%), and object-oriented metrics were mainly preferred. The top five most preferred machine learning algorithms are Naïve Bayes, Support Vector Machines, Logistic Regression, Artificial Neural Networks, and Decision Trees. Researchers mostly preferred Object-Oriented metrics. Only a few studies applied deep learning algorithms including Long Short-Term Memory (LSTM), Deep Belief Networks (DBN), and Deep Neural Networks (DNN). This is the first study that systematically reviews software defect prediction research focused on mobile applications. It will pave the way for further research in mobile software fault prediction and help both researchers and practitioners in this field.


Diagnostic value of circRNA in coronary heart disease: a meta-analysis.
Aim: Studies have indicated that circRNAs have diagnostic value for coronary heart disease (CHD), but the efficacy varies greatly; therefore, a meta-analysis was conducted to assess the diagnostic value of circRNAs in CHD. Materials & methods: 16 studies with 3962 subjects (2239 cases and 1723 controls) were included by searching PubMed, Web of Science and MEDLINE. The pooled sensitivity and specificity, summary receiver operating characteristic and area under the curve, positive likelihood ratio and negative likelihood ratio were calculated. Results: The pooled area under the curve of circRNAs for the diagnosis of CHD was 0.80 (sensitivity and specificity were 0.77 and 0.68, respectively), and more indexes were calculated. Conclusion: circRNAs may be good biomarkers for diagnosing CHD.


Spatial distribution of the electric potential from photosystem I reaction centers in lipid vesicles.
Photosynthetic reaction centers are integral membrane complexes that produce a net transmembrane charge separation in response to light. The Photosystem I (PSI) complex is a thoroughly studied reaction center that has been proposed as a nanoscale photovoltaic structure in diverse applications, including activation of excitable cells by triggering of voltage-gated ion channels. An electrostatic model of a spherical lipid vesicle embedded with PSI and suspended in an aqueous medium is presented. The distribution of the electric potential is obtained by solving the nonlinear Poisson-Boltzmann equation with the finite-element method. The model predicts a maximum potential difference of 1.3 V between charges. This value depends mostly on the intrinsic dielectric constants of the reaction center and distance between charges. However, the potential distribution near the reaction center depends on the ionic strength of the aqueous medium. When the ionic strength is zero, the vesicle develops a transmembrane potential that increases linearly with the density of reaction centers. When the ionic strength increases, this potential difference approaches to zero. The main results of the simulations are consistent with previously reported experimental data. Based on the presented results, the potential application of PSI to light activation of voltage-gated ion channels is discussed.


Electronic nicotine delivery system (ENDS) use during smoking cessation: a qualitative study of 40 Oklahoma quitline callers.
Approximately 10% (40 000) of US quitline enrollees who smoke cigarettes report current use of electronic nicotine delivery systems (ENDS); however, little is known about callers' ENDS use. Our aim was to describe why and how quitline callers use ENDS, their beliefs about ENDS and the impact of ENDS use on callers' quit processes and use of FDA-approved cessation medications. Qualitative interviews conducted 1-month postregistration. Interviews were recorded, transcribed, double-coded and analysed to identify themes. Oklahoma Tobacco Helpline. 40 callers aged ≥18 who were seeking help to quit smoking were using ENDS at registration and completed ≥1 programme calls. At 1-month postregistration interview, 80% of callers had smoked cigarettes in the last 7 days, almost two-thirds were using ENDS, and half were using cessation medications. Nearly all believed ENDS helped them quit or cut down on smoking; however, participants were split on whether they would recommend cessation medications, ENDS or both together for quitting. Confusion and misinformation about potential harms of ENDS and cessation medications were reported. Participants reported using ENDS in potentially adaptive ways (eg, using ENDS to cut down and nicotine replacement therapy to quit, and stepping down nicotine in ENDS to wean off ENDS after quitting) and maladaptive ways (eg, frequent automatic ENDS use, using ENDS in situations they did not previously smoke, cutting down on smoking using ENDS without a schedule or plan to quit), which could impact the likelihood of quitting smoking or continuing ENDS use. These qualitative findings suggest quitline callers who use ENDS experience confusion and misinformation about ENDS and FDA-approved cessation medications. Callers also use ENDS in ways that may not facilitate quitting smoking. Opportunities exist for quitlines to educate ENDS users and help them create a coordinated plan most likely to result in completely quitting combustible tobacco.


A novel polyamine allosteric site of SpeG from Vibrio cholerae is revealed by its dodecameric structure.
Spermidine N-acetyltransferase, encoded by the gene speG, catalyzes the initial step in the degradation of polyamines and is a critical enzyme for determining the polyamine concentrations in bacteria. In Escherichia coli, studies have shown that SpeG is the enzyme responsible for acetylating spermidine under stress conditions and for preventing spermidine toxicity. Not all bacteria contain speG, and many bacterial pathogens have developed strategies to either acquire or silence it for pathogenesis. Here, we present thorough kinetic analyses combined with structural characterization of the VCA0947 SpeG enzyme from the important human pathogen Vibrio cholerae. Our studies revealed the unexpected presence of a previously unknown allosteric site and an unusual dodecameric structure for a member of the Gcn5-related N-acetyltransferase superfamily. We show that SpeG forms dodecamers in solution and in crystals and describe its three-dimensional structure in several ligand-free and liganded structures. Importantly, these structural data define the first view of a polyamine bound in an allosteric site of an N-acetyltransferase. Kinetic characterization of SpeG from V. cholerae showed that it acetylates spermidine and spermine. The behavior of this enzyme is complex and exhibits sigmoidal curves and substrate inhibition. We performed a detailed non-linear regression kinetic analysis to simultaneously fit families of substrate saturation curves to uncover a simple kinetic mechanism that explains the apparent complexity of this enzyme. Our results provide a fundamental understanding of the bacterial SpeG enzyme, which will be key toward understanding the regulation of polyamine levels in bacteria during pathogenesis.


Acrylonitrile insertion reactions of cationic palladium alkyl complexes.
The reactions of acrylonitrile (AN) with "L(2)PdMe+" species were investigated; (L(2) = CH(2)(N-Me-imidazol-2-yl)(2) (a, bim), (p-tolyl)(3)CCH(N-Me-imidazol-2-yl)(2) (b, Tbim), CH(2)(5-Me-2-pyridyl)(2) (c, CH(2)py'(2)), 4,4'-Me(2)-2,2'-bipyridine (d), 4,4'-(t)Bu(2)-2,2'-bipyridine (e), (2,6-(i)Pr(2)-C(6)H(3))N=CMeCMe=N(2,6-(i)Pr(2)-C(6)H(3)) (f)). [L(2)PdMe(NMe(2)Ph)][B(C(6)F(5))(4)] (2a-c) and [{L(2)PdMe}(2)(mu-Cl)][B(C(6)F(5))(4)] (2d-f) react with AN to form N-bound adducts L(2)Pd(Me)(NCCH=CH(2))(+) (3a-f). 3a-e undergo 2,1 insertion to yield L(2)Pd{CH(CN)Et}+, which form aggregates [L(2)Pd{CH(CN)Et}](n)(n)(+) (n = 1-3, 4a-e) in which the Pd units are proposed to be linked by PdCHEtCN- - -Pd bridges. 3f does not insert AN at 23 degrees C. 4a-e were characterized by NMR, ESI-MS, IR and derivatization to L(2)Pd{CH(CN)Et}(PR(3))+ (R = Ph (5a-e), Me (6a-c)). 4a,b react with CO to form L(2)Pd{CH(CN)Et}(CO)+ (7a,b). 7a reacts with CO by slow reversible insertion to yield (bim)Pd{C(=O)CH(CN)Et}(CO)+ (8a). 4a-e do not react with ethylene. (Tbim)PdMe+ coordinates AN more weakly than ethylene, and AN insertion of 3b is slower than ethylene insertion of (Tbim)Pd(Me)(CH(2)=CH(2))(+) (10b). These results show that most important obstacles to insertion polymerization or copolymerization of AN using L(2)PdR+ catalysts are the tendency of L(2)Pd{CH(CN)CH(2)R}+ species to aggregate, which competes with monomer coordination, and the low insertion reactivity of L(2)Pd{CH(CN)CH(2)R}(substrate)+ species.


Phialosimplex salinarum, a new species of Eurotiomycetes from a hypersaline habitat.
Salt mines represent an extreme environment with hypersaline conditions, complete darkness, and low nutrient availability. The diversity of filamentous fungi in such habitats is largely unknown. Eight strains of an unknown fungus were isolated from water samples of the salt mine in Berchtesgaden (Bavaria, Germany). They could be assigned to the ascomycete genus Phialosimplex, based on their common characteristics of producing conidia in chains or in heads on single phialides. Species of this genus are hitherto known to cause mycoses in dogs and have been found in mummies. Using molecular and morphological methods, the isolates are established as a new species, Phialosimplex salinarum sp. nov. Basipetospora halophila is also transferred to Phialosimplex as P. halophila comb. nov.


Surgery of spinal nerve sheath tumors with special reference to neurofibromatosis.
We conducted a retrospective study of 87 patients with spinal nerve sheath tumors to determine the overall clinical outcome and specific features in 20 patients affected with neurofibromatosis Types 1 and 2 (NF-1 and NF-2, respectively). Case records, operation notes, outpatient files, and radiological examinations were analyzed for all patients treated between September 1977 and August 1994. Additional follow-up data were obtained using outpatient examinations, questionnaires, and telephone calls. During the study period, 128 spinal neuromas (i.e., schwannomas) and 6 neurofibromas in 87 patients were treated. Fifty-seven neuromas were associated with NF-2 in 17 patients and six neurofibromas with NF-1 in 3 patients. Patients with NF-2 and symptomatic neuromas presented with more severe neurological deficits compared to patients without NF-2. Eighty-six percent of the neuromas were removed completely. On average, most preoperative deficits or symptoms improved in patients without NF-2, whereas neurological symptoms remained unchanged in patients with NF-2. Multiple regression analysis revealed that partial removal, surgery of a recurrent tumor, NF-2, and old age predisposed for tumor recurrence. No increased risk of recurrence was observed for patients with NF-1. For patients without NF-2, we observed overall recurrence rates of 10.7% after 5 years and 28.2% after 10 and 15 years, respectively, as determined by Kaplan-Meier analysis. For NF-2, the recurrence rate at 5 years was 39.2%, and all tumors had recurred by 9 years. Spinal nerve sheath tumors carry an excellent prognosis in patients with NF-1 and in patients without neurofibromatosis. Symptomatic neuromas occurring in association with NF-2 present with more severe neurological deficits, demonstrate little postoperative improvement, and have a very high recurrence rate.


Reducing interparental conflict among parents in contentious child custody disputes: an initial investigation of the Working Together Program.
Interparental conflict is one of the primary risk factors for negative outcomes for children whose parents separate, and it is likely to be high while parents are separating. Results are mixed regarding the effectiveness of interventions aimed at reducing interparental conflict. This study examined co-parents who were court-ordered to attend a 12-hr co-parenting intervention and completed pre-postassessments (n = 20) and 2-month follow-up assessments (n = 17). The results demonstrated increases in co-parents' relationship functioning and confidence in co-parenting. Both men and women reported decreased amounts of conflict in the presence of their children; however, only women reported decreases in general negative communication with the co-parent. These changes were generally maintained at a 2-month follow-up assessment. These findings suggest that interventions for high-conflict co-parents may increase their ability to work cooperatively.


Measuring unconditional stimulus expectancy during evaluative conditioning strengthens explicit conditional stimulus valence.
During evaluative conditioning, a neutral conditional stimulus (CS) becomes pleasant or unpleasant after pairings with a positive/negative unconditional stimulus (US). Measures of US expectancy are commonly assessed during conditioning but it is unclear whether this affects evaluative learning. In Experiment 1, we examined whether the concurrent assessment of US expectancy alongside measures of CS valence would influence the acquisition, extinction, and reinstatement of explicit CS valence. Participants rated both valence and expectancy during conditioning (valence/expectancy group) or only CS valence (valence only group). Evaluative conditioning was acquired in both groups during acquisition, but its magnitude was enhanced in the valence/expectancy group. Measuring US expectancy did not influence the extinction or reinstatement of conditional valence. In Experiment 2, we confirmed the enhancement of evaluative conditioning due to concurrent measurement of US expectancy in an explicit measure, but did not find corresponding evidence in an implicit measure of conditional valence. In Experiment 3, we replicated the results using a different US expectancy scale and demonstrated that measuring CS valence multiple times throughout conditioning also strengthens conditional valence. Overall, the results suggest that the measurement of US expectancy and CS valence throughout conditioning draws attention to the contingencies and strengthens explicit evaluative learning.


Repetitive negative thinking following exposure to a natural stressor prospectively predicts altered stress responding and decision-making in the laboratory.
Repetitive negative thinking (RNT) represents a transdiagnostic risk factor for affective disorders, and stress is theorized to exacerbate this vulnerability. One mechanism by which stress may influence individual differences in psychiatric symptoms is through altered decision-making, and loss aversion in particular. The present study uses multiple methods to investigate the relationships between RNT, stress, and decision-making. We measured RNT in young adults (N = 90) recently exposed to a natural stressor, Hurricane Irma, and tested the influence of RNT on changes in affect, cortisol, and decision-making during a laboratory stress induction two months later. Post-hurricane RNT predicted greater increases in loss averse decision-making (β = 0.30 [0.14, 0.47], p < .001; rp2 = 0.079) and negative affect (β = 0.59 [0.37, 0.81], p < .001; rp2 = 0.319) during the early-phase response to the laboratory stressor, as well as poorer cortisol recovery (β = 0.32, [0.10, 0.54], p = .005; rp2 = 0.095) in the late-phase stress response. Results highlight the role of loss aversion and stress in understanding RNT as an affective vulnerability factor.


[Knowledge on polypharmacy in a group of 65-year-old people or older living in a sector of the metropolitan area of Puerto Rico].
Addressing the high utilization of medications among the elderly, this study explored the degree of knowledge of polypharmacy and its consequences, as well as the pattern of utilization by a group of elders 65 years of age and over in the San Juan metropolitan area of Puerto Rico. A dual technique was utilized: focus groups and a survey. Two focus groups were performed in order to explore issues pertaining the following domains: quality of life, doctor-patient and pharmacist-patient relationships, degree of knowledge of polypharmacy, and need of information. A questionnaire was administered to obtain information regarding their pattern of drug utilization. Results of focus groups indicated that the elderly have learned how to cope with their chronic conditions and be able to continue with quality of life. Additionally, results suggested a need form the elderly to develop more assertiveness and closeness with their health care providers, both doctor and pharmacist; as well as a lack of sufficient knowledge of the serious implications that polypharmacy brings. Results from the survey revealed and confirmed their inappropriate utilization of medications, and suggest that this segment consults multiple physicians, all of which may bring potential problems of adverse drug interactions. Further investigation is needed to examine fully the issue of polypharmacy, as well as the need of education that results in empowerment of patients, families and communities.


Neonatal zingerone protects against the development of high-fructose diet-induced metabolic syndrome in adult Sprague-Dawley rats.
During the early postnatal period, dietary manipulations can alter the developmental trajectory of the growing offspring, causing beneficial or adverse health outcomes later in adult life. We investigated the potential preventive effects of neonatal zingerone intake on the development of fructose-induced metabolic derangements in rats.Four-day old male and female Sprague-Dawley rat pups (n = 79) were randomly grouped and administered: 10 ml/kg body weight (bwt) of distilled water (W), 10 ml/kg bwt 20% fructose solution (FS), 10 ml/kg bwt fructose solution + 40 mg/kg bwt of zingerone in distilled water (ZF) or 40 mg/kg bwt of zingerone in distilled water (ZW) pre-weaning. After weaning, W and ZW continued on unlimited tap water, while FS and ZF continued on unlimited fructose solution for 10 weeks. Body mass and food and fluid intake were evaluated, plasma was collected for metabolic assays and visceral fat was quantified.Food intake was decreased, fructose and overall caloric intake were increased due to fructose feeding in both sexes (P < 0.05). When compared with the controls, the high-fructose diet significantly raised the terminal body masses of females (P < 0.0001), concentrations of triglycerides, total cholesterol, LDL-c, TG:HDL-c ratio and visceral fat mass relative to bwt in both sexes (P < 0.05). Zingerone prevented (P < 0.05) the fructose-induced increase in body mass (females) and hypercholesterolemia (both sexes). Levels of HDL-c, glycaemic parameters and adiponectin were not affected by the interventions (P > 0.05). Sex-related differences were observed in food, fluid and caloric intake, terminal mass, cholesterol subtypes and visceral fat percentage (P < 0.05).Zingerone could be used strategically in the neonatal phase as a prophylatic management of high-fructose diet-induced metabolic syndrome.


[Methicillin-resistant Staphylococcus aureus (MRSA) in an intensive care unit: a one-year survey].
Methicillin-resistant Staphylococcus aureus (MRSA) is frequently isolated in nosocomial outbreaks. In our study, we analysed the occurrence of colonisation and infection in an Intensive Care Unit of our hospital during a 12-month period. We also evaluated the possibility of using automated ribotyping as a molecular method in order to type the isolates. Twice a week a nasal swab and a rectal swab were performed on all patients; from ventilator-assisted patients, a sputum culture was also taken. All the MRSA isolated were identified by using commonly phenotypic procedures and on all isolates susceptibility tests were performed. An automated ribotyping using EcoRI was also done. Out of 292 patients enrolled in the study, 205 were never colonised (group N); among the other 87 who were colonised by MRSA (29.8%), 40 patients (group A) were MRSA carriers at the time of admission, while 47 (group B) were colonised in the ICU. Twenty-seven patients (11 from group A, 15 from group B and 1 from group N) developed 31 infections due to MRSA. Patients from group A exhibited, as a rule, worse clinical conditions than those from the other two groups. For the former group, MRSA infection was frequently systemic (sepsis), while in group B pneumonia was the predominant infection. The prevalence of colonisations in our study was 30%, which is a value comparable to those presented by other authors in similar cases. MRSA colonisation is a necessary condition for subsequent infections in almost all cases, with an average lag of 7 days. Susceptibility tests were non-discriminating among the isolates: all the strains were susceptible to glycopeptides; nearly all of them were resistant to erythromycin, clindamycin, ciprofloxacin and gentamicin. Automated ribotyping allowed us to distinguish 12 different ribogroups, the most frequent of which was composed of 146 isolates. In our study, this molecular method was able to define a possible endemic clone that should be better investigated by using methods with a higher discriminatory power, such as RAPD or PFGE. The method that we employed is highly reliable, easy to perform and not time-consuming. In our opinion, it could be the method of choice in the first screening of high numbers of isolates.


Lymph folliculitis in ulcerative colitis.
Preferential involvement of the appendix has recently been confirmed in ulcerative colitis. Since the appendix is an aggregate of lymph follicles, this new observation implies a critical role of the lymph follicles, of both the large bowel and the appendix, in an etiopathogenesis of ulcerative colitis. This report presents two cases of ulcerative colitis in which lymph folliculitis and lymphoid hyperplasia were observed. Lymph folliculitis was observed endoscopically in a border between an established lesion and an uninvolved area. Case 1, proctitis type, relapsing remitting, mild in severity, showed lymph folliculitis in a proximal border of an established rectal lesion. Case 2, with left-sided colitis, mild in severity, had a skip appendiceal orifice inflammation. Lymph folliculitis was observed in the cecum surrounding established appendiceal orifice inflammation. In both cases, lymphoid hyperplasia was observed in an uninvolved area with clear vascular patterns. These two cases clearly demonstrate the involvement of gut lymph follicles in ulcerative colitis. Lymph folliculitis and/or lymphoid hyperplasia was proposed to be early lesions in ulcerative colitis. In addition, the need for microbiology targeting lymph follicles of the large bowel and appendix is stressed in order to disclose the casual microbial agents in ulcerative colitis.


Peruvian Vibrio cholerae O1 El Tor strains possess a distinct region in the Vibrio seventh pandemic island-II that differentiates them from the prototype seventh pandemic El Tor strains.
A collection of environmental and clinical strains of Vibrio cholerae O1 isolated from the beginning of the Latin American epidemic of cholera in 1991 to 2003 from multiple locations in Peru were characterized and compared with V. cholerae O1 El Tor strains of the seventh pandemic from the rest of the world (Asia, Africa, Australia and Europe) using a multilocus virulence gene profiling strategy and DNA sequencing. Peruvian strains differed from El Tor strains from the rest of the world by the failure of PCR to amplify genes VC0512, VC0513, VC0514 and VC0515 in the Vibrio seventh pandemic island-II (VSP-II) gene cluster. Sequencing of the VSP-II gene cluster and its flanking regions in one Peruvian strain (PERU-130) confirmed the PCR results, indicating that the Peruvian strain had low DNA homology (46.6 %) compared to the reference strain N16961 within the VSP-II region encompassing genes VC0511 to VC0515. Based on these differences in VSP-II, and based on the overall similarity between the pulsotypes of the Peruvian strains and the El Tor reference strain N16961, we concluded that the Peruvian, Eurasian and African strains belonged to the same clonal complex, and that the Peruvian strains represented variants that had independently evolved for a relatively short time. Since these ORFs in VSP-II of Peruvian strains are unique and conserved, they could form the basis for tracking the origin of the Peruvian strains and therefore of the Latin American pandemic.


Three-dimensional sensor-based face recognition.
We describe a face recognition system based on two different three-dimensional (3D) sensors. We use 3D sensors to overcome the pose-variation problems that cannot be effectively solved in two-dimensional images. We acquire input data based on a structured-light system and compare it with 3D faces that are obtained from a 3D laser scanner. Owing to differences in structure between the input data and the 3D faces, we can generate the range images of the probe and stored images. For estimating the head pose of input data, we propose a novel error-compensated singular-value decomposition that geometrically estimates the rotation angle. Face recognition rates obtained with principal component analysis on various range images of 35 people in different poses show promising results.


Fast-track programmes for hepatopancreatic resections: where do we stand?
Fast-track (FT) programmes represent a series of multimodal concepts that may reduce surgical stress and speed up convalescence after surgery. The aim of this systematic review was to evaluate FT programmes for patients undergoing hepatopancreatic surgery. PubMed, Embase and the Cochrane Library databases were searched for studies of FT vs. conventional recovery strategies for liver and pancreatic resections. For liver surgery, three cohort studies were included. Primary hospital stay was significantly reduced after FT care in two of the three studies. There were no significant differences in rates of readmission, morbidity and mortality. For pancreatic surgery, three cohort studies and one case-control study were included. Primary hospital stay was significantly shorter after FT care in three out of the four studies. One study reported a significantly decreased readmission rate (7% vs. 25%; P= 0.027), and another study showed lower morbidity (47.2% vs. 58.7%; P < 0.01) in favour of the FT group. There was no difference in mortality between the FT and control groups. FT rehabilitation for liver and pancreatic surgical patients is feasible. Future investigation should focus on optimizing individual elements of the FT programme within the context of liver and pancreatic surgery.


[Antihypoxic effectiveness of alimentary fasting].
The effect of 14-day alimentary fasting on duration of cats stay at the 12-km "altitude" (till a respiratory standstill up to 10 sec) was studied as well as on writing performance of volunteers breathing with nitrogen mixture. The fasting increased the stay duration by more than a factor of 2 under the conditions of acute hypoxia in these functional tests. With subsequent feeding, the acquired resistance to hypoxia disappeared. The main physiological mechanisms responsible for the high antihypoxia efficiency of the alimentary fasting seem to involve a decrease of oxygen consumption in the organism and its delayed release under acute hypoxia.


Localization of neuroblastoma in vivo with tumor-specific antibodies.
Studies of the mouse C-1300 neuroblastoma were undertaken in order to isolate tumor-specific antibodies and harness them for detection of tumors in vivo. Preliminary investigations demonstrated the strain-growth specificity of the neuroblastoma in A/Jax male mice and established the requirement for tumor viability for successful adoptive passage. Intradermally passaged tumor permitted extended survival of mice so that serum could be sampled at intervals for the presence of tumor-specific antibodies. By means of an indirect radioimmunoassay with glutaraldehyde-fixed identified in the serum of tumor-bearing hosts 6 days after inoculation, with a steady increase in antibody levels observed through Day 22. An eluate in which immunoglobulin G antibodies were identified by immunoelectrophoresis was obtained from purified tumor cells by acid buffer incubation. These antibodies were labeled with 125-I, absorbed with normal tissues, and injected into tumor-bearing mice. A selectively collimated single-probe isotope localization was positioned over the intradermal tumor, while the rest of the animal was shielded with lead. With this device, 125-neuroblastoma eluate was significantly taken up in the neuroblastoma but not in the mouse head or in a reticulum cell sarcoma control. Increasing uptake of MOPC 141 125-I-immunoglobulin G was not observed in either tumor. These studies suggest that the mouse neuroblastoma may provide a source of tumor-specific, antibodies and that, with sensitive monitoring devices, these antibodies may be utilized to localize occult neoplastic tissue in vivo.


Advances in targeted therapy for melanoma.
Metastatic melanoma remains an aggressive malignancy conferring a very poor prognosis, and standard chemotherapeutic and immunologic treatments have not demonstrated an overall survival benefit. No molecularly targeted therapy is approved for the treatment of advanced melanoma. Melanoma is a molecularly heterogeneous malignancy, and optimal treatment in a given patient is likely to depend on the presence of specific molecular abnormalities. Aberrations in components of signal transduction pathways have been identified that modulate melanoma proliferation and survival. Mutations that activate the mitogen activated protein kinase (MAPK) pathway via BRAF or NRAS are present in the majority of melanomas arising on skin intermittently exposed to the sun. Mutations that activate the KIT oncogene are more commonly present in melanomas arising from mucosal, acral, or chronic sun-damaged sites. Inhibitors of the MAPK pathway and of KIT are currently undergoing clinical investigation. In this article, we review advances in targeted strategies to treat different subgroups of patients with melanoma.


From Protease to Decarboxylase: THE MOLECULAR METAMORPHOSIS OF PHOSPHATIDYLSERINE DECARBOXYLASE.
Phosphatidylserine decarboxylase (PSDs) play a central role in the synthesis of phosphatidylethanolamine in numerous species of prokaryotes and eukaryotes. PSDs are unusual decarboxylase containing a pyruvoyl prosthetic group within the active site. The covalently attached pyruvoyl moiety is formed in a concerted reaction when the PSD proenzyme undergoes an endoproteolytic cleavage into a large β-subunit, and a smaller α-subunit, which harbors the prosthetic group at its N terminus. The mechanism of PSD proenzyme cleavage has long been unclear. Using a coupled in vitro transcription/translation system with the soluble Plasmodium knowlesi enzyme (PkPSD), we demonstrate that the post-translational processing is inhibited by the serine protease inhibitor, phenylmethylsulfonyl fluoride. Comparison of PSD sequences across multiple phyla reveals a uniquely conserved aspartic acid within an FFXRX6RX12PXD motif, two uniquely conserved histidine residues within a PXXYHXXHXP motif, and a uniquely conserved serine residue within a GS(S/T) motif, suggesting that PSDs belong to the D-H-S serine protease family. The function of the conserved D-H-S residues was probed using site-directed mutagenesis of PkPSD. The results from these mutagenesis experiments reveal that Asp-139, His-198, and Ser-308 are all essential for endoproteolytic processing of PkPSD, which occurs in cis. In addition, within the GS(S/T) motif found in all PSDs, the Gly-307 residue is also essential, but the Ser/Thr-309 is non-essential. These results define the mechanism whereby PSDs begin their biochemical existence as proteases that execute one autoendoproteolytic cleavage reaction to give rise to a mature PSD harboring a pyruvoyl prosthetic group.


The incidence of late-detected developmental dysplasia of the hip and its functional outcomes: a 17-year cohort study using selective ultrasound screening.
We aimed to establish the incidence of late-detected developmental dysplasia of the hip (DDH) with a selective ultrasound (US) examination over 17 years using the femoral head coverage (FHC) as a US measurement. The secondary aim was to establish the everyday function using patient-reported outcome measures (PROMs). The incidence of late-detected DDH was based on 60,844 children. Patients diagnosed for the first time after 3 months and before the age of 8 years were included. In the second part of the study, consent to participate was mandatory. PROMIS-25 Pediatric, PROMIS-25 Parent, and EQ-5D-5L were used according to the patient's age to assess everyday function. The incidence of late-detected DDH was 0.48/1,000. The median age at diagnosis was 8 months (range 4-41 months), with a tendency to require repeated treatment with open surgery if DDH was diagnosed later. Most children reported no or minor health problems with a mean of 18 years' follow-up. We found that selective US examination of the hips by measuring the FHC is a reliable method to examine newborns for DDH resulting in a low incidence of late-detected DDH amounting to 0.48/1,000 newborn children.


Solubility and dissolution properties of generic rifampicin raw materials.
Rifampicin shows polymorphism; therefore, it is necessary to select a suitable crystal form at an early stage of development to ensure optimum solubility and dissolution rates. This study was an investigation into the crystal properties of several rifampicin raw materials currently being used by manufacturers of generic rifampicin raw materials in South Africa. Powders were characterized by X-ray diffraction (XRD), infrared (IR) spectroscopy, and differential scanning calorimetry (DSC). The solubility in water and dissolution properties in water, buffer pH 7.4 and 0.1 M HCl, were also measured. The main difference between the powders was the amorphous content. XRD, IR, and DSC methods could detect the presence of amorphous rifampicin. In contrast to expectations, an increase in amorphous content significantly reduced the dissolution rate of the powders in water and buffer pH 7.4. This behavior was attributed to the electrostatic properties of the very fine particles in the amorphous powders. The results of this study showed that the physical properties of rifampicin raw materials varied not only among manufacturers, but also among batches from the same manufacturer.


Dose-response of superparamagnetic iron oxide labeling on mesenchymal stem cells chondrogenic differentiation: a multi-scale in vitro study.
The aim of this work was the development of successful cell therapy techniques for cartilage engineering. This will depend on the ability to monitor non-invasively transplanted cells, especially mesenchymal stem cells (MSCs) that are promising candidates to regenerate damaged tissues. MSCs were labeled with superparamagnetic iron oxide particles (SPIO). We examined the effects of long-term labeling, possible toxicological consequences and the possible influence of progressive concentrations of SPIO on chondrogenic differentiation capacity. No influence of various SPIO concentrations was noted on human bone marrow MSC viability or proliferation. We demonstrated long-term (4 weeks) in vitro retention of SPIO by human bone marrow MSCs seeded in collagenic sponges under TGF-β1 chondrogenic conditions, detectable by Magnetic Resonance Imaging (MRI) and histology. Chondrogenic differentiation was demonstrated by molecular and histological analysis of labeled and unlabeled cells. Chondrogenic gene expression (COL2A2, ACAN, SOX9, COL10, COMP) was significantly altered in a dose-dependent manner in labeled cells, as were GAG and type II collagen staining. As expected, SPIO induced a dramatic decrease of MRI T2 values of sponges at 7T and 3T, even at low concentrations. This study clearly demonstrates (1) long-term in vitro MSC traceability using SPIO and MRI and (2) a deleterious dose-dependence of SPIO on TGF-β1 driven chondrogenesis in collagen sponges. Low concentrations (12.5-25 µg Fe/mL) seem the best compromise to optimize both chondrogenesis and MRI labeling.


Challenges With the Use of Digital Sham: Systematic Review and Recommendations.
Digital therapeutics (DTx) are software-based products that prevent, manage, or treat a medical condition and are delivered through a smartphone app, web application, or wearable device. Clinical trials assessing DTx pose challenges, foremost among which is designing appropriate digital shams (or digital placebos), which should ideally mimic DTx (in terms of design, components, and duration of treatment) while omitting the active principle or component. The objective of our review was to understand how digital shams are being used in clinical research on DTx in neuroscience, which is the most common therapy area for DTx. We conducted a systematic literature review of DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) with a focus on controlled clinical trials involving digital shams. Studies were identified from trial registries (ClinicalTrials.gov, the European Union Clinical Trials Register, and Trial Trove) and through structured searches in MEDLINE and Embase (both via the Embase website) and were limited to articles in English published from 2010 onward. These were supplemented by keyword-based searches in PubMed, Google, and Google Scholar and bibliographic searches. Studies assessing DTx in neuroscience (including neurodevelopmental, neurodegenerative, and psychiatric disorders) were included. Details related to the publication, DTx, comparator, patient population, and outcomes were extracted and analyzed. Our search criteria identified 461 neuroscience studies involving 213 unique DTx. Most DTx were extended reality based (86/213, 40.4%) or mobile device based (56/213, 26.3%); 313 were comparative, of which 68 (21.7%) used shams. The most common therapeutic areas assessed in these studies were stroke (42/213, 19.7%), depression (32/213, 15%), and anxiety (24/213, 11.3%). The most common treatments were cognitive behavioral therapy or behavioral therapy (67/213, 32.4%), physical rehabilitation (60/213, 28.2%), and cognitive training (41/213, 19.2%). We identified the following important issues related to the use of digital shams in neuroscience: shams were not validated before use in studies, they varied widely in design (from being nearly identical to the DTx to using different software programs altogether), and the level of patient engagement or satisfaction with the sham and the impact of the sham on study outcomes were infrequently reported. Digital shams are critical for the clinical development of DTx in neuroscience. Given the importance of sham controls in evaluating DTx efficacy, we provide recommendations on the key information that should be reported in a well-designed DTx trial and propose an algorithm to allow the correct interpretation of DTx study results. Sham-controlled studies should be routinely used in DTx trials-in early-phase studies-to help identify DTx active components and-in late-phase studies-to confirm the efficacy of DTx. The use of shams early in development will ensure that the appropriate sham control is used in later confirmatory trials.


Genetic aspects concerning drip loss and water-holding capacity of porcine meat.
The amount and distribution of water inside the meat has a considerable influence on its properties. High losses of fluid in the form of drip may affect financial output, nutritional value, consumer appeal and/or technological properties of porcine meat. Therefore, a deeper insight into the traits water-holding capacity (WHC) and drip is favourable on behalf of producers, industry and consumers. Similar to most meat quality traits, WHC and drip loss (DRIP) are moderately heritable. The genetic correlation between these two traits is high. Correlation to other meat quality traits, such as pH value, cooking loss, reflectance, etc. is existent as predictable. Two major genes are known, RYR1 on chromosome 6 and RN on chromosome 15, to influence meat quality in general and WHC in particular. Furthermore, a number of candidate genes exist, e.g. phosphoglycerate mutase 2. Within the variety of quantitative trait loci (QTL) experiments, a number of QTL have been identified. QTL for DRIP and/or WHC have been found on chromosome 1, 2, 4, 5, 6, 11, 13, 14, 15, 18; for cooking loss on 7, 14 and18, and for pH value on nearly all chromosomes. Recently, a QTL study for meat quality and body composition traits in a Duroc-Pietrain (DUPI) resource population has been conducted at the University of Bonn, Germany. Four QTL for DRIP were identified on chromosomes 2, 3, 5 and 18. The QTL regions are in agreement with previously published QTL for this and other related traits. Further research and finemapping has begun and candidate genes located within the QTL regions are currently under investigation. Combination and comparison of results should lead to deeper insights in the genetic background of meat quality and DRIP.


Molecular Aggregation Structure and Surface Properties of Biomimetic Catechol-Bearing Poly[2-(perfluorooctyl)ethyl acrylate] and Its Application to Superamphiphobic Coatings.
The molecular aggregation structure and surface properties of a catechol-bearing fluoropolymer, P(FAC8-co-DOPAm), which was synthesized by conventional radical copolymerization of 2-(perfluorooctyl)ethyl acrylate (FAC8) and N-(3,4-dihydroxyphenethyl)acrylamide (DOPAm), and its application to the superamphiphobic surfaces are presented. The crystallinity of P(FAC8-co-DOPAm) was lower than that of poly[2-(perfluorooctyl)ethyl acrylate] (PFAC8). The perfluoroalkyl (Rf) groups were ordered on the surface with CF3 terminals exposed to air, and the Rf ordering was influenced by thermal history: the thermally annealed film exhibited higher Rf ordering than the unannealed one. The surface free energy was estimated to be γ = 7.32 mJ m-2 for both the unannealed and annealed films. Based on contact angle measurement, various interfacial structures of water and oils in accordance with the surface aggregation structure of Rf groups were proposed. Dewetting of the PFAC8 film at elevated temperature was suppressed by the introduction of catechol groups in the backbone. The degradation temperature of PFAC8 was improved significantly, and the evaporation of the low molar mass-polymer was inhibited by the introduction of catechol groups under both nitrogen and air atmospheres. The hydrophobicity of the copolymer films could be healed after the surface was damaged by vacuum ultraviolet (VUV) irradiation. This copolymer was used to create superamphiphobic fabrics and halloysite nanotube (HNT)-based organic/inorganic hybrid coatings successfully. Wetting behaviors of the superamphiphobic fabrics and coatings both follow the Cassie-Baxter wetting model.


Nonhierarchical Dispersal Promotes Stability and Resilience in a Tritrophic Metacommunity.
Community interactions (e.g., predation, competition) can be characterized by two factors: their strengths and how they are structured between and within species. Both factors play a role in determining community dynamics. In addition to trophic interactions, dispersal acts as an interaction between separate populations. As with other interactions, the structure of dispersal can affect the stability of a system. However, the primary structure that has been studied in consumer-resource models has been hierarchical dispersal, where between-patch dispersal rates increase with trophic level. Here we use analytical, numerical, and simulation approaches on a two-patch, three-species metacommunity model to investigate the relationship between structure and community stability and resilience. We show that metacommunity stability is greater in systems with both weak and strong dispersal rates. Our system is stabilized by the formation of patterns when predators disperse frequently and herbivores disperse rarely, and via asynchrony when both predators and herbivores disperse infrequently. Our results show how interaction strengths within both trophic and spatial networks shape metacommunity stability.


The content of the medical curriculum at McMaster University: graduates' evaluation of their preparation for postgraduate training.
This paper describes McMaster University medical graduates' perceptions of how well their medical curriculum prepared them for postgraduate training. The graduates view their overall preparation for postgraduate work as sound. These perceptions were compared with independent assessments by internship supervisors for one graduated class. The graduates suggest their preparation for postgraduate work differs somewhat from fellow interns. Graduates reported feeling very well prepared compared to fellow postgraduate trainees in independent learning, self-evaluation and problem solving skills. They also judge their preparation in data gathering skills, behavioural science knowledge, ability to deal with social and emotional problems of patients, medical record keeping skills, preventive, follow-up and in-patient care as very good compared to peers. They identified two content areas, pharmacology and the basic medical sciences, as requiring more attention in the curriculum. These findings are discussed and related to the approach to medical education at McMaster University.


Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants.
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.


The relationship between birth unit design and safe, satisfying birth: developing a hypothetical model.
Recent advances in cross-disciplinary studies linking architecture and neuroscience have revealed that much of the built environment for health-care delivery may actually impair rather than improve health outcomes by disrupting effective communication and increasing patient and staff stress. This is also true for maternity care provision, where it is suggested that the design of the environment can also impact on the experiences and outcomes for birthing women. The aim of this paper is to describe the development of a conceptual model based on literature and understandings of design, communication, stress and model of care. The model explores potential relationships among a set of key variables that need to be considered by researchers wishing to determine the characteristics of optimal birth environments in relation to birth outcomes for women and infants. The conceptual model hypothesises that safe satisfying birth is reliant on the level of stress experienced by a woman and the staff around her, stress influences the quality of communication with women and between staff, and this process is mediated by the design of the birth unit and model of care. The conceptual model is offered as a starting point for researchers who have an appreciation of the complexity of birth and the ability to bring together colleagues from a range of disciplines to explore the pre-requisites for safe and effective maternity care in new ways.


Sedentary Time and Physical Activity Across Occupational Classifications.
To examine differences in activity patterns across employment and occupational classifications. Cross-sectional. A 2005-2006 Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants with valid accelerometry data (n = 2068). Uniaxial accelerometry data (ActiGraph 7164), accumulated during waking hours, were summarized as mean activity counts (counts/min) and time spent (min/d) in long-bout sedentary (≥30 minutes, SED≥30), short-bout sedentary (<30 minutes, SED<30), light physical activity (LPA), short-bout moderate-to-vigorous physical activity (<10 minutes, MVPA<10), and long-bout MVPA (≥10 minutes, MVPA≥10) using Freedson cut-points. Employment status was self-reported as full time, part time, unemployed, keeping house, or raising children. Self-reported job duties were categorized into 23 major groups using the 2010 Standard Occupational Classification. Omnibus differences were analyzed using adjusted analysis of covariance and repeated after stratification by race (black/white) and sex (female/male). SED≥30, SED<30, LPA, and MVPA<10 differed significantly by employment and occupational categories (P ≤ .05), while MVPA≥10 did not (P ≥ .50). SED≥30, SED<30, and LPA differed by occupational classification in men, women, blacks, and whites (P < .05). Mean activity counts, MVPA<10, and MVPA≥10 were significantly different across occupational classifications in whites (P ≤ .05), but not in blacks (P > .05). Significant differences in mean activity counts and MVPA<10 across occupational classifications were found in males (P ≤ .001), but not in females (P > .05). Time within activity intensity categories differs across employment and occupational classifications and by race and sex.


Successful short-segment instrumentation and fusion for thoracolumbar spine fractures: a consecutive 41/2-year series.
A retrospective review of all the surgically managed spinal fractures at the University of Missouri Medical Center during the 41/2-year period from January 1989 to July 1993 was performed. Of the 51 surgically managed patients, 46 were instrumented by short-segment technique (attachment of one level above the fracture to one level below the fracture). The other 5 patients in this consecutive series had multiple trauma. These patients were included in the review because this was a consecutive series. However, they were grouped separately because they were instrumented by long-segment technique because of their multiple organ system injuries. The choice of the anterior or posterior approach for short-segment instrumentation was based on the Load-Sharing Classification published in a 1994 issue of Spine. The purpose of this review was to demonstrate that grading comminution by use of the Load-Sharing Classification for approach selection and the choice of patients with isolated fractures who are cooperative with spinal bracing for 4 months provide the keys to successful short-segment treatment of isolated spinal fractures. The current literature implies that the use of pedicle screws for short-segment instrumentation of spinal fracture is dangerous and inappropriate because of the high screw fracture rate. Charts, operative notes, preoperative and postoperative radiographs, computed tomography scans, and follow-up records of all patients were reviewed carefully from the time of surgery until final follow-up assessment. The Load-Sharing Classification had been used prospectively for all patients before their surgery to determine the approach for short-segment instrumentation. Denis' Pain Scale and Work Scales were obtained during follow-up evaluation for all patients. All patients were observed over 40 months except for 1 patient who died of unrelated causes after 35 months. The mean follow-up period was 66 months (51/2 years). No patient was lost to follow-up evaluation. Prospective application of the Load-Sharing Classification to the patients' injury and restriction of the short-segment approach to cooperative patients with isolated spinal fractures (excluding multisystem trauma patients) allowed 45 of 46 patients instrumented by the short-segment technique to proceed to successful healing in virtual anatomic alignment. The Load-Sharing Classification is a straightforward way to describe the amount of bony comminution in a spinal fracture. When applied to patients with isolated spine fractures who are cooperative with 3 to 4 months of spinal bracing, it can help the surgeon select short-segment pedicle-screw-based fixation using the posterior approach for less comminuted injuries and the anterior approach for those more comminuted. The choice of which fracture-dislocations should be strut grafted anteriorly and which need only posterior short-segment pedicle-screw-based instrumentation also can be made using the Load-Sharing Classification.


Cognitive functioning and survival among patients with chronic obstructive pulmonary disease.
An earlier study by the authors had demonstrated neuropsychological impairment among 66 clinically stable patients suffering from chronic obstructive pulmonary disease (COPD), and had found that the deficits were directly associated with the amount of oxygen available to body tissue. We were able to follow 62 of the patients for three years when retrospective analyses were performed to determine the relationship of the neuropsychological test scores with the patients' three-year survival status. Patients who survived had scored significantly (p less than 0.01) higher on the neuropsychological tests than those who had died. Individual analyses of variance indicated that the significant relationship between the neuropsychological tests and survival status was attributable primarily to the Benton Visual Motor Retention Test and the digit symbol subtest of the Wechsler Adult Intelligence Scale. The latter test had, in the earlier study, shown the strongest relationship with partial pressure of oxygen and with a pulmonary function test. These findings suggest that certain neuropsychological tests may reflect both the progress of COPD and three-year survival probability among the patients.


Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells.
Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small interfering RNA both in cultured cells and in vascular smooth muscle cells in vivo was associated with a significant reduction of the cGMP-dependent Ca(2+)-activated Cl(-) current, whereas the magnitude of the classic Ca(2+)-activated Cl(-) current was not affected. The majority of previous suggestions that bestrophins are a new Cl(-) channel family were based on heterologous expression in cell culture studies. Our present results demonstrate that at least 1 family member, bestrophin-3, is essential for a well-defined endogenous Ca(2+)-activated Cl(-) current in smooth muscles in the intact vascular wall.


Incidence of Football and Futsal Injuries Among Youth in Malaysian Games 2018.
Football and futsal were the main sports in the Malaysian Games. However, they were associated with a risk of injury. The purpose of the study was to analyse the incidence, circumstances, and characteristics of football and futsal injuries during the Malaysian Games of 2018. During the tournament, 14 teams participated in men's football, 12 teams in men's futsal and 11 teams in women's futsal. The biannual event involved athletes aged under 21 years. A medical report form used by FIFA Medical Assessment and Research Centre (F-Marc), was provided to the physiotherapists and team doctors of all the teams to report all injuries after each match. The response rate was 84.62% in football and 59.76% in futsal. A total of 48 injuries were reported from 26 football matches, equivalent to 64.64 injuries per 1000 match hours (95%CI 46.35 to 82.93). In futsal, a total of 48 injuries from 41 matches were reported, equivalent to 292.42 injuries per 1000 match hours (95% CI 209.7 to 375.14). The rate of injury in women futsal players was higher compared to men: 358.21 versus 247.04 injuries per 1000 match hours (p=0.224). Futsal recorded higher injuries per 1000 match hours than football (p<0.001). The rate of severe injury in futsal and football recorded in the study as compared to previous studies gave rise to serious concerns. Hence, there was an urgent need to pay more attention to injury prevention strategies.


Surgical Management and Outcomes of Rectal Cancer with Synchronous Prostate Cancer: A Multicenter Experience from the GRECCAR Group.
Synchronous prostate cancer (PC) and rectal cancer (RC) is a rare clinical situation. While combining curative-intent management for both cancers can be challenging, available data for guiding the multidisciplinary strategy are lacking. Consecutive patients undergoing rectal resection for a mid-low RC with synchronous PC treated at 9 tertiary-care centers between 2008 and 2018 were included. Management strategy and data on postoperative and long-term outcomes were retrospectively analyzed. Overall, 25 patients underwent curative-intent RC resection combined with PC management. Nine (36%), 10 (40%) and 6 (24%) patients had low-, intermediate-, and high-risk PC, respectively. Management mostly consisted of chemoradiotherapy combined in 18 patients (72%) with either TME in 12 patients or pelvic exenteration for resection of both cancers in 6 patients. Most patients underwent RC resection using a laparoscopic approach (n = 16, 64%). Anastomosis was performed in 18 patients (72%) of whom 13 received diverting ileostomy. The complete R0 resection rate was 96% (n = 24). The overall morbidity rate was 64% (n = 16) and 5 patients (20%) experienced severe surgical morbidity of which two died within 90 days of surgery after pelvic exenteration. Among patients with anastomosis, 2 patients (11%) experienced anastomotic leak requiring surgical management. After a median follow-up of 31.2 months, 3-year OS and RFS were 80.2% (CI 95% 58.8-92.2) and 68.6% (CI 95% 42.3-84.8), respectively. This series is the largest to report that simultaneous curative-intent management of synchronous PC and RC is feasible and safe. Pelvic exenteration might be a better option when RC complete resection seems not achievable through TME.


Antioxidant enzymatic activities in Alzheimer's disease: the relationship to acetylcholinesterase inhibitors.
The mode of action of acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD) is mainly by potentiating neuronal transmission. Animal studies have also consistently described a role for AChEIs in enhancement of antioxidants and attenuation of oxidative stress. The influence of AChEIs on blood antioxidants in AD patients has not been established before. Furthermore, AChEI treatment, or lack of it, may have contributed to the inconsistent antioxidant data reported by other studies so far. Here we sought to investigate the potential modulation effect of AChEIs on blood antioxidants in AD patients. Catalase (CAT) and glutathione reductase (GR) activities were analyzed in 25 drug naïve patients (Group A), 43 patients receiving AChEIs (Group B) and 34 cognitively unimpaired controls (Group C). A statistically significant difference for CAT and GR was observed between the two AD groups (A and B) when compared to the control group C (KW-H = 36.530, p < 0.001; post hoc tests p < 0.001 and KW-H = 37.814, p < 0.001; post hoc tests p < 0.001, respectively). In contrast, CAT and GR activities did not differ significantly between the two AD groups, and were not influenced by AChEI treatment. Hence, these results do not replicate the extensively reported data from animal studies and question whether AChEI efficacy in AD is mediated by processes beyond neuron to neuron enhancement of transmission. Studies assessing a wider range of oxidative/inflammatory markers taking into account type, dosage, and treatment duration of the various acetylcholinesterase inhibitors are now needed.


Use of embedded strain gages for the in-vitro study of proximal tibial cancellous bone deformation during knee flexion-extension movement: development, reproducibility and preliminary results of feasibility after frontal low femoral osteotomy.
This paper reports the development of an in-vitro technique allowing quantification of relative (not absolute) deformations measured at the level of the cancellous bone of the tibial proximal epiphysis (CB(TPE)) during knee flexion-extension. This method has been developed to allow a future study of the effects of low femoral osteotomies consequence on the CB(TPE). Six strain gages were encapsulated in an epoxy resin solution to form, after resin polymerisation, six measurement elements (ME). The latter were inserted into the CB(TPE) of six unembalmed specimens, just below the tibial plateau. Knee motion data were collected by three-dimensional (3D) electrogoniometry during several cycles of knee flexion-extension. Intra- and inter-observer reproducibility was estimated on one specimen for all MEs. Intra-specimen repeatability was calculated to determine specimen's variability and the error of measurement. A varum and valgum chirurgical procedure was realised on another specimen to observed CB(TPE) deformation after these kind of procedure. Average intra-observer variation of the deformation ranged from 8% to 9% (mean coefficient of variation, MCV) respectively for extension and flexion movement. The coefficient of multiple correlations (CMC) ranged from 0.93 to 0.96 for flexion and extension. No phase shift of maximum strain peaks was observed. Inter-observer MCV averaged 23% and 28% for flexion and extension. The CMC were 0.82 and 0.87 respectively for extension and flexion. For the intra-specimen repeatability, the average of mean RMS difference and the mean ICC were calculated only for flexion movement. The mean RMS variability ranged from 7 to 10% and the mean ICC was 0.98 (0.95-0.99). A Pearson's correlation coefficient was calculated showing that RMS was independent of signal intensity. For the chirurgical procedure, valgum and varum deviation seems be in agree with the frontal misalignment theory. Results show that the methodology is reproducible within a range of 10%. This method has been developed to allow analysis the indirect reflect of deformation variations in CB(TPE) before and after distal femoral osteotomies. The first results of the valgum and varum deformation show that our methodology allows this kind of measurement and are encourageant for latter studies. It will therefore allow quantification and enhance the understanding of the effects of this kind of surgery on the CB(TPE) loading.


Practitioner review: How can epidemiology help us plan and deliver effective child and adolescent mental health services?
This review focuses on ways in which epidemiological research can inform mental health service development and clinical practice. Data from epidemiological studies can provide cross-sectional and secular estimates of the prevalence of psychopathology to support rational service development. Epidemiological surveys have difficulties in finding large enough samples of children with rare disorders, although these disorders are often severely debilitating and require extensive service input. Systematic surveillance provides a rigorous method for studying rare disorders and events. Only a minority of children with impairing psychopathology reach mental health services, although a larger proportion have mental health related contacts with other services. The gap in provision is such that an expansion of mental health services is unlikely to reach all children who could benefit, suggesting that mental health professionals need to develop innovative strategies to increase the number of children seen and the effectiveness of interventions that they receive. Training and supervision of non-mental-health professionals working with children in the identification and management of mental health problems is also extremely important. Most studies suggest that the children with the severest problems are getting to specialist mental health services, and service contact is more likely if important adults can perceive the child's difficulty or find it to be burdensome. The latter suggests that education of key adults would improve detection if services had the capacity to cope. Studies consistently suggest that the region in which the child lives affects the likelihood of service contact, but studies of other characteristics predicting service contact are so contradictory that studies should only be (cautiously) applied to similar populations to assess which types of children may currently be falling through gaps in service provision. Academics are beginning to explore the use of structured measures developed for epidemiological studies in clinical assessment and outcome monitoring.


1H Magnetic resonance spectroscopy study of dorsolateral prefrontal cortex in unipolar mood disorder patients.
Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1H MRS examination localized to an 8-cm3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future 1H MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder.


Polarization-dependent optical 2D Fourier transform spectroscopy of semiconductors.
Optical 2D Fourier transform spectroscopy (2DFTS) provides insight into the many-body interactions in direct gap semiconductors by separating the contributions to the coherent nonlinear optical response. We demonstrate these features of optical 2DFTS by studying the heavy-hole and light-hole excitonic resonances in a gallium arsenide quantum well at low temperature. Varying the polarization of the incident beams exploits selection rules to achieve further separation. Calculations using a full many-body theory agree well with experimental results and unambiguously demonstrate the dominance of many-body physics.


Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes.
We tested the hypothesis that alterations in the intestinal microbiota are linked with the progression of type 1 diabetes (T1D). Herein, we present results from a study performed in subjects with islet autoimmunity living in the U.S. High-throughput sequencing of bacterial 16S rRNA genes and adjustment for sex, age, autoantibody presence, and HLA indicated that the gut microbiomes of seropositive subjects differed from those of autoantibody-free first-degree relatives (FDRs) in the abundance of four taxa. Furthermore, subjects with autoantibodies, seronegative FDRs, and new-onset patients had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy control subjects with no family history of autoimmunity. Further analysis revealed trends toward increased and reduced abundances of the Bacteroidetes genera Bacteroides and Prevotella, respectively, in seropositive subjects with multiple versus one autoantibody. Canonical discriminant analysis suggested that the gut microbiomes of autoantibody-positive individuals and seronegative FDRs clustered together but separate from those of new-onset patients and unrelated healthy control subjects. Finally, no differences in biodiversity were evident in seropositive versus seronegative FDRs. These observations suggest that altered intestinal microbiota may be associated with disease susceptibility.


Search for color singlet technicolor particles in p&pmacr; collisions at radicals = 1.8 TeV
We search for color singlet technirho and technipion production in p&pmacr; collisions at sqrt[s] = 1.8 TeV recorded with the Collider Detector at Fermilab. These exotic technimesons are present in a model of walking technicolor. The signatures studied are lepton plus two jets plus E(T) and multijet final states. No excess of events is seen in either final state. We set an upper limit on the technirho production cross section and exclude a region in the technipion mass versus technirho mass plane.


Review: Weak radiofrequency radiation exposure from mobile phone radiation on plants.
The aim of this article was to explore the hypothesis that non-thermal, weak, radiofrequency electromagnetic fields (RF-EMF) have an effect on living plants. In this study, we performed an analysis of the data extracted from the 45 peer-reviewed scientific publications (1996-2016) describing 169 experimental observations to detect the physiological and morphological changes in plants due to the non-thermal RF-EMF effects from mobile phone radiation. Twenty-nine different species of plants were considered in this work. Our analysis demonstrates that the data from a substantial amount of the studies on RF-EMFs from mobile phones show physiological and/or morphological effects (89.9%, p < 0.001). Additionally, our analysis of the results from these reported studies demonstrates that the maize, roselle, pea, fenugreek, duckweeds, tomato, onions and mungbean plants seem to be very sensitive to RF-EMFs. Our findings also suggest that plants seem to be more responsive to certain frequencies, especially the frequencies between (i) 800 and 1500 MHz (p < 0.0001), (ii) 1500 and 2400 MHz (p < 0.0001) and (iii) 3500 and 8000 MHz (p = 0.0161). The available literature on the effect of RF-EMFs on plants to date observed the significant trend of radiofrequency radiation influence on plants. Hence, this study provides new evidence supporting our hypothesis. Nonetheless, this endorses the need for more experiments to observe the effects of RF-EMFs, especially for the longer exposure durations, using the whole organisms. The above observation agrees with our earlier study, in that it supported that it is not a well-grounded method to characterize biological effects without considering the exposure duration. Nevertheless, none of these findings can be directly associated with human; however, on the other hand, this cannot be excluded, as it can impact the human welfare and health, either directly or indirectly, due to their complexity and varied effects (calcium metabolism, stress proteins, etc.). This study should be useful as a reference for researchers conducting epidemiological studies and the long-term experiments, using whole organisms, to observe the effects of RF-EMFs.


New therapeutic strategies in systemic lupus erythematosus management.
The current treatment approach for systemic lupus erythematosus (SLE), as outlined in the recommendations by international medical associations including EULAR and the ACR, is mostly eminence-based rather than evidence-based. However, knowledge on SLE is growing quickly, and such new advances need to be translated into clinical practice. Questions remain regarding the choice and timing of drug administration and tapering until withdrawal, which both can affect the balance between the control of disease activity and damage to organs triggered by long-standing and/or disproportionate immunosuppression. Currently, the treating physicians of patients with SLE are required to weigh the present with the future situation of their patients in an optimized balance between therapeutic harm and benefit. In this Review, the available therapeutic strategies and main challenges in the approach to SLE treatment are discussed. Remission and low disease activity are desirable therapeutic goals. Although the drug armamentarium for SLE has not expanded much in the past few decades, there are nonetheless opportunities to make better choices and explore combination therapies; such opportunities offer the potential of a personalized medicine strategy.