Nosocomial SARS-CoV-2 transmission in postoperative infection and mortality: analysis of 14 798 procedures.

This study used a national administrative database to estimate perioperative SARS-CoV-2 infection risk, and associated mortality, relative to nosocomial transmission rates. The impact of nosocomial transmission was greatest after major emergency surgery, whereas laparoscopic surgery may be protective owing to reduced duration of hospital stay. Procedure-specific risk estimates are provided to facilitate surgical decision-making and informed consent. Estimated risks.

Bilateral Scapulothoracic Fusions Fixed with High-Strength Suture Tapes for Facioscapulohumeral Dystrophy: A Case Report.

CASE: A 32-year-old male right-hand dominant school-bus driver with facioscapulohumeral dystrophy (FSHD) was referred to an upper limb specialist for consideration for scapulothoracic fusion (STF) because of limited upper limb function and cosmetic issues. Staged bilateral STFs were performed with seven high-strength suture tapes tensioned to secure a standard tubular plate in situ. CONCLUSION: STF may be a desirable treatment option for patients with FSHD. The use of high-strength suture tapes in cases of STF allows for secure fixation of the scapulothoracic joint. This potentially confers a reduction in operative time while ensuring adequate tensioned fixation and minimizing the risk of iatrogenic pneumothorax.

Enhanced expression of transferrin receptor 1 contributes to oncogenic signalling by sphingosine kinase 1.

Sphingosine kinase 1 (SK1) is a lipid kinase that catalyses the formation of sphingosine-1-phosphate (S1P). Considerable evidence has implicated elevated cellular SK1 in tumour development, progression and disease severity. In particular, SK1 has been shown to enhance cell survival and proliferation and induce neoplastic transformation. Although S1P has been found to have both cell-surface G-protein-coupled receptors and intracellular targets, the specific downstream pathways mediating oncogenic signalling by SK1 remain poorly defined. Here, using a gene expression array approach, we have demonstrated a novel mechanism whereby SK1 regulates cell survival, proliferation and neoplastic transformation through enhancing expression of transferrin receptor 1 (TFR1). We showed that elevated levels of SK1 enhanced total as well as cell-surface TFR1 expression, resulting in increased transferrin uptake into cells. Notably, we also found that SK1 activation and localization to the plasma membrane, which are critical for its oncogenic effects, are necessary for regulation of TFR1 expression specifically through engagement of the S1P G-protein coupled receptor, S1P2. Furthermore, we showed that blocking TFR1 function with a neutralizing antibody inhibits SK1-induced cell proliferation, survival and neoplastic transformation of NIH3T3 fibroblasts. Similar effects were observed following antagonism of S1P2. Together these findings suggest that TFR1 has an important role in SK1-mediated oncogenesis.

Analysis of ten Brucella genomes reveals evidence for horizontal gene transfer despite a preferred intracellular lifestyle.

The facultative intracellular bacterial pathogen Brucella infects a wide range of warm-blooded land and marine vertebrates and causes brucellosis. Currently, there are nine recognized Brucella species based on host preferences and phenotypic differences. The availability of 10 different genomes consisting of two chromosomes and representing six of the species allowed for a detailed comparison among themselves and relatives in the order Rhizobiales. Phylogenomic analysis of ortholog families shows limited divergence but distinct radiations, producing four clades as follows: Brucella abortus-Brucella melitensis, Brucella suis-Brucella canis, Brucella ovis, and Brucella ceti. In addition, Brucella phylogeny does not appear to reflect the phylogeny of Brucella species' preferred hosts. About 4.6% of protein-coding genes seem to be pseudogenes, which is a relatively large fraction. Only B. suis 1330 appears to have an intact beta-ketoadipate pathway, responsible for utilization of plant-derived compounds. In contrast, this pathway in the other species is highly pseudogenized and consistent with the "domino theory" of gene death. There are distinct shared anomalous regions (SARs) found in both chromosomes as the result of horizontal gene transfer unique to Brucella and not shared with its closest relative Ochrobactrum, a soil bacterium, suggesting their acquisition occurred in spite of a predominantly intracellular lifestyle. In particular, SAR 2-5 appears to have been acquired by Brucella after it became intracellular. The SARs contain many genes, including those involved in O-polysaccharide synthesis and type IV secretion, which if mutated or absent significantly affect the ability of Brucella to survive intracellularly in the infected host.

Club-based and non-club-based physiotherapists' views on the psychological content of their practice when treating sports injuries.

The aim of the present study was to explore whether there were any differences in the psychological content of practice between club-contracted and non-club-contracted physiotherapists when treating sports injuries. Eighty-seven certified physiotherapists (non-club contracted N = 42, club contracted N = 45) from the United Kingdom completed a modified version of the Athletic Training and Sport Psychology Questionnaire (ATSPQ). Results revealed significant between-group differences in psychological skills use and the importance of psychological skills knowledge. Non-club-contracted physiotherapists reported a higher use of improving social support and higher-order psychological skills (e.g., reducing depression, stress, and anxiety) and rated knowledge of these psychological skills to be more important whilst club-contracted physiotherapists reported a higher use of short-term goal settings. These findings suggest that non-club-based physiotherapists may approach the treatment of injured athletes in a different way to their club-based counterparts. Results suggest athletes treated outside of the club system may experience a different recovery process.

An emerging cyberinfrastructure for biodefense pathogen and pathogen-host data.

The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host-pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

Influences of the perception of self-motion on postural parameters.

We examined how spatial and temporal characteristics of the perception of self-motion, generated by constant velocity visual motion, was reflected in orientation of the head and whole body of young adults standing in a CAVE, a virtual environment that presents wide field of view stereo images with context and texture. Center of pressure responses from a force plate and perception of self-motion through orientation of a hand-held wand were recorded. The influence of the perception of self-motion on postural kinematics differed depending upon the plane and complexity of visual motion. Postural behaviors generated through the perception of self-motion appeared to contain a confluence of the cortically integrated visual and vestibular signals and of other somatosensory inputs. This would suggest that spatial representation during motion in the environment is modified by both ascending and descending controls. We infer from these data that motion of the visual surround can be used as a therapeutic tool to influence posture and spatial orientation, particularly in more visually sensitive individuals following central nervous system (CNS) impairment.

Setting standards for training and competence: the UK alcohol treatment trial.

AIMS: To examine factors that influence the recruitment and training of therapists and their achievement of competence to practise two psychological therapies for alcohol dependence, and the resources required to deliver this. METHODS: The protocol for the UK Alcohol Treatment Trial required trial therapists to be competent in one of the two trial treatments: Social Behaviour and Network Therapy (SBNT) or Motivational Enhancement Therapy (MET). Therapists were randomised to practise one or other type of therapy. To ensure standardisation and consistent delivery of treatment in the trial, the trial training centre trained and supervised all therapists. RESULTS: Of 76 therapists recruited and randomised, 72 commenced training and 52 achieved competence to practise in the trial. Length of prior experience did not predict completion of training. However, therapists with a university higher qualification, and medical practitioners compared to other professionals, were more likely to complete. The average number of clients needed to be treated before the trainee achieved competence was greater for MET than SBNT, and there was a longer duration of training for MET. CONCLUSIONS: Training therapists of differing professional backgrounds, randomised to provide a specific therapy type, is feasible. Supervision after initial training is important, and adds to the training costs.

Robotics and virtual reality: the development of a life-sized 3-D system for the rehabilitation of motor function.

We have been developing and combining state-of-art devices that allow humans to visualize and feel synthetic objects superimposed on the real world. This effort stems from the need of platform for extending experiments on motor control and learning to realistic human motor tasks and environments, not currently represented in the practice of research. This paper's goal is to outline our motivations, progress, and objectives. Because the system is a general tool, we also hope to motivate researchers in related fields to join in. The platform under development, an augmented reality system combined with a haptic-interface robot, will be a new tool for contributing to the scientific knowledge base in the area of human movement control and rehabilitation robotics. Because this is a prototype, the system will also guide new methods by probing the levels of quality necessary for future design cycles and related technology. Inevitably, it should also lead the way to commercialization of such systems.

Postural research and rehabilitation in an immersive virtual environment.

We have united an immersive dynamic virtual environment with motion of a posture platform to record biomechanical and physiological responses to combined visual, vestibular, and proprioceptive inputs. A 6 degree-of-freedom force plate provides measurements of moments exerted on the base of support. Kinematic data from the head, trunk, and lower limb is collected using 3-D video motion analysis. The virtual image is projected via a stereo-capable projector mounted behind the back-projection screen. This system allows us to explore complex behaviors necessary for rehabilitation. We are currently examining how a dynamic visual field affects posture and spatial orientation, and whether visual task demands interfere with our ability to react to a loss of balance in healthy adults and in adults with labyrinthine deficit. Our data suggest that when there is a confluence of meaningful inputs, none of the inputs are suppressed in healthy adults; the postural response is modulated by all existing sensory signals in a non-additive fashion. Labyrinthine deficient adults suppress visual inputs. Individual perception of the sensory structure also appears to be a significant component of the postural response in these protocols. We will discuss the implications of these results for the design of clinical interventions for balance disorders.

The neuroblastoma amplified gene, NAG: genomic structure and characterisation of the 7.3 kb transcript predominantly expressed in neuroblastoma.

Amplification of the MYCN oncogene in neuroblastoma is associated with poor prognosis. The amplified unit of DNA can be up to 1 Mb in size and so could contain additional genes which affect tumour phenotype. The neuroblastoma amplified gene (NAG) gene was initially located 400 kb telomeric to MYCN at 2p24 and reported to be co-amplified in 5/8 (63%) cell lines and 9/13 (70%) tumours. The sequence of a 4.5 kb transcript was proposed from the analysis of overlapping cDNA clones. However, our Northern blot hybridisation experiments indicate that the main RNA species expressed in neuroblastoma is 7-8 kb in size. We describe for the first time the cloning and sequencing of the 7.3 kb transcript of the NAG gene together with its precise genomic location and full exon structure. The 5' end of the gene is located 30 kb telomeric to DDX1, with the two genes lying in opposite orientations. The 52 exons of the 7.3 kb transcript cover 420 kb of genomic DNA. In vitro translation studies confirmed the protein coding potential of the transcript. Co-amplification of the entire NAG gene with MYCN was found in 1/6 (17%) neuroblastoma cell lines and 10/50 (20%) primary tumours. Previous studies had measured co-amplification of only the 5' end of the gene, nearest to MYCN. In this study, co-amplification of the NAG gene was found to be significantly associated with low disease stage in MYCN-amplified tumours (P=0.0063).

Control variables in mechanical muscle models: a mini-review and a new model.

A new mechanical model of isolated muscle is proposed in which spring with variable slack length is the force-generating element. Based on the review of experimental studies in isolated muscle, it is suggested that spring slack length Xo is the control variable in the model and is a function of motor unit firing rate. In the presence of sensory feedback, the Sliding Spring model is equivalent to the Rack and Pinion model. However, sensory feedback is essential in the Rack and Pinion model but complementary in the Sliding Spring model. How the new control variable in the model of isolated muscle affects the interpretation of control processes up the motor system hierarchy is discussed in light of certain controversies associated with the Lambda and Alpha models of control of movement. It is argued that the Sliding Spring model of isolated muscle can be used as a basis for developing models of control of movement.

The influence of an immersive virtual environment on the segmental organization of postural stabilizing responses.

We examined the effect of a 3-dimensional stereoscopic scene on segmental stabilization. Eight subjects participated in static sway and locomotion experiments with a visual scene that moved sinusoidally or at constant velocity about the pitch or roll axes. Segmental displacements, Fast Fourier Transforms, and Root Mean Square values were calculated. In both pitch and roll, subjects exhibited greater magnitudes of motion in head and trunk than ankle. Smaller amplitudes and frequent phase reversals suggested control of the ankle by segmental proprioceptive inputs and ground reaction forces rather than by the visual-vestibular signals. Postural controllers may set limits of motion at each body segment rather than be governed solely by a perception of the visual vertical. Two locomotor strategies were also exhibited, implying that some subjects could override the effect of the roll axis optic flow field. Our results demonstrate task dependent differences that argue against using static postural responses to moving visual fields when assessing more dynamic tasks.

Application of neural networks to the analysis of pyrolysis mass spectra.

Pyrolysis mass spectrometry is a data rich analysis technique now becoming widely applied in microbiology. Data analysis is a key step in the exploitation of the technique and the application of neural network analysis to pyrolysis mass spectrometric data offers new opportunities for classification, identification and inter-strain comparison of microorganisms in biotechnology and clinical microbiology. The use of a supervised neural network for the identification of members of a streptomycete species-group is described.

Analysis of candidate gene co-amplification with MYCN in neuroblastoma.

Previous studies have revealed that the MYCN gene spans approximately 7kb, while the amplicon has been estimated to be 100 kb to 1 Mb long [1-3]. This implies that several other genes may be present on the MYCN amplicon. Such co-amplified genes could contribute to the malignant phenotype and might provide an explanation for why not all patients with MYCN amplification have a poor outcome. We investigated 7 neuroblastoma cell lines and 167 primary tumours for the co-amplification of candidate genes known to be present near the MYCN locus: ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box protein gene, DDX1. We also investigated further the pG21 expressed sequence previously reported to be co-amplified with MYCN. No co-amplification with the first 3 genes was found in any of the cell lines or tumour samples. DDX1 was found to be amplified along with MYCN in 4/6 (67%) cell lines and 18/38 (47%) of the MYCN amplified tumours. No amplification of DDX1, ODC1, RRM2 or syndecan-1 was found in the absence of MYCN amplification. DDX1 co-amplification was observed to occur mainly in stage 4 or 4S patients. With the exclusion of those with 4S disease, patients with DDX1 co-amplification had a significantly shorter mean (+/- SE) disease-free interval (4.1 +/- 1.4, n = 8 months) compared with patients with MYCN amplification alone (19.6 +/- 4.5, n = 17) (P = 0.04, Welch's unpaired t-test). The pG21 sequence was identical to part of the DDX1 gene. These observations indicate that there is at least 1 other gene co-amplified with MYCN in a proportion of cases and that those patients with DDX1 co-amplification tend to relapse more quickly. It also implies that the MYCN amplicon is of varied size and/or position relative to the MYCN gene.

Monitoring for occupational exposure to 4,4'-methylenebis(2-chloroaniline) by gas chromatographic-mass spectrometric analysis of haemoglobin adducts, blood, plasma and urine.

The feasibility of using plasma, blood and haemoglobin adducts for monitoring occupational exposure to the suspected human carcinogen 4,4'-methylenebis(2-chloroaniline) (MOCA) was investigated. A method utilising capillary gas chromatography-negative-ion chemical-ionisation mass spectrometry (GC-MS) for the determination of pentafluoropropionyl (PFP) derivatives of MOCA, released by alkaline hydrolysis from protein adducts and conjugates, was both sensitive and selective. When selected ion monitoring was used, sub-femtomole amounts of PFP-MOCA could be measured. The detection limit for haemoglobin adducts of MOCA was below 10 fmol/g Hb, well below the levels found for occupationally exposed individuals. Capillary GC with electron-capture detection also had the required sensitivity for the determination of MOCA in blood samples, however, the presence of interfering compounds in some samples limited its use. The levels of MOCA in the blood and urine of five individuals who were exposed to MOCA during the manufacture of polyurethane elastomers were determined by the GC-MS method. The MOCA concentrations for the various blood fractions and urine were within the following ranges: haemoglobin adducts, 0.73-43.3 pmol MOCA/g Hb; plasma alkaline hydrolysate, 0.05-22.0 nmol/l; whole blood, 0.13-17.4 nmol/l; urine, 4.5-2390 nmol/l. Because the products of MOCA in the blood reflect metabolic activation of MOCA and integrate exposure over a period of weeks, the use of blood samples for monitoring exposure to MOCA offers advantages over the currently used urinary MOCA measurements.

Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group.

Although N-myc amplification is strongly associated with a poor prognosis, not all patients with neuroblastomas having N-myc amplification fare badly. To investigate whether genes other than N-myc are responsible for contributing to the prognosis, we examined seven cell lines and 87 primary tumours for co-amplification of candidate genes known to be present near the normal N-myc locus: ornithine decarboxylase (ODC), ribonucleotide reductase (RRM2), syndecan-1 and a DEAD box protein gene, DDX1. Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene. No co-amplification with the first three genes was found in any of the cell lines or tumour samples. DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours. Co-amplification of DDX1 and N-myc was found more frequently in stage 4 or 4S tumours than lower stage (1-3) tumours. With the exclusion of a single 4S case, there was a highly significant reduction in the mean disease-free interval from 24.4 +/- 4.7 (SE, n = 10) months for cases with co-amplification of N-myc and DDX1 compared with 9.2 +/- 1.8 (SE, n = 5) months for those cases showing amplification of N-myc alone (P = 0.0056, Welch's unpaired t-test). No amplification of DDX1, ODC, RRM2, or syndecan-1 was found in the absence of N-myc amplification. These observation indicate that the N-myc amplicon is of varied size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene frequently co-amplified with N-myc. Further studies are required to confirm the biological and prognostic significance of DDX1 co-amplification and to elucidate the role that DDX1 plays in tumour genesis and progression.

Normal vestibular function in chicks after partial exposure to microgravity during development.

Sixty-four fertilized chicken eggs, half at developmental Day 2 and half at Day 9, were exposed to micro-gravity for 5 days aboard the shuttle. Postflight examination showed that none of the Day 2 flight embryos had survived, whereas the Day 9 flight group and both groups of synchronous ground control embryos appeared viable. One-half of the Day 9 flight and ground control embryos were dissected and the temporal bones preserved in acetone for morphological examination. The other half was allowed to hatch to examine vestibularly related behavioral changes. Morphology of the lagenar otoconia was evaluated by scanning electron microscopy. Behavioral changes were accessed by a battery of reflex tests and recordings of spontaneous and vestibularly driven head movements. The results from both the morphological and behavioral studies showed no consistent difference between the flight and the control animals. Several hypotheses may account for this negative result. Because all the Day 2 embryos failed to survive, the remaining Day 9 chicks may have passed the critical developmental period of the chick's vestibular system. Also, the reexposure of the developing chick embryo to earth's 1-g environment may have masked any adverse behavioral effects that exposure to Microgravity may have caused.