Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study.
Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.


Association between HLA-A1 and -A2 types and Epstein-Barr virus status of post-transplant lymphoproliferative disorder.
The susceptibility to Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder (PTLD) may be affected by the human leukocyte antigen (HLA) type. We investigated HLA-A and HLA-B allele frequencies, focusing on HLA-A1 and -A2, in a population-based case series of EBV + (n = 60) and EBV- (n = 44) PTLD after solid organ transplantation. The proportion of EBV + PTLD was highest in HLA-A1 homozygotes (100%), lower in carriers of HLA-A1/AX (79%), HLA-A1/A2 (55%), HLA-A2/AX (54%), and lowest in HLA-A2 homozygotes (37%). HLA-A1 type was overrepresented (22% versus 7%, p = 0.05) and HLA-A2 type underrepresented (57% versus 80%, p = 0.01) in patients with EBV + compared with EBV - PTLD. EBV + PTLD in HLA-A1 carriers developed almost exclusively in already EBV-seropositive individuals. EBV status of PTLD was not related to any other HLA-A or HLA-B type. Our findings suggest that HLA-A1 carriers may have an increased risk of EBV + PTLD due to a decreased ability to control the latent EBV infection.


Studying environmental and economic considerations on tourism activities in achieving sustainable development goals: implications for sustainability.
The study aims to extend the understanding of environmental and economic considerations on tourism activities in achieving sustainable development goals. The motivation of the study is to provide the empirical inference of variables based on study topicality and the implications to achieve SDG 8 and SDG 9 specifically. The study used panel data from 2000 to 2021 to check for cross-sectional dependency and performed various panel unit root tests to verify the unit root properties of the variables. With the help of Pedroni and Kao's statistical results, we confirm variables are integrated. The results from OLS modified and dynamic demonstrate the correlation between transformation, measured by patents and publications, and higher economic performance and lower environmental hazard, emphasizing the role of transformation. The results also show that tourism arrivals have a significant positive effect on reducing pollution hazards and increasing economic performance, which shows progress toward sustainable development. Based on the study, it was determined that the contribution of asylum seekers did not positively impact the host countries' economic conditions or environmental improvement initiatives. It was found that higher levels of education play a crucial role in promoting sustainable development through economic growth and mitigating environmental risks. To achieve sustainable development in the G20 economies, promoting tourism, undertaking transformational measures, and enhancing higher education are recommended. These results have significant implications for policymakers, firms, and an agenda of the United Nations sustainable development program.


The Dynamic and Correlation of Skin Temperature and Cardiorespiratory Fitness in Male Endurance Runners.
During endurance exercise, skin temperature (Tsk) plays a fundamental role in thermoregulatory processes. Environmental temperature is the biggest determinant of the Tsk. During exercise, the response of the skin temperature might be influenced by aerobic fitness (VO2peak). The aim of this study was to analyze and compare the dynamic of Tsk in high (HF) and moderately (MF) fit endurance runners during a progressive maximal stress test. Seventy-nine male endurance runners were classified into HF (n = 35; VO2peak = 56.62 ± 4.31 mL/kg/min) and MF (n = 44; VO2peak = 47.86 ± 5.29 mL/kg/min) groups. Tsk and cardiovascular data were continuously monitored during an incremental exercise, followed by a recovery period of five minutes. Results revealed that the MF group exhibited lower VO2peak, Speedpeak, ventilation (VE), muscle mass %, and higher BMI and fat mass % than the HF group (all p < 0.001). HF had significantly higher Tsk at baseline, and at 60% and 70% of peak workload (all p < 0.05). Tskpeak correlated with age, fat mass %, muscle mass %, VO2peak, Speedpeak, HR and VE (all p < 0.05). These findings indicate that VO2peak was positively associated with increased Tsk during incremental exercise in male endurance runners.


Integrated catheter for 3-D intracardiac echocardiography and ultrasound ablation.
A catheter device with integrated ultrasound imaging array and ultrasound ablation transducer is introduced. This device has been designed for use in interventional cardiac procedures in which the cardiac anatomy is first imaged using real-time three-dimensional (3-D) ultrasound, then ablated to treat arrhythmias. The imaging array includes 112 elements operating at 5.4 MHz arranged in a 2-D matrix. Individual elements have a bandwidth of 21% and an insertion loss of 80 dB. The array has an azimuth resolution of 12 degrees and an elevation resolution of 8.7 degrees. The ablation transducer is a concentric piezoelectric transducer PZT-4 ring (outside diameter (O.D.), 4.5 mm, inside diameter (I.D.), 3.1 mm) operating at 10 MHz that surrounds the imaging array. It can produce a spatial-peak, temporal-average intensity up to 16 W/cm2. The entire device fits into a 9 Fr lumen with a 14 Fr tip to accommodate the ablation ring. With this device we have imaged, in realtime 3-D, a variety of targets including wire phantoms, fixed sheep hearts, and fresh bovine tissue. The ablation ring has been used to heat tissue-mimicking rubber 14 degrees C, as well as create lesions in fresh bovine tissue.


A chronicle of the pancreatoduodenectomy technique development - from the surgeon's hand to the robotic arm.
Pancreatoduodenectomy (PD) remains one of the most challenging abdominal surgical procedures. A review of the literature regarding the history of PD, starting from the pioneers, Walter Kausch and Alan Whipple, through the great surgeons of the last century, up to the present day. The greatest development of the PD technique took place at the end of the twentieth century. Over the last 40 years, there have been huge technological advances in medicine, which have resulted in the introduction of laparoscopic and robotic techniques for abdominal surgery. However, it turns out that PD is still performed as it used to be "by the surgeon's hand" via laparotomy rather than using the most modern robot or laparoscope and is currently recommended by experts for treatment of pancreatic head cancer (PHC). This is mainly caused by not many data comparing these three PD methods. Moreover, increasingly the results achieved by surgeons advanced in minimally invasive pancreatic resections are comparable to or even better than those achieved by the open method in reference centres. Robot-assisted PD appears to be gaining an advantage over laparoscopic technique in the efficacy of PHC treatment. The obstacles most inhibiting the use of surgical robotics are the high cost of the device and procedure, and the long learning curve. A bright future lies ahead for both methods, with the robotic technique in the forefront. Despite significant advances in access and surgical technique, PD remains a challenging surgical procedure requiring a big surgeon's experience.


Inhibition of Inflammasome-Dependent Interleukin 1β Production by Streptococcal NAD+-Glycohydrolase: Evidence for Extracellular Activity.
Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD+-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion. Here, we used a set of isogenic GAS mutants and a macrophage infection model and report that streptococcal NADase inhibits the innate immune response by decreasing inflammasome-dependent interleukin 1β (IL-1β) release from infected macrophages. Regulation of IL-1β was independent of phagocytosis and ensued also under conditions not allowing SLO-dependent translocation of NADase into the host cell cytosol. Thus, our data indicate that NADase not only acts intracellularly but also has an immune regulatory function in the extracellular niche.IMPORTANCE In the mid-1980s, the incidence and severity of invasive infections caused by serotype M1 GAS suddenly increased. The results of genomic analyses suggested that this increase was due to the spread of clonal bacterial strains and identified a recombination event leading to enhanced production of the SLO and NADase toxins in these strains. However, despite its apparent importance in GAS pathogenesis, the function of NADase remains poorly understood. In this study, we demonstrate that NADase inhibits inflammasome-dependent IL-1β release from infected macrophages. While previously described functions of NADase pertain to its role upon SLO-mediated translocation into the host cell cytosol, our data suggest that the immune regulatory function of NADase is exerted by nontranslocated enzyme, identifying a previously unrecognized extracellular niche for NADase functionality. This immune regulatory property of extracellular NADase adds another possible explanation to how increased secretion of NADase correlates with bacterial virulence.


Successive approximations for charged particle motion
Single-particle dynamics in electron microscopes, ion or electron lithographic instruments, particle accelerators, and particle spectrographs is described by weakly nonlinear ordinary differential equations. Therefore, the linear part of the equation of motion is usually solved and the nonlinear effects are then found in successive order by iteration methods. When synchrotron radiation is not important, the equation can be derived from a Hamiltonian or a Lagrangian. The Hamiltonian nature can lead to simplified computations of particle transport through an optical device when a suitable computational method is used. H. Rose and his school have contributed to these techniques by developing and intensively using the eikonal method [1-3]. Many ingenious microscopic and lithographic devices were found by Rose and his group due to the simple structure of this method [4-6]. The particle optical eikonal method is either derived by propagating the electron wave or by the principle of Maupertuis for time-independent fields. Maybe because of the time-dependent fields which are often required, in the area of accelerator physics the eikonal method has never become popular, although Lagrange methods had been used sometimes already in early days [7]. In this area classical Hamilitonian dynamics is usually used to compute nonlinear particle motion. Here the author will therefore derive the eikonal method from a Hamiltonian quite familiar to the accelerator physics community and reformulate it in a simplifying way. With the event of high-energy polarized electron beams [8] and plans for high-energy proton beams [9], nonlinear effects in spin motion have become important in high-energy accelerators. The author introduces a successive approximation for the nonlinear effects in the coupled spin and orbit motion of charged particles which resembles some of the simplifications resulting from the eikonal method for the pure orbit motion.


Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.
Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4(-)CD8(+) (cytotoxic) and CD4(+)CD8(+) (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.


Evidence for epigenetic alterations in Turner syndrome opens up feasibility of new pharmaceutical interventions.
DNA methylation is an important regulatory component which influences phenotypes by modulating gene expression. Changes in DNA methylation may lead to altered phenotypes and ability of an organism to respond to stress leading to subsequent manifestation of life style diseases, cancer, etc. The human X chromosome represents a classical model for epigenetic processes governing differential regulation of homologous chromosomes. X monosomy (45, XO) leads to Turner's syndrome in human with mild to severe phenotypes. Using a novel cDNA based high throughput approach of assessing genome wide methylation; we have examined the methylation landscape in human fibroblasts in 45, XO and 46, XX individuals. We report here that as expected methylation of X linked genes is different in these two situations. It was observed that methylation of several autosomal genes is also affected in this X monosomy state. Genes involved in bone remodeling, glucose sensitivity and ovarian function appear to be altered in addition to genes involved in epigenetic regulatory processes. This opens up interesting possibility of misregulation of DNA methylation in the X monosomy state resulting in altered gene expression and altered phenotypes. This may be one of the reasons for the variance, differential severity and penetrance in case of Turner's syndrome. We propose that a systematic analysis of the molecular genetic mechanisms governing this epigenetic regulation will open up new therapeutic interventions which will certainly help in reducing severity of the disease and help in better management of X monosomy (Turner's syndrome).


A content analysis of ideal, ought, and feared selves in patients with chronic low back pain.
Patients with chronic pain are not only faced with disabilities but are also challenged to maintain a valued sense of self. This sense of self is in part determined by the extent to which patients can accomplish their identity-related goals. The present study explores the content of three domains of the self, namely the ideal, ought and feared self and examines how the content relates to disability and depression. The ideal, ought and feared attributes of 80 chronic low back pain patients were analyzed and categorized in eight general goal-domains: interpersonal attributes, personal abilities, physical, emotional and psychological well-being, close interpersonal relationships, self-expression abilities, achievement-related attributes, physical appearance, and religion. Results showed that most of the attributes that patients generated involved interpersonal attributes. Comparisons between the self-guides revealed that ideal attributes were more intrapersonally focused while ought and feared attributes were interpersonally focused. The content appeared to be related to disability but not to depression. More specifically, the more disabled patients were, the more they listed well-being related attributes as part of their ought self. None of the other goal-domains was related to disability or depression. The present study provides additional insight into the goals of patients with chronic pain at the level of identity and has shown that these are, at least in part, related to the level of functional disability. These results might be useful for future studies incorporating the role of identity in chronic pain, such as psychological interventions.


Publicly available signal databases containing seismocardiographic signals - the state in early 2023.
The development of information and communication technologies (ICT) changed many aspects of our lives, including cardiovascular research. This area of research is affected by the availability of open databases that can help conduct basic and applied research. In this study, we summarize the current state of knowledge in publicly available signal databases with seismocardiographic (SCG) signals in January 2023. Based on Google search results for the expression "seismocardiography dataset", we have found and described five databases with seismocardiograms, including three databases that contain SCG signals from healthy subjects, one database with data from porcine subjects, and one signal database with data obtained from human patients with valvular heart disease (VHD). All contain additional signals for reference points in the cardiac cycle. The most significant limitations of the described data sets are gender bias toward male subjects, the imbalance between healthy subjects, and subjects with two cardiovascular diseases (VHD and hemorrhage).


Brain shift during bur hole-based procedures using interventional MRI.
OBJECT.: Brain shift during minimally invasive, bur hole-based procedures such as deep brain stimulation (DBS) electrode implantation and stereotactic brain biopsy is not well characterized or understood. We examine shift in various regions of the brain during a novel paradigm of DBS electrode implantation using interventional imaging throughout the procedure with high-field interventional MRI. Serial MR images were obtained and analyzed using a 1.5-T magnet prior to, during, and after the placement of DBS electrodes via frontal bur holes in 44 procedures. Three-dimensional coordinates in MR space of unique superficial and deep brain structures were recorded, and the magnitude, direction, and rate of shift were calculated. Measurements were recorded to the nearest 0.1 mm. Shift ranged from 0.0 to 10.1 mm throughout all structures in the brain. The greatest shift was seen in the frontal lobe, followed by the temporal and occipital lobes. Shift was also observed in deep structures such as the anterior and posterior commissures and basal ganglia; shift in the pallidum and subthalamic region ipsilateral to the bur hole averaged 0.6 mm, with 9% of patients having over 2 mm of shift in deep brain structures. Small amounts of shift were observed during all procedures; however, the initial degree of shift and its direction were unpredictable. Brain shift is continual and unpredictable and can render traditional stereotactic targeting based on preoperative imaging inaccurate even in deep brain structures such as those used for DBS.


Miscellaneous treatments for neuroleptic-induced tardive dyskinesia.
Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of neuroleptic medication. This review, one in a series examining the treatment of tardive dyskinesia, will cover miscellaneous treatments not covered elsewhere. The primary objective of this review was to determine whether the following interventions were associated with a reduction of TD in people with schizophrenia, or others chronic mental illnesses: botulin toxin, endorphin, estrogen, essential fatty acid, EX11582A, ganglioside, lithium, naloxone, periactin, phenylalanine, piracetam, stepholidine, tryptophan, neurosurgery, or ECT. Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH (1995) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of the interventions listed above versus placebo or no intervention. Forty references describing 31 different trials were identified by the search strategy. Of 31 trials, 15 trials were excluded, six trials were included, eight awaiting assessment and a further two trials are pending (awaiting translation, unable to locate). Data were independently extracted by each reviewer and the odds ratio or the average differences were estimated. The reviewers assumed that people who dropped out had no improvement. Data were available about the efficacy and safety of cerultide, essential fatty acids, estrogen, lithium and insulin. There was a significant improvement in TD associated with the use of insulin compared to placebo (OR = 0.04, 95%CI 0.01-0.24). No significant differences between the other compounds and placebo were identified. There is no strong evidence to support the use of any of the agents included in this review, however because of the small sample sizes, all results must be considered inconclusive. The association between low dose insulin and improvement of TD requires replication.


Heavy metals concentration relationship with Perna viridis physical properties in Mengkabong Lagoon, Sabah, Malaysia.
Perna viridis (P. viridis) has been identified as a good biological indicator in identifying environmental pollution, especially when there are various types of Heavy Metals Accumulations (HMA) inside its tissue. Based on the potential of P. viridis to accumulate heavy metals and the data on its physical properties, this study proffers to determine the relationships between both properties. The similarities of the physical properties are used to mathematical model their relationships, which included the size (length, width, height) and weight (wet and dry) of P. viridis, whilst the heavy metals are focused on concentrations of Pb, Cu, Cr, Cd and Zn. The concentrations of metal elements are detected by using Flame Atomic Adsorption Spectrometry. Results show that the mean concentration of Pb, Cu, Cr, Cd, Zn, length, width, height, wet weight and dry weight are: 1.12 +/- 1.00, 2.36 +/- 1.65, 2.12 +/- 2.74, 0.44 +/- 0.41 and 16.52 +/- 10.64 mg kg(-1) (dry weight), 105.08 +/- 14.35, 41.64 +/- 4.64, 28.75 +/- 3.92 mm, 14.56 +/- 3.30 and 2.37 +/- 0.86 g, respectively. It is also found out that the relationships between the Heavy Metals Concentrations (HMA) and the physical properties can be represented using Multiple Linear Regressions (MLR) models, relating that the HMA of Zinc has affected significantly the physical growth properties of P. viridis.


Targeting virus entry and membrane fusion through specific peptide/MHC complexes using a high-affinity T-cell receptor.
The T-cell receptor (TCR) determines the specificity of T-cell recognition by binding to peptide fragments of intracellular proteins presented at the cell surface in association with molecules of the major histocompatibility complex (MHC). Engagement of the TCR by its cognate peptide/MHC ligand, with appropriate co-stimulatory signals, leads to activation of T-cell effector functions. Here we show that the attachment proteins of attenuated measles viruses, engineered to display a high-affinity single-chain TCR (scTCR), can recognize and bind to specific peptide-MHC complexes and thereby mediate targeted virus-cell entry and cell-to-cell fusion. Using the 2C TCR and its peptide/MHC ligand (SIYRYYGL/mouse K(b)), we show that a scTCR grafted onto the measles virus H protein confers new specificity to virus entry and cell fusion. The efficiency of TCR-mediated virus entry was dependent on the number of peptide/MHC complexes expressed on the target cells, increasing progressively above densities higher than 2500 complexes per cell. This work introduces a new paradigm for targeting virus entry and membrane fusion by extending the repertoire of targets to specific peptide-MHC ligands and offering a novel quantitative readout for the cellular expression of peptide-MHC complexes.


Structural linkage between ligand discrimination and receptor activation by type I interferons.
Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFNα2 and IFNω reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand "anchor points" interspersed among ligand-specific interactions that "tune" the relative IFN-binding affinities, in an apparent extracellular "ligand proofreading" mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns.


Platelet-rich plasma versus hyaluronic acid injections for knee osteoarthritis: a propensity-score analysis.
Intra-articular injections of viscosupplements have been an option in the treatment of knee osteoarthritis. Platelet-rich plasma is an experimental treatment in osteoarthritis. Previous studies have shown that platelet-rich plasma reduces osteoarthritis symptoms in similar proportions as viscosupplements. The aim of this study was to compare platelet-rich plasma versus viscosupplements in terms of symptoms' relief and time to arthroplasty. A total of 190 patients included in this retrospective study received either intra-articular injections of platelet-rich plasma (94 patients) or hyaluronic acid (86 patients) between January 2014 and October 2017. Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, and range of motion were measured before injection, at 15 days, 6 months, 12 months, and at last follow-up. We compared outcomes between these two groups using propensity score analysis for risk adjustment in multivariate analysis and for one-to-one matching. Hyaluronic acid-treated patients experienced a higher arthroplasty rate (36.0% vs 5.3%, p < 0.001), lower range of motion, worse Visual Analogue Scale and Western Ontario and McMaster Universities Osteoarthritis Index scores, and increased risk of any arthroplasty occurrence (log-rank < 0.001) than platelet-rich plasma patients. Cox proportional hazards analysis revealed a tendency to decrease the risk of knee arthroplasty for the patients treated by platelet-rich plasma (hazard ratio = 0.23, 95% confidence interval, 0.05-1.05, p = 0.058). When the treatment method was adjusted for propensity score in the propensity score-matched pairs (n = 78), we found that platelet-rich plasma group still showed significant improvement over the hyaluronic acid group in arthroplasty rate (12.8% vs 41.0%, p = 0.010), Visual Analogue Scale and Western Ontario and McMaster Universities Osteoarthritis Index scores, but not in the range of motion, during the mean follow-up of 16.7 months. Intra-articular injections of platelet-rich plasma associated with better outcomes than hyaluronic acid in knee osteoarthritis. Platelet-rich plasma might prolong the time to arthroplasty and provide a valid therapeutic option in selected patients with knee osteoarthritis not responding to conventional treatments. Further larger studies are needed to validate this promising treatment modality.


[Pharmacokinetics of 113mIn-indifor].
113mIn-indifor pharmacokinetics was studied in 82 patients with malignant tumors (breast and lung carcinoma, reticulum cell sarcoma) in the first 2 hrs after i. v. injection. The drug redistribution in the first minutes occurred mainly between the osseous tissue and the urinary system, the value of radioactivity in the urinary bladder by the 1st hour was 50% of the injected value making it possible to visualize the kidneys. A high gradient of the drug accumulation in the osseous tissues and the adjacent organs and tissues made it possible to obtain high quality scintigrams. Radiation exposure of the skeleton was 7.0 mu Gy/MBq, that of the urinary bladder 61 mu Gy/MBq.


Immunophenotyping of Murine Precursor B-Cell Leukemia/Lymphoma: A Comparison of Immunohistochemistry and Flow Cytometry.
In humans and in mouse models, precursor B-cell lymphoblastic leukemia (B-ALL)/lymphoblastic lymphoma (B-LBL) can be classified as either the pro-B or pre-B subtype. This is based on the expression of antigens associated with the pro-B and pre-B stages of B-cell development. Antigenic markers can be detected by flow cytometry or immunohistochemistry (IHC), but no comparison of results from these techniques has been reported for murine B-ALL/LBL. In our analysis of 30 cases induced by chemical or viral mutagenesis on a WT or Pax5+/- background, 18 (60%) were diagnosed as pro-B by both flow cytometry and IHC. Discordant results were found for 12 (40%); 6 were designated pro-B by IHC and pre-B by flow cytometry and the reverse for the remaining 6 cases. Discordance occurred because different markers were used to define the pro-B-to-pre-B transition by IHC vs flow cytometry. IHC expression of cytoplasmic IgM (μIgM) defined the pre-B stage, whereas the common practice of using CD25 as a surrogate marker in flow cytometry was employed here. These results show that CD25 and μIgM are not always concurrently expressed in B-ALL/LBL, in contrast to normal B-cell development. Therefore, when subtyping B-ALL/LBL in mice, an IHC panel of B220, PAX5, TdT, c-Kit/CD117, CD43, IgM, and ΚLC should be considered. For flow cytometry, cytoplasmic IgM may be an appropriate marker in conjunction with the surface markers B220, CD19, CD43, c-Kit/CD117, BP-1, and CD25.


Transitioning to a Commercial Dashboarding System: Socio-technical Observations and Opportunities.
Many long-established, traditional manufacturing businesses are becoming more digital and data-driven to improve their production. These companies are embracing visual analytics in these transitions through their adoption of commercial dashboarding systems. Although a number of studies have looked at the technical challenges of adopting these systems, very few have focused on the socio-technical issues that arise. In this paper, we report on the results of an interview study with 17 participants working in a range of roles at a long-established, traditional manufacturing company as they adopted Microsoft Power BI. The results highlight a number of socio-technical challenges the employees faced, including difficulties in training, using and creating dashboards, and transitioning to a modern digital company. Based on these results, we propose a number of opportunities for both companies and visualization researchers to improve these difficult transitions, as well as opportunities for rethinking how we design dashboarding systems for real-world use.


The tumor-suppressive function of Connexin43 in keratinocytes is mediated in part via interaction with caveolin-1.
Connexin43 (Cx43) is known to have tumor-suppressive effects, but the underlying mechanisms are still poorly understood. In keratinocytes, we previously showed that the COOH-terminal domain of Cx43 directly interacts with the tumor suppressor Cav-1. We now show that rat epidermal keratinocytes (REK) that are reduced in Cx43 present features of epithelial-to-mesenchymal transition and are more invasive than their control counterparts, whereas overexpression of Cx43 inhibited the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- and epidermal growth factor (EGF)-induced invasive properties. Carbenoxolone did not alter the inhibitory effect of Cx43 against TPA- and EGF-induced cell invasion, indicating the involvement of a gap junctional intercellular communication-independent mechanism. Interestingly, the association of Cx43 with Cav-1 was found to be reduced after TPA and EGF treatment. Accordingly, the colocalization of Cx43 with Cav-1 was diminished in cells from a human epidermal squamous cell carcinoma, as well as in sections from human keratinocyte tumors, suggesting that Cx43/Cav-1 interaction plays a protective role against keratinocyte transformation. As opposed to cells that overexpress Cx43-GFP, invasion could be induced in rat epidermal keratinocytes that overexpressed a GFP-tagged truncated mutant of Cx43 (Delta244-GFP) that we previously showed not to interact with Cav-1, as well as in cells that overexpressed Cx43-GFP but were reduced in Cav-1. Our data show that Cx43 possesses tumor-suppressive properties in keratinocytes and provide the first evidence that the Cx43/Cav-1 interaction is altered in keratinocyte transformation processes, as well as in human keratinocyte tumors, and that this association might play a role in Cx43-mediated tumor suppression.


Comparative evaluation of the pharmacokinetics of N-methylthiotetrazole following administration of cefoperazone, cefotetan, and cefmetazole.
The comparative pharmacokinetics and in vivo production of N-methylthiotetrazole (NMTT) were evaluated following administration of cefoperazone, cefotetan, and cefmetazole. In a randomized-crossover manner, 11 healthy male volunteers received single 2-g intravenous doses of each agent and serial blood and urine samples were collected. Concentrations of NMTT and the parent compound in plasma, urine, and the reconstituted antibiotic solution were determined by high-pressure liquid chromatography. The amounts of NMTT administered were 6.06 +/- 0.46, 14.4 +/- 0.87, and 17.4 +/- 1.06 mg for cefoperazone, cefotetan, and cefmetazole, respectively (P less than 0.05). The mean NMTT plasma concentration-time profiles following administration of each cephalosporin were markedly different. Six hours after dosing, NMTT concentrations in plasma following cefoperazone administration were higher than those following administration of cefmetazole and cefotetan. Urinary recoveries of NMTT averaged 137.0 +/- 37.1, 38.3 +/- 6.98, and 25.2 +/- 5.95 mg following administration of cefoperazone, cefotetan, and cefmetazole, respectively (P less than 0.01). The apparent amount of NMTT produced in vivo, calculated by subtracting the amount of NMTT administered from the amount of NMTT excreted in urine, was significantly lower following cefmetazole administration than after administration of cefoperazone and cefotetan (P less than 0.01). The discrepancy between in vitro NMTT production (cefmetazole greater than cefotetan greater than cefoperazone) and the amount of NMTT formed in vivo and excreted unchanged (cefoperazone greater than cefotetan greater than cefmetazole) suggests that in vivo production of NMTT is dependent on the disposition of the parent cephalosporin. These results further suggest that cephalosporins which undergo extensive biliary excretion, such as cefoperazone, are associated with the greatest amount of in vivo NMTT release, whereas cephalosporins which are primarily renally excreted, such as cefmetazole, are associated with the lowest in vivo production of NMTT.


New species and records of Asymmetrasca (Hemiptera: Cicadellidae: Typhlocybinae: Empoascini) from China and name changes in Empoasca (Matsumurasca).
Six new species of Asymmetrasca Dlabola are described from China: A. dahaituoensis, A. helica, A. hypercurvata, A. liaoensis, A. reflexilis, A. uncus spp. nov. In addition, A. cienka Dworakowska, 1982, n. comb.; A. decedens Paoli, 1932 and A. sakaii Dworakowska 1971, n. comb., are recorded from China for the first time. The following additional new combinations from Empoasca are also proposed: A. cisiana (Dworakowska, 1971); A. kaicola (Dworakowska, 1982), A. lutowa (Dworakowska, 1971), A. mona (Dworakowska, 1994), A. nipponica (Dworakowska 1982), A. rybiogon (Dworakowska, 1971), and A. uniprossicae (Sohi, 1977). Empoasca (Empoasca) kishtwarensis Sharma, 1984 is proposed as a new synonym of Asymmetrasca kaicola (Dworakowska, 1982). Habitus photos and illustrations of the male genitalia of the new species and a key to Chinese species are provided. New names are proposed to replace two junior homonyms in Empoasca (Matsumurasca).


Determination of antibacterial and antioxidant potential of some medicinal plants from saurashtra region, India.
Many plants used in Saurashtra folk medicine have been reported to exhibit high antibacterial and antioxidant activities. In the present study, some parts of five plants, Guazuma ulmifolia L., Manilkara zapota L., Melia azedarach L., Syzygium cumini L. and Wrightia tomentosa R.& S., were evaluated for their antibacterial activity, total phenol content, flavonoid content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity and phytochemical analysis, using successive extraction by cold percolation method with petroleum ether, ethyl acetate, methanol and water. In vitro antibacterial activity was evaluated against five bacterial strains viz. Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and Enterobacter aerogenes by agar well diffusion method. Among the plants screened, W. tomentosa leaf and fruit showed the best antibacterial activity. The Gram-positive bacteria were more susceptible than Gram-negative bacteria. Methanol extract of M. zapota showed the best 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. Highest total phenol content was shown by M. zapota and S. cumini in methanol extract, while highest flavonoid content was shown by W. tomentosa stem in petroleum ether extract and ethyl acetate extract. In all the plants, cardiac glycosides and triterpenes were more as compared to other phytoconstituents.


Structure-activity correlations among rifamycin B amides and hydrazides.
Structure-antibacterial activity correlation equations have been developed for aseries of 44 amides and 25 hydrazides of rifamycin B in five bacterial systems. The best amide equations show that activity is a parabolic function of log P. A wide variation in log Po was found for the various bacterial systems. The most important correlation parameter in the hydrazide equations is omicron*. The significance of this finding is somewhat obscured by the high degree of collinearity among the parameters evaluated (omicron*, E-s, log P). Two rifamycin B amides were prepared and evaluated as a result of this study. The correlation equations quantitatively predicted their activity in five of six tests.


Infant feeding and childhood cognition at ages 3 and 7 years: Effects of breastfeeding duration and exclusivity.
Breastfeeding may benefit child cognitive development, but few studies have quantified breastfeeding duration or exclusivity, nor has any study to date examined the role of maternal diet during lactation on child cognition. To examine relationships of breastfeeding duration and exclusivity with child cognition at ages 3 and 7 years and to evaluate the extent to which maternal fish intake during lactation modifies associations of infant feeding with later cognition. Prospective cohort study (Project Viva), a US prebirth cohort that enrolled mothers from April 22, 1999, to July 31, 2002, and followed up children to age 7 years, including 1312 Project Viva mothers and children. Duration of any breastfeeding to age 12 months. Child receptive language assessed with the Peabody Picture Vocabulary Test at age 3 years, Wide Range Assessment of Visual Motor Abilities at ages 3 and 7 years, and Kaufman Brief Intelligence Test and Wide Range Assessment of Memory and Learning at age 7 years. Adjusting for sociodemographics, maternal intelligence, and home environment in linear regression, longer breastfeeding duration was associated with higher Peabody Picture Vocabulary Test score at age 3 years (0.21; 95% CI, 0.03-0.38 points per month breastfed) and with higher intelligence on the Kaufman Brief Intelligence Test at age 7 years (0.35; 0.16-0.53 verbal points per month breastfed; and 0.29; 0.05-0.54 nonverbal points per month breastfed). Breastfeeding duration was not associated with Wide Range Assessment of Memory and Learning scores. Beneficial effects of breastfeeding on the Wide Range Assessment of Visual Motor Abilities at age 3 years seemed greater for women who consumed 2 or more servings of fish per week (0.24; 0.00-0.47 points per month breastfed) compared with less than 2 servings of fish per week (−0.01; −0.22 to 0.20 points per month breastfed) (P = .16 for interaction). Our results support a causal relationship of breastfeeding duration with receptive language and verbal and nonverbal intelligence later in life.


Nanoscale characterization of effect of L-arginine on Streptococcus mutans biofilm adhesion by atomic force microscopy.
A major aetiological factor of dental caries is the pathology of the dental plaque biofilms. The amino acid L-arginine (Arg) is found naturally in saliva as a free molecule or as a part of salivary peptides and proteins. Plaque bacteria metabolize Arg to produce alkali and neutralize glycolytic acids, promoting a less cariogenous oral microbiome. Here, we explored an alternative and complementary mechanism of action of Arg using atomic force microscopy. The nanomechanical properties of Streptococcus mutans biofilm extracellular matrix were characterized under physiological buffer conditions. We report the effect of Arg on the adhesive behaviour and structural properties of extracellular polysaccharides in S. mutans biofilms. High-resolution imaging of biofilm surfaces can reveal additional structural information on bacterial cells embedded within the surrounding extracellular matrix. A dense extracellular matrix was observed in biofilms without Arg compared to those grown in the presence of Arg. S. mutans biofilms grown in the presence of Arg could influence the production and/or composition of extracellular membrane glucans and thereby affect their adhesion properties. Our results suggest that the presence of Arg in the oral cavity could influence the adhesion properties of S. mutans to the tooth surface.


[Induction of membrane excitability in Xenopus oocytes].
Immature oocytes from the African toad Xenopus laevis are not known to be excitable cells, which means that they do not generate an action potential in response to small depolarizations. However, a regenerative response is produced if successive depolarizing currents of large magnitude are applied to the oocyte membrane. This response is characterized by the occurrence of a positive transmembrane potential that can last for several minutes. The opening of voltage-dependent channels, highly selective for sodium ions, underlies the depolarization thus obtained. These channels exhibit unconventional electrophysiological and pharmacological properties, which set them apart from other types of voltage-dependent sodium channels found in excitable tissues. The opening of the oocyte sodium channels is a complex process, which includes an induction phase. During this phase, the channels change from an electrical state of inexcitability into an excitable voltage-dependent state. The induction mechanism is modulated by the temperature of the bathing medium, by the activation of enzymes (namely a phospholipase C and a protein kinase C) and by the release of calcium ions from intracellular phosphatidyl-inositol trisphosphate stores. The results summarized in this review point out the possible role that these sodium channels may play in the physiology of the oocyte.


Physical Activity Levels of Physiotherapists across Practice Settings: A Cross-Sectional Comparison Using Self-Report Questionnaire and Accelerometer Measures.
Purpose: This article describes the physical activity of physiotherapists in British Columbia and examines differences across practice settings using self-report questionnaire and accelerometer-derived measures. Methods: Public and private practice physiotherapists aged 18-65 years were recruited through employee email lists and word of mouth to this cross-sectional study. Participants (n=98) completed the International Physical Activity Questionnaire-Long Form (IPAQ-L) online to quantify self-reported physical activity across various domains (occupational, leisure time, domestic, and transportation). Of these, 38 agreed to wear an accelerometer for 7 days to objectively measure physical activity. Descriptive statistics were used to describe self-reported and accelerometer-measured physical activity across domains, and inferential statistics were used to compare physical activity patterns across practice sites. The correlation and agreement between self-report questionnaire and accelerometer measures were also calculated. Results: Almost all (99%) of the physiotherapists self-reported meeting physical activity guidelines, and only 58% were classified as meeting guidelines when using accelerometers. Public practice physiotherapists self-reported more total, occupational, and domestic physical activity and had higher measured occupational physical activity than private practice physiotherapists. Overall, there was poor agreement between self-report questionnaires and accelerometers. Conclusions: Physiotherapists are an active group, with those in public practice reporting and participating in more physical activity than those in private practice.


Twelve-year natural history of a gastric adenocarcinoma of fundic gland type.
A 77-year-old woman underwent an upper gastrointestinal (UGI) endoscopy screening examination, and a 10-mm reddish, submucosal tumor-like lesion was found on the posterior wall of the fornix. Biopsy was performed, but there was no evidence of malignancy, so annual follow-up by UGI endoscopy was decided upon. After 12 years, examination of another biopsy specimen revealed an adenocarcinoma of the fundic gland type. There had been no significant change in the size or shape of the lesion over the long follow-up period. Endoscopic submucosal dissection (ESD) was performed, and en bloc resection was achieved. Histopathologically, the tumor appeared as a flat elevated lesion measuring 11 × 10 mm. It was composed of irregularly shaped glands and invaded the submucosa up to 300 µm. Immunohistochemical examination involving specific antibodies to pepsinogen I, MIST-1, MUC6, and H+/K+-ATPase confirmed the fundic gland differentiation of the irregularly shaped glands together with a very low Ki-67 labeling index. Thus, gastric adenocarcinoma of the fundic gland type (GAFG) was diagnosed. Four years have passed since the ESD, and there has been no recurrence. To the best of our knowledge, this is the first report of the long-term natural history of GAFG. Over the 12 years, no morphologic changes were observed; the tumor remained within the submucosal layer. Our observations in this case strengthen the notion that GAFG is a specific type of gastric adenocarcinoma of low-grade malignancy.


Histopathological, Ultrastructural and Apoptotic Changes in Diabetic Rat Placenta.
The exchange of substances between mother and fetus via the placenta plays a vital role during development. A number of developmental disorders in the fetus and placenta are observed during diabetic pregnancies. Diabetes, together with placental apoptosis, can lead to developmental and functional disorders. Histological, ultrastructural and apoptotic changes were investigated in the placenta of streptozotocin (STZ) induced diabetic rats. Animal experimentation. In this study, a total of 12 female Wistar Albino rats (control (n=6) and diabetic (n=6)) were used. Rats in the diabetic group, following the administration of a single dose of STZ, showed blood glucose levels higher than 200 mg/dL after 72 hours. When pregnancy was detected after the rats were bred, two pieces of placenta and the fetuses were collected on the 20(th) day of pregnancy by cesarean incision under ketamine/ xylazine anesthesia from in four rats from the control and diabetic groups. Placenta tissues were processed for light microscopy and transmission electron microscopy (TEM). Hematoxylin-eosin (HE) and periodic acid Schiff-diastase (PAS-D) staining for light microscopic and caspase-3 staining for immunohistochemical investigations were performed for each placenta. Electron microscopy was performed on thin sections contrasted with uranyl acetate and lead nitrate. Weight gain in the placenta and fetuses of diabetic rats and thinning of the decidual layer, thickening of the hemal membrane, apoptotic bodies, congestion in intervillous spaces, increased PAS-D staining in decidual cells and caspase-3 immunoreactivity were observed in the diabetic group. After the ultrastructural examination, the apoptotic appearance of the nuclei of trophoblastic cells, edema and intracytoplasmic vacuolization, glycogen accumulation, dilation of the endoplasmic reticulum and myelin figures were observed. In addition, capillary basement membrane thickening, capillary endothelial cells chromatin condensation in the nucleus and corrugation of the nucleus were found. Diabetes causes histomorphometric, ultrastructural and apoptotic changes in rat placenta.


The effects of prophylactic dolasetron and induction with propofol on postoperative nausea and vomiting after thyroidectomy.
Postoperative nausea and vomiting (PONV) is a common problem in patients undergoing thyroidectomy. In this study we evaluated the effects of prophylactic dolasetron and/or induction with propofol on PONV. Two hundred three patients scheduled thyroidectomy under general anesthesia with sevoflurane were included and were randomly allocated to one of four groups. In control (group C) and dolasetron groups (group D), the patients received thiopental sodium 4-5 mg/kg intravenously for the induction of anesthesia, and the patients in group D received prophylactic intravenous dolasetron 210 microgram/kg. In propofol (group P) and dolasetron + propofol groups (group D + P), the patients received propofol 2 mg/kg intravenously for the induction of anesthesia, and the patients in group D + P received prophylactic intravenous dolasetron 210 microgram/kg. The incidence and severity of PONV, the need for rescue antiemetics, adverse events were assessed during 0 to 1 hour and 1 to 24 hours postoperatively. During the first 24 hours after anesthesia, the incidences of PONV and postoperative vomiting were significantly reduced in group D + P compared with group C (P < 0.05, respectively). There were no significant differences in postoperative nausea, need for rescue antiemetics, severity of PONV, and adverse events of antiemetics among the four groups. In patients with thyroidectomy, combination of prophylactic dolasetron administration and induction with propofol was found to reduce the incidence of PONV during the first 24 hours after anesthesia, compared with that of routine induction with thiopental sodium.


Exploring Scotland's influenza pandemic of 1918-19: lest we forget.
The 1918-1919 influenza pandemic resulted in more deaths than any other medical event in human history; the most recent scholarship puts the death toll worldwide at 100 million. Scotland suffered a proportionate loss of life but it was little reported at the time and has been little studied by social historians since. The Great War had been such a traumatic experience that the authorities, and the general public, could take no more tragic news and the result was an uncanny silence. There is little information on the way in which people were affected by the pandemic. Such information could now be valuable as we plan a response to a pandemic of avian flu. This article aims to initiate study of an important episode in healthcare in Scotland.


Sleep and Circadian Rhythm Disturbance in Remitted Schizophrenia and Bipolar Disorder: A Systematic Review and Meta-analysis.
Sleep and circadian rhythm disturbances in schizophrenia are common, but incompletely characterized. We aimed to describe and compare the magnitude and heterogeneity of sleep-circadian alterations in remitted schizophrenia and compare them with those in interepisode bipolar disorder. EMBASE, Medline, and PsycINFO were searched for case-control studies reporting actigraphic parameters in remitted schizophrenia or bipolar disorder. Standardized and absolute mean differences between patients and controls were quantified using Hedges' g, and patient-control differences in variability were quantified using the mean-scaled coefficient of variation ratio (CVR). A wald-type test compared effect sizes between disorders. Thirty studies reporting on 967 patients and 803 controls were included. Compared with controls, both schizophrenia and bipolar groups had significantly longer total sleep time (mean difference [minutes] [95% confidence interval {CI}] = 99.9 [66.8, 133.1] and 31.1 [19.3, 42.9], respectively), time in bed (mean difference = 77.8 [13.7, 142.0] and 50.3 [20.3, 80.3]), but also greater sleep latency (16.5 [6.1, 27.0] and 2.6 [0.5, 4.6]) and reduced motor activity (standardized mean difference [95% CI] = -0.86 [-1.22, -0.51] and -0.75 [-1.20, -0.29]). Effect sizes were significantly greater in schizophrenia compared with the bipolar disorder group for total sleep time, sleep latency, and wake after sleep onset. CVR was significantly elevated in both diagnoses for total sleep time, time in bed, and relative amplitude. In both disorders, longer overall sleep duration, but also disturbed initiation, continuity, and reduced motor activity were found. Common, modifiable factors may be associated with these sleep-circadian phenotypes and advocate for further development of transdiagnostic interventions that target them.


Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of postconcussion symptoms following a mild traumatic brain injury: a systematic review.
Mild traumatic brain injury (mTBI) has been insufficiently researched, and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalisability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes, but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict postconcussion symptoms following an mTBI. Searches of MEDLINE, Embase, CENTRAL, CINAHL, Web of Science, PsycBITE and PsycINFO up to October 2016. Two reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach. A total of 23 298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurological disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous traumatic brain injury (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was postconcussion syndrome using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI. Most studies have recruited samples that are not representative and generalisable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict postconcussion symptoms.


Worm wounding increases levels of pollen-related food allergens in soybean (Glycine max).
The levels of food allergens in worm-wounded or non-wounded green soybeans (edamame) and mature soybeans were investigated by immunoblotting and enzyme-linked immunosorbent assay (ELISA), using allergen-specific antibodies. Non-wounded and worm-wounded soybeans showed similar total protein profiles after Coomassie brilliant blue staining, but some protein bands were observed to have been changed by worm wounding. Immunoblotting with specific antibodies for major soybean allergens (Gly m 5, Gly m 6, Gly m Bd 30 K, and Kunitz soybean trypsin inhibitor) revealed that protein band profiles and intensities were not significantly changed by worm wounding. In contrast, levels of the pollen-related soybean allergens Gly m 4 and Gly m 3 were strongly increased by worm wounding in both green and mature soybeans, as detected by immunoblotting and ELISA. These results suggested that the pollen-related food allergen risk (i.e., oral allergy syndrome; OAS) from soybeans might be enhanced by worm wounding of soybeans.


Relationships between the cytotoxicity of tiazofurin and its metabolism by cultured human lung cancer cells.
The antitumor activity of the antineoplastic agent, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), has previously been shown to require intracellular anabolism of the drug to a nicotinamide adenine dinucleotide (NAD) analog (2-beta-D-ribofuranosylthiazole-4-carboxamide adenine dinucleotide or "tiazofurin adenine dinucleotide"), which then acts as a potent inhibitor of the target enzyme inosine monophosphate (IMP) dehydrogenase. Inhibition of the latter enzyme in turn brings about a profound depletion of intracellular guanosine nucleotides essential for tumor cell growth and replication. In the present study, the cytotoxicity and metabolism of tiazofurin have been examined in six human lung cancer cell lines. At the pharmacologically attainable drug concentration of 100 microM, colony survival was less than 1.5% in three cell lines ("sensitive"), while survival in the remaining three was greater than 50% ("resistant"). The metabolism of tritiated tiazofurin was examined at concentrations ranging from 0.5 to 100 microM following both brief (6 h) and protracted (14 d) exposures. The sensitive lines accumulated concentrations of tiazofurin adenine dinucleotide that were approximately 10 times those achieved by the resistant lines at both time points. We also observed tendencies for the sensitive cell lines to exhibit: (a) higher specific activities of NAD pyrophosphorylase, the enzyme required for the synthesis of tiazofurin adenine dinucleotide, (b) significantly lower levels of a phosphodiesterase which degrades the latter dinucleotide, (c) greater inhibition of the target enzyme IMP dehydrogenase, and (d) greater depressions of guanosine nucleotide pools after drug treatment. By contrast, the basal levels of IMP dehydrogenase and purine nucleotides in these six lines did not correlate in any obvious way with their responsiveness or resistance. The accumulation and monophosphorylation of parent drug were also not prognostic variables. These studies thus suggest that the extent of accumulation of tiazofurin adenine dinucleotide, as regulated by its synthetic and degradative enzyme activities, is the single most predictive determinant of the responsiveness of cultured human lung tumor cells to tiazofurin.


Serious neck injuries in U19 rugby union players: an audit of admissions to spinal injury units in Great Britain and Ireland.
To obtain data regarding admissions of U19 rugby players to spinal injury units in Great Britain and Ireland and to compare this with a recent peak in presentation in Scotland. To assess the current state of data collection and subsequent analysis of serious neck injuries. To analyse the mechanism of injury in this group of at-risk players. Retrospective case series. Spinal injury units in Great Britain and Ireland. Annual frequency of serious neck injuries. Analysis of injury types, neurological deficit and mechanism of injury. 36 Injuries were recorded. 10 Of these occurred in Scotland since 1996 of which six have occurred in the past 4 years. This compared with 14 in Ireland over the same period. 12 Cases were traced in England and Wales since 2000; records were not available before this date. No prospective collation of data is performed by the home unions and inconsistency of data collection exists. The mean age was 16.2 years. 16 Of the 36 admissions had complete neurological loss, 9 had incomplete neurological injury and 11 had cervical column injury without spinal cord damage. The mechanism of injury was tackle in 17 (47%), scrum in 13 (36%), two each due to the maul and collision, and one each due to a kick and a ruck. Some degree of spinal cord injury occurred in 92% of scrum injuries (61% complete) and 53% of tackle injuries (29% complete). U19 rugby players continue to sustain serious neck injuries necessitating admission to spinal injury units with a low but persistent frequency. The recent rate of admission in Scotland is disproportionately high when the respective estimated playing populations are considered. While more injuries were sustained in the tackle, spinal cord injury was significantly more common in neck injury sustained in the scrum (p<0.001). No register of catastrophic neck injuries exists despite repeated calls over the past three decades, and a study such as this has not been reported before. Data collection of this serious category of injury is incomplete and very variable across the home unions, as a consequence a large proportion of the serious neck injuries that have occurred in U19 players over the past 14 years have not been analysed. Rigorous data collection and analysis have to be established so that problem areas of the game such as scrum engagement and the tackle can be made safer.


Chondroitin Sulfate Induces Depression of Synaptic Transmission and Modulation of Neuronal Plasticity in Rat Hippocampal Slices.
It is currently known that in CNS the extracellular matrix is involved in synaptic stabilization and limitation of synaptic plasticity. However, it has been reported that the treatment with chondroitinase following injury allows the formation of new synapses and increased plasticity and functional recovery. So, we hypothesize that some components of extracellular matrix may modulate synaptic transmission. To test this hypothesis we evaluated the effects of chondroitin sulphate (CS) on excitatory synaptic transmission, cellular excitability, and neuronal plasticity using extracellular recordings in the CA1 area of rat hippocampal slices. CS caused a reversible depression of evoked field excitatory postsynaptic potentials in a concentration-dependent manner. CS also reduced the population spike amplitude evoked after orthodromic stimulation but not when the population spikes were antidromically evoked; in this last case a potentiation was observed. CS also enhanced paired-pulse facilitation and long-term potentiation. Our study provides evidence that CS, a major component of the brain perineuronal net and extracellular matrix, has a function beyond the structural one, namely, the modulation of synaptic transmission and neuronal plasticity in the hippocampus.


Basic instinct undressed: early spatiotemporal processing for primary sexual characteristics.
This study investigates the spatiotemporal dynamics associated with conscious and non-conscious processing of naked and dressed human bodies. To this effect, stimuli of naked men and women with visible primary sexual characteristics, as well as dressed bodies, were presented to 20 heterosexual male and female participants while acquiring high resolution EEG data. The stimuli were either consciously detectable (supraliminal presentations) or were rendered non-conscious through backward masking (subliminal presentations). The N1 event-related potential component was significantly enhanced in participants when they viewed naked compared to dressed bodies under supraliminal viewing conditions. More importantly, naked bodies of the opposite sex produced a significantly greater N1 component compared to dressed bodies during subliminal presentations, when participants were not aware of the stimulus presented. A source localization algorithm computed on the N1 showed that the response for naked bodies in the supraliminal viewing condition was stronger in body processing areas, primary visual areas and additional structures related to emotion processing. By contrast, in the subliminal viewing condition, only visual and body processing areas were found to be activated. These results suggest that naked bodies and primary sexual characteristics are processed early in time (i.e., <200 ms) and activate key brain structures even when they are not consciously detected. It appears that, similarly to what has been reported for emotional faces, sexual features benefit from automatic and rapid processing, most likely due to their high relevance for the individual and their importance for the species in terms of reproductive success.


Second cancer following cancer of the urinary system in Connecticut, 1935-82.
The risk of second primary cancer was assessed in persons who developed cancer of the urinary tract in Connecticut during 1935-82. Among 12,384 patients with a first primary tumor of the bladder or urethra, a second cancer was reported in 1,151 (or 9%). A significantly elevated relative risk (RR) of 1.23 was due to excess cancers of the lung, larynx, prostate, and kidney, and acute nonlymphocytic leukemia. Among 5,115 persons with a first primary tumor of the kidney, renal pelvis or ureter, a second cancer was reported in 374 (or 7%) that yielded a significantly elevated RR of 1.54 due to excess tumors of the bladder and prostate and second primary kidney neoplasms. The role of common etiologic factors, such as cigarette smoking, the multifocal tendency of tumors of the urinary tract, and heightened medical surveillance are discussed in relation to these findings.


Valsartan-induced improvement in insulin sensitivity is not paralleled by changes in microvascular function in individuals with impaired glucose metabolism.
Individuals with impaired glucose metabolism (IGM) are at high risk of developing type 2 diabetes (T2DM). The renin-angiotensin system (RAS) is activated in insulin-resistant states and its inhibition resulted in delayed onset of T2DM. The underlying mechanisms may include improvement in microvascular structure and function, which may increase glucose and insulin delivery to insulin-sensitive tissues. We hypothesized that functional and structural capillary density is impaired in insulin-resistant individuals with IGM and that treatment with the angiotensin-receptor blocker valsartan (VAL) will improve insulin sensitivity and microvascular function. In this randomized controlled trial, individuals with IGM (n = 48) underwent a hyperinsulinaemic-euglycaemic clamp to assess insulin sensitivity (M-value) and capillaroscopy to examine baseline skin capillary density (BCD), capillary density after arterial occlusion (PRH) and capillary density during venous occlusion (VEN) before and after 26 weeks of VAL or placebo (PLB). Sixteen BMI-matched individuals with normal glucose metabolism (NGM) served as controls. Individuals with IGM were more insulin resistant (P < 0.001) and had impaired microvascular function compared with those with NGM (all P < 0.01). Univariate associations were found for microvascular function (BCD, PRH, VEN) and M-value (all P < 0.005). The relations were independent of age, sex and BMI. VAL improved insulin sensitivity (P = 0.034) and lowered blood pressure as compared with PLB, whereas microvascular function remained unchanged. In insulin-resistant individuals with IGM, impaired functional and structural capillary density was inversely associated with insulin sensitivity. VAL improved insulin sensitivity without affecting the functional and structural capillary density, indicating that other mechanisms may be stronger determinants in the VAL-mediated insulin-sensitizing effect.


Proteolytic cleavage of a C-terminal prosequence, leading to autoprocessing at the N Terminus, activates leucine aminopeptidase from Pseudomonas aeruginosa.
At high bacterial cell density the gene expression program of Pseudomonas aeruginosa is regulated by quorum sensing. Among the gene products highly up-regulated by this system is an exoprotease, leucine aminopeptidase (PA-LAP), which is coexpressed with several known virulence factors and secreted as a proenzyme. We undertook a study of its activation by expressing the full-length proform of PA-LAP recombinantly in Escherichia coli (here termed, rLAP55) and characterizing individual steps in its conversion to an active enzyme. Activation is initiated with the proteolytic removal of a C-terminal prosequence. Removal of approximately 20 amino acids is accomplished by Pseudomonas elastase, which is also positively regulated by quorum sensing. Activation is also mediated by other proteases that cleave rLAP55 near its C terminus. The importance of the C terminus was confirmed by showing that C-terminal deletions of 1-24 amino acids produce a fully active enzyme. The removal of C-terminal prosequences either by proteolysis or deletion leads to an unusual autoprocessing event at the N terminus. Autoprocessing is apparently an intramolecular event, requires the active site of LAP, and results in the removal of 12 N-terminal amino acids. Furthermore, a detailed analysis of the C-terminal prosequence suggests that the proenzyme state is dependent on the presence of a basic side chain contributed by the last amino acid, lysine 536. Our data support a model whereby full-length PA-LAP is activated in a two-step process; proteolytic cleavage at the C terminus is followed by an intramolecular autocatalytic removal of a 12-amino acid propeptide at the N terminus.


Heterogeneity of high-mobility-group protein 2. Enrichment of a rapidly migrating form in testis.
A determination of the absolute amounts of high-mobility-group proteins 1 and 2 (HMG1 and HMG2) in rat tissues demonstrated that amounts of HMG2 were low in non-proliferating tissues, somewhat higher in proliferating and lymphoid tissues, but were extremely elevated in the testis. This increase was due to a germ-cell-specific form of HMG2 with increased mobility relative to somatic HMG2 on acid/urea/polyacrylamide-gel electrophoresis. To determine if the findings in the rat were a general feature of spermatogenesis, testis (germinal), spleen (lymphoid), and liver (non-proliferating) tissues from various vertebrate species were examined for their relative amounts of HMG1 and HMG2, and for HMG2 heterogeneity. Bull, chimpanzee, cynomologus monkey, dog, gopher, guinea pig, hamster, mouse, opossum, rabbit, rat, rhesus monkey, squirrel and toad (Xenopus) tissues were analysed. Nearly all species showed relatively high contents of HMG2 in testis tissue, whereas HMG1 contents were similar in all species and tissues. Ten of thirteen species showed a rapidly migrating HMG2 subtype in testis tissue, separable by acid/urea/polyacrylamide-gel electrophoresis. Xenopus, which lacks HMG2 in somatic tissues, showed an HMG2-like protein in testis tissue. Although the rapidly migrating HMG2 subtype in species other than rat was not testis-specific, it was always enriched in the testis. This study indicates that increased amounts of HMG2 and the enrichment of a rapidly migrating HMG2 subtype are general features of spermatogenic cells.


The omentum of obese girls harbors small adipocytes and browning transcripts.
Severe obesity (SO) affects about 6% of youth in the United States, augmenting the risks for cardiovascular disease and type 2 diabetes. Herein, we obtained paired omental adipose tissue (omVAT) and abdominal subcutaneous adipose tissue (SAT) biopsies from girls with SO undergoing sleeve gastrectomy (SG), to test whether differences in cellular and transcriptomic profiles between omVAT and SAT depots affect insulin sensitivity differently. Following weight loss, these analyses were repeated in a subgroup of subjects having a second SAT biopsy. We found that omVAT displayed smaller adipocytes compared with SAT, increased lipolysis through adipose triglyceride lipase phosphorylation, reduced inflammation, and increased expression of browning/beiging markers. Contrary to omVAT, SAT adipocyte diameter correlated with insulin resistance. Following SG, both weight and insulin sensitivity improved markedly in all subjects. SAT adipocytes' size became smaller, showing increased lipolysis through perilipin 1 phosphorylation, decreased inflammation, and increased expression in browning/beiging markers. In summary, in adolescent girls with SO, both omVAT and SAT depots showed distinct cellular and transcriptomic profiles. Following weight loss, the SAT depot changed its cellular morphology and transcriptomic profiles into more favorable ones. These changes in the SAT depot may play a fundamental role in the resolution of insulin resistance.


Psychological Functioning of Children and Adolescents With Eosinophil-Associated Gastrointestinal Disorders.
This study examined health-related quality of life and adjustment among children with eosinophil- associated gastrointestinal disorders (EGID) compared with an age-matched sample without acute or chronic illness. Participants were youth ages 2 to 18 years. Children and caregivers completed measures of psychological symptoms and health-related quality of life (HRQOL). Significant group differences were found for child report of depressive, as well as anxiety symptoms. Significant group differences were also found for caregiver report of psychological symptoms and social skills. Finally, based on parent and youth report, HRQOL and greater school absenteeism were associated with EGID diagnosis.


Prognostic value of magnetic resonance arthrography for Czerny stage II and III acetabular labral tears.
To assess the intraobserver reliability and prognostic value of magnetic resonance arthrography (MRA) on the basis of postoperative outcome measures following arthroscopic acetabular labral debridement (partial limbectomy). Between January 1999 and November 2000, 24 patients (13 females, 11 males) with an average age of 37.1 years (range, 21 to 56 years) underwent hip arthroscopy for the treatment of presumed acetabular labral tears. All patients underwent preoperative MRA and/or magnetic resonance imaging (MRI); images were evaluated by a single musculoskeletal radiologist on 2 independent occasions. Hip arthroscopy was performed on all patients. Outcomes were assessed by means of the Modified Harris Hip Score (MHHS) and the Short Form-36 (SF-36) questionnaires, which were completed by patients an average of 24.1 months (range, 12 to 55 months) postoperatively. The accuracy of the initial read, as well as the prognostic value of the Czerny MRA classification system for stage II (intrasubstance tears) and stage III (complete avulsions) acetabular labral tears, was assessed. Twenty-two of 23 tears (96%) were detected on the initial read. On the basis of intraoperative findings, 1 false-positive MRA, 1 false-negative MRA, and 1 incident of MRA overstaging were reported. On repeat interpretation, 23 of 23 (100%) tears were identified, and intraobserver reliability for recording the presence of a tear was excellent (kappa coefficient = 0.96). No difference was noted in outcomes between patients with or without arthroscopic evidence of chondromalacia (all P > .29), or between patients older or younger than 30 years (all P > .34). Likewise, no difference in outcome was seen between 15 patients with Czerny stage II tears revealed on MRA versus 9 patients with Czerny stage III tears (all P > .79). MRA is sensitive and accurate for the detection of acetabular labral tears, with excellent intraobserver reliability. Arthroscopic partial limbectomy is successful in two thirds of patients. Patients with Czerny stage II and III tears do not appear to have significantly different outcomes following arthroscopic labral debridement. Level IV, prognostic case series.


Chemoprevention of gastrointestinal cancer.
Gastrointestinal cancer remains a significant public health threat in developed countries. Even with breath-taking gains in our understanding of the molecular underpinnings of the most common GI cancers, it is clear that the best hope in the foreseeable future lies in the chemoprevention of recurrent cancer and its associated precursors. Colon cancer is an ideal disease for the application of chemopreventive strategies. The molecular biology of colon cancer has been well studied and it is an excellent model for the development of chemopreventive interventions. This fact allows clinical investigators to utilize what is known about discrete biological phases of colon carcinogenesis to tailor clinical trial protocols that may attenuate a future risk for cancer. Among the agents currently in clinical trial testing are anti-oxidants, modulators of metabolism, and antiproliferatives. Current clinical trials have often incorporated the use of biomarkers as intermediate endpoints to assess the efficacy of particular preventives. The current status of ongoing colon cancer prevention trials suggests that this disease, in particular, may well be suited to chemopreventive approaches.


Early EEG Grade and Outcome at 5 Years After Mild Neonatal Hypoxic Ischemic Encephalopathy.
More than half of all infants with neonatal hypoxic ischemic encephalopathy (HIE) are graded as mild and do not meet current criteria for therapeutic hypothermia. These infants are often not enrolled in follow-up, and hence our knowledge of their long-term outcome is sparse. We wished to compare 5-year outcomes in a group of infants with mild, moderate, and severe HIE, graded with both early EEG and clinical assessment, none of whom were treated with therapeutic hypothermia. Term infants with HIE and a healthy comparison group were recruited at birth. Both groups had early continuous EEG recordings. Cognitive and motor outcome was assessed at 5 years. Outcome was available in 53 infants with HIE and 30 infants in the comparison group at 5 years. Infants with mild HIE at birth (n = 22) had significantly lower full-scale IQ, verbal IQ, and performance IQ than comparison infants (n = 30) at 5 years (P = .001, .001, and 0.004, respectively). No difference in cognitive measures was seen between infants with mild and moderate grades HIE. Intact survival at 5 years varied across EEG grade HIE at 6 hours after birth; 75% in mild, 46% in moderate, 43% in major abnormalities, and 0% with inactive EEGs, compared with 97% in the comparison group. Survivors of mild HIE, graded clinically or by early EEG, have higher rates of disability than their peers and have cognitive outcomes similar to that of children with moderate encephalopathy in an uncooled HIE cohort.


5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal cancer.
In patients with Peutz-Jeghers syndrome (PJS), causative germline mutations in the LKB1/STK11 gene on chromosome 19p13.3 have been identified. Because of the loss of heterozygosity (LOH) at 19p13.3 in hamartomas and the cancer susceptibility of patients with PJS, LKB1/STK11 is suggested to act as a tumour suppressor. However, the frequency of genetic and epigenetic inactivation of LKB1/STK11 in sporadic tumours is unclear. To investigate the LKB1/STK11 gene for promoter hypermethylation and allelic loss in tumour specimens of patients with sporadic colorectal cancer. DNA from 50 consecutive paraffin embedded sporadic colorectal adenocarcinomas and corresponding normal epithelium was extracted. After bisulphite treatment, specimens were analysed for methylation of the LKB1/STK11 promoter 5'-CpG island by methylation specific polymerase chain reaction (MSP). In addition, tumours were analysed for LOH of chromosome 19p13.3. In tumours exhibiting LOH, LKB1/STK11 was sequenced. MSP was successful in 48 of 50 tumour specimens. Of those, four (8%) demonstrated hypermethylation of the LKB1/STK11 promoter 5'-CpG island. Moreover, LOH at either D19S886 or D19S878 was observed in five of 38 (13%) informative tumours. All five tumours showing LOH at 19p13.3 were advanced and four of five were located in the left sided colon. There was no correlation between LOH and LKB1/STK11 promoter hypermethylation or somatic mutation. In sporadic colorectal cancer, hypermethylation of the LKB1/STK11 promoter and allelic loss at the STK 11 gene locus are rare events. LOH at 19p13.3 was associated with advanced tumour stage and left sided location but not with LKB1/STK11 promoter hypermethylation or somatic mutation.


Cycle-phase dependent associations between CRP, leptin, and reproductive hormones in an urban, Canadian sample.
To assess the relationships among reproductive hormones, follicular development, inflammation, and adiposity in a sample of urban, Canadian women. Participants (n = 41) had blood collected every 3 days through one interovulatory interval (IOI) to measure estradiol, progesterone, LH, FSH, leptin, and C-reactive protein (CRP). Participants underwent daily transvaginal ultrasound examinations during the IOI to quantify all follicles > 2 mm. CRP and leptin tertiles were used to compare conditions of high and low inflammatory processes and adiposity, respectively. Luteal phase estradiol, luteal phase LH, and follicular phase progesterone were lower among individuals in the highest CRP tertile (adjusted r(2) = 0.63, 0.70, 0.76, respectively). Luteal and follicular phase follicle diameter was greatest in the high CRP tertile (adjusted r(2) = 0.68, 0.71). Follicular phase progesterone was lowest among individuals in the highest leptin tertile, and follicular phase FSH was lowest among individuals in the lowest leptin tertile (adjusted r(2) = 0.54, 0.45). Luteal phase follicle diameter was highest among those in the moderate leptin tertile (adjusted r(2) = 0.49). This study is a first comprehensive assessment of the relationship between multiple ovarian function components and inflammatory biomarkers. The results are interpreted to mean that inflammatory and energetic stressors produce differential effects depending on population, adiposity, and cycle phase. Am J Phys Anthropol 160:389-396, 2016. © 2016 Wiley Periodicals, Inc.


Breaking radial dipole symmetry in planar macrocycles modulates edge-edge packing and disrupts cofacial stacking.
Dipolar interactions are ever-present in supramolecular architectures though their impact is typically revealed by making dipoles stronger. While it is also possible to assess the role of dipoles by altering their orientations using synthetic design, doing so without altering molecular shape is not straightforward. We do this by flipping one triazole unit in a rigid macrocycle, tricarb. The macrocycle is composed of three carbazoles (2 Debye) and three triazoles (5 Debye) defining an array of dipoles aligned radially but organized alternately in and out. These dipoles are believed to dictate edge-to-edge tiling and face-to-face stacking. We modified our synthesis to prepare isosteric macrocycles with the orientation of one triazole dipole rotated 40°. The new dipole orientations guide edge-edge contacts to reorder the stability of two surface-bound 2D polymorphs. The impact on dipole-enhanced π stacking, however, was unexpected. Our stacking model identified an unchanged set of short-range (3.4 Å) anti-parallel dipole contacts. Despite this situation, the reduction in self-association was attributed to long-range (~6.4 Å) dipolar repulsions between π-stacked macrocycles. This work highlighted our ability to control the build-up and symmetry of macrocyclic skeletons by synthetic design, and the work needed to further our understanding of how dipoles control self-assembly.


Biomechanical analysis of the brachioradialis as a donor in tendon transfer.
Anatomic and biomechanical properties of the passive brachioradialis muscle were investigated to understand the limited excursion of this muscle seen during tendon transfer surgery. First, architectural measurements were performed on three fiber bundles obtained from four regions of the brachioradialis (10 specimens) chosen to represent the range of muscle fiber lengths across the brachioradialis. Next, in separate specimens (eight specimens), passive excursion was measured by securing the distal tendon stump to a servomotor. A constant load of 4.9 N was applied to the tendon, while the distal tendon was released from the surrounding tissue in 3-cm increments. Within the four regions studied, muscle fiber length varied significantly from 104.2 +/- 6.2 mm to 179.8 +/- 6.1 mm. As the brachioradialis was released, an average of 3 mm of mobility was obtained for each interval whereas for the succeeding three intervals, an average of 5.3 mm of mobility was obtained. This resulted in 22.2 +/- 2.3 mm of mobility when each specimen was fully released. These data show that there is no intrinsic muscle fiber length limitation to excursion, but that excursion is limited by other intermuscular connections to adjacent connective tissue and other muscles.


Differential vascular alpha1-adrenoceptor antagonism by tamsulosin and terazosin.
In patients with lower urinary tract symptoms suggestive of benign prostatic obstruction the alpha1-adrenoceptor antagonist terazosin lowers blood pressure whereas only very small if any alterations were reported with the alpha1-adrenoceptor antagonist tamsulosin. Therefore, we have compared the vascular alpha1-adrenoceptor antagonism of tamsulosin and terazosin directly. Ten healthy subjects were investigated in a randomized, single-blind, three-way cross-over design and received a single dose of 0.4 mg tamsulosin, 5 mg terazosin or placebo on 3 study days at least 1 week apart. Before and 1, 3, 5, 7, 10 and 23.5 h after drug intake, alterations of diastolic blood pressure and other haemodynamic parameters in response to a graded infusion of the alpha1-adrenoceptor agonist phenylephrine were determined non-invasively. At most time points tamsulosin inhibited phenylephrine-induced diastolic blood pressure elevations significantly less than terazosin (5 h time point: median difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand, phenylephrine-induced changes of cardiac output, heart rate and stroke volume were similar during both active treatments. In doses equi-effective for treatment of lower urinary tract symptoms tamsulosin causes less inhibition of vasoconstriction than terazosin.


Non-vascularised Fibular Autograft for Reconstruction of Paediatric Bone Defects: An Analysis of 10 Cases.
Fibular autograft is a known technique for the reconstruction of traumatic and non-traumatic bone defects in both adult and paediatric populations. We aim to describe our outcomes using various stabilisation methods for non-vascularised fibular autograft to reconstruct both benign and malignant tumours in a paediatric population in a National Paediatric Centre over the past 14 years. This was a retrospective review of 10 paediatric cases with non-traumatic primary bone defects in a National Paediatric Centre. Criteria for inclusion were all non-traumatic primary bone defects requiring reconstruction with a non-vascularised fibular autograft in the diaphyseal or metaphyseal regions of the bone. The primary outcome measures were union and time to union (weeks). Time to union was illustrated using Kaplan-Meier curves. Secondary outcome measures included postoperative fracture, infection (deep and superficial), time to full weight-bearing and all-cause revision surgery. The mean length of follow-up was 63 months for the entire cohort (9-168, SD = 48.6). There was no loss to follow-up. Six lesions were located in the tibia, two in the femur and the remaining two were located in the ulna and third metacarpal. Union was ultimately achieved in 8 of the 10 patients using this donor autograft. The mean time to union was 28 weeks (10-99, SD = 29.8). There were four complications of autograft fracture. The mean time to fracture was 17 weeks (9-32, SD = 10.71). In all four of these cases, the patient achieved union at final follow-up. There were two superficial and two deep infections recorded. Three resolved with the use of antimicrobial therapy and one deep infection ultimately required insertion of an intercalary prosthesis to treat the infected non-union of the fibular graft site. The use of non-vascularised fibular autograft for the reconstruction of tumours is an effective surgical technique in a paediatric cohort. We report the largest known series of malignant paediatric tumours treated with this technique to date. Non-vascularised fibular autograft is successful in the reconstruction of large bone defects secondary to malignant paediatric bone tumours. Sheridan GA, Cassidy JT, Donnelly A, et al. Non-vascularised Fibular Autograft for Reconstruction of Paediatric Bone Defects: An Analysis of 10 Cases. Strategies Trauma Limb Reconstr 2020;15(2):84-90.


Spread like a wildfire--the omnipresence of porcine circovirus type 2 (PCV2) and its ever-expanding association with diseases in pigs.
The discovery of porcine circovirus type 2 (PCV2) in 1998 initiated intensive research on arguably the most economically important pathogen facing the global swine industry today. PCV2 infection is now widespread worldwide, and increasing numbers of disease conditions have been linked to PCV2 infection in pigs. In this special issue of Virus Research, leading experts in the field review the history, epidemiology, transmission, clinical and pathological features, immunology, pathogenesis, molecular biology and vaccine development of PCV2 and porcine circovirus associated disease (PCVAD). In addition, circovirus-like DNA sequences recently identified from humans and other animal species and their biological significances are also reviewed. The articles in this special issue identify gaps in current PCV2 research and offer insights for the direction of future research.


Cognitive deficits in clinical and familial high risk groups for psychosis are common as in first episode schizophrenia.
The aim of this study is to compare the neurocognitive functions in individuals with clinical or genetic risk for psychosis, in patients with first-episode schizophrenia (FES) and in healthy controls. We compared cognitive functions of 52 individuals at ultra high risk (UHR) for psychosis, 53 patients with FES, their 30 healthy siblings (familial high risk group, FHR) and controls. FES group had worse neuropsychological performance than controls in all of the domains. UHR group had worse performance in verbal learning, attention, and working memory than controls. Additionally, individuals at UHR with familial risk had worse performance on executive functions than the control group. FES group had lower global composite score than UHR group, and worse sustained attention than FHR group. FHR group had worse performance on executive functions and attention than controls. We found no difference in cognitive performances of UHR and FHR groups. Cognitive deficits in UHR and FHR groups were largely similar to those with FES. These findings support that cognitive deficits may arise before the first episode of schizophrenia.


Beta 2 microglobulin enhances the infectivity of cytomegalovirus and when bound to the virus enables class I HLA molecules to be used as a virus receptor.
We have previously demonstrated that human cytomegalovirus (CMV) binds the host protein beta 2 microglobulin (beta 2m) from body fluids or from cell culture media. In this report we have examined the effect of the beta 2m on viral infectivity. We have shown that the addition of human purified beta 2m, or a fraction of foetal calf serum corresponding to bovine beta 2m, to culture medium increased the amount of infectious extracellular CMV, compared to that from cells grown in serum-free medium. Metabolic labelling experiments demonstrated that this effect was not due to an increase in the amount of extracellular virus but to an increase in the infectivity of the virus present in extracellular fluids. We concluded that the binding of beta 2m by CMV increased its infectivity. We have shown that CMV and beta 2m compete for binding sites on fibroblasts. As the main binding site on cells for beta 2m is the class I HLA heavy chain we compared the binding of CMV to the Raji and Daudi cell lines which express or lack expression of class I HLA molecules. The binding of radiolabelled beta 2m-coated CMV was significantly higher to Raji cells than to Daudi cells. Furthermore, CMV could compete with beta 2m for binding to Raji cells, although the reverse was not true. These results demonstrate that CMV can use class I HLA molecules as a virus receptor. We propose that when coated with beta 2m, CMV has the capacity to displace beta 2m from the class I HLA heavy chain-beta 2m dimer on the cell surface and bind to cells. The fact that beta 2m enhances infectivity suggests that such binding leads to productive infection of cells.