Collagen-induced arthritis in mice: a major role for tumor necrosis factor-alpha.
Collagen-induced arthritis is the most widely used animal model for the evaluation of novel therapeutic strategies for rheumatoid arthritis. The disease is induced by immunization of genetically susceptible strains of mice or rats with type II collagen in adjuvant. Susceptibility to collagen-induced arthritis is associated with major histocompatibility complex (MHC) class II genes, although non-MHC genes also play a role. Both B- and T-lymphocytes are important in the pathogenesis of collagen-induced arthritis, with the peak of the T-cell response occurring around the time of disease onset. Histopathological assessment of the joints of animals with collagen-induced arthritis reveal a proliferative synovitis with infiltration of polymorphonuclear and mononuclear cells, the formation of an erosive pannus, cartilage degradation, and fibrosis. As in human rheumatoid arthritis, a number of both pro- and anti-inflammatory cytokines are expressed in the joints of mice with collagen-induced arthritis, including tumor necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta, IL-6, IL-1Ra, IL-10, and transforming growth factor beta. The use transgenic and knockout strains of mice, as well as biological inhibitors, have revealed important pathological roles for multiple cytokines. Of these, TNFalpha emerged as a valid therapeutic target for rheumatoid arthritis and this led to the setting up of clinical trials of anti-TNFalpha antibody therapy. Three anti-TNFalpha biologics(infliximab, etanercept, and adalimumab) are now approved for use and TNFalpha blockade therefore represents an important advance in our ability to treat rheumatoid arthritis.


A framework for image segmentation using shape models and kernel space shape priors.
Segmentation involves separating an object from the background in a given image. The use of image information alone often leads to poor segmentation results due to the presence of noise, clutter or occlusion. The introduction of shape priors in the geometric active contour (GAC) framework has proved to be an effective way to ameliorate some of these problems. In this work, we propose a novel segmentation method combining image information with prior shape knowledge, using level-sets. Following the work of Leventon et al., we propose to revisit the use of PCA to introduce prior knowledge about shapes in a more robust manner. We utilize kernel PCA (KPCA) and show that this method outperforms linear PCA by allowing only those shapes that are close enough to the training data. In our segmentation framework, shape knowledge and image information are encoded into two energy functionals entirely described in terms of shapes. This consistent description permits to fully take advantage of the Kernel PCA methodology and leads to promising segmentation results. In particular, our shape-driven segmentation technique allows for the simultaneous encoding of multiple types of shapes, and offers a convincing level of robustness with respect to noise, occlusions, or smearing.


Sex-Specific Asymmetrical Attack Rates in Combined Sexual-Vectorial Transmission Epidemics.
In 2015-2016, South America went through the largest Zika epidemic in recorded history. One important aspect of this epidemic was the importance of sexual transmission in combination with the usual vectorial transmission, with asymmetrical transmissibilities between sexual partners depending on the type of sexual contact; this asymmetry manifested itself in data as an increased risk to women. We propose a mathematical model for the transmission of the Zika virus including sexual transmission via all forms of sexual contact, as well as vector transmission, assuming a constant availability of mosquitoes. From this model, we derive an expression for R 0 , which is used to study and analyze the relative contributions of the male to female sexual transmission route vis-à-vis vectorial transmission. We also perform Bayesian inference of the model's parameters using data from the 2016 Zika epidemic in Rio de Janeiro.


Clinical outcomes after anterior cruciate ligament injury: panther symposium ACL injury clinical outcomes consensus group.
A stringent outcome assessment is a key aspect for establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. The aim of this consensus statement was to establish what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used and at what follow-up time those outcomes should be assessed. To establish a standardized approach to assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, PA; USA, in June 2019. The group reached consensus on nine statements by using a modified Delphi method. In general, outcomes after ACL treatment can be divided into four robust categories-early adverse events, patient-reported outcomes, ACL graft failure/recurrent ligament disruption and clinical measures of knee function and structure. A comprehensive assessment following ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained re-injuries, validated knee-specific PROs and Health-Related Quality of Life questionnaires. In the mid- to long-term follow-up, the presence of osteoarthritis should be evaluated. This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment. V.


Targeting Arousal and Sleep through Noninvasive Brain Stimulation to Improve Mental Health.
Arousal and sleep represent fundamental physiological domains, and alterations in the form of insomnia (difficulty falling or staying asleep) or hypersomnia (increased propensity for falling asleep or increased sleep duration) are prevalent clinical problems. Current first-line treatments include psychotherapy and pharmacotherapy. Despite significant success, a number of patients do not benefit sufficiently. Progress is limited by an incomplete understanding of the -neurobiology of insomnia and hypersomnia. This work summarizes current concepts of the regulation of arousal and sleep and its modulation through noninvasive brain stimulation (NIBS), including transcranial magnetic, current, and auditory stimulation. Particularly, we suggest: (1) characterization of patients with sleep problems - across diagnostic entities of mental disorders - based on specific alterations of sleep, including alterations of sleep slow waves, sleep spindles, cross-frequency coupling of brain oscillations, local sleep-wake regulation, and REM sleep and (2) targeting these with specific NIBS techniques. While evidence is accumulating that the modulation of specific alterations of sleep through NIBS is feasible, it remains to be tested whether this translates to clinically relevant effects and new treatment developments.


Multi-box mass balance model of PFOA and PFOS in different regions of San Francisco Bay.
We present a model to predict the long-term distribution and concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in estuaries comprising multiple intercommunicated sub-embayments. To that end, a mass balance model including rate constants and time-varying water inputs was designed to calculate levels of these compounds in water and sediment for every sub-embayment. Subsequently, outflows and tidal water exchanges were used to interconnect the different regions of the estuary. To calculate plausible risks to population, outputs of the model were used as inputs in a previously designed model to simulate concentrations of PFOA and PFOS in a sport fish species (Cymatogaster aggregata). The performance of the model was evaluated by applying it to the specific case of San Francisco Bay, (California, USA), using 2009 sediment and water sampled concentrations of PFOA and PFOS in North, Central and South regions. Concentrations of these compounds in the Bay displayed exponential decreasing trends, but with different shapes depending on region, compound, and compartment assessed. Nearly stable PFOA concentrations were reached after 50 years, while PFOS needed close to 500 years to stabilize in sediment and fish. Afterwards, concentrations stabilize between 4 and 23 pg/g in sediment, between 0.02 and 44 pg/L in water, and between 7 and 104 pg/g wet weight in fish, depending on compound and region. South Bay had the greatest final concentrations of pollutants, regardless of compartment. Fish consumption is safe for most scenarios, but due to model uncertainty, limitations in monthly intake could be established for North and South Bay catches.


Rotational Stability and Visual Outcomes of V4c Toric Phakic Intraocular Lenses.
To investigate the clinical outcomes and rotational stability following implantation of V4c toric implantable collamer lenses (ICLs) (STAAR Surgical Company, Monrovia, CA) and to analyze the factors that influence rotational stability. In this prospective observational case series, the authors analyzed the visual outcomes and rotational stability in 52 eyes of 52 patients immediately and 3 and 6 months after implantation. Postoperative rotation was defined as the angle between the adjusted axis and alignment axis. Central vaulting of the ICL was measured in a non-accommodative state using Visante optical coherence tomography (Carl Zeiss Meditec, Jena, Germany). Vector analysis of refractive astigmatism was performed. Regression analysis was used to investigate the association between the degree of rotation 6 months postoperatively and the associated variables. The mean efficacy index and safety index 6 months postoperatively were 1.35 ± 0.19 and 1.38 ± 0.22, respectively. In vector analysis, the magnitude of error was -0.20 diopters (D), indicating slight undercorrection. Absolute degree of rotation was 2.81° ± 1.87° immediately after the operation and 3.75° ± 2.92° and 3.87° ± 3.07° at 3 and 6 months postoperatively, respectively (P = .009). Bonferroni-adjusted post-hoc comparison showed that the absolute degree of rotation immediately after the operation was significantly smaller than that after 3 (P = .043) and 6 (P = .023) months, with barely any change after 3 months. No explanatory variable relevant to the absolute degree of rotation was discovered. The V4c toric ICL is predictable, safe, and effective in correcting low and high levels of astigmatism, showing relatively good postoperative rotational stability. [J Refract Surg. 2018;34(7):489-496.].


Implant treatment of patients with edentulous jaws: a 20-year follow-up.
Implant-supported prostheses are today often used in rehabilitation of partially or totally edentulous patients. Both patients and the dental profession often regard implant treatment as successful in a life perspective. Therefore, studies with a long-term follow-up are important. The aim was to investigate the outcome of implant treatment with fixed prostheses in edentulous jaws after 20 years, with special reference to survival rate of implants and prostheses and frequency of peri-implantitis. The patient material was a group of patients treated in the early 1980s. The original patient group comprised the first 48 consecutive patients treated with implant-supported prostheses at Umeå University. All patients were edentulous in one or two jaws. The patients had a mean age at the implant insertion of 54.3 years (range 40-74). At the planning of this study 20 years after treatment, 19 of the 48 patients were found to be deceased. Of the 29 patients still alive, 21 patients with altogether 23 implant-supported prostheses could be examined clinically and radiographically. All patients were treated ad modum Brånemark (Nobel Biocare AB, Göteborg, Sweden) with a two-stage surgical procedure. The implants had a turned surface. Abutment connections were performed 3 to 4 months after fixture insertion in the mandible, and after a minimum of 6 months in the maxilla. The prostheses were fabricated with a framework of gold alloy and acrylic artificial teeth. The 21 patients (with 23 implant prostheses) examined had at the time of treatment got 123 implants (27 in the upper jaw and 96 in the lower jaw) inserted. Only one of these implants had been lost (about 2 years after loading) giving a survival rate of 99.2%. Very small changes occurred in the marginal bone level. Between the 1 and 20-year examinations, the mean bone loss was 0.53 mm and the mean bone level at the final examination was 2.33 mm below the reference point. This follow-up over two decades of implant-supported prostheses demonstrates a very good prognosis for the treatment performed. The frequencies of peri-implantitis, implant failures, or other complications were very small, and the original treatment concept with a two-stage surgery and a turned surface of the implants will obviously give very good results.


Horizontal and vertical diversity jointly shape food web stability against small and large perturbations.
The biodiversity of food webs is composed of horizontal (i.e. within trophic levels) and vertical diversity (i.e. the number of trophic levels). Understanding their joint effect on stability is a key challenge. Theory mostly considers their individual effects and focuses on small perturbations near equilibrium in hypothetical food webs. Here, we study the joint effects of horizontal and vertical diversity on the stability of hypothetical (modelled) and empirical food webs. In modelled food webs, horizontal and vertical diversity increased and decreased stability, respectively, with a stronger positive effect of producer diversity on stability at higher consumer diversity. Experiments with an empirical plankton food web, where we manipulated horizontal and vertical diversity and measured stability from species interactions and from resilience against large perturbations, confirmed these predictions. Taken together, our findings highlight the need to conserve horizontal biodiversity at different trophic levels to ensure stability.


The refined crystal structure of Bacillus cereus oligo-1,6-glucosidase at 2.0 A resolution: structural characterization of proline-substitution sites for protein thermostabilization.
The crystal structure of oligo-1,6-glucosidase (dextrin 6-alpha-glucanohydrolase, EC 18.104.22.168) from Bacillus cereus ATCC7064 has been refined to 2.0 A resolution with an R-factor of 19.6% for 43,328 reflections. The final model contains 4646 protein atoms and 221 ordered water molecules with respective root-mean-square deviations of 0.015 A for bond lengths and of 3.166 degrees for bond angles from the ideal values. The structure consists of three domains: the N-terminal domain (residues 1 to 104 and 175 to 480), the subdomain (residues 105 to 174) and the C-terminal domain (residues 481 to 558). The N-terminal domain takes a (beta/alpha)8-barrel structure with additions of an alpha-helix (N alpha6') between the sixth strand Nbeta6 and the sixth helix N alpha6, an alpha-helix (N alpha7') between the seventh strand Nbeta7 and the seventh helix N alpha7 and three alpha-helices (N alpha8', N alpha8" and N alpha8'" between the eighth strand Nbeta8 and the eighth helix N alpha8. The subdomain is composed of an alpha-helix, a three-stranded antiparallel beta-sheet, and long intervening loops. The C-terminal domain has a beta-barrel structure of eight antiparallel beta-strands folded in double Greek key motifs, which is distorted in the sixth strand Cbeta6. Three catalytic residues, Asp199, Glu255 and Asp329, are located at the bottom of a deep cleft formed by the subdomain and a cluster of the two additional alpha-helices N alpha8' and N alpha8" in the (beta/alpha)8-barrel. The refined structure reveals the locations of 21 proline-substitution sites that are expected to be critical to protein thermostabilization from a sequence comparison among three Bacillus oligo-1,6-glucosidases with different thermostability. These sites lie in loops, beta-turns and alpha-helices, in order of frequency, except for Cys515 in the fourth beta-strand Cbeta4 of the C-terminal domain. The residues in beta-turns (Lys121, Glu208, Pro257, Glu290, Pro443, Lys457 and Glu487) are all found at their second positions, and those in alpha-helices (Asn109, Glu175, Thr261 and Ile403) are present at their N1 positions of the first helical turns. Those residues in both secondary structures adopt phi and phi values favorable for proline substitution. Residues preceding the 21 sites are mostly conserved upon proline occurrence at these 21 sites in more thermostable Bacillus oligo-1,6-glucosidases. These structural features with respect to the 21 sites indicate that the sites in beta-turns and alpha-helices have more essential prerequisites for proline substitution to thermostabilize the protein than those in loops. This well supports the previous finding that the replacement at the appropriate positions in beta-turns or alpha-helices is the most effective for protein thermostabilization by proline substitution.


Refining a taxonomy for guideline implementation: results of an exercise in abstract classification.
To better understand the efficacy of various implementation strategies, improved methods for describing and classifying the nature of these strategies are urgently required. The aim of this study was to develop and pilot the feasibility of a taxonomy to classify the nature and content of implementation strategies. A draft implementation taxonomy was developed based on the Cochrane Effective Practice and Organisation of Care (EPOC) data collection checklist. The draft taxonomy had four domains (professional, financial, organisational and regulatory) covering 49 distinct strategies. We piloted the draft taxonomy by using it to classify the implementation strategies described in the conference abstracts of the implementation stream of the 2010 Guideline International Network Conference. Five authors classified the strategies in each abstract individually. Final categorisation was then carried out in a face-to-face consensus meeting involving three authors. The implementation strategies described in 71 conference abstracts were classified. Approximately 15.5% of abstracts utilised strategies that could not be categorised using the draft taxonomy. Of those strategies that could be categorised, the majority were professionally focused (57%). A total of 41% of projects used only one implementation strategy, with 29% using two and 31% three or more. The three most commonly used strategies were changes in quality assurance, quality improvement and/or performance measurement systems, changes in information and communication technology, and distribution of guideline materials (via hard-copy, audio-visual and/or electronic means). Further refinement of the draft taxonomy is required to provide hierarchical dimensions and granularity, particularly in the areas of patient-focused interventions, those concerned with audit and feedback and quality improvement, and electronic forms of implementation, including electronic decision support.


Infection with the insect virus Hz-2v alters mating behavior and pheromone production in female Helicoverpa zea moths.
The effect of Hz-2V virus infection on the reproductive physiology and behavior of infected Helicoverpa zea female moths was examined. In the absence of males, infected females exhibited calling behavior and called as often but for shorter periods on average than control females. As expected, control females mated with males for extend periods when they were present and did not call after mating, while virus-infected females made many frequent contacts with males and continued to call even after these contacts. Virus-infected females were found to produce five to seven times more pheromone than control females and attracted twice as many males as did control females in flight tunnel experiments. The ability of Hz-2V to alter the physiology and behavior of infected females observed here may serve to facilitate the transmission of virus in insect populations.


Decreased expression of heparin-binding epidermal growth factor-like growth factor as a newly identified pathogenic mechanism of antiphospholipid-mediated defective placentation.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays a role in blastocyst implantation and is down-regulated in preeclampsia and in hypertensive pregnancy disorders associated with defective extravillous trophoblast invasion. Defective placentation and severe preeclampsia are also features of the antiphospholipid syndrome (APS). The purpose of this study was to investigate whether abnormal HB-EGF expression plays a pathogenic role in antiphospholipid antibody (aPL)-mediated defective placentation. HB-EGF expression in placental tissue was evaluated by Western blotting and messenger RNA analysis in normal and APS placentae. Polyclonal IgG fractions or monoclonal beta(2)-glycoprotein I-dependent aPL and their respective controls were investigated for the following 4 features: their binding to human trophoblast monolayers, as determined by cell enzyme-linked immunosorbent assay (ELISA); their effect on HB-EGF expression by Western blotting in trophoblast cell extracts as well as by ELISA as a protein secreted in the culture supernatants; their inhibitory effect on in vitro trophoblast invasiveness, as evaluated by Matrigel assay; and their inhibitory effect on matrix metalloproteinase (MMP) levels, as measured by gelatin zymography. Experiments were also performed in the presence of serial concentrations of heparin or recombinant HB-EGF. Placental APS tissue displayed reduced expression of HB-EGF. Polyclonal and monoclonal aPL bound to trophoblast monolayers and significantly reduced the in vitro synthesis and secretion of HB-EGF. Heparin inhibited aPL binding and restored HB-EGF expression in a dose-dependent manner. Addition of recombinant HB-EGF reduced the in vitro aPL-induced inhibition of Matrigel invasiveness as well as MMP-2 levels. These preliminary findings suggest that the reduction of aPL-mediated HB-EGF represents an additional mechanism that is responsible for the defective placentation associated with APS and that heparin protects from aPL-induced damage by inhibiting antibody binding.


Comparison of pathogenic domains of rabies and African rabies-related lyssaviruses and pathogenicity observed in mice.
Several lyssavirus species occur in Africa (Rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus), displaying a high sequence diversity between isolates belonging to the same species. There is limited information about comparative pathogenesis of these African lyssaviruses and this precludes authoritative opinion on the potential public and veterinary health impact. In this study, an analysis of representative African lyssaviruses attempted to correlate viral genomic sequence similarities and differences with the corresponding pathogenic profiles observed in mice. The study demonstrated that the virus isolates evaluated could be lethal to mice when introduced intramuscularly and that different isolates of the same lyssavirus species differ in their virulence. Using real-time polymerase chain reaction (PCR), viral RNA was detected in brain tissue, but no viral RNA was detected in the salivary glands or blood of mice that succumbed to infection. Comparison of known pathogenic domains indicated that pathogenicity is likely to be dependent on multiple domains. Cumulatively, our results re-emphasised the realisation that the pathogenicity of a lyssavirus species cannot be deduced based on studies of only a single isolate of the species or a single pathogenic domain.


Smoke or fog? The usefulness of retrospectively reported information about smoking.
To investigate the reliability and validity of retrospectively reported information on smoking. Nationally representative retrospective data from longitudinal surveys and contemporaneous data from repeated cross-sectional surveys were used. Adult respondents to three of the four samples of the National Longitudinal Surveys Original Cohort 1966-68; the National Longitudinal Survey of Youth 1979; and various waves of the US National Health Interview Survey. Reliability was investigated by calculating kappa statistics for repeated measures of ever-smoking and annual-smoking status. Validity was investigated by comparing smoking prevalence rates generated by retrospective data with contemporaneously measured rates. Kappa statistics indicated the repeated measures of ever-smoking status show substantial agreement; repeated measures of annual-smoking status show moderate agreement. Retrospective reports on smoking behavior produced prevalence rates that match reasonably well with those from contemporaneous reports of smoking behavior. Retrospective data on smoking can be an important resource for tobacco addiction research.


The John Charnley Award: Redefining the Natural History of Osteoarthritis in Patients With Hip Dysplasia and Impingement.
Structural hip deformities including developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI) are thought to predispose patients to degenerative joint changes. However, the natural history of these malformations is not clearly delineated. (1) Among patients undergoing unilateral THA who have a contralateral hip without any radiographic evidence of hip disease, what is the natural history and progression of osteoarthritis in the native hip based on morphological characteristics? (2) Among patients undergoing unilateral THA who have a contralateral hip without any radiographic evidence of hip disease, what are the radiographic parameters that predict differential rates of degenerative change? We identified every patient 55 years of age or younger at our institution who received unilateral primary THA from 1980 to 1989 (n = 722 patients). Preoperative radiographs were reviewed on the contralateral hip and only hips with Tönnis Grade 0 degenerative change that had minimum 10-year radiographic followup were included. A total of 172 patients met all eligibility criteria with the following structural diagnoses: 48 DDH, 74 FAI, and 40 normal morphology, and an additional 6% (10 of the 172 patients) met all eligibility criteria but were lost to followup before the 10-year minimum. Mean age at the time of study inclusion was 47 years (range, 18-55 years), and 56% (91 of 162) of the patients in this study were female. Mean followup was 20 years (range, 10-35 years). Radiographic metrics, in conjunction with the review of two experienced arthroplasty surgeons, determined the structural hip diagnosis as DDH, FAI, or normal morphology. Every available followup AP radiograph was reviewed to determine progression from Tönnis Grade 0 to 3 until the time of last followup or operative intervention with THA. Survivorship was analyzed by Kaplan-Meier methodology, hazard ratios, and multistate modeling. Thirty-five patients eventually underwent THA: 16 (33%) DDH, 13 (18%) FAI, and six (15%) normal morphology. Degenerative change was most rapid in patients with DDH followed by FAI and normal morphology. Among patients who recently developed Tönnis 1 degenerative change, the probability of undergoing THA in 10 years based on hip morphology was approximately one in three for DDH and one in five for both FAI and normal morphology hips, whereas the approximate probability at 20 years was two in three for DDH and one in two for both FAI and normal morphology hips. The likelihood of radiographic degeneration was increased in patients with the following findings: femoral head lateralization > 8 mm, femoral head extrusion index > 0.20, acetabular depth-to-width index < 0.30, lateral center-edge angle < 25°, and Tönnis angle > 8°. Degenerative change occurred earliest in patients with DDH, whereas the natural history of patients with FAI was quite similar to structurally normal hips. However, patients with cam deformities and concomitant acetabular dysplasia developed osteoarthritis more rapidly. Although the results of this study cannot be directly correlated to highly active patients with FAI, these findings suggest that correction of FAI to a normal morphology may only minimally impact the natural history, especially if intervention takes place beyond Tönnis 0. Analysis of radiographic parameters showed that incremental changes toward dysplastic morphology increase the risk of degenerative change. Level III, prognostic study.


Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.
Post-ERCP pancreatitis is poorly understood. The goal of this study was to comprehensively evaluate potential procedure- and patient-related risk factors for post-ERCP pancreatitis over a wide spectrum of centers. Consecutive ERCP procedures were prospectively studied at 11 centers (6 private, 5 university). Complications were assessed at 30 days by using established consensus criteria. Pancreatitis occurred after 131 (6.7%) of 1963 consecutive ERCP procedures (mild 70, moderate 55, severe 6). By univariate analysis, 23 of 32 investigated variables were significant. Multivariate risk factors with adjusted odds ratios (OR) were prior ERCP-induced pancreatitis (OR 5.4), suspected sphincter of Oddi dysfunction (OR 2.6), female gender (OR 2.5), normal serum bilirubin (OR 1.9), absence of chronic pancreatitis (OR 1.9), biliary sphincter balloon dilation (OR 4.5), difficult cannulation (OR 3.4), pancreatic sphincterotomy (OR 3.1), and 1 or more injections of contrast into the pancreatic duct (OR 2.7). Small bile duct diameter, sphincter of Oddi manometry, biliary sphincterotomy, and lower ERCP case volume were not multivariate risk factors for pancreatitis, although endoscopists performing on average more than 2 ERCPs per week had significantly greater success at bile duct cannulation (96.5% versus 91.5%, p = 0.0001). Combinations of patient characteristics including female gender, normal serum bilirubin, recurrent abdominal pain, and previous post-ERCP pancreatitis placed patients at increasingly higher risk of pancreatitis, regardless of whether ERCP was diagnostic, manometric, or therapeutic. Patient-related factors are as important as procedure-related factors in determining risk for post-ERCP pancreatitis. These data emphasize the importance of careful patient selection as well as choice of technique in the avoidance of post-ERCP pancreatitis.


Heterogeneity in the developmental potential of motor neuron progenitors revealed by clonal analysis of single cells in vitro.
The differentiation of neural progenitors into distinct classes within the central nervous system occurs over an extended period during which cells become progressively restricted in their fates. In the developing spinal cord, Sonic Hedgehog (Shh) controls neural fates in a concentration-dependent manner by establishing discrete ventral progenitor domains characterized by specific combinations of transcription factors. It is unclear whether motor neuron progenitors can maintain their identities when expanded in vitro and whether their developmental potentials are restricted when exposed to defined extracellular signals. We have generated mice expressing the enhanced green fluorescent protein under the control of the Nkx6.1 promoter, enabling fluorescence-activated cell sorting (FACS), purification and culture of individual spinal progenitors at clonal density, and analysis of their progeny. We demonstrate that cells isolated after progenitor domains are established are heterogeneous with respect to maintaining their identity after in vitro expansion. Most Nkx6.1+ progenitors lose their ventral identity following several divisions in culture, whereas a small subset is able to maintain its identity. Thus, subtype-restricted progenitors from the Nkx6.1+ region are present in the ventral spinal cord, although at a lower frequency than expected. Clones that maintain a motor neuron identity assume a transcriptional profile characteristic of thoracic motor neurons, despite some having been isolated from non-thoracic regions initially. Exposure of progenitors to Bone Morphogenetic Protein-4 induces some dorsal cell type characteristics in their progeny, revealing that lineage-restricted progenitor subtypes are not fully committed to their fates. These findings support a model whereby continuous Shh signaling is required to maintain the identity of ventral progenitors isolated from the spinal cord, including motor neuron progenitors, after in vitro expansion. They also demonstrate that pre-patterned neural progenitors isolated from the central nervous system can change their regional identity in vitro to acquire a broader developmental potential.


Efficacy and safety of biodegradable collagen-glycosaminoglycan polymer as a material for scleral buckling.
To test the efficacy and safety of a biodegradable collagen-glycosaminoglycan (CG) polymer as the material for scleral buckling in rabbit eyes. Segmental scleral buckling was performed by using a silicone sponge in one eye and a biodegradable CG polymer in the other eye of 20 rabbits. Wound and conjunctival reactions were evaluated by external photographs 1 day and then every week after surgery. Echography was used to evaluate the extent of the buckling effect. Electroretinograms were used to evaluate the retinal function after scleral buckling. Histology and immunohistochemistry were used to check the tissue reaction and distribution of myofibroblasts during wound healing. Scanning electronic microscopy of buckling materials was used to analyze structural changes after episcleral implantation. Biodegradable collagen initially achieved a buckling effect comparable to a silicone sponge; the buckling effect decreased after 1 month. Within 8 to 12 weeks, the collagen was gradually absorbed. After implantation, the collagen matrix degraded, and the pore size decreased as a result of compression and degradation. In contrast, no major structural changes were observed in silicone sponges, except some cell debris, fibrin, and blood cells were detected inside the porous structure of the sponge. The inflammatory responses were comparable between sponge and collagen in most areas of peribuckling histology. In areas of degraded collagen, a foreign body reaction was observable. Electroretinography revealed no detectable difference in retinal function between control and experimental eyes. Biodegradable collagen was used effectively and safely as a material for scleral buckling.


Serum IL-10 as a marker of severe dengue infection.
Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in severe dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult dengue patients with varying severity of dengue infection. Serum IL-10 levels were determined in 259 of whom 40 had severe dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = -0.23, p = 0.0002) and lymphocyte counts (R = -0.29, p < 0.0001) but significantly and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01) and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did not have a good predictive value in discriminating those who were likely to develop SD (AUC = 0.66). Serum IFNγ levels were also significantly higher (p = 0.04) in patients with SD when compared to non SD. There was no difference (p = 0.34) in serum IFNα levels and serum MIF levels (p = 0.15) in patients with SD and non SD. Although serum IL-10 was significantly elevated in patients with SD it had a poor discriminatory value in identifying those with SD and non SD and therefore, is unsuitable to be used as a robust biomarker in this cohort.


A transposon-related palindromic repetitive sequence from C. elegans.
A family of transposon-like sequences in the C. elegans genome is described. This family, termed the Tc6 family, consists mostly of conserved, 1.6 kb elements. Four Tc6 elements or partial elements have been cloned and the DNA sequences of three were determined. One appears to be a complete element of 1603 nucleotides, consisting of a palindrome of 765 nucleotides, with a central, non-palindromic region of 73 nucleotides. Another has an identical structure except for an internal deletion. A third is a partial element terminating at a probable internal restriction site used for cloning. A fourth clone contained portions of the Tc6 sequence juxtaposed to non-Tc6 sequences. All C. elegans strains examined contain 20-30 Tc6 elements. The ends of Tc6 elements are conserved and have sequence similarity to the ends of C. elegans transposons Tc1 and Tc3. The ends of Tc6 elements also have sequence similarity to the heptamer portion of the immunoglobulin and T-cell receptor recombination signal sequence, raising the possibility of wide phylogenetic conservation of the recombination mechanism. Tc6 elements also share sequence motifs with plant-pathogenic viroid RNA's, possibly indicative of a Tc6 RNA replicative phase.


Sublethal concentrations of ichthyotoxic alga Prymnesium parvum affect rainbow trout susceptibility to viral haemorrhagic septicaemia virus.
Ichthyotoxic algal blooms are normally considered a threat to maricultured fish only when blooms reach lethal cell concentrations. The degree to which sublethal algal concentrations challenge the health of the fish during blooms is practically unknown. In this study, we analysed whether sublethal concentrations of the ichthyotoxic alga Prymnesium parvum affect the susceptibility of rainbow trout Oncorhynchus mykiss to viral haemorrhagic septicaemia virus (VHSV). During exposure to sublethal algal concentrations, the fish increased production of mucus on their gills. When fish were exposed to the algae for 12 h prior to the addition of virus, a marginal decrease in the susceptibility to VHSV was observed compared to fish exposed to VHSV without algae. If virus and algae were added simultaneously, inclusion of the algae increased mortality by 50% compared to fish exposed to virus only, depending on the experimental setup. We concluded that depending on the local exposure conditions, sublethal concentrations of P. parvum could affect susceptibility of fish to infectious agents such as VHSV.


Prescaled phase-locked loop using phase modulation and spectral filtering and its application to clock extraction from 160-Gbit/s optical-time-division multiplexed signal.
We propose a prescaled phase-locked loop (PLL) using a simple optoelectronic phase comparator based on phase modulation and spectral filtering. Our phase comparator has a high dynamic range of over 9 dB and a high sensitivity comparable to that using an electrical mixer. A PLL composed of our phase comparator enables to extract a low-noise 10-GHz clock from a 160-Gbit/s optical-time-division multiplexed (OTDM) signal.


Continuing Professional Development via Social Media or Conference Attendance: A Cost Analysis.
Professional development is essential in the health disciplines. Knowing the cost and value of educational approaches informs decisions and choices about learning and teaching practices. The primary aim of this study was to conduct a cost analysis of participation in continuing professional development via social media compared with live conference attendance. Clinicians interested in musculoskeletal care were invited to participate in the study activities. Quantitative data were obtained from an anonymous electronic questionnaire. Of the 272 individuals invited to contribute data to this study, 150 clinicians predominantly from Australia, United States, United Kingdom, India, and Malaysia completed the outcome measures. Half of the respondents (78/150, 52.0%) believed that they would learn more with the live conference format. The median perceived participation costs for the live conference format was Aus $1596 (interquartile range, IQR 172.50-2852.00). The perceived cost of participation for equivalent content delivered via social media was Aus $15 (IQR 0.00-58.50). The majority of the clinicians (114/146, 78.1%, missing data n=4) indicated that they would pay for a subscription-based service, delivered by social media, to the median value of Aus $59.50. Social media platforms are evolving into an acceptable and financially sustainable medium for the continued professional development of health professionals. When factoring in the reduced costs of participation and the reduced loss of employable hours from the perspective of the health service, professional development via social media has unique strengths that challenge the traditional live conference delivery format.


Experimental infection of calves with two strains of bovine virus diarrhoea virus: virus recovery and clinical reactions.
Fifteen calves were inoculated with a mixture of two strains of bovine virus diarrhoea virus (BVDV), the cytopathogenic NADL strain which had been passaged over 20 times n vitro, and the non-cytopathogenic FCS strain, passaged only once after isolation from fetal calf serum. In a second experiment, seven calves received the NADL strain, and eight the FCS strain. The clinical and virological results of the two experiments were compared. In dual infections, the NADL strain interfered with the replication of the FCS strain resulting in less severe disease than the FCS strain alone. The FCS-BVDV was recovered from nasopharyngeal swabs and buffy coat cells whereas the NADL-BVDV was recovered only from nasopharyngeal swabs. The cytopathogenicity of the two strains did not change after passage in vivo. The differences observed are discussed in relation to cultural history and cytopathogenicity.


Incorporation of steroidogenic pathways which produce cortisol and aldosterone from cholesterol into nonsteroidogenic cells.
Cortisol production from cholesterol requires the activity of four steroid hydroxylases: cholesterol side chain cleavage cytochrome P-450 (P-450scc), 17 alpha-hydroxylase cytochrome P-450 (P-45017 alpha), 21-hydroxylase cytochrome P-450 (P-450C21) and 11 beta-hydroxylase cytochrome P-450 (P-45011 beta). We have previously shown that transformed, nonsteroidogenic COS 1 cells derived from monkey kidney are a useful system for expression of various forms of cytochrome P-450. The present study shows that COS 1 cell cultures multiply transfected with six plasmids containing all four steroid hydroxylases, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta HSD) and adrenodoxin produce cortisol and aldosterone when 22(R)-hydroxycholesterol is supplied to the system. When pregnenolone is used as substrate, various intermediate metabolites are detected at different time points further establishing the incorporation of complete functional steroidogenic pathways into the nonsteroidogenic cell cultures. Since the first and the last reactions in these pathways take place in the mitochondrion, the movement of various intermediate metabolites from mitochondrion to endoplasmic reticulum and back to mitochondrion occurs in and between COS 1 cells.


Burnout Prevalence and Associated Factors Among Brazilian Medical Students.
This study aims to identify the prevalence of burnout and associated factors in Brazilian medical students. In the largest medical school from Central Brazil, the Maslach Burnout Inventory-Student Survey and a socio-demographic questionnaire were adopted in this cross-sectional study. Correlations among the three dimensions of burnout were verified. The evaluation of 399 students revealed a frequency of 12.0% of burnout. Women had a higher rate of burnout (8.0%) than men (4.0%). The fifth period had the higher frequency of burnout (27.1%), while the seventh grade had the lower frequency (2.1%). The students showed high scores only in emotional exhaustion (63.2%). Between the dimensions "emotional exhaustion" and "disbelief" found a significant correlation. The fifth period of the Medicine course and the female gender are the most affected by burnout syndrome and therefore, the preventive actions to reduce stress among medical students should be directed mainly at these higher risk categories. The low burnout rate found in our study can attest that the PBL methodology and medical schools strategically located to meet regional demand may represent strategies for the prevention of burnout among medical students.


Assessment of PLGA-PEG-PLGA copolymer hydrogel for sustained drug delivery in the ear.
Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEGPLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications.


Rho and Rac exert antagonistic functions on spreading of macrophage-derived multinucleated cells and are not required for actin fiber formation.
Multinucleated giant cells (MNGC) derived from avian blood monocytes present, like osteoclasts, an unusual cytoskeletal organization characterized by (1) cortical rings of actin filaments, (2) unique adhesion structures called podosomes and (3) vinculin containing focal complexes which are not visibly connected to F-actin structures. The Rho family of small GTPases plays an essential role in the regulation and organization of cellular cytoskeletal structures including F-actin and vinculin associated structures. Using bacterial toxins such as modified exoenzyme C3 (C3B) and toxin B or overexpression of constitutively active Rac and Rho proteins fused to the green fluorescent protein (GFP), we show that Rac and Rho play antagonistic roles in regulating the morphology of osteoclast-like cells. Inhibition of Rho by C3B triggered MNGC spreading whereas activated Rho promoted cell retraction. However, inhibition or activation of Rho led to complete disorganization of fibrillar actin structures, including podosomes. Toxin B inhibition of Rho, Rac and Cdc42 induced a time dependent F-actin and vinculin reorganization. Initially, actin fibers with associated adhesion plaques formed and disappeared subsequently. Finally, only small focal complexes remained at the MNGC periphery before retracting. At the time when actin fibers formed, we observed that Rac was already inhibited by toxin B. By combining C3B treatment and overexpression of a dominant negative form of Rac (N17Rac), we show that the formation of these focal adhesion and actin fiber structures required neither Rho nor Rac activity. Moreover, our results show that podosomes are extremely unstable structures since any modifications of Rho or Rac activity resulted in their dissociation.


The role of cardiac autonomic function in hypertension and cardiovascular disease.
Autonomic nervous system abnormality, clinically manifested as a hyperkinetic circulation characterized by elevations in heart rate, blood pressure, plasma norepinephrine levels, and cardiac output, has been repeatedly demonstrated in hypertension. Increased release of norepinephrine from the brain has also been described in hypertension, and increased sympathetic activity has been demonstrated using spectral analysis of heart rate variability, particularly in the early stage of hypertension and in white-coat hypertension. Studies performed with microneurographic assessment also have found a marked increase in muscle sympathetic nervous activity in subjects with both borderline and established hypertension. A transition from the early hyperkinetic state to a high-resistance, established hypertension has been documented in longitudinal studies. The high blood pressure induces vascular hypertrophy, which in turn leads to increased vascular resistance. Cardiac output returns from elevated to normal values as beta-adrenergic receptors are downregulated and stroke volume decreases. In parallel with the hemodynamic transition, the sympathetic tone is reset in the course of hypertension. Autonomic nervous system abnormality is also associated with such pressure-unrelated cardiovascular risk factors as tachycardia, high hematocrit, insulin resistance, and obesity. Mechanisms of this association are discussed.


Development and Validation of the Social Network Addiction Scale (SNAddS-6S).
The use of social networks has increased exponentially, especially among youth. These tools offer many advantages but also carry some risks such as addiction. This points to the need for a valid multifactorial instrument to measure social network addiction, focusing on the core components of addiction that can serve researchers and practitioners. This study set out to validate a reliable multidimensional social network addiction scale based on the six core components of addiction (SNAddS-6S) by using and adapting the Bergen Facebook Addiction Scale. A total of 369 users of social networks completed a questionnaire. Exploratory and confirmatory factor analyses were performed, and different competing models were explored. The external validity of the scale was tested across its relations with different measures. Evidence for the validity and reliability of both the multidimensional SNAddS-6S and the unidimensional Short SNAddS-6S was provided. The SNAddS-6S was composed of 18 items and five different factors (time-management, mood modification, relapse, withdrawal, and conflict), with the time-management factor as a higher-order factor integrated by salience and tolerance as sub-factors. The Short SNAddS-6S was composed of six items and a unifactorial structure. This scale could be of relevance for researchers and practitioners to assess the extent to which individuals suffer from social network addiction and to study the potential predictors and risks of such addiction.


A Prospective Evaluation of the Accuracy of Weight Estimation Using the Broselow Tape in Overweight and Obese Pediatric Patients in the Emergency Department.
The aims of the study were to examine the predictive accuracy of Broselow tape (BT) weight estimation and body mass index-based weight categorization in overweight and obese pediatric patients and to develop an adjustment factor that improves the BT weight estimate in overweight and obese pediatric patients. A prospective observational study was conducted. We enrolled noncritical pediatric patients presenting to a tertiary care pediatric emergency department with nonurgent complaints. Patients had their weights, heights, abdominal circumferences, and actual BT measurements documented by research staff. One hundred seventy-eight patients aged 2 to 18 years were enrolled. Using the Centers for Disease Control and Prevention's definition of body mass index classification, 71 patients (39.89%) had normal BMI, 43 patients (24.16%) were overweight, and 64 patients (35.96%) were obese. The accuracy of the BT-estimated weight range, compared with the actual weight, is 40.5% in our study population. When stratified by BMI classification, the accuracy proportions were the following: 71.8% for normal, 41.9% for overweight, and 4.7% for obese patients. The adjustment formula ([0.014 × waistline in cm + 0.3] × BT weight) improved overall weight estimation from 40.5% to 65.2%. The greatest improvement was noted in obese children, where the BT accuracy improved from 4.7% to 59.4%. The growing pediatric obesity epidemic has challenged the BT's ability to accurately estimate the weights in overweight and obese pediatric patients. Our study demonstrated inverse relationship between the accuracy of BT and body weight. An adjustment factor significantly improved BT accuracy in obese children.


Inhibition patterns of a model complex mimicking the reductive half-reaction of sulphite oxidase.
Different inhibition types of the saturation kinetics involving a synthesized model complex, [Bu4N]3[MoVIO2(mnt)2] (E) (where mnt2- = 1,2-dicyanoethylenedithiolate), and HSO3- as the substrate (S) by structurally similar anions SO4(2-), H2PO4- and H2PO3- have been shown for the first time in relevance to the reductive half reaction of the native enzyme sulphite oxidase. SO4(2-) acts as a competitive inhibitor. The mixed-type non-competitive inhibition by H2PO4- and the sigmoidal-type inhibition by H2PO3- are explained by a diamond-configuration random-order model. This involves a random binding sequence of the substrate and the inhibitor, and forms, in addition to two binary complexes [enzyme-substrate (ES) and enzyme-inhibitor (EI)], one enzyme-substrate-inhibitor-type ternary complex (ESI) by participation of at least one more binding site in addition to the catalytic site. This is possible in the present case only by co-ordination enhancement of molybdenum in E. This co-ordination expansion is brought about by nucleophilic attack of the substrate or the inhibitor at the molybdenum, forming a hepta-coordinated binary complex with the generation of an oxoanionic functional site, called the allosteric site. Analysis of the experimental data suggests that the inhibition by H2PO4- is due to the mechanism following either equilibrium conditions or a combination of steady-state and equilibrium conditions. With H2PO3-, the inhibition is due to the mechanism following the steady-state conditions. It is also shown that the ternary complex involving the enzyme, substrate and H2PO4- or H2PO3- is productive, but at a lower rate than that of the enzyme-substrate binary complex. Mixed-type inhibition with H2PO4- is actually of the type called "partially mixed competitive and non-competitive' as the inhibitor binds both to the catalytic site and to the allosteric site. The sigmoidal-type inhibition by H2PO3- is similar to heterotropic allosteric effect of mixed V,K type with the distinction, however, that the significance of co-operativity in this case is of kinetic importance only.


Defects in courtship and vision caused by amino acid substitutions in a putative RNA-binding protein encoded by the no-on-transient A (nonA) gene of Drosophila.
The Drosophila no-on-transient A (nonA) gene is involved in the visual behaviors and courtship song of the fly. The NONA polypeptide contains two copies of the RNA-recognition motif (RRM), a hallmark of proteins involved in RNA binding, and an adjacent conserved charged region. This 311-amino-acid region is found in four other proteins and largely overlaps the Drosophila-Behavior/Human Splicing (or DBHS) domain. The newest family member, Drosophila nAhomo, was discovered in a database search, and encodes a protein with 80% identity to NONA. In this study, three nonA mutations generated by chemical mutagenesis were sequenced and found to fall within the conserved region. Site-directed mutagenesis of the two RRMs, and within a (conserved) charged region located C-terminal to them, was performed to determine the significance of these domains with respect to whole-organismal phenotypes. Behavior and viability were assessed in transformed flies, the genetic background of which lacks the nonA locus. Point mutations of amino acid 548 in the charged region confirmed the etiology of the nonAdiss courtship-song mutation and showed that a milder substitution at this site produced intermediate singing behavior, although it failed to rescue visual defects. Mutagenesis of the RRM1 domain resulted in effects on viability, vision, and courtship song. However, amino acid substitutions in RNP-II of RRM2 led to near-normal phenotypes, and the in vivo nonA mutations located in or near RRM2 caused visual defects only. Thus, we suggest that the first RRM could be important for all functions influenced by nonA, whereas the second RRM may be required primarily for normal vision.


Simplifying Tumor Volume Estimation from Linear Dimensions for Intra-Cranial Lesions Treated with Stereotactic Radiosurgery.
This study aims to derive simple yet robust formula(s) for the calculation of cranial tumor volume using linear tumor dimensions in anterioposterior (AP), mediolateral (ML) and craniocaudal (CC) directions and also propose a reproducible methodology for tumor dimension measurements. Magnetic resonance images (MRI) of 337 patients planned for Gammaknife Stereotactic Radiosurgery for different types of brain tumors were analyzed using Leksell Gamma Plan (LGP) software. Tumor volume in three dimensional was outlined and maximum tumor diameters were measured in three orthogonal directions AP, ML, and CC on the MRI. Formulas were derived to calculate tumor volume from AP, ML, and CC diameters using linear regression technique. An agreement between the calculated volume and standard volume observed from LGP software was determined using Bland Altman (B-A) plot. A comparison was made between the volume calculated using traditionally used formula of ellipsoid, standard volume obtained from LGP software and volume calculated from formulas derived in the present study. The tumors were divided into two categories based on their size for better volume prediction. The tumors having product of their diameters in the range 0-2.5cc were called "small tumors" and the formula proposed for their volume estimation (V = 1.513) × (AP × ML × CC) + 0.047 ) was found to predict the tumor volume with an average bias of 0.0005cc. For "large tumors," having product of diameters in the range 2.5-36cc, the proposed formula (V = 0.444 × (AP × ML × CC) + 0.339 ) predicted the tumor volume with an average bias of 0.007cc. The two formulas proposed in the study are more accurate as compared to the commonly used formula that considers the tumors as ellipsoids. The methodology proposed in the study for measurement of linear tumor dimensions is simple and reproducible.


Whispers, echoes, friends and fears: forms and functions of voice-hearing in adolescence.
Despite the high prevalence of voice-hearing in childhood, research with adolescents aged under 16 years is scarce. Theoretical connections between clinical and developmental conceptualizations of voice-hearing are limited, resulting in missed opportunities to explore unusual sensory experiences with young people. Demographic, contextual and qualitative data were collected through a web-based survey with 68 adolescents (M = 14.91; SD = 2.77) from Australia, Canada, Ireland, New Zealand, Spain, the United Kingdom and United States of America. A Foucauldian-informed narrative analysis captured phenomenologically meaningful individual accounts and systemically informed narratives. Analytic layers attended specifically to the form and function of voices, including relational, protective, distressing and nuanced experiences, offering new insights into individual, systemic and cultural interpretative narratives surrounding voice-hearing to inform research, policy and tailored support. The average self-reported age of onset of voices was 9 years, 5 months. Reciprocal relationships with pleasant voices were evidenced through the narratives and characterization of voices, while distressing voices were described without reciprocity and the voices held greater power over the young person. Positive aspects of negative voices were discussed and are illustrated with a continuum matrix reflecting interpretation and related affect. Voice-hearing is a heterogeneous and often complex relational experience for young people, with structural inequalities, relational traumas and social isolation attributed causes of voice-hearing. Developing personal meaning-making mitigated voice-related distress through contextualizing the origin of the voices in past experiences, without attribution to mental illness. Recommendations are proposed for assessment, formulation and relational interventions that recognize the potential impact of the voice-child-other relationship upon psychosocial functioning and wellbeing.


Fabry-Perot optical binary switch for aircraft applications.
An optical binary switch for aircraft applications is demonstrated. A fiber Fabry-Perot interferometer (FFPI) bonded to a cantilever is used as the sensing element. A white-light interferometry system with two bulk Michelson interferometers sharing the same motor-driven translation stage is utilized to monitor the elongation of the FFPI. The system exhibits excellent linearity as a force sensor; the experimental results are in good agreement with theoretical calculated values. With a properly set threshold value, the system produces a binary output.


SAMP1/YitFc mouse strain: a spontaneous model of Crohn's disease-like ileitis.
The SAMP1/YitFc mouse strain represents a model of Crohn's disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Different from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/YitFc mice occurs spontaneously, without genetic, chemical, or immunological manipulation. In addition, SAMP1/YitFc mice possess remarkable similarities to the human condition with regard to disease location, histologic features, incidence of extraintestinal manifestations, and response to conventional therapies. SAMP1/YitFc mice also display a well-defined time course of a predisease state and phases of acute and chronic ileitis. As such, the SAMP1/YitFc model is particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic, established ileitis. In this review we summarize important contributions made by our group and others that uncover potential mechanisms in the pathogenesis of CD using this unique murine model of chronic intestinal inflammation.


A one-year prospective, randomized, placebo-controlled, quadruple-blinded, phase II safety pilot trial of combination therapy with interferon beta-1a and mycophenolate mofetil in early relapsing-remitting multiple sclerosis (TIME MS).
Mycophenolate mofetil (MMF) is an oral DNA base synthesis inhibitor with immunomodulatory effects on B cells, T cells, and macrophages. To conduct a safety and tolerability pilot study of interferon beta-1a (IFN-b1a) in combination with either placebo or oral MMF in multiple sclerosis (MS). Twenty-four treatment-naïve R-RMS patients participated in a one-year prospective, placebo-controlled, blinded, safety pilot clinical trial. Every patient injected weekly intramuscular interferon beta-1a. The cohort was then randomized (1 : 1) to either active oral MMF or identical-appearing placebo tablets. Clinical evaluations were assessed every 3 months, along with brain MRI scans performed at baseline and repeated every 60 days for one year. Comprehensive laboratory assessments were monitored for safety, along with adverse events. In this small pilot investigation, no differences were identified between the two treatment groups with respect to patient-reported adverse events, MRI metrics, or laboratory abnormalities. Notwithstanding these observations, and the limited number of patients treated, trends appeared to favor the combination therapy regimen. The combination treatment regimen of interferon beta-1a and MMF appeared to be well tolerated in this pilot study. Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of MMF in MS appears warranted.


Esophageal Pressure Measurements in Patients With Acute Respiratory Distress Syndrome.
Esophageal balloons are used in the respiratory monitoring of critical care patients. After the esophageal pressure is measured, the corresponding pleural pressure in the thorax can be projected, enabling lung-thorax compliance to be partitioned into chest-wall compliance and lung compliance. The esophageal balloon allows determination of transpulmonary pressures and a correspondingly individually tailored approach to respiratory care, such as patient-specific titration of positive end-expiratory pressure for patients with extrapulmonary acute respiratory distress syndrome. Esophageal balloon monitoring provides critical information for selecting ventilation strategies to use in patients with acute respiratory distress syndrome.


Association of chronic divalproex sodium use and brain atrophy in Alzheimer's disease.
Divalproex sodium has been widely use for the treatment of bipolar disorder, behavioral control in schizophrenia, seizure and agitation in Alzheimer's disease. With the advent of other mood stabilizers and anticonvulsants, the use of divaplroex sodium has been slightly decreased; however, it has been a major mediation for the treatment of such medical conditions. Beyond symptomatic effects on such neuropsychiatric conditions, it has also been proposed to hold some neurotoxicity effects, including reversible brain atrophy (which may be a serious complication associated with substantial cognitive decline), although it has shown neuroprotective effects. Common adverse events include sedation, tiredness and gastrointestinal symptoms. According to a recent study, divalproex treatment was associated with accelerated brain volume loss over 1 year, which could possibly lead to greater cognitive impairment. Hence, this article will discuss clinical and further research implications of this study, as well as the potential limitations and significance of the research.


Polyphasic taxonomic analysis establishes Mycobacterium indicus pranii as a distinct species.
Mycobacterium indicus pranii (MIP), popularly known as Mw, is a cultivable, non-pathogenic organism, which, based on its growth and metabolic properties, is classified in Runyon Group IV along with M. fortuitum, M. smegmatis and M. vaccae. The novelty of this bacterium was accredited to its immunological ability to undergo antigen driven blast transformation of leukocytes and delayed hypersensitivity skin test in leprosy patients, a disease endemic in the Indian sub-continent. Consequently, MIP has been extensively evaluated for its biochemical and immunological properties leading to its usage as an immunomodulator in leprosy and tuberculosis patients. However, owing to advances in sequencing and culture techniques, the citing of new strains with almost 100% similarity in the sequences of marker genes like 16S rRNA, has compromised the identity of MIP as a novel species. Hence, to define its precise taxonomic position, we have carried out polyphasic taxonomic studies on MIP that integrate its phenotypic, chemotaxonomic and molecular phylogenetic attributes. The comparative analysis of 16S rRNA sequence of MIP by using BLAST algorithm at NCBI (nr database) revealed a similarity of > or =99% with M. intracellulare, M. arosiense, M. chimaera, M. seoulense, M. avium subsp. hominissuis, M. avium subsp. paratuberculosis and M. bohemicum. Further analysis with other widely used markers like rpoB and hsp65 could resolve the phylogenetic relationship between MIP and other closely related mycobacteria apart from M. intracellulare and M. chimaera, which shares > or =99% similarity with corresponding MIP orthologues. Molecular phylogenetic analysis, based on the concatenation of candidate orthologues of 16S rRNA, hsp65 and rpoB, also substantiated its distinctiveness from all the related organisms used in the analysis excluding M. intracellulare and M. chimaera with which it exhibited a close proximity. This necessitated further analysis of MIP with more sensitive and segregating parameters to ascertain its precise taxonomic position as a new species. The analysis of MIP and its comparison with other mycobacterial reference strains based on cellular and biochemical features, growth characteristics and chemotaxonomic studies like FAME profiling confirmed that MIP is uniquely endowed with diverse metabolic attributes that effectively distinguishes it from all the closely related mycobacteria including M. intracellulare and M. chimaera. The results presented in this study coupled with the non-pathogenic nature and different biochemical and immunomodulatory properties of MIP affirm it as a distinct species belonging to M. avium complex (MAC). It is further proposed to use an earlier suggested name Mycobacterium indicus pranii for this newly established mycobacterial species. This study also exemplifies the growing need for a uniform, consensus based broader polyphasic frame work for the purpose of taxonomy and speciation, particularly in the genus Mycobacterium.


Differential gene expression of TGF beta inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue.
TGF beta/Smad signaling pathway members are potent tumor suppressors for many types of cancers. We hypothesize that breast tumors differentially express these genes and that this expression pattern plays a role in the proliferation of breast cancer. We examined the mRNA levels of TIEG, Smad7, Smad2, and Bard1 using real-time RT/PCR in 14 normal breast, five non-invasive, 57 invasive (including 29 with outcome data), and five metastatic breast tumor tissues. TIEG and Smad7 mRNA levels were lower in non-invasive tumors compared to normal breast tissues. TIEG, Bard1, and Smad2 mRNA levels were lower in invasive cancers compared to normal breast tissues. In addition, TIEG, Smad2, and Bard1, provided discriminatory ability to potentially distinguish between normal and tumor samples, N- and N+ tumors, and N-/good (no recurrence for at least 5 years) and N-/bad (recurrence within 3 years) outcome patients. TIEG mRNA levels accurately discriminated between normal breast tissue and primary tumors with a sensitivity and specificity of 96 and 93%, respectively. TIEG, in combination with Smad2, distinguished between N+ and N- primary tumors with a sensitivity and specificity of 75 and 85%, respectively. TIEG in combination with Bard1 discriminated between N-/bad outcome from N-/good tumors with a sensitivity and specificity of 83 and 82%, respectively. Our results support the hypothesis that the differential gene expression of TIEG, Smad2, and Bard1, which are tumor suppressor genes, plays a significant role in the proliferation of breast cancer. Further investigation is necessary to validate the ability of these genes to discriminate between different populations of breast cancer patients.


Identification and characterization of an antigen I/II family protein produced by group A Streptococcus.
Group A Streptococcus (GAS) is a gram-positive human bacterial pathogen that causes infections ranging in severity from pharyngitis to life-threatening invasive disease, such as necrotizing fasciitis. Serotype M28 strains are consistently isolated from invasive infections, particularly puerperal sepsis, a severe infection that occurs during or after childbirth. We recently sequenced the genome of a serotype M28 GAS strain and discovered a novel 37.4-kb foreign genetic element designated region of difference 2 (RD2). RD2 is similar in gene content and organization to genomic islands found in group B streptococci (GBS), the major cause of neonatal infections. RD2 encodes seven proteins with conventional gram-positive secretion signal sequences, six of which have not been characterized. Herein, we report that one of these six proteins (M28_Spy1325; Spy1325) is a member of the antigen I/II family of cell surface-anchored molecules produced by oral streptococci. PCR and DNA sequence analysis found that Spy1325 is very well conserved in GAS strains of distinct M protein serotypes. As assessed by real-time TaqMan quantitative PCR, the Spy1325 gene was expressed in vitro, and Spy1325 protein was present in culture supernatants and on the GAS cell surface. Western immunoblotting and enzyme-linked immunosorbent assays indicated that Spy1325 was produced by GAS in infected mice and humans. Importantly, the immunization of mice with recombinant Spy1325 fragments conferred protection against GAS-mediated mortality. Similar to other antigen I/II proteins, recombinant Spy1325 bound purified human salivary agglutinin glycoprotein. Spy1325 may represent a shared virulence factor among GAS, GBS, and oral streptococci.


Saliency from orthogonal velocity component in texture segregation.
We found that a moving target line, more-vertical than 45 deg-oriented background lines, pops-out (d'=1.2) although it moves at the same speed of background elements and although it is invisible in static presentation (d'=.7). We suggest that the moving more-vertical target is more salient because the motion system responds to the orthogonal-velocity-component (V(perpendicular)=Delta d/Delta t sin theta) that is larger for the more-vertical target than for distracters. However, motion does not produce high d' when the target is more horizontal than background (d'=.6). This result is not expected if saliency resulted from the sum of saliency of orientation and motion independently coded but is instead predicted by visual search asymmetry. A line length effect on the moving target saliency also suggests that V(perpendicular) is extracted on the whole line and this operation is facilitated by line length in the same way for more-vertical and more-horizontal targets. Altogether, these results demonstrate that speed-based segmentation operating on V(perpendicular) not only affects speed and direction of motion discrimination, as previously demonstrated, but accounts for high saliency of image features that would otherwise prove undetectable of the basis of orientation-contrast.


Green Hope: Perspectives on Cannabis from People who Use Opioids.
While states are implementing policies to legalize cannabis for medical or recreational purposes, it remains a Schedule 1 controlled substance with no medical uses according to US federal law. The perception of cannabis depends on social and cultural norms that impact political institutions involved in implementing policy. Because of negative social constructions, such as the "gateway hypothesis," legalization of cannabis has been slow and contentious. Recent studies suggest that cannabis can help combat the opioid epidemic. This paper fills a gap in our understanding of how cannabis is viewed by people who are actively misusing opioids and not in treatment. Using ethnographic methods to recruit participants living in a state that legalized cannabis and a state where cannabis was illegal, survey and interview data were analyzed informed by a social constructionist lens. Findings from their "insider perspective" suggest that for some people struggling with problematic opioid use, cannabis can be beneficial.


Acute alcohol effects on attentional bias are mediated by subcortical areas associated with arousal and salience attribution.
Acute alcohol ingestion increases attentional bias to alcohol-related stimuli; however, the underlying cognitive and brain mechanisms remain unknown. We combined functional magnetic resonance imaging (fMRI) with performance of a dual task that probed attentional distraction by alcohol-related stimuli during 'conflict' processing: the Concurrent Flanker/Alcohol-Attentional bias task (CFAAT). In this task, an Eriksen Flanker task is superimposed on task-unrelated background pictures with alcohol-associated or neutral content. Participants respond to the direction of a central 'target' arrow and ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) 'flanking' arrows. Using a between-subject design, 40 healthy moderate-to-heavy social drinkers received either no alcohol (placebo), 0.4 g/kg (low dose), or 0.8 g/kg (high dose) of alcohol, and underwent fMRI while performing the CFAAT. The low alcohol dose, relative to placebo, increased response latencies on trials with alcohol-associated backgrounds and, under low cognitive load, increased the activity evoked by these pictures within a medial hypothalamic region. Under high cognitive load, the low alcohol dose, relative to placebo, elicited greater activity within a more lateral hypothalamic region, and reduced activity within frontal motor areas. The high alcohol dose, relative to placebo, did not reliably affect response latencies or neural responses to background images, but reduced overall accuracy under high cognitive load. This effect correlated with changes in reactivity within medial and dorsal prefrontal cortices. These data suggest that alcohol at a low dose primes attentional bias to alcohol-associated stimuli, an effect mediated by activation of subcortical hypothalamic areas implicated in arousal and salience attribution.


Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids.
The regulated expression of ADAMTS2 (a disintegrin and metalloproteinase with thrombospondin motifs), a secreted metalloproteinase involved in the processing of procollagen to collagen, was studied in peripheral blood mononuclear cells (PBMC). Stimulation with glucocorticoids (GC) resulted in a pronounced dose- and time-dependent increase of ADAMTS2 mRNA levels in PBMC. The increase of ADAMTS2 expression was specific for CD14++ monocytes (440-fold) and alveolar macrophages (200-fold), whereas CD3+ (T lymphocytes), phytohemagglutinin-activated CD3+ (T lymphocytes), and CD19+ (B lymphocytes) showed no significant changes in ADAMTS2 mRNA after GC treatment. Treatment of monocyte-derived macrophages (MDM) with GC also resulted in an increase of ADAMTS2 protein in the culture tissue media. Using the GC analog RU486, GC-mediated induction of ADAMTS2 mRNA was blocked, implicating that GC acts specifically via the GC-receptor. In agreement with findings in blood monocytes, cell lines of the monocytic lineage (MM6, THP-1) showed significant GC-induced significant increases in ADAMTS2 mRNA, while in epithelial cells (A549, Calu-3, Colo320, BT-20) and fibroblast (MRC-5, WI-38, and two NHDF-c cell types from adult cheek and upper arm), they showed no or little responsiveness to GC. As macrophages have important functions in immune defense and tissue homeostasis, these findings suggest that GC-mediated specific induction of ADAMTS2 in these cells may play a crucial role in the resolution of inflammation and wound repair.


Tandem trapped ion mobility spectrometry.
There is currently a strong interest in the use of ion mobility spectrometry-mass spectrometry (IMS-MS) instrumentation for structural biology. In these applications, momentum transfer cross sections derived from IMS-MS measurements are used to reconstruct the three-dimensional analyte structure. Recent reports indicate that additional structural information can be extracted from measuring changes in cross sections in response to changes of the analyte structure. To further this approach, we constructed a tandem trapped IMS analyser (TIMS-TIMS) and incorporated it in a QqTOF mass spectrometer. TIMS-TIMS is constructed by coupling two TIMS analysers via an "interface region" composed of two apertures. We show that peptide oligomers (bradykinin) and native-like protein (ubiquitin) ions can be preserved through the course of an experiment in a TIMS-TIMS analyser. We demonstrate the ability to collisionally-activate as well as to trap mobility-selected ions, followed by subsequent mobility-analysis. In addition to inducing conformational changes, we show that we can fragment low charge states of ubiquitin at >1 mbar between the TIMS analysers with significant sequence coverage. Many fragment ions exhibit multiple features in their TIMS spectra, which means that they may not generally exist as the most stable isomer. The ability of TIMS-TIMS to dissociate mobility-selected protein ions and to measure the cross sections of their fragment ions opens new possibilities for IMS-based structure elucidation.


Role of perceived neighbourhood crime in the longitudinal association between perceived built environment and type 2 diabetes mellitus: a moderated mediation analysis.
We examined to what extent perceived neighbourhood crime moderates, associations between type 2 diabetes mellitus (T2DM) and perceived local amenities, recreational facilities, footpaths and public transit, and potential mediation of environmental characteristics-T2DM association by physical activity, social contact, sleep and body mass index (BMI). The 45 and Up Study data of 36, 224 individuals collected from 2010 to 2015 were analysed in 2019 using multilevel logistic regression to examine the association between T2DM and clustering of unfavourable built environment, and any difference in the association with increasing unfavourable environment and area disadvantage. We performed causal mediation analyses stratified by crime to examine whether crime moderated the strength of identified local amenities-T2DM pathways. The results showed that irrespective of crime, perceived lack of local amenities was associated with increased odds of developing T2DM, and BMI mediated 40% and 30.3% of this association among those who reported unsafe and safe daytime crime, respectively. The proportion mediated by BMI among those who reported unsafe and safe night-time crime was 27.3% and 35.1%, respectively. Walking mediated 5.7% of the local amenities-T2DM association among those who reported safe daytime crime. The odds of T2DM increased with rising unfavourable environment and area disadvantage. The results suggest that the availability of neighbourhood amenities may lower T2DM risk by increasing walking and reducing BMI regardless of area crime. Policies to enhance access to local amenities and prevent crime, especially in disadvantaged areas, may support healthy behaviour and physical health that can potentially reduce T2DM risk.


Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach.
To perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes. Serum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography-mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD. We identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology. Our results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.


Ocular complications of oak processionary caterpillar setae in the Netherlands; case series, literature overview, national survey and treatment advice.
During early summer 2019, the Netherlands experienced an outbreak of the exotic oak processionary caterpillar. The vast number of caterpillars, which live in large nests on oak trees before they turn into moths, possess thousands of small, barbed hairs (setae) that are disseminated with the wind. The hairs cause a range of primarily dermatologic problems. However, Dutch ophthalmologists started reporting patients with ophthalmologic complaints caused by the penetrating hairs of the oak processionary caterpillar. This paper focuses on the ophthalmologic complications caused by the caterpillar hairs. We collected a series of four cases with reports ranging from a corneal erosion with hairs lodged into the cornea, to a sterile endophthalmitis in which hairs were found in the vitreous. A literature review for similar cases was performed using the PubMed and Embase database. Together with the Dutch Ophthalmic Society (Nederlands Oogheelkundig Gezelschap, NOG), a national survey was issued to determine the scale of this new problem. This showed that oak processionary caterpillar related complaints are primarily limited to the south of the Netherlands. Suggested ophthalmic treatment guidelines are presented. With the next summer at the doorstep, and limited preventative measures against the caterpillar hairs, we expect a new wave of ophthalmologic complaints coming year as well.


Living for the moment: men situating risk-taking after the death of a friend.
The primary cause of death for men under the age of 30 is unintentional injury and, despite health-promotion efforts and programme interventions, male injury and death rates have not decreased in recent years. Drawing on 22 interviews from a study of men, risk and grief, we describe how a risk-related tragedy shaped the participants' understandings of and practices of risk-taking. The findings indicate that most participants did not alter their perceptions and engagement in risky practices, which reflected their alignment to masculine ideals within specific communities of practice where risk-taking was normalised and valorised. Continued reliance on risky practices following the death of a friend was predominantly expressed as 'living for the moment,' where caution and safety were framed as conservative practices that undermined and diluted the robustness ideally embodied by this subgroup of young men. Two main themes: living life, accepting death and upping the ante illustrate how risk-taking can persist following a death. A smaller group of participants articulated a different viewpoint; reining in risk practices, to describe their risk management approaches after the death of a male friend. This novel study confirms the ongoing challenge of reducing men's risk-taking practices, even after the death of a friend.


Self-sampling for group B streptococcus in women 35 to 37 weeks pregnant is accurate and acceptable: a randomized cross-over trial.
In Canada, screening for group B Streptococcus (GBS) in pregnant women is recommended at 35 to 37 weeks' gestation. Since there is normally no other indication for pelvic examination at this stage of pregnancy, women may be more comfortable performing the test themselves. We assessed the accuracy of self- sampling versus clinician sampling for GBS and women's preference for each collection method. Consecutive patients presenting between October 2003 and April 2005 to a maternity centre in Hamilton for their 35- to 37-week prenatal visit were randomly allocated to having vaginal-rectal swabs self-collected, and then collected by a clinician, or to having the swabs clinician-collected, and then self-collected. The main outcomes were prevalence of infection and sensitivity of the two methods. Other analyses compared women who refused participation in the study with those who participated, and preference for sampling method before and after conducting the tests. Of the 386 women approached, 330 (85.5%) agreed to participate. The prevalence of GBS was 17.0% (56/330) and 18.8% (62/330) in the self-obtained and clinician-obtained specimens respectively (difference =1.8%; 95% confidence intervals [CI] -2.0-6.0). Sensitivity was 87.5% (95% CI 77.0-93.8) and 96.9% (95% CI 88.7-99.8) for the self-obtained and clinician-obtained specimens respectively. Women who declined to participate in self-sampling were significantly more likely not to have completed high school and to prefer clinician sampling. Prior to testing, 79% of women preferred self-sampling or had no preference. Preference was unchanged for approximately two-thirds of women after sampling. Self-sampling for GBS is an accurate and acceptable alternative for the majority of pregnant women. Less-educated women may be hesitant to self-sample, and clinician sampling should remain an option.


Patellar tendon rupture. The importance of timely recognition and repair.
Patellar tendon rupture is not uncommon in active adults, although it occurs less often than rupture of the ligaments. The diagnosis is easily missed on initial examination. Delay of surgical treatment leads to a complicated repair and a less functional outcome. The key physical finding is inability to actively extend the affected leg. Patients may also have severe, rapid swelling and depression in the infrapatellar region. The mechanism of injury usually involves forced hyperflexion or rapid extension from a weight-bearing position. Radiographic findings include patella alta and possible subluxation. This case report described an infrapatellar tendon rupture in a patient with no underlying systemic disease or history of repetitive trauma.


Circular dichroism spectra of cytochrome c oxidase.
Circular dichroism spectra of bovine heart aa(3)-type cytochrome c oxidase have been studied with a major focus on the Soret band π → π* transitions, B(0(x,y)), in the two iron porphyrin groups of the enzyme. The spectra of the fully reduced and fully oxidized enzyme as well as of its carbon monoxide and cyanide complexes have been explored. In addition, CD spectra of the reduced and oxidized ba(3)-type cytochrome c oxidase from Thermus thermophilus were recorded for comparison. An attempt is made to interpret the CD spectra of cytochrome c oxidase with the aid of a classical model of dipole-dipole coupled oscillators taking advantage of the known 3D crystal structure of the enzyme. Simultaneous modeling of the CD and absorption spectra shows that in the bovine oxidase, the dipole-dipole interactions between the hemes a and a(3), although contributing significantly, cannot account either for the lineshape or the magnitude of the experimental spectra. However, adding the interactions of the hemes with 22 aromatic amino acid residues located within 12 Å from either of the two heme groups can be used to model the CD curves for the fully reduced and fully oxidized oxidase with reasonable accuracy. Interaction of the hemes with the peptide bond transition dipoles is found to be insignificant. The modeling indicates that the CD spectra of cytochrome oxidase in both the reduced and oxidized states are influenced significantly by interaction with Tyr244 in the oxygen-reducing center of the enzyme. Hence, CD spectroscopy may provide a useful tool for monitoring the redox/ionization state of this residue. The modeling confirms wide energy splitting of the orthogonal B(x) and B(y) transitions in the porphyrin ring of heme a.


Phenotypic plasticity in response to nitrate supply of an inherently fast-growing species from a fertile habitat and an inherently slow-growing species from an infertile habitat.
The aim of the present study was to investigate possible differences in plasticity between a potentially fast-growing and a potentially slow-growing grass species. To this end, Holcus lanatus (L.) and Deschampsia flexuosa (L.) Trin., associated with fertile and infertile habitats, respectively, were grown in sand at eight nitrate concentrations. When plants obtained a fresh weight of approximately 5 g, biomass allocation, specific leaf area, the rate of net photosynthesis, the organic nitrogen concentration of various plant parts and the root weight at different soil depths were determined. There were linear relationships between the morphological and physiological features studied and the In-transformed nitrate concentration supplied, except for the specific leaf area and root nitrogen concentration of H. lanatus, which did not respond to the nitrate concentration. The root biomass of H. lanatus was invariably distributed over the soil layers than that of D. flexuosa. However, D. flexuosa allocated more root biomass to lower soil depths with decreasing nitrate concentration, in contrast to H. lanatus, which did not respond. The relative response to nitrate supply, i.e. the value of a character at a certain nitrate level relative to the value of that character at the highest nitrate supply, was used as a measure for plasticity. For a number of parameters (leaf area ratio, root weight ratio, root nitrogen concentration, vertical root biomass distribution and rate of net photosynthesis per unit leaf weight) the potentially slow-growing D. flexuosa exhibited a higher phenotypic plasticity than the potentially fast-growing H. lanatus. These findings are in disagreement with current literature. Possible explanations for this discrepancy are discussed in terms of differences in experimental approach as well as fundamental differences in specific traits between fast- and slow-growing grasses.


Transmission of Still Images Using Low-Complexity Analog Joint Source-Channel Coding.
An analog joint source-channel coding (JSCC) system designed for the transmission of still images is proposed and its performance is compared to that of two digital alternatives which differ in the source encoding operation: Joint Photographic Experts Group (JPEG) and JPEG without entropy coding (JPEGw/oEC), respectively, both relying on an optimized channel encoder-modulator tandem. Apart from a visual comparison, the figures of merit considered in the assessment are the structural similarity (SSIM) index and the time required to transmit an image through additive white Gaussian noise (AWGN) and Rayleigh channels. This work shows that the proposed analog system exhibits a performance similar to that of the digital scheme based on JPEG compression with a noticeable better visual degradation to the human eye, a lower computational complexity, and a negligible delay. These results confirm the suitability of analog JSCC for the transmission of still images in scenarios with severe constraints on power consumption, computational capabilities, and for real-time applications. For these reasons the proposed system is a good candidate for surveillance systems, low-constrained devices, Internet of things (IoT) applications, etc.


A first overview of textile fibers, including microplastics, in indoor and outdoor environments.
Studies about microplastics in various environments highlighted the ubiquity of anthropogenic fibers. As a follow-up of a recent study that emphasized the presence of man-made fibers in atmospheric fallout, this study is the first one to investigate fibers in indoor and outdoor air. Three different indoor sites were considered: two private apartments and one office. In parallel, the outdoor air was sampled in one site. The deposition rate of the fibers and their concentration in settled dust collected from vacuum cleaner bags were also estimated. Overall, indoor concentrations ranged between 1.0 and 60.0 fibers/m3. Outdoor concentrations are significantly lower as they range between 0.3 and 1.5 fibers/m3. The deposition rate of the fibers in indoor environments is between 1586 and 11,130 fibers/day/m2 leading to an accumulation of fibers in settled dust (190-670 fibers/mg). Regarding fiber type, 67% of the analyzed fibers in indoor environments are made of natural material, primarily cellulosic, while the remaining 33% fibers contain petrochemicals with polypropylene being predominant. Such fibers are observed in marine and continental studies dealing with microplastics. The observed fibers are supposedly too large to be inhaled but the exposure may occur through dust ingestion, particularly for young children.