In-flight corrections in free-flying barn owls (Tyto alba) during sound localization tasks.
Barn owls localize a stationary auditory target with high accuracy. They might also be able to hit a target that is intermittently moving while the owl is approaching. If so, there should be a critical delay before strike initiation, up to which the owl can adapt its flight path to a new stimulus position. In this study, this critical stimulus delay was determined in a three-dimensional free-flight paradigm. Barn owls localized a pulsed broadband noise while sitting on a perch in total darkness. This initial signal stopped with the owl's take-off and an in-flight stimulus (target sound), lasting 200 ms, was introduced at variable time delays (300-1200 ms) during the approximate flight time of 1300 ms. The owls responded to the in-flight signal with a corrective head and body turn. The percentage of trials in which correction turns occurred (40-80%) depended upon the individual bird, but was independent of the stimulus delay within a range of 800 ms after take-off. Correction turns strongly decreased at delays >or=800 ms. The landing precision of the owls, defined as their distance to the in-flight speaker, did not decrease with increasing stimulus delay, but decreased if the owl failed to perform a correction turn towards that speaker. Landing precision was higher for a short (50 cm) than for a large (100 cm) distance between the initial and the new target. Thus, the ability of barn owls to adapt their flight path to a new sound target depends on the in-flight stimulus delay, as well as on the distance between initial and novel targets.


Larval fish assemblages in selected Brazilian estuaries: Species-environment relationships under different anthropogenic influences.
We investigate the effects of spatial changes in environmental conditions and anthropogenic influences on larval fish communities in two tropical estuaries with varying levels of human impact. Our findings revealed a distinct structure of larval fish assemblages between the two estuaries located in northeastern Brazil, and we observed that eutrophication, characterized by high concentrations of nutrients, had adverse effects on the abundance and richness of larval fish assemblages. Additionally, we observed that a decrease in rainfall had an impact on larval fish assemblages, particularly during the dry season, when intermittent upstream rivers lead to changes in salinity and species composition within the estuaries. This study contributed to evaluating the community descriptors of two tropical estuaries under different levels of human influence, providing insights into the vulnerability of larval fish assemblages to climate change, specifically in relation to human influences and hypersalinity and the effects of marinization in shallow tropical estuaries in this region.


Designing phase 0 cancer clinical trials.
Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents before initiating more traditional phase I testing. One of the major objectives of phase 0 trials is to interrogate and refine a target or biomarker assay for drug effect in human samples implementing procedures developed and validated in preclinical models. Thus, close collaboration between laboratory scientists and clinical investigators is essential to the design and conduct of phase 0 trials. Given the relatively small number of patients and tissue samples, showing a significant drug effect in phase 0 trials requires precise and reproducible assay procedures and innovative statistical methodology. Furthermore, phase 0 trials involving limited exposure of a study agent administered at low doses and/or for a short period allow them to be initiated under the Food and Drug Administration exploratory investigational new drug guidance with less preclinical toxicity data than usually required for traditional first-in-human studies. Because of the very limited drug exposure, phase 0 trials offer no chance of therapeutic benefit, which can impede patient enrollment, particularly if invasive tumor biopsies are required. The challenges to accrual are not insurmountable, however, and well-designed and executed phase 0 trials are feasible and have great potential for improving the efficiency and success of subsequent trials, particularly those evaluating molecularly targeted agents.


Reducing liver function tests for statin monitoring: an observational comparison of two clinical commissioning groups.
Current liver function testing for statin monitoring is largely unnecessary and costly. Statins do not cause liver disease. Both reduction in test frequency and use of a single alanine transaminase (ALT) rather than a full seven analyte liver function test (LFT) array would reduce cost and may benefit patients. To assess LFT testing in relation to statin use and evaluate an intervention to reduce full-array LFTs ordered by GPs for statin monitoring. Two-year cross-sectional time series in two east London clinical commissioning groups (CCGs) with 650 000 patients. One CCG received the intervention; the other did not. The intervention comprised local guidance on LFTs for statin monitoring and access to a single ALT rather than full LFT array. Of the total population, 17.6% were on statins, accounting for 43.2% of total LFTs. In the population without liver disease, liver function tests were 3.6 times higher for those on statins compared with those who were not. Following intervention there was a significant reduction in the full LFT array per 1000 people on statins, from 70.3 (95% confidence interval [CI] = 66.3 to 74.6) in the pre-intervention year, to 58.1 (95% CI = 55.5 to 60.7) in the post-intervention year (P<0.001). In the final month, March 2016, the rate was 53.2, a 24.3% reduction on the pre-intervention rate. This simple and generalisable intervention, enabling ordering of a single ALT combined with information recommending prudent rather than periodic testing, reduced full LFT testing by 24.3% in people on statins. This is likely to have patient benefit at reduced cost.


The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone.
The embryonic subventricular zone (SVZ) is a critical site for generating cortical projection neurons; however, molecular mechanisms regulating neurogenesis specifically in the SVZ are largely unknown. The transcription factor Eomes/Tbr2 is transiently expressed in cortical SVZ progenitor cells. Here we demonstrate that conditional inactivation of Tbr2 during early brain development causes microcephaly and severe behavioral deficits. In Tbr2 mutants the number of SVZ progenitor cells is reduced and the differentiation of upper cortical layer neurons is disturbed. Neurogenesis in the adult dentate gyrus but not the subependymal zone is abolished. These studies establish Tbr2 as a key regulator of neurogenesis in the SVZ.


Binding of chloramphenicol and a fragment of aminoacyl-transfer ribonucleic acid to ribosomes and a ribosome precursor from a mutant of Escherichia coli.
During exponential growth, the mutatn strain Escherichia coli 15-28 accumulates 47S particles, which are unusual precursors to 50S ribosomal subunits. The 47S particles have little ability to bind chloramphenicol, but binding of a fragment of aminoacyl-tRNA is about half that by completed subunits. The 70S (and 50S) ribosomes of strain 15-28 and its parent (strain 15TP) do not differ in chloramphenicol binding. Although ribosomes from the mutant are less able than those from the parent to bind the fragment, this difference is not as marked as was found previously [Sims & Wild (1976) Biochem. J. 160, 721-726] for the binding of an analogue of peptidyl-tRNA and for peptidyltransferase activity. The altered activities may arise because strain 15-28 misassembles 50S subunits of altered conformation and because the few proteins that 47S patricles lack have vital functions in some of the partial reactions of protein synthesis.


IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients.
Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.


Modeling and inferring cleavage patterns in proliferating epithelia.
The regulation of cleavage plane orientation is one of the key mechanisms driving epithelial morphogenesis. Still, many aspects of the relationship between local cleavage patterns and tissue-level properties remain poorly understood. Here we develop a topological model that simulates the dynamics of a 2D proliferating epithelium from generation to generation, enabling the exploration of a wide variety of biologically plausible cleavage patterns. We investigate a spectrum of models that incorporate the spatial impact of neighboring cells and the temporal influence of parent cells on the choice of cleavage plane. Our findings show that cleavage patterns generate "signature" equilibrium distributions of polygonal cell shapes. These signatures enable the inference of local cleavage parameters such as neighbor impact, maternal influence, and division symmetry from global observations of the distribution of cell shape. Applying these insights to the proliferating epithelia of five diverse organisms, we find that strong division symmetry and moderate neighbor/maternal influence are required to reproduce the predominance of hexagonal cells and low variability in cell shape seen empirically. Furthermore, we present two distinct cleavage pattern models, one stochastic and one deterministic, that can reproduce the empirical distribution of cell shapes. Although the proliferating epithelia of the five diverse organisms show a highly conserved cell shape distribution, there are multiple plausible cleavage patterns that can generate this distribution, and experimental evidence suggests that indeed plants and fruitflies use distinct division mechanisms.


The exocyst is required for melanin exocytosis from melanocytes and transfer to keratinocytes.
Skin pigmentation involves the production of the pigment melanin by melanocytes, in melanosomes and subsequent transfer to keratinocytes. Within keratinocytes, melanin polarizes to the apical perinuclear region to form a protective cap, shielding the DNA from ultraviolet radiation-induced damage. Previously, we found evidence to support the exocytosis by melanocytes of the melanin core, termed melanocore, followed by endo/phagocytosis by keratinocytes as a main form of transfer, with Rab11b playing a key role in the process. Here, we report the requirement for the exocyst tethering complex in melanocore exocytosis and transfer to keratinocytes. We observed that the silencing of the exocyst subunits Sec8 or Exo70 impairs melanocore exocytosis from melanocytes, without affecting melanin synthesis. Moreover, we confirmed by immunoprecipitation that Rab11b interacts with Sec8 in melanocytes. Furthermore, we found that the silencing of Sec8 or Exo70 in melanocytes impairs melanin transfer to keratinocytes. These results support our model as melanocore exocytosis from melanocytes is essential for melanin transfer to keratinocytes and skin pigmentation and suggest that the role of Rab11b in melanocore exocytosis is mediated by the exocyst.


A collaborative backbone resource for comparative studies of subterranean evolution: The World Asellidae database.
Transition to novel environments, such as groundwater colonization by surface organisms, provides an excellent research ground to study phenotypic evolution. However, interspecific comparative studies on evolution to groundwater life are few because of the challenge in assembling large ecological and molecular resources for species-rich taxa comprised of surface and subterranean species. Here, we make available to the scientific community an operational set of working tools and resources for the Asellidae, a family of freshwater isopods containing hundreds of surface and subterranean species. First, we release the World Asellidae database (WAD) and its web application, a sustainable and FAIR solution to producing and sharing data and biological material. WAD provides access to thousands of species occurrences, specimens, DNA extracts and DNA sequences with rich metadata ensuring full scientific traceability. Second, we perform a large-scale dated phylogenetic reconstruction of Asellidae to support phylogenetic comparative analyses. Of 424 terminal branches, we identify 34 pairs of surface and subterranean species representing independent replicates of the transition from surface water to groundwater. Third, we exemplify the usefulness of WAD for documenting phenotypic shifts associated with colonization of subterranean habitats. We provide the first phylogenetically controlled evidence that body size of males decreases relative to that of females upon groundwater colonization, suggesting competition for rare receptive females selects for smaller, more agile males in groundwater. By making these tools and resources widely accessible, we open up new opportunities for exploring how phenotypic traits evolve in response to changes in selective pressures and trade-offs during groundwater colonization.


Utilization of the Department of Defense Peer-Reviewed Orthopaedic Research Program (PRORP): Combating Musculoskeletal Disease With PRORP.
Established in 2009, the Department of Defense (DoD) Peer-Reviewed Orthopaedic Research Program (PRORP) is an annual funding program for orthopaedic research that seeks to develop evidence for new clinical practice guidelines, procedures, technologies, and drugs. The aim was to help reduce the burden of injury for wounded Service members, Veterans, and civilians and to increase return-to-duty and return-to-work rates. Relative to its burden of disease, musculoskeletal injuries (MSKIs) are one of the most disproportionately underfunded conditions. The focus of the PRORP includes a broad spectrum of MSKI in areas related to unique aspect of combat- and some noncombat-related injuries. The PRORP may serve as an important avenue of research for nonmilitary communities by offering areas of shared interests for the advancement of military and civilian patient cohort MSKI care. The purpose of this study was to provide a descriptive analysis of the DoD PRORP, which is an underrecognized but high value source of research funding for a broad spectrum of both combat- and noncombat-related MSKIs. The complete PRORP Funding Portfolio for FY2009-FY2017 was obtained from the Congressionally Directed Medical Research Programs (CDMRP), which includes 255 awarded grants. Information pulled from the CDMRP included awardee descriptors (sex, education level, affiliated institution type, research specialty, and previous award winner [yes/no]) and grant award descriptors (grant amount, year, primary and secondary awarded topics, research type awarded, and mechanism of award). Distribution statistics were broken down by principal investigator specialty, sex, degree, organization type, research type, mechanism, and research topics. Distribution and statistical analysis was applied using R software version 3.6.3. From FY2009 to 2017, $285 million was allocated for 255 PRORP-funded research studies. The seven major orthopaedic subspecialties (foot and ankle, hand, musculoskeletal oncology, pediatrics, spine, sports medicine, and trauma) were represented. Trauma and hand subspecialists received the largest amount of funding, approximately $28 (9.6%) and $22 million (7.1%), respectively. However, only 22 (8.6%) and 26 (10.2%) of the primary investigators were trauma and hand subspecialists, respectively. The primary research categories were diverse with the top five funded PRORP topics being rehabilitation ($53 million), consortia ($39 million), surgery ($37 million), device development ($30 million), and pharmacology ($10 million). The CDMRP funding represents an excellent resource for orthopaedic medical research support that includes trauma and nontrauma orthopaedic conditions. This study serves to promote and communicate the missions of the PRORP both within and beyond the DoD to raise awareness and expand access of available funding for orthopaedic focused research. A likelihood exists that this project will provide sustained and powerful influence on future research by promoting awareness of orthopaedic funding sources. Level III.


Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin.
To define predictive parameters of long progression-free survival (PFS) in patients undergoing radioembolisation of neuroendocrine liver metastases. The following clinical and magnetic resonance imaging (MRI) parameters of 45 radioembolised patients (median age, 62 years; range, 43-75) were reviewed: age, gender, levels of chromogranin A and neuron-specific enolase (NSE), primary tumour site, Ki-67 proliferation index, hepatic tumour load, number of metastases, signal intensity characteristics, vascularisation, haemorrhagic and necrotic transformation and fluid-fluid levels. PFS was assessed according to RECIST 1.0. Statistical analysis included univariate Cox regression, Kaplan-Meier and multivariate regression. Median PFS was 727 days (95 % CI, 378-964). In the univariate regression analysis, hypovascular metastases progressed earlier (111 vs 727 days; P < 0.05). A Ki-67 ≤2 % was associated with a longer PFS than a Ki-67 of 3-20 % or >20 % (911 vs 727 vs 210 days, respectively; P < 0.05). Low NSE predicted longer PFS (911 vs 378 days; P < 0.05). In the adjusted multivariate analysis, vascularisation (hypervascularisation vs. no hypervascularisation; P = 0.0009) and NSE level (low vs high; P = 0.0119) had the strongest influence on PFS. Response to radioembolisation in patients with neuroendocrine liver metastases can be predicted by the metastatic vascularisation pattern, the NSE level and the Ki-67. • Radioembolisation is an effective treatment in hepatic metastases of neuroendocrine origin. • Pre-therapeutic vascularisation patterns of metastases on MRI can predict long progression-free survival. • Assessment of pre-therapeutic markers provides better therapy planning.


Acupuncture in dermatology: an historical perspective.
Classical acupuncture focuses primarily on treating the person, and secondarily treating the illness. The "symptoms" are regarded as "branch" expressions of a "root" (constitutional) imbalance. Different root imbalances can produce the same symptoms. Five patients with eczema, for example, may reveal five distinct root imbalances and would all be treated very differently. Because acupuncture treats the whole person, it has something to offer almost every condition. In many cases, acupuncture aims to bring about a complete cure; in others, it aims to manage the problem. Acupuncture remains a substantial part of the traditional Chinese medicine, which is used to treat many conditions including acne, alopecia, dermatitis, pruritus, psoriasis, rosacea, systemic lupus erythematosus, urticaria, herpes zoster, chicken pox, impetigo, leprosy, vitiligo, and tinea. This review introduces the historical context of acupuncture within Chinese medicine and how it relates to skin disease. Specifically, a key question is, what can we learn from the ancients with regard to their use of acupuncture as part of a holistic system of medicine, and how does this relate to the practice of modern dermatology?


Discovery of blue singlet exciton fission molecules via a high-throughput virtual screening and experimental approach.
Singlet exciton fission is a mechanism that could potentially enable solar cells to surpass the Shockley-Queisser efficiency limit by converting single high-energy photons into two lower-energy triplet excitons with minimal thermalization loss. The ability to make use of singlet exciton fission to enhance solar cell efficiencies has been limited, however, by the sparsity of singlet fission materials with triplet energies above the bandgaps of common semiconductors such as Si and GaAs. Here, we employ a high-throughput virtual screening procedure to discover new organic singlet exciton fission candidate materials with high-energy (>1.4 eV) triplet excitons. After exploring a search space of 4482 molecules and screening them using time-dependent density functional theory, we identify 88 novel singlet exciton fission candidate materials based on anthracene derivatives. Subsequent purification and characterization of several of these candidates yield two new singlet exciton fission materials: 9,10-dicyanoanthracene (DCA) and 9,10-dichlorooctafluoroanthracene (DCOFA), with triplet energies of 1.54 eV and 1.51 eV, respectively. These materials are readily available and low-cost, making them interesting candidates for exothermic singlet exciton fission sensitization of solar cells. However, formation of triplet excitons in DCA and DCOFA is found to occur via hot singlet exciton fission with excitation energies above ∼3.64 eV, and prominent excimer formation in the solid state will need to be overcome in order to make DCA and DCOFA viable candidates for use in a practical device.


Pesticide use and residues on Queensland wool.
To determine practices for control of louse infestation and blowfly strike in Queensland sheep flocks that are associated with organophosphorous and synthetic pyrethroid residues on wool. Information on residues was obtained from a survey of Queensland wool clips. Information on pesticide use was obtained from a trace-back postal survey. The association between pesticide use and residues was assessed using generalised linear models, controlling for potential confounding by flock location. Between 1995 and 1997 Queensland wool clips were randomly sampled. Samples were tested for the presence and amount (mg per kg of greasy wool) of organophosphorous and synthetic pyrethroid pesticides. A questionnaire seeking information on flock characteristics and pesticide use was sent to the manager of each flock from which a wool sample was tested. The median amount of OP and SP residue was 0.8 and 0.25 mg/kg, respectively, and 91 and 95% of wool samples contained < 8 mg/kg of OP and SP residues, respectively. The frequency of OP pesticide use for louse control was significantly (P = 0.005) associated with mean OP residue amount, and the timing of SP use for louse control, in relation to shearing, was significantly (P < 0.001) associated with mean SP residue amount. Most Queensland wool clips have acceptable amounts of residues after the use of OP and SP pesticides, but wool growers can further reduce residues by effectively controlling louse infestation with pesticide applications early after shearing and the use of non-chemical methods of ectoparasite control.


Immunogenic properties of a recombinant fusion protein containing the C-terminal 19 kDa of Plasmodium falciparum merozoite surface protein-1 and the innate immunity agonist FliC flagellin of Salmonella typhimurium.
In a recent study, we demonstrated the immunogenic properties of a new malaria vaccine polypeptide based on a 19 kDa C-terminal fragment of the merozoite surface protein-1 (MSP1(19)) from Plasmodium vivax and an innate immunity agonist, the Salmonella enterica serovar Typhimurium flagellin (FliC). Herein, we tested whether the same strategy, based on the MSP1(19) component of the deadly malaria parasite Plasmodium falciparum, could also generate a fusion polypeptide with enhanced immunogenicity. The His(6)FliC-MSP1(19) fusion protein was expressed from a recombinant Escherichia coli and showed preserved in vitro TLR5-binding activity. In contrast to animals injected with His(6)MSP1(19), mice subcutaneously immunised with the recombinant His(6)FliC-MSP1(19) developed strong MSP1(19)-specific systemic antibody responses with a prevailing IgG1 subclass. Incorporation of other adjuvants, such as CpG ODN 1826, complete and incomplete Freund's adjuvants or Quil-A, improved the IgG responses after the second, but not the third, immunising dose. It also resulted in a more balanced IgG subclass response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response, as determined by the detection of antigen-specific interferon-gamma secretion by immune spleen cells. MSP1(19)-specific antibodies recognised not only the recombinant protein, but also the native protein expressed on the surface of P. falciparum parasites. Finally, sera from rabbits immunised with the fusion protein alone inhibited the in vitro growth of three different P. falciparum strains. In summary, these results extend our previous observations and further demonstrate that fusion of the innate immunity agonist FliC to Plasmodium antigens is a promising alternative to improve their immunogenicity.


Zoledronic Acid: Pleiotropic Anti-Tumor Mechanism and Therapeutic Outlook for Osteosarcoma.
Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce osteolysis induced by bone metastasis and exhibit highly selective localization and retention in bone, thus making them attractive agents in the treatment of bone metastasis. Studies have shown that zoledronic acid exerts pleiotropic anti-tumor effects against osteosarcoma cells in vitro, including anti-proliferative, anti-angiogenic, and immunomodulatory effects. However, the efficacy of zoledronic acid against primary tumor growth and pulmonary metastasis of osteosarcoma is controversial, which has limited its clinical application. The present review summarizes the controversial effects of zoledronic acid on primary tumor burden and pulmonary metastases in osteosarcoma. We also analyze the clinical effectiveness of zoledronic acid alone and in combination with chemotherapeutic drugs for the treatment of osteosarcoma. Zoledronic acid exhibits diverse anti-tumor effects in osteosarcoma in vitro, however, the in vivo effect is still controversial. Further preclinical and clinical studies are needed to clarify the effects of zoledronic acid in osteosarcoma.


The hump columellar strut: a reliable technique for correction of nasal tip underprojection.
Nasal tip under projection is often found in rhinoplasty cases both for congenital or post-traumatic deformity. Nasal trauma may result in alteration of the external and internal nasal structures with following aesthetic impairment and difficulties in breathing. Post-traumatic surgery is frequent, but restoration of pre-traumatic form and function remains a challenge. The present paper describes a new method to increase tip projection by a columellar strut harvested from the autologous nasal bone and cartilage of the resected hump. A total of 15 cases (11 women/4 men, mean age 32.6 ± 12.3 years) of major tip projection/misalignment abnormalities to be corrected by increased nasal tip projection were drawn, and all underwent closed or open rhinoplasty with the placement of a bony columellar strut harvested from the resected hump of the patient. Short and long-term advantages of this procedure are to be underlined. Harvesting is routinely performed during dorsal resection and preparation of the graft is easy. Differently from bone of the vomer or the inferior turbinate, this is cortical bone straight in shape and rigid in framework, and therefore ideal to gain reliable tip support overtime. No additional harvesting areas are needed. Placement of this bony strut is carried out in the standard fashion without additional dissection or further procedures. Long-term follow-up shows maintained projection over time. This graft can be combined with various grafting or suturing techniques usually applied according to each surgeon's experience and the needs of each patient.


Leptomeningeal cyst in a child after head trauma: a case report.
Leptomeningeal cyst is an uncommon complication of paediatric skull fractures. To report a case of leptomeningeal cyst in a nine year old female. A nine-year-old girl presented with a 13 month history of recurrence seizures. Full clinical evaluation was undertaken. This was followed by radiological investigations. The patient presented with a 13-month history of repeated seizures with no associated fever. The child had fallen from a one-storey building at the age of four years with temporary loss of consciousness and massive right sided head swelling but no radiological investigations were carried out at that time and she gradually recovered on conservative management. Physical examination showed a pulsatile depression on the right side of her head. Imaging studies confirmed this to be a leptomeningeal cyst, post traumatic cyst or growing fracture Conclusion: It is very important to carry out radiological investigations of all head injury patients no matter how subtle and to repeat such investigations especially when skull fractures are seen on initial investigations.


The ROVT Elan Valved Biplex Conduits for the Reconstruction of the Right Ventricular Outflow Tract.
The reconstruction of the right ventricular outflow tract (RVOT) system represents a considerable challenge for both manufacturers and surgeons because the patients requiring this type of devices have a very diverse set of anatomical challenges that can lead to complications and subsequent early device failures. We conducted an indepth investigation of a porcine-valve conduit explanted from a patient following an adverse event. A control device was analyzed as a reference. The rapid aging of the porcine valve in the right side of the heart together with major thrombus formation raises several questions. The difficulties encountered with materials used and also the design features of the conduits are once again highlighted. This group of patients continues to increase in number due to success in the surgical outcomes in early childhood. Therefore, there is a greater demand for an appropriate device. However, much work is still needed to achieve this goal, and the best approach to achieving success remains unanswered.


[Hypokalemia-induced paraplegia secondary to acute diarrhea].
Hypokalemia can give a variety of syntomatology but more often courses without it or with inespecific clinical manifestations. In our enviroment the etiology of hypokalemia is wide but one of the most common causes in third world countries are diarrheas. We describe a case of severe hypokalemia due to acute diarrhea which was manifested with severe neurologic symtoms but improves with conventional treatment.


Sustaining practice change one year after completion of the national depression management leadership initiative.
This report describes the sustainability of quality improvement interventions for depression care in psychiatric practice one year after the completion of the National Depression Management Leadership Initiative (NDMLI) in 2006. The main intervention involved continued use of the nine-item depression scale of the Patient Health Questionnaire (PHQ-9) for routine care of patients with depressive disorders. One year after project completion, lead psychiatrists from the 17 participating practices were surveyed about the sustainability of key practice interventions and dissemination of the interventions. All 14 practices that provided baseline and follow-up data reported sustained use of the PHQ-9 for screening, diagnosis, or monitoring purposes. Moreover, practices reported dissemination of this approach to clinicians within and outside their practices. Psychiatrists reported sustainability and dissemination of PHQ-9 use one year after the conclusion of the NDMLI. The model has potential as a depression care improvement strategy and is worthy of additional study.


Enhanced Tribological Properties of Electrodeposited Fe-W Alloy Coatings through Carburization.
Carburization is a promising surface-hardening approach to maximize the tribological and mechanical properties of metals and alloys by making thin-layer surface carbides. The current study investigates the effect of carburizing on the electrodeposited Fe-W alloy coating. This process involeves the thermal decomposition of ethanol in an argon (Ar) atmosphere at varying temperatures. The amorphous electrodeposits of Fe-W alloy coating formed at optimized current density (500 A/cm2) are transformed to the uniform W-rich reinforced bimetallic carbide (Fe3W3C) layers at a carburizing temperature of 850 °C. The sample Fe-50WC (850 °C) shows enhanced hardness and highest wear resistance with a lowest specific wear rate (10-7 mm3/Nm) as compared to the as-electrodeposited Fe-W alloy and other Fe-W, Co-W, and hard chromium coatings reported in the literature. The present strategy can be applied to develop alternative, low cost, and environmentally friendly W-based composite coatings to replace the toxic chromium coatings.


Single-molecule dynamics reveals cooperative binding-folding in protein recognition.
The study of associations between two biomolecules is the key to understanding molecular function and recognition. Molecular function is often thought to be determined by underlying structures. Here, combining a single-molecule study of protein binding with an energy-landscape-inspired microscopic model, we found strong evidence that biomolecular recognition is determined by flexibilities in addition to structures. Our model is based on coarse-grained molecular dynamics on the residue level with the energy function biased toward the native binding structure (the Go model). With our model, the underlying free-energy landscape of the binding can be explored. There are two distinct conformational states at the free-energy minimum, one with partial folding of CBD itself and significant interface binding of CBD to Cdc42, and the other with native folding of CBD itself and native interface binding of CBD to Cdc42. This shows that the binding process proceeds with a significant interface binding of CBD with Cdc42 first, without a complete folding of CBD itself, and that binding and folding are then coupled to reach the native binding state. The single-molecule experimental finding of dynamic fluctuations among the loosely and closely bound conformational states can be identified with the theoretical, calculated free-energy minimum and explained quantitatively in the model as a result of binding associated with large conformational changes. The theoretical predictions identified certain key residues for binding that were consistent with mutational experiments. The combined study identified fundamental mechanisms and provided insights about designing and further exploring biomolecular recognition with large conformational changes.


Anthropogenic nutrients and harmful algae in coastal waters.
Harmful algal blooms (HABs) are thought to be increasing in coastal waters worldwide. Anthropogenic nutrient enrichment has been proposed as a principal causative factor of this increase through elevated inorganic and/or organic nutrient concentrations and modified nutrient ratios. We assess: 1) the level of understanding of the link between the amount, form and ratio of anthropogenic nutrients and HABs; 2) the evidence for a link between anthropogenically generated HABs and negative impacts on human health; and 3) the economic implications of anthropogenic nutrient/HAB interactions. We demonstrate that an anthropogenic nutrient-HAB link is far from universal, and where it has been demonstrated, it is most frequently associated with high biomass rather than low biomass (biotoxin producing) HABs. While organic nutrients have been shown to support the growth of a range of HAB species, insufficient evidence exists to clearly establish if these nutrients specifically promote the growth of harmful species in preference to benign ones, or if/how they influence toxicity of harmful species. We conclude that the role of anthropogenic nutrients in promoting HABs is site-specific, with hydrodynamic processes often determining whether blooms occur. We also find a lack of evidence of widespread significant adverse health impacts from anthropogenic nutrient-generated HABs, although this may be partly due to a lack of human/animal health and HAB monitoring. Detailed economic evaluation and cost/benefit analysis of the impact of anthropogenically generated HABs, or nutrient reduction schemes to alleviate them, is also frequently lacking.


Pharmacokinetics and allometric scaling of levormeloxifene, a selective oestrogen receptor modulator.
The pharmacokinetics of a new selective oestrogen receptor modulator levormeloxifene was investigated in mice, rats, cynomolgus monkeys and humans by compartmental pharmacokinetics. Levormeloxifene was administered as an oral solution in all studies. Allometric scaling was used to predict human pharmacokinetic parameters and the performance of the approach was evaluated. Mean values of clearance confounded by F(CL/F) were 0.073, 0.29, 3.18 and 2.4 l/h in mice, rats, monkeys and humans, respectively. Values of distribution volume at steady state confounded by F(V(ss)/F) were 0.073 and 7.5 l in mice and rats. In monkeys, values of the central volume F(V(c)/F) and volume at steady state F(V(ss)/F) were 28.9 and 57.9 l, respectively. In humans, values of V(c)/F and V(ss)/F were 106 and 587 l, respectively. Predicted CL/F and V(ss)/F showed a linear relationship when plotted vs BW on a log-log scale; for CL/F, r was 0.95-0.98 and for V(ss)/F, r was 0.99. Using allometric scaling the predicted human V(ss)/F deviated 3-fold from the experimentally determined values. Observed values of CL/F deviated 21-25 fold from the predicted, the latter depending on the scaling method. Confidence intervals for the predicted parameters showed major lack of precision for all the allometric scaling methods.


Ascorbyl coumarates as multifunctional cosmeceutical agents that inhibit melanogenesis and enhance collagen synthesis.
L-Ascorbic acid (AA) and p-coumaric acid (p-CA) are naturally occurring antioxidants that are known to enhance collagen synthesis and inhibit melanin synthesis, respectively. The purpose of this study was to examine hybrid compounds between AA and p-CA as multifunctional cosmeceutical agents. Ascorbyl 3-p-coumarate (A-3-p-C), ascorbyl 2-p-coumarate (A-2-p-C), and their parent compounds were tested for their effects on cellular melanin synthesis and collagen synthesis. At 100 μM, A-3-p-C and A-2-p-C decreased melanin content of human dermal melanocytes stimulated by L-tyrosine, by 65 and 59%, respectively, compared to 11% inhibition of AA and 70% inhibition of p-CA. A-3-p-C and A-2-p-C were less effective than p-CA but more effective than AA at inhibiting tyrosinase activity. A-3-p-C and A-2-p-C were more effective than p-CA at inhibiting the autoxidation of L-3,4-dihydroxyphenylalanine. At 100-300 μM, A-3-p-C and A-2-p-C augmented collagen release from human dermal fibroblasts by 120-144% and 125-191%, respectively, compared to 126-133% increase of AA and 120-146% increase of p-CA. They increased procollagen type I C-peptide release (A-3-p-C, and A-2-p-C) like AA, and decreased matrix metalloproteinase 1 level (A-2-p-C) like p-CA, implicating that they might regulate collagen metabolism by multiple mechanisms. This study suggests that A-3-p-C and A-2-p-C could be used as multifunctional cosmeceutical agents for the attenuation of certain aspects of skin aging.


Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells Reduces Growth of Recurrent Glioblastoma.
Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to GBM therapy. In this study, we identify several EphRs that mark a therapeutically targetable GSC population in treatment-refractory, recurrent GBM (rGBM). Using a highly specific EphR antibody panel and CyTOF (cytometry by time-of-flight), we characterized the expression of all 14 EphR in primary and recurrent patient-derived GSCs to identify putative rGBM-specific EphR. EPHA2 and EPHA3 coexpression marked a highly tumorigenic cell population in rGBM that was enriched in GSC marker expression. Knockdown of EPHA2 and EPHA3 together led to increased expression of differentiation marker GFAP and blocked clonogenic and tumorigenic potential, promoting significantly higher survival in vivo Treatment of rGBM with a bispecific antibody against EPHA2/A3 reduced clonogenicity in vitro and tumorigenic potential of xenografted recurrent GBM in vivo via downregulation of AKT and ERK and increased cellular differentiation. In conclusion, we show that EPHA2 and EPHA3 together mark a GSC population in rGBM and that strategic cotargeting of EPHA2 and EPHA3 presents a novel and rational therapeutic approach for rGBM.Significance: Treatment of rGBM with a novel bispecific antibody against EPHA2 and EPHA3 reduces tumor burden, paving the way for the development of therapeutic approaches against biologically relevant targets in rGBM. Cancer Res; 78(17); 5023-37. ©2018 AACR.


Caries experience and dental attendance of Somali children living in a British city.
To facilitate the planning of future dental services, this study sought baseline data, relating to caries experience and dental attendance, for Somali children resident in Sheffield, UK. A convenience sample of 4 to 14 year old Somali children was drawn from pupils attending Somali religious education classes, youth groups and selected schools in Sheffield. During 1998 and 1999, 238 Somali children were subjected to a dental examination and a structured interview. The mean age of the study population was 9.4 years with equal male and female distribution. The majority of children (58%) had been born in Somalia compared with 29% in the UK or 13% in another country. Just over half of the sample had English-speaking mothers. The mean dmft for 4 to 6 year olds was 2.12 and 50% demonstrated a past caries experience. In the 7 to 10 year old group, mean dmft was 2.05 and caries had again affected 50% of subjects. Mean DMFT for 11 to 14 year olds was 1.37 and 58% showed evidence of previous caries experience. The mother's reported ability to speak English was a strong predictor of caries experience in the group as a whole. Interestingly, an English-speaking mother was associated with low caries prevalence in young children, but with high caries prevalence in children over the age of 7 years. Finally, only 57% of subjects had seen a dentist within the previous 12 months, and almost half of these visits had been prompted because of a specific problem. It is evident that some Somali children have a high caries experience, with mother's ability to speak English being the greatest predictor of dental disease. Preventive strategies need to be developed for this population and regular dental attendance should be encouraged.


microRNA-218 Inhibits Oxygen-induced Retinal Neovascularization via Reducing the Expression of Roundabout 1.
The mechanisms of pathological retinal neovascularization (RNV) remain unknown. Several microRNAs were reported to be involved in the process of RNV. Oxygen-induced retinopathy (OIR) is a useful model to investigate RNV. Our present work explored the expression and the role of microRNA-128 (miR-218) in oxygen-induced RNV. OIR was used to establish RNV model. The expression level of miR-218 in the retina from OIR mice was assessed by quantitative real-time reverse transcriptase polymerase chain reaction. Fluorescein angiography was performed in retinae of OIR mice, and RNV was quantified by hematoxylin and eosin staining to evaluate the effect of pCDH-CMV-miR-218 intravitreal injection on RNV in OIR mice. Roundabout 1 (Robo1) expression was detected by Western blotting in mouse retinal vascular endothelial cells expressing a high or low level of miR-218 and retinal tissues from OIR mice. Cell migration was evaluated by scratch wound assay. In OIR mice, the expression level of miR-218 was significantly down-regulated (P = 0.006). Retinal Robo1 expression was significantly increased at both mRNA and protein levels (P = 0.001, 0.008; respectively). miR-218 intravitreal injection inhibited retinal angiogenesis in OIR mice, and the restoration of miR-218 in retina led to down-regulation of Robo1. Our experiments showed that restoration of miR-218 inhibited retinal angiogenesis via targeting Robo1. MiR-218 contributed to the inhibition of retinal angiogenesis and miR-218 might be a new therapeutic target for preventing RNV.


[Research progress in measurement of human basal metabolic rate].
Basal metabolic rate (BMR) is of great significance to the setting of daily energy requirements and the scientific diet guidance for the population. There are 3 kinds of measurement methods for BMR, including the direct calorimetry, the indirect calorimetry, and the equation estimation. The direct calorimetry method is difficult to implement and is only used in some special populations. The indirect calorimetry and the equation estimation are two methods that are currently used commonly. The indirect calorimetry is highly accurate and suitable for individual for basal metabolic measurement or datum collection via equation estimation. The equation estimation is simple and convenient, which is suitable for large samples.


The Lasting Effects of COVID-19 on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
It is estimated that around 30% of the population living in Western countries has metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression toward inflammation and irreversible fibrosis metabolic dysfunction-associated steatohepatitis (MASH). With inflammation being a key component of the transition to MASH, it raises the question of whether the ongoing COVID-19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of MASLD. Specifically, it remains unclear if the potential chronic sequelae of COVID-19 in patients who recovered from it may increase the predisposition for MASH. Since MASH maintains a high risk for hepatocellular carcinoma, liver failure, and the need for a liver transplant, the potential additive effects of COVID-19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID-19 could have chronic sequelae that affect the progression of MASLD pathogenesis. It was hypothesized that severe cases of COVID-19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes in the liver, similar to those seen in MASH. A scoping review of the literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug-induced liver injury (DILI), and hypoxia seen in COVID-19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of MASLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, gastrointestinal tract, portal system, or systemic circulation. Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes were unlikely, but the direct viral insult of cholangiocytes was a potential complication. High serum levels of IL-1, TNF-a, and MCP-1, in COVID-19 were found as potential risk factors for MASH development. Hypoxia, altered lipid metabolism, and iatrogenic DILI were also proposed as potential precipitators of MASH development. Notably, lasting changes in gut microbiome were also frequently observed and correlated closely with those seen in MASH.


Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review.
RABORAL V-RG® is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control programs using the vaccine in multiple species and countries; and (3) discusses current and future challenges faced by programs seeking to control or eliminate wildlife rabies.


Replicating receptive fields of simple and complex cells in primary visual cortex in a neuronal network model with temporal and population sparseness and reliability.
We propose a new principle for replicating receptive field properties of neurons in the primary visual cortex. We derive a learning rule for a feedforward network, which maintains a low firing rate for the output neurons (resulting in temporal sparseness) and allows only a small subset of the neurons in the network to fire at any given time (resulting in population sparseness). Our learning rule also sets the firing rates of the output neurons at each time step to near-maximum or near-minimum levels, resulting in neuronal reliability. The learning rule is simple enough to be written in spatially and temporally local forms. After the learning stage is performed using input image patches of natural scenes, output neurons in the model network are found to exhibit simple-cell-like receptive field properties. When the output of these simple-cell-like neurons are input to another model layer using the same learning rule, the second-layer output neurons after learning become less sensitive to the phase of gratings than the simple-cell-like input neurons. In particular, some of the second-layer output neurons become completely phase invariant, owing to the convergence of the connections from first-layer neurons with similar orientation selectivity to second-layer neurons in the model network. We examine the parameter dependencies of the receptive field properties of the model neurons after learning and discuss their biological implications. We also show that the localized learning rule is consistent with experimental results concerning neuronal plasticity and can replicate the receptive fields of simple and complex cells.


Serologic survey of birds for West Nile flavivirus in southern Moravia (Czech Republic).
A serosurvey for West Nile virus (WNV) was carried out in 54 domestic birds (geese and ducks bred on fishponds) and 391 wild birds representing 28 migratory and resident species, using a plaque-reduction neutralization microtest with Vero cells and Egyptian topotype Eg-101 strain as test virus. The birds were sampled in the South-Moravian fishpond ecosystem between 2004 and 2006. Antibodies to WNV were not detected in domestic waterfowl, but 23 (5.9%) free-living birds of 10 species showed a positive response. These were the common coot (Fulica atra, 5 positive/18 examined), common kingfisher (Alcedo atthis, 1/1), reed warbler (Acrocephalus scirpaceus, 2/80), sedge warbler (A. schoenobaenus, 3/80), marsh warbler (A. palustris, 2/28), Savi's warbler (Locustella luscinioides, 3/12), reed bunting (Emberiza schoeniclus, 1/28), blackcap (Sylvia atricapilla, 2/11), penduline tit (Remiz pendulinus, 1/14), blue tit (Parus caeruleus, 1/1), and starling (Sturnus vulgaris, 2/4). The antibody titers were comparatively low (1:20-1:40), and the only high titer (1:160) was found in an adult marsh warbler. When 14 of the sera reacting with WNV were titrated in parallel with Usutu Flavivirus, 12 were interpreted as having specific antibodies to WNV, one coot had a higher titer against Usutu virus, and another one could not be attributed to either of the two viruses. In conclusion, 13 (3.3%) of 391 wild birds had specific antibodies to WNV. The results indicate that WNV activity in southern Moravia was limited during 2004-2006.


External validation of structure-biodegradation relationship (SBR) models for predicting the biodegradability of xenobiotics.
Biodegradation is an important mechanism for eliminating xenobiotics by biotransforming them into simple organic and inorganic products. Faced with the ever growing number of chemicals available on the market, structure-biodegradation relationship (SBR) and quantitative structure-biodegradation relationship (QSBR) models are increasingly used as surrogates of the biodegradation tests. Such models have great potential for a quick and cheap estimation of the biodegradation potential of chemicals. The Estimation Programs Interface (EPI) Suite™ includes different models for predicting the potential aerobic biodegradability of organic substances. They are based on different endpoints, methodologies and/or statistical approaches. Among them, Biowin 5 and 6 appeared the most robust, being derived from the largest biodegradation database with results obtained only from the Ministry of International Trade and Industry (MITI) test. The aim of this study was to assess the predictive performances of these two models from a set of 356 chemicals extracted from notification dossiers including compatible biodegradation data. Another set of molecules with no more than four carbon atoms and substituted by various heteroatoms and/or functional groups was also embodied in the validation exercise. Comparisons were made with the predictions obtained with START (Structural Alerts for Reactivity in Toxtree). Biowin 5 and Biowin 6 gave satisfactorily prediction results except for the prediction of readily degradable chemicals. A consensus model built with Biowin 1 allowed the diminution of this tendency.


Secreted parasite Pin1 isomerase stabilizes host PKM2 to reprogram host cell metabolism.
Metabolic reprogramming is an important feature of host-pathogen interactions and a hallmark of tumorigenesis. The intracellular apicomplexa parasite Theileria induces a Warburg-like effect in host leukocytes by hijacking signaling machineries, epigenetic regulators and transcriptional programs to create a transformed cell state. The molecular mechanisms underlying host cell transformation are unclear. Here we show that a parasite-encoded prolyl-isomerase, TaPin1, stabilizes host pyruvate kinase isoform M2 (PKM2) leading to HIF-1α-dependent regulation of metabolic enzymes, glucose uptake and transformed phenotypes in parasite-infected cells. Our results provide a direct molecular link between the secreted parasite TaPin1 protein and host gene expression programs. This study demonstrates the importance of prolyl isomerization in the parasite manipulation of host metabolism.


[Orbital cellulitis in childhood. Medical-surgical treatment].
Orbital cellulitis is an uncommon complication resulting from a spectrum of disorders commonly found in pediatric practice. It usually occurs as a complication of infection of the paranasal sinuses, although it also can be caused by eyelid or dental juries, dental infection and external ocular infection. We studied the clinical, microbiological, and therapeutic features of 152 children diagnosed as periorbital cellulitis and 27 children with orbital cellulitis admitted to our hospital in a 16-year period from January 1983 to December 1998. Twenty-four percent of patients (43 cases) had positive cultures. Thirty children with septal or preseptal cellulitis developed neurological or ophthalmological complications. Intravenous or oral antibiotic administration was effective in 150 patients, but a significant proportion required surgery of the paranasal sinus or orbit (16%).


Binding of warfarin by human albumin in the presence of a perfluorochemical blood substitute.
The effect of a perfluorochemical blood substitute on ligand binding by human albumin was examined using warfarin as a model drug. Binding of warfarin by four per cent human albumin solutions diluted with either buffer or blood substitute, and by blood substitute diluted with buffer was examined. Solutions containing 2 or 10 micrograms/ml warfarin were quantitated by liquid scintillation counting using 14C-warfarin. The per cent warfarin free at room temperature was determined by centrifugation followed by supernatant ultrafiltration. Warfarin was weakly bound by the blood substitute and the overall effect of albumin dilution with the blood substitute was an increase in per cent warfarin free. Blood substitute binding of warfarin may explain the decrease of per cent warfarin free observed when albumin solutions were diluted to 50 and 75% v/v with blood substitute rather than buffer. However, the per cent warfarin free increased when albumin solutions were diluted to 25% v/v with blood substitute rather than buffer. The fraction free increased by 39.0% and 30.4% at total warfarin concentrations of 2 and 10 micrograms/ml, respectively. This relative increase in per cent warfarin free may be the result of a direct and/or indirect displacement of albumin bound warfarin by a component(s) of the blood substitute.


An examination of the concordance between self-reported collisions, driver records, and insurance claims in older drivers.
Background Previous studies of older drivers have found that there are discrepancies between their retrospective self-reports of collisions and the official jurisdictional record. Objectives The purpose of this study was to examine how older drivers self-report collisions in comparison to what was recorded in their official driver abstract as well as insurance claims, in a prospective study. Methods Participants (n = 125, age ≥ 70 years) in this study were part of the University of Manitoba site of the Candrive longitudinal study of older drivers. During the operation of the Manitoba site (2009 to 2013), participants were periodically asked to report on any collisions (at-fault or not) in which they were involved, while they were enrolled in the study. In addition, driver records (abstracts and insurance claims) from the provincial licensing agency and public insurer (Manitoba Pubic Insurance; MPI) were provided annually. Results In total there were 101 separate instances of collisions (regardless of at-fault status), whether self-reported, or recorded by MPI. There were 20 at-fault collisions that were recorded on the driver abstract. Eighteen of these collisions were self-reported by participants. In total, our participants were involved in 70 insurance claims (42 at-fault) - 61 of these were self-reported to study staff. In addition, there were 31 collisions that were self-reported to study staff, that were not reported to MPI. Conclusions In this prospective study, older drivers were diligent in reporting collisions in which they were involved. While some collisions were not reported that ultimately became a claim or part of their driver abstract, the biggest discrepancy was in the collisions that were reported to study staff but that were not reported to authorities.


Effect of calmodulin antagonists on lysosomal enzyme secretion and phospholipid metabolism in guinea-pig macrophages.
The effects of calmodulin antagonists on the secretion of lysosomal enzyme and lipid metabolism in guinea-pig peritoneal macrophages were studied. Calmodulin antagonists, such as trifluoperazine, dibucaine and quinacrine, inhibited the secretion of N-acetyl-beta-d-glucosaminidase from cytochalasin B-treated macrophages when the macrophages were stimulated by the chemotactic peptide, formylmethionyl-leucyl-phenylalanine (f Met-Leu-Phe) or the Ca(2+) ionophore A23187. The effect of calmodulin antagonists on the incorporation of [(32)P]P(i) or [(3)H]glycerol into glycerolipids as well as on the redistribution of [(14)C]glycerol or [(3)H]arachidonic acid in [(14)C]glycerol- or [(3)H]arachidonic acid-prelabelled lipids were examined. Trifluoperazine, dibucaine or quinacrine stimulated [(32)P]P(i) incorporation into phosphatidic acid (PtdA) and phosphatidylinositol (PtdIns) without significant effect on the labelling of phosphatidylethanolamine (PtdEtn), phosphatidylserine (PtdSer), lysophosphatidylcholine (lyso-PtdCho) and lysophosphatidylethanolamine (lyso-PtdEtn). The incorporation of [(32)P]P(i) into phosphatidylcholine (PtdCho) was, on the contrary, inhibited. When calmodulin antagonists were added to macrophages stimulated by fMet-Leu-Phe, [(32)P]P(i) incorporation into PtdIns and PtdA was synergistically increased compared with that induced only by calmodulin antagonists. Trifluoperazine inhibited the incorporation of [(3)H]glycerol into PtdCho, triacylglycerol and PtdEtn. Also in this case, the incorporation of [(3)H]glycerol into PtdA and PtdIns was greatly enhanced. But [(3)H]glycerol incorporation into PtdSer, lyso-PtdEtn and lyso-PtdCho was not affected by the drug. On the other hand, diacylglycerol labelling with [(3)H]glycerol was maximally activated by 10mum-trifluoperazine and levelled off with the increasing concentration. When the effect of calmodulin antagonists on the redistribution of [(14)C]glycerol among lipids was examined in pulse-chase experiments, no significant effect on [(14)C]glycerol redistribution in PtdEtn, PtdCho, PtdIns, PtdSer, PtdA and tri- and di-acylglycerol could be detected. When macrophages prelabelled with [(3)H]arachidonic acid were treated with trifluoperazine, dibucaine or quinacrine, the [(3)H]arachidonic acid moiety in PtdEtn and PtdCho was decreased and that in PtdA was increased. The formation of [arachidonate-(3)H]diacylglycerol and non-esterified [(3)H]-arachidonic acid was also enhanced, but the increase in [(3)H]arachidonic acid was only observed at concentrations between 1 and 50mum. [Arachidonate-(3)H]PtdIns was not significantly affected. The activated formation of [arachidonate-(3)H]PtdA, diacylglycerol and non-esterified arachidonic acid by these drugs was synergistically enhanced in the presence of fMet-Leu-Phe.


Integration of a Lean Daily Management System into an Antimicrobial Stewardship Program.
Growing demands and limited guidance on efficient use of resources to advance stewardship initiatives challenge antimicrobial stewardship programs (ASP). The primary aim was to incorporate a Lean Readiness and Metrics Board (RMB) into ASP and assess team member accountability and satisfaction with weekly 15-minute huddle participation within 1 year of implementation. ASP team survey data were analyzed for comments regarding Lean integration, team communication, and productivity. The second aim was to develop 5 shared metrics associated with quality, people, delivery, safety, and stewardship and evaluate ASP team productivity by assessing the impact of projects targeted at each specific metric. Pharmacist-physician ASP scheduling conflicts were addressed through identified rounding times under the "People" metric. The "Quality" metric assessed ASP intervention disagreement rate and collaborations that occurred to reduce disagreement. ASP tracked the number of individuals educated by ASP monthly through the "Delivery" metric. Since August 2018, ASP replaced hour-long monthly meetings with weekly huddles at the RMB. On average, 14 members (88%) of the ASP participate weekly. Team members report improvement in communication and satisfaction with Lean integration. Metric utilization enhanced productivity. For the metrics under "People," "Quality," and "Delivery," reduced scheduling conflicts occurred, the ASP intervention disagreement rate decreased (37.0%-25.6%; P < 0.001), and the ASP educated an average of 79 learners per month. Weekly huddles at the RMB enhanced communication and team accountability while visually displaying program needs, progress, and achievements. The RMB helps to ensure ongoing institutional commitment, and Lean methods show promise for evaluating and improving ASP productivity.


Circulating levels of the macrophage colony stimulating factor CSF-1 in primary and metastatic breast cancer patients. A pilot study.
Earlier results [1], suggesting an autocrine tumor cell stimulation by CSF-1, are in agreement with data by Fildermann et al. [2], showing an enhanced motility and invasiveness in the CSF-1 receptor expressing BT20 breast cancer cell line upon stimulation with recombinant CSF-1. Tumor-cell secreted CSF-1 has also been shown to cause monocyte recruitment, but not cytotoxicity [3]. Down-regulation of monocyte class II antigen expression after exposure to high concentrations of CSF-1 [4] may decrease macrophage-mediated tumor cytotoxicity and favor tolerance. Raised CSF-1 serum levels may thus increase tumor metastatic behavior as well as cause immune suppression in advanced stage disease. We set out to evaluate serum CSF-1 levels in primary and metastatic breast cancer. Serum samples from one hundred and eighteen primary breast cancer patients and seventy-five patients with metastatic disease were assayed by radio-immuno-assay (RIA) for circulating colony-stimulating factor 1. Mean serum levels were significantly higher in the metastatic population (9.7 ng/ml +/- 0.8) as compared to the patients with primary tumors (4.2 +/- 0.2) (p = 0.0001). Patients with early stage tumors (T0/T1/T2) had significantly lower levels than patients with tumors of larger size (T3/T4) (p = 0.0001). Relapse and survival statistics were analyzed using Kaplan-Meier estimates. Samples from 118 primary breast cancer patients were available to study. The median follow up was 85 months (range: 1-108). An elevated CSF-1 concentration (> 6.6 ng/ml or > 550 Units/ml) was associated with a shorter disease free interval (p = 0.03). In a multivariate analysis, including T (clinical tumor size), N (clinical node status), histological grade, and hormone receptor status, CSF-1 remained significantly associated with a poorer outcome (relative risk of relapse: RR: 3.3 [1.3-8.5]), together with tumor size (RR: 2.8[1-8.2]) and clinically involved nodes (RR: 4.1[2.1-8]). These results were not modified following adjustment for type of treatment. We conclude that raised circulating CSF-1 levels may be an indicator of early metastatic relapse.


Methods for quantifying breast cancer-related lymphedema in patients undergoing a contralateral prophylactic mastectomy.
Patients treated for breast cancer are at risk of developing breast cancer-related lymphedema (BCRL). A significant proportion of patients treated for breast cancer are opting to undergo a contralateral prophylactic mastectomy (CPM). Currently, it remains unclear as to whether the relative volume change (RVC) equation may be used as an alternative to the weight adjusted change (WAC) equation to quantify BCRL in patients who undergo CPM. In order to simplify BCRL screening, our cohort of patients who underwent a CPM (n=310) was matched by BMI to a subset of patients who underwent unilateral breast surgery (n=310). Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6-12 months. The correlation of ipsilateral RVC and WAC values for those who underwent bilateral surgery was calculated (r=0.60). Contralateral WAC values for patients in both cohorts were compared, and there was no significant difference between the two distributions in variance (p=0.446). The RVC equation shows potential to be used to quantify ipsilateral postoperative arm volume changes for patients who undergo a CPM. However, a larger trial in which RVC and WAC values are prospectively assessed is needed.


The combined percentage of Gleason patterns 4 and 5 is the best predictor of cancer progression after radical prostatectomy.
Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.


Opioid-mediated placebo responses boost pain endurance and physical performance: is it doping in sport competitions?
The neurobiological investigation of the placebo effect has shown that placebos can activate the endogenous opioid systems in some conditions. So far, the impact of this finding has been within the context of the clinical setting. Here we present an experiment that simulates a sport competition, a situation in which opioids are considered to be illegal drugs. After repeated administrations of morphine in the precompetition training phase, its replacement with a placebo on the day of competition induced an opioid-mediated increase of pain endurance and physical performance, although no illegal drug was administered. The placebo analgesic responses were obtained after two morphine administrations that were separated as long as 1 week from each other. These long time intervals indicate that the pharmacological conditioning procedure has long-lasting effects and that opioid-mediated placebo responses may have practical implications and applications. For example, in the context of the present sport simulation, athletes can be preconditioned with morphine and then a placebo can be given just before competition, thus avoiding administration of the illegal drug on the competition day. However, these morphine-like effects of placebos raise the important question whether opioid-mediated placebo responses are ethically acceptable in sport competitions or whether they have to be considered a doping procedure in all respects.


On the pull: periplasmic trapping of sugars before transport.
Bacteria have evolved many routes for taking up nutrients, demonstrating great versatility in the types and mechanism of uptake used in different physiological conditions. The discovery of a single transporter in the bacterium Advenella mimigardefordensis for the uptake of five different sugars, including L-glucose and D-xylose, is described in this issue (Meinert et al., ), providing yet another example of the surprising adaptability of bacterial transport strategies. The transporter identified is a tripartite ATP-independent (TRAP) transporter, not previously associated with sugar transport, and in fact does not transport the sugars directly at all, rather requiring them to be converted in the periplasm to their respective sugar acid forms before transport through what appears to be a novel general sugar acid transporter. In this commentary, I describe how this process is consistent with the known mechanisms of TRAP transporters and consider how the role of sugar oxidation, or oxidative fermentation, operates with multiple hexose and pentose sugars. Finally I suggest that the periplasmic conversion of nutrients acquired across the outer membrane, before transport across the inner membrane, could have potentially useful biological functions in Gram negative bacteria.


Resting-state oscillatory brain dynamics in Alzheimer disease.
Altered oscillatory brain activity in Alzheimer disease (AD) may reflect underlying neuropathological changes, and its characterization might lead to new diagnostic possibilities. The present study using quantitative magnetoencephalography was set up to examine power spectrum changes in AD patients, and their diagnostic strength. Whole-head 151-channel magnetoencephalography was recorded during an eyes-closed resting state. Magnetoencephalography channels were grouped in 10 cortical regions, and both global and regional relative power was analyzed for the commonly used frequency bands. Eighteen AD patients [mean age 72.1 years +/- 5.6 (SD); 7 women; mean Mini Mental State Examination score 19.2, range: 13-25] and 18 healthy controls [mean age 69.1 +/- 6.8 (SD), 11 women; mean Mini Mental State Examination score 29, range: 27-30] were recruited, controls being mainly spouses of patients. Relative power analysis showed significant differences in most frequency bands, particularly in the temporo-parietal regions, with some relation to Mini Mental State Examination scores. Greatest diagnostic accuracy was found in the beta band, especially in the right occipital area (sensitivity 94%, specificity 78%). Quantitative relative power analysis of magnetoencephalography recordings is able to show widespread abnormalities in oscillatory brain dynamics in AD patients. By analyzing distinct cortical regions, this study provides a more detailed topographical view of abnormal brain activity in AD.


[Pontine and extrapontine myelinolysis].
Myelinolysis is defined as acute demyelinating disorder, associated with flaccid quadriplegia, speech and swallowing impairment. The pathogenesis is usually related to hydroelectrolytic imbalance, particularly with severe hyponatremia and its rapid correction. The imagiologic diagnostic is commonly done by magnetic resonance imaging. The authors present a clinical case focusing on the follow up, rehabilitation program, and giving importance to functionality gains. The main clinical intercurrences related to the late diagnosis are also reported. A female patient with documented past psychiatric history and polidipsia was admitted with repeated seizures unsuccessfully controlled by drugs. Hyponatremia was identified and corrected. After the correction, a quadriplegia and a generalized hypotonia were noticed and the patient underwent magnetic resonance imaging. The imaging findings were consistent with the diagnosis of central pontine and extrapontine myelinolysis.


Placing neuroanatomical models of executive function in a developmental context: imaging and imaging--genetic strategies.
Children show gradual and protracted improvement in an array of behaviors involved in the conscious control of thought and emotion. Behavioral research has shown that these abilities, collectively referred to as executive functions (EF), can be dissociated into separable processes, such as inhibition and working memory. Furthermore, noninvasive neuroimaging shows that these component processes often rely on separable neural circuits involving areas of the frontal cortex and nuclei of the basal ganglia. As additional noninvasive methodologies become available, it is increasingly possible to continue to dissect and dissociate components of EF and also test predictions made by a number of theoretical neuroanatomical models. One method of late is genetics, which is noninvasive and readily used in concert with neuroimaging. The biological data obtained with neuroimaging and genetics is particularly able to inform neuroanatomical models that link specific brain systems with higher more abstract process models derived from purely behavioral work. As much progress in this area continues to occur, we seek to evaluate the age dependency and manner in which certain aspects of EF and certain anatomical circuits show changes and interactions as children develop. Some examples are taken from research on children with the developmental disability attention deficit hyperactivity disorder. A review of selected developmental research shows that current cognitive and neuroanatomical models of EF offer a great many system- and synaptic-level hypotheses that can be tested using imaging and imaging genetics in longitudinal and cross-sectional study designs. Here, we focus on age-related changes in inhibition and working memory.


The Development, Fine Specificity, and Importance of High-Avidity Antibodies to VAR2CSA in Pregnant Cameroonian Women Living in Yaoundé, an Urban City.
Pregnant women infected with Plasmodium falciparum often produce antibodies (Abs) to VAR2CSA, a ligand that binds to placental chondroitin sulfate A causing placental malaria (PM). Antibodies to VAR2CSA are associated with improved pregnancy outcomes. Antibody avidity is a surrogate marker for the extent of maturation of the humoral immune response. Little is known about high avidity Abs to VAR2CSA for women living in urban African cities. Therefore, this study sought to determine: i) if high avidity Abs to full-length VAR2CSA (FV2) increase with gravidity in women in Yaoundé, Cameroon exposed to ~ 0.3-1.1 infectious mosquito bites per month, ii) if high avidity Abs to FV2 are directed against a specific region of VAR2CSA, and iii) if having high avidity Abs to FV2 improve pregnancy outcomes. Plasma samples collected at delivery from 695 women who had Abs to FV2 were evaluated. Ab levels and the Avidity Index (AI), defined as the percent Abs remaining bound to FV2 after incubation with 3M NH4SCN, were determined. Similar Ab levels to FV2 were present in women of all gravidities (G1 through 6+; p=0.80), except significantly lower levels were detected in PM-negative (PM-) primigravidae (p <0.001). Median Ab avidities increased between gravidity 1 and 2 (p<0.001) and remained stable thereafter (G3-G6+: p=0.51). These results suggest that B cell clonal expansion began during the first pregnancy, with clonal selection primarily occurring during the second. However, the majority of women (84%) had AI <35, a level of high avidity Abs previously reported to be associated with improved pregnancy outcomes. When plasma from 107 Cameroonian women was tested against 8 different regions of FV2, high avidity Abs were predominately restricted to DBL5 with median AI of 50 compared to AI <25 for the other domains. The only significance influence of high avidity Abs on pregnancy outcome was that babies born to mothers with AI above the median were 104 g heavier than babies born to women with AI below the median (p=0.045). These results suggest that a vaccine that boosts maturation of the immune response to VAR2CSA may be beneficial for women residing in urban areas.


Trunk biomechanics and its association with hip and knee kinematics in patients with and without patellofemoral pain.
Patellofemoral pain (PFP) is a common lower extremity condition observed in sports clinics. Recently, it has been suggested that trunk motion could affect hip and knee biomechanics in the frontal plane. Thus, the purpose of the study was compare trunk kinematics, strength and muscle activation between people with PFP and healthy participants. In addition, the associations among trunk biomechanics, hip and knee kinematics were analysed. Thirty people with PFP and thirty pain-free individuals participated. The peak ipsilateral trunk lean, hip adduction, and knee abduction were evaluated with an electromagnetic tracking system, and the surface electromyographic signals of the iliocostalis and external oblique muscle were recorded during single-leg squats. Trunk extension and trunk flexion with rotation isometric strength and side bridge tests were quantified using a handheld dynamometer. Compared with the control group, the PFP group demonstrated increased ipsilateral trunk lean, hip adduction and knee abduction (p = 0.02-0.04) during single-leg squat accompanied with decreased trunk isometric strength (p = < 0.001-0.009). There was no between-group difference in trunk muscle activation. Only in the control group, ipsilateral trunk lean was significantly correlated with hip adduction (r = -0.66) and knee abduction (r = 0.49); also, the side bridge test correlated with knee abduction (r = -0.51). Differences in trunk, hip and knee biomechanics were found in people with PFP. No relationship among trunk, hip and knee biomechanics was found in the PFP group, suggesting that people with PFP show different movement patterns compared to the control group.


Synaptic mitochondria regulate hair-cell synapse size and function.
Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through CaV1.3 channels initiates mitochondrial-Ca2+ (mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+ uptake in mature cells depresses presynaptic-Ca2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+ uptake coincides with spontaneous rises in presynaptic-Ca2+ influx. Spontaneous mito-Ca2+ loading lowers cellular NAD+/NADH redox and downregulates ribbon size. Direct application of NAD+ or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+ couple to confer proper presynaptic function and formation.


Myocardial reperfusion reverses the J-curve association of cardiovascular risk and diastolic blood pressure in patients with left ventricular dysfunction and heart failure after myocardial infarction: insights from the EPHESUS trial.
The described association of low diastolic blood pressure (DBP) with increased cardiovascular outcomes could be due to reduced coronary perfusion or is simply due to reverse causation. If DBP is physiologically relevant, coronary reperfusion after myocardial infarction (MI) might influence DBP-risk association. The relation of achieved DBP with cardiovascular death or cardiovascular hospitalization, cardiovascular death, and all-cause death was explored in 5929 patients after acute myocardial infarction (AMI) with impaired left ventricular function, signs and symptoms of heart failure, or diabetes in the EPHESUS trial according to their reperfusion status. Cox regression models were used to assess the impact of reperfusion status on the association of DBP and systolic blood pressure (SBP) with outcomes in an adjusted fashion. In patients without reperfusion, lower DBP <70 mmHg was associated with increased risk for all-cause death [adjusted hazard ratios (HRs) 1.80, 95% confidence interval (CI) 1.41-2.30; P < 0.001], cardiovascular death (HR 1.70, 95% CI 1.3-3.22; P < 0.001), cardiovascular death or cardiovascular hospitalization (HR 1.54, 95% CI 1.26-1.87; P < 0.001). In patients with reperfusion, the risk increase at low DBP was not observed. At low SBP, risk increased independently of reperfusion. A sensitivity analysis in the subgroup of patients with optimal SBP of 120-130 mmHg showed again risk reduction of reperfusion at low DBP. Adding the treatment allocation to eplerenone or placebo into the models had no effects on the results. Patients after AMIs with a low DBP had an increased risk, which was sensitive to reperfusion therapy. Low blood pressure after MI identifies in patients with particular higher risk. These data support the hypothesis that low DBP in patients with stenotic coronary lesions is associated with risk, potentially involving coronary perfusion pressure and the recommendations provided by guidelines suggesting lower DBP boundaries for these high-risk patients.


Biomagnification of mercury through the benthic food webs of a temperate estuary: Masan Bay, Korea.
The authors examined food web magnification factors of total mercury (THg) and methylmercury (MeHg) for the benthic organisms in Masan Bay, a semiclosed, temperate estuary located on the southeastern coast of Korea. For benthic invertebrates, concentrations of THg and MeHg (%MeHg) ranged from 9.57 to 195 and 2.56 to 111 ng/g dry weight (12.2-85.6%), respectively. Benthic fish THg and MeHg (%MeHg) concentrations ranged widely from 10.8 to 618 and 2.90 to 529 ng/g dry weight (22.9-93.9%), respectively. The linear regression slopes of log [Hg] relative to δ(15)N (i.e., food web magnification factors) found for the Masan Bay benthic organisms were 0.119 for THg and 0.168 for MeHg. These values are similar to the food web magnification factors of benthic organisms and lower than those of pelagic organisms of various coastal marine environments. It suggests that pelagic organisms might be at greater risk of THg and MeHg accumulation than benthic biota.


Characteristics of selected parameters of body posture in patients with hip osteoarthritis.
Osteoarthritis is the most common disorder of the musculoskeletal system. A unilateral change in the hip joint changes the position of the pelvis and spine, and therefore the patient's body posture. Due to the uneven loading of the lower limbs asymmetry occurs in the trunk. Detailed dependencies of that have not been thorougly described in the available literature. The aim of the study was to characterize the posture parameters in patients with unilateral osteoarthritis of the hip. The study population consisted of 40 patients with unilateral hip osteoarthritis. There were 21 women and 19 men in the group, aged 41-80 years. The mean patient age was 65.39+/-8.69, the mean body mass was 82.98 ± 11.79 kg, the mean body height was 167.64 ± 8.59, and the mean Body Mass Index (BMI) was 29.6 ± 4.36. Statistically significant differences were found on a number of parameters: lumbar inclination, thoraco-lumbar inclination and torso inclination were lower in patients with hip arthrosis, comparing to control group. Angle of thoracic kyphosis, depth of thoracic kyphosis, angle of lumbar lordosis, depth of lumbar lordosis were smaller in patients with hip arthrosis. Pelvic asymmetry in coronal plane was bigger in patients with hip arthrosis. Body posture in patients with unilateral osteoarthritis characterizes a decrease of lumbar lordosis and thoracic kyphosis while the whole body tilt forward. The asymmetry of the pelvis and trunk settings should be taken be taken into account during physical therapy of patients with coxarthrosis also during the post-operative postural re-education process.


Use of the Pyrithiamine-Induced Thiamine Deficient Animal Model of Korsakoff's Syndrome for Exploratory Research Activities in Undergraduate Physiological Psychology.
Undergraduate neuroscience laboratory activities frequently focus on exercises that build student's wet/dry laboratory skills, foster critical thinking, and provide opportunities for hands-on experiences. Such activities are, without a doubt, extremely important, but sometimes fall short of modeling actual research and often lack the 'unknown' hypothetical nature accompanying empirical studies. In this article we report a series of research activities using an animal model of Korsakoff's syndrome in a Physiological Psychology course. The activities involve testing hypotheses regarding performance of animals with experimentally-induced Korsakoff's syndrome and the effectiveness of glucose as a memory-enhancer in this model. Students were given a set of 24 articles for use in answering a series of laboratory report questions regarding the activities. At the conclusion of the course, students were asked to complete a questionnaire designed to assess the effectiveness of the laboratory activities. Results of the laboratory exercises indicated that locomotor activity, environmental habituation, and anxiety were unaffected in the Korsakoff condition, and glucose had no effect. Results of performance in the T-maze indicated that Korsakoff animals had significantly fewer spontaneous alternations than controls, but Korsakoff animals given glucose did not reveal this difference. Results of the student assessments indicated that the activities were considered educational, challenging, and more interesting than standard laboratory activities designed to reproduce reliable phenomena.


Healthcare-associated infections in neonates.
To identify important findings in the recent literature related to healthcare-associated infections in neonatal care. Bloodstream infection remains the leading healthcare-associated infection in the neonatal unit, but multimodal interventions have been shown to successfully reduce this life-threatening complication. Emerging pathogens such as methicillin-resistant Staphylococcus aureus, extended-spectrum-beta-lactamase-producing Gram-negative organisms and pan-resistant Acinetobacter baumannii or Serratia marcescens complicate the use of standard antibiotic treatment and are a particular concern in this setting because of the limitation in antibiotic classes among neonates. Community-acquired methicillin-resistant S. aureus infections are increasing in frequency and are particularly worrisome. Fluconazole prophylaxis offers a simple solution for the prevention of invasive Candida infection and has been already widely adopted. Although there is evidence for its efficacy, there is still some debate about the pros and cons of azole prophylaxis in the prevention of invasive Candida infections. Furthermore, its use in low-prevalence settings remains highly questionable. The introduction of restrictive guidelines limiting the use of antibiotics in early-onset neonatal infections has proved to be safe and efficient and may also reduce the incidence of late-onset infection. Outbreaks remain an ongoing concern in neonatal care and are increasingly complicated by emerging multiresistant pathogens. Healthcare-associated infections remain a permanent challenge among neonates.


A whole blood immunoassay using gold nanoshells.
A rapid immunoassay capable of detecting analyte within complex biological media without any sample preparation is described. This was accomplished using gold nanoshells, layered dielectric-metal nanoparticles whose optical resonance is a function of the relative size of its constituent layers. Aggregation of antibody/nanoshell conjugates with extinction spectra in the near-infrared was monitored spectroscopically in the presence of analyte. Successful detection of immunoglobulins was achieved in saline, serum, and whole blood. This system constitutes a simple immunoassay capable of detecting sub-nanogram-per-milliliter quantities of various analytes in different media within 10-30 min.


Socioemotional processing of morally-laden behavior and their consequences on others in forensic psychopaths.
A large body of evidence supports the view that psychopathy is associated with anomalous emotional processing, reduced guilt and empathy, which are important risk factors for criminal behaviors. However, the precise nature and specificity of this atypical emotional processing is not well understood, including its relation to moral judgment. To further our understanding of the pattern of neural response to perceiving and evaluating morally-laden behavior, this study included 155 criminal male offenders with various level of psychopathy, as assessed with the Psychopathy Check List-Revised. Participants were scanned while viewing short clips depicting interactions between two individuals resulting in either interpersonal harm or interpersonal assistance. After viewing each clip, they were asked to identify the emotions of the protagonists. Inmates with high levels of psychopathy were more accurate than controls in successfully identifying the emotion of the recipient of both helpful and harmful actions. Significant hemodynamic differences were detected in the posterior superior temporal sulcus, amygdala, insula, ventral striatum, and prefrontal cortex when individuals with high psychopathy viewed negative versus positive scenarios moral scenarios and when they evaluated the emotional responses of the protagonists. These findings suggest that socioemotional processing abnormalities in psychopathy may be somewhat more complicated than merely a general or specific emotional deficit. Rather, situation-specific evaluations of the mental states of others, in conjunction with sensitivity to the nature of the other (victim vs. perpetrator), modulate attention to emotion-related cues. Such atypical processing likely impacts moral decision-making and behavior in psychopaths.


Corrosion resistance and earth-abundance FeS-based heterojunction catalyst for seawater splitting at industrial grade density.
The strategic progression toward highly efficient transition metal electrocatalytic electrodes is crucial to achieving efficiency and long-term stability in hydrogen production from authentic seawater sources. This work reports the development of a self-supporting, heterogeneous and corrosion-resistant iron sulfur-based catalytic electrode via a streamlined, one-step process involving sulfide etching and electroless plating on an iron foam substrate (IF). This new electrode, named NiS-FeS@IF, involves a nanostructured NiS-FeS catalytic material that combines in situ, resulting in a thin, ultrathin nanospherical layer on the IF. This construction has low overpotentials of merely 322 mV for the hydrogen evolution reaction (HER) and 563 mV for the oxygen evolution reaction (OER) with a current density of 500 mA cm-2 in alkaline simulated seawater electrolytes. Importantly, the NiS-FeS@IF electrode enduring more than 500 h at an industrial grade high current density of 1 A cm-2 without noteworthy performance deterioration. The unique and uniformly dispersed morphology of NiS-FeS facilitates intensified interfacial electron transfer, optimizes active site exposure and provides efficient channels for the rapid release and mass transfer of gas bubbles. This work introduces a novel approach for the facile preparation of efficient electrode materials.


Cerebrospinal fluid phospholipid changes following traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, with approximately 1.4 million people suffering a TBI each year. With TBI, a cascade of events is initiated including the activation of phospholipases, which leads to the disruption of the lipid bilayer of the membrane of neurons and neuroglia. The purpose of this study is to describe phospholipid changes following TBI. A total of 39 cerebrospinal fluid samples were obtained from the ventricular catheter system of 10 participants who received a TBI as a result of a motor vehicle crash, being struck by a vehicle as a pedestrian, or a fall. Phospholipids were extracted from samples and measured by normal-phase high-performance liquid chromatography with ultraviolet detector at a wavelength of 206 nm. The highest mean concentration of lysophosphatidylcholine occurred on Day 1 after injury. The concentration of phosphatidylserine was variable, with the highest mean concentration occurring on Day 2 after injury. The highest mean concentrations of phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin occurred on Day 4 after injury. Findings provide preliminary evidence for disruption of central nervous system membrane phospholipids following TBI.