Fluctuations of visual evoked potential amplitudes and of contrast sensitivity in Uhthoff's symptom.
Visual evoked potentials (VEPs) to pattern reversal and psychophysical contrast sensitivity (CS) were tested in five patients with Uhthoff's symptom before and after exercise. Four of the cases were related to a demyelinating disease and one patient had a severe brain injury. Uhthoff's symptom occurred also in neuropathies without previous clinical neuritis and in eyes with normal latency time of the VEPs. A depression of CS was observed by all five patients after exercise; a transient "overshoot" of CS following the depression was present in three of the patients. VEP amplitudes were reduced by exercise in three cases. Responses by stimulation with small checks were more affected. Paradoxical increased VEP amplitudes after exercise in the presence of a loss of psychophysical CS were found in one case.


Simulated rugby performance at 1550-m altitude following adaptation to intermittent normobaric hypoxia.
Team-sport athletes who normally reside at sea level occasionally play games at altitudes sufficient to impair endurance performance. To investigate the effect of intermittent normobaric hypoxic exposure on performance in generic and game-specific tests at altitude, 22 senior club level rugby players performed baseline tests before single-blind random assignment to one of three groups: hypoxia-altitude (n=9), normoxia-altitude (n=6), and normoxia-sea level (n=7). The hypoxia-altitude group underwent 9-13 sessions of intermittent hypoxic exposure (concentration of inspired oxygen=13-10%) over 15 days, then repeated the performance tests within 12h of travelling to 1550m. The normoxia-altitude group underwent placebo exposures by breathing room air before repeating the tests at altitude, whereas the normoxia-sea level group underwent placebo exposures before repeating the tests at sea level. Hypoxic exposure consisted of alternately breathing 6min hypoxic gas and 4min ambient air for 1h at rest. Performance measures gathered at each testing session were maximum speed, sub-maximum heart-rate speed and sub-maximum lactate speed during a 20-m incremental running test, mean time in six 70-m sprints, repetitive explosive power and other measures from seven 5.5-min circuits of a rugby simulation. Repetitive explosive power ( approximately -16%) and 20-m shuttle performance ( approximately -3%) decreased substantially at altitude compared to sea level. Acclimatisation to hypoxia had a beneficial effect on sub-maximum heart rate and lactate speed but little effect on other performance measures. In conclusion, 1550-m altitude substantially impaired some measures of performance and the effects of prior adaptation via 9-13 sessions of intermittent hypoxia were mostly unclear.


The Sentinel Lymph Node in Treatment Planning: A Narrative Review of Lymph-Flow-Guided Radiotherapy.
The sentinel lymph node technique is minimally invasive and used routinely by surgeons, reducing the need for morbid extensive lymph node dissections, which is a significant advantage for cancer staging and treatment decisions. The sentinel lymph node could also help radiation oncologists to identify tumor drainage for each of their patients, leading to a more personalized radiotherapy, instead of a probabilistic irradiation based on delineation atlases. The aim is both to avoid recurrence in unexpected areas and to limit the volume of irradiated healthy tissues. The aim of our study is to evaluate the impact of sentinel lymph node mapping for radiation oncologists. This concept, relying on sentinel lymph node mapping for treatment planning, is known as lymph-flow-guided radiotherapy. We present an up-to-date narrative literature review showing the potential applications of the sentinel lymph node technique for radiotherapy, as well as the limits that need to be addressed before its routine usage.


First International Conference between West and East-Leonardo and Lao-Tze. Western Science Meets Eastern Wisdom. Experiences of Scientists and Intellectuals for the Creation of a New Paradigm of Modern Science.
The Conference was organized and supported by: Nei Dan School (European School of Internal Martial Arts), NIB (Laboratory of Molecular Biology and Stem Cell Bioengineering, National Institute of Biostructures and Biosystems, Institute of Cardiology, S.Orsola-Malpighi Hospital, Bologna), WACIMA (Worldwide Association Chinese Internal Martial Arts), Arti D'Oriente(Magazine of Eastern culture and traditions), Nuovo Orizzonte (Taiji Quan School in Florence), Samurai (Journal on Martial Arts), and Pinus (First National Institute for the Unification of Medical Strategies). Nei Dan School (www.taichineidan.com, firstname.lastname@example.com) was in charge of the organization. Future meetings of the Centro studi 'Tao and Science' will take place in spring 2007 in Firenze and in October 2007 in Bologna. For information: E-mail: email@example.com; web site: www.taichineidan.com, www.taoandscience.com.


[The clinical and pathologic study of embeded supernumerary teeth].
To analyse the clinic and pathologic features of 100 embedded supernumerary teeth, to find out the rule of cystic change of supernumerary teeth and its relationship to malocclusion, and to present the methods of therapy. Analysis of clinical data, X-ray manifestation,comparison of the findings on operation and pathological changes demonstrated the correct diagnosis of supernumerary teeth. On statistics and analysis,66% of the crowns of the supernumerary teeth were showed different sizes of circular photic shades,but only 35% were proved to be cystic change by biopsies. This study showed that 35% had cystic change among 100 cases,so if the diagnosis can be made in these cases with indication of operation the extraction of the supernumerary teeth must be done as soon as possible.


Extended protocol for demonstration of dual AV nodal physiology.
The incidence of dual atrioventricular (AV) nodal physiology was evaluated in 22 patients (14 males, 8 females, age 52 +/- 18 years) undergoing electrophysiology studies for evaluation of ventricular tachycardia/nonsustained ventricular tachycardia (n = 11), supraventricular tachycardia (n = 5), and syncope (n = 6). Patients with AV node reentrant tachycardia were excluded. Thirteen patients had normal left ventricular function and nine patients (seven with coronary artery disease, two with dilated cardiomyopathy) had depressed left ventricular function. Single atrial extrastimuli (A2) were introduced after eight-beat drives at paced cycle lengths of 550 msec and 400 or 450 msec beginning at coupling intervals of 650 and 500 or 550 msec, respectively. The coupling interval was decreased at 10-msec intervals until AV node or atrial refractoriness. A second atrial extrastimulus (A3) was then added. A2 was fixed at 50 msec greater than the atrial or AV nodal refractory period. A3 was coupled to A2 at 650 and 500 or 550 msec and decremented as with single extrastimulation. Dual AV nodal physiology was defined by a 50-msec increase in A2H2 or A3H3 with a 10-msec decrement in the coupling interval or a discontinuous H1H2 versus A1A2 or H2H3 versus A2A3 curve. Using a single extrastimulus, 1 of 22 patients demonstrated dual AV nodal physiology. Using double extrastimuli, an additional four patients with dual AV nodal physiology were identified. The occurrence of dual AV nodal physiology determined using double extrastimuli is increased compared to using only a single extrastimulus (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)


Widespread density dependence of bacterial growth under acid stress.
Many microbial phenotypes are density-dependent, including group-level phenotypes emerging from cooperation. However, surveys for the presence of a particular form of density dependence across diverse species are rare, as are direct tests for the Allee effect, i.e., positive density dependence of fitness. Here, we test for density-dependent growth under acid stress in five diverse bacterial species and find the Allee effect in all. Yet social protection from acid stress appears to have evolved by multiple mechanisms. In Myxococcus xanthus, a strong Allee effect is mediated by pH-regulated secretion of a diffusible molecule by high-density populations. In other species, growth from low density under acid stress was not enhanced by high-density supernatant. In M. xanthus, high cell density may promote predation on other microbes that metabolically acidify their environment, and acid-mediated density dependence may impact the evolution of fruiting-body development. More broadly, high density may protect most bacterial species against acid stress.


Freeze-fracture electron microscopy of non-myelinated nerve fibres in the human dental pulp.
Freeze-fracture replicas from the subodontoblast region gave a good three-dimensional comprehension of the structure of non-myelinated nerve fibres. Each Schwann cell ensheathed 1-15 axons with a mean diameter of 0.4 micron (0.1-1.2 micron). Many axons were not entirely ensheathed but were exposed to the extracellular space to various degrees. Tightening membrane specializations were not found in the mesaxons. The Schwann-cell plasmalemma exhibited caveolae with necks surrounded by evenly-sized intramembranous particles, typical of endocytosis. The nuclear envelope of Schwann cells showed a few typical pores and perinuclear cisterna. In tangential fractures, the axolemma displayed intramembranous particles evenly distributed over the axolemmal fracture planes. There was a marked difference in particle density between the P (600-650/micron2) and E (150-200/micron2) faces.


Stimulation of multipotential, erythroid and other murine haematopoietic progenitor cells by adherent cell lines in the absence of detectable multi-CSF (IL-3).
It is well established that murine multipotential and committed erythroid progenitor cells require the presence of a glycoprotein, termed multi-CSF (multi-colony-stimulating factor, IL-3) for clonal proliferation and differentiation in vitro. The initial proliferation of these cells can also be stimulated by two other glycoproteins, granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF), although continued proliferation and differentiation requires the subsequent presence of multi-CSF. Here we report the stimulation of multipotential, erythroid and other haematopoietic progenitor cells by a number of adherent cell lines including a cloned bone marrow cell line (B.Ad). The positive cell lines, as feeder layers, exhibit colony-stimulating, erythropoietin-like and burst-promoting (BPA) activities. Optimal erythropoietic stimulation by the B.Ad line requires close cell-cell contact. The cell lines also support the in vitro clonal growth of multipotential colony-forming cells and progenitors of six other haematopoietic lineages. The biological activities observed seem not to be mediated by known multipotential or erythroid colony-stimulating factors (multi-CSF, IL-3, MCGF, HCGF, PSF, BPA).


Author Correction: High-throughput screening reveals higher synergistic effect of MEK inhibitor combinations in colon cancer spheroids.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Variability of vigilance and ventilation: studies on the control of respiration during sleep.
Ventilation is under metabolic as well as under behavioural control. This causes a complex interaction between states of 'vigilance' and respiration. This paper briefly summarizes sleep-related changes of respiration and presents an experimental study on the course of respiratory CO2-sensitivity during a whole night's sleep in ten healthy volunteers. The feedback control of breathing was challenged by continuous step changes of inspired CO2 every 7 min, resulting in 60, 3-step steady-state hypercapnic ventilatory responses (HCVR) per night in each subject. We analysed the variability of baseline ventilation and the effects of hypercapnia on ventilation with respect to sleep stages. There were only small differences in baseline PCO2 and ventilation between sleep stages, but a high variability of the slope of the CO2-response curves in the course of the night, ranging from 0.5 to 3.0 L min(-1) Torr(-1). The HCVR was significantly lower during REM sleep than during all stages of NREM sleep. Due to a compensatory left shift of the flattened CO2-response curves, however, ventilation at baseline CO2 as well as during slight hypercapnia varied much less than would be expected from the high variability of slopes. We conclude that the characteristics of the CO2-sensitive feedback control system of respiration, are highly variable during sleep, but due to offsetting effects, PCO2 and ventilation remain quite stable in the physiological range.


In vitro fertilization outcomes and alcohol consumption in at-risk drinkers: the effects of a randomized intervention.
Women's use of alcohol in pregnancy is associated with an increased risk of fetal loss and birth defects. Also, alcohol use in women decreases the success of infertility treatment, such as in vitro fertilization (IVF). Our goal was to determine if there were differences in IVF outcomes and alcohol use parameters among at-risk drinkers randomized to a brief intervention (BI) versus assessment only (AO). We conducted a randomized controlled trial to determine the effect of BI or AO among at-risk drinkers on IVF. We studied 37 women (AO = 21; BI = 16). While the BI group had a significantly greater decrease in the number of drinks/drinking day compared to the AO group (p = .04), there were no differences in the likelihood of implantation failure, chemical pregnancy, spontaneous abortion, preterm birth, or live birth. BI and AO contributed to a decrease in alcohol use and did not demonstrate differences in IVF outcomes. A larger study may confirm these preliminary findings. Our results will assist care providers in treating alcohol use in pregnancy in an effective way, such that IVF cycles and the chance of pregnancy are optimized.


The effect of natural polyphenols on the oxidative stress markers in patients with diabetic nephropathy.
Nephropathy remains a significant cause of morbidity and mortality in the diabetic population and is the leading cause of end-stage renal failure, hence kidney transplantations. As a result of the diabetic milieu, increased generation of reactive oxygen species is thought to play a key role in the progression of diabetic nephropathy. Aim of this study was to evaluate the effect of Pycnogenol (Pyc), the extract from Pinus pinaster, on the level of glucose, advanced glycation end products (AGE) and oxidative stress markers in patients with Diabetic nephropathy (DN). To double blind randomised placebo controlled exploratory study were enrolled 20 men with DN received daily Pyc (120mg) or a placebo. Patients were investigated before, one and three months after Pyc administration and after termination of drugs supplementation. The level of glucose, AGEs, malondialdehyde (MDA), 8-isoprostanes (8-Iso), as well as protein carbonyls (PC) were increased in comparison to control group. We have found lower level of glucose, AGEs, MDA and 8-Iso after 3 months of Pyc administration in comparison to the beginning state and to placebo group, but these results did not reach significance. CP and TAS were not affected. Our data allow us to conclude that Pycnogenoladministration reduces oxidative damage to lipids rather through the decreased glucose level than through the influence of antioxidant capacity of plasma. This study was supported by grant Ministry of Health 2012/8-ukba-8.


Light-Driven Self-Oscillation of Thermoplasmonic Nanocolloids.
Self-oscillation-the periodic change of a system under a non-periodic stimulus-is vital for creating low-maintenance autonomous devices in soft robotics technologies. Soft composites of macroscopic dimensions are often doped with plasmonic nanoparticles to enhance energy dissipation and generate periodic response. However, while it is still unknown whether a dispersion of photonic nanocrystals may respond to light as a soft actuator, a dynamic analysis of nanocolloids self-oscillating in a liquid is also lacking. This study presents a new self-oscillator model for illuminated colloidal systems. It predicts that the surface temperature of thermoplasmonic nanoparticles and the number density of their clusters jointly oscillate at frequencies ranging from infrasonic to acoustic values. New experiments with spontaneously clustering gold nanorods, where the photothermal effect alters the interplay of light (stimulus) with the disperse system on a macroscopic scale, strongly support the theory. These findings enlarge the current view on self-oscillation phenomena and anticipate the colloidal state of matter to be a suitable host for accommodating light-propelled machineries. In broad terms, a complex system behavior is observed, which goes from periodic solutions (Hopf-Poincaré-Andronov bifurcation) to a new dynamic attractor driven by nanoparticle interactions, linking thermoplasmonics to nonlinearity and chaos.


How pulmonary valve regurgitation after tetralogy of fallot repair changes the flow dynamics in the right ventricle: An in vitro study.
Tetralogy of Fallot is the most common cyanotic congenital disease, affecting 10% of children with congenital heart disease. The surgical management of patients with Tetralogy of Fallot leads, however, to significant detrimental effects on the right ventricle including pulmonary valve regurgitation. This experiment aimed to simulate different cases of pulmonary valve regurgitation with varying degrees of severity in order to observe the changes in flow structures present in the right ventricle. Planar time-resolved particle image velocimetry measurements have been performed on a custom-made double activation simulator reproducing flow conditions in a model of a right ventricle. Changes in flow characteristics in the right ventricle have been evaluated in terms of velocity fields and profiles, tricuspid inflow jet orientation and viscous energy dissipation. Our results show that pulmonary valve regurgitation significantly alters the flow in the right ventricle mostly by impairing the diastolic inflow through the tricuspid valve and by increasing viscous energy loss. This fundamental work should allow for a better understanding of such changes in the RV flow dynamics. It may also help in developing new strategies allowing for a better follow-up of patients with repaired TOF and for decision-making in terms of pulmonary valve replacement.


Intensifying anoxic ammonium removal by manganese ores and granular active carbon fillings in constructed wetland-microbial fuel cells: Metagenomics reveals functional genes and microbial mechanisms.
The conventional biological ammonium removal process is challenged for lack of electron acceptors. A lab-scale integrated constructed wetland coupled with microbial fuel cells (CW-MFC) filling manganese ores (MO) and granular active charcoal (GAC) has been developed, named CW-CM. It enhanced the nitrogen removal two times over the control. A metagenomic-based study illustrated the functional genes and taxonomic groups related to N transformations, explored metabolic mechanisms of nitrogen and carbon sources, and then revealed some characteristics of the extracellular electron transfer (EET). Many nitrifying bacteria and autotrophic and heterotrophic denitrifiers were enriched in CW-CM. Furthermore, most nitrification and denitrification reactions except for the conversion of ammonium to hydroxylamine were significantly enhanced in CW-CM. Glycolysis and the TCA cycle were also improved. Overall, a novel anoxic ammonia removal process was achieved in the experimental group with no need of anammox functional bacteria and anammox key genes.


Diagnosis and Treatment Algorithm for Blood Flow Obstructions in Patients With Left Ventricular Assist Device.
Thrombosis is an uncommon, but severe complication of left ventricular assist devices (LVADs). This study analyzed experience with obstruction of blood flow through the LVAD with the purpose of developing optimal diagnosis and treatment of LVAD-related thrombosis. Between October 2009 and July 2015, a total of 652 LVAD were implanted in 557 patients. Blood flow abnormalities in patients with LVAD (n = 524) were identified and classified as "high-power" and "low-flow" events. Three types of late blood flow obstructions were identified: 1) pre-pump via thrombus obstructing the inflow cannula (26 events; 0.037 events per patient-year); 2) intra-pump (70 events; 0.1 events per patient-year); and 3) post-pump via thrombosis of the outflow graft or stenosis of the anastomosis to the aorta (4 events; 0.006 events per patient-year). Pre-pump obstruction was treated by washout maneuver in 9 cases (success rate, 100%), thrombolysis in 9 patients (success rate, 56%), and pump exchange in 9 cases (success rate, 100%); 1 patient died without treatment and 2 were weaned from LVAD. Intra-pump obstruction was treated by thrombolysis (n = 9; success rate, 33%), pump exchange (n = 53; success rate, 94%), and removal due to myocardial recovery (n = 3; success rate, 100%); 7 patients died without treatment and parameters spontaneously normalized in 2 cases. Post-pump obstruction was treated in 2 patients by stenting (success rate, 100%), and was left untreated in 2 cases. We identified 3 types of LVAD-related blood flow obstruction, and developed an algorithm for optimal diagnosis and treatment.


Suggested Guidelines for Reporting Keratoprosthesis Results: Consensus Opinion of the Cornea Society, Asia Cornea Society, EuCornea, PanCornea, and the KPRO Study Group.
To propose a series of standardized guidelines for reporting keratoprosthesis (KPRO) results. At the most recent KPRO Study Group Meeting (Barcelona, 2015), representatives of the 4 multinational corneal societies (Cornea Society, Asia Cornea Society, EuCornea, and PanCornea) and the KPRO Study Group agreed to propose consistent terminology for reporting KPRO results, especially in describing the length of follow-up and in the description of the KPRO itself. Consensus was reached for minimal reporting guidelines. The 4 multinational corneal societies and the KPRO Study Group agreed to standardized terminology for reporting the length of follow-up, preoperative diagnosis grouping, and data stratification based on the KPRO type used. Guidelines suggesting minimal reporting standards will assist in both data collection and reporting and will allow for better comparative analysis and pooling of the available data.


Antinuclear antibodies (ANAs): diagnostically specific immune markers and clues toward the understanding of systemic autoimmunity.
The convergence of studies in the clinical and basic sciences has resulted in the definitive identification of many intracellular antigens which are the targets of autoantibodies in patients with systemic lupus erythematosus, scleroderma, dermatomyositis/polymyositis, Sjogren's syndrome, mixed connective tissue disease, and drug-induced autoimmunity. Some of this new knowledge includes the identification of the Sm and RNP antigens as ribonucleoprotein particles involved in splicing of precursor messenger RNA, Scl-70 as DNA topoisomerase I, proliferating cell nuclear antigen as auxiliary protein of DNA polymerase delta, and certain antigens in myositis as aminoacyl transfer RNA synthetases. This information confirms, at a molecular level, the presence of specific profiles of autoimmune responses so that autoantibodies can be used in clinical medicine as diagnostically useful immune markers. In addition the data give compelling reasons to consider that certain autoimmune diseases are antigen-driven. Many auto-antibodies have the interesting feature of recognizing epitopes on the antigens which are active or functional sites of the molecule. It is suggested that the data provide clues to the nature of the intracellular particle initiating the immune response and may help to elucidate some of the early mechanisms of the autoimmune process.


Purification, characterisation and coal depolymerisation activity of lignin peroxidase from Lenzitus betulina MTCC-1183.
Lignin peroxidase from the culture filtrate of Lenzitus betulina MTCC-1183 has been purified to homogeneity using concentration by ultrafiltration and anion exchange chromatography on DEAE cellulose. The molecular weight of the purified lignin peroxidase using SDS-PAGE analysis was 43 kDa. Specific activity of the enzyme was 29.58 IU/mg. The K(m) values for veratryl alcohol and H2O2 for the purified enzyme were 54 microM and 81 microM, respectively. The k(cat) value of the purified enzyme was 2.3 s(-1) using 3,4-dimethoxybenzyl alcohol as the substrate. The optimal conditions for the lignin peroxidase assay were detected at pH 2.4 and 22 degrees C. Thermal stability of the purified enzyme has also been studied and its activation energy for deactivation was 287 kJ/mol. The purified lignin peroxidase depolymerised humic acid in presence of H2O2. Depolymerisation of coal by the L. betulina MTCC-1183 has been demonstrated using humic acid as a model of coal.


Defecating proctography: A pictorial essay.
To provide an illustrative description of the technique and spectrum of findings in defecating proctography. Important findings on defecating proctography include rectocoele, enterocoele, sigmoidocoele, cystocoele, intussusception, rectal prolapse, descending perineum, incomplete emptying, anismus, and faecal incontinence. This review article illustrates these key findings with examples. Defecating proctography is a well-established and cost-effective method of assessing disordered defecation. In conjunction with clinical information and other diagnostic tests, findings on defecating proctography can guide appropriate multidisciplinary management and may lead to improvement in embarrassing and debilitating symptoms in many patients. This review article provides a suggested technique and covers the spectrum of findings on defecating proctography.


Immunosuppression with generic tacrolimus and mycophenolate mofetil in renal transplant recipients: preliminary report in Chile.
The association of tacrolimus (TAC) and mycophenolate mofetil (MMF) in renal transplant patients has diminished the incidence of acute rejection. We evaluated the use of generic TAC and MMF as primary immunosuppression in 6 living related (LR) and 11 cadaveric (C) donor renal transplant recipients (9 men, 8 women) of mean age 37 +/- 12 years (range, 17-56 years) between May 2006 and June 2007. From day 0 all patients received TAC, MMF, and prednisone without antibody induction. They were followed for the development of acute rejection, graft loss, side effects, and mortality. Mean follow-up was 7.6 months (range, 2-15 months). No biopsy-proven acute rejection episodes, graft loss, or recipient deaths were observed. Creatinine levels at the end of the study were 1.90 +/- 1.0 mg/dL (range, 0.62-4.25 mg/dL for C recipients and 1.19 +/- 0.15 mg/dL (range, 0.91-1.35 mg/dL) for LR recipients. Mean systolic and diastolic blood pressures were 130/73 mm Hg with 12 patients (70.5%) on antihypertensive therapy with calcium antagonists and beta-blockers. Mean (range) of total cholesterol, triglycerides, and glucose were 172 (110-244) mg/dL, 139 (69-277) mg/dL, and 89 (63-129) mg/dL, respectively. MMF was suspended in 1 patient due to diarrhea and 1 other because of leukopenia. We observed that generic TAC and MMF yielded effective and safe immunosuppression in terms of mortality, biopsy-proven acute rejection, and graft loss with a low incidence of adverse effects during the study period.


Nutrient-limited microbial growth kinetics: overview and recent advances.
Traditional concepts of nutrient uptake and growth kinetics as linked by cell yield are presented. Phenomena affecting the kinetics are examined along with a discussion of those which lead to ambiguity. Concepts of flux control are presented to help understand the distribution of material along metabolic pathways. Specific affinity is described to relate nutrient accumulation rates to transporter density. It is shown to be a primary kinetic constant and the best available index of nutrient collection ability. As an aid to understanding, specific affinity is reexpressed in terms of membrane permeability. Formulations of nutrient transport rate as a function of cellular composition, particularly transporter and enzyme content and known as janusian kinetics, are described as an improvement to specific affinity theory. Procedures for quantified unidirectional fluxes are reviewed to identify the difference between gross and net transport rates of substrate. Collision frequency theory is used to show that in addition to total biomass, cell size and transporter density should also be included in rate equations describing microbial growth. Theory diversity suggests that one reason for microbial metabolic is that the likelihood of additional collisions of substrate molecules with a cell surface, after an initial collision, requires only a sparse distribution of transporter sites for maximal rate, leaving room for additional transporters able to collect other substrate types.


Digesting recent findings: gut alpha-synuclein, microbiome changes in Parkinson's disease.
Two hallmarks of Parkinson's disease (PD) are the widespread deposition of misfolded alpha-synuclein (αSyn) protein in the nervous system and loss of substantia nigra dopamine neurons. Recent research has suggested that αSyn aggregates in the enteric nervous system (ENS) lead to prodromal gastrointestinal (GI) symptoms such as constipation in PD, then propagating to the brain stem and eventually triggering neurodegeneration and motor symptoms. Additionally, whether the microbiome changes in PD contribute to the primary pathogenesis or, alternatively, are consequential to either the disease process or medication is still unclear. In this review, we discuss the possible roles of αSyn and microbiome changes in the GI system in PD and consider if and how the changes interact and contribute to the disease process and symptoms.


Tcrb-V3+ T-cell deletion and a new mouse mammary tumor provirus, Mtv-44.
Genes encoding endogenous superantigens causing Tcrb-V3+ T-cell deletion co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-3, Mtv-6, and Mtv-13. In addition Mtv-1 has been implicated in deletion of these T cells. We have examined levels of Tcrb-V3+ T cells and Mtv integrations in the following offspring and their parental strains, [(CBA-T6 x NZW)F1 x CBA], [(CBA x C3H/He)F1 x CBA], and [(B10.S (9R) x NOD]F1 mice. We show that a new Mtv (Mtv-44) from NZW mice and Mtv-1 from C3H/He mice cosegregate with genes encoding ligands for partial deletion of Tcrb-V3+ T cells and that some NOD mice have an additional Mtv (Mtv-45) which is closely linked to Mtv-3.


Multicentric infantile myofibromatosis.
Infantile myofibromatosis (IM) is a rare tumor of infancy and childhood, typically presenting as a firm, nodular mass involving soft tissue, bone or viscera. Approximately one-third of cases involve the head and neck. These tumors can be solitary or multicentric. Biopsy reveals tumor cells that resemble myofibroblasts. Spontaneous regression may occur. A high degree of suspicion is necessary to differentiate this entity from other more aggressive processes histiocytosis, fibrosarcoma, rhabdomyosarcoma. We describe the case of a male infant with multicentric myofibromatosis, presenting with multiple thoraco-abdominal subcutaneous nodules and lytic mass lesions of the temporal bone and calvarium. The characteristic clinical, radiologic and histopathologic features of this process are reviewed along with diagnostic and therapeutic options.


Monitor: an expert system that validates and interprets time-dependent partial data based on a cystic fibrosis home monitoring program.
The use of health diaries to monitor patients with chronic diseases has often been complicated by difficulties encountered in data quality assurance and interpretation. An expert system, Monitor, has been developed to predict the health status of cystic fibrosis patients based on daily home measurements of pulse, respiratory rate, weight, inspired vital capacity, and a check list of symptoms of acute illness. This system ensures data reliability beyond what can be achieved in most current automatic error detection procedures by validating inputs against patient-specific expectations. Its explicit representation of the time dimension and the hierarchical structure of its knowledge base facilitate the abstraction of trends and relationships among the time-dependent data. Dynamically imposed expectations also lend flexibility to the interpretation process by allowing the processing of partial (incomplete) data. Monitor correctly classified 86 percent (three-category classification) and 94 percent (two-category classification) of 111 cases. This demonstrates that expert systems can be a feasible approach in building more robust diary monitoring systems.


A divergent clade of circular single-stranded DNA viruses from pig feces.
Using metagenomics and molecular cloning methods, we characterized five novel small, circular viral genomes from pig feces that are distantly related to chimpanzee and porcine stool-associated circular viruses, (ChiSCV and PoSCV1). Phylogenetic analysis placed these viruses into a highly divergent clade of this rapidly growing new viral family. This new clade of viruses, provisionally named porcine stool-associated circular virus 2 and 3 (PoSCV2 and PoSCV3), encodes a stem-loop structure (presumably the origin of DNA replication) in the small intergenic region and a replication initiator protein commonly found in other biological systems that replicate their genomes via the rolling-circle mechanism. Furthermore, these viruses also exhibit three additional overlapping open reading frames in the large intergenic region between the capsid and replication initiator protein genes.


Hedonic Overeating-Questionnaire: Exploring interactive effects between wanting, liking, and dyscontrol on body mass index.
The Hedonic Overeating-Questionnaire is a brief self-report measure for the trait assessment of liking (pleasure to eat; consummatory reward component), wanting (food craving; anticipatory reward component), and dyscontrol (loss of control over eating). In the original validation study, higher scores on each of the three subscales related to higher body mass index (BMI). However, theories on food reward and self-regulation suggest that overeating and obesity may also result from interactions between these aspects. Therefore, we reanalyzed the data of the original, cross-sectional study (N = 2504, 53% female) and explored whether liking, wanting, and dyscontrol scores interactively predicted BMI. Indeed, there was a significant interaction effect Wanting × Dyscontrol on BMI such that higher dyscontrol scores related to higher BMI, particularly at high wanting scores. The other two-way interactions and the three-way interaction were not significant. Results do not support certain theories on food reward (e.g., the incentive-sensitization theory of addiction and its application to obesity), which would suggest an interactive effect between liking and wanting on BMI. However, they do support dual systems models of self-regulation that suggest that overeating and obesity result from an interplay of strong bottom-up impulses (here: wanting) and weak top-down control (here: dyscontrol).


Factors affecting time to rehospitalization in Han Chinese patients with schizophrenic disorder in Taiwan.
Schizophrenic disorder is a lifelong illness. Hospitalization is a major event for the patient and his/her family, often indicating that the clinical symptoms have reached an intolerable level. The purpose of this study was to investigate the risk factors affecting the time to rehospitalization. Rehospitalization status was monitored for all schizophrenic patients discharged from Kai-Suan Psychiatric Hospital from January 1, 2002 to December 31, 2002. Patients were followed-up regarding rehospitalization until December 31, 2003. The Kaplan-Meier method was used to calculate the mean time to rehospitalization. Risk factors associated with rehospitalization were examined by Cox proportional hazards regression model. Three hundred and thirty-six patients were recruited for this study. The mean time to rehospitalization was 239 +/- 7 days, with a rehospitalization rate of 54.5%. The mean time to discontinuation was 329 +/- 5 days. Age at onset (hazard ratio = 0.978, 95% CI = 0.959-0.998, p = 0.031) and the number of previous hospitalizations (hazard ratio = 1.108, 95% CI = 1.058-1.161, p < 0.001) were found to be risk factors of shorter time to rehospitalization within 1 year after discharge. Further research should be carried out to test risk factors in a prospective study, and to assess the cost-effectiveness of interventions to prevent rehospitalization.


Comparison of body distribution of poly(vinyl alcohol) with other water-soluble polymers after intravenous administration.
The body distribution of poly(vinyl alcohol) (PVA) with molecular weights (MW) from 14,800 to 434,000 Da was investigated after intravenous administration and compared with that of other water-soluble polymers such as poly(ethylene glycol) (PEG), gelatin, dextran, and pullulan. The half-life of PVA in the circulation was prolonged from 90 min (MW 14,800 Da) to 23 h (MW 434,000 Da), similar to that of PEG which had a half-life of 30 min (MW 6000) and 20 h (MW 170,000). However, the half-life of PVA was much longer than that of other polymers when compared at a similar molecular weight. PVA was located in most organs but with very small accumulation. An insignificant interaction of PVA with cell components, such as macrophages and blood cells, was observed. Similar to PEG, the excretion rate of PVA at the glomeruli was rapidly reduced around 30,000 Da, as the molecular weight increased. These results indicate that the half-life of intravenously injected PVA in the blood was mainly determined by the permeation characteristics of the kidney.


The permeation of organic acids through lecithin bilayers. Resemblance to diffusion in polymers.
1. The fluxes of aliphatic acids and their derivatives through black lipid membranes made of egg lecithin in decane were measured by means of a proton titration method. 2. Permeability coefficients were calculated and these were divided by the partition coefficient of the diffusing solute in different solvent systems: n-decane, olive oil, ether and octanol. The logarithms of the diffusion coefficients thus obtained were plotted against the logarithm of the molecular weight. The data could not be fitted to a single regression line in any solvent system. 3. When the logarithm of the diffusion coefficients were correlated to the logarithm of the molecular volume (equals molecular weight/ specific gravity) all the diffusants could be fitted to the same regression line, indicating that the molecular volume is a better index of molecular size and shape than the molecular weight. 4. Analysis of the experimental results assuming a model of diffusion through soft polymers (Lieb, W.R. and Stein, W. D. (1971) Current Topics in Membranes and Transport, vol. 2, pp. 1-39, Academic Press, New York) showed that decane and olive oil are not adequate model solvents for planar lecithin membranes but ether and octanol are good models. 5. The differential mass selectivity coefficient was found to be similar to that for soft polymers and biological membranes, i.e. greater than 3.0. 6. Water could be fitted by the same regression line, thus emphasizing the generality of passive transfer and implying that water crosses lipid membranes as single molecules.


Association of robotic approach with patient-reported outcomes after pancreatectomy: a prospective cohort study.
Robotic-assisted pancreatectomy continues to proliferate despite limited evidence supporting its benefits from the patient's perspective. We compared patient-reported outcomes (PROs) between patients undergoing robotic and open pancreatectomies. PROs, measured with the FACT-Hep, FACT-G, and HCS, were assessed in the immediate postoperative (i.e., preoperative to discharge) and recovery (i.e., discharge to three months postoperative) periods. Linear mixed models estimated the association of operative approach on PROs. Minimally important differences (MIDs) were also considered. Among 139 patients, 105 (75.5%) underwent robotic pancreatectomies. Compared to those who underwent open operations, those who underwent robotic operations experienced worse FACT-Hep scores that were both statistically and clinically significant (mean difference [MD] 8.6 points, 95% CI 1.0-16.3). Declines in FACT-G (MD 4.3, 95% CI -1.0 to 9.6) and HCS (MD 4.3, 95% CI 0.8-7.9) scores appeared to contribute equally in both operative approaches to the decline in total FACT-Hep score. Patients who underwent robotic versus open operations both statistically and clinically significantly improved due to improvements in HCS (MD 6.1, 95% CI 2.3-9.9) but not in FACT-G (MD 1.2, 95% CI - 5.1-7.4). The robotic approach to pancreas surgery might offer, from the patient's perspective, greater improvement in symptoms over the open approach by three months postoperatively.


Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers.
N-glycans from plant and invertebrate allergens can induce extensive immunoglobulin-E (IgE) cross-reactivity in vitro. IgE antibodies against these N-glycans, also termed cross-reactive carbohydrate determinants or CCDs, are prevalent in alcohol drinkers. This study investigated the prevalence and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers. A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects. Eleven heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation with a glycoconjugate containing bromelain-type N-glycans. The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls. There was no relationship between immunoblot reactivity and consumption of any specific type of wine. No patient reported symptoms of hypersensitivity to Hymenoptera venom, food, or wine. In conclusion, heavy drinkers frequently show IgE reactivity to the N-glycans of wine glycoproteins. Glycans and wine glycoprotein extracts can induce basophil activation in sensitized alcoholics. The clinical significance of these findings remains to be elucidated.


The effect of Bacillus subtilis Vru1 encapsulated in alginate - bentonite coating enriched with titanium nanoparticles against Rhizoctonia solani on bean.
This research investigated the colonization efficiency and survival rate of nanoencapsulated Bacillus subtilis Vru1 prepared with sodium alginate (NaAlg), starch and bentonite and, their efficiency for controlling Rhizoctonia solani. The XRD and FTIR analysis in this research indicated the absence of chemical reactions, and correct mixing efficiency was funded with alginate, bentonite and starch. The highest release of B. subtilis Vru1 was 4 × 109 in 45th day of storage. The quantity of colonization by B. subtilis Vru1 nanocapsules was lower than that of free B. subtilis Vru1 at days 5-20 and was significantly higher than that of free B. subtilis VRU1 and encapsulated B. subtilis VRU1 without Titanium dioxide nanoparticle, after day 35. This level was maintained for up to 45th day. The results of this experiments indicated that the highest and lowest inhibition of R. solani on bean observed in Vru1 nanocapsules with 90% and free Vru1 with 60% respectively. and Vru1 capsule without titanium nanoparticles (TNs) decreased the disease by 75%. The nanoencapsulated B. subtilis Vru1 strain significantly increased the bean vegetative growth parameters. This finding was probably attributed to the enhancement in the number of the bacterium and the high level of metabolite production such as indole-3-acetic acid. Thus, nanocapsule formulation is a potential alternative for sustainable agriculture.


Trends and Exceptions in the Interaction of Hydroxamic Acid Derivatives of Common Di- and Tripeptides with Some 3d and 4d Metal Ions in Aqueous Solution.
By using various techniques (pH-potentiometry, UV-Visible spectrophotometry, 1H and 17O-NMR, EPR, ESI-MS), first time in the literature, solution equilibrium study has been performed on complexes of dipeptide and tripeptide hydroxamic acids-AlaAlaNHOH, AlaAlaN(Me)OH, AlaGlyGlyNHOH, and AlaGlyGlyN(Me)OH-with 4d metals: the essential Mo(VI) and two half-sandwich type cations, [(η6-p-cym)Ru(H2O)3]2+ as well as [(η5-Cp*)Rh(H2O)3]2+, the latter two having potential importance in cancer therapy. The tripeptide derivatives have also been studied with some biologically important 3d metals, such as Fe(III), Ni(II), Cu(II), and Zn(II), in order to compare these new results with the corresponding previously obtained ones on dipeptide hydroxamic acids. Based on the outcomes, the effects of the type of metal ions, the coordination number, the number and types of donor atoms, and their relative positions to each other on the complexation have been evaluated in the present work. We hope that these collected results might be used when a new peptide-based hydroxamic acid molecule is planned with some purpose, e.g. to develop a potential metalloenzyme inhibitor.


Timing and indication of surgery for ruptured intracranial aneurysms with regard to cerebral vasospasm.
The authors survey 443 cases of intracranial aneurysms treated in the past seven years. 403 cases were operated upon with microsurgical techniques. The operative mortality was 5.4 per cent, and 82.4 per cent of surgically treated cases are well and working, leading useful social lives. It was found that cases submitted to surgery in the first three days after subarachnoid haemorrhage (SAH) (the day of SAH being counted as the first day) showed good results, little appearance of postoperative vasospasm, and no mortality due to vasospasm. Cases operated upon after one week from the insult of SAH also showed good results, whereas fatal postoperative vasospasm was seen in cases operated upon on the 4th--7th day after SAH. Cisternal, ventricular, and epidural drainage are recommended after the clipping of aneurysms in the acute stage of SAH. There were 68 cases with preoperative vasospasm. There was no case in which vasospasm was identified during the first four days after SAH, while 66 per cent of the cases exhibited vasospasm between the sixth and ninth days after SAH. These 68 cases can be classified into four groups: 1. 8 cases died from vasospasm before surgery: 2. 8 cases had renewed bleeding mainly when vasospasm began to subside. 3. 22 cases underwent surgery after vasospasm had subsided, the duration of vasospasm ranging from 8 to 24 days, on an average 14 days; 4. 30 cases underwent surgery while vasospasm was still present; of this group, (4E) 15 cases submitted to surgery, on an average 4.5 days after the onset of vasospasm, manifested deterioration of clinical states because of aggravation or new appearance of vasospasm; (4L, 15 cases which underwent surgery, on an average 7.4 days after the onset of vasospasm, showed no such deterioration. In the follow-up, well and working cases were seen in 45.5 per cent (3.), 60 per cent (4E), and 80 per cent (4L), respectively. The authors classified vasospasm into three types: Type 1, extensive diffuse, Type 2, multi-segmental, and Type 3, local. Type 1 was prognostically worst, Type 3 good, and Type 2 was located between these two types.


Pediatric musculoskeletal magnetic resonance imaging.
MRI has demonstrated clinical applicability and improved diagnostic capability in the musculoskeletal system to a degree rivaling its success in the neurologic system. For certain regions such as the joints, the superficial nature of these structures is ideal for the application of localized radiofrequency coils, enabling considerably improved signal, spatial resolution, and detectable contrast. The multiplanar capability is often invaluable in assessing such regions as the weight-bearing surfaces of the hips. It has been shown to be the most sensitive single test for diagnosing avascular necrosis, and has yielded very high resolution images of the internal architecture of the joints and soft tissues in an entirely noninvasive manner and without the need for the administration of exogenous contrast agents. Short TE images are quite useful in evaluating fatty background regions of interest, such as the bone marrow and subcutaneous tissue, whereas long TR and TE studies are frequently more suitable for soft tissue pathology. The lack of ionizing radiation and the continued failure of intensive research to disclose any deleterious effects at the levels used for clinical diagnostic imaging make this tool especially appealing for application to the pediatric population. With the continual development of new pulsing sequences, contrast agents, and further advances in imaging/spectroscopic correlation, magnetic resonance imaging of the musculoskeletal system is ensured of a solid role in the clinical diagnostic evaluation of the pediatric population.


HIF-1α regulates the expression of the non-conventional isoform of the cd5 gene in T cells under the hypoxic condition: A potential mechanism for CD5neg/low phenotype of infiltrating cells in solid tumors.
CD5, a T-cell receptor (TCR) negative regulator, is reduced on the surface of CD8+ lymphocytes in the tumor microenvironment (TME). Reduced surface CD5 expression (sCD5) occurs due to the preferential transcription of HERV-E derived exon E1B, i.e., anon-conventional formofthe cd5gene instead of its conventional exon E1A. A tumor employs several mechanisms to evade anti-tumor response, and hypoxia is one such mechanism that prevails in the TME and modulates the infiltrated T lymphocytes. We identified hypoxia response elements (HREs) upstream of E1B. We showed binding of HIF-1α onto these HREs and increased E1B mRNA expression in hypoxic T cells. This results in decreased sCD5 expression and increased cytoplasmic accumulation in T cells. We also validated our study in a solid tumor, i.e., colorectal cancer (CRC) patient samples. This hypoxia-driven mechanism reduces the surface CD5 expression on infiltrated T-cells in solid tumors.


Four-dimensional imaging and computer-assisted track analysis of nuclear migration in root hairs of Arabidopsis thaliana.
Nuclear migration is a fundamental mechanism necessary for the proper growth and development of many eukaryotic organisms. In this study root hairs of Arabidopsis thaliana were used as a research model to gain insight into the dynamics of nuclear migration. Root hairs are long tubular outgrowths of epidermal cells and are responsible for the uptake of water and nutrients. During the development of root hairs, the nucleus migrates into the hair after the bulge is formed. The position of the nucleus relative to the tip plays an essential role in the growth process. However, what is happening to the nucleus in full-grown root hairs is still unclear. To study nuclear dynamics in living root hair cells, stably transformed plants with the fusion proteins Histone2B-YFP and NLS-GFP-GUS were used. Four-dimensional confocal laser scanning microscopy made it possible to monitor the exact position of the nucleus in different root hairs. To analyse the sequential positions of the nuclei in the root hairs, a new computer-assisted method was developed. After track analysis a number of parameters could be extracted from the movies, such as the average speed, the amplitude, direction factor and the range of movement in the root hairs. Our results show that nuclei do not reach a final position in full-grown root hairs and this sustained movement seems to be more similar in root hairs lying close to each other. Moreover, with this methodology it could be quantitatively demonstrated that the integrity of actin is necessary for nuclear movement.


The morphology and systematics of Rhabdochona paski Baylis, 1928 (Nematoda: Rhabdochonidae), a widespread parasite of freshwater fishes in Africa.
Nematodes of the genus Rhabdochona Railliet, 1916, identified as R. paski Baylis, 1928, were collected from the intestine of Hydrocynus forskahlii (Cuvier) (Characiformes: Alestidae), Oreochromis niloticus (Linnaeus) and Tilapia zillii (Gervais) (both Perciformes: Cichlidae) from Lake Turkana, Kenya during 2007-2009. Their morphology was studied in detail using light and scanning electron microscopy. Paratypes of R. paski and museum specimens of R. congolensis Campana-Rouget, 1961 from six other host species were examined for comparison. Based on these studies and the available literature data, Rhabdochona congolensis, R. aegyptiaca El-Nafar & Saoud, 1974 (emend.) and R. vesterae Boomker & Petter, 1993 are considered to be junior synonyms of R. paski. The occurrence of this widely distributed African nematode in many fish species belonging to different families and orders suggests that most of them are probably not definitive hosts of this parasite, but only serve as paratenic, paradefinitive or postcyclic hosts (sensu Odening, 1976). True definitive hosts of R. paski appear to be characiform species belonging to some genera (e.g., Alestes, Brycinus, Hydrocynus) of the family Alestidae.


Ticlopidine-induced phenytoin toxicity.
To report a probable case of ticlopidine-induced phenytoin toxicity. A 72-year-old white man suddenly developed combative behavior, refused to leave his room, stopped eating, and began falling to the floor 6 weeks after being given ticlopidine. The total phenytoin concentration was measured at 43.6 micrograms/mL; the dosage of phenytoin was decreased and the symptoms later resolved. After ticlopidine was discontinued, the patient was rechallenged with the same dose of phenytoin without symptoms of toxicity. Possible mechanisms of the drug interaction are discussed with emphasis on cytochrome P450 metabolism. Clinicians should be aware of this potentially serious drug interaction and either avoid the phenytoin-ticlopidine combination, or monitor closely for phenytoin toxicity.


Current considerations in the management of rectovaginal fistula from Crohn's disease.
Rectovaginal fistulas are dreaded complications of Crohn's disease. Accurate assessment is essential for planning management. Treatment options range from observation to medical therapeutics to the need for surgical intervention. Ultimately, establishing reasonable expectations is mandatory when treatment algorithms are considered. In this article, we review the evaluation of these fistulas and the current options to consider in the treatment of Crohn's related rectovaginal fistula.


Post-traumatic High-flow Priapism: Multidetector Computed Tomography Demonstration.
High-flow priapism due to pseudoaneurysm is a relatively rare urologic condition. Clear anatomic delineation of the number and origin of feeding vessels facilitates pre-embolization planning. Computed tomographic angiography can afford a three-dimensional display of the feeding vessels. We present a 26-year-old man with post-traumatic high-flow priapism, which is the first case studied with computed tomographic angiography.


An easy and safe technique for ventricular septal defect closure in hearts with atrioventricular discordant connection and dextrocardia.
When ventricular septal defect exists in hearts with atrioventricular discordant connection and dextrocardia, closure of the defect can most easily be accomplished by exposure through the left atrium and retracted tricuspid valve leaflets. This approach provides good visualization of all aspects of the defect and keeps the suture line away from the conduction tissue, thus reducing the possibility of iatrogenic heart block.


Interspecific predation as a mortality factor among overwintering spiders.
Results from field experiments indicate that predation occurs among spruce-living spiders during winter in SW Sweden. Field observations of natural activity showed that Philodromus spp and Pityohyphantes phrygianus together make up 80% of the spiders active on spruce in winter. They are therefore potential predators on other overwintering spiders. Laboratory experiments were performed at +4° C to assess the importance of such predation between spiders. Small spiders (length <2.5 mm) had a mean winter mortality of 58% when kept together with large spiders (≧2.5 mm) which had a mean mortality of 3% only. Among the small spiders the Erigninae spp seemed to be more vulnerable to predation than other taxonomic groups. Predation also occurred when large P. phrygianus were kept together, but such predation caused mortality of less importance to the spider populations than the mortality among small spiders. Differences in spider density and food availability did not change this pattern. Considerable weight increase occurred in subadult P. phrygianus when fed during winter. This suggests that winter foraging specimens increase their fitness. Interspecific predation among spiders is suggested to be an important mortality factor in natural populations at high spider densities in November and December, when the ambient temperature often is above 0° C and when the density of large spiders is not yet substantially reduced by bird predation.


Total Knee Arthroplasty and Intra-Articular Pressure Sensors: Can They Assist Surgeons with Intra-Operative Decisions?
Soft tissue imbalance, presenting as instability or stiffness, is an important cause of revision total knee arthroplasty (TKA). Traditional methods of determining soft tissue balance of the knee lack precision and are not reliable between operators. Use of intra-operative pressure sensors offers the potential to identify and avoid soft tissue imbalance following TKA. This review aims to summarise the literature supporting the clinical indication for the use of intra-articular pressure sensors during TKA. Analytical validation studies suggest that intra-operative pressure sensors demonstrate 'moderate' to 'good' intra-observer reliability and 'good' to 'excellent' interobserver reliability throughout the flexion arc. However, there are important errors associated with measurements when devices are used out-with the stated guidelines and clinicians should be aware of the limitations of these devices in isolation. Current evidence regarding patient benefit is conflicting. Despite positive early results, several prospective studies have subsequently failed to demonstrate significant differences in overall survival, satisfaction, and patient-reported outcome measures within 1 year of surgery. Surgeon-defined soft tissue stability appears to be significantly different from the absolute pressures measured by the intra-operative sensor. Whilst it could be argued that this confirms the need for intra-articular sensor guidance in TKA; the optimal 'target' balance remains unclear and the relationship with outcome in patients is not determined. Future research should (1) identify a suitable reference standard for comparison; (2) improve the accuracy of the sensor outputs; and (3) demonstrate that sensor-assisted TKA leads to patient benefit in patient-reported outcome measures and/or enhanced implant survival.


Novel Management of Granuloma Formation Secondary to Dermal Filler with Intralesional 1444 nm Nd:YAG Laser Technique.
Background: Dermal fillers for soft tissue for the treatment of face sagging, volume loss, and wrinkles have become popular among patients of all ages and ethnicities, and their use is becoming increasingly widespread. Aim: the goal of this study was to evaluate the effectiveness and safety of a micro-pulsed, 1444 nm Nd:YAG laser on dermal filler complications, in particular on granuloma management. Methods: A subcutaneous, 1444 nm Nd:YAG laser was used on five female patients (range age 52-68 years) with hyaluronic filler granulomas located on the face (two on the cheek area and three on the lips); three patients had self-injected the filler, buying it online. Before and after the therapy, the patients received a skin ultrasound to determine the form and location of the granulomas and to determine if there had been a full or partial resolution. During this study, all possible adverse effects at the treatment site were monitored. The 5-point Global Aesthetic Improvement Scale (GAIS) (0 point-no change; 1 point-25%, mild improvement; 2 points-50%, moderate improvement; 3 points-75%, good improvement; 4 points-100%, excellent improvement) was recorded at a 3-month follow-up. Results: good results were obtained in the treatment of filler granulomas with the intralesional 1444 nm laser, even if just a single treatment was performed (one intervention was effective for curing granulomas up to 5 mm in diameter). Three patients were satisfied with excellent improvement, and two patients experienced good improvement. The results are functional and aesthetically satisfying, as shown by photographic assessment. At the last follow-up, the granuloma had reduced or completely disappeared in all cases, and no infections, burns, scarring or fibrosis, episodes of severe bleeding, or other serious adverse effects had been reported. All subjects tolerated the post-treatment period well. Conclusions: Our findings showed that granuloma treatment with an intralesional 1444 nm Nd:YAG laser is a minimally invasive, easy, fast, efficient, and low-risk procedure.


Tight encapsulation of a "naked" chloride in an imidotitanium hexanuclear host.
Treating the imidotitanium dimer [Ti(μ-NAr)(NMe2)2]2 (Ar = 2,6-(i)Pr2C6H3) with excess Me3SiCl affords the hexanuclear complex [{Ti(═NAr)Cl2}6(Cl)](-)[Q](+). The self-assembled hexameric cage arrangement encapsulates a chloride ion guest that provides evidence of new host-guest chemistry in this area, while the cationic part is composed of mixtures of the Q(+) cations Me2NHSiMe3(+) and Me2N(SiMe3)2(+).


ω-6/ω-3 fatty acid ratio as an essential predictive biomarker in the management of type 2 diabetes mellitus.
Intake of dietary fatty acid may play a major role in the prevention and management of lifestyle-related diseases such as type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to find an association between ω-6 to ω-3 fatty acid ratio and T2DM. Fasting plasma glucose, glycated hemoglobin, and insulin were measured using commercially available kits. Fatty acid methyl esters were prepared using standard protocols. Delta-5 desaturase (D5D) and delta-6 desaturase (D6D) activities were determined from product-to-precursor ratios of individual fatty acids in plasma. Statistical analysis was performed using SPSS version 20. The ratio of ω-6 to ω-3 was higher in the group with diabetes (13:1) when compared with the group without diabetes (4:1) and was statistically significant (P < 0.0001). Further association studies showed that univariate model with the ω-6 to ω-3 ratio and a multivariate model with D5D, D6D, and ω-6 to ω-3 ratio could serve as predictive polyunsaturated fatty acid pathway models for T2DM. From the study results, it is evident that ω-6 to ω-3 fatty acid ratios can serve as essential predictive biomarkers in the management of patients with T2DM. This would not only help in management but would also aid in prevention of increased T2DM incidence in India. These results potentiate the need to maintain an ideal balance of ω-6 to ω-3, as prevention is always better than cure.


CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA.
The all-protein cytosine base editor DdCBE uses TALE proteins and a double-stranded DNA-specific cytidine deaminase (DddA) to mediate targeted C•G-to-T•A editing. To improve editing efficiency and overcome the strict TC sequence-context constraint of DddA, we used phage-assisted non-continuous and continuous evolution to evolve DddA variants with improved activity and expanded targeting scope. Compared to canonical DdCBEs, base editors with evolved DddA6 improved mitochondrial DNA (mtDNA) editing efficiencies at TC by 3.3-fold on average. DdCBEs containing evolved DddA11 offered a broadened HC (H = A, C or T) sequence compatibility for both mitochondrial and nuclear base editing, increasing average editing efficiencies at AC and CC targets from less than 10% for canonical DdCBE to 15-30% and up to 50% in cell populations sorted to express both halves of DdCBE. We used these evolved DdCBEs to efficiently install disease-associated mtDNA mutations in human cells at non-TC target sites. DddA6 and DddA11 substantially increase the effectiveness and applicability of all-protein base editing.


Burnout among healthcare professionals in Qatar: A systematic review.
This systematic review aims to cover studies addressing the topic of burnout among the various types of healthcare professionals in Qatar. PubMed, Scopus and Google Scholar were searched with no filters. All studies using the Maslach Burnout Inventory (MBI) were included. The Newcastle-Ottawa Scale was used for quality assessment of the studies included. The reporting of the study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The results indicate that the pooled prevalence rate of burnout among healthcare professionals in Qatar are, 17% and 20% based on fixed effect and random effect models, respectively.


Longitudinal Surveillance for SARS-CoV-2 Among Staff in Six Colorado Long-Term Care Facilities: Epidemiologic, Virologic and Sequence Analysis.
SARS-CoV-2 emerged in 2019 and has become a major global pathogen. Its emergence is notable due to its impacts on individuals residing within long term care facilities (LTCFs) such as rehabilitation centers and nursing homes. LTCF residents tend to possess several risk factors for more severe SARS-CoV-2 outcomes, including advanced age and multiple comorbidities. Indeed, residents of LTCFs represent approximately 40% of SARS-CoV-2 deaths in the United States. To assess the prevalence and incidence of SARS-CoV-2 among LTCF workers, determine the extent of asymptomatic SARS-CoV-2 infection, and provide information on the genomic epidemiology of the virus within these unique care settings, we collected nasopharyngeal swabs from workers for 8-11 weeks at six Colorado LTCFs, determined the presence and level of viral RNA and infectious virus within these samples, and sequenced 54 nearly complete genomes. Our data reveal a strikingly high degree of asymptomatic/mildly symptomatic infection, a strong correlation between viral RNA and infectious virus, prolonged infections and persistent RNA in a subset of individuals, and declining incidence over time. Our data suggest that asymptomatic SARS-CoV-2 infected individuals contribute to virus persistence and transmission within the workplace, due to high levels of virus. Genetic epidemiology revealed that SARS-CoV-2 likely spreads between staff within an LTCF. Colorado State University Colleges of Health and Human Sciences, Veterinary Medicine and Biomedical Sciences, Natural Sciences, and Walter Scott, Jr. College of Engineering, the Columbine Health Systems Center for Healthy Aging, and the National Institute of Allergy and Infectious Diseases.


Draft Genome Sequence of Streptomyces ahygroscopicus subsp. wuyiensis CK-15, Isolated from Soil in Fujian Province, China.
We report the first high-quality draft genome sequence of an antibiotic (wuyiencin)-producing strain, Streptomyces ahygroscopicus subsp. wuyiensis CK-15, isolated from soil samples collected from Fujian Province, China. The 9.41-Mb genome comprises 8,311 protein-coding sequences, encodes 89 structural RNAs, and shows a G+C content of 72.25%.


Multiplatform biomarker identification using a data-driven approach enables single-sample classification.
High-throughput gene expression profiles have allowed discovery of potential biomarkers enabling early diagnosis, prognosis and developing individualized treatment. However, it remains a challenge to identify a set of reliable and reproducible biomarkers across various gene expression platforms and laboratories for single sample diagnosis and prognosis. We address this need with our Data-Driven Reference (DDR) approach, which employs stably expressed housekeeping genes as references to eliminate platform-specific biases and non-biological variabilities. Our method identifies biomarkers with "built-in" features, and these features can be interpreted consistently regardless of profiling technology, which enable classification of single-sample independent of platforms. Validation with RNA-seq data of blood platelets shows that DDR achieves the superior performance in classification of six different tumor types as well as molecular target statuses (such as MET or HER2-positive, and mutant KRAS, EGFR or PIK3CA) with smaller sets of biomarkers. We demonstrate on the three microarray datasets that our method is capable of identifying robust biomarkers for subgrouping medulloblastoma samples with data perturbation due to different microarray platforms. In addition to identifying the majority of subgroup-specific biomarkers in CodeSet of nanoString, some potential new biomarkers for subgrouping medulloblastoma were detected by our method. In this study, we present a simple, yet powerful data-driven method which contributes significantly to identification of robust cross-platform gene signature for disease classification of single-patient to facilitate precision medicine. In addition, our method provides a new strategy for transcriptome analysis.


Population pharmacokinetics of arbekacin in different infectious disease settings and evaluation of dosing regimens.
The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (≧8). A daily arbekacin dose of 4-6 mg/kg is primarily used for the treatment of MRSA infection. However, clinical pharmacokinetic studies of arbekacin that evaluate changes in patients with different infectious diseases have been limited. This study was to evaluate the pharmacokinetics of arbekacin in different infectious diseases and to evaluate its dosing regimens. This work describes a single-centre, retrospective study. The pharmacokinetic parameters of arbekacin were calculated from individual serum-concentration data using WinNonlin ver. 6.3. A total of 331 serum samples were obtained from 170 patients. Our drug concentration-time data were well described by a two-compartment open model. The final model showed that drug clearance was related to creatinine clearance and that the total distribution volume (Vd) was related to actual body weight and the presence of bacteremia. The individual Vd in bacteremia patients was significantly higher than those of other patients (bacteremia: 29.7 ± 0.5 L, pneumonia: 20.8 ± 0.4 L, other infections: 21.4 ± 0.4 L; p < 0.05). Additionally, Monte Carlo simulation showed that target (Cpeak/MIC ≧ 8) attainment was only 10.1%, even at a dose of 6 mg/kg, especially for MRSA bacteremia patients with an arbekacin MIC = 2 μg/mL. In conclusion, our study revealed that the Vd may be higher in bacteremia patients than in patients with other infectious diseases. Therefore, an increase in the daily dose of arbekacin should be considered for bacteremia patients.


The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery.
Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Pa(CO2) during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-alpha (8.4 versus 5.0 microg/mL) and sICAM-1 (52.7 versus 27.5 microg/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1. Reductions of tidal volume, with subsequently decreased peak airway pressures, may reduce some alveolar inflammatory responses seen with mechanical ventilation.


A colorimetric sensor array for recognition of 32 Chinese traditional cereal vinegars based on "turn-off/on" fluorescence of acid-sensitive quantum dots.
Colorimetric sensor array is a sensitive, rapid, and inexpensive detection technology which simulates human olfaction system based on various organic dyes. In this work, a sensor array based on acid-sensitive CdTe QDs coupled with chemometrics method was developed and proved to be a rapid, accurate and sensitive method for identification of 32 kinds of Chinese traditional cereal vinegars (CTCV). The specificity of identification of this method was mainly depends on the organic acids and melanoidins of CTCV. Among them, organic acids can quench the fluorescence of QDs through enhancing their electron transfer (hydrogen bond) and resonance energy transfer, and the fluorescence intensity of melanoidin was closely related to the brewing technology and aging year of CTCV. The types and aging time of 32 CTCV can be 100% identified at a dilution of 1000 by partial least squares discriminant analysis, when the latent variables were 4. And only one kind of QDs is needed instead of various organic dyes to this kind of colorimetric sensor array. Except for vinegar, this method can also be used in the identification of other food which rich in organic acid.


Zika & heart: A systematic review.
Zika virus infection affects more than 80 countries in the world, mainly those with a tropical climate. Although the most frequent clinical presentation is characterized by rash, conjunctivitis, myalgia, arthralgia and fever, in some cases it is associated with cardiovascular manifestations, such as myocarditis, pericarditis, heart failure and arrhythmias. Furthermore, maternal transmission of the virus generates congenital Zika syndrome, which is associated with cardiac septal defects. Early recognition and treatment of Zika's cardiovascular complications are essential to reduce morbidity and mortality in these patients. There is no specific antiviral treatment or vaccine in humans, so the development of public health strategies to prevent its transmission is of paramount importance. The "Neglected Tropical Diseases and other Infectious Diseases" (NET-Heart project) is an initiative to systematically review all these devastating endemic conditions affecting the heart to spread knowledge and propose algorithms for early diagnosis and treatment.


Structural basis of the strong cell-cell junction formed by cadherin-23.
Cadherin-23, a giant atypical cadherin, forms homophilic interactions at the cell-cell junction of epithelial cells and heterophilic interactions with protocadherin-15 at the tip-links of neuroepithelial cells. While the molecular structure of the heterodimer is solved, the homodimer structure is yet to be resolved. The homodimers play an essential role in cell-cell adhesion as the downregulation of cadherin-23 in cancers loosen the intercellular junction resulting in faster-migration of cancer cells and a significant drop in patient survival. In vitro studies have measured a stronger aggregation-propensity of cadherin-23 compared to typical E-cadherin. Here, we deciphered the unique trans-homodimer structure of cadherin-23 in solution, and show that it consists of two electrostatic-based interfaces extended up to two terminal domains. The interface is robust, with a low off-rate of ~8x10-4 s-1 that supports its strong aggregation-propensity. We identified a point-mutation, E78K, that disrupts this binding. Interestingly, a mutation at the interface was reported in skin cancer. Overall, the structural basis of the strong cadherin-23 adhesion may have far-reaching applications in the fields of mechanobiology and cancer.


Reflectivity of cholesteric liquid crystals with spatially varying pitch.
Solids with spatially varying photonic structure offer gaps to light of a wider range of frequencies than do simple photonic systems. We solve numerically the field distribution in a cholesteric with a linearly varying inverse pitch (helical wavevector) using equations we derive for the general case. The simple idea that the position where the Bragg condition is locally satisfied is where reflection takes place is only true in part. Here, reflection is due to a region where the waves are forced to become evanescent, and the rate of variation of structure determines over which distance the waves decay and therefore how complete reflection is. The approximate local Bragg-de Vries schemes are shown to break down in detail at the edges of the gap, and an analytical estimate is given for the transmission coefficient.


The excited state dipole moment of 2-[(4-methoxyphenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)-quinoxaline from thermochromic shifts.
The excited state dipole moment of 2-[(4-methoxyphenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)-quinoxaline has been determined in ethyl acetate solution using the method of thermochromic shifts. Three different models have been tested and are compared to each other and to the results of ab initio calculations at the coupled cluster CC2/cc-pVTZ and SCS-CC2/cc-pVTZ level of theory. Good agreement is obtained for solvent polarity functions as defined by Bilot and Kawski (L. Bilot and A. Kawski, Z. Naturforsch., 1962, 17A, 621-627), while the original Lippert-Mataga type polarity functions fail to describe the excited state dipole moment correctly. We report an excited state dipole moment of the title compound of 8.5 D and a change upon excitation of 5.5 D.


Mediation of self-concept and moderation of teacher support between SES and reading achievement: Evidence from China and the United States.
Socioeconomic status (SES) is important in students' reading development. The mechanism of how they are linked, however, is underexplored. This research aimed to explore whether reading self-concept mediates the link between SES and reading achievement and whether teacher support moderates the direct and indirect link between SES and reading achievement. Using PISA 2018 database, we selected 17,346 15-year-olds from 537 schools in B-S-J-Z (China) and the United States (U.S.). Multilevel linear models were calculated to explore the potential mediation of self-concept and the potential moderation of teacher support between SES and reading achievement. Results reveal that reading self-concept mediated the link between SES and reading achievement at student level both in China and the United States, and teacher support moderated the link between SES and reading self-concept both at student level and school level only in China, but not in the United States. Our research highlights the importance of self-concept and teacher support in improving students' reading achievement, especially for students of low SES, which has important theoretical significance and practical enlightenment for reading instruction.


Self-assembly of poly(ionic liquid) functionalized mesoporous magnetic microspheres for the solid-phase extraction of preservatives from milk samples.
In this work, a novel, rapid, and simple analytical method was proposed for the detection of parabens in milk sample by gas chromatography coupled with mass spectrometry. At the same time, milk sample was pretreated by magnetic solid phase extraction, which detected up to five parabens. A series of important parameters of magnetic solid phase extraction were investigated and optimized, such as pH value of loading buffer, amount of material, adsorption time, ionic strength, eluting solvents, and eluting time. Under the optimized conditions, the corresponding values were more than 0.9991, limits of detection and the limit of quantification were 0.1 and 0.5 ng/mL, respectively. In addition, the recoveries were achieved in range of 95-105%, the liner range were within 0.1-600 ng/mL, and the relative standard deviations were even lower than 5%.


Toward a Mechanistic Understanding of DNA Methylation Readout by Transcription Factors.
Epigenetic DNA modification impacts gene expression, but the underlying molecular mechanisms are only partly understood. Adding a methyl group to a cytosine base locally modifies the structural features of DNA in multiple ways, which may change the interaction with DNA-binding transcription factors (TFs) and trigger a cascade of downstream molecular events. Cells can be probed using various functional genomics assays, but it is difficult to disentangle the confounded effects of DNA modification on TF binding, chromatin accessibility, intranuclear variation in local TF concentration, and rate of transcription. Here we discuss how high-throughput in vitro profiling of protein-DNA interactions has enabled comprehensive characterization and quantification of the methylation sensitivity of TFs. Despite the limited structural data for DNA containing methylated cytosine, automated analysis of structural information in the Protein Data Bank (PDB) shows how 5-methylcytosine (5mC) can be recognized in various ways by amino acid side chains. We discuss how a context-dependent effect of methylation on DNA groove geometry can affect DNA binding by homeodomain proteins and how principled modeling of ChIP-seq data can overcome the confounding that makes the interpretation of in vivo data challenging. The emerging picture is that epigenetic modifications affect TF binding in a highly context-specific manner, with a direction and effect size that depend critically on their position within the TF binding site and the amino acid sequence of the TF. With this improved mechanistic knowledge, we have come closer to understanding how cells use DNA modification to acquire, retain, and change their identity.


Guest editorial: Economic forecasting in times of COVID-19.
Why was economic forecasting so difficult during COVID-19? To answer this question, we organized an online workshop in July 2020, sponsored by the International Institute of Forecasters (IIF) and hosted by American University. Below you will find some of the lessons that can be drawn from the special issue we edited.


SEMG power spectrum changes during a sustained 50% Maximum Voluntary Isometric Torque do not depend upon the prior knowledge of the exercise duration.
Endurance time (Tlim) is a relevant indicator of muscular resistance to fatigue. It has been recently shown that SEMG changes computed during shorter periods (sub-maximal durations) than the whole test duration could serve to predict Tlim. The aim of the present study was to test whether the prior knowledge of the sub-maximal duration had any influence on Tlim prediction throughout SEMG changes. For this purpose, we compared myoelectric changes estimated over a 30-s isometric contraction whose duration was known by the subjects, to those changes measured during the first 30 s of a test prolonged until exhaustion. The effort intensity was set at 50% of the maximal voluntary isometric torque (MVIT). The myoelectric manifestations of muscle fatigue appeared to change in a similar way during both sessions for temporal and spectral analyses. In conclusion, the prior knowledge of the duration of sustained isometric contraction did not influence the motor unit recruitment strategy throughout surface EMG evaluation. These results confirmed that the use of SEMG changes computed over shorter periods than expected endurance time may be applied to investigate the capability of the initial rate of SEMG changes to predict muscle endurance capacity at 50%MVIT. This may be of particular interest for patient evaluation in the clinical field.


Pancreatic neuroendocrine tumors associated with von Hippel Lindau disease: diagnostic and management recommendations.
von Hippel Lindau disease (VHL) is an inherited syndrome characterized by tumors of the kidney, adrenal, central nervous system, and pancreas. The incidence and natural history of pancreatic neuroendocrine tumors occurring in VHL are not known. From December 1988 through November 1997, 256 patients with VHL were screened with imaging studies, and these data were reviewed from a prospective database. Thirty (12%) of 256 patients had solid pancreatic lesions consistent with neuroendocrine tumors. Fourteen patients underwent resection, and 4 with metastases on imaging studies underwent biopsy only. Of the 14 patients who underwent resection, 11 remain free of disease, 2 have experienced recurrence, and 1 has died of unrelated causes (mean follow-up, 25 months; range, 3 to 73 months). The size of the primary tumor (median, 5 cm; range, 3 to 8 cm) in patients with liver metastases was significantly larger than the size of the primary tumor (median, 2 cm; range, 1 to 5 cm) in patients without liver metastases (P = .0013). Solid pancreatic lesions were detected in 12% of patients with VHL. Larger primary tumors were associated with liver metastases. Pancreatic imaging to identify neuroendocrine tumors and resection when they reach 2 to 3 cm may prevent the development of hepatic metastases.


Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level.
The role of nitric oxide (NO) in cancer progression has largely been studied in the context of tumor NOS2 expression. However, pro- versus anti-tumor signaling is also affected by tumor cell-macrophage interactions. While these cell-cell interactions are partly regulated by NO, the functional effects of NO flux on proinflammatory (M1) macrophages are unknown. Using a triple negative murine breast cancer model, we explored the potential role of macrophage Nos2 on 4T1 tumor progression. The effects of NO on macrophage phenotype were examined in bone marrow derived macrophages from wild type and Nos2-/- mice following in vitro stimulation with cytokine/LPS combinations to produce low, medium, and high NO flux. Remarkably, Nos2 induction was spatially distinct, where Nos2high cells expressed low cyclooxygenase-2 (Cox2) and vice versa. Importantly, in vitro M1 polarization with IFNγ+LPS induced high NO flux that was restricted to cells harboring depolarized mitochondria. This flux altered the magnitude and spatial extent of hypoxic gradients. Metabolic and single cell analyses demonstrated that single cell Nos2 induction limited the generation of hypoxic gradients in vitro, and Nos2-dependent and independent features may collaborate to regulate M1 functionality. It was found that Cox2 expression was important for Nos2high cells to maintain NO tolerance. Furthermore, Nos2 and Cox2 expression in 4T1 mouse tumors was spatially orthogonal forming distinct cellular neighborhoods. In summary, the location and type of Nos2high cells, NO flux, and the inflammatory status of other cells, such as Cox2high cells in the tumor niche contribute to Nos2 inflammatory mechanisms that promote disease progression of 4T1 tumors.


Stratified distribution of nutrients and extremophile biota within freshwater ice covering the surface of Lake Baikal.
Biological entities and gradients of selected chemicals within the seemingly barren ice layers covering Lake Baikal were investigated. Ice cores 40-68 cm long were obtained from in shore and offshore sites of Southern Lake Baikal during the cold period of a year (March-April) in 2007 and 2008. In microscopic observations of the melted ice, both algae and bacteria were found in considerable numbers (>10(3) cells/L and >10(4) cells/ml, respectively). Among all organisms found, diatom was generally the most predominant taxon in the ice. Interestingly, both planktonic and benthic algae were present in considerable numbers (2-4×10(4) cells/L). Dominant phototrophic picoplankton were comprised of small green algae of various taxa and cyanobacteria of Synechococcus and Cyanobium. The bacterial community consisted mostly of short rod and cocci cells, either free-living or aggregated. Large numbers of yeast-like cells and actinomycete mycelium were also observed. Concentrations of silica, phosphorus, and nitrate were low by an order of magnitude where biota was abundant. The profile of the ice could be interpreted as vertical stratification of nutrients and biomass due to biological activities. Therefore, the organisms in the ice were regarded to maintain high activity while thriving under freezing conditions. Based on the results, it was concluded that the freshwater ice covering the surface of Lake Baikal is considerably populated by extremophilic microorganisms that actively metabolize and form a detritus food chain in the unique large freshwater ecosystem of Lake Baikal.


Acute upper extremity deep venous thrombosis: safety and effectiveness of superior vena caval filters.
To evaluate the safety and effectiveness of percutaneous filter placement in the superior vena cava for prevention of pulmonary embolism (PE) due to acute upper extremity deep venous thrombosis (DVT) in patients with contraindications to or unsuccessful anticoagulation. Forty-one patients with acute upper extremity DVT and contraindications to or unsuccessful anticoagulation underwent percutaneous placement of a superior vena caval filter for prevention of PE. Four types of filters were used. Follow-up chest radiographs were used to detect filter migration, dislodgment, and fracture. Placements of central venous and Swan-Ganz catheters after filter insertion were recorded. Patients were followed up clinically for evidence of superior vena cava syndrome and PE. Kaplan-Meier survival rates were determined. Follow-up was 1 day to 221 weeks. No complications such as filter migration, dislodgment, or fracture occurred (median follow-up, 12 weeks). No patients developed clinical evidence of PE due to upper extremity thrombosis or superior vena cava syndrome (median follow-up, 15 weeks). Catheters were placed subsequent to filter placement in 23 patients (56%) without complication. Percutaneous filter placement in the superior vena cava is a safe and effective method for preventing symptomatic PE due to acute upper extremity DVT in patients in whom therapeutic anticoagulation has failed or is contraindicated.


Latino Mother/Daughter Dyadic Attachment as a Mediator for Substance Use Disorder and Emotional Abuse.
To date, no studies have investigated emotional abuse of adult Latina women by their mothers despite evidence that emotional maternal abuse may significantly contribute to the emotional abuse experienced by Latina women in their lifetime. Cross-sectional data including 316 women was analyzed using mediation and logistic regression. Overall, 7.1 % of mothers and 24.1 % of daughters abused drugs; and, 19.5 % of daughters were emotionally abused by their mothers. Mother's attachment to her daughter mediated the association between mother's drug abuse and emotionally abusing her adult daughter (indirect effect: 0.863). Latina women can serve as perpetrators of emotional abuse of their adult children. Since drug-abusing daughters are more likely to be victims of emotional abuse by their mothers and drug-abusing mothers are more likely to abuse their daughters, drug-rehabilitation practitioners should incorporate a family abuse component into rehabilitation programs.


Examining factors that influence erroneous phosphorylation site localization via competing fragmentation and rearrangement reactions during ion trap CID-MS/MS and -MS(3.).
Factors influencing the magnitude of competing fragmentation and intramolecular phosphate group rearrangement reactions during CID-MS/MS and CID-MS(3) of protonated phosphopeptide ions in ion trap mass spectrometers, and their effect on phosphorylation site localization using automated search algorithms, have been examined by systematically varying the peptide composition, the identity, number, and position of the phosphorylated "donor" and nonphosphorylated "acceptor" residues, and the proton mobility of the precursor ion charge states for a synthetic phosphopeptide library. CID-MS(3) of product ions formed via combined neutral losses of HPO3 and H2 O, rather than direct loss of H3 PO4 from phosphotyrosine containing peptides yielded incorrect phosphorylation site assignments, while correct phosphorylation site assignments for phosphothreonine and phosphoserine containing peptides were highly dependant on the relative abundance of these competing fragmentation pathways. Abundant phosphate group rearrangement product ions were observed from CID-MS/MS of multiply protonated phosphopeptide ions, with increased rearrangement under nonmobile or partially mobile protonation conditions, and as a function of the identity and number of the donor and acceptor residues. A clear inverse trend was observed between the amplitude of these rearrangement reactions and the confidence for phosphorylation site localization, and rearrangement played a contributing role in erroneous phosphorylation site assignment for several peptides.


Effect of acrolein, a hazardous air pollutant in smoke, on human middle ear epithelial cells.
Acrolein is a hazardous air pollutant. Tobacco smoke and indoor air pollution are the main causes of human exposure. Acrolein has been shown to cause cytotoxicity in the airways and induce inflammation and mucin production in pulmonary cells. We investigated whether acrolein caused cytotoxicity, induced inflammation or increased expression of mucin in immortalized human middle ear epithelial cell lines (HMEECs). Cytotoxicity following acrolein treatment was investigated using the MTT assay, flow cytometry, and Hoechst 33342 staining of HMEECs. We measured expression of inflammatory cytokines tumor necrosis factor (TNF)-α and cyclo-oxygenase (COX)-2 and the mucin gene MUC5AC using semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. Exposure to >50 μg/mL acrolein caused a decrease in cell viability. Acrolein induced apoptosis and necrosis at 50 μg/mL. Acrolein at 5-50 μg/mL increased expression of TNF-α and COX-2, as shown by RT-PCR and Western blotting. Acrolein exposure at 5-50 μg/mL for 2-24h increased MUC5AC expression, as determined by RT-PCR. Acrolein decreased cell viability, induced an inflammatory response, and increased mucin gene expression in HMEECs. These findings support the hypothesis that acrolein, a hazardous air pollutant in tobacco smoke and ambient air, is a risk factor for otitis media.


Complete white out of a single transplanted lung in the immediate postoperative period.
Vascular complications are rare but serious events following lung transplantation. Of the potential adverse events post lung transplant, pulmonary vein thrombosis is rare but often fatal. Our case describes a 54 year-old male who underwent single left lung transplantation and suddenly became hemodynamically unstable shortly after the procedure. The diagnosis of acute pulmonary vein thrombosis was made with the use of trans-esophageal echocardiography identifying complete occlusion of the left upper pulmonary vein which led to successful surgical thrombectomy and revision of the anastomosis.


Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19.
Acute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19. Prospective cohort study. Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020. 19 urinary biomarkers of injury, inflammation, and repair. Composite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome. Out of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine. Small sample size with low number of composite outcome events. Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.