Hourly rounding for falls prevention: a change initiative.
Fall-related injuries are a particular concern within the elderly population, and trends toward an aging demographic will keep this issue at the forefront in health care. We are challenged to develop creative strategies to significantly reduce harm and fall rates among the elderly. This article describes the process of establishing an hourly rounding initiative in a health care facility. Hourly rounding is supported by the literature as an effective strategy for falls prevention and patient safety. When the initiative was not successfully adopted initially, the implementation process was critically examined and an innovative sustainability plan was developed to ensure that the change would be embedded in the organization's culture. Through this opportunity, nurses and allied health members from all levels were able to collaborate on strategies for this patient safety initiative.


Discrete Femtolitre Pipetting with 3D Printed Axisymmetrical Phaseguides.
The capacity to precisely pipette femtoliter volumes of liquid enables many applications, for example, to functionalize a nanoscale surface and manipulate fluids inside a single-cell. A pressure-controlled pipetting method is the most preferred, since it enables the widest range of working liquids. However, precisely controlling femtoliter volumes by pressure is challenging. In this work, a new concept is proposed that makes use of axisymmetrical phaseguides inside a microfluidic channel to pipette liquid in discrete steps of known volume. An analytical model for the design of the femtopipettes is developed and verified experimentally. Femtopipettes are fabricated using a multi-scale 3D printing strategy integrating a digital light processing printed part and a two-photon-polymerization printed part. Three different variants are designed and fabricated with pipetting resolutions of 10 picoliters, 180 femtoliters and 50 femtoliters. As a demonstration, controlled amounts of a water-glycerol mixture were first aspirated and then dispensed into a mineral oil droplet.


Vascular recovery following hemorrhage in the dogfish shark Squalus acanthias.
Cardiovascular regulatory systems were examined in the dogfish shark after hemorrhage of 1% of body weight. An immediate 45% decrease in mean dorsal aortic pressure and delayed increases in plasma epinephrine concentration and plasma norepinephrine concentration were noted. During the recovery period following hemorrhage, the catecholamine levels peaked (epinephrine 203% of control, norepinephrine 148% of control) and then returned toward control values. Hematocrit, however, continued to decline as blood pressure recovered. Phentolamine pretreatment, which in itself caused a 55% decrease in dorsal aortic pressure, did not prevent the recovery of blood pressure after hemorrhage. This study indicates that 1) hemorrhage causes an increase in circulatory catecholamine concentration, possibly by a baroreceptor reflex; 2) volume recruitment, as indicated by the drop in hematocrit, is a major mechanism contributing to the recovery of dorsal aortic pressure after hypotension; and 3) alpha-adrenergic receptors are not necessary for the recovery of dorsal aortic pressure after hemorrhage.


Effect of gemifloxacin on viability of Chlamydia pneumoniae (Chlamydophila pneumoniae) in an in vitro continuous infection model.
Persistent infection with Chlamydia pneumoniae (Chlamydophila pneumoniae) has been implicated in the development of atherosclerosis, asthma and other chronic diseases. However, data on treatment of C. pneumoniae infections are limited. Microbiological failure of antimicrobial therapy has been described, even after prolonged courses of treatment with azithromycin, doxycycline and erythromycin. Gemifloxacin is an enhanced-affinity fluoroquinolone with excellent activity against most common respiratory pathogens, including C. pneumoniae. The effect of prolonged treatment with gemifloxacin, compared with azithromycin, on viability of C. pneumoniae was investigated in a continuous infection model. Gemifloxacin at final con-centrations of 0.25 and 2.5 mg/L reduced the viability of C. pneumoniae by 5 log(10), which was similar to the effect of azithromycin. However, both antimicrobials failed to completely eliminate C. pneumoniae from continuously infected cells, even after 30 days of treatment. Both antibiotics decreased levels of interleukin-6 and interleukin-8 in this model, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms.


T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease.
Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (μ) and standard deviation (σ) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-μ in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-σ and FLAIR-σ) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-μ decreased and T1-σ and FLAIR-σ increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients.


Pain Management in Primary Care: A Randomized Controlled Trial of a Computerized Decision Support Tool.
Primary care providers manage most patients with chronic pain. Pain is a complex problem, particularly in underserved populations. A technology-enabled, point-of-care decision support tool may improve pain management outcomes. We created an electronic health record (EHR)-based decision support tool, the Pain Management Support System-Primary Care (PMSS-PC), and studied the tool-plus-education in 6 Federally Qualified Health Center practices using a randomized, wait-list controlled design. The PMSS-PC generated "best practice alerts," gave clinicians access to a pain assessment template, psychological distress and substance use measures, guidelines for drug and non-drug therapies, and facilitated referrals. Practices were randomly assigned to early vs delayed (after 6 months) implementation of the intervention, including technical support and 6 webinars. The primary outcome was change in worst pain intensity scores after 6 months, assessed on the Brief Pain Inventory-Short Form. Changes in outcomes were compared between the practices using linear multilevel modeling. The EHR provided clinician data on PMSS-PC utilization. The 256 patients in the early implementation practices had significantly improved worst pain (standardized effect size [ES] = -.32) compared with the 272 patients in the delayed implementation practices (ES = -.11). There was very low clinician uptake of the intervention in both conditions. Early implementation of the PMSS-PC improved worst pain, but this effect cannot be attributed to clinician use of the tool. Further PMSS-PC development is not indicated, but practice-level interventions can improve pain, and studies are needed to identify the determinants of change.


Oscillatory potentials of X-linked carriers of congenital stationary night blindness.
ERG oscillatory potentials (OPs) were recorded from obligate carriers of CSNB and from age-matched normal subjects. The OPs were recorded under four stimulus conditions and were analyzed in the time and frequency domains. The results, first of all, provide confirmation of the previous report that the OP amplitude is reduced in carriers. Second, the results show that, of four stimulus conditions examined, the best condition for discriminating the carriers and normal subjects was when the flash was blue and the eye was dark-adapted. Third, the results show that, in the frequency domain, optimal discrimination occurs when examining the power content of the OP at a center frequency of about 130 Hz using a 70 Hz bandwidth window. In the time domain, optimal discrimination occurs when examining the amplitude of the third peak of the response.


Recurrent Third Nerve Palsy Secondary to Instrinsic Schwannoma of the Third Cranial Nerve.
A 78 year-old woman has experienced multiple episodes of transient right third nerve palsy over the course of 15 years and has undergone multiple imaging studies as well as investigations for myasthenia gravis and giant cell arteritis in search for the diagnosis. When seen after the most recent episode, MRI with contrast and Fast-Imaging Employing Steady-State Acquisition protocol revealed a subtle enlargement and enhancement of the cisternal and proximal cavernous portions of the right third cranial nerve. An empiric diagnosis of schwannoma intrinsic to third cranial nerve was made. All patients with cyclical third nerve palsies should have appropriate neuroimaging to rule out subtle structural lesions before other investigations are undertaken.


Plasmid double locus sequence typing for IncHI2 plasmids, a subtyping scheme for the characterization of IncHI2 plasmids carrying extended-spectrum beta-lactamase and quinolone resistance genes.
IncHI2 plasmids are frequently encountered in clinical enterobacterial strains associated with the dissemination of relevant antimicrobial resistance genes. These plasmids are usually >250 kb, and technical difficulties can impair plasmid DNA purification and comparison by restriction fragment length polymorphism. We analysed the available IncHI2 whole DNA plasmid sequences to devise a rapid typing scheme to categorize the members of this plasmid family into homogeneous groups. We compared the available full IncHI2 plasmid sequences, identifying conserved and variable regions within the backbone of this plasmid family, to devise an IncHI2 typing method based on sequence typing and multiplex PCRs. A collection of IncHI2 plasmids carrying extended-spectrum beta-lactamase and quinolone resistance genes, identified in strains from different sources (animals and humans) and geographical origins, was tested by these typing systems. We devised a plasmid double locus sequence typing (pDLST) scheme and a multiplex PCR discriminating IncHI2 plasmid variants. These systems were tested on a collection of IncHI2 plasmids, demonstrating that the plasmids carrying blaCTX-M-2 and blaCTX-M-9 belonged to two major plasmid variants, which were highly conserved among different enterobacterial species disseminated in several European countries. The ability to recognize and subcategorize plasmids by pDLST in homogeneous groups on the basis of their phylogenetic relatedness can be helpful to analyse their distribution in nature and to discover of their evolutionary origin.


How equitable is the uptake of conditional cash transfers for maternity care in India? Evidence from the Janani Suraksha Yojana scheme in Odisha and Jharkhand.
In 2005, the Indian Government introduced the Janani Suraksha Yojana (JSY) scheme - a conditional cash transfer program that incentivizes women to deliver in a health facility - in order to reduce maternal and neonatal mortality. Our study aimed to measure and explain socioeconomic inequality in the receipt of JSY benefits. We used prospectively collected data on 3,682 births (in 2009-2010) from a demographic surveillance system in five districts in Jharkhand and Odisha state, India. Linear probability models were used to identify the determinants of receipt of JSY benefits. Poor-rich inequality in the receipt of JSY benefits was measured by a corrected concentration index (CI), and the most important drivers of this inequality were identified using decomposition techniques. While the majority of women had heard of the scheme (94% in Odisha, 85% in Jharkhand), receipt of JSY benefits was comparatively low (62% in Odisha, 20% in Jharkhand). Receipt of the benefits was highly variable by district, especially in Jharkhand, where 5% of women in Godda district received the benefits, compared with 40% of women in Ranchi district. There were substantial pro-rich inequalities in JSY receipt (CI 0.10, standard deviation (SD) 0.03 in Odisha; CI 0.18, SD 0.02 in Jharkhand) and in the institutional delivery rate (CI 0.16, SD 0.03 in Odisha; CI 0.30, SD 0.02 in Jharkhand). Delivery in a public facility was an important determinant of receipt of JSY benefits and explained a substantial part of the observed poor-rich inequalities in receipt of the benefits. Yet, even among public facility births in Jharkhand, pro-rich inequality in JSY receipt was substantial (CI 0.14, SD 0.05). This was largely explained by district-level differences in wealth and JSY receipt. Conversely, in Odisha, poorer women delivering in a government institution were at least as likely to receive JSY benefits as richer women (CI -0.05, SD 0.03). JSY benefits were not equally distributed, favouring wealthier groups. These inequalities in turn reflected pro-rich inequalities in the institutional delivery. The JSY scheme is currently not sufficient to close the poor-rich gap in institutional delivery rate. Important barriers to institutional delivery remain to be addressed and more support is needed for low performing districts and states.


Aneurysm-related ischemic ventricular tachycardia: safety and efficacy of catheter ablation.
Left ventricular aneurysm (LVA) postmyocardial infarction (MI) might be an arrhythmogenic substrate. We examined the safety and efficacy of catheter ablation of LVA-related ventricular tachycardia (VT).Thirty-three consecutive patients who underwent primary catheter ablation of ischemic VT were divided into LVA group (11 patients, mean age 61.9 years, 10 men) and none LVA group. Acute procedural outcomes, complications, and long-term outcomes were assessed.In LVA group, average number of induced VTs were 3.2 ± 2.6 (range 1-7), clinical VTs were located in the ventricular septum scar zone in 4 (36.4%) patients, acute success was achieved in 7 (63.6%) patients, partial success in 3 (27.3%) and failure in 1 patient, while none LVA group showing a statistically similar distribution of acute procedural outcomes (P = 0.52). There were no major or life-threatening complications. VT-free survival rate at median 19 (1-44) months follow-up was numerically but not significantly lower in LVA versus none LVA group (48.5% vs 62.8%, log-rank P = 0.40).Catheter ablation of ischemic VT in the presence of LVA appears feasible and effective, with about one-third of cases having septal ablation targets. Further studies are warranted.


Treatment of industrial effluents by electrochemical generation of H2O2 using an RVC cathode in a parallel plate reactor.
Electrochemical techniques have been used for the discolouration of synthetic textile industrial wastewater by Fenton's process using a parallel plate reactor with a reticulated vitreous carbon (RVC) cathode. It has been shown that RVC is capable of electro-generating and activating H2O2 in the presence of Fe(2+) added as catalyst and using a stainless steel mesh as anode material. A catholyte comprising 0.05 M Na2SO4, 0.001 M FeSO4.7H2O, 0.01 M H2SO4 and fed with oxygen was used to activate H2O2.The anolyte contained only 0.8 M H2SO4. The operating experimental conditions were 170 mA (2.0 V < ΔECell < 3.0 V) to generate 5.3 mM H2O2. Synthetic effluents containing various concentrations (millimolar - mM) of three different dyes, Blue Basic 9 (BB9), Reactive Black 5 (RB5) and Acid Orange 7 (AO7), were evaluated for discolouration using the electro-assisted Fenton reaction. Water discolouration was measured by UV-VIS absorbance reduction. Dye removal by electrolysis was a function of time: 90% discolouration of 0.08, 0.04 and 0.02 mM BB9 was obtained at 14, 10 and 6 min, respectively. In the same way, 90% discolouration of 0.063, 0.031 and 0.016 mM RB5 was achieved at 90, 60 and 30 min, respectively. Finally, 90% discolouration of 0.14, 0.07 and 0.035 mM AO7 was achieved at 70, 40 and 20 min, respectively. The experimental results confirmed the effectiveness of electro-assisted Fenton reaction as a strong oxidizing process in water discolouration and the ability of RVC cathode to electro-generate and activate H2O2 in situ.


Infant gender differences regarding acute established pain.
The purpose of this study was to ascertain if any gender differences existed in the behaviors of infants experiencing different levels of acute established pain and different levels of arousal within each level of pain. To do this, the behaviors of 152 two-week- to 12-month-old infants were videotaped and compared. Levels of pain were assessed by a panel of expert pediatric nurses. Results indicated that female 2-week- to 6-month-old infants performed more generally broadcast crying than did males and that the cries of female 7- to 12-month-old infants were of higher pitch than those of males. There was no gender difference in any facial or other bodily behavior. One cannot interpolate from these results that there are any gender differences in pain thresholds, only that there seem to be gender differences in behavioral responses to acute established pain.


Pituitary tumor with gigantism, acromegaly and preclinical Cushing's disease diagnosed from the 10th row.
A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.


Surveillance strategies for colitis-associated cancer: state of the art and future perspectives.
Colitis-associated cancer (CAC) represents a concrete risk of morbidity and mortality in patients with long lasting inflammatory bowel diseases. Surveillance colonoscopy is a rapidly evolving research field with profound changes from the traditional approach based on scheduled controls and random biopsy protocols. Areas covered: A literature search was performed using PubMed/Embase to review the latest evidence supporting the need for surveillance colonoscopy. By focusing on the most promising recent advances in this field, we provide a state-of-the-art overview of the current gold standards for the diagnosis and management of colitis-associated dysplasia. Expert commentary: Evidence-based and emerging data have questioned the efficacy and effectiveness of both standard surveillance colonoscopy and random biopsy protocols. The latest guidelines endorse early initiation of surveillance programs, risk-profiling assessment of colonoscopy intervals and standardized use of advanced imaging modalities to detect early dysplasia. Current trends clearly reveal increased attention to direct visualization and endoscopic management of visible dysplastic lesions, even in patients with longstanding colitis. Emerging technological advances in gastrointestinal endoscopy are expected to change the endoscopic surveillance protocols in the near future.


LC-MS/MS-ESI method for simultaneous quantification of darolutamide and its active metabolite, ORM-15341 in mice plasma and its application to a pharmacokinetic study.
A sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous quantitation of darolutamide and its active metabolite i.e. ORM-15341 in 50μL mice plasma using bicalutamide as an internal standard (I.S.) as per regulatory guidelines. Sample processing was accomplished through liquid-liquid extraction. Chromatographic separation was achieved using an Atlantis C18 column with an isocratic mobile phase comprising 0.2% formic acid:acetonitrile (35:65, v/v) at a flow rate of 0.8mL/min within 2.5min. Detection and quantitation were done by multiple reaction monitoring on a triple quadrupole mass spectrometer following the transitions: m/z 397→202, 395→202 and 429→255 for darolutamide, ORM-15341 and I.S, respectively in the negative ionization mode. The calibration curve was linear from 0.61-1097ng/mL for both darolutamide and ORM-15341. The intra- and inter-day precisions were in the range of 1.34-13.8 and 4.85-12.9 and 3.91-13.7 and 6.54-14.2%, for darolutamide and ORM-15341, respectively. Darolutamide and ORM-15341 were found to be stable under different stability conditions. The validated method was applied to a pharmacokinetic study in mice.


[Current indications for the surgical treatment of pulmonary tuberculosis].
A marked worldwide increase in the prevalence of pulmonary tuberculosis has occurred over the past 15 years. The reasons for this change include the worldwide epidemic of AIDS, poverty and the unprecedented extent of migration. We selected 47 patients with pulmonary tuberculosis or its sequelae for 51 surgical operations, with a high prevalence of subjects under 50 years of age (48.9%). There were three major non-fatal complications, and three minor complications. One patient died on postoperative day 1 as a result of unrelated causes. At present, surgery for tuberculosis of the lungs is mainly indicated when all medical treatments have proved ineffective or in circumstances where complete control of complications or disease sequelae is necessary, provided there is a correct indication and a flawless execution.


Detection and isolation of Toxoplasma gondii from fresh semen of naturally infected dogs in Southern Brazil.
The aim of this study was to isolate Toxoplasma gondii and determine the viability of the parasite in fresh semen samples of clinically healthy adult dogs naturally infected. Eleven seropositive dogs with T. gondii IgG antibodies from southern Brazil were selected to confirm the presence and viability of T. gondii in fresh semen samples using in vitro isolation in Vero cell culture, polymerase chain reaction (PCR) and sequencing analysis. The presence of viable T. gondii was confirmed by in vitro isolation and PCR in five semen samples. The ITS1 region of the isolated protozoa (TG S4) was amplified and sequenced. The nucleotide sequence obtained was 99% compatible with the T. gondii DNA sequences stored in the GenBank. It has been shown that T. gondii tachyzoites may be isolated in vitro from fresh semen samples of clinically healthy dogs seropositive for T. gondii.


[Kinetics of cellular elements of the vascular wall in atherosclerosis].
Reviews current notions on the role of the vascular wall in atherogenesis. Discusses some aspects of cellular cooperation in the intima of the arteries and the role of this cooperation in this formation of foam cells and in desmoplastic reactions. Presents the findings of ultrastructural analysis of atherosclerotic involvement in coronary patients. Considers the problems of phenotypical modification of smooth muscle cells and of the contribution of activated cells to lipoprotein capture or to collagen synthesis. Emphasizes the role of vascular wall in atherogenesis, the fact to be borne in mind when planning and carrying out measures for the prevention and therapy of atherosclerosis.


On the identity of Bufo diptychus Cope, 1862 (Anura: Bufonidae).
The enigmatic toad Bufo diptychus was described by Cope (1862) based on a single individual (USNM 5841, now lost) of about 25 mm of SVL, collected during the expedition to La Plata River and tributaries, conducted by Captain Page between 1853 and 1856. As no dwarf species of toad was ever recorded in the surveyed area, and based on some tips that arise from Page's narrative, we postulate that the description was based on a toadlet. With this hypothesis in mind, we compared Cope's characterization of B. diptychus with juveniles of all species of Rhinella present in the region, finding an exact match in almost all characters shown by the juveniles of the common "cururú" or "rococo" toad, Rhinella schneideri (Werner 1894). Henceforth, we postulate that R. schneideri is a junior synonym of B. diptychus, under the combination Rhinella diptycha (Cope 1862).


Seasickness susceptibility, personality factors, and salivation.
The present study investigates the possible relationship between motion sickness susceptibility, personality factors and salivation. Personality factors, as evaluated by the Eysenck Personality Questionnaire, and salivary composition and flow were measured in a group of 29 subjects highly susceptible to seasickness and in a group of 25 non-susceptible subjects. The non-susceptible group had significantly higher psychoticism scores and significantly lower salivary amylase levels compared to the highly susceptible group. A significant positive correlation was found between psychoticism scores and the amount of the increase in salivary flow in response to gustatory stimulation. These results provide more data in support of a connection between motion sickness susceptibility, personality, and the autonomic nervous system.


Endoscopic resection of subepithelial tumors.
Management of subepithelial tumors (SETs) remains challenging. Endoscopic ultrasound (EUS) has improved differential diagnosis of these tumors but a definitive diagnosis on EUS findings alone can be achieved in the minority of cases. Complete endoscopic resection may provide a reasonable approach for tissue acquisition and may also be therapeutic in case of malignant lesions. Small SET restricted to the submucosa can be removed with established basic resection techniques. However, resection of SET arising from deeper layers of the gastrointestinal wall requires advanced endoscopic methods and harbours the risk of perforation. Innovative techniques such as submucosal tunneling and full thickness resection have expanded the frontiers of endoscopic therapy in the past years. This review will give an overview about endoscopic resection techniques of SET with a focus on novel methods.


Ab initio study on the rare-earth iron-pnictides RFeAsO (R = Pr, Nd, Sm, Gd) in the low-temperature Cmma phase.
We present density functional theory calculations on the iron-based pnictides RFeAsO (R = Pr, Nd, Sm, Gd). The calculations have been carried out using plane waves and the projector augmented wave (PAW) pseudopotential approach. Structural, magnetic and electronic properties are studied within the generalized gradient approximation (GGA) and also within GGA + U in order to investigate the influence of electron correlation effects. The low-temperature Cmma structure is fully optimized by the GGA considering both non-magnetic and magnetic cells. We have found that the spin-polarized structure improves the agreement with experiments on equilibrium lattice parameters, particularly the c lattice parameter and the Fe-As bond-lengths. The electronic band structure, total density of states, and spin-dependent orbital-resolved density of states are also analyzed and discussed in the frameworks of GGA and GGA + U. For all materials, by including an on-site Coulomb correction, the rare-earth 4f states move away from the Fermi level and the Fermi level features of the systems are found to be mostly defined by the 3d electron-electron correlations in Fe.


Mycotic aneurysm of the external carotid artery.
Mycotic aneurysms of the extracranial carotid arteries are extremely rare. A case is reported of an external carotid artery aneurysm that developed in a patient with infective endocarditis. We review 15 previously reported cases of mycotic aneurysms of the cervical carotid arteries, one of which occurred in a patient with infective endocarditis. None of them occurred in the external carotid artery. Most cases were due to local trauma, a contiguous focus of infection or bacteremia. Surgical resection and appropriate antibiotic treatment lead to cure in most cases.


The Impact of Mechanical Energy Assessment on Mechanical Ventilation: A Comprehensive Review and Practical Application.
Mechanical ventilation (MV) provides basic organ support for patients who have acute hypoxemic respiratory failure, with acute respiratory distress syndrome as the most severe form. The use of excessive ventilation forces can exacerbate the lung condition and lead to ventilator-induced lung injury (VILI); mechanical energy (ME) or power can characterize such forces applied during MV. The ME metric combines all MV parameters affecting the respiratory system (ie, lungs, chest, and airways) into a single value. Besides evaluating the overall ME, this parameter can be also related to patient-specific characteristics, such as lung compliance or patient weight, which can further improve the value of ME for characterizing the aggressiveness of lung ventilation. High ME is associated with poor outcomes and could be used as a prognostic parameter and indicator of the risk of VILI. ME is rarely determined in everyday practice because the calculations are complicated and based on multiple equations. Although low ME does not conclusively prevent the possibility of VILI (eg, due to the lung inhomogeneity and preexisting damage), individualization of MV settings considering ME appears to improve outcomes. This article aims to review the roles of bedside assessment of mechanical power, its relevance in mechanical ventilation, and its associations with treatment outcomes. In addition, we discuss methods for ME determination, aiming to propose the most suitable method for bedside application of the ME concept in everyday practice.


Searching for a Mate: Pheromone-Directed Movement of the Benthic Diatom Seminavis robusta.
Diatoms are species-rich microalgae that often have a unique life cycle with vegetative cell size reduction followed by size restoration through sexual reproduction of two mating types (MT(+) and MT(-)). In the marine benthic diatom Seminavis robusta, mate-finding is mediated by an L-proline-derived diketopiperazine, a pheromone produced by the attracting mating type (MT(-)). Here, we investigate the movement patterns of cells of the opposite mating type (MT(+)) exposed to a pheromone gradient, using video monitoring and statistical modeling. We report that cells of the migrating mating type (MT(+)) respond to pheromone gradients by simultaneous chemotaxis and chemokinesis. Changes in movement behavior enable MT(+) cells to locate the direction of the pheromone source and to maximize their encounter rate towards it.


Interaction of fluorouracil and interferon in human colon cancer cell lines: cytotoxic and cytokinetic effects.
Fluorouracil (FUra) is the most active agent in advanced colorectal carcinoma, and this activity can be enhanced by various modulating agents both in vitro and in vivo. To determine whether interferon (IFN) is capable of augmenting the cytotoxic and cytokinetic effects of FUra, combinations of FUra and IFN alpha, -beta, and -gamma were tested against 2 human colon cancer cell lines in vitro. In a clonogenic assay, IFN alpha and -beta, at concentrations that produced less than 1 log cell kill, significantly increased the cytotoxic effects of FUra in both cell lines. IFN gamma also enhanced the cytotoxic effects of FUra, but unlike IFN alpha and -beta, only at the highest concentrations tested. Median effects analysis demonstrated that all 3 IFNs exhibited synergy with FUra. Combinations of IFNs were no more effective at modulating FUra activity than single agent IFN. Flow cytometric studies indicated that these effects did not correlate with cytokinetic alterations. Only the combination of FUra and IFN beta produced cytokinetic effects different from those of FUra alone. Incubation with IFN alpha or IFN gamma for 24 h resulted in only modest cytokinetic alterations, and they did not modify the effects of FUra. These results indicate that IFN is capable of increasing the cytotoxic actions of FUra and that this is separable from any cytokinetic effects produced by the interferons.


Home care goes corporate.
Some 18,000 home health agencies dot today's landscape--one of health care's last cottage industries. But the spread of managed care, plus long-promised Medicare payment reform, will change all that. Waves of consolidation and cost-cutting won't be far behind.


A case of delayed brain abscess due to a retained intracranial wooden foreign body: a case report and review of the last 20 years.
A 13-year-old female is presented. When she was six years old, she had fallen, holding wooden chopsticks and got stuck with a chopstick in the right upper eyelid. She was brought to a physician immediately, but a residual foreign body was missed and no particular symptom had developed during 7 years. She visited our department with fever and headache, and a brain abscess and an intracranial foreign body were found on computed tomography (CT) and magnetic resonance image (MRI) 7 years after the penetrating injury. She underwent removal of the object and abscess by craniotomy and recovered without neurological abnormalities. Since intracranial retained wooden foreign bodies frequently cause delayed complications of severe central nervous system infection, surgical removal is necessary even in the absence of symptoms.


How to manage treatment failure in prosthetic joint infection.
Management for prosthetic joint infections remains a challenging area for both infectious diseases and orthopaedic surgery, particularly in the setting of treatment failure. This is compounded by a lack of level 1 evidence to guide approaches. The optimal management of prosthetic joint infections requires a multi-disciplinary approach combined with shared decision making with the patient. This article describes the approach to prosthetic joint infections in the setting of treatment failure. Narrative review based on literature review from PubMed. There was no time limit on the studies included. In addition, the reference list for included studies were reviewed for literature saturation with manual searching of clinical guidelines. Management approaches described incorporate evidence- and eminence-based recommendations from expert guidelines and clinical studies, where applicable. The surgical and antimicrobial approaches for prosthetic joint infections are described for first-line treatment of prosthetic joint infections and approaches in the event of treatment failure. Management approaches are based on an understanding of the role the biofilm plays in the pathogenesis of prosthetic joint infections. The management of these infections aims to fulfil two key goals: to eradicate the biofilm-associated microorganisms and, to maintain a functional joint and quality of life. In treatment failure, these goals are not always feasible, and the role of the multi-disciplinary team and shared-decision making are prominent. Prosthetic joint surgery is a high-volume surgery, and the demand for this surgery is continually increasing. With this, the number of infections requiring expert care will also increase. Eminence-based management approaches have been established to guide treatment failure until knowledge gaps in optimal management are addressed by well-designed, clinical trials.


[Familial mucosal neuromatosis: a minor form of the MEN-2b syndrome].
When the alert ophthalmologist found visible corneal nerves on a clear stroma, he must remind about the multiple endocrine neoplasia syndrome (M.E.N.-2b) and look for the medullary carcinoma of thyroid and the pheochromocytomas. Recognition of these ocular lesions as components of the syndrome is of the utmost importance because prompt identification of individuals affected by multiple endocrine neoplasia type 2 b facilitates early treatment of associated medullary thyroid carcinomas and pheochromocytomas. These endocrine neoplasias must be carefully searched by endocrine means. We present for the first time, in our knowledge, one family with M.E.N.-2b syndrome without endocrine neoplasias at this moment. We think it can be one minor presentation. We call this form "familial multiple mucosal neuromas".


Shear bond strengths of a single-step bonding system to enamel and dentin.
An experimental primer was developed as a single-step bonding system for resin-modified glass ionomer cements (GIC). Efficacy of this primer on adhesion of resin-modified GICs and resin composite to enamel and dentin was evaluated by shear bond test and SEM observation. Good bond strengths to enamel were obtained (> 11 MPa), whereas significantly low bond strengths to dentin were obtained using a single coat of the primer. However, double-coating improved the bond strengths to dentin (> 8 MPa). SEM observations indicated that the primer functioned as a mild conditioner to remove the smear layer on enamel or dentin surfaces. A hybrid layer was observed at the cross-sectional view of the GIC/dentin interface. These findings suggested that good adhesion to enamel and dentin could be achieved using a single-step bonding system.


The interrelationship of beta endorphin, ACTH and cortisol in depressive illness: a controlled study.
Plasma cortisol, ACTH and beta endorphin were measured before and after dexamethasone in 8 severely depressed patients and 8 age- and sex-matched controls to examine the relationship of ACTH and endogenous opioids to cortisol in depression. Despite having significantly higher plasma levels of cortisol than the controls, the depressed patients did not have correspondingly elevated plasma levels of ACTH. Beta-endorphin levels were also similar in the two groups. All three hormones suppressed to some degree after dexamethasone, but cortisol suppressed less in patients than controls. Our findings suggest that in severe depressive illness abnormalities exist in the hypothalamic-pituitary-adrenal axis peripherally as well as centrally.


[The effect of fructose-1,6-diphosphate, cytochrome c and their combination on the size of the necrotic area in transient myocardial ischemia].
The effect of fructose-1, 6-diphosphate (200 mg/kg), cytochrome C (20 mg/kg) and their combinations on the size of the zone of necrosis 4 and 72 h after 15-min transitory myocardial ischemia was studied. Combination of the compounds under study inhibited considerably the development of post-occlusion and reperfusion arrhythmias and reduced the size of necrosis 4 h after their administration as prophylactic and arresting measures (to 23.8 +/- 2.9 and 29.3 +/- 3.6% of the ischemic zone, respectively, in 42.8 +/- 3.8% in the control). A combined course of cytochrome C and fructose diphosphate also limited the size of the necrotic zone 72 h after transitory ischemia. Separate single administration of fructose diphosphate and cytochrome C caused no essential changes in the size of myocardial necrosis recorded 72 h after transitory myocardial ischemia.


Computer diagnosis in cardiology.
This article reports upon the emergence of a novel cognitive, computer-based technology which may lead to significantly improved methods of cardiological diagnosis and a rapid and inexpensive method of cardiological screening.The technology 'Virtual Scanning' illustrates how, in blood, the reaction of proteins and their reactive substrates releases light; that the colour and intensity of this bioluminescence is unique to each reaction and it's rate; and that the development of pathologies influence cognition and visual perception. This illustrates that the function of the autonomic nervous system is linked to that of the physiological systems and that the rate of biochemical reactions, and the progression of disease, can be measured by a cognitive test procedure and used as an indication of the disease(s) affecting heart function.The article discusses the limitations of the conventional biomarker technique, and the potential value of non-invasive cognitive techniques, such as Virtual Scanning, to the medical practitioner. Finally, it discusses how the ability of Virtual Scanning to diagnose disease from its presymptomatic origins may lead to improved diagnostic accuracy and significantly reduced costs.


Isolated mouse pancreatic beta-cells show cell-specific temporal response pattern.
The length of the silent lag time before elevation of the cytosolic free Ca2+ concentration ([Ca2+]i) differs between individual pancreatic beta-cells. One important question is whether these differences reflect a random phenomenon or whether the length of lag time is inherent in the individual beta-cell. We compared the lag times, initial dips, and initial peak heights for [Ca2+]i from two consecutive glucose stimulations (with either 10 or 20 mM glucose) in individual ob/ob mouse beta-cells with the fura 2 technique in a microfluorimetric system. There was a strong correlation between the lengths of the lag times in each beta-cell (10 mM glucose: r = 0.94, P < 0.001; 20 mM glucose: r = 0.96, P < 0.001) as well as between the initial dips in [Ca2+]i (10 mM glucose: r = 0.93, P < 0.001; 20 mM glucose: r = 0.79, P < 0.001) and between the initial peak heights (10 mM glucose: r = 0.51, P < 0.01; 20 mM glucose: r = 0.77, P < 0.001). These data provide evidence that the response pattern, including both the length of the lag time and the dynamics of the subsequent [Ca2+]i, is specific for the individual beta-cell.


Local electrogram assessment of unidirectional isthmus block is sufficient to predict the acute and long-term success of cavo-tricuspid isthmus ablation.
This study investigated whether a minimal approach to typical atrial flutter ablation using an 8 mm tip catheter with a 150 W generator with only the documentation of clockwise block by means of local criteria predicts a good long-term outcome. Seventy patients underwent typical atrial flutter ablation. A multipolar catheter was inserted into the coronary sinus (CS) and an 8 mm tip ablation catheter was used to ablate and map the isthmus. The ablation line was performed in the posteroseptal region. The clockwise block was confirmed by recording a corridor of double potentials along the line and by counterclockwise activation of the portion of the isthmus just beyond the lesion line as demonstrated by measuring the conduction times during CS pacing. In case of block, the mean distance between the two split atrial electrograms was 129 +/- 31 ms. Acute isthmus block was achieved in all 70 patients. The median of the radiofrequency pulses was 10 (range 1-36). No immediate or late complications were noted. The long-term follow-up (19.5 +/- 4 months) revealed recurrence of typical atrial flutter in 2 cases (2.8%). Our results demonstrate that the acute success rate following typical atrial flutter isthmus ablation using an 8 mm tip catheter with a 150 W generator is high. No complications occurred. Moreover, the documentation of just the clockwise isthmus block using a minimal approach according to local electrogram criteria is a good predictor of the long-term success.


Structural models of the different trimers present in the core of phycobilisomes from Gracilaria chilensis based on crystal structures and sequences.
Phycobilisomes (PBS) are accessory light harvesting protein complexes that directionally transfer energy towards photosystems. Phycobilisomes are organized in a central core and rods radiating from it. Components of phycobilisomes in Gracilaria chilensis (Gch) are Phycobiliproteins (PBPs), Phycoerythrin (PE), and Phycocyanin (PC) in the rods, while Allophycocyanin (APC) is found in the core, and linker proteins (L). The function of such complexes depends on the structure of each component and their interaction. The core of PBS from cyanobacteria is mainly composed by cylinders of trimers of α and β subunits forming heterodimers of Allophycocyanin, and other components of the core including subunits αII and β18. As for the linkers, Linker core (LC) and Linker core membrane (LCM) are essential for the final emission towards photoreaction centers. Since we have previously focused our studies on the rods of the PBS, in the present article we investigated the components of the core in the phycobilisome from the eukaryotic algae, Gracilaria chilensis and their organization into trimers. Transmission electron microscopy provided the information for a three cylinders core, while the three dimensional structure of Allophycocyanin purified from Gch was determined by X-ray diffraction method and the biological unit was determined as a trimer by size exclusion chromatography. The protein sequences of all the components of the core were obtained by sequencing the corresponding genes and their expression confirmed by transcriptomic analysis. These subunits have seldom been reported in red algae, but not in Gracilaria chilensis. The subunits not present in the crystallographic structure were modeled to build the different composition of trimers. This article proposes structural models for the different types of trimers present in the core of phycobilisomes of Gch as a first step towards the final model for energy transfer in this system.


Comparison of Cell and Organoid-Level Analysis of Patient-Derived 3D Organoids to Evaluate Tumor Cell Growth Dynamics and Drug Response.
3D cell culture models have been developed to better mimic the physiological environments that exist in human diseases. As such, these models are advantageous over traditional 2D cultures for screening drug compounds. However, the practicalities of transitioning from 2D to 3D drug treatment studies pose challenges with respect to analysis methods. Patient-derived tumor organoids (PDTOs) possess unique features given their heterogeneity in size, shape, and growth patterns. A detailed assessment of the length scale at which PDTOs should be evaluated (i.e., individual cell or organoid-level analysis) has not been done to our knowledge. Therefore, using dynamic confocal live cell imaging and data analysis methods we examined tumor cell growth rates and drug response behaviors in colorectal cancer (CRC) PDTOs. High-resolution imaging of H2B-GFP-labeled organoids with DRAQ7 vital dye permitted tracking of cellular changes, such as cell birth and death events, in individual organoids. From these same images, we measured morphological features of the 3D objects, including volume, sphericity, and ellipticity. Sphericity and ellipticity were used to evaluate intra- and interpatient tumor organoid heterogeneity. We found a strong correlation between organoid live cell number and volume. Linear growth rate calculations based on volume or live cell counts were used to determine differential responses to therapeutic interventions. We showed that this approach can detect different types of drug effects (cytotoxic vs cytostatic) in PDTO cultures. Overall, our imaging-based quantification workflow results in multiple parameters that can provide patient- and drug-specific information for screening applications.


Correlation between serum transforming growth factor β1, interleukin-6 and neonatal respiratory distress syndrome.
Trend and correlation of transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) in serum of children with neonatal respiratory distress syndrome (NRDS) were investigated. A total of 75 NRDS children born in the Xiangyang Central Hospital from July 2015 to August 2017 were analyzed retrospectively. A total of 45 NRDS premature infants who received pulmonary surfactant (PS) within 12 h after birth were treated as PS group, 30 who did not receive PS treatment as non-PS group, and 32 premature infants without NRDS in the same period were selected as control group. Serum levels of TGF-β1 and IL-6 were detected by enzyme linked immunosorbent assay (ELISA) at various time points after birth and their correlation was analyzed. The expression level of TGF-β1 in serum of children in PS group was significantly higher than that in control group on days 1 and 3 after birth (P<0.05). The expression level of TGF-β1 in non-PS group increased continuously with the increase of number of days and was significantly higher than that in control group on days 1, 3 and 7 after birth (P<0.05), and significantly higher than that in PS group on days 3 and 7 after birth (P<0.05). The analysis of the correlation between the severity of the disease and the expression levels of TGF-β1 and IL-6 showed that the expression levels were elevated with the increase of the disease severity. The expression levels of TGF-β1 and IL-6 were positively correlated with severity of the disease (r=0.7509, P<0.05; r=0.8056, P<0.05). The expression levels of TGF-β1 and IL-6 in PS and non-PS groups were positively correlated (r=0.9042, P<0.05; r=0.8905, P<0.05). The results showed that serum TGF-β1 and IL-6 were elevated in NRDS children, and there was a positive correlation between them.


The Added Value of Statistical Modeling of Backscatter Properties in the Management of Breast Lesions at US.
To develop a classification method based on the statistical backscatter properties of tissues that can be used as an ancillary tool to the usual Breast Imaging Reporting and Data System (BI-RADS) classification for solid breast lesions identified at ultrasonography (US). This study received institutional review board approval, and all subjects provided informed consent. Eighty-nine women (mean age, 50 years; age range, 22-82 years) with 96 indeterminate solid breast lesions (BI-RADS category 4-5; mean size, 13.2 mm; range, 2.6-44.7 mm) were enrolled. Prior to biopsy, additional radiofrequency US images were obtained, and a 3-second cine sequence was used. The research data were analyzed at a later time and were not used to modify patient management decisions. The lesions were segmented manually, and parameters of the homodyned K distribution (α, k, and μn values) were extracted for three regions: the intratumoral zone, a 3-mm supratumoral zone, and a 5-mm infratumoral zone. The Mann-Whitney rank sum test was used to identify parameters with the best discriminating value, yielding intratumoral α, supratumoral k, and infratumoral μn values. The 96 lesions were classified as follows: 48 BI-RADS category 4A lesions, 16 BI-RADS category 4B lesions, seven BI-RADS category 4C lesions, and 25 BI-RADS category 5 lesions. There were 24 cancers (25%). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval: 0.65, 0.86). Overall, 24% of biopsies (in 17 of 72 lesions) could have been spared. By limiting analysis to lesions with a lower likelihood of malignancy (BI-RADS category 4A-4B), this percentage increased to 26% (16 of 62 lesions). Among benign lesions, the model was used to correctly classify 10 of 38 fibroadenomas (26%) and three of seven stromal fibroses (43%). The statistical model performs well in the classification of solid breast lesions at US, with the potential of preventing one in four biopsies without missing any malignancy.


Untangling chronic pain and post-concussion symptoms: the significance of depression.
Post-concussion-like symptoms (PCS) are common in patients without a history of brain injury, such as those with chronic pain (CP). This exploratory study examined neuro-cognitive and psychological functioning in patients with PCS following mild traumatic brain injury (mTBI) or CP, to assess unique and overlapping phenomenology. In this case-control study, participants (n = 102) with chronic symptoms after mTBI (n = 45) were matched with mTBI recovered (n = 31) and CP groups (n = 26), on age, gender, ethnicity and education. Psychological status, cognitive functioning, health symptoms, beliefs and behaviours were examined. Participants who had not recovered from an mTBI and participants with CP did not differ in terms of PCS symptoms, quality of life, distress or illness behaviours, however, the CP group endorsed fewer subjective cognitive problems, more negative expectations about recovery and more distress (p < 0.05). On cognitive testing participants who had not recovered from an mTBI demonstrated greater difficulties with attention (p < 0.01) although differences disappeared when depression was controlled in the analyses. Unique patterns associated with each condition were evident though caution is required in attributing PCS and cognitive symptoms to a brain injury in people with mTBI presenting with chronic pain and/or depression. Psychological constructs such as illness and recovery beliefs appear to be important to consider in the development of treatment interventions.


CVAK104 is a novel poly-L-lysine-stimulated kinase that targets the beta2-subunit of AP2.
Isolated clathrin adaptor protein (AP) preparations are known to co-fractionate with endogenous kinase activities, including poly-L-lysine-stimulated kinases that target various constituents of the clathrin coat. We have identified CVAK104 (a coated vesicle-associated kinase of 104 kDa) using a mass spectroscopic analysis of adaptor protein preparations. CVAK104 is a novel serine/threonine kinase that belongs to the SCY1-like family of protein kinases, previously thought to be catalytically inactive. We found that CVAK104 co-fractionates with adaptor protein preparations extracted from clathrin-coated vesicles and directly binds to both clathrin and the plasma membrane adaptor, AP2. CVAK104 binds ATP, and kinase assays indicate that it functions in vitro as a poly-L-lysine-stimulated kinase that is capable of autophosphorylation and phosphorylating the beta2-adaptin subunit of AP2.


Gravitational corrections to Yukawa and phi{4} interactions.
We consider the lowest order quantum gravitational corrections to Yukawa and phi{4} interactions. Our results show that quantum gravity leads to contributions to the running coupling constants if the particles are massive and therefore alters the scaling behavior of the standard model. Furthermore, we find that the gravitational contributions to the running of the masses vanish.


Enzymatically synthesized glycogen inhibits colitis through decreasing oxidative stress.
Inflammatory bowel diseases are a group of chronic inflammation conditions of the gastrointestinal tract. Disruption of the mucosal immune response causes accumulation of oxidative stress, resulting in the induction of inflammatory bowel disease. In this study, we investigated the effect of enzymatically synthesized glycogen (ESG), which is produced from starch, on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Oral administration of ESG suppressed DSS- and TNBS-induced shortening of large intestine in female mice and significant decreased DSS-induced oxidative stress and TNBS-induced pro-inflammatory cytokine expression in the large intestine. ESG increase in the expression levels of heme oxygenase-1 (HO-1) and NF-E2-related factor-2 (Nrf2), a transcription factor for HO-1 expressed in the large intestine. Furthermore, ESG-induced HO-1 and Nrf2 were expressed mainly in intestinal macrophages. ESG is considered to be metabolized to resistant glycogen (RG) during digestion with α-amylase in vivo. In mouse macrophage RAW264.7 cells, RG, but not ESG decreased 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced reactive oxygen species (ROS). Knockdown of Nrf2 inhibited RG-induced HO-1 expression and negated the decrease in AAPH-induced ROS brought about by RG. RG up-regulated the protein stability of Nrf2 to decrease the formation of Nrf2-Keap1 complexes. RG-induced phosphorylation of Nrf2 at Ser40 was suppressed by ERK1/2 and JNK inhibitors. Our data indicate that ESG, digested with α-amylase to RG, suppresses DSS- and TNBS-induced colitis by increasing the expression of HO-1 in the large intestine of mice. Furthermore, we demonstrate that RG induces HO-1 expression by promoting phosphorylation of Nrf2 at Ser40 through activation of the ERK1/2 and JNK cascade in macrophages.


Coronary implantation of silicone-carbide-coated Palmaz-Schatz stents in patients with high risk of stent thrombosis without oral anticoagulation.
Coronary stenting in bail-out situations is effective but associated with increased stent thrombosis and bleeding rates. Silicone-carbide coating reduces fibrinogen activation on alloplastic surfaces and thus may also reduce stent thromboses. A total of 44 patients received 58 silicone-carbide-coated stents for threatened (80%) or abrupt (20%) closure. In addition to heparin, patients were treated with aspirin and ticlopidine (75%) or aspirin (25%) only. Two patients (4.5%) died in the hospital. The combined in-hospital complication rate including death, emergency revascularization, stent-related myocardial infarction, and stent thrombosis was 9% (4 of 44 patients). Major bleeding occurred in 4 patients (9%). Six-month follow-up angiography was obtained in all eligible patients (42 of 44), revealing a restenosis rate of 21% (9 of 42). Thus, coronary implantation of silicone-carbide-coated stents is feasible in bail-out situations without oral anticoagulation and with a low complication rate. Further studies are required to optimize the anticoagulation regimen with this type of coating.


The incidence and risk factors of contralateral knee arthroplasty after primary unilateral unicompartmental knee arthroplasty.
Unicompartmental knee arthroplasty (UKA) is one of the commonly used surgical methods for unicompartmental osteoarthritis in recent years. Although the prognosis of the operated knee has been widely studied, there are relatively little data on the natural history of the contralateral knee after unilateral replacement. The aim of this study was to explore the incidence and risk factors of consequential knee arthroplasty in patients with bilateral knee osteoarthritis (KOA) after receiving primary unilateral UKA, so as to provide a theoretical basis for making a more comprehensive treatment strategy for patients with KOA.We conducted a retrospective study and enrolled patients with bilateral KOA received unilateral UKA from June 2015 to December 2019 in the third department of joint orthopedics, the third hospital of Hebei Medical University. The patients were divided into replacement group and non-replacement group according to whether the contralateral knee joint received knee arthroplasty. Information about treatment of contralateral knee joint was collected from medical records to determine the incidence. Univariate analysis and multivariate logistic regression analysis were performed to identify the independent risk factors.A total of 502 patients were enrolled in this study. The incidence of contralateral knee arthroplasty was 38.64%. In the univariate analysis, vertical angle of mechanical axis, knee joint's internal and external joint space, Kellgren-Lawrence (K-L) classification, femoral tibial angle were the significant risk factors for contralateral knee arthroplasty. In the multivariate model, only vertical angle of mechanical axis ≥3.03° (odds ratio [OR] 4.36, 95% confidence interval [CI], 2.47-9.11), K-L classification grades 3 and 4 (OR 2.46,3.72; 95%CI, 1.31-4.25, 1.98-6.87), and femoral tibial angle ≥187.32° (OR 6.32, 95%, 2.23-18.87) remained associated with the occurrence of knee arthroplasty.About a quarter of patients with bilateral KOA received unilateral UKA will receive contralateral knee arthroplasty. Higher K-L classification, femoral tibial angle, and mechanical axis vertical angle are identified risk factors.


Rotational magnetic endosome microrheology: viscoelastic architecture inside living cells.
The previously developed technique of magnetic rotational microrheology [Phys. Rev. E 67, 011504 (2003)] is proposed to investigate the rheological properties of the cell interior. An endogeneous magnetic probe is obtained inside living cells by labeling intracellular compartments with magnetic nanoparticles, following the endocytosis mechanism, the most general pathway used by eucaryotic cells to internalize substances from an extracellular medium. Primarily adsorbed on the plasma membrane, the magnetic nanoparticles are first internalized within submicronic membrane vesicles (100 nm diameter) to finally concentrate inside endocytotic intracellular compartments (0.6 microm diameter). These magnetic endosomes attract each other and form chains within the living cell when submitted to an external magnetic field. Here we demonstrate that these chains of magnetic endosomes are valuable tools to probe the intracellular dynamics at very local scales. The viscoelasticity of the chain microenvironment is quantified in terms of a viscosity eta and a relaxation time tau by analyzing the rotational dynamics of each tested chain in response to a rotation of the external magnetic field. The viscosity eta governs the long time flow of the medium surrounding the chains and the relaxation time tau reflects the proportion of solidlike versus liquidlike behavior (tau=eta/G, where G is the high-frequency shear modulus). Measurements in HeLa cells show that the cell interior is a highly heterogeneous structure, with regions where chains are embedded inside a dense viscoelastic matrix and other domains where chains are surrounded by a less rigid viscoelastic material. When one compound of the cell cytoskeleton is disrupted (microfilaments or microtubules), the intracellular viscoelasticity becomes less heterogeneous and more fluidlike, in the sense of both a lower viscosity and a lower relaxation time.


The Snow Must Go On: Ground Ice Encasement, Snow Compaction and Absence of Snow Differently Cause Soil Hypoxia, CO2 Accumulation and Tree Seedling Damage in Boreal Forest.
At high latitudes, the climate has warmed at twice the rate of the global average with most changes observed in autumn, winter and spring. Increasing winter temperatures and wide temperature fluctuations are leading to more frequent rain-on-snow events and freeze-thaw cycles causing snow compaction and formation of ice layers in the snowpack, thus creating ice encasement (IE). By decreasing the snowpack insulation capacity and restricting soil-atmosphere gas exchange, modification of the snow properties may lead to colder soil but also to hypoxia and accumulation of trace gases in the subnivean environment. To test the effects of these overwintering conditions changes on plant winter survival and growth, we established a snow manipulation experiment in a coniferous forest in Northern Finland with Norway spruce and Scots pine seedlings. In addition to ambient conditions and prevention of IE, we applied three snow manipulation levels: IE created by artificial rain-on-snow events, snow compaction and complete snow removal. Snow removal led to deeper soil frost during winter, but no clear effect of IE or snow compaction done in early winter was observed on soil temperature. Hypoxia and accumulation of CO2 were highest in the IE plots but, more importantly, the duration of CO2 concentration above 5% was 17 days in IE plots compared to 0 days in ambient plots. IE was the most damaging winter condition for both species, decreasing the proportion of healthy seedlings by 47% for spruce and 76% for pine compared to ambient conditions. Seedlings in all three treatments tended to grow less than seedlings in ambient conditions but only IE had a significant effect on spruce growth. Our results demonstrate a negative impact of winter climate change on boreal forest regeneration and productivity. Changing snow conditions may thus partially mitigate the positive effect of increasing growing season temperatures on boreal forest productivity.


Subunit Arrangement in GpsB, a Regulator of Cell Wall Biosynthesis.
GpsB, a key regulator of cell division in Gram-positive bacteria, interacts with a key peptidoglycan synthase at the cell division septum, the penicillin binding protein PBP1 (a.k.a. PonA). Bacillus subtilis GpsB has been reported to interact with other components of the cell division machinery, including EzrA, MreC, and PrkC. In this study, we report an analysis of the arrangement of subunits in Listeria monocytogenes GpsB by small-angle X-ray scattering. The resulting model has an elongated shape with residues critical for interaction with PBP1 and the cell membrane clustered at one end of the molecule. Mutations that destabilize the hexameric assembly of the wild-type protein have a gpsB null phenotype, indicating that oligomerization is critical for the correct function of GpsB. We suggest a model in which a single GpsB hexamer can interact with multiple PBP1 molecules and can therefore influence the arrangement of PBP1 molecules within the cell division machinery, a dynamic multiprotein complex called the divisome, consistent with a role for GpsB in modulating the synthesis of the cell wall.


Human OGG1 undergoes serine phosphorylation and associates with the nuclear matrix and mitotic chromatin in vivo.
OGG1 is the major DNA glycosylase in human cells for removal of 7,8 dihydro-8-oxoguanine (8-oxoG), one of the most frequent endogenous base lesions formed in the DNA of aerobic organisms. During replication, 8-oxoG will frequently mispair with adenine, thus forming G:C --> T:A transversions, a common somatic mutation associated with human cancers. In the present study, we have constructed a stable transfectant cell line expressing hOGG1 fused at the C-terminal end to green fluorescent protein (GFP) and investigated the cellular distribution of the fusion protein by fluorescence analysis. It is shown that hOGG1 is preferentially associated with chromatin and the nuclear matrix during interphase and becomes associated with the condensed chromatin during mitosis. Chromatin-bound hOGG1 was found to be phosphorylated on a serine residue in vivo as revealed by staining with an anti-phosphoserine-specific antibody. Chromatin-associated hOGG1 was co-precipitated with an antibody against protein kinase C (PKC), suggesting that PKC is responsible for the phosphorylation event. Both purified and nuclear matrix-associated hOGG1 were shown to be substrates for PKC-mediated phosphorylation in vitro. This appears to be the first demonstration of a post-translational modification of hOGG1 in vivo.


Is psychological treatment efficacious for attention deficit hyperactivity disorder (ADHD)? Review of non-pharmacological treatments in children and adolescents with ADHD.
Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children and adolescents, and has a great impact on the psychological development of affected patients. Even though its efficacy is proven, the use of medication for ADHD has several limitations, and non-pharmacological interventions are considered a necessary component of treatment. This work is a review of evidence-based non-pharmacological treatments with demonstrated efficacy for ADHD in children and adolescents, analyzed by age groups. Non-pharmacological treatments that have shown scientific evidence of efficacy are psychological and psychoeducational interventions. Psychological interventions include behavioral therapy, parent training (PT) and social skills training. Psychoeducational interventions include a set of practices to improve learning and are carried out in the school setting. Scientific evidence of efficacy in preschool children is limited to PT, while different psychological and psychoeducational interventions have been shown to be beneficial in school-age children. The available evidence for non-pharmacological treatment in adolescence is so far insufficient. Though more randomized controlled trials are necessary for non-pharmacological interventions to become established practices, there are clear indications of their efficacy. For more severe cases of ADHD, a combination of non-pharmacological and pharmacological treatment is recommended.


[Subcranial approach. Technical aspects and application in craneofacial traumatic pathology].
INTRODUCTION. Suitable approach to anterior cranial base is mandatory to get global satisfactory surgical outcomes. In the beginning it depends on the exactly anatomical position into the cranial fossa and tridimensional spread. Surgical approach implies the evaluation of the patient status, reconstructive options and surgical team experience. Subcranial approach is a safe surgical option in the treatment of frontal traumatic pathology. It allows adequate management of frontal sinus and its obliteration with easy radiologic follow-up. OBJECTIVES. To analyse subcranial approach as a treatment option in traumatic pathology of the anterior cranial base and to present our review of subcranial approach. Valuation of surgical technical aspects. and related complications. MATERIAL AND METHODS. Retrospective analysis of 50 patients operated (subcranial approach) from January 2004 to December 2009 by Maxillofacial and Neurosurgery Department, University Hospital 12 de Octubre, Madrid. 34 patients presented craniofacial trauma or postraumatic sequela and 16 patients presented craniofacial tumours. Oncological cases offers experience to discuss surgical aspects. Results are related to traumatic pathology and sequela. Main items review were surgical technique including materials used for frontal sinus obliteration, associated traumatic pathology, hospital stay and complication rates. RESULTS. No perioperatory mortality was found. Patients´ age ranged 15-76 years. 22 were male and 12 female. Description of frontal fractures involved. Frontal sinus obliteration was made with calvarian bone dust. Morbidity rates was 29% in posttraumatic patients. Mean hospital stay was 13 days. Subcranial approach to anterior cranial base is a safe and reliable treatment option to the pathology of this area. It allows outstanding exposure of the nasal cavity, orbits, ethmoidal cells-sphenoid sinus and great access to anterior fossa without frontal lobe retraction.


Alzheimer's disease symptom severity in blacks and whites.
In order to determine whether there are racial differences in Alzheimer's Disease (AD) symptom severity and vascular comorbidities, we compared African-American (black) and Caucasian (white) patients with AD from similar socioeconomic backgrounds at the time the disease was first recognized. Cross-sectional observational study from a population-based dementia registry. Patients were enrolled from an HMO base population of 23,000 persons more than age 60 in Seattle, Washington. This study examines 453 subjects with probable AD (38 blacks (mean age 76.5, SD 6.4), and 415 whites (mean age 79.7, SD 6.7)). Measured were patient demographics, age at onset of AD, AD symptom duration, Mini-Mental State Exam (MMSE) score, Blessed Dementia Rating Scale, presence of psychiatric symptoms, and vascular comorbidities. Blacks had significantly lower mean cognitive scores (MMSE = 17.2, SD 5.6) compared with whites (MMSE = 20.2, SD 5.2, unpaired t test P < .01). The significant racial difference in MMSE scores persisted after controlling for education, duration of AD symptoms, age, and ADL impairment. Blacks and whites did not differ significantly regarding gender distribution, education level, income, or percent with early age of onset of AD. No statistically significant race-related differences were found in impairments in activities of daily living or symptoms of paranoia, hallucinations, or agitation. Blacks had significantly higher rates of hypertension (56%) compared with whites (34%) (Fisher's exact test, P = .013), but the rates of stroke and ischemic heart disease were similar. Despite uniform detection methods and controlling for reported duration of dementia symptoms, measured cognitive impairment is significantly more severe when AD is recognized in blacks compared with whites. The significantly higher prevalence of hypertension among black AD cases was not associated with excess cerebrovascular disease comorbidity. This study highlights a need for normative measurements of cognitive function in minority AD groups in order to distinguish differential cognitive symptom severity from possible measurement bias.


Does lumbar cerebrospinal fluid reflect ventricular cerebrospinal fluid? A prospective study in patients with external ventricular drainage.
Ventriculitis may sometimes occur after an external ventricular drain has been removed, and diagnosis has to be made by lumbar puncture. But are the lumbar findings comparable to previously obtained ventricular results? In a prospective study, sample pairs of ventricular and lumbar cerebrospinal fluid (CSF) were obtained at an interval of <30 min in 25 patients with increased intracranial pressure suffering from cerebral hemorrhage (n = 15), meningitis/encephalitis (n = 6), cerebral infarction (n = 3), and meningeosis carcinomatosa (n = 1). CSF was analyzed for protein, albumin, IgG, IgA, IgM, glucose, lactate, and leukocytes including cytological differentiation. A significant ventriculo-lumbar increase was observed for protein, albumin, and the immunoglobulins. Lactate was distributed equally in ventricular and lumbar CSF, as well as glucose in the cerebral hemorrhage subgroup (n = 15). Cell count failed to show a clear ventriculo-lumbar ratio. Cytological distribution was comparable in lumbar and ventricular CSF, except for macrophages showing a significant rostrocaudal decrease. In conclusion, in cases of clinically suspected bacterial central nervous system infection after removal of an external ventricular drain, lumbar CSF lactate, glucose, and cytology are comparable to previously determined ventricular values, and thus may help physicians to choose the best treatment.


Gracilis Free Flap in a Patient with Sickle Cell Disease.
Free tissue transfer in the sickle cell population presents many challenges to the reconstructive surgeon. There are few reported cases of successful free tissue transfers within the sickle cell population. The majority of successful cases involve fasciocutaneous free flaps with few successful muscle flaps. This case report describes the successful utilization of a gracillis free flap to reconstruct a multifocal soft tissue defect following a closed distal tibia fracture in a patient with sickle cell disease (SCD). This is a 20-year-old female with past medical history significant for sickle cell anemia, cardiomyopathy secondary to a ventricular septal defect and multiple occurrences of osteomyelitis who underwent gracilis free flap transfer to reconstruct soft tissue loss around the ankle after surgical fixation of a left pathological tibia fracture. The use of free flaps in sickle cell patients has shown to be extremely challenging due to the high risks of sickling and subsequent pedicle thrombosis associated with this population. However, there have been an increasing number of successful cases of free tissue transfers with most of these flaps arising from muscular origins. Therefore, more cases regarding free flaps in the sickle cell population are needed to fully understand the best protocols to follow. The techniques utilized among successful cases, regarding protocols prior to the surgery along with successful graft location selection, can help advance future cases and shows promise for future sickle cell patients.


Assessment of people who have been tasered.
The use of Tasers® by the police is subject to intense scrutiny and controversy. With increasing numbers of police officers carrying Tasers, it is important that nurses in pre-hospital, emergency department and police custody settings understand how Tasers work, and the physiological effects. This article describes Tasers, their mechanisms and physiological effects, and explains how nurses should undertake assessment of people who have been subjected to Taser discharge.


Prognostic value of venous invasion in resected T3 pancreatic adenocarcinoma: Depth of invasion matters.
Incomplete evaluation of venous invasion has led to conflicting results regarding the prognosis of patients undergoing pancreatectomy with a synchronous venous resection. This study evaluates the prognostic value associated with the presence and the depth of venous invasion in T3 pancreatic adenocarcinoma. This study evaluated retrospectively 181 consecutive pancreatoduodenectomies performed for T3N0M0 and T3N1M0 pancreatic adenocarcinomas (stages IIA and IIB) from January 2006 to December 2014. Univariate and multivariate Cox analyses were performed to assess survival prognostic factors. Pancreatoduodenectomies with a segmental venous resection was performed on 91 patients, while 90 other patients had a standard pancreatoduodenectomies without venous resection. Pathologic venous invasion was detected in 68 (74%) of the 91 venous resection patients. Depth of venous invasion was into the adventitia (n = 25), media (n = 28), and intima (n = 15). The overall survival rates at 1, 3, 5, and 10 years were 75%, 33%, 21%, and 6%, respectively. There were no differences in survival between patients undergoing standard pancreatoduodenectomies and pancreatoduodenectomies with venous resection (27 vs 22 months; P = .28) or between patients with and without venous invasion (20 vs 27 months; P = .08). In multivariate analysis, depth of venous invasion into the intima (hazard ratio, 2.25; 95% confidence interval, 1.16-4.34; P = .0001) and adjuvant chemotherapy (hazard ratio, 0.16; 95% confidence interval, 0.09-0.43; P ≤ .0001) were identified as independent prognostic factors of overall survival. Depth of venous invasion into the intima indicates poor survival in pancreatic T3 adenocarcinoma. Preoperative identification of this factor could be helpful for better selection of patients for curative operation.


Intercellular adhesion molecule-1 (ICAM-1) is involved in the cytolytic T lymphocyte interaction with a human synovial cell line.
The cell surface molecules involved in the human cytolytic T lymphocyte (CTL)-synovial cell interaction may play an important role in T cell interactions with connective tissue mesenchymal cells. To examine the molecular basis for the CTL-synovial cell interaction, we immortalized synovial cell explants to establish the cell line SYN.SPP. The SYN.SPP cell line was compared to the established B lymphoblastoid cell line JY. Cell surface immunofluorescence demonstrated significantly different levels of the immunologically relevant cell surface molecules ICAM-1 and LFA-3. Both cell lines were used to stimulate CTL precursors. After several months in culture, CTL lines stimulated by the SYN.SPP and JY cell lines demonstrated HLA class I-directed cytolytic activity. The cell surface molecules utilized by the anti-SYN.SPP and anti-JY CTL lines were identified by monoclonal antibody (MAb) inhibition. MAb recognizing the CTL cell surface molecules CD3, CD8 and LFA-1 (CD11a) significantly inhibited CTL-mediated lysis of both target cells. An interesting observation was that the anti-SYN.SPP CTL line appeared to utilize the ICAM-1 and not the LFA-3 target cell molecule. In contrast, the anti-JY CTL line utilized the LFA-3 and not the ICAM-1 membrane molecule. These results indicate that CTL interactions with connective tissue mesenchymal cells may be regulated by a unique pattern of antigen nonspecific cell-cell interaction molecules.


Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume.
Larger surgical caseload is associated with better patient outcome for many complex procedures. We examined the volume-outcome relationship for transsphenoidal pituitary tumor surgery using the Nationwide Inpatient Sample, 1996-2000. Multivariate regression adjusted for patient demographics, acuity measures, medical comorbidities, and endocrine status. A total of 5497 operations were performed at 538 hospitals by 825 surgeons. Outcome measured at hospital discharge was: death (0.6%), discharge to long-term care (0.9%), to short-term rehabilitation (2.1%), or directly home (96.2%). Outcomes were better after surgery at higher-volume hospitals (OR 0.74 for 5-fold-larger caseload, P = 0.007) or by higher-volume surgeons (OR 0.62, P = 0.02). A total of 5.4% of patients were not discharged directly home from lowest-volume-quartile hospitals, compared with 2.6% at highest-volume-quartile hospitals. In-hospital mortality was lower with higher-volume hospitals (P = 0.03) and surgeons (P = 0.09). Mortality rates were 0.9% at lowest-caseload-quartile hospitals and 0.4% at highest-volume-quartile hospitals. Postoperative complications (26.5% of admissions) were less frequent with higher-volume hospitals (P = 0.03) or surgeons (P = 0.005). Length of stay was shorter with high-volume hospitals (P = 0.02) and surgeons (P < 0.001). Hospital charges were lower for high-volume hospitals, but not significantly. This analysis suggests that higher-volume hospitals and surgeons provide superior short-term outcomes after transsphenoidal pituitary tumor surgery with shorter lengths of stay and a trend toward lower charges.


Effect of substituted benzamides on feeding and hypothalamic neuropeptide Y-like immunoreactivity (NPY-LI) in rats.
The study was conducted: (i) to evaluate the effects of three substituted benzamides on feeding behaviour in rats with free access to food and in those with access to food limited either to the light or to the dark phase of the diurnal cycle; and (ii) to determine whether the hypothalamic neuropeptide Y (NPY) system is involved in the action of these drugs on feeding. In free-feeding rats, a single dose of eticlopride (1 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.) decreased 24-h food intake, whereas remoxipride (3 mg/kg, i.p.) produced no effect. Single doses of eticlopride and raclopride but not of remoxipride decreased hypothalamic neuropeptide Y-like immunoreactivity (NPY-LI). Eticlopride administered once daily for 14 days decreased both food intake and hypothalamic NPY-LI. When given for 14 days, raclopride and remoxipride decreased food intake in rats with access to food in the dark (19.00-07.00) but not in thelight (07.00-19.00) phase of the diurnal cycle; both these compounds decreased hypothalamic NPY-LI only in the former group of rats. The results suggest that the effects of substituted benzamides on feeding behaviour depend on the drug and the time of administration and that these effects are related to the altered function of the hypothalamic NPY system.


[A bibliometric review of infant feeding in Mexico].
a bibliometric analysis on published articles about infant feeding, in Mexican biomedical journals, during 2000-2009, is presented. six journals, edited by public institutions or medical associations, published at least one article dealing with the selected theme. From a total of 3,077 articles published, only 2.5% were about infant feeding (78). Title, abstracts, frequency of keywords and institutional affiliation of main author of those articles were analyzed; the contents were classified in seven thematic nodes. the most frequent node was feeding model;breastfeeding appeared 10 times as key word; the authorial institutional affiliation followed Lotka's Law. The results indicate a predominant univocal feeding model; the assumption on universality of mother-infant dyad; the focus on medical and clinical entities; and an absence about social agents involved in the feeding process. hence,if the bibliometry elucidates the explicit knowledge and illustrates the current biomedical discourses, this analysis shows that the required knowledge for design and operation of public policies related to maternal and infant welfare, in Mexico, are still insufficient for fulfilling international public health recommendations.


Satisfaction in open access versus traditional referral for upper endoscopy in children.
In traditional access endoscopy (TAE), patients are booked for endoscopy following a gastroenterology clinic assessment. In contrast, open access endoscopy (OAE) patients are seen for the first time on the day of the procedure, providing same day procedural consent. Controversy exists over the use of OAE in adults, both with the consent process and with patient satisfaction. No literature exists describing satisfaction with OAE in pediatrics. We therefore aimed to assess pediatric patient and caregiver satisfaction in OAE compared with TAE. Consecutive pediatric patients, and their caregivers, undergoing elective upper endoscopy from May to December 2012 at the Stollery Children's Hospital (Edmonton, Alberta, Canada) were consented for a cross-sectional survey. Seven preprocedure and 5 postprocedure questions were completed regarding mood and satisfaction with the wait time and the information provided. Group demographics and endoscopy wait times were collected. Median wait time with OAE was less compared with TAE (57 days vs 196 days, P < 0.001). OAE patients reported worse mood preprocedure than TAE patients (35.3% vs 10.7%, P = 0.046). OAE caregivers and patients reported more mood disturbance if required to wait longer for endoscopy by attending clinic preprocedure (OAE caregivers 62.2%, OAE patients 64.7%). OAE is associated with worse preendoscopy patient mood; however, children and caregivers seem concerned about longer wait times associated with TAE. Given the significantly shorter wait times in OAE, identifying methods to minimize present limitations of OAE will be useful to improve clinical practices in pediatric gastroenterology.


Effects of media multitasking frequency on a novel volitional multitasking paradigm.
The effect of media multitasking (e.g., listening to podcasts while studying) on cognitive processes has seen mixed results thus far. To date, the tasks used in the literature to study this phenomenon have been classical paradigms primarily used to examine processes such as working memory. While perfectly valid on their own, these paradigms do not approximate a real-world volitional multitasking environment. To remedy this, as well as attempt to further validate previously found effects in the literature, we designed a novel experimental framework that mimics a desktop computer environment where a "popup" associated with a secondary task would occasionally appear. Participants could choose to attend to the popup, or to ignore it. Attending to the popup would prompt a word stem completion task, while ignoring it would continue the primary math problem verification task. We predicted that individuals who are more impulsive, more frequent media multitaskers, and individuals who prefer to multitask (quantified with the Barratt Impulsiveness Scale, a modified version of the Media Use Questionnaire, and the Multitasking Preference Inventory) would be more distracted by popups, choose to switch tasks more often and more quickly, and be slower to return to the primary task compared to those who media multitask to a lesser degree. We found that as individuals media multitask to a greater extent, they are slower to return to the previous (primary) task set and are slower to complete the primary task overall whether a popup was present or not, among other task performance measures. We found a similar pattern of effects within individuals who prefer to multitask. Our findings suggest that overall, more frequent media multitaskers show a marginal decrease in task performance, as do preferential multitaskers. Attentional impulsivity was not found to influence any task performance measures, but was positively related to a preference for multitasking. While our findings may lack generalizability due to the modifications to the Media Use Questionnaire, and this initial study is statically underpowered, this paradigm is a crucial first step in establishing a more ecologically valid method to study real-world multitasking.


Investigation of Mating Pheromone-Pheromone Receptor Specificity in Lentinula edodes.
The B mating-type locus of Lentinula edodes, a representative edible mushroom, is highly complex because of allelic variations in the mating pheromone receptors (RCBs) and the mating pheromones (PHBs) in both the Bα and Bβ subloci. The complexity of the B mating-type locus, five Bα subloci with five alleles of RCB1 and nine PHBs and three Bβ subloci with 3 alleles of RCB2 and five PHBs, has led us to investigate the specificity of the PHB-RCB interaction because the interaction plays a key role in non-self-recognition. In this study, the specificities of PHBs to RCB1-2 and RCB1-4 from the Bα sublocus and RCB2-1 from the Bb sublocus were investigated using recombinant yeast strains generated by replacing STE2, an endogenous yeast mating pheromone receptor, with the L. edodesRCBs. Fourteen synthetic PHBs with C-terminal carboxymethylation but without farnesylation were added to the recombinant yeast cells and the PHB-RCB interaction was monitored by the expression of the FUS1 gene-a downstream gene of the yeast mating signal pathway. RCB1-2 (Bα2) was activated by PHB1 (4.3-fold) and PHB2 (2.1-fold) from the Bα1 sublocus and RCB1-4 (Bα4) was activated by PHB5 (3.0-fold) and PHB6 (2.7-fold) from the Bα2 sublocus and PHB13 (3.0-fold) from the Bα5 sublocus. In particular, PHB3 from Bβ2 and PHB9 from Bβ3 showed strong activation of RCB2-1 of the Bβ1 sublocus by 59-fold. The RCB-PHB interactions were confirmed in the monokaryotic S1-10 strain of L. edodes by showing increased expression of clp1, a downstream gene of the mating signal pathway and the occurrence of clamp connections after the treatment of PHBs. These results indicate that a single PHB can interact with a non-self RCB in a sublocus-specific manner for the activation of the mating pheromone signal pathways in L. edodes.


Simon Bolivar's medical labyrinth: an infectious diseases conundrum.
According to history books, tuberculosis was responsible for the death of Simon Bolivar at the age of 47 years in 1830. The results of an autopsy performed by Alexandre Prospère Révérend, the French physician who cared for him during the terminal phase of his illness, have long been regarded as proof of the diagnosis. On careful reanalysis of Bolivar's medical history and post mortem examination, we reach a different conclusion. On the basis of several critical clinical, epidemiological, and pathological features of his fatal disorder, we conclude that either paracoccidioidomycosis or bacterial bronchiectasis complicating chronic arsenic intoxication was more likely responsible for his death than was tuberculous "consumption."


Neuropharmacology of delta-aminolaevulinic acid--I. Effect of acute administration in rodents.
Delta-aminolaevulinic acid (ALA) is suspected of being responsible for the neuropsychiatric symptoms of acute porphyria. The object of this study was to examine the effects of ALA in vivo on a range of behavioural and physiological functions which are known to be affected in the acute porphyric attack. Aminolaevulinic acid was administered by intraperitoneal or subcutaneous injection to mice in doses up to 1000 mg/kg and effects on nociception (hot-plate and abdominal constriction tests), CNS excitability (pentobarbitone sleep-time and pentylenetetrazole-induced seizures), motor co-ordination and grip (rotating rod test) were studied. Rats were given intravenous injections or infusions of ALA of up to 24 mg and changes in blood pressure, heart rate and ED50 for noradrenaline, acetylcholine and isoprenaline examined. No statistically significant effects were noted, using buffered solutions of ALA (pH 7.0-7.4). However, unbuffered solutions of ALA caused significant bradycardia and hypotension. These results do not support the hypothesis that ALA has significant acute neuropharmacological activity in vivo when the blood-brain barrier is intact.


Exploring tattoo artists' understanding of decorative non-medical professional tattooing as a method of scar camouflage and decoration.
Research surrounding the use of decorative tattooing by non-medical professional tattooists as a form of scar camouflage or decoration is limited. This study provides critical and deepening insights into tattoo artists' experiences of tattooing scars, to help inform a more in-depth understanding of its uses from a health and wellbeing perspective. Specifically, it aimed to explore qualitatively, the different methods and techniques used by non-medical tattoo professionals to cover up or decorate scars, which can have a psychological impact on those affected. Six tattoo artists from legitimate UK based studios were identified through snowballing and purposive sampling methods. Data collection involved semi-structured telephone interviews. The data was then transcribed, and thematic analysis was then performed. Five themes were identified: Personal Opinion of Scar Camouflage Tattooing, Tattooing Methods, Scars and Tattooing Risks, Positive Impact, and Understanding of Customer Experience. These themes were then broken down into more specific sub-themes. The discussion considers these findings in relation to theory and existing literature, for example, around understanding of role, and makes recommendations for future study in this field.


p27 small interfering RNA induces cell death through elevating cell cycle activity in cultured cortical neurons: a proof-of-concept study.
Recent research has demonstrated that cell cycle-associated molecules are activated in multiple forms of cell death in mature neurons, and raised a hypothesis that unscheduled cell cycle activity leads to neuronal cell death. But there is little evidence that changes in endogenous level of these molecules are causally associated with neuronal cell death. Here we transfected small interfering RNA (siRNA) targeting cyclin-dependent kinase (CDK) inhibitor p27, which plays an important role in cell cycle arrest at G1-S phase, into cultured cortical neurons. Transfection of p27 siRNA reduced neuronal viability in a time-dependent manner. p27 siRNA induced phosphorylation of retinoblastoma protein (Rb), a marker of cell cycle progression at late G1 phase. Moreover, phosphorylation of Rb and neuronal cell death provoked by p27 siRNA were abrogated by pharmacological CDK inhibitors, olomoucine and purvalanol A. Our data demonstrate that a decrease in endogenous p27 induces neuronal cell death through elevating cell cycle activity.


Analysis of exercise tolerance on the basis of six-minute walk test - 6MWT and Borg RPE scale in men with inguinal hernia before and after Lichtenstein repair.
Introduction: Assessment of exercise tolerance (ET) plays an important role in qualifications for treatment and rehabilitation.
Aim: The aim of the study was to assess ET in patients before and after inguinal hernia operations with Lichtenstein method.
Material and methods: The cohort study included men with inguinal hernia divided into the study group (SG) (n = 50) and control (CG) (n = 50) undergone the Lichtenstein surgery. Patients from the SG met the criterion of coexistence of cardiovascular and respiratory diseases. Day before and on the second day after surgery, patients performed 6MWT and subjectively rate the exertion according to Borg- RPE- Scale (before, immediately after and 10 minutes after the test). 6MWT distance, Borg scale ratings were analysed. On the second day after surgery 66% of patients from the SG and 58% from the CG did not complete the test. Patients from the SG before (500,07 ± 40,38 m) and on the second day after surgery (243,46 ± 18,18 m) achieved shorter distances compared to the CG (565,93 ± 20,41 m; 249,47 ± 26,66 m), p < 0,001 i p = 0,481. A statistically significant negative correlation between 6MWT distance before surgery and age of the patients was confirmed. Patients who did not develop complications achieved significantly longer distances on admission (p = 0,003 for SG, p = 0,004 for CG). For 6MWT before surgery and 2 days after surgery, patients from the SG showed a significantly higher level of fatigue compared to the CG after the test (before: p = 0,001, after: p = 0,001). Patients form the SG often discontinued 6MWT and less tolerated effort compared to the CG. Hence, 6MWT is useful tool for ascertaining physical capacity and ET.


Promoting interdisciplinarity through educational initiative: a qualitative evaluation.
This paper describes a multi-professional teaching innovation that took place at The University of Manchester during October 2001. Ideas for the project were first established in December 2000 when a multi-professional team of educationalists began exploring ways in which three disparate student groups could be brought together as part of an integrated learning activity (). For this reason, a problem-based learning scenario was developed to encourage nursing, midwifery, and medical students to share their previous knowledge and principles of care. In addition, the students were also asked to identify the type(s) of information they felt should be included in a user guide for new parents regarding the uncomplicated labour and puerperium. In total 10-second year nursing, 17-third year midwifery and 13-fourth year medical students volunteered to take part. These were subsequently divided into five integrated problem-based learning groups each supported by two teachers reflecting similar multi-professional backgrounds. In this paper, the discussion will explore a series of themes identified as being of major import by students and tutors during the qualitative phase of the study namely: