From college to clinic: reasoning over memorization is key for understanding anatomy.
Anatomy and physiology are taught in community colleges, liberal arts colleges, universities, and medical schools. The goals of the students vary, but educators in these diverse settings agree that success hinges on learning concepts rather than memorizing facts. In this article, educators from across the postsecondary educational spectrum expand on several points: (1) There is a problem with student perception that anatomy is endless memorization, whereas the ability to manage information and use reasoning to solve problems are ways that professionals work. This misperception causes students to approach the subject with the wrong attitude. (2) The process of learning to use information is as important as the concepts themselves. Using understanding to explain and make connections is a more useful long-term lesson than is memorization. Anatomy should be presented and learned as a dynamic basis for problem solving and for application in the practice and delivery of quality health care. (3) Integration of form and function must be explicit and universal across all systems. (4) Using only models, images, audiovisuals, or computers cannot lead students to the requisite reasoning that comes from investigative dissection of real tissue. (5) Some undergraduate courses require students to memorize excessive musculoskeletal detail. (6) Learning tissue biology is a particular struggle for medical students who have no background from an undergraduate course. (7) Medical professors and students see benefits when students have taken undergraduate courses in anatomy, histology, and physiology. If medical schools suggest these electives to applicants, medical students might arrive better prepared and, thus, be able to learn clinical correlations more efficiently in the limited allocated time of medical school curricula.


[The dermatological indications of laser: beyond cosmetic target.]
During the last 30 years, the use of lasers in dermatology has gone far beyond the spectrum of aesthetic and cosmetic applications. Techniques are more than simple removal by CO2 Laser. Increasing knowledge, understanding, and experience have helped to effectively treat numerous important skin diseaes by the use of lasers. However, high-quality clinical trials are sparse in this domain. Consequently, so far only the treatment of hemangiomas and warts is a laser indication reimbursed by insurance companies. This article discusses three types of skin diseases where substantial progress has been reported in the scientific literature in 2016, namely pigmentary disorders, vascular diseases, and inflammatory dermatoses.


Shaping up for action: the path to physiological maturation in the renal tubules of Drosophila.
The Malpighian tubule is the main organ for excretion and osmoregulation in most insects. During a short period of embryonic development the tubules of Drosophila are shaped, undergo differentiation and become precisely positioned in the body cavity, so they become fully functional at the time of larval hatching a few hours later. In this review I explore three developmental events on the path to physiological maturation. First, I examine the molecular and cellular mechanisms that generate organ shape, focusing on the process of cell intercalation that drives tubule elongation, the roles of the cytoskeleton, the extracellular matrix and how intercalation is coordinated at the tissue level. Second, I look at the genetic networks that control the physiological differentiation of tubule cells and consider how distinctive physiological domains in the tubule are patterned. Finally, I explore how the organ is positioned within the body cavity and consider the relationship between organ position and function.


Barriers to Radiation-Induced In Situ Tumor Vaccination.
The immunostimulatory properties of radiation therapy (RT) have recently generated widespread interest due to preclinical and clinical evidence that tumor-localized RT can sometimes induce antitumor immune responses mediating regression of non-irradiated metastases (abscopal effect). The ability of RT to activate antitumor T cells explains the synergy of RT with immune checkpoint inhibitors, which has been well documented in mouse tumor models and is supported by observations of more frequent abscopal responses in patients refractory to immunotherapy who receive RT during immunotherapy. However, abscopal responses following RT remain relatively rare in the clinic, and antitumor immune responses are not effectively induced by RT against poorly immunogenic mouse tumors. This suggests that in order to improve the pro-immunogenic effects of RT, it is necessary to identify and overcome the barriers that pre-exist and/or are induced by RT in the tumor microenvironment. On the one hand, RT induces an immunogenic death of cancer cells associated with release of powerful danger signals that are essential to recruit and activate dendritic cells (DCs) and initiate antitumor immune responses. On the other hand, RT can promote the generation of immunosuppressive mediators that hinder DCs activation and impair the function of effector T cells. In this review, we discuss current evidence that several inhibitory pathways are induced and modulated in irradiated tumors. In particular, we will focus on factors that regulate and limit radiation-induced immunogenicity and emphasize current research on actionable targets that could increase the effectiveness of radiation-induced in situ tumor vaccination.


Bioavailability of vitamin A sources for cattle.
An experiment was conducted to evaluate the bioavailability of 5 sources of vitamin A. It was hypothesized that some vitamin A products have protective coatings that are more resistant than others to rumen destruction and that such protection would result in greater tissue concentrations of vitamin A. Fifty-three yearling Angus x Brahman cattle, consisting of 39 steers and 14 heifers, were stratified by BW and sex and randomly assigned to 6 high-concentrate diet groups receiving no vitamin A supplementation (control) or vitamin A supplemented from the following sources: Microvit A (Adisseo, Acworth, GA), Rovamix A (DSM, Parsippany, NJ), Sunvit A, Lutavit A, and Microvit A DLC (Adisseo). The vitamin A treatment groups were fed daily 80,000 IU of retinol/animal in a low-retinol concentrate diet (78.5% oats, 10% cottonseed hulls, 8% molasses, and 2% cottonseed meal; DM basis) and a free-choice, poor quality (low carotene) hay for 84 d. Every 28 d, BW was determined and liver biopsies and plasma were collected and analyzed for retinol concentrations. All retinol treatments showed significant increases in liver retinol concentrations compared with control animals (P < 0.0001), which steadily decreased over time. At all collection times, Microvit A led to numerically, but not significantly, greater concentrations of retinol in liver than did all other treatments. However, at the end of the experiment, there was no significant difference in liver retinol concentration among Microvit A, Rovamix A, Lutavit A, and Microvit A DLC diets. When liver retinol concentrations at all collection times were considered, Microvit A and Rovamix A appeared to provide the most bioavailable vitamin A.


Applying Organizational Change to Promote Lesbian, Gay, Bisexual, and Transgender Inclusion and Reduce Health Disparities.
Lesbian, gay, bisexual, and transgender (LGBT) populations face numerous barriers when accessing and receiving healthcare, which amplify specific LGBT health disparities. An effective strategic approach is necessary for academic health centers to meet the growing needs of LGBT populations. Although effective organizational change models have been proposed for other minority populations, the authors are not aware of any organizational change models that specifically promote LGBT inclusion and mitigate access barriers to reduce LGBT health disparities. With decades of combined experience, we identify elements and processes necessary to accelerate LGBT organizational change and reduce LGBT health disparities. This framework may assist health organizations in initiating and sustaining meaningful organizational change to improve the health and healthcare of the LGBT communities.


Murine cytomegalovirus infection model in Balb/c mice--1. Virological and pathological profiles in mice inoculated with various virus doses.
By intraperitoneal injection of murine cytomegalovirus (MCMV) in Balb/c mice at doses of 2 X 10(6), 2 X 10(5) and 2 X 10(4) pfu per mouse, lethal, acute but non-lethal and asymptomatic infection were produced respectively. 100% mortality was found in mice infected with the lethal dose, as well as high MCMV titres in liver and spleen, severe necrosis of the spleen and severe degeneration of the liver. In these mice leukocyte counts in blood was not raised and inflammatory responses in the peritoneum, spleen and liver were not observed. Mice with acute but non-lethal infection showed less severe pathological changes, moderate spleen necrosis was followed by spleen enlargement. In this group of mice, severe mononucleosis was observed, and moderate inflammatory reactions were noted in the peritoneum, liver and spleen. Mice asymptomatically infected exhibited slight mononucleosis in the blood and splenomegaly.


Do not touch the sternum--thoracotomy incisions for HVAD implantation.
Median sternotomy is associated with specific complications, and sternal wound infections carry a high risk for left ventricular assist device patients. Techniques using thoracotomy incisions and sparing the sternum are therefore being developed to reduce complications and increase patient safety. The HeartWare ventricular assist device (HVAD) continuous flow pump is a miniaturized full support device that lends itself especially well for lateral implantation. We here present our techniques for HVAD implantation with outflow to either the ascending or the descending aorta.


Epidermal Growth Factor Receptor T790M Mutation Testing in Non-Small Cell Lung Cancer: An International Collaborative Study to Assess Molecular EGFR T790M Testing in Liquid Biopsy.
The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a powerful tool to determine the T790M mutation status. Several liquid biopsy platforms with varying degrees of accuracy are available to test for T790M mutations, and sensitivities may differ among these methods. As no standard exists for the testing of T790M mutation in liquid biopsy, we performed a collaborative study to describe and compare the sensitivity of different in-house liquid biopsy platforms for the detection of the T790M mutation, EGFR exon 19 deletion (del19) and EGFR L858R mutation (L858R) across multiple participating laboratories in seven Central and Eastern European countries. Of the 25 invited laboratories across Central and Eastern Europe, 21 centers participated and received 10 plasma samples spiked with cell-line DNA containing the T790M, del19, or L858R mutation in different concentrations. In-house PCR-based and NGS-based methods were used accordingly, and results were reported as in routine clinical practice. Two laboratories, which used the AmoyDx® EGFR 29 Mutations Detection Kit (AmoyDx) with Cobas® cfDNA Sample Preparation Kit and QX200 Droplet Digital PCR (ddPCR) with the QIAamp Circulating Nucleic Acid Kit identified all ten samples correctly. Cobas® EGFR Mutation Test v2 (Cobas), the NGS methods, and the IdyllaTM detection method used in this study performed within the known sensitivity range of each detection method. If a negative result was obtained from methods with lower sensitivity (e.g., Cobas), repeated liquid biopsy testing and/or tissue biopsy analysis should be performed whenever possible, to identify T790M-positive patients to allow them to receive the optimal second-line treatment with a third-generation EGFR TKI.


Lasers for nonlinear microscopy.
Various versions of nonlinear microscopy are revolutionizing the life sciences, almost all of which are made possible because of the development of ultrafast lasers. In this article, the main properties and technical features of short-pulse lasers used in nonlinear microscopy are summarized. Recent research results on fiber lasers that will impact future instruments are also discussed.


Effect of stachydrine on endoplasmic reticulum stress-induced apoptosis in rat kidney after unilateral ureteral obstruction.
Our study aimed at determining the effect of stachydrine on the PERK, CHOP, and caspase-3 in rat kidney with RIF. Rats were randomly divided into control group, model group, enalapril group, high stachydrine group, medium stachydrine group, and low stachydrine group. RIF models of five groups were developed by unilateral ureteral obstruction except the control group. The rats were sacrificed 12 days after surgery and blood samples were collected. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected. Renal tubular damage index was determined by HE staining. The area percentage of RIF was determined by the Masson method. Expressions of PERK, CHOP, and caspase-3 in kidney were determined by immunohistochemistry. Tubulointerstitial injury index, RIF, serum Scr, BUN level, and expressions of PERK, CHOP, and caspase-3 were different between the model and treatment groups (P < 0.05; P < 0.01). The expressions of PERK, CHOP, and caspase-3 in nephridial tissue were reduced (P < 0.05), tubulointerstitial injury and RIF were reduced (P < 0.05), and Scr and BUN were lower (P < 0.05) in the high stachydrine group than those in the enalapril group. The expressions of PERK, CHOP, and caspase-3 were reduced in the endoplasmic reticulum stress-related apoptosis pathway after stachydrine treatment. Consequently, apoptosis was prevented, and RIF was inhibited.


Writing case reports--author guidelines for acupuncture in medicine.
Case reports are particularly valuable in specialist clinical areas such as acupuncture to report new adverse events and to suggest possible new hypotheses. They can also be used to report events that have been reported previously but are rare or serious, in order to illustrate their frequency. They may illuminate the wider side of clinical practice by describing personal experiences of one practitioner. Constraints to writing case reports include finding time, working in isolation, and not having enough experience at the task. This article reproduces and develops a set of guidelines that were previously published, in an attempt to help authors to write thorough but succinct reports in a structured manner. The format for case reports includes an abstract, description of the case, literature search, discussion and summary or conclusions. Recommendations are made for the material to be included in each section. The policy of Acupuncture in Medicine is to require patient consent before accepting a report for publication.


An evaluation of the GeroRich program for infusing social work curriculum with aging content.
There is a national shortage of social workers who have the knowledge and skill competencies needed for practice with our rapidly growing older adult population. In the last decade, research has identified many reasons for the lack of interest in gerontological social work and steps that could be pursued within social work education to remedy the situation. The Geriatric Enrichment in Social Work Education (GeroRich) Program, funded through the John A. Hartford Foundation, engaged 67 social work programs throughout the United States in a process of curriculum change to increase the amount of gerontological content in the foundation social work curriculum. This study examined how the GeroRich program was instrumental in infusing gerontological content into the curriculum. Based on common outcome measures, the GeroRich program was found to be effective in (1) increasing the amount of gerontological content in the curriculum, (2) engaging faculty in the change process, and (3) exposing students to gerontological content. Relatively few variations were found among different program types or geographic settings. The model of curricular change implemented by the GeroRich program may be effective with other curriculum enrichment efforts.


Midlife women's cardiovascular symptoms: A cluster analysis.
Menopausal transition, in which biological and psychosocial changes are caused due to estrogen fluctuations, has been reported to increase cardiovascular risk among midlife women. The purposes of this study were to identify the clusters of midlife women by cardiovascular symptoms and to examine racial/ethnic differences in the clusters. This was a secondary analysis, in which hierarchical cluster and multinomial logistic analyses were conducted with the data (N = 966) collected in two previous studies. Three clusters were adopted: Cluster 1 (high vasomotor and low cardiorespiratory), Cluster 2 (low vasomotor and high cardiorespiratory and high discomfort/pain), and Cluster 3 (high discomfort/pain and high indigestion).


Expression, purification, and characterization of cold-adapted inorganic pyrophosphatase from psychrophilic Shewanella sp. AS-11.
In the presence of divalent cations, inorganic pyrophosphatase is activated to hydrolyze inorganic pyrophosphate to inorganic phosphate. Here, we clone, express, purify, and characterize inorganic pyrophosphatase from the psychrophilic Shewanella sp. AS-11 (Sh-PPase). The recombinant Sh-PPase was expressed in Escherichia coli BL21 (DE3) at 20°C using pET16b as an expression vector and purified from the cell extracts by a combination of ammonium sulfate fractionation and anion-exchange chromatography. Sh-PPase was found to be a family II PPase with a subunit molecular mass of 34 kD that preferentially utilizes Mn²⁺ over Mg²⁺ ions for activity. The functional characteristics of Sh-PPase, such as activity, temperature dependency, and thermal inactivation, were greatly influenced by manganese ions. Manganese ion activation increased the enzyme's activity at low temperatures; therefore, it was required to gain the cold-adapted characteristics of Sh-PPase.


MD-TASK: a software suite for analyzing molecular dynamics trajectories.
Molecular dynamics (MD) determines the physical motions of atoms of a biological macromolecule in a cell-like environment and is an important method in structural bioinformatics. Traditionally, measurements such as root mean square deviation, root mean square fluctuation, radius of gyration, and various energy measures have been used to analyze MD simulations. Here, we present MD-TASK, a novel software suite that employs graph theory techniques, perturbation response scanning, and dynamic cross-correlation to provide unique ways for analyzing MD trajectories. MD-TASK has been open-sourced and is available for download from https://github.com/RUBi-ZA/MD-TASK , implemented in Python and supported on Linux/Unix. email@example.com.


Carbon Dioxide Emissions and Environmental Impact of Different Surgical Modalities of Hysterectomies.
The objectives of this study were to determine carbon dioxide (CO2) emissions generated from nonreusable waste and compare across different types of hysterectomies for benign and malignant indications. Overall greenhouse gas emissions were not examined. This is a prospective cohort study that identified women undergoing a robotic assisted, laparoscopic, vaginal, or abdominal hysterectomy for any indication. The amount of waste generated was collected for each case, along with patient demographics, and details of the procedure. Weight of waste was converted to kilograms of CO2 emissions using the following formula: Carbon dioxide emissions = Waste in pounds × 1 Short ton/2000 pounds × Emission factor kg CO2/short ton× Global warming potential (GWP)We extrapolated the amount of CO2 emissions produced to the number of hysterectomies performed annually in the United States. We found that robotic hysterectomies generated the highest mean CO2 emissions (12.01 kg CO2), while vaginal hysterectomies produced the lowest mean CO2 emissions of 4.48 kg (p < .0001).Our sample size of 100 hysterectomies was equivalent to 1099.4 kg CO2 emissions. When our results were extrapolated, all hysterectomies in the United States produce 5.7 million kg of CO2 emissions. This is equivalent to 234,513 airplane miles, and 95 trips cross-country across the USA from New York, New York to Los Angeles, California. Robotic hysterectomies generated a statistically significant majority of CO2 emissions. Therefore, robotic surgery, as currently practiced, may offer a good initial opportunity for decreasing the carbon footprint of surgery.


Significance of 18F-Fluorodeoxyglucose Uptake at the Gastroesophageal Junction: Comparison of PET to Esophagogastroduodenoscopy.
Positron emission tomography-computed tomography (PET/CT) occasionally reveals unexpected uptake of (18)F-fluorodeoxyglucose ((18)F-FDG) at the gastroesophageal junction (GEJ). The aim of this study was to determine the importance of unexpected (18)F-FDG uptake at the GEJ on PET/CT by correlating this finding with endoscopy results. We reviewed medical records from June 2009 to October 2012 to identify patients in our Veterans Affairs Medical Center who had an esophagogastroduodenoscopy (EGD) performed within 6 months of a PET/CT. Metabolic activity at the GEJ was quantified with standardized uptake values (SUV) and correlated with EGD and histopathology results. A total of 219 patients were identified and assigned to one of five groups based upon EGD findings: esophageal malignancy (n = 34), esophagitis (n = 21), Barrett's esophagus (n = 8), other non-malignant disorders (n = 5), and normal (n = 151). The mean SUV Max for the groups was 6.72, 2.47, 2.40, 3.48, and 2.06, respectively. SUV Max and SUV Mean were significantly higher in the esophageal malignancy group than in all other groups (p < 0.001). SUV for patients with high-grade esophagitis was greater than in patients with low-grade esophagitis. A SUV Max ≥ 3.5 was found to predict necessity for EGD with a positive predictive value of 79 %. A SUV Max ≤ 2.2 yielded a negative predictive value of 86 %. Differentiation between benign and potentially significant disease at the GEJ may be possible with quantification of incidental (18)F-FDG uptake at PET/CT. Our results suggest thresholds that may help determine need for further endoscopic evaluation in patients with abnormal metabolic activity at the GEJ.


Antidepressant-like effects of intracerebroventricular FGF2 in rats.
The fibroblast growth factor (FGF) system is altered in post-mortem brains of individuals with major depressive disorder (MDD), but the functional relevance of this observation remains to be elucidated. To this end, we tested whether administering agents that act on FGF receptors would have antidepressant-like effects in rodents. We microinjected either FGF2 (200 ng, i.c.v.) or the FG loop (FGL) of neural cell adhesion molecule (NCAM) (5 microg, i.c.v.) into the lateral ventricle of rats and tested them on the forced swim test. Activating FGF receptors acutely had an antidepressant-like effect in the forced swim test. Furthermore, chronic FGF2 decreased depression-like behavior as assessed by two independent tests. Finally, the FGF system itself was altered after FGF2 administration. Specifically, there was an increase in FGFR1 mRNA in the dentate gyrus 24 h post-FGF2, suggesting the potential for self-amplification of the initial signal. These results support the potential therapeutic use of FGF2 or related molecules in the treatment of MDD and point to alternate mechanisms of neuronal remodeling that may be critical in this treatment.


Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance.
Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe (Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together influence NSC recruitment, cell cycle duration, and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the 'mother' cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.


Hyperbranched Polymer Dots with Strong Absorption and High Fluorescence Quantum Yield for In Vivo NIR-II Imaging.
In order to improve the fluorescence quantum yield (QY) of NIR-II-emitting nanoparticles, D-A-D fluorophores are typically linked to intramolecular rotatable units to reduce aggregation-induced quenching. However, incorporating such units often leads to a twisted molecular backbone, which affects the coupling within the D-A-D unit and, as a result, lowers the absorption. Here, we overcome this limitation by cross-linking the NIR-II fluorophores to form a 2D polymer network, which simultaneously achieves a high QY by well-controlled fluorophore separation and strong absorption by restricting intramolecular distortion. Using the strategy, we developed polymer dots with the highest NIR-II single-particle brightness among reported D-A-D-based nanoparticles and applied them for imaging of hindlimb vasculatures and tumors as well as fluorescence-guided tumor resection. The high brightness of the polymer dots offered exceptional image quality and excellent surgical results, showing a promising performance for these applications.


Efficacy of Current Practices for Pain Assessment in Premature Ventilated Infants in the NICU Exposed to a High Number of Pain-Associated Procedures.
To study infant factors, characteristics of pain scores, and analgesic practices associated with patient-days in the NICU with a high frequency of pain-associated procedures (defined as >10 pain-associated procedures in the day). This is a secondary analysis of data from a cross-sectional study that used medical record audits of premature, ventilated infants. The primary two-institution study yielded data for 196 patient-days. Data included 804 pain scores and 836 pain-associated procedures. A high frequency of pain-associated procedures occurred in 8% of days at Site A and in 25% of days at Site B. Prevalence of days with high frequency of pain-associated procedures differed by institution, and was higher at the institution where infants were more mature at birth and had fewer surgical procedures. High frequency of pain-associated procedures was related to endotracheal intubation at both institutions. There were no elevated pain scores and no documented analgesic administrations on days with over 20 pain-associated procedures. High exposure to pain-associated procedures during a 24-hour period for a premature, ventilated infant is rarely associated with elevated pain scores or analgesic administration. Prevalence of days with high-procedural exposure at an institution appears to be closely related to use of invasive ventilation and to individual institutional practices. Examination and discussion of the daily frequency of pain-associated procedures for premature, ventilated infants (especially for those receiving invasive ventilation) may be helpful in developing approaches for attenuating the cumulative pain experience for these babies. Resources that are expended on regular pain reassessment documentation processes in the NICU may need to be reconsidered in light of the very low yield for clinical alterations in care in this setting.


An experimental study of steady flow patterns of a new trileaflet mechanical aortic valve.
Hemodynamic research shows that thrombosis formation is closely tied to flow field turbulent stress. Design limitations cause flow separation at leaflet edges and the annular valve base, vortex mixing downstream, and high turbulent shear stress. The trileaflet design opens like a physiologic valve with central flow. Leaflet curvature approximates a completely circular orifice, maximizing effective flow area of the open valve. Semicircular aortic sinuses downstream of the valve allow vortex formation to help leaflet closure. The new trileaflet design was hemodynamically evaluated via digital particle image velocimetry and laser-Doppler anemometry. Measurements were made during peak flow of the fully open valve, immediately downstream of the valve, and compared with the 27-mm St. Jude Medical (SJM) bileaflet valve. The trileaflet valve central flow produces sufficient pressure to inhibit separation shear layers. Absence of downstream turbulent wake eddies indicates smooth, physiologic blood flow. In contrast, SJM produces strong turbulence because of unsteady separated shear layers where the jet flow meets the aortic sinus wall, resulting in higher turbulent shear stresses detrimental to blood cells. The trileaflet valve simulates the physiologic valve better than previous designs, produces smoother flow, and allows large scale recirculation in the aortic sinuses to help valve closure.


Nonlinear elasticity, proteinquakes, and the energy landscapes of functional transitions in proteins.
Large-scale motions of biomolecules involve linear elastic deformations along low-frequency normal modes, but for function nonlinearity is essential. In addition, unlike macroscopic machines, biological machines can locally break and then reassemble during function. We present a model for global structural transformations, such as allostery, that involve large-scale motion and possible partial unfolding, illustrating the method with the conformational transition of adenylate kinase. Structural deformation between open and closed states occurs via low-frequency modes on separate reactant and product surfaces, switching from one state to the other when energetically favorable. The switching model is the most straightforward anharmonic interpolation, which allows the barrier for a process to be estimated from a linear normal mode calculation, which by itself cannot be used for activated events. Local unfolding, or cracking, occurs in regions where the elastic stress becomes too high during the transition. Cracking leads to a counterintuitive catalytic effect of added denaturant on allosteric enzyme function. It also leads to unusual relationships between equilibrium constant and rate like those seen recently in single-molecule experiments of motor proteins.


Caries reductions between 1995, 1997 and 1999 in preschool children in Diadema, Brazil.
This study aimed to assess changes in caries prevalence and severity in preschool children in Diadema, Brazil. Three cross-sectional surveys were conducted, using the same protocol, in 1995, 1997 and 1999. The first survey included children aged 5-35 months, and the second and third, children aged 5-59 months. Participants were selected from all children attending a National Day of Children's Vaccination; 548, 992 and 690 in 1995, 1997 and 1999, respectively. This approach was sound as uptake rates for all years studied were above 90% for children aged between 1 and 59 months in all three surveys. Caries experience was measured using the World Health Organization (WHO) def index. Time-lag and quasi-longitudinal analysis were carried out. Time-lag analysis showed a marked and statistically significant decline in the prevalence and severity of coronal and rampant caries between 1995 and 1999. There were reductions of 36.5% in the prevalence of caries in 2-year-olds between 1995 and 1997 (P < 0.002) and 36.0% between 1997 and 1999 (P = 0.041). The mean def-s at the same age decreased from 2.0 in 1995 to 1.1 in 1997 (P < 0.001) and to 1.0 in 1999 (P > 0.05). The quasi-longitudinal analysis showed a statistically significantly increase in the percentage of children with caries between 1995 and 1997 and 1997 and 1999 (P < 0.001), but not for 2-year-old children between 1995 and 1997 (P > 0.05). The same pattern was observed for severity of dental caries. Oral health in preschool children in Diadema improved markedly during 1995-99.


[Biomechanical comparative study on proximal femoral locking plate and Gamma3 for treatment of stable intertrochanteric fracture].
To compare the biomechanical properties between the proximal femoral locking plate and Gamma3 for fixing stable intertrochanteric fracture so as to provide a theoretical basis for selecting internal fixation in the clinical application. Five pairs of antiseptic femur specimens were selected. Specimens of each pair of matching were randomly divided into groups A and B (n=5). All specimens were made the intertrochanteric fracture of 31A1.1 type according to AO/Association for the Study of Internal Fixation (AO/ASIF) classification. Fracture was fixed with Gamma3 in group A and with proximal femoral locking plate in group B. The axial compression, destruction, and torsion tests were carried out on the mechanical testing machine. Axial compression test: The load-displacement curve of groups A and B was basically a straight line; axial stiffness of groups A and B was (621.00 ± 36.48) N/mm and (542.55 ± 46.94) N/mm respectively, showing significant difference (t = 3.648, P = 0.036). Destruction test: The maximum yield load of groups A and B was (4,394.82 ± 450.37) N and (2,987.54 ± 112.14) N respectively, showing significant difference (t = 5.433, P = -0.032). After loading maximum yield load, femoral fracture occurred again, and internal fixation and bone interface loosening were observed in group A; bending and breaking of proximal locking screw for internal fixation were found in group B, but loosening of internal fixation and bone interface was more obvious in group A than in group B. Torsion test: The torque of specimens in 2 groups increased with the increase of torsion angle (P < 0.05), the torque corresponding to the torsion angle in group B was larger than that in group A, but the difference was not significant (P > 0.05). The torsional stiffness of groups A and B was (1.78 ± 0.16) N·mm/deg and (2.01 ± 0.08) N·mm/deg respectively, showing no significant difference (t = -3.833, P = 0.162). Proximal femoral locking plate and Gamma3 in the treatment of stable intertrochanteric fracture have good biomechanical properties, which can meet the requirements of minimal invasion, strong internal fixation, and early activity.


Evaluation of Depression in Subacute Low Back Pain: A Case Control Study.
Low back pain (LBP) is the most common musculoskeletal disorder affecting the general population and it is believed to be associated with depression. The study aim was to describe and compare the impact in a sample of people with subacute LBP (SLBP) and patients without LBP with normalized reference values in the light of the scores obtained with regard using the Beck Depression Inventory (BDI). This was a case-control study. Physiotherapist area at a care center. A sample of 164 participants of a mean age of 41.45 ± 0.97 came to a physical therapy clinic where self-reported data were registered, informants' professional activity was determined, and the scores obtained were compared in the BDI. Total BDI scores at SLBP and their controls were 21.52 ± 6.93 (11 - 43) and 17.30 ± 5.09 (11 - 30), respectively (P < 0.001). The SLBP patient has 2.12 times more likely to have moderate depression (OR 2.12 (1.07 - 4.18) and 18.82 times more likely to have serious depression (OR 18.82 (1.06 - 331.81) compared to their controls (P < 0.05). The study was not a randomized controlled trial. Although primary outcome data were self-reported, the assessor was not blinded. People with SLBP also have a significant increase in depression based on BDI scores, regardless of gender.


[Psychological aspects associated with the diagnosis and treatment of cancer].
Cancer and its treatments have numerous psychological consequences for patients. The consequences are related to the phase and the type of illness, and to the type and duration of the treatments. All these factors influence the apparition of adjustment difficulties or disorders. The present article review actual concepts and data related to the psychological problems secondary to cancer, its evolution and treatment.


Effects of hydrogen sulfide-releasing L-DOPA derivatives on glial activation: potential for treating Parkinson disease.
The main lesion in Parkinson disease (PD) is loss of substantia nigra dopaminergic neurons. Levodopa (L-DOPA) is the most widely used therapy, but it does not arrest disease progression. Some possible contributing factors to the continuing neuronal loss are oxidative stress, including oxidation of L-DOPA, and neurotoxins generated by locally activated microglia and astrocytes. A possible method of reducing these factors is to produce L-DOPA hybrid compounds that have antioxidant and antiinflammatory properties. Here we demonstrate the properties of four such L-DOPA hybrids based on coupling L-DOPA to four different hydrogen sulfide-donating compounds. The donors themselves were shown to be capable of conversion by isolated mitochondria to H(2)S or equivalent SH(-) ions. This capability was confirmed by in vivo results, showing a large increase in intracerebral dopamine and glutathione after iv administration in rats. When human microglia, astrocytes, and SH-SY5Y neuroblastoma cells were treated with these donating agents, they all accumulated H(2)S intracellularly as did their derivatives coupled to L-DOPA. The donating agents and the L-DOPA hybrids reduced the release of tumor necrosis factor-alpha, interleukin-6, and nitric oxide from stimulated microglia, astrocytes as well as the THP-1 and U373 cell lines. They also demonstrated a neuroprotective effect by reducing the toxicity of supernatants from these stimulated cells to SH-SY5Y cells. L-DOPA itself was without effect in any of these assays. The H(2)S-releasing L-DOPA hybrid molecules also inhibited MAO B activity. They may be useful for the treatment of PD because of their significant antiinflammatory, antioxidant, and neuroprotective properties.


Priapism after spinal cord injury - a case report and review of the literature.
Involuntary unwanted erections are extremely rare after spinal cord injury (SCI). A sudden loss of sympathetic tone to the pelvic vasculature following SCI causes an increase in the parasympathetic tone and uncontrolled arterial blood flow into the penile sinusoidal spaces. When occurring immediately after an acute SCI, it is generally self-limiting and settles within a few hours. In contrast, recurrent, unwanted erections in patients with chronic SCI are more unpredictable in frequency and duration and may require treatment. We present a case of recurrent involuntary unwanted erections in a patient with chronic SCI after a stab wound to his neck and review the pathophysiology and available management options.


Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity.
The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35-55-induced progressive, as well as PLP138-151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice. The decline in both progression and relapse of EAE occurred as a result of reduced demyelination and myeloid cell infiltration into the CNS tissue. DC numbers were restored in the spleen of C57BL/6 and peripheral blood of SJL/J mice along with a decreased TH17 phenotype within CD4+ T-cells. The effects of CLEC12A blocking were further validated using CLEC12A knockout (KO) animals wherein EAE disease induction was delayed and reduced disease severity was observed. These studies reveal the utility of a DC-specific mechanism in designing new therapeutics for MS.


Assessing the Brazilian surgical system with six surgical indicators: a descriptive and modelling study.
Brazil boasts a health scheme that aspires to provide universal coverage, but its surgical system has rarely been analysed. In an effort to strengthen surgical systems worldwide, the Lancet Commission on Global Surgery proposed a collection of 6 standardised indicators: 2-hour access to surgery, surgical workforce density, surgical volume, perioperative mortality rate (POMR) and protection against impoverishing and catastrophic expenditure. This study aims to characterise the Brazilian surgical health system with these newly devised indicators while gaining understanding on the complexity of the indicators themselves. Using Brazil's national healthcare database, commonly reported healthcare variables were used to calculate or simulate the 6 surgical indicators. Access to surgery was calculated using hospital locations, surgical workforce density was calculated using locations of surgeons, anaesthesiologists and obstetricians (SAO), and surgical volume and POMR were identified with surgical procedure codes. The rates of protection against impoverishing and catastrophic expenditure were modelled using cost of surgical inpatient hospitalisations and a γ distribution of incomes based on Gini and gross domestic product/capita. In 2014, SAO density was 34.7/100 000 population, surgical volume was 4433 procedures/100 000 people and POMR was 1.71%. 79.4% of surgical patients were protected against impoverishing expenditure and 84.6% were protected against catastrophic expenditure due to surgery each year. 2-hour access to surgery was not able to be calculated from national health data, but a proxy measure suggested that 97.2% of the population has 2-hour access to a hospital that may be able to provide surgery. Geographic disparities were seen in all indicators. Brazil's public surgical system meets several key benchmarks. Geographic disparities, however, are substantial and raise concerns of equity. Policies should focus on stimulating appropriate geographic allocation of the surgical workforce and better distribution of surgical volume. In some cases, where benchmarks for each indicator are met, supplemental analysis can further inform our understanding of health systems. This measured and systematic evaluation should be encouraged for all nations seeking to better understand their surgical systems.


Toxoplasma gondii in small ruminants in northeastern areas of Colombia: Seroprevalence and risk factors.
Sheep and goats are susceptible to infections with Toxoplasma gondii and could play an important role in the transmission of the zoonotic parasite to human. We conducted a cross sectional study to estimate the seroprevalence and to assess the risk factors for T. gondii seropositivity in small ruminants under traditional husbandry systems. This study was carried out from November 2015 to April 2016 in randomly selected small ruminants (n = 1038) from 48 farms located in Colombia, in the departments of northern Cesar in the north and La Guajira in the south. An indirect ELISA was used to detect IgG antibodies to T. gondii in the animals. A standardized questionnaire was used to obtain information on putative risk factors. We conducted the association analyses by using univariable and multivariate logistic regression and report odds ratios (OR) with 95% confidence interval (C.I). The overall seroprevalence in small ruminants was 23.5% (C.I: 21-26.2%). Sheep showed a higher seroprevalence (25.1% C.I: 22.4-28.6%) than goats (18.4% C.I: 22.4-28.6%). The association analysis recognized as risk factors for T. gondii seropositivity farming pigs in addition to small ruminants (OR = 1.96 C.I: 1.414-2.743), the inexistence of manure heap (OR = 2.254 C.I: 1.480-3.433) and drinking water from locally aqueducts (OR = 1.489 C.I: 1.006-2.204). The results of the study confirmed that exposure to T. gondii is common in sheep and goats in dry Caribbean regions of Colombia.


High frequency jet ventilation in tracheobronchoplasty. An experimental study.
An experimental study on dogs was performed to determine the optimal driving gas pressure and frequency in high-frequency jet ventilation (HFJV) during tracheobronchoplasty. Right thoracotomy, sleeve upper lobectomy and sleeve pneumonectomy were done with various HFJV settings and insufflation via a 3.0 mm catheter with 2.4 mm internal diameter. In sleeve lobectomy, HFJV to the reconstructed lung improved the peroperative ventilation. Driving gas pressure 0.5-1.0 kg/cm2 and frequency 6-10 Hz were the optimal settings for sleeve lobectomy. In sleeve pneumonectomy adequate ventilation and oxygenation were achieved with HFJV to the contralateral lung, and the optimal HFJV settings were 1.0-2.0 kg/cm2 driving gas pressure and 6-10 Hz frequency.


Priority-driven plan optimization in locally advanced lung patients based on perfusion SPECT imaging.
Limits on mean lung dose (MLD) allow for individualization of radiation doses at safe levels for patients with lung tumors. However, MLD does not account for individual differences in the extent or spatial distribution of pulmonary dysfunction among patients, which leads to toxicity variability at the same MLD. We investigated dose rearrangement to minimize the radiation dose to the functional lung as assessed by perfusion single photon emission computed tomography (SPECT) and maximize the target coverage to maintain conventional normal tissue limits. Retrospective plans were optimized for 15 patients with locally advanced non-small cell lung cancer who were enrolled in a prospective imaging trial. A staged, priority-based optimization system was used. The baseline priorities were to meet physical MLD and other dose constraints for organs at risk, and to maximize the target generalized equivalent uniform dose (gEUD). To determine the benefit of dose rearrangement with perfusion SPECT, plans were reoptimized to minimize the generalized equivalent uniform functional dose (gEUfD) to the lung as the subsequent priority. When only physical MLD is minimized, lung gEUfD was 12.6 ± 4.9 Gy (6.3-21.7 Gy). When the dose is rearranged to minimize gEUfD directly in the optimization objective function, 10 of 15 cases showed a decrease in lung gEUfD of >20% (lung gEUfD mean 9.9 ± 4.3 Gy, range 2.1-16.2 Gy) while maintaining equivalent planning target volume coverage. Although all dose-limiting constraints remained unviolated, the dose rearrangement resulted in slight gEUD increases to the cord (5.4 ± 3.9 Gy), esophagus (3.0 ± 3.7 Gy), and heart (2.3 ± 2.6 Gy). Priority-driven optimization in conjunction with perfusion SPECT permits image guided spatial dose redistribution within the lung and allows for a reduced dose to the functional lung without compromising target coverage or exceeding conventional limits for organs at risk.


Primary squamous cell carcinoma arising from an epithelium-lined cyst of the lacrimal gland.
A 66-year-old man presented with a slowly enlarging, nontender left orbital mass of 2 months' duration. CT and MRI showed a left lacrimal gland mass with enhancement and internal irregularity of cystic structures. Histopathologic analysis of the biopsy specimen revealed a squamous cell carcinoma arising from an epithelium-lined cyst. The patient underwent left orbital exenteration followed by radiation treatment. No evidence of tumor recurrence was observed after a follow-up of 30 months. We believe this primary squamous cell carcinoma may have arisen either from preexisting lacrimal duct cyst (dacryops) with areas of squamous metaplasia or, less likely, from a choristomatous epithelium-lined cyst of the lacrimal gland. Although rare, this entity should be included in the differential diagnosis of cystic lesions of the lacrimal gland.


[The new culture of dematerialized health].
With the Electronic Health Record, which has been provided by law by the Italian State, all health data and information regarding the citizens are dematerialized and move within regional networking eHealth graphs, which are interoperable at the national and then European level. Data generated by the interaction between a patient and a doctor - through a visit, a diagnostic exam or a hospitalization - are shared at the speed of light among all the professionals who are interested in the patient's care pathway, and then with the citizen, in a process producing his/her empowerment.This personalized information, stored and enriched online throughout one's life, makes it possible to reconstruct and actualize the clinical history of the assisted person's, through the demolition of space and time barriers. The interaction between the doctor and the assisted user is thus supported by the communicational power of Health networks, generating powerful data fluxes along the care pathway and serving the purposes of assistential continuity.


Acute and long-term efficacy and safety of catheter cryoablation of the cavotricuspid isthmus for treatment of type 1 atrial flutter.
Atrial flutter (AFL) is commonly treated by radiofrequency catheter ablation. Catheter-based cryoablation may be an effective alternative with potential advantages. The purpose of this study was to study the acute and long-term safety and efficacy of catheter-based cryoablation for treatment of cavotricuspid isthmus-dependent (typical and reverse typical) AFL. Catheter-based cryoablation was performed with a 10Fr catheter in 160 patients with cavotricuspid isthmus-dependent AFL (122 men and 38 women; mean age 63.1 +/- 9.3 years, mean left ventricular ejection fraction 54.6% +/- 10.4%); 94 (58.8%) of these patients also had atrial fibrillation (AF). All patients underwent right atrial (RA) activation mapping and pacing at the cavotricuspid isthmus to demonstrate concealed entrainment and confirm cavotricuspid isthmus dependence of AFL. Catheter-based cryoablation of the cavotricuspid isthmus was performed with multiple freezes (average freeze time 2.3 +/- 0.5 minutes) until bidirectional block was demonstrated during pacing from the low lateral RA and coronary sinus, respectively. Patients were evaluated at 1, 3, and 6 months and underwent weekly and symptomatic event monitoring. Acute procedural success was defined as cavotricuspid isthmus block persisting 30 minutes after ablation. Long-term success was defined as absence of AFL during follow-up. Acute success was achieved in 140 (87.5%) of 160 patients. Total procedure time was 200 +/- 71 minutes, ablation time (including a 30-minute waiting period after ablation) was 139 +/- 62 minutes, and fluoroscopy time was 35 +/- 26 minutes. An average of 20.5 +/- 11.3 freezes, for a total ablation time of 47.4 +/- 24.3 minutes, were required to achieve cavotricuspid isthmus block, with average and nadir temperatures of -81.5 degrees C +/- 3.7 degrees C and -85.6 degrees +/- 3.6 degrees C, respectively. Four patients (2.5%) had procedure-related adverse events. Of 132 patients with acute efficacy who completed 6-month follow-up, 8 (6%) were lost to follow-up or were noncompliant with event recordings. Using survival analysis, 106 (80.3%) remained free of AFL on strict analysis of event recordings only, and 119 (90.2%) remained clinically free of AFL. This large pivotal study demonstrated the acute and long-term efficacy and safety of catheter-based cryoablation for cavotricuspid isthmus-dependent AFL, similar to rates previously reported for radiofrequency catheter ablation.


Molecular self-assembly of solid-supported protein crystals.
Highly ordered protein arrays have been proposed as a means for templating the organization of nanomaterials. Toward this end, we investigate the ability of the protein streptavidin to self-assemble into various configurations on solid-supported phospholipids. We identify two genetic variants of streptavidin (comprising amino acids 14-136 and 13-139) and examine their molecular organization at the liquid-solid interface. Our results demonstrate that the structural differences between these two protein variants affect both crystalline lattice and domain morphology. In general, these results for the liquid-solid interface are similar and consistent with those at the air-water interface with a few notable differences. Analogous to crystallization at the air-water interface, both forms of streptavidin yield H-like domains with lattice parameters that have C222 symmetry at pH 7. At pH 4, the native, truncated form of streptavidin yields needle-like domains consisting of molecules arranged in P1 symmetry. Unlike crystalline domains grown at the air-water interface, however, the lattice parameters of this P1 crystal are unique and have not yet been reported. The presence of a solid substrate does not appear to dramatically alter streptavidin's two-dimensional crystallization behavior, suggesting that local intermolecular interactions between proteins are more significant than interactions between the interface and protein. Our results also demonstrate that screening the electrostatic repulsion between protein molecules by modulating ionic strength will increase growth rate while decreasing crystalline domain size and macroscopic defects. Finally, we show that these domains are indeed functional by attaching biotinylated gold nanoparticles to the crystals. The ability to modulate molecular configuration, crystalline defects, and domain size on a functional array supports the potential application of this system toward materials assembly.


The proteasome activator REGγ promotes diabetic endothelial impairment by inhibiting HMGA2-GLUT1 pathway.
Diabetic vascular endothelial impairment is one of the main causes of death in patients with diabetes lacking adequately defined mechanisms or effective treatments. REGγ, the 11S proteasome activator known to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner, emerges as a new regulator in the cardiovascular system. Here, we found that REGγ was upregulated in streptozocin (STZ)-induced diabetic mouse aortic endothelium in vivo and high glucose (HG)-treated vascular endothelial cells (ECs) in vitro. REGγ deficiency ameliorated endothelial impairment in STZ-induced diabetic mice by protecting against a decline in cellular glucose uptake and associated vascular ECs dysfunction by suppressing high mobility group AT-hook 2 (HMGA2) decay. Mechanically, REGγ interacted with and degraded the transcription factor HMGA2 directly, leading to decreased HMGA2 transcriptional activity, subsequently lowered expression of glucose transporter type 1 (GLUT1), and reduced cellular glucose uptake, vascular endothelial dysfunction, and impaired diabetic endothelium. Ablation of endogenous GLUT1 or HMGA2 or overexpressing exogenous HMGA2 in vascular ECs significantly blocked or reestablished the REGγ-dependent action on cellular glucose uptake and vascular endothelial functions of HG stimulation in vitro. Furthermore, exogenously introducing HMGA2 improved diabetic mice endothelial impairment features caused by REGγ in vivo, thereby substantiating a REGγ-HMGA2-GLUT1 pathway in diabetic endothelial impairment. Our findings indicate that modulating REGγ-proteasome activity may be a potential therapeutic approach for diabetic disorders with endothelial impairment.


[Cutaneous flaps].
The use of skin flaps has long been known. Since the beginning of the 20th century, with better knowledge of skin vascularisation and technological development, the plastic surgeon has had at his disposition a wide choice: skin flaps, fasciocutaneous flaps, myocutaneous flaps, blood-carrying flaps and free flaps. The use of a flap for healing should be considered with regard to grafting techniques or directed healing. The criteria for choosing the type of flap are important, in order to obtain a good quality of skin cover with minimum scarring and loss of function.


Use of a retrograde nail for ankle arthrodesis in Charcot neuroarthropathy: a limb salvage procedure.
Charcot neuroarthropathy is a serious complication associated with diabetic neuropathy. This complication probably is most serious when the ankle is involved because of the instability and progressive deformity, which often leads to ulceration, osteomyelitis, and amputation. Arthrodesis before the ulcerated lesion appears is considered a limb salvage treatment. One of the most effective techniques for an unstable ankle in Charcot neuroarthropathy is retrograde transcalcaneal nailing. Eighteen diabetic patients, without a history of ulceration, were treated from July, 2003, to November, 2005, with panarthrodesis of the ankle using intramedullary retrograde transcalcaneal nailing. The average follow up was 14 +/- 10.1 months. All patients completed the unloaded postoperative period with a fiberglass cast (3 months nonweightbearing and 3 months partial weightbearing) and commenced walking in shoes with a stiff rocker sole and a molded insole. During the followup period there were no major complications. In three patients, removal of one of the proximal screws used for anchoring the nail to the tibia was done because of protrusion causing skin breakdown. Fourteen patients had a stable fusion and four patients had fibrous union. The percentage of limb salvage was 100% in the followup period. Our study confirms that this operative technique is effective and safe.


Self-reported generalised pruritus among community-dwelling older adults in Malaysia.
The ageing skin is more susceptible to pruritic dermatoses, which are associated with adverse psychosocial effects and reduced quality of life among older adults. This cross-sectional study aimed to identify the burden of pruritus and factors associated with its presence and severity among older adults recruited to the Malaysian Elders Longitudinal Research study. Seven hundred seventy individuals aged 55 years (lower age limit) and above were interviewed as to whether they experienced pruritus during the preceding week and the locations involved if present. The association between generalised pruritus, sleep quality, and major systemic risk factors were explored. 5.97% of respondents reported generalised pruritus. Generalised pruritus was associated with poorer sleep quality, with Pittsburgh Sleep Quality Index score above 6. Mean haemoglobin level was lower in subjects with generalised pruritus (13.14 g/dL) but there was no significant difference in the frequency of generalised pruritus and severe generalized pruritus between subjects with clinically defined anaemia. Also, there were no significant associations between other major systemic risk factors and generalised pruritus in this population-based study. There was no association between generalised pruritus with depression, anxiety or stress. The negative effect of pruritus on sleep quality suggests a possible deleterious effect of pruritus on health and quality of life. Further prospective research on the longer-term effects of pruritus on health status is now warranted. (222 words).


The validity of explicit indicators of prescribing appropriateness.
To assess, from the perspective of UK hospital doctors, the content validity and operational validity of a set of 14 previously developed explicit indicators of the appropriateness of long-term prescribing started during a hospital admission. A combination of data extraction from medical records and qualitative interviews with a maximum variability sample of hospital doctors. The indicators were applied to 132 new prescriptions, intended for long-term use, prescribed for 61 patients; 36 doctors, of various grades, were purposively selected for interview. Appropriate prescribing was viewed as prescribing that was indicated, necessary, evidence based (using a broad meaning of 'evidence') and of acceptable cost and risk-benefit ratio. These concepts applied to individual drugs for individual patients, rather than at a more general, public health level. Where drugs had failed an indicator, rationales were explored. Often, it was missing data in the medical notes that had resulted in the drug failing the indicator. The 14 indicators were considered to have content validity, reflecting all aspects of appropriate prescribing discussed by the doctors. Their operational validity was less clear-cut, due to the lack of necessary data in the medical notes. This has implications for the use of explicit indicators for assessing prescribing appropriateness, as these hospital doctors did not consider that the data required for objective, systematic assessment of prescribing would ever be recorded in hospital medical notes.


[Effect of pathologic changes in the urinary epithelium on the absorption of ethoglucide (Epodyl) from the bladder].
Studies on the absorption of Ethoglucid from human urinary bladder, utilizing a photometric method to determine Ethoglucid in biological fluids, gave the following results: The intact uroepithelium prevents absorption of interluminal Ethoglucid as well as no significant increase of absorption was seen in the presence of superficial, highly differentiated cancers or inflammatory alterations of the bladder. Urothelial lesions after transurethral resection or infiltrating cancers permit an intercellular diffusion of Ethoglucid from the bladder cavity into the systemic circulation, due to a loss of intercellular gaps between the urothelial elements.


Variation rhythms of lymphocyte subsets during healthy aging.
Immunological alterations associated with aging (immunosenescence) do not represent a simple unidirectional decline in all functions but develop as a complex remodeling of the immune system, involving multiple reorganization and developmentally regulated changes. In general, most data available about aging were obtained at particular age intervals and most of them come from Caucasian individuals from either Europe or the United States. Here, we report the frequencies of major lymphocyte subsets in healthy Brazilian individuals from 2 distinct geographic regions (Southeast and South) at several age intervals spanning a lifetime period (0-86 years). Overall, we demonstrated that changes in the frequencies of cells related to both innate and adaptive immunity clearly occur with aging in these individuals. These changes were not progressive and equally steady for all cell populations tested but instead showed an oscillatory or rhythmic behavior that was distinctive of each population at different age intervals. We also observed that abrupt changes in the frequencies of immune cells may occur in healthy individuals over 75 years old, suggesting there is an impaired flexibility of the immune system at late stages of life to sustain homeostasis via immune mechanisms. We presented reference ranges for healthy Brazilian individuals at all ages. The knowledge of these parameters in further detail will allow interventions to optimize immune function in advanced age and to improve the quality of life in the elderly.


Human neutrophils oxidize low-density lipoprotein by a hypochlorous acid-dependent mechanism: the role of vitamin C.
Oxidatively modified low-density lipoprotein (LDL) has been strongly implicated in the pathogenesis of atherosclerosis. Peripheral blood leukocytes, such as neutrophils, can oxidize LDL by processes requiring superoxide and redox-active transition metal ions; however, it is uncertain whether such catalytic metal ions are available in the artery wall. Stimulated leukocytes also produce the reactive oxidant hypochlorous acid (HOCl) via the heme enzyme myeloperoxidase. Since myeloperoxidase-derived HOCl may be a physiologically relevant oxidant in atherogenesis, we investigated the mechanisms of neutrophil-mediated LDL modification and its possible prevention by the antioxidant ascorbate (vitamin C). As a sensitive marker of LDL oxidation, we measured LDL thiol groups. Stimulated human neutrophils (5x10(6) cells/ml) incubated with human LDL (0.25 mg protein/ml) time-dependently oxidized LDL thiols (33% and 79% oxidized after 10 and 30 min, respectively). Supernatants from stimulated neutrophils also oxidized LDL thiols (33% oxidized after 30 min), implicating long-lived oxidants such as N-chloramines. Experiments using specific enzyme inhibitors and oxidant scavengers showed that HOCl, but not hydrogen peroxide nor superoxide, plays a critical role in LDL thiol oxidation by neutrophils. Ascorbate (200 microM) protected against neutrophil-mediated LDL thiol oxidation for up to 15 min of incubation, after which LDL thiols became rapidly oxidized. Although stimulated neutrophils accumulated ascorbate during oxidation of LDL, pre-loading of neutrophils with ascorbate did not attenuate oxidant production by the cells. Thus, activated neutrophils oxidize LDL thiols by HOCl- and N-chloramine-dependent mechanisms and physiological concentrations of vitamin C delay this process, most likely due to scavenging of extracellular oxidants, rather than by attenuating neutrophil oxidant production.


Access of autonomic nerves through the optic canal, and their orbital distribution in man.
The notion that autonomic nerves from the internal carotid plexus are transmitted to the orbit with the ophthalmic artery through the optic canal has been variously assumed, disregarded, or denied, but never demonstrated. The objective of this study was to examine the contents of the canal, identify any autonomic nerves, and follow their passage within the orbit. The soft tissues of the optic canal, and the apical tissues of the orbit were removed and examined histologically using 10 cadaver preparations. Additionally, tissues from an orbital exenteration and 10 ocular enucleation or donor specimens were prepared. Some of the latter material was examined with an electron microscope. Numerous autonomic nerves (four to 25, ranging in diameter from 23 to 130 microm) entered the orbit from the internal carotid plexus in the periosteum of the optic canal, the optic nerve dura mater, or the adventitia of the ophthalmic artery. In the orbit they advanced in the loose connective tissue covering the optic nerve dura and joined ciliary nerves close to the eye or entered the eye directly. None were observed to penetrate the dura, apart from a nerve accompanying the central retinal artery. Others were distributed with the ophthalmic artery and its branches. It is concluded that the optic canal is a regular, and often major, route for autonomic nerve distribution to the eye and orbit.


Effect of olive ripeness on chemical properties and phenolic composition of Chétoui virgin olive oil.
The aim of the present work was to investigate the influence of fruit ripening on oil quality in an attempt to establish an optimum harvesting time for Chétoui olives, the second main olive variety cultivated in Tunisia. Our results showed that many analytical parameters, i.e., peroxide value, UV absorbance at 232 and 270 nm, chlorophyll pigments, carotenoids and oleic acid contents decreased during ripening, whilst oil content and linolenic acid increased. Free acidity remained practically stable with a very slight rise at the highest maturity index. The trend of oxidative stability, total phenols and o-diphenols, showed an increase at the early stages followed by a reduction at more advanced stages of maturity. The major phenolic compounds, such as hydroxytyrosol, ligstroside aglycon, elenolic acid, acetoxy-pinoresinol and oleuropein aglycon, seemed to have the same behaviour. In the case of tyrosol, a strong decrease was observed directly related with the ripening progress. On the basis of the evolution of the analytical parameters studied, the best stage of Chétoui olive fruits for oil processing seems to be at ripeness index higher than 2.0 and lower than 3.0.


Adenovirus 2 E1B-55K protein relieves p53-mediated transcriptional repression of the survivin and MAP4 promoters.
It is well established that adenovirus E1B-55K protein functions as an inhibitor of the tumor suppressor protein p53 by binding and inactivating p53 as a transcriptional activator protein. Here we show that the adenovirus 2 E1B-55K protein also blocks p53 as a transcriptional repressor protein of the survivin and the MAP4 promoters. The repression is dependent on the ability of E1B-55K to bind to p53 and is enhanced by coexpression of the adenovirus E4orf6 protein. Overexpression of the transcriptional corepressor protein Sin3A partially relieves the inhibitory effect of E1B-55K, suggesting that E1B-55K blocks p53 functions by interfering with the Sin3 complex.


Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness.
The synthetic double-stranded RNA poly(I:C) is commonly used as an adjuvant to boost CD8 T-cell function; however, polyinosinic:polycytidylic acid [poly(I:C)] can also suppress autoimmune disease. The mechanism by which a single adjuvant achieves two distinct immunoregulatory roles is unknown. Although it is clear that coadministration of poly(I:C) with antigen elicits strong adjuvant effects in mice, we found that poly(I:C) injection before antigen substantially reduced antigen-dependent CD8 T-cell responses. Notably, CD8 T cells sensitized in poly(I:C)-pretreated mice failed to fully up-regulate IL-33R (ST2), which led to impaired T-cell receptor-independent responses to IL-33. In contrast, nonsensitized effector CD8 T cells responded robustly to IL-33 using a two-signal cytokine mechanism. During an acute lung response to Staphylococcus aureus enterotoxin, peripheral injection of poly(I:C) manifested a suppressive process by inhibiting the differentiation of both antigen- and IL-33-responsive CD8 effectors systemically. These findings highlight that early exposure to double-stranded RNA reverses its role as an adjuvant and, importantly, prevents IL-33R up-regulation on CD8 effector T cells to dampen inflammation.


Analysis of key genes and modules during the courses of traumatic brain injury with microarray technology.
Gene expression data acquired at different times after traumatic brain injury (TBI) were analyzed to identify differentially expressed genes (DEGs). Interaction network analysis and functional enrichment analysis were performed to extract valuable information, which may benefit diagnosis and treatment of TBI. Microarray data were downloaded from Gene Expression Omnibus and pre-treated with MATLAB. DEGs were screened out with the SAM method. Interaction networks of the DEGs were established, followed by module analysis and functional enrichment analysis to obtain insight into the molecular mechanisms. A total of 39 samples at six time points (30 min, 4, 8, 24 , 72 h, and 21 days) were analyzed and generated 377 DEGs. Eight modules were identified from the networks and network ontology analysis revealed that cell surface receptor-linked signaling pathway, response to wounding and signaling pathway were significantly overrepresented. Altered risk genes and modules in TBI were uncovered through comparing the gene expression data acquired at various time points. These genes or modules could be potential biomarkers for diagnosis and treatment of TBI.


Somatoform dissociation and posttraumatic stress syndrome - two sides of the same medal? A comparison of symptom profiles, trauma history and altered affect regulation between patients with functional neurological symptoms and patients with PTSD.
History of traumatic experience is common in dissociative disorder (DD), and similarity of symptoms and characteristics between DD and posttraumatic stress disorder (PTSD) encouraged to consider DD as trauma-related disorder. However, conceptualization of DD as a trauma-related syndrome would critically affect diagnosis and treatment strategies. The present study addressed overlap and disparity of DD and PTSD by directly comparing correspondence of symptoms, adverse/traumatic experience, and altered affect regulation between patients diagnosed with dissociative disorder (characterized by negative functional neurological symptoms) and patients diagnosed with PTSD. Somatoform and psychoform dissociation, symptoms of posttraumatic stress, general childhood adversities and lifetime traumata, and alexithymia as index of altered affect regulation were screened with standardized questionnaires and semi-structured interviews in 60 patients with DD (ICD-codes F44.4, F44.6, F44.7), 39 patients with PTSD (ICD-code F43.1), and 40 healthy comparison participants (HC). DD and PTSD patients scored higher than HC on somatoform and psychoform dissociative symptom scales and alexithymia, and reported more childhood adversities and higher trauma load. PTSD patients reported higher symptom severity and more traumata than DD patients. Those 20 DD patients who met criteria of co-occuring PTSD did not differ from PTSD patients in the amount of reported symptoms of somatoform dissociation, physical and emotional childhood adversities and lifetime traumata, while emotional neglect/abuse in childhood distinguished DD patients with and without co-occuring PTSD (DD patients with co-occuring PTSD reporting more emotional maltreatment). The pattern of distinctive somatoform and psychoform dissociative symptom severity, type of childhood and lifetime traumata, and amount of alexithymia suggests that DD and PTSD are distinctive syndromes and, therefore, challenges the conceptualization of DD as trauma-related disorder. Together with the detected close correspondence of symptom and experience profiles in DD patients with co-occuring PTSD and PTSD patients, these findings suggest that adverse/traumatic experience may intensify dissociative symptoms, but are not a necessary condition in the generation of functional neurological symptoms. Still, diagnosis and treatment of DD need to consider this impact of traumata and post-traumatic stress symptoms.


Loss mechanisms in resonant spectrophones.
Quality factors and resonant frequencies of a resonant spectrophone have been measured as a function of pressure and the results compared to theoretical predictions which took into account classical surface and volumetric losses and molecular relaxation. Buffer gases investigated included the five noble gases, H(2), N(2), O(2), CO(2), N(2)O, and SF(6). Typically 95% of the cavity losses were accounted for theoretically. Frequency shifts due to relaxational dispersion, nonideal gas behavior, and classical boundary layer effects were observed; all behaved as predicted by theory.


Evolutionary game theory of continuous traits from a causal perspective.
Modern evolutionary game theory typically deals with the evolution of continuous, quantitative traits under weak selection, allowing the incorporation of rich biological detail and complicated nonlinear interactions. While these models are commonly used to find candidates for evolutionary endpoints and to approximate evolutionary trajectories, a less appreciated property is their potential to expose and clarify the causal structure of evolutionary processes. The mathematical step of differentiation breaks a nonlinear model into additive components which are more intuitive to interpret, and when combined with a proper causal hypothesis, partial derivatives in such models have a causal meaning. Such an approach has been used in the causal analysis of game-theoretical models in an informal manner. Here we formalize this approach by linking evolutionary game theory to concepts developed in causal modelling over the past century, from path coefficients to the recently proposed causal derivative. There is a direct correspondence between the causal derivative and the derivative used in evolutionary game theory. Some game theoretical models (e.g. kin selection) consist of multiple causal derivatives. Components of these derivatives correspond to components of the causal derivative, to path coefficients, and to edges on a causal graph, formally linking evolutionary game theory to causal modelling. This article is part of the theme issue 'Half a century of evolutionary games: a synthesis of theory, application and future directions'.


Sex Differences and Predictors of Changes in Body Weight and Noncommunicable Diseases in a Random, Newly-Arrived Group of Refugees Followed for Two Years.
We have reported that none of the psychological/mental variables examined predicted the increase in BMI and non-communicable diseases (NCDs) in Iraqi refugees after 1 year resettlement in Michigan. We continuously followed the same cohort of refugees for 2 years (Y2 FU) to further determine the gender difference in predicting of increased BMI and NCDs. Only 20% of the BMI variability could be accounted for by the factors examined. Number of dependent children and depression were positively and stress negatively associated with BMI in male refugees but not in females. Number of dependent children was negatively associated with changes in BMI and in males only. Two-third of the NCD variability was accounted for by gender, BMI, employment status, depression, posttraumatic stress disorders and coping skills. Unmarried, unemployed and with high PTSD scores at Y2 in males were positively and number of dependent children was negatively associated with NCD changes in females. Factors such as dietary patterns and lifestyle may have contributed to the increased BMI and NCDs in these refugees at 2 years post-settlement.


Epinephrine-stimulated glucose production is not diminished by starvation: evidence for an effect on gluconeogenesis.
We infused physiological doses of epinephrine (1.2 microgram/m2 X min) into six healthy obese subjects in the postabsorptive state and after 3-4 days of starvation. During starvation, a reduction in hepatic glycogen stores was demonstrated by the absence of a rise in plasma glucose and glucose production (using [3-3H]glucose) in response to glucagon infusion. The increases in plasma epinephrine and glucose during the epinephrine infusion were comparable before and after starvation. Most importantly, the increase in endogenous glucose production produced by epinephrine was virtually unaffected, i.e. the initial rise in glucose production (59% vs. 49%), the incremental area under the curve (2.6 vs. 3.1 g/m2), and the spike-decline pattern of the response were no different before and after starvation, respectively. Similarly, epinephrine-induced elevations in gluconeogenic precursors (lactate and alanine) were not altered by starvation. However, starvation accentuated the rise in FFA by 200%. We conclude that starvation does not diminish the rise in endogenous glucose production in response to stress-like elevations of epinephrine. This occurs even though the liver fails to respond to high physiological doses of glucagon, possibly because epinephrine enhances the mobilization of gluconeogenic precursors and FFA. These data suggest that epinephrine is a potent stimulator of gluconeogenesis and may be more effective than glucagon in accelerating glucose production in patients with depleted glycogen stores.


Continuous retrograde cardiac perfusion decreases risk of reoperative coronary artery bypass grafting.
Embolization of atheromatous debris from old saphenous vein grafts is a major factor that increases the risk of reoperative coronary artery bypass grafting (CABG) when compared with primary CABG. To decrease this risk, a technique consisting of minimal dissection of the heart prior to cross clamping, continuous retrograde coronary sinus perfusion with 32 degrees C blood, and temporary posterior cardiac interventricular vein occlusion, during which time all dissection and anastomoses are performed, was evaluated prospectively in 130 consecutive patients from January 2, 1991, through February 28, 1995. This group was compared with a cohort of 1107 patients undergoing primary CABG performed concurrently. The two groups were similar in age (median sixty-eight years), incidence of hypercholesterolemia, peripheral vascular disease, smoking history, and left main stem stenosis. More patients undergoing reoperative CABG had previous myocardial infarctions (61.5% vs 54.5%), a higher incidence of triple-vessel coronary artery disease (89.2% vs 77.1%, P = 0.002), and a lower ejection fraction (54.0% vs 56.9%). The median interval from primary CABG to reoperative CABG was one hundred twenty-seven months with a range of 2.5 to two hundred seventy-nine months. The cross clamp time (median one hundred three vs sixty-nine minutes, P = 0.000001) and perfusion time (median one hundred thirty-four vs ninety-four minutes, P = 0.000001) were significantly higher in the reoperative CABG group. The requirements for inotropic support postoperatively, perioperative myocardial infarction (1.5% vs 2.4%, P = 0.397), and mortality (3.1% vs 3.4%, P = 0.54) were statistically equivalent in the two groups. These data reveal that continuous retrograde coronary sinus perfusion, posterior cardiac interventricular vein occlusion, and single cross-clamping technique improve outcomes of reoperative CABG to that approaching primary CABG.


Overview and diagnosis of acute retinal necrosis syndrome.
Acute retinal necrosis (ARN) syndrome, also known as Kirisawa's uveitis, is one of the most serious ocular diseases, and is characterized by a combination of peripheral, confluent, necrotizing retinitis, retinal arteritis, and intraocular inflammation. ARN syndrome is caused by the herpesvirus family, including herpes simplex virus (HSV) and varicella-zoster virus (VZV). The diagnosis of ARN syndrome is fundamentally based on clinical appearance and the demonstration of viral infection. Recently, polymerase chain reaction techniques permit detection of very small amounts of viral DNA in intraocular specimens. This knowledge can help in both the diagnosis and design of therapeutic strategy for ARN syndrome. Here we review the clinical presentation and the current advances in the diagnosis of ARN syndrome.


Evaluation of the in vitro performance of generic and original adapalene gel.
The aim was to evaluate the difference of the in vitro behavior between the commercially available generic adapalene gel and original product with Topical Classification System (TCS), and to analyze the effect of changes of excipients on the release behavior. Establishing in vitro performance assays to understand the impact of formulation variables on the critical quality attributes (CQA) is critical for the quality assessment of semi-solid generic drug. In vitro release (IVR), in vitro permeation (IVP), viscosity, and pH measurement methods for adapalene gels were established and validated. The differences between generic adapalene gel from 7 companies and original products were evaluated by correlation analysis (CA) and principal component analysis (PCA), and the relationship among 4 parameters was elucidated. The effect of excipients on the above variables was examined by univariate tests. There were some differences between the gels of 5 of the 7 imitation enterprises and reference listed drug (RLD). There were varying degrees of correlation between viscosity, pH, the adapalene amount retained in skin and release rate. The result validated the key role of IVR, and identified that pH value, type of suspending agent, the amount of carbomer, etc. had certain effects on the release rate. The factors mentioned above should be considered when developing and manufacturing generic adapalene gels, and the application of TCS in the evaluation of generic topical drugs was advanced. Additionally, our research revealed some discrepancies from USP<1724>, which could be valuable information for the revision.


Awareness and perceived necessity of dietary guidelines among urban Koreans by gender.
We examined an urban population's awareness of dietary guidelines to determine whether they perceived them to be necessary, and identified the factors affecting this awareness and perceived necessity. Data were collected via physical examinations and face-to-face interviews. Health indicators were collected from health examinations, and information on individual characteristics, including awareness, perceived necessity, and dietary status were obtained from the interviews. The subjects' sociodemographic, health and dietary status were examined as potential factors influencing awareness and perceived necessity. Descriptive statistics, contingency tables, and logistic regression modeling were used in the analysis. Low awareness of the dietary guidelines was displayed by the elderly and poorly educated individuals, and those without a spouse. Most people who were not aware of the dietary guidelines thought the guidelines unnecessary. Males with hypertension and lower hemoglobin levels, and females with less education had low awareness. Elderly females with lower bone density had less perceived necessity. Males and females with poor dietary status reported low perceived necessity.


Immediately loaded implants in a patient with involuntary mandibular movements: a clinical report.
Immediately loaded implant prostheses have been used to successfully rehabilitate completely edentulous arches. Risk factors for successful treatment have not included involuntary mandibular movements. The treatment was completed on a patient with a history of neuroleptic medications who had remaining mandibular teeth extracted and then developed involuntary mandibular movements. The patient was dissatisfied with a mandibular removable prosthesis and wanted a fixed prosthesis. The immediate implant loading of a complete arch fixed prosthesis was delivered, and the patient lost 3 of the 6 implants. The patient continued to have problems with her definitive prostheses as the symptoms of her involuntary mandibular movements worsened.


Identification and Quantification of Glucosinolates in Kimchi by Liquid Chromatography-Electrospray Tandem Mass Spectrometry.
A novel and simple method for detecting five glucosinolates (glucoalyssin, gluconapin, glucobrassicanapin, glucobrassicin, and 4-methoxyglucobrassicin) in kimchi was developed using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). The chromatographic peaks of the five glucosinolates were successfully identified by comparing their retention times, mass spectra. The mobile phase was composed of A (acetonitrile) and B (water). As for glucosinolate, the relative quantities were found through sinigrin, and five different compounds that have not been previously discovered in kimchi were observed. Monitoring was carried out on the glucosinolate in 20 kimchis distributed in markets, and this study examined the various quality and quantity compositions of the five components. The glucoalyssin content ranged from 0.00 to 7.07 μmol/g of day weight (DW), with an average content of 0.86 μmol/g of DW, whereas the gluconapin content ranged from 0.00 to 5.85 μmol/g of DW, with an average of 1.17 μmol/g of DW. The content of glucobrassicanapin varied between 0.00 and 11.87 μmol/g of DW (average = 3.03 μmol/g of DW), whereas that of glucobrassicin varied between 0.00 and 0.42 μmol/g of DW (average = 0.06 μmol/g of DW). The 4-methoxyglucobrassicin content ranged from 0.12 to 9.36 μmol/g of DW (average = 3.52 μmol/g of DW). A comparison of the contents revealed that, in most cases, the content of 4-methoxyglucobrassicin was the highest.


Modelling the emergence of synchrony from decentralized rhythmic interactions in animal communication.
To communicate, an animal's strategic timing of rhythmic signals is crucial. Evolutionary, game-theoretical, and dynamical systems models can shed light on the interaction between individuals and the associated costs and benefits of signalling at a specific time. Mathematical models that study rhythmic interactions from a strategic or evolutionary perspective are rare in animal communication research. But new inspiration may come from a recent game theory model of how group synchrony emerges from local interactions of oscillatory neurons. In the study, the authors analyse when the benefit of joint synchronization outweighs the cost of individual neurons sending electrical signals to each other. They postulate there is a benefit for pairs of neurons to fire together and a cost for a neuron to communicate. The resulting model delivers a variant of a classical dynamical system, the Kuramoto model. Here, we present an accessible overview of the Kuramoto model and evolutionary game theory, and of the 'oscillatory neurons' model. We interpret the model's results and discuss the advantages and limitations of using this particular model in the context of animal rhythmic communication. Finally, we sketch potential future directions and discuss the need to further combine evolutionary dynamics, game theory and rhythmic processes in animal communication studies.


The role of respiratory measures to assess mental load in pilot selection.
While cardiovascular measures have a long tradition of being used to determine operator load, responsiveness of the respiratory system to mental load has rarely been investigated. In this study, we assessed basic and variability measures of respiration rate (RR), partial pressure of end-tidal carbon dioxide (petCO2) as well as performance measures in 63 male pilot candidates during completion of a complex cognitive task and subsequent recovery. Mental load was associated with an increase in RR and a decrease in respiratory variability. A significant decrease was also found for petCO2. RR and respiratory variability showed partial and complete effects of recovery, respectively, whereas petCO2 did not return to baseline level. Overall, a good performance was related to a stronger reactivity in RR. Our findings suggest that respiratory parameters would be a useful supplement to common measures for the assessment of mental load in pilot selection. Practitioner Summary: Respiratory measures are a promising yet poorly investigated approach to monitor operator load. For pilot selection, we assessed respiration in response to multitasking in 63 candidates. Task-related changes as well as covariation with performance strongly support the consideration of respiratory parameters when evaluating reactivity to mental load.


[Acute ischemic stroke: time is brain!].
Care of patients with acute ischemic stroke in dedicated stroke units reduces the rates of death and disability independently from any specific treatment. The only validated treatment for acute ischemic stroke is thrombolysis with intravenous alteplase. Its efficacy is strongly time-dependent. It is currently demonstrated for an administration up to 3 hours after symptom onset. Intravenous fibrinolysis for acute ischemic stroke is associated with an increased risk of symptomatic intracerebral haemorrhage. This can be reduced by rigorous application of recommendations for drug prescription. The efficacy of intravenous alteplase is relatively weak in patients with large artery occlusion. Combined therapies, using transcranial ultrasound, intraarterial thrombolysis, or clot retrieval devices are being evaluated to improve the efficacy of thrombolysis.


Dopamine agonists and the risk of cardiac-valve regurgitation.
Case reports and echocardiographic studies suggest that the ergot-derived dopamine agonists pergolide and cabergoline, used in the treatment of Parkinson's disease and the restless legs syndrome, may increase the risk of cardiac-valve regurgitation. We used data from the United Kingdom General Practice Research Database to identify a population-based cohort comprising 11,417 subjects 40 to 80 years of age who were prescribed antiparkinsonian drugs between 1988 and 2005. We conducted a nested case-control analysis within this cohort in which each patient with newly diagnosed cardiac-valve regurgitation was matched with up to 25 control subjects from the cohort, according to age, sex, and year of entry into the cohort. Incidence-rate ratios for cardiac-valve regurgitation with the use of different dopamine agonists were estimated by conditional logistic-regression analysis. Of 31 case patients with newly diagnosed cardiac-valve regurgitation, 6 were currently exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had not been exposed to any dopamine agonist within the previous year. The rate of cardiac-valve regurgitation was increased with current use of pergolide (incidence-rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3) and cabergoline (incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6), but not with current use of other dopamine agonists. In this study, use of the dopamine agonists pergolide and cabergoline was associated with an increased risk of newly diagnosed cardiac-valve regurgitation.


Myocardial and vascular effects of perindopril, a new converting enzyme inhibitor, during hypertension development in spontaneously hypertensive rats.
The effects of a new angiotensin I converting enzyme inhibitor (ACEI), perindopril (P), on genetic hypertension development (GHD), on mesenteric arteriolar compliance and reactivity to noradrenaline and on myocardial and aortic hypertrophy, have been investigated at intervals in SHRs. P (4 mg/kg, q.d.) was administered by gavage from the 4th to the 20th week of age and measurements were performed 20 hr after the preceding drug intake. P completely prevented GHD, maintaining systolic blood pressure (SBP) below 130 mmHg during the whole treatment period. Furthermore, 7 weeks after treatment withdrawal, SBP of previously treated SHRs was still significantly lower than that of controls. Vascular compliance and internal diameter of the mesenteric arteriole were significantly increased in P-treated SHRs as compared to controls at the age of 20 weeks but these effects did not persist 7 weeks after treatment withdrawal. P did not affect mesenteric arteriolar reactivity to noradrenaline. Finally, P significantly reduced myocardial and aortic hypertrophy in SHRs. Thus P strongly opposed the morphological and functional vascular alterations which usually occur in SHRs during GHD. This property, presumably related to converting enzyme inhibition within the vascular wall, probably contributes to a large extent to, but is not exclusively responsible for, the drug-induced prevention of GHD.


[A case of mucinous adenocarcinoma of the prostate].
A mucinous adenocarcinoma of the prostate is rate, and a doubtful diagnosis should be verified to determine that the tumor surely does arise from the prostate, since a mucinous adenocarcinoma arising from the gastrointestinal tract is not as rare and often metastasizes to the prostate. We herein report on a case of a mucinous adenocarcinoma of the prostate, the origin of which was proved to be the prostate by immunohistochemical staining for a prostate-specific antigen and prostate-specific acid phosphatase.


Mode of action of the antimicrobial compound 5-bromo-5-nitro-1,3-dioxane (bronidox).
The mode of action of the antimicrobial agent, 5-bromo-5-nitro-1,3-dioxane (bronidox), was studied in detail for gram-positive and gram-negative bacteria, yeast and fungi. The studies included MIC testing, thiol inhibition of activity, intracellular leakage, oxygen consumption, incorporation of 3H-uridine, scanning electron microscopy, inhibition of enzyme activity (papain) and in vitro oxidation of thiols to disulfides. It appears that the primary mode of action of bronidox is the same as, or similar to, that of bronopol, i.e. the oxidation of essential protein thiol causing inhibition of enzyme activity and subsequent inhibition of microbial growth.


[Interventional radiological procedures in the therapy for colorectal liver metastases].
Microtherapeutic procedures performed by interventional radiologists pose a viable alternative or additive to systemic chemotherapy for local tumour control in cases of non-operable (for technical, functional, and comorbidity reasons or at the patient's wish) liver metastases. A main focus includes local therapies such as radiofrequency ablation and interstitial brachytherapy which are performed under ultrasound, CT or MRI guidance to achieve a thermal or radiogenic ablation of the malignancy. Although highly effective, these procedures are limited to oligonodular manifestations. For disseminated metastases, locoregional techniques like the yttrium-90 radioembolisation have become established. Here, the active principle in the form of radioactively labelled microspheres is introduced into the liver through an arterial catheter under angiographic guidance. The present article focuses on metastases of colorectal cancer as the most frequent tumour entity encountered in interventional radiotherapy.


Hollow Carbon Sphere Nanoreactors Loaded with PdCu Nanoparticles: Void-Confinement Effects in Liquid-Phase Hydrogenations.
Nanoreactors with hollow structures have attracted great interest in catalysis research due to their void-confinement effects. However, the challenge in unambiguously unraveling these confinement effects is to decouple them from other factors affecting catalysis. Here, we synthesize a pair of hollow carbon sphere (HCS) nanoreactors with presynthesized PdCu nanoparticles encapsulated inside of HCS (PdCu@HCS) and supported outside of HCS (PdCu/HCS), respectively, while keeping other structural features the same. Based on the two comparative nanoreactors, void-confinement effects in liquid-phase hydrogenation are investigated in a two-chamber reactor. It is found that hydrogenations over PdCu@HCS are shape-selective catalysis, can be accelerated (accumulation of reactants), decelerated (mass transfer limitation), and even inhibited (molecular-sieving effect); conversion of the intermediate in the void space can be further promoted. Using this principle, a specific imine is selectively produced. This work provides a proof of concept for fundamental catalytic action of the hollow nanoreactors.