Perception of Health Problems Among Competitive Runners: A Qualitative Study of Cognitive Appraisals and Behavioral Responses.
Approximately 2 of every 3 competitive runners sustain at least 1 health problem each season. Most of these problems are nontraumatic injuries with gradual onset. The main known risk indicator for sustaining a new running-related injury episode is a history of a previous injury, suggesting that behavioral habits are part of the causal mechanisms. Identification of elements associated with purposeful interpretations of body perceptions and balanced behavioral responses may supply vital information for prevention of health problems in runners. This study set out to explore competitive runners' cognitive appraisals of perceived symptoms on injury and illness and how these appraisals are transformed into behavior. Cross-sectional study; Level of evidence, 3. The study population consisted of Swedish middle- and long-distance runners from the national top 15 list. Qualitative research methods were used to categorize interview data and perform a thematic analysis. The categories resulting from the analysis were used to construct an explanatory model. Saturation of the thematic classification required that data from 8 male and 6 female runners (age range, 20-36 years) were collected. Symptoms interpreted to be caused by illness or injury with a sudden onset were found to lead to immediate action and changes to training and competition programs (activity pacing). In contrast, perceptions interpreted to be due to injuries with gradual onset led to varied behavioral reactions. These behavioral responses were planned with regard to short-term consequences and were characterized by indifference and neglect of long-term implications, consistent with an overactivity behavioral pattern. The latter pattern was consistent with a psychological adaptation to stimuli that is presented progressively to the athlete. Competitive runners appraise whether a health problem requires immediate withdrawal from training based on whether the problem is interpreted as an illness and/or has a sudden onset. The ensuing behaviors follow 2 distinct patterns that can be termed "activity pacing" and "overactivity."


Medical care for terrorists--to treat or not to treat?
With the escalation of terrorism worldwide in recent years, situations arise in which the perpetration of violence and the defense of human rights come into conflict, creating serious ethical problems. The Geneva Convention provides guidelines for the medical treatment of enemy wounded and sick, as well as prisoners of war. However, there are no comparable provisions for the treatment of terrorists, who can be termed unlawful combatants or unprivileged belligerents. Two cases of severely injured terrorists are presented here to illustrate the dilemmas facing the medical staff that treated them. It is suggested that international legal and bioethical guidelines are required to define the role of the physician and auxiliary medical staff vis a vis injured terrorists. There are extreme situations where the perpetration of violence and the defense of human rights come into conflict, leading to serious ethical and psychological discord. Terrorists, using violence to create fear in order to further their political objectives, might require life-saving medical care if injured during the course of their terror activities.


Recommendations for Determining the Validity of Consumer Wearables and Smartphones for the Estimation of Energy Expenditure: Expert Statement and Checklist of the INTERLIVE Network.
Consumer wearables and smartphone devices commonly offer an estimate of energy expenditure (EE) to assist in the objective monitoring of physical activity to the general population. Alongside consumers, healthcare professionals and researchers are seeking to utilise these devices for the monitoring of training and improving human health. However, the methods of validation and reporting of EE estimation in these devices lacks rigour, negatively impacting on the ability to make comparisons between devices and provide transparent accuracy. The Towards Intelligent Health and Well-Being Network of Physical Activity Assessment (INTERLIVE) is a joint European initiative of six universities and one industrial partner. The network was founded in 2019 and strives towards developing best-practice recommendations for evaluating the validity of consumer wearables and smartphones. This expert statement presents a best-practice validation protocol for consumer wearables and smartphones in the estimation of EE. The recommendations were developed through (1) a systematic literature review; (2) an unstructured review of the wider literature discussing the potential factors that may introduce bias during validation studies; and (3) evidence-informed expert opinions from members of the INTERLIVE network. The systematic literature review process identified 1645 potential articles, of which 62 were deemed eligible for the final dataset. Based on these studies and the wider literature search, a validation framework is proposed encompassing six key domains for validation: the target population, criterion measure, index measure, testing conditions, data processing and the statistical analysis. The INTERLIVE network recommends that the proposed protocol, and checklists provided, are used to standardise the testing and reporting of the validation of any consumer wearable or smartphone device to estimate EE. This in turn will maximise the potential utility of these technologies for clinicians, researchers, consumers, and manufacturers/developers, while ensuring transparency, comparability, and replicability in validation. PROSPERO ID: CRD42021223508.


ATM-Dependent Recruitment of BRD7 is required for Transcriptional Repression and DNA Repair at DNA Breaks Flanking Transcriptional Active Regions.
Repair of DNA double-strand breaks (DSBs) is essential for genome integrity, and is accompanied by transcriptional repression at the DSB regions. However, the mechanisms how DNA repair induces transcriptional inhibition remain elusive. Here, it is identified that BRD7 participates in DNA damage response (DDR) and is recruited to the damaged chromatin via ATM signaling. Mechanistically, BRD7 joins the polycomb repressive complex 2 (PRC2), the nucleosome remodeling and histone deacetylation (NuRD) complex at the damaged DNA and recruits E3 ubiquitin ligase RNF168 to the DSBs. Furthermore, ATM-mediated BRD7 phosphorylation is required for recruitment of the PRC2 complex, NuRD complex, DSB sensor complex MRE11-RAD50-NBS1 (MRN), and RNF168 to the active transcription sites at DSBs, resulting in transcriptional repression and DNA repair. Moreover, BRD7 deficiency sensitizes cancer cells to PARP inhibition. Collectively, BRD7 is crucial for DNA repair and DDR-mediated transcription repression, which may serve as a therapeutic target. The findings identify the missing link between DNA repair and transcription regulation that maintains genome integrity.


Risk factors of conversion in laparoscopic cholecystectomies for lithiasic acute cholecystitis. Results of a monocentric study and review of the literature.
Nowadays, laparoscopic cholecystectomy has become the gold standard in the management of lithiasic acute cholecystitis. However, the rate of conversion to laparotomy remains considerable, greater than that of uncomplicated lithiasis. Some factors, related to the patient, the disease or the surgeon, are associated with a high risk of conversion. To identify the factors associated with a significant risk of conversion in laparoscopic cholecystectomy for acute cholecystitis. Between January 2011 and December 2015, all patients operated on for acute cholecystitis at the Department of General and Digestive Surgery of Farhat Hached University Hospital of Sousse - Tunisia were divided into two groups: A for the laparoscopic approach and B for conversion. We compared the two groups. The conversion rate was 21.9% (43 patients). At the end of this work, we found that the conversion rate was significantly increased for males (p = 0.044), ulcerative disease (p = 0.004), smokers (p = 0.007), ASA score = II (p = 0.005), abdominal guarding (p = 0.001), fever (p = 0.001), perivesicular effusion on ultrasound (p = 0.041), ultrasound Murphy's sign (p = 0.023), delayed cholecystectomy (p = 0.038), perivascular adhesions (p <10-3) and gangrenous cholecystitis (p = 0.009). The conversion is sometimes badly perceived by the surgeon. However, it should in no way be considered a failure, but rather a change of strategy to ensure patient safety. Conversion should not be delayed, especially as risk factors have been identified.


Broadband transmission noise reduction of smart panels featuring piezoelectric shunt circuits and sound-absorbing material.
The possibility of a broadband noise reduction of piezoelectric smart panels is experimentally studied. A piezoelectric smart panel is basically a plate structure on which piezoelectric patches with electrical shunt circuits are mounted and sound-absorbing material is bonded on the surface of the structure. Sound-absorbing material can absorb the sound transmitted at the midfrequency region effectively while the use of piezoelectric shunt damping can reduce the transmission at resonance frequencies of the panel structure. To be able to reduce the sound transmission at low panel resonance frequencies, piezoelectric damping using the measured electrical impedance model is adopted. A resonant shunt circuit for piezoelectric shunt damping is composed of resistor and inductor in series, and they are determined by maximizing the dissipated energy through the circuit. The transmitted noise-reduction performance of smart panels is tested in an acoustic tunnel. The tunnel is a square cross-sectional tube and a loudspeaker is mounted at one side of the tube as a sound source. Panels are mounted in the middle of the tunnel and the transmitted sound pressure across panels is measured. When an absorbing material is bonded on a single plate, a remarkable transmitted noise reduction in the midfrequency region is observed except for the fundamental resonance frequency of the plate. By enabling the piezoelectric shunt damping, noise reduction is achieved at the resonance frequency as well. Piezoelectric smart panels incorporating passive absorbing material and piezoelectric shunt damping is a promising technology for noise reduction over a broadband of frequencies.


Centrosome inheritance in insects: fertilization and parthenogenesis.
Centrosome biogenesis is unclear, although much structural and biochemical research has been performed in several experimental systems. An alternative model to study the assembly of functional centrosomes could be the process of zygotic centrosome formation at the beginning of embryonic development. Although it seems obvious that the sperm cell provides the centrosome at fertilization, some pieces of evidence are not in line with this point of view and give controversial results. Such an analysis could provide useful information if applied to a large variety of organisms. Since insects are a highly diverse group of organisms they provide a variety of models in which to study the process of centrosome reconstitution during fertilization. Moreover, many insect species reproduce by parthenogenesis, a special mode of reproduction in which embryonic development occurs without male contribution. Studies of unfertilized parthenogenetic eggs may therefore teach us much about the process of centrosome assembly in the absence of preexisting centrioles.


Establishment, value assignment, and characterization of new WHO reference reagents for six molecular forms of human chorionic gonadotropin.
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group to investigate means of improving the comparability of immunoassays for human chorionic gonadotropin (hCG), which was selected as a prototype glycoprotein analyte. The Working Group identified development of unambiguous nomenclature and production of new highly purified International Reference Reagents calibrated in substance concentrations as its primary objectives. Preparations of intact hCG, nicked hCG, hCG beta-subunit, nicked hCG beta-subunit, hCG alpha-subunit, and hCG beta-core fragment were purified from a crude urinary hCG preparation, ampouled, lyophilized, and assigned values in substance concentrations (mol/L). Value assignment and accelerated degradation studies were carried out in accordance with WHO protocols for International Reference Reagents. The ampouled standards were assigned final values based on the recovery of immunoreactive material after reconstitution. The degradation studies showed that the standards were highly stable. The nomenclature of hCG-related molecules and immunoassays has been adopted by the IFCC, and the standards prepared and characterized by the Working Group have been formally adopted by the WHO as the First International Reference Reagents for six hCG-related molecules. These developments will enable better understanding of what assays for hCG measure and should ultimately help to improve the clinical application of these assays.


Vasopressin effects on lung liquid volume in fetal sheep.
The normal switch from placental to pulmonary gas exchange at birth requires rapid removal of liquid from the lungs. Previous reports contend that vasopressin may be important in regulating this process, but this notion derives from studies in which fetal sheep received very large doses of vasopressin that yielded plasma concentrations at least 10 times greater than those that have been measured during normal labor. To study the physiologic effects of vasopressin on lung liquid volume in fetal sheep, we made three sets of experiments. First, we measured plasma vasopressin concentrations [VP] in 15 late-gestation fetal sheep, five of which were at various stages of spontaneous labor. [VP] in these fetuses ranged from < 1 (prelabor) to 31 (during labor) microU/mL; postmortem extravascular lung water (EVLW) ranged from 4.5 to 14.5 g/g dry lung tissue. In a second series of studies, we measured EVLW in five sets of near-term (138 +/- 1 d, term = 147 d) twin fetal sheep that received an 8-h i.v. infusion of either isotonic saline (control twin) or AVP (AVP-treated twin) at a rate of approximately 1 (mU/kg)/min. This dose was chosen to mimic [VP] measured in fetuses that had been studied during labor. [VP] did not change in the control twins, whereas [VP] increased from 1.8 +/- 1.0 to 27.7 +/- 3.5 microU/mL in treated twins. There was a small, statistically significant difference in EVLW between twins that received AVP and untreated twins (11.9 +/- 1.8 versus 14.6 +/- 2.8 g/g dry lung).(ABSTRACT TRUNCATED AT 250 WORDS)


Surgical management of trigeminal neuralgia in elderly patients using a small retrosigmoidal approach: analysis of efficacy and safety.
Trigeminal neuralgia is one of the most common causes of facial pain with the highest incidence in individuals > 60 years old. Despite the proven efficacy and safety of microvascular decompression (MVD) for the treatment of trigeminal neuralgia, some physicians are reluctant to perform the procedure in elderly patients because of potential complications. In the present study, we analyze the outcome of MVDs performed over a 10-year period in elderly patients and compare the results with those obtained in younger patients. A total of 32% of the patients were ≥ 65 years of age at the time of diagnosis. All of the patients were treated via a small retrosigmoidal approach because of reluctance for medical treatment. Overall, 87% of the patients exhibited microvascular compression of the fifth nerve in the root entry zone and were treated using MVD; the remainder of the patients were treated using a trigeminal root compression technique when a vessel was not compressing the fifth nerve. After the procedure, 93% reported complete relief of pain with a recurrence rate of 10.8% over a mean time of 43 months. A total of 10% of the patients experienced severe complications related to the operation with no mortality. MVD continues to be the procedure of choice for the treatment of trigeminal neuralgia in patients reluctant to medical treatment, including elderly patients because age is not a contraindication.


Oxygen Reduction Mechanism of Monometallic Rhodium Hydride Complexes.
The reduction of O2 to H2O mediated by a series of electronically varied rhodium hydride complexes of the form cis,trans-Rh(III)Cl2H(CNAd)(P(4-X-C6H4)3)2 (2) (CNAd = 1-adamantylisocyanide; X = F (2a), Cl (2b), Me (2c), OMe (2d)) was examined through synthetic and kinetic studies. Rhodium(III) hydride 2 reacts with O2 to afford H2O with concomitant generation of trans-Rh(III)Cl3(CNAd)(P(4-X-C6H4)3)2 (3). Kinetic studies of the reaction of the hydride complex 2 with O2 in the presence of HCl revealed a two-term rate law consistent with an HX reductive elimination (HXRE) mechanism, where O2 binds to a rhodium(I) metal center and generates an η(2)-peroxo complex intermediate, trans-Rh(III)Cl(CNAd)(η(2)-O2)(P(4-X-C6H4)3)2 (4), and a hydrogen-atom abstraction (HAA) mechanism, which entails the direct reaction of O2 with the hydride. Experimental data reveal that the rate of reduction of O2 to H2O is enhanced by electron-withdrawing phosphine ligands. Complex 4 was independently prepared by the addition of O2 to trans-Rh(I)Cl(CNAd)(P(4-X-C6H4)3)2 (1). The reactivity of 4 toward HCl reveals that such peroxo complexes are plausible intermediates in the reduction of O2 to H2O. These results show that the given series of electronically varied rhodium(III) hydride complexes facilitate the reduction of O2 to H2O according to a two-term rate law comprising HXRE and HAA pathways and that the relative rates of these two pathways, which can occur simultaneously and competitively, can be systematically modulated by variation of the electronic properties of the ancillary ligand set.


Rb may act as a transcriptional co-activator in undifferentiated F9 cells.
The reversible interaction of the retinoblastoma susceptibility gene product (Rb) with the cellular transcription factor E2F has recently been demonstrated. Activation of the adenovirus E2a promoter by the products of the viral E1a gene correlates with the ability of both early E1a proteins to sequester Rb, thereby releasing E2F from inactive complexes with this protein. The E2a promoter is also efficiently stimulated by a product (17.5 kDa) of the viral E4 gene. The specific interaction of this E4 protein with E2F results in the formation of complexes that bind cooperatively to the two neighboring E2F binding sites in the E2a promoter. We have previously shown that in undifferentiated F9 cells (F9EC) the E2a promoter is refractory to E2F-mediated activation by E1a, but not by E4. Using both band-shift and transfection experiments, we now demonstrate (i) that in F9EC cells the E4 product, in combination with E2F, recruits Rb into a stable multiprotein complex and (ii) that in these undifferentiated cells, as opposed to their differentiated counterpart, Rb is actively involved in the transcriptional stimulation of the E2a promoter by E4. Our results suggest that, depending on the cell state, Rb may behave either as a transcriptional activator (F9EC cells) or as a transcriptional inhibitor (differentiated F9 cells).


Mechanisms of organic cation transport in kidney plasma membrane vesicles: 1. Countertransport studies.
Transport for organic cations has been described in both luminal and antiluminal membranes. The two transport systems difer from one another on the basis of kinetic parameters and countertransport. By using N1-[3H]methylnicotinamide as the indication cation, a series of organic cations (which were known to be secreted) were tested for their capacity to stimulate countertransport. The phenomenon of countertransport was symmetrical in that it was observed for both influx and efflux in both membranes. However, under appropriate conditions, certain organic cations were effective in producing "uphill" transport of N1-[3H]methylnicotinamide in the luminal membrane and the effect was limited to that membrane exclusively. Detailed analysis of countertransport in the luminal membrane showed quantitative differences in the maximal stimulation produced by the various cations: giving rise to the relationship that the concentration of organic cation which gave one-half maximal N1-[3H]methylnicotinamide countertransport approximated its affinity constant. The data were interpreted to suggest that all the members of the organic cation series tested are translocated across the luminal membrane by the same carrier but that they are moved at different rates.


Accuracy in Cement Hydration Investigations: Combined X-ray Microtomography and Powder Diffraction Analyses.
Cement hydration is a very complex set of processes. The evolution of the crystalline phases during hydration can be accurately followed by X-ray powder diffraction data evaluated by the Rietveld method. However, accurate measurements of some microstructural features, including porosity and amorphous content developments, are more challenging. Here, we combine laboratory X-ray powder diffraction and computed microtomography (μCT) to better understand the results of the μCT analyses. Two pastes with different water-cement ratios, 0.45 and 0.65, filled within capillaries of two sizes, ϕ = 0.5 and 1.0 mm, were analysed at 50 days of hydration. It was shown that within the spatial resolution of the measured μCTs, ~2 μm, the water capillary porosity was segmented within the hydrated component fraction. The unhydrated part could be accurately quantified within 2 vol% error. This work is a first step to accurately determining selected hydration features like the hydration degree of amorphous phases of supplementary cementitious materials within cement blends.


A systematic review of the use of simulation and reflection as summative assessment tools to evaluate student outcomes following interprofessional education activities.
Despite the increasing emphasis on interprofessional education (IPE) in curricula and the potential benefits for student learning, there appears to be a lack of evidence directing authentic and accurate assessment of student-learning outcomes and translation of assessment data into scores and grades. Given the increasing importance of reflection and simulation in IPE, the purpose of this systematic review was to identify, appraise, and synthesize published literature using reflection and simulation as summative assessment tools to evaluate student outcomes following IPE activities. The Crowe Critical Appraisal Tool was used to appraise the included articles for quality. This systematic review yielded only five studies of marginal quality that could highlight the limited rigorous use of either reflection or simulation for summative assessment purposes. This review has identified a need for summative IPE assessment alongside formative assessments. Furthermore, training needs to be offered to both faculty assessors, to ensure they are competent and results are reproducible, and students, to equip them with the knowledge, critical thinking skills, and attitude for becoming reflective practitioners who are able to practice interprofessionally. The assessment of IPE remains a challenge, and there is a clear gap in the literature where research needs to grow.


[Characteristics of headache associated with cerebral arteriovenous malformations].
and purposes. The purpose of this study was to identify the specific characteristics of headaches associated with cerebral arteriovenous malformations in order to differentiate them from other known entities of headaches such as migraine, cluster headache, and trigeminal neuralgia. This differentiation allows an early diagnosis of cAVM and a treatment to be administrated before any cerebral hemorrhage. The study included 700 patients with cAVM and treated by radiosurgery. Out of this series, only 109 (48 males, 61 females, mean age of 33) presented with headaches. Headaches were studied as a possible revelation mode of a cAVM, either as an isolated sign, preceding an epileptic seizure, a cerebral hemorrhage, or associated with a neurological deficit. Analysis concerned 13 clinical parameters and 30 anatomic parameters based on angiography. Headaches were found in 15.6%; they were isolated in 6%. They preceded a cerebral hemorrhage in 12.6%, constituting an early alarm signal when increasing in intensity, frequency and duration. They were associated with seizures or a neurological deficit in 9.6%. We found a predominant female sex-ratio (0.78) and occurrence at a young age (72.3% between 10 and 40 years). Headaches were non-pulsating in 95.3%; nausea, vomiting, light or sound phobia were only found in 4.7%. Headaches were unilateral and homolateral to the malformation in 80%, corresponding to the malformation topography in 97.4% in posterior location and 80% in anterior location. Associated neurological symptoms existed in 20.2%; related to the malformation and lasting 5 to 30 minutes. Duration of pain episodes was less than 3 hours in 77% with a frequency of 1 to 2 per month in 82.5%. Pain was mild and responded to simple analgesics. A family migraine was found in only 3 patients. The angiographic characteristics of the malformations were meningeal afferences, superficial venous drainage and posterior location. Headaches associated with cerebral arterio-venous malformations form a distinct category that can be determined from specific characteristics; this should help an early diagnosis of cerebral arterio-venous malformations in order to start a treatment before the occurrence of cerebral hemorrhage.


Sodium glucose transporter 2 (SGLT2) inhibition and ketogenesis.
Sodium glucose transporter 2 (SGLT2) inhibitors are a recently developed class of drug that have been approved for use in type 2 diabetes. Their unique extra-pancreatic glucuretic mode of action has encouraged their usage in type 1 diabetes as well. At the same time, reports of pseudo ketoacidosis and ketoacidosis related to their use have been published. No clear mechanism for this phenomenon has been demonstrated so far. This communication delves into the biochemical effects of SGLT2 inhibition, discusses the utility of these drugs and proposes steps to maximize safe usage of the molecules.


Intraventricular antibiotics for bacterial meningitis in neonates.
Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm. To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone. MEDLINE, EMBASE, The Cochrane Library, Issue 2, 2004, Science Citation Index, and the Oxford Database of Perinatal Trials were searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 - April 2004) as were reference lists of identified trials and personal files. No language restrictions were applied. Selection criteria for study inclusion were: Randomized or quasi-randomized controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalization, neonatal and/or infant mortality, neurodevelopmental outcome, duration of hospitalization, duration of culture positivity of CSF and side effects. All reviewers abstracted information for outcomes reported and one reviewer checked for discrepancies and entered data into RevMan 4.2. Relative risk (RR), risk difference (RD), number needed to treat (NNT) or number needed to harm (NNH), and mean difference (MD), using the fixed effects model are reported with 95% confidence intervals (CI). The fixed effect model was used for meta-analysis. One study was included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone [RR 3.43 (95% CI, 1.09, 10.74; RD 0.30 (95% CI, 0.08, 0.53); NNH was 3 (95% CI; 2 ,13)]. Duration of CSF culture positivity did not differ significantly (MD -1.20 days (95% CI, -2.67, 0.27). In one trial, enrolling infants with gram negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a 3 fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.


Interferon-β and temozolomide combination therapy for temozolomide monotherapy-refractory malignant gliomas.
Interferon-β (IFN-β) has been found to downregulate O6-methyl-guanine-DNA methyltransferase and sensitize glioma cells to chemoradiation therapy. The effectiveness of IFN-β and temozolomide (TMZ) combination therapy for newly diagnosed glioblastomas was previously reported. However, there is no clinical report of recurrent of malignant gliomas treated with the combination of IFN-β and TMZ. In the present study, we reported 7 cases of gliomas classified as uncontrollable with adjuvant TMZ monotherapy, who were then treated with IFN-β and TMZ combination therapy. The magnetic resonance imaging findings and clinical symptoms improved in the majority of the cases, with tolerable adverse events and minimal residual disability. The overall survival (OS) time from the date of the initial surgery exceeded 13 months, suggesting that this combination therapy was successful in improving the prognosis of malignant gliomas refractory to adjuvant TMZ monotherapy.


Strategies to Improve Annual Diabetic Foot Screening Compliance at a Family Clinic.
Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an effort to increase the percentage of patients with diabetes at a family clinic who receive annual foot screenings.


Effects of anisotropic material property on the spring constant and the resonant frequency of atomic force microscope cantilever.
Atomic force microscope (AFM) is a powerful tool for force measurement in nanoscale. Many methods have been developed to obtain the precise cantilever's spring constant for improving the accuracy of force measurement. AFM cantilevers are usually made by single crystal silicon of which the anisotropic material property seriously affects the spring constant of cantilevers and has not considered before. In this paper, the density function theory was used to calculate the anisotropic stiffness matrix of crystal silicon, which was used in the finite element analysis to calculate lateral, axial, bending spring constants, and resonant frequencies of rectangular AFM cantilevers. These results were compared with those derived from other theoretical methods and with those provided by the manufacturers. The results showed that the anisotropic material property significantly affected the spring constants and the resonant frequencies of the AFM cantilever. The assumption of equivalent isotropic property of the rectangular AFM cantilever would cause an error up to 29.72%. Furthermore, two equations were proposed to obtain the spring constants and the resonant frequencies of crystal silicon AFM cantilever with the axis located at different cantilever-crystal angles.


High-energy extracorporeal shock wave treatment of nonunions.
Forty-three consecutive patients who did not have healing of tibial or femoral diaphyseal and metaphyseal fractures and osteotomies for at least 9 months after injury or surgery were examined prospectively for use of high-energy extracorporeal shock waves. Former treatment modalities (cast, external fixator, plate osteosynthesis, limitation of weightbearing) remained unchanged. In all cases a 99mTechnetium dicarboxyphosphonate regional two-phase bone scintigraphy was performed before one treatment with 3,000 impulses of an energy flux density of 0.6 mJ/mm2. Radiologic and clinical followups were done at 4-week intervals starting 8 weeks after shock wave treatment. The success criterion was bridging of all four cortices in the anteroposterior and lateral radiographic views, in oblique views, or by conventional tomography. An independent observer described bony consolidation in 31 of 43 cases (72%) after an average of 4 months (range, 2-7 months). Twenty-nine of 35 (82.9%) patients with a positive bone scan had healing of the pseudarthrosis compared with two of eight (25%) patients with a negative bone scan. Six of these eight patients with negative scans were heavy smokers. No complications were observed. High-energy shock wave therapy seemed to be an effective noninvasive tool for stimulation of bone healing in properly selected patients with a diaphyseal or metaphyseal nonunion of the femur or tibia. Additional controlled studies are mandatory.


Anti-Inflammatory Functions of Methanol Extract from Malus baccata (L.) Borkh. Leaves and Shoots by Targeting the NF-κB Pathway.
Malus baccata (L.) Borkh. is a widely used medical plant in Asia. Since the anti-inflammatory mechanism of this plant is not fully understood, the aim of this study was to explore the anti-inflammatory function and mechanism of Malus baccata (L.) Borkh. methanol extract (Mb-ME). For in vitro experiments, nitric oxide production assay, PCR, overexpression strategy, immunoblotting, luciferase reporter assay, and immunoprecipitation were employed to explore the molecular mechanism and the target proteins of Mb-ME. For in vivo experiments, an HCl/EtOH-induced gastritis mouse model was used to confirm the anti-inflammatory function. Mb-ME showed a strong ability to inhibit the production of nitric oxide and the expression of inflammatory genes. Mb-ME decreased NF-κB luciferase activity mediated by MyD88 and TRIF. Moreover, Mb-ME blocked the activation of Src, Syk, p85, Akt, p50, p60, IKKα/β, and IκBα in LPS-induced RAW264.7 cells. Overexpression and immunoprecipitation analyses suggested Syk and Src as the target enzymes of Mb-ME. In vitro results showed that Mb-ME could alleviate gastritis and relieve the protein expression of p-Src, p-Syk, and COX-2, as well as the gene expression of COX-2 and TNF-α. In summary, this study implied that Mb-ME performs an anti-inflammatory role by suppressing Syk and Src in the NF-κB signaling pathway, both in vivo and in vitro.


Expression of functional beta-galactosidase containing the coxsackievirus 3C protease as an internal fusion.
Alpha complementation of beta-galactosidase (beta gal) is intracistronic and requires interaction between the alpha donor region (residues 3-41) and alpha acceptor fragment (produced by M15). We have constructed two plasmids which direct the synthesis of hybrid beta gal: coxsackievirus proteins in Escherichia coli. One plasmid, pBD1045, encodes an enzymatically active 3C protease of coxsackievirus B3 fused between the amino-terminal 79 amino acids of beta gal (containing the alpha donor region) and amino acids 80 to 1023 (alpha acceptor region). A second plasmid, pBD1043 encodes an inactive 3C protease and results in a fusion of 260 coxsackievirus amino acids between residues 79 and 80 of the beta gal monomer. Both hybrid proteins expressed by these constructs have beta-galactosidase activity regardless of whether the viral protease (183 amino acids) is autocatalytically cleaved out of the chimeric protein (pBD1045) or remains as part of a fusion protein (pBD1043). The implications of these results for structural flexibility of the complemented beta-galactosidase enzyme are discussed.


Causes of institutionalism: patient and staff perspectives.
Institutionalism is a pattern of passive, dependent behavior observed among psychiatric inpatients, characterized by hospital attachment and resistance to discharge. Survey research was conducted with 211 staff and 47 "institutionalized" patients in a public psychiatric hospital to determine their beliefs on the causes of institutionalism. Four explanatory models of institutionalism were investigated: the predisposition model, the total institution model, the asylum model, and the symptoms model. Patients and staff differed on all models. Responses indicated acceptance of multiple causes for the phenomenon, with patients and staff showing highest agreement on the need for hospitalization as asylum from the world. Patients and staff differed most on the role of the institution in promoting institutionalism. Job classification of staff also resulted in significant differences in beliefs on all models except the asylum model.


Downregulation of microRNA-324-3p inhibits lung cancer by blocking the NCAM1-MAPK axis through ALX4.
Lung cancer remains the principal cause of cancer-related death worldwide. As microRNAs (miRNAs) are critically involved in lung cancer, we investigated the potential role of miR-324-3p in lung cancer via the ALX4/NCAM1/MAPK axis. The expression of miR-324-3p and ALX4 was detected in clinical samples, and their interaction confirmed by miRNA-targeted luciferase reporter assay. The mechanisms involved in the miR-324-3p-ALX4 interaction in lung cancer cell biological processes were analyzed through gain- and loss-of function approaches. In addition, cultured lung cancer cells were treated with the p38MAPK pathway activator P79350 in order to explore the role of this pathway in the abovementioned axis. Further, a tumor xenograft model in nude mice was constructed to confirm the in vitro findings. miR-324-3p was highly expressed in lung cancer tissues and cells, and inhibited the expression of ALX4 in A549 cells. After confirming the targeted inhibition of ALX4 by miR-324-3p, we showed that this interaction upregulated the expression of NCAM1 and activated the MAPK pathway. The inhibition of miR-324-3p could suppress lung cancer cell invasion, migration, and autophagy, and retarded the growth of subcutaneous tumors in nude mice. Downregulation of ALX4 or NCAM1 overexpression reversed these favorable effects of decreased miR-324-3p. Our study demonstrated the promotive effect of miR-324-3p on the development and progression of lung cancer, thus suggesting a new target for treatment of this devastating disease.


Association between the IL1B -31C > T polymorphism and Helicobacter pylori infection in Asian and Latin American population: A meta-analysis.
Host genetic factors that control the production of cytokines, including interleukin-1β (IL-1β), possibly affect susceptibility to many Helicobacter pylori-related diseases. There is a complex interplay between H. pylori infection, the subsequent production of certain cytokines, and H. pylori-related diseases. We conducted a meta-analysis to clarify the association between the IL1B -31C > T polymorphism and H. pylori infection, and possible subsequent pathogenic mechanisms. Published literature contained within PubMed, Embase, and the Cochrane Library was used in our meta-analysis. Data were analyzed with the STATA 13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Egger's regression test, Begg's rank correlation test, and Begg's funnel plot were used to test publication bias. A total of 12 case-control studies comprising 5827 subjects (3335 cases and 2492 controls) were available for our meta-analysis. The IL1B -31C > T polymorphism was associated with an increased risk of H. pylori infection in Asian and Latin American population (TT + CT vs. CC, OR = 1.29, 95% CI = 1.14-1.46; TT vs. CT + CC, OR = 1.23, 95% CI = 1.09-1.39; TT vs. CC, OR = 1.43, 95% CI = 1.22-1.67; T allele vs. C allele, OR = 1.19, 95% CI = 1.10-1.29). A significant association was also found for all genetic models in various subgroups (cancer and no-cancer, hospital- and population-based). Our meta-analysis demonstrated that IL1B -31C > T polymorphism might increase H. pylori infection risk in Asian and Latin American population. Further studies with different ethnicities and larger sample size are required to validate this result.


Contrasting Patterns and Drivers of Soil Fungal Communities between Two Ecosystems Divided by the Treeline.
The treeline is a sensitive region of the terrestrial ecosystem responding to climate change. However, studies on the composition and formation mechanisms of soil fungal communities across the treeline are still lacking. In this study, we investigated the patterns of soil fungal community composition and interactions among functional guilds above and below the treeline using Illumina high-throughput sequencing and ecological network analysis. The results showed that there were significant differences in the soil environment and soil fungal community composition between the two ecosystems above and below the treeline. At the local scale of this study, geographic distance and environmental factors affected the composition of the soil fungal community. Soil temperature was an important environmental predictor of soil fungal community composition. Species in soil fungal communities in the subalpine meadow were more closely related to each other compared to those in the montane forest. Furthermore, the soil fungal community in montane forest was more stable. Our findings contribute to a better understanding of how mountain ecological functions respond to global climate change.


Intersex, infertility and the future: early diagnoses and the imagined life course.
Infertility is often recognised as a status that is medically identified in adulthood after unsuccessful attempts to conceive. This paper develops existing literature by illustrating how current conceptualisations of infertility do not incorporate a full range of experiences. Drawing on detailed, reflective diaries and in-depth interviews with five participants, I explore how infertility is experienced and understood by women with variations of sex characteristics (VSCs) or intersex traits. I argue that greater consideration needs to be applied to intersex people and the circumstances of an infertility status that may be received in infancy, childhood or adolescence, before or outside of attempts to conceive, and without undergoing fertility treatment. Through discussions of time and futurity, this paper seeks to explore how visions of the future coalesce with an infertile status that is received in combination with an atypical sex status early in life. The paper indicates that early infertility can hinder some intersex children and young people's ambitions. However, infertility is not understood to be pathological or consistently prohibitive throughout the lives of everyone affected. Intersex women's conceptions of a potentially childless future are varied, complex, ambivalent and, in some cases, transitional throughout the life course.


[Anomalies of the adenylate cyclase system in platelets of the SHR rat].
The hormone-sensitive adenylate cyclase system of plasma membrane is composed of at least three types of proteins: hormone receptors, activatory (Gs) and inhibitory (Gi) guanine nucleotide-regulatory proteins and the catalytic unit (C). Abnormal hormonal regulations of platelet adenylate cyclase in both humans and experimental animals have been reported to occur in hypertension. However, little is known about the mechanisms for these alterations. The aim of the present study was to compare the activity of C and the inhibitory capacity of Gi in platelet membranes from spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). Adenylate cyclase activity of 40,000 g membranes was assessed at pH 7.5 with 0.1 mM (alpha-32P) ATP and an appropriate bivalent cation (Mn2+ or Mg2+). Under incubation conditions that uncoupled C from Gs and Gi (25 mM MnCL2, 100 microM forskolin), a significantly lower adenylate cyclase activity was measured in membranes from SHR rats (2.07 +/- 0.12 vs 2.36 +/- 0.1 nmol cAMP/mn/mg of protein, p less than 0.05). This difference between the two strains was also observed in platelet homogenates. In a second kind of experiments, membranes were incubated with 2.1 mM MgCl2 instead of MnCl2. In both strains of rats, low concentrations of Gpp (NH)p (10 to 300 nM) inhibited adenylate cyclase activity when stimulated by 50 microM forskolin. However, the maximal extent of inhibition was significantly reduced in hypertensive rats (49.7 +/- 2.4 vs 60.5 +/- 2.3 p. 100, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Promising avenues of therapeutics for bipolar illness.
Basic scientific advances in understanding the neuropsychobiology of bipolar disorder have given us a multitude of opportunities to explore and exploit new avenues of therapeutics. Pharmacotherapeutic approaches include: neuropeptides (agonists such as thyrotropin-releasing hormone and antagonists such as corticotropin-releasing hormone), neurotrophic factors (especially brain-derived neurotrophic factor), and glutamatergic mechanisms (such as riluzole, ketamine, and antagonists of the NR-2B subunit of the glutamate receptor). Physiological interventions that would offer alternatives to electroconvulsive therapy include: repeated transcranial magnetic stimulation, especially at more intense stimulation parameters; magnetic stimulation therapy (seizures induced more focally by magnetic rather than electrical stimulation with resulting reduced meaning loss); vagal nerve stimulation, and deep brain stimulation. However, these, as well as the panoply of existing treatments, require further intensive investigation to place each of them in the proper therapeutic sequence and combination for the individual patient, based on development of better clinical and biological predictors of response. Large clinical trial networks and development of systematic research in clinical practice settings, such as that featured by the National Cancer Institute for cancer chemotherapy, would greatly accelerate the progress in incorporating new, as well as existing, agents into the best treatment strategies. The bipolar disorders, which are increasingly recognized as complex, highly comorbid conditions with a high morbidity and mortality, of which the majority start in childhood and adolescence, are not likely to respond completely to any single new treatment agent, and new public health initiatives and research strategies are needed as much as any new single treatment advance.


Non polymeric nanoparticles for photodynamic therapy applications: recent developments.
Photodynamic therapy has emerged as an alternative to chemotherapy and radiotherapy for cancer treatment. Nanoparticles have recently been proposed as effective carriers for photosensitizers. Depending on their chemical composition, these can be used for diagnosis and therapy due to the selective accumulation of the photosensitizer in cancer cells in vitro or in tumors in vivo. Multifunctional nanoplatforms combining several applications within the same nano-object emerge as potential important theranostic tools. This review, based on the chemical nature of the nanoparticles will discuss recent advances in the area of non polymeric nanoparticles for photodynamic therapy applications.


Fat grafting and platelet-rich plasma in wound healing: a review of histology from animal studies.
Stem cells could form the basis of a novel, autologous treatment for chronic wounds like diabetic foot ulcers. Fat grafts contain adipose-derived stem cells (ADSC) but low survival of cells within the grafts is a major limitation. Platelet-rich plasma (PRP) may increase graft survival. This review examines the histology from animal studies on fat grafting, ADSC and PRP in wound healing. A literature review of major electronic databases was undertaken, and narrative synthesis performed. Data from 30 animal studies were included. ADSC increase angiogenesis over 14 days and often clinically accelerated wound healing. ADSC had a greater effect in animals with impaired wound healing (e.g. diabetes). Activated PRP increased viability of fat grafts. Despite the high number of studies, the quality is variable which weakens the evidence. It does suggest there is a benefit of ADSC, particularly in impaired wound healing. High-quality evidence in humans is required, to establish its clinical usefulness.


Ultraviolet Photodetectors Based on Polymer Microwire Arrays toward Wearable Medical Devices.
Polymer micro/nanoarchitectures have attracted intense interest for wearable medical applications due to their excellent mechanical flexibility, solution processability, and tunable optoelectronic properties. Based on polymer micro/nanostructures, high-performance ultraviolet (UV) photodetectors can not only functionalize the accurate image sensing but also sustain the biocomfortable flexible devices for real-time health monitoring. The main challenges are focused on the integration of medical wearable devices, which requires large-scale assembly of polymer micro/nanostructures with controlled morphology and strict alignment. Herein, we utilized a confined assembly system through the cautious regulation for the growth of high-quality polymer 1D arrays. UV photodetectors based on these polymer microwire arrays perform a high on/off ratio of 137 and responsivity of 19.1 mA W-1. Polymer microarray photodetectors facilitate the scale-up fabrication of 14 × 18 multiplexed image sensors for highly accurate capturing the signals of Arabic numerals "1," "2," and "3." Flexible UV photodetectors based on these arrays present excellent flexibility and bending durability, maintaining 97% of their original on/off ratio after 4000 cycles with a 10 mm bending radius. UV photodetection signals were also collected from the attached flexible devices on the back skin of the mouse, demonstrating the great potential in wearable medical photodetection.


Oscillatory systems driven by noise: frequency and phase synchronization.
The phenomenon of effective phase synchronization in stochastic oscillatory systems can be quantified by an average frequency and a phase diffusion coefficient. A different approach to compute the noise-averaged frequency is put forward. The method is based on a threshold crossing rate pioneered by Rice. After the introduction of the Rice frequency for noisy systems we compare this quantifier with those obtained in the context of other phase concepts, such as the natural and the Hilbert phase, respectively. It is demonstrated that the average Rice frequency <omega>R typically supersedes the Hilbert frequency <omega>H, i.e. <omega>R > or = <omega>H. We investigate next the Rice frequency for the harmonic and the damped, bistable Kramers oscillator, both without and with external periodic driving. Exact and approximative analytic results are corroborated by numerical simulation results. Our results complement and extend previous findings for the case of noise-driven inertial systems.


[Resting state functional MRI in neurology and psychiatry].
Resting state functional magnetic resonance imaging (fMRI) is a neuroimaging technique based on analyzing spontaneous, low frequency fluctuations in the activity of brain areas by measuring by their MRI signal to investigate the functional architecture of the brain during rest. The use of resting state fMRI opens up possibilities for assessing brain functional relationships in both normal conditions and in different CNS pathologies in order to clarify the disturbed mechanisms of brain functioning and develop approaches for therapeutic non-invasive neuromodulation. Understanding the acquisition of data, the features of their preprocessing and analysis is very important for clinicians who use resting state fMRI in their studies, since it is neurologists, psychiatrists, and neurosurgeons who set research tasks and are the final consumers of the results. The article details the methodological features of obtaining and analyzing resting state fMRI data, the advantages and disadvantages of the method. The article is intended for a wide range of specialists using this method in their work or planning to include it in their research.


Mitochondrial transcription is regulated via an ATP "sensing" mechanism that couples RNA abundance to respiration.
The information encoded in both the nuclear and mitochondrial genomes must be coordinately regulated to respond to changes in cellular growth and energy states. Despite identification of the mitochondrial RNA polymerase (mtRNAP) from several organisms, little is known about mitochondrial transcriptional regulation. Studying the shift from fermentation to respiration in Saccharomyces cerevisiae, we have demonstrated a direct correlation between in vivo changes in mitochondrial transcript abundance and in vitro sensitivity of mitochondrial promoters to ATP concentration (K(m)ATP). Consistent with the idea that the mtRNAP itself senses in vivo ATP levels, we found that transcript abundance correlates with respiration, but only when coupled to mitochondrial ATP synthesis. In addition, we characterized mutations in the mitochondrial promoter and the mtRNAP accessory factor Mtf1 that alter both in vitro K(m)ATP and in vivo transcription in response to respiratory changes. We propose that shifting cellular pools of ATP coordinately control nuclear and mitochondrial transcription.


Ultrasound morphology of the Achilles in asymptomatic patients with and without diabetes.
The prevalence of tendinopathies is increased in subjects with diabetes mellitus. However, there are few data on the structural abnormalities of Achilles tendons in asymptomatic diabetic patients. The aim of the study was to assess the morphologic characteristics of the Achilles tendon in subjects with diabetes in comparison with controls without diabetes. Participants were consecutively recruited from an outpatient population. Ultrasound longitudinal and transverse scans were performed bilaterally along the full length of Achilles tendon from the musculotendinous junction to the insertion. Degenerative features (abnormal fibrillar pattern, hypo-hyperechoic areas), signs of enthesopathy (bony erosion, enthesophytes, and bursitis), and intratendinous neovessel formation were recorded. Asymptomatic sonographic abnormalities (ASA) were significantly increased in subjects with diabetes (35/136 [25.7%] vs 32/273 [11.7%], P = .0003). Sixty tendons with ASA were observed in the first group and 45 in the latter because ASA were bilateral in 25 and in 13 subjects, respectively. ASA were more frequently localized at the enthesis (32/60 [53.3%] vs 9/45 [20%], P = .0005) in the diabetes group, whereas, on the contrary, they were more prevalent at the midportion in controls (38/45 [84.4%] vs 36/60 [60%], P < .006). Diabetes may predispose to Achilles tendinopathy and particularly to Achilles enthesopathy. Longitudinal studies, evaluating the progression of the lesions not only in the midportion of the tendon but also at the insertion are needed to support this conclusion. Level III, comparative series.


Fibrous CdS/CdSe quantum dot co-sensitized solar cells based on ordered TiO2 nanotube arrays.
A new kind of fibrous quantum dot sensitized solar cell has been designed and fabricated by using CdS and CdSe co-sensitized TiO(2) nanotubes on Ti wire as the photoanode and highly active Cu(2)S as the counter electrode. By optimizing the CdSe deposition time and the length of the nanotube, a power conversion efficiency of 3.18% has been obtained under AM 1.5 illumination (100 mW cm(-2)). The potential application of this kind of solar cell has also been discussed in this paper.


p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase.
cdc2+ encodes a protein kinase that is required during both G1 and G2 phases of the cell division cycle in fission yeast. suc1+ is an essential gene that was originally identified as a plasmid-borne sequence that could rescue certain temperature-sensitive cdc2 mutants. To investigate the role of the suc1+ gene product in the cell cycle p13suc1 has been expressed in Escherichia coli and purified. An immunoaffinity purified anti-p13suc1 polyclonal serum has been prepared and used to identify p13suc1 in fission yeast. The abundance of this protein did not alter either during the cell cycle or during entry into stationary phase. p13suc1 was found in yeast lysates in a complex with the cdc2+ gene product. Approximately 5% of cellular p34cdc2 was associated with p13suc1, and this fraction of p34cdc2 was active as a protein kinase. The stability of the complex was disrupted in yeast strains carrying temperature-sensitive alleles of cdc2 that are suppressible by overexpression of suc1+. The level of association between p13suc1 and p34cdc2 was not affected by cell cycle arrest in adverse nutritional conditions. p13suc1 is not a substrate of the p34cdc2 protein kinase. We propose instead that it acts as a regulatory component of p34cdc2 that facilitates interaction with other proteins.


Oxidative response gene polymorphisms and risk of adult brain tumors.
Oxidative stress is believed to play a key role in tumor formation. Although this mechanism could be especially pertinent for brain tumors given the high oxygen consumption of the brain, very little has been published regarding brain tumor risk with respect to genes mediating oxidative stress. Using data from non-Hispanic whites in a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n=362), meningioma (n=134), and acoustic neuroma (n=69) compared to noncancer controls (n=494) with respect to nine single nucleotide polymorphisms from seven genes involved in oxidative stress response (CAT, GPX1, NOS3, PON1, SOD1, SOD2, and SOD3). We observed increased risk of glioma (odds ratio [OR](CT/CC)=1.3; 95% confidence interval [95% CI], 1.0-1.7) and meningioma (OR(CT/CC)=1.7; 95% CI, 1.1-2.7) with the C variant of SOD3 rs699473. There was also indication of increased acoustic neuroma risk with the SOD2 rs4880 Ala variant (OR(CT/CC)=2.0; 95% CI, 1.0-4.2) and decreased acoustic neuroma risk with the CAT rs1001179 T allele variant (OR(CT/TT)=0.6; 95% CI, 0.3-1.0). These relationships persisted when major groups of disease controls were excluded from the analysis. Our results suggest that common variants in the SOD2, SOD3, and CAT genes may influence brain tumor risk.


Craniofacial injuries from television tip-over.
Craniofacial injuries caused by television (TV) sets falling on small children are becoming a frequent event seen in emergency departments. Injuries occur primarily to the head and neck regions and range from contusions to intracerebral hemorrhage, which at times can be fatal. Epidemiology and potential complications from TV tip-over injuries are presented. Three cases of craniofacial injuries are described from blunt trauma incurred from TV tip-over events. It is important to teach parents about the dangers of the new large slim TV sets and the occurrence of injuries when these are not secured properly or placed away from the reach of the child.


[A case of adult pilocytic astrocytoma in the right temporal lobe].
A case of adult pilocytic astrocytoma in the right temporal lobe is reported here. The patient was a twenty-four year old man, who came to the neurological division of our hospital on October 6, 1987 because of repeated consciousness-loss attacks accompanied with uncinate fit. He had no neurological deficits. However, an EEG revealed spike-and-wave complexes in the right temporal region, and a CT scan showed a small cystic lesion in the right temporal lobe. A diagnosis of psychomotor seizure was made, and the administration of anticonvulsants was started. The incidence of attack then decreased, but after approximately two years of drug therapy the attacks increased again. A CT scan was again performed, and revealed that the lesion in the right temporal lobe was enlarging. Also a noticeable enhanced lesion, identified as a mural nodule was found in the post-contrast enhancement study. A brain tumor was then suspected, and he was admitted to the neurosurgical division on October 11, 1989. He had no neurological deficits on admission. An MRI showed a low intensity lesion in the T1 weighted image, and a high intensity lesion in the T2 weighted image. A cystic lesion with a marked enhanced mural nodule was also found in the base of the right temporal lobe, according to the Gd enhancement study. Perifocal edema was not recognized. Cerebral angiography showed no positive findings. Positron emission tomography (PET), using H2(15)O, revealed low perfusion at or around the lesion, and PET using [11C]-methionine revealed an accumulation of methionine at the lesion. A diagnosis of low-grade glioma was made, and a right temporal craniotomy, for the purpose of totally removing the tumor was performed on October 26, 1989.(ABSTRACT TRUNCATED AT 250 WORDS)


[Sleep-related respiratory disorders: from syndromes to risk factors].
In the past, sleep related breathing disorders (SRBD) have been described rather heterogeneously in terms of complex diseases, syndromes. During the past ten years, the relevant pathogenetic mechanisms of most of the SRBD could be defined, and data concerning their epidemiology were collected. Epidemiology and dangerousness being relevant criteria, the obstructive sleep apnea syndrome must be regarded as the most considerable SRBD. According to ICSD, the prevalence of a manifest obstructive sleep apnea syndrome is estimated at 1% of the entire population at least. Our measurings have shown that more than 10% of the middle-aged (20 to 60 years) male population suffer from 10 and more mixed obstructive apneas per hour of sleep. In this group, also the other pathogenetic factors for the obstructive sleep apnea syndrome, namely hyperventilation and fragmentation of sleep due to central arousal reactions, are found. All these patients snore, and there is a broad transition from primary snoring, which has no effects on the cardiovascular system and the blood gases, via obstructive snoring up to inter-apneic snoring. With the help of today's technical equipment, it is possible to determine the role of subclinical SRBDs in terms of risk factors, e.g. for cardiovascular diseases. We expect a plain contribution to the clearing up of instances of arterial hypertonus, early invalidity, and mortality.


Health-related quality of life in outpatients with primary central nervous system lymphoma after radiotherapy and high-dose methotrexate chemotherapy.
Chemoradiotherapy for primary central nervous system lymphoma (PCNSL) is associated with a considerable risk of long-term neurotoxicity. The present study aimed to assess the health-related quality of life (HRQOL) of outpatients with PCNSL who have received radiotherapy and high-dose methotrexate (HDMTX) chemotherapy, and to determine the factors that cause a decline in HRQOL and interfere with home living. A total of 37 patients were surveyed 0.9-14.2 years after their initial diagnosis and treatment. Each patient completed a multi-part HRQOL questionnaire that was used to examine the associations of HRQOL scores with leukoencephalopathy, Karnofsky performance status (KPS) scores, age, history of recurrence and HDMTX-based chemoradiotherapy. The results demonstrated that the history of recurrence, number of cycles of MTX chemotherapy and age affected the development of leukoencephalopathy. Reductions in KPS score were associated with a history of recurrence (P=0.03), but not with leukoencephalopathy (P=0.8). KPS score, leukoencephalopathy and age were significantly associated with a decline in HRQOL score. A decline in the HRQOL associated with a reduction in KPS score was also observed by multivariate analyses. Deterioration of the HRQOL among outpatients with PCNSL post-chemoradiotherapy was significantly associated with older age (≥66 years) and decreased KPS score. Older patients with a history of recurrence had a higher risk for deteriorated QOL due to development of leukoencephalopathy. Therefore, it is recommended that clinicians monitor the KPS score among outpatients with PCNSL. QOL examination for older patients with a lower KPS score was found to be particularly important for identifying any obstacles for home living.


Genome-wide analysis of wheat calcium ATPases and potential role of selected ACAs and ECAs in calcium stress.
P2- type calcium ATPases (ACAs-auto inhibited calcium ATPases and ECAs-endoplasmic reticulum calcium ATPases) belong to the P- type ATPase family of active membrane transporters and are significantly involved in maintaining accurate levels of Ca2+, Mn2+ and Zn2+ in the cytosol as well as playing a very important role in stress signaling, stomatal opening and closing and pollen tube growth. Here we report the identification and possible role of some of these ATPases from wheat. In this study, ACA and ECA sequences of six species (belonging to Poaceae) were retrieved from different databases and a phylogenetic tree was constructed. A high degree of evolutionary relatedness was observed among P2 sequences characterized in this study. Members of the respective groups from different plant species were observed to fall under the same clade. This pattern highlights the common ancestry of P2- type calcium ATPases. Furthermore, qRT-PCR was used to analyse the expression of selected ACAs and ECAs from Triticum aestivum (wheat) under calcium toxicity and calcium deficiency. The data indicated that expression of ECAs is enhanced under calcium stress, suggesting possible roles of these ATPases in calcium homeostasis in wheat. Similarly, the expression of ACAs was significantly different in plants grown under calcium stress as compared to plants grown under control conditions. This gives clues to the role of ACAs in signal transduction during calcium stress in wheat. Here we concluded that wheat genome consists of nine P2B and three P2A -type calcium ATPases. Moreover, gene loss events in wheat ancestors lead to the loss of a particular homoeolog of a gene in wheat. To elaborate the role of these wheat ATPases, qRT-PCR was performed. The results indicated that when plants are exposed to calcium stress, both P2A and P2B gene expression get enhanced. This further gives clues about the possible role of these ATPases in wheat in calcium management. These findings can be useful in future for genetic manipulations as well as in wheat genome annotation process.


Nearest-neighbor parameters for G.U mismatches: [formula; see text] is destabilizing in the contexts [formula; see text] and [formula; see text] but stabilizing in [formula; see text].
Thermodynamic parameters derived from optical melting studies are reported for duplex formation by a series of oligoribonucleotides containing G.U mismatches. The results are used to determine nearest-neighbor parameters for helix propagation by G.U mismatches. Surprisingly, the [formula; see text] nearest-neighbor free energy increment in unfavorable in the contexts [formula; see text], and [formula; see text] but favorable in the context [formula; see text]. This is a non-nearest-neighbor effect. In contrast, the [formula; see text] free energy increment is favorable and independent of context. Circular dichroism and imino proton NMR spectra of several sequences do not reveal an obvious structural basis for this dichotomy. For example, all the G.U mismatches have two slowly exchanging imino protons. The imino resonances for the G.U mismatches in GGAGUUCC, GUCGUGAC, and CCUGUAGG, however, broaden at lower temperature than the imino resonances for the interior Watson-Crick base pairs. In contrast, the imino resonances for the G.U mismatches in GGAUGUCC remain sharp at high temperature. The improved parameters for G.U mismatches should improve predictions of RNA structure from sequence.


Fatty infiltration of the liver: demonstration by proton spectroscopic imaging. Preliminary observations.
Two normal volunteers and three patients with CT evidence of fatty infiltration of the liver (two nonuniform, one diffuse) were studied to determine whether magnetic resonance imaging using a pulse sequence designed to differentiate fat and water could be used to detect fatty infiltration of the liver in human beings. The magnetic resonance technique used a modified spin echo technique (simple proton spectroscopic imaging) that was designed specifically to exploit the difference in the rate of precession between the protons in a water molecule and the protons in a fatty acid molecule. Images were obtained using in-phase and opposed techniques and were added or subtracted in order to obtain pure water and pure fat images. Quantitative data showed that fatty liver can be separated from normal liver using the spin echo technique, and that the opposed image of the proton spectroscopic technique is more sensitive to small changes in hepatic fatty content than in-phase images with any echo time.


Photodynamic therapy with verteporfin following transpupillary thermotherapy for CNV evolving from an initially occult to a predominantly classic form, in patients with AMD.
The purpose of this paper is to evaluate photodynamic therapy (PDT) in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) that converted from occult CNV to classic CNV after treatment with transpupillary thermotherapy (TTT). One hundred and fifty-four eyes of 130 patients with symptomatic occult CNV were treated between June 2000 and August 2001. We have analyzed data from patients treated with PDT because of a conversion from occult to classic CNV after TTT. The results were that twenty-four of 154 eyes developed a predominantly classic CNV; 20 eyes of 19 consecutive patients were treated with PDT with verteporfin. The mean follow-up period was 10 months. The mean delay for retreatment with TTT was 3 months; 3 eyes initially presented a pure occult CNV, 15 a minimally classic CNV, 1 an occult CNV with pigment epithelial detachment, and 1 a large macular subretinal hemorrhage with a subfoveal focal hot spot. The average classic component within a lesion before TTT was 20%. Recurrence of classic CNV was noted in the first 3 months for 14 eyes. Visual acuity improved in 5 eyes by >/=2 lines, and in 2 eyes by 1 line; 4 of 20 eyes had stabilized visual acuity; 7 eyes had a visual acuity decline of >/=2 lines; 2 eyes lost 1 line. All patients had reduction of metamorphopsia and reduction of exudation; 14 eyes had a little subretinal fibrosis and some partially atrophic areas; 6 eyes had slightly increased leakage in the late phase of the angiogram. In conclusion, association of TTT and PDT appears to be safe and may help practitioners to manage some difficult cases. This study seems to confirm the great efficacy of PDT in CNV with recent activity.


[Contribution of the Duke's classification in the emergency department in the early management of infective endocarditis].
The diagnosis of infective endocarditis is based on multiple clinical signs than on a single positive test result. The contribution of echocardiography is an indispensable asset to avoid misdiagnosis or delayed correct diagnosis. A 24-year old woman is admitted to the emergency room. She has a poor general condition, pyrexia and necrotic lesions on the body. After examination, the diagnosis of multiple organ failure and severe sepsis from infective endocarditis from intravenous injections of cocaine is made and the patient is transferred to ICU. She is treated with vancomycin for 4 weeks and gentamicin for 8 days. Her clinical improvement allows her to be transferred to a hospital unit at day 6. She goes home after 28 days of hospitalization. Several sets of criteria for the diagnosis of infective endocarditis are described. The most commonly accepted are revised Duke's criteria that take into account echocardiography. This article aims, through a clinical case, to describe this classification too little used in the emergency room.


The effect of co-dependent (thinking in motion [TIM]) versus single-modality (CogniFit) interventions on cognition and gait among community-dwelling older adults with cognitive impairment: a randomized controlled study.
Cognition and motor skills are interrelated throughout the aging process and often show simultaneous deterioration among older adults with cognitive impairment. Co-dependent training has the potential to ameliorate both domains; however, its effect on the gait and cognition of older adults with cognitive impairment has yet to be explored. The aim of this study is to compare the effects of the well-established single-modality cognitive computerized training program, CogniFit, with "Thinking in Motion (TIM)," a co-dependent group intervention, among community-dwelling older adults with cognitive impairment. Employing a single-blind randomized control trial design, 47 community-dwelling older adults with cognitive impairment were randomly assigned to 8 weeks of thrice-weekly trainings of TIM or CogniFit. Pre- and post-intervention assessments included cognitive performance, evaluated by a CogniFit battery, as a primary outcome; and gait, under single- and dual-task conditions, as a secondary outcome. CogniFit total Z scores significantly improved from baseline to post-intervention for both groups. There was a significant main effect for time [F (1, 44) = 17.43, p < .001, ηp2 = .283] but not for group [F (1, 44) = 0.001, p = .970]. No time X group interaction [F (1, 44) = 1.29, p = .261] was found. No changes in gait performance under single and dual-task performance were observed in both groups. The findings show that single-modality (CogniFit) and co-dependent (TIM) trainings improve cognition but not gait in older adults with cognitive impairment. Such investigations should be extended to include various populations and a broader set of outcome measurements. ACTRN12616001543471. Date: 08/11/2016.


Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran.
Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction-restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy-Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44-4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200-2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.


Unravelling the mystery of Nanga Parbat.
Since the disappearance of Günther Messner, brother of the world-famous mountaineer Reinhold Messner, on an expedition to Nanga Parbat in 1970, the circumstances of his death have given rise to controversy. Reinhold Messner claimed that he and Günther descended the Diamir face together when an avalanche killed his brother, while other expedition members argued that Günther was abandoned by Reinhold to descend the Rupal face. Now, 35 years after the event, Günther's remains have been found at the Diamir face and have been identified by forensic DNA fingerprinting. The location of the remains supports Messner's version, thus putting to rest one of the climbing communities' most publicised controversies.


The male sterile G cytoplasm of wild beet displays modified mitochondrial respiratory complexes.
Cytoplasmic male sterility (CMS) in higher plants has been mainly studied in cultivated species. In most cases, pollen abortion is linked to the presence of an additional mitochondrial polypeptide leading to organelle dysfunction in reproductive tissues. In wild beet, both CMS and hermaphrodite plants coexist in natural populations. The G cytoplasm is widely distributed along the Western European coast, and previous genetic studies have demonstrated that this cytoplasm confers male sterility in beet. In the present study, we have identified two mutations of G mitochondrial genes, each of which results in the production of a respiratory chain complex subunit with an altered molecular weight; the NAD9 subunit has a C-terminal extension while the COX2 subunit has a truncated C-terminus. NADH dehydrogenase activity was unchanged in leaves, but cytochrome c oxidase activity was reduced by 50%. Moreover, Western blot analyses revealed that alternative oxidase was more abundant in male sterile G plants than in a fertile control (Nv), suggesting that this alternative pathway might compensate for the cytochrome c oxidase deficiency. Implications of respiratory chain changes and a putative link with CMS are discussed.


Setting a standard for low reading proficiency: A comparison of the bookmark procedure and constrained mixture Rasch model.
In order to draw pertinent conclusions about persons with low reading skills, it is essential to use validated standard-setting procedures by which they can be assigned to their appropriate level of proficiency. Since there is no standard-setting procedure without weaknesses, external validity studies are essential. Traditionally, studies have assessed validity by comparing different judgement-based standard-setting procedures. Only a few studies have used model-based approaches for validating judgement-based procedures. The present study addressed this shortcoming and compared agreement of the cut score placement between a judgement-based approach (i.e., Bookmark procedure) and a model-based one (i.e., constrained mixture Rasch model). This was performed by differentiating between individuals with low reading proficiency and those with a functional level of reading proficiency in three independent samples of the German National Educational Panel Study that included students from the ninth grade (N = 13,897) as well as adults (Ns = 5,335 and 3,145). The analyses showed quite similar mean cut scores for the two standard-setting procedures in two of the samples, whereas the third sample showed more pronounced differences. Importantly, these findings demonstrate that model-based approaches provide a valid and resource-efficient alternative for external validation, although they can be sensitive to the ability distribution within a sample.


Z-DNA structure of a modified DNA hexamer at 1.4-A resolution: aminohexyl-5'-d(pCpGp[br5C]pGpCpG).
Oligonucleotides with modification at the 5'-end have been used for various biochemical applications. As a first step to better assess the effects of those modifications on DNA conformation, we determined at 1.4-A resolution the left-handed Z-DNA structure of a DNA hexamer, aminohexyl-5'-d(pCpGp[br5C]pGpCpG), by X-ray diffraction analysis. This hexamer was crystallized in the monoclinic C2 (a = 51.13 A, b = 18.44 A, c = 34.67 A, and beta = 120.9 degrees) space group. Its structure has been refined by the restrained least-squares refinement to a final R factor of 0.164 using 3727 [> 2.0 sigma (F)] observed reflections. The overall conformation of the double helix resembles that of the canonical Z-DNA. The terminal 5'-phosphate groups of the dC residues adopt conformations (beta approximately 180 degrees and gamma approximately 60 degrees) similar to phosphodiester's conformation of the internal dC residues. Two types of interhelical stackings are observed, one of which may serve as a model for a single-strand nick in the backbone of DNA double helix. A barium ion is found to bridge two side-by-side Z-DNA helices by coordinating to the O6 and N7 atoms of two guanines simultaneously. This "cross-linking" ability of barium ion may be a useful property in promoting the reversible aggregation of nucleic acids.


A mathematical model of hiPSC cardiomyocytes electromechanics.
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are becoming instrumental in cardiac research, human-based cell level cardiotoxicity tests, and developing patient-specific care. As one of the principal functional readouts is contractility, we propose a novel electromechanical hiPSC-CM computational model named the hiPSC-CM-CE. This model comprises a reparametrized version of contractile element (CE) by Rice et al., 2008, with a new passive force formulation, integrated into a hiPSC-CM electrophysiology formalism by Paci et al. in 2020. Our simulated results were validated against in vitro data reported for hiPSC-CMs at matching conditions from different labs. Specifically, key action potential (AP) and calcium transient (CaT) biomarkers simulated by the hiPSC-CM-CE model were within the experimental ranges. On the mechanical side, simulated cell shortening, contraction-relaxation kinetic indices (RT50 and RT25 ), and the amplitude of tension fell within the experimental intervals. Markedly, as an inter-scale analysis, correct classification of the inotropic effects due to non-cardiomyocytes in hiPSC-CM tissues was predicted on account of the passive force expression introduced to the CE. Finally, the physiological inotropic effects caused by Verapamil and Bay-K 8644 and the aftercontractions due to the early afterdepolarizations (EADs) were simulated and validated against experimental data. In the future, the presented model can be readily expanded to take in pharmacological trials and genetic mutations, such as those involved in hypertrophic cardiomyopathy, and study arrhythmia trigger mechanisms.


The interface between metabolic and stress signalling.
It is becoming increasingly clear that stress and metabolic signalling networks interact and that this interaction is important in plant responses to herbivory, pathogen attack, drought, cold, heat and osmotic stresses including salinity. At the interface between these two major signalling systems are the hormone abscisic acid (ABA) and signalling factors including protein kinases and transcription factors. This briefing reviews links between ABA, stress and sugar signalling, focusing on the roles of sucrose non-fermenting-1-related protein kinases (SnRKs), SnRK1-activating protein kinases (SnAKs), calcium-dependent protein kinases (CDPKs) and ABA response element binding proteins (AREBPs, which are transcription factors). Links between stress and nitrogen / amino acid signalling are also described, including the roles of a protein kinase called general control non-derepressible (GCN)-2 in regulating protein synthesis through phosphorylation of the alpha-subunit of translation initiation factor-2 (eIF2alpha) in response not only to decreases in amino acid levels but also to a range of stresses. Evidence of a link between sugar and amino acid signalling is explored, with nitrate reductase being a target for regulation by both SnRK1 and GCN2 through different mechanisms; possible links between SnRK1 and GCN2 via a pathway including the protein kinase target of rapamycin (TOR)-1 are described. The significance of these interactions to the concept of signalling networks as opposed to simple cascades and pathways, and the importance of the subject in the context of the predicted increase in severity and range of stresses that plants will have to withstand as a result of global climate change are discussed.


Respiratory health associated with exposure to automobile exhaust. II. Personal NO2 exposure levels according to distance from the roadside.
We have conducted several studies to investigate the effect of automobile exhaust on respiratory symptoms. This study was designed to explore differences in personal exposure levels among residents of zones located varying distances from trunk roads with heavy traffic in Tokyo. Personal nitrogen dioxide (NO2) concentration levels for residents and NO2 concentrations inside and outside the residences of each study participant were measured during ten seasons over three years. Three residential zones were determined as follows: Zone A was 0-20 m from the roadside; Zone B was 20-150 m; and Zone C, a reference zone, was a residential district in a suburban area. Approximately fifty residents were selected as the subjects of NO2 measurements. Study participants were female, between 40 and 60 years of age, and nonsmokers. All participants used gas cooking stoves with electric ignition. Outdoor NO2 concentrations in Zone A were always the greatest among the three zones during the study periods, and those in Zone C were consistently the lowest. Personal exposure levels in Zone A were generally higher than those in the other zones, and concentrations in Zone C were the lowest during seasons when no indoor heating was used. The highest mean values for personal exposure levels in Zones A, B, and C were 63.4, 61.0, and 55.3 ppb, respectively. In analyses in which participants were stratified by heater type, the mean personal exposure levels in Zone A were the highest and the levels in Zone C were the lowest for participants without unvented heaters; differences of NO2 levels between Zones A and C ranged from 10.0 to 23.9 ppb. When there were no indoor NO2 sources except gas cooking stoves, both indoor and personal levels of NO2 were attributable primarily to motor vehicle exhaust. In contrast, the use of unvented heaters during the heating seasons could cause NO2 exposures comparable to those attributable to motor vehicles.


In vitro susceptibility studies with oxiconazole (Ro 13-8996).
Oxiconazole (Ro 13-8996) is a recently described imidazole derivative intended for topical use. 128 isolates of pathogenic fungi were tested in vitro against oxiconazole, miconazole, and ketoconazole using an agar dilution method. Results indicated that miconazole was markedly more active than either oxiconazole or ketoconazole against Candida albicans while ketoconazole was the more active compound against Candida parapsilosis. A species specific difference in the susceptibilities of isolates of Aspergillus fumigatus and Aspergillus flavus to all three imidazoles with A. flavus being more susceptible was noted. Both Mucor and Rhizopus were more susceptible to oxiconazole than to either miconazole or ketoconazole. There were no noticeable differences among the dermatophytes in tests with the three drugs with all geometric mean minimum inhibition concentrations (MIC) being less than 1.0 micromilligram-1. The dematiaceous fungi also demonstrated no major differences in susceptibility to the three drugs. One isolate of Pseudallescheria boydii was relatively resistant to all three drugs (MIC greater than or equal to 16 micromilligrams-1).


Adenosquamous carcinoma of the skin: a report of 10 cases.
Cutaneous squamous carcinoma with true glandular differentiation has only rarely been documented. Ten patients with such tumors are presented. There were six men and four women, aged 48 to 87 years. The tumors were located on the central face (eight), scalp (one), and hand (one) and consisted of minimally elevated, indurated, keratotic plaques, up to 6 cm in size. Microscopically, the neoplasms exhibited multifocal origin from the epidermis; deep, dispersed, infiltrative growth; perineural invasion; and stromal desmoplasia. Squamous differentiation was most marked superficially. Glandular differentiation was more obvious in deeper areas. Lumens typically developed within squamous nests and were often lined by cells with cytoplasmic vacuoles, some of which contained mucin. The neoplastic cells had obvious cytologic atypia and easily identified mitotic figures. Immunohistochemically, nine neoplasms studied contained carcinoembryonic antigen in glandular foci. Each patient had one or more surgical resections, and six also received radiation and/or chemotherapy. Five patients died with uncontrolled local recurrence, and two are alive with extensive disease and clinical evidence of regional lymph node involvement. Two individuals with small, superficial neoplasms that could be completely removed are disease free. One patient died of unrelated causes shortly after diagnosis. Cutaneous adenosquamous carcinoma is more aggressive than the usual carcinoma of the skin. It must be distinguished from the cytologically bland, microcystic adnexal (sclerosing sweat duct) carcinoma which is capable of recurring but rarely, if ever, proves fatal. The question of whether adenosquamous carcinoma is an epidermally derived squamous tumor with divergent differentiation or should be viewed as a newly recognized adnexal carcinoma remains to be resolved.


LC-MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin.
Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities. Recently, it has been brought into focus for its potential to treat liver failure. In this study, a rapid and sensitive liquid chromatography electrospray-ionization tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of linarin and its three metabolites (acacetin, apigenin, and p-hydroxy benzaldehyde) in plasma and liver tissue samples of normal rats and rats with d-galactosamine (d-GalN)-induced liver injury. After liquid-liquid extraction (LLE) with ethyl acetate, chromatographic separation of the four analytes was achieved using an ACQUITY UPLC BEH-C18 (1.7 μm, 2.1 × 50 mm) with a mobile phase of 0.01% formic acid in methanol and 0.01% formic acid at a flow rate of 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the negative ionization mode. The method had a good linearity over the concentration range of 1.00-200 ng/mL for linarin and its metabolites. The validated method was successfully applied to the pharmacokinetic and liver tissue distribution study of linarin and its metabolites after a single oral administration of linarin (90 mg/kg) to rats.


[Artificial illness as a result of non-medical use of anabolic androgenic steroids: A case report and a review of literature].
A 42-year-old female body builder who had used anabolic androgenic steroids (AASs) for 18 years to build up muscle mass died from liver rupture. The cause of the latter was multiple abscesses caused by Actinomyces, which developed in the presence of immunodeficiency. The postmortem changes in different organs were due to hormonal imbalance. The paper gives the data available in the literature pertaining to the analysis of the effects of AASs taken in supraphysiological doses on the body and their non-medical application.


The Role of the Plant Antioxidant System in Drought Tolerance.
Water deficiency compromises plant performance and yield in many habitats and in agriculture. In addition to survival of the acute drought stress period which depends on plant-genotype-specific characteristics, stress intensity and duration, also the speed and efficiency of recovery determine plant performance. Drought-induced deregulation of metabolism enhances generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which in turn affect the redox regulatory state of the cell. Strong correlative and analytical evidence assigns a major role in drought tolerance to the redox regulatory and antioxidant system. This review compiles current knowledge on the response and function of superoxide, hydrogen peroxide and nitric oxide under drought stress in various species and drought stress regimes. The meta-analysis of reported changes in transcript and protein amounts, and activities of components of the antioxidant and redox network support the tentative conclusion that drought tolerance is more tightly linked to up-regulated ascorbate-dependent antioxidant activity than to the response of the thiol-redox regulatory network. The significance of the antioxidant system in surviving severe phases of dehydration is further supported by the strong antioxidant system usually encountered in resurrection plants.


Toxicity and bioaccumulation of the wood preservative copper dimethyldithiocarbamate in tissues of Long-Evans rats.
This study examined the toxicity and accumulation of copper in the livers and kidneys of Long-Evans rats after a subacute exposure to copper dimethyldithiocarbamate (CDCC) wood preservative. CDDC was recently introduced as an alternative to chromated copper arsenate (CCA) preserved wood. Female rats (220-270 g) were treated with 0, 25, 50, or 75 mg/kg CDDC by oral gavage for 3 wk. Light microscopy revealed that higher doses of CDDC induced diffuse necrosis and a loss of sinusoids in the livers of Long-Evans rats with vacuolization in the highest dose. Rats treated with 25 mg/kg CDDC displayed a thickening of the basement membrane of Bowman's capsule and the mesangium. Exposure to higher CDDC concentrations (50 and 75 mg/kg) showed moderate to marked expansion of the mesangial matrix and glomerular necrosis with an overall loss of glomerular structure seen in the highest dose. The concentration of copper was significantly increased in the tissues of animals exposed to CDDC in a dose-dependent manner. Western blot analysis revealed the induction of the stress protein Hsp70 and the formation of 4-hydroxy-2-nonenal (4HNE) adducts in liver and renal tissues, indicating peroxidative damage. CDDC was shown to be toxic to the livers and kidneys, at all doses used, and this toxicity is related to peroxidative insult.


Usefulness of dual echo volumetric isotropic turbo spin echo acquisition (VISTA) in MR imaging of the temporomandibular joint.
We investigated the ability to detect the articular disk and joint effusion of the temporomandibular joint (TMJ) of a method of dual echo volumetric isotropic turbo spin echo acquisition (DE-VISTA) additional fusion images (AFI). DE-VISTA was performed in the 26 TMJ of 13 volunteers and 26 TMJ of 13 patients. Two-dimensional (2D) dual echo turbo spin echo was performed in the 26 TMJ of 13 volunteers. On a workstation, we added proton density-weighted images (PDWI) and T2 weighted images (T2WI) of the DE-VISTA per voxel to reconstruct DE-VISTA-AFI. Two radiologists reviewed these images visually and quantitatively. Visual evaluation of the articular disk was equivalent between DE-VISTA-AFI and 2D-PDWI. The sliding thin-slab multiplanar reformation (MPR) method of DE-VISTA-AFI could detect all articular disks. The ratio of contrast (CR) of adipose tissue by the articular disk to that of the articular disk itself was significantly higher in DE-VISTA-AFI than DE-VISTA-PDWI (P<0.05) in patients and volunteers with closed or open mouth. In volunteers, the CR between adipose tissue and the disk on DE-VISTA-AFI was marginally significant to that on 2D-PDWI at opened mouth (P=0.071) and not significantly different (P=0.18) from that at closed mouth. Joint effusion could be identified in DE-VISTA-AFI in all 8 joints that had joint effusion in DE-VISTA-T2WI but in only 3 of those joints in 2D-T2WI. The CR of joint effusion to adipose tissue on DE-VISTA-AFI did not differ significantly from that on DE-VISTA-PDWI. However, using DE-VISTA-T2WI in addition to DE-VISTA-PDWI, we could visually identify joint effusion on DE-VISTA-AFI that could not be identified on DE-VISTA-PDWI alone. DE-VISTA-AFI can depict the articular disk and a small amount of joint effusion by the required plane of MPR using the sliding thin-slab MPR method.


Watery and dark axons in Wallerian degeneration of the opossum's optic nerve: different patterns of cytoskeletal breakdown?
In this paper we report a qualitative morphological analysis of Wallerian degeneration in a marsupial. Right optic nerves of opossums Didelphis marsupialis were crushed with a fine forceps and after 24, 48, 72, 96 and 168 hours the animals were anaesthetized and perfused with fixative. The optic nerves were immersed in fixative and processed for routine transmission electron microscopy. Among the early alterations typical of axonal degeneration, we observed nerve fibers with focal degeneration of the axoplasmic cytoskeleton, watery degeneration and dark degeneration, the latter being prevalent at 168 hours after crush. Our results point to a gradual disintegration of the axoplasmic cytoskeleton, opposed to the previous view of an "all-or-nothing" process (Griffin et al 1995). We also report that, due to an unknown mechanism, fibers show either a dark or watery pattern of axonal degeneration, as observed in axon profiles. We also observed fibers undergoing early myelin breakdown in the absence of axonal alterations.