[Effects of non-ionogenic surface active compounds on yeast protoplasts].
The lytic effect of non-ionogenic surface active compounds (SAC), based on polyoxyethylated fatty acids and alkylphenols on the yeast protoplast cytoplasmic membranes and the extracting ability of the SAC with respect to intracellular proteins of intact yeast cells, were studied. It was shown that the lytic activity of the SAC under study depends on the overall effect of the size of their hydrophobic and hydrophylic fragments rather than on the level of the hydrophylic-lypolytic equilibrium of SAC. The absence of correlation between the lytic activity and the extracting ability of SAC is accounted for by the differences in the mechanisms of membrane degradation under the action of SAC on the protoplasts and intact cells. The data obtained support the previously made assumption that the correlation between the size of SAC mycelles and that of the cell wall pores is the limiting factor of the SAC induced protein extraction from the intact cells.


Copper and lead concentrations in salt marsh plants on the Suir Estuary, Ireland.
Concentrations of Cu and Pb were determined in the roots and shoots of six salt marsh plant species, and in sediment taken from between the roots of the plants, sampled from the lower salt marsh zone at four sites along the Suir Estuary in autumn 1997. Cu was mainly accumulated in the roots of monocotyledonous and dicotyledonous species. Pb was mainly accumulated in the roots of monocotyledons, while dicotyledons tended to accumulate Pb in the shoots. In the case of Aster tripolium there was a clear differentiation in the partitioning of Pb within the plant, between low and high salinity sites. At the low salinity sites, Pb accumulated only in the roots while at the high salinity sites there was a marked translocation to the shoots. The increase in Pb concentrations in roots and shoots of A. tripolium was accompanied by a concomitant decrease in sediment concentrations of Pb. This inverse correlation between sediment and plant concentrations of Pb was also recorded for Spartina spp. and Schoenoplectus tabernaemontani but in the case of these species the roots contained higher concentrations of Pb regardless of salinity levels. These differences in accumulation of Cu and Pb in various salt marsh species, and the influence of salinity on the translocation of Pb in A. tripolium in particular, should be taken into account when using these plants for biomonitoring purposes.


Value of whole-body magnetic resonance imaging for screening multifocal osteonecrosis in patients with polymyositis/dermatomyositis.
To assess the value of coronal short-tau inversion recovery whole-body MRI (STIR-WBMRI) for screening osteonecrosis in patients with polymyositis (PM)/dermatomyositis (DM). The imaging and medical records of 129 patients with PM/DM who met the Bohan and Peter diagnostic criteria were retrospectively analyzed. STIR-WBMRI was performed in all patients. 18 patients had follow-up STIR-WBMRI. 12 patients underwent regional knee and/or hip MRI while 25 patients underwent radiography of the lower extremities. STIR-WBMRI detected osteonecrosis in 15 (11.6%) patients. 38 joints were affected (mean, 2.5 per patient; range, 1-5 joints). Of the 38 joints affected by osteonecrosis, 33 had no clinical symptoms. Among the 12 patients who underwent regional MRI, STIR-WBMRI detected all 10 osteonecrotic sites seen on the regional MRI. The location, shape and size of the osteonecrotic lesions revealed on regional MRI were in accordance with those displayed on STIR-WBMRI. Of the 15 patients with osteonecrosis, 6 performed routine radiography of the affected joints and revealed no osteonecrotic lesions. Follow-up WBMRI detected new osteonecrosis in two patients whose first WBMRI revealed that there was no osteonecrosis in any skeleton. In addition to displaying muscle inflammation, STIR-WBMRI can efficiently detect early multifocal osteonecrosis in the whole bodies of patients with PM/DM. Advances in knowledge: In patients with PM/DM, WBMRI which takes 12-15 min can display muscular involvement and detect early multisite osteonecrosis in the whole body at the same time. Osteonecrotic lesions revealed by WBMRI are in accordance with those displayed on regional WBMRI.


Transformation between continuous and discrete representations of images: a perceptual approach.
The transformation of image signals between the continuous domain of the real world and the discrete domain of modern data processing can have a significant effect on quality and efficiency. Analysis based on perceptual rather than mathematical considerations has been carried out. A series of experiments based on the analysis has shown that substantial improvement over usual techniques can be achieved by the use of a cascade of a presharpening filter combined with Gaussian presampling and interpolation filters. The resulting ``sharpened Gaussian'' filter, although not exactly circularly symmetrical, gives a high degree of isotropy. Each element in the cascade is separable, so that computational efficiency is high. A favorable tradeoff is achieved among sharpness, smoothness, and the effects of aliasing. Subjective testing, in comparison with other commonly used filters, has shown the clear superiority of this filter.


The evolution of genetic canalization under fluctuating selection.
If the direction of selection changes from generation to generation, the ability to respond to selection is maladaptive: the response to selection in one generation leads to reduced fitness in the next. Because the response is determined by the amount of genetic variance expressed at the phenotypic level, rapidly fluctuating selection should favor modifier genes that reduce the phenotypic effect of alleles segregating at structural loci underlying the trait. Such reduction in phenotypic expression of genetic variation has been named "genetic canalization." I support this argument with a series of two- and multilocus models with alternating linear selection and Gaussian selection with fluctuating optimum. A canalizing modifier gene affects the fitness of its carriers in three ways: (1) it reduces the phenotypic consequences of genetic response to previous selection; (2) it reduces the genetic response to selection, which is manifested as linkage disequilibrium between the modifier and structural loci; and (3) it reduces the phenotypic variance. The first two effects reduce fitness under directional selection sustained for several generations, but improve fitness when the direction of selection has just been reversed. The net effect tends to favor a canalizing modifier under rapidly fluctuating selection regimes (period of eight generations or less). The third effect improves fitness of the modifier allele if the fitness function is convex and reduces it if the function is concave. Under fluctuating Gaussian selection, the population is more likely to experience the concave portion of the fitness function when selection is stronger. Therefore, only weak to moderately strong fluctuating Gaussian selection favors genetic canalization. This paper considerably broadens the conditions that favor genetic canalization, which so far has only been postulated to evolve under long-term stabilizing selection.


Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation.
Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block. The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation. We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts. H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade. Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation.


Ultrastructural tissue morphometry of the distribution of extracellular matrix vesicles in remodeling rat tibial bone six days after injury.
A study of the distribution of extracellular matrix vesicles on the 6th day of bone healing was performed by methods of transmission electron microscopy combined with computerized morphometry. The vesicles were detected on the electron micrographs and grouped according to their diameters, distance from the calcified front and type. The different types were selected as follows: vesicles with electron-lucent contents, i.e., 'empty'; vesicles with amorphous electron-opaque contents, i.e., 'amorphous'; vesicles containing crystalline depositions, i.e., 'crystal', and vesicles containing crystalline structures with ruptured membranes, i.e., 'rupture'. Most of the vesicles were concentrated between diameters of 0.02 and 0.22 microns. Most of the vesicles were found within a distance of less than 3 micron from the calcified front. The vesicles were distributed according to their types: 'empty', 'amorphous', 'crystal' and 'rupture' in 14, 39, 34 and 13%, respectively. The diameters of the 'crystal' and 'rupture' vesicles were significantly larger than those of the 'empty' and 'amorphous' types. The sequence of distances from the calcified front was recorded as follows: 'rupture', 'crystal', 'amorphous' and 'empty', the 'rupture' type being the closest to the front. The results of the present study confirm the accepted hypothesis on calcification via extracellular matrix vesicles. It is thought that the cell secretes 'empty' vesicles that accumulate amorphous Ca and P to form a hydroxy-apatite crystal. This is followed by rupture of the vesicular membrane. The propagation of the process is accompanied by increase in the vesicular diameter and its approximation to the calcifying front.


Fecal microbiota transplantation in the treatment of Clostridium difficile infection: state of the art and literature review.
Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection.


Hypoxia stimulates proliferation of human hepatoma cells through the induction of hexokinase II expression.
In a hypoxic state, a glycolytic system is operating as a salvage pathway of generating ATP, and hexokinase II, the first enzyme in this system, might be over-expressed in hepatocellular carcinomas (HCCs). This study was to evaluate if hexokinase II is participating in HCC cell survival in a hypoxic state, and to analyze the mechanism of cell death caused by hexokinase II-specific inhibition. Human hepatoma cell lines were grown either in a normoxic or hypoxic condition. Hexokinase II and hypoxia-inducible factor-1alpha (HIF-1alpha) expression were evaluated using immunoblot techniques. Cell growth was assessed using the MTS assay. Apoptotic signaling cascades were explored by immunoblot analysis. Hypoxia stimulated HCC cellular growth through HIF-1alpha-dependent induction of hexokinase II expression. The hexokinase II-specific inhibitor, 3-bromopyruvate, significantly suppressed cellular growth in a hypoxic state compared to cells in a normoxic condition. This suppression was due to the induction of apoptosis through activating mitochondrial apoptotic signaling cascades. This study demonstrates that hypoxia stimulates HCC cellular growth through hexokinase II induction, and its inhibition induces apoptotic cell death. Therefore, hexokinase II induction may participate in HCC progression and the blockage of this enzyme may therapeutically be efficacious in human HCCs.


Hepatic tumors: a continuous challenge to achieve further improvements.
Bucharest (Romania) hosted this year's annual meeting of the International Association of Surgeons, Gastroenterologists and Oncologists. The president of the Congress was Irinel Popescu of the University of Bucharest (Romania) and the meeting was held under the auspices of the International Association of Surgeons, Gastroenterologists and Oncologists president Masatoshi Makuuchi (Japanese Red Cross Medical Center, Tokyo, Japan) and its general secretary, Nicolas J Lygidakis (Athens Medical Center, Greece). The organizing committee of the Congress has made considerable efforts to promote the globalization of medical knowledge and to maintain the values of Médecins Sans Frontières. The Congress was a model of scientific professionalism, and was attended by more than 850 delegates. Approximately 250 specialists from 43 countries on five continents described their most recent advances, providing the delegates with an intense and very rich program. The program included symposia, video presentations, free papers and poster presentations. This article highlights the newest and most original results concerning the treatment of liver tumors, particularly in cirrhotic patients.


Anemia among Adult Diabetic Patients Attending a General Hospital in Eastern Ethiopia: a Cross-sectional Study.
Although anemia is a common condition among patients with diabetes mellitus, there is little evidence on anemia among this segment of population in Ethiopia at large and in the study setting in particular. Thus, this study aimed at assessing the magnitude of anemia and its associated factors among adult diabetic patients attending a general hospital in Eastern Ethiopia. A health facility-based cross-sectional study was conducted among 325 randomly selected adult diabetes mellitus patients attending a follow-up clinic at Gelemso General Hospital, Eastern Ethiopia. Data were collected through an interview using a pre-tested and structured questionnaire followed by physical and laboratory measurements. Data were then entered into EpiData Version.3.1 and analyzed by using STATA version 16.0. Binary logistic regression models were fitted to identify factors associated with anemia. All statistical tests were declared significant at p-value < 0.05. The magnitude of anemia among adult diabetic patients was 30.2% (95% confidence interval (CI): 25.4%-35.4%). Anemia was higher in males (36%) than females (20.5%). Male gender (Adjusted Odds Ratio (AOR) = 2.1, 95% CI: 1.2, 3.8), DM duration of ≥5 years (AOR= 1.9, 95% CI: 1.0, 3.7), presence of comorbidity (AOR= 1.9, 95% CI: 1.0, 3.7), and having diabetic complications (AOR= 2.3, 95% CI: 1.3, 4.2) were significantly associated with anemia. Anemia was a moderate public health problem among adult DM patients in the study setting. Being male in gender, duration of DM, presence of DM complications, and DM co-morbidities were factors associated with anemia. Therefore, routine screening and appropriate management of anemia targeting males, DM patients with longer duration of DM, and those with complications and co-morbidities should be devised to improve patients' quality of life. Early diagnosis and regular monitoring of DM could also help to minimize further complications.


Laparoscopic paraesophageal hernia repair.
The last 2 decades have witnessed a revolution in the treatment of patients with paraesophageal hernia (PEH). Nowadays, the laparoscopic repair with fundoplication is considered as the primary treatment modality in most academic centers for symptomatic patients. Three findings have clearly emerged: (1) this procedure is technically demanding; (2) it is associated with relief of symptoms in most patients; and (3) most recurrences are small and asymptomatic. This article describes our approach step-by-step to the repair of a paraesophageal hiatal hernia, focusing on several technical controversies.


Skeletal muscle blood flow responses to hypoperfusion at rest and during rhythmic exercise in humans.
We evaluated the contribution of changes in systemic arterial pressure and local vasodilation to blood flow restoration in contracting human muscles during acute hypoperfusion. Healthy subjects (n=10) performed rhythmic forearm exercise (10% and 20% of maximum) while a balloon in the brachial artery located above the elbow was inflated. Each trial included 3 min of rest, exercise, exercise with balloon inflation, and exercise after balloon deflation. Forearm blood flow (FBF) was measured using Doppler ultrasound. Blood pressure on both sides of the balloon was measured using a brachial artery catheter (distal pressure), and Finometer for proximal (systemic) arterial pressure. Balloon inflation during exercise reduced distal arterial pressure, and FBF fell 37-41%. There was also a surprising acute increase in forearm vascular resistance (distal pressure/FBF). This was followed by recovery of distal arterial pressure and forearm vasodilation that caused a marked (approximately 75%) restoration of flow that was not associated with significant changes in systemic arterial pressure. During validation trials (n=6) at rest and with exercise both balloon and brachial artery diameters were stable when the balloon was inflated. Our findings indicate that at these exercise intensities 1) the restoration of FBF during exercise with hypoperfusion relied primarily on local dilator responses in conjunction with restoration of distal perfusion pressure likely as a result of increased collateral flow around the elbow, and 2) a loss of pulsatile flow and elastic recoil in the forearm may have contributed to the acute increase in vascular resistance seen at the onset of hypoperfusion.


Enhancement of Fracture Toughness of Epoxy Nanocomposites by Combining Nanotubes and Nanosheets as Fillers.
In this work the fracture toughness of epoxy resin has been improved through the addition of low loading of single part and hybrid nanofiller materials. Functionalised multi-walled carbon nanotubes (f-MWCNTs) was used as single filler, increased the critical strain energy release rate, GIC, by 57% compared to the neat epoxy, at only 0.1 wt% filler content. Importantly, no degradation in the tensile or thermal properties of the nanocomposite was observed compared to the neat epoxy. When two-dimensional boron nitride nanosheets (BNNS) were added along with the one-dimensional f-MWCNTs, the fracture toughness increased further to 71.6% higher than that of the neat epoxy. Interestingly, when functionalised graphene nanoplatelets (f-GNPs) and boron nitride nanotubes (BNNTs) were used as hybrid filler, the fracture toughness of neat epoxy is improved by 91.9%. In neither of these hybrid filler systems the tensile properties were degraded, but the thermal properties of the nanocomposites containing boron nitride materials deteriorated slightly.


Use of neuroimaging to measure neurocognitive engagement in health professions education: a scoping review.
To map the current literature on functional neuroimaging use in medical education research as a novel measurement modality for neurocognitive engagement, learning, and expertise development. We searched PubMed, Embase, Cochrane, ERIC, and Web of Science, and hand-searched reference lists of relevant articles on April 4, 2019, and updated the search on July 7, 2020. Two authors screened the abstracts and then full-text articles for eligibility based on inclusion criteria. The data were then charted, synthesized, and analyzed descriptively. Sixty-seven articles published between 2007 and 2020 were included in this scoping review. These studies used three main neuroimaging modalities: functional magnetic resonance imaging, functional near-infrared spectroscopy, and electroencephalography. Most of the publications (90%, n = 60) were from the last 10 years (2011-2020). Although these studies were conducted in 16 countries, 68.7% (n = 46) were from three countries: the USA (n = 21), UK (n = 15), and Canada (n = 10). These studies were mainly non-experimental (74.6%, n = 50). Most used neuroimaging techniques to examine psychomotor skill development (57%, n = 38), but several investigated neurocognitive correlates of clinical reasoning skills (22%, n = 15). This scoping review maps the available literature on functional neuroimaging use in medical education. Despite the heterogeneity in research questions, study designs, and outcome measures, we identified a few common themes. Included studies are encouraging of the potential for neuroimaging to complement commonly used measures in education research and may help validate/challenge established theoretical assumptions and provide insight into training methods. This review highlighted several areas for further research. The use of these emerging technologies appears ripe for developing precision education, establishing viable study protocols for realistic operational settings, examining team dynamics, and exploring applications for real-time monitoring/intervention during critical clinical tasks.


[Prevention of Cardiovascular Events: Are All Recommendations Applicable to Elderly Patients With Senile Asthenia?]
Primary prevention of cardiovascular events is based on achievement of optimal control of risk factors - arterial hypertension, dyslipidemia, glycemia - in accordance with current recommendations of scientific societies. But most rapidly growing segment of population - elderly and old individuals - have been underrepresented in randomized clinical trials underlying recommendations on primary and secondary prevention. That is why it is problematic to directly apply recommendations to patients from this group of population. In addition, old patients are characterized by accumulation of functional deficits, development of syndrome of senile asthenia ("frailty"), and multimorbidity. Effect of these characteristics on prognosis often exceeds that of risk factors. Other important factor is high susceptibility of old patients to risk of development of unfavorable effects because of both changes of pharmacokinetics and pharmacodynamics of drugs and the need for multiple medicines (polypragmasy). While applying existing recommendations to old people one should recognize limitations of current knowledge on best ways of realization of approaches to prevention of cardiovascular prevention which effectiveness has been proved in younger individuals. Improvement of awareness and development of special skills of physicians involved in management of old patients is required for timely detection of the syndrome of senile asthenia. Special geriatric approaches should be implemented in cooperation with specialists in geriatric medicine.


Simplification of complex physiologically based pharmacokinetic models of monoclonal antibodies.
Monoclonal antibodies (mAbs) exhibit biexponential profiles in plasma that are commonly described with a standard two-compartment model with elimination from the central compartment. These models adequately describe mAb plasma PK. However, these models ignore elimination from the peripheral compartment. This may lead to underestimation of the volume of distribution of the peripheral compartment and thus over-predicts concentration in the peripheral compartment. We developed a simple and physiologically relevant model that incorporates information on binding and dissociation rates between mAb and FcRn receptor, mAb uptake, reflection, and catabolic degradation. We employed a previously published PBPK model and, with assumptions regarding rates of processes controlling mAb disposition, reduced the complex PBPK model to a simpler circular model with central, peripheral, and lymph compartments specifying elimination from both central and peripheral. We successfully applied the model to describe the PK of an investigational mAb. Our model presents an improvement over standard two-compartmental models in predicting whole-body average tissue concentrations while adequately describing plasma PK with minimal complexity and physiologically more meaningful parameters.


Deciphering the synergistic effects of photolysis and biofiltration to actuate elimination of estrogens in natural water matrix.
The presence of estrogens in water environments has raised concerns for human health and ecosystems balance. These substances possess potent estrogenic properties, causing severe disruptions in endocrine systems and leading to reproductive and developmental problems. Unfortunately, conventional treatment methods struggle to effectively remove estrogens and mitigate their effects, necessitating technological innovation. This study investigates the effectiveness of a novel sequential photolysis-granular activated carbon (GAC) sandwich biofiltration (GSBF) system in removing estrogens (E1, E2, E3, and EE2) and improving general water quality parameters. The results indicate that combining photolysis pre-treatment with GSBF consistently achieved satisfactory performance in terms of turbidity, dissolved organic carbon (DOC), UV254, and microbial reduction, with over 77.5 %, 80.2 %, 89.7 %, and 92 % reduction, respectively. Furthermore, this approach effectively controlled the growth of microbial biomass under UV irradiation, preventing excessive head loss. To assess estrogen removal, liquid chromatography-tandem mass spectrometry (LC-MS) measured their concentrations, while bioassays determined estrogenicity. The findings demonstrate that GSBF systems, with and without photolysis installation, achieved over 96.2 % removal for estrogens when the spike concentration of each targeted compound was 10 µg L-1, successfully reducing estrogenicity (EA/EA0) to levels below 0.05. Additionally, the study evaluated the impact of different thicknesses of GAC layer filling (8 cm, 16 cm, and 24 cm) and found no significant difference (p>0.05) in estrogen and estrogenicity removal among them.


Adult cerebral malaria in Zambia: preliminary report of clinical findings and treatment response.
Fifty-six adult patients diagnosed as having 'cerebral malaria' were admitted and treated over a 4 month period. The presenting symptoms were similar to those of control patients with malaria without cerebral manifestations except that vomiting and convulsions were significantly more frequent and joint pains were less frequent in the cases than in the controls. Physical examination revealed significantly more frequent occurrence of nuchal rigidity, positive Kernig's sign, confusion, muteness, pallor and jaundice in the cases than controls, while splenomegaly was significantly more common in controls than cases. Laboratory data showed that cerebral malaria cases had significantly lower haemoglobin and significantly higher reticulocyte count and erythrocyte sedimentation rate than controls. There was no significant difference in the parasite density between the cases and controls. All patients were treated with 200 mg base of intravenous chloroquine in 250 ml of isotonic saline infused over 2 h and repeated 12 hourly till oral therapy was possible. This proved to be efficacious and the recovery rate was over 90%. Five patients died and the diagnosis was confirmed in three in whom autopsy was permitted. A simple staging system is proposed which retrospectively seems to have prognostic value. It is recommended that the validity of this system be tested prospectively.


A2A adenosine receptors from rat striatum and rat pheochromocytoma PC12 cells: characterization with radioligand binding and by activation of adenylate cyclase.
Binding assays and assays of activation of adenylate cyclase with the agonists 5'-N-ethylcarboxyamidoadenosine (NECA) and CGS21680 have been used to compare adenosine receptors in rat pheochromocytoma PC12 cells and in rat striatum. The [3H]NECA binding showed two components, whereas [3H]CGS21680 bound to one component in both tissues. The Kd value for the high affinity site labeled with [3H]NECA in PC12 cell membranes (2.3 nM) was lower than that in striatum (6.5 nM). The [3H]CGS21680 binding site showed a Kd value of 6.7 nM and 11.3 nM in PC12 cells and striatum, respectively. In the presence of GTP the KD values of [3H]NECA and [3H]CGS21680 for the high affinity site were increased severalfold, whereas the low affinity sites for [3H]NECA were no longer detected with filtration assays. A comparison of the ability of a series of agonists and antagonists to inhibit high affinity binding of [3H]NECA to A2 receptors in PC12 cell and striatal membranes indicated that agonists had higher affinities and antagonists had lower affinities in PC12 cells, compared with affinities in striatal membranes. Analysis of activation of adenylate cyclase in PC12 cell membranes suggested that the dose-dependent stimulation by NECA involved two components, whereas CGS21680 stimulated via one component. The maximal stimulation by NECA significantly exceeded that caused by CGS21680. In intact PC12 cells, NECA caused a greater accumulation of AMP than did CGS21680, as was the case in membranes. In striatal membranes, NECA and CGS21680 showed similar maximal stimulations of adenylate cyclase. Both NECA and CGS21680 were more potent in PC12 cell membranes than in striatal membranes, in agreement with binding data. However, in contrast to binding data, antagonists were not less potent versus stimulation of adenylate cyclase by NECA or CGS21680 in PC12 cell membranes, compared with striatal membranes. In toto, the results suggest that A2A receptors in striatum are virtually identical to the A2A receptors in PC12 cells. But, in addition to an A2A receptor, it appears that a lower affinity functional receptor, probably an A2B receptor, is present in PC12 cells and PC12 cell membranes, whereas such a functional low affinity receptor is not detectable in striatal membrane.


Isolation, characterization, and biological activity of retinyl phosphate from hamster intestinal epithelium.
Epithelial cells from hamster small intestine, in short term culture, incorporated [carbinol-14C]retinol into a compound that is identical to synthetic retinyl phosphate, as judged by chromatography on DEAE-cellulose, silicic acid, and thin layers of silica gel. The biological compound displays the same absorption spectrum as does synthetic retinyl phosphate with a maximum at 325 nm. Hydrolysis with mild alkali yields anhydroretinol, as it does for synthetic retinyl phosphate, with absorption maxima at 388, 368, and 346 nm. Enzymic hydrolysis by alkaline phosphatase releases 9% of the radioactivity as [14C]retinol. Under the same conditions, 9% of synthetic retinyl phosphate is hydrolyzed to retinol. The biological compound was tested for biological activity. At a concentration of 5.5 x 10-8 M it was as active as retinol and retinyl phosphate in reversing keratinization induced in hamster tracheal epithelium by vitamin A deficiency. It is concluded that hamster intestinal cells synthesize retinyl phosphate.


The rest-dependent depression of action potential duration in rabbit myocardium and the possible role of the transient outward current. A pharmacological analysis.
A pharmacological approach has been used to investigate the mechanism of the action potential depression after a 1 min rest in rabbit myocardium. This paradoxical depression was not prevented by potentiators of the slow inward current (isoproterenol and 5'-guanylylimidodiphosphate). This depression was completely removed by a specific blocker of the transient outward current, 4-aminopyridine. It appears reasonable to assume that rabbit ventricular fibers have a transient outward current and the activation of this current coupled to the masking of the slow inward current probably accounts for the depression of the rested action potential plateau phase.


Optimal cut-off values of BMI, waist circumference and waist:height ratio for defining obesity in Chinese adults.
It has not been established which specific measures of obesity might be most appropriate for predicting CVD risk in Asians. The objectives of the present study were to determine the associations of BMI, waist circumference (WC) and waist:height ratio (WHtR) with CVD risk factors and to evaluate the optimal cut-off values to define overweight or obesity in Chinese adults. Data collected from seven nationwide health examination centres during 2008 and 2009 were analysed. The BMI, WC and WHtR of 244 266 Chinese adults aged ≥ 20 years included in the study were measured. Logistic regression models were fit to evaluate the OR of each CVD risk factor according to various anthropometric indices. Receiver operating characteristic (ROC) analyses were conducted to assess the optimal cut-off values to predict the risk of diabetes, hypertension, dyslipidaemia and the metabolic syndrome. WHtR had the largest areas under the ROC curve for all CVD risk factors in both sexes, followed by WC and BMI. The optimal cut-off values were approximately 24·0 and 23·0 kg/m2 for BMI, 85·0 and 75·0 cm for WC, and 0·50 and 0·48 for WHtR for men and women, respectively. According to well-established cut-off values, BMI was found to be a more sensitive indicator of hypertension in both men and women, while WC and WHtR were found to be better indicators of diabetes and dyslipidaemia. A combination of BMI and central obesity measures was found to be associated with greater OR of CVD risk factors than either of them alone in both sexes. The present study demonstrated that WHtR and WC may be better indicators of CVD risk factors for Chinese people than BMI.


Whole blood folate concentrations: comparison between Stratus Folate (DADE) and radioassay (DPC) methods.
The analytical performance of the Stratus Folate assay for intra-erythrocyte folate determination in normal subjects and in patients affected by folate-related diseases was compared with that of the radioassay (DPC) routinely employed by us. Folate concentrations were measured in freshly obtained EDTA whole blood from 100 subjects. Haemolysis was performed with the appropriate lysis reagent. In addition, to compare two different haemolysis procedures folate determination was carried out in 51 samples haemolysed according to the two procedures in parallel. Data were analyzed using Wilcoxon's test and standardized principal component analysis. Stratus Folate assay and radioassay performances were comparable in terms of analytical characteristics as well as in individual intraerythrocyte folate values across the range of whole blood concentrations examined in the survey. Significant differences were detected between the two different haemolysis procedures only for the radioassay. In conclusion, we observed no significant differences between the two folate determination methods despite their different analytical principles, which indicates the suitability of routine use of the automated non-isotopic Stratus Folate assay for clinical purposes. Moreover, with the latter assay the laboratory staff could choose the more convenient haemolysis procedure.


Range of confidence scale and consumer knowledge calibration.
The study examined the effect of range of a confidence scale on consumer knowledge calibration, specifically whether a restricted range scale (25%-100%) leads to difference in calibration compared to a full range scale (0%-100%), for multiple-choice questions. A quasi-experimental study using student participants (N = 434) was employed. Data were collected from two samples; in the first sample (N=167) a full range confidence scale was used, and in the second sample (N = 267) a restricted range scale was used. No differences were found between the two scales on knowledge calibration. Results from studies of knowledge calibration employing restricted range and full range confidence scales are thus comparable.


Cost-effectiveness of docetaxel in high-volume hormone-sensitive metastatic prostate cancer.
Three pivotal trials have considered the addition of docetaxel (D) chemotherapy to conventional androgen-deprivation therapy (ADT) for the treatment of metastatic hormone- sensitive prostate cancer (HSPC). While an initial small trial was inconclusive, two larger trials demonstrated significant clinical benefit, including pronounced survival benefits (added 17 months) among patients with high-volume metastatic disease. Given the evolving clinical evidence, the cost-effectiveness of this approach warrants exploration. The cost-effectiveness of six cycles of ADT+D compared to ADT alone to treat patients with high-volume metastatic HSPC was assessed from a Canadian public payer perspective. We included three health states: HSPC, metastatic castration-resistant prostate cancer (CRPC), and death. Survival data were obtained from the CHAARTED trial, which reported outcomes specifically for high-volume disease. We used Ontario costs data and utilities from the literature. In the base case analysis, ADT+D cost an additional $25 757 and produced an extra 1.06 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of $24 226/QALY gained. Results from one-way sensitivity analysis across wide ranges of estimates and a range of scenarios, including an alternate model structure, produced ICERs below $35 000/QALY gained in all cases. The use of D with ADT in high-volume metastatic HSPC appears to be an economically attractive treatment approach. The findings were consistent with other studies and robust in sensitivity analysis across a variety of scenarios.


Less is better than more with resection of periacetabular tumors - A retrospective 16 years study and literature review.
Wide resections of periacetabular tumors create a sizeable bony defect that inevitably results in severe loss of function. Reconstruction of such defects usually requires using large metal implants, a feature associated with considerable surgery extension and complications. The aim of this study is to report resection with no reconstruction of the bony defect. In this retrospective study, we reviewed a consecutive series of 16 patients diagnosed with malignant periacetabular tumors and underwent en-bloc resection without reconstructing their remaining bone defect. Records were reviewed of 16 consecutive patients diagnosed with malignant periacetabular tumors and underwent en-bloc resection without reconstructing their remaining bony defect. Measurements included: the duration of surgery, blood loss, hemoglobin levels and the need for blood transfusions, data on other hospitalization characteristics, and intraoperative and postoperative complications. Sixteen patients with malignant periacetabular bone tumors and extensive bone destruction underwent wide periacetabular tumor resection with a mean follow-up of 75 months and a mean age of 53 years. The average HOOS score was 46 (range: 20 to 76), and the mean MSTS score was 13% (range: 0 to 15). The mean operative time was 4.1 h, and the mean blood loss was 1200 ml. At their most recent follow-up, patients had a mean shortening of their operated extremity of 4.8 cm, and all could ambulate with assisting devices. Wide resection of periacetabular tumors without reconstruction provides acceptable levels of function and was associated with shorter surgical time, less blood loss and fewer postoperative complications compared to resection with reconstruction. Therefore, this approach may be considered a viable surgical option in patients with an extensive malignant periacetabular. Retrospective study.


RDX loss in a surface soil under saturated and well drained conditions.
On military training ranges, low-order, incomplete detonations deposit RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) into surface soils. In this study, we evaluated RDX biodegradation in surface soils obtained from a military training range in Alaska. Two factors were compared: (i) soil water potential during the incubations; and (ii) the use of acetonitrile (ACN) as an RDX carrier to spike samples. Organic solvents have been used in laboratory studies to dissolve slightly water-soluble contaminants before addition to soil. We added ACN to obtain final soil ACN concentrations of 0 mg kg(-1) (0%), 1000 mg kg(-1) (0.1%) and 10 000 mg kg(-1) (1%). We then compared RDX attenuation in the soil under saturated and unsaturated conditions. RDX fell below the limit of detection within 3 wk of study initiation under the saturated condition. A maximum degradation rate of 0.15 mg RDX L(-1) d(-1) was measured. Under the unsaturated condition, 42% of the original RDX was still present at study termination (5 wk). The addition of acetonitrile at 0.1 or 1.0% had no affect on RDX loss in the saturated soil. In the unsaturated soil, however, ACN at 1.0% inhibited RDX loss by as much as 25%. These findings indicate that soil water potential and carrier solvent concentrations can impact the rate and extent to which RDX is attenuated in a surface soil.


Shiga toxin-producing Escherichia coli isolates from cases of human disease show enhanced adherence to intestinal epithelial (Henle 407) cells.
Shiga toxin-producing Escherichia coli (STEC) strains are a diverse group of organisms which are known to cause diarrhea and hemorrhagic colitis in humans. We have recently described a large food-borne outbreak of STEC disease caused by contaminated semidry fermented sausage (A. W. Paton, R. Ratcliff, R. M. Doyle, J. Seymour-Murray, D. Davos, J. A. Lanser, and J. C. Paton, J. Clin. Microbiol. 34:1622-1627, 1996). STEC strains belonging to several O serotypes were isolated from the contaminated food source, but of these, only a subset were isolated from patients with diarrhea or hemolytic-uremic syndrome (HUS). In the present study, we characterized these STEC isolates with respect to the presence of putative virulence-associated genes and the capacity to adhere to a human intestinal epithelial cell line (Henle 407). The O111:H- STEC strain 95NR1 (isolated from one of the outbreak HUS patients) was shown to adhere to Henle 407 cells in a dose-dependent, mannose-resistant fashion. Microscopic examination revealed a diffuse pattern of adherence for this as well as several other STEC strains. Interestingly, the adherence of STEC strains from HUS cases (both outbreak related and sporadic) was significantly greater than that of STEC strains found in the contaminated food source but not found in any patients. These studies support the hypothesis that an enhanced capacity to adhere to intestinal cells is one of the factors which distinguishes human-virulent STEC strains from those of lesser clinical significance.


Transcranial direct current stimulation modulates the spinal plasticity induced with patterned electrical stimulation.
Patterned sensory electrical stimulation (PES) has been shown to induce plasticity in spinal reciprocal Ia inhibition of the calf muscles. To study the cortical modulation of spinal plasticity, we examined the effects of giving transcranial direct current stimulation (tDCS) to the motor cortex before PES. Seven healthy volunteers participated in this study. PES involved stimulating the left common peroneal nerve at the fibular head with a train of 10 pulses at 100 Hz every 1.5s for 20 min using an intensity equal to the motor threshold of the tibialis anterior. tDCS was applied for 10 min before PES. For anodal stimulation, the electrode was placed over the motor cortex, and the cathodal electrode over the contralateral supraorbital area. For cathodal stimulation, the electrodes were reversed. Reciprocal inhibition was assessed using a soleus H reflex conditioning-test paradigm. PES increased disynaptic reciprocal inhibition from the peroneal nerve to the soleus H reflex. When cathodal tDCS was applied before PES, PES no longer increased reciprocal inhibition. Applying tDCS before PES modulated the effects of PES on spinal reciprocal inhibition in a polarity specific manner. We suggest that the motor cortex may play a role in spinal plasticity.


Six Candidate miRNAs Associated With Early Relapse in Pediatric B-Cell Acute Lymphoblastic Leukemia.
Few studies have evaluated the role of miRNAs in pediatric acute lymphoblastic leukemia (ALL) relapse and a consensus of a clinically significant miRNA signature is yet to be identified. In this study, we evaluated miRNAs associated with pediatric B-ALL early relapse in two independent sample sets. We performed global miRNA profiling on diagnostic bone marrow specimens from six early relapse (≤3 years after diagnosis) and six age- and cytogenetics-matched prolonged remission (≥4 years) patients (first set) and an independent set of 14 early relapse and 14 matched prolonged remission specimens (second set). Twelve and 39 top differentially expressed miRNAs were observed in the first and second sets, respectively; however, there was no overlap between the top candidates. In post-hoc analyses six miRNAs (miR-101-3p, miR-4774-5p, miR-1324, miR-631, miR-4699-5p and miR-922) among the top candidates in the second, but not the first set, were consistently upregulated in early relapse compared to remission specimens in both first (fold change=1.13-2.19, q<0.38) and second (fold change=1.48-4.78, all q<0.05) sets. Four (miR-631, mir-101-3p, miR-922 and miR-1324) of these miRNAs have been previously implicated in key functional oncogenic pathways in adult cancers. This study suggests that six candidate miRNAs, not previously implicated in pediatric ALL, are associated with early relapse in pediatric B-ALL. Validation and investigation of mechanistic roles of these miRNAs in a larger cohort are warranted, so that they may be used as prognostic markers for early relapse of pediatric B-ALL.


Independent prognostic value of high-risk ventricular premature complexes during exercise or recovery in asymptomatic patients: A meta-analysis of observational studies.
Ventricular premature contractions (VPCs) are a common finding during cardiac stress tests. The independent prognostic value of these findings in patients in asymptomatic patients is unclear. We conducted a systematic review and meta-analysis of observational studies exploring the independent prognostic value of VPCs to predict all-cause mortality. The secondary outcome was cardiovascular (CV) mortality. We excluded studies that did not report outcomes after adjusting for ≥1 confounder. Random effect meta-analyses were used to predict cumulative hazard ratios. We stratified results based on VPC during exercise or recovery. We found 7 studies with 24,518 patients that met our inclusion criteria. Two studies reported all-cause mortality only, 1 study reported CV mortality only, rest 4 reported both. There was significant heterogeneity in the baseline population, definition of high-risk VPCs, and variables used in adjusted models. Using multivariable summary estimates from individual studies, only VPCs during exercise were associated with a higher risk of all-cause mortality (HR 1.27, 95 % CI 1.07, 1.48). Both VPCs during exercise and recovery were associated with a higher risk CV mortality (HR 1.69, 95 % CI 1.19, 2.20, I2 = 17.6 % and 1.62, 95 % CI 1.25, 2.00, p < 0.001 for both). High-risk VPCs during exercise is associated with increased risk of all-cause and CV mortality, while those during recovery are associated with an increased risk of CV mortality only.


Non-carious cervical lesions associated with gingival recessions: a decision-making process.
A method to predetermine the maximum root coverage level (MRC) was recently demonstrated to be reliable in predicting the position of the soft tissue margin after root coverage surgery. The aim of the present study is to suggest a decision-making process for treating non-carious cervical lesions (NCCLs) associated with gingival recessions based upon the topographic relationship between the MRC and NCCL and to assess patient and independent-periodontist esthetic evaluations. Five treatments were performed in 94 patients with NCCLs associated with a single gingival recession: 1) coronally advanced flap (CAF); 2) bilaminar procedure; 3) coronal odontoplasty plus restoration plus root odontoplasty plus CAF; 4) restoration plus CAF; and 5) restorative therapy. Clinical and esthetic evaluations made by the patient and an independent periodontist were done 1 year after treatments. The satisfaction of the patient and periodontist with esthetics was very high in all NCCL treatments and Miller Class gingival recessions. The patient satisfaction and evaluation of root coverage and the periodontist evaluation of root coverage were statistically correlated with color-match evaluations and not with the amount of root coverage clinically achieved in each patient. The proposed approaches provided good esthetic appearance and correct emergence profile for the great majority of NCCLs associated with gingival recessions.


Synergies and compromises between charge and energy transfers in three-component organic solar cells.
In this paper, we developed different three-component organic heterojunction structures supported by PET/ITO substrates with the aim to study the possible synergies and/or compromises between charge transfer (CT) and energy transfer (ET) processes in organic solar cells (OSCs). As components, we employed poly(3-hexylthiophene-2,5-diyl) (P3HT; donor), [6,6]-phenyl-C61-butyric acid methyl ester (PCBM; acceptor) and poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) that is known to give good ET to P3HT. At first, we observed that in a planar heterojunction (PHJ) solar cell, F8BT has to be properly located in between P3HT and PCBM to get a cascade energy level configuration allowing for a better CT and power conversion efficiency. Then, we observed that by producing a P3HT:F8BT blend, the energy transfer process can be improved in the P3HT:F8BT/PCBM active layer. This may enable decreasing the thickness of the active layer while maintaining a similar PCE that is very interesting for the development of transparent OSCs. However, the P3HT:F8BT blend limits the P3HT-PCBM CT with respect to a P3HT/F8BT/PCBM PHJ, showing that a compromise between CT and ET is needed to get a higher PCE or higher transparency. By the above approach, in this paper, we developed highly transparent heterojunction structures for solar cell devices with PCEs comparable to those observed from the colorful reference P3HT/PCBM PHJ solar cells on PET/ITO substrates.


Residents' perceptions of an integrated longitudinal curriculum: a qualitative study.
The purpose of this study was to explore family medicine residents' perceptions of a newly restructured integrated longitudinal curriculum. A purposeful sample of 16 family medicine residents participated in focus group interviews conducted from a grounded theory perspective to identify the characteristics of this training model that contribute to and that challenge learning. Eight key themes were identified: continuity of care, relevance to family medicine, autonomy, program-focused preparation, professional development as facilitated by role modeling, patient volume, clarity of expectations for learners, and logistics. Positive learning experiences were marked by high levels of autonomy, continuity, and relevance to family medicine. Less favorable learning experiences were characterized by limited opportunities for continuity of care, limited relevance to family medicine practice and unclear expectations for the resident's role. Family physician-led learning experiences contributed to residents' understanding of the full scope of family medicine practice, more so than specialist-led experiences. The logistics of implementing the integrated block were challenging and negatively impacted continuity and learning. This study suggests that an integrated longitudinalized family medicine block training model has the potential to support the principles of a longitudinal integrated competency-based curriculum to effectively prepare residents for family medicine practice.


Kinetic analysis of subunit oligomerization of the legume lectin soybean agglutinin.
The reconstitution of soybean agglutinin (SBA), a tetrameric GalNAc/Gal-specific legume lectin, after denaturation in urea has been studied using fluorescence, far-UV CD, a hemagglutination assay, and chemical cross-linking with glutaraldehyde as a bifunctional reagent. The reconstituted protein exhibits similar quaternary structure and activity as of native lectin. The kinetics of subunit oligomerization has been determined from the cross-linking reaction of the reconstituting protein followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Monomers and tetramers could be quantitatively analyzed during reconstitution. Dimers are not detectable. The reassociation reaction follows second-order kinetics. The results are described by a kinetic mechanism in which the monomer-to-dimer association (characterized by a second-order rate constant (k(1)) of 1.4 x 10(4) M(-1) s(-1) at 37 degrees C) is involved in the rate-determining step of the oligomerization reaction.


Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects.
Inhaled corticosteroids (ICSs) are the preferred treatment for achieving asthma control. However, little is known regarding the factors contributing to treatment response and whether treatment response differs by population group. We sought to assess behavioral, sociodemographic, and genetic factors related to ICS response among African American and European American subjects with asthma. Study participants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). The analytic sample included asthmatic subjects aged 12 to 56 years with greater than 12% bronchodilator reversibility and percent predicted FEV1 of between 40% and 90%. Participants received 6 weeks of inhaled beclomethasone dipropionate. The primary measure of ICS response was a change in Asthma Control Test (ACT) score; the secondary measure was a change in prebronchodilator FEV1. Adherence was measured with electronic monitors. Genetic ancestry was estimated for African American participants by using genome-wide genotype data. There were 339 study participants; 242 self-identified as African American and 97 as European American. Baseline ACT score, percent predicted FEV1, degree of bronchodilator response, and ICS adherence were significantly associated with ICS response. A baseline ACT score of 19 or less was useful in identifying those who would respond, as evidenced by the significant dose-response relationship with ICS adherence. Neither self-reported race-ethnicity among all participants nor proportion of African ancestry among African American participants was associated with ICS responsiveness. Our findings suggest that baseline lung function measures and self-reported asthma control predict ICS response, whereas self-reported race-ethnicity and genetic ancestry do not.


An Adaptive, Situation-Based Risk Assessment and Security Enforcement Framework for the Maritime Sector.
Maritime processes involve actors and systems that continuously change their underlying environment, location and threat exposure. Thus, risk mitigation requires a dynamic risk assessment process, coupled with an adaptive, event driven security enforcement mechanism, to efficiently deal with dynamically evolving risks in a cost efficient manner. In this paper, we propose an adaptive security framework that covers both situational risk assessment and situational driven security policy deployment. We extend MITIGATE, a maritime-specific risk assessment methodology, to capture situations in the risk assessment process and thus produce fine-grained and situation-specific, dynamic risk estimations. Then, we integrate DynSMAUG, a situation-driven security management system, to enforce adaptive security policies that dynamically implement security controls specific to each situation. To validate the proposed framework, we test it based on maritime cargo transfer service. We utilize various maritime specific and generic systems employed during cargo transfer, to produce dynamic risks for various situations. Our results show that the proposed framework can effectively assess dynamic risks per situation and automate the enforcement of adaptive security controls per situation. This is an important improvement in contrast to static and situation-agnostic risk assessment frameworks, where security controls always default to worst-case risks, with a consequent impact on the cost and the applicability of proper security controls.


Adverse Events of Intravesical OnabotulinumtoxinA Injection between Patients with Overactive Bladder and Interstitial Cystitis--Different Mechanisms of Action of Botox on Bladder Dysfunction?
Intravesical onabotulinumtoxinA (BoNT-A) injections have been proposed to treat both overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) in patients with refractory conditions. We compared adverse events (AEs) after BoNT-A treatment between IC/BPS and OAB in women. IC/BPS patients who failed conventional treatments were enrolled to receive suburothelial injections of BoNT-A (100 U) followed by hydrodistention. Age matched OAB female patients refractory to antimuscarinic agents underwent BoNT-A (100 U) injections. The bladder capacity, maximum flow rate (Qmax), post-void residual (PVR), and voiding efficiency (VE) at baseline, 3 and 6 months, and the post-treatment AEs were analyzed between groups. Finally, 89 IC/BPS and 72 OAB women were included. In the OAB group, the bladder capacity and PVR increased, and VE decreased significantly at three and six months after BoNT-A treatment. In the IC/BPS group, the Qmax increased significantly at six months. There were significant differences in changes of capacity, Qmax, PVR and VE between the two groups. Moreover, OAB patients suffered more frequently from events of hematuria, UTI, and large PVR (>200 mL), but less frequently from events of straining to void. In conclusion, OAB women had higher PVR volume and lower VE than those in IC/BPS after BoNT-A injections. These results imply that the bladder contractility of OAB patients are more susceptible to BoNT-A, which might reflect the different mechanisms of action of Botox on bladder dysfunction. Further investigations to confirm this hypothesis are warranted.


Local delivery of nicotine does not mitigate fibrosis but may lead to angiogenesis.
As with most implanted biomaterials, the wound healing response following implantation of a silicone breast implant leads to the formation of a fibrotic capsule. This can result in capsular contracture, a painful complication that often necessitates the removal of implant. It is well established that nicotine and nicotinic agonists inhibit inflammatory signaling. Based on the link between the inflammatory response and capsule formation, we hypothesized that local delivery of nicotine from the implant may lead to the reduction in inflammation and capsule thickness, which may ultimately reduce the incidence of capsular contracture. Nicotine was loaded into PDMS membranes using a previously established method. The loaded materials were implanted into the submammary pockets between the third and fourth mammary glands of rats. To confirm that the nicotine was acting locally and not systemically, serum cotinine, the primary metabolite of nicotine, was measured by ELISA at 3 days. Thirty days post implantation, the animals were euthanized and the tissue samples were fixed for histological analysis. Blood vessel density was measured immunohistochemically, while the capsule thickness was evaluated microscopically. While the presence of the nicotine metabolite, cotinine, in the serum at the early time points demonstrated that the nicotine was released locally from the devices, there were no significant differences in the capsule thickness between the control and experimental implants. However, the results indicated that there were differences in angiogenesis with the local delivery of nicotine, which may have other implications for the development of biomaterials.


"ALS reversals": demographics, disease characteristics, treatments, and co-morbidities.
To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with "amyotrophic lateral sclerosis (ALS) reversals" and those with typically progressive ALS. Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure. Controls were participants in the Pooled Resource Open-Access ALS Clinical Trials database and the National ALS Registry. Cases and controls were compared using descriptive statistics. ALS reversals were more likely to be male, have limb onset disease, and initially progress faster. The prevalences of myasthenia gravis (MG) and purely lower motor neuron disease in cases were higher than estimates of these prevalences in the general population. The odds of taking curcumin, luteolin, cannabidiol, azathioprine, copper, glutathione, vitamin D, and fish oil were greater for cases than controls. When compared to patients with typically progressive ALS, patients with reversals differed in their demographics, disease characteristics, and treatments. While some of these patients may have had a rare antibody-mediated ALS mimicker, such as atypical myasthenia gravis, details of their exams, EMGs and family histories argue that this was unlikely. Instead, our data suggest that ALS reversals warrant evaluation for mechanisms of disease resistance and that treatments associated with multiple ALS reversals deserve further study.


Community analysis reveals close affinities between endophytic and endolichenic fungi in mosses and lichens.
Endolichenic fungi live in close association with algal photobionts inside asymptomatic lichen thalli and resemble fungal endophytes of plants in terms of taxonomy, diversity, transmission mode, and evolutionary history. This similarity has led to uncertainty regarding the distinctiveness of endolichenic fungi compared with endophytes. Here, we evaluate whether these fungi represent distinct ecological guilds or a single guild of flexible symbiotrophs capable of colonizing plants or lichens indiscriminately. Culturable fungi were sampled exhaustively from replicate sets of phylogenetically diverse plants and lichens in three microsites in a montane forest in southeastern Arizona (USA). Intensive sampling combined with a small spatial scale permitted us to decouple spatial heterogeneity from host association and to sample communities from living leaves, dead leaves, and lichen thalli to statistical completion. Characterization using data from the nuclear ribosomal internal transcribed spacer and partial large subunit (ITS-LSU rDNA) provided a first estimation of host and substrate use for 960 isolates representing five classes and approximately 16 orders, 32 families, and 65 genera of Pezizomycotina. We found that fungal communities differ at a broad taxonomic level as a function of the phylogenetic placement of their plant or lichen hosts. Endolichenic fungal assemblages differed as a function of lichen taxonomy, rather than substrate, growth form, or photobiont. In plants, fungal communities were structured more by plant lineage than by the living vs. senescent status of the leaf. We found no evidence that endolichenic fungi are saprotrophic fungi that have been "entrapped" by lichen thalli. Instead, our study reveals the distinctiveness of endolichenic communities relative to those in living and dead plant tissues, with one notable exception: we identify, for the first time, an ecologically flexible group of symbionts that occurs both as endolichenic fungi and as endophytes of mosses.


Honest olfactory ornamentation in a female-dominant primate.
Sexual selection theory predicts that potential mates or competitors signal their quality to conspecifics. Whereas evidence of honest visual or vocal signals in males abounds, evidence of honest signalling via scent or by females is scarce. We previously showed that scent marks in male lemurs seasonally encode information about individual heterozygosity - a reliable predictor of immunocompetence and survivorship. As female lemurs dominate males, compete over resources, and produce sexually differentiated scent marks that likely evolved via direct selection, here we tested whether females also advertise genetic quality via olfactory cues. During the breeding season specifically, individual heterozygosity correlated negatively with the diversity of fatty acids (FAs) expressed in labial secretions and positively with the diversity of heavy FA esters. As odour-gene relationships predictive of health and survivorship emerged during a period critical to mate choice and female competition, we posit that genital scent marks function as honest olfactory ornaments in females.


Effect of particles on ultraviolet light penetration in natural and engineered systems.
The effect of light scattering on measurement of UV absorbance and penetration of germicidal UVC irradiance in a UV reactor were studied. Using a standard spectrophotometer, absorbance measurements exhibited significant error when particles that scatter light were present but could be corrected by integrating sphere spectroscopy. Particles from water treatment plants and wastewater effluents exhibited less scattering (20%-30%) compared with particles such as clay (50%) and alumina (95%-100%). The distribution of light intensity in a UV reactor for a scattering suspension was determined using a spherical chemical actinometry method. Highly scattering alumina particles increased the fluence rate in the reactor near the UV lamp, whereas clay particles and absorbing organic matter reduced the fluence rate. A radiative transfer fluence rate model reasonably predicted the fluence rate of absorbing media and highly scattering suspensions in the UV reactor.


[Function of the pancreatic insular apparatus in growth retardation].
Function of the insular apparatus of the pancreas was studied in 12 healthy children and in 86 patients with growth retardation. The content of immunoreactive insulin (IRI) in the blood serum was examined with the aid of sets for radioimmunological determination on fasting stomach and in dynamics during the standard glucose-tolerance test. Investigations carried out showed the changes in insulin secretion in the patients with growth retardation to be in different direction; these changes were independent of the form of nanism. Normal IRI curves were revealed in 36.1%, and pathological ones--in 63.9% of the patients with growth retardation. Four types were distinguished among the pathological curves; they were hyposecretory (10.5%), torpid (15.1%), hypersecretory (30.2%), paradoxic (8.1%). The established disturbances in the function of the insular apparatus of the pancreas could serve as one of the pathogenetic moments causing or aggravating the growth retardation.


Direct anterior screw fixation for recent and remote odontoid fractures.
The management of odontoid fractures remains controversial. Only direct anterior screw fixation provides immediate stabilization of the spine and may preserve normal C1-2 motion. To determine the indications, optimum timing, and results for direct anterior screw fixation of odontoid fractures, the authors reviewed the surgery-related outcome of patients who underwent this procedure at two institutions. One hundred forty-seven consecutive patients (98 males and 49 females) who underwent direct anterior screw fixation for recent (< or = 6 months postinjury [129 patients]) or remote (> or = 18 months postinjury [18 patients]) Type II (138 cases) or III (nine cases) odontoid fractures at the University of Utah (94 patients) and National Institute of Traumatology in Budapest, Hungary (53 patients) between 1986 and 1998 are included in this study (mean follow up 18.2 months). Data obtained from clinical examination, review of hospital charts, operative findings, and imaging studies were used to analyze the surgery-related results in these patients. In patients with recent fractures there was an overall bone fusion rate of 88%. The rate of anatomical bone fusion of recent fractures was significantly (p < or = 0.05) higher in fractures oriented in the horizontal and posterior oblique direction (compared with anterior oblique), but this finding was independent (p > or = 0.05) of age, sex, number of screws placed (one or two), and the degree or the direction of odontoid displacement. In patients with remote fractures there was a significantly lower rate of bone fusion (25%). Overall, complications related to hardware failure occurred in 14 patients (10%) and those unrelated to hardware in three patients (2%). There was one death (1%) related to surgery. Direct anterior screw fixation is an effective and safe method for treating recent odontoid fractures (<6 months postinjury). It confers immediate stability, preserves C1-2 rotatory motion, and achieves a fusion rate that compares favorably with alternative treatment methods. In contradistinction, in patients with remote fractures (> or = 18 months postinjury) a significantly lower rate of fusion is found when using this technique, and these patients are believed to be poor candidates for this procedure.


Neuromuscular fatigue during exercise: Methodological considerations, etiology and potential role in chronic fatigue.
The term fatigue is used to describe a distressing and persistent symptom of physical and/or mental tiredness in certain clinical populations, with distinct but ultimately complex, multifactorial and heterogenous pathophysiology. Chronic fatigue impacts on quality of life, reduces the capacity to perform activities of daily living, and is typically measured using subjective self-report tools. Fatigue also refers to an acute reduction in the ability to produce maximal force or power due to exercise. The classical measurement of exercise-induced fatigue involves neuromuscular assessments before and after a fatiguing task. The limitations and alternatives to this approach are reviewed in this paper in relation to the lower limb and whole-body exercise, given the functional relevance to locomotion, rehabilitation and activities of daily living. It is suggested that under some circumstances, alterations in the central and/or peripheral mechanisms of fatigue during exercise may be related to the sensations of chronic fatigue. As such, the neurophysiological correlates of exercise-induced fatigue are briefly examined in two clinical examples where chronic fatigue is common: cancer survivors and people with multiple sclerosis. This review highlights the relationship between objective measures of fatigability with whole-body exercise and perceptions of fatigue as a priority for future research, given the importance of exercise in relieving symptoms of chronic fatigue and/or overall disease management. As chronic fatigue is likely to be specific to the individual and unlikely to be due to a simple biological or psychosocial explanation, tailored exercise programmes are a potential target for therapeutic intervention.


History of allergic rhinitis and risk of asthma; a systematic review and meta-analysis.
Allergic rhinitis has been suspected to be a risk factor for asthma in several studies but this association is not firmly established. The objective of this study was to synthesize the evidence of the association between allergic rhinitis and the risk of asthma through a systematic review and meta-analysis. We performed a search in Medline, Scopus, ISI Proceedings databases and other databases from inception until February 2019, followed by manual search to identify potentially relevant case-control and cohort studies that reported relative risk estimates and confidence intervals of the association between allergic rhinitis and asthma. Cross-sectional studies were excluded. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed and random effects models and quality of studies was assessed through a modified version of the Newcastle-Ottawa scale. Twenty-nine eligible studies, 22 cohort and 7 case-control studies, with a total of 274489 subjects, were included in the meta-analysis. The results show that history of allergic rhinitis is significantly associated with the occurrence of asthma (OR = 3.82; 95% CI: 2.92-4.99). European studies showed a stronger association (OR = 4.35; (95% CI: 3.12-6.06) than non-European studies (OR = 2.75; 95% CI: 2.16-3.50), and case-control studies showed a stronger association (OR = 4.71; 95% CI: 3.58-6.17) than cohort studies (OR = 3.42; 95% CI: 2.60-4.50). This meta-analysis shows that allergic rhinitis is strongly associated with asthma. Further prospective studies on the effect of treatment of allergic rhinitis on the development of asthma are needed. Relief of airway allergic manifestations may need dual control of allergic rhinitis and asthma. PROSPERO database with registration number CRD42017055156.


Adult and paediatric cough guidelines: Ready for an overhaul?
Cough is one of the most common reasons that patients seek medical attention. Cough guidelines from numerous countries and societies are available to assist the clinician to investigate and manage patients with cough. We review some of the recent progress in the field of cough that may lead to revision of these guidelines. In adults with chronic cough, new causes such as obstructive sleep apnoea have been identified. A new terminology, cough hypersensitivity syndrome (CHS), has been proposed for patients with chronic cough, which emphasises cough reflex hypersensitivity as a key feature. New therapeutic options are now available, particularly for patients with refractory or idiopathic chronic cough, which include gabapentin, speech pathology management and morphine. There has been great progress in the assessment of cough with the development of validated quality of life questionnaires and cough frequency monitoring tools. In children, common aetiologies differ from adults and those managed according to guidelines have better outcomes compared to usual care. New diagnostic entities such as protracted bacterial bronchitis have been described. Paediatric-specific cough assessment tools such as the Parent/Child Quality of Life Questionnaire will help improve the assessment of patients. Further research is necessary to improve the evidence base for future clinical guideline recommendations. Guidelines in future should also aim to reach a wider audience that includes primary care physicians, non-specialists and patients.


Surgical nuances for removal of tuberculum sellae meningiomas with optic canal involvement using the endoscopic endonasal extended transsphenoidal transplanum transtuberculum approach.
Tuberculum sellae meningiomas frequently extend into the optic canals. Radical tumor resection including the involved dural attachment, underlying hyperostotic bone, and intracanalicular tumor in the optic canal offers the best chance of a Simpson Grade I resection to minimize recurrence. Decompression of the optic canal with removal of the intracanalicular tumor also improves visual outcome since this portion of the tumor is usually the cause of asymmetrical visual loss. The purely endoscopic endonasal extended transsphenoidal approach offers a direct midline trajectory and immediate access to tuberculum sellae meningiomas without brain retraction and manipulation of neurovascular structures. Although the endoscopic approach has been previously criticized for its inability to remove tumor within the optic canals, complete Simpson Grade I tumor removal including intracanalicular tumor, dural attachment, and involved hyperostotic bone can be achieved in properly selected patients. Excellent visualization of the suprasellar region and the inferomedial aspects of both optic canals allows for extracapsular, extraarachnoid dissection of the tumor from the critical structures using bimanual microsurgical dissection. In this report, the authors describe the operative nuances for removal of tuberculum sellae meningiomas with optic canal involvement using a purely endoscopic endonasal extended transsphenoidal (transplanum transtuberculum) approach. They specifically highlight the technique for endonasal bilateral optic nerve decompression and removal of intracanalicular tumor to improve postoperative visual function, as demonstrated in 2 illustrative cases. Special attention is also given to cranial base reconstruction to prevent CSF leakage using the vascularized pedicled nasoseptal flap.


Volociximab in cancer.
Volociximab is a first-in-class chimeric monoclonal antibody that targets α5β1 integrin. Preclinical studies have shown the ability of volociximab to inhibit tumor neoangiogenesis by blocking the interaction between α5β1 and fibronectin. Volociximab's safety profile, pharmacokinetics and pharmacodynamics have been established. Ongoing clinical trials are evaluating its efficacy in the treatment of different types of solid tumors as a single agent or in combination with chemotherapy. In this review we focus on the biological effect of volociximab and results of completed clinical trials. This review summarizes the structures and functions of integrin α5β1 and its ligand fibronectin, provides an overview of the early development of volociximab, a targeted monoclonal antibody that specifically binds and inhibits activation of integrin α5β1, and discusses the relevant data from pre-clinical and clinical studies. Volociximab has been well tolerated as monotherapy or in combination with chemotherapy. It has shown promising activity in different types of cancer. Randomized trials are required to validate those early results.


CEDAR, an online resource for the reporting and exploration of complexome profiling data.
Complexome profiling is an emerging 'omics' approach that systematically interrogates the composition of protein complexes (the complexome) of a sample, by combining biochemical separation of native protein complexes with mass-spectrometry based quantitation proteomics. The resulting fractionation profiles hold comprehensive information on the abundance and composition of the complexome, and have a high potential for reuse by experimental and computational researchers. However, the lack of a central resource that provides access to these data, reported with adequate descriptions and an analysis tool, has limited their reuse. Therefore, we established the ComplexomE profiling DAta Resource (CEDAR, www3.cmbi.umcn.nl/cedar/), an openly accessible database for depositing and exploring mass spectrometry data from complexome profiling studies. Compatibility and reusability of the data is ensured by a standardized data and reporting format containing the "minimum information required for a complexome profiling experiment" (MIACE). The data can be accessed through a user-friendly web interface, as well as programmatically using the REST API portal. Additionally, all complexome profiles available on CEDAR can be inspected directly on the website with the profile viewer tool that allows the detection of correlated profiles and inference of potential complexes. In conclusion, CEDAR is a unique, growing and invaluable resource for the study of protein complex composition and dynamics across biological systems.


Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression.
The term 'field effect' (also known as field defect, field cancerization, or field carcinogenesis) has been used to describe a field of cellular and molecular alteration, which predisposes to the development of neoplasms within that territory. We explore an expanded, integrative concept, 'etiologic field effect', which asserts that various etiologic factors (the exposome including dietary, lifestyle, environmental, microbial, hormonal, and genetic factors) and their interactions (the interactome) contribute to a tissue microenvironmental milieu that constitutes a 'field of susceptibility' to neoplasia initiation, evolution, and progression. Importantly, etiological fields predate the acquisition of molecular aberrations commonly considered to indicate presence of filed effect. Inspired by molecular pathological epidemiology (MPE) research, which examines the influence of etiologic factors on cellular and molecular alterations during disease course, an etiologically focused approach to field effect can: (1) broaden the horizons of our inquiry into cancer susceptibility and progression at molecular, cellular, and environmental levels, during all stages of tumor evolution; (2) embrace host-environment-tumor interactions (including gene-environment interactions) occurring in the tumor microenvironment; and, (3) help explain intriguing observations, such as shared molecular features between bilateral primary breast carcinomas, and between synchronous colorectal cancers, where similar molecular changes are absent from intervening normal colon. MPE research has identified a number of endogenous and environmental exposures which can influence not only molecular signatures in the genome, epigenome, transcriptome, proteome, metabolome and interactome, but also host immunity and tumor behavior. We anticipate that future technological advances will allow the development of in vivo biosensors capable of detecting and quantifying 'etiologic field effect' as abnormal network pathology patterns of cellular and microenvironmental responses to endogenous and exogenous exposures. Through an 'etiologic field effect' paradigm, and holistic systems pathology (systems biology) approaches to cancer biology, we can improve personalized prevention and treatment strategies for precision medicine.


cGMP produced by NO-sensitive guanylyl cyclase essentially contributes to inflammatory and neuropathic pain by using targets different from cGMP-dependent protein kinase I.
A large body of evidence indicates that the release of nitric oxide (NO) is crucial for the central sensitization of pain pathways during both inflammatory and neuropathic pain. Here, we investigated the distribution of NO-sensitive guanylyl cyclase (NO-GC) in the spinal cord and in dorsal root ganglia, and we characterized the nociceptive behavior of mice deficient in NO-GC (GC-KO mice). We show that NO-GC is distinctly expressed in neurons of the mouse dorsal horn, whereas its distribution in dorsal root ganglia is restricted to non-neuronal cells. GC-KO mice exhibited a considerably reduced nociceptive behavior in models of inflammatory or neuropathic pain, but their responses to acute pain were not impaired. Moreover, GC-KO mice failed to develop pain sensitization induced by intrathecal administration of drugs releasing NO or carbon monoxide. Surprisingly, during spinal nociceptive processing, cGMP produced by NO-GC may activate signaling pathways different from cGMP-dependent protein kinase I (cGKI), whereas cGKI can be activated by natriuretic peptide receptor-B dependent cGMP production. Together, our results provide evidence that NO-GC is crucially involved in the central sensitization of pain pathways during inflammatory and neuropathic pain.


A prospective audit on the effect of training and educational workshops on the incidence of urethral catheterization injuries.
The incidence of iatrogenic urethral catheterization (UC) injuries is approximately 0.3%. Resultant complications are associated with patient morbidity and unnecessary healthcare costs. Our aim was to investigate whether educational training workshops decreased the incidence of UC-related injuries. A prospective audit was performed to calculate incidence, morbidity, and costs associated with iatrogenic UC injury from January to July 2015. Educational workshops were then conducted with healthcare staff and training modules for junior doctors. UC-related incidence, morbidity, and costs in the subsequent six-month period were recorded prospectively and compared with the previous data. The incidence of iatrogenic UC injuries was reduced from 4.3/1000 catheters inserted to 3.8/1000 catheters after the intervention (p=0.59). Morbidity from UC increased in the second half in the form of increase in cumulative additional inpatient hospital stay (22 to 79 days; p=0.25), incidence of urosepsis (n=2 to n=4), and need for operative intervention (n=1 to n=2). The cost of managing UC injuries almost doubled in the period after the training intervention (€50 449 to €90 100). Current forms of educational and training interventions for UC did not significantly change morbidity or cost of iatrogenic UC injuries despite a decrease in incidence. Improved and intensive training protocols are necessary for UC to prevent avoidable iatrogenic complications, as well as a safer urethral catheter design.


Comparison of an infective avirulent and canine virulent Bordetella bronchiseptica.
Two Bordetella bronchiseptica isolates, S-55 and D-2, were evaluated in dogs for inducement of (i) infection, (ii) clinical bordetellosis, and (iii) histopathologic changes on tracheal and bronchiole tissues. Further, each isolate was characterized for variance in (i) toxicity for mice and (ii) intracellular proteins. Both S-55 and D-2 were detectable in test dog groups during the 26-day test period, although 545 times more D-2 was recovered than was S-55. In dogs inoculated with D-2, clinical infectious tracheobronchitis appeared in 4 days and continued for 22 days. Bordetellosis was not observed in dogs given S-55 or in noninoculated dogs. Tracheal and bronchiole tissues from dogs inoculated with the S-55 and D-2 isolates were microscopically examined for lesions. Dogs inoculated with S-55 did not have tracheal or bronchiole lesions. Lesions were not observed in noninoculated dogs. Dogs inoculated with D-2 had marked lesions in the tracheal and bronchiole tissues. The D-2 whole cells were an average 4.8 times as lethal as S-55 whole cells in mice (given intraperitoneal inoculation), whereas cell-free culture supernatants from S-55 and D-2 isolates were nontoxic. Cell-free sonicated extracts of S-55 and D-2 proved toxic to mice (intraperitoneal inoculation), but after the extracts were heated at 56 C for 30 minutes, both were nontoxic. Intracellular proteins of approximately 116,000 and 44,000 daltons were found in higher concentration in D-2 cells than in S-55 cells.


Effect of iron on accumulation of exotoxin A-specific mRNA in Pseudomonas aeruginosa.
A DNA probe from an internal fragment of the exotoxin A structural gene was used to study the effects of selected culture conditions on steady-state levels of exotoxin-specific mRNA in Pseudomonas aeruginosa. Cells grown under conditions of iron deprivation began to synthesize and excrete the exotoxin A polypeptide during the late exponential phase of growth and throughout the stationary phase of growth, concomitant with a sharp increase in exotoxin A mRNA pools in P. aeruginosa cells. The addition of iron to the medium resulted in the failure of these cells to synthesize exotoxin A mRNA, despite significantly enhanced growth. The inhibition of the production of exotoxin A and the accumulation of its mRNA by iron was dose dependent, with a half-maximal inhibitory concentration of FeSO4 of 5 to 10 microM. A blockade of the initiation of transcription by rifampin resulted in the decay of exotoxin A mRNA, with a half-life of approximately 8 to 10 min, depending on the media used for growth. The addition of iron to cells actively engaged in exotoxin A synthesis also resulted in a gradual decrease in the amount of this mRNA in bacteria. However, the rate of decline of mRNA induced by iron was relatively slow (half-life, 90 min), with a considerable lag time between the iron addition and the first detectable effect on mRNA. While iron clearly appears to influence the production of exotoxin A at the transcriptional level, the molecular basis of this effect may involve several interacting factors affecting the initiation of transcription and perhaps mRNA turnover.


Prognostic implications of CD-57 expression in oral squamous cell carcinoma cases.
Natural killer (NK) cells are one of the most important effector T -lymphocytes having antitumor effect. Only a few studies are present in the literature, correlating the expression of cluster of differentiation 57 (CD-57) in NK cells in oral squamous cell carcinoma (OSCC). To analyze the effect of the presence of NK cells in the stroma of OSCC and their effect on the tumor progression and prognosis. A retrospective study was performed over 122 OSCC patients who had undergone surgical treatment between 2014 and 16. Wax blocks were obtained and subjected to immunohistochemical (IHC) analysis for CD-57 expression. Patients were followed up for 3 years and 100 cases were finally included in the study and divided into three groups. The association between variable were studied through the Chi-square test, Kruskal-Wallis test, and Mann-Whitney U test. A total of 91% of cases showed positive staining for CD-57. Maximum positive expression (96.6%) was observed in the patients who were alive and without recurrence (Group-II) as compared to dead patients (Group-I) and in well-differentiated squamous cell carcinoma (WDSCC) cases (96.8%) than in poorly differentiated cases. Also, the mean CD-57 positive cells count was found to be highest in Group-II and WDSCC cases. A significant correlation was observed between CD-57 expression and patients' health status. As the expression of CD-57 increased in the tumor stroma of OSCC, the chances for the patient to be alive were increased; therefore, it may serve as a good prognostic marker.


Multijunction solar cells for conversion of concentrated sunlight to electricity.
Solar-cell efficiencies have exceeded 40% in recent years. The keys to achieving these high efficiencies include: 1) use of multiple materials that span the solar spectrum, 2) growth of these materials with near-perfect quality by using epitaxial growth on single-crystal substrates, and 3) use of concentration. Growth of near-perfect semiconductor materials is possible when the lattice constants of the materials are matched or nearly matched to that of a single-crystal substrate. Multiple material combinations have now demonstrated efficiencies exceeding 40%, motivating incorporation of these cells into concentrator systems for electricity generation. The use of concentration confers several key advantages.


The feasibility of point-of-care ankle ultrasound examination in patients with recurrent ankle sprain and chronic ankle instability: Comparison with magnetic resonance imaging.
To evaluate the feasibility of point-of-care ankle ultrasound compared with magnetic resonance imaging (MRI) for diagnosing major ligaments and Achilles tendon injuries in patients with recurrent ankle sprain and chronic instability, and to evaluate inter-observer reliability between an emergency physician and a musculoskeletal radiology fellow. A prospective cross-sectional study was conducted in an emergency department. Patients with recurrent ankle sprain and chronic instability were recruited. An emergency physician and a musculoskeletal radiology fellow independently evaluated the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), distal anterior tibiofibular ligament (ATiFL), deltoid ligament, and Achilles tendon using point-of-care ankle ultrasound. Findings were classified normal, partial tear, and complete tear. MRI was used as the reference standard. We calculated diagnostic values for point-of-care ankle ultrasound for both reviewers and compared them using DeLong's test. Intra-class correlation coefficients (ICCs) were calculated for agreement between each reviewer and the reference standard, and between the two reviewers. Eighty-five patients were enrolled. Point-of-care ankle ultrasound showed acceptable sensitivity (96.4-100%), specificity (95.0-100%), and accuracy (96.5-100%); these performance markers did not differ significantly between reviewers. Agreement between each reviewer and the reference standard was excellent (emergency physician, ICC=0.846-1.000; musculoskeletal radiology fellow, ICC=0.930-1.000), as was inter-observer agreement (ICC=0.873-1.000). Point-of-care ankle ultrasound is as precise as MRI for detecting major ankle ligament and Achilles tendon injuries; it could be used for immediate diagnosis and further pre-operative imaging. Moreover, it may reduce the interval from emergency department admission to admission for surgical intervention, and may save costs.


[Use of the edema test of the extremities in white mice for studying purulent Proteus infection].
The injection of non-enterotoxigenic Proteus strains into the paw pad of white mice caused paw edema, its intensity being proportional to the dose used for the test. The exudate consisted of granulocytes. Immunization with isolated Proteus antigens prevented the development of edema. This test is recommended as a model of local purulent infection. The optimal methods for the statistical analysis of the results thus obtained is proposed.


Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gynecologic cancer.
Advanced gynecologic cancers have historically lacked effective treatment options. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration for the treatment of cervical cancer and endometrial cancer, offering durable responses for some patients. In addition, many immunotherapy strategies are under investigation for the treatment of earlier stages of disease or in other gynecologic cancers, such as ovarian cancer and rare gynecologic tumors. While the integration of ICIs into the standard of care has improved outcomes for patients, their use requires a nuanced understanding of biomarker testing, treatment selection, patient selection, response evaluation and surveillance, and patient quality of life considerations, among other topics. To address this need for guidance, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline. The Expert Panel drew on the published literature as well as their own clinical experience to develop evidence- and consensus-based recommendations to provide guidance to cancer care professionals treating patients with gynecologic cancer.


Post-traumatic amnesia.
Of patients hospitalised for traumatic brain injury (TBI), most pass through a state of altered consciousness known as "post-traumatic amnesia" (PTA). Despite the lack of a consistent definition, PTA is widely used as a construct in neurosurgical practice to guide decision-making and prognosis. Accurate PTA assessment is important, because over-evaluation leads to excess social, financial and opportunity costs, whilst under-evaluation risks patient welfare. Whilst anterograde memory is certainly disrupted in PTA, PTA in fact involves a far more extensive memory disturbance. More instructively, the complete "post-TBI syndrome" also comprises an extensive cognitive deficit which includes a confusional state, as well as a behavioural disturbance characterised by acute agitation. Recently, impairments in attention and executive functioning have also been emphasised; indeed, some consider these the primary disturbance with PTA. Although all of these features were fully described (or implied) by the earliest pioneers, most current PTA scores do not assess the complete "post-TBI syndrome". Currently, the Westmead PTA scale (WPTAS) directs most in-hospital TBI management throughout Australasia: however, in addition to general defects, specific limitations have been identified in the levels of evidence for WPTAS validity. We review the literature regarding PTA and, in particular, the continued role of the WPTAS in directing neurosurgical practice.