SIMENS-LIS4SC, a Laboratory Information System for Biological Tests of Sickle Cell Screening and Healthcare.
Neonatal screening and ongoing follow-up of children with sickle cell disease are essential to reduce the mortality caused by this disease. To ensure care continuity, it is essential to include in the patient's record the history and details of biological tests. Thus, it is necessary to provide a Laboratory Information System for electronic management of biological test prescription and results, and the laboratory system must integrate well with Health Information Systems. In this paper, we propose a Laboratory Information System for the management of biological tests for the neonatal screening and healthcare of sickle cell disease in Senegal.


Noncoding RNA mediated traffic of foreign mRNA into chloroplasts reveals a novel signaling mechanism in plants.
Communication between chloroplasts and the nucleus is one of the milestones of the evolution of plants on earth. Proteins encoded by ancestral chloroplast-endogenous genes were transferred to the nucleus during the endosymbiotic evolution and originated this communication, which is mainly dependent on specific transit-peptides. However, the identification of nuclear-encoded proteins targeted to the chloroplast lacking these canonical signals suggests the existence of an alternative cellular pathway tuning this metabolic crosstalk. Non-coding RNAS (NcRNAs) are increasingly recognized as regulators of gene expression as they play roles previously believed to correspond to proteins. Avsunviroidae family viroids are the only noncoding functional RNAs that have been reported to traffic inside the chloroplasts. Elucidating mechanisms used by these pathogens to enter this organelle will unearth novel transport pathways in plant cells. Here we show that a viroid-derived NcRNA acting as a 5'UTR-end mediates the functional import of Green Fluorescent Protein (GFP) mRNA into chloroplast. This claim is supported by the observation at confocal microscopy of a selective accumulation of GFP in the chloroplast of the leaves expressing the chimeric vd-5'UTR/GFP and by the detection of the GFP mRNA in chloroplasts isolated from cells expressing this construct. These results support the existence of an alternative signaling mechanism in plants between the host cell and chloroplasts, where an ncRNA functions as a key regulatory molecule to control the accumulation of nuclear-encoded proteins in this organelle. In addition, our findings provide a conceptual framework to develop new biotechnological tools in systems using plant chloroplast as bioreactors. Finally, viroids of the family Avsunviroidae have probably evolved to subvert this signaling mechanism to regulate their differential traffic into the chloroplast of infected cells.


[Clinical value of preoperative serum VEGF, CRP and IL-6 levels in colorectal carcinoma].
To determine the preoperative serum VEGF, IL-6, and CRP levels in colorectal carcinoma, and to explore their correlation with disease status and prognosis. Serum VEGF and IL-6 levels were assessed using ELISA, and CRP was measured by immunoturbidimetry. They were compared between the colorectal carcinoma group and the control group. The five-year survival rate and poor prognostic factors were analyzed by Kaplan-Meier and Log-rank method, respectively. The serum VEGF, IL-6, and CRP levels in colorectal carcinoma were (591 ± 312) pg/ml, (13.2 ± 3.7) pg/ml, and (1.14 ± 0.87) mg/dl, respectively, higher than that in the control group. The two groups showed significant difference in VEGF and CRP (P < 0.001, P = 0.002). VEGF expression was higher in male than that in female [(638 ± 387) pg/ml vs. (552 ± 271) pg/ml, P = 0.042]. The cases with tumor size smaller than 5 cm had lower VEGF expression compared with that in cases with tumor size ≥ 5 cm [(538 ± 275) pg/ml vs. (647 ± 331) pg/ml, P = 0.009]. IL-6 expression showed significant difference in males (11.7 ± 3.2) and females (15.2 ± 4.0) pg/ml, (P = 0.011). The five-year survival rate in the group with VEGF < 591 pg/ml was 86.8% (33/38), higher than that in the ≥ 591 pg/m group. High VEGF level tended to reduce survival (χ(2) = 0.933, P = 0.344). VEGF ≥ 591 pg/ml was a factor of poor prognosis in colorectal carcinoma, assessed by Log-rank methods (P < 0.05). Tumor size and VEGF concentration were risk factors of prognosis (P = 0.032, OR = 0.985; P = 0.011, OR = 0.976). Serum VEGF and IL-6 expressions have gender differences. Serum VEGF can be used as a biomaker of clinical diagnosis of colorectal cancer, and has an important significance on the prognosis of patients.


CHANGES IN SPERMATOGENESIS AFTER SIMULATED INGUINAL HERNIA REPAIR IN EXPERIMENT.
The Lichtenstein method revolutionized the treatment of inguinal hernias. But this method is accompanied by serious complications, as evidenced by the publications of recent years. Such complications include the development of fibrous changes in the scrotum, deejaculation, obstructive azoospermia, oligospermia. Therefore, in the treatment of inguinal hernia, the so-called isolation methods are becoming more and more relevant, which implies complete isolation from the rope mesh and does not affect spermatogenesis. Aim of the study - to compare the morphological parameters of sperm before and after hernia surgery in the groups that underwent modeled herniaplasty by Lichtenstein's method and with spermatic cord isolation from a mesh by Gvenetadze. 16 male rabbits aged 12 months ± 3 months, weighing 3.5 ± 0.5 kg were included in the study. Of these, 8 (50%) underwent hernioplasty by Lichtenstein's method, and 8 (50%) - with complete isolation of Bagirak. Gvenetadze's method. Rabbits were divided into two groups. The first group: 8 rabbits, which underwent Lichtenstein's hernia surgery. The second group: 8 rabbits, which underwent hernioplasty with complete isolation of the sacrum using the Gvenetadze method. In both groups, a spermomorphocytological study was performed 2 days before the operation and 3 months and 6 months after the operation. The study included a complete spermomorphocytological examination by studying the following sperm parameters: sperm volume, color, turbidity, ejaculatory time, stickiness, odor, PH, number of spermatozoa in 1 ml, number of spermatozoa in the whole ejaculate, live spermatozoa, motile spermatozoa, progressive motile spermatozoa, Normal morphological of permatozoites Molds, leukocytes, erythrocytes, lipoid bodies, spermagglutination, fungi, bacteria, mucus. Semen were collected 2 days before surgery, 3 months after surgery, and 6 months after surgery. The sperm was obtained using the so-called "artificial vagina". Our study showed that inguinal hernia repair with spermatic cord isolation does not affect spermatogenesis.


Unopposed cathepsin G, neutrophil elastase, and proteinase 3 cause severe lung damage and emphysema.
Cigarette smoking is a major factor for the development of pulmonary emphysema because it induces abnormal inflammation and a protease-rich local milieu that causes connective tissue breakdown of the lungs. As a result of its capacity to degrade lung tissue and the high risk of patients lacking α1-antitrypsin to develop emphysema, much interest has focused on neutrophil elastase (NE). Two similar neutrophil serine proteases (NSPs), cathepsin G and proteinase 3, coexist with NE in humans and mice, but their potential tissue-destructive role(s) remains unclear. Using a gene-targeting approach, we observed that in contrast to their wild-type littermates, mice deficient in all three NSPs were substantially protected against lung tissue destruction after long-term exposure to cigarette smoke. In exploring the underlying basis for disrupted wild-type lung air spaces, we found that active NSPs collectively caused more severe lung damage than did NE alone. Furthermore, NSP activities unleashed increased activity of the tissue-destructive proteases macrophage elastase (matrix metalloproteinase-12) and gelatinase B (matrix metalloproteinase-9). These in vivo data provide, for the first time, compelling evidence of the collateral involvement of cathepsin G, NE, and proteinase 3 in cigarette smoke-induced tissue damage and emphysema. They also reveal a complex positive feed-forward loop whereby these NSPs induce the destructive potential of other proteases, thereby generating a chronic and pathogenic protease-rich milieu.


Medium chain triglyceride and medium-and long chain triglyceride: metabolism, production, health impacts and its applications - a review.
Structured lipid is a type of modified form of lipid that is "fabricated" with the purpose to improve the nutritional and functional properties of conventional fats and oils derived from animal and plant sources. Such healthier choice of lipid received escalating attention from the public for its capability to manage the rising prevalence of metabolic syndrome. Of which, medium-chain triacylglycerol (MCT) and medium-and long-chain triacylglycerol (MLCT) are the few examples of the "new generation" custom-made healthful lipids which are mainly composed of medium chain fatty acid (MCFA). MCT is made up exclusively of MCFA whereas MLCT contains a mixture of MCFA and long chain fatty acid (LCFA), respectively. Attributed by the unique metabolism of MCFA which is rapidly metabolized by the body, MCFA and MCT showed to acquire multiple physiological and functional properties in managing and reversing certain health disorders. Several chemically or enzymatically oils and fats modification processes catalyzed by a biological or chemical catalyst such as acidolysis, interesterification and esterification are adopted to synthesis MCT and MLCT. With their purported health benefits, MCT and MLCT are widely being used as nutraceutical in food and pharmaceutical sectors. This article aims to provide a comprehensive review on MCT and MLCT, with an emphasis on the basic understanding of its structures, properties, unique metabolism; the current status of the touted health benefits; latest routes of production; its up-to-date applications in the different food systems; relevant patents filed and its drawbacks.


The world of dementia beyond 2020.
Counterpoised against dire projections of the tripling of the prevalence of dementia over the next 40 years are major developments in diagnostic biomarkers, neuroimaging, the molecular biology of Alzheimer's disease (AD), epidemiology of risk and protective factors, and drug treatments-mainly targeting the amyloid pathway, tau protein, and immunotherapy-that may have the potential to modify the progression of AD. Drug combinations and presymptomatic treatments are also being investigated. Previous trials of dementia-modifying drugs have not shown benefit, and even if current Phase III trials prove successful, these drugs will not eradicate other dementias, could (if not curative) increase dementia duration and prevalence, and are unlikely to come onto the market before 2020. In the meantime, delaying the onset of dementia by even 2 years would have significant economic and societal effects. This article provides an overview of current achievements and potentials of basic and clinical research that might affect the development of dementia prevalence and care within the near future.


Effects of membrane fluidizing agents on renal brush border proton permeability.
H+ permeability (PH) of brush border membrane vesicles isolated from rabbit renal cortex was measured from the rate of collapse of preformed pH gradients using acridine orange fluorescence quenching. n-Alkanols increased PH from 0.005 to 0.1 cm/s in a dose-dependent manner. At 25 degrees C, PH increased to 0.01 cm/s at [n-alkanol] = 90 mM (butanol), 30 mM (pentanol), 7 mM (hexanol), and 1.8 mM (heptanol). Activation energy (Ea) of PH was 21.6 kcal/mol (5-50 degrees C), which decreased to 18.5 kcal/mol in the presence of either 200 mM butanol or 12 mM hexanol. Membrane fluidity was estimated from diphenylhexatriene anisotropy (r). n-Alkanols decreased r from 0.25 to 0.18 in a dose-dependent manner. At 25 degrees C, r = 0.22 at [n-alkanol] = 200 mM (butanol), 27 mM (pentanol), 9.5 mM (hexanol), and 2 mM (heptanol). The effects of n-alkanols on PH and r correlated well with known n-alkanol lipid-water partition coefficients. Similar increases in PH and decreases in r were observed for nonalkanol lipid anesthetics. The effects of n-alkanols on the Na+-H+ antiporter and on osmotically driven water transport were also studied. At concentrations of n-alkanol that resulted in a 10-fold increase in PH, there was no significant effect on either Na+-H+ exchange or water transport. These results suggest a lipid pathway for brush border H+ diffusion that is distinct from both the Na+-H+ antiporter and the water transport pathway.


Spectroscopic investigation of high-pressure femtosecond two-photon laser-induced fluorescence of carbon monoxide up to 20 bar.
Extension of laser diagnostic methods to high pressure is critically important because most practical combustion systems operate at elevated pressures. However, increased collisional quenching, fluorescence trapping, and other spectroscopic complications make high-pressure laser diagnostics extremely challenging. As the pressure increases, collisional effects broaden and shift excitation spectral lines, reducing the excitation quantum efficiency of the laser-induced fluorescence (LIF) technique, in particular when using conventional narrowband, nanosecond (ns)-duration laser pulses. In this work, spectroscopic investigation of broadband, femtosecond two-photon LIF (fs-TPLIF) of carbon monoxide (CO) was performed in a high-pressure static gas cell, up to total pressures of 20 bar. The fluorescence emission spectrum broadened marginally at the highest pressure investigated and hence can be neglected in most cases. The subquadratic dependence of the CO fs-TPLIF signal on the laser fluence increased as the pressure is increased. Moreover, the CO fs-TPLIF signal decays more slowly with increasing pressure compared to the previously reported ns-TPLIF data. The signal drop when the total pressure is increased from 1 to 13 bar is approximately 30% in the fs excitation, as compared to approximately a 60% drop in the ns excitation in CO/N2/O2 mixtures. The pressure effects on the fluorescence signal were observed to be similar in the Ångström and third positive bands, suggesting that the third positive band could also be used for CO measurements with broadband fs laser pulses. Furthermore, experimentally investigated are the effect of pressure on the CO fluorescence signal in different quenching gases using fixed CO mole fractions, as well as number densities. Overall, the fs-TPLIF scheme is shown to be a promising diagnostics tool for CO detection in practical combustion systems at elevated pressures.


[Current views on rare diseases research and orphan drugs development].
Interest in rare diseases research and orphan drugs development has been increased distinctly in recent years. The number of affected people with rare diseases is considerable around the world and the formulation of national and international incentive policies to accelerate orphan drugs development, aiming at offering facilities and necessary conditions for patient access to treatment, gains favorable results. In particular, more measures should be taken to catalyze further progress due to behindhand level in this field in China. Additionally, therapeutic methods of rare diseases were also discussed.


An idealized human cardiomyocyte finite element model for studying the interaction between the cross-bridge state and cell mechanical response.
The mechanical state of cardiomyocyte is directly related to the structure and function of internal sarcomeres. In the field of computational cardiac mechanics, attempts to establish models of human cardiomyocyte with a detailed representation of sarcomere cross-bridge (XB) are rare. In this study, we established a computational model for a cardiomyocyte with idealized geometry while containing a representative sarcomere composed of thick filament, thin filament, titin filament, and Z-disc. The formation of XB with passive tension in the model was simulated with the finite element (FE) method, and stochastic FE analyses were further carried out in conjunction with six sigma analysis to explore the interaction between the S1 power stroke and the twitch mechanics of cardiomyocyte. The proposed modeling method may help us better understand the working state of cardiomyocyte, and offer a potential means for exploring the cell-level mechanisms of cardiac diseases.


The effectiveness of individual schema therapy in older adults with borderline personality disorder: A multiple-baseline case series design.
The aim of this study was to explore the effectiveness of schema therapy (ST) in older adults with borderline personality disorder (BPD). Multiple baseline case series design with five BPD patients, with a mean age of 66. After a baseline phase with random length, patients received weekly ST sessions for a year, followed by follow-up sessions during 6 months. Participants rated the credibility of negative core beliefs weekly; various secondary outcome measures were assessed every 6 months (severity of BPD, early maladaptive schemas, schema modes, personality functioning, maladaptive personality traits, psychological distress and quality of life), and BPD diagnosis was assessed before baseline and after follow-up. Data were analysed with mixed regression analyses and paired t-tests. Results revealed that ST led to a significant decrease in credibility of negative core beliefs, with high effect sizes. All participants remitted from their BPD diagnosis. This is the first study exploring the effectiveness of ST for BPD in older adults, and it suggests that ST can be a powerful intervention for this group of patients.


[Function of substance-P projection from superior colliculus to lateral geniculate nucleus of rats].
Substance P immunoreactive terminals arising from the superior colliculus have been observed in the dorsal lateral geniculate nucleus of the rat. However, the functional role of this tachykininergic projection is still unknown. We studied the effects of substance P on voltage-dependent ion channels of lateral geniculate neurons in rat's in vitro brain slice with a single-electrode-voltage-clamp technique. It was found that substance P caused a depolarizing shift of membrane potential with a decrease of membrane conductance, suggesting that substance P depressed the linear potassium leak current. In addition, substance P inhibited the slowly inactivated potassium current, low threshold (T-) calcium current and inward rectifier (H- or Q-) current. Probably, the transient potassium (A-) current was also depressed by substance P. Therefore, the effects of substance P were considered to transfer activities of lateral geniculate neurons from burst response mode or oscillatory state to relay response mode, and to facilitate synaptic transmission, so that retinal visual signals could be relayed to the visual cortex with less distortion faithfully.


Perceived duration of auditory sequences.
Pure tone auditory sequences were presented in a successive comparison task to Ss who were required to make judgments as to which sequence was longer. Experiment 1 was designed to test an hypothesis that sequences with small differences in frequency between adjacent tones would be perceived as shorter in duration than would sequences with large differences. Results did not support this hypothesis. Experiment 2 considered a systematic variation of the amount of frequency change in a sequence upon its perceived duration. These data indicated a direct relationship between perceived duration and the amount of stimulus change. A presentation order effect (POE) was found in Experiment 1 but not in Experiment 2 and it was suggested that the presence or absence of a significant POE was related to the ability of the S to store the sequences in memory.


Observation of Electron Coherence and Fabry-Perot Standing Waves at a Graphene Edge.
Electron surface states in solids are typically confined to the outermost atomic layers and, due to surface disorder, have negligible impact on electronic transport. Here, we demonstrate a very different behavior for surface states in graphene. We probe the wavelike character of these states by Fabry-Perot (FP) interferometry and find that, in contrast to theoretical predictions, these states can propagate ballistically over micron-scale distances. This is achieved by embedding a graphene resonator formed by gate-defined p-n junctions within a graphene superconductor-normal-superconductor structure. By combining superconducting Aharanov-Bohm interferometry with Fourier methods, we visualize spatially resolved current flow and image FP resonances due to p-n-p cavity modes. The coherence of the standing-wave edge states is revealed by observing a new family of FP resonances, which coexist with the bulk resonances. The edge resonances have periodicity distinct from that of the bulk states manifest in a repeated spatial redistribution of current on and off the FP resonances. This behavior is accompanied by a modulation of the multiple Andreev reflection amplitude on-and-off resonance, indicating that electrons propagate ballistically in a fully coherent fashion. These results, which were not anticipated by theory, provide a practical route to developing electron analog of optical FP resonators at the graphene edge.


Chimpanzees modify intentional gestures to coordinate a search for hidden food.
Humans routinely communicate to coordinate their activities, persisting and elaborating signals to pursue goals that cannot be accomplished individually. Communicative persistence is associated with complex cognitive skills such as intentionality, because interactants modify their communication in response to another's understanding of their meaning. Here we show that two language-trained chimpanzees effectively use intentional gestures to coordinate with an experimentally naive human to retrieve hidden food, providing some of the most compelling evidence to date for the role of communicative flexibility in successful coordination in nonhumans. Both chimpanzees (named Panzee and Sherman) increase the rate of non-indicative gestures when the experimenter approaches the location of the hidden food. Panzee also elaborates her gestures in relation to the experimenter's pointing, which enables her to find food more effectively than Sherman. Communicative persistence facilitates effective communication during behavioural coordination and is likely to have been important in shaping language evolution.


Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club.
This consensus article reviews the various aspects of the non-pharmacological management of osteoporosis, including the effects of nutriments, physical exercise, lifestyle, fall prevention, and hip protectors. Vertebroplasty is also briefly reviewed. Non-pharmacological management of osteoporosis is a broad concept. It must be viewed as an essential part of the prevention of fractures from childhood through adulthood and the old age. The topic also includes surgical procedures for the treatment of peripheral and vertebral fractures and the post-fracture rehabilitation. The present document is the result of a consensus, based on a systematic review and a critical appraisal of the literature. Diets deficient in calcium, proteins or vitamin D impair skeletal integrity. The effect of other nutriments is less clear, although an excessive consumption of sodium, caffeine, or fibres exerts negative effects on calcium balance. The deleterious effects of tobacco, excessive alcohol consumption and a low BMI are well accepted. Physical activity is of primary importance to reach optimal peak bone mass but, if numerous studies have shown the beneficial effects of various types of exercise on bone mass, fracture data as an endpoint are scanty. Fall prevention strategies are especially efficient in the community setting, but less evidence is available about their effectiveness in preventing fall-related injuries and fractures. The efficacy of hip protectors remains controversial. This is also true for vertebroplasty and kyphoplasty. Several randomized controlled studies had reported a short-term advantage of vertebroplasty over medical treatment for pain relief, but these findings have been questioned by recent sham-controlled randomized clinical studies.


Terpenoids: shape and non-covalent interactions. The rotational spectrum of cis-verbenol and its 1 : 1 water complex.
Verbenols are aromatic terpenoids whose bioactivity is attracting considerable experimental efforts. Exploiting the chirped-pulse Fourier transform technique, the rotational spectra of cis-verbenol, its hydroxyl deuterated form, and all 13C-monosubstituted isotopologues have been assigned, allowing for the structure determination, as the knowledge of its shape is crucial to understanding its molecular activity. Unlike in the solid state, in the gas phase, the most stable conformer exhibits an anti HO-CH arrangement, analogous to that of simpler allyl alcohol compounds. Observation of the 1 : 1 water complex showed that the conformation of cis-verbenol is still anti where water not only acts mainly as a proton donor to the hydroxyl group, but also as a proton acceptor, forming a secondary C-HO interaction with the hydrogen atom of alkyl verbenol.


Opioid peptide receptor studies. 7. The methylfentanyl congener RTI-4614-4 and its four enantiomers bind to different domains of the rat mu opioid receptor.
Mutational analysis of opioid receptors supports the hypothesis that dissimilar receptor domains contribute to the binding affinity of different ligands. To determine whether enantiomeric ligands can serve to distinguish between different binding pockets (which focuses the analysis on asymmetric structural factors while avoiding confounding changes in physiochemical characteristics), we analyzed the binding of the 3-methylfentanyl congeners RTI-4614-4 [(+/-)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N- phenylpropanamide HCl)], its four stereoisomers [(2S,3R,4S)-1a, (2R,3R,4S)-1b, (2R,3S,4R)-1c, and (2S,3S,4R)-1d], and other mu agonists with cloned rat mu opioid receptors stably expressed in HEK-293 cells and mu/kappa receptor chimeras. Chimera III (kappa[aminoacids 1-141]/mu[aminoacids 151-398]), chimera IV (mu[aminoacids 1-150]/kappa[aminoacids 142-380]), and chimera XII (kappa[aminoacids 1-262]/mu[aminoacids 269-398]) bound [(125)I]IOXY (6beta-iodo-3,14-dihydoxy-17-cyclopropylmethyl-4,5alpha++ +-epoxymorphinan) with high affinities. The Ki values of 1a, 1b, 1c, and 1d at the wild-type mu receptor were 0.55 nM, 0.66 nM, 124 nM, and 59.2 nM, respectively. When the region from the N terminal to the start of the transmembrane helix 3 (TMH3) of the mu receptor was substituted by that of the kappa receptor (chimera III), the Ki value of 1b was increased (relative to the mu receptor) 590-fold compared to a 73-fold increase for 1a. When this portion of the kappa receptor was replaced by that of the mu receptor (chimera IV), the loss of affinity was not as great: 11.7-fold for 1a and 58.5-fold for 1b. Replacement of the middle of the third intracellular loop and third extracellular loop (e3) of the kappa receptor with that of the mu receptor (chimera XII) lowered (relative to their Ki values at the kappa receptor) the Ki values of [D-Ala2,D-Leu5]enkephalin and [D-Ala2-MePhe4,Gly-ol5]enkephalin to a much greater extent than the Ki values of the isomers. The kappa/chimera XII shift was greater for isomers 1c and 1d than for 1b and 1a. Viewed collectively, these data suggest that the region from the N terminal to the start of the TMH3 of the mu opioid receptor determines the binding affinity of RTI-4614-4 and its isomers and that the e3 loop also plays a major role in determining the binding affinity of mu agonist peptides. These data also show that the stereoisomers of RTI-4614-4 probably bind to different domains of the mu receptor and suggest that manipulation of stereochemistry may be a useful tool for designing domain-specific ligands.


Differential accumulation of ribonucleotide reductase subunits in clam oocytes: the large subunit is stored as a polypeptide, the small subunit as untranslated mRNA.
Within minutes of fertilization of clam oocytes, translation of a set of maternal mRNAs is activated. One of the most abundant of these stored mRNAs encodes the small subunit of ribonucleotide reductase (Standart, N. M., S. J. Bray, E. L. George, T. Hunt, and J. V. Ruderman, 1985, J. Cell Biol., 100:1968-1976). Unfertilized oocytes do not contain any ribonucleotide reductase activity; such activity begins to appear shortly after fertilization. In virtually all organisms, this enzyme is composed of two dissimilar subunits with molecular masses of approximately 44 and 88 kD, both of which are required for activity. This paper reports the identification of the large subunit of clam ribonucleotide reductase isolated by dATP-Sepharose chromatography as a relatively abundant 86-kD polypeptide which is already present in oocytes, and whose level remains constant during early development. The enzyme activity of this large subunit was established in reconstitution assays using the small subunit isolated from embryos by virtue of its binding to the anti-tubulin antibody YL 1/2. Thus the two components of clam ribonucleotide reductase are differentially stored in the oocyte: the small subunit in the form of untranslated mRNA and the large subunit as protein. When fertilization triggers the activation of translation of the maternal mRNA, the newly synthesized small subunit combines with the preformed large subunit to generate active ribonucleotide reductase.


Does gender inequality matter for access to and utilization of maternal healthcare services in Bangladesh?
There is a high prevalence of gender gap in Bangladesh which might affect women's likelihood to receive maternal healthcare services. In this backdrop, we aim to investigate how gender inequality measured by intrahousehold bargaining power (or autonomy) of women and their attitudes towards intimate partner violence (IPV) affects accessing and utilizing maternal health care services. We used Bangladesh Demographic and Health Survey (BDHS) data of 2014 covering 5460 women who gave birth at least one child in the last three years preceding the survey. We performed logistic regression to estimate the effect of women's autonomy and their attitude towards IPV on access to and utilization of maternal healthcare services. Besides, we employed different channels to understand the heterogeneous effect of gender inequality on access to maternal healthcare services. We observed that women having autonomy positively influenced attaining five required antenatal care (ANC) services (AOR: 1.17; 95% CI: 0.98-1.41) and women's negative attitudes towards IPV were positively associated with five ANC services (AOR: 1.42; 95% CI: 1.02-1.97), sufficient ANC visits (COR: 1.55; CI: 1.19-2.01), skilled birth attendant (SBA) (AOR: 1.43; 95% CI: 1.05-1.94) and postnatal care (PNC) services (AOR: 1.44; 95% CI: 1.12-1.84). Besides, rural residency, religion, household wealth, education of both women and husband were found to have some of the important channels which were making stronger effect of gender inequality on access to maternal healthcare services. The findings of our study indicate a significant association between access to maternal healthcare services and women's autonomy as well as attitude towards IPV in Bangladesh. We, therefore, recommend to protect women from violence at home and mprove their intrahousehold bargaining power to increase their access to and utilization of required maternal healthcare services.


The cross-level effect of team safety-specific transformational leadership on workplace safety behavior: The serial mediating role of team safety climate and team safety motivation.
Workplace safety not only impairs individual health but also affects economic and social development. Based on social learning theory, collective social learning theory, and expectancy-valence theory, using cluster random sampling method, 630 employees from 66 different work teams out of around 800 employees in a domestic petroleum enterprise were selected to participate in the research. The safety-specific transformational leadership, safety climate, safety motivation and workplace safety behavior scales were used. Data were collected in two stages. SPSS22.0 and Mplus7.0 were used to analyze the data to explore the relationship between team safety-specific transformational leadership and workplace safety behavior, as well as the serial mediating effect of team safety climate and team safety motivation. The results showed that: (a) team safety-specific transformational leadership can positively influence safety compliance and safety participation; (b) team safety climate mediates the relationship between team safety-specific transformational leadership and safety compliance and safety participation; (c) team safety motivation mediates the relationship between team safety-specific transformational leadership and safety compliance and safety participation; and (d) team safety climate and team safety motivation play a serial mediating role between team safety-specific transformational leadership and safety compliance and safety participation. This research has both theoretical and practical significance.


Encrusted cystitis after definitive radiotherapy for cervical cancer: a case report.
Encrusted cystitis is a rare chronic inflammatory disease characterized by calcified plaques of the bladder, previously altered by varies conditions as urological procedures, caused by urea-splitting bacteria. Only one case has been reported on encrusted cystitis occurring after surgery and radiation therapy for a pelvic neoplasm. We report on encrusted cystitis occurred after definitive radiotherapy for bulky uterine cervix cancer, and examine the doses to the bladder wall and the procedure of radiation treatment performed as a possible cause of the onset of the disease. A 52-year-old female developed encrusted cystitis, caused by Corynebacterium spp., after 14 months from definitive chemo-radiotherapy and 2/D brachytherapy treatment for FIGO stage IB2 uterine cervix cancer. For pelvic radiotherapy, the mean bladder dose was 48.47 Gy (range 31.20-51.91); maximal bladder point doses at each brachytherapy insertions were 7.62 Gy, 4.94 Gy and 6.27 Gy at first, second, and third fraction, respectively. Total biological effective dose (BED) at bladder point was 140.05 Gy3. The patient was administered antibiotic therapy with linezolid and urine acidification with vitamin C; dietary norms were also suggested. After therapy, complete remission of symptoms and radiological findings were achieved, and the planned surgery for removing the calcified plaques was not completed. After 5 years from the cervical cancer diagnosis, the patient was disease-free without urinary symptoms. The high doses administered to the bladder wall and the repeated catheterizations performed at each brachytherapy insertions may have favored the infection and promoted the occurrence of the encrusted cystitis.


Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats.
The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 μg Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D₂ receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders.


Seeing genes at work in the living brain with non-invasive molecular imaging.
Over the past ten years, a variety of imaging techniques have been developed that allow non-invasive detection of gene expression within the brain of intact mammals, ranging from mouse to man. The basic concepts of these imaging techniques, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and spectroscopy, bioluminescence imaging and fluorescent imaging, are discussed. The expression of imaging reporter genes can be detected and quantified by these imaging techniques, which allow to unravel the temporospatial dynamics of gene expression within the intact living animal. Different imaging reporter genes have been developed each with their specific use in the basic and clinical neurosciences. Applications of reporter gene imaging can be found in neurooncology, infectious disease of the central nervous system, brain gene transfer, neural cellular therapy and in transgenic mice. Strategies that aim to image gene expression based on detection of mRNA levels have also been developed. We anticipate that these techniques will have a strong impact on preclinical neuroscience and will be of utmost importance in the implementation of gene and cell therapy for diseases of the brain.


Machine Learning Algorithms Can Use Wearable Sensor Data to Accurately Predict Six-Week Patient-Reported Outcome Scores Following Joint Replacement in a Prospective Trial.
Tracking patient-generated health data (PGHD) following total joint arthroplasty (TJA) may enable data-driven early intervention to improve clinical results. We aim to demonstrate the feasibility of combining machine learning (ML) with PGHD in TJA to predict patient-reported outcome measures (PROMs). Twenty-two TJA patients were recruited for this pilot study. Three activity trackers collected 35 features from 4 weeks before to 6 weeks following surgery. PROMs were collected at both endpoints (Hip and Knee Disability and Osteoarthritis Outcome Score, Knee Osteoarthritis Outcome Score, and Veterans RAND 12-Item Health Survey Physical Component Score). We used ML to identify features with the highest correlation with PROMs. The algorithm trained on a subset of patients and used 3 feature sets (A, B, and C) to group the rest into one of the 3 PROM clusters. Fifteen patients completed the study and collected 3 million data points. Three sets of features with the highest R2 values relative to PROMs were selected (A, B and C). Data collected through the 11th day had the highest predictive value. The ML algorithm grouped patients into 3 clusters predictive of 6-week PROM results, yielding total sum of squares values ranging from 3.86 (A) to 1.86 (C). This small but critical proof-of-concept study demonstrates that ML can be used in combination with PGHD to predict 6-week PROM data as early as 11 days following TJA surgery. Further study is needed to confirm these findings and their clinical value.


Impaired Skin Barrier Function and Downregulated Expression of Caspase-14 in Moderate to Severe Chronic Hand Eczema.
To investigate whether the skin barrier function is impaired with regard to the pH value, water content, transepidermal water loss (TEWL), and the integrity of the stratum corneum, and whether the expression of caspase-14 is altered in moderate to severe chronic hand eczema (CHE). Thirty patients with moderate to severe CHE treated at our institute and 30 healthy volunteers were included in this study. The pH value, water content, TEWL, and the integrity of the stratum corneum were measured in all subjects. Significantly increased pH value, decreased water content, elevated TEWL, and impaired integrity of the stratum corneum were observed in the lesional skin of CHE patients compared with the nonlesional skin of CHE patients and the normal skin of healthy volunteers. The expression of caspase-14 decreased in the lesional and nonlesional skin of CHE patients compared with the normal skin of healthy volunteers, especially prominent in the nonlesional skin. The mean optical density (OD) value of immunohistochemical staining for caspase-14 was significantly lower in the nonlesional skin than in the lesional skin and normal skin (p < 0.01 for both). Although the mean OD value was lower in the lesional skin than in the normal skin, the difference was not statistically significant (p > 0.05). Skin barrier dysfunction indeed occurs in CHE patients, which may be related to mechanisms associated with a downregulated expression of caspase-14.


Possible role for cell-surface carbohydrate-binding molecules in lymphocyte recirculation.
We are investigating the hypothesis that carbohydrate-binding molecules on the cell surface are involved in the recirculation of lymphocytes from the bloodstream into lymphoid organs. This phenomenon requires the specific attachment of circulating lymphocytes to the endothelial cells of postcapillary venules. Using an in vitro assay to measure the adhesive interaction between lymphocytes and postcapillary venules, we have found that L-fucose, D mannose, and the L-fucose-rich, sulfated polysaccharide fucoidin specifically inhibit this binding interaction. L-fucose shows stereo-selective inhibitory activity at concentrations greater than 18 mM while fucoidin produces 50% inhibition at approximately 1-5 X 10(-8) M. Fucoidin appears to interact with the lymphocyte, and not the postcapillary venule, to inhibit binding. These data suggest that cell surface carbohydrates (fucoselike) and carbohydrate-binding molecules (cell surface lectins) may contribute to the specific attachment of lymphocytes to postcapillary venules.


Pubertal timing and Mexican-origin girls' internalizing and externalizing symptoms: the influence of harsh parenting.
Early-maturing girls are at risk for internalizing and externalizing problems. Research concerning pubertal timing and mental health among Mexican Americans or the influence of parenting behaviors on these relations has been scarce. This study addressed these gaps. This was a prospective examination of 362 Mexican-origin girls and their mothers in 3 waves of data. Measures included girls' self-report of pubertal development and girls' and mothers' report of maternal harsh parenting and daughters' mental health. Using structural equation modeling, we examined whether pubertal timing in 5th grade predicted girls' internalizing and externalizing outcomes in 10th grade. We also examined the mediating and moderating effects of harsh parenting on the relations between pubertal timing and internalizing and externalizing behaviors, as well as the influence of mothers' and daughters' nativity on these relations. Results differed depending on reporter and maternal nativity. Using daughters' report, we found that Mexican American mothers' harsh parenting acted as a moderator. At high levels of harsh parenting, early pubertal timing predicted higher externalizing scores, while at low levels of harsh parenting, early timing predicted lower externalizing scores. For Mexican immigrant mothers, harsh parenting mediated the effects of pubertal timing on girls' internalizing and externalizing problems. There were no significant pubertal effects for mothers' report. Findings suggest that maternal harsh parenting plays a key role in the relations between early pubertal timing and behavioral and emotional outcomes among Mexican-origin girls.


Developement of health risk rating scale for indoor airborne fungal exposure.
This paper aims to quantify airborne fungal load in air-conditioned rooms and develop a health risk rating scale for different indoor environments. Five sampling locations in Kolkata frequented by a heterogeneous human population, containing various types of fungal growth-promoting substances (FGPS) like old documents, food items, waste hair, etc. were chosen as sampling locations where an Andersen Two-Stage Cascade Impactor was ran using Rose Bengal agar and Potato Dextrose agar media plates. Total spore load (CFU/m3), species diversity, species dominance, human exposure time, susceptible age and FGPS were considered the risk factors for this study. A risk rating scale was developed after evaluating the relative importance of these different factors in relation to human health. The most dominant genera were Aspergillus, followed by Penicillium. Maximum CFU was observed at library, followed by computer room.


'Online' geriatric assessment procedure for older adults referred for geriatric assessment during an acute care episode for consideration of reliability of triage decisions.
Comprehensive geriatric assessment has been shown to improve patient outcomes, but the geriatricians who deliver it are in short-supply. A web-based method of comprehensive geriatric assessment has been developed with the potential to improve access to specialist geriatric expertise. The current study aims to test the reliability and safety of comprehensive geriatric assessment performed "online" in making geriatric triage decisions. It will also explore the accuracy of the procedure in identifying common geriatric syndromes, and its cost relative to conventional "live" consultations. The study population will consist of 270 acutely hospitalized patients referred for geriatric consultation at three sites. Paired assessments (live and online) will be conducted by independent, blinded geriatricians and the level of agreement examined. This will be compared with the level of agreement between two independent, blinded geriatricians each consulting with the patient in person (i.e. "live"). Agreement between the triage decision from live-live assessments and between the triage decision from live-online assessments will be calculated using kappa statistics. Agreement between the online and live detection of common geriatric syndromes will also be assessed using kappa statistics. Resource use data will be collected for online and live-live assessments to allow comparison between the two procedures. If the online approach is found to be less precise than live assessment, further analysis will seek to identify patient subgroups where disagreement is more likely. This may enable a protocol to be developed that avoids unsafe clinical decisions at a distance. ACTRN12611000936921.


The formation of cluster elliptical galaxies as revealed by extensive star formation.
The most massive galaxies in the present-day Universe are found to lie in the centres of rich clusters. They have old, coeval stellar populations suggesting that the bulk of their stars must have formed at early epochs in spectacular starbursts, which should be luminous phenomena when observed at submillimetre wavelengths. The most popular model of galaxy formation predicts that these galaxies form in proto-clusters at high-density peaks in the early Universe. Such peaks are indicated by massive high-redshift radio galaxies. Here we report deep submillimetre mapping of seven high-redshift radio galaxies and their environments. These data confirm not only the presence of spatially extended regions of massive star-formation activity in the radio galaxies themselves, but also in companion objects previously undetected at any wavelength. The prevalence, orientation, and inferred masses of these submillimetre companion galaxies suggest that we are witnessing the synchronous formation of the most luminous elliptical galaxies found today at the centres of rich clusters of galaxies.


Pre-treatment optimisation with pulmonary rehabilitation of elderly lung cancer patients with frailty for surgery.
Frailty develops as a result of age-related decline in many physiological systems and is associated with increased vulnerability to adverse outcomes following thoracic surgery. We prospectively tested our hypothesis that pre-operative pulmonary rehabilitation (Prehab) improves frailty, as suggested by a frailty index > 3 (FI > 3) and fitness, and thereby reduces the risk of post-surgical complications and death in vulnerable elderly lung cancer patients. 221 surgical patients, 80 with FI > 3 vs. 141 patients with FI < 3, following Prehab proceeded to surgery. Their Frailty index (FI), dyspnoea scores, performance status (PS), level of activity (LOA) and six-minute walk test (6MWT) prior to and following Prehab were determined. The post-operative length of hospital stay (LOHS), complications, mortality and mid-term survival at 1100 days were compared. Similarly, outcomes for elderly patient ≥ 70 years with FI > 3 (≥ 70,FI > 3) were compared with younger patients < 70 years with FI ≤ 3 (< 70,FI ≤ 3). Patients with FI > 3 were significantly older, had lower 6MWT and higher thoracoscores hence, 82.5% of patients with FI > 3 vs. 33.3% (p = 0.02) with FI ≤ 3 were considered high risk for surgery and postoperative adverse events. With Prehab there was significant improvement in the FI, dyspnoea scores, PS, LOA and 6MWT. Following surgery, there were no differences in major complication rates (8.8% vs. 9.2% p = ns); LOHS median (IQR) [7 (6.8) vs. 8 (5.5) days]; mortality at 30-days (3.7% vs. 0.7%, p = ns); 90-days (6.3% vs. 2.8%, p = ns) and 1-year survival (81.1% vs. 83.7% p = ns). Survival at 1100 days was (63.2% vs. 71.1%, p = 0.19). Likewise, 87.7% elderly ≥ 70,FI > 3 patients were considered high-risk for surgery and postoperative adverse events vs. 35.1% younger patients < 70,FI ≤ 3 (p = 0.0001). Following Prehab and surgery, there were no significant differences in complications, LOHS, mortality at 365 days between the two groups. Survival at 1100 days for ≥ 70,FI > 3 was 55.2% vs. 79.96% for < 70,FI ≤ 3; (p = 0,01). Our study suggests that Prehab optimises vulnerable high-risk elderly lung cancer patients with frailty allowing them to undergo surgery with outcomes of post-surgical complications, LOHS and mortality at 365 days no different to patients with no frailty. However, mid-term survival was lower for elderly patients with frailty.


Specific localization of lysosomal aminopeptidases in type II alveolar epithelial cells of the rat lung.
We previously demonstrated that lysosomal cysteine proteinases, cathepsins B, H, and L were localized in lysosomes of alveolar macrophages and bronchial epithelial cells in the rat lung, while cathepsin H, a typical aminopeptidase, was additionally distributed in lamellar bodies containing surfactant in type II alveolar epithelial cells (ISHII et al., 1991). The present immunohistochemical study further examined the localization of lysosomal aminopeptidases, cathepsin C, and tripeptidyl peptidase I (TPP-I) in the rat lung. Western blotting confirmed the presence of cathepsin C and TPP-I as active forms in the pulmonary tissue, showing 25 kD and 47 kD, respectively. Immunohisto/cytochemical observations demonstrated that positive staining for cathepsin C and TPP-I was more intensely localized in alveolar epithelial regions than in bronchial or bronchiolar epithelial cells. By double immunostaining using confocal laser microscopy, immunoreactivity for cathepsin H was found to be co-localized with that for cathepsin C or TPP-I in both type II cells and macrophages. Moreover, when doubly stained with anti-cathepsin C and ED2, single-positive type II cells could be clearly distinguished from double-positive macrophages in the alveolar region. Immunoelectron microscopy revealed the gold labeling of cathepsin C or TPP-I in multivesicular and composite bodies, and lamellar bodies of Type II cells. These results showing that lysosomal aminopeptidases such as cathepsin H, cathepsin C and TPP-I are localized in lamellar bodies of type II alveolar epithelial cells strongly argue for the participation of lysosomal aminopeptidases in the formation process of surfactant containing specific proteins.


[A method for the surgical treatment of patients with chronic postoperative osteomyelitis of the sternum].
The authors share their experiences with diagnosing and surgical treatment of chronic postoperative osteomyelitis of sternum developed in 36 patients after operations on the heart, lungs and organs of mediastinum. The purulent process can be liquidated in all the patients due to performing saving resection of the sternum and plasty of the bone defect with local tissues, application of a gauze-cotton roll pressing the subcutaneous fat into the bone defects formed after treatment of the affected portions of the sternum, administration of antibiotics according to sensitivity of the microflora.


Influence of Probiotics on the Development of Clostridioides difficile Infection in Patients Receiving Fluoroquinolones.
Fluoroquinolones are associated with an increased risk of Clostridioides difficile infection (CDI). Probiotic supplementation has been shown to reduce the risk of antibiotic-associated diarrhea with variable effects on CDI. The objective of this study was to evaluate receipt of probiotics on development of primary CDI among hospitalized patients receiving fluoroquinolones. A retrospective cohort was evaluated that consisted of two groups of 100 patients each, admitted August 2018 through August 2020 that received ≥3 days of definitive monotherapy with levofloxacin or ciprofloxacin within 72 h of admission. Primary outcome was incidence of CDI. Secondary outcomes included rates of C. difficile diagnostic stool testing, additional infectious diagnostic testing, and non-CDI related gastrointestinal side effects. Patients on fluoroquinolones who received probiotics had a non-statistically significantly lower incidence in overall cases of CDI compared to those who did not receive probiotics (0% vs. 3%, p = 0.246). Patients who received probiotics had statistically significantly fewer C. difficile diagnostic stool tests performed (4% vs. 16%, p = 0.005) and fewer additional infectious diagnostic testing performed (4% vs. 10%, p = 0.096), respectively. Further research is warranted to optimize and standardize probiotic prescribing in high-risk patients.


Molecular structure and stability of dissolved lithium polysulfide species.
The ability to predict the solubility and stability of lithium polysulfide is vital in realizing longer lasting lithium-sulfur batteries. Herein we report combined experimental and computational analyses to understand the dissolution mechanism of lithium polysulfide species in an aprotic solvent medium. Multinuclear NMR, variable temperature ESR and sulfur K-edge XAS analyses reveal that the lithium exchange between polysulfide species and solvent molecules constitutes the first step in the dissolution process. Lithium exchange leads to de-lithiated polysulfide ions (Sn(2-)) which subsequently form highly reactive free radicals through dissociation reaction (Sn(2-) → 2Sn/2˙(-)). The energy required for the dissociation and possible dimer formation reactions of the polysulfide species is analyzed using density functional theory (DFT) based calculations. Based on these findings, we discuss approaches to optimize the electrolyte in order to control the polysulfide solubility.


Preceptor development: providing effective feedback.
Feedback plays a significant role in precepting and is indispensable in residency training. As described by the Accreditation Council for Graduate Medical Education, the goal of any postgraduate residency program is to prepare individual trainees to function as qualified practitioners. Although feedback and evaluations have traditionally been synonymous, our goal is to differentiate the two and describe the role of each within resident performance. The goal of this article is to provide preceptors with the tools to provide timely, effective, and quality feedback to residents on a regular basis. Although the focus of this article is on residency training, these concepts can be utilized in student rotations as well.


Knowledge and Attitudes for the Management of Behavioral Variant of Frontotemporal Dementia.
Background: The diagnosis of the behavioral variant of frontotemporal dementia (bvFTD) can be especially challenging and is relatively underdiagnosed. There is scarce information on training and attitudes from care providers facing bvFTD in settings with limited resources. We aim to describe clinical knowledge and attitudes facing bvFTD from neurologists, psychiatrists, and residents in Peru. Methods: Potential participants received invitations by email to complete an online questionnaire. In addition, we reviewed 21 curricula from undergraduate medical schools' programs offered by the main schools of medicine in Peru during 2020 and 2021. Results: A total of 145 participants completed the survey. The responders were neurologists (51%), psychiatrists (25%), and residents in neurology or psychiatry (24%). Only 26% of the respondents acknowledged receiving at least one class on bvFTD in undergraduate medical training, but 66.6% received at least some training during postgraduate study. Participants identified isolated supportive symptoms for bvFTD; however, only 25% identified the possible criteria and 18% the probable bvFTD criteria. They identified MoCA in 44% and Frontal Assessment Battery (39%) as the most frequently used screening test to assess bvFTD patients. Memantine and Acetylcholinesterase inhibitors were incorrectly indicated by 40.8% of participants. Seventy six percentage of participants indicated that they did not provide education and support to the caregiver. The dementia topic was available on 95.2%, but FTD in only 19%. Conclusion: Neuropsychiatry medical specialists in Peru receive limited training in FTD. Their clinical attitudes for treating bvFTD require appropriate training focused on diagnostic criteria, assessment tools, and pharmacological and non-pharmacological management.


GLUT-4, tumour necrosis factor, essential fatty acids and daf-genes and their role in glucose homeostasis, insulin resistance, non-insulin dependent diabetes mellitus, and longevity.
GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes seem to play an important and essential role in the maintenance of glucose homeostasis, and in the pathobiology of obesity and non-insulin dependent diabetes mellitus (NIDDM). Daf-genes encode for proteins which are 35% identical to the human insulin receptor, a transforming growth factor-beta (TGF-beta) type signal and can also enhance the expression of superoxide dismutase (SOD). On the other hand, EFAs and their metabolites can increase the cell membrane fluidity and thus, enhance the expression of GLUT-4 and insulin receptors. In addition, EFAs can suppress TNF-alpha production and secretion and thus, are capable of reversing insulin resistance. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Hence, it is likely that there is a close interaction between GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin that may have relevance to the development of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.


Refereeing the public health.
Between January 2009 and October 2013, 49 states and the District of Columbia passed laws focusing on mitigating the consequences of traumatic brain injuries (TBIs) in organized youth sports. Using historical, contextual, and empirical methods, this Article describes the content, goals, and structure of youth sports TBI laws, while hypothesizing about their underlying legislative logic and long-term public health consequences. The Article's empirical evidence suggests two key findings: first, that a dominant interest group, the National Football League, helped to define the problem and its associated solutions for the vast majority of states, thus curving the legislative story are in favor of its policy prescriptions; second, that existing youth sports TBI laws are focused on secondary, not primary, prevention, and may thus shift attention away from more comprehensive solutions. Finally, the Article explains why such state laws will likely fail to substantially resolve the larger untackled problem--significantly reducing the overall rate and number of TBIs in youth sports. After explaining why existing state youth sports TBI laws fail to accomplish this broader goal, the Article queries whether alternative policy or public health measures might offer more robust solutions.


Peptides Acting as Cognitive Enhancers.
The aim of this paper is to present an overview of three peptides that, by improving synaptic function, enhance learning and memory in laboratory rodents. We summarize their structure, their mechanisms of action, and their effects on synaptic and cognitive function. First we describe FGL, a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K signaling pathway it promotes synapse and spine formation and enhances hippocampal dependent memory. Lastly, we describe a new peptide derived from the well-known tumor suppressor PTEN that prevents pathological interactions between PTEN and PDZ proteins at synapses during exposure to Amyloid beta. This action prevents memory deterioration in mouse model of Alzheimer's disease. Together, this review indicates how learning and memory can be improved by manipulating synaptic function and number through pharmacological treatment with peptides, and it establishes synaptic function as a valid target for cognitive enhancement.


Debate article: Antipsychotic medications are clinically useful for the treatment of delirium.
Prescribing of antipsychotic medications for patients with delirium remains controversial. Concerns exist that these vulnerable and frail patients may be prescribed antipsychotics inappropriately as a substitute for non-pharmacological approaches when identifiable causes are not found or they challenge ward processes. Moreover, recent evidence suggests that antipsychotics may cause more harm than good in the palliative care patient group with delirium. On the other hand, guidelines in the United Kingdom and the Netherlands support prescribing of antipsychotics in certain circumstances, and a large European survey has revealed that antipsychotics tend to be prescribed first line for hyperactive delirium. Never before, therefore, is there a greater need to examine whether indeed these medications are clinically useful for the treatment of delirium. With this in mind, evidence-based arguments for and against prescribing antipsychotics for the treatment of delirium are presented in this debate article. The paper concludes with a moderation piece to help guide clinical practice.


Photoreactivation in an archaeon from geothermal environments.
UV-inactivated cells of Sulfolobus acidocaldarius rapidly regained viability when exposed to white light This recovery was strictly dependent upon illumination with visible light and was not attenuated by prior dark-incubation. The kinetics of photoreactivation were determined at several temperatures and at several wavelengths of light. The results obtained in vivo were consistent with a DNA photolyase having a broad action spectrum. Photoreactivation of S. acidocaldarius apparently represents the first DNA repair process to be measured in an archaeon which grows optimally near 80°C.


Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk.
STK15/Aurora-A is a serine/threonine kinase essential for chromosome segregation and cytokinesis, and is considered to be a cancer susceptibility gene in mice and humans. Two coding single nucleotide polymorphisms in Aurora-A, 91T>A [phenylalanine/isoleucine (F/I)] and 169G>A [valine/isoleucine (V/I)], create four haplotypes, 91T-169G, 91A-169G, 91T-169A, and 91A-169A. We evaluated the association between these coding single nucleotide polymorphisms and esophageal cancer risk by genotyping 197 esophageal cancer cases and 146 controls. Haplotype 91A-169A (I31/I57) was observed to be statistically more frequent in cancer cases (odds ratio, 3.1452; 95% confidence interval, 1.0258-9.6435). Functional differences among the four isoforms were then analyzed to reveal the source of the cancer risk. Kinase activity levels of I31/I57 and F31/I57 were reduced to 15% and 40% compared with I31/V57 in vivo and in vitro. We considered the differences between the kinase activities and divided individuals into four categories of Aurora-A haplotype combination. Category I had 57.5% or less kinase activity compared with the most common category, category III, and had a significantly higher estimated cancer risk (odds ratio, 5.5328; 95% confidence interval, 1.8149-16.8671). Abnormal nuclear morphology, a characteristic of genomic instability, was observed to be 30 to 40 times more frequent in human immortalized fibroblast cells overexpressing I31/I57 or F31/I57 compared with the others. Furthermore, significantly higher levels of chromosomal instability were observed in cancers in category I (homozygote 91T-169A) than those in category III (homozygous 91A-169G). These results indicate that the less kinase active Aurora-A haplotype combinations might induce genomic instability and increase esophageal cancer risk either in a recessive or a dominant manner.


Metabolite profiling of tomato (Lycopersicon esculentum) using 1H NMR spectroscopy as a tool to detect potential unintended effects following a genetic modification.
The maize transcription factors LC and C1 were simultaneously overexpressed in tomato with the aim of producing lines with increased amounts of flavonols. The metabolite composition of these genetically modified tomatoes has been compared with that of azygous (nonmodified) controls grown side-by-side under the same conditions. It has been possible to observe metabolic changes in both types at different stages of maturity. (1)H NMR spectra showed that the levels of glutamic acid, fructose, and some nucleosides and nucleotides gradually increase from the immature to the ripe stage, whereas some amino acids such as valine and gamma-aminobutyric acid were present in higher amounts in unripe tomatoes. Apart from the significantly increased content of six main flavonoid glycosides (mainly kaempferol-3-O-rutinoside, with additional increases in kaempferol-3,7-di-O-glucoside (1), kaempferol-3-O-rutinoside-7-O-glucoside (2), kaempferol-3-O-glucoside, a dihydrokaempferol-O-hexoside (3), and naringenin-7-O-glucoside), the levels of at least 15 other metabolites were found to be different between the two types of red tomato. Among them were citric acid, sucrose, phenylalanine, and trigonelline. However, although statistically significant, these changes in mean values were relatively minor (less than 3-fold) and within the natural variation that would be observed in a field-grown crop. Nevertheless, this study clearly showed that NMR combined with chemometrics and univariate statistics can successfully trace even small differences in metabolite levels between plants and therefore represents a powerful tool to detect potential unintended effects in genetically modified crops.


Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake.
Serum amyloid A is an acute phase protein that is carried in the plasma largely as an apolipoprotein of high density lipoprotein (HDL). In this study we investigated whether SAA is a ligand for the HDL receptor, scavenger receptor class B type I (SR-BI), and how SAA may influence SR-BI-mediated HDL binding and selective cholesteryl ester uptake. Studies using Chinese hamster ovary cells expressing SR-BI showed that (125)I-labeled SAA, both in lipid-free form and in reconstituted HDL particles, functions as a high affinity ligand for SR-BI. SAA also bound with high affinity to the hepatocyte cell line, HepG2. Alexa-labeled SAA was shown by fluorescence confocal microscopy to be internalized by cells in a SR-BI-dependent manner. To assess how SAA association with HDL influences HDL interaction with SR-BI, SAA-containing HDL was isolated from mice overexpressing SAA through adenoviral gene transfer. SAA presence on HDL had little effect on HDL binding to SR-BI but decreased (30-50%) selective cholesteryl ester uptake. Lipid-free SAA, unlike lipid-free apoA-I, was an effective inhibitor of both SR-BI-dependent binding and selective cholesteryl ester uptake of HDL. We have concluded that SR-BI plays a key role in SAA metabolism through its ability to interact with and internalize SAA and, further, that SAA influences HDL cholesterol metabolism through its inhibitory effects on SR-BI-mediated selective lipid uptake.


Effect of illumination and Se vacancies on fast oxidation of ultrathin gallium selenide.
Gallium selenide (GaSe) has recently emerged as a unique platform due to its exciting properties, namely, large and fast photo-response, high carrier mobility and non-linear optical properties. However, exposure for a few days causes the fast oxidation of ultrathin GaSe under ambient conditions and the oxidation mechanism remains unclear. By means of density functional theory calculations and ab initio molecular dynamics simulations, we comprehensively investigated the possible sources that cause oxidation of ultrathin GaSe. Our results show that illumination and Se vacancies induce the fast oxidation of GaSe. Under illumination, photo-excited electrons from the surface of GaSe are effectively transferred to oxygen molecules and thus, superoxide anions (O2-) are generated that react with GaSe. Moreover, Se vacancies directly react with O2. In both the cases, the Ga-Se bonds are continually replaced by Ga-O bonds, which eventually leads to complete degradation of GaSe, accompanied with the formation of the oxidation products Ga2O3 and elemental Se. The comprehensive degradation mechanism unveiled herein lays an important foundation for the development of suitable protecting strategies in GaSe-based devices.


A tumorigenic actin mutant alters fibroblast morphology and multicellular assembly properties.
Tumor initiation and progression are accompanied by complex changes in the cytoarchitecture that at the cellular level involve remodeling of the cytoskeleton. We report on the impact of a mutant β-actin (G245D-actin) on cell structure and multicellular assembly properties. To appreciate the effects of the Gly245Asp substitution on the organization of the actin cytoskeleton, we examined the polymerization properties of G245D-actin in vitro by pyrene polymerization assays and total internal reflection fluorescence microscopy (TIRF). The mutant actin on its own has a significantly reduced polymerization efficiency compared to native actin but also modifies the polymerization of actin in copolymerization experiments. Comparison of the structure of Rat-2 fibroblasts and a stably transfected derivate called Rat-2-sm9 revealed the effects of G245D-actin in a cellular environment. The overall actin levels in Rat-2-sm9 show a 1.6-fold increase with similar amounts of mutant and wild-type actin. G245D-actin expression renders Rat-2-sm9 cells highly tumorigenic in nude mice. In Rat-2-sm9 monolayers, G245D-actin triggers the formation of extensive membrane ruffles, which is a characteristic feature of many transformed cells. To approximate complex cell-cell and cell-matrix interactions that occur in tumors and might modulate the effects of G245D-actin, we extended our studies to scaffold-free 3D spheroid cultures. Bright field and scanning electron microscopy (SEM) show that Rat-2-sm9 and Rat-2 cells share essential features of spheroid formation and compaction. However, the resulting spheroids exhibit distinct phenotypes that differ mainly in surface structure and size. The systematic comparison of transformed and normal spheroids by SEM provides new insights into scaffold-free fibroblast spheroid formation.


Evidence for 'lock and key' character in an anti-phosphonate hydrolytic antibody catalytic site augmented by non-reaction centre recognition: variation in substrate selectivity between an anti-phosphonate antibody, an anti-phosphate antibody and two hydrolytic enzymes.
The substrate selectivities of an anti-phosphonate and an anti-phosphate kinetically homogeneous polyclonal catalytic antibody preparation and two hydrolytic enzymes were compared by using hapten-analogous and truncated carbonate and ester substrates each containing a 4-nitrophenolate leaving group. Syntheses of the truncated substrates devoid of recognition features in the non-leaving group parts of the substrates are reported. The relatively high kinetic selectivity of the more active anti-phosphonate antibody preparation is considered to depend on a relatively rigid catalytic site with substantial reaction centre specificity together with other important recognition interactions with the extended non-leaving group part of the substrate. In contrast, the less catalytically active, more flexible anti-phosphate antibody exhibits much lower kinetic selectivity for the substrate reaction centre comparable with that of the hydrolytic enzymes with activity much less dependent on recognition interactions with the non-leaving group part of the substrate. The ways in which haptenic flexibility and IgG architecture might contribute to the differential kinetic selectivities are indicated.


Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice.
Inhibitory luminopsins (iLMO2) integrate opto- and chemo-genetic approaches and allow for cell-type specific inhibition of neuronal activity. When exposed to a Renilla luciferase substrate, Coelenterazine (CTZ), iLMO2 generates bioluminescence-mediated activation of its amino-terminal halorhodopsin, resulting in neuronal inhibition. Moderate daily exercise in the form of interval treadmill-training (IT) applied following a peripheral nerve injury results in enhanced motor axon regeneration and muscle fiber reinnervation in female mice. We hypothesized that iLMO2 mediated inhibition of motoneuron activity during IT would block this enhancement. Unilateral intramuscular injections of Cre-dependent AAV2/9-EF1a-DIO-iLMO2 (∼8.5 x 1013 vg/ml) were made into the gastrocnemius and tibialis anterior muscles of young female ChAT-IRES-Cre mice, thereby limiting iLMO2 expression specifically to their motoneurons. Four to six weeks were allowed for retrograde viral transduction after which a unilateral sciatic nerve transection (Tx) and repair was performed. Animals were randomized into four groups: IT only, IT + CTZ, CTZ only, and untreated (UT). Three weeks post Tx-repair, the maximal amplitude direct muscle responses (M-max) in both muscles in the IT only group were significantly greater than in UT mice, consistent with the enhancing effects of this exercise regimen. Inhibiting motoneuron activity during exercise by a single injection of CTZ, administered 30 minutes prior to exercise, completely blocked the enhancing effect of exercise. Similar treatments with CTZ in mice without iLMO2 had no effect on regeneration. Neuronal activity is required for successful enhancement of motor axon regeneration by exercise.


Comparative study of apatite formation on CaSiO3 ceramics in simulated body fluids with different carbonate concentrations.
Apatite formation on CaSiO3 ceramics was investigated using two different simulated body fluids (SBF) proposed by Kokubo (1990) and Tas (2000) and three sample/SBF (S/S) ratios (1.0, 2.5 and 8.3 mg/ml) at 36.5 degrees C for 1-25 days. The CaSiO3 ceramic was prepared by firing coprecipitated gel with Ca/Si = 0.91 at 1400 degrees C. The bulk density was 2.14 g/cm3 and the relative density about 76%. The two SBF solutions contain different concentrations of HCO3- and Cl- ions, the concentrations of which are closer to human blood plasma in the Tas SBF formulation than in the Kokubo formulation. The pH values in the former solution are also more realistic. The CaSiO3 ceramics show apatite formation in SBF (Kokubo) after soaking for only 1 day at all S/S ratios whereas different phases were formed at each S/S ratio in SBF (Tas). The crystalline phases formed were mainly apatite at S/S = 1.0 mg/ml, carbonate-type apatite at 2.5 mg/ml and calcite at 8.3 mg/ml. At higher S/S ratios the increase in the Ca concentration became higher while the P concentration became lower in the reacted SBF. These changes in SBF concentrations and increasing pH occurred at higher S/S ratios, producing more favorable conditions in the SBF for the formation of carbonate bearing phases, finally leading to the formation of calcite instead of apatite in the higher HCO3- ion concentration SBF (Tas). Apatite is, however, formed in the lower HCO3- ion concentration SBF (Kokubo) even though the Ca and P concentrations change in a similar manner to SBF (Tas).


The role of the home-based provider in disaster preparedness of a vulnerable population.
Veterans receiving home-based primary care (HBPC) are an especially vulnerable population served by the Veterans Health Administration (VHA) due to high rates of physical, functional, and psychological limitations. These vulnerabilities may prevent these persons from being adequately prepared for disasters. HBPC providers connect the community-dwelling population with their regional health care system and thus are appropriate partners for assessing preparedness. The limited literature on this topic suggests that there are issues with the development and implementation of emergency management plans, dissemination to staff, and inconsistencies with preparedness strategies across agencies. To further explore identified issues regarding emergency management planning for patients receiving medical care in their home, including ways in which policy and procedures support the routine assessment of disaster preparedness for patients. This exploratory pilot project, carried out in a single VHA HBPC program located in an urban area, involved seven 15- to 25-min semistructured interviews with practitioners and leadership. Transcripts of the interviews were analyzed using content analysis techniques to develop themes to describe information obtained through the interviews. Six themes emerged from the data: (1) a national policy regarding the inclusion of disaster preparedness assessment in routine HBPC assessment exists in only a skeletal manner and individual HBPC programs are tasked with developing their own policies; (2) the tools used at the initial assessment were rudimentary and, in some cases, individually developed by providers; (3) the comprehension of criteria for assigning risk categories (i.e. acuity levels) varied among providers; (4) the primary challenges identified by respondents to patient engagement in emergency preparedness activities included cognitive impairments, patients' willingness to invest in preparedness activities, and limited resources; (5) providers received limited formal training on how to prepare their patients for a disaster, and (6) provider recommendations included training to focus on better strategies to get patients to participate, more consistent time spent on patient education, formalization of the initial assessment, and having emergency preparedness be formally addressed on a more consistent basis. Formal standardized strategies regarding disaster preparedness assessment for HBPC patients, which leave room for flexibility in consideration of local factors, could assist in creating more comprehensive emergency management planning agendas and community collaboration.


Human/robotic interaction: vision limits performance in simulated vitreoretinal surgery.
Compare accuracy and precision in XYZ of stationary and dynamic tasks performed by surgeons with and without the use of a tele-operated robotic micromanipulator in a simulated vitreoretinal environment. The tasks were performed using a surgical microscope or while observing a video monitor. Two experienced and two novice surgeons performed tracking and static tasks at a fixed depth with hand-held instruments on a Preceyes Surgical System R0.4. Visualization was through a standard microscope or a video display. The distances between the instrument tip and the targets (in μm) determined tracking errors in accuracy and precision. Using a microscope, dynamic or static accuracy and precision in XY (planar) movements were similar among test subjects. In Z (depth) movements, experience lead to more precision in both dynamic and static tasks (dynamic 35 ± 14 versus 60 ± 37 μm; static 27 ± 8 versus 36 ± 10 μm), and more accuracy in dynamic tasks (58 ± 35 versus 109 ± 79 μm). Robotic assistance improved both precision and accuracy in Z (1-3 ± 1 μm) in both groups. Using a video screen in combination with robotic assistance improved all performance measurements and reduced any differences due to experience. Robotics increases precision and accuracy, with greater benefit observed in less experienced surgeons. However, human control was a limiting factor in the achieved improvement. A major limitation was visualization of the target surface, in particular in depth. To maximize the benefit of robotic assistance, visualization must be optimized.


Does the MIND diet decrease depression risk? A comparison with Mediterranean diet in the SUN cohort.
To prospectively evaluate the association of the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet and the Mediterranean diet (and their components), and depression risk. We followed-up (median 10.4 years) 15,980 adults initially free of depression at baseline or in the first 2 years of follow-up. Food consumption was measured at baseline through a validated food-frequency questionnaire, and was used to compute adherence to the MIND and the Mediterranean diets. Relationships between these two diets and incident depression were assessed through Cox regression models. We identified 666 cases of incident depression. Comparing the highest versus the lowest quartiles of adherence, we found no association of the MIND diet and incident depression. This relation was statistically significant for the Mediterranean diet {hazard ratio (HR) 0.75, [95% confidence interval (95% CI) 0.61, 0.94]; p < 0.01}, although with departure from linearity. A reduced depression risk was associated with higher consumption of both fruits and nuts [HR 0.82 (95% CI 0.69, 0.96); p = 0.02], moderate nuts consumption [HR 0.77 (95% CI 0.64, 0.93); p = 0.01], and avoidance of fast/fried food [HR 0.63 (95% CI 0.41, 0.96); p = 0.03]. The Mediterranean diet was associated with reduced depression risk, but we found no evidence of such an association for the MIND diet.


Langerhans Cell Histiocytosis in an Adult: A Discussion of Epidemiology and Treatment Options.
Langerhans cell histiocytosis (LCH) is a rare disorder defined by the abnormal proliferation of Langerhans cells. While LCH can present at any age, it is classically described as a pediatric condition, and is therefore overlooked in the adult patient. Additionally, depending on tumor burden and location, LCH can manifest with a host of oral and systemic symptoms which further confuses the clinical presentation and ultimate diagnosis.The authors present a unique report of an elderly Hispanic male diagnosed with mandibular LCH who sought primary tumor excision after neoadjuvant chemotherapy. In this study, a fibula-free flap was used for subsequent reconstruction.The purpose of the study is 2-fold: to highlight the variability of LCH in both patient symptomatology and demographics, as well as the role of plastic reconstructive surgery in definitive LCH management, particularly in the setting of single system unifocal disease.


Presenting research risks and benefits to parents: does format matter?
Several studies suggest that many parents and research participants have poor understanding of the elements of consent, particularly the risks and benefits. However, some data suggest that the format and framing of research risks and benefits may be an important determinant of subject understanding. We examined the effect of tabular and graphical presentation of risks and benefits on parents' understanding of a research study. Parents of children scheduled to undergo an elective surgical procedure (n = 408) were randomized to receive information about the risks and benefits of a sham study of postoperative pain control using text, tables, or pictographs and then completed a questionnaire to examine their gist (essential) and verbatim (actual) understanding of the information. Parent demographics were recorded and their literacy and numeracy skills measured. Parents randomized to receive information using tables or pictographs had significantly (P < 0.025) greater gist and verbatim understanding than did parents who received the information using standard text. Tables and pictographs were also superior to text in promoting understanding among parents with low numeracy and literacy skills. Many parents and patients have difficulty in assimilating and interpreting risk/benefit information for both research and treatment. This is due, in part, to the manner in which risks and benefits are communicated and to the literacy and numeracy abilities of the individual. The results of this study suggest a simple and practical method for enhancing understanding of risk/benefit statistics for parents with varying numeracy and literacy skills.


Meso-Structuring of SiCN Ceramics by Polystyrene Templates.
A simple one-pot synthesis of well-defined PS-silazane nano-composites (polystyrene, PS) is described. In contrast to the, thus far, used two-step procedure ((1) assembly of a PS template bed and (2) careful filling of the voids between the PS spheres), which is restricted to macro structuring, we are able to simply mix the PS template and a commercially available silazane precursor HTT-1800 in toluene. The key is the alteration of the zeta potential of the PS template leading to a homogeneous dispersion in the silazane-toluene mixture. Removal of solvent gives rise to a highly ordered PS-silazane nano-composites and subsequent pyrolysis leads to mesoporous silicon carbonitride (SiCN) materials. The one-pot procedure has two advantages: easy upscaling and the use of PS spheres smaller than 100 nm in diameter, here 60 nm. The PS template was characterized by photon correlation spectroscopy, zeta potential measurements, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA). The resulting mesoporous SiCN materials were analyzed by SEM, transmission electron microscopy (TEM), nitrogen sorption analysis, and Fourier transform infrared measurements (FT-IR).


[Translated article] Subtalar dislocations: Analysis of a case series. Our urgent treatment algorithm.
Subtalar dislocations are a rare entity (<1%) in traumatic foot injuries. There is a loss of anatomical relationship between the talus, calcaneus and scaphoid. There are only small-published series. We present a series of patients (N=13) with subtalar dislocations in which a descriptive analysis of the main epidemiological, clinical and radiological variables was carried out, from which an urgent treatment algorithm is proposed. Cases with fractures of the neck of the talus, body of the calcaneus, or isolated Chopart fracture-dislocations were excluded. The median age was 48.5 years with a predominance of males (69.23%). Five patients suffered falls or sprained ankles and the other eight suffered high-energy mechanisms. The medial dislocations (nine) predominated over the lateral ones (four). In addition, four patients presented open dislocations, two of them type IIIC that required amputation. CT scans were requested in 76.93% of patients and 10 presented associated bone lesions of the foot. Open reduction surgery was performed in all open lesions and in one case in which closed reduction failed. Five patients required a delta-type external fixator. Subchondral articular sclerosis was observed in 77.77% of cases; although only one required subtalar arthrodesis. Subtalar dislocations are a traumatic emergency that require early reduction and subsequent immobilisation. Transarticular temporary external fixation is a good immobilisation option in open dislocations. They are serious lesions with a high probability of early osteoarthritis.


Ultralight, Structurally Stable Electrospun Sponges with Tailored Hydrophilicity as a Novel Material Platform.
Sponges based on short electrospun fibers have received significant attention due to their ultrahigh porosity, lightweight, and multifunctional characteristics. In particular, polyimide (PI) sponges have been researched due to their exceptional mechanical properties and thermal stability. Nevertheless, a number of sponges, including PI, are usually hydrophobic and synthesized in toxic, nonwater solvents (e.g., 1,4-dioxane). Conversely, hydrophilic sponges disintegrate upon contact with water. Here, we suggest a new strategy to fabricate PI sponges in water by introducing a suitable surfactant, sodium dodecylbenzenesulfonate (SDBS) (sPI sponges). With less than 1 wt % of SDBS with respect to PI short fibers, they can be homogeneously dispersed in water and mixed well with poly(amic acid) (PAA) solution. The synthesized sponge, depending on the concentration of SDBS, showed hydrophilic properties and substantial water uptake above 5000%. The hydrophilic properties of the sponges, which are not common, and the preparation from aqueous solution introduce new research opportunities. Such hydrophilic sponges are particularly special because they do not swell in contact with water, which makes them dimensionally stable. The methods presented here can serve as a milestone for the future development of various kinds of hydrophilic sponges applied for various applications, ranging from tissue engineering to oil/water separation.


Morphological differences in adolescent idiopathic scoliosis: a histological and ultrastructural investigation.
Histological and ultrastructural evaluation of cell morphologies at the concave and convex side of apical intervertebral discs (IVD) of adolescent idiopathic scoliosis (AIS). To determine changes in cell morphology, viability, and cell death after asymmetric disc loading in AIS and to compare the findings with the tilt angles. The reaction of cells to loading stimuli in the IVD seems to be specific. Although dynamic loads are more beneficial to the disc cells and maintain the matrix biosynthesis, static compressive loads suppress gene expression. Apical IVDs (Th8-Th9 to L1-L2) from 10 patients with AIS were studied histologically (including TUNEL [TdT-mediated dUTP-biotin nick end labeling] staining to identify disc cell death by apoptosis) and ultrastructurally for matrix evaluations and to quantify healthy, balloon, chondroptotic, apoptotic, and necrotic cells on the concave and convex sides. Patients' spines were classified according to the Lenke classification. Degeneration was assessed according to the Pfirrmann grading system. Two groups were established; group 1 (G1) with a tilt of 5° to 9° and group 2 (G2) with a tilt of 10° to 19°. Balloon cells were found in significantly higher numbers at the concave side (G1-annulus fibrosus [AF]: mean 16%), with almost none found at the convex side. Mean numbers of healthy cells did not show differences comparing both sides. Significantly higher numbers of healthy cells were found with increasing tilt angle at the concave side. Necrosis (mean, 47%) increased toward the center of the disc but did not differ between the sides of the IVDs. The fibrils found in the outer AF on the convex side were 30% thinner. This study was able to show significant differences in cell morphologies in the AF on both sides and in correlation to the different tilt angles. The type and magnitude of load seem to influence disc cells. Further studies are required to provide more information on disc and cell changes in scoliosis.


Towards comprehensive syntactic and semantic annotations of the clinical narrative.
To create annotated clinical narratives with layers of syntactic and semantic labels to facilitate advances in clinical natural language processing (NLP). To develop NLP algorithms and open source components. Manual annotation of a clinical narrative corpus of 127 606 tokens following the Treebank schema for syntactic information, PropBank schema for predicate-argument structures, and the Unified Medical Language System (UMLS) schema for semantic information. NLP components were developed. The final corpus consists of 13 091 sentences containing 1772 distinct predicate lemmas. Of the 766 newly created PropBank frames, 74 are verbs. There are 28 539 named entity (NE) annotations spread over 15 UMLS semantic groups, one UMLS semantic type, and the Person semantic category. The most frequent annotations belong to the UMLS semantic groups of Procedures (15.71%), Disorders (14.74%), Concepts and Ideas (15.10%), Anatomy (12.80%), Chemicals and Drugs (7.49%), and the UMLS semantic type of Sign or Symptom (12.46%). Inter-annotator agreement results: Treebank (0.926), PropBank (0.891-0.931), NE (0.697-0.750). The part-of-speech tagger, constituency parser, dependency parser, and semantic role labeler are built from the corpus and released open source. A significant limitation uncovered by this project is the need for the NLP community to develop a widely agreed-upon schema for the annotation of clinical concepts and their relations. This project takes a foundational step towards bringing the field of clinical NLP up to par with NLP in the general domain. The corpus creation and NLP components provide a resource for research and application development that would have been previously impossible.


Office hysteroscopy and compliance: mini-hysteroscopy versus traditional hysteroscopy in a randomized trial.
Diagnostic hysteroscopy has not yet been generally accepted as a well-tolerated office procedure. The aim of our study was to verify compliance, side-effects and haemodynamic variations when a mini-hysteroscope is used. A prospective randomized trial on office hysteroscopy was performed by comparing the use of a traditional 5 mm hysteroscope (group A) and of a 3.3 mm mini-hysteroscope (group B). Two patient groups (A and B), each comprising 100 cases, were formed on the basis of a randomized computer-generated list. A marked reduction in the mean (+/- SD) pelvic pain score during office hysteroscopy was seen in group B (2.3 +/- 2.1) as compared with group A (4.6 +/- 2.2) (P < 0.0001, Mann-Whitney test). This result was also confirmed when using an alternative approach: four classes of pelvic pain at the visual analogue score (VAS). A significant reduction was observed in the incidence of moderate and severe pelvic pain in group B at the end of the examination (P = 0.001) and 5-10 min later (P < 0.05). The use of mini-hysteroscopes (3.3 mm with diagnostic sheath) lowers considerably the level of pelvic pain the patients feel: it is halved in comparison with traditional calibre hysteroscopes (2.3 +/- 2.1, on a 0-10 VAS). Furthermore the outpatient hysteroscopy failure rate is less than half (2%) with the mini-hysteroscope compared with the traditional 5 mm hysteroscope (5%). As for side-effects and haemodynamic parameters, no differences were observed except for an increase (P < 0.05) in bradycardia in group B. The advantage of this technique is self-evident, if the patients' compliance is taken into account: in many cases the introduction or withdrawal of the vaginal speculum was reported as the greatest discomfort.


Molecularly Imprinted Nanomaterials for Sensor Applications.
Molecular imprinting is a well-established technology to mimic antibody-antigen interaction in a synthetic platform. Molecularly imprinted polymers and nanomaterials usually possess outstanding recognition capabilities. Imprinted nanostructured materials are characterized by their small sizes, large reactive surface area and, most importantly, with rapid and specific analysis of analytes due to the formation of template driven recognition cavities within the matrix. The excellent recognition and selectivity offered by this class of materials towards a target analyte have found applications in many areas, such as separation science, analysis of organic pollutants in water, environmental analysis of trace gases, chemical or biological sensors, biochemical assays, fabricating artificial receptors, nanotechnology, etc. We present here a concise overview and recent developments in nanostructured imprinted materials with respect to various sensor systems, e.g., electrochemical, optical and mass sensitive, etc. Finally, in light of recent studies, we conclude the article with future perspectives and foreseen applications of imprinted nanomaterials in chemical sensors.