Buckyballs.
Buckyballs represent a new and fascinating molecular allotropic form of carbon that has received a lot of attention by the chemical community during the last two decades. The unabating interest on this singular family of highly strained carbon spheres has allowed the establishing of the fundamental chemical reactivity of these carbon cages and, therefore, a huge variety of fullerene derivatives involving [60] and [70]fullerenes, higher fullerenes, and endohedral fullerenes have been prepared. Much less is known, however, of the chemistry of the uncommon non-IPR fullerenes which currently represent a scientific curiosity and which could pave the way to a range of new fullerenes. In this review on buckyballs we have mainly focused on the most recent and novel covalent chemistry of fullerenes involving metal catalysis and asymmetric synthesis, as well as on some of the most significant advances in supramolecular chemistry, namely H-bonded fullerene assemblies and the search for efficient concave receptors for the convex surface of fullerenes. Furthermore, we have also described the recent advances in the macromolecular chemistry of fullerenes, that is, those polymer molecules endowed with fullerenes which have been classified according to their chemical structures. This review is completed with the study of endohedral fullerenes, a new family of fullerenes in which the carbon cage of the fullerene contains a metal, molecule, or metal complex in the inner cavity. The presence of these species affords new fullerenes with completely different properties and chemical reactivity, thus opening a new avenue in which a more precise control of the photophysical and redox properties of fullerenes is possible. The use of fullerenes for organic electronics, namely in photovoltaic applications and molecular wires, complements the study and highlights the interest in these carbon allotropes for realistic practical applications. We have pointed out the so-called non-IPR fullerenes - those that do not follow the isolated pentagon rule - as the most intriguing class of fullerenes which, up to now, have only shown the tip of the huge iceberg behind the examples reported in the literature. The number of possible non-IPR carbon cages is almost infinite and the near future will show us whether they will become a reality.


A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart.
Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of β-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2-5 and GATA4 in stabilized-β-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/β-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing β-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/β-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway.


Comparison of the effect of platinum on producers in aquatic environment.
An enhanced worldwide application of platinum group elements (PGE), in particular platinum, has been observed during recent decades. An increased concentration of PGE was determined in collected samples of great amount of aqueous ecosystems.The aim was to compare phytotoxic effect of platinum (PtCl4) by performing two different bioassays on green algae Pseudokirchneriella subcapitata and macrophyte duckweed, Lemna minor. MEDTHODS: The algal experiment (Pseudokichneriella subcapitata) followed OECD 201, the concentration row for PtCl4 was: 0.05; 0.01; 0.25; 0.5; 1 µM. The duckweed (Lemna minor) experiment was conducted according to OECD 221, employed PtCl4 concentrations were: 5; 10; 25; 50; 100 µM. Plants were cultivated as a microbiotest, using micro-volumes. The results of the algal test showed significant growth inhibition of the final biomass. The values of 72hEC5(µ), 72hEC10(µ), 72hEC20(µ) counted on a basis of average specific growth rate (µ) were 0.31 µM, 0.58 µM and 1.12 µM of PtCl4, respectively. The values, obtained on a basis of the area under the growth curves (A), were 0.04 µM (72hEC5(A)), 0.24 µM (72hEC10(A)) and 0.64 µM (72hEC20(A)). The experiment with duckweed showed 50% of growth inhibition and the values of 168hEC50(µ) were 19.55 µM and 168hEC50(A) 13.63 µM of PtCl4. The fronds of duckweed showed strong adverse effect of platinum influence (chlorosis, necrosis). The algal test and the estimation of 72hEC5(A) appears to be the most sensitive.


Prevention of premature senescence requires JNK regulation of Bcl-2 and reactive oxygen species.
Premature senescence is considered as a cellular defense mechanism to prevent tumorigenesis. Although recent evidences show that c-Jun N-terminal kinase (JNK) is involved in the senescence process, the mechanism for this regulation is not fully understood. Here, we examined the role of JNK in premature senescence of tumor cells. Treatment of cells with the JNK-specific inhibitor SP600125 caused phenotypical changes of senescence and triggered a rapid increase in mitochondrial reactive oxygen species (ROS) production and DNA-damage response (DDR) in MCF7 breast carcinoma cells. ROS generation was attributed to the suppression of B-cell lymphoma-2 (Bcl-2) phosphorylation, and resulted in DNA damage and p53 activation. Bax did not change their localization to the mitochondria, which is required for apoptosis. The essential roles of JNK and phosphorylated Bcl-2 in preventing premature senescence were confirmed using RNA interference and ectopic expression of mutants of Bcl-2, including phosphomimetic and nonphosphorylatable forms. These findings were evidenced in H460 lung carcinoma cells and primary human embryonic fibroblasts. Altogether, our results showed that loss of JNK activity triggers a Bcl-2/ROS/DDR signaling cascade that ultimately leads to premature senescence, indicating that basal JNK activity is essential in preventing premature senescence.


Mechanism of anemia in Schistosoma mansoni-infected school children in Western Kenya.
A better understanding of the mechanism of anemia associated with Schistosoma mansoni infection might provide useful information on how treatment programs are implemented to minimize schistosomiasis-associated morbidity and maximize treatment impact. We used a cross-sectional study with serum samples from 206 Kenyan school children to determine the mechanisms in S. mansoni-associated anemia. Serum ferritin and soluble transferrin receptor levels were measured by using an enzyme-linked immunosorbent assay. Results suggest that S. mansoni-infected persons are more likely (odds ratio = 3.68, 95% confidence interval = 1.33-10.1) to have levels of serum ferritin (> 100 ng/mL) that are associated with anemia of inflammation (AI) than S. mansoni-uninfected children. Our results suggest that AI is the most common form of anemia in S. mansoni infections. In contrast, the mechanism of anemia in S. mansoni-uninfected children was iron deficiency. Moreover, the prevalence of AI in the study participants demonstrated a significant trend with S. mansoni infection intensity (P < 0.001). Our results are consistent with those observed in S. japonicum-associated anemia.


On the Evolving World of What Constitutes Qualitative Synthesis.
As the body of available qualitatively derived knowledge expands, there is increasing temptation to capitalize on it to generate knowledge synthesis products. Concurrently, in the wake of an ever-expanding enthusiasm for evidence-based practice knowledge in health care, scholars are facing pressure to forgo the more narrative or interpretive form of literature review in favor of reviews that are positioned as explicitly systematic. This has created a context in which both new and seasoned scholars are, in increasing numbers, working with extant bodies of qualitative literature in ways that counter the very motivations that drove health researchers into qualitative methods in the first place. In this commentary, I trace the evolution of this trend, illustrating how a reasonable original intent has taken a misguided turn in the context of competing understandings and priorities in health care knowledge development. On this basis, I propose a strategic direction for this journal as a leader in what constitutes the meaningful application of qualitative research methodological approaches, including that which purports to represent synthesis of available knowledge, for the purposes of addressing the inherently complex challenges of the health field.


Optimizing self-consistent field theory block copolymer models with X-ray metrology.
A block copolymer self-consistent field theory (SCFT) model is used for direct analysis of experimental X-ray scattering data obtained from thin films of polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) made from directed self-assembly. In a departure from traditional approaches, which reconstruct the real space structure using simple geometric shapes, we build on recent work that has relied on physics-based models to determine shape profiles and extract thermodynamic processing information from the scattering data. More specifically, an SCFT model, coupled to a covariance matrix adaptation evolutionary strategy (CMAES), is used to find the set of simulation parameters for the model that best reproduces the scattering data. The SCFT model is detailed enough to capture the essential physics of the copolymer self-assembly, but sufficiently simple to rapidly produce structure profiles needed for interpreting the scattering data. The ability of the model to produce a matching scattering profile is assessed, and several improvements are proposed in order to more accurately recreate the experimental observations. The predicted parameters are compared to those extracted from model fits via additional experimental methods and with predicted parameters from direct particle-based simulations of the same model, which incorporate the effects of fluctuations. The Flory-Huggins interaction parameter for PS-b-PMMA is found to be in agreement with reported ranges for this material. These results serve to strengthen the case for relying on physics-based models for direct analysis of scattering and light signal based experiments.


Fatigue-induced increase in intracortical communication between mid/anterior insular and motor cortex during cycling exercise.
In the present study, intracortical communication between mid/anterior insular and motor cortex was investigated during a fatiguing cycling exercise. From 16 healthy male subjects performing a constant-load test at 60% peak oxygen consumption (VO(2peak)) until volitional exhaustion, electroencephalography data were analysed during repetitive, artefact-free periods of 1-min duration. To quantify fatigue-induced intracortical communication, mean intra-hemispheric lagged phase synchronization between mid/anterior insular and motor cortex was calculated: (i) at the beginning of cycling; (ii) at the end of cycling; and (iii) during recovery cycling. Results revealed significantly increased lagged phase synchronization at the end of cycling, which returned to baseline during recovery cycling after subjects' cessation of exercise. Following previous imaging studies reporting the mid/anterior insular cortex as an essential instance processing a variety of sensory stimuli and signalling forthcoming physiological threat, our results provide further evidence that during a fatiguing exercise this structure might not only integrate and evaluate sensory information from the periphery, but also act in communication with the motor cortex. To the best of our knowledge, this is the first study to empirically demonstrate that muscle fatigue leads to changes in interaction between structures of a brain's neural network.


All stressed out without ATM kinase.
Ataxia-telangiectasia (A-T) is a rare, neurodegenerative, inherited disease arising from mutations in the kinase A-T mutated (ATM), which promotes cell cycle checkpoints and DNA double-strand break repair. Puzzlingly, these ATM activities fail to fully explain A-T neuropathologies, which instead have links to stress induced by reactive oxygen species (ROS). However, a landmark discovery reveals an unexpected intersection of ROS and kinase signaling: ATM can be directly activated by oxidation to form a disulfide-linked dimer in a mechanism distinct from DNA damage activation. When combined with notable structural-based insights into the ATM homolog DNA-PK (DNA-protein kinase) and mTOR (mammalian target of rapamycin), these results suggest conformation and assembly mechanisms to signal oxidative stress through an ATM nodal point. These findings fundamentally affect our understanding of ROS and ATM signaling and of the A-T phenotype, with implications for altering signaling in cancer cells to increase sensitivities to current therapeutic interventions.


TRPV1 marks synaptic segregation of multiple convergent afferents at the rat medial solitary tract nucleus.
TRPV1 receptors are expressed on most but not all central terminals of cranial visceral afferents in the caudal solitary tract nucleus (NTS). TRPV1 is associated with unmyelinated C-fiber afferents. Both TRPV1+ and TRPV1- afferents enter NTS but their precise organization remains poorly understood. In horizontal brainstem slices, we activated solitary tract (ST) afferents and recorded ST-evoked glutamatergic excitatory synaptic currents (ST-EPSCs) under whole cell voltage clamp conditions from neurons of the medial subnucleus. Electrical shocks to the ST produced fixed latency EPSCs (jitter<200 µs) that identified direct ST afferent innervation. Graded increases in shock intensity often recruited more than one ST afferent and ST-EPSCs had consistent threshold intensity, latency to onset, and unique EPSC waveforms that characterized each unitary ST afferent contact. The TRPV1 agonist capsaicin (100 nM) blocked the evoked TRPV1+ ST-EPSCs and defined them as either TRPV1+ or TRPV1- inputs. No partial responses to capsaicin were observed so that in NTS neurons that received one or multiple (2-5) direct ST afferent inputs--all were either blocked by capsaicin or were unaltered. Since TRPV1 mediates asynchronous release following TRPV1+ ST-evoked EPSCs, we likewise found that recruiting more than one ST afferent further augmented the asynchronous response and was eliminated by capsaicin. Thus, TRPV1+ and TRPV1- afferents are completely segregated to separate NTS neurons. As a result, the TRPV1 receptor augments glutamate release only within unmyelinated afferent pathways in caudal medial NTS and our work indicates a complete separation of C-type from A-type afferent information at these first central neurons.


Rituximab in the treatment of rheumatoid arthritis.
Rheumatoid arthritis is a chronic, disabling condition and the most common form of inflammatory arthritis affecting approximately 1% of the population. The outlook has improved considerably over the last decade with the recognition that better outcomes accompany early and optimal suppression of synovitis. In some patients, this can be achieved with conventional, oral disease-modifying anti-rheumatic drugs. For those with more severe disease, the introduction of biologic therapies targeting the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha has led to further, significant improvements in outcome. However, in general, these drugs are being used for long-term maintenance therapy and are associated with a very high expense that limits their availability in most healthcare economies. Furthermore, approximately a third of patients fail to achieve clinically significant responses. There is therefore a need for new, effective approaches to therapy, in particular for those patients refractory to TNF blockade. Rituximab, a B cell-depleting antibody, is the first biologic targeting B cells to be approved in the USA and Europe for the treatment of active rheumatoid arthritis in anti-TNF non-responders. This article reviews the background to this therapeutic approach and the encouraging clinical trial data to date indicating that enduring responses can be achieved in a majority of patients after a single treatment cycle comprising two rituximab infusions given 2 weeks apart.


Molecular malaria surveillance using a novel protocol for extraction and analysis of nucleic acids retained on used rapid diagnostic tests.
The use of malaria rapid diagnostic tests (RDTs) as a source for nucleic acids that can be analyzed via nucleic acid amplification techniques has several advantages, including minimal amounts of blood, sample collection, simplified storage and shipping conditions at room temperature. We have systematically developed and extensively evaluated a procedure to extract total nucleic acids from used malaria RDTs. The co-extraction of DNA and RNA molecules from small volumes of dried blood retained on the RDTs allows detection and quantification of P. falciparum parasites from asymptomatic patients with parasite densities as low as 1 Pf/µL blood using reverse transcription quantitative PCR. Based on the extraction protocol we have developed the ENAR (Extraction of Nucleic Acids from RDTs) approach; a complete workflow for large-scale molecular malaria surveillance. Using RDTs collected during a malaria indicator survey we demonstrated that ENAR provides a powerful tool to analyze nucleic acids from thousands of RDTs in a standardized and high-throughput manner. We found several, known and new, non-synonymous single nucleotide polymorphisms in the propeller region of the kelch 13 gene among isolates circulating on Bioko Island, Equatorial Guinea.


The Relationship between Virtual Self Similarity and Social Anxiety.
In virtual reality (VR), it is possible to embody avatars that are dissimilar to the physical self. We examined whether embodying a dissimilar self in VR would decrease anxiety in a public speaking situation. We report the results of an observational pilot study and two laboratory experiments. In the pilot study (N = 252), participants chose an avatar to use in a public speaking task. Trait public speaking anxiety correlated with avatar preference, such that anxious individuals preferred dissimilar self-representations. In Study 1 (N = 82), differences in anxiety during a speech in front of a virtual audience were compared among participants embodying an assigned avatar whose face was identical to their real self, an assigned avatar whose face was other than their real face, or embodied an avatar of their choice. Anxiety differences were not significant, but there was a trend for lower anxiety with the assigned dissimilar avatar compared to the avatar looking like the real self. Study 2 (N = 105) was designed to explicate that trend, and further investigated anxiety differences with an assigned self or dissimilar avatar. The assigned dissimilar avatar reduced anxiety relative to the assigned self avatar for one measure of anxiety. We discuss implications for theories of self-representation as well as for applied uses of VR to treat social anxiety.


Identification of nuclear and cytoplasmic mRNA targets for the shuttling protein SF2/ASF.
The serine and arginine-rich protein family (SR proteins) are highly conserved regulators of pre-mRNA splicing. SF2/ASF, a prototype member of the SR protein family, is a multifunctional RNA binding protein with roles in pre-mRNA splicing, mRNA export and mRNA translation. These observations suggest the intriguing hypothesis that SF2/ASF may couple splicing and translation of specific mRNA targets in vivo. Unfortunately the paucity of endogenous mRNA targets for SF2/ASF has hindered testing of this hypothesis. Here, we identify endogenous mRNAs directly cross-linked to SF2/ASF in different sub-cellular compartments. Cross-Linking Immunoprecipitation (CLIP) captures the in situ specificity of protein-RNA interaction and allows for the simultaneous identification of endogenous RNA targets as well as the locations of binding sites within the RNA transcript. Using the CLIP method we identified 326 binding sites for SF2/ASF in RNA transcripts from 180 protein coding genes. A purine-rich consensus motif was identified in binding sites located within exon sequences but not introns. Furthermore, 72 binding sites were occupied by SF2/ASF in different sub-cellular fractions suggesting that these binding sites may influence the splicing or translational control of endogenous mRNA targets. We demonstrate that ectopic expression of SF2/ASF regulates the splicing and polysome association of transcripts derived from the SFRS1, PABC1, NETO2 and ENSA genes. Taken together the data presented here indicate that SF2/ASF has the capacity to co-regulate the nuclear and cytoplasmic processing of specific mRNAs and provide further evidence that the nuclear history of an mRNA may influence its cytoplasmic fate.


Peano-HASEL actuators: Muscle-mimetic, electrohydraulic transducers that linearly contract on activation.
Soft robotic systems are well suited to unstructured, dynamic tasks and environments, owing to their ability to adapt and conform without damaging themselves or their surroundings. These abilities are crucial in areas such as human-robot interaction. Soft robotic systems are currently limited by the soft actuators that power them. To date, most soft actuators are based on pneumatics or shape-memory alloys, which have issues with efficiency, response speed, and portability. Dielectric elastomer actuators (DEAs) are controlled and powered electrically and excel with muscle-like actuation, but they typically require a rigid frame and prestretch to perform effectively. In addition, DEAs require complex stacks or structures to achieve linear contraction modes. We present a class of soft electrohydraulic transducers, termed Peano-HASEL (hydraulically amplified self-healing electrostatic) actuators, that combine the strengths of fluidic actuators and electrostatic actuators, while addressing many of their issues. These actuators use both electrostatic and hydraulic principles to linearly contract on application of voltage in a muscle-like fashion, without rigid frames, prestretch, or stacked configurations. We fabricated these actuators using a facile heat-sealing method with inexpensive commercially available materials. These prototypical devices demonstrated controllable linear contraction up to 10%, a strain rate of 900% per second, actuation at 50 hertz, and the ability to lift more than 200 times their weight. In addition, these actuators featured characteristics such as high optical transparency and the ability to self-sense their deformation state. Hence, this class of actuators demonstrates promise for applications such as active prostheses, medical and industrial automation, and autonomous robotic devices.


A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis.
Patients undergoing high-dose chemotherapy for hematological malignancies are susceptible to development of oral mucositis, and no effective modality has been reported for its prophylaxis and treatment. The aim of this study was to evaluate the effectiveness of zinc mouthwash on chemotherapy-induced oral mucositis lesions. In this double-blind randomized trial, patients under chemotherapy for acute leukemia were divided into two test and control groups of 15 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The test group received 10ml 0.2% zinc sulfate mouthwash, and the control group received 10ml 0.2% chlorhexidine gluconate mouthwash, twice a day for a period of two weeks. Spijkervet scale was used to grade the severity of mucositis at every other week during eight weeks. The severity scores were analyzed with repeated measure ANOVA using SPSS 13.0 computer software. Mean severity scores were generally lower in the test group compared to the controls at all four time intervals evaluated; but only, the differences in weeks of 2 and 3 were statistically significant (P=0.025). Zinc mouthwash used in conjunction with chemotherapy may reduce the severity of oral mucositis lesions in patients with leukaemia.


A Novel Anticancer Agent, 8-Methoxypyrimido[4',5':4,5]thieno(2,3-b) Quinoline-4(3H)-One Induces Neuro 2a Neuroblastoma Cell Death through p53-Dependent, Caspase-Dependent and -Independent Apoptotic Pathways.
Neuroblastoma is the most common cancer in infants and fourth most common cancer in children. Despite recent advances in cancer treatments, the prognosis of stage-IV neuroblastoma patients continues to be dismal which warrant new pharmacotherapy. A novel tetracyclic condensed quinoline compound, 8-methoxypyrimido [4',5':4,5]thieno(2,3-b) quinoline-4(3H)-one (MPTQ) is a structural analogue of an anticancer drug ellipticine and has been reported to posses anticancer property. Study on MPTQ on neuroblastoma cells is very limited and mechanisms related to its cytotoxicity on neuroblastoma cells are completely unknown. Here, we evaluated the anticancer property of MPTQ on mouse neuro 2a and human SH-SY5Y neuroblastoma cells and investigated the mechanisms underlying MPTQ-mediated neuro 2a cell death. MPTQ-mediated neuro 2a and SH-SY5Y cell deaths were found to be dose and time dependent. Moreover, MPTQ induced cell death reached approximately 99.8% and 90% in neuro 2a and SH-SY5Y cells respectively. Nuclear oligonucleosomal DNA fragmentation and Terminal dUTP Nick End Labelling assays indicated MPTQ-mediated neuro 2a cell death involved apoptosis. MPTQ-mediated apoptosis is associated with increased phosphorylation of p53 at Ser15 and Ser20 which correlates with the hyperphosphorylation of Ataxia-Telangiectasia mutated protein (ATM). Immunocytochemical analysis demonstrated the increased level of Bax protein in MPTQ treated neuro 2a cells. MPTQ-mediated apoptosis is also associated with increased activation of caspase-9, -3 and -7 but not caspase-2 and -8. Furthermore, increased level of caspase-3 and cleaved Poly (ADP Ribose) polymerase were observed in the nucleus of MPTQ treated neuro 2a cells, suggesting the involvement of caspase-dependent intrinsic but not extrinsic apoptotic pathway. Increased nuclear translocation of apoptosis inducing factor suggests additional involvement of caspase-independent apoptosis pathway in MPTQ treated neuro 2a cells. Collectively, MPTQ-induced neuro 2a cell death is mediated by ATM and p53 activation, and Bax-mediated activation of caspase-dependent and caspase-independent mitochondrial apoptosis pathways.


Use of carbon-based composites to enhance performance of TiO2 for the simultaneous removal of nitrates and organics from aqueous environments.
The simultaneous photocatalytic removal of nitrate from aqueous environment in presence of organic hole scavenger using TiO2 has long been explored. However, the use of unmodified TiO2 in such reaction resulted in non-performance or release of significant amount of undesirable reaction products in the process, a problem that triggered surface modification of TiO2 for enhanced photocatalytic performance. Previous studies focused on decreasing rate of charge carrier recombination and absorption of light in the visible region. Yet, increasing active sites and adsorption capacity by combining TiO2 with a high surface area adsorbent such as activated carbon (AC) remains unexploited. This study reports the potential of such modification in simultaneous removal of nitrates and oxalic acid in aqueous environment. The adsorptive behaviour of nitrate and oxalic acid on TiO2 and TiO2/AC composites were studied. The Langmuir adsorption coefficient for nitrate was four times greater than that of oxalic acid. However, the amount of oxalic acid adsorbed was about 10 times greater than the amount of nitrate taken up. Despite this advantage, the materials did not appear to produce more active photocatalysts for the simultaneous degradation of nitrate and oxalic acid. The photocatalytic activity of TiO2 and its carbon-based composites was improved by combination with Cu2O particles. Consequently, 2.5 Cu2O/TiO2 exhibited the maximum photocatalytic performance with 57.6 and 99.8% removal of nitrate and oxalic acid, respectively, while selectivity stood at 45.7, 12.4 and 41.9% for NH4+, NO2- and N2, respectively. For the carbon based, 2.5 Cu2O/TiO2-20AC showed removal of 12.7% nitrate and 80.3% oxalic acid and achieved 21.6, 0 and 78.4% selectivity for NH4+, NO2- and N2, respectively. Using the optimal AC loading (20 wt%) resulted in significant decrease in the selectivity for NH4+ with no formation of NO2-, which unveils that selectivity for N2 and low/no selectivity for undesirable products can be manipulated by controlling the rate of consumption of oxalic acid. In contract, no nitrate reduction was observed with Cu2O promoted TiO2-T and its TiO2-(T)-20AC, which may be connected to amorphous nature of TiO2-T and perhaps served as charge carrier trapping sites that impeded activity.


Global tobacco control and economic norms: an analysis of normative commitments in Kenya, Malawi and Zambia.
Tobacco control norms have gained momentum over the past decade. To date 43 of 47 Sub-Saharan African countries are party to the Framework Convention on Tobacco Control (FCTC). The near universal adoption of the FCTC illustrates the increasing strength of these norms, although the level of commitment to implement the provisions varies widely. However, tobacco control is enmeshed in a web of international norms that has bearing on how governments implement and strengthen tobacco control measures. Given that economic arguments in favor of tobacco production remain a prominent barrier to tobacco control efforts, there is a continued need to examine how economic sectors frame and mobilize their policy commitments to tobacco production. This study explores the proposition that divergence of international norms fosters policy divergence within governments. This study was conducted in three African countries: Kenya, Malawi, and Zambia. These countries represent a continuum of tobacco control policy, whereby Kenya is one of the most advanced countries in Africa in this respect, whereas Malawi is one of the few countries that is not a party to the FCTC and has implemented few measures. We conducted 55 key informant interviews (Zambia = 23; Kenya = 17; Malawi = 15). Data analysis involved deductive coding of interview transcripts and notes to identify reference to international norms (i.e. commitments, agreements, institutions), coupled with an inductive analysis that sought to interpret the meaning participants ascribe to these norms. Our analysis suggests that commitments to tobacco control have yet to penetrate non-health sectors, who perceive tobacco control as largely in conflict with international economic norms. The reasons for this perceived conflict seems to include: (1) an entrenched and narrow conceptualization of economic development norms, (2) the power of economic interests to shape policy discourses, and (3) a structural divide between sectors in the form of bureaucratic silos.


An information infrastructure for long-term care.
Emerging trends promise to alter the way long-term care is practiced. These include: changing regulation of the nursing home industry with emphasis on outcome and assessment, a trend in medical informatics away from expert systems and toward on-line decision support and reminder systems, and the application of industrial statistical quality management techniques to the realm of human services. Emerging standards such as the Arden Syntax and Unified Medical Language Systems and technologies such as Rapid Application Development Tools will facilitate the use of modern computing to mold and implement these converging trends.


This work describes the bioethics situation in Nicaragua, with information on the circumstances and the context of activities in medical education and health care providers.The development of a new model of comprehensive health care-the implementation of health care policies that guarantee Nicaraguans better access to care and services free of charge, and the changes that have occurred in medical care, due in part to the growing recognition of greater patient autonomy and the increase in the use of new medical technologies-all have contributed in some part to current obstacles and dilemmas in medical clinics and between health care personnel.Bioethics in Nicaragua is in the initial stage of development. It is neither institutionalized nor is it subject to formal mechanisms that permit the resolution of complex ethical problems, thus presenting an important challenge for institutions of higher learning and decision-makers in health.


Parental characteristics in relation to depressive disorders.
Using a reliable and valid measure of reported parental care and overprotection (the Parental Bonding Instrument) patients with two types of depressive disorder were compared with a control group, and the relationships to depressive experience examined in a non-clinical group as well. Bipolar manic-depressive patients scored like controls whereas neurotic depressives reported less parental care and greater maternal overprotection. Depressive experience in the non-clinical group was negatively associated with low parental care and weakly associated with parental overprotection.


Effect of sesame oil on diuretics or Beta-blockers in the modulation of blood pressure, anthropometry, lipid profile, and redox status.
The study was undertaken to investigate the effect of sesame oil in hypertensive patients who were on antihypertensive therapy either with diuretics (hydrochlorothiazide) or Beta-blockers (atenolol). Thirty-two male and 18 female patients aged 35 to 60 years old were supplied sesame oil (Idhayam gingelly oil) and instructed to use it as the only edible oil for 45 days. Blood pressure, anthropometry, lipid profile, lipid peroxidation, and enzymic and non-enzymic antioxidants were measured at baseline and after 45 days of sesame oil substitution. Substitution of sesame oil brought down systolic and diastolic blood pressure to normal. The same patients were asked to withdraw sesame oil consumption for another 45 days, and the measurements were repeated at the end of withdrawal period. Withdrawal of sesame oil substitution brought back the initial blood pressure values. A significant reduction was noted in body weight and body mass index (BMI) upon sesame oil substitution. No significant alterations were observed in lipid profile except triglycerides. Plasma levels of sodium reduced while potassium elevated upon the substitution of sesame oil. Lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) decreased while the activities of superoxide dismutase (SOD), catalase (CAT), and the levels of vitamin C, vitamin E, Beta-carotene, and reduced glutathione (GSH) were increased. The results suggested that sesame oil as edible oil lowered blood pressure, decreased lipid peroxidation, and increased antioxidant status in hypertensive patients.


Human sulfotransferase SULT1C1: cDNA cloning, tissue-specific expression, and chromosomal localization.
We have isolated and sequenced a cDNA that encodes an apparent human orthologue of a rat sulfotransferase (ST) cDNA that has been referred to as "ST1C1"-although it was recently recommended that sulfotransferase proteins and cDNAs be abbreviated "SULT." The new human cDNA was cloned from a fetal liver-spleen cDNA library and had an 888-bp open reading frame. The amino acid sequence of the protein encoded by the cDNA was 62% identical with that encoded by the rat ST1C1 cDNA and included signature sequences that are conserved in all cytosolic SULT enzymes. Dot blot analysis of mRNA from 50 human tissues indicated that the cDNA was expressed in adult human stomach, kidney, and thyroid, as well as fetal kidney and liver. Northern blot analyses demonstrated that the major SULT1C1 mRNA in those same tissues was 1.4 kb in length. We next determined the partial human SULT1C1 gene sequence for a portion of the 5'-terminus of one intron. That sequence was used to design SULT1C1 gene-specific primers that were used to perform the PCR with DNA from human/rodent somatic cell hybrids to demonstrate that the gene was located on chromosome 2. PCR amplifications performed with human chromosome 2/rodent hybrid cell DNA as template sublocalized SULT1C1 to a region between bands 2q11.1 and 2q11.2.


A decade of international change in abortion law: 1967-1977.
Modern thinking on abortion, reflected in recent legal developments around the world, has turned from concentration upon criminality in favor of female and family well-being. New laws enacted during the last decade are coming to focus upon conditions of health and social welfare of women and their existing families as indications for lawful termination of pregnancy. Regulations governing the delivery of services may be restrictive, however, so as to limit in practice access to means of safe, legal abortion made available in theory. Requirements may be imposed that only medical personnel with unduly high qualifications perform procedures, or that they be undertaken only in institutions meeting standards higher than similar health care requires. Approval procedures may be established involving second medical opinions or committees to monitor observance of the law, which may delay abortions and therefore increase their hazards. Parental and spousal consent requirements may exist in addition with the same effects, or to veto a pregnant female's request. Regulations may be employed more positively, however, to encourage contraceptive practice. A disappointment with legislative reform is that it may fail to improve circumstances if public resources are not applied to achieve the supply of services newly rendered legitimate, and illegal practice may persist.


A novel ultrasensitive immunosensor based on disposable graphite paper electrodes for troponin T detection in cardiovascular disease.
Troponin T, which is a biomarker of cardiovascular disease, is vital for acute myocardial infarction (AMI). AMI is the most well-known cause of death in the world. In the present work, we designed a novel immunosensor using disposable, cheap, and very conductive graphite paper electrodes (GP). The proposed immunosensor was modified with hydrochloric acid (HCl) for immobilization of anti-TnT antibody. After carboxyl group formation on the surface, the GP electrodes were incubated with EDC/NHS pair as a cross-linker. Electrochemical impedance spectroscopy (EIS), single frequency impedance (SFI), cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques were used for electrochemical characterization of the label-free immunosensor. Furthermore, the fabrication process of the proposed immunosensor was examined by using scanning electron microscopy (SEM). The proposed electrochemical immunosensor had a wide detection range (0.5 fg - 1000 fg/mL), and low limit of detection (LOD) and low limit of quantification (LOQ) at 1.28 fg/mL and 4.29 fg/mL, respectively. The designed immunosensor exhibited very good sensitivity, reproducibility, repeatability, reusability and long storage life. Additionally, the immunosensor was successfully applied to detection of TnT in human serum.


An unusual case of primary spontaneous tension pneumothorax in a jamaican female.
Spontaneous pneumothorax is a well-recognized entity with a classical presentation of acute onset chest pain and shortness of breath. It may be complicated by the development of a tension pneumothorax or a haemopneumothorax. We report an interesting case of a spontaneous tension haemopneumothorax which presented atypically and was diagnosed on computed tomography (CT) scan of the chest. The clinical and pathophysiological characteristics and treatment of this unusual entity is discussed.


Oral cancer incidence and survival rates in the Republic of Ireland, 1994-2009.
Oral cancer is a significant public health problem world-wide and exerts high economic, social, psychological, and physical burdens on patients, their families, and on their primary care providers. We set out to describe the changing trends in incidence and survival rates of oral cancer in Ireland between 1994 and 2009. National data on incident oral cancers [ICD 10 codes C01-C06] were obtained from the National Cancer Registry Ireland from 1994 to 2009. We estimated annual percentage change (APC) in oral cancer incidence during 1994-2009 using joinpoint regression software (version 22.214.171.124). The lifetime risk of oral cancer to age 79 was estimated using Irish incidence and population data from 2007 to 2009. Survival rates were also examined using Kaplan-Meier curves and Cox proportional hazard models to explore the influence of several demographic/lifestyle covariates with follow-up to end 2012. Data were obtained on 2,147 oral cancer incident cases. Men accounted for two-thirds of oral cancer cases (n = 1,430). Annual rates in men decreased significantly during 1994-2001 (APC = -4.8 %, 95 % CI: -8.7 to -0.7) and then increased moderately (APC = 2.3 %, 95 % CI: -0.9 to 5.6). In contrast, annual incidence increased significantly in women throughout the study period (APC = 3.2 %, 95 % CI: 1.9 to 4.6). There was an elevated risk of death among oral cancer patients who were: older than 60 years of age; smokers; unemployed or retired; those living in the most deprived areas; and those whose tumour was sited in the base of the tongue. Being married and diagnosed in more recent years were associated with reduced risk of death. Oral cancer increased significantly in both sexes between 1999 and 2009 in Ireland. Our analyses demonstrate the influence of measured factors such as smoking, time of diagnosis and age on observed trends. Unmeasured factors such as alcohol use, HPV and dietary factors may also be contributing to increased trends. Several of these are modifiable risk factors which are crucial for informing public health policies, and thus more research is needed.


Adrenocortical suppression in workers manufacturing synthetic glucocorticoids.
A man who had worked for 16 years in the manufacture of a potent corticosteroid was found to be suffering from chronic adrenocortical insufficiency attributed to chronic absorption of the glucocorticoid. Eleven other symptom-free workers were therefore screened. Two of these workers, like the first patient, gave grossly abnormal responses to the Synacthen (tetracosactrin) test; one had been employed for only seven months. All 12 men had facial plethora, suggesting absorption of the drug in spite of their having adhered to the safety precautions. All workers manufacturing potent steroids should therfore be screened regularly by measurement of their plasma cortisol concentrations and should be moved regularly to processing other drugs.


Eszopiclone for late-life insomnia.
Insomnia, the most common sleep disturbance in later life, affects 20%-50% of older adults. Eszopiclone, a short-acting nonbenzodiazepine hypnotic agent developed for the treatment of insomnia, has been available in Europe since 1992 and in the US since 2005. Although not yet evaluated for transient insomnia in older adults, eszopiclone has been shown to be safe and efficacious for short-term treatment (2 weeks) of chronic, primary insomnia in older adults (64-91 years). Clinical studies in younger adults (mean = 44 years) have shown eszopiclone can be used for 6-12 months without evidence of problems. Because the oldest participant in these longer-term trials was 69, it not known whether eszopiclone is effective for older adults [particularly the old old (75-84 years) and oldest old (85+)] when used over longer periods. This is unfortunate, because older individuals frequently suffer from chronic insomnia. Cognitive-behavioral therapy for insomnia, which effectively targets the behavioral factors that maintain chronic insomnia, represents an attractive treatment alternative or adjuvant to eszopiclone for older adults. To date, no studies have compared eszopiclone to other hypnotic medications or to nonpharmacological interventions, such as cognitive-behavioral therapy for insomnia, in older adults. All of the clinical trials reported herein were funded by Sepracor. This paper provides an overview of the literature on eszopiclone with special emphasis on its use for the treatment of late-life insomnia. Specific topics covered include pharmacology, pharmacodynamics, pharmacokinetics, clinical trial data, adverse events, drug interactions, tolerance/dependence, and economics/cost considerations for older adults.


Epithelioid leiomyosarcoma of uterus.
Fibroid most commonly presents in the reproductive age group and presence of fibroid with postmenopausal bleeding is a rare entity and all investigations and measures should be done to rule out leiomyosarcoma. A 45-year-old female had attained menopause 3 year back and developed postmenopausal bleeding since 2 months, with palpable mass, of 24 weeks size. Ultrasonography showed multiple whorled mass lesions, endometrium and myometrium could not be seen separately. Total abdominal hysterectomy with bilateral salpingoophorectomy was performed. Intraoperative findings showed 24 weeks uterine mass with size 17.5×15.5×11.5 cm and weight 1.9 kg with multiple, intramural fibroids. Cut section of removed specimen showed black and yellow necrotic and haemorrhagic areas with degenerative changes suggestive of malignancy. Histopathology reported epithelioid leiomyosarcoma.


Detection and classification of thyroid follicular lesions based on nuclear structure from histopathology images.
Follicular lesions of the thyroid are traditionally difficult and tedious challenges in diagnostic surgical pathology in part due to lack of obvious discriminatory cytological and microarchitectural features. We describe a computerized method to detect and classify follicular adenoma of the thyroid, follicular carcinoma of the thyroid, and normal thyroid based on the nuclear chromatin distribution from digital images of tissue obtained by routine histological methods. Our method is based on determining whether a set of nuclei, obtained from histological images using automated image segmentation, is most similar to sets of nuclei obtained from normal or diseased tissues. This comparison is performed utilizing numerical features, a support vector machine, and a simple voting strategy. We also describe novel methods to identify unique and defining chromatin patterns pertaining to each class. Unlike previous attempts in detecting and classifying these thyroid lesions using computational imaging, our results show that our method can automatically classify the data pertaining to 10 different human cases with 100% accuracy after blind cross validation using at most 43 nuclei randomly selected from each patient. We conclude that nuclear structure alone contains enough information to automatically classify the normal thyroid, follicular carcinoma, and follicular adenoma, as long as groups of nuclei (instead of individual ones) are used. We also conclude that the distribution of nuclear size and chromatin concentration (how tightly packed it is) seem to be discriminating features between nuclei of follicular adenoma, follicular carcinoma, and normal thyroid.


Intestinal microflora and metabolic diseases.
Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity-such as found in the intestinal microflora-and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease-to cite but a few-the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.


Discontinuities in recurrent neural networks.
This article studies the computational power of various discontinuous real computational models that are based on the classical analog recurrent neural network (ARNN). This ARNN consists of finite number of neurons; each neuron computes a polynomial net function and a sigmoid-like continuous activation function. We introduce arithmetic networks as ARNN augmented with a few simple discontinuous (e.g., threshold or zero test) neurons. We argue that even with weights restricted to polynomial time computable reals, arithmetic networks are able to compute arbitrarily complex recursive functions. We identify many types of neural networks that are at least as powerful as arithmetic nets, some of which are not in fact discontinuous, but they boost other arithmetic operations in the net function (e.g., neurons that can use divisions and polynomial net functions inside sigmoid-like continuous activation functions). These arithmetic networks are equivalent to the Blum-Shub-Smale model, when the latter is restricted to a bounded number of registers. With respect to implementation on digital computers, we show that arithmetic networks with rational weights can be simulated with exponential precision, but even with polynomial-time computable real weights, arithmetic networks are not subject to any fixed precision bounds. This is in contrast with the ARNN that are known to demand precision that is linear in the computation time. When nontrivial periodic functions (e.g., fractional part, sine, tangent) are added to arithmetic networks, the resulting networks are computationally equivalent to a massively parallel machine. Thus, these highly discontinuous networks can solve the presumably intractable class of PSPACE-complete problems in polynomial time.


Human iPSC-derived mesoangioblasts, like their tissue-derived counterparts, suppress T cell proliferation through IDO- and PGE-2-dependent pathways.
Human mesoangioblasts are currently in a phase I/II clinical trial for the treatment of patients with Duchenne muscular dystrophy. However, limitations associated with the finite life span of these cells combined with the significant numbers of mesoangioblasts required to treat all of the skeletal muscles in these patients restricts their therapeutic potential. Induced pluripotent stem cell (iPSC)-derived mesoangioblasts may provide the solution to this problem. Although, the idea of using iPSC-derived cell therapies has been proposed for quite some time, our understanding of how the immune system interacts with these cells is inadequate. Herein, we show that iPSC-derived mesoangioblasts (HIDEMs) from healthy donors and, importantly, limb-girdle muscular dystrophy 2D patients exert immunosuppressive effects on T cell proliferation. Interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) play crucial roles in the initial activation of HIDEMs and importantly indoleamine 2,3 dioxygenase (IDO) and prostaglandin E2 (PGE-2) were identified as key mechanisms involved in HIDEM suppression of T cell proliferation. Together with recent studies confirming the myogenic function and regenerative potential of these cells, we suggest that HIDEMs could provide an unlimited alternative source for mesoangioblast-based therapies.


From the American Academy of Pediatrics: Policy statement--Impact of music, music lyrics, and music videos on children and youth.
Music plays an important role in the socialization of children and adolescents. Popular music is present almost everywhere, and it is easily available through the radio, various recordings, the Internet, and new technologies, allowing adolescents to hear it in diverse settings and situations, alone or shared with friends. Parents often are unaware of the lyrics to which their children are listening because of the increasing use of downloaded music and headphones. Research on popular music has explored its effects on schoolwork, social interactions, mood and affect, and particularly behavior. The effect that popular music has on children's and adolescents' behavior and emotions is of paramount concern. Lyrics have become more explicit in their references to drugs, sex, and violence over the years, particularly in certain genres. A teenager's preference for certain types of music could be correlated or associated with certain behaviors. As with popular music, the perception and the effect of music-video messages are important, because research has reported that exposure to violence, sexual messages, sexual stereotypes, and use of substances of abuse in music videos might produce significant changes in behaviors and attitudes of young viewers. Pediatricians and parents should be aware of this information. Furthermore, with the evidence portrayed in these studies, it is essential for pediatricians and parents to take a stand regarding music lyrics.


Case-control study of high-speed exercise history of Thoroughbred and Quarter Horse racehorses that died related to a complete scapular fracture.
Identification of exercise history patterns that are related to catastrophic scapular fracture will facilitate prevention of racehorse fatalities. To determine if exercise patterns are associated with scapular fracture in Thoroughbred (TB) and Quarter Horse (QH) racehorses. High-speed exercise histories for 65 TB and 26 QH racehorses that had a complete scapular fracture (cases) and 2 matched control racehorses were retrospectively studied. Exercise variables were created from lifetime race and official timed workout reports. Associations between exercise variables and scapular fracture were investigated using conditional logistic regression. Thoroughbreds with a scapular fracture had a greater number of workouts, events (combined works and races), and mean event distances than QHs with a scapular fracture. Quarter Horses worked less frequently and accumulated distance at a lower rate than TBs. Breed differences were not found for career race number or length, time between races or lay-up variables for horses with ≥1 lay-up. For both breeds, cases had fewer events, lower recent accumulated distance and fewer active days in training than controls; however, a subset of TB cases with >10 events since lay-up had a longer active career than controls. For QHs that had a lay-up, total and mean lay-up times were greater for cases than controls. Multivariable models revealed that odds ratios (OR) of scapular fracture were greater for TBs that had not yet raced (OR = 23.19; 95% confidence interval (CI) 3.03-177.38) and lower for QHs with more events (OR = 0.71; 95% CI 0.54-0.94). Racehorses that are in early high-speed training but behind that of their training cohort should be examined for signs of scapular stress remodelling. Quarter Horses that had a prolonged lay-up and TBs that have endured high-speed training for a longer duration than that of their training cohort also were at greater risk.


Vitamin D Deficiency Is Associated with Rapid Decline in Exercise Capacity in Male Patients with Chronic Obstructive Pulmonary Disease.
Vitamin D is suggested to play a role in airway and systemic inflammation in chronic obstructive pulmonary disease (COPD). Low serum 25-hydroxyvitamin D (25-OHD) levels have been suggested to be associated with lower lung function and poorer exercise capacity in COPD. The main purpose of this study was to investigate the effects of vitamin D deficiency on the change in exercise capacity in male COPD patients. A total of 156 male subjects were selected from the Korean Obstructive Lung Disease cohort. Vitamin D deficiency was subdivided into three subgroups: mild, moderate, and severe deficiency groups. Rapid decline was defined as an annual rate of change in exercise capacity ≥17 m. Exercise capacity was assessed by 6-minute walk distance (6MWD). Significant differences were observed in the serum levels of 25-OHD, the number of patients with vitamin D sufficiency, and moderate-to-severe deficiency between rapid decliners (n = 40) and non-rapid decliners (n = 116). No differences were found between the groups for age, smoking status, lung function, and 6MWD. Multivariate analysis showed that vitamin D deficiency was independently related to rapid decline in exercise capacity (p = 0.028). A statistically significant difference was observed among the subgroups of vitamin D deficiency in terms of the change in exercise capacity (p < 0.001). The annual decline in exercise capacity was prominent in the severe deficiency group (23.1 m/year). This study shows that vitamin D deficiency is associated with rapid decline in exercise capacity in male patients with COPD.


Mode of action and choice of antimalarial drugs for intermittent preventive treatment in infants.
Intermittent preventive treatment in infants (IPTi) is an effective and safe malaria control strategy. However, it remains unclear what antimalarials should be used to replace sulfadoxine-pyrimethamine (SP) when and where SP is no longer an effective drug for IPTi. Work recently conducted in Tanzania, combined with the findings of previous studies, indicates that IPTi is essentially intermittent chemoprophylaxis; consequently, long-acting antimalarials that provide a long period of post-treatment prophylaxis will be the most effective alternative to SP. However, because of concerns about development of drug resistance, new combinations of long-acting drugs are urgently needed.


The internal structure of the phenomenology of auditory verbal hallucinations.
Auditory verbal hallucinations (AVH) do not have uniform pathological significance. They affect patients with different brain disorders, and vary along multiple phenomenological dimensions. Evidence indicates that some of the phenomenological variables have specific neural substrates. Therefore, a comprehensive characterization of the phenomenological variations of AVH and the interrelationship between these variables was undertaken. Twenty phenomenological variables were identified; on each AVH had a binary value (present or absent). Information about 11 of these variables were obtained from 30 patients. Hierarchical cluster (HC) and multidimensional scaling (MDS) analyses were performed to investigate the hidden structure and dimensions of these variables. HC yielded two main clusters with further sub-clusters in each. The first cluster included hallucinations with low linguistic complexity, repetitive content, attributed to self, located in outer space, and associated with different kinds of control strategies. The second cluster included hallucinations with high linguistic complexity, systematized content, multiple voices, attributed to others, and located in inner space. In MDS, three dimensions were identified: linguistic complexity, self-other attribution, and inner-outer space location. The patterns of clustering and dimensional configuration of AVH characteristics were in accord with intuitive expectation and validated the patients' descriptions of their experiences. These findings could reflect aspects of the neural mechanisms of AVH. For example, the presence of neural specificity for each phenomenological variable, intermediate neural commonality for groups of variables, and a final common pathway for all subtypes of AVH. Another example is a differential level of language dysfunction according to the linguistic complexity of AVH.


A novel information retrieval model for high-throughput molecular medicine modalities.
Significant research has been devoted to predicting diagnosis, prognosis, and response to treatment using high-throughput assays. Rapid translation into clinical results hinges upon efficient access to up-to-date and high-quality molecular medicine modalities. We first explain why this goal is inadequately supported by existing databases and portals and then introduce a novel semantic indexing and information retrieval model for clinical bioinformatics. The formalism provides the means for indexing a variety of relevant objects (e.g. papers, algorithms, signatures, datasets) and includes a model of the research processes that creates and validates these objects in order to support their systematic presentation once retrieved.We test the applicability of the model by constructing proof-of-concept encodings and visual presentations of evidence and modalities in molecular profiling and prognosis of: (a) diffuse large B-cell lymphoma (DLBCL) and (b) breast cancer.


Effects of oil spill response technologies on the physiological performance of the Arctic copepod Calanus glacialis.
A mesocosm study with oil in ice was performed in Van Mijenfjorden in Svalbard to compare effects of the oil spill responses (OSR) in situ burning, chemical dispersion and natural attenuation on the physiological performance of the Arctic copepod Calanus glacialis. Seawater collected from the mesocosms in winter and spring was used in laboratory incubation experiments, where effects on fecal pellet production, egg production and hatching success were investigated over a period of 14 days. Polycyclic aromatic hydrocarbon (PAH) seawater concentrations were lowest in winter. Brine channel formation in spring resulted in an 18 times increase in PAH concentration in the chemical dispersion treatment (1.67 μg L-1), and a 3 fold increase in the natural attenuation (0.36 μg L-1) and in situ burning (0.04 μg L-1) treatments. The physiological performance of female C. glacialis was unaffected by the PAH seawater concentrations. However, a higher mortality and deformity of nauplii was observed in the chemical dispersion treatment, highlighting the importance of considering secondary effects on next generation in future environmental risk assessment of OSR. This study shows that during the ice-covered period, chemical dispersion of oil spills leads to higher PAH exposure than natural attenuation and in situ burning, with potential consequences for recruitment of Arctic copepods.


Abdominal magnetic resonance imaging at 3.0 T: problem or a promise for the future?
The development of transmit-receive body coils and local and phased-array radiofrequency receive coils for 3.0-T magnetic resonance imaging (MRI) systems, and their recent approval in Europe and North America has promoted a move toward higher field, whole-body MRI. With approximately double the signal-noise ratio of a 1.5-T system, 3.0-T MR systems can substantially improve image quality and image acquisition speed; 3.0 T can potentially deliver square root(2) improvement in resolution in the same acquisition time of a comparable study at 1.5 T or one-half slice thickness with identical coverage or 4-fold speedup in scanning time for identical resolution settings. Parallel imaging, multiple coil elements, specific absorption rate, and altered MR physical properties at 3.0 T (T1 relaxation times, susceptibility, T2*) are important issues during optimization of sequences at high field. Possible future applications in the abdomen include high-resolution, contrast-enhanced imaging of the liver and pancreas; MR angiography; and MR spectroscopy. In this article, we will present our initial experience with optimization of sequences for abdominal MRI at 3.0 T and will include a short description of parallel imaging because of its importance for imaging at 3.0 T, general remarks comparing some of the physical properties of 1.5 T and 3.0 T, and some of the challenges during sequence optimization for the abdomen at 3.0 T with examples of abdominal MRI at 3.0 T with 4- and 8-channel coils.


Moving East: how the transnational tobacco industry gained entry to the emerging markets of the former Soviet Union-part I: establishing cigarette imports.
To identify British American Tobacco's (BAT) reasons for targeting the former Soviet Union following its collapse in 1991 and the initial strategies BAT used to enter the region. Analysis of tobacco industry documents held at the Guildford BAT archive. Desire to expand to new markets was based in part on the decline in old markets. The large population, proximity to China, scope to expand sales to women and, in Central Asia, a young population with high growth rates made the former Soviet Union particularly attractive. High consumption rates and unfilled demand caused by previous shortages offered potential for rapid returns on investment. A series of steps were taken to penetrate the markets with the initial focus on establishing imports. The documents suggest that BAT encouraged the use of aid money and barter trade to fund imports and directed the smuggling of cigarettes which graduated from an opportunistic strategy to a highly organised operation. In establishing a market presence, promotion of BAT's brands and corporate image were paramount, and used synonymously to promote both the cigarettes and the company. The tobacco industry targeted young people and women. It used the allure of western products to promote its brands and brand stretching and corporate imagery to pre-empt future marketing restrictions. BAT used the chaotic conditions in the immediate post-transition period in the former Soviet Union to exploit legislative loopholes and ensure illegal cigarette imports. Governments of countries targeted by the tobacco industry need to be aware of industry tactics and develop adequate tobacco control policies in order to prevent the exploitation of vulnerable populations. Marketing restrictions that focus on advertising without restricting the use of brand or company promotions will have a limited impact.


Respiratory sympathetic modulation is augmented in chronic kidney disease.
Respiratory modulation of sympathetic nerve activity (respSNA) was studied in a hypertensive rodent model of chronic kidney disease (CKD) using Lewis Polycystic Kidney (LPK) rats and Lewis controls. In adult animals under in vivo anaesthetised conditions (n = 8-10/strain), respiratory modulation of splanchnic and renal nerve activity was compared under control conditions, and during peripheral (hypoxia), and central, chemoreceptor (hypercapnia) challenge. RespSNA was increased in the LPK vs. Lewis (area under curve (AUC) splanchnic and renal: 8.7 ± 1.1 vs. 3.5 ± 0.5 and 10.6 ± 1.1 vs. 7.1 ± 0.2 μV.s, respectively, P < 0.05). Hypoxia and hypercapnia increased respSNA in both strains but the magnitude of the response was greater in LPK, particularly in response to hypoxia. In juvenile animals studied using a working heart brainstem preparation (n = 7-10/strain), increased respSNA was evident in the LPK (thoracic SNA, AUC: 0.86 ± 0.1 vs. 0.42 ± 0.1 μV.s, P < 0.05), and activation of peripheral chemoreceptors (NaCN) again drove a larger increase in respSNA in the LPK with no difference in the response to hypercapnia. Amplified respSNA occurs in CKD and may contribute to the development of hypertension.


A case of fulminant pneumococcus meningoencephalitis progressing with white matter involvement despite two doses of conjugated pneumococcus vaccine.
Streptococcus pneumonia is a cause of serious mortality and morbidity, especially among small children. However, currently, it causes lower rates of invasive infections due to successful vaccination programs Case. We report an exceptional case of a 6-month-old child with meningoencephalitis caused by Streptococcus pneumonia despite the administration of two doses of pneumococcal conjugate vaccine (PCV). Meningitis progressed rapidly and led to widespread damage in parenchymal brain tissue with the emergence of fulminant meningoencephalitis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed widespread brain lesions, suggesting extensive parenchymal injury. Such diffuse white matter lesions among pediatric patients with Streptococcus pneumonia meningoencephalitis despite two doses of PCV have not been reported previously.


Effect of dietary soybean oil and soybean protein concentration on the concentration of digestible amino acids in soybean products fed to growing pigs.
An experiment was conducted to measure the effect of adding soybean oil to soybean meal (SBM) and soy protein concentrate (SPC) on apparent (AID) and standardized (SID) ileal digestibility of CP and AA by growing pigs. A second objective was to compare AID and SID of AA in a new high-protein variety of full fat soybeans (FFSB) to values obtained in other soybean products. Commercial sources of FFSB (FFSB-CV), SBM, and SPC, and of a new high-protein variety of FFSB (FFSB-HP) were used in the experiment. Four diets were prepared using each soybean product as the sole source of CP and AA in 1 diet. Two additional diets were formulated by adding soybean oil (7.55 and 7.35%, respectively) to the diets containing SBM and SPC. A nitrogen-free diet was also used to measure basal endogenous losses of CP and AA. The 2 sources of FFSB were extruded at 150 degrees C before being used in the experiment. Seven growing barrows (initial BW = 26.2 kg) were prepared with a T-cannula in the distal ileum and allotted to a 7 x 7 Latin square design. Ileal digesta were collected from the pigs on d 6 and 7 of each period. All digesta samples were lyophilized and analyzed for DM, CP, AA, and chromium, and values for AID and SID of CP and AA were calculated. The addition of oil improved (P < 0.05) the SID of most indispensable AA in SBM and SPC. The SID for 6 of the indispensable AA in FFSB-HP were greater (P < 0.05) than in FFSB-CV, and the SID for all indispensable AA except Met was greater (P < 0.05) in FFSB-HP than in SBM. However, the SID for most AA in FFSB-HP was similar to SBM with oil and SPC, but these values were lower (P < 0.05) than in SPC with oil. In conclusion, the addition of oil improved the SID of most AA in SBM and SPC fed to growing pigs, and the SID of AA in FFSB-HP were greater than in SBM and similar to the SID of AA in SBM with oil and in SPC.


Analysis of Patient Safety Incidents in Primary Care Reported in an Electronic Registry Application.
(1) To describe the epidemiology of patient safety (PS) incidents registered in an electronic notification system in primary care (PC) health centres; (2) to define a risk map; and (3) to identify the critical areas where intervention is needed. Descriptive analytical study of incidents reported from 1 January to 31 December 2018, on the TPSC Cloud™ platform (The Patient Safety Company) accessible from the corporate website (Intranet) of the regional public health service. 24 Catalan Institute of Health PC health centres of the Tarragona region (Spain). Professionals from the PC health centres and a Patient Safety Functional Unit. Data obtained from records voluntarily submitted to an electronic, standardised and anonymised form. Data recorded: healthcare unit, notifier, type of incident, risk matrix, causal and contributing factors, preventability, level of resolution and improvement actions. A total of 1544 reports were reviewed and 1129 PS incidents were analysed: 25.0% of incidents did not reach the patient; 66.5% reached the patient without causing harm, and 8.5% caused adverse events. Nurses provided half of the reports (48.5%), while doctors reported more adverse events (70.8%; p < 0.01). Of the 96 adverse events, 46.9% only required observation, 34.4% caused temporary damage that required treatment, 13.5% required (or prolonged) hospitalization, and 5.2% caused severe permanent damage and/or a situation close to death. Notably, 99.2% were considered preventable. The main critical areas were: communication (27.8%), clinical-administrative management (25.1%), care delivery (23.5%) and medicines (18.4%); few incidents were related to diagnosis (3.6%). PS incident notification applications are adequate for reporting incidents and adverse events associated with healthcare. Approximately 75% and 10% of incidents reach the patient and cause some damage, respectively, and most cases are considered preventable. Adequate and strengthened risk management of critical areas is required to improve PS.


PHD and TFIIS-Like domains of the Bye1 transcription factor determine its multivalent genomic distribution.
The BYpass of Ess1 (Bye1) protein is a putative S. cerevisiae transcription factor homologous to the human cancer-associated PHF3/DIDO family of proteins. Bye1 contains a Plant Homeodomain (PHD) and a TFIIS-like domain. The Bye1 PHD finger interacts with tri-methylated lysine 4 of histone H3 (H3K4me3) while the TFIIS-like domain binds to RNA polymerase (Pol) II. Here, we investigated the contribution of these structural features to Bye1 recruitment to chromatin as well as its function in transcriptional regulation. Genome-wide analysis of Bye1 distribution revealed at least two distinct modes of association with actively transcribed genes: within the core of Pol II- and Pol III-transcribed genes concomitant with the presence of the TFIIS transcription factor and, additionally, with promoters of a subset of Pol II-transcribed genes. Specific loss of H3K4me3 abolishes Bye1 association to gene promoters, but doesn't affect its binding within gene bodies. Genetic interactions suggested an essential role of Bye1 in cell fitness under stress conditions compensating the absence of TFIIS. Furthermore, BYE1 deletion resulted in the attenuation of GAL genes expression upon galactose-mediated induction indicating its positive role in transcription regulation. Together, these findings point to a bimodal role of Bye1 in regulation of Pol II transcription. It is recruited via its PHD domain to H3K4 tri-methylated promoters at early steps of transcription. Once Pol II is engaged into elongation, Bye1 binds directly to the transcriptional machinery, modulating its progression along the gene.


Study of the blood-aqueous barrier in choroidal melanoma.
Aqueous flare was used to determine the frequency and amount of blood-aqueous barrier breakdown and correlate it with tumour variables. Aqueous flare was analysed prospectively by laser flare photometry in 139 consecutive patients seen in the oncology unit for choroidal melanoma. Both eyes of patients were examined with a laser flare cell meter in a standard fashion. Mean flare difference between healthy and tumour eyes was 3.01 (SD 2.5) photons per millisecond (ph/ms) in 32 cases of small melanomas (p < 0.0001), 10.74 (13.9) ph/ms in 92 cases of medium and large melanomas (p < 0.0001), and 19.23 (11.8) ph/ms in 15 cases of very large melanomas (p < 0.0001). This mean differential flare was significantly higher in medium and large than in small melanomas (p < 0.002) and in very large melanomas than in medium and large melanomas (p < 0.028). A difference of > or = 7 ph/ms between affected and healthy eyes was noted in 70 of 139 melanomas (50.4%). It was found in 3/32 small melanomas (9.4%), in 53/92 medium and large melanomas (57.6%), and in 14/15 very large melanomas (93.3%). Multiple linear regression analysis showed that flare was most strongly correlated with tumour volume (r = 0.43; p < 0.0001) and tumour height (r = 0.41; p < 0.0008).


Targeting the MLL complex in castration-resistant prostate cancer.
Resistance to androgen deprivation therapies and increased androgen receptor (AR) activity are major drivers of castration-resistant prostate cancer (CRPC). Although prior work has focused on targeting AR directly, co-activators of AR signaling, which may represent new therapeutic targets, are relatively underexplored. Here we demonstrate that the mixed-lineage leukemia protein (MLL) complex, a well-known driver of MLL fusion-positive leukemia, acts as a co-activator of AR signaling. AR directly interacts with the MLL complex via the menin-MLL subunit. Menin expression is higher in CRPC than in both hormone-naive prostate cancer and benign prostate tissue, and high menin expression correlates with poor overall survival of individuals diagnosed with prostate cancer. Treatment with a small-molecule inhibitor of menin-MLL interaction blocks AR signaling and inhibits the growth of castration-resistant tumors in vivo in mice. Taken together, this work identifies the MLL complex as a crucial co-activator of AR and a potential therapeutic target in advanced prostate cancer.


Cortisol reactivity and suicidal behavior: Investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators.
Every 40s a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participants. One hundred and sixty participants were recruited to a previous attempt, a suicidal ideation or a control group. Participants completed background questionnaires before completing the Maastricht Acute Stress Test (MAST). Cortisol levels were assessed throughout the stress task. Measures of suicide behavior were measured at baseline, 1 month and 6 month follow-up. Participants who had made a previous suicide attempt exhibited significantly lower aggregate cortisol levels during the MAST compared to participants in the control group; suicide ideators were intermediate to both groups. This effect, however, was driven by participants who made an attempt within the past year, and to some degree by those with a family history of attempt. Participants who made a suicide attempt and had a family history of suicide exhibited the lowest levels of cortisol in response to stress. Finally, lower levels of cortisol in response to the MAST were associated with higher levels of suicidal ideation at 1-month follow-up in the suicide attempter group. These results are consistent with other findings indicating that blunted HPA axis activity is associated with some forms of suicidal behavior. The challenge for researchers is to elucidate the precise causal mechanisms linking stress, cortisol and suicide risk.


Chromosomal abnormalities subdivide neuroepithelial tumors into clinically relevant groups.
Gliomas are the most common primary brain tumor, and are histopathologically classified according to their cell type and the degree of malignancy. However, sometimes diagnosis can be controversial,and tumors of the same entity possibly have a wide range of survival. Genetic analysis of these tumors is considered to have great importance in terms that it can provide clinically relevant classification of the tumors and compensate for the limitation of the histological classification. Previous studies using comparative genomic hybridization (CGH) demonstrated that copy number aberrations(CNAs) were frequently recognized in these tumors, and revealed that a gain on chromosomal arm 7q was the most common CNA in diffuse astrocytomas, whereas a small population of the tumor showed losses on 1p/19q which characterizes oligodendrogliomas with good responsiveness to chemotherapeutic regime using procarbazine, nitrosourea and vincristine. High grade (malignant) gliomas(i.e. anaplastic astrocytomas, anaplastic oligodendrogliomas and glioblastomas) have been reported to have a gain on 7p and losses on 9p and 10q. In case of ependymomas, frequent chromosomal aberrations in intracranial tumors were a gain on 1q and losses on 6q, and, on the other hand, a gain on chromosome 7 was recognized almost exclusively in spinal cord tumors. These data suggest that intracranial and spinal cord ependymomas are different genetic diseases and comprise different subgroups within one histological entity. In conclusion, genetic analysis of gliomas may help to classify these tumors and provide leads concerning their initiation and progression. The relationship of these aberrations to patient outcome needs to be addressed.


Techniques for the improvement of the internal nasal valve in functional-cosmetic nasal surgery.
The internal nasal valve (INV) refers to the slit-like region between the caudal end of the upper lateral cartilage (ULC) and the nasal septum. It is the narrowest portion and primary regulator of the nasal airway. Reduction rhinoplasty decreases the nasal airway cross-sectional area and may cause symptoms, unless additional surgical measures are taken. Rhinoplasty or septorhinoplasty was performed for 76 patients with a nasal hump, using an external approach. As a consequence of the nasal hump removal, the ULCs were separated from the septal cartilage. All patients underwent one of the three forms of cartilaginous nasal dorsum reconstruction: primary closure (PC) (50 patients); spreader graft (SG) (19 patients); or upper lateral splay graft (ULSG) (7 patients). At least 3 months postoperatively. INV obstruction was evaluated by asking the patients about nasal obstruction symptoms and visually examining the INV with an otoscope. Nasal obstruction complaints and INV constriction found among patients in the PC. SG and ULSG groups were 16 (32%), 2 (10.5%) and none, respectively. The results of the PC group were compared statistically with the combined results of the SG and the ULSG groups. The patients in the combined SG-ULSG group had significantly less nasal obstruction complaints and INV angle constriction compared with the PC group. Due to the higher rate of postoperative INV stenosis. PC should be avoided. The author uses ULSG when the septal cartilage appears straight and sturdy and SGs when the straightened septal cartilage looks weak and vulnerable, since SGs not only improve the INV, but also reinforce the septal cartilage.


Residential proximity to a major roadway is associated with features of asthma control in children.
While several studies suggest that traffic-related air pollutants are detrimental for respiratory health, few studies have examined relationships between residential proximity to a major roadway and asthma control in children. Furthermore, a major limitation of existing research is reliance on self-reported outcomes. We therefore determined the spatial relationship between the distance from a major roadway and clinical, physiologic and inflammatory features of asthma in a highly characterized sample of asthmatic children 6-17 years of age across a wide range of severities. We hypothesized that a closer residential proximity to a major roadway would be associated with increased respiratory symptoms, altered pulmonary function and a greater magnitude of airway and systemic inflammation. 224 children 6-17 years with confirmed asthma completed questionnaires and underwent spirometry, plethysmography, exhaled nitric oxide determination, exhaled breath condensate collection and venipuncture. Residential distance from a major roadway was determined by mapping the geographic coordinates of the residential address in Geographic Information System software. The distance between the home address and the nearest major roadway was calculated according to the shortest distance between the two points (i.e., "as the crow flies"). Asthmatic children living in closer proximity to a major roadway had an increased frequency of wheezing associated with increased medication requirements and more hospitalizations even after controlling for potential confounders. These children also had increased airway resistance, increased airway inflammation reflected by a lower breath condensate pH, and higher plasma EGF concentrations. These findings suggest that closer residential proximity to a major roadway is associated with poorer asthma control in school-age children. Assessment of residential proximity to major roadways may be useful in the clinical evaluation of asthma in children.


The impact of electronic health records on client safety in aged care homes.
This study collects and critically reviews the published literature to synthesize the risk factors for client safety in residential aged care and the potential contributions of electronic health records to reducing these risks. Three major types of risk factors for client safety were identified: risk factors related to the person's health; those related to the health and aged care system serving the person and those related to human error. Multiple strategies at all levels of an aged care organization are needed to reduce risks and improve client safety. Electronic health records can be one of the effective organizational mechanisms because it improves access to better information and integrates intelligent functions to support point-of-care decision making.


Antibody-conjugated nanoparticles for therapeutic applications.
A great challenge to clinical development is the delivery of chemotherapeutic agents, known to cause severe toxic effects, directly to diseased sites which increase the therapeutic index whilst minimizing off-target side effects. Antibody-conjugated nanoparticles offer great opportunities to overcome these limitations in therapeutics. They combine the advantages given by the nanoparticles with the ability to bind to their target with high affinity and improve cell penetration given by the antibodies. This specialized vehicle, that can encapsulate several chemotherapeutic agents, can be engineered to possess the desirable properties, allowing overcoming the successive physiological conditions and to cross biological barriers and reach a specific tissue or cell. Moreover, antibody-conjugated nanoparticles have shown the ability to be internalized through receptor-mediated endocytosis and accumulate in cells without being recognized by the P-glycoprotein, one of the main mediators of multi-drug resistance, resulting in an increase in the intracellular concentration of drugs. Also, progress in antibody engineering has allowed the manipulation of the basic antibody structure for raising and tailoring specificity and functionality. This review explores recent developments on active drug targeting by nanoparticles functionalized with monoclonal antibodies (polymeric micelles, liposomes and polymeric nanoparticles) and summarizes the opportunities of these targeting strategies in the therapy of serious diseases (cancer, inflammatory diseases, infectious diseases, and thrombosis).


Brown-sequard syndrome after endovascular embolization of vertebral hemangioma.
Several causes of Brown-Sequard syndrome have been described. Endovascular embolization can be used to treat symptomatic vertebral hemangiomas. We describe a previously undocumented case of Brown-Sequard syndrome followed by endovascular embolization with microcoils of a vertebral hemangioma. We also provide a clinical-radiological correlation of this finding and review the relevant literature. A 39-year-old male was referred to our hospital for endovascular treatment of a right T9 hemivertebral hemangioma with compromise of the spinal canal. Fifteen minutes after the procedure, the patient developed right lower limb weakness and numbness on the left leg. The emergency magnetic resonance imaging (MRI) of the spine showed no abnormalities. Five days later, a new spinal MRI revealed an infarction in the right half of the spinal cord at T6 and T7 level. This stroke was probably caused by a microcoil ended up in the right sulcocommisural artery. One week after surgery, the patient was able to raise the right leg against gravity, but sensory deficit showed no improvement. To the best of our knowledge this is the first case of a Brown-Sequard syndrome related to vertebral hemangioma embolization, a relatively safe technique with no important complications made known until this report. Clinicians should always weight the benefits with the potential devastating complications of this therapeutic option.


Medical aptitude and its assessment.
The assessment of the suitability of an individual for the profession of medical science is carried out worldwide on the basis of several yardsticks. While a few methods assess domain knowledge of sciences, others focus on evaluating the cognitive aptitude skills of the candidate, while few others assess communicative skills. Though it has been considered that the possession of an aptitude for the profession is a prerequisite, considering its strenuous demands from the candidate, a comprehensive assessment of these areas under the construct of medical aptitude has not been analysed so far, though medical aptitude has been socially defined. This article attempts to develop a comprehensive construct to 'Medical aptitude', meant for the pre-medical student, which has been encapsulated with respect to the areas of its assessment. We did an extensive survey of the literature pertaining to the mode of selection of students towards medical profession and analysed their areas of assessments for admittance. This enabled to identify similarities in the areas of assessment which were then classified under several domains of assessment. Special reference to the keywords involving 'Aptitude' and 'Medical Aptitude' was made. We analysed the definitions to the construct of aptitude from the literature with respect to its relevance in the profession of medical science to be possessed by the pre-medical aspirant-in context. From this, a new construct of medical aptitude was formulated incorporating the existing construct of medical aptitude. Medical aptitude is a comprehensive construct that encompasses the dimensions of a consistent core, a peripheral content and the support of a scaffold. Each of these dimensions have their importance and distinct objective in being assessed in the pre-medical student. A perfect intertwining of these 3 dimensions can prove beneficial in assessing individuals to be fit for the profession of medical science.


Vitamin D status and its determinants during autumn in children at northern latitudes: a cross-sectional analysis from the optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study.
Sufficient summer/autumn vitamin D status appears important to mitigate winter nadirs at northern latitudes. We conducted a cross-sectional study to evaluate autumn vitamin D status and its determinants in 782 Danish 8-11-year-old children (55°N) using baseline data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study, a large randomised controlled trial. Blood samples and demographic and behavioural data, including 7-d dietary recordings, objectively measured physical activity, and time spent outdoors during school hours, were collected during September-November. Mean serum 25-hydroxyvitamin D (25(OH)D) was 60·8 (sd 18·7) nmol/l. Serum 25(OH)D levels ≤50 nmol/l were found in 28·4 % of the children and 2·4 % had concentrations <25 nmol/l. Upon multivariate adjustment, increasing age (per year) (β -2·9; 95 % CI -5·1, -0·7 nmol/l), female sex (β -3·3; 95 % CI -5·9, -0·7 nmol/l), sampling in October (β -5·2; 95 % CI -10·1, -0·4 nmol/l) and November (β -13·3; 95 % CI -17·7, -9·1), and non-white ethnicity (β -5·7; 95 % CI -11·1, -0·3 nmol/l) were negatively associated with 25(OH)D (all P<0·05). Likewise, immigrant/descendant background was negatively associated with 25(OH)D, particularly in females (β -16·3; 95 % CI -21·9, -10·7) (P<0·001) (P interaction=0·003). Moderate-to-vigorous physical activity (MVPA) (min/d) (β 0·06; 95 % CI 0·01, 0·12), outdoor walking during school hours (min/week) (β 0·4; 95 % CI 0·1, 0·6) and intake of vitamin D-containing supplements ≥3 d/week (β 8·7; 95 % CI 6·4, 11·0) were positively associated with 25(OH)D (all P<0·05). The high proportion of children with vitamin D status below the recommended sufficiency level of 50 nmol/l raises concern as levels expectedly drop further during winter months. Frequent intake of vitamin D supplements was strongly associated with status. MVPA and outdoor activity during school hours should be investigated further in interventions to improve autumn vitamin D status in children at northern latitudes.


The effect of Rowland ghost on sub-micromachining using Femtosecond pulsed laser.
The unique ability of the ultrafast lasers to perform sub-spot size machining has been proved to be advantageous over conventional lasers for sub-micron-machining. To achieve this, a Gaussian laser beam free of spatial defects is essential. In this research work, submicron holes with clear edge and symmetric shape on thin metal films using a Ti:Sapphire regenerative amplified femtosecond pulsed laser are produced. While analysing, it is observed that there are two shallow pits accompanying the produced hole, symmetrically located at the two sides of the hole, especially when the holes are in the sub-micron range. A careful study on the effects of these shallow pits and the methods to eliminate the same are presented in this letter. It has been concluded that the shallow pits are Rowland ghosts raised by deficiencies of grating space present in the two pairs of gratings used for pulse stretching and compressing. Methods of eliminating these ghosts to achieve features with better edge acuity and quality are also presented.


HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway.
HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit(+)/Sca-1(+)--positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.


Effects of cholesterol and saturated sphingolipids on acyl chain order in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers--a comparative study with phase-selective fluorophores.
Saturated sphingolipids have high acyl chain order. Our aim was to study how palmitoylated sphingomyelin (PSM), ceramide (PCer), glucosyl (GlcPCer)-, and galactosylceramide (GalPCer) were able to order the bulk acyl chains of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), in comparison with cholesterol. For this reason, we used lipid probes which had preferred phases that were either the disordered phase (1-oleoyl-2-propionyl[DPH-sn-glycero-3-phosphcholine (18:1-DPH-PC) or the ordered phase (trans parinaric acid (tPA). DPH was also used, although it has no clear phase preference. We measured steady-state anisotropy (all probes) and performed fluorescence lifetime analysis (tPA) as a function of composition and temperature. At concentrations where the saturated sphingolipids were not aggregated into ordered domains (and 23 °C), they did not increase POPC acyl chain order as determined from 18:1-DPH-PC anisotropy. As expected, cholesterol increased the POPC acyl chain order linearly as a function of concentration (0-28 mol %). Since PCer already forms ordered domains below 5 mol % (at 23 °C), we measured the acyl chain ordering effect of PCer at 50 °C (0-13 mol %) and observed that PCer ordered POPC acyl chains as efficiently as cholesterol. We conclude that the bulk acyl chain order of POPC was not markedly affected in bilayers where disordered and ordered domains coexist.


A Case of Multifocal Eosinophilic Granuloma Involving Spine and Pelvis in a Young Adult: A Radiopathological Correlation.
We present a case of multiple osteolytic lesions in a 28-year-old adult who presented with headache, back pain, and hip pain of 6 months. There was no history of localized swelling or rise of temperature, no history of weight loss or evening rise of temperature. On examination, there were no focal neurological deficits. Routine laboratory investigations, including total leukocyte counts, differential leukocyte counts, hemoglobin, and platelet counts, were within normal limits. There was a borderline elevation of erythrocyte sedimentation rate. Non enhanced computer tomography (NECT) demonstrated no abnormality in the brain or skull bones. However, incidentally, a lytic lesion involving the third cervical (C3) vertebral body and the neural arch was detected which also demonstrated a soft tissue component adjacent to the lytic lesion. These findings warranted further work up; and magnetic resonance imaging of whole spine and pelvis was performed that revealed multiple bony lesions involving the cervical vertebrae, head and neck, bilateral femur, sacrum, and iliac bones. Computed tomography-guided biopsy was performed from the C3 vertebral lytic lesion which showed features of eosinophilic granuloma on histopathological evaluation.