Anillin facilitates septin assembly to prevent pathological outfoldings of central nervous system myelin.
Myelin serves as an axonal insulator that facilitates rapid nerve conduction along axons. By transmission electron microscopy, a healthy myelin sheath comprises compacted membrane layers spiraling around the cross-sectioned axon. Previously we identified the assembly of septin filaments in the innermost non-compacted myelin layer as one of the latest steps of myelin maturation in the central nervous system (CNS) (Patzig et al., 2016). Here we show that loss of the cytoskeletal adaptor protein anillin (ANLN) from oligodendrocytes disrupts myelin septin assembly, thereby causing the emergence of pathological myelin outfoldings. Since myelin outfoldings are a poorly understood hallmark of myelin disease and brain aging we assessed axon/myelin-units in Anln-mutant mice by focused ion beam-scanning electron microscopy (FIB-SEM); myelin outfoldings were three-dimensionally reconstructed as large sheets of multiple compact membrane layers. We suggest that anillin-dependent assembly of septin filaments scaffolds mature myelin sheaths, facilitating rapid nerve conduction in the healthy CNS.


Dendritic cells inversely regulate airway inflammation in cigarette smoke-exposed mice.
The recruitment and activation of inflammatory cells into the respiratory system is considered a crucial feature in the pathophysiology of chronic obstructive pulmonary disease (COPD). Because dendritic cells (DCs) have a pivotal role in the onset and regulation of immune responses, we investigated the effect of modulating DC subsets on airway inflammation by acute cigarette smoke (CS) exposure. CS-exposed mice (5 days) were treated with fms-like tyrosine kinase 3 ligand (Flt3L) and 120g8 antibody to increase total DC numbers and deplete plasmacytoid DCs (pDCs), respectively. Flt3L treatment decreased the number of inflammatory cells in the bronchoalveolar lavage (BALF) of the smoke-exposed mice and increased these in lung tissue. DC modulation reduced IL-17 and increased IL-10 levels, which may be responsible for the suppression of the BALF cells. Furthermore, depletion of pDCs led to increased infiltration of alveolar macrophages while restricting the presence of CD103(+) DCs. This study suggests that DC subsets may differentially and compartment-dependent influence the inflammation induced by CS. pDC may play a role in preventing the pathogenesis of CS by inhibiting the alveolar macrophage migration to lung and increasing CD103(+) DCs at inflammatory sites to avoid extensive lung tissue damage.


Comparative Functional Analysis of Class II Potassium Transporters, SvHKT2;1, SvHKT2;2, and HvHKT2;1, on Ionic Transport and Salt Tolerance in Transgenic Arabidopsis.
Class II high-affinity potassium transporters (HKT2s) mediate Na+-K+ cotransport and Na+/K+ homeostasis under K+-starved or saline conditions. Their functions have been studied in yeast and X. laevis oocytes; however, little is known about their respective properties in plant cells. In this study, we characterized the Na+ and K+ transport properties of SvHKT2;1, SvHKT2;2 and HvHKT2;1 in Arabidopsis under different ionic conditions. The differences were detected in shoot K+ accumulation and root K+ uptake under salt stress conditions, K+ accumulation in roots and phloem sap under K+-starved conditions, and shoot and root Na+ accumulation under K+-starved conditions among the HKT2s transgenic lines and WT plants. These results indicate the diverse ionic transport properties of these HKT2s in plant cells, which could not be detected using yeast or X. laevis oocytes. Furthermore, Arabidopsis expressing HKT2s showed reduced salt tolerance, while over-expression of HvHKT2;1 in barley, which has the ability to sequestrate Na+, showed enhanced salt tolerance by accumulating Na+ in the shoots. These results suggest that the coordinated enhancement of Na+ accumulation and sequestration mechanisms in shoots could be a promising strategy to confer salt tolerance to glycophytes.


Application of near infrared spectroscopy (NIR), X-ray fluorescence (XRF) and chemometrics to the differentiation of marmora samples from the Mediterranean basin.
Near-infrared (NIR) and X-ray fluorescence spectra were recorded for 15 different samples of marmora, from the Mediterranean Basin and of different colours. After appropriate pretreatment (SNV transform + second derivative), the results were subjected to principal component analysis (PCA) treatment with a view to differentiating them. The observed differences among the samples were chemically interpreted by highlighting the NIR wavelengths and minerals, respectively, contributing the most to the PCA models. Moreover, a mid-level data fusion protocol allowed integrating the information from the different techniques and, in particular, to correctly identify (based on the distance in the score space) three test samples of known type. Moreover, it should be stressed that positive results on the differentiation and identification of marmora were obtained using two completely non-invasive, non-destructive and relatively inexpensive techniques, which can also be used in situ.


Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study.
To examine the effects of sleep traits on glycated hemoglobin (HbA1c). This study triangulated evidence across multivariable regression (MVR) and one- (1SMR) and two-sample Mendelian randomization (2SMR) including sensitivity analyses on the effects of five self-reported sleep traits (i.e., insomnia symptoms [difficulty initiating or maintaining sleep], sleep duration, daytime sleepiness, napping, and chronotype) on HbA1c (in SD units) in adults of European ancestry from the UK Biobank (for MVR and 1SMR analyses) (n = 336,999; mean [SD] age 57 [8] years; 54% female) and in the genome-wide association studies from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) (for 2SMR analysis) (n = 46,368; 53 [11] years; 52% female). Across MVR, 1SMR, 2SMR, and their sensitivity analyses, we found a higher frequency of insomnia symptoms (usually vs. sometimes or rarely/never) was associated with higher HbA1c (MVR 0.05 SD units [95% CI 0.04-0.06]; 1SMR 0.52 [0.42-0.63]; 2SMR 0.24 [0.11-0.36]). Associations remained, but point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency across methods, with some but not all providing evidence of an effect. Our results suggest that frequent insomnia symptoms cause higher HbA1c levels and, by implication, that insomnia has a causal role in type 2 diabetes. These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycemia and prevent diabetes.


The Biomedicine Convention as an object and a stimulus for comparative research in the European Journal of Health Law.
The European Association for Health Law has ambitious objectives. Two of them are "to encourage and facilitate co-operation among health lawyers throughout Europe" and "to encourage and support the development of health law in European and international relations". Comparative legal research will be an important means to reach these objectives. In this contribution the author takes a closer look at this Convention as an object but also as a stimulus for comparative research in health law. To this end relevant articles have been analyzed that have been published in this journal from its creation in 1994 until the end of 2007.


Changes in the physico-chemical properties of the xanthan produced by Xanthomonas citri subsp. citri in grapefruit leaf extract.
Xanthan is a virulence factor produced by Xanthomonas spp. We previously demonstrated that this exopolysaccharide is not only essential for pathogenicity by contributing with bacterial survival but also its pyruvate substituents interfere with some plant defense responses. Deepening our studies about xanthan properties and structure, the aim of this work was to analyze the characteristics of xanthan produced by Xanthomonas in different culture media. We analyzed the xanthan produced by Xanthomonas citri subsp. citri (Xcc) in leaf extracts from grapefruit (a susceptible host of this bacterium) and compared it with the xanthan produced in a synthetic culture medium. We found that the xanthan produced in the grapefruit extract (Xan-GLE) presented shorter and more disordered molecules than xanthan produced in the synthetic medium (Xan-PYM). Besides, Xan-GLE resulted less viscous than Xan-PYM. The disordered molecular conformation of Xan-GLE could be attributed to its higher pyruvilation degree and lower acetylation degree compared with those detected in Xan-PYM. Meanwhile, the difference in the viscosity of both xanthans could be due to their molecules length. Finally, we cultured Xcc in the presence of the Xan-GLE or Xan-PYM and observed the formation of biofilm-like structures in both cases. We found significant differences in biofilm architecture between the two conditions, being the biofilm produced in presence of Xan-GLE similar to that formed in canker lesions developed in lemon plant leaves. Together, these results show how xanthan structure and properties changed when Xcc grew in a natural substrate and can contribute to better understand the biological role of xanthan.


Structure design and mechanical performance analysis of three kinds of bioresorbable poly-lactic acid (PLA) stents.
Vascular stent implantation has become an important choice for the treatment of severe cardiovascular and cerebrovascular blockage. Rational design is vital to ensure the mechanical properties of the vascular stents, which are important both to the implantation and service as for clinical treatment of coronary heart disease. Therefore we proposed a wholly new non-uniform honeycomb stent E and compared with an inverted honeycomb-like shaped stent F and a honeycomb-like shaped stent G. To evaluate their properties, a finite element method (FEM) was used to simulate the implantation process (crimp, crimp recoil, expand, and expand recoil) of these three different kinds of stents. Results showed that the stent E exhibits better mechanical behaviour than the other two stents F and G as far as radial strength and axial shortening performances and that the distribution of equivalent stress among the stent E is more uniform than that among the other two stents F and G. After that, a three-point bending method was used to study the bending flexibility of these three vascular stents. Stent E shows high bending stiffness compared with stents F and G due to the existence of additional support bridges in its structure. This study can be helpful to the rational design of optimizable PLA stents for its practical clinical performance and therefore possibly improve the prognosis of patients.


Clinical comparison of immunoradiometric assays for intact versus beta-specific human chorionic gonadotropin.
Monoclonal immunoradiometric assays (IRMA) for human chorionic gonadotropin (hCG) are available for either intact hCG (IhCG) or beta subunit hCG (beta hCG). The authors evaluated the clinical applications of both methods. Serum samples (N = 180) were divided into the following five clinical groups: Group 1: elevated luteinizing hormone (LH), follicular stimulating hormone (FSH), and thyroid-stimulating hormone (TSH), which share alpha subunits with hCG; Group 2: pregnancy; Group 3: trophoblastic tumors; Group 4: malignancy; and Group 5: positive rheumatoid factor or anti-nuclear antibody (ANA). The values of beta hCG versus IhCG for Group 1 showed statistical significance but no clinical significance, indicating negligible cross-reactivity in the alpha subunit group. beta hCG values, although exceeding the IhCG values, correlated well (r = 0.97) in intrauterine pregnancies; however, these values were not believed to be clinically significant. There is negligible interference by alpha subunits, elevated rheumatoid factor, ANA, or malignancy in the determination of IhCG versus beta hCG. The authors conclude that either the IhCG or beta hCG assays may be used in clinical conditions in which a potential exists for interference of alpha subunits, autoantibodies, or heterophile antibodies or in malignancy.


Inhibition of neutrophil elastase by alpha-1-proteinase inhibitor oxidized by activated neutrophils.
The present study was aimed at testing whether neutrophil-oxidized alpha 1-proteinase inhibitor (alpha 1PI) is a slow-binding inhibitor of neutrophil elastase like N-chlorosuccinimide-oxidized alpha 1PI or whether it does not inhibit this enzyme at all as currently thought. alpha 1PI was reacted with phorbol-myristate-acetate-activated neutrophils and isolated from the oxidation medium by fast protein liquid chromatography on an anion exchange column. When sufficient time was allowed for oxidized alpha 1PI to react with neutrophil elastase (2 h), enzyme-inhibitor complex formation could be demonstrated by three means: (1) inhibition of elastase activity, (2) detection of the complex using an enzyme-linked immunosorbent assay specific for the native alpha 1PI-elastase complex, and (3) SDS-polyacrylamide gel electrophoresis, which evidenced a complex with a molecular weight of 80,000. Porcine pancreatic elastase was not inhibited. Neutrophil-oxidized alpha 1PI behaved as an irreversible inhibitor of neutrophil elastase, as revealed by the kinetic analysis of the inhibition reaction. The rate constant for the inhibition of neutrophil elastase by neutrophil-oxidized alpha 1PI (0.76 +/- 0.22 x 10(4) M-1 s-1) was close to that for the inhibition of the enzyme by N-chlorosuccinimide-oxidized alpha 1PI (0.96 +/- 0.24 x 10(4) M-1 s-1), but it was more than three orders of magnitude lower than that for the reaction of native alpha 1PI with neutrophil elastase. Both native and oxidized alpha 1PI were temporary elastase inhibitors: the enzyme slowly and spontaneously escaped the complex with formation of an inactive alpha 1PI derivative with a molecular weight of 49,000.(ABSTRACT TRUNCATED AT 250 WORDS)


Hardware implementation of associative memory characteristics with analogue-type resistive-switching device.
We have investigated the analogue memory characteristics of an oxide-based resistive-switching device under an electrical pulse to mimic biological spike-timing-dependent plasticity synapse characteristics. As a synaptic device, a TiN/Pr0.7Ca0.3MnO3-based resistive-switching device exhibiting excellent analogue memory characteristics was used to control the synaptic weight by applying various pulse amplitudes and cycles. Furthermore, potentiation and depression characteristics with the same spikes can be achieved by applying negative and positive pulses, respectively. By adopting complementary metal-oxide-semiconductor devices as neurons and TiN/PCMO devices as synapses, we implemented neuromorphic hardware that mimics associative memory characteristics in real time for the first time. Owing to their excellent scalability, resistive-switching devices, shows promise for future high-density neuromorphic applications.


Mechanism studies of the conversion of 13C-labeled n-butane on zeolite H-ZSM-5 by using 13C magic angle spinning NMR spectroscopy and GC-MS analysis.
By using 13C MAS NMR spectroscopy (MAS = magic angle spinning), the conversion of selectively 13C-labeled n-butane on zeolite H-ZSM-5 at 430-470 K has been demonstrated to proceed through two pathways: 1) scrambling of the selective 13C-label in the n-butane molecule, and 2) oligomerization-cracking and conjunct polymerization. The latter processes (2) produce isobutane and propane simultaneously with alkyl-substituted cyclopentenyl cations and condensed aromatic compounds. In situ 13C MAS NMR and complementary ex situ GC-MS data provided evidence for a monomolecular mechanism of the 13C-label scrambling, whereas both isobutane and propane are formed through intermolecular pathways. According to 13C MAS NMR kinetic measurements, both pathways proceed with nearly the same activation energies (E(a) = 75 kJ mol(-1) for the scrambling and 71 kJ mol(-1) for isobutane and propane formation). This can be rationalized by considering the intermolecular hydride transfer between a primarily initiated carbenium ion and n-butane as being the rate-determining stage of the n-butane conversion on zeolite H-ZSM-5.


Salmonella Interaction with and Passage through the Intestinal Mucosa: Through the Lens of the Organism.
Salmonella enterica serotypes are invasive enteric pathogens spread through fecal contamination of food and water sources, and represent a constant public health threat around the world. The symptoms associated with salmonellosis and typhoid disease are largely due to the host response to invading Salmonella, and to the mechanisms these bacteria employ to survive in the presence of, and invade through the intestinal mucosal epithelia. Surmounting this barrier is required for survival within the host, as well as for further dissemination throughout the body, and subsequent systemic disease. In this review, we highlight some of the major hurdles Salmonella must overcome upon encountering the intestinal mucosal epithelial barrier, and examine how these bacteria surmount and exploit host defense mechanisms.


Further evidence of X-linkage of hypoxanthine phosphoribosyl-transferase in the mouse.
A variant of the HPRT-A9 mouse cell line was fused with wild type diploid mouse bone marrow cells to obtain an HPRT+ line. The unique chromosomal features of the A9 parent, including the presence of a t(X;3) translocation and the absence of normal chromosomes 15,16, 17, 18, and the X, have permitted use of this intraspecific hybrid for chromosome mapping. Back-selection of hybrid cells in 8-azaguanine for loss of HPRT resulted in the loss of the Xchromosome derived from the diploid parent, providing evidence of the X-linkage of the HPRT locus.


Self-reported long-term effects of diving and decompression illness in recreational scuba divers.
The aim of this study was to examine the long-term effects of neurological decompression illness (NDCI) on recreational divers. Thirty-seven divers who had been treated for neurological decompression illness at least 2 years previously, and a control group of 50 divers with no history of decompression illness, responded to a postal questionnaire. Divers in the accident group reported more symptoms of neurological damage, were more likely to believe that diving had a deleterious effect on their health and were more likely to indicate symptoms of psychiatric morbidity. The quantity of diving in the year preceding the survey was associated with reports of neurological damage in both groups and with symptoms of psychiatric morbidity in the accident group. Although requiring confirmation from a longitudinal study, these results suggest that recreational diving can have negative long-term consequences for health, particularly after decompression illness.


Diastolic dysfunction revisited: A new, feasible, and unambiguous echocardiographic classification predicts major cardiovascular events.
Echocardiographic classification of DDF has been widely discussed. The aim of this study was to investigate the independent prognostic value of established echocardiographic measures in a community-based population and create a new classification of DDF. Within the Copenhagen City Heart Study, a prospective, community-based study, 1851 participants were examined by echocardiography including Tissue Doppler Imaging (TDI) in 2001 to 2003 and followed with regard to MACE (median, 10.9 years). We found that persons with impaired myocardial relaxation as defined by low peak early diastolic mitral annular velocity e' by TDI had higher incidence of clinical and echocardiographic markers of cardiac dysfunction and increased risk of MACE. Among persons with impaired relaxation, only echocardiographic indices of increased filling pressures such as LAVi≥34 mL/m2 (HR 1.97 (1.13-3.45, P=.017), E/e' ≥ 17 (HR 1.89 (1.34-2.65), P<.001), and E/A>2 (HR 5.24 (1.91-14.42), P=.001) provided additional and independent prognostic information on MACE. Based on these findings, we created a new classification of DDF where all grades were significant predictors of MACE independently of age, sex, and cardiac clinical risk markers (Mild DDF: HR 1.99 (1.23-3.21), P=.005; Moderate DDF: HR 3.11 (1.81-5.34), P<.001; Severe DDF: HR 4.20 (1.81-9.73), P<.001). Increasing severity of DDF was linearly associated with increasing plasma proBNP concentrations. In the general population, the presence of echocardiographic markers of elevated filling pressures in persons with impaired relaxation increased the risk of MACE significantly. Based on this, we present a new, feasible, and unambiguous classification of DDF capable of accurate risk prediction in the community.


Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes.
The pX sequence of human T-cell leukemia virus type I codes for three products: p40x, p27x-III, and p21x-III. p40x is a transcriptional trans-activator that activates not only the viral long terminal repeat but also cellular genes for interleukin 2 and its receptor. p27x-III and p21x-III are not required for transcriptional activation, and their functions were unknown. Cotransfection experiments with defective human T-cell leukemia virus type I proviruses and various pX expression plasmids revealed that p27x-III, in addition to p40x, was required for gag gene expression. Furthermore, it was shown that p27x-III induced accumulation of a high level of unspliced viral gag mRNA. These results indicate that p27x-III is a post-transcriptional modulator of viral RNA whose transcription has been fully activated by p40x.


The bone marrow transplant clinical nurse specialist in hemato-oncology: an interview with Anthony Nolan Nurse Specialist Susan Paskar.
Susan Paskar speaks to Sebastian Dennis-Beron, Commissioning Editor: Susan qualified in 1997 as a registered nurse and has 20 years of experience, in a range of specialties including hematology, medical and surgical oncology, general surgery, bariatric, breast, endocrine, head & neck, liver, urology and bone marrow/stem cell transplant. Working in both the UK and the USA, in regional transplant centers since 2002, she is considered expert in care of the bone marrow transplant patient from point of referral to long term follow-up care and palliation. She has been responsible for development and implementation of a Nurse-led late-effects post-bone marrow transplant service at the Freeman Hospital in Newcastle upon Tyne, as their Anthony Nolan Nurse Specialist.


Numerical description and experimental validation of a rheology model for non-Newtonian fluid flow in cancellous bone.
Fluids present or used in biology, medicine and (biomedical) engineering are often significantly non-Newtonian. Furthermore, they are chemically complex and can interact with the porous matrix through which they flow. The porous structures themselves display complex morphological inhomogeneities on a wide range of length scales. In vertebroplasty, a shear-thinning fluid, e.g. poly(methyl methacrylate) (PMMA), is injected into the cavities of vertebral trabecular bone for the stabilization of fractures and metastatic lesions. The main objective of this study was therefore to provide a protocol for numerically investigating the rheological properties of PMMA-based bone cements to predict its spreading behavior while flowing through vertebral trabecular bone. A numerical upscaling scheme based on a dimensionless formulation of the Navier-Stokes equation is proposed in order to relate the pore-scale rheological properties of the PMMA that were experimentally estimated using a plate rheometer, to the continuum-scale. On the pore length scale, a viscosity change on the order of one magnitude was observed whilst the shear-thinning properties caused a viscosity change on the order of only 10% on the continuum length scale and in a flow regime that is relevant for vertebroplasty. An experimental validation, performed on human cadaveric vertebrae (n=9), showed a significant improvement of the cement spreading prediction accuracy with a non-Newtonian formulation. A root mean square cement surface prediction error of 1.53mm (assuming a Newtonian fluid) and 1.37mm (assuming a shear-thinning fluid) was found. Our findings highlight the importance of incorporating the non-Newtonian fluids properties in computational models of porous media at the appropriate length scale.


Environmental DNA Time Series in Ecology.
Ecological communities change in time and space, but long-term dynamics at the century-to-millennia scale are poorly documented due to lack of relevant data sets. Nevertheless, understanding long-term dynamics is important for explaining present-day biodiversity patterns and placing conservation goals in a historical context. Here, we use recent examples and new perspectives to highlight how environmental DNA (eDNA) is starting to provide a powerful new source of temporal data for research questions that have so far been overlooked, by helping to resolve the ecological dynamics of populations, communities, and ecosystems over hundreds to thousands of years. We give examples of hypotheses that may be addressed by temporal eDNA biodiversity data, discuss possible research directions, and outline related challenges.


Clonazepam, haloperidol, and clonidine in tic disorders.
We reviewed the treatment outcomes of 81 patients with multifocal tic disorders followed in our movement disorders clinic. From the three drugs used, rank orders of effectiveness were haloperidol, clonazepam, and clonidine. Because of the risk of tardive dyskinesia, we suggest first a trial with clonazepam, later combined with clonidine if clonazepam alone is not effective. Haloperidol should be reserved for the most disabling cases, and given only after trials with both clonazepam and clonidine have failed.


Under Construction: One State's Approach to Creating Health Homes for Individuals with Serious Mental Illness.
Changes to the health care market associated with the Patient Protection and Affordable Care Act (ACA) are creating both need and opportunity for states, health plans, and providers to improve quality, outcomes, and satisfaction through better integration of traditionally separate health care delivery systems. Applications of the term "integrated care" vary widely and include, but are not limited to, the integration of care for Medicare-Medicaid dually enrolled beneficiaries, the integration of mental health and substance abuse (also known as behavioral health), and the integration of mental health and substance abuse with medical care, most commonly primary care. In this article, integrated care refers to well-coordinated physical health and behavioral health care. Medicaid Health Homes are emerging as a promising practice, with sixteen states having adopted the Health Home model through approved State Plan Amendments. This article describes one state's journey towards establishing Health Homes with a behavioral health focus. We discuss a partnership model between the relevant state organizations, the contracted providers, and the behavioral health managed care organization responsible for many of the supportive administrative functions. We highlight successes and operational challenges and offer recommendations for future Health Home development efforts.


Effects of cadmium stress on alternative oxidase and photosystem II in three wheat cultivars.
The effects of Cd stress (200 micromol/L, 8 days) on respiration and photosynthesis of three wheat cultivars were investigated: Chuanyu 12 (CY12), Chuanmai 42 (CM42), and Chuanmai 47 (CM47). Fifteen-day-old seedlings were exposed to 200 micromol/L CdCl2 for 4 days and 8 days, respectively. The results indicated that Cd was accumulated largely in roots, but little in leaves of all three cultivars. CY12 accumulated the highest level of Cd in roots and showed the weakest resistance. On the contrary, the other two cultivars, CM42 and CM47, adapted better to Cd stress, and their thiobarbituric acid-reactive substances (TBARS) contents were lower than in CY12, but the chlorophyll contents and water contents were higher than in CY12. Additionally, Cd stress prompted the alternative oxidase (AOX) activity and upregulated the cyanide-resistant respiration in CM42 and CM47 after 8 days; no such induction was observed for CY12. The CO2 assimilation rate, leaf stomatal conductance and chlorophyll fluorescence were inhibited by Cd stress in all cultivars, but more severe in the CY12 cultivar. Western blots indicated that the content of the photosystem II proteins LHCII and D1 decreased in CY12, but did not change in CM42 and CM47. While the content of the mitochondrial AOX protein increased markedly in CM42 and CM47, it did not in CY12. These results suggested that AOX and LHCII could be regarded as indicators of plant's resistance to heavy metals.


[Orthopathy in 19th century Peru: Sebastián Lorente and the Catechism of hygiene].
Orthopathy appeared in Peru in the 19th century in various guises and different spheres that transcended the activities of doctors. Sebastián Lorente, a doctor and educator, promoted hygiene education for schoolchildren through the publication of a Catechism of Hygiene, which went through multiple editions in the second half of the century. The structure and content of the Catechism is linked to European medical traditions such as the miasmatic interpretation of diseases, but also to local traditions like the medical topography of Hipólito Unanue, both of which had a vision of imposing "healthy" behaviors on the population, which assimilated the work of Johann Peter Frank.


Genetic and nutrient modulation of acetyl-CoA levels in Synechocystis for n-butanol production.
There is a strong interest in using photosynthetic cyanobacteria as production hosts for biofuels and chemicals. Recent work has shown the benefit of pathway engineering, enzyme tolerance, and co-factor usage for improving yields of fermentation products. An n-butanol pathway was inserted into a Synechocystis mutant deficient in polyhydroxybutyrate synthesis. We found that nitrogen starvation increased specific butanol productivity up to threefold, but cessation of cell growth limited total n-butanol titers. Metabolite profiling showed that acetyl-CoA increased twofold during nitrogen starvation. Introduction of a phosphoketolase increased acetyl-CoA levels sixfold at nitrogen replete conditions and increased butanol titers from 22 to 37 mg/L at day 8. Flux balance analysis of photoautotrophic metabolism showed that a Calvin-Benson-Bassham-Phosphoketolase pathway had higher theoretical butanol productivity than CBB-Embden-Meyerhof-Parnas and a reduced butanol ATP demand. These results demonstrate that phosphoketolase overexpression and modulation of nitrogen levels are two attractive routes toward increased production of acetyl-CoA derived products in cyanobacteria and could be implemented with complementary metabolic engineering strategies.


Clinical and genetic analysis of a large Dutch family with autosomal dominant vascular retinopathy, migraine and Raynaud's phenomenon.
We describe an extended Dutch family with a new hereditary disorder: autosomal dominant vascular retinopathy, migraine and Raynaud's phenomenon. Information was obtained on 289 family members (151 males, 138 females), of whom 198 were personally interviewed. Retinopathy was found in 20 (6.9%) of the family members, migraine in 65 (22.5%) and Raynaud's phenomenon in 50 (17.3%). A combination of all three symptoms was found in 11 subjects. In a genetic linkage analysis we firstly excluded several candidate loci. Subsequently, 75% of the autosomal genome was excluded in a genome-wide search. The following conclusions were drawn. First, genetic factors are involved in Raynaud's phenomenon. Secondly, the genetic linkage of migraine with vascular retinopathy and Raynaud's phenomenon supports a vascular aetiology of this disorder. Finding the gene for this family may help to elucidate the genetic background of migraine and of vascular disorders in general.


Anatomical analysis of an aye-aye brain (Daubentonia madagascariensis, primates: Prosimii) combining histology, structural magnetic resonance imaging, and diffusion-tensor imaging.
This report presents initial results of a multimodal analysis of tissue volume and microstructure in the brain of an aye-aye (Daubentonia madagascariensis). The left hemisphere of an aye-aye brain was scanned using T2-weighted structural magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) prior to histological processing and staining for Nissl substance and myelinated fibers. The objectives of the experiment were to estimate the volume of gross brain regions for comparison with published data on other prosimians and to validate DTI data on fiber anisotropy with histological measurements of fiber spread. Measurements of brain structure volumes in the specimen are consistent with those reported in the literature: the aye-aye has a very large brain for its body size, a reduced volume of visual structures (V1 and LGN), and an increased volume of the olfactory lobe. This trade-off between visual and olfactory reliance is likely a reflection of the nocturnal extractive foraging behavior practiced by Daubentonia. Additionally, frontal cortex volume is large in the aye-aye, a feature that may also be related to its complex foraging behavior and sensorimotor demands. Analysis of DTI data in the anterior cingulum bundle demonstrates a strong correlation between fiber spread as measured from histological sections and fiber spread as measured from DTI. These results represent the first quantitative comparison of DTI data and fiber-stained histology in the brain.


Disease emergence in multi-host epidemic models.
Most pathogens are capable of infecting multiple hosts. These multiple hosts provide many avenues for the disease to emerge. In this investigation, we formulate and analyse multi-host epidemic models and determine conditions under which the disease can emerge. In particular, SIS and SIR epidemic models are formulated for a pathogen that can infect n different hosts. The basic reproduction number is computed and shown to increase with n, the number of hosts that can be infected. Therefore, the possibility of disease emergence increases with the number of hosts infected. The SIS model for two hosts is studied in detail. Necessary and sufficient conditions are derived for the global stability of an endemic equilibrium. Numerical examples illustrate the dynamics of the two- and three-host epidemic models. The models have applications to hantavirus in rodents and other zoonotic diseases with multiple hosts.


Use of dabigatran vs. warfarin with low-molecular-weight heparin bridging in catheter ablation for atrial fibrillation patients with a low CHADS2 score.
The purpose of the present study was to compare the efficacy and safety of dabigatran and interrupted warfarin with low-molecular-weight heparin bridging in non-valvular atrial fibrillation (AF) catheter ablation. Previously, there has been concerns that bridging therapy increases bleeding events without the benefit of stroke prevention. It has been suggested that bridging therapy should be considered only for patients at high-risk of thrombosis. Nevertheless, bridging therapy in AF patients with a low CHADS2 score may be safe and effective. The authors performed a prospective, observational study that included consecutive 240 patients undergoing AF ablation in P.R. China. A total of 139 patients received 110 mg dabigatran twice daily and 101 patients took dose-adjusted warfarin that had been bridged with low-molecular-weight heparin. The mean patient age was 55.48 years with 72.1% being men and 74.2% having paroxysmal AF. One thromboembolic complication occurred in the dabigatran group compared to none in the warfarin group. Both the groups presented a similar major bleeding rate, total bleeding rate, and bleeding and thromboembolic complications. In patients undergoing AF ablation, the risk of bleeding or thromboembolic complications was similar for both dabigatran and interrupted warfarin with bridging therapy. Bridging therapy appeared to be safe and effective for the low-risk population.


High prevalence of human papillomavirus type 58 in HIV infected men who have sex with men: A preliminary report in Central Italy.
Human papillomavirus (HPV) infection and type-specific prevalence at anal, oral, coronal sulcus, and urethral mucosa in fifty HIV positive men having sex with men (MSM) were evaluated; patients were enrolled in a non-metropolitan area of Central Italy. Clinical and socio-demographic information, drug, and sexual behaviors were obtained for each participant. HPV was detected by PCR from an overall of 200 specimens, and genotyping was performed by both Restriction Fragment Length Polymorphism analysis and sequencing. HPV DNA was found in 60.0% (n = 30) of HIV positive MSM, and prevalence was higher at anal canal (n = 28, 56.0%) compared to all the other anatomical sites (χ(2) test P < 0.01) of coronal sulcus (n = 11, 22.0%), oral (n = 8, 16.0%), and urethral mucosa (n = 5, 10.0%). We found 63.3% (n = 19) of MSM with at least one high-risk genotype, and HPV-58 was more frequently detected (n = 9, 47.4%) respect to HPV-16 (n = 6, 31.6%). This is the first report on HPV detected at four anatomical sites involved in sexual practices in HIV positive MSM. We found an unusual distribution of oncogenic genotypes with an exceeding prevalence of HPV-58 respect to HPV-16. Hence, the recently licensed nonavalent vaccine should be suitable to prevent a larger number of infections caused by potentially emerging high-risk genotypes.


Prevalence of colorectal cancer and survival in patients from the Gampaha District, North Colombo region.
The prevalence and survival of colorectal cancer in Sri Lankans has not been previously reported. We did a retrospective and a prospective survey, in the region of North Colombo, Sri Lanka between 1992 and 2004. The aim was to study cancer burden, sites of colorectal cancer and survival after surgery. The records of 175 patients with colorectal cancer between 1992 and 1997 in the selected region of were analysed retrospectively. A prospective study was performed in 220 new patients with colorectal cancer between 1996 and 2004. Data evaluated were demographics, tumour stage and survival. Between 1992 and 1997 the crude annual incidence of colorectal cancer was 1.9 per 100,000, which increased over the years. The current national crude annual incidence is 3.2 per 100,000 in women and 4.9 in men. Median age at presentation was 60 years with similar prevalence of cancer in men and women. In the entire group, 28% of cancers were in those less than 50 years old. Survival at 2 and 5 years was 69% and 52%. The majority of cancer related deaths were within the first 2 years after surgery. The burden of colorectal cancer in Sri Lanka is on the rise. Up to a third of cancers occur in those under 50 years, and the majority of cancers are in the rectum or rectosigmoid region. Flexible sigmoidoscopy offers a useful screening tool.


Efficacy of cisplatin combined with vinorelbine as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer.
The aim of this study was to assess the therapeutic efficacy of a cisplatin and vinorelbine combination as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer. We retrospectively reviewed the medical records of patients with advanced ovarian cancer who were treated with cisplatin (60 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 8) every 3 weeks between January 2004 and March 2021. Treatment responses, progression-free survival (PFS), and overall survival (OS) were assessed; laboratory data were reviewed to determine toxicity. Thirty-two patients with advanced ovarian cancer were treated with a combination of vinorelbine and cisplatin. The objective response rate (ORR) was 18.8% and the disease control rate was 75.1%. The median PFS was 4.13 months (95% confidence interval [CI], 2.4-5.8 months). The median OS was 56.9 months (95% CI, 50.5-63.7 months). The ORR (42.9% vs 9.1%; P = .035) was higher in the platinum-sensitive group than in the platinum-resistant group. The median PFS tended to be longer in the platinum-sensitive group (5.3 vs 3.8 months; P = .339) and the median OS was significantly longer in the platinum-sensitive group than in the platinum-resistant group (69.6 vs 24 months; P < .001). All patients developed hematological toxicities, with 56% experiencing grade 3 to 4 neutropenia. Two (6.2%) patients developed febrile neutropenia, but no treatment-related death occurred. This combination therapy may be effective in patients with heavily treated advanced ovarian cancer, particularly in platinum-sensitive patients.


Phosphoinositides and synaptic function in NG108-15 neuroblastoma x glioma hybrid cells.
1. The second-messengers system of bradykinin (BK) receptors was examined in NG108-15 neuroblastoma x glioma hybrid cells. 2. An application of BK induced an immediate outward (K+) current and acetylcholine (ACh) release, which are generated through inositol 1,4,5-trisphosphate (InsP3)-dependent Ca2+ ions. 3. Application of phorbol dibutyrate (a protein kinase C activator) produced a voltage-dependent inward current and inhibited another K+ (M)-current. 4. A similar current response has been produced by ACh in NG108-15 cells transfected with rodent muscarinic ACh receptor I and III subtype genes. 5. These results suggest a dual and time-dependent role for these two intracellular messengers in the control of neuronal signalling by BK and ACh.


Characterization of the hydrogen-bond network of water around sucrose and trehalose: Microwave and terahertz spectroscopic study.
Modification of the water hydrogen bond network imposed by disaccharides is known to serve as a bioprotective agent in living organisms, though its comprehensive understanding is still yet to be reached. In this study, aiming to characterize the dynamical slowing down and destructuring effect of disaccharides, we performed broadband dielectric spectroscopy, ranging from 0.5 GHz to 12 THz, of sucrose and trehalose aqueous solutions. The destructuring effect was examined in two ways (the hydrogen bond fragmentation and disordering) and our result showed that both sucrose and trehalose exhibit an obvious destructuring effect with a similar strength, by fragmenting hydrogen bonds and distorting the tetrahedral-like structure of water. This observation strongly supports a chaotropic (structure-breaking) aspect of disaccharides on the water structure. At the same time, hydration water was found to exhibit slower dynamics and a greater reorientational cooperativity than bulk water because of the strengthened hydrogen bonds. These results lead to the conclusion that strong disaccharide-water hydrogen bonds structurally incompatible with native water-water bonds lead to the rigid but destructured hydrogen bond network around disaccharides. Another important finding in this study is that the greater dynamical slowing down of trehalose was found compared with that of sucrose, at variance with the destructuring effect where no solute dependent difference was observed. This discovery suggests that the exceptionally greater bioprotective impact especially of trehalose among disaccharides is mainly associated with the dynamical slowing down (rather than the destructuring effect).


Accurate Gaussian basis sets for atomic and molecular calculations obtained from the generator coordinate method with polynomial discretization.
Accurate Gaussian basis sets for atoms from H to Ba were obtained by means of the generator coordinate Hartree-Fock (GCHF) method based on a polynomial expansion to discretize the Griffin-Wheeler-Hartree-Fock equations (GWHF). The discretization of the GWHF equations in this procedure is based on a mesh of points not equally distributed in contrast with the original GCHF method. The results of atomic Hartree-Fock energies demonstrate the capability of these polynomial expansions in designing compact and accurate basis sets to be used in molecular calculations and the maximum error found when compared to numerical values is only 0.788 mHartree for indium. Some test calculations with the B3LYP exchange-correlation functional for N2, F2, CO, NO, HF, and HCN show that total energies within 1.0 to 2.4 mHartree compared to the cc-pV5Z basis sets are attained with our contracted bases with a much smaller number of polarization functions (2p1d and 2d1f for hydrogen and heavier atoms, respectively). Other molecular calculations performed here are also in very good accordance with experimental and cc-pV5Z results. The most important point to be mentioned here is that our generator coordinate basis sets required only a tiny fraction of the computational time when compared to B3LYP/cc-pV5Z calculations.


Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage.
HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.


Curcumin Inhibits LIN-28A through the Activation of miRNA-98 in the Lung Cancer Cell Line A549.
Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, LIN28A level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro.


Gamma Radiation Chemistry of Polydimethylsiloxane Foam in Radiation-Thermal Environments: Experiments and Simulations.
The γ radiolysis behavior of polydimethylsiloxane (PDMS) in the radiation-thermal environments (dose rate, 0.2 Gy/s) is studied to pinpoint the basic knowledge of the temperature (20-70 °C) effects. The non-monotonous temperature effects on the formation of gas products, paramagnetic species in silica, and cross-linking density are proposed to correlate with the complex chemical reaction mechanisms. Besides, molecular dynamics simulation and theoretical calculation are first performed simultaneously based on the radical chemistry and intricate material composition, making it easier to comprehend and further harness the radiolysis mechanisms and structure deterioration of PDMS. The γ radiation-induced primary gas products and dominant cross-linking phenomena are reproduced by the molecular dynamics simulations with a reactive force field, and the reaction mechanisms and physicochemical interactions among PDMS chains, gas products, reactive radicals, and silica fillers are thoroughly studied at the atomic scale. The thermochemistry of the barrierless radical coupling reactions and reactions with explicit high-barrier transition states is calculated at the M06-2X theoretical level with the 6-311g(d, p) basis set. The barrierless reactions are all exothermal with the heat release of 321-618 kJ/mol, while the potential barriers for reactions with explicit transition states vary between 37 and 229 kJ/mol. The results show that γ radiation-induced radicals are crucial for the ensuing gas formation and cross-linking reactions, especially for the radical coupling reactions. The radical chemistry involved in the radiolytic PDMS is the key to understand and simulate its radiolysis behavior, according to the experimental and simulated results.


Three-dimensional organization of testicular interstitial tissue and lymphatic space in the rat.
Rat testes fixed by vascular perfusion were examined by scanning and transmission electron microscopy. This revealed a complex organization of the interstitial tissue and an extensive "testicular lymphatic space" composed of continuous "peritubular lymphatic sinusoids." No cellular connections exist between the interstitium and the tubules. Each sinusoid completely surrounds an individual seminiferous tubule, and adjacent sinusoids communicate freely through fenestrae in the interstitium. Thus, material must enter the lymph to gain access to the tubules. The sinusoids are delimited by separate endothelial cell layers over the tubules and interstitium. The layer over the interstitium is discontinuous in specific areas according to the geometry of the tubule packing. Interstitial tissue located in the flattened biconcave interstices between two adjacent tubules is consistently covered with endothelial cells, while that located in the open, triangular interstices between three or more tubules consistently lacks an endothelium. Most of the Leydig cells are located in the "open interstitium" and are directly exposed to the lymph. Physiological implications of the "testicular lymphatic space" and additional features of the interstitium are discussed.


Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters.
In this paper is described a synthesis of enantiomerically enriched, configurationally stable organozinc reagents by catalytic enantioselective carbozincation of a vinylboronic ester. This process furnishes enantiomerically enriched α-borylzinc intermediates that are shown to undergo stereospecific reactions, producing enantioenriched secondary boronic ester products. The properties of the intermediate α-borylzinc reagent are probed and the synthetic utility of the products is demonstrated by application to the synthesis of (-)-aphanorphine and (-)-enterolactone.


[Biomechanico-clinical study of gunshot wounds (general problems--II)].
Whenever the surgeon finds himself face to face with a wound (probably this is the only opportunity for a meeting between physician and pathology which seems to be able to leave the "illness" on one side, almost forgotten, as it were), even when immersed in routine, he can hardly help making a number of considerations of a general nature, to which the sentence above in brackets is not entirely extraneous. In practice, we cannot help asking ourselves an apparently simple, almost banal, question: what exactly is trauma? This triggers off a whole series of secondary queries, such as, for instance, what the relationship is between trauma and classical pathology? In the first place, it should be pointed out that "traumatic" pathology is undoubtedly the only instance of pathology in which, as a rule, at least at the outset, one can justifiably talk about the "isolated" role of what can certainly be regarded as an out-of-body factor. If, then, we consider the specifically morphological and pathophysiological aspects of the period subsequent to the traumatic insult, we find ourselves in an even more embarrassing position: we are faced with irreparably devastated organ and body structures, or with a situation which is already on the way to convalescence. One last alternative is that the traumatic insult is merely a memory, a key finding in the case history, a past reality which to all intent and purposes has ceased to exist, and we are faced with extremely complex clinical pictures which we tend to label as complications. A few examples by way of explanation: shock, adult respiratory distress syndrome (ARDS), stress ulcer, acute post-traumatic cholecystitis, haemorrhagic pancreatitis, and problems caused by resolving the hypovolaemia-ischaemia situation and by implementing reperfusion (oxygen radicals). Trauma favours - and surgeons concerned with organ transplants are well aware of this - the only possibility of death which, perhaps with a grain of excessive optimism, we may even accept as fruitful, in that it occurs without all the destructive deterioration involved in the process of dying. The above consideration probably plays a major role in our attitudes of almost fatalistic resignation towards the youthful victims of trauma.(ABSTRACT TRUNCATED AT 400 WORDS)


Slab coupled optical fiber sensor calibration.
This paper presents a method for calibrating slab coupled optical fiber sensors (SCOS). An automated system is presented for selecting the optimal laser wavelength for use in SCOS interrogation. The wavelength calibration technique uses a computer sound card for both the creation of the applied electric field and the signal detection. The method used to determine the ratio between the measured SCOS signal and the applied electric field is also described along with a demonstration of the calibrated SCOS involving measuring the dielectric breakdown of air.


Comparative study of bilateral putamen for patients with severe Parkinson's disease detected by 1H magnetic resonance spectroscopy.
The diagnosis of Parkinson's disease (PD) is challenging because the clinical symptoms overlap with other neurodegenerative diseases. The discovery of reliable biomarkers is highly expected to facilitate clinical diagnosis. Through the analysis of the 1H magnetic resonance spectroscopy (1H-MRS) in the putamen, the purpose of the study was to discuss the possibility of the difference in metabolite concentrations between the left and right putamen as biomarkers for patients with severe PD. We collected 1H-MRS of unilateral or bilateral putamen from 41 patients and used the independent sample t-test and paired t-test to analyze 4 metabolite concentrations, including choline (Cho), total N-acetyl aspartate (tNAA), total creatine (tCr), and combined glutamate and glutamine; Bonferroni correction was used to correct P values for multiple comparisons. We designed 4 controlled experiments as follows: (I) PD patients versus healthy controls (HCs) in the left putamen; (II) PD patients versus HCs in the right putamen; (III) the left putamen versus the right putamen for PD patients; and (IV) the left putamen versus the right putamen for HCs. No statistically significant differences (P>0.05) were detected among 4 metabolites in the ipsilateral and bilateral putamen for the PD and HCs groups, except for tCr in the left putamen (PD 6.426±0.557, HCs 6.026±0.460, P=0.046) for ipsilateral comparisons. In the bilateral putamen of severe PD patients, there was no statistically significant difference in the 4 metabolites. The difference (P<0.05) in tCr in the left putamen might be a potential biomarker to distinguish HCs from severe patients in clinic. This might provide a reference for the clinical diagnosis and acquisition strategy of 1H-MRS in severe PD.


Neutrophil Lymphocyte Ratio: APrognostic Marker in Acute ST Elevation Myocardial Infarction.
To investigate if neutrophil lymphocyte ratio (NLR) predicts in-hospital adverse events and mortality, and shortterm (30-day) mortality in ST-elevated myocardial infarction (STEMI) patients thrombolysed with streptokinase (SK). An observational study. Rawalpindi Institute of Cardiology, from June 2014 till January 2015. The STEMI patients, thrombolysed with SK had blood samples at admission, analysed for complete blood counts and NLR calculated. They were grouped into two, low and high NLR, taking 4.50 as cut-off. Chi square test was used to compare rate of adverse events and death in hospital stay. Mann-Whitney test was used to compare median NLR between patients died and discharged alive. Logistic regression analysis was used to estimate predictive ability of NLR for 30-day mortality. Atotal of 145 (45.3%) patients had complications; 49 (15.3%) died in hospital, and 13 (4.06%) died in 30 days. Patients in high NLR group had higher rate of complications (63.5% vs. 25.5%, p <0.0001) and death (19.2% vs. 11.1%, p=0.046) in hospital than those in low NLR group. Cardiogenic shock (27.5% vs.11.1%, p <0.0001), heart failure (19.2% vs. 7.2%, p=0.002), arrhythmias (18% vs. 6.5%, p <0.0001), reinfarct/angina (9.6% vs.2% p=0.004) occurred more in high NLR group. Median NLR in patients died was higher than those discharged alive (7.46 vs. 4.70, p <0.0001). Regression analysis showed NLR an independent predictor of mortality (OR 1.131 at 95% CI, p = 0.029). Age, serum creatinine, Killip class were other predictors (p=0.002 and p=0.02, respectively). ROC curve showed AUC 0.908 (p <0.0001). Ahigh NLR predicted increased in hospital complication rate, and in-hospital as well as 30-day mortality in STEMI patients thrombolysed with streptokinase.


Medical image quality as a socio-technical phenomenon.
The study aims to interpret image quality in laparoscopic surgery not only as a technical parameter but also as the result of the situation of use. Observational studies of laparoscopy in use, semi-structured and informal interviews with laparoscopists. When medical images are digitized to exploit novel technical possibilities, image quality becomes a paramount issue. Image quality is often discussed exclusively in technical terms, but the socio-technical study of image quality in surgical telemedicine presented in this paper showed that it is definitely more than a purely technical parameter. While the resulting quality of the image was significantly shaped by the persons involved, the concept of "quality" itself was also relative and changing with the situation of use. A given technology does not determine image quality. Rather than focusing only on the technical quality, the attention of designers and decision makers should also be directed to the socio-technical network surrounding the image and its use.


Realizing a Realtime Shared Patient Chart using a Universal Message Forwarding Architecture.
The goal of this paper is to describe the clinical needs and the informational methodology which led to the realization of a realtime shared patient chart. It is an integral part of the communications infrastructure of the Patient Data Management System (PDMS) ICUData which is in routine use at the intensive care unit (ICU) of the Department for Anesthesiology and Intensive Care Medicine at the University Hospital of Giessen, Germany, since February 1999. ICUData utilizes a four tier system architecture consisting of modular clients, message forwarders, application servers and a relational database management system. All layers communicate with health level seven messages. The innovative aspect of this architecture consists of the interposition of a message forwarder layer which allows for instant exchange of patient data between the clients without delays caused by database access. This works even in situations with high workload as in patient monitoring. Therefore a system with many workstations acts a blackboard for patient data allowing shared access under realtime conditions. Realized first as an experimental feature, it has been embraced by the clinical users and served well during the documentation of more than 18000 patient stays.


Evaluation of a self-directed smoking prevention and cessation program.
This study evaluates a youth subject-directed smoking prevention and cessation program titled Breathe Easy! The program was delivered at two sites and a control group was recruited from two additional sites. Surveys were administered prior to the program and either 1 month or 6 months after completion at the exposure sites. The same survey administration procedure was used as the control. After controlling for invalid responses and including only those that completed both surveys, 251 exposure subjects and 159 control subjects remained for analysis. At sites with 1-month follow-up, no significant difference was noted between intervention and control groups. At the sites with 6-month follow-up, prevalence dropped from 18.7% to 8.9%, which is statistically significant, while at the control site prevalence changed from 14.1% to 9.4%, which is not significant. Additional outcomes examined in the exposed group showed trends toward smoking cessation and prevention at higher rates than those of the unexposed group.


[Influence of methylenetetrahydrofolate reductase gene polymorphisms on antidepressant response].
To assess the influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment. Two hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks, among whom 275 were followed up for 8 weeks. Hamilton depression scale 17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects. Single nucleotide polymorphisms (SNPs) of the MTHFR gene were determined using gene chips. Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software. No significant differences in gender, age, year of education, family history, episode times, and antidepressant agents were found between responders and non-responders (all P U+003E 0.05), while the baseline scores of HAMD-17 was significantly different(t=2.891, P=0.004). There was also no significant difference between age, years of education, family history, baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P U+003E 0.05), while proportion of male patients was significantly higher in non-remission group than remission group (t=2.381, P=0.018), and episode times in non-remission group was significantly higher (t=-1.983, P=0.049). Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P U+003E 0.05). On the other hand, haplotype A-C of MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (U+03C7 2=11.39, P=0.0007), male subgroup (U+03C7 2=8.767, P=0.003) and serotonin noradrenaline reuptake inhibitors (SNRIs) subgroup (U+03C7 2=10.51, P=0.001). Particular haplotype of MTHFR gene may be related with antidepressant effect, in which the haplotype (rs1801131, rs1801133) A-C type may be associated with better antidepressant efficacy, particularly in males and patients receiving SNRIs drugs.


A rare case of racemose neurocysticercosis and its complications. Case report.
Neurocysticercosis is a central nervous system infection caused by the pork tapeworm Taenia solium. The disease is endemic in Central and South America, Asia and Africa. Racemose neurocysticercosis refers to cysts in the subarachnoid space and is characterized by proliferative lobulated cysts without a scolex. We report a case of a 43-year-old woman with an eight-month history of headaches, ataxia and loss of vision. CT and MRI showed an intraventricular cyst, causing entrapment of Monro foramina and hydrocephalus, smaller cysts at subarachnoid space in temporal lobes, Sylvian fissures, supra-selar and perimesencephalic cisterns, and an intra-orbital cyst. Additionally, there were acute ischemic vascular lesions on the left thalamus and corpus callosum splenium and subacute ischemic lesions of both occipital lobes. The diagnosis of racemose cysticercosis was made after biopsy and drainage of the intraventricular cyst. It is important to recognize neurocysticercosis as a differential diagnosis in intra-cranial cysts, not only intraparenchymal cysts.


Psychological treatments for anorexia nervosa: a review of published studies and promising new directions.
To review the existing literature on the psychological treatments for anorexia nervosa (AN), especially randomized clinical trials that have been published. In addition, new psychological approaches will be described. An extensive literature review was conducted to identify the psychological treatment trials on AN that have been published over the past 3 decades. Fewer than 20 controlled clinical trials were identified, evaluating the effectiveness of various types of psychotherapy in AN treatment. Evidence for the effectiveness of these interventions, with the exception of family therapy for younger patients with shorter duration of illness, remains questionable. Promising new approaches include motivational enhancement therapy and psychotherapies aimed at relapse prevention. Currently, there is little empirical evidence on which to base treatment decisions regarding the psychological treatments for AN. There is a desperate need for further research in this area, especially examining relapse prevention and motivational enhancement strategies for AN.


CD4/CD8 Ratio in Mediastinal Lymph Nodes Involved by Sarcoidosis: Analysis of Flow Cytometry Data Obtained by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration.
Despite mixed results in the literature, some clinicians continue to consider an elevated CD4/CD8 ratio in bronchoalveolar lavage (BAL) fluid to be supportive of a diagnosis of sarcoidosis. However, the CD4/CD8 ratio in mediastinal lymph nodes involved by sarcoidosis has not been extensively studied. The primary aim of this study was to evaluate the utility of the CD4/CD8 ratio in mediastinal lymph node aspirates obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosing sarcoidosis. Our archives were searched for EBUS-TBNAs in which mediastinal lymph node aspirates had been submitted for flow cytometry (n=160). Clinical and pathologic findings in these cases were reviewed retrospectively. Cases were included in the study if they had (1) a clinical diagnosis of sarcoidosis supported by cytopathologic confirmation of non-necrotizing granulomas in EBUS-TBNA-derived lymph node aspirates (23 cases), or (2) a pathologically confirmed non-neoplastic diagnosis other than sarcoidosis (7 cases). Cases that did not fulfil these criteria were excluded (130 cases). The CD4/CD8 ratios in mediastinal lymph nodes and BAL fluid were compared. The CD4/CD8 ratio was elevated in mediastinal lymph nodes in 12/23 (52%) cases of sarcoidosis and 3/7 (43%) pathologically confirmed nonsarcoid cases. BAL fluid had been concurrently submitted for flow cytometry in 20/23 cases of sarcoidosis and 5/7 nonsarcoid cases. CD4/CD8 was elevated in BAL fluid in 9/20 (45%) cases of sarcoidosis and 2/5 (40%) nonsarcoid cases. As in BAL fluid, the CD4/CD8 ratio in mediastinal lymph nodes involved by sarcoid granulomas is highly variable and does not reliably confirm or exclude sarcoidosis.


[Morphological changes in leukocytes].
The major inherited and acquired morphologic changes in the peripheral blood leukocytes are described. The diseases associated with such changes are enumerated and the author's observations are presented of a phenomenon of selected hyposegmentation of eosinophilic granulocyte nuclei and of some morphologic changes in these nuclei, that appear to be explained by their deranged maturation.


[Changes in the guanylate cyclase activity of human thrombocytes during ADP-inducible aggregation].
Activity of guanylate cyclase (GC) and its capacity for sodium nitroprusside (SNP) activation were determined in platelets with different state of aggregation. The development of ADP-induced reversible aggregation was accompanied by a decrease in the basal GC activity and by an increase in the SNP activation of GC. It was shown that elevation of GC sensitivity to SNP during the aggregation might be due to the decrease in the state of enzyme blood deficiency. Preincubation of platelets with SNP before ADP adding markedly diminished or even prevented aggregation, depending on SNP concentration. GC parameters in platelets with prevented aggregation were just the same as in control. It is suggested that the regulatory role of cGMP system in platelet aggregation may be seen in the increase in GC sensitivity to endogenous activator, presumably to NO.


Medical student attitudes and perceptions of psychedelic-assisted therapies.
Although certain psychedelic agents may soon gain federal approval for use in treating specific psychiatric conditions, the utilization of such therapies in clinical practice will depend largely on the attitudes of healthcare providers. Therefore, this study assesses the current attitudes, knowledge, exposure, and acceptance of psychedelics and psychedelic-assisted therapies amongst medical students. In fall semester of 2022, surveys were emailed to 580 medical students attending medical institutions in the state of Nevada in the United States. Utilizing knowledge and attitude items from previously published studies, the survey collected demographic data and assessed student attitudes with five-point Likert-scale variables. Data was analyzed using summary statistics and Kruskal-Wallis tests for differences in mean survey scores (i.e., attitudes towards psychedelics) based on demographic factors. 132 medical students participated in the survey (22.7% response rate). Medical students demonstrated overall positive attitudes towards psychedelics, lack of knowledge regarding psychedelics, and uncertainty towards neurocognitive risks of psychedelics. Overall, 78.6% of students agreed that psychedelics have therapeutic potential, while 95.2% agreed that psychedelics deserves further research in assessing this potential. Additionally, there was no statistically significant effect of demographic variables, including age, sex, and level of training, on attitudes. Although students are overall curious and optimistic about psychedelics, they demonstrate a lack of knowledge regarding recent research efforts. As the field of psychiatry prepares to implement psychedelics and psychedelic-assisted therapies, education and awareness of such agents should be initiated early on in medical clinical training.


3-[[3-(Triethoxysilyl)propyl]amino]propane-1-sulfonic acid-poly(vinyl alcohol) cross-linked zwitterionic polymer electrolyte membranes for direct methanol fuel cell applications.
Recently, organic-inorganic nanocomposite zwitterionic polymer electrolyte membranes (PEMs) have attracted remarkable interest for application to the direct methanol fuel cell (DMFC) operated at intermediate temperature (100-200 degrees C). In this paper, we report the synthesis of an organic-inorganic hybrid zwitterionomer silica precursor with ammonium and sulfonic acid functionality by the ring-opening of 3-propanesultone under mild heating conditions and the preparation procedure of a proton-conductive and stable organic-inorganic zwitterion-poly(vinyl alcohol) (PVA) cross-linked PEM by sol-gel in aqueous media. Developed PEMs were extensively characterized by studying their physicochemical and electrochemical properties under DMFC operating conditions. These membranes were designed to possess all of the required properties of a proton-conductive membrane, namely, reasonable swelling, good mechanical, dimensional, and oxidative strength, flexibility, and low methanol permeability along with reasonable proton conductivity (4.85 x 10(-2) S cm(-1)) due to zwitterionic functionality. Moreover, from the selectivity parameter among all developed membranes, ZI-70 [zwitterionomer membrane with 70 wt % of PVA of 3-[[3-(triethoxysilyl)propyl]amino]propane-1-sulfonic acid in the membrane matrix], exhibited the best results in comparison to the Nafion117 membrane for DMFC applications.


Differential regulation of fibronectin synthesis in three different types of corneal cells.
The production of fibronectin (FN) and its response to serum or epidermal growth factor (EGF) were investigated in three different types of rabbit corneal cells cultured in vitro. The corneal epithelial cells, stromal fibroblasts (keratocytes) and endothelial cells were separately cultured in different media: basic medium containing minimal serum (0.5%), basic medium with supplementary serum at a final concentration of 10% and basic medium with 100 ng/ml EGF, respectively. FN production by each type of cell was examined either by the immunofluorescent staining method or by the metabolic labeling method followed by immunoprecipitation of FN in the culture medium. Each type of corneal cell produced and secreted FN. FN secretion into the culture medium by keratocytes and by endothelial cells was enhanced by the addition of EGF. However, FN secretion by epithelial cells was lowered by the additional serum or EGF. Furthermore, when the epithelial cells were cultured in the basic medium, DNA synthesis was low but FN secretion was high. These results suggest that the control mechanism of FN production differs between epithelial cells and keratocytes or endothelial cells.


[Effect of critical shoulder angle on deltoid muscle strength reduction in patients with rotator cuff tears].
To investigate the synergistic interaction between the deltoid muscle and the rotator cuff muscle group in patients with rotator cuff tears (RCT), as well as the impact of the critical shoulder angle (CSA) on deltoid muscle strength. A retrospective analysis was conducted on clinical data from 42 RCT patients who met the selection criteria and were treated between March 2022 and March 2023. There were 13 males and 29 females, with an age range of 42-77 years (mean, 60.5 years). Preoperative visual analogue scale (VAS) score was 6.0±1.6. CSA measurements were obtained from standard anteroposterior X-ray films before operation, and patients were divided into two groups based on CSA measurements: CSA>35° group (group A) and CSA≤35° group (group B). Handheld dynamometry was used to measure the muscle strength of various muscle group in the shoulder (including the supraspinatus, infraspinatus, subscapularis, and anterior, middle, and posterior bundles of the deltoid). The muscle strength of the unaffected side was compared to the affected side, and muscle imbalance indices were calculated. Muscle imbalance indices between male and female patients, dominant and non-dominant sides, and groups A and B were compared. Pearson correlation analysis was used to examine the relationship between muscle imbalance indices and CSA as well as VAS scores. Muscle strength in all muscle groups on the affected side was significantly lower than on the unaffected side ( P<0.05). The muscle imbalance indices for the supraspinatus, subscapularis, infraspinatus, and anterior, middle, and posterior bundles of the deltoid were 14.8%±24.4%, 5.9%±9.7%, 7.2% (0, 9.1%), 17.2% (5.9%, 26.9%), 8.3%±21.3%, and 10.2% (2.8%, 15.4%), respectively. The muscle imbalance indices of the anterior bundle of the deltoid, supraspinatus, and infraspinatus were significantly lower in male patients compared to female patients ( P<0.05); however, there was no significant difference in muscle imbalance indices among other muscle groups between male and female patients or between the dominant and non-dominant sides ( P>0.05). There was a positive correlation between the muscle imbalance indices of infraspinatus and VAS score ( P<0.05), and a positive correlation between CSA and the muscle imbalance indices of middle bundle of deltoid ( P<0.05). There was no correlation between the muscle imbalance indices of other muscle groups and VAS score or CSA ( P>0.05). Preoperative CSA ranged from 17.6° to 39.4°, with a mean of 31.1°. There were 9 cases in group A and 33 cases in group B. The muscle imbalance indices of the anterior bundle of the deltoid was significantly lower in group A compared to group B ( P<0.05), while there was no significant difference in muscle imbalance indices among other muscle groups between group A and group B ( P>0.05). Patients with RCT have a phenomenon of deltoid muscle strength reduction, which is more pronounced in the population with a larger CSA.


Interplay between chronic hepatitis B and atherosclerosis: Innovative perspectives and theories.
Elaboration of carotid atherosclerosis in the setting of hepatitis B virus (HBV) infection should emphasize the significance of extrahepatic manifestations of the infection pathogenesis. Diverse processes comprise the pathoevolution of HBV infection, rendering it a multi-systemic disease in its essence. Our work not only exemplified atherosclerosis as an often-underestimated contributor to the severity of HBV infection but has also highlighted the bidirectional relationship between the two. Therefore, it is suggested that HBV-induced inflammation is one of the root causes of atherosclerosis, which in turn has a consequent effect on the severity of the chronic infection disease state, creating a vicious cycle. Additionally, we coupled prior data with the current concepts of HBV infection to postulate intriguing perspectives and theories.


Joseph Godwin Greenfield: The father of neuropathology (1884-1958).
The systematic study of neuropathology was initiated by Godwin Greenfield in the early part of the 20(th) century. He worked at the National Hospital, Queen Square, London for the major period of his life and worked on various subjects like cerebrospinal fluid, intracranial tumours, cerebellar ataxias, dystrophia myotonica, disseminated sclerosis, subacute combined degeneration of the spinal cord, and the like. After his retirement he visited the National Institute of Neurological Diseases and Blindness in Bethesda, Maryland, USA, from time to time and there he died suddenly from myocardial infarction.


Surfactant treatment in experimental hyaline membrane disease.
Premature newborn rabbits obtained by hysterotomy on day 27 of gestation were ventilated artificially under standardized conditions, serving as experimental model of neonatal hyaline membrane disease. Natural surfactant with a phospholipid concentration of approximately 8 mg/ml was administered as 50-microliter doses after 10 min of ventilation and at subsequent 30-min intervals. Initial values for lung-thorax compliance were significantly improved following two doses of surfactant, whereas compliance levels of non-treated littermates remained unchanged. Treatment with surfactant resulted in increased alveolar air expansion. Bronchiolar epithelial lesions were present in both surfactant-treated animals and controls, but the severity of these lesions was clearly reduced after surfactant treatment. We conclude that surfactant substitution is an effective treatment in experimental hyaline membrane disease, even when given after an initial period of artificial ventilation.


Preferential Adsorption of l-Histidine onto DOPC/Sphingomyelin/3β-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol Liposomes in the Presence of Chiral Organic Acids.
We investigated the effect of organic acids such as mandelic acid (MA) and tartaric acid (TA) on the adsorption behavior of both histidine (His) and propranolol (PPL) onto liposomes. A cationic and heterogeneous liposome prepared using 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/sphingomyelin (SM)/3β-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Ch) in a ratio of (4/3/3) showed the highest adsorption efficiency of MA and TA independent of chirality, while neutral liposome DOPC/SM/cholesterol = (4/3/3) showed low efficiency. As expected, electrostatic interactions were dominant in MA or TA adsorption onto DOPC/SM/DC-Ch = (4/3/3) liposomes, suggesting that organic acids had adsorbed onto SM/DC-Ch-enriched domains. The adsorption behaviors of organic acids onto DOPC/SM/DC-Ch = (4/3/3) were governed by Langmuir adsorption isotherms. For adsorption, the membrane polarities slightly decreased (i.e., membrane surface was hydrophilic), but no alterations in membrane fluidity were observed. In the presence of organic acids that had been preincubated with DOPC/SM/DC-Ch = (4/3/3), the adsorption of l- and d-His onto those liposomes was examined. Preferential l-His adsorption was dramatically prevented only in the presence of l-MA, suggesting that the adsorption sites for l-His and l-MA on DOPC/SM/DC-Ch = (4/3/3) liposomes are competitive, while those for l-His and d-MA, l-TA, and d-TA are isolated.


Calcium channel functions in pain processing.
Voltage-gated calcium channels (VGCC) play obligatory physiological roles, including modulation of neuronal: functions, synaptic plasticity, neurotransmitter release and gene transcription. Dysregulation and maladaptive changes in VGCC expression and activities may occur in the sensory pathway under various pathological conditions that could contribute to the development of pain. In this review, we summarized the most recent findings on the regulation of VGCC expression and physiological functions in the sensory pathway, and in dysregulation and maladaptive changes of VGCC under pain-inducing conditions. The implications of: these changes in understanding the mechanisms of pain transduction and in new drug design are also discussed.


What Happens after a Diagnosis of High-Risk Breast Lesion at Stereotactic Vacuum-assisted Biopsy? An Observational Study of Postdiagnosis Management and Imaging Adherence.
Purpose To assess adherence with annual or biennial screening mammography after a diagnosis of high-risk lesion(s) at stereotactic biopsy with or without surgical excision and to identify clinical factors that may affect screening adherence after a high-risk diagnosis. Materials and Methods This institutional review board-approved HIPAA-compliant retrospective study included 208 patients who underwent stereotactic biopsy between January 2012 and December 2014 that revealed a high-risk lesion. Whether the patient underwent surgical excision and/or follow-up mammography was documented. Adherence of these women to a protocol of subsequent mammography within 1 year (9-18 months) or within 2 years (9-30 months) was compared with that of 45 508 women with normal screening mammograms who were imaged during the same time period at the same institution. Possible factors relevant to postdiagnosis management and screening adherence were assessed. Consultation with a breast surgeon was identified by reviewing clinical notes. Uptake of pharmacologic chemoprevention following diagnosis (patient decision to take chemopreventive medications) was assessed. The Fisher exact test was used to compare annual or biennial screening adherence rates. Binary logistic regression was used to identify factors predictive of whether women returned for screening within selected time frames. Results In total, 913 (1.3%) of 67 874 women were given a recommendation to undergo stereotactic biopsy, resulting in diagnosis of 208 (22.8%) of 913 high-risk lesions. Excluding those with a prior personal history of breast cancer or upgrade to cancer at surgery, 124 (66.7%) of 186 women underwent surgery and 62 (33.3%) did not. Overall post-high-risk diagnosis adherence to annual or biennial mammography was similar to that in control subjects (annual, 56.4% vs 50.8%, P = .160; biennial, 62.0% vs 60.1%, P = .630). Adherence was significantly better in the surgical group than in the nonsurgical group for annual mammography (70.0% vs 32.0%; odds ratio [OR] = 5.0; 95% confidence interval [CI]: 2.4, 10.1; P < .001) and for biennial mammography (74.3% vs 40.0%; OR = 4.3; 95% CI: 2.1, 8.8; P < .001). Among the patients in the nonsurgical group, those adherent to annual or biennial mammography were significantly more likely to have seen a breast surgeon than the nonadherent women (annual, 77.3% vs 35.7%, P = .005; biennial, 67.9% vs 36.4%, P = .045). All patients receiving chemopreventive agents underwent a surgical consultation (100%; n = 21). Conclusion Although diagnosis of a high-risk lesion at stereotactic breast biopsy did not compromise overall adherence to subsequent mammographic screening, patients without surgical excision, particularly those who did not undergo a surgical consultation, had significantly lower imaging adherence and chemoprevention uptake as compared with their counterparts who underwent surgery, suggesting that specialist care may be important in optimizing management. © RSNA, 2018.


Icterogenic hepatocellular carcinoma and polygonal cell carcinoma with fibrous stroma (fibrolamellar hepatocarcinoma).
Hepatocellular carcinoma (HCC) associated with obstructive jaundice by direct invasion or migration of tumor tissue into the biliary system has been described as icterogenic hepatocellular carcinoma (IHCC) or icteric type hepatoma. Fifty-eight such cases have been reported in literature since 1947. Curative treatment and prognosis depend directly on early appearance of icterus and its correct interpretation. Recently, attention has been paid to polygonal cell carcinoma with fibrous stroma (PCFS) as a well differentiated, low grade and transient type of HCC, probably distinguishable from classic HCC by etiological and epidemiological features. The combination of IHCC and PCFS is very rare; to our knowledge only one such case has been reported yet. We had the opportunity to observe and treat such a case, which will be reported in this article and will be compared with cases described in the literature.


Human monoclonal IgM with autoantibody activity against intermediate filaments.
Monoclonal IgMs from two patients with Waldenström macroglobulinemia were found to react with intermediate filaments. This was shown by (a) immunostaining of various tissues and cultured cells and (b) immunological characterization of the reactive antigen after blotting of polypeptides separated from total cell extracts by gel electrophoresis or purified intermediate filaments on nitrocellulose sheets. One monoclonal IgM had an activity directed only against vimentin, whereas the other reacted with four different classes of intermediate filaments--vimentin, desmin, glial fibrillary protein, and keratins. All of the reactivity of the latter IgM was absorbed by purified vimentin, suggesting that different classes of proteins of intermediate filaments share common antigenic determinant(s). The significance of such autoantibody activity of human monoclonal IgM is discussed in the light of the startling frequency of IgM anti-intermediate filaments antibodies in various diseases.


Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors.
Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades.


Chronic subdural hematoma of the neonate: report of two cases and literature review.
We report the cases of 2 infants who were born with macrocephaly and bulging fontanelles and were subsequently found to have chronic subdural hematomas on imaging studies. The etiology of 1 infant was likely due to an inherent coagulopathy, while no etiology could be found for the other. The subdural hematomas were managed by craniotomy in 1 infant and serial subdural taps in the other. There are currently only 8 other case reports of chronic subdural hematoma of the neonate in the literature. Our cases and a brief review of the literature are presented.


Ectopic Expression of Retrotransposon-Derived PEG11/RTL1 Contributes to the Callipyge Muscular Hypertrophy.
The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous +Mat/CLPGPat animals receiving the CLPG mutation from their father express the phenotype. +Mat/CLPGPat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep.


Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development.
We identified homozygous truncating mutations in HOXA1 in three genetically isolated human populations. The resulting phenotype includes horizontal gaze abnormalities, deafness, facial weakness, hypoventilation, vascular malformations of the internal carotid arteries and cardiac outflow tract, mental retardation and autism spectrum disorder. This is the first report to our knowledge of viable homozygous truncating mutations in any human HOX gene and of a mendelian disorder resulting from mutations in a human HOX gene critical for development of the central nervous system.


Diversity of capsular polysaccharide synthesis gene clusters in Streptococcus pneumoniae.
Streptococcus pneumoniae comprises 90 serotypes, each one having its own specific polysaccharide capsule. In order to explore the diversity of capsular polysaccharide synthesis (cps) gene clusters in S. pneumoniae, we performed cross-hybridizations between the 12 cps genes of S. pneumoniae serotype 14 and chromosomal DNA of 26 strains comprising 26 different capsule types. Large variations in the hybridization patterns were observed. The genes cps14A to cps14D are conserved in most serotypes. Sequences homologous to cps14I to cps14L were only observed in the four types of serogroup 15, which all have a capsule structure similar to that of type 14. By using a cps14E knock-out construct, cpsE mutants of the pneumococcal types 9N, 13, and 15B were obtained. These mutants were unencapsulated and showed reduced glycosyltransferase activity, indicating that the pneumococcal types 9N, 13, and 15B express a glucosyl-1-phosphate transferase which is homologous to Cps14E. Glycosyltransferase assays showed that among 21 pneumococcal types which contain glucose in the core of their capsule polysaccharide, 19 types express glucosyl-1-phosphate transferase activity. However, not all of these types hybridized strongly with Cps14E, the type 14 glucosyl-1-phosphate transferase gene. Thus, pneumococci possess glucosyltransferase genes distinct from cps14E, but encoding enzymes with identical activity. All serotypes which synthesized lipid-linked lactose intermediates in glycosyltransferase activity assays (type 11B, 13, 15F, 15A, 15B, 15C) hybridized with cps14G. This gene encodes a galactosyltransferase which catalyzes the addition of 1,4-linked beta-galactose to lipid-linked glucose. The cps14G homologues in type 11B, 13, 15F, 15A, 15B, and 15C may encode a similar beta-galactosyltransferase activity as cps14G in type 14.


Fall experience and cognitive function in middle aged and elderly population.
This study estimates the association between the fall experience in the last 2 years and cognitive function and further evaluate the differences in this association between men and women and across different age groups. Data from the Korean Longitudinal Study of Ageing from 2006 to 2016 was used and 9279 research samples were included at baseline in 2006. To analyze the association between fall experience for the last 2 years and cognitive function, generalized estimating equation model and chi-square test were used. After adjusting for all confounders, those with fall experience were significantly associated with cognitive decline. With non-fall experience as reference: fall experience, B = -0.013 (P = .017). In the 64 years or less group, fall experience was significantly associated with cognitive decline (P-value: 0.006) to those with non-fall experience. In male group, with non-fall experience as reference: fall experience, B = -0.017 (P = .041). Fall experience in the last 2 years is associated with cognitive decline, especially in those 64 years or less and male group. Therefore, self-reported screening for fall experience might aid population-based prevention strategies for cognitive decline, especially in 64 years or less and male.


Atypical strains of Candida albicans recovered from AIDS patients.
By using multilocus enzyme electrophoresis (MLEE) we have analyzed the genetic diversity encountered among chlamydospore-positive Candida albicans strains. While the type II strains of the former C. stellatoidea were genetically indistinguishable from those of C. albicans, type I strains constituted a distinct subgroup compared with C. albicans strains. Nevertheless, all these strains remained genetically very closely related compared with other species of Candida (e.g. C. tropicalis, C. krusei and C. glabrata). These results corroborate the synonymy between C. stellatoidea and C. albicans. Chlamydospore-positive C. albicans strains with atypical sugar assimilation patterns displayed a great genetic divergence from the cluster constituted by C. albicans and the strains of the former C. stellatoidea. However, these atypical strains were more closely related to C. albicans than they were to C. tropicalis, C. krusei or C. glabrata. These strains represent a genetically entity distinct from the typical C. albicans strains used in this study. The data also support the view that the atypical strains described here belong to the same genetic group as atypical C. albicans strains previously described by others.


Limits to the experimental detection of nonlinear synchrony.
Chaos synchronization is often characterized by the existence of a continuous function between the states of the components. However, in coupled systems without inherent symmetries, the synchronization set can be extremely complicated. We describe and illustrate three typical complications that can arise, and we discuss how existing methods for detecting synchronization will be hampered by the presence of these features.


Draft Genome Sequence of the Yeast Kodamaea ohmeri, a Symbiont of the Small Hive Beetle.
Kodamaea ohmeri is a symbiont of the small hive beetle (SHB), which is a scavenger of honey bee colonies. The SHB causes absconding of the economically important honey bee (Apis mellifera) and deposits K. ohmeri in the honeycomb. We describe long-read sequencing and further analyses of the K. ohmeri genome.