Deregulation of estrogen induced telomerase activity in tamoxifen-resistant breast cancer cells.
Telomerase, a ribonucleoprotein enzyme that functions as a reverse transcriptase, is detected exclusively in immortal cells such as germ cells, stem cells and cancer cells. Telomerase activity is present in almost all human cancers. Telomerase activation is considered to be essential to maintain the integrity of the replicating tumor cell and to establish immortality. Based on this concept antiestrogen should initially regulate estrogen-stimulated telomerase but the enzyme would be expected to be constitutive in tamoxifen-resistant tumor cells. We have studied the estrogen regulation of telomerase in T47D:A18 breast cancer cells with a TRAPEZE Telomerase detection kit. Estradiol significantly increased telomerase activity after a 2-day treatment. Telomerase activity induced by estradiol was up to 10-fold higher within 4 days. Antiestrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780 were inactive alone and significantly blocked estradiol-stimulated increase in telomerase. These effects were correlated with changes in cell replications and changes in the cell cycle. In contrast, 4-OHT resistant T47D:A18 cells (T47D:A18/4-OHT, cultured in 1 microM 4-OHT for 6 months) grew spontaneously and had no changes in the cell cycle with estrogen treatment. The estrogen receptor (ERalpha) was present and still regulated at an estrogen responsive luciferase reporter gene with estrogen despite the fact that progesterone receptor was not increased in response to estradiol in T47D:A18/4-OHT cells. However, telomerase activity was increased about 40-fold in T47D:A18/4-OHT cells and this was not regulated by ICI 182,780. We conclude that the differential regulation of telomerase gene might be an important transition for tamoxifen resistance in T47D:A18 breast cancer cells.


[Quality of life more than five years after breast cancer--secondary publication].
In this national survey, long-term breast cancer survivors (BCS) (n = 1,316) reported quality of life comparable to data from the general Danish female population, but a significantly higher prevalence of chronic pain (42% versus 32%). Paraesthesia, phantom sensation, allodynia, and swelling of arm/shoulder were also reported, and every fifth woman felt that these sequelae limited her daily activities. Health care utilization indicated chronic morbidity. Relatively young age, short education, and former radiotherapy were risk factors for issues such as pain.


Re-repair of the failed mitral valve: insights into aetiology and surgical management.
Mitral valve (MV) repair is the gold standard for treatment of degenerative mitral regurgitation. A variety of surgical techniques allow surgeons to achieve a high rate of MV repair even with MV diseases of other aetiologies. However, a certain number of repairs fail over time. The aim of this study was to review our single-centre experience of MV re-repair and analyse the mode of repair failure, re-repair safety and efficiency in relation to the initial aetiology. Between 1997 and 2015, 91 patients underwent redo MV re-repair. The first MV repair was performed in our institution in 59% of cases. Follow-up information was available for 93% of our patients. The median follow-up was 56 months. The initial aetiology was degenerative disease in 40 (44%) patients, rheumatic disease in 25 (27.5%), endocarditis in 10 (11%), ischaemic in 6 (7%), severe mitral annulus calcification in 5 (5.5%), congenital disease in 4 (4%) and unknown in 1 (1%). The mean age was 58 ± 15 years. The median delay between the 1st and 2nd repair was 49 months with 6 early re-repairs. Re-repair was urgent or emergent in 19% of cases; indications for surgery were mitral regurgitation in 48%, stenosis in 19%, endocarditis in 19%, mitral disease in 11%, ring thrombosis in 2% and systolic anterior motion in 1%. The main mechanisms of failure included technical error (30%), progression of disease (35%), new disease (29%) and unknown (6%.) Re-repair was performed through a median sternotomy in 96% of cases, and 34% of patients had concomitant procedures. Eight (9%) postoperative deaths (4 of mitral annulus calcification, 2 of endocarditis, 1 of degenerative disease, 1 of ischaemia) and 5 (6%) early failures occurred (3 of rheumatic disease, 1 of degenerative disease, 1 of a congenital condition), requiring MV replacement in 4 and new repair in 1. Overall survival at 5 and 10 years was 76% and 57%, 83% and 49% in patients with degenerative diseases and 95% and 95% in patients with rheumatic disease. Overall freedom from reoperation at 5 and 10 years was 82% and 61%, 94% and 87% with degenerative disease and 60% and 45% with rheumatic disease. MV re-repair is feasible and has good mid-term results in patients with degenerative MV disease. Rheumatic MV disease is associated with a certain risk of failure over time; nevertheless, these patients show excellent survival after re-repair.


Vasodilatory effect of ghrelin, an endogenous peptide from the stomach.
Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, which is identified as an endogenous ligand for GH secretagogues receptor. Although both ghrelin and its specific receptor are expressed in blood vessels, the cardiovascular effects of ghrelin remain unknown. To clarify whether ghrelin has a vasodilatory effect in humans, the response of forearm blood flow (FBF) to intra-arterial infusion of ghrelin was examined in eight healthy volunteers using a plethysmograph. In addition, hormonal responses to ghrelin were studied. Ghrelin increased FBF in a dose-dependent manner. Pretreatment with NG-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor, did not inhibit the FBF response to ghrelin, although l-NMMA significantly inhibited GH release. Serum insulin-like growth factor-I (IGF-I) level was not altered by ghrelin administration. Plasma cyclic guanosine 3', 5'-monophosphate level, a second messenger of nitric oxide, was also not altered. These results suggest that ghrelin has vasodilatory effects possibly through GH/IGF-I/nitric oxide-independent mechanisms.


Covert preparation of a manual response in a 'go'/'no-go' saccadic task is driven by execution of the eye movement and not by visual stimulus occurrence.
It has been recently demonstrated that visually guided saccades are linked to changes in muscle excitability in the relaxed upper limb, which are compatible with a covert motor plan encoding a hand movement toward the gaze target. In this study we investigated whether these excitability changes are time locked to the visual stimulus, as predicted by influential attention models, or are strictly dependent on saccade execution. Single-pulse transcranial magnetic stimulation was applied to the motor cortex at eight different time delays during a 'go'/'no-go' task, which involved overt or covert orienting of attention. By analyzing the time course of excitability in three hand muscles, synchronized with the onset of either the attentional cue or the eye movement, we demonstrated that side- and muscle-specific excitability changes were strictly time locked to the saccadic response and were not correlated to the onset of the visual attentive stimulus. Furthermore, muscle excitability changes were absent following a covert shift of attention. We conclude that a sub-threshold manual motor plan is automatically activated by the saccade decision-making process, as part of a covert eye-hand coordination program. We found no evidence for a representation of spatial attention within the upper limb motor map.


Body image and weight reduction attempts among adolescent girls involved in physical activity.
The aim of the current study was to examine associations between adolescent girls' body image and the character of engagement in physical activity in a representative sample of Kaunas high school girls. A total of 405 girls (mean age 16.9+/-0.4) filled in a self-constructed questionnaire (reliability 90.3%), aimed at assessing the engagement in physical activity and weight related body image. Most kinds of sports emphasizing body image such as fitness, dancing, gymnastics were most popular among the irregular participants (82.7%), and among regular participant, too (62.7%). The main reason to engage in physical activity was to improve the body image (45.2%), while the health improvement motive was left out in the second place (33.6%). Satisfaction with the body shape and the overall appearance strongly depended on body mass index (BMI, kg/m2), but not on the participation or the character of participation in physical activity. Irregular participants showed more attempts to reduce weight compared to regular exercisers and nonparticipants, while both groups participating in sport reported healthier ways of weight reduction practice. Satisfaction with body shape and overall appearance strongly depends on body mass index, but not on the participation in physical activity. Irregular engagement in physical activity could be an indicator of more frequent attempts to reduce body weight among adolescent girls.


Primary relationship scripts among lower-income, African American young adults.
Research on romantic relationships among lower income, African American young adults has mostly focused on problem behaviors, and has infrequently documented nonpathological relationship processes that are widely studied among middle-class college students, their wealthier and largely European American counterparts [Journal of Black Studies 39 (2009) 570]. To identify nonpathological cultural concepts related to heterosexual romantic relationships, we interviewed 144 low to low-mid income, African American young adults aged 19-22 from the San Francisco Bay Area, CA, metropolitan Chicago, IL, and Greater Birmingham, AL. We identified 12 gender-shared scripts related to the romantic relationship in areas of (1) defining the relationship, (2) processes of joining, (3) maintaining balance, and (4) modulating conflict. Understanding romantic relationship scripts is important as successful romantic relationships are associated with improved mental and physical health among lower income individuals as compared with individuals without romantic partners [Social Science & Medicine 52 (2001) 1501].


Relationship between core histone acetylation and histone H1(0) gene activity.
In this study we show a striking correlation between histone H1(0) gene expression and histone acetylation. Trichostatin A, a highly specific inhibitor of histone deacetylase, efficiently induces H1(0) gene expression. Moreover, using a cell line sensitive to trichostatin A (FM3A) and a derived cell line selected for its resistance to this inhibitor (TR303), it is shown that the level of H1(0) gene expression is related to the extent of chromatin acetylation. After showing the S-phase-dependent activation of H1(0) gene expression, we demonstrate that hyperacetylation has a dominant effect on H1(0) gene expression, since it enhances the expression of the gene independent of the position of cells in the cell cycle. This response to deacetylase inhibitors is specific to H1(0), since it is not shared by other cell-cycle-dependent histone genes (H1 and H4). Finally, by transfection of trichostatin-A-resistant and trichostatin-A-sensitive cells with a plasmid containing a H1(0) promoter, we show that the exogenous H1(0) promoter is also highly sensitive to trichostatin A treatment and that activation of transcription follows exactly the same pattern as activation of the endogenous gene. These data show that histone acetylation may be used to modulate H1(0) gene activity and offers insight into a possible mechanism in which the developmentally regulated chromatin acetylation acts to potentiate H1(0) gene expression.


Machine learning phase space quantum dynamics approaches.
Derived from phase space expressions of the quantum Liouville theorem, equilibrium continuity dynamics is a category of trajectory-based phase space dynamics methods, which satisfies the two critical fundamental criteria: conservation of the quantum Boltzmann distribution for the thermal equilibrium system and being exact for any thermal correlation functions (even of nonlinear operators) in the classical and harmonic limits. The effective force and effective mass matrix are important elements in the equations of motion of equilibrium continuity dynamics, where only the zeroth term of an exact series expansion of the phase space propagator is involved. We introduce a machine learning approach for fitting these elements in quantum phase space, leading to a much more efficient integration of the equations of motion. Proof-of-concept applications to realistic molecules demonstrate that machine learning phase space dynamics approaches are possible as well as competent in producing reasonably accurate results with a modest computation effort.


The change of break modulus drives human fibroblast differentiation in 3D collagen gels.
Extracellular matrix is one of the key environmental factors influencing cell survival and provides signals for cell morphological change, migration, proliferation and differentiation. However, the mechanism through which denatured collagen modulates the biological properties of fibroblasts, is unclear. We investigated the regulation of human fibroblast differentiation in vitro grown in collagen gels with different properties. The break modulus of collagen with denatured collagen and half-load normal collagen was reduced compared with that of normal collagen gel. Fibroblasts cultured in denatured collagen gels showed increased expression of matrix metalloproteinase9 ( MMP-9), tissue inhibitor of metalloproteinase 2 (TIMP2), α-smooth muscle actin (α-SMA), osteoblast cadherin, phosphorylated Myosin phosphatase target subunit1 (p-MYPT1), connective tissue growth factor, type I collagen, type III collagen, α-smooth muscle actin messenger RNA, RhoA, rho-associated protein kinase, and transforming growth factor β receptors 1 and 2 compared with that in cells cultured in normal collagen gel. But there was no significant difference regarding expression level between denatured collagen gel and half-load normal collagen gel .These findings suggest that the change in break modulus caused by decreasing normal collagen concentration may be the key factor inducing fibroblast differentiation.


Efficacy and Safety of Manual Partial Red Cell Exchange in the Management of Severe Complications of Sickle Cell Disease in a Developing Country.
The realization of red cell exchange (RCE) in Africa faces the lack of blood, transfusion safety, and equipment. We evaluated its efficacy and safety in severe complications of sickle cell disease. Manual partial RCE was performed among sickle cell patients who had severe complications. Efficacy was evaluated by clinical evolution, blood count, and electrophoresis of hemoglobin. Safety was evaluated on adverse effects, infections, and alloimmunization. We performed 166 partial RCE among 44 patients including 41 homozygous (SS) and 2 heterozygous composites SC and 1 S/β0-thalassemia. The mean age was 27.9 years. The sex ratio was 1.58. The regression of symptoms was complete in 100% of persistent vasoocclusive crisis and acute chest syndrome, 56.7% of intermittent priapism, and 30% of stroke. It was partial in 100% of leg ulcers and null in acute priapism. The mean variations of hemoglobin and hematocrit rate after one procedure were, respectively, +1.4 g/dL and +4.4%. That of hemoglobin S after 2 consecutive RCE was -60%. Neither alloimmunization nor viral seroconversion was observed. This work shows the feasibility of manual partial RCE in a low-resource setting and its efficacy and safety during complications of SCD outside of acute priapism.


[Regulation of insulin receptor expression and its gene].
The insulin receptor is a membrane macromolecule whose expression on the cell surface is essential for cell sensitivity to insulin. Current knowledge on the regulation of expression of the insulin receptor and its gene in human and animal cells is presented. Although ubiquitously distributed, the insulin receptor and its messenger RNA (mRNA) are mainly expressed in metabolically active cells such as hepatocytes and adipocytes. Two receptor isoforms, generated by alternative splicing of exon 11, have been identified. Isoform B (exon 11+) predominates in liver and adipocytes, and isoform A (exon 11-) in brain, spleen and leukocytes. In vivo and in several cell models, the expression of the insulin receptor and/or its mRNA is under positive regulation by glucocorticoid hormones and negative regulation by insulin. Glucocorticoid hormones stimulate receptor gene transcription and receptor protein synthesis. Insulin stimulates receptor protein degradation and, in certain cell types, decreases receptor mRNA level. Vanadate (an insulinomimetic agent) corrects, in vivo, the hyperexpression of the liver receptor observed in experimental insulinopenic diabetes, but its effects on receptor expression in vitro are complex and vary with the cell type. In vivo the insulin receptor and/or its mRNA are expressed early in fetal development with a high level, in liver, of isoform A. Maximal expression is reached at the end of gestation and then decreases after birth. In several cell models, receptor protein and/or mRNA expression is affected by cell growth and/or differentiation. Several cis- and trans-acting factors regulating the expression of the human insulin receptor gene and its response to glucocorticoid hormones have been identified.


Endoscopic treatment of a gastrocutaneous fistula using the over-the-scope-clip system: a case report.
The over-the-scope-clip (OTSC; Ovesco Endoscopy GmbH, Tuebingen, Germany) system is a newly designed method for the mechanical compression of large areas in the gastrointestinal tract. So far, indications for OTSC application are hemostasis of primary or postinterventional bleeding, closure of iatrogenic full-thickness or covered perforations. Recently closure of gastrointestinal tract fistulas using this device has been described. A 44-year-old man developed a gastrocutaneous fistula after surgical treatment for a perforated gastric ulcer. We describe the successful endoscopic closure of the fistula using the OTSC system. The patient's clinical followup was uneventful. Fistula closure was successfully implemented as it was documented by imaging and endoscopic examinations performed on the 2nd day and 6th week after the application of the clip. Endoscopic application of the OTSC device was safe and effective for the treatment of a gastrocutaneous fistula.


Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS.
Neurodegeneration refers to a large clinically and pathologically heterogeneous disease entity associated with slowly progressive neuronal loss in different anatomical and functional systems of the brain. Neurodegenerative diseases often affect cognition, e.g. Alzheimer's disease (AD), dementia with Lewy bodies and vascular dementia, or different aspects of the motor system, e.g., amyotrophic lateral sclerosis, Parkinson's disease and ataxic disorders. Owing to increasing knowledge about the mechanisms leading to neurodegeneration, the development of treatments able to modify the neurodegenerative process becomes possible for the first time. Currently, clinical outcome measures are used to assess the efficacy of such treatments. However, most clinical outcome measures have a low test-retest reliability and thus considerable measurement variance. Therefore, large patient populations and long observation times are needed to detect treatment effects. Furthermore, clinical outcome measures cannot distinguish between symptomatic and disease-modifying treatment effects. Therefore, alternative biomarkers including neuroimaging may take on a more important role in this process. Because MR scanners are widely available and allow for non-invasive detection and quantification of changes in brain structure and metabolism, there is increasing interest in the use of MRI/MRS to monitor objectively treatment effects in clinical trials of neurodegenerative diseases. Particularly volumetric MRI has been used to measure atrophy rates in treatment trials of AD because the relationship between atrophic changes and neuron loss is well established and correlates well with clinical measures. More research is needed to determine the value of other MR modalities, i.e. diffusion, perfusion and functional MRI and MR spectroscopy, for clinical trials with neuroprotective drugs.


A tale of five cities: Using recycling frameworks to analyse inclusive recycling performance.
'Recycling' is a source of much confusion, particularly when comparing solid waste systems in high-income countries with those in low- and middle-income countries. Few analysts can explain why the performance and structure of recycling appears to be so different in rich countries from poor ones, nor why well-meaning efforts to implement recycling so often fail. The analysis of policy drivers, and the Integrated Sustainable Waste Management (ISWM) framework, come close to an explanation.This article builds on these earlier works, focusing in on five cities profiled in the 2010 UN-Habitat publication (Scheinberg A, Wilson DC and Rodic L (2010) Solid Waste Management in the World's Cities. UN-Habitat's Third Global Report on the State of Water and Sanitation in the World's Cities. Newcastle-on-Tyne, UK: Earthscan Publications). Data from these cities and others provides the basis for developing a new tool to analyse inclusive recycling performance. The points of departure are the institutional and economic relationships between the service chain, the public obligation to remove waste, pollution, and other forms of disvalue, and the value chain, a system of private enterprises trading valuable materials and providing markets for recyclables. The methodological innovation is to use flows of materials and money as indicators of institutional relationships, and is an extension of process flow diagramming.The authors are using the term 'recycling framework analysis' to describe this new form of institutional analysis. The diagrams increase our understanding of the factors that contribute to high-performance inclusive recycling. By focusing on institutional relationships, the article seeks to improve analysis, planning, and ultimately, outcomes, of recycling interventions.


RPR 107393, a potent squalene synthase inhibitor and orally effective cholesterol-lowering agent: comparison with inhibitors of HMG-CoA reductase.
Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl pyrophosphate to form squalene and is the first committed step in sterol synthesis. A specific inhibitor of squalene synthase would inhibit cholesterol biosynthesis but not prevent the formation of other products of the isoprenoid pathway, such as dolichol and ubiquinone. RPR 107393 [3-hydroxy-3-[4-(quinolin-6-yl)phenyl]-1-azabicyclo[2-2-2]octane dihydrochloride] and its R and S enantiomers are potent inhibitors of rat liver microsomal squalene synthase, with IC50 values of 0.6 to 0.9 nM. One hour after oral administration to rats, RPR 107393 inhibited de novo [14C]cholesterol biosynthesis from [14C]mevalonate in the liver with an ED50 value of 5 mg/kg. Diacid metabolites of [14C]farnesyl pyrophosphate were identified after acid treatment of the livers of these animals. These results support in vitro data demonstrating that these compounds are inhibitors of squalene synthase. In rats, RPR 107393 (30 mg/kg p.o. b.i.d. for 2 days) reduced total serum cholesterol by < or = 51%. In the same paradigm, the HMG-CoA reductase inhibitor lovastatin failed to lower serum cholesterol in rats. In marmosets, RPR 107393 (20 mg/kg b.i.d.) reduced plasma cholesterol concentration by 50% after 1 week of administration; this was greater than the reduction observed with lovastatin or pravastatin, neither of which produced > 31% reduction in plasma cholesterol when administered for 1 week at a dose of 50 mg/kg b.i.d. The R and S enantiomers of RPR 107393 (20 mg/kg p.o. q.d. for 7 days) reduced plasma low density lipoprotein cholesterol by 50% and 43%, respectively, whereas high density lipoprotein cholesterol was unchanged. In summary, RPR 107393 is a potent inhibitor of squalene synthase. It is an orally effective hypocholesterolemic agent in rats and marmosets that has greater efficacy than lovastatin or pravastatin in the marmoset.


Study on oxidative stress and inflammatory/antioxidant substance levels in autism spectrum disorder.
The etiology of autism spectrum disorder (ASD) includes oxidative stress and brain inflammation. We investigated the relationship among oxidative stress markers, in vivo inflammatory substances, and antioxidants that can be easily measured in the clinic and compared them between children with ASD and those with typical development (TD). Sixty-one children with TD and 199 with untreated ASD were investigated. They were Japanese children aged 2-15 years and were divided into those aged <7 and ≥7 years. Serum levels of reactive oxygen metabolites (ROMs), high-sensitivity C-reactive protein (hsCRP), prolactin (PRL), albumin (Alb), total bilirubin (T-Bil), and uric acid (UA) were measured. These measurements were compared between TD and ASD, and the relationship between oxidative stress and relevant laboratory parameters was analyzed. The hsCRP and PRL levels were significantly higher in patients with ASD than in those with TD. Among those aged <7 years, hsCRP and PRL were significantly higher in those with ASD than in those with TD. Among those aged ≥7 years, ROMs, hsCRP, and PRL were significantly higher in those with ASD than in those with TD. In ASD, ROMs were significantly correlated with hsCRP, Alb, T-Bil, and PRL. In contrast, no significant correlations were found in the TD group except for the relationship between ROMs and hsCRP in those aged <7 years. The results suggest that serum levels of in vivo inflammatory substances, stress-related substances, and antioxidants are altered in ASD under oxidative stress.


The Control Method of Autonomous Flight Avoidance Barriers of UAVs in Confined Environments.
This paper proposes an improved 3D-Vector Field Histogram (3D-VFH) algorithm for autonomous flight and local obstacle avoidance of multi-rotor unmanned aerial vehicles (UAVs) in a confined environment. Firstly, the method employs a target point coordinate system based on polar coordinates to convert the point cloud data, considering that long-range point cloud information has no effect on local obstacle avoidance by UAVs. This enables UAVs to effectively utilize obstacle information for obstacle avoidance and improves the real-time performance of the algorithm. Secondly, a sliding window algorithm is used to estimate the optimal flight path of the UAV and implement obstacle avoidance control, thereby maintaining the attitude stability of the UAV during obstacle avoidance flight. Finally, experimental analysis is conducted, and the results show that the UAV has good attitude stability during obstacle avoidance flight, can autonomously follow the expected trajectory, and can avoid dynamic obstacles, achieving precise obstacle avoidance.


Two-step drug education in Norway.
A survey of drug education in Norwegian lower secondary schools showed that almost one-fourth of the programs were based on a two-step model, which is described in this article. The intensive courses were socially successful, and created motivation, enthusiasm, and changes of attitudes. More than 90 percent of the participants carried out the second step of the teaching. There were important differences from one school to another in regard to how the pilot pupils, and their teaching program, were received. They found it difficult to find sufficient time for their programs, and sometimes hard to keep their classmates in order. Most of the classmates found the teaching in the second step interesting, but they had little belief in the preventive effect.


Combining high-field EPR with site-directed spin labeling reveals unique information on proteins in action.
In the last decade, joint efforts of biologists, chemists and physicists have helped in understanding the dominant factors determining specificity and directionality of transmembrane transfer processes in proteins. In this endeavor, electron paramagnetic resonance (EPR) spectroscopy has played an important role. Characteristic examples of such determining factors are hydrogen-bonding patterns and polarity effects of the microenvironment of protein sites involved in the transfer process. These factors may undergo characteristic changes during the reaction and, thereby, control the efficiency of biological processes, e.g. light-induced electron and proton transfer across photosynthetic membranes or ion-channel formation of bacterial toxins. In case the transfer process does not involve stable or transient paramagnetic species or states, site-directed spin labeling with suitable nitroxide radicals still allows EPR techniques to be used for studying structure and conformational dynamics of the proteins in action. By combining site-directed spin labeling with high-field/high-frequency EPR, unique information on the proteins is revealed, which is complementary to that of X-ray crystallography, solid-state NMR, FRET, fast infrared and optical spectroscopic techniques. The main object of this publication is twofold: (i) to review our recent spin-label high-field EPR work on the bacteriorhodopsin light-driven proton pump from Halobacterium salinarium and the Colicin A ion-channel forming bacterial toxin produced in Escherichia coli, (ii) to report on novel high-field EPR experiments for probing site-specific pK(a) values in protein systems by means of pH-sensitive nitroxide spin labels. Taking advantage of the improved spectral and temporal resolution of high-field EPR at 95 GHz/3.4 T and 360 GHz/12.9 T, as compared to conventional X-band EPR (9.5 GHz/0.34 T), detailed information on the transient intermediates of the proteins in biological action is obtained. These intermediates can be observed and characterized while staying in their working states on biologically relevant timescales. The paper concludes with an outlook of ongoing high-field EPR experiments on site-specific protein mutants in our laboratories at FU Berlin and Osnabrück.


Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice.
We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN) and zona incerta (ZI); both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100-250 mg/kg) or saline either over 30 hours followed by either a two-hour or six-day survival period (acute model) or over five weeks followed by a three-week survival period (chronic model). NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30-45%) the increase in Fos(+) cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number). In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin.


3-Cyclo-hexyl-1-(3,5-dinitro-benzo-yl)thio-urea.
The structure of the title thio-urea derivative, C(14)H(16)N(4)O(5)S, features an almost planar central C(2)N(2)OS fragment (r.m.s. deviation = 0.005 Å), an arrangement stabilized by an intra-molecular N-H⋯O hydrogen bond. The terminal rings are twisted out of this plane, the dihedral angle formed with the benzene ring being 33.22 (10)°. The cyclo-hexyl ring is disordered, with two orientations (50:50) being resolved. The mean plane passing through the atoms of each disordered component forms dihedral angles of 65.7 (2) and 82.4 (3)° with the central plane. Centrosymmetric dimers mediated by an eight-membered {⋯HNC=S}(2) synthon occur in the crystal.


Role of MMP1 and MMP10 in local invasion and distant metastasis in different levels of oral squamous cell carcinoma - A immunohistochemical comparative study.
Matrix metalloproteinases (MMPs) are basically a part of a large family of proteolytic enzymes. They play an important role in degrading extracellular matrix and basement membrane, which is a basic mechanism in local invasion and tumour metastasis. The aim of this study was to evaluate immunohistochemically the expression of MMP1 and MMP10 in tumour invasion locally and at distant levels, including lymph nodes at different levels in oral squamous cell carcinoma (OSCC). A total of 50 tissue samples with clinically confirmed OSCC and 15 normal oral mucosal tissues will be included in the study. Immunohistochemical staining will be performed for the demonstration of MMP1 and MMP10 in lesional tissue, perilesional tissue, and lymph nodes of different levels that were evaluated with respect to microscopic features. All OSCC cases had MMP1 and MMP10 expression levels. The expression increased as the nodal level increased from level I to level V. This difference was statistically significant at P < 0.001 Both MMPs were not expressed in normal epithelial cells. There was no significant correlation between MMP1 and MMP10 expression. This study showed that MMP1 and MMP10 are expressed in the tissues of OSCC and may serve as prognostic indicators for the disease.


Comparison of second-generation stents for application in the superficial femoral artery: an in vitro evaluation focusing on stent design.
To examine and compare in an ex vivo study different nitinol stent designs intended for the superficial femoral artery (SFA) with regard to the appearance of fracture. Seven different 8-×40-mm nitinol stents were evaluated (Misago, Absolute, Smart, Luminexx, Sentinol, Lifestent NT, and Sinus-Superflex). Finite element analysis (FEA) was used for digitalized stent design comparison; the strain during stent movement was calculated for bending, compression, and torsion. Additional mechanical fatigue tests for bending (70°), compression (40%), and torsion (twisted counterclockwise by 180°) were performed up to 650,000 cycles or until a fracture was observed. The FEA bending test showed that only the Misago, LifeStent, and Absolute stents presented no zones of high strain; in the torsion test, the Smart stent also had no zones of high strain. Macroscopic evaluation after mechanical bending indicated that the LifeStent performed the best (no stent fracture after 650,000 cycles). Misago and Absolute stents showed fractures at 536,000 cycles and 456,667 cycles, respectively (range 320,000-650,000 cycles). After compression and torsion testing, Misago showed no stent fracture after 650,000 cycles. The worst performing stent was Luminexx during all test cycles. The 7 SFA stents showed differences in the incidence of high strain zones, which indicates a potential for stent fracture, as demonstrated by the mechanical fatigue tests. Differences in stent design might play a major role in the appearance of stent strut fracture related to restenosis and reocclusion.


[An overview of medical informatization in Zhejiang Province].
Medical modernization is based on the informatization. This paper introduces the present situation of medical modernization construction in Zhejiang Province, including provincial health E-government affairs, the public health system, digital hospitals, community health services, and the new rural cooperative medical system, and analyses the problems exiting, and points out the future construction tasks.


An unusual cause of hypercalcemia.
We describe a case of pronounced symptomatic hypercalcemia as a consequence of thyrotoxicosis alone. Primary hyperparathyroidism and other secondary causes of hypercalcemia were excluded. Hypercalcemia completely abated after treatment of thyrotoxicosis. Notwithstanding that hypercalcemia is an unusual manifestation of hyperthyroidism, asymptomatic elevation of serum calcium concentration had been documented in up to one-fourth of patients with proved hyperthyroidism. The current case is unusual in that the patient demonstrated a significant degree of hypercalcemia secondary to hyperthyroidism alone, with a serum calcium level as high as 3.14 mmol/L. We further discuss the putative pathophysiology of this "thyroid bone disease," highlighting the repercussion on calcium and bone metabolism in hyperthyroidism.


Photochemical cross-linking of neighboring residues in protein-nucleic acid complexes: rnase and pyrimidine nucleotide inhibitors.
Iradiation of the stable complexes formed between RNase and its competitive inhibitors cytidine 2'(3'),5'-diphosphate (pCp), and uridine 2'(3'),5'-diphosphate (pUp), resulted in covalent bond formation between the pyrimidine nucleotides and the enzyme. The photochemical reactions were initiated by ultraviolet light of lambda greater than 300 mn, employing acetone as a photosensitizer. This method was found to yield less undesired by-products, particularly photolyzed amino acids and aggregates resulting from protein-to-protein cross-linking, than the direct method of irradiation with light of lambda 260 nm. Tryptic digrestion of the modified protein, and chromatographic analysis of the peptides thus obtained, revealed a single and specific peptide which bacame covalently linked to both nucleotide inhibitors. The amino acid composition of this peptide is consistent with the sequence Asn-67-Arg-85 of RNase. Part of this peptide (residues 78 through 83) is close to the enzyme's binding site for the pyrimidine moiety of the nucleotides. Denatured RNase failed to cross-link to the inhibitors, and the extent of pUp cross-linking could be reduced by the addition of another competitive inhibitor (3'-UMP). Finally, the presence of excess inhibitor in the irradiation mixture did not lead to nonspecific cross-linking. This indicates that specificity is also achieved due to the fact that unbound excited inhibitor molecules do not react with the protein but prefer to follow different and faster reaction paths.


[Enteral zond feeding in patients with insolvensy of duodenum stump].
The most effective method of insolvency duodenum stump treatment is an active drenage of stump--zone within enteral zond feeding. Using of Y-shaped enterostomia with compressive intestine anastomosis avows to fulfill feeding during a long period of time. It is not followed with new complication even in peritonitis case. The method allows to lower the death level in two times.


Identification of amino acid residues associated with modulation of flavin-containing monooxygenase (FMO) activity by imipramine: structure/function studies with FMO1 from pig and rabbit.
The activity of the flavin-containing monooxygenase (FMO) can be modulated by a number of nitrogen-containing compounds in a manner that is both isoform and modulator-dependent. We now show that the direction (activation or inhibition) and extent of modulation can also be dependent on substrate concentration. Imipramine activates methimazole metabolism catalyzed by rabbit FMO1 or FMO2 at methimazole concentrations greater than 50 or 100 microM, respectively, and inhibits at lower methimazole concentrations. The extent of the activation increases as the substrate concentration increases, and the extent of inhibition increases as the substrate concentration decreases. With either inhibition or activation, the magnitude of the effect shows a similar, direct dependency on imipramine concentration. In contrast, imipramine inhibits the metabolism of methimazole catalyzed by pig FMO1 at all substrate concentrations. The structural basis for this unique ortholog difference between the responses of rabbit and pig FMO1 to imipramine was studied by random chimeragenesis and site-directed mutagenesis. Results with chimeras indicated that modulation of FMO1 activity by imipramine is controlled to a great extent by two areas of the FMO primary structure (residues 381-432 and 433-465). Four amino acids in these regions (positions 381, 400, 420 and 433) and one additional residue (position 186) were identified by site-directed mutagenesis as primary determinants of the imipramine response. When the residues at these positions in rabbit FMO1 are exchanged for the corresponding residues of pig FMO1, a mutant with the functional properties of pig FMO1 is produced. Our results suggest that the response of FMO1 to imipramine involves a distribution between two sites that is regulated by structural features that do not alter the overall binding. The inhibition observed, although it appears to be competitive, likely does not involve competition for a binding site since alteration of imipramine metabolism has no effect on the parameters of methimazole metabolism.


Modeling of autonomous problem solving process by dynamic construction of task models in multiple tasks environment.
Traditional reinforcement learning (RL) supposes a complex but single task to be solved. When a RL agent faces a task similar to a learned one, the agent must re-learn the task from the beginning because it doesn't reuse the past learned results. This is the problem of quick action learning, which is the foundation of decision making in the real world. In this paper, we suppose agents that can solve a set of tasks similar to each other in a multiple tasks environment, where we encounter various problems one after another, and propose a technique of action learning that can quickly solve similar tasks by reusing previously learned knowledge. In our method, a model-based RL uses a task model constructed by combining primitive local predictors for predicting task and environmental dynamics. To evaluate the proposed method, we performed a computer simulation using a simple ping-pong game with variations.


A comparison of automated and manual co-registration for magnetoencephalography.
Magnetoencephalography (MEG) is a neuroimaging technique that accurately captures the rapid (sub-millisecond) activity of neuronal populations. Interpretation of functional data from MEG relies upon registration to the participant's anatomical MRI. The key remaining step is to transform the participant's MRI into the MEG head coordinate space. Although both automated and manual approaches to co-registration are available, the relative accuracy of two approaches has not been systematically evaluated. The goal of the present study was to compare the accuracy of manual and automated co-registration. Resting MEG and T1-weighted MRI data were collected from 90 participants. Automated and manual co-registration were performed on the same subjects, and the inter-method reliability of the two methods assessed using the intra-class correlation. Median co-registration error for both methods was within acceptable limits. Inter-method reliability was in the "good" range for co-registration error, and the "good" to "excellent" range for translation and rotation. These results suggest that the output of the automated co-registration procedure is comparable to that achieved using manual co-registration.


Identification of a distinct type IV collagen alpha chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome.
We have identified and extensively characterized a type IV collagen alpha chain, referred to as alpha 5(IV). Four overlapping cDNA clones isolated contain an open reading frame for 543 amino acid residues of the carboxyl-terminal end of a collagenous domain, a 229-residue carboxyl-terminal noncollagenous domain, and 1201 base pairs coding for a 3' untranslated region. The collagenous Gly-Xaa-Yaa repeat sequence has five imperfections that coincide with those in the corresponding region of the alpha 1(IV) chain. The noncollagenous domain has 12 conserved cysteine residues and 83% and 63% sequence identity with the noncollagenous domains of the alpha 1(IV) and alpha 2(IV) chains, respectively. The alpha 5(IV) chain has less sequence identity with the putative bovine alpha 3(IV) and alpha 4(IV) chains. Antiserum against an alpha 5(IV) synthetic peptide stained a polypeptide chain of about 185 kDa by immunoblot analysis and immunolocalization of the chain in human kidney was almost completely restricted to the glomerulus. The gene was assigned to the Xq22 locus by somatic cell hybrids and in situ hybridization. This may be identical or close to the locus of the X chromosome-linked Alport syndrome that is believed to be a type IV collagen disease.


Physicochemical and crystalline properties of heat-moisture-treated rice starch: combined effects of moisture and duration of heating.
Currently there is much interest in the application of physical modification techniques such as heat-moisture treatment (HMT). The effects of HMT on normal and waxy rice starches, subject to different levels of moisture content and duration of heating, were investigated. Water solubility index (determined at 90 °C) decreased after HMT for normal and waxy rice starches, while swelling power (determined at 90 °C) showed inconsistent results (decrease for normal type, increase for waxy type) after HMT. Values in pasting parameters of normal and waxy rice starch increased initially, but the extent of increase slowed down with moisture content and length of treatment increasing. HMT decreased gelatinization temperatures with 4 h and 8 h treatment, but when length of treatment was prolonged to 16 h gelatinization temperature increased. Degree of crystallinity decreased for all treatments, and decreased much more at higher levels of moisture content. Variations in levels of moisture content and duration of heating had significant effects on physicochemical and crystalline properties to different extents.


Solvothermally-derived nanoglass as a highly bioactive material.
A highly bioactive glass solvBG76 in a binary system 76SiO2-24CaO (wt%) was prepared following a solvothermal path of the synthesis. The facile synthesis, in terms of the steps and reagents needed, enabled the achievement of a mesoporous material. Many factors such as nano-size (<50 nm), different morphology (non-spherical), use of an unconventional network modifier (calcium hydroxide) during the synthesis, a structure free of crystalline impurities, and textural properties greatly enhanced the kinetic deposition process of hydroxyapatite (HA) when contacting with physiological fluids. The formation of a HA layer on the glass was analyzed by various techniques, namely XRD, IR-ATR, Raman, XPS, EDS analyses, SEM, and HR-TEM imaging. The results obtained were compared to the 45S5 glass tested as a reference biomaterial as well as 70S30C-a glass with similar size and composition to reported solvBG76 but obtained by the conventional sol-gel method. For the first time, superior apatite-mineralization ability in less than 1 h in a physiological-like buffer was achieved. This unique bioactivity is accompanied by biocompatibility and hemocompatibility, which was indicated by a set of various assays in human dermal fibroblasts and MC3T3 mouse osteoblast precursor cells, as well as hemolytic activity determination.


Is personal oral hygiene advice effective in preventing coronal dental caries?
Data sources PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases.Study selection PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases were searched for studies published in English between January 1950 and February 2017.Data extraction and synthesis Data were extracted independently by two reviewers and risk of bias assessed using a modified Jadad scale. Heterogeneity was evaluated using the chi-squared statistic and meta-analysis performed.Results Three randomised trials were included, involving 681 participants; all children 10-13 years old. Two trials were conducted in the USA and one in the UK. Two studies tested school-based, daily supervised oral hygiene (including plaque staining and removal and supervised flossing) against control groups; one study tested the same intervention every two weeks against controls. Two studies measured decayed, missing or filled surfaces (DMFS) scores at three years and one trial at 29 months. Personal oral hygiene interventions failed to influence the incidence of dental caries, (DMFS = -0.11; 95% CI -0.91, 0.69: P value <0.79). Four non-randomised trials were retained to conduct sensitivity analyses.Conclusions Personal oral hygiene interventions delivered to school children failed to show a reduction in coronal dental carious lesion incidence over three years when compared to control groups.


Tick-Borne Encephalitis Virus Antibodies in Roe Deer, the Netherlands.
To increase knowledge of tick-borne encephalitis virus (TBEV) circulation in the Netherlands, we conducted serosurveillance in roe deer (Capreolus capreolus) during 2017 and compared results with those obtained during 2010. Results corroborate a more widespread occurrence of the virus in 2017. Additional precautionary public health measures have been taken.


[Treatment of varices in the elderly].
Age is not a contra-indication to the various methods of treatment that may be considered. Only the somatic and vascular assessments of the patient need to be taken into account. Sclerosis can almost always be considered, except when the tissues are obviously unhealthy. It is carried out with weak iodinated solutions or with trombovar. This will give substantial protection from threatening ulcer or rupture of a varix. Surgery is reduced to a minimum, and is followed by supplementary sclerosis. Elastic support is considered in all cases, though it may often be difficult to achieve in arthritic or obese patients. Thermal cures are possible in all cases, though the general contra-indications should be respected (major physiological deficiencies, severe cardiac or renal disease). Phlebotonics will also be prescribed in all cases.


Public Health Nursing and Community Health Worker Teams: A Community-Based Preventive Services Clinic Exemplar.
Since 2009, a community-based, collaborative exemplar in Richmond, Virginia, involving 8 satellite clinics of the state health department, has been implemented within public housing units to focus on prevention and access to care. These satellite centers, known a resource center (RCs), are staffed by public health nurses, community health workers, and nurse practitioners working in complementary roles. The RCs have provided education to 2609 clients on family planning, safe sex practices, safe car seat use, and screening for sexually transmitted infections and have made 9591 patient referrals to health, social, and community services.


[Chemical constituents from marine alga Chaetomorpha basiretorsa].
To investigate the chemical constituents of marine alga Chaetomorpha basiretorsa. Compounds were isolated by normal phase silica gel and Sephadex LH-20 gel colum chromatography, reverse phase MPLC, reverse phase HPLC and recrystallization. Their structures were elucidated by spectroscopic methods including MS, IR, NMR, and X-ray crystalography. Cytotoxicity of the compounds were screened by using standard MTT method. Nine compounds were isolated from C. basiretorsa and their structures were identified as N-phenyl-2-naphthalenamine( I ), dibutyl phthalate( II ), diisobutyl phthalate( III ), 1-phenyl-ethane-1, 2-diol( IV ), 2-hydrox-gamma-benzaldehyde( V ), diethyleneglycol monobenzoate( VI ), uracil( VII ), thymine( VIII ) and thymidine( IX ). All these compounds were obtained from this genus for the first time, N-phenyl-2-naphthalenamine and diethyleneglycol monobenzoate were first reported from the marine organisms. Compound I and VII showed moderate activity against KB cell(IC50 10.15 microg x mL(-1) for I and 3.79 microg x mL(-1) for VII ) and MCF-7 cell(IC50 3.24 microg x mL(-1) for VII).


Human ovarian cancer stem cells.
The isolation and identification of stem-like cells in solid tumors or cancer stem cells (CSCs) have been exciting developments of the last decade, although these rare populations had been earlier identified in leukemia. CSC biology necessitates a detailed delineation of normal stem cell functioning and maintenance of homeostasis within the organ. Ovarian CSC biology has unfortunately not benefited from a pre-established knowledge of stem cell lineage demarcation and functioning in the normal organ. In the absence of such information, some of the classical parameters such as long-term culture-initiating assays to isolate stem cell clones from tumors, screening and evaluation of other epithelial stem cell surface markers, dye efflux, and label retention have been applied toward the putative isolation of CSCs from ovarian tumors. The present review presents an outline of the various approaches developed so far and the various perspectives revealed that are now required to be dealt with toward better disease management.


Physicochemical properties of proteinases from selected psychrotrophic bacteria.
The physicochemical properties of eight extracellular proteinases secreted by psychrotrophic bacteria of dairy origin have been studied. Seven of these proteinases were able to withstand ultra heat treatment (UHT) with D values at 140 degrees C ranging from 2 to 300 s. The six Pseudomonas fluorescens proteinases were glycoproteins of mol. wt 47000-49500. The two Serratia marcescens proteinases, of mol. wt of 51000, did not contain carbohydrate but in other respects were similar to the Pseudomonas proteinases. The proteinases were inhibited by various metal chelators and all contained Ca and Zn in similar proportions. Their amino acid compositions were similar, with alanine as the N-terminal group, cysteine completely absent and very low levels of methionine. Isoelectric points ranged from 5.10 to 8.25. Their physical and chemical properties enabled them to be classified as alkaline metalloendopeptidases. A similarity index (S delta n) was used to predict sequence homology between ten proteinases of known amino acid composition. Comparisons of S delta n of these proteinases showed only minor sequence differences except for those of Ps. fluorescens MC60. Heat resistance could not be related wholly to similarities in protein sequence, but could be related both to the strength of stabilizing Ca2+-protein interactions and to the randomness inherent within the folding of the peptide chain.


Accountable Care Communities: Moving from Health Care Delivery Systems to Systems of Health.
Research has shown that individuals' health outcomes often have more to do with the conditions in which they live, learn, work, and age than the medical care they receive. However, traditional health care is not designed to address the social, behavioral, and economic factors (eg, housing, transportation, access to healthy food, education, and health behaviors) that impact health outcomes. Accountable care communities are showing that it is possible to design systems that are successful at both addressing social and economic factors and improving population health.


Usefulness of Atrial Premature Complexes on Routine Electrocardiogram to Determine the Risk of Atrial Fibrillation (from the REGARDS Study).
Atrial premature complexes (APCs) serve as acute triggers for atrial fibrillation (AF), but it is currently unknown whether the association between APCs and AF varies by race or sex. We examined the association between APCs and AF in 13,840 (mean age = 63 ± 8.4 years; 56% women; 37% black) participants from the REasons for Geographic And Racial Differences in Stroke study. APCs were detected on baseline electrocardiograms (2003 to 2007). Incident AF was identified by study-scheduled electrocardiograms and self-reported history at a follow-up examination. Logistic regression was used to compute odds ratios (OR) and 95% confidence intervals for the association between APCs and incident AF. A total of 950 participants (6.9%) had APCs at the baseline visit. After a median follow-up of 9.4 years, 1015 incident AF cases (7.3%) were detected. APCs were associated with an increased risk of AF (odds ratios = 1.92, 95% confidence intervals = 1.57, 2.35). The relation between APCs and AF did not vary by race (interaction p value = 0.56) or sex (interaction p value = 0.66). In conclusion, APCs detected on a routine electrocardiogram are associated with an increased risk of AF development, and this association does not vary by race or sex. The findings of this analysis suggest that the risk of AF associated with atrial ectopy does not account for the differential risk of AF that is observed in whites compared with blacks, and in men compared with women.


Optical analysis of cellular oxygen sensing.
Molecular imaging of the assembly of hypoxia inducible factor (HIF) complexes in living cells may lead to a deeper understanding of cellular oxygen sensing. Sophisticated live cell imaging has extended the toolbox to study the molecular response to changes in oxygen supply. In this respect fluorescence resonance energy transfer (FRET) as a technique to investigate protein-protein interaction in the nanoscale range gets increasing interest. Herein, we review FRET studies related to hypoxia research, emphasizing on recent progress, but also demonstrating how FRET studies are complementary or potentially superior to conventional biochemical as well as histochemical techniques. Technical advances in the application of FRET in living cells will overcome restrictions to end-point analysis on the population rather than single cell level and will thereby provide progress in understanding the cellular hypoxic response by HIF.


Severe mitral valve involvement in a child with hypereosinophilia secondary to parasitic infection.
An 11-year-old boy with severe mitral regurgitation due to hypereosinophilia caused by infection with a filaria (Mansonella perstans) required mitral valve replacement with a prosthetic valve. During recurrent postoperative hypereosinophilia, the patient experienced severe mitral stenosis due to thrombosis of the mitral prosthesis. Despite adequate anticoagulation, the prosthesis had to be replaced as an emergency with a second prosthetic valve. Permanent control of the eosinophil count was achieved with chronic oral steroid administration. In contrast to other microfilariae, M. perstans is non-pathogenic to humans; nevertheless, longstanding hypereosinophilia may lead to severe cardiac involvement endangering the patient's life.


Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates.
Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.


Origin, activation, and targeted therapy of glioma-associated macrophages.
The glioma tumor microenvironment plays a crucial role in the development, occurrence, and treatment of gliomas. Glioma-associated macrophages (GAMs) are the most widely infiltrated immune cells in the tumor microenvironment (TME) and one of the major cell populations that exert immune functions. GAMs typically originate from two cell types-brain-resident microglia (BRM) and bone marrow-derived monocytes (BMDM), depending on a variety of cytokines for recruitment and activation. GAMs mainly contain two functionally and morphologically distinct activation types- classically activated M1 macrophages (antitumor/immunostimulatory) and alternatively activated M2 macrophages (protumor/immunosuppressive). GAMs have been shown to affect multiple biological functions of gliomas, including promoting tumor growth and invasion, angiogenesis, energy metabolism, and treatment resistance. Both M1 and M2 macrophages are highly plastic and can polarize or interconvert under various malignant conditions. As the relationship between GAMs and gliomas has become more apparent, GAMs have long been one of the promising targets for glioma therapy, and many studies have demonstrated the therapeutic potential of this target. Here, we review the origin and activation of GAMs in gliomas, how they regulate tumor development and response to therapies, and current glioma therapeutic strategies targeting GAMs.


The Effect of Ethanol Associated with Universal Adhesive on Resin Composite Adhesion to Different Dentin Depths: A Long-Term In Vitro Study.
To evaluate the ethanol wet-bonding protocol with a universal adhesive in etch-andrinse and self-etch modes on microleakage and microtensile bond strength (μTBS) of resin composite to different dentin depth. Molars were distributed into groups according to protocol and dentin depth: universal adhesive (C - control), ethanol + universal adhesive (E), and phosphoric acid etch + ethanol + universal adhesive (PA+E). All protocols were applied to dentin at superficial, middle and deep depths. The specimens (n = 10) were submitted to microleakage and μTBS tests. Half of specimens were submitted to thermocycling (10,000 cycles; 5∘C/55∘C). Data were submitted to Spearman correlation (μTBS x microleakage) and three-way ANOVA (protocol, aging and depth), followed by Bonferroni post hoc test (α=0.05). PA+E group showed highest μTBS and lowest microleakage mean values in 24h. All groups presented similar μTBS mean values after thermocycling. The deep dentin showed less stable μTBS results. PA+E group presented highest microleakage mean values after thermocycling. Spearman's correlation showed a strong correlation between microleakage and μTBS. The PA+E group improved immediate adhesion and E group promoted a more stable μTBS in the long-term adhesion of universal adhesive. The aging for all protocols jeopardized the stability of the hybrid layer. The ethanol wet bonding technique associated with universal adhesive has enhanced the immediate result of the resin composite adhesion.


Duncan's dermatosis: from the "terra firma-forme" to a possible syndromic condition. The story of a dirty disease.
Since its first description by Duncan, Tschen and Knox in 1987 in the former Archives of Dermatology (1), "Terra firma-forme dermatosis" has been variously described in medical literature, representing a strange, probably underestimated, cutaneous disease. During the last 40 years, the condition has been recorded as an undesirable as well as unexplained event, occurring mainly in childhood, characterized by a brownish-black appearance of the whole skin, resembling dirt. Recently, authors described several cases of atypical patterns of the disease, sometimes with impressing topographic clinical pictures, evocative for syndromic phenotypes. Thanks to more careful examination of the tegument, often with the aid of non-invasive diagnostic tools, attention to this disease is growing. This brief review summarizes the state of the art on the topic, through an historical overview of what is known of this 'dirty' dermatosis.


Changing markets - Medicinal plants in the markets of La Paz and El Alto, Bolivia.
Given the importance of local markets as a source of medicinal plants for both healers and the population, literature on market flows and the value of the plant material traded is rather scarce. This stands in contrast to wealth of available information for other components of Bolivian ethnobotany. The present study attempts to remedy this situation by providing a detailed inventory of medicinal plant markets in the La Paz-El Alto metropolitan area, hypothesizing that both species composition, and medicinal applications, have changed considerably over time. From October 2013-October 2015 semi-structured interviews were conducted with 39 plant vendors between October 2013 and October 2015 in the Mercado Rodriguez, Mercado Calle Santa Cruz, Mercado Cohoni, Mercado Cota Cota, and Mercado Seguencoma and Mercado El Alto in order to elucidate more details on plant usage and provenance. The results of the present study were then compared to previous inventories of medicinal plants in La Paz and El Alto studies to elucidate changes over time and impact of interview techniques. In this study we encountered 163 plant species belonging to 127 genera and 58 families. In addition, 17 species could not be identified. This species richness is considerably higher than that reported in previous studies (2005, 129 species of 55 families; 2015, 94 identified species). While the overall distribution of illness categories is in line with older reports the number of species used per application, as well as the applications per species, were much higher in the present study. Overall, informant consensus was relatively low, which might be explained by the large number of new species that have entered the local pharmacopoeia in the last decade, although some species might simply have been missed by previous studies. In course of the present study it became apparent that even well known species might often be replaced by other apparently similar but botanically unrelated species due to environmental and market forces CONCLUSIONS: The present study indicated that, while the floristic composition of markets in the La Paz metropolitan area remained relatively constant over the last decade, with this inventory adding about 20% of species to previous studies, the number of indications for which certain species were used increased tremendously, and that profound differences exist even between markets in close proximity. The dramatic increase in previously not used species used per indication might pose serious risks for consumers. We found serious problems due to species replacements. Even plants that have a well established vernacular name, and are easily recognizable botanically, can be replaced by other species that can pose a serious health risk. Vendor education and stringent identification of the material sold in public markets are clearly needed.


Expression of decorin mRNA in the nervous system of rat.
A rat cDNA clone (pCD67) isolated from a cDNA library of regenerating sciatic nerve by differential hybridization screening revealed 75% homology on the nucleic acid level and 81% homology (including conservative amino acid changes) to the deduced amino acid sequence of the core protein of human dermatan/chondroitin sulfate proteoglycan decorin (PGII, PG40, PG-S2). Two transcripts of 1.3 and 1.75 KB very similar in size to the two decorin mRNA species previously identified in connective tissue were detected by Northern blotting in both normal and injured sciatic nerve and in the mature and embryonic rat brain. The steady-state level of the decorin 1.3 KB mRNA was very much higher in peripheral nerve than in the central nervous system or in other non-neural tissues (skeletal muscle, heart, colon, kidney). In situ hybridization experiments indicated that decorin mRNA is expressed by Schwann cells and vascular cells in peripheral nerve. In the spinal cord the ventral horn motor neurons and other neurons in gray matter showed specific hybridization signals. Furthermore, in situ hybridization indicated decorin expression in Purkinje neurons and cells of the molecular layer in cerebellum, and in neurons of the primary olfactory cortex and brainstem (pons). Our data clearly demonstrate decorin mRNA expression in distinct neural cell populations, suggesting yet unknown functions of this proteoglycan in the peripheral and central nervous system.


Lactate and Echocardiography Before Veno-Venous Extracorporeal Membrane Oxygenation Support.
Lactate has been recognised as a prognostic factor in several critical conditions. Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is a well-established therapy in patients with Acute Respiratory Disease Syndrome (ARDS) unresponsive to conventional therapy and echocardiography pre ECMO initiation has been recently reported to help in risk stratifying these patients. We assessed whether the detection of hyperlactataemia could be associated with the presence of left ventricle (LV) or right ventricle (RV) dysfunction in 121 consecutive patients with refractory ARDS. The mortality rate was 42.9% (52/121). Higher dosages of norepinephrine and dobutamine were administered to non survivors (p=0.023 and p=0.047, respectively) who showed significantly higher levels of lactate (p=0.002). At echocardiography, non survivors showed higher values of systolic pulmonary artery pressure (sPAP) (p=0.05) and a higher incidence of RV dysfunction (as indicated by lower Tricuspid Annular Plane Excursion (TAPSE)) and RV dilatation (p=0.001). At multivariate logistic regression analysis, the following variables were independent predictors of death: body mass index (BMI) (OR: 0.914, 95%CI 0.857-0.975, p=0.006), RV dilatation (OR: 0.239, 95%CI 0.101-0.561, p=0.001) and lactate (OR: 1.292, 95%CI 1.015-1.645, p=0.038). Lactate values were directly correlated with the simplified acute physiology score (SAPS) II (r=0.38, p<0.001), while they showed an indirect correlation with left ventricular ejection fraction (LVEF) (r=-0.24, p=0.009) and TAPSE (r=-0.21, p=0.024). In refractory ARDS, hyperlactataemia before VVV-ECMO identified a subset of patients at higher risk of death, being an independent predictor of in-Intensive Care Unit (ICU) mortality. Lactate values are mainly related to disease severity (as indicated by SAPS II) and haemodynamic impairment (as inferred by LVEF) and RV failure, as (indicated by TAPSE).


Molecular weight of cytoplasmic malate dehydrogenase, mitochondrial malate dehydrogenase and lactate dehydrogenase of a freshwater catfish.
The multiple molecular forms of cytoplasmic malate dehydrogenase (cMDH), mitochondrial malate dehydrogenase (mMDH) and lactate dehydrogenase (LDH) were studied in the liver and skeletal muscle of the freshwater catfish, Clarias batrachus. There were two electrophoretically distinguishable bands (AA and BB) of cMDH and mMDH which suggests that they are apparently encoded at two gene loci (A and B) in both the tissues. However, the presence of a single band (LDH-1) of LDH in liver and double bands (LDH-1 and LDH-2) in skeletal muscle in which LDH-2 was predominant reflects the differential expression of LDH genes in different metabolic tissues to meet the requirement of energy production. The AA isoform (74 kd) of liver cMDH was smaller than those of the AA form (110 kd) of skeletal muscle. In contrast, the BB isoform of liver (42 kd) and skeletal muscle (54 kd) were more or less similar in size. Unlike the case of cMDH, the molecular weight of AA isoform (115 kd) of liver mMDH was higher than those of the AA form (87 kd) of skeletal muscle. Whereas the molecular weight of BB isoform (58 kd) of liver was in proximity to the weight of BB form (44 kd) of skeletal muscle mMDH. The size of AA isoform (74 kd) of liver cMDH was smaller, while the AA isoform (110 kd) of skeletal muscle was larger as compared to AA form of mMDH in the liver (115 kd) and skeletal muscle (87 kd). But the size of BB isoform of both the isozymes was almost equal in these metabolic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)


Historical perspective of cell transplantation in Parkinson's disease.
Cell grafting has been considered a therapeutic approach for Parkinson's disease (PD) since the 1980s. The classical motor symptoms of PD are caused by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrement in dopamine release in the striatum. Consequently, the therapy of cell-transplantation for PD consists in grafting dopamine-producing cells directly into the brain to reestablish dopamine levels. Different cell sources have been shown to induce functional benefits on both animal models of PD and human patients. However, the observed motor improvements are highly variable between individual subjects, and the sources of this variability are not fully understood. The purpose of this review is to provide a general overview of the pioneering studies done in animal models of PD that established the basis for the first clinical trials in humans, and compare these with the latest findings to identify the most relevant aspects that remain unanswered to date. The main focus of the discussions presented here will be on the mechanisms associated with the survival and functionality of the transplants. These include the role of the dopamine released by the grafts and the capacity of the grafted cells to extend fibers and to integrate into the motor circuit. The complete understanding of these aspects will require extensive research on basic aspects of molecular and cellular physiology, together with neuronal network function, in order to uncover the real potential of cell grafting for treating PD.


Factors Determining the Success of Therapeutic Lifestyle Interventions in Diabetes - Role of Partner and Family Support.
Background and aims: Knowledge of therapeutic lifestyle interventions is one of the most important pillars of diabetes care; however, its incorporation in real-world settings is poor. This review evaluates the role of partner and family support in diabetes management. Methods: Literature searches were performed in PubMed, Medline and Embase for articles published before July 2018, using the terms "therapeutic lifestyle intervention" [MeSH Terms], OR "diet changes" [All Fields], OR "spousal participation" [All Fields], OR "lifestyle interventions" [All Fields], "lifestyle changes" [All Fields] AND "diabetes" [All Fields]. The search was not restricted to English-language literature; literature in Spanish, French and German were also evaluated. Results: A total of 66 of articles were reviewed, which included 33 original work, 21 review articles, and 12 systematic reviews and meta-analyses. Studies and meta-analyses have showed that if one partner has type-2 diabetes this increases the risk in other by 5-26%. Partner and family have similar diet, lifestyle, and micro- and macro-environments which could explain the similar increased risk of diabetes and non-communicable diseases. Studies have consistently shown that spousal and family support plays a key role in overcoming negative behaviours and optimising behaviours in diabetes control. Partner support has major role in prevention and control of diabetes distress, associated depression, and medication non-compliance which have an adverse impact in glycaemic outcomes. These data are predominantly available from observational studies. There is paucity of data from interventional trials evaluating effects of family and spousal participation on health, glycaemic control and quality of life. Conclusion: The support of family and spouse/partner is beneficial to improve adherence to the lifestyle interventions and pharmacotherapy required to achieve optimum glycaemic control and avoid associated complications.


Denitrification in tertiary filtration: application of an up-flow filter.
The present paper shows the results obtained through an experimental work performed at the wastewater treatment plant of Rome, aimed at studying the performances of a tertiary filter regarding combined removal of suspended solids, COD, and nitrates. The up-flow sand filter was fed by the effluent coming from the secondary settling tank of the plant. The filter bed height was of 80 cm of silica sand. After a start up period, a study of particulate and soluble COD removal process was made, to establish the need of methanol in the denitrification process. Total COD removal efficiency was 60% on average, 55% due by soluble COD removal and 5% by particulate one. In the last phase of the experimental activity methanol was fed as carbon source, sodium sulfite was supplied to produce anoxic environment within the filter and the denitrification efficiency was studied. Nitrates removal rates after an acclimation period of 10 days increased up to 60%, with an effluent NO3-N of 8 mg/L. Denitrification rate was 2.4 kg/m3 d for water temperatures of 25 degrees C. Regarding methanol demand and biologic kinetics, the biomass yield coefficient was 0.3 kg(COD-X)/kg(me). Consequently 2.7 kg of methanol was required per kilogram of denitrified nitrogen.


Stereoselective metabolism, pharmacokinetics and biliary elimination of phenylethylhydantoin (Nirvanol) in the dog.
The influence of stereoisomerism on pharmacokinetics and rates of hepatic drug metabolism was investigated in four dogs using the enantiomers of phenylethylhydantoin (PEH) as model substances. After single i.v. administration of 98 micromoles of the pure enantiomers per kg b.wt., concentrations were measured by gas-liquid chromatography. The l-form exhibited a longer plasma half-life (23.3 +/- S.E. 1.0 hour) than the d-form (16.3 +/- 1.0 hour, P less than .005). Volumes of distribution and renal clearances were practically identical. The differences in plasma half-lives of PEH were explained by stereoselectivity of hepatic hydroxylation: an approximately 10-fold differences was found in urinary excretion of their major metabolities, d- and l-hydroxyphenylethylhydantoin (HPEH). Furthermore, in bile 7.3 +/- 1.6 mumol of of d-HPEH were eliminated within the first 6 hours, whereas l-HPEH could not be detected. The preference in biliary output of d- compared with l-PEH is consistent with the idea that both hepatic uptake and microsomal hydroxylation of PEH contribute to the high degree of stereoselectivity. In view of similar extrahepatic, but different metabolic behavior of these enantiomers, they represent an interesting research tool for in vivo studies of drug metabolism: in otherwise identical conditions, two different rates of PEH hydroxylation may be studied.


Patient satisfaction with dentures made by dentists and denturologists.
Within Quebec and elsewhere in Canada, patients requiring removable prostheses consult either dentists or denturologists. In this article, we describe the socioeconomic characteristics of 410 edentulous individuals seeking replacement of their dentures, and compare the levels of satisfaction experienced by the patient groups provided with conventional dentures by dentists and by denturologists. All subjects responded to announcements seeking participants in a clinical trial. The announcements indicated that all participants would receive new prostheses. Data were collected via telephone interviews. Sociodemographic variables included sex, age, education level and family income. Subjects were asked to evaluate their present maxillary and mandibular prostheses for general satisfaction, stability, comfort, ability to chew, ability to clean and appearance. Age, cost and the provider (dentist or denturologist) of the original prostheses were also recorded, and responses were then compared between the groups of subjects treated by dentists (N = 91) and denturologists (N = 319). There were no significant differences in the sociodemographic characteristics of the two groups, except for a small difference in mean age (two years). Both groups had paid approximately the same amount for their complete prostheses. As expected, most individuals were satisfied with their maxillary prostheses, but dissatisfied with their mandibular prostheses. Significantly more subjects in the denturologist treatment group than the dentist treatment group gave their mandibular prostheses a poor rating for general satisfaction (p = 0.003), comfort (p = 0.04) and stability (p = 0.016). These results suggest that the edentulous patients treated by dentists and denturologists share similar sociodemographic characteristics, and pay a similar cost for treatment. However, those treated by denturologists seem to be more dissatisfied with their mandibular prostheses than those treated by dentists.


Reduced fetal androgen exposure compromises Leydig cell function in adulthood.
Disruption of normal fetal development can influence functioning of organs and cells in adulthood. Circumstantial evidence suggests that subtle reductions in fetal androgen production may be the cause of adult male reproductive disorders due to reduced testosterone production. The mechanisms through which these fetal events affect adult testosterone levels are largely unknown. A recent paper of Kilcoyne et al. provides evidence that fetal reduction in androgen production or signaling results in a reduced Leydig stems cell number after birth and concomitant Leydig cell failure in adulthood. This implies that fetal androgen deficiency can lead to negative programming of adult Leydig cell (ALC) function, which may have implications for general health, aging, and longevity.


Effects of natural and recombinant hirudin on VEGF expression and random skin flap survival in a venous congested rat model.
We aim to investigate the effects of locally injected natural and recombinant hirudin on vascular endothelial growth factor (VEGF) expression and flap survival in venous congested skin flaps using a rat model. A dorsal random skin flap (10 × 3 cm) was prepared on each of 30 Wistar rats to establish a venous congested model. The rats were randomly divided into 2 treatment groups [receiving subcutaneous injection of either natural hirudin (6 U) or recombinant hirudin (6 U)] and a control group, which received subcutaneous injection of physiologic saline. After treatment, skin flap survival rates were calculated. VEGF messenger RNA levels and VEGF-positive vessel density as a marker for VEGF levels were measured in the flaps during and after treatment. The skin flap VEGF messenger RNA levels increased in the natural hirudin-treated group. The VEGF-positive vessel density was increased in all 3 groups. Statistically significant increases of VEGF levels were observed in the natural and recombinant hirudin-treated groups compared with the control group (P < 0.05). The skin flap survival rates were improved in both hirudin treated groups. Natural and recombinant hirudin can increase VEGF expression in random skin flaps, which can potentially improve random skin flap survival in rats through angio genic mechanisms. Our results showed that hirudin treatment led to an increase in VEGF expression in the congested skin flaps. Natural hirudin demonstrated more pronounced effects than recombinant hirudin. Further studies are needed to understand the specific mechanisms.


Comparison of the Shaping Ability of WaveOne Reciprocating Files with or without Glide Path in Simulated Curved S-shaped Root Canals.
The aim was to compare the shaping ability of WaveOne reciprocating files with or without glide path in simulated curved S-shaped root canals. Forty ISO #15, 0.02 taper, clear resin Endo Training Bloc-S blocks were studied. The simulated curved S-shaped canals were dyed using ink, preinstrumentation images were scanned, and resin blocks were prepared and divided into Group A: PathFile and WaveOne and Group B: WaveOne. All canals were postoperatively scanned. Pre- and postoperative images were superimposed and evaluated at 12 defined measuring points. The efficacy of the systems was compared based on the amount and direction of canal transportation, centering ability, amount of material removed, and presence of canal aberrations. Mann-Whitney U-test and independent t-test were used for statistical comparison. Both systems produced transportation at all levels and straightened the curved S-shaped canals. No significant differences in the amount and direction of transportation and amount of material removed were observed between the groups at each level (P > 0.05). However, Group A had significantly greater centering ability at the coronal straight zone (P = 0.018) and apical curvature (P = 0.014) levels than did Group B. Moreover, Group B showed more canal aberrations than did Group A. Within the limitations of the present study, the creation of a glide path with the PathFile system improved the centering ability of the WaveOne reciprocating file in the apical and straight coronal portions of the simulated curved S-shaped root canals and reduced the incidence of canal aberrations.


An automated method for the evaluation of ram libido in real mating conditions.
We investigated if sexual behaviour of rams can be assessed with an electronic Alpha-Detector (AD) which automatically records mounts of mating rams. To evaluate the rams' libido (i.e. all sexual activities), we used six intact and six vasectomised rams in pen tests in three different seasons (late spring, autumn and early spring). The pen tests consisted of 30-min visual observations of each ram placed in a group of six Merino ewes (three ewes in oestrus and three ewes not in oestrus). In the pen tests, sexual behaviour was recorded and divided into two categories: pre-copulatory and copulatory. For validation purposes, during the pen tests the 12 rams were equipped with the AD and the number of times the 18 oestrous ewes were mounted were counted over a period of 3 days. Of the 1191 mounts visually identified in the six 30-min sessions, 1026 were recorded automatically by the AD (i.e. 94%). The paddock test is an automated method consisting of the same rams wearing an AD and placed in a flock of ~250 Merino ewes on two occasions (late spring (spring 1) and early spring of the following year (spring 2)), their copulatory activities were automatically recorded over a 5-day period. The results of the pen tests in the three seasons revealed no difference between the two types of rams (breeding v. detecting rams). Based on live observations high correlations (r=+0.81, P<0.003 for breeding and r=+0.76, P<0.02 for detecting rams) were found between pre-copulatory and copulatory behaviours. The libido of the two types of rams measured in pen tests showed high repeatability across the three seasons (83 and 75%, P<0.05 for copulatory and pre-copulatory behaviours, respectively). When measured automatically in paddock tests over two consecutive springs, even higher repeatability was observed in both breeding (94%; P<0.01) and detecting rams (97%; P<0.004) in the number of mounts. In addition, high correlations (+0.89<r<+0.94) between copulatory behaviours, as measured by live observations, and those measured by the AD were obtained. The automatic measurement of ram libido in paddock tests appears to be more reliable than pen tests and far less time consuming. We therefore recommend this automated method to estimate the libido of rams. In addition, this method can be used at any season of the year provided that ewes in oestrus are present in the flock.


Blocking Autophagy in M1 Macrophages Enhances Virus Replication and Eye Disease in Ocularly Infected Transgenic Mice.
Macrophages are one of the first innate immune infiltrates in the cornea of mice following ocular infection with herpes simplex virus 1 (HSV-1). Using gamma interferon (IFN-γ) and interleukin-4 (IL-4) injections to polarize macrophages into M1 and M2, respectively, and in M1 and M2 conditional knockout mice, we have shown that M1 macrophages play an important role in suppressing both virus replication in the eye and eye disease in HSV-1-infected mice. Autophagy is also important in controlling HSV infection and integrity of infected cells. To determine if blocking autophagy in M1 and M2 macrophages affects HSV-1 infectivity and eye disease, we generated two transgenic mouse strains expressing the HSV-1 γ34.5 autophagy gene under the M1 promoter (M1-γ34.5) or the M2 promoter (M2-γ34.5). We found that blocking autophagy in M1 macrophages increased both virus replication in the eyes and eye disease in comparison to blocking autophagy in M2 macrophages or wild-type (WT) control mice, but blocked autophagy did not affect latency-reactivation. However, blocking autophagy affected fertility in both M1 and M2 transgenic mice. Analysis of 62 autophagy genes and 32 cytokines/chemokines from infected bone marrow-derived macrophages from M1-γ34.5, M2-γ34.5, and WT mice suggested that upregulation of autophagy-blocking genes (i.e., Hif1a, Mtmr14, mTOR, Mtmr3, Stk11, and ULK2) and the inflammatory tumor necrosis factor alpha (TNF-α) gene in M1-γ34.5 transgenic mice correlated with increased pathogenicity, while upregulation of proautophagy genes (Nrbf2 and Rb1cc1) in M2-γ34.5 macrophages correlated with reduced pathogenicity. The in vivo and in vitro responses of M1-γ34.5 and M2-γ34.5 transgenic mice to HSV-1 infection were independent of the presence of the γ34.5 gene in wild-type HSV-1. Our results suggest that M1 macrophages, but not M2 macrophages, play an important role in autophagy relative to primary virus replication in the eye and eye disease in infected mice. IMPORTANCE Autophagy plays a critical role in clearing, disassembling, and recycling damaged cells, thus limiting inflammation. The HSV-1 γ34.5 gene is involved in neurovirulence and immune evasion by blocking autophagy in infected cells. We found that blocking autophagy in M1 macrophages enhances HSV-1 virus replication in the eye and eye disease in ocularly infected transgenic mice. Our results also show the suppressive effects of γ34.5 on immune responses to infection, suggesting the importance of intact autophagy in M1 but not M2 macrophages in controlling primary infection and eye disease.


Effect of cellulose and lignin content on the mechanical properties and drop-weight impact damage of injection-molded polypropylene-flax and -pine fiber composites.
Designing bio-composites for structural applications requires a thorough understanding of their mechanical behavior. In this study, we examined the differences in the tensile strength and drop-weight impact response between polypropylene reinforced with flax fibers and that reinforced with pinewood short fibers, as both fibers differ in composition (cellulose, hemicellulose, and lignin) and length-to-diameter ratio. We found that flax fibers, which have higher cellulose content and are twice as long as pine fibers, increased the stiffness and shock resistance of bio-composite materials. However, pine fibers, which contain more lignin, showed increased material ductility and energy absorption. Impulse excitation, acoustic emission and micro-CT techniques were used to evaluate the post-impact mechanical properties and the contribution of each damage mechanism to the final material failure (tearing). The experimental results were used to validate a model based on finite elements. Our results revealed that the experimental and finite-element analyses were in good agreement.


Implicit transitive inference and the human hippocampus: does intravenous midazolam function as a reversible hippocampal lesion?
Recent advances have led to an understanding that the hippocampus is involved more broadly than explicit or declarative memory alone. Tasks which involve the acquisition of complex associations involve the hippocampus whether the learning is explicit or implicit. One hippocampal-dependent implicit task is transitive inference (TI). Recently it was suggested that implicit transitive inference does not depend upon the hippocampus (Frank, M. J., O'Reilly, R. C., & Curran, T. 2006. When memory fails, intuition reigns: midazolam enhances implicit inference in humans. Psychological Science, 17, 700-707). The authors demonstrated that intravenous midazolam, which is thought to inactivate the hippocampus, may enhance TI performance. Three critical assumptions are required but not met: 1) that deactivations of other regions could not account for the effect 2) that intravenous midazolam does indeed deactivate the hippocampus and 3) that midazolam influences explicit but not implicit memory. Each of these assumptions is seriously flawed. Consequently, the suggestion that implicit TI does not depend upon the hippocampus is unfounded.


Assessment of atherosclerosis by carotid intimomedial thickness in patients with rheumatoid arthritis.
To determine the prevalence of subclinical (asymptomatic) atherosclerosis in patients with rheumatoid arthritis (RA) and to study the variables affecting such an occurrence. Case control study which included 100 patients with RA having disease duration more than 5 years and 100 healthy age and sex matched controls. Cases and controls symptomatic for atherosclerosis or having traditional risk factors for atherosclerosis were excluded. Both cases and controls were subjected to carotid ultrasound examination in addition to detailed history and physical examination. The study population (both cases and controls) included 94 females and 6 males. The mean age of cases and controls was similar (44.06 +/- 11.32 years and 44.1 +/- 11.52 years). The mean disease duration was 155.04 +/- 48.8 months. The mean carotid intimo-medial thickness (CIMT) of the RA patients (0.519 +/- 0.18 mm) was significantly greater than the controls (0.387 +/- 0.085). Age and disease duration were the only factors found to significantly affect CCIMT. RA patients had higher prevalence of carotid plaques (21%) compared to controls (1%). Erosions on hand radiographs were the only significant predictor of plaques in patients with RA. Patients with RA exhibit premature atherosclerosis by way of increased CIMT and carotid plaques when compared to age and sex matched controls.


pynk : Breast Cancer Program for Young Women.
CONSIDER THIS SCENARIO: A 35-year-old recently married woman is referred to a surgeon because of a growing breast lump. After a core biopsy shows cancer, she undergoes mastectomy for a 6-cm invasive lobular cancer that has spread to 8 axillary nodes. By the time she sees the medical oncologist, she is told that it is too late for a fertility consultation, and she receives a course of chemotherapy. At clinic appointments, she seems depressed and admits that her husband has been less supportive than she had hoped. After tamoxifen is started, treatment-related sexuality problems and the probability of infertility contribute to increasing strain on the couple's relationship. Their marriage ends two years after the woman's diagnosis.Six years after her diagnosis, this woman has completed all treatment, is disease-free, and is feeling extremely well physically. However, she is upset about being postmenopausal, and she is having difficulty adopting a child as a single woman with a history of breast cancer. Could this woman and her husband have been offered additional personalized interventions that might have helped them better cope with the breast cancer diagnosis and the effects of treatment?Compared with their older counterparts, young women with breast cancer often have greater and more complex supportive care needs. The present article describes the goals, achievements, and future plans of a specialized interdisciplinary program-the first of its kind in Canada-for women 40 years of age and younger newly diagnosed with breast cancer. The program was created to optimize the complex clinical care and support needs of this population, to promote research specifically targeting issues unique to young women, and to educate the public and health care professionals about early detection of breast cancer in young women and about the special needs of those women after their diagnosis.


Enhanced plastic deformations of nanofibrillated cellulose film by adsorbed moisture and protein-mediated interactions.
Biological composites are typically based on an adhesive matrix that interlocks rigid reinforcing elements in fiber composite or brick-and-mortar assemblies. In nature, the adhesive matrix is often made up of proteins, which are also interesting model systems, as they are unique among polymers in that we know how to engineer their structures with atomic detail and to select protein elements for specific interactions with other components. Here we studied how fusion proteins that consist of cellulose binding proteins linked to proteins that show a natural tendency to form multimer complexes act as an adhesive matrix in combination with nanofibrillated cellulose. We found that the fusion proteins are retained with the cellulose and that the proteins mainly affect the plastic yield behavior of the cellulose material as a function of water content. Interestingly, the proteins increased the moisture absorption of the composite, but the well-known plastifying effect of water was clearly decreased. The work helps to understand the functional basis of nanocellulose composites as materials and aims toward building model systems for molecular biomimetic materials.