Driving chemical reactions with polariton condensates.
When molecular transitions strongly couple to photon modes, they form hybrid light-matter modes called polaritons. Collective vibrational strong coupling is a promising avenue for control of chemistry, but this can be deterred by the large number of quasi-degenerate dark modes. The macroscopic occupation of a single polariton mode by excitations, as observed in Bose-Einstein condensation, offers promise for overcoming this issue. Here we theoretically investigate the effect of vibrational polariton condensation on the kinetics of electron transfer processes. Compared with excitation with infrared laser sources, the vibrational polariton condensate changes the reaction yield significantly at room temperature due to additional channels with reduced activation barriers resulting from the large accumulation of energy in the lower polariton, and the many modes available for energy redistribution during the reaction. Our results offer tantalizing opportunities to use condensates for driving chemical reactions, kinetically bypassing usual constraints of fast intramolecular vibrational redistribution in condensed phase.


Monohafnium oxide clusters HfO(n)- and HfO(n) (n = 1-6): oxygen radicals, superoxides, peroxides, diradicals, and triradicals.
The electronic and structural properties of monohafnium oxide clusters, HfO(n)(-) and HfO(n) (n = 1-6), are investigated using anion photoelectron spectroscopy and density-functional theory at the B3LYP level. The observed ground-state adiabatic detachment energy is low for HfO(-) (0.5 ± 0.1 eV) and HfO(2)(-) (2.125 ± 0.010 eV), roughly constant for HfO(3)(-) (3.6 ± 0.1 eV), HfO(4)(-) (3.67 ± 0.05 eV), and HfO(5)(-) (3.9 ± 0.1 eV), and substantially higher for HfO(6)(-) (4.9 ± 0.1 eV). Activated oxygen species, such as radical, superoxide, peroxide, diradical, and triradical, are identified in the HfO(n)(-) and HfO(n) clusters. The Hf center is shown to be flexible to accommodate the oxygen species. The sum of formal Hf-O bond orders around the Hf center is equal to four for all of the neutral clusters studied, and five for all of the anions. The O-rich HfO(n)(-) and HfO(n) (n = 3-6) clusters provide well-defined molecular models to understand O(2) adsorption and activation on an Hf center.


Contribution of TNF/TNF receptor and of Fas ligand to toxicity in murine models of endotoxemia and bacterial peritonitis.
Fas/Fas ligand and TNF/TNF receptors are involved in apoptosis. Whether both systems are involved in septic shock has not been determined so far. We investigated the role of TNF/TNFR and Fas/Fas ligand in models of endotoxemia and of speticemia in mice. Upon LPS challenge, TNF and TNFR p55 were involved in the process inducing lethality. FasL did not contribute to enhance lethality, as evidenced in gld mice, lacing FasL. Following an intraperitoneal injection of live E. coli, TNF and TNFR p55 were necessary to combat infection. Disruption of either gene was associated with enhanced lethality and failure to clear the bacteria. No effect observed in gld mice in this peritonitis model. Thus, these observations confirmed the pathogenic role of TNF/TNFR in endotoxemia and its beneficial role in local bacterial infections. In addition the data ruled out a major role for Fas/FasL in septic shock in mice.


Topically Applied Cross-Linked Hyaluronan Attenuates the Formation of Spinal Epidural Fibrosis in a Swine Model of Laminectomy.
Epidural fibrosis is an inevitable aspect of the postoperative healing process which is one of the causes of failed back surgery syndrome following spinal surgery. The aim of the present study was to examine the inhibitory effect of 1,4-butanediol diglycidyl ether-crosslinked hyaluronan (cHA) on spinal epidural fibrosis in a swine model. Epidural fibrosis was induced through conduction of hemi-laminotomy (L2 and L3) or laminectomy (L4 and L5), while L1 was assigned as the control group in six pigs. The cHA was applied to L3 and L5 surgical sites. MRI evaluation, histologic examination, expressions of matrix metalloproteinases (MMPs), and cytokines in scar tissue were assessed four months after surgery. cHA treatment significantly decreased the scar formation in both hemi-laminotomy and laminectomy sites. cHA also significantly increased MMP-3 and MMP-9 expression in scar tissue. Further, the epithelial-mesenchymal transition -related factors (transforming growth factor-β and vimentin) were suppressed and the anti-inflammatory cytokines (CD44 and interleukin-6) were increasingly expressed in cHA-treated sites. The current study demonstrated that cHA may attenuate spinal epidural fibrosis formation after laminectomy surgery by enhancing the expression of MMPs and anti-inflammatory pathways.


Acanthamoeba keratitis: study of the 5-year incidence in Israel.
Acanthamoeba keratitis (AK) is not a notifiable disease in Israel, so there are no accurate incidence rates for this condition in Israel. The aim of this study was to estimate the incidence of AK in Israel for the years 2008-2012. We distributed a survey questionnaire to laboratory managers in Israel. The laboratories were affiliated to medical institutes that either provided ophthalmology services or served community ophthalmology clinics. Our questionnaire requested survey respondents to provide information regarding the methods used to diagnose AK, and the number of positive and negative cultures for Acanthamoebae species performed for each of the years from 2008 to 2012. Six laboratories used non-nutrient agar with Escherichia coli as the culture medium, one used calcofluor-white staining with fluorescent microscopy, and two used PCR for diagnosing AK. Twenty-three AK cases were identified, to give an estimated incidence of 1/1 668 552. AK is mostly attributable to the use of contact lenses. As contact lenses are popular in Israel, we expected a higher incidence rate. A lower than expected incidence rate may indicate insufficient awareness of AK in Israel.


AMP analogs: their function in the activation of glycogen phosphorylase b.
A series of AMP analogs has been selected in order to better understand the structural requirements (a) for the efficient binding of the activator molecule at the correct site on phosphorylase b from rabbit skeletal muscle and (b) for the activation which is observed. Two types of activation are known, according to Black and Wang [J. Biol. Chem. 243, 5892-5898 (1968)]: either a cooperative response with respect to the activator concentration (like the one which is obtained for AMP itself) or a non-cooperative response observed in the case of IMP. It is shown that the 5'-phosphate moiety is absolutely required for the analog to bind at the correct site (adenine or adenosine bind at another enzymic site), and that the free enthalpy, delta G, corresponding to the association process varies in a complex manner with respect to the substitution of the different positions of the AMP molecule. Moreover, the differences delta G (analog) - delta G (AMP) = delta G obtained for two types of substitution separately do not add up to the same energy difference as the one obtained when the two substitutions are made simultaneously on the AMP molecule. It appears that all the mononucleotides which have been tested up to now may be divided into two classes. Class I (AMP class) is characterized, apart from a strong activation, by the following features: (a) one molecule of analog expels two molecules of bound glucose 6-phosphate as it binds on the enzyme; (b) bound analog protects slowly one crucial cysteinyl residue against attack by 5,5'-dithio-bis(2-nitrobenzoic acid) at 4 degrees C; (c) association of two molecules of dimer is strengthened at 4 degrees C in the presence of the analog. Class II (IMP class) is associated with a weak activation and with the following set of properties: (a) a single molecule of bound glucose 6-phosphate is released as the first molecule of analog binds on the dimer; (b) two slowly reacting cysteinyl residues per subunit are immediately protected against 5,5'-dithio-bis(2-nitrobenzoic acid) by the binding of the analog at 4 degrees C; (c) the analog dissociates the low amount of tetramer which is present at 4 degrees C in the absence of AMP into two molecules of dimer. These results are discussed according to a plausible scheme of transconformations taking place in glycogen phosphorylase b, a model which has been derived earlier by relaxation studies.


H2MBH2 and M(μ-H)2BH2 Molecules Isolated in Solid Argon: Interelement M-B and M-H-B Bonds (M = Ge, Sn).
Laser-ablated boron atoms react with GeH4 molecules to form novel germylidene borane H2GeBH2, which undergoes a photochemical rearrangement to the germanium tetrahydroborate Ge(μ-H)2BH2 upon irradiation with light of λ = 405 nm. For comparison, the boron atom reactions with SnH4 only gave the tin tetrahydroborate Sn(μ-H)2BH2. Infrared matrix-isolation spectroscopy with deuterium substitution and the state-of-the-art quantum-chemical calculations are used to identify these species in solid argon. A planar structure of H2GeBH2 with an electron-deficient B-Ge bond with a partial multiple bond character (bond order = 1.5) is predicted by quantum-chemical calculations. In the case of M(μ-H)2BH2 (M = Ge, Sn) two 3c-2e B-H-M hydrogen bridged bonds are formed by donation of electrons from the B-H σ-bonds into empty p-orbitals of M.


Multi-level determinants of parasitic fly infection in forest passerines.
The study of myiasis is important because they may cause problems to the livestock industry, public health, or wildlife conservation. The ecology of parasitic dipterans that cause myiasis is singular, as they actively seek their hosts over relatively long distances. However, studies that address the determinants of myiasis dynamics are very scarce. The genus Philornis include species that may be excellent models to study myiasis ecology, as they exclusively parasitize bird nestlings, which stay in their nests until they are fully fledged, and larvae remain at the point of entry until the parasitic stage is over, thus allowing the collection of sequential individual-level infection data from virtually all the hosts present at a particular area. Here we offer a stratified multi-level analysis of longitudinal data of Philornis torquans parasitism in replicated forest bird communities of central Argentina. Using Generalized Linear Models and Generalized Linear Mixed Models and an information theory approach for model selection, we conducted four groups of analyses, each with a different study unit, the individual, the brood, the community at a given week, and the community at a given year. The response variable was larval abundance per nestling or mean abundance per nestling. At each level, models included the variables of interest of that particular level, and also potential confounders and effect modifiers of higher levels. We found associations of large magnitude at all levels, but only few variables truly governed the dynamics of this parasite. At the individual level, the infection was determined by the species and the age of the host. The main driver of parasite abundance at the microhabitat level was the average height of the forest, and at the community level, the density of hosts and prior rainfall. This multi-level approach contributed to a better understanding of the ecology of myiasis.


PtAg18 superatoms costabilized by phosphines and halides: synthesis, structure, and catalysis.
Reported herein is the facial synthesis, molecular structure, and catalysis of a Pt/Ag nanocluster costabilized by organic ligands of phosphines and inorganic ligands of chlorides. The nanocluster with molecular formula of [PtAg18(dppp)6Cl8](SbF6)2 has been obtained facilely by the one pot method. The structure of the cluster could be anatomized as the stabilizaiton of PtAg12-centered icosahedral core by the metalloligand of dppp-Ag-Cl, in which Cl- not only caps the surface Ag atoms but also binds the core and surface motifs. Featuring eight free electrons in its structure, the cluster exhibits high stability. More interestingly, the exposure of surface metal sites endows the cluster with counterintutively high catalytic activity in hydrogenation reactions.


Transient level-set topology optimization of a planar acoustic lens working with short-duration pulse.
With the advance of additive manufacturing, many researchers are increasingly interested in planar acoustic lenses that are not only easier to fabricate than typical convex/concave lenses, but also have excellent imaging performance. However, the planar acoustic lenses reported so far cannot work for a short-duration pulse used in conventional imaging systems due to their inherent dispersive characteristics. This study addresses the challenge by devising a transient topology optimization formulation to design a planar acoustic lens that works effectively for a short-duration pulse. A planar lens consists of two materials where optimal combination and distribution are obtained with a crisp interface via the level-set method. Design is based on the transient acoustic responses, which are calculated from a time-dependent acoustic model solved by the Newmark method. The proposed method uses the area-fraction approach to compute the acoustic properties of a cut element by the interface. A localizing time-window function is introduced so that acoustic energy can be focused within the desired time range as much as possible. We obtain optimum design solutions designed with the proposed method and verify its effectiveness through the numerical investigations.


Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells.
CD4(+) regulatory T cells play a critical role in tolerance induction in transplantation. CD8(+) suppressor T cells have also been shown to control alloimmune responses in preclinical and clinical models. However, the exact nature of the CD8(+) suppressor T cells, their induction and mechanism of function in allogeneic transplantation remain elusive. In this study, we show that functionally suppressive, alloantigen-specific CD8(+) Foxp3(+) T cells can be induced and significantly expanded by stimulating naïve CD8(+) T cells with donor dendritic cells in the presence of IL-2, TGF-β1 and retinoic acid. These CD8(+) Foxp3(+) T cells express enhanced levels of CTLA-4, CCR4 and CD103, inhibit the up-regulation of costimulatory molecules on dendritic cells, and suppress CD4 and CD8 T cell proliferation and cytokine production in a donor-specific and contact-dependent manner. Importantly, upon adoptive transfer, the induced CD8(+) Foxp3(+) T cells protect full MHC-mismatched skin allografts. In vivo, the CD8(+) Foxp3(+) T cells preferentially traffic to the graft draining lymph node where they induce conventional CD4(+) Foxp3(+) T cells and concurrently suppress effector T cell expansion. We conclude that donor-specific CD8(+) Foxp3(+) suppressor T cells can be induced and exploited as an effective form of cell therapy for graft protection in transplantation.


Fluorescence resonance energy transfer analysis of escherichia coli RNA polymerase and polymerase-DNA complexes.
Fluorescence resonance energy transfer (FRET) is a technique allowing measurements of atomic-scale distances in diluted solutions of macromolecules under native conditions. This feature makes FRET a powerful tool to study complicated biological assemblies. In this report we review the applications of FRET to studies of transcription initiation by Escherichia coli RNA polymerase. The versatility of FRET for studies of a large macromolecular assembly such as RNA polymerase is illustrated by examples of using FRET to address several different aspects of transcription initiation by polymerase. FRET has been used to determine the architecture of polymerase, its complex with single-stranded DNA, and the conformation of promoter fragment bound to polymerase. FRET has been also used as a binding assay to determine the thermodynamics of promoter DNA fragment binding to the polymerase. Functional conformational changes in the specificity subunit of polymerase responsible for the modulation of the promoter binding activity of the enzyme and the mechanistic aspects of the transition from the initiation to the elongation complex were also investigated.


Expanding the chronic care framework to improve diabetes management: the REACH case study.
Reducing the burden of chronic conditions among minorities requires novel approaches to prevent and manage disease. This paper describes the expansion of the Chronic Care Model (CCM) to include a community focus for improving diabetes self-management and reducing health disparities. The literature review assesses the concept of "community" in improving outcomes as viewed by proponents of the CCM for chronic disease. The CCM was then modified and informed by experiences of a major community-based participatory action initiative to improve diabetes outcomes, the Racial and Ethnic Approaches to Community Health (REACH) Charleston and Georgetown Diabetes Coalition. Based on our experiences with community-based and health systems diabetes interventions, we present examples of improvements within both health delivery practice sites and other community systems that are essential for improving diabetes outcomes and reducing disparities. Building on the Centers for Disease Control and Prevention's (CDC) principles of community involvement, our coalition activities provide examples of working with community partners to frame this enhanced ecologically grounded Community CCM (CCCM). The resulting CCCM integrates expanded conceptual frameworks, evidence-based practice, community-based evidence and participatory actions, and highlights the possibilities and challenges for improving chronic disease outcomes and reducing disparities via community programs that foster individual, systems, community, and policy change.


Early recognition of toxicity by assessing nervous system function.
Many industrial substances, such as pesticides, solvents, and heavy metals, are toxic to the human nervous system. Nervous system function provides an excellent means for assessing the early effects of toxic substances. A large percentage of occupational chemicals that are recognized to produce adverse health effects in general also adversely affect the nervous system. Reliable and low-cost methods, including psychometric tests and nerve conduction velocity assessment, have been developed for evaluating nervous system function. By monitoring nervous system function in workers exposed to neurotoxic chemicals, early signs of chemical toxicity can be detected. Appropriate action following detection of early signs of neurotoxicity may then avert permanent and debilitating nervous system disorder and may help to limit exposure to toxic substances affecting other organ systems as well as the nervous system. A monitoring program along with its rationale is described in this paper.


Ultrathin and Conformal Initiated Chemical-Vapor-Deposited Layers of Systematically Varied Surface Energy for Controlling the Directed Self-Assembly of Block CoPolymers.
Directed self-assembly (DSA) of block copolymer (BCP) thin films is a promising approach to enable next-generation patterning at increasingly smaller length scales. DSA utilizes interfacial wetting layers to force the BCP domains to self-assemble with the desired orientation with respect to the substrate. Here, we demonstrate that initiated chemical-vapor-deposited (iCVD) polydivinylbenzene (pDVB) ultrathin films can direct the self-assembly of poly(styrene- block-methylmethacrylate). We found that the methyl radicals formed at increased filament temperatures during the iCVD process result in the backbone methylation of pDVB. By tuning the degree of backbone methylation, we systematically changed the wetting properties of the iCVD pDVB from a slight poly(methylmethacrylate) preference to complete poly(styrene) preference. Additionally, we utilize the conformal nature of the iCVD to form a wetting layer over a topographical line and space pattern, which is subsequently used to produce self-assembled BCP films with both perpendicular orientation and long-range alignment.


Are Explicit Solvent Models More Accurate than Implicit Solvent Models? A Case Study on the Menschutkin Reaction.
In this work, contemporary quantum mechanical (QM) implicit solvent models (SMD, SM12, and COSMO-RS) and a molecular mechanical (MM) explicit solvent model were used to predict the aqueous free energy barrier of a simple Menschutkin reaction (NH3 + CH3Cl). Surprisingly, the explicit solvent approach performed the worst, while the implicit solvent models yielded reasonably accurate values that are in accord with available experimental data. The origin of the large error in the explicit solvent model was due to the use of a fixed set of Lennard-Jones parameters during the free energy perturbation (FEP) calculations. Further analyses indicate that M06-2X/6-31+G(d,p) yielded solute-solvent interaction energies that are in good agreement with benchmark DLPNO-CCSD(T)/CBS values. When end-state MM to M06-2X/6-31+G(d,p) corrections were added using FEP, it significantly improved the accuracy of the explicit solvent MM result and demonstrated that the accuracy of these models may be systematically improved with end-state corrections based on a validated QM level of theory.


Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?).
A single determinant factor for autoimmunity does not exist; disease development probably involves contributions from genetics, the environment and immune dysfunction. Type 1 diabetes is no exception. Genomewide-associated studies (GWAS) analysis in T1D has proved disappointing in revealing contributors to disease prediction; the only reliable marker has been human leucocyte antigen (HLA). Specific HLAs include DR3/DR4/DQ2/DQ8, for example. Because HLA molecules present antigen to T cells, it is reasonable that certain HLA molecules have a higher affinity to present self-antigen. Recent studies have shown that additional polymorphisms in HLA that are restricted to autoimmune conditions are further contributory. A caveat is that not all individuals with the appropriate 'pro-autoimmune' HLA develop an autoimmune disease. Another crucial component is autoaggressive T cells. Finding a biomarker to discriminate autoaggressive T cells has been elusive. However, a subset of CD4 helper cells that express the CD40 receptor have been described as becoming pathogenic. An interesting function of CD40 on T cells is to induce the recombination-activating gene (RAG)1/RAG2 T cell receptor recombination machinery. This observation is contrary to immunology paradigms that changes in TCR molecules cannot take place outside the thymic microenvironment. Alteration in TCR, called TCR revision, not only occurs, but may help to account for the development of autoaggressive T cells. Another interesting facet is that type 1 diabetes (T1D) may be more than a single disease; that is, multiple cellular components contribute uniquely, but result ultimately in the same clinical outcome, T1D. This review considers the process of T cell maturation and how that could favor auto-aggressive T cell development in T1D. The potential contribution of TCR revision to autoimmunity is also considered.


A simplified model to estimate nonlinear turbulent transport by linear dynamics in plasma turbulence.
A simplified model to estimate nonlinear turbulent transport only by linear calculations is proposed, where the turbulent heat diffusivity in tokamak ion temperature gradient(ITG) driven turbulence is reproduced for a wide parameter range including near- and far-marginal ITG stability. The optimal nonlinear functional relation(NFR) between the turbulent diffusivity, the turbulence intensity [Formula: see text], and the zonal-flow intensity [Formula: see text] is determined by means of mathematical optimization methods. Then, an extended modeling for [Formula: see text] and [Formula: see text] to incorporate the turbulence suppression effects and the temperature gradient dependence is carried out. The simplified transport model is expressed as a modified nonlinear function composed of the linear growth rate and the linear zonal-flow decay time. Good accuracy and wide applicability of the model are demonstrated, where the regression error of [Formula: see text] indicates improvement by a factor of about 1/4 in comparison to that in the previous works.


Alcohol intake and insulin levels. The Normative Aging Study.
Much remains to be clarified in the apparently protective effect of moderate alcohol use against coronary heart disease risk. Insulin levels are positively associated with coronary heart disease risk, so recent reports of decreased insulin sensitivity among nondrinkers and lower fasting insulin levels with increasing alcohol intake suggest the possibility that insulin may play a role. Between 1987 and 1991, the authors examined fasting insulin concentrations and the empiric fasting insulin resistance index in relation to reported alcohol intake (mean, 15.3 g/day; standard deviation, 19.6; range, 0-120.6) and potential confounders. The latter included age, obesity, fat distribution, smoking, energy, saturated fat intake, antihypertensive medication, and physical activity. Participants in this cross-sectional analysis were 938 nondiabetic men from the Boston, Massachusetts, area who were part of the Normative Aging Study. Unadjusted fasting insulin levels were significantly different (p = 0.008) between categories of alcohol intake, as were fasting insulin resistance index values (p = 0.01). After adjustment for potential confounders, analysis revealed that subjects consuming moderate amounts of alcohol had the lowest fasting insulin and fasting insulin resistance index values. Compared with values from moderate drinkers, fasting insulin resistance index values were higher in those subjects reporting no alcohol intake (p = 0.011), low intake (p = 0.004), and high intake (p = 0.04). A similar pattern was observed for fasting insulin values. Among this sample of nondiabetic men, moderate drinkers had the lowest levels of fasting insulin resistance index and fasting insulin, consistent with lower levels of insulin resistance and thus lower risk for coronary heart disease. These findings suggest the possibility that the coronary heart disease-protective effects of moderate alcohol use are at least partially mediated by insulin.


Polyacrylamide hydrogel encapsulated E. coli expressing metal-sensing green fluorescent protein as a potential tool for copper ion determination.
A simple, inexpensive and field applicable metal determination system would be a powerful tool for the efficient control of metal ion contamination in various sources e.g. drinking-water, water reservoir and waste discharges. In this study, we developed a cell-based metal sensor for specific and real-time detection of copper ions. E. coli expressing metal-sensing green fluorescent protein (designated as TG1/(CG)6GFP and TG1/H6CdBP4GFP) were constructed and served as a metal analytical system. Copper ions were found to exert a fluorescence quenching effect, while zinc and cadmium ions caused minor fluorescence enhancement in the engineered bacterial suspension. To construct a user-friendly and reagentless metal detection system, TG1/H6CdBP4GFP and TG1/(CG)6GFP were encapsulated in polyacrylamide hydrogels that were subsequently immobilized on an optical fiber equipped with a fluorescence detection module. The sensor could be applied to measure metal ions by simply dipping the encapsulated bacteria into a metal solution and monitoring fluorescence changes in real time as a function of the metal concentration in solution. The sensor system demonstrated high specificity toward copper ions. The fluorescence intensities of the encapsulated TG1/(CG)6GFP and TG1/H6CdBP4GFP were quenched by approximately 70 % and 80 % by a high-dose of copper ions (50 mM), respectively. The level of fluorescence quenching exhibited a direct correlation with the copper concentration, with a linear correlation coefficient (r) of 0.99. The cell-based metal sensor was able to efficiently monitor copper concentrations ranging between 5 M and 50 mM, encompassing the maximum allowed copper contamination in drinking water (31.15 M) established by the WHO. Furthermore, the cell-based metal sensor could undergo prolonged storage for at least 2 weeks without significantly influencing the copper sensitivity.


Forensic drug analysis and microfluidics.
The analysis of drugs of abuse in microfluidic devices has the potential to provide solutions to today's on-site analysis challenges. The use of such devices has not been limited to miniaturising conventional analytical methods used routinely in forensic laboratories; new and interesting approaches have been implemented in microfluidics and benefit from the ability to control minute amounts of liquids in the small channels. The microfluidic platforms developed so far have been used successfully to carry out single or multiple analytical processes and offer a great opportunity for new technologies for on-site drug testing.


[Analysis of variables associated to undetectable viral load and therapeutic failure in HIV-infected individuals].
To date, antiretroviral therapies have not led to total HIV eradication in infected individuals. The achievement of undetectable viremia levels has been regarded as essential when monitorizing the efficacy of these therapies. The objectives of our study were to assess the time needed to achieve viral load (VL) undetectable levels and subsequent VL risings, as well as to determine the clinical variables associated with both events. Owing to a follow-up period greater than 1,000 days, 314 patients were retrospectively selected. We determined the percentages of patients with undetectable VL levels and of those with subsequent VL rising. Times needed to reach both events were calculated by Kaplan-Meier analysis. 182 individuals (58%; 95% CI, 52.3-63.5) reached undetectable VL levels with a median follow-up time of 862 days. A more regular VL quantitation was associated with such event. The VL level of 38 out of these individuals (20.9%; 95% CI, 15.2-27.5) increased subsequently (> 30,000 RNA copies/ml) with a mean time of 328 days (after the first undetectable VL determination); this event was associated with changes in the clinical centre where the patient was being cared for. In our series, the proportion of individuals with undetectable VL levels and therapeutic failure was low. The frequency of VL determination was a determining factor in the evolution of these patients.


Image Projection Network: 3D to 2D Image Segmentation in OCTA Images.
We present an image projection network (IPN), which is a novel end-to-end architecture and can achieve 3D-to-2D image segmentation in optical coherence tomography angiography (OCTA) images. Our key insight is to build a projection learning module (PLM) which uses a unidirectional pooling layer to conduct effective features selection and dimension reduction concurrently. By combining multiple PLMs, the proposed network can input 3D OCTA data, and output 2D segmentation results such as retinal vessel segmentation. It provides a new idea for the quantification of retinal indicators: without retinal layer segmentation and without projection maps. We tested the performance of our network for two crucial retinal image segmentation issues: retinal vessel (RV) segmentation and foveal avascular zone (FAZ) segmentation. The experimental results on 316 OCTA volumes demonstrate that the IPN is an effective implementation of 3D-to-2D segmentation networks, and the uses of multi-modality information and volumetric information make IPN perform better than the baseline methods.


Clustering behaviors in networks of integrate-and-fire oscillators.
Clustering behavior is studied in a model of integrate-and-fire oscillators with excitatory pulse coupling. When considering a population of identical oscillators, the main result is a proof of global convergence to a phase-locked clustered behavior. The robustness of this clustering behavior is then investigated in a population of nonidentical oscillators by studying the transition from total clustering to the absence of clustering as the group coherence decreases. A robust intermediate situation of partial clustering, characterized by few oscillators traveling among nearly phase-locked clusters, is of particular interest. The analysis complements earlier studies of synchronization in a closely related model.


Immunologic renal injury.
This review summarizes recent progress in the immunologic aspects of parenchymal renal disease. Progress in understanding basic immune mechanisms of glomerular injury is outlined, including the roles of chemoattractants, adhesion molecules, metalloproteinases, and cytokines. Current basic and clinical studies of focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, minimal-change nephropathy, and IgA nephropathy are summarized. Finally, research in glomerular involvement in systemic disorders, such as lupus nephritis, antineutrophil cytoplasmic antibody-associated syndromes, and human immunodeficiency virus-associated nephropathy, is reviewed.


Thirst neurons anticipate the homeostatic consequences of eating and drinking.
Thirst motivates animals to drink in order to maintain fluid balance. Thirst has conventionally been viewed as a homeostatic response to changes in blood volume or tonicity. However, most drinking behaviour is regulated too rapidly to be controlled by blood composition directly, and instead seems to anticipate homeostatic imbalances before they arise. How this is achieved remains unknown. Here we reveal an unexpected role for the subfornical organ (SFO) in the anticipatory regulation of thirst in mice. By monitoring deep-brain calcium dynamics, we show that thirst-promoting SFO neurons respond to inputs from the oral cavity during eating and drinking and then integrate these inputs with information about the composition of the blood. This integration allows SFO neurons to predict how ongoing food and water consumption will alter fluid balance in the future and then to adjust behaviour pre-emptively. Complementary optogenetic manipulations show that this anticipatory modulation is necessary for drinking in several contexts. These findings provide a neural mechanism to explain longstanding behavioural observations, including the prevalence of drinking during meals, the rapid satiation of thirst, and the fact that oral cooling is thirst-quenching.


Effects of glucose oxidase on growth performance, clinical symptoms, serum parameters, and intestinal health in piglets challenged by enterotoxigenic Escherichia coli.
Glucose oxidase (GOD) could benefit intestinal health and growth performance in animals. However, it is unknown whether GOD can protect piglets against bacterial challenge. This study aimed to evaluate the protective effects of GOD on growth performance, clinical symptoms, serum parameters, and intestinal health in piglets challenged by enterotoxigenic Escherichia coli (ETEC). A total of 44 male weaned piglets around 38 days old were divided into four groups (11 replicates/group): negative control (NC), positive control (PC), CS group (PC piglets +40 g/t colistin sulfate), and GOD group (PC piglets +200 g/t GOD). All piglets except those in NC were challenged with ETEC (E. coli K88) on the 11th day of the experiment. Parameter analysis was performed on the 21st day of the experiment. The results showed that the ETEC challenge elevated (p < 0.05) the rectal temperature and fecal score of piglets at certain time-points post-challenge, reduced (p < 0.05) serum glucose and IgG levels but increased (p < 0.05) serum alanine aminotransferase activity, as well as caused (p < 0.05) intestinal morphology impairment and inflammation. Supplemental GOD could replace CS to reverse (p < 0.05) the above changes and tended to increase (p = 0.099) average daily gain during the ETEC challenge. Besides, GOD addition reversed ETEC-induced losses (p < 0.05) in several beneficial bacteria (e.g., Lactobacillus salivarius) along with increases (p < 0.05) in certain harmful bacteria (e.g., Enterobacteriaceae and Escherichia/Shigella). Functional prediction of gut microbiota revealed that ETEC-induced upregulations (p < 0.05) of certain pathogenicity-related pathways (e.g., bacterial invasion of epithelial cells and shigellosis) were blocked by GOD addition, which also normalized the observed downregulations (p < 0.05) of bacterial pathways related to the metabolism of sugars, functional amino acids, nucleobases, and bile acids in challenged piglets. Collectively, GOD could be used as a potential antibiotic alternative to improve growth and serum parameters, as well as attenuate clinical symptoms and intestinal disruption in ETEC-challenged piglets, which could be associated with its ability to mitigate gut microbiota dysbiosis. Our findings provided evidence for the usage of GOD as an approach to restrict ETEC infection in pigs.


Rotational Stability of Scaphoid Osteosyntheses: An In Vitro Comparison of Small Fragment Cannulated Screws to Novel Bone Screw Sets.
The current standard of care for operative repair of scaphoid fractures involves reduction and internal fixation with a single headless compression screw. However, a compression screw in isolation does not necessarily control rotational stability at a fracture or nonunion site. The single screw provides rotational control through friction and bone interdigitation from compression at the fracture site. We hypothesize that osteosyntheses with novel bone screw sets (BSS) equipped with anti-rotational elements provide improved rotational stability. Stability of osteosynthesis under increasing cyclic torsional loading was investigated on osteotomized cadaveric scaphoids. Two novel prototype BSS, oblique type (BSS-obl.) and longitudinal type (BSS-long.) were compared to three conventional screws: Acutrak2®mini, HCS®3.0 and Twinfix®. Biomechanical tests were performed on scaphoids from single donors in paired comparison and analyzed by balanced incomplete random block design. Loading was increased by 50 mNm increments with 1,000 cycles per torque level and repeated until a rotational clearance of 10°. Primary outcome measure was the number of cycles to 10° clearance, secondary outcome measure was the maximum rotational clearance for each torque level. BSS-obl. performed significantly better than Acutrak2®mini and HCS® (p = 0.015, p<0.0001). BSS-long. performed significantly better than HCS® (p = 0.010). No significant difference in performance between BSS-obl. and BSS-long. (p = 0.361), between BSS obl. and Twinfix® (p = 0.50) and BSS long. and Twinfix® (p = 0.667) was detected. Within the torque range up to 200 mNm, four of 21 (19%) BSS-long. and four of 21 (19%) BSS-obl. preparations showed early failure. The same loading led to early failure in four (29%) Twinfix®, seven (50%) Acutrak2®mini and 10 (71%) HCS® of 14 screw samples, respectively. For both BSS and to a lesser extent for Twinfix® (as dual-component screw), higher rotational stabilities were identified in comparison to single component headless compression screws.


Acute effect of different time periods of passive static stretching on the hamstring flexibility.
Several factors are associated with the presence of chronic low back pain; one of them is the flexibility of the hamstring muscles that influences the posture of the pelvic spine. Investigate the influence of two different time periods of passive static stretching on the flexibility of the hamstring. Forty-six physiotherapy students were divided into two groups performing stretching exercises: 30 s and 60 s duration. The collections consisted of: (1) pre-test: evaluation of the flexibility of the hip and knee, using a manual goniometer by means of the following tests: Straight Leg Raise Test (SLR), Passive Hip Flexion Test (PHFT) and Modified Knee Extension Test (MKET), (2) intervention: stretching with different runtimes, (3) post-test: reappraisal of flexibility, conducted immediately after the intervention. Significant difference was observed intra groups, group that did stretching exercises lasting 30 seconds (G30) (SLR p = 0.000. PHFT p = 0.003 and MKET p = 0.000) and group that did stretching exercises lasting 60 seconds (G60) (SLR p = 0.000. PHFT p = 0.001 and MKET p = 0.002). Comparing the groups, no significant difference was found (SLR p = 0.307; PHFT p = 0.904; MKET p = 0.132). Thus it can be inferred that 30 seconds are sufficient for increased flexibility of young women. Therefore the time-treatment sessions can be optimized. Only the acute effect of stretching was observed; further investigation of the long-term effect is required.


From fisherman to fibrillation: an unbroken line of progress.
The modern era of cardiac arrhythmia surgery was initiated by Dr Will C. Sealy in May 1968, when he performed the first successful surgical division of an accessory pathway for the treatment of the Wolff-Parkinson-White syndrome. During the subsequent 25 years, arrhythmia operations evolved through a series of innovative surgical procedures capable of curing essentially all refractory clinical arrhythmias. The lessons learned during the development of these surgical procedures ultimately led to the refinement and eventual success of less invasive catheter techniques that have now replaced most of these surgical techniques. The surgical experience gained during these years also made possible the current surgical procedure that is used to treat the most complex, and the most common, of all cardiac arrhythmias, atrial fibrillation. Few areas of any specialty are as clearly defined as the unbroken line of progress that extends from Dr Sealy's first procedure in 1968 to the successful surgical treatment of atrial fibrillation in 1994.


Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal.
To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions. Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to "ex vivo" normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3). Profiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels. Our comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis.


Cross-cultural adaptation and validation of the Italian version of the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score.
The Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow score is a reliable and sensitive tool to measure the performance of overhead athletes. The purpose of this study was to carry out a cross-cultural adaptation and validation of the KJOC questionnaire in Italian and to assess its reliability, validity, and responsiveness. Ninety professional athletes with a painful shoulder were included in this study and were assigned to the "injury group" (n = 32) or the "overuse group" (n = 58); 65 were managed conservatively and 25 were treated by arthroscopic surgery. To assess the reliability of the KJOC score, patients were asked to fill in the questionnaire at baseline and after 2 weeks. To test the construct validity, KJOC scores were compared to those obtained with the Italian version of the Disabilities of the Arm, Shoulder, and Hand (DASH) scale, and with the DASH sports/performing arts module. To test KJOC score responsiveness, the follow-up KJOC scores of the participants treated conservatively were compared to those of the patients treated by arthroscopic surgery. Statistical analysis demonstrated that the KJOC questionnaire is reliable in terms of the single items and the overall score (ICC 0.95-0.99); that it has high construct validity (r s = -0.697; p < 0.01); and that it is responsive to clinical differences in shoulder function (p < 0.0001). The Italian version of the KJOC Shoulder and Elbow score performed in a similar way to the English version and demonstrated good validity, reliability, and responsiveness after conservative and surgical treatment. II.


Hospitalization costs ofTAVI in one Belgian university hospital.
Considering the sizeable cost of transcatheter aortic valve implantation (TAVI) and conflicting cost-effectiveness studies, it is useful to gain more insight into the cost structure of the TAVI hospitalization. This study provides such a cost analysis and starts to evaluate options to soften the hospitalization cost burden in order to make TAVI economically more feasible. Costs forTAVI hospitalization in the University Hospital of Antwerp were analysed uni- and bivariately. Graphical and numerical displays of the data are supplemented with the non-parametric Wilcoxon rank sum statistic and Spearman rank rho correlation. Overall, 47 percent of the cost could be attributed to the implanted valve and 21 percent was accounted for by the room costs. Further, costs seemed highly insensitive to pre-existing patient characteristics. Only patients with pulmonary hypertension were characterized with systematically higher costs (Wilcoxon rank sum P-value of 0.049). Complications related to TAVI had a significant upward impact on the costs and there was also evidence for a learning effect on total costs. In general the analyses showed that only limited options remain for cost reduction of the TAVI hospitalization cost. The most promising option is the reduction of the valve price. Avoidance of complications is hard to achieve given the current state of the art although this would significantly reduce overall costs.


Do glycemic markers predict occurrence of complications after total knee arthroplasty in patients with diabetes?
Patients with diabetes have increased risk of infections and wound complications after total knee arthroplasty (TKA). Glycemic markers identifying patients at risk for complications after TKA have not yet been elucidated. We aimed to determine the correlations among four commonly used glycemic markers and to identify the glycemic markers most strongly associated with the occurrence of surgical site infections and postoperative wound complications in patients with diabetes mellitus after undergoing TKA. Our retrospective study included 462 patients with diabetes, who underwent a total of 714 TKAs. Blood levels of glycemic markers, including preoperative fasting blood glucose (FBG), postprandial glucose (PPG2), glycated hemoglobin (HbA1c), and levels obtained from random glucose testing on postoperative days 2, 5, and 14, were collected on all patients as part of a medical clearance program and an established clinical pathway for patients with diabetes at our center. Complete followup was available on 93% (462 of 495) of the patients. Correlations among markers were assessed. Associations between the markers and patient development of complications were analyzed using multivariate regression analyses of relevant cutoff values. We considered any of the following as complications potentially related to diabetes, and these were considered study endpoints: surgical site infection (superficial and deep) and wound complications (drainage, hemarthrosis, skin necrosis, and dehiscence). During the period of study, there were no fixed criteria applied to what levels of glycemic control patients with diabetes needed to achieve before undergoing arthroplasty, and there were wide ranges in the levels of all glycemic markers; for example, whereas the mean HbA1c level was 7%, the range was 5% to 11.3%. There were positive correlations among the levels of the four glycemic markers; the strongest correlation was found between the preoperative HbA1c and PPG2 levels (R = 0.502, p < 0.001). After controlling for potential confounding variables using multivariate analysis, the HbA1c cutoff level of 8 (odds ratio [OR], 6.1; 95% confidence interval [CI], 1.6-23.4; p = 0.008) and FBG 200 mg/dL or higher (OR, 9.2; 95% CI, 2.2-38.2; p = 0.038) were associated with superficial surgical site infection after TKA. In general, there is a positive correlation among the various available glycemic markers among patients with diabetes undergoing TKA, and patients undergoing surgery with HbA1c ≥ 8 and/or FBG ≥ 200 mg/dL were associated with superficial surgical site infection. These findings should be considered in patient selection and preoperative counseling for patients with diabetes undergoing TKA. Level III, prognostic study.


The anesthetic management and the role of extracorporeal membrane oxygenation for giant mediastinal tumor surgery.
Mediastinal tumors are a remarkably diverse category. They include malignant and benign forms with different rates of disease progression and tissue invasion. Anesthesiologists may encounter significant difficulties in managing patients with giant mediastinal tumors due to the non-negligible occurrence of severe cardiorespiratory collapse. Respiratory complications ensue from the compression of the airways induced by the mediastinal mass: the compressive effects may be exacerbated by positioning or anesthesia induction. Furthermore, the compression or invasion of major vessels may elicit acute cardiovascular collapse. The specter of sudden cardiorespiratory deterioration should lead the anesthesiologist to careful planning: acknowledging clinical and radiological signs that may presage an increased risk of life-threatening complications is of pivotal importance. This review aims to present a strategy for treating patients with mediastinal masses, starting with the pathophysiological elements and moving through preoperative care, intraoperative behavior, and the recovery period. We will also focus on respiratory and cardiovascular issues, emphasizing the need for extracorporeal membrane oxygenation (ECMO) as a rescue and crucial component of the anesthesia strategy. Understanding the physiological alterations after anesthesia induction can aid in identifying and treating potential problems. In addition, we attempted to offer insight into multimodal anesthesia and analgesia management: we emphasize the importance of a thorough preoperative assessment and the need for reviewing extracorporeal support not just a resuscitative strategy but as an integrated component of the perioperative care.


Noninvasive diagnostics for extremity compartment syndrome following traumatic injury: A state-of-the-art review.
Acute compartment syndrome (ACS) is a serious medical condition that can occur following traumatic injury to an extremity. If left undiagnosed, ACS can eventuate in amputation of the limb or even death. Because of this, fasciotomy to release the pressure within the muscle and restore tissue perfusion is often performed upon suspicion of ACS, as the sequelae to fasciotomy are less severe than those associated with not performing the fasciotomy. Currently, the "gold standard" of diagnosis is based on clinical assessment of such symptoms as pain out of proportion to the injury, obvious high pressure and swelling, pain on passive stretch of the muscles in the affected compartment, and deficits in sensory and/ormotor functions. Diagnosis is often confirmed using invasive measurements of intramuscular pressure (IMP); however, controversy exists as to how direct IMP measurement should be accomplished and threshold pressures for accurate diagnosis. Because of this and the attendant issues with invasive measurements, investigators have been searching over the last 25 years for a noninvasive means to quantitatively measure IMP or perfusion to the limb. The purpose of this review is to summarize the current state of the art of noninvasive devices that could potentially be used to diagnose ACS accurately and objectively. To do this, we divide the discussion into those medical devices that primarily measure mechanical surrogates of IMP (e.g., tissue hardness or myofascial displacement) and those that primarily measure indices of tissue perfusion (e.g., tissue oxygen saturation via near-infraredspectroscopy). While near-infrared spectroscopy-basedtechnologies have shown the most promise, whether such technologies will be of diagnostic benefit await the completion of ongoing clinical trials. LEVEL OF EVIDENCE: Systematic Review, level II.


Evaluation of the complex transcriptional topography of mesenchymal stem cell chondrogenesis for cartilage tissue engineering.
Mesenchymal stem cells (MSCs) are a promising cell source for cartilage tissue engineering given their chondrogenic potential. This potential has yet to be fully realized, as the mechanical properties of MSC-based constructs are lower than those of chondrocyte-based constructs cultured identically. The aim of this study was to better understand the transcriptional underpinnings of this functional limitation. Matched chondrocytes and MSCs from three donors were cultured in agarose in a defined medium containing transforming growth factor beta3 (TGF-beta3). We evaluated the compressive mechanical properties and matrix deposition of maturing constructs over 56 days. Transcriptional differences between the two cell types were assessed on day 0 and 28 via microarray analysis and real-time polymerase chain reaction; differential deposition of matrix molecules was assessed by immunohistochemistry. Although the mechanical and biochemical properties of cell-seeded constructs improved with culture duration, MSC values plateaued at day 28, and remained lower than chondrocyte values. Using microarray analysis, 324 genes were identified as mis-expressed during chondrogenesis. Differential expression of 18 genes was validated, and differential deposition of proteoglycan 4 and TGF-beta-induced 68 kDa protein (TGFBI) was confirmed. Temporal expression profiles of these 18 genes showed that some genes were never expressed (chondromodulin), some were expressed at lower levels (proteoglycan 4), and some were expressed only at later time points (TGFBI) in MSCs compared to chondrocytes. These findings further define the complex transcriptional topography of MSC chondrogenesis, and provide new benchmarks for optimizing the growth of MSC-based engineered cartilage.


Loneliness, Spirituality, and Health-Related Quality of Life in Hispanic English-Speaking Cancer Caregivers: A Qualitative Approach.
Hispanic caregivers experiencing higher caregiving burden than their non-Hispanic cohorts, due in part to contextual factors, such as barriers to accessing health care, challenging employment environments, low education and income, immigration issues, and minority stress. Spirituality may serve as a coping strategy for Hispanic caregivers that influences health-related quality of life (HRQoL), possibly by modifying loneliness associated with caregiving. We explored these concepts using semi-structured interviews (N = 10 Hispanic caregivers). Participants shared perceptions of loneliness, spirituality, and how these factors related to HRQoL. Five themes emerged: caregiver experience, coping strategies, loneliness, religion and spirituality to gain strength. Findings suggested that spirituality and religion improved HRQoL partially by reducing loneliness. Future programs to improve HRQoL in Hispanic English-speaking cancer caregivers should address spirituality.


[Corrigendum] Icaritin promotes the osteogenesis of bone marrow mesenchymal stem cells via the regulation of sclerostin expression.
Following the publication of the above article, the authors have contacted the Editorial Office to explain that they had assembled the cellular morphological images in Fig. 1A on p. 819 incorrectly; essentially, the cell morphology of 2 passages of hBMSCs (centre panel) should have been shown as the data panel for 3 passages of hBMSCs (right-hand panel), and likewise, the cell morphology of 3 passages of hBMSCs should have been shown as the data panel for 2 passages of hBMSCs. The revised version of Fig. 1 is shown below. The authors confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 45: 816-824, 2020; DOI: 10.3892/ijmm.2020.4470].


Luteolin potentiates the effects of aminoglycoside and β-lactam antibiotics against methicillin-resistant Staphylococcus aureus in vitro.
Methicillin-resistant Staphylococcus aureus (MRSA) infection has become a serious clinical problem worldwide, and alternative natural or combination drug therapies are required for its treatment. The aim of the present study was to examined the antimicrobial activity of luteolin (LUT) against MRSA. Luteolin is a polyphenolic flavonoid compound with a wide spectrum of biological activities. The antimicrobial activities of LUT and the antibiotics ampicillin (AM), oxacillin (OX) and gentamicin (GT), used alone or in combination, were evaluated against five clinical MRSA isolates and two reference strains using a minimum inhibitory concentration (MIC) assay, MTT colorimetric assay, checkerboard dilution test and time-kill assay. The MIC of LUT against all strains was found to be 62.5 µg/ml. The combinations of LUT and antibiotics exhibited a synergistic effect against MRSA in the majority of cases, as determined by the checkerboard method. Time-kill curves revealed that a combination of LUT with AM, OX or GT significantly reduced bacterial counts, which dropped below the lowest detectable limit after 24 h. These results indicate that LUT potentiates the effects of β-lactam and aminoglycoside antibiotics against MRSA.


Elastomer Nanocomposites: Effect of Filler-Matrix and Filler-Filler Interactions.
The reinforcement of elastomers is essential in the rubber industry in order to obtain the properties required for commercial applications. The addition of active fillers in an elastomer usually leads to an improvement in the mechanical properties such as the elastic modulus and the rupture properties. Filled rubbers are also characterized by two specific behaviors related to energy dissipation known as the Payne and the Mullins effects. The Payne effect is related to non-linear viscoelastic behavior of the storage modulus while the Mullins or stress-softening effect is characterized by a lowering in the stress when the vulcanizate is extended a second time. Both effects are shown to strongly depend on the interfacial adhesion and filler dispersion. The basic mechanisms of reinforcement are first discussed in the case of conventional rubber composites filled with carbon black or silica usually present in the host matrix in the form of aggregates and agglomerates. The use of nanoscale fillers with isotropic or anisotropic morphologies is expected to yield much more improvement than that imparted by micron-scale fillers owing to the very large polymer-filler interface. This work reports some results obtained with three types of nanoparticles that can reinforce rubbery matrices: spherical, rod-shaped and layered fillers. Each type of particle is shown to impart to the host medium a specific reinforcement on account of its own structure and geometry. The novelty of this work is to emphasize the particular mechanical behavior of some systems filled with nanospherical particles such as in situ silica-filled poly(dimethylsiloxane) networks that display a strong polymer-filler interface and whose mechanical response is typical of double network elastomers. Additionally, the potential of carbon dots as a reinforcing filler for elastomeric materials is highlighted. Different results are reported on the reinforcement imparted by carbon nanotubes and graphenic materials that is far below their expected capability despite the development of various techniques intended to reduce particle aggregation and improve interfacial bonding with the host matrix.


ORAL PENICILLIN.
It is possible to attain serum concentrations of penicillin after oral administration comparable to those attained after intramuscular injection by the use of approximately five times as much penicillin. As the concentrations attained following the ingestion of penicillin by four different methods were all of the same order of magnitude, it would seem that the present problem in oral administration is analogous to that with intramuscular administration, i.e., to find the ideal vehicle whereby the duration of the serum concentration can be prolonged.


Proteomic analysis of lysosomal acid hydrolases secreted by osteoclasts: implications for lytic enzyme transport and bone metabolism.
Osteoclasts, the bone-digesting cells, are polarized cells that secrete acid hydrolases into a resorption lacuna where bone degradation takes place. The molecular mechanisms underlying this process are poorly understood. To analyze the nature of acid hydrolases secreted by osteoclasts, we used the mouse myeloid Raw 264.7 cell line that differentiates in vitro into mature osteoclasts in the presence of the receptor activator of NF-kappaB ligand. Upon differentiation, we observed a strong increase in the secretion of mannose 6-phosphate-containing acid hydrolases. A proteomic analysis of the secreted proteins captured on a mannose 6-phosphate receptor affinity column revealed 58 different proteins belonging to several families of acid hydrolases of which 16 are clearly involved in bone homeostasis. Moreover these acid hydrolases were secreted as proproteins. The expression of most of the identified acid hydrolases is unchanged during osteoclastogenesis. Thus, our data strongly support the notion that the polarized secretion of acid hydrolases by osteoclasts results from a reorganization of key steps of membrane traffic along the lysosomal pathway rather than from a fusion of lysosomes with the membrane facing the resorption lacuna.


Oncologic and functional outcomes of open surgery in early supraglottic tumors: is it still a valid technique?
In this study, we aimed to analyze the oncologic and functional outcomes of supraglottic laryngectomy. Medical records of 91 cases (85 males, 6 females; mean age 55.4 years; range 30 to 75 years) who underwent surgery due to early supraglottic laryngeal cancer in our clinic were retrospectively analyzed. Statistical analysis was performed using chi-square test and Fisher's exact test. Mean values were estimated by means of t-test, while survival curves were drawn using Kaplan-Meier method. With respect to oncologic assessment, disease-free survival rate was 81%, the rate of regional recurrence was 6%, the rate of local recurrence was 8%, the rate of distant metastasis was 7% and the rate of occult neck metastasis was 25%. Metastatic neck disease and extracapsular invasion in the lymphatic ganglia were found to be the most critical parameters in terms of survival. With respect to functional assessment, the mean time of decannulation was 41 days, while the mean time of nasogastric tube removal was 19 days. It was observed that cases with a Forced Expiratory Volume in 1 second (FEV-1) of <75% experienced more aspiration-related problems. The functional outcomes were worse in the cases who underwent bilateral neck dissection and postoperative radiotherapy. Open surgery is a more effective treatment modality in the early supraglottic tumors in terms of oncologic and functional outcomes. It should be continued to be use as an alternative method to the novel and expensive technologies including transoral robotic surgery or transoral laser surgery.


Active immunization against transforming growth factor beta1 prevents hepatic fibrosis in a rat model of liver disease.
Transforming growth factor beta1 (TGF-β1) plays an important role in hepatic fibrogenesis. In this study, we documented the effects of active immunization against TGF-β1 on hepatic fibrosis in an animal model of chronic liver disease. BALB/c mice were immunized against 3 different peptides of TGF-β1 ligated into hepatitis B virus core protein (HBVc). Titers of TGF-β1 antibodies were documented by enzyme linked immunoassays and antibody activity by cell membrane receptor binding and proliferation assays. The most immunogenic recombinant HBVc + TGF-β1 peptide (HBVc + C) then served as a vaccine in Sprague-Dawley rats with dimethylnitrosamine-induced chronic liver disease. Hepatic fibrosis was documented by serum hyaluronic acid levels, liver histology, and reverse transcriptase polymerase chain reaction for hepatic collagen I (α1) and smooth muscle alpha actin mRNA expression. Relative to control rats vaccinated with HBVc alone, recombinant HBVc + C vaccinated animals had significantly lower serum hyaluronic acid levels, less histologic evidence of hepatic fibrosis, and reduced expression of collagen I (α1) and smooth muscle alpha actin mRNA in the liver. The results of this proof-of-concept study suggest that active immunization against TGF-β1 is a worthwhile strategy to pursue in efforts to prevent hepatic fibrosis associated with chronic liver disease.


Oral Microbiota, Periodontal Status, and Osteoporosis in Postmenopausal Females.
Alterations in hormone levels during menopause decrease bone density and may worsen oral health, favoring the growth of periodontal pathogens, whose detection could improve the diagnosis of periodontitis. The aim of this study is to detect and quantify the main periodontal pathogens in the oral microbiota of postmenopausal females and to explore the relationship between clinical and periodontal parameters. This was an observational cross-sectional study of 76 postmenopausal females. Dental examinations and sampling for microbiologic evaluation were performed, and a history of osteoporosis/osteopenia was collected. Real-time polymerase chain reaction was used for detecting and quantifying Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Campylobacter rectus (Cr), and Tannerella forsythia (Tf). The results obtained were subjected to statistical analyses. Statistical significance was defined as P <0.05. Periodontitis was detected in 77.1% of females with osteoporosis/osteopenia (P >0.05). A significant correlation was found between osteoporosis and missing teeth. T. forsythia and C. rectus were detected in 100% of the samples, Fn and Pg in 98.7%, and Aa in 73.7%. Osteoporosis did not influence the prevalence of periodontitis among postmenopausal females. The presence of periodontopathogenic bacteria was not sufficient to confirm disease. A preventive maintenance program for postmenopausal females, particularly osteoporotic females, who are at greater risk of tooth loss, could minimize the potential effects of bone loss on periodontal tissues.


The LEF1/beta -catenin complex activates movo1, a mouse homolog of Drosophila ovo required for epidermal appendage differentiation.
Drosophila ovo/svb (dovo) is required for epidermal cuticle/denticle differentiation and is genetically downstream of the wg signaling pathway. Similarly, a mouse homolog of dovo, movo1, is required for the proper formation of hair, a mammalian epidermal appendage. Here, we provide biochemical evidence that movo1 encodes a nuclear DNA binding protein (mOvo1a) that binds to DNA sequences similar to those that dOvo binds to, further supporting the notion that mOvo1a and dOvo are genetically and biochemically homologous proteins. Additionally, we show that the movo1 promoter is activated by the lymphoid enhancer factor 1 (LEF1)/beta-catenin complex, a transducer of wnt signaling. Collectively, our findings suggest that movo1 is a developmental target of wnt signaling during hair morphogenesis in mice, and that the wg/wnt-ovo link in epidermal appendage regulatory pathways has been conserved between mice and flies.


Peritoneal dialysis after failed kidney allograft: Comparing patients with and without pd before transplant.
The result of published studies on the clinical outcome of peritoneal dialysis (PD) after kidney allograft failure is conflicting. There are also few published data on the outcome of patients who had PD before kidney transplant and then return to PD after allograft failure. We reviewed 100 patients who were started on PD after kidney allograft failure between 2001 and 2020 (failed transplant group); 50 of them received PD before transplant. We compared the clinical outcome to 200 new PD patients matched for age, sex, and diabetic status (control group). The patients were followed for 45.8 ± 40.5 months. the 2-year patient survival rate was 83.3% and 87.8% for the failed transplant and control groups, respectively (log rank test, p = 0.2). The corresponding 2-year technique survival rate 66.5% and 71.7% (p = 0.5). The failed transplant and control groups also had similar hospitalization rate and peritonitis rate. In the failed transplant group, there was also no difference in patient survival, technique survival, hospitalization, or peritonitis rate between those with and without PD before transplant. In the failed transplant group, patients who had PD before transplant and then returned to PD after allograft failure had substantial increase in D/P4 (0.585 ± 0.130 to 0.659 ± 0.111, paired t-test, p = 0.032) and MTAC creatinine (7.74 ± 3.68 to 9.73 ± 3.00 ml/min/1.73m2, p = 0.047) from the time before the transplant to the time after PD was resumed after failed allograft. The clinical outcome of PD patients with a failed kidney allograft is similar to other PD patients. However, patients who have a history of PD before kidney transplant and then return to PD after allograft failure have increased peritoneal transport parameters.


The use of marine-derived bioactive compounds as potential hepatoprotective agents.
The marine environment may be explored as a rich source for novel drugs. A number of marine-derived compounds have been isolated and identified, and their therapeutic effects and pharmacological profiles are characterized. In the present review, we highlight the recent studies using marine compounds as potential hepatoprotective agents for the treatment of liver fibrotic diseases and discuss the proposed mechanisms of their activities. In addition, we discuss the significance of similar studies in Oman, where the rich marine life provides a potential for the isolation of novel natural, bioactive products that display therapeutic effects on liver diseases.


Usefulness of collagen plugging with VasoSeal after PTCA as compared to manual compression with identical sheath dwell times.
This study investigated the usefulness of collagen plugging with VasoSeal in patients after PTCA compared to a control group having identical sheath dwell times and therefore comparable levels of anticoagulation. A total of 150 patients were enrolled in this prospective and randomized study. Sheaths were pulled at exactly 5 h after arterial puncture. Time to hemostasis and local complications were determined. There were no statistical differences in baseline characteristics. The mean time to hemostasis in the collagen group was significantly shorter (3 +/- 3 min) than that of the control group (17.4 +/- 7 min). At 24 h, 23% of the collagen group patients had a small, 1% a medium and 4% a large hematoma. In the control group, 32% had a small, 4% a medium sized, but no patient a large hematoma. After collagen, one patient developed a pseudoaneurysm needing vascular surgery. In the control group, no major complication occurred. Compared to patients with manual compression at an identical sheath dwell time and an identical level of anticoagulation, there was a significant reduction in time to hemostasis but no statistical difference regarding local complications. Although the incidence of medium or large hematoma was low, the trend towards a decreased risk of smaller hematomas seemed to be counterbalanced by an increased risk of larger hematomas.


Determining the geographic origin of invasive populations of the mealybug Planococcus ficus based on molecular genetic analysis.
Determining the most likely source of an invasive pest species might help to improve their management by establishing efficient quarantine measures and heading the search of efficient biological control agents. Planococcus ficus is an invasive mealybug pest of vineyards in Argentina, California, Mexico, Peru and South Africa. This mealybug pest had a previously known geographic distribution spanning southern Europe, the Middle East, and parts of northern Africa. In North America, Pl. ficus was first discovered in the early 1990s and soon thereafter in Mexico. To determine the origin of invasive populations in North America, Pl. ficus from California and Mexico were compared with material throughout its presumptive native range in the Mediterranean region, as well as material collected from an older invasion in South Africa and recently invaded Argentina. From each sample location, genomic DNA was sequenced for the nuclear internal transcribed spacer one (ITS1) and the mitochondrial cytochrome c. oxidase one (CO1). Phylogenetic analyses of CO1, ITS1 and concatenated CO1 and ITS1 data-sets using Bayesian and neighbor-joining analysis support two major divisions: a European grouping (Europe, Tunisia, Turkey) and a Middle Eastern grouping (Israel and Egypt). The invasive populations in Argentina and South Africa align with the European group and the invasive populations in North America align with the Middle Eastern group, with one Israel sample aligning closely with the North American clade, suggesting that Israel was the origin of those populations.


Enhancing breastfeeding rates among African American women: a systematic review of current psychosocial interventions.
The goals of this article are to provide a review of key interventions and strategies that impact initiation and duration of breastfeeding with particular focus on low-income African American mothers' maternal psychological vulnerabilities during the early postpartum period using a social ecological perspective as a guiding framework. Although modest gains have been achieved in breastfeeding initiation rates in the United States, a projected gap remains between infant feeding practices and national Healthy People breastfeeding goals set for 2020, particularly among African Americans. These disparities raise concerns that socially disadvantaged mothers and babies may be at increased risk for poor postnatal outcomes because of poorer mental health and increased vulnerability to chronic health conditions. Breastfeeding can be a protective factor, strengthening the relationship between mother and baby and increasing infant health and resilience. Evidence suggests that no single intervention can sufficiently address the multiple breastfeeding barriers faced by mothers. Effective intervention strategies require a multilevel approach. A social ecological perspective highlights that individual knowledge, behavior, and attitudes are shaped by interactions between the individual woman, her friends and family, and her wider historical, social, political, economic, institutional, and community contexts, and therefore effective breastfeeding interventions must reflect all these aspects. Current breastfeeding interventions are disjointed and inadequately meet all African American women's social and psychological breastfeeding needs. Poor outcomes indicate a need for an integrative approach to address the complexity of interrelated breastfeeding barriers mothers' experience across layers of the social ecological system.


The clinical and demographical profile of Coronavirus illness: The tale of Tablighi Jamaat and Zaireen in Quarantine / Isolation center at Sukkur and Hyderabad.
To determine the clinical and demographical profile of corona-virus illness among Tablighi Jamaat and Zaireen kept in quarantine / isolation center at Sukkur and Hyderabad Sindh. The cross-sectional descriptive study (late March-2020 to mid of April-2020) was conducted at Diagnostic & Research Laboratory LUMHS Jamshoro / Hyderabad. All the suspected cases for COVID-19 were recruited and screened for corona virus infection. The study explored the data of the suspected and diagnosed (confirmed) case of COVID-2019 (Tablighi Jamaat and Zaireen) reported by Diagnostic Research Laboratory Liaquat University of Medical and Health Sciences (LUMHS) Jamshoro who belonged to various parts of the country in general and province Sindh in particular. All the individuals regardless of age and gender presented either as asymptomatic, critical ill or having non-specific symptoms as fever, flu, cough; sore throat and shortness of breath were screened for COVID-19 by real time PCR after taking informed consent whereas the frequency / percentages (%) and means ±SD computed for study variables. During study period total 920 patients were explored and screened for Corona virus infection. The mean ± SD for age (yrs) of overall population of city Sukkur and Hyderabad was 57.83±8.84 and 59.62±9.72 respectively. The 700 people from Sukkur city was screened and out of them 276 (39.4%) were positive and 424 (60.5) were negative while the cure rate was 245 (88.7%) along with mean ± SD for recovery time was 9.41±2.97. The 220 people from Hyderabad city was screened and out of them 106 (48.1%) were positive and 114 (51.8%) were negative while the cure rate was 106 (100%) along with mean ± SD for recovery time was 11.54±3.42. The majority of cases at both centers were asymptomatic (90%), symptomatic (7%) and critically ill (3%). The mortality accounted for 2.8% cases at Hyderabad isolation center and all were having smoking history and co-morbidities as ischemic heart diseases, diabetes mellitus, obstructive lung disease and cerebrovascular accident whereas no mortality was observed at Sukkur isolation center. RT-PCR measure allowed fast, delicate, and explicit discovery of SARS-CoV in biochemical diagnosis. The majority of cases at both centers were asymptomatic while the mortality was identified in 2.8% cases (having co-morbidities) at Hyderabad isolation center whereas no mortality was observed at Sukkur isolation center.


An approach to separating the levels of hierarchical structure building in language and mathematics.
We aimed to dissociate two levels of hierarchical structure building in language and mathematics, namely 'first-level' (the build-up of hierarchical structure with externally given elements) and 'second-level' (the build-up of hierarchical structure with internally represented elements produced by first-level processes). Using functional magnetic resonance imaging, we investigated these processes in three domains: sentence comprehension, arithmetic calculation (using Reverse Polish notation, which gives two operands followed by an operator) and a working memory control task. All tasks required the build-up of hierarchical structures at the first- and second-level, resulting in a similar computational hierarchy across language and mathematics, as well as in a working memory control task. Using a novel method that estimates the difference in the integration cost for conditions of different trial durations, we found an anterior-to-posterior functional organization in the prefrontal cortex, according to the level of hierarchy. Common to all domains, the ventral premotor cortex (PMv) supports first-level hierarchy building, while the dorsal pars opercularis (POd) subserves second-level hierarchy building, with lower activation for language compared with the other two tasks. These results suggest that the POd and the PMv support domain-general mechanisms for hierarchical structure building, with the POd being uniquely efficient for language.


Differential effects of lithium on muscarinic cholinoceptor-stimulated CMP-phosphatidate accumulation in cerebellar granule cells, CHO-M3 cells, and SH-SY5Y neuroblastoma cells.
The ability of lithium to potentiate muscarinic cholinoceptor-stimulated CMP-phosphatidate (CMP.PA) accumulation has been examined in various cells in which muscarinic cholinoceptor agonists evoke a phosphoinositide response. Cell types examined include rat cerebellar granule cells, Chinese hamster ovary cells transfected to express the human muscarinic M3 receptor (CHO-M3 cells), and SH-SY5Y neuroblastoma cells. Neither carbachol (1 mM) nor lithium (10 mM) caused significant increases in CMP.PA accumulation in rat cerebellar granule cells; however, when added together for 20 min a linear 17-fold increase over basal levels was observed. The increase was dependent on the concentration of carbachol and lithium present, and the effect could be reversed by addition of exogenous myo-inositol (10 mM). Addition of carbachol alone to CHO-M3 cells caused a five-fold increase in CMP.PA accumulation. In the presence of lithium, a 70-fold increase was observed at 20 min after carbachol plus lithium addition. This latter response was concentration dependent and could be abolished by preincubation in the presence of 10 mM myo-inositol. In contrast, whereas carbachol elicited a three-fold increase in CMP.PA accumulation in SH-SY5Y neuroblastoma cells, which reached a plateau 10 min after agonist addition, the response could neither be augmented by addition of lithium nor inhibited by addition of myo-inositol. These results emphasise that the ability of lithium to affect agonist-stimulated CMP.PA accumulation is not simply a function of stimulus strength, but is also crucially dependent on the intracellular concentration of inositol.


[Inhibition of proliferation, adhesion and invasion ability of human lung carcinoma cell A549 by tumor necrosis factor-alpha converting enzyme (TACE)].
We constructed prokaryotic expression vectors for different domains of TACE gene and expressed the fusion proteins, so as to explore their effects on the proliferation, adhesion and invasion potential of tumor cells in vitro. The total RNA was isolated from THP1 cell. TACE cDNA was amplified by RT-PCR and subcloned into pMD18-T vector to construct pMD-18T-TACE vector. The different cDNA fragment of TACE were amplified from plasmid pMD-18T-TACE and then cloned into pET-28a( + ) to construct expression vector pET28a( + )- 300, pET28a( + )-T800, and pET28a( + )-T1300, which respectively transformed into E. coli BL21 (DE3). The expression of His-tagged fusion proteins were induced with IPTG and purified through BBST NTA resin. The proliferation ability was examined by MTT assay. The adhesive and invasive ability were examined by plated adhesion model and Transwell assay. The protein pET28a( + )-T300 and pET28a( + )-T1300 can reduce the proliferation, adhesion and invasion ability of human lung carcinoma cell A549 in vitro, but otherwise the protein pET28a( + )-T800 had not shown the inhibitive function. The fusion protein of disintegrin domain of TACE have the similar biological function to other disintegrins, which can be used for further research on function of TACE in inflammation and tumor.


Catch-and-release probes applied to semi-intact cells reveal ubiquitin-specific protease expression in Chlamydia trachomatis infection.
Protein ubiquitylation controls many cellular pathways, and timely removal of ubiquitin by deubiquitylating enzymes (DUBs) is essential to govern these different functions. To map endogenous expression of individual DUBs as well as that of any interacting proteins, we developed a catch-and-release ubiquitin probe. Ubiquitin was equipped with an activity-based warhead and a cleavable linker attached to a biotin affinity-handle through tandem site-specific modification, in which we combined intein chemistry with sortase-mediated ligation. The resulting probe is cell-impermeable and was therefore delivered to the cytosol of perfringolysin O (PFO)-permeabilized cells. This allowed us to retrieve and identify 34 DUBs and their interacting partners. We also noted the expression, in host cells infected with Chlamydia trachomatis, of two additional DUBs. Furthermore, we retrieved and identified chlamydial DUB1 (ChlaDUB1) and DUB2 (ChlaDUB2), demonstrating by experiment that ChlaDUB2, the presence and activity of which had not been detected in infected cells, is in fact expressed during the course of infection.


Muscimol inactivation of caudal fastigial nucleus and posterior interposed nucleus in monkeys with strabismus.
Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in strabismic monkeys. The SOA receives afferent projections from the caudal fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the cerebellum. The objectives of the present study were to investigate the potential roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye alignment in strabismic monkeys. We used unilateral injections of the GABAA agonist muscimol to reversibly inactivate the cFN (4 injections in exotropic monkey S1 with ≈ 4° of exotropia; 5 injections in esotropic monkey S2 with ≈ 34° of esotropia) and the PIN (3 injections in monkey S1). cFN inactivation induced horizontal saccade dysmetria in all experiments (mean 39% increase in ipsilesional saccade gain and 26% decrease in contralesional gain). Also, mean contralesional smooth-pursuit gain was decreased by 31%. cFN inactivation induced a divergent change in eye alignment in both monkeys, with exotropia increasing by an average of 9.8° in monkey S1 and esotropia decreasing by an average of 11.2° in monkey S2 (P < 0.001). Unilateral PIN inactivation in monkey S1 resulted in a mean increase in the gain of upward saccades by 13% and also induced a convergent change in eye alignment, reducing exotropia by an average of 2.7° (P < 0.001). We conclude that cFN/PIN influences on conjugate eye movements in strabismic monkeys are similar to those postulated in normal monkeys and cFN/PIN play important and complementary roles in maintaining the steady-state misalignment in strabismus.


Quantifying Head Impacts in Collegiate Lacrosse.
Concussion and repetitive head impact in sports has increased interest and concern for clinicians, scientists, and athletes. Lacrosse is the fastest growing sport in the United States, but the burden of head impact in lacrosse is unknown. The goal of this pilot study was to quantify head impact associated with practicing and playing collegiate lacrosse while subjects were fitted with wearable accelerometers. Descriptive epidemiology study. In a single year, a collegiate cohort of 14 women's and 15 men's lacrosse players wore mastoid-patch accelerometers to measure the frequency and severity of head impacts during official practices and games. Average impact severity, mean number of impacts, and cumulative acceleration were evaluated, stratified by sport and event type. Men's and women's collegiate lacrosse players did not significantly differ in the number of head impacts received during games (11.5 for men vs 9.2 for women) or practices (3.1 vs 3.1). Men's lacrosse players had significantly higher average head acceleration per impact during games compared with women (21.1g vs 14.7g) but not during practices (21.3g vs 18.1g). For both men and women, more impacts occurred during games than during practices (men, 11.5 vs 3.1; women, 9.2 vs 3.1), but impact severity did not significantly differ between events for either sport (men, 21.1g vs 21.3g; women, 14.7g vs 18.1g). The study data suggest a higher impact burden during games compared with practices, but this effect is driven by the quantity rather than severity of impacts. In contrast, sex-based effects in impact burden are driven by average impact severity rather than quantity. Data collected from larger multisite trials and/or different age groups could be used to inform ongoing debates, including headgear and practice regulations, that might appreciably affect the burden of head impacts in lacrosse. While most head impacts do not result in a clinical diagnosis of concussion, evidence indicates that subconcussive head impacts may increase susceptibility to concussion and contribute to long-term neurodegeneration.


[Ochratoxin A content in baby food].
The purpose of this study was to investigate the ochratoxin A content in baby food. The analysis of ochratoxin A were performed by immunoaffinity column clean-up and HPLC with fluorescence detection. The detection limit was 0.2 mg/kg. Ochratoxin A was detected in 22.5% of 40 samples up to 1.2 mg/kg. Mean level was 0.15 and 0.31 mg/kg. Ochratoxin A level was higher in oat-based samples. Calculations made on the basis of the obtained means showed that the daily ochratoxin A dietary intake were up to 1.72 ng/kg b.w.


Changes in gastric ECL cells and parietal cells after long-term administration of high-dose omeprazole to patients with Barrett's esophagus.
Long-term administration of PPI causes hyperplastic changes of the gastric parietal cells; however, the detailed mechanism remains to be clarified. We administered high-dose omeprazole to patients with Barrett's esophagus for 2 years, and investigated changes in gastric ECL (Enterochromaffin-like) cells using endoscopic biopsy specimens to clarify the etiology of hyperplasia of the parietal cells. The subjects were 69 patients who were diagnosed as having Barrett's esophagus (39 males, 30 females). We established two groups, an omeprazole-treated group and a ranitidine-treated group. Upper digestive tract endoscopy was performed before administration, and 12 and 24 months after the start of administration. Biopsy was performed in the greater curvature of the gastric body. The ECL/parietal cell counts and the grade of hyperplasia of the gastric mucosa were determined under a microscope. In addition, the fasting serum gastrin level was measured, and statistical analysis was performed. In the omeprazole-treated group, the ECL cell count was markedly increased 12 months after the start of administration, but was lower than the pretreatment value 24 months after the start of administration. The parietal and ECL cell counts significantly increased. Furthermore, there were no changes in mucosa thickness. The fasting serum gastrin level significantly increased. In the ranitidine-treated group, there was no increase in the ECL cell count, and the parietal cell count was decreased. There was no significant increase in mucosa thickness. The fasting serum gastrin level increased, although the rate of increase was markedly smaller than that in the omeprazole-treated group. Not the direct pharmacological actions of PPI but hypergastrinemia-associated secondary changes may be etiologically involved in hyperplasia of the parietal cells related to long-term administration of PPI.


Unilateral Blinking: Insights from Stereo-EEG and Tractography.
To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.


[Neurological deficit following a lesion in the parietal area 7b in the monkey].
The effect of unilateral surgical ablations of lateral part of inferior parietal lobule (area 7b) has been studied in the macaque monkey. The following neurological deficits were found: 1) A hemi-inattention for tactile stimuli applied to the hemiface and hand contralateral to the lesion; 2) A hemi-inattention for visual stimuli in the contralateral peripersonal space; 3) A reluctance to use the contralateral arm; 4) A mild and transient deficit in mouth grasping movements towards stimuli contralaterally presented; 5) Postural abnormalities of the hand contralateral to the lesion. It is proposed that area 7b is involved in the perception of the peripersonal space and in the organization of movements towards stimuli presented in that space.


Proacrosin-deficient mice and zona pellucida modifications in an experimental model of multifactorial infertility.
In humans, male and female partners contribute more or less equally to the infertility problem. In approximately 20% of infertile couples, the concurrence of male and female factors is suggested to be responsible for infertility. Neither of these factors are known nor is there a model system to prove this assumption. We present such a model system in the mouse, in which the lack of acrosin in the male and modifications of the zona pellucida (ZP) in the female result in a significant reduction of the fertilization rate in vitro. We generated mice carrying a deletion in the proline-rich region (PRR) of the proacrosin gene, resulting in the absence of proacrosin in the homozygous PRR(-/-) male mouse. Under normal conditions, sperm from the proacrosin-deficient mice are still capable of ZP penetration and fertilization. In this study, modifications of the ZP of oocytes after superovulation were achieved by treatment with dimethylsulphoxide or aroclor-1254 or by in-vitro ageing. It is known that under these conditions, a time-dependent hardening of the ZP occurs. The rates of fertilization in vitro of treated and aged oocytes using sperm from PRR(-/-) mice were found to be significantly reduced when compared with those reached with wild-type sperm. The relevance of the acrosin status and ZP condition for fertilization success were further substantiated by the finding that the fertilization rate with PRR(-/-) sperm is affected by the thickness of the ZP. Our results demonstrate that the lack of acrosin in sperm in combination with modifications to the ZP can affect fertility and can be an experimental model for the study of unexplained infertility in human couples in which both male- and female-derived factors are suggested to be the underlying causes.


Automatic detection of clinical mastitis is improved by in-line monitoring of somatic cell count.
This study explored the potential value of in-line composite somatic cell count (ISCC) sensing as a sole criterion or in combination with quarter-based electrical conductivity (EC) of milk, for automatic detection of clinical mastitis (CM) during automatic milking. Data generated from a New Zealand research herd of about 200 cows milked by 2 automatic milking systems during the 2006-2007 milking season included EC, ISCC, monthly laboratory-determined SCC, and observed cases of CM that were treated with antibiotics. Milk samples for ISCC and laboratory-determined SCC were taken sequentially at the end of a cow milking. Both samples were derived from a composite cow milking obtained from the bottom of the milk receiver. Different time windows were defined in which true-positive, false-negative, and false-positive alerts were determined. Quarters suspected of having CM were visually checked and, if CM was confirmed, sampled for bacteriological culturing and treated with an antibiotic treatment. These treated quarters were considered as gold-standard positives for comparing CM detection models. Alert thresholds were adjusted to achieve a sensitivity of 80% in 3 detection models: using ISCC alone, EC alone, or a combination of these. The success rate (also known as the positive predictive value) and the false alert rate (number of false-positive alerts per 1,000 cow milkings) were used to evaluate detection performance. Normalized ISCC estimates were highly correlated with normalized laboratory-determined SCC measurements (r = 0.82) for SCC measurements >200 x 10(3) cells/mL. Using EC alone as a detection tool resulted in a range of 6.9 to 11.0% for success rate, and a range of 4.7 to 7.8 for the false alert rate. Values for the ISCC model were better than the model using EC alone with 12.7 to 15.6% for the success rate and 2.9 to 3.7 for the false alert rate. Combining sensor information to detect CM, by using a fuzzy logic algorithm, produced a 2- to 3-fold increase in the success rate (range 21.9 to 32.0%) and a 2- to 3-fold decrease in the false alert rate (range 1.2 to 2.1) compared with the models using ISCC or EC alone. Results suggest that the performance of a CM detection system improved when ISCC information was added to a detection model using EC information.