Relationship between stroke volume and sympathetic nerve activity: new insights about autonomic mechanisms of syncope.
Head-up tilt table experiments conducted in astronauts prior to and immediately after the NASA Neurolab Space Mission (STS-90) revealed that a reduction in stroke volume induced by moving from the supine to upright posture was associated with increased muscle sympathetic nerve activity (MSNA). Although this finding was not unexpected, lower average stroke volume and greater average MSNA measured after space flight in both supine and upright postures were positioned in a linear fashion on the same stroke volume-MSNA stimulus-response relationship as the average pre-flight stroke volume and MSNA responses. Since all astronauts who participated in the Neurolab orthostatic experiments completed the 10-min tilt table tests, these observations supported the notion that sympathetic reflex responses were not altered but functioned adequately after space flight in non-presyncopal subjects. In contrast to the Neurolab results, development of orthostatic hypotension and presyncopal events reported in astronauts during standing after space flight have been accompanied by attenuated peripheral vasoconstriction and less elevation in plasma concentrations of norepinephrine. The association between circulating norepinephrine (NE) and peripheral vascular resistance in presyncopal astronauts after space flight led to the conclusion that postflight presyncope can be attributed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic function. In the present investigation, we used graded levels of lower body negative pressure (LBNP) to produce linear reductions in stroke volume and performed direct measurements of MSNA to test the hypotheses that (1) elevations in MSNA during central hypovolemia are proportional (i.e., linear) with reductions in stroke volume and; (2) that the slope of the stroke volume-MSNA relationship will be reduced in presyncopal subjects.


Mechanism of aromatic amine carcinogen bypass by the Y-family polymerase, Dpo4.
Bulky DNA damage inhibits DNA synthesis by replicative polymerases and often requires the action of error prone bypass polymerases. The exact mechanism governing adduct-induced mutagenesis and its dependence on the DNA sequence context remains unclear. In this work, we characterize Dpo4 binding conformations and activity with DNA templates modified with the carcinogenic DNA adducts, 2-aminofluoene (AF) or N-acetyl-2-aminofluorene (AAF), using single-molecule FRET (smFRET) analysis and DNA synthesis extension assays. We find that in the absence of dNTPs, both adducts alter polymerase binding as measured by smFRET, but the addition of dNTPs induces the formation of a ternary complex having what appears to be a conformation similar to the one observed with an unmodified DNA template. We also observe that the misincorporation pathways for each adduct present significant differences: while an AF adduct induces a structure consistent with the previously observed primer-template looped structure, its acetylated counterpart uses a different mechanism, one consistent with a dNTP-stabilized misalignment mechanism.


Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Therapeutics.
The recent progress in harnessing the efficient and precise method of DNA editing provided by CRISPR/Cas9 is one of the most promising major advances in the field of gene therapy. However, the development of safe and optimally efficient delivery systems for CRISPR/Cas9 elements capable of achieving specific targeting of gene therapy to the location of interest without off-target effects is a primary challenge for clinical therapeutics. Nanoparticles (NPs) provide a promising means to meet such challenges. In this review, we present the most recent advances in developing innovative NP-based delivery systems that efficiently deliver CRISPR/Cas9 constructs and maximize their effectiveness.


Power-Dependent Optical Characterization of the InGaN/GaN-Based Micro-Light-Emitting-Diode (LED) in High Spatial Resolution.
Spatially resolved photoluminescence at the sub-micro scale was used to study the optical non-uniformity of the micro-LED under varied power density excitation levels. The trend of the efficiency along injection levels were found to be highly dependent on the location of the chip mesa. The sidewall was 80% lower than the center under low-power density excitation, but was 50% higher under high-power density excitation. The external quantum efficiency droop at the center and the sidewall was 86% and 52%, respectively. A 2 µm band area near the sidewall was characterized where the efficiency and its trends changed rapidly. Beyond such band, the full width at half maximum and peak wavelength variation across the chip varied less than 1 nm, indicating high uniformity of the material composition. The sudden change = in the band, especially under high level excitation indicates the indium composition change formed by ion residues on the sidewall affect the distribution of charge carriers. These findings contribute to the understanding of cause of efficiency disadvantage and non-uniformity problems in small-size micro-LEDs.


Experimental studies on the initial focus of invasion of group A streptococci.
Rabbits were infected with group A streptococci type 12 by an aerosol method, that seems to resemble closely the human natural infection, in order to investigate the mechanism of invasion, especially the initial focus of invasion of streptococci. Living streptococci and FITC-labelled streptococci were exposed to several groups of rabbits, which were sacrificed and divided according to the duration after exposure. The specimens of organs were examined by light microscopy, fluorescent microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Histologically, the adherence of streptocossi was found on the pharyngeal mucosa and tonsils and the mucocilial clearance in the larynx and the trachea. Phagocytosis was also found in the bronchus and lung. By SEM, invading streptococci and cell debris-like masses were observed in the micropore of the tonsillar crypt of the rabbit. From these results it was supposed that there should be differences of tissue tropisms and defence mechanisms against streptococci among the mucosa and that micropores of the tonsillar crypts should play an important role in the initial focus of invasion of group A streptococci.


Topical carbonic anhydrase inhibitors and visual function in glaucoma and ocular hypertension.
Dorzolamide and brinzolamide are topical carbonic anhydrase inhibitors (CAI) indicated for patients with glaucoma and ocular hypertension. An evidence-based review of clinical trials of dorzolamide and brinzolamide was undertaken to determine an effect of these medications on visual function (primarily visual field) in open-angle glaucoma and ocular hypertension. Using the keywords 'dorzolamide' and 'brinzolamide', all articles describing trials of these medications reporting on visual acuity, contrast sensitivity and visual field from September 1966 to July 2009 were found in MEDLINE and EMBASE databases. No information from other sources was included in this review. A relatively modest number of trials was identified, where impact of therapy on one or more of the visual function modes was reported. In the studies of less than 1 year duration (3 days to 1 year, 23 studies) in all but three studies treatment with topical CAIs did not influence visual function, in two studies with dorzolamide some improvement in the contrast sensitivity was observed and in one open-label retrospective no-control-group study with dorzolamide visual field indices improved significantly. A different picture was seen in long-term studies, which were designed and powered to detect changes in visual field. One large study (European Glaucoma Prevention Study) with dorzolamide versus placebo failed to detect significant protective effect of the drug on glaucoma occurrence in ocular hypertensives. Several interesting aspects of this study are discussed in detail. The other two long-term studies reported on the superiority of adding dorzolamide over timolol therapy alone, and the superiority of the combination of dorzolamide and timolol over brinzolamide and timolol in terms of improving ocular blood flow (retrobulbar Color Doppler Imaging--CDI parameters) as well as in terms of visual field preservation in glaucoma patients over 4 to 5 years. For the first time one study could demonstrate that an improvement in ocular blood flow in the long run results in preservation of visual field in glaucoma patients. Dorzolamide, combined with the beta-blocker timolol, seems to be superior in this regard to brinzolamide plus timolol.


Pseudo-lesions of a Tortuous Right Coronary Artery During Percutaneous Coronary Intervention: Accordion Phenomena.
Guidewire-induced pseudo-lesions are referred to accordion phenomenon and are infrequent occurrences during percutaneous coronary intervention of tortuous coronary arteries. Their occurrence can be a diagnostic challenge to the interventionist and might lead to unnecessary intervention. Ischemia and hemodynamic compromise are possible complications, if not managed promptly. The differential diagnosis includes coronary dissection, thrombus, and spasm. We describe a patient who developed pseudo-lesions of the tortuous right coronary artery in multiple segments during PCI. The pseudo-lesions were refractory to intracoronary nitrogycerin.


Discovering new physics in the decays of black holes.
If the scale of quantum gravity is near a TeV, the CERN Large Hadron Collider (LHC) will be producing one black hole (BH) about every second, thus qualifying as a BH factory. With the Hawking temperature of a few hundred GeV, these rapidly evaporating BHs may produce new, undiscovered particles with masses approximately 100 GeV. The probability of producing a heavy particle in the decay depends on its mass only weakly, in contrast with the exponentially suppressed direct production. Furthermore, backgrounds in the BH sample can be made small. Using the Higgs boson as an example, we show that it may be found at the LHC on the first day of its operation, even with incomplete detectors.


Some critical issues in the application of quantum mechanics/molecular mechanics methods to the study of transition metal complexes.
The application of quantum mechanics/molecular mechanics (QM/MM) methods in transition metal chemistry is growing steadily. It becomes therefore appropriate to assess the importance of a number of technical issues associated to their implementation. This work presents the discussion of several of these issues, including the eventual need for conformational searches, the choice of the MM force field and the possibility of its tuning. The examples presented here prove that a proper handling of these technical aspects can lead to an improvement in the efficiency and quality of QM/MM calculations.


MicroRNA-142-5p promotes cell growth and migration in renal cell carcinoma by targeting BTG3.
Some microRNA (miRNA) levels have been found to be dysregulated in cancer patients, suggesting the potential usefulness of miRNAs in cancer therapies. The purpose of this study was to investigate the expression of miR-142-5p in human renal cell carcinoma (RCC) and its potential role in tumor growth and metastasis. The expression level of miR-142-5p in human RCC tissue and cell lines was determined by quantitative reverse transcription polymerase chain reaction analysis. MTT, colony formation, Transwell, and cell cycle assays were performed to explore the potential functions of miR-142-5p in human RCC cells. The potential target gene of miR-142-5p was identified and confirmed via luciferase reporter assays. miR-142-5p expression was elevated in RCC tissues and cell lines. Overexpression of miR-142-5p significantly promoted cell proliferation and colony formation and could prevent G1 phase arrest among RCC 786-O cells. Meanwhile, the migration potential of 786-O cells was greater than that of control cells. BTG3 was identified as a direct target of miR-142-5p, and re-expression of BTG3 reversed the miR-142-5p-induced cell proliferation. miR-142-5p promoted the proliferation and migration of RCC cells by targeting BTG3. With this potential onco-miRNA role in the progression of RCC, miR-142-5p may be a therapeutic target for the treatment of RCC.


NHS Lanarkshire's leadership development programme's impact on clinical practice.
The purpose of this paper is to explore the effect of a clinical leadership programme on senior clinicians within National Health Service Lanarkshire, in terms of key constituents for fostering leadership development, specific skills developed and impact this has had on clinical practice. A qualitative research design was employed over several stages, involving 44 senior clinical managers, with member validation substantiating findings and thematic analysis used to analyse data collected. The programme's impact was evident in acknowledged change to participants' attitude, behaviour and performance with examples conveyed to demonstrate both the effect on clinical practice and perceived organisational benefits gained. The use of role play, scenario planning and enquiry-based learning approaches were deemed critical in achieving such change. Time constraints merited two different cohorts being examined simultaneously during the various stages of the programme. A longitudinal study is underway encompassing the evaluations of several cohorts through various stages of the programme to enable time-based comparisons to be made and enhance the rigour and scrutiny of the programme's impact on clinical practice. The paper is foremost in determining structure and processes employed on the programme, specific leadership skills developed, subsequent effect on clinical practice and perceived organisational benefits gained but not necessarily contemplated by staff prior to embarking on the programme, such as the emergence of communities of practice.


Urinary diagnosis of gonorrhoea and Chlamydia in men in remote aboriginal communities.
(1) To evaluate the acceptability and validity of an intervention based on urine tests for diagnosis and treatment of gonorrhoea and chlamydia in men in remote Aboriginal communities. (2) To provide a prevalence estimate of these infections in the male population in the surveyed communities. First-void urine samples from 460 men in remote communities and 33 men in the Alice Springs Gaol were tested for gonorrhoea and chlamydia with at least one of polymerase chain reaction (PCR), enzyme immunoassay (EIA) and culture (gonorrhoea only). One hundred and three men (20.9%) were infected with gonorrhoea or chlamydia. The prevalence of infection for gonorrhoea only was 11.7%, for chlamydia only 4.1% and for dual infection 5.1%. Eighty-eight infected men and 45 of their sexual partners were recorded as having been treated within two months of testing. PCR tests detected the largest number of infections and were the easiest to use. The prevalence of these infections was higher than anticipated. Urine PCR tests were acceptable to men and are well suited to the remote-community setting. As an effective alternative to urethral swabs, they permit a range of community-based strategies to address high rates of infection with gonorrhoea and chlamydia.


Adaptation of the endogenous Salmonella enterica serovar Typhi clyA-encoded hemolysin for antigen export enhances the immunogenicity of anthrax protective antigen domain 4 expressed by the attenuated live-vector vaccine strain CVD 908-htrA.
Bacterial live-vector vaccines aim to deliver foreign antigens to the immune system and induce protective immune responses, and surface-expressed or secreted antigens are generally more immunogenic than cytoplasmic constructs. We hypothesize that an optimum expression system will use an endogenous export system to avoid the need for large amounts of heterologous DNA encoding additional proteins. Here we describe the cryptic chromosomally encoded 34-kDa cytolysin A hemolysin of Salmonella enterica serovar Typhi (ClyA) as a novel export system for the expression of heterologous antigens in the supernatant of attenuated Salmonella serovar Typhi live-vector vaccine strains. We constructed a genetic fusion of ClyA to the reporter green fluorescent protein and showed that in Salmonella serovar Typhi CVD 908-htrA, the fusion protein retains biological activity in both domains and is exported into the supernatant of an exponentially growing live vector in the absence of detectable bacterial lysis. The utility of ClyA for enhancing the immunogenicity of an otherwise problematic antigen was demonstrated by engineering ClyA fused to the domain 4 (D4) moiety of Bacillus anthracis protective antigen (PA). A total of 11 of 15 mice immunized intranasally with Salmonella serovar Typhi exporting the protein fusion manifested fourfold or greater rises in serum anti-PA immunoglobulin G, compared with only 1 of 16 mice immunized with the live vector expressing cytoplasmic D4 (P = 0.0002). In addition, the induction of PA-specific gamma interferon and interleukin 5 responses was observed in splenocytes. This technology offers exceptional versatility for enhancing the immunogenicity of bacterial live-vector vaccines.


Endoplasmic reticulum stress in chronic obstructive lung diseases.
Chronic airway inflammation characterizes several airway diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The altered airway milieu that results from the pathogenic processes in these disorders affects the airway epithelia, leading to an up-regulation of their innate defense. In human airway epithelia, luminal inflammatory stimuli induce an adaptation characterized by an expansion of the endoplasmic reticulum (ER) and its Ca(2+) stores. This epithelial adaption mediates Ca(2+)-dependent "hyperinflammatory" responses, and recent studies have shown that activation of the unfolded protein response (UPR) by ER stress is involved in the process. The UPR is also known to be activated by cigarette smoke, the primary trigger for development of COPD. These studies illustrate the functional role of UPR pathways during airway inflammation and suggest that targeting the UPR may be a therapeutic strategy for obstructive airway diseases. This article reviews the link between airway epithelial inflammation and activation of the UPR, and discusses how UPR activation might be relevant for CF and COPD airways disease.


An integrated multi-layered analysis of the metabolic networks of different tissues uncovers key genetic components of primary metabolism in maize.
Primary metabolism plays a pivotal role in normal plant growth, development and reproduction. As maize is a major crop worldwide, the primary metabolites produced by maize plants are of immense importance from both calorific and nutritional perspectives. Here a genome-wide association study (GWAS) of 61 primary metabolites using a maize association panel containing 513 inbred lines identified 153 significant loci associated with the level of these metabolites in four independent tissues. The genome-wide expression level of 760 genes was also linked with metabolite levels within the same tissue. On average, the genetic variants at each locus or transcriptional variance of each gene identified here were estimated to have a minor effect (4.4-7.8%) on primary metabolic variation. Thirty-six loci or genes were prioritized as being worthy of future investigation, either with regard to functional characterization or for their utility for genetic improvement. This target list includes the well-known opaque 2 (O2) and lkr/sdh genes as well as many less well-characterized genes. During our investigation of these 36 loci, we analyzed the genetic components and variations underlying the trehalose, aspartate and aromatic amino acid pathways, thereby functionally characterizing four genes involved in primary metabolism in maize.


The lung clearance index as a monitoring tool in cystic fibrosis: ready for the clinic?
In cystic fibrosis, (CF) there is an urgent need for objective tests that can capture and track preclinical lung disease. The lung clearance index (LCI), the primary outcome measure of the multiple breath washout test, is an established endpoint in clinical trials but the clinical utility of the test remains poorly defined. The purpose of this review is to examine the key studies over the past years that have advanced our understanding of the role of the LCI in clinical practice. The variability of LCI measurements increases with lung disease severity, and new evidence shows that between-visit changes in the LCI are therefore best expressed as a relative rather than an absolute change. A relative change of greater than 15% between visits is likely outside the intrinsic variability of the test and physiologically relevant. The LCI is feasible to perform and is a more sensitive outcome measure than forced expiratory volume in one second (FEV1). The LCI correlates with outcome measures such as structural MRI, and shows great promise in the routine clinical monitoring of CF lung disease, particularly in younger patients with milder disease. Recent studies have progressed our understanding of the role of the LCI in clinical practice, but the exact clinical utility of the test in monitoring CF lung disease is still uncertain.


[The Sense of Family - Developmental Lines and Problems].
The Sense of Family - Developmental Lines and Problems In spite of multiple criticism and diversification of family types family remains a "destination of yearning". Family stays always in contradiction to the culture of the surrounding society. The sense of family describes the sense of one's own family as a whole. It is composed of the experiences in dyads, triads, tetrades and polyades as well as the emotional atmosphere and the life style of the family as a whole. To the construction of the family as a whole as an internal object, the inner self-image of the family and corresponding the sense of family contribute the "missions" the family passes on to the children, the dynamics of loyalty, the multigenerational network, family narratives and family myths as mediators of the collective memory as well as the active shaping of relationships by the activity of the child itself. The change of family structures by "verticalisation", new communication technologies, and the "anthropo-technologies" of reproduction are still to be explored in respect to their possible consequences for the sense of family.


Hindered cluster rotation and 45Sc hyperfine splitting constant in distonoid anion radical Sc3N@C80-, and spatial spin-charge separation as a general principle for anions of endohedral fullerenes with metal-localized lowest unoccupied molecular orbitals.
DFT calculations of Sc(3)N@C(80) in the neutral and anionic states are performed which revealed that in the neutral state of the nitride clusterfullerene the lowest energy structure has C(3) symmetry, while in the anionic and dianionic states the C(3v) conformer has the lowest energy. Barriers to the cluster rotation inside the cage are also found to increase in the charge states. The (45)Sc hyperfine slitting constant, a(Sc), in Sc(3)N@C(80) anion radical is calculated by different theoretical approaches and in different conformations of Sc(3)N cluster. It is found that a(Sc) is strongly dependent on the cluster orientation with respect to the cage, covering a range form -10 to +25 Gauss at the B3LYP/6-311G*//PBE/TZ2P level of theory. A thorough analysis of the computed values as well as comparison of unrestricted and orbital-restricted calculations revealed that the polarization contribution to a(Sc) is about -10 Gauss and does not depend on the cluster orientation. Dependence of the predicted a(Sc) values on the density functional form (LSDA, BP, PBE, BLYP, OLYP, TPSS, B3LYP, and TPSSh), the basis set, as well as on the scalar-relativistic and spin-orbit corrections were investigated. The analysis of the charge distribution in the Sc(3)N@C(80)(-) anion radical revealed an interesting peculiarity of its electronic structure: while the spin density mostly resides on the cluster, only a slight decrease of its charge is found using both Bader and Mulliken definitions of atomic charges. A set of other endohedral metallofullerenes, including nitride clusterfullerenes Sc(3)N@C(2n) (2n = 68, 70, 78) and Y(3)N@C(2n) (2n = 78-88), carbide clusterfullerenes Sc(2)C(2)@C(68), Sc(2)C(2)@C(82), Sc(3)C(2)@C(80), Ti(2)C(2)@C(78), Y(2)C(2)@C(82), and dimetallofullerenes Sc(2)@C(76), Y(2)@C(82), La(2)@C(2n) (2n = 72, 78, 80), was also studied in the neutral and anionic state, and a spatial charge-spin separation is found to be a general rule for all endohedral fullerenes with high contribution of metal atoms to the LUMO.


Sterilization of N95 respirators: The time for action is upon us!
Re-processing of primary protective equipment is the need of the hour with healthcare systems all over the world strained due to the shortage precipitated by severe acute respiratory syndrome coronavirus 2. The common methods of re-sterilization do not hold well for filtering facepiece respirators (FFRs) as they affect their structure and function. We propose the validation and eventual use of gamma irradiation, an already existing method of re-sterilization, to disinfect FFRs in bulk.


Application of high-performance capillary electrophoresis to the analysis of H1 histones.
High-performance capillary electrophoresis for the separation of rat testis H1 histone variants and their phosphorylated modifications is described. The influence of buffer pH, hydroxypropylmethyl cellulose, and buffer concentration has been investigated. Under optimized conditions (500 mM phosphate buffer, pH 2, 0.03% hydroxypropylmethyl cellulose) using an uncoated capillary, eight H1 histone subfractions, including two H1(0) histones and H1t and their phosphorylated modifications, are resolved. Application of capillary electrophoresis to the separation of H1 histones provides an important new alternative to high-performance liquid chromatography (HPLC) and traditional gel electrophoresis.


Directly-grown and square-patterned arrays of metal oxide nanowires for high-performance catalyst support platforms.
This research reports novel and efficient electrocatalyst support systems. Tin dioxide nanowires grown directly on current collecting substances are introduced as high-performance support platforms. For this propose, palladium or platinum catalysts are impregnated on these nanowire scaffolds and exhibit improved electrocatalytic performance for methanol oxidation in alkaline and acidic environments. These nanowire support platforms could be demonstrated to maximize the electrocatalytic activity because of the effective charge transport provided by the direct connection between the nanowire supports and current collectors. More significantly, grid-patterned nanowire arrays grown directly on current collectors are, for the first time, demonstrated as a milestone to enhance the electrocatalytic performance. The empty space between the patterned nanowire arrays acts as a channel to facilitate the electrolyte diffusion. The metal catalysts incorporated into the patterned nanowire supports show an 8-fold improvement in the catalytic performance for methanol electrooxidation, most likely because of the synergetic effects of the enhanced charge transport and mass transfer attributed to the structural advantages of the patterned nanowire array supports.


Direct Measurement of Pore Dynamics and Leakage Induced by a Model Antimicrobial Peptide in Single Vesicles and Cells.
Antimicrobial peptides are promising therapeutic alternatives to counter growing antimicrobial resistance. Their precise mechanism of action remains elusive, however, particularly with respect to live bacterial cells. We investigated the interaction of a fluorescent melittin analogue with single giant unilamellar vesicles, giant multilamellar vesicles, and bilamellar Gram-negative Escherichia coli (E. coli) bacteria. Time-lapse fluorescence lifetime imaging microscopy was employed to determine the population distribution of the fluorescent melittin analogue between pore state and membrane surface state, and simultaneously measure the leakage of entrapped fluorescent species from the vesicle (or bacterium) interior. In giant unilamellar vesicles, leakage from vesicle interior was correlated with an increase in level of pore states, consistent with a stable pore formation mechanism. In giant multilamellar vesicles, vesicle leakage occurred more gradually and did not appear to correlate with increased pore states. Instead pore levels remained at a low steady-state level, which is more in line with coupled equilibria. Finally, in single bacterial cells, significant increases in pore levels were observed over time, which were correlated with only partial loss of cytosolic contents. These observations suggested that pore formation, as opposed to complete dissolution of membrane, was responsible for the leakage of contents in these systems, and that the bacterial membrane has an adaptive capacity that resists peptide attack. We interpret the three distinct pore dynamics regimes in the context of the increasing physical and biological complexity of the membranes.


High pressure synthesis of marcasite-type rhodium pernitride.
Marcasite-type rhodium nitride was successfully synthesized in a direct chemical reaction between a rhodium metal and molecular nitrogen at 43.2 GPa using a laser-heated diamond-anvil cell. This material shows a low zero-pressure bulk modulus of K0 = 235(13) GPa, which is much lower than those of other platinum group nitrides. This finding is due to the weaker bonding interaction between metal atoms and quasi-molecular dinitrogen units in the marcasite-type structure, as proposed by theoretical studies.


Acute rupture of the lateral ligament of the ankle. To suture or not to suture?
One hundred patients with acute ruptures of the lateral ligaments of the ankle were randomly allocated either to conservative treatment in a plaster cast or to operative repair. With the aid of stress tenography, the extent of the injury was established. There were 30 patients with isolated anterior talofibular ruptures and 20 with additional calcaneofibular ligament ruptures in each treatment group. Operative repair was associated with a higher incidence of complications in the first weeks, and slightly delayed the patients' return to work. At an independent two-year review there was no evidence that operative repair offered improved symptomatic or functional benefit.


Impaired Collateral Vessel Formation in Sickle Cell Disease.
The adaptive response to vascular injury is the formation of functional collateral vessels to maintain organ integrity. Many of the clinical complications associated with sickle cell disease can be attributed to repeated bouts of vascular insufficiency, yet the detailed mechanisms of collateral vessel formation after injury are largely unknown in sickle cell disease. Here, we characterize postischemic neovascularization in sickle cell disease and the role of neutrophils in the production of reactive oxygen species. We induced hindlimb ischemia by ligation of the femoral artery in Townes SS (sickle cell) mice compared with AA (wild type) mice. Perfusion recovery, ascertained using LASER (light amplification by stimulated emission of radiation) Doppler perfusion imaging, showed significant diminution in collateral vessel formation in SS mice after hindlimb ischemia (76±13% AA versus 34±10% in SS by day 28; P<0.001; n=10 per group). The incidence of amputation (25% versus 5%) and foot necrosis (80% versus 15%) after hindlimb ischemia was significantly increased in the SS mice. Motor function recovery evaluation by the running wheel assay was also impaired in SS mice (36% versus 97% at 28 days post-hindlimb ischemia; P<0.001). This phenotype was associated with persistent and excessive production of reactive oxygen species by neutrophils. Importantly, neutrophil depletion or treatment with the antioxidant N-acetylcysteine reduced oxidative stress and improved functional collateral formation in the SS mice. Our data suggest dysfunctional collateral vessel formation in SS mice after vascular injury and provide a mechanistic basis for the multiple vascular complications of sickle cell disease.


On the general properties of symmetric incomplete Airy beams.
We study the general properties of a class of Airy beams symmetric under reflection of the transverse coordinates. Following a recent proposal, their angular spectra depend on the absolute value of the third power of the transverse components of the wave vector. The proposed beams are shown to be described by symmetric superpositions of incomplete Airy special functions. Their angular spectra do not correspond to any of those described by standard catastrophe optics. However, the morphologies of the symmetric beams are similar to some of those already classified within that scheme, differing mainly on the scaling exponents. Finally, the structural stability of three-dimensional symmetric incomplete Airy beams is experimentally probed.


Retrospective clinical analysis of 320 cases of microvascular decompression for hemifacial spasm.
To investigate effects of microvascular decompression (MVD) surgical treatment on hemifacial spasm.A retrospective analysis of 320 adult patients (95 male cases, 29.7% and 225 female cases, 70.3%) with hemifacial spasm treated by surgery was conducted between February 2007 to June 2016, with an average age of 49.3 years and average disease course of 4.9 years. All the 320 cases of patients received MVD. After surgery, all patients were followed up for an average of 2.3 years. Surgical effects were evaluated based on the patients' symptoms and signs. As this is just a retrospective study that does not involve any interventions, ethical approval was not necessary according to the rules of the hospital.All patients were followed up, no death occurred. Symptom was completely disappeared in 241 cases (75.3%), 50 cases (15.6%) improved; the total effective rate of surgery was 90.9%. No obvious changes of hemifacial spasm were happened in 29 cases (9.1%). There was no deteriorated case.MVD is one of the preferred treatments of hemifacial spasm, the intraoperative electrophysiological monitoring of abnormal muscle response signals contributes to the determination of responsible vessels and fully understanding of delayed resolution is helpful to the accuracy of surgical evaluation.


Metabolomic Analysis Provides New Insight Into Tolerance of Huanglongbing in Citrus.
There have been efforts to develop citrus cultivars that are tolerant of Huanglongbing (HLB), a catastrophic phloem-limited disease. Previous studies demonstrated that continuous plant growth with phloem regeneration is one of the major characteristics of HLB tolerance. In this study, the metabolic mechanisms of HLB tolerance in citrus were elucidated using a multiple pathway-targeted metabolomic approach. Comparative analysis of healthy and infected HLB-tolerant and HLB-sensitive mandarin cultivars (Citrus reticulata) revealed differentially expressed metabolic responses among different groups. Pathway enrichment analysis indicated aspartate and glutamate metabolism, purine metabolism, and biosynthesis of plant hormones were upregulated in the tolerant group, except salicylic acid signaling. Catabolic pathways linked to energy-yielding metabolism were also upregulated in the tolerant group. These metabolisms and pathways were interconnected with each other, unveiling a pivotal metabolic network associated with HLB tolerance. In the network, auxins and cytokinins, the plant hormones responsible for plant growth and phloem regeneration, were accumulated. In addition, purine metabolites serving as energy carriers and nitrogen sources of plants were increased. Only salicylic acid-related metabolites for plant defense responses were decreased in the tolerant group. Our findings may evidence the strategy of HLB-tolerant cultivars that sustain plant growth and phloem formation rather than displaying direct plant defense to overcome the disease.


Multiple T-cell responses are associated with better control of acute HIV-1 infection: An observational study.
Cytotoxic T lymphocyte (CTL) responses play pivotal roles in controlling the replication of human immunodeficiency virus type 1 (HIV-1), but the correlation between CTL responses and the progression of HIV-1 infection are controversial on account of HIV immune escape mutations driven by CTL pressure were reported.The acute HIV-1-infected patients from Beijing were incorporated into our study to investigate the effects of CTL response on the progression of HIV-1 infection.A longitudinal study was performed on acute HIV-1-infected patients to clarify the kinetic of T-cell responses, the dynamic of escape mutations, as well as the correlation between effective T-cell response and the progression of HIV infection.Seven human leukocyte antigen-B51+ (HLA-B51+) individuals were screened from 105 acute HIV-1 infectors. The detailed kinetic of HLA-B51-restricted CTL responses was described through blood sampling time points including seroconversion, 3 and 6 months after HIV-1 infection in the 7 HLA-B51+ individuals, by using 16 known HLA-B51 restricted epitopes. Pol743-751 (LPPVVAKEI, LI9), Pol283-289 (TAFTIPSI, TI8), and Gag327-3459 (NANPDCKTI, NI9) were identified as 3 dominant epitopes, and ranked as starting with LI9, followed by TI8 and NI9 in the ability to induce T-cell responses. The dynamics of escape mutations in the 3 epitopes were also found with the same order as T-cell response, by using sequencing for viral clones on blood sampling at seroconversion, 3 and 6 months after HIV-1 infection.We use solid evidence to demonstrate the correlation between T-cell response and HIV-1 mutation, and postulate that multiple T-cell responses might benefit the control of HIV-1 infection, especially in acute infection phase.


The effect of almonds on vitamin E status and cardiovascular risk factors in Korean adults: a randomized clinical trial.
Almonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic populations but this relationship has never been tested in Koreans. Thus, we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors. We conducted a randomized, crossover trial in a free-living setting with a 2-week run-in period, two 4-week intervention phases, and a 2-week washout period between interventions. Eighty four overweight/obese participants (11 M/73 F; 52.4 ± 0.6 year; 25.4 ± 0.22 kg/m2) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks. Mean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by 192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased by the almonds, but body weight, waist circumference, and body composition were not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C, and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control (P ≤ 0.05). Almonds increased plasma α-tocopherol by 8.5% (P ≤ 0.05) from the baseline and tended to increase its value as compared to cookies (P = 0.055). Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL. Of serum inflammatory markers, IL-10 was decreased by almond intake (P ≤ 0.05), and ICAM-1, IL-1β, and IL-6 tended to be lower with almonds, compared to the cookies. Almonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and decreasing % energy intake from carbohydrate. Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus, including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD.


The difference between benign and malignant tumours explained with the 4-mutation paradigm for carcinogenesis.
In recent years a 4-mutation paradigm for carcinogenesis was developed for mutations in tumour suppressor genes. The major tenet of this paradigm is that transformation of a normal cell into a malignant cell is the result of an accumulation of a set of 4 specific cancer mutations. In this paper we show that this paradigm can explain the characteristic differences between benign and malignant tumours. We surmise that benign tumour cells are due to 2 or 3 specific cancer mutations, whereas malignant tumour cells contain 4 specific cancer mutations and 1-3 tumour progression mutations. The following characteristics, essential for differentiating benign and malignant tumours, are explained by our paradigm: (a) differentiation--anaplasia, (b) rate of growth, (c) encapsulation--invasion, (d) metastasis, and (e) the differences in size of benign epithelial and mesenchymal tumours and the relation between tumour size and malignancy.


Rare case of pediatric cecal volvulus.
An 11-year-old female child presented with abdominal pain, vomiting and constipation. An exploratory laparotomy revealed a cecal volvulus due to a congenital band and malfixation of the cecum. This was treated by excision of the band, derotation and decompression of cecum though an appendiceal stump suction.


European Lipoprotein Club: report of the 20th annual conference, Tutzing, 8-11 September 1997.
The year 1997 celebrated the 20th anniversary of the European Lipoprotein Club. Sessions explored topics in the line of classical concepts and forthcoming advances in the field of basic and clinical research on lipoproteins. Participants from 18 European countries attended the conference. Recent Developments in Lipoprotein Research, were reviewed by Thomas Olivecrona (Umea, Sweden), who gave a perspective on lipolysis; and Gerd Assmann (Münster, Germany), who overviewed epidemiological data of the PROCAM study and focused on the biochemical and genetic components of reverse cholesterol transport. Session I, chaired by Katriina Aalto Setälä (Tampere, Finland) and Marten Hofker (Leiden, Netherlands) was dedicated to 'Lipoprotein receptors (old and new)'. Various structural and functional aspects were reported for the newcomers in the ever enriching LDL receptor gene family (VLDLR, LR7/8B, LR11, Megalin, RAP-related proteins). However, a decade of identification of LDL receptors gene defects reveals now that phenocopies of familial hypercholesterolemia may be linked to a third, yet unknown locus. Identification of pathways which clear HDL is underway. Session II, chaired by David Bowyer (Cambridge, United Kingdom) and Richard W James (Geneva, Switzerland), was entitled 'Significance of lipoprotein heterogeneity (metabolic and pathological aspects)'. Factors involved in lipoprotein modification (dense LDL, oxidation), transient production (post prandial, VLDL synthesis) or degradation (complement activation) and controversial hypotheses on their links with atherosclerosis were discussed. Session III on 'Novel methodologies for lipoprotein research' was chaired by Rudolph Poledne (Prague, Czech Republic) and Armin Steinmetz (Marburg, Germany). Simple technologies for routine assessment of lipoprotein metabolism, as well as the most sophisticated ones, to study lipid and free radical exchanges between particles, were presented.


Module-Assembled Elastomer Showing Large Strain Stiffening Capability and High Stretchability.
Elastomers are indispensable materials due to their flexible, stretchable, and elastic nature. However, the polymer network structure constituting an elastomer is generally inhomogeneous, limiting the performance of the material. Here, a highly stretchable elastomer with unprecedented strain-stiffening capability is developed based on a highly homogeneous network structure enabled by a module assembly strategy. The elastomer is synthesized by efficient end-linking of a star-shaped aliphatic polyester precursor with a narrow molecular-weight distribution. The resulting product shows high strength (≈26 MPa) and remarkable stretchability (stretch ratio at break ≈1900%), as well as good fatigue resistance and notch insensitivity. Moreover, it shows extraordinary strain-stiffening capability (>2000-fold increase in the apparent stiffness) that exceeds the performance of any existing soft material. These unique properties are due to strain-induced ordering of the polymer chains in a uniformly stretched network, as revealed by in situ X-ray scattering analyses. The utility of this great strain-stiffening capability is demonstrated by realizing a simple variable stiffness actuator for soft robotics.


Comparison of biomarker expression between proximal and distal colorectal adenomas: The Tennessee-Indiana Adenoma Recurrence Study.
It is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n = 380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or "equivalent both sides." Eight biomarkers in the most advanced adenomas were evaluated by immunohistochemistry (Ki-67, COX-2, TGFβRII, EGFR, β-catenin, cyclin D1, c-Myc) or TUNEL (apoptosis). After an adjustment for pathological features, there were no significant differences between proximal and distal adenomas for any biomarker. Conversely, expression levels did vary by other features, such as their size, villous component, and synchronousness. Large adenomas had higher expression levels of Ki-67(P < 0.001), TGFβRII (P < 0.0001), c-Myc (P < 0.001), and cyclin D1 (P < 0.001) in comparison to small adenomas, and tubulovillous/villous adenomas also were more likely to have similar higher expression levels in comparison to tubular adenomas. Adenoma location is not a major determinant of the expression of these biomarkers outside of other pathological features. This study suggests similarly important roles of Wnt/β-catenin and TGF-β pathways in carcinogenesis in both the proximal and distal colorectum. © 2016 Wiley Periodicals, Inc.


Quality assurance programme for nursing.
This article describes a conceptual and methodological framework for evaluating nursing care quality. The conceptual framework is based on Orem's theory of self-care which emphasizes the importance of decisions in the selection of nursing process based on patient status and problems. The primary outcome criteria is self-care. The methodological framework is based on Greenfield's criteria maps methodology for linking patient status (problems or diagnoses) to decisions about nursing interventions and linking these specific nursing intervention criteria to desired outcomes for self-care. The article further describes a multiagency quality assurance programme for nursing. The programme includes: a definition of criteria and standards across agencies; nursing care management protocols that define standards of care; continuing education courses for nursing based on management protocols; the maps method of auditing actual and recorded nursing process and patient outcomes as defined in the management protocol.


The influences of methylphenidate on heart rate and behavioral measures of attention in hyperactive children.
Reaction-time performance and heart-rate responses associated with attention were used to assess the hyperactive child's attentional deficit and his response to methylphenidate. Attentional deficits shown by long response latencies were reflected in heart-rate responses theoretically incompatible with sustained attention. Subjects exhibiting the greatest attentional deficit displayed the most favorable response to methylphenidate in both reaction-time performance and physiological measures. However, subjects who showed the greatest improvement in social behavior were those who showed the least improvement in reaction-time performance.


Does body scanning through visual imagery improve perception and function in patients after anterior cruciate ligament-reconstruction? An exploratory study.
Many people who have undergone Anterior Cruciate Ligament (ACL)-reconstruction do not return to their pre-injury level, with nonphysical factors recognized as barriers to recovery. Fear of movement has been linked to body schema distortions, and interventions directed at the body schema have shown potential to improve function. 1) Describe participants' ability to perform a visual imagery intervention (Body Scan); 2) investigate knee perception differences; 3) investigate if Body Scan led to improvements in perceptual differences; and 4) determine if some individuals improved in functional measures following the intervention. A single-arm intervention study was undertaken in people >12-month post ACL-reconstruction (n = 30). Body Scan was delivered using a standardized script developed for this study. Participants were assessed regarding their capacity to perform the Body Scan, perceptual differences between the knees and how perception changed following the intervention. Functional measures (vertical hop, triple hop, mSEBT, quadriceps strength, and hamstring strength) were taken. 96.7% were able to perform a Body Scan, with 93.1% demonstrating a difference in perception between the knees. Of participants with perceptual differences, 92.5% demonstrated improvement in perception following the intervention. Ten participants had a clinically significant improvement in a functional measure following the intervention. Most participants could perform Body Scanning. The majority perceived perceptual differences between operated and non-operated knees, and reported more symmetric perception following the intervention. One-third of participants also showed improvements in a functional performance measure. Results suggest this intervention may be a helpful adjunct to rehabilitation post ACL-reconstruction, with further research warranted.


The effect of dietary components on inflammatory lung diseases - a literature review.
Anti-inflammatory treatment in chronic inflammatory lung diseases usually involves glucocorticosteroids. With patients suffering from serious side effects or becoming resistant, specific nutrients, that are suggested to positively influence disease progression, can be considered as new treatment options. The dietary inflammatory index is used to calculate effects of dietary components on inflammation and lung function to identify most potent dietary components, based on 162 articles. The positive effects of n-3 PUFAs and vitamin E on lung function can at least partially be explained by their anti-inflammatory effect. Many other dietary components showed only small or no effects on inflammation and/or lung function, although the number of weighted studies was often too small for a reliable assessment. Optimal beneficial dietary elements might reduce the required amounts of anti-inflammatory treatments, thereby decreasing both side effects and development of resistance as to improve quality of life of patients suffering from chronic inflammatory lung diseases.


Molecular cloning of a major human gall bladder mucin: complete C-terminal sequence and genomic organization of MUC5B.
Gall bladder mucin has been shown to play a central role in the pathogenesis of cholesterol gallstone disease. While cloning and sequencing studies have provided a wealth of information on the structure of other gastrointestinal and respiratory mucins, nothing is known about the primary structure of human gall bladder mucin. In this study, we show that the tracheobronchial mucin MUC5B is a major mucin gene product expressed in the gall bladder. Antibodies directed against deglycosylated human gall bladder mucin were used to screen a gall bladder cDNA expression library, and most of the isolated clones contained repetitive sequences nearly identical with those in the tandem repeat region of MUC5B. An additional clone (hGBM2-3) contained an open reading frame coding for a 389 residue cysteine-rich sequence. The arrangement of cysteine residues in this sequence was very similar to that in the C-terminal regions of MUC2, MUC5AC and human von Willebrand factor. This cysteine-rich sequence was connected to a series of degenerate MUC5B tandem repeats in a 7.5 kb HincII genomic DNA fragment. This fragment, with ten exons and nine introns, contained MUC5B repeats in exon 1 and a 469 residue cysteine-rich sequence in exons 2-10 that provided a 152 nucleotide overlap with cDNA clone hGBM2-3. Interestingly, the exon-intron junctions in the MUC5B genomic fragment occurred at positions equivalent to those in the D4 domain of human von Willebrand factor, suggesting that these proteins evolved from a common evolutionary ancestor through addition or deletion of exons encoding functional domains.


[Plasmid pUDKH gene therapy of rat acute hindlimb ischemia: an experimental study].
To investigate the effect of plasmid pUDKH carrying human hepatocyte growth factor (HGF) gene on rat acute limb ischemia and to find the lowest effective dosage. Ligation of femoral artery of one hindlimb in Wistar rats was performed. The rats were randomly divided into 5 groups of 10 rats: pUDKH 50 microg, 100 microg, 200 microg, and 400 microg groups and a vacant vector pUDK group (control group). The plasmids were injected once directly into the ischemic limb muscle (5 sites around ligation position) immediately after ligation. At day 10, the muscles were removed and stained with H.E. to assess histologically the blood vessel formation. HGF expression was detected in the muscle tissue of another 12 rats on days 3, 5, 10, 14, 21, 30 after injection of pUDKH or pUDK, 200 microg each per animal. HGF expression was detected clearly in muscle tissue on days 3, 5, 10, 14 in pUDKH groups. In HGF-transfected animals (except for 50 microg group) neoformation of blood vessels in muscles and soft tissues was found, while it was not seen in controls. By semi-quantitation of the degree of vessel formation, significant differences between pUDKH groups (0.96 +/- 0.07, 1.97 +/- 0.91, 2.26 +/- 1.00 for 100 microg, 200 microg, 400 microg, respectively) and the control group (0.27 +/- 0.04) (P < 0.05) were noted. In addition, injection of pUDKH could alleviate the severity of degeneration of muscular tissue due to ischemia. Human HGF gene therapy is effective in treating rat acute limb ischemia with the lowest effective dose of 100 microg.


Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation.
T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells. Using a well-established ex vivo protocol of canonical T-cell receptor signaling, we generated genome-wide chromatin maps of naïve T-cells from pediatric donors in quiescent or recently activated states. We identified thousands of individual chromatin accessibility peaks that are associated with T-cell activation, the majority of which were annotated intronic and intergenic enhancer regions. A core set of 3268 gene promoters underwent chromatin remodeling and concomitant changes in gene expression in response to activation, and were enriched in multiple pathways controlling cell cycle regulation, metabolism, inflammatory response genes and cell survival. Leukemia inhibitory factor (LIF) was among those factors that gained the highest accessibility and expression, in addition to IL2-STAT5 dependent chromatin remodeling in the T-cell activation response. Using publicly available data we found the chromatin response was far more dynamic at 24-h compared with 72-h post-activation. In total 546 associations were reproduced at both time-points with similar strength of evidence and directionality of effect. At the pathways level, the IL2-STAT5, KRAS signalling and UV response pathways were replicable at both time-points, although differentially modulated from 24 to 72 h post-activation.


Fit for purpose and modern validity theory in clinical outcomes assessment.
The US Food and Drug Administration (FDA), as part of its regulatory mission, is charged with determining whether a clinical outcome assessment (COA) is "fit for purpose" when used in clinical trials to support drug approval and product labeling. In this paper, we will provide a review (and some commentary) on the current state of affairs in COA development/evaluation/use with a focus on one aspect: How do you know you are measuring the right thing? In the psychometric literature, this concept is referred to broadly as validity and has itself evolved over many years of research and application. After a brief introduction, the first section will review current ideas about "fit for purpose" and how it has been viewed by FDA. This section will also describe some of the unique challenges to COA development/evaluation/use in the clinical trials space. Following this, we provide an overview of modern validity theory as it is currently understood in the psychometric tradition. This overview will focus primarily on the perspective of validity theorists such as Messick and Kane whose work forms the backbone for the bulk of high-stakes assessment in areas such as education, psychology, and health outcomes. We situate the concept of fit for purpose within the broader context of validity. By comparing and contrasting the approaches and the situations where they have traditionally been applied, we identify areas of conceptual overlap as well as areas where more discussion and research are needed.


Omega-3 fatty acids and the cardiometabolic syndrome.
Benefits of fish consumption in patients with the cardiometabolic syndrome relate to the high biologic value of protein, omega-3 fatty acids, as well as certain minerals and vitamins in fish. Recently, the American Heart Association issued new guidelines for the intake of omega-3 oils for the prevention of coronary heart disease. The objective of this paper is to evaluate the potential health benefits of fish consumption and/or fish oil supplements in reducing cardiometabolic syndrome risk factors. The consumption of fish or fish oil containing omega-3 polyunsaturated fatty acids reduces the risk of coronary heart disease, decreases triglyceride, blood pressure, and inflammatory markers, improves endothelial function, prevents certain cardiac arrhythmias, reduces platelet aggregation (including reactivity and adhesion), reduces vasoconstriction, enhances fibrinolysis, reduces fibrin formation, and decreases the risk of microalbuminuria and sudden cardiac death. Thus, fish intake or fish oil supplement use is beneficial to reduce cardiometabolic risk factors.


Improving the diffuse optical imaging spatial resolution of the cerebral hemodynamic response to brain activation in humans.
We compare two geometries of sources and detectors for optimizing the diffuse optical imaging resolution of brain activation in humans. Because of limitations in the instruments' dynamic range, most diffuse optical brain activation images have used only nonoverlapping measurements. We demonstrate theoretically and with a human experiment that a simple geometry of sources and detectors can provide overlapping measurements within the limitation of instrumentation dynamic range and produce an image resolution and localization accuracy that is twofold better.


Characterization of leucocyte phagocytic stimulatory material released by activated human platelets.
The action of material released by activated human platelets on the phagocytic activity of human neutrophils and monocytes has been examined under conditions where there was a low background level of exposure of the leucocytes to platelet release products ( PRPr ). Incubation with PRPr produced an approximate three-fold stimulation of particle ingestion by both cell types. Material with stimulatory activity passed through ultrafiltration membranes capable of retaining molecules greater than 500 Daltons. This low molecular weight stimulator was inactivated by ATP diphosphopyrolase to suggest it could be one or more of the nucleotide di- or triphosphates in PRPr . Comparison with the action of specific nucleotides revealed only ADP and ATP exerted equivalent stimulatory effects at concentrations consistent with those of nucleotides normally present in PRPr . This effect was mediated by induction of a change in leucocyte behaviour which was sustained in the absence of continued exposure to the stimulatory agent. Stimulation of phagocytosis was also produced by high molecular weight material in PRPr , but this appeared to be mediated by dissociation of low molecular weight stimulator from a high molecular weight complex. These observations extend the range of biological functions known to respond to nucleotides in PRPr , and have implications for the interpretation of leucocyte phagocytic activity assessed in vitro in view of the potential modification of this process by exposure of leucocytes to PRPr during the isolation of leucocytes from peripheral blood.


Maintenance of subcutaneous cavities with CO2.
Since mechanical retractors in endoscopic plastic surgery cause certain drawbacks, we developed a model in dogs, which, by insufflating CO2 into a subcutaneous cavity, we were able to maintain. We evaluated the magnitude of subcutaneous emphysema and absorption of CO2 by insufflating different pressures and the efficacy of external pressure on the skin with the purpose of limiting the subcutaneous emphysema. Sixteen dogs were divided in 3 groups, A, B, and C. We controlled the pulmonary function by using a volume-cycle ventilator. In all groups, we maintained a subcutaneous cavity by insufflating CO2. Groups A and C were insufflated at 15 mm Hg; group B, at 8 mm Hg. We placed circumferential Esmarch bandages on the thorax of groups B and C to delimit superiorly and inferiorly the surgical area. Arterial blood gas analyses (ABGA) were taken from the femoral artery 60 minutes after intubation, 60 minutes after Esmarch bandage was placed and at the end of the CO2 insufflation. Statistically, results were analyzed by Wilcoxon test. P < 0.05 was considered statistically significant. Group A showed extensive subcutaneous emphysema. Two dogs died. The systemic increase of the CO2 showed a median of 9.6 mm Hg (P < 0.05). In Group B, Esmarch bandages caused increase in CO2, with a median of 1.65 mm Hg (P < 0.028). None of these dogs showed subcutaneous emphysema during the insufflation after CO2 insufflation pressure augmented with a median of 3.7 mm Hg (P < 0.028). In Group C, chest restriction increased CO2 median of 6.1 mm Hg (P < 0.043), and subcutaneous emphysema shown was less extensive than group A. The CO2 increased after insufflation a median of 16 mm Hg (P < 0.043). Subcutaneous cavities can be maintained open with CO2 insufflation at 8 mm Hg, limiting perfectly the surgical area; as done with Esmarch bandages, it reduces CO2 absorption and makes this procedure safe.


Immunocytochemical localization of growth hormone-releasing hormone-like peptide in the brain of the tiger frog, Rana tigrina.
Using antisera directed against carp growth hormone-releasing hormone (cGHRH), we found more extensive brain distribution of GHRH-like immunoreactive (ir) neurons in the tiger frog, Rana tigrina, than reported in previous studies, which employed mammalian GHRH antibodies. In the telencephalon, GHRH-ir perikarya were present in the pallium dorsale, pallium laterale (pars dorsalis and pars ventralis), pallium mediale, nucleus entopeduncularis, amygdala pars medialis, and in the ventral portion of the lateral preoptic area. Most GHRH somata were present in the nucleus infundibularis ventralis located around the third ventricle, extending from the region posterior to the optic chiasma to the caudal end of infundibulum. In the thalamic region, GHRH-ir perikarya occurred in the area ventrolateralis thalami, the nuclei posterocentralis thalami, and the posterolateralis thalami. The ir cell bodies in the nucleus posteroventralis tegmenti mesencephali represented the caudal-most brain GHRH perikarya. Extensive GHRH-ir fibers occurred around the nonreactive cells in the ventral preoptic area and ventral area of the infundibulum. GHRH-ir fibers were present in the outer layers of the median eminence, but not in the neural lobe or pars distalis of the pituitary gland. This wider neuroanatomical distribution of GHRH-like peptide in the brain of R. tigrina should, provide the basis for future studies to establish the exact role of GHRH-like peptides in anuran brain.


[Analysis and state of HCV genotype 6a infection].
To investigate the infection state of hepatitis C virus genotype 6a in China. Three (95, 126, 150)HCV genotype 6a serum samples were identified by digesting 5'NCR with compound enzyme method. Then, HCV 5'NCR and NS5B fragments were amplified from these samples by RT-PCR assay and sequenced. The phylogenetic trees of the samples were analyzed and compared with 24 HCV complete gene sequences from GenBank. The sequencing reports on 5'NCR showed "CA" bases in 3 serum samples (95,126,150) were inserted into -145 site, and the sequences of 3 serum samples had the highest homology with sequence Y12083( 0.934, 0.930, and 0.926, respectively). The results of the phylogenetic trees suggested these 3 serum samples belonged to HCV genotype 6a. The sequencing reports on NS5B showed the 3 serum samples also had the highest homology with HC-J4(0.934, 0.930, and 0.926, respectively), and the results of the phylogenetic trees suggested these 3 serum samples belonged to HCV genotype 1b. To exclude the influence of amplification efficiency of primers, NS5B fragments were amplified by HCV genotype 6a specific primers and no amplification products appeared. There are different results of HCV genotype by analyzing 5'NCR and NS5B in 3 samples infected with HCV genotype 6a. It may be related with gene recombination. It suggests HCV genotype should be analyzed on more than two regions.


Nitric oxide activates TRP channels by cysteine S-nitrosylation.
Transient receptor potential (TRP) proteins form plasma-membrane cation channels that act as sensors for diverse cellular stimuli. Here, we report a novel activation mechanism mediated by cysteine S-nitrosylation in TRP channels. Recombinant TRPC1, TRPC4, TRPC5, TRPV1, TRPV3 and TRPV4 of the TRPC and TRPV families, which are commonly classified as receptor-activated channels and thermosensor channels, induce entry of Ca(2+) into cells in response to nitric oxide (NO). Labeling and functional assays using cysteine mutants, together with membrane sidedness in activating reactive disulfides, show that cytoplasmically accessible Cys553 and nearby Cys558 are nitrosylation sites mediating NO sensitivity in TRPC5. The responsive TRP proteins have conserved cysteines on the same N-terminal side of the pore region. Notably, nitrosylation of native TRPC5 upon G protein-coupled ATP receptor stimulation elicits entry of Ca(2+) into endothelial cells. These findings reveal the structural motif for the NO-sensitive activation gate in TRP channels and indicate that NO sensors are a new functional category of cellular receptors extending over different TRP families.


Controlling magnon-magnon entanglement and steering by atomic coherence.
Here we show that it is possible to control magnon-magnon entanglement in a hybrid magnon-atom-cavity system based on atomic coherence. In a four-level V-type atomic system, two strong fields are applied to drive two dipole-allowed transitions and two microwave cavity modes are coupled with two dipole forbidden transitions as well as two magnon modes simultaneously. It is found that the stable magnon-magnon entanglement, one-way steering and two-way EPR steering can be generated and controlled by atomic coherence according to the following two points: (i) the coherent coupling between magnon and atoms is established via exchange of virtual photons; (ii) the dissipation of magnon mode is dominant over amplification since one of the atomic states mediated one-channel interaction always keeps empty. The coherent control of magnon-magnon correlations provides an effective approach to modify macroscopic quantum effects using the laser-driven atomic systems.


The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial.
To determine the epidemiology of CA-125 in women without ovarian cancer. We analyzed demographic, medical and lifestyle characteristics related to CA-125, measured using the Centocor CA-125II RIA assay, among 25,608 multi-ethnic U.S. women aged 55-74 years enrolled in a cancer screening trial and found to have no evidence of ovarian cancer. Mean CA-125 level was 11.9 U/ml (SD 8.3); median 10.0 U/ml, interquartile range 8.0-14.0. High levels, using the clinical cut point of >or=35 U/ml, were associated with increased age (p<0.001) and former smoking (p<0.021), while hysterectomy and obesity were protective (p<0.001). Mean levels were higher with increasing age (p<0.001), ever use of hormone therapy (p<0.001), former smoking (p<0.017) and history of breast cancer (p<0.002), but lower (p<0.001) with non-White status, previous hysterectomy, current smoking, and obesity. Current hormone therapy use was not associated with CA-125 in women without a uterus. In post-menopausal women without ovarian cancer, CA-125 level is influenced by a number of factors, including race/ethnicity, age, hysterectomy, smoking history and obesity.


Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system.
The amyloid precursor superfamily is composed of three highly conserved transmembrane glycoproteins, the amyloid precursor protein (APP) and amyloid precursor-like proteins 1 and 2 (APLP1, APLP2), whose functions are unknown. Proteolytic cleavage of APP yields the betaA4 peptide, the major component of cerebral amyloid in Alzheimer's disease. Here we show that five post-translationally modified, full-length species of APP and APLP2 (but not APLP1) arrive at the mature presynaptic terminal in the fastest wave of axonal transport and are subsequently rapidly cleared (mean half-life of 3.5 h). Rapid turnover of presynaptic APP and APLP2 occurs independently of visual activity. Turnover of the most rapidly arriving APP species was accompanied by a delayed accumulation of a 120-kDa, APP fragment lacking the C terminus, consistent with presynaptic APP turnover via constitutive proteolysis. Turnover of APLP2 was not accompanied by detectable APLP2 fragment peptides, suggesting either that APLP2 either is more rapidly degraded than is APP or is retrogradely transported shortly after reaching the terminus. A single 150-kDa APLP2 species containing the Kunitz protease inhibitor domain is the major amyloid precursor superfamily protein transported to the presynapse. Presynaptic APP and APLP2 are sialylated and N- and O-glycosylated, and some also carry chondroitin sulfate glycosaminoglycan and/or dermatan sulfate glycosaminoglycan. The rapid kinetics for turnover of APP and APLP2 predict a sensitive balance of synthesis, transport, and elimination rates that may be critical to normal neuronal functions and metabolic fates of these proteins.


Evaluation of the nutritional status of 1st-year school children in Campinas, Brazil.
We present findings from a study of nutritional status amongst 1st year primary school children in Brazil. The study was based on a 10% stratified random sample of children in Campinas, Sao Paulo State. The primary schools in the city were grouped into four socio-economic strata (high, medium, low and very low) based on the type of school maintenance (private or maintained by the local or by the State government) and the socio-economic characteristics of the school's catchment area. The nutritional status of 1942 children was assessed by looking at the distributions of z-scores of weight-for-age, height-for-age and weight-for-height in relation to growth charts of the National Center for Health Statistics reference population. In the overall population, 22% of the children were found to be stunted (z-score of height-for-age less than -1.0), 15% wasted (z-score of weight-for-height less than -1.0), 22% underweight (z-score of weight-for-age less than -1.0) and 5% overweight (z-score of weight-for-height greater than 2.0). These figures represent an excess of 6% of stunted children and also 6% of underweight children in comparison with the expected values in the NCHS reference population, and an excess of 2% overweight. The data were analysed by age, sex, ethnic group and socio-economic level. Both stunting and low weight-for-age were observed in 32% of children from the very low socio-economic level, with the highest percentages amongst the oldest children. A total of 11.6% of children from the high socio-economic stratum were obese. These results emphasize the need for different programmes to deal with nutritional problems in different groups of the population.


Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase.
Doxorubicin is a highly effective anticancer chemotherapy agent, but its use is limited by its cardiotoxicity. To develop a drug that prevents this toxicity, we established a doxorubicin-induced cardiomyopathy model in zebrafish that recapitulates the cardiomyocyte apoptosis and contractility decline observed in patients. Using this model, we screened 3000 compounds and found that visnagin (VIS) and diphenylurea (DPU) rescue the cardiac performance and circulatory defects caused by doxorubicin in zebrafish. VIS and DPU reduced doxorubicin-induced apoptosis in cultured cardiomyocytes and in vivo in zebrafish and mouse hearts. VIS treatment improved cardiac contractility in doxorubicin-treated mice. Further, VIS and DPU did not reduce the chemotherapeutic efficacy of doxorubicin in several cultured tumor lines or in zebrafish and mouse xenograft models. Using affinity chromatography, we found that VIS binds to mitochondrial malate dehydrogenase (MDH2), a key enzyme in the tricarboxylic acid cycle. As with VIS, treatment with the MDH2 inhibitors mebendazole, thyroxine, and iodine prevented doxorubicin cardiotoxicity, as did treatment with malate itself, suggesting that modulation of MDH2 activity is responsible for VIS' cardioprotective effects. Thus, VIS and DPU are potent cardioprotective compounds, and MDH2 is a previously undescribed, druggable target for doxorubicin-induced cardiomyopathy.


Scaling out of electrolyte free electrosynthesis in a micro-gap flow cell.
The electro-reductive coupling of activated olefins and benzyl bromide derivatives has been selected to compare the performance of single and multiple channel (scaled-out) micro-gap electrochemical flow reactors. Two working electrode configurations were evaluated; in the first a single set of electrodes was used in conjunction with a multiple flow manifold to give two and four separate flow channels; in the second independent electrodes were used within the same flow manifold. Problems with shunt currents and Joule heating in the first configuration meant that only the second configuration was reliable, giving results comparable to those obtained for the single flow cell. Excellent yields of the coupling products such as 2-benzyl-succinic acid dimethyl ester and derivatives were obtained. This demonstrates micro reactor scale-out for unsupported electrosyntheses.


Caregiving for a loved one with dementia at the end of life: an emergent theory of rediscovering.
Millions face the challenges of caregiving for a loved one with dementia. A classic Glaserian grounded theory methodology was used to discover the problem that caregivers of individuals with dementia face at the end of life and how they attempt to resolve that problem. Data were collected from a theoretical sample of 101 participants through in-person interviews, online interviews, book and blog memoirs of caregivers, and participant observation. Constant comparative method revealed a basic social psychological problem of role entrapment. Caregivers attempt to resolve this problem through a 5-stage basic social psychological process of rediscovering including missing the past, sacrificing self, yearning for escape, reclaiming identity, and finding joy. Health care professionals can support caregivers through this journey by validating, preparing caregivers for future stages, and encouraging natural coping strategies identified in this process. This study provides a substantive theory that may serve as a framework for future studies.


Data collection in a multisite project: Teleform.
Data collection, entry, validation, and management are salient time- and resource-consuming dimensions of all research projects. This is especially true for multisite studies, which pose unique, additional challenges because of their research design requirements. To save time and reduce the number of manual data entry errors, automated processing systems are becoming more widely used. Our research team chose Teleform for data entry and collection for the Smoking Cessation or Reduction in Pregnancy Trial study. This article presents our experience with this new technology.


Complete appendiceal intussusception induced by primary appendiceal adenocarcinoma in tubular adenoma: a case report.
A case of complete intussusception induced by appendiceal carcinoma is reported. The patient was a 49-year-old man complaining of rectal bleeding. Barium enema and colonoscopy revealed a cecal polyp; it was interpreted as an inverted appendix with a tumor. Computed tomography showed an invaginated appendix into the cecal cavity. During surgery, the appendix was found to be inverted completely into the cecum; ileocecal resection with regional lymph node dissection was performed. Microscopic examination revealed well-differentiated adenocarcinoma in tubular adenoma. Diagnosis of intussusception with carcinoma of the appendix is often difficult because appendiceal carcinoma with intussusception of the appendix is a rare condition. Although this condition can be diagnosed by radiographic imaging or colonoscopy, computed tomography has also been useful. The clinical manifestation of appendiceal intussusception with primary appendiceal tumor resembles a large cecal polyp, but its treatment differs greatly. Failure to recognize this condition may result in unexpected complications such as consequent peritonitis in case of endoscopic removal.


No harm done.
People who take a drug overdose or otherwise harm themselves do not always receive a good reception in A&E. But in Kent an award-winning scheme is helping people to avoid the repetition of self-harming behaviour.


A quadriceps femoris motor pattern for efficient cycling.
In cycling, propulsion is generated by the muscles of the lower limbs and hips. After the first reports of pedal/crank force measurements in the late 1960s, it has been assumed that highly trained athletes have better power transfer to the pedals than recreational cyclists. However, motor patterns indicating higher levels of performance are unknown. To compare leg muscle activation between trained (3.5-4.2 W/kgbw) and highly trained (4.3-5.1 W/kgbw) athletes we applied electromyography, lactate, and bi-pedal/crank force measurements during a maximal power test, an individual lactate threshold test and a constant power test. We show that specific activation patterns of the rectus femoris (RF) and vastus lateralis (VL) impact on individual performance during high-intensity cycling. In highly trained cyclists, we found a strong activation of the RF during hip flexion. This results in reduced negative force in the fourth quadrant of the pedal cycle. Furthermore, we discovered that pre-activation of the RF during hip flexion reduces force loss at the top dead center (TDC) and can improve force development during subsequent leg extension. Finally, we found that a higher performance level is associated with earlier and more intense coactivation of the RF and VL. This quadriceps femoris recruitment pattern improves force transmission and maintains propulsion at the TDC of the pedal cycle. Our results demonstrate neuromuscular adaptations in cycling that can be utilized to optimize training interventions in sports and rehabilitation.


A Pulse Rate Detection Method for Mouse Application Based on Multi-PPG Sensors.
Heart rate is an important physiological parameter for healthcare. Among measurement methods, photoplethysmography (PPG) is an easy and convenient method for pulse rate detection. However, as the PPG signal faces the challenge of motion artifacts and is constrained by the position chosen, the purpose of this paper is to implement a comfortable and easy-to-use multi-PPG sensor module combined with a stable and accurate real-time pulse rate detection method on a computer mouse. A weighted average method for multi-PPG sensors is used to adjust the weight of each signal channel in order to raise the accuracy and stability of the detected signal, therefore reducing the disturbance of noise under the environment of moving effectively and efficiently. According to the experiment results, the proposed method can increase the usability and probability of PPG signal detection on palms.


Supramolecular sky-blue phosphorescent polymer iridium complexes for single-emissive-layer organic light-emitting diodes.
Novel supramolecular phosphorescent polymers (SPPs) are synthesized as a new class of solution-processable electroluminescent emitters. The formation of these SPPs takes advantage of the efficient non-bonding assembly between bis(dibenzo-24-crown-8)-functionalized iridium complex monomer and bis(dibenzylammonium)-tethered co-monomer, which is monitored by (1) H NMR spectroscopy and viscosity measurements. These SPPs show good film morphology and an intrinsic glass transition with a Tg of 94-116 °C. Noticeably, they are highly photoluminescent in solid state with quantum efficiency up to ca. 78%. The photophysical and electroluminescent properties are strongly dependent on the molecular structures of the iridium complex monomers.


Moral uncertainty and the farming of human-pig chimeras.
It may soon be possible to generate human organs inside of human-pig chimeras via a process called interspecies blastocyst complementation. This paper discusses what arguably the central ethical concern is raised by this potential source of transplantable organs: that farming human-pig chimeras for their organs risks perpetrating a serious moral wrong because the moral status of human-pig chimeras is uncertain, and potentially significant. Those who raise this concern usually take it to be unique to the creation of chimeric animals with 'humanised' brains. In this paper, we show how that the same style of argument can be used to critique current uses of non-chimeric pigs in agriculture. This reveals an important tension between two common moral views: that farming human-pig chimeras for their organs is ethically concerning, and that farming non-chimeric pigs for food or research is ethically benign. At least one of these views stands in need of revision.


Multiple sevoflurane anesthesia in pregnant mice inhibits neurogenesis of fetal hippocampus via repressing transcription factor Pax6.
Sevoflurane is widely used in non-obstetric surgeries of pregnant women, but its influences on fetal brain are still not fully known. We set out to assess the effects of multiple maternal sevoflurane exposure on neurogenesis and cognitive dysfunction in fetus and offspring. Pregnant mice (gestational day 15.5) and cultured mouse neural stem cells (NSCs) received daily sevoflurane exposure (2.5%×2h and 4.1%×2h respectively) for three consecutive days. Cognitive function of the offspring was determined with the Morris water maze. The expression of Ccnd1 and Pax6 in fetal brains and NSCs were analyzed by immunofluorescence, Western blot and qPCR. The neurogenesis was evaluated by BrdU staining. Results showed that multiple sevoflurane exposure in pregnant mice caused the decrease of Pax6 and Ccnd1 expression, the inhibition of NSCs proliferation and fetal hippocampus neurogenesis, which may contribute to the impaired learning and memory in offspring at P28. Moreover, lithium mitigated the sevoflurane-induced reduction in Pax6, Ccnd1 and neurogenesis. All these results suggest that multiple sevoflurane exposure may induce detrimental effects in the developing brains of fetus and offspring by the depression of neurogenesis through Pax6 pathway.


The validation of a diabetes patient knowledge test.
Diabetes knowledge tests, used in conjunction with measures of patient attitudes and behaviors, can provide a useful basis for assessing educational needs and designing appropriate instructional experiences. Accurate decisions require instruments that measure patient knowledge of diabetes and its management with high reliability and validity. Data obtained from more than 950 administrations of two parallel forms of a Diabetes Patient Knowledge Test have provided documentation of patient knowledge levels, insight into the effectiveness of educational programs, and support for ongoing program revisions. These data have also allowed study of the psychometric properties of the test instruments, including factor structure, reliability, and validity. Each test form has an overall reliability of 0.89 and the forms are of equal difficulty. Five subcomponents (factors) labeled "Carbohydrates," "Blood Sugar," "Basics," "Food Exchanges," and "Insulin Administration" are measured in the tests. Evidence of content, construct, concurrent, and discriminant validity has been demonstrated.


Risk-reducing salpingectomy in Canada: a survey of obstetrician-gynaecologists.
Performing risk-reducing salpingectomy (RRS) at the time of hysterectomy or as a method of tubal ligation has been suggested as a way to reduce the incidence of high grade serous carcinoma (HGSC) of the ovary, since this type of cancer is hypothesized to originate in the fallopian tube. We conducted a survey of Canadian obstetrician-gynaecologists to better understand the uptake and knowledge of implementing this procedure, and to identify barriers to doing so. An anonymous, web-based survey using both quantitative and qualitative methods was sent to obstetrician-gynaecologist members of the Society of Obstetricians and Gynaecologists of Canada and the Society of Gynecologic Oncology of Canada. The survey contained questions about demographics, knowledge and beliefs about RRS, and possible barriers to its implementation in women at average risk for ovarian cancer. One hundred ninety-two physicians responded to the survey, a response rate of 25%. Respondents varied in their duration in practice, came from all provinces, and spent a large proportion of their time practising gynaecology. Ninety percent of respondents had heard of RRS; however, 37% were unaware of the evidence supporting the hypothesis that HGSC originates in the fallopian tube, and 38% were unsure whether there would be any population benefit from performing RRS at the time of other gynaecologic surgery. Multiple barriers to implementation were identified. Most Canadian obstetrician-gynaecologists responding to our survey were aware of RRS as a possible method to prevent ovarian cancer in women at average risk; however, barriers still exist to widespread implementation. Further research is needed to quantify the population benefit of this procedure.


Targeted Approaches to the Management of Follicular Lymphoma.
Despite high rates of response to initial chemoimmunotherapy, patients with follicular lymphoma experience frequent relapses, and better treatment options are needed. Several novel biologic agents have been developed based on a greater understanding of the intrinsic factors driving the development of this heterogeneous disease. Such therapies target extracellular surface proteins and intracellular signaling pathways, as well as manipulate and engage the tumor microenvironment. Many of these agents have shown great promise in early-phase studies and are the focus of ongoing clinical investigations.


Transient receptor potential channels in mechanosensing and cell volume regulation.
Transient receptor potential (TRP) channels are unique cellular sensors responding to a wide variety of extra- and intracellular signals, including mechanical and osmotic stress. In recent years, TRP channels from multiple subfamilies have been added to the list of mechano- and/or osmosensitive channels, and it is becoming increasingly apparent that Ca(2+) influx via TRP channels plays a crucial role in the response to mechanical and osmotic perturbations in a wide range of cell types. Although the events translating mechanical and osmotic stimuli into regulation of TRP channels are still incompletely understood, the specific mechanisms employed vary between different TRP isoforms, and probably include changes in the tension and/or curvature of the lipid bilayer, changes in the cortical cytoskeleton, and signaling events such as lipid metabolism and protein phosphorylation/dephosphorylation. This chapter describes candidate mechanosensitive channels from mammalian TRP subfamilies, discusses inherent and technical issues potentially confounding evaluation of mechano- and/or osmosensitivity, and presents methods relevant to the study of TRP channel regulation by mechanical and osmotic stimuli and involvement in cell volume regulation.


Ankylosing spondylitis - specific aspects related to surgical treatment of cervical fracture - case report.
Ankylosing spondylitis (AS) or else Bechterews or Marie-Strümpells disease is a chronic inflammatory autoimmune disease affecting preferentially the spine in the form of sacroileitis and spondylitis [1,2]. Due to acquired skeletal fragility, compared to healthy spine there is a significantly different response of the organism to the mechanical load [3] and therefore in patients with AS, spinal trauma is much more dangerous. Unlike predominantly elastic injuries in healthy cervical spine in AS patients this elasticity is lost and the spine then behaves like a tubular bone [4,5]. A simple X-ray picture is often insufficient because these fractures are difficult to be found in the field of extensive bone alterations typical for AS [6,7,8]. We present a case report of cervical spondylogenic myelopathy in posttraumatic pseudoarthrosis with a prolapse of C6/7 in the field of an old fracture in an AS patient with a typical initial underestimation of diagnosis in minor trauma. The patient therefore experienced a typical late deterioration of the neurological condition. At our department, we have completed the diagnosis and proceeded to perform the surgery with which we have the greatest experience. Although slightly at variance with established procedures, the surgery provides a sufficient solution for the patient also in postoperative follow-up.


Reductively Degradable Poly(2-hydroxyethyl methacrylate) Hydrogels with Oriented Porosity for Tissue Engineering Applications.
Degradable poly(2-hydroxyethyl methacrylate) hydrogels were prepared from a linear copolymer (Mw = 49 kDa) of 2-hydroxyethyl methacrylate (HEMA), 2-(acethylthio)ethyl methacrylate (ATEMA), and zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC). The deprotection of ATEMA thiol groups by triethylamine followed by their gentle oxidation with 2,2'-dithiodipyridine resulted in the formation of reductively degradable polymers with disulfide bridges. Finally, a hydrogel 3D structure with an oriented porosity was obtained by gelation of the polymer in the presence of needle-like sodium acetate crystals. The pore diameter and porosity of resulting poly(2-hydroxyethyl methacrylate-co-2-(acethylthio)ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) [P(HEMA-ATEMA-MPC)] hydrogels varied between 59 and 65 μm and between 70 and 79.6 vol % according to Hg porosimetry, and complete degradation of these materials was reached in 86 days in 0.33 mmol solution of l-cysteine/L in phosphate buffer. The cross-linked P(HEMA-ATEMA-MPC) hydrogels were evaluated as a possible support for human mesenchymal stem cells (MSCs). No cytotoxicity was found for the un-cross-linked thiol-containing and protected P(HEMA-ATEMA-MPC) chains up to a concentration of 5 and 1 wt % in α-minimum essential medium, respectively.


Pd-catalyzed chemoselective carbonylation of aminophenols with iodoarenes: alkoxycarbonylation vs aminocarbonylation.
Palladium-catalyzed chemoselective carbonylation of aminophenols with iodoarenes was realized by changing ligand and base. 3- or 4-Aminophenols afforded esters in high yields and selectivities using 1,3-bis(diphenylphosphino)propane as the ligand and K2CO3 as the base, and gave amides in high yields and selectivities using 1,3-bis(diisobutylphosphino)propane as the ligand and DBU as the base. 2-Aminophenol only gave amides in high yields under both conditions.


Dislocation mean free paths and strain hardening of crystals.
Predicting the strain hardening properties of crystals constitutes a long-standing challenge for dislocation theory. The main difficulty resides in the integration of dislocation processes through a wide range of time and length scales, up to macroscopic dimensions. In the present multiscale approach, dislocation dynamics simulations are used to establish a dislocation-based continuum model incorporating discrete and intermittent aspects of plastic flow. This is performed through the modeling of a key quantity, the mean free path of dislocations. The model is then integrated at the scale of bulk crystals, which allows for the detailed reproduction of the complex deformation curves of face-centered cubic crystals. Because of its predictive ability, the proposed framework has a large potential for further applications.


Polymers in small-interfering RNA delivery.
This review will cover the current strategies that are being adopted to efficiently deliver small interfering RNA using nonviral vectors, including the use of polymers such as polyethylenimine, poly(lactic-co-glycolic acid), polypeptides, chitosan, cyclodextrin, dendrimers, and polymers-containing different nanoparticles. The article will provide a brief and concise account of underlying principle of these polymeric vectors and their structural and functional modifications which were intended to serve different purposes to affect efficient therapeutic outcome of small-interfering RNA delivery. The modifications of these polymeric vectors will be discussed with reference to stimuli-responsiveness, target specific delivery, and incorporation of nanoconstructs such as carbon nanotubes, gold nanoparticles, and silica nanoparticles. The emergence of small-interfering RNA as the potential therapeutic agent and its mode of action will also be mentioned in a nutshell.


Macular changes in congenital retinoschisis.
Nine patients with congenital retinoschisis were examined. Two patients showed only the stellate c cystoid macular schisis without peripheral changes. Most of the affected eyes demonstrated a vision between 6/15 and 6/21. Fluorescein angiography did not reveal any macular abnormalities, even though changes were ophthalmoscopically visible. Patients in their twenties developed nonspecific macular degeneration, but did not have acceleration of visual deterioration.


Simultaneous self-assembly of a cage-like silver(I) complex encapsulating an Ag6 neutral cluster core and carbon dioxide fixation.
A novel mixed-valent Ag(I)/Ag(0) T(h)-Ag(34) cage was obtained by a one-pot ultrasonic reaction. In the shell of the cage, CO(3)(2-) anion is derived from atmospheric CO(2) and adopts a rare μ(6) bridging mode to link the Ag(I) ions. In the core of the cage, an unprecedented neutral metal cluster with six zero-valent silver atoms is encapsulated.


Involvement of cathepsins B and H in lysosomal degradation of horseradish peroxidase endocytosed by the proximal tubule cells of the rat kidney: II. Immunocytochemical studies using protein A-gold technique applied to conventional and serial sections.
Immunoelectron microscopic localizations of cathepsins B and H and injected horseradish peroxidase (HRP) in the lysosomal system of rat kidney proximal tubules were investigated by a protein A-gold technique. Kidneys were fixed by perfusion at fixed intervals after intravenous injection of HRP. At 5 to 15 minutes after the injection, the endocytic apparatus--including the apical vesicles, tubules, and vacuoles (endosomes)--were stained for HRP, but they were negative for cathepsins. Within 15 to 30 minutes after the HRP injection, HRP-containing endosomes were fusing with preexisting lysosomes. In the S1 segment, they accumulated in the apical cytoplasm and formed giant phagosomes, which increased markedly in number and size after 1 hour. These phagosomes were composed of a peripheral clear matrix and electron-dense inclusions. The clear matrix was stained heavily for cathepsins and HRP, whereas the electron-dense inclusions were consistently negative for cathepsins and HRP. The same results also were obtained after the double-labeling and serial sectioning techniques. The dense inclusions were fragmented gradually as the phagosomes decreased in size. After 3 hours, the size and number of phagosomes returned to their normal state (before the HRP injection). These results indicate that the endocytic apparatus of the proximal tubule cells does not contain cathepsins. Phagosomes are formed by the fusion of endosomes containing the internalized protein with the preexisting lysosomes. The degradation of HRP in giant phagosomes occurred rapidly. The coexistence of cathepsins B and H with the endocytosed HRP suggests that these cystein proteinases are involved in the degradation of protein in heterophagosomes of the proximal tubule cells.