OPTIMALITY THEORY, GOMPERTZ' LAW, AND THE DISPOSABLE SOMA THEORY OF SENESCENCE.
The "disposable soma" theory for the evolution of senescence suggests that senescence arises from an optimal balancing of resources between reproduction and somatic repair. Dynamic programming models are constructed and analyzed to determine the optimal relationship between reproduction, diversion of resources from repair, and added senescent mortality. Of particular interest is the relationship between the repair-reproduction trade-off and the form of the mortality-rate-versus-age curve predicted. The models analyzed in the greatest detail assume that the relationship between reproduction and added senescent mortality does not change with age. These suggest that mortality should increase at an increasing rate with age, but may approach a linear rate as mortality becomes very high. General results are derived for the shape of the mortality curves early and late in the senescing part of the life span, and mortality curves for specific trade-off functions are illustrated. An exponential increase in death rate with age (Gompertz' Law) corresponds to only one of many possible relationships between reproduction and aging. The "Law" is unlikely to hold generally if the disposable soma theory accounts for a large fraction of the observed senescent increase in mortality with age. However, support for the generality of Gompertz' Law is weak, and other theories have not produced an evolutionary explanation for the law. The disposable soma theory is consistent with some of the exceptions to Gompertz' Law that have been observed.


A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma.
Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development.


Relation of estrogen and its receptor to rat liver growth and regeneration.
A variety of hormones have been implicated in the process of liver regeneration. Despite the demonstration of specific estrogen receptors (ER) in mammalian liver and the identification of responses to estrogen which occur in liver, there has been little or no investigation of the relation of that hormone or its receptor to liver regeneration or liver growth. This report provides information which indicates: (a) the effect of 17 beta-estradiol on the mass of both intact and regenerating rat liver; (b) the percentage of hepatocytes in neonatal and adult normal intact livers which contain ER, i.e., the estrogen receptor index (ERI); (c) changes in ERI and in nuclear ER occurring in that cell population following partial hepatectomy (PH) and/or 17 beta-estradiol administration; and (d) the temporal relation of the changes in ER with those related to DNA synthesis and liver regeneration and to liver growth. Approximately 55 to 60% of parenchymal cells from intact livers in adult rats were found to contain ER which was entirely located in the cytoplasm. No nuclear ER was evident in such cells. By 1 hr, and subsequently following 17 beta-estradiol administration to such animals, there resulted a depletion in the number of ER-containing cells and the identification of nuclear ER. These changes were followed by the onset of increased DNA synthesis and an increase in liver weight (p less than 0.001). Subsequent to 70% PH, a similar series of events occurred in liver remnants. Not only was there a decrease in the ERI from 60% at the time of PH to 40% 3 hr later and 30% after 72 hr, there was a decrease in cytosol ER as well. Accompanying the decrease was an increase in the number of cells with nuclear ER. By 24 hr post-PH, 29% of the cells with ER displayed that receptor in their nuclei. At that time, DNA synthesis was at its peak, and liver regeneration was taking place. When 17 beta-estradiol was administered at the time of PH, there was a more rapid onset of translocation of ER to the nuclei of parenchymal cells. At PH, when 17 beta-estradiol was given, no cells displayed nuclear ER. One hr later, 18% of cells with ER had nuclear ER, in contrast to the finding that only 3% of cells had nuclear ER 1 hr post-PH when 17 beta-estradiol was not administered. Regeneration was greater (59 versus 73%; p = 0.003) when animals received 17 beta-estradiol prior to PH.(ABSTRACT TRUNCATED AT 400 WORDS)


Isolation of a crystal matrix protein associated with calcium oxalate precipitation in vacuoles of specialized cells.
The formation of calcium (Ca) oxalate crystals is considered to be a high-capacity mechanism for regulating Ca in many plants. Ca oxalate precipitation is not a stochastic process, suggesting the involvement of specific biochemical and cellular mechanisms. Microautoradiography of water lettuce (Pistia stratiotes) tissue exposed to 3H-glutamate showed incorporation into developing crystals, indicating potential acidic proteins associated with the crystals. Dissolution of crystals leaves behind a crystal-shaped matrix "ghost" that is capable of precipitation of Ca oxalate in the original crystal morphology. To assess whether this matrix has a protein component, purified crystals were isolated and analyzed for internal protein. Polyacrylamide gel electrophoresis revealed the presence of one major polypeptide of about 55 kD and two minor species of 60 and 63 kD. Amino acid analysis indicates the matrix protein is relatively high in acidic amino acids, a feature consistent with its solubility in formic acid but not at neutral pH. 45Ca-binding assays demonstrated the matrix protein has a strong affinity for Ca. Immunocytochemical localization using antibody raised to the isolated protein showed that the matrix protein is specific to crystal-forming cells. Within the vacuole, the surface and internal structures of two morphologically distinct Ca oxalate crystals, raphide and druse, were labeled by the antimatrix protein serum, as were the surfaces of isolated crystals. These results demonstrate that a specific Ca-binding protein exists as an integral component of Ca oxalate crystals, which holds important implications with respect to regulation of crystal formation.


Preparation of a "chemical vaccine" against tumor progression.
A synthetic antigen containing the presumed receptor site for wheat-germ agglutinin (a lectin capable of specifically agglutinating tumor cells) elicits an immune response in mice capable of cross-reacting with receptor sites for wheat-germ agglutinin on tumor-cell surfaces. Mice immunized against the antigen in complete Freund's adjuvant are able to reject five times as many transplanted myeloma tumor cells as are rejected by otherwise identically treated control mice. Methylcholanthrene-induced tumors appear later in mice immunized against the antigen than in controls. The protection of mice against tumor transplants can be transferred to unimmunized mice with spleen cells, but not with serum from immunized donors. Immunization of mice against the wheat-germ agglutinin receptor seemed to have no marked deleterious effect on biological processes in normal dividing cells.


Assessment of aircrew radiation exposure by further measurements and model development.
A methodology is presented for collecting and analysing exposure measurements from galactic cosmic radiation using a portable equipment suite and encapsulating these data into a semi-empirical model/Predictive Code for Aircrew Radiation Exposure (PCAIRE) for the assessment of aircrew radiation exposure on any flight over the solar cycle. The PCAIRE code has been validated against integral route dose measurements at commercial aircraft altitudes during experimental flights made by various research groups over the past 5 y with code predictions typically within +/-20% of the measured data. An empirical correlation, based on ground-level neutron monitoring data, is detailed further for estimation of aircrew exposure from solar particle events. The semi-empirical models have been applied to predict the annual and career exposure of a flight crew member using actual flight roster data, accounting for contributions from galactic radiation and several solar energetic-particle events over the period 1973-2002.


Anterior cruciate ligament reconstruction with LARS artificial ligament: a multicenter study with 3- to 5-year follow-up.
The aim of this multicenter study was to evaluate the clinical outcome of anterior cruciate ligament (ACL) reconstruction by use of the Ligament Advanced Reinforcement System (LARS) artificial ligament (Surgical Implants and Devices, Arc-sur-Tille, France) with 3- to 5-year follow-up. From August 2004 to July 2006, 159 patients with ACL rupture underwent arthroscopic ACL reconstruction with LARS artificial ligament at 4 orthopaedic sports medicine centers in China. They were retrospectively followed up for 50 +/- 6 months (range, 36 to 62 months). Outcome assessment included physical examination, KT-1000 arthrometer testing (MEDmetric, San Diego, CA), magnetic resonance imaging, radiography, Lysholm score, Tegner score, International Knee Documentation Committee score, and subjective satisfaction rate. Quadriceps and hamstring isokinetic strength was evaluated in 68 patients. The side-to-side difference in anterior translation (injured side - uninjured side) measured by KT-1000 arthrometer was 1.5 +/- 1.6 mm (range, -1 to 7 mm) postoperatively, and knee stability was significantly improved compared with preoperative data (P < .0001). Quadriceps and hamstring isokinetic peak torque of the injured limb expressed as a percentage of the contralateral limb was 93.6 +/- 10.7 and 95.8 +/- 12.0, respectively. The Lysholm score improved from 65.1 +/- 12.3 points (range, 30 to 95 points) preoperatively to 94.5 +/- 7.0 points (range, 65 to 100 points) postoperatively (P < .0001). The Tegner score improved from 3.1 +/- 1.6 (range, 0 to 6) preoperatively to 6.1 +/- 1.5 (range, 1 to 9) postoperatively (P < .0001). According to the International Knee Documentation Committee score, 94% of patients were graded A or B at last follow-up. Ninety-three percent of patients were very satisfied or satisfied with their outcome. LARS artificial ligament rupture occurred in 3 patients; knee synovitis developed in 1 of these patients. ACL reconstruction with LARS artificial ligament used in patients with the ACL stump preserved in the acute and chronic phases has a very good outcome at mean of 50 months' follow-up. The overall complication rate for ACL reconstruction with LARS artificial ligament is 5.7%, and knee synovitis developed in only 1 case. Level IV, therapeutic case series.


CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner.
Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, CXCL10 was produced in HAV-infected cells, not in neighboring uninfected cells. Moreover, these chemokines were significantly increased in the sera of acute hepatitis A patients. The production of IFN-λs was also robustly induced by HAV infection, and the blocking of secreted IFN-λs partially abrogated the production of CCL4 and CCL5 in HAV-infected cells. However, CXCL10 production was not decreased by the blocking of IFN-λs. Instead, CXCL10 production was reduced by silencing the expression of RIG-I-like receptor (RLR) signal molecules, such as mitochondrial antiviral signaling protein and interferon regulatory factor 3, in HAV-infected cells. In conclusion, HAV infection strongly induces the production of helper 1 T cell-associated chemokines, particularly CXCL10 via RLR signaling, even without secreted IFNs.


Inhibition of EphA7 up-regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery.
Functional impairment after spinal cord injury (SCI) is partially attributed to neuronal cell death, with further degeneration caused by the accompanying apoptosis of myelin-forming oligodendrocytes. The Eph receptor protein tyrosine kinase family and its cognate ligands, the ephrins, have been identified to be involved in axonal outgrowth, synapse formation, and target recognition, mainly mediated by repulsive activity. Recent reports suggest that ephrin/Eph signaling might also play a role as a physiological trigger for apoptosis during embryonic development. Here, we investigated the expression profile of EphA7, after SCI, by using a combination of quantitative real-time PCR (QRT-PCR) and immunohistochemical techniques. QRT-PCR analysis showed an increase in the expression of full-length EphA7 at 7 days postinjury (DPI). Receptor immunoreactivity was shown mostly in astrocytes of the white matter at the injury epicenter. In control animals, EphA7 expression was observed predominantly in motor neurons of the ventral gray matter, although some immunoreactivity was seen in white matter. Furthermore, blocking the expression of EphA7 after SCI using antisense oligonucleotides resulted in significant acceleration of hindlimb locomotor recovery at 1 week. This was a transient effect; by 2 weeks postinjury, treated animals were not different from controls. Antisense treatment also produced a return of nerve conduction, with shorter latencies than in control treated animals after transcranial magnetic stimulation. We identified EphA7 receptors as putative regulators of apoptosis in the acute phase after SCI. These results suggest a functional role for EphA7 receptors in the early stages of SCI pathophysiology.


Vaginal progesterone to reduce preterm birth among HIV-infected pregnant women in Zambia: a feasibility study protocol.
Women infected with HIV have a risk of preterm birth (PTB) that is twice that among uninfected women, and treatment with antiretroviral therapy (ART) may further increase this risk. Progesterone supplementation reduces the risk of preterm delivery in women who have a shortened cervix in the midtrimester. We propose to study the feasibility of a trial of vaginal progesterone (VP) to prevent PTB among HIV-infected women receiving ART in pregnancy. Given low adherence among women self-administering vaginal study product in recent microbicide trials, we plan to investigate whether adequate adherence to VP can be achieved prior to launching a full-scale efficacy trial. One hundred forty HIV-infected pregnant women in Lusaka, Zambia, will be randomly allocated to daily self-administration of either VP or matched placebo, starting between 20 and 24 gestational weeks. The primary outcome will be adherence, defined as the proportion of participants who achieve at least 80% use of study product, assessed objectively with a validated dye stain assay that confirms vaginal insertion of returned single-use applicators. Secondary outcomes will be study uptake, retention, and preliminary efficacy. We will concurrently perform semi-structured interviews with participants enrolled in the study and with women who decline enrollment to assess the acceptability of VP to prevent PTB and of enrollment to a randomized controlled trial. We hypothesize that VP could prevent PTB among women receiving ART in pregnancy. In preparation for a trial to test this hypothesis, we plan to assess whether participants will be adherent to study product and protocol. ClinicalTrial.gov, NCT02970552.


A biophysical model for cardiac microimpedance measurements.
Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way. Our analyses take advantage of a three-dimensional structural framework in which interstitial, intracellular, and membrane components are coupled to one another on the fine size scale, and electrodes are separated from one another as in arrays we fabricate routinely. With this arrangement, determination of passive tissue resistances can be made from measurements taken on top of the currents flowing in active tissue. In particular, our results show that measurements taken at multiple frequencies and electrode separations provide powerful predictions of the underlying tissue resistances in all geometric dimensions. Because of the small electrode size, separation of interstitial from intracellular compartment contributions is readily achieved.


Classically conditioned enhancement of hyperinsulinemia in the ob/ob mouse.
The obese (C57BL/6J ob/ob) mouse is a commonly used animal model of non-insulin-dependent diabetes mellitus. Recent experiments have shown that stress hyperglycemia can be classically conditioned in the obese but not in the lean mouse. In the present study, classical conditioning of insulin secretion was attempted in C57BL/6J obese and lean animals. For 21 days, obese and lean mice were exposed to a conditioned olfactory stimulus prior to and during eating. On the 22nd day, blood was sampled for all animals following presentation of the conditioned stimulus; testing was repeated 2 weeks later following an additional 4 days of conditioning. Results indicated an effect of conditioning, with significantly greater plasma insulin for trained than for untrained obese mice. That insulin secretion can be more easily conditioned in the obese mouse suggests that a cholinergic mechanism may be involved in the hyperinsulinemia characteristic of this animal.


Current trends in the management of myasthenia gravis: plasmapheresis and immunosuppressive therapy.
In recent years a considerable body of evidence has accumulated to demonstrate autoimmune mechanisms in myasthenia gravis. This evidence has important implications for the aetiology, diagnosis and management of the disease. The primary abnormality in myasthenia gravis is related to the presence of antibody which reacts with the acetylcholine receptor. Measurement of this IgG antibody in the serum has become the most reliable diagnostic adjunct to the edrophonium test, and in an individual patient, the level of the serum antibody relates closely to the clinical indices. In cases of myasthenia where control with anticholinesterase drugs is unsatisfactory, methods to lower the antiacetylcholine receptor antibody are indicated: these may include thymectomy, immunosuppressive therapy of plasmapheresis. Two patients with very severe disease are described in whom all types of therapy were used and in whom survival depended ultimately on the use of plasmapheresis. These patients illustrate the importance of receptor antibody in the clinical manifestations of myasthenia gravis and in its management.


Standard and rapid scan infrared spectroscopic studies of o-xylene transformations in terms of pore arrangement of 10-ring zeolites - 2D COS analysis.
This study attempts to offer an insight into o-xylene isomerization process in terms of steric constraints of 10-ring zeolites. The zeolites under investigation, i.e. ZSM-5, IM-5 and TNU-9, have purely microporous structures and crystals with the same shape and offer comparable protonic functionality, both in manner of amount and strength of Si(OH)Al groups. Under these conditions, micropore topology is recognised to deliver differentiated catalytic performance of each zeolitic structure. Moreover, 10-ring zeolites of reduced dimensionality, i.e. TNU-10 and ZSM-22, are chosen as reference materials. The 2D COS analysis of IR spectra reveal that interaction and catalytic activity in o-xylene isomerization process are strongly influenced by diffusion of reagents in rigid microporous environment and the formation of intermediate species is characterised by IR bands at 1485 and 1455 cm-1. With a prolonged time of the reaction (15 min), the formation of the latter species is observed for zeolite IM-5 characterised by limited 3-dimensionality. Rapid scan experiments show that in a shorter reaction time (4 min), these intermediate moieties are present for all the structure studied. The intermediate species are believed to originate from arenium ions such as methylbenzenium CH3-C6H5+-CH3 and/or methyl-substituted cycloheptatrienyl ions CH3-C7H7+. Their amount is strictly related to the rigidity of the microporous system: the most spacious environment for o-xylene transformation, e.g. TNU-9, is characterised by the lowest population of intermediates, whereas structures offering sufficiently tight geometry, e.g. TNU-10, can accommodate intermediate species in higher quantities, finally leading to the production of p-xylene with high selectivity.


Histone post-translational modifications in frontal cortex from human donors with Alzheimer's disease.
Alzheimer's disease (AD) is the sixth leading cause of death and the most costly disease in the US. Despite the enormous impact of AD, there are no treatments that delay onset or stop disease progression currently on the market. This is partly due to the complexity of the disease and the largely unknown pathogenesis of sporadic AD, which accounts for the vast majority of cases. Epigenetics has been implicated as a critical component to AD pathology and a potential "hot spot" for treatments. Histone post-translational modifications (PTMs) are a key element in epigenetic regulation of gene expression and are known to be associated with the pathology of numerous diseases. Investigation of histone PTMs can help elucidate AD pathology and identify targets for therapies. A multiple reaction monitoring mass spectrometry assay was used to measure changes in abundance of several histone PTMs in frontal cortex from human donors affected with AD (n = 6) and age-matched, normal donors (n = 6). Of the changes observed, notable decreases in methylation of H2B residue K108 by 25 % and H4 residue R55 by 35 % were measured and are likely associated with hydrogen bonding networks important for nucleosome stability. Additionally, a 91 % increase in ubiquitination of K120 on H2B was measured as well as an apparent loss in acetylation of the region near the N-terminus of H4. Our method of quantification was also determined to be precise and robust, signifying measured changes were representative of true biological differences between donors and sample groups. We are the first to report changes in methylation of H2B K108, methylation of H4 R55, and ubiquitination of H2B K120 in frontal cortex from human donors with AD. These notable PTM changes may be of great importance in elucidating the epigenetic mechanism of AD as it relates to disease pathology. Beyond the structural and functional impacts of the changes we have measured, the sites of altered PTMs may be used to identify enzymes responsible for their modulation, which could be used as prospective drug targets for highly specific AD therapies.


[A case of sporadic and transient bradyarrhythmias in a patient with a glioma in the medulla oblongata].
In a 20-year-old female patient with a brain stem glioma in the medulla oblongata in association with paraplegia and respiratory paralysis, bradyarrhythmias such as sinus bradycardia and sinus arrest repeated sporadically and transiently, but soon subsided as radiotherapy was being delivered to the glioma in the medulla oblongata. The bradyarrhythmias were differentiated from sick sinus syndrome in their sporadic and transient character. The patient responded normally to atropine, isoproterenol, and phenylephrine. Parasympathetic nerve reflexes induced by Aschner's, Czermak's, and Valsalva's maneuvers and sympathetic nerve reflex induced by change of body position were within normal limits. Although EKG abnormalities associated with diseases of the central nervous system are frequently due to intracranial hypertension and/or irritation of the hypothalamus, the bradyarrhythmias in this patient were possibly due to vagus stimulation caused by the glioma in the medulla.


Deoxyribocytidine is salvaged not only into DNA but also into phospholipid precursors. IV. Exogenous deoxyribocytidine can be used with the same efficacy as (ribo)cytidine for lipid activation.
Utilisation of exogenous (ribo)cytidine (3H-CR) and deoxyribocytidine (3H-CdR) for DNA/RNA synthesis and for activation of phospholipid intermediates was compared in human tonsillar lymphocytes. Incorporation of 3H-CdR into dCDP-choline and into dCDP-DAG was similar or even higher than labelling of CDP-choline and CDP-DAG from 3H-CR. No interconversion was found between CDP-DAG and dCDP-DAG, as shown by TLC separation of the ribo- and deoxyribocytidine derivatives. Moreover, a strict separation was found between the salvage pathways of deoxyribocytidine and (ribo)cytidine, as 4000-fold excess of non labelled (ribo)cytidine did not show any specific effect on 3H-dCDP-DAG labelling from exogenous 3H-CdR.


Monogenic autoinflammatory disorders: beyond the periodic fever.
The past two decades have seen an exponential increase in the number of monogenic autoinflammatory disorders described, coinciding with improved genetic sequencing techniques. This group of disorders has evolved to be heterogeneous and certainly more complex than the original four 'periodic fever syndromes' caused by innate immune over-activation. This review aims to provide an update on the classic periodic fever syndromes as well as introducing the broadening spectrum of clinical features seen in more recently described conditions.


Biological activities of Eikenella corrodens outer membrane and lipopolysaccharide.
Highly purified preparations of the outer membrane and lipopolysaccharide (LPS) of Eikenella corrodens strain ATCC 23834 and the outer membrane fraction (OMF) of strain 470 were tested in in vitro biological assays. The OMFs of both strains were found to be mitogenic for BDF and C3H/HeJ murine splenocytes. The E. corrodens LPS was mitogenic for BDF spleen cells; however, doses of LPS as high as 50 micrograms/ml failed to stimulate C3H/HeJ cells. When incubated with T-lymphocyte-depleted C3H/HeJ splenocytes, the strain 23834 OMF demonstrated significant mitogenic activity, indicating that the OMF is a B-cell mitogen by a mechanism other than that elicited by conventional LPS. The E. corrodens 23834 OMF and LPS were stimulators of bone resorption when tested in organ cultures of fetal rat long bones. In contrast, the strain 470 OMF was only weakly stimulatory. Both OMFs and LPSs demonstrated "endotoxic" activity, since as little as 0.062 micrograms of E. corrodens LPS and 0.015 micrograms of the OMFs induced gelation in the Limulus amebocyte clotting assay. Thus, despite having a "nonclassical" LPS biochemistry, the E. corrodens LPS elicits classical endotoxic activities. These results also indicate that the surface structures of E. corrodens have significant biological activities as measured in vitro. The expression of such activities in vivo may play an important role in the pathogenesis of periodontitis as well as other E. corrodens infections.


[Prostatic sarcoma: Report of two cases].
Prostatic sarcomas are very rare tumours with a very poor prognosis. They may coexist with prostatic adenocarcinoma, in which case they are only diagnosed on histological examination of the operative specimen with identification of sarcoma on immunohistochemical analysis. Due to their rapidly invasive potential, they must be detect early in the course, particularly in young subjects. Certain clinical signs, such as obstructive urinary symptoms in a young man or rectal symptoms in an elderly man are suggestive of sarcoma. In this article, the authors report two cases of prostatic sarcoma surgically treated and present a review of the literature on this disease.


Effectiveness of resin infiltration (ICON) and microabrasion-remineralization technique with two remineralizing agents (Tooth Mousse and Toothmin) on permanent incisor hypoplasia - A randomized clinical trial.
The study aims to compare the effect of resin infiltration and microabrasion-remineralization (MAb-Re) with Tooth Mousse and Toothmin on permanent incisor hypoplasia. The study included children with permanent incisor hypoplasia above 9 years of age, 171 teeth divided randomly into four groups: Group A - ICON, Group B - MAb-Re using Tooth Mousse, Group C - MAb-Re using Toothmin, and Group D - control group. Process involved taking standardized photographs at T1 - before intervention, T2 - immediately after treatment, and T3 - 6-month follow-up. Color evaluation, area calculation, participant and expert opinion using a Likert scale, treatment time, and cost-effectiveness were all taken into consideration during the assessment. Data were collected, entered into a computer, and analyzed; one-way ANOVA was used for intergroup assessment. Overall color change was evident immediately after treatment in the ICON group compared to other groups (P < 0.05). However, no significant difference in color change was visible between the groups after 6 months. Reduction in hypoplastic area was seen in all the groups. The mean time was similar for all the groups. Toothmin was found to be the most cost-effective in comparison with the other two interventions. ICON proved to be more effective immediately after treatment for masking incisor hypoplasia. However, at 6-month follow-up interval, all the groups gave similar results.


Albumin micro/nanoparticles entrapping liposomes for itraconazole green formulation.
Itraconazole-loaded micro/nanoparticles containing albumin and liposomes were prepared by a technological process that avoids the use of organic solvents and crosslinker agents. The particles were characterized, lyophilized and formulated as tablets. Dynamic light scattering was used to determine the hydrodynamic diameter and zeta potential of the particles; optical and scanning-electron microscopy was used to evaluate their morphology. Spherical shaped particles of different sizes and zeta potential were obtained. An exponential relationship between the zeta potential and the albumin/cationic lipid molar ratio was established. Drug entrapment efficiency values were in the range of 51-68%, with no statistical differences among albumin feeding concentrations. Mannitol was used as lyophilization additive and the freeze-dried cake was directly compressed into tablets, suitable for vaginal administration. The results from the in vitro drug delivery assay show the influence of albumin on the itraconazole delivery profile; a rapid release was observed for particles with higher albumin amount compared to those with lower protein content. According to the results of this study, albumin particles entrapping liposomes prove to be a green pharmaceutical vehicle with a high potential for delivery of hydrophobic and highly albumin-bound drugs.


Evaluation of North American Association of Central Cancer Registries' (NAACCR) data for use in population-based cancer survival studies.
Follow-up procedures vary among cancer registries in North America. US registries are funded by the Surveillance, Epidemiology, and End Results (SEER) Program and/or the National Program of Cancer Registries (NPCR). SEER registries ascertain vital status and date of last contact to meet follow-up standards. NPCR and Canadian registries primarily conduct linkages with local and national death records to ascertain deaths. Data on patients diagnosed between 2002 through 2006 and followed through 2007 were obtained from 51 registries. Registries that met follow-up standards or, at a minimum, conducted linkages with local and national death records had comparable age-standardized five-year survival estimates (all sites and races combined): 63.9% SEER, 63.1% NPCR, and 62.6% Canada. Estimates varied by cancer site. Survival data from registries using different follow-up procedures are comparable if death ascertainment is complete and all nondeceased patients are presumed to be alive to the end of the study period.


The influence of dietary sunflower oil, rich in n-6 polyunsaturated fatty acids, in combination with vitamin C on ram semen parameters, sperm lipids and fertility.
Dietary fats, fed to ruminant animals, have been observed to improve reproductive function. Sunflower oil is one of the richest sources of polyunsaturated fatty acids (PUFAs), over 60% of which is linoleic acid (C18:2). With regard to recommendations for increased consumption of PUFAs, special emphasis has been given to the importance of consuming more antioxidants to prevent lipid peroxide formation. This study evaluated the effects of dietary n-6 PUFAs and vitamin C (VC) in rams - in particular, on semen quality, blood metabolites, sperm lipids and overall fertility. Diets supplemented with SFO and VC increased the proportion of motile sperms and their progressive motility improved (P < 0.01). Rams fed a diet containing SFO had an increased proportion of sperms with normal acrosomes in their semen samples (P < 0.01). The highest levels of lactate dehydrogenase activity (LDH) enzyme were found in control rams (2.60 U mL-1 ). Feeding SFO significantly affected blood triglyceride and cholesterol concentrations (P < 0.05). Diets containing SFO increased the proportion of C18:2c, C20:4, C20:3 and C22 in the sperm lipid composition (P < 0.05). Semen of SFO and VC-fed rams was more fertile than that of control rams when it was artificially inseminated to ewes. Feeding rams with supplemental SFO and VC increased semen quality and improved fertility rates. © 2019 Society of Chemical Industry.


Low- and high-voltage-activated calcium currents in rat spinal dorsal horn neurons.
1. Calcium currents in immature rat spinal dorsal horn neurons in transverse slices were studied with the single-electrode voltage-clamp technique. Using experimental conditions that minimized voltage-dependent Na+ and K+ currents, we distinguished low- and high-voltage-activated calcium currents on the basis of their voltage dependence and sensitivity to the Ca2(+)-channel agonist and antagonist drugs. 2. The low-voltage-activated transient calcium current is evoked with weak depolarizing voltage commands. It begins to activate at potentials positive to -70 mV and increases in amplitude and rate of decay with depolarization, the peak values being reached between -40 and -30 mV. The current is fully activated at a holding potential of about -110 mV. Steady-state inactivation is complete at potentials in the range of -60 to -50 mV. 3. The transient component of the high-threshold calcium current appears at membrane potentials close to -40 mV and slowly decays within several hundreds of milliseconds. The amplitude of the current increases with more negative holding potentials (-100 to -40 mV). 4. The sustained component of the high-threshold calcium current seems to activate at potentials positive to -40 mV and exhibits little inactivation during 0.3- to 0.5-s depolarizing commands. This component is better isolated at more depolarized holding potentials (between -40 and -30 mV) that inactivate the transient components of the low- and high-threshold calcium currents. 5. A rundown of calcium currents was seen in dorsal horn cells. The time stability of the transient and sustained components of the high-threshold calcium current was lower than that of the low-threshold transient current. The latter current seemed to be insensitive up to 1 h. 6. (-)-Bay K 8644 (1-10 microM), a dihydropyridine agonist, enhanced the high-threshold calcium current, in particular the sustained component, but not the transient low-threshold calcium current. The dihydropyridine antagonist nifedipine (5-50 microM) selectively reduced the sustained component of the high-threshold calcium current while having little or no effect on the transient components of the low- and high-threshold calcium currents. 7. Cadmium ions (60-100 microM) and cobalt ions (2 mM) markedly reduced both components of the high-threshold calcium current, and Cd2+ only slightly decreased the low-threshold transient current. However, all three components are indiscriminately blocked by higher concentrations of Cd2+ and Co2+.(ABSTRACT TRUNCATED AT 400 WORDS)


The prevalence of musculoskeletal diseases among casual dock workers.
This study identified the prevalence of work-related musculoskeletal disorders among casual dockworkers. This is a retrospective and quantitative study, the data sources of which included the medical files of dockworkers from 2000 to 2009. Data were collected in a medical service for dockworkers using a previously developed form; descriptive quantitative analysis was performed. Ethical aspects were complied with. A total of 15.8% of the diagnoses identified among male workers referred to musculoskeletal disorders. Individuals older than 52 years of age and with more than 21 years working in the field predominated. The most frequent musculoskeletal diseases included low back pain (38.8%), tendinitis (19.7%), and neck pain (12.5%). These diseases can be prevented through health interventions, confirming the importance of developing clinical support in nursing in order to improve the quality of life of dockworkers.


Quantitative analysis of favipiravir and hydroxychloroquine as FDA-approved drugs for treatment of COVID-19 using synchronous spectrofluorimetry: application to pharmaceutical formulations and biological fluids.
Coronavirus disease 2019 (COVID-19) is a contagious viral infection caused by coronavirus 2 (SARS-CoV-2) that causes severe acute respiratory syndrome. It has ravaged several countries and burdened many healthcare systems. As the process of authorizing a novel treatment for human use is extensive and involves multiple phases to obtain safety information and identify potential concerns. Therefore, the fastest and easiest choice was to use United States Food and Drug Administration (US FDA)-approved drugs such as favipiravir and hydroxychloroquine. For the simultaneous estimation of both medications, a simple synchronous spectrofluorimetric approach was established in which both drugs were measured at 372 and 323 nm, respectively in the presence of each other without interference at Δλ 60 nm. The effect of various experimental conditions on synchronous fluorescence intensities were thoroughly investigated and optimized. The maximum synchronous fluorescence intensities were obtained at pH 5.4 using acetate buffer (0.2 M, 0.5 ml) and ethanol as a diluent. Excellent linearity ranges were obtained using 1.0-18.0 ng/ml and 10.0-120.0 ng/ml for favipiravir and hydroxychloroquine, respectively. The approach exhibited high sensitivity with detection limits down to 0.25 ng/ml and 1.52 ng/ml and quantitation limits down to 0.77 ng/ml and 4.62 ng/ml, respectively. Spiking human plasma samples with the studied drugs yielded high % recoveries, allowing a significant bioanalytical application. Moreover, the method was validated according to International Conference on Harmonization guidelines and further applied to commercial pharmaceutical preparations with good results.


HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance.
The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4+ T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4+ T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.


Clinical utility of the Hopkins Competency Assessment Test on an inpatient geropsychiatry unit.
This study examined the clinical use of routine administration of the Hopkins Competency Assessment Test on an inpatient geropsychiatry unit. The purpose was to determine whether the Hopkins Competency Assessment Test results influenced the psychiatrist's capacity assessment or confidence in that determination. The test was administered to all patients admitted voluntarily during an 18-week period. The attending psychiatrist determined treatment consent capacity and rated confidence in that determination, before and after review of the test results. Fifty seven patients were assessed. After review of the test results, the psychiatrist's capacity rating changed in only 2 (3.5%) cases. However, the test increased the psychiatrist's confidence ratings, particularly among the patients with cognitive impairment. The Hopkins Competency Assessment Test is not suited for routine administration among geropsychiatry inpatients. However, the test may serve a role as a supplementary tool for assessing treatment consent capacity among patients with evidence of cognitive impairment.


Three passive arm-support exoskeletons have inconsistent effects on muscle activity, posture, and perceived exertion during diverse simulated pseudo-static overhead nutrunning tasks.
Arm-support exoskeletons (ASEs) are an emerging technology with the potential to reduce physical demands during diverse tasks, especially overhead work. However, limited information is available about the effects of different ASE designs during overhead work with diverse task demands. Eighteen participants (gender-balanced) performed lab-based simulations of a pseudo-static overhead task. This task was performed in six different conditions (3 work heights × 2 hand force directions), with each of three ASEs and in a control condition (i.e., no ASE). Using ASEs generally reduced the median activity of several shoulder muscles (by ∼12-60%), changed working postures, and decreased perceived exertion in several body regions. Such effects, though, were often task-dependent and differed between the ASEs. Our results support earlier evidence of the beneficial effects of ASEs for overhead work but emphasize that: 1) these effects depend on the task demands and ASE design and 2) none of the ASE designs tested was clearly superior across the tasks simulated.


Effects of weighted and un-weighted pendulum exercises on ultrasonographic acromiohumeral distance in patients with subacromial impingement syndrome.
Although functional results of combined rehabilitation programs are reported, there have been no reports studying the effects of solo pendulum exercises on ultrasonographic measurements of acromiohumeral distance (AHD). To investigate the effects of weighted and un-weighted pendulum exercises on ultrasonographic AHD and clinical symptoms in patients with subacromial impingement syndrome. Patients with subacromial impingement syndrome were randomized to performing weighted (1.5 kilograms hand held dumbbell, N= 18) or un-weighted (free of weight, N= 16) pendulum exercises for 4 weeks, 3 sessions/day. Exercises were repeated for each direction of shoulder motion in each session (ten minutes). Clinical situation was evaluated by Constant score and Shoulder Pain Disability Index (SPADI). Ultrasonographic measurements of AHD at 0°, 30° and 60° shoulder abduction were performed. All clinical and ultrasonographic evaluations were performed at the beginning of the exercise program and at end of 4 weeks of exercise program. Thirty-four patients (23 females, 11 males; mean age 41.7 ± 8.9 years) were evaluated. Significant clinical improvements were detected in both exercise groups between pre and post-treatment evaluations (p < 0.05). There was no significant difference for pre and post-treatment AHD measurements at 0°, 30°, and 60° shoulder abduction between groups (p > 0.05). There was no significant difference for pre and post-treatment narrowing of AHD (narrowing of 0°-30°, and 0°-60°) between groups (p > 0.05). While significant clinical improvements were achieved with both weighted and un-weighted solo pendulum exercises, no significant difference was detected for ultrasonographic AHD measurements between exercise groups.


[Report of Cancer Incidence and Mortality in China, 2014].
Objective: The registration data of local cancer registries in 2014 were collected by National Central Cancer Registry (NCCR)in 2017 to estimate the cancer incidence and mortality in China. Methods: The data submitted from 449 registries were checked and evaluated, and the data of 339 registries out of them were qualified and selected for the final analysis. Cancer incidence and mortality were stratified by area, gender, age group and cancer type, and combined with the population data of 2014 to estimate cancer incidence and mortality in China. The age composition of standard population of Chinese census in 2000 and Segi's population were used for age-standardized incidence and mortality in China and worldwide, respectively. Results: Total covered population of 339 cancer registries (129 in urban and 210 in rural) in 2014 were 288 243 347 (144 061 915 in urban and 144 181 432 in rural areas). The mortality verified cases (MV%) were 68.01%. Among them, 2.19% cases were identified through death certifications only (DCO%), and the mortality to incidence ratio was 0.61. There were about 3, 804, 000 new cases diagnosed as malignant cancer and 2, 296, 000 cases dead in 2014 in the whole country. The incidence rate was 278.07/100, 000 (males 301.67/100, 000, females 253.29/100, 000) in China, age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 190.63/100, 000 and 186.53/100, 000, respectively, and the cumulative incidence rate (0-74 age years old) was 21.58%. The cancer incidence and ASIRC in urban areas were 302.13/100, 000 and 196.58/100, 000, respectively, whereas in rural areas, those were 248.94/100, 000 and 182.64/100, 000, respectively. The cancer mortality in China was 167.89/100, 000 (207.24/100, 000 in males and 126.54/100, 000 in females), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population were 106.98/100, 000 and 106.09/100, 000, respectively. And the cumulative incidence rate (0-74 age years old) was 12.00%. The cancer mortality and ASMRC in urban areas were 174.34/100, 000 and 103.49/100, 000, respectively, whereas in rural areas, those were 160.07/100, 000 and 111.57/100, 000, respectively. Lung cancer, gastric cancer, colorectal cancer, liver cancer, female breast cancer, esophageal cancer, thyroid cancer, cervical cancer, encephala and pancreas cancer, were the most common cancers in China, accounting for about 77.00% of the new cancer cases. Lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, breast cancer, encephala, leukemia and lymphoma were the leading causes of death and accounted for about 83.36% of cancer deaths. Conclusions: The progression of cancer registry in China develops rapidly in these years, with the coverage of registrations is expanded and the data quality was improved steadily year by year. As the basis of cancer prevention and control program, cancer registry plays an important role in making the medium and long term of anti-cancer strategies in China. As China is still facing the serious cancer burden and the cancer patterns varies differently according to the locations and genders, effective measures and strategies of cancer prevention and control should be implemented based on the practical situation.


Non-invasive evaluation of coronary vasospasm using a combined hyperventilation and cold-pressure-test perfusion CMR protocol.
Coronary vasospasm is a severe vasoconstriction of an epicardial coronary artery, which may lead to myocardial ischemia and cause symptoms of angina. The gold-standard for diagnosing coronary vasospasm is to perform an intracoronary provocation test and to demonstrate the epicardial vasoconstriction by coronary angiography. We report the case of a patient with coronary vasospasm in whom we succeeded to non-invasively provoke and subsequently non-invasively demonstrate myocardial ischemia by perfusion cardiovascular magnetic resonance (CMR).


Marek's disease virus: lytic replication, oncogenesis and control.
Marek's disease (MD) is caused by a ubiquitous, lymphotropic alphaherpesvirus, MD virus (MDV). MD has been a major concern in the poultry industry owing to the emergence of increasingly virulent strains over the last few decades that were isolated in the face of comprehensive vaccination. The disease is characterized by a variety of clinical signs; among them are neurological symptoms, chronic wasting and, most notably, the development of multiple lymphomas that manifest as solid tumors in the viscera and musculature. Much work has been devoted to study MD-induced oncogenesis and the genes involved in this process. Among the many genes encoded by MDV, a number have been shown recently to affect the development of tumors in chickens, one protein directly causing transformation of cells (Meq) and another being involved in maintaining transformed cells (vTR). Other MDV gene products modulate and are involved in early lytic in vivo replication, thereby increasing the chance of transformation occurring. In this review, we will summarize specific genes encoded by MDV that are involved in the initiation and/or maintenance of transformation and will focus mostly on current vaccination and control strategies against MD, particularly how modern molecular biological methods may be used to improve strategies to combat the disease in the future.


Inter-institutional variation of systolic time intervals in normal subjects.
The study was designed to evaluate inter-institutional variability in systolic time interval (STI) measurement. STI records were obtained from 8 institutions in Czechoslovakia. Altogether 262 normal subjects of both sexes were evaluated. The conclusions of three independent investigators were compared for inter-observer variability assessment. No significant differences were found among the participating centres for electromechanical systole, left ventricular ejection time and pre-ejection time dependence on heart rate and for ratio preejection time-left ventricular ejection time. The regression equations obtained for these indicators were suggested as a national standard for normal subjects.


Effects of group identity on resource use in a simulated commons dilemma.
In a review of research on in-group categorization and group identity, Brewer (1979) proposed that cooperative solutions to social dilemmas, such as Hardin 's (1968) "tragedy of the commons ", may be achieved by exploiting the positive consequences arising from a common social-group identity. Three laboratory experiments were conducted to assess the effects of making salient either a superordinate (collective) or subordinate (differentiating) group identity in heterogeneous groups. In the first two experiments, naturally occurring social categories were used as a basis for group differentiation. In the third, the level of social-group identity was manipulated by varying the common fate of the group members. It was predicted that individual restraint would be most likely when a superordinate group identity was made salient and under conditions in which feedback indicated that the common resource was being depleted. Results from all three experiments provide support for this general hypothesis, indicating that cooperative responding is enhanced even when the basis for superordinate group identity is minimal.


The Effect of Bone Morphogenetic Protein-2 (BMP-2) on Volumetric and Histometric Outcomes for Peri-Implant Defects in the Animal Model: A Systematic Review and Meta-Analysis.
Purpose: To study the effect of BMP-2 on the volumetric and histometric changes in peri-implant defect treatments in animal models. Materials and Methods: An electronic search of four databases and a manual search of peer-reviewed journals for relevant articles were performed. Animal studies with data that compared the volumetric and/or histometric outcomes of peri-implant defect treatment with and without the use of BMP-2 were included. Meta-analyses were performed to analyze the weighted mean difference (WMD) and confidence interval (CI) for the recorded variables. Results: After completing the search process, 21 randomized controlled trials were included. The results of the meta-analyses showed that the WMD of bone-to-implant contact (%BIC) with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.50% (95% CI = 3.28% to 27.72%, P = .01) and 16.17% (95% CI = 11.17% to 21.16%, P < .00001), respectively, favoring the BMP-2 group. The WMD for the percentage of defect fill with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.88% (95% CI = 3.90% to 27.86%, P = .009) and 10.48% (95% CI = 0.95% to 20.02%, P = .03), respectively, favoring the BMP-2 group. The WMD for the vertical bone gain with 8 to 16 weeks of follow-up was 1.63 mm (95% CI = 0.58 to 2.67 mm, P = .002), also favoring the BMP-2 group. Conclusion: This review demonstrated that the use of BMP-2 in treating peri-implant defects showed better clinical and histometric outcomes than defects not treated with BMP-2 in animal models.


Astragaloside IV Protects Against IL-1β-Induced Chondrocyte Damage via Activating Autophagy.
Osteoarthritis (OA) is a chronic inflammatory condition that affects the articular cartilage. Astragaloside IV (AS-IV) constitutes the primary active component of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV demonstrates anti-inflammatory and anti-apoptotic attributes, exhibiting therapeutic potential across various inflammatory and apoptosis-related disorders. Nevertheless, its pharmaceutical effects in OA are yet to be fully defined. This study aimed to investigate the protective impact of AS-IV on rat chondrocytes treated with IL-1β and ascertain whether autophagy plays a role in this effect. Chondrocytes were isolated and cultivated from the knee joints of neonatal SD mice. The study included the blank control group, the model group, and the AS-IV concentration gradient group (50, 100, 200 µmol/L) to intervene with chondrocytes. The MTT assay was employed to assess cell viability at varying culture periods, enabling the determination of suitable concentration and duration. Subsequently, chondrocytes were treated with the optimal AS-IV concentration and divided into three groups: the model group replicated IL-1β-induced inflammatory chondrocyte injury, the AS-IV group received a co-culture of AS-IV and IL-1β, and a blank control group was established. Changes in cell morphology and structure were observed using ghost pen cyclic peptide staining. ELISA was used to measure TNF-α and GAG levels in cell supernatants. RT-qPCR assessed p62 and LC3 mRNA expression, while Western Blot evaluated p62 and LC3Ⅱ/Ⅰ protein expression. AS-IV promoted chondrocyte proliferation and concurrently inhibited cell apoptosis. An optimal AS-IV dose of 200 µmol/L and a suitable reaction time of 48 h were identified. Ghost pen cyclic peptide staining indicated that the model group's cytoskeleton exhibited fusiform changes with reduced immunofluorescence intensity, as opposed to the blank control group. The AS-IV group displayed more polygonal cytoskeletal morphology with increased immunofluorescence intensity. AS-IV reduced TNF-α levels and elevated GAG levels in the culture supernatant. Additionally, AS-IV lowered p62 mRNA and protein expression while increasing LC3 mRNA expression in cultured chondrocytes. Our findings suggest that AS-IV mitigates inflammatory chondrocyte injury, safeguarding chondrocytes through a potential autophagy suppression mechanism. These results imply that AS-IV could offer preventive advantages for OA.


Isoprenoid diphosphate utilization by recombinant human farnesyl:protein transferase: interactive binding between substrates and a preferred kinetic pathway.
The catalytic utilization of dimethylallyl, geranyl, farnesyl, and geranylgeranyl diphosphates in the reaction catalyzed by recombinant human farnesyl:protein transferase (hFPTase) has been examined in the presence of three different protein substrates, Ras-CVLS, Ras-CVIM, and Ras-CAIL. hFPTase catalyzed both farnesylation and geranylation of Ras-CVLS and of Ras-CVIM but not of Ras-CAIL. Geranylgeranylation was observed, but only when Ras-CVIM was the acceptor substrate. Steady-state initial velocity and dead-end inhibitor studies indicate that hFPTase-catalyzed geranylation, like bovine FPTase-catalyzed farnesylation, proceeds through a random order, sequential mechanism. Surprisingly, however, Michaelis constants for a given protein acceptor substrate varied depending upon which isoprenoid diphosphate was used as the donor substrate, showing that these substrates do not bind independently to the enzyme (under catalytic conditions). In addition, at very high concentrations of Ras-CVIM, substrate inhibition was observed in the presence of both FPP and GPP. Isotope partitioning studies showed that, at high concentrations of Ras-CVIM, more than 80% of the bound farnesyl diphosphate (FPP) can be trapped as product, suggesting that the binary complex is catalytically competent and that the ternary complex proceeds to product faster than it releases FPP. The release rate of FPP from the binary complex was calculated to be 0.05 s-1, which is only about eight times greater than kcat. Thus, the binding of FPP to the enzyme in the presence of the protein substrate is not an equilibrium situation.(ABSTRACT TRUNCATED AT 250 WORDS)


Modification of bacterial microcompartments with target biomolecules via post-translational SpyTagging.
Bacterial microcompartments (BMCs) are proteinaceous organelle-like structures formed within bacteria, often encapsulating enzymes and cellular processes, in particular, allowing toxic intermediates to be shielded from the general cellular environment. Outside of their biological role they are of interest, through surface modification, as potential drug carriers and polyvalent antigen display scaffolds. Here we use a post-translational modification approach, using copper free click chemistry, to attach a SpyTag to a target protein molecule for attachment to a specific SpyCatcher modified BMC shell protein. We demonstrate that a post-translationally SpyTagged material can react with a SpyCatcher modified BMC and show its presence on the surface of BMCs, enabling future investigation of these structures as polyvalent antigen display scaffolds for vaccine development. This post-translational 'click' methodology overcomes the necessity to genetically encode the SpyTag, avoids any potential reduction in expression yield and expands the scope of SpyTag/SpyCatcher vaccine scaffolds to form peptide epitope vaccines and small molecule delivery agents.


Molecular properties determined from the relaxation of long-lived spin states.
The populations of long-lived spin states, in particular, populations of singlet states that are comprised of antisymmetric combinations of product states, |alpha(I)beta(S)> - |beta(I)alpha(S)>, are characterized by very long lifetimes because the dipole-dipole interaction between the two "active" spins I and S that are involved in such states is inoperative as a relaxation mechanism. The relaxation rate constants of long-lived (singlet) states are therefore determined by the chemical shift anisotropy (CSA) of the active spins and by dipole-dipole interactions with passive spins. For a pair of coupled spins, the singlet-state relaxation rate constants strongly depend on the magnitudes and orientations of the CSA tensors. The relaxation properties of long-lived states therefore reveal new information about molecular symmetry and structure and about spectral density functions that characterize the dynamic behavior.


A rural/urban comparison of the roles of the general practitioner in colorectal cancer management.
To identify and compare the roles of urban, rural and remote general practitioners (GPs) in colorectal cancer (CRC) management. Semistructured interviews exploring GP views of their role in CRC management. Urban, rural and remote general practices in north Queensland. Fifteen GPs in urban, rural and remote practice. Self-reported roles in the management of CRC patients and factors influencing these roles. All GPs, regardless of location of practice, played a role in diagnosis, referral, postoperative care, psychosocial counselling, follow up and palliative care. Involvement in treatment of CRC patients was only performed by remote GPs. In general, rural and remote GPs played greater roles in care coordination, clinical and psychosocial care. Rural and remote GPs were more heavily involved throughout the entire illness progression when compared with their urban counterparts. The results of this study indicate that rural and remote GPs in north Queensland play a greater role than urban GPs in the management of CRC. In order to maintain and enhance the roles of rural and remote GPs in CRC care, appropriate guidelines and remuneration should be provided. Palliative care support might also be useful to rural and remote GPs.


Tear nitric oxide levels in Behçet's disease.
The aim of this study was to evaluate the tear nitric oxide (NO) level in patients with Behçet's disease and to compare it with that in healthy subjects. MATERIAL AND METHODS. The subjects were divided into 3 groups: the active disease, inactive disease, and control groups. NO concentrations were determined by a nitrate/nitrite colorimetric assay kit and measured spectrophotometrically at 540 nm. RESULTS. The tear nitrate/nitrite levels were 0.06 nmol/μL (SD, 0.05) in the active disease group, 0.05 nmol/μL (SD, 0.05) in the inactive disease group, and 0.02 nmol/μL (SD, 0.01) in the control group. The tear nitrate/nitrite levels of both active and inactive groups were higher than those of the control group (P=0.001 and P=0.047, respectively), but there was no significant difference between the active and inactive groups. CONCLUSION. Our results demonstrated that the tear NO levels were elevated in the patients with Behçet's disease. We imply that a better understanding of NO function in the pathogenesis of Behçet uveitis is necessary to develop new therapies based on the inhibitors of NO synthases.


Differential effects of phorbol ester on tumor cells induced by avian sarcoma virus.
Avian sarcoma virus-induced tumors usually grow progressively for several weeks and then regress. We have injected phorbol myristate acetate (PMA) directly into tumors in an effort to stimulate neoplastic growth. The results show instead that PMA exerted an inhibitory effect in this regard and, in fact, caused an acceleration of tumor regression. At the same time, treatment of cultured avian sarcoma cells with PMA resulted in greatly diminished levels of the kinase activity associated with the src gene product, pp60src. PMA-treated tumor cells from regressing sarcomas were, however, stimulated to express viral antigens at their surface and produced more progeny virus than did untreated tumor cells.


Born-Oppenheimer molecular dynamics studies of Pb(ii) micro hydrated gas phase clusters.
In this work, a theoretical investigation was made to assess the coordination properties of Pb(ii) in [Pb(H2O)n]2+ clusters, with n = 4, 6, 8, 12, and 29, as well as to study proton transfer events, by means of Born-Oppenheimer molecular dynamics simulations at the B3LYP/aug-cc-pVDZ-pp/6-311G level of theory, that were calibrated in comparison with B3LYP/aug-cc-pVDZ-PP/aug-cc-pVDZ calculations. Hemidirected configurations were found in all cases; the radial distribution functions (RDFs) produced well defined first hydration shells (FHSs) for n = 4,6,8, and 12, that resulted in a coordination number CN = 4, whereas a clear-cut FHS was not found for n = 29 because the RDF did not have a vacant region after the first maximum; however, three water molecules remained directly interacting with the Pb ion for the whole simulation, while six others stayed at average distances shorter than 4 Å but dynamically getting closer and farther, thus producing a CN ranging from 6 to 9, depending on the criterion used to define the first hydration shell. In agreement with experimental data and previous calculations, proton transfer events were observed for n≤8 but not for n≥12. For an event to occur, a water molecule in the second hydration shell had to make a single hydrogen bond with a water molecule in the first hydration shell.


Microfluidic-CFPA Chip for the Point-of-Care Detection of African Swine Fever Virus with a Median Time to Threshold in about 10 min.
The outbreak of African swine fever has brought serious public safety problems to the world, and there is a need for reliable diagnostic tools to prevent and control the epidemic. Here, we successfully established a portable microfluidic-circular fluorescent probe-mediated isothermal nucleic acid amplification (CFPA) system for the rapid, high-throughput, accurate, and sensitive detection of African swine fever virus at point-of-care settings. This detection system has a detection limit of 10 copies/μL, good stability (C.V. < 5%), and 92.73% sensitivity, and 100% specificity when tested on 220 pig samples collected for the diagnosis of African swine fever virus, with a median time to threshold of 10.8 min. This novel integrated diagnostic tool is urgently needed and has promising applications for the monitoring and control of African swine fever epidemics worldwide and, in particular, the serious outbreak in China.


Predicting risk of breast cancer recurrence using gene-expression profiling.
The molecular profiling of breast tumors using the powerful microarray technology has uncovered the molecular heterogeneity of breast tumors and has offered novel insight into breast tumorigenesis. The estrogen receptor (ER) has been shown to be the most important discriminator dichotomizing breast cancer into two main subsets. At the same time, proliferation, as captured by the recently developed Genomic Grade Index (GGI) has been found to be the most important prognostic factor in breast cancer, far beyond ER status. Interestingly, this index encompasses a significant portion of the predictive power of many published prognostic signatures. The challenge now is to integrate all the prognostic gene signatures available to date towards a comprehensive genomic fingerprint of the primary tumor. In the future, we should be able to offer individualized treatment to our patients based on a clinical decision-making algorithm that takes into account the clinicopathological parameters, the genomic profile of the primary tumor, the presence of micrometastatic cells and pharmacogenetic data for drug response.


The future impact of population growth and aging on coronary heart disease in China: projections from the Coronary Heart Disease Policy Model-China.
China will experience an overall growth and aging of its adult population in coming decades. We used a computer model to forecast the future impact of these demographic changes on coronary heart disease (CHD) in China. The CHD Policy Model is a validated state-transition, computer simulation of CHD on a national scale. China-specific CHD risk factor, incidence, case-fatality, and prevalence data were incorporated, and a CHD prediction model was generated from a Chinese cohort study and calibrated to age-specific Chinese mortality rates. Disability-adjusted life years (DALYs) due to CHD were calculated using standard methods. The projected population of China aged 35-84 years was entered, and CHD events, deaths, and DALYs were simulated over 2000-2029. CHD risk factors other than age and case-fatality were held at year 2000 levels. Sensitivity analyses tested uncertainty regarding CHD mortality coding, the proportion of total deaths attributable to CHD, and case-fatality. We predicted 7.8 million excess CHD events (a 69% increase) and 3.4 million excess CHD deaths (a 64% increase) in the decade 2020-2029 compared with 2000-2009. For 2030, we predicted 71% of almost one million annual CHD deaths will occur in persons >or=65 years old, while 67% of the growing annual burden of CHD death and disability will weigh on adults <65 years old. Substituting alternate CHD mortality assumptions led to 17-20% more predicted CHD deaths over 2000-2029, though the pattern of increases in CHD events and deaths over time remained. We forecast that absolute numbers of CHD events and deaths will increase dramatically in China over 2010-2029, due to a growing and aging population alone. Recent data suggest CHD risk factor levels are increasing, so our projections may underestimate the extent of the potential CHD epidemic in China.


Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review.
Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.


Dietary intake before and after gastric bypass and gastroplasty for morbid obesity in women.
Fifty-one morbidly obese women were randomized to surgical treatment with gastric bypass (GBY) or gastroplasty (GPL). Their dietary intake was assessed preoperatively and 12 months postoperatively by two methods: diet history and 4-day weighted intake. Their protein intake was also checked against urinary nitrogen losses. There was a good correspondence between the results of the two dietary methods and also between estimated protein intake and urinary loss. This makes the results reliable. After 1 year the GBY patients demonstrated a mean weight loss of 41.6 +/- 10.8 kg (P less than 0.001 versus GPL) and a mean energy intake preoperatively of about 2400 kcal/day and postoperatively of 1050 kcal/day (P less than 0.05 versus GPL). The GPL patients lost 28.9 +/- 9.6 kg as a mean and had a preoperative intake of about 2500 kcal/day and a postoperative intake of about 1300 kcal/day. There were only minor changes in the quality of the food from the preoperative to the postoperative situation. Postoperatively the daily intake of several nutrients was below minimum values of recommended or required intake.


Vitamin E supplementation may ameliorate oxidative stress in type 1 diabetes mellitus patients.
Increasing evidence in both experimental and clinical studies suggests that free radical mediated oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Proteins and lipids are among the prime targets for oxidative stress. In this study we evaluated oxidative stress in Type 1 Diabetes Mellitus (insulin dependent diabetes mellitus, IDDM) patients by estimating lipid peroxidation and the effect of vitamin E on oxidative stress and metabolic parameters. A total of 40 children (20 Type 1 Diabetes Mellitus patients + 20 healthy controls) were examined in the study. Oxidative stress parameters malondialdehyde (MDA), antioxidants, reduced glutathione (GSH), vitamin E and metabolic parameters were studied. All the type 1 Diabetes Mellitus patients were supplemented with 600 mg/daily vitamin E for three months. After three months of supplementation all the parameters mentioned above were studied again. Reduced glutathione and vitamin E levels were lower and malondialdehyde levels were higher in Type 1 Diabetes Mellitus patients compared to healthy controls (p < 0.05). After supplementation with vitamin E in diabetic patients a significant decrease (p < 0.05) in MDA levels and significant increase in GSH (p < 0.05) and vitamin E (p < 0.05) levels were found. A negative correlation between MDA and vitamin E, between MDA and GSH and a positive correlation between vitamin E and GSH was found. Significant changes were not observed in metabolic parameters in Type 1 Diabetes Mellitus patients after vitamin E supplementation (p > 0.05). Vitamin E ameliorates oxidative stress in Type 1 Diabetes Mellitus patients and improves antioxidant defense system. However, vitamin E does not have any advantage for metabolic parameters.


Mechanism of polymorphonuclear leukocyte activation by myristate. Involvement of calcium ion and protein kinase C.
The stimulative effects of myristate on the superoxide generation and depolarization of membrane potential of polymorphonuclear leukocytes (PMN) are particularly strong, yet myristate does not affect the intracellular free Ca2+ level ([Ca2+]i) in the presence of 1 microM free calcium in calcium-EGTA buffer. The half maximum concentration of myristate was 10 microM. Myristate inhibited the transitory changes in [Ca2+]i induced by formylmethionyl-leucyl-phenylalanine (FMLP), but stimulated further the FMLP-induced superoxide generation; these effects are similar to those of phorbol myristate acetate (PMA). The myristate-induced superoxide generation was partially inhibited by H-7, a specific inhibitor of protein kinase C. Myristate stimulated the activity of Ca2+- and phospholipid-dependent protein kinase (protein kinase C) in a concentration-dependent manner in the presence of 10(-6) M Ca2+. The Ka was 100 microM. These results suggested that there is no relation between the superoxide generation and the [Ca2+]i change in PMNs and that the effects of myristate are similar to those of PMA against PMN.


Corneal eccentricity as a tool for the diagnosis of keratoconus.
Ninety-nine eyes with keratoconus of 64 patients were examined using the sagittal radii method to determine the corneal flattening and compared with 100 eyes of 50 healthy controls. To express the degree of this flattening, four numerical eccentricity (E) values for each eye were calculated. The highest E value of the four was chosen as a parameter for diagnosis of the disease. In keratoconus patients in whom the highest E values of keratoconus eyes were > or = 0.8, the specificity of the test was 98% and the sensitivity was 97%. This abnormal eccentricity was observed in keratoconus eyes with a visual acuity of 1.0, whereas slit-lamp examination showed no abnormalities. This study demonstrates that eccentricity can be helpful to diagnose keratoconus at an early stage.


Attracting RNs to nursing homes: nurses' work experience and perceived importance of organization and job attributes.
Applicant attraction theories stipulate that employment inducements be customized to meet the desires and specific characteristics of potential applicants. This study examined the relationship between nurses' level of work experience and perceived importance of organization and job attributes in attracting them to nursing home jobs. Importance ratings of recruitment factors varied significantly by nurses' level of work experience. Unique variation was attributed to education opportunities, potential for career advancement, compensation issues, benefits, and work flexibility.


Moderate Alcohol Consumption Is Associated with Reduced Pain and Fibromyalgia Symptoms in Chronic Pain Patients.
Moderate alcohol consumption has been associated with improved health outcomes including reduced risk of heart disease; however, less is known regarding alcohol's effects on chronic pain. The aim of this study was to assess associations between pain, fibromyalgia symptoms, and moderate alcohol use in a large chronic pain sample. A total of 2,583 new chronic pain patients presenting at a university pain clinic reported alcohol use and completed validated measures; 592 (23%) patients reported drinking, with 502 (85%) classified as moderate drinkers (females ≤7 and males ≤14 drinks/wk). General linear models (GLM) assessed the effects of moderate drinking on pain and symptom outcomes. The sample was stratified by gender and fibromyalgia (FM) status in secondary analyses. Moderate alcohol users reported significantly lower FM symptoms (widespread pain and symptom severity), pain severity, interference, anxiety, depression, and catastrophizing, and they reported higher physical function. Similar findings were observed in gender-stratified analysis, minus associations with FM symptom severity in females and anxiety in males. In patients meeting FM criteria, moderate drinking was associated with lower pain severity, interference, and depression, and higher physical function. Results in non-FM patients were similar to the total sample. Moderate alcohol consumption in chronic pain patients was associated with decreased pain severity and interference, fewer painful body areas, lower somatic and mood symptoms, and increased physical function. A similar effect was observed in non-FM patients, but to a lesser extent in FM patients, suggesting chronic pain patients with less centralized forms of pain may benefit most from moderate alcohol consumption.


Characterizing variability of in vivo Raman spectroscopic properties of different anatomical sites of normal colorectal tissue towards cancer diagnosis at colonoscopy.
This study aims to characterize the in vivo Raman spectroscopic properties of normal colorectal tissues and to assess distinctive biomolecular variations of different anatomical locations in the colorectum for cancer diagnosis. We have developed a novel 785 nm excitation fiber-optic Raman endoscope that can simultaneously acquire in vivo fingerprint (FP) spectra (800-1800 cm(-1)) and high-wavenumber (HW) Raman spectra (2800-3600 cm(-1)) from the subsurface of colorectal tissue. We applied the FP/HW Raman endoscope for in vivo tissue Raman measurements of various normal colorectal anatomical locations (i.e., ascending colon (n = 182), transverse colon (n = 249), descending colon (n = 124), sigmoid (n = 212), and rectum (n = 362)) in 50 subjects. Partial least-squares (PLS)-discriminant analysis (DA) was employed to evaluate the interanatomical variability. The normal colorectal tissue showed a subtle interanatomical variability in molecular constituents (i.e., proteins, lipids, and water content) and could be divided into three major clusterings: (1) ascending colon and transverse colon, (2) descending colon, and (3) sigmoid and rectum. The PLS-DA multiclass algorithms were able to identify different tissue sites with varying sensitivities (SE) and specificities (SP) (ascending colon: SE: 1.10%, SP: 91.02; transverse colon: SE: 14.06%, SP: 78.78; descending colon: SE: 40.32%, SP: 81.99; sigmoid: SE: 19.34%, SP: 87.90; rectum: SE: 71.55%, SP: 77.84). The interanatomical molecular variability was orders of magnitude less than neoplastic tissue transformation. Further PLS-DA modeling on in vivo FP/HW tissue Raman spectra yielded a diagnostic accuracy of 88.8% (sensitivity: 93.9% (93/99); specificity 88.3% (997/1129) for colorectal cancer detection. This work discloses that interanatomical Raman spectral variability of normal colorectal tissue is subtle compared to cancer tissue, and the simultaneous FP/HW Raman endoscopic technique has promising potential for real-time, in vivo diagnosis of colorectal cancer at the molecular level.


Perioperative management of pheochromocytoma: the heart of the issue.
Pheochromocytoma is an endocrine tumor derived from the adrenal medulla and paraganglia. Pheochromocytoma presents with a wide spectrum of symptoms, from a silent adrenal mass to cardiac arrest. Perioperative management of pheochromocytoma is critical for preventing perioperative cardiovascular complications. Traditionally, perioperative management focuses on blood pressure control, which has generated considerable controversy. In this review, we suggest that perioperative management should focus more on treating subclinical and clinical pheochromocytoma-induced cardiomyopathy. We first describe the natural history of pheochromocytoma and illustrate that cardiomyopathy is present to various degrees in patients with pheochromocytoma. We then classify pheochromocytomas into 3 groups according to the risks of developing clinical cardiomyopathy. After going over perioperative physiological changes, we propose that the need for preoperative preparation depends on the risk level of the pheochromocytoma. We present the regimens for perioperative management, emphasizing that the goals of perioperative management should extend beyond blood pressure control and include improvement of cardiac function. Perioperative management in unique clinical situations is also discussed.


The Facile Hydrolysis of Imidazolinium Chlorides (N-Heterocyclic Carbene Precursors) Under Basic Aqueous Conditions.
The hydrolysis of imidazolinium chlorides takes place readily in a basic water/dichloromethane biphasic mixture at room temperature. Experimental parameters were optimized to afford full conversions and high yields of γ-aminoformamides starting from twelve symmetrical substrates with alkyl or aryl substituents on their nitrogen atoms, and five unsymmetrical 1-alkyl-3-arylimidazolinium chlorides. NMR and XRD analyses showed that the cleavage of unsymmetrical salts led to γ-alkylamino-N-arylformamides with a high regioselectivity and that bulky alkyl or aryl groups on the formamide moiety led to the isolation of the (E)-isomer in high stereoisomeric purity (>95 %), whereas smaller and more flexible alkyl substituents afforded mixtures of (E)- and (Z)-rotamers. Control experiments showed that the hydrolysis of 1,3-dimesitylimidazolinium chloride (SIMes ⋅ HCl) did not occur readily in pure or acidic water and that the presence of bulky aromatic substituents on the nitrogen atoms of 1,3-bis(2,6-diisopropylphenyl)imidazolinium chloride (SIDip ⋅ HCl) efficiently slowed down its hydrolysis under basic aqueous conditions. Most strikingly, this work highlighted the critical influence of the counteranion on the reactivity of imidazolinium cations. Indeed, the chloride salts underwent a facile hydrolysis in the presence of water and Na2 CO3 , whereas various other NHC ⋅ HX derivatives reacted much slower or remained essentially inert under these conditions.


Medical nephrectomy. The use of metallic salts for the control of massive proteinuria in the nephrotic syndrome.
Two patients with intractable massive proteinuria and uremia were followed and treated with standard mecial therapy and dialysis. After a period of study and demonstration of clinical deterioration both patients were given solutions containing sodium mercaptomerin. Within days there was a decline in urine protein excretion and a variable increase in serum protein concentration. The patients demonstrated an increase in blood pressure, which made hemodialysis treatment possible. No deleterious effects from the mercury salts were noted. These observations suggest that in selected cases nephrotoxic agents may be of value in decreasing massive proteinuria, and improving protein homeostasis in uremic patients. Table I: Possible advantages of medical nephrectomy. 1. Reversal of hypotension and shock 2. Ability to perform hemodialysis 3. No anesthesia or surgical risk 4. No angiography related complications 5. Preservation of endocrine function of kidney. Possible advantages of medical nephrectomy (Table I), are: 1) Correction of proteinuria and hypotension; 2) Ability to perform hemodialysis; 3) No anesthesia or surgical risk; 4) No angiography related complications; and 5) Preservation of remaining endocrine function of the kidney, including erythropoietic and vitamin D action. The ideal agent should be non-toxic to other organs and produce selective renal ablation. Obviously mercury is not the ideal agent, although in these cases it did not produce observable side effects. It appears that this agent should be used with caution and only in patients with irreversible renal failure.


Clinical Significance of Serum IL-12 Level in Patients with Early Breast Carcinoma and Its Correlation with Other Tumor Markers.
To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio. Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded. BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio. IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value.


Clinically Oriented Subtyping of Chronic Insomnia of Childhood.
To identify different profiles of pediatric insomnia, based on the most frequent clinical presentations (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings). A structured parent interview was conducted in 338 children (mean age 21.29 months, SD 10.56) referred by pediatricians because of insomnia resistant to behavioral approaches and common drug treatments. The aim was to assess the characteristics of insomnia in children, together with family sleep-related history. A latent class analysis was run to identify profiles of insomnia. ANOVA and the χ2 test were used to examine differences between profiles. A 3-class model was built by latent class analysis: 17% (n = 58) of children constituted the first class, characterized by difficulties in falling asleep, with restlessness, nocturnal restlessness, and awakenings during the night; the second class, characterized by early morning awakenings, comprised 21% (n = 71) of children; 62% (n = 209) of children fell within the third class because of their high frequency of nocturnal awakenings and difficulties in falling asleep. The first class reported longer sleep latency and the presence of restless legs syndrome and anemia in the family history; depression and/or mood disorders were more frequent in class 2 and allergies and/or food intolerance were more frequent in class 3. Our study suggests the existence of 3 different phenotypes of insomnia in children, based on clinical, personal, and familial data. The identification of these different phenotypes might help to optimize the assessment and treatment of insomnia in young children.


Efficient responses in a murine renal tumor model by electroloading dendritic cells with whole-tumor lysate.
Electroporation of dendritic cells (DCs) with tumor lysate elicited greater antitumor responses in vitro and in vivo, using less lysate than standard coincubation. Electroloaded DCs had normal surface marker expression and matured into competent antigen-presenting cells. In a renal carcinoma (RENCA) model, mice were pretreated with lysate-loaded DCs before tumor challenge. Mice that received DCs electroloaded with RENCA lysate had significantly smaller tumors (9+/-6 mm2) than mice given DCs coincubated with the same lysate (23+/-5 mm2). To evaluate a metastatic therapeutic tumor model, mice were first injected with Lewis lung carcinoma (LLC) and then given 2 doses of cryopreserved LLC lysate-loaded DCs. Mice treated with electroloaded DCs had a 50% reduction in lung metastases compared with control mice that received no DCs or DCs loaded with liver lysate. In contrast, DCs coincubated with LLC lysate were indistinguishable from controls. Tumor lysate-electroloaded but not-coincubated DCs also primed syngeneic mouse splenocytes in vitro to produce interferon-gamma and, specifically, lyse tumor cells. The electroloaded DCs elicited specific T-cell responses with less lysate than the amount reported in standard coincubation procedures. This approach may be particularly useful when small amounts of tumor material are available.


[Progress in mesenchymal stem cells aging].
To comprehensively analyze the recent advancements in the field of mesenchymal stem cells (MSCs) aging, and summary its achievements and its difficulty at the present. The literature about MSCs aging was reviewed and analyzed. Inducible telomerase reactivation of MSCs is successful to extend the life span of senescent cells, but it also has potential safety hazard. The age range presented in the research of age-related cell senescence is inconsistent, resulting in different outcomes. Many ways to improve cell in vitro culture conditions will help delay aging. Recent research indicates that oxidative stress theory is seemed to not completely explain cell aging. Further research of MSCs aging mechanism will help the tissue engineering transform to clinical application.


Enhanced Room Temperature Oxygen Sensing Properties of LaOCl-SnO2 Hollow Spheres by UV Light Illumination.
In this paper, a facile and elegant Green Chemistry method for the synthesis of SnO2 based hollow spheres has been investigated. The influences of doping, crystallite morphology, and operating condition on the O2 sensing performances of SnO2 based hollow-sphere sensors were comprehensively studied. It was indicated that, compared with undoped SnO2, 10 at. % LaOCl-doped SnO2 possessed better O2 sensing characteristics owing to an increase of specific surface area and oxygen vacancy defect caused by LaOCl dopant. More importantly, it was found that O2 sensing properties of the 10 at. % LaOCl-SnO2 sensor were significantly improved by ultraviolet light illumination, which was suited for room-temperature O2 sensing applications. Besides, this sensor also had a better selectivity to O2 with respect to H2, CH4, NH3, and CO2. The remarkable increase of O2 sensing properties by UV light radiation can be explained in two ways. On one hand, UV light illumination promotes the generation of electron-hole pairs and oxygen adsorption, giving rise to high O2 response. On the other hand, UV light activates desorption of oxygen adsorbates when exposed to pure N2, contributing to rapid response/recovery speed. The results demonstrate a promising approach for room-temperature O2 detection.


The effects of load location and misalignment on shear/peel testing of direct bonded orthodontic brackets--a finite element model.
A finite element model (FEM) of an orthodontic bracket bonded with glass ionomer cement was developed. The loading on the model simulated shear loading conditions associated with the testing of bonding system strength. The primary purpose of this project was to ascertain the effects of shear load placement and misalignment on the calculated stresses within the cement layer. Over the range of values considered, peak stress values depend profoundly on the location of force application. Peak stresses are less affected by shear force angulation.


X-ray microanalysis of non-aldehyde-fixed glycogen contrast stained with OsVIIIO4, OsVIIIFeIII, or OsVIFeII complex in vitro.
Fibrin-enrobed, commercially produced glycogen was treated, without prior glutaraldehyde fixation, to a form of post-fixation with solutions of OsVIIIO4 or with a mixture of either OsVIIIO4 plus K3FeIII(CN)6 or K2OsVIO4 plus K4FeII(CN)6. Only the last mixture gave contrast staining of the glycogen in unstained ultrathin sections. The first mixture rendered the glycogen just barely visible but the glycogen contrast was increased by lead staining. The glycogen treated with the OsVIIIO4 solution was not contrast stained an was just observable after lead staining. Qualitative X-ray microanalysis of the glycogen in the ultrathin sections confirmed the presence of osmium and iron in the glycogen treated with both mixtures. The glycogen treated with OsVIIIO4 alone was difficult to analyse. Quantitative X-ray microanalysis showed that, in the glycogen treated with the OsVIIIO4 mixture plus K3FeIII(CN)6, the mean atomic osmium to iron ratio was 1:5. In the glycogen treated with K2OsVIO4 plus K4FeII(CN)6, this ratio was 1:17. However, th mean net osmium intensity in the latter case was 15 times higher than in the former case and for the iron even 40 times higher.


An alternative strategy for count and storage of Kekulé and longer range resonance valence bond structures.
In this paper, we suggest a simple representation for notation of Kekulé valence bond (KVB) structures and longer range resonance valence bond (RVB) structures, which is called "the adjacency bonding array". In this representation, only an N component one-dimensional array is needed for inscribing each KVB or longer range RVB structure for an N-carbon system. Based on the adjacency bonding arrays, we develop very efficient algorithms for the systematic search of KVB and RVB structures as well as evaluation of the basis set overlap and Hamiltonian matrices.


Case of pediatric traditional serrated adenoma resected via endoscopic submucosal dissection.
Traditional serrated adenoma (TSA) is a type of serrated polyp of the colorectum and is thought to be a precancerous lesion. There are three types of serrated polyps, namely, hyperplastic polyps, sessile serrated adenomas/polyps, and TSAs. TSA is the least common of the three types and accounts for about 5% of serrated polyps. Here we report a pediatric case of TSA that was successfully resected by endoscopic submucosal dissection (ESD). This rare case report describes a pediatric patient with no family history of colonic polyp who was admitted to our hospital with hematochezia. On colonoscopy, we found a polypoid lesion measuring 10 mm in diameter in the lower rectum. We selected ESD as a surgical option for en bloc resection, and histopathological examination revealed TSA. The findings in this case suggest that TSA with precancerous potential can occur in children, and that ESD is useful for treating this lesion.


Isothermal equation of state of crystalline and glassy materials from optical measurements in diamond anvil cells.
Here, we present a method to study the equation of state of opaque amorphous and crystalline materials in diamond anvil cells. The approach is based on measurements of sample dimensions using high-resolution optical microscopy. Data on the volumetric strain as a function of pressure allow deriving the isothermal equation of state of the studied material. The analysis of optical images is fully automatized and allows measuring the sample dimensions with the precision of about 60 nm. The methodology was validated by studying isothermal compression of ω-Ti up to 30 GPa in a Ne pressure transmitting medium. Within the accuracy of the measurements, the bulk modulus of ω-Ti determined using optical microscopy was similar to that obtained from x-ray diffraction. For glassy carbon compressed to ∼30 GPa, the previously unknown bulk modulus was found to be equal to K0 = 28 (2) GPa [K' = 5.5(5)].