[Spinal sinovial cysts: Surgical treatment and clinical outcomes in a series of 18 cases].
A series of 18 patients with symptomatic synovial cysts was analysed from May 2009 to November 2013. Different approaches were performed for their removal. The study included 18 patients, 8 men and 10 women, aged between 50 and 77 years. An analysis was made of the variables including age, gender, symptoms, imaging studies, histopathology, surgery, follow-up, complications, and clinical outcome. An articular synovial cyst was diagnosed in 17 cases, and a ganglion in one cases. The most common symptom was back pain with radiculopathy (94%). Motor deficits occurred in 4 cases (22%), and 1 case (5%) presented with urinary incontinence. The most common level was L4- L5 (67%), with one atypical case observed in the D12 -L1 location. Hemi-laminectomy was performed in 14 cases, with 9 of them having an interspinous spacer (ISP) device inserted. A laminectomy with a fusion procedure was performed in 3 patients and 1 patient had a bilateral decompression using a unilateral approach. The patients were followed-up for between 6 months to 2 years. Synovial cysts are a cause of radiculopathy/neurogenic claudication. Spinal cysts are commonly found at the L4-L5 level. MRI is the tool of choice for diagnosis. The most common symptom was back pain with radiculopathy. Synovial cysts resistant to conservative therapy should be treated surgically. In our series, surgical resection of symptomatic juxtafacet cysts showed a good clinical outcome, but the optimal approach for patients with juxtafacet cysts remains unclear.


Development of a multi-jurisdictional syndromic surveillance system.
We have identified several potential barriers to shared public health informatics systems in the context of developing a syndromic surveillance. A formal charter process successfully navigated these barriers. A flexible development process enabled building of system to proceed while policy issues were addressed.


Chronic functional consequences of adult infraorbital nerve transection for rat trigeminal subnucleus interpolaris.
In adult rats, transection of the infraorbital nerve and subsequent regeneration have been shown to result in altered somatotopic organization and changes in response properties of primary afferents within the trigeminal ganglion. The present study examined how these changes affect the postsynaptic targets of these neurons within subnucleus interpolaris of the trigeminal brainstem. Extracellular recordings were made from 330 cells in normal rats and 424 cells in rats surviving 57-290 days after transection of the infraorbital nerve in adulthood. Adult infraorbital nerve transection resulted in significant functional reorganization within subnucleus interpolaris. Relative to normal rats, the major changes can be summarized as follows: (1) a decrease in the dorsoventral extent of infraorbital representation; (2) a disruption of inter- and intradivisional somatotopic organization; (3) an increase in the proportion of cells with no discernible receptive field; (4) an increase in receptive field size for cells with infraorbital receptive field components; (5) the appearance of a significant proportion of cells with discontinuous receptive fields; (6) an increase in the proportion of cells exhibiting interdivisional convergence; (7) significant changes in the types of receptor surfaces activating local-circuit neurons with infraorbital receptive field components; (8) the appearance of a significant proportion of cells exhibiting convergence of different receptor surfaces; (9) significant changes in the dynamic response characteristics of cells with infraorbital receptive field components; and (10) an increase in the proportion of spontaneously active infraorbital-responsive cells. The changes observed were quite similar to those reported in adult subnucleus interpolaris following neonatal infraorbital nerve transection. The majority of changes observed in both studies can be most parsimoniously explained by alterations of primary afferents. However, central mechanisms may be more likely substrates for others. Regardless of the mechanism, the mature rodent trigeminal system appears capable of considerable functional reorganization following peripheral nerve damage.


Functional importance of the NH2-terminal insertion sequence of lung surfactant protein B.
Lung surfactant protein B (SP-B) is required for proper surface activity of pulmonary surfactant. In model lung surfactant lipid systems composed of saturated and unsaturated lipids, the unsaturated lipids are removed from the film at high compression. It is thought that SP-B helps anchor these lipids closely to the monolayer in three-dimensional cylindrical structures termed "nanosilos" seen by atomic force microscopy imaging of deposited monolayers at high surface pressures. Here we explore the role of the SP-B NH(2) terminus in the formation and stability of these cylindrical structures, specifically the distribution of lipid stack height, width, and density with four SP-B truncation peptides: SP-B 1-25, SP-B 9-25, SP-B 11-25, and SP-B 1-25Nflex (prolines 2 and 4 substituted with alanine). The first nine amino acids, termed the insertion sequence and the interface seeking tryptophan residue 9, are shown to stabilize the formation of nanosilos while an increase in the insertion sequence flexibility (SP-B 1-25Nflex) may improve peptide functionality. This provides a functional understanding of the insertion sequence beyond anchoring the protein to the two-dimensional membrane lining the lung, as it also stabilizes formation of nanosilos, creating reversible repositories for fluid lipids at high compression. In lavaged, surfactant-deficient rats, instillation of a mixture of SP-B 1-25 (as a monomer or dimer) and synthetic lung lavage lipids quickly improved oxygenation and dynamic compliance, whereas SP-B 11-25 surfactants showed oxygenation and dynamic compliance values similar to that of lipids alone, demonstrating a positive correlation between formation of stable, but reversible, nanosilos and in vivo efficacy.


Diversity in prevalent PCR ribotypes of clinical strains of C. difficile.
In 2009, a programme of Clostridium difficile ribotyping was established in the north east. The aim of this project was to profile circulating ribotypes in the region, In all, 50 notified north east Clostridium difficile cases were ribotyped. The majority of cases occurred in patients over 70 years and in hospital in-patients. The most common ribotype identified was 027 (n = 12, 24%) and 005 (n = 8, 16%). Ribotype 078 was also detected (n = 5, 10%). Comparison with a 2009 national ribotyping study demonstrated that there were a number of ribotypes identified in the north east that were not identified during the national study and visa versa. The results of this study point to the existence of regional variation in circulating Clostridium difficile strains in Ireland. A reference facility for Ireland is urgently required to provide a central point for enhanced testing and epidemiological analysis of national and regional Clostridium difficile trends.


Contributions of the histidine side chain and the N-terminal alpha-amino group to the binding thermodynamics of oligopeptides to nucleic acids as a function of pH.
Interactions of histidine with nucleic acid phosphates and histidine pK(a) shifts make important contributions to many protein-nucleic acid binding processes. To characterize these phenomena in simplified systems, we quantified binding of a histidine-containing model peptide HWKK ((+)NH(3)-His-Trp-Lys-Lys-NH(2)) and its lysine analogue KWKK ((+)NH(3)-Lys-Trp-Lys-Lys-NH(2)) to a single-stranded RNA model, polyuridylate (polyU), by changes in tryptophan fluorescence as a function of salt concentration and pH. For both HWKK and KWKK, equilibrium binding constants, K(obs), and magnitudes of log-log salt derivatives, SK(obs) identical with (partial differential logK(obs)/partial differential log[Na(+)]), decreased with increasing pH in the manner expected for a titration curve model in which deprotonation of the histidine and alpha-amino groups weakens binding and reduces its salt-dependence. Fully protonated HWKK and KWKK exhibit the same K(obs) and SK(obs) within uncertainty, and these SK(obs) values are consistent with limiting-law polyelectrolyte theory for +4 cationic oligopeptides binding to single-stranded nucleic acids. The pH-dependence of HWKK binding to polyU provides no evidence for pK(a) shifts nor any requirement for histidine protonation, in stark contrast to the thermodynamics of coupled protonation often seen for these cationic residues in the context of native protein structure where histidine protonation satisfies specific interactions (e.g., salt-bridge formation) within highly complementary binding interfaces. The absence of pK(a) shifts in our studies indicates that additional Coulombic interactions across the nonspecific-binding interface between RNA and protonated histidine or the alpha-amino group are not sufficient to promote proton uptake for these oligopeptides. We present our findings in the context of hydration models for specific vs nonspecific nucleic acid binding.


Generation of human induced pluripotent stem cell lines encoding for genetically encoded calcium indicators RCaMP1h and GCaMP6f.
Calcium plays a key role in cardiomyocytes (CMs) for the translation of the electrical impulse of an action potential into contraction forces. A rapid, not-invasive fluorescence imaging technology allows for the monitoring of calcium transients in human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) to investigate the cardiac electrophysiology in vitro and after cell transplantation in vivo. The genetically encoded calcium indicators (GECIs) GCaMP6f or RCaMP1h were successfully transfected in the previously established hiPSC line MHHi001-A, together with a cardiac specific antibiotic selection cassette facilitating the monitoring of the calcium handling in highly pure populations of hiPSC-CMs.


Chain formation of spheres in oscillatory fluid flows.
A collection of spherical particles subjected to horizontal oscillatory fluid flow is known to form chains perpendicular to the direction of the oscillation. We have developed computer simulations to model such a system and have validated them against experiments carried out in a small fluid-filled cell. In both experiment and simulation we find that the particles go through the same stages of evolution from a dispersed initial configuration to an ordered chain structure. We then use our computer simulations to investigate in detail the interactions responsible for chain formation and the interaction between fully formed chains.


Correlation Between Body Temperature and Survival Rate in Patients With Hospital-Acquired Bacteremia: A Prospective Observational Study.
Fever is a complex and major sign of a patient's acute response to infection. However, analysis of the risks and benefits associated with the change in body temperature of an infected host remains controversial. To examine the relationship between the intensity of the change in body temperature and the mortality of patients with hospital-acquired bacteremia. A prospective observational study. Subjects were hospitalized adult patients who developed clinical signs of infection 48 hr or more after admission and had documented bacterial growth in blood culture. The maximum body temperature (maxTe) during the early period of infection measurements (i.e., the day before, the day of, and 2 days after the day of blood culture) was used to indicate the intensity of the body temperature response. Patients were categorized as discharged alive or died in hospital. Cox regression analysis was employed to analyze the data. The cohort consisted of 502 subjects. The mean maxTe of subjects was 38.6°C, and 14.9% had a maxTe lower than 38.0°C. The in-hospital mortality rate was 18.9%. The highest in-hospital mortality was found in subjects with a maxTe lower than 38°C (30.7%). Multivariate Cox regression analysis determined that the maxTe and the severity of comorbidity are the two variables associated with in-hospital mortality. Lack of a robust febrile response may be associated with greater risk of mortality in patients with bacteremia. Clinicians must be vigilant in identifying patients at risk for a blunted febrile response to bacteremia for more intensive monitoring.


Ca2+-dependent and Ca2+-independent regulation of the thyroid epithelial junction complex by protein kinases.
The integrity of epithelial cell junctions is controlled by E-cadherin-mediated (Ca2+-dependent) cell-cell adhesion. In thyroid follicular cells the dissociation of junctions induced by transfer to low Ca2+ medium (Ca2+ switch) is prevented by thyrotropin acting via cyclic AMP/protein kinase A (cAMP/PKA) (Nilsson et al., Eur. J. Cell Biol. 56, 308-318, 1991). In MDCK kidney epithelial cells protein kinase inhibitors elicit a similar response which, however, is cadherin-independent (Citi, J. Cell Biol. 117,169-178,1992; Citi et al., J. Cell Sci. 107, 683-692, 1994). As such inhibitors also may interfere with PKA, we examined in a single cell type, filter-cultured pig thyrocytes, the effects and possible interactions of the cAMP/PKA agonist forskolin (or thyrotropin) and the kinase inhibitor H-7 in Ca2+ switch experiments. We found that the epithelial barrier dysfunction, comprising loss of transepithelial resistance, increased transepithelial flux of [3H]inulin and redistribution of junction proteins (cadherin and ZO-1), which follows Ca2+ removal were inhibited by TSH, forskolin, and H-7. All agents were also able to induce recovery of resistance in low Ca2+. The maximal recovery effects of forskolin and H-7 were additive when given simultaneous with Ca2+ chelator. In contrast, forskolin-induced recovery initiated 10 min after Ca2+ removal was antagonized by H-7. The protection of junctions by forskolin in low Ca2+ was rapidly abolished by light trypsinization (0.001%), whereas the same concentration of trypsin had little or no effect on the corresponding action of H-7 or staurosporine, another potent kinase inhibitor. In H-7-treated cells kept in low Ca2+, trypsin caused redistribution of ZO-1 from the plasma membrane to the cytoplasm while the transepithelial resistance remained high. Taken together, the data indicate that TSH via cAMP/PKA and the protein kinase inhibitor H-7 reinforce the thyroid epithelial barrier under low Ca2+ conditions by distinct although interacting mechanisms. The high sensitivity to proteolysis in the absence of Ca2+ suggests that the cAMP-regulated mechanism is cadherin-dependent. H-7 promotes or inhibits the cAMP/PKA-mediated recovery of transepithelial resistance depending on the duration of the preceding low Ca2+ period. The trypsin-induced displacement of ZO-1 in H-7-treated cells in low Ca2+ suggests that the localization of ZO-1 to the tight junction is not necessary for the maintenance of junctional tightness.


Regulation of breathing during exercise.
This paper reviewed in short neural and humoral factors which might be responsible for inducing exercise hyperpnea. As one of the neural factors afferent signals which arise in the exercising limbs and are transmitted via group III or IV high threshold sensory fibres were involved. The other neural factor is command signals originating in the central nervous system and being fed onto the respiratory center. Hypothalamic locomotor region is assumed to be a possible locus to integrate these peripheral and central neural signals. There are enough evidences to believe that humoral factors mediated via cardiac output is also essential for the hyperpnea. Changes in VCO2 is well correlated with those of VE in dynamic as well as in steady-state response. Oscillations in PaCO2 can be assumed to play a role to link metabolic CO2 changes to those in ventilation. Thus, no single factor can explain the whole process of exercise hyperpnea. Poon's optimization model may give a key to integrate complicated and coflicting experimental results in a unique concept.


Attention and information processing in end stage renal disease and effect of hemodialysis: a bedside study.
The neurobehavioral syndrome of uremia in chronic kidney disease affects the functioning of the central nervous system. Cognitive impairment is one of the most important manifestations of this dysfunction. The process of hemodialysis is known to bring about conflicting changes in the cognitive status of patients. In the present study an assessment of cognitive status of patients with end stage renal disease was done in comparison to controls before and after a session of hemodialysis using simple bedside paper-pencil tests. Thirty patients of end stage renal disease on maintenance dialysis for at least one month with MMSE score >24 were assessed one hour before and one hour after hemodialysis using Digit Symbol Substitution Test, One Letter and Three Letter Cancellations tasks. Their results were compared to age and sex matched healthy controls. The patients with end stage renal disease had significantly lower performance in cognitive tests in comparison to controls. The performance improved 1 hour after hemodialysis in comparison to pre-dialysis values. However, the values after dialysis were significantly lower than in controls, thereby indicating that though the cognitive functions improved after hemodialysis, they did not reach the control levels. There was also a significant change in the biochemical parameters after dialysis. We conclude that patients with end stage renal disease suffered from cognitive impairment which improved on hemodialysis due to removal of metabolic waste products.


A general method for the identification of transcribed retrovirus sequences (R-U5 PCR) reveals the expression of the human endogenous retrovirus loci HERV-H and HERV-K in teratocarcinoma cells.
During the past decade, different types of endogenous retroviral sequences have been defined in the human genome usually by low stringency hybridization employing DNA probes of evolutionary conserved animal retrovirus genes. Although all human genomic loci sequenced were found to be defective or interspersed with stop codons, indirect evidence is accumulating that human endogenous retroviral loci are expressed at least in some instances. One example is the synthesis of retroviral particles in human teratocarcinoma cell lines observed by electron microscopy. To establish a link between virus expression and genomic loci we searched for retroviral RNA in human cellular mRNA populations using a generally applicable method. A tRNA-derived primer complementary to a putative retroviral primer binding site was extended by reverse transcription and this product was elongated with a homopolymeric stretch and amplified by PCR (R-U5 PCR). Cloning and sequencing of such products revealed that the endogenous retroviral loci HERV-H and HERV-K are expressed in those human teratocarcinoma cell lines which produce retroviral particles. The size distribution of four HERV-K mRNAs detected in Northern blots is reminiscent of the complex expression pattern seen with a number of exogenous retroviruses.


Bcl-2 gene rearrangements in primary B-cell lymphoma of the gastrointestinal tract reveal follicular lymphoma as a subtype.
The principal objective of this study was to investigate whether follicular center cell lymphomas occur among B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We used a molecular genetic/immunohistochemical approach and analysed 21 cases with the primary site in the gastrointestinal tract. Only two bcl-2 gene rearrangements were detected in our series and were found in two out of seven lymphomas with a nodular growth pattern. A chromosomal translocation t(14;18) was demonstrated by comigration of rearranged bcl-2 and JH sequences in one of these two cases. Additionally, both lymphomas showed bcl-2 protein positive neoplastic follicles, CD10 expression, and lack of vimentin. Therefore, these two cases were defined as follicular lymphomas. In contrast to the two follicular lymphomas of MALT, three other, nodular growing, bcl-2 protein positive lymphomas were found to have no bcl-2 gene rearrangements, to be CD10 negative and to express vimentin. These three lymphomas might be composed of neoplastic extrafollicular cells which secondarily invaded reactive follicles. We conclude that the presence of bcl-2 protein positive follicles is consistent with both a follicular and extrafollicular origin of a B lymphoma of MALT. However, the detection of a bcl-2 gene rearrangement is the most valuable criterion in such a situation, and additional immunophenotypic criteria, such as CD10 expression and lack of vimentin within the neoplastic population, further substantiate the diagnosis of a follicular lymphoma in MALT.


Osteoarthritic Subchondral Bone Release Exosomes That Promote Cartilage Degeneration.
Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA.


Deprotonative Functionalization of the Difluoromethyl Group.
The functionalization of 3-(difluoromethyl)pyridine has been developed via direct deprotonation of -CHF2 with a lithiated base and subsequent trapping with various electrophiles in THF. In situ quenching gives access to 3-pyridyl-CF2-SiMe2Ph as a new silylated compound, which can be postfunctionalized with a fluoride source to obtain a larger library of 3-(difluoroalkyl)pyridines that could not be accessed via direct deprotonation.


Bifunctional nanoparticles with fluorescence and magnetism via surface-initiated AGET ATRP mediated by an iron catalyst.
Fluorescent/magnetic nanoparticles are of interest in many applications in biotechnology and nanomedicine for its living detection. In this study, a novel method of surface modification of nanoparticles was first used to modify a fluorescent monomer on the surfaces of magnetic nanoparticles directly. This was achieved via iron(III)-mediated atom-transfer radical polymerization with activators generated by electron transfer (AGET ATRP). Fluorescent monomer 9-(4-vinylbenzyl)-9H-carbazole (VBK) was synthesized and was grafted from magnetic nanoparticles (ferroferric oxide) via AGET ATRP using FeCl(3)·6H(2)O as the catalyst, tris(3,6-dioxaheptyl)amine (TDA-1) as the ligand, and ascorbic acid (AsAc) as the reducing agent. The initiator for ATRP was modified on magnetic nanoparticles with the reported method: ligand exchange with 3-aminopropyltriethoxysilane (APTES) and then esterification with 2-bromoisobutyryl bromide. After polymerization, a well-defined nanocomposite (Fe(3)O(4)@PVBK) was yielded with a magnetic core and a fluorescent shell (PVBK). Subsequently, well-dispersed bifunctional nanoparticles (Fe(3)O(4)@PVBK-b-P(PEGMA)) in water were obtained via consecutive AGET ATRP of hydrophilic monomer poly(ethylene glycol) methyl ether methacrylate (PEGMA). The chemical composition of the magnetic nanoparticles' surface at different surface modification stages was investigated with Fourier transform infrared (FT-IR) spectra. The magnetic and fluorescent properties were validated with a vibrating sample magnetometer (VSM) and a fluorophotometer. The Fe(3)O(4)@PVBK-b-P(PEGMA) nanoparticles showed an effective imaging ability in enhancing the negative contrast in magnetic resonance imaging (MRI).


A critical examination of OSHA's assessment of risk associated with workplace exposure to environmental tobacco smoke.
In response to a request for information on indoor air quality problems, the U.S. Occupational Health and Safety Administration (OSHA) has proposed a rule addressing indoor air quality in general, and especially environmental tobacco smoke (ETS), in indoor work environments. As justification for the proposed rule, OSHA relies on a quantitative risk assessment used to provide estimates of lifetime risk of lung cancer and heart disease associated with workplace exposure to ETS. However, there are a number of concerns regarding the OSHA risk assessment. (i) The form of the underlying mathematical model used in the risk assessment is inappropriate. (ii) OSHA was highly selective in choosing what data values to use in their risk assessment. (iii) Many data values required as input to the OSHA risk assessment model are simply not known at this time. When such values are required, known, but possibly inappropriate, values were substituted. The conclusions arrived at by OSHA on the basis of this risk assessment seem unwarranted.


Green Platinum Nanoparticles Interaction With HEK293 Cells: Cellular Toxicity, Apoptosis, and Genetic Damage.
Metal nanoparticles are widely used in industry, agriculture, textiles, drugs, and so on. The adverse effect of green platinum nanoparticles on human embryonic kidney (HEK293) cells is not well established. In the current study, green platinum nanoparticles were synthesized using leaf extract of Azadirachta indica L. Green platinum nanoparticles were characterized by dynamic light scattering and transmission electron microscope. The cytotoxicity of green platinum nanoparticle was observed in HEK293 cells by applying 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and Neutral red uptake (NRU) assays. Cell viability of the cells was decreased in a concentration and duration-dependent manner. Generation of reactive oxygen species (ROS) in HEK293 cells due to green platinum nanoparticles was examined using fluorescent dye 2,7-dichlorofluorescein diacetate (DCFDA), and ROS was increased according to exposure pattern. The cytotoxicity of HEK293 cells was correlated with increased caspase 3, depolarization of mitochondrial membrane potential, and DNA fragmentation. The abovementioned finding confirmed that mitochondria play an important role in genotoxicity and cytotoxicity induced by nanoparticles in HEK293 cells. Further, we determined other oxidative stress biomarkers, lipid peroxide (LPO) and glutathione (GSH); LPO was increased and GSH was decreased in HEK293 cells. It is also important to indicate that HEK293 cells appear to be more susceptible to green platinum nanoparticles exposure after 24 hours. This result provides a dose- and time-dependent apoptosis and genotoxicity of green nanoparticles on HEK293 cells.


Does CNS Myelin Inhibit Axon Regeneration?
Membrane proteins on oligodendrocytes and CNS myelin (NI35/250) have been shown to block axon out-growth in culture, and this is thought to be one of the major reasons for severely limited regeneration of severed axons in the CNS of higher vertebrates. In a recent study, adult dorsal root ganglion (DRG) neurons, which are sensitive to these inhibitory proteins, regenerated successfully after transplantation into two white matter tracts of the rat brain without any intervention to suppress the inhibitory activity of CNS myelin. The results and implications of these two studies are considered.


[Levels of P27Kip1 expression and apoptosis in HL-60 cells after treatment with TGF-ß1 and/or arsenic trioxide].
This study was purposed to investigate the effects of TGF-beta1 and arsenic trioxide (As₂O₃) on cell apoptosis, cell cycle and changes of P27(Kip1), endogenous TGF-ß1, cyclin E and BCL-2 in HL-60 cells, and to explore the relationship between expression of P27(Kip1) and apoptosis induced by As₂O₃ and/or TGFß1. Cell apoptosis and cell cycle changes of HL-60 cells treated with As₂O₃ and/or TGFß1 were detected by cytomorphologic observation and flow cytometry, the protein expressions of P27(Kip1), TGF-ß1, cyclin E and BCL-2 were measured by immunohistochemistry. The results showed the effect of 5 μmol/L of As₂O₃ was the most strong among the different concentration of As₂O₃ ,and the effect on apoptosis at 48 hour was more strong than that at 24 hours (p < 0.05). The TGF-beta1 (5 ng/ml) induced arrest of cells in G₁ phase (p < 0.05) compared with As₂O₃ alone and As₂O₃ combined with TGF-ß1, while there was no difference with control. P27(Kip1) expression was up regulated (p < 0.05), cyclin E and BCL-2 expression was down-regulated (p < 0.05) in TGFß1-treated group. BCl-2 expression was down regulated, endogenesis TGFß1 expression was up regulated (p < 0.05), and the level of P27(kip1) and cyclin E were not changed in As₂O₃-treated group (p > 0.05). The down-regulating effect of TGF-ß1 combined with As₂O₃ on BCL-2 protein was more strong than that in single factor treated group (p < 0.05). It is concluded that TGFß1 induces cell cycle arrest and apoptosis in HL-60 cells, while the P27(kip1) expression is up regulated. P27 protein is the key effector of TGFß-induced cell cycle arrest. The effect of TGF-ß1 combined with As₂O₃ on apoptosis as well as the down-regulation of BCL-2 protein in HL-60 cells is more strong than that in single factor-treated groups, that indicates the passages linking up each other.


Relationship between patient acceptable symptom state and disease scores in psoriasis.
Patient acceptable symptom state (PASS) is a patient-reported outcome that reflects patients' perspective well. The relationship between the PASS and disease scores in psoriasis has not been described. The aim of the present study was to investigate the association of PASS with Psoriasis Area and Severity Index (PASI) and body surface area (BSA) affected by lesions in patients with psoriasis. A sectional study was conducted. PASS was evaluated by a binary question on the patient's feeling that they have about their symptoms. Clinical data including PASI, BSA, and other patient characteristics were collected. Logistic regression was used to investigate the associations. Receiver-operator curve (ROC) analysis was utilized to determine the PASI/BSA thresholds for PASS. A total of 198 participants (27.8% female, mean age 41.9 ± 12.6 years, mean disease duration 10.2 ± 8.6 years) completed this study. Of patients with mild psoriasis, 71.4% based on PASI and 76.3% based on BSA considered their symptom state acceptable. Female sex (adjusted odds ratio [OR] = 0.47; 95% confidence interval [CI = 0.42-0.92) and patients with exposed skin involved (adjusted OR = 0.38; 95% CI = 0.19-0.76) were less likely to report acceptable symptom state. The threshold for differentiating psoriasis patients in PASS was 3.85 (area under the curve [AUC], 0.67; sensitivity, 0.67; specificity, 0.60) for PASI and 2.85% (AUC, 0.66; sensitivity, 0.79; specificity, 0.54) for BSA, respectively. These results showed that mild psoriasis based on PASI/BSA score align well with PASS status. Female and exposed skin involved are risk factors for acceptable status. Both PASI and BSA have limited capability in differentiating acceptable symptom state in psoriasis.


Non-invasive screening for subclinical liver graft injury in adults via donor-specific anti-HLA antibodies.
The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression. Therefore, graft injury was assessed in 133 liver biopsies with normal/near normal liver enzymes from a prospective liver biopsy program. Cytokeratin-18 cell death marker (M65) and donor specific anti-HLA antibodies (DSA) were measured as non-invasive markers in paired plasma samples in addition to routine parameters. M65 was associated with subclinical graft injury but this association was too weak for reasonable clinical application. DSA positivity was associated with more graft inflammation (OR = 5.4) and more fibrosis (OR = 4.2). Absence of DSA excluded fibrosis in 87-89%, while presence of DSA excluded histological criteria for immunosuppression minimization attempts in 92-97%. While CK18 cell death marker had no diagnostic value for the detection of subclinical liver graft injury, DSA testing can help to preselect patients for immunosuppression reduction in case of DSA negativity, while DSA positivity should prompt elastography or liver biopsy for the assessment of subclinical graft injury.


Paradoxical eczema in patients with psoriasis receiving biologics: a case series.
Atopic eczema and psoriasis are chronic, inflammatory dermatoses that can significantly affect the quality of life of those affected. Although both diseases are common, they rarely occur together. Severe psoriasis can be treated with biologic therapies targeting specific cytokine pathways involved in disease pathogenesis. There are reports of paradoxical eczema developing in biologic-treated patients with psoriasis, sometimes necessitating treatment discontinuation and thus leading to poor disease control. This retrospective case series identified 36 such events occurring in 23 patients. All currently available biologic classes were implicated. Eosinophilia (n = 19) and elevated serum IgE (n = 3) were identified in some cases. Treatment strategies included no treatment, topical corticosteroids, broad-acting systemic agents, and discontinuation or switch of biologic therapy. Two patients had persistent eczema and psoriasis despite discontinuation of all biologic therapies.


Differing dialysis treatment strategies and outcome.
The choice of a dialysis treatment depends on many factors, both medical and non-medical. A full and rational treatment requires easy access to a transplantation programme and to all dialysis modalities, extracorporeal or peritoneal. Presently, haemodialysis (HD) is used almost exclusively for in-centre or limited care treatment, peritoneal dialysis (PD) being preferred for home treatment. On HD, bicarbonate buffer is used in preference to acetate. Mixed convective-diffusive HD techniques have a very limited utilization world-wide because of their cost. Use of PD and automated PD continues to grow, although slowly. In our single-centre experience on a large number of patients, 10-year patient survival is not different on CAPD and HD, and there is initial lower risk of death on CAPD for patients > or = 75 years of age. Drop-out from CAPD has increased in recent years, mainly due to the patient/partner 'burn-out'. Drop-out is less for the elderly, and the difference in modality change between CAPD and HD decreases with increasing patient age, suggesting a clear indication for CAPD in the elderly, or in adults waiting for a transplant. The clinical background, e.g. the presence of diabetes mellitus, cardiovascular disease, dyslipidaemia or obesity, is also important in the choice of method.


Use of twinkling artifact in sonographic detection of intestinal pneumatosis.
Intestinal pneumatosis is a relatively rare condition that has been associated with a wide variety of abnormalities. Traditionally, this entity has been diagnosed by radiographic films, contrast series, or more accurately by computed tomography. However, reports describing findings of intestinal pneumatosis on sonographic examination, which is an important initial diagnostic tool for abdominal diseases, are limited. We suggest that twinkling artifact may be of value in the sonographic diagnosis of this condition. We report two cases of intestinal pneumatosis that were diagnosed initially by sonography with the aid of twinkling artifact.


Increased efficiency in the second-hand tire trade provides opportunity for dengue control.
Dengue fever is increasing in geographical range, spread by invasion of its vector mosquitoes. The trade in second-hand tires has been implicated as a factor in this process because they act as mobile reservoirs of mosquito eggs and larvae. Regional transportation of tires can create linkages between rural areas with dengue and disease-free urban areas, potentially giving rise to outbreaks even in areas with strong local control measures. In this work we sought to model the dynamics of mosquito transportation via the tire trade, in particular to predict its role in causing unexpected dengue outbreaks through vertical transmission of the virus across generations of mosquitoes. We also aimed to identify strategies for regulating the trade in second-hand tires, improving disease control. We created a mathematical model which captures the dynamics of dengue between rural and urban areas, taking into account the movement and storage time of tires, and mosquito diapause. We simulate a series of scenarios in which a mosquito population is introduced to a dengue-free area via movement of tires, either as single or multiple events, increasing the likelihood of a dengue outbreak. A persistent disease state can be induced regardless of whether urban conditions for an outbreak are met, and an existing endemic state can be enhanced by vector input. Finally we assess the potential for regulation of tire processing as a means of reducing the transmission of dengue fever using a specific case study from Puerto Rico. Our work demonstrates the importance of the second-hand tire trade in modulating the spread of dengue fever across regions, in particular its role in introducing dengue to disease-free areas. We propose that reduction of tire storage time and control of their movement can play a crucial role in containing dengue outbreaks.


Diminishing returns on the road to diagnostic certainty.
In the quest for diagnostic certainty, one can be led into a false sense of accomplishment by the results of sensitive, specific, and well-executed diagnostic tests that provide little or no diagnostic information. This is a consequence of the fact that as one approaches diagnostic certainty the useful information returned by diagnostic tests and observations approaches zero. This can be demonstrated by calculating the quantity of useful information provided by a test in a given clinical environment as one approaches certainty of diagnosis.


Discovery and Development of Dolastatin 10-Derived Antibody Drug Conjugate Anticancer Drugs.
Dolastatin 10 is an extremely potent broad-spectrum antitubulin anticancer pentapeptide isolated from Dolabella auricularia. The two-dimensional structure was elucidated by NMR and mass spectrometric analyses. The absolute configuration was determined by a convergent total synthesis. SAR studies established that modifications at C- and N-terminals were tolerated for cytotoxic activity. Human clinical trials of dolastatin 10 and auristatin PE (a C-terminal analog) showed occasional signs of efficacy but failed due to lack of separation of toxicity and efficacy. Nanomolar cytotoxicity helped transition this class of pentapeptides to the next phase of development as antibody drug conjugates (ADCs) by reducing systemic toxicity. Four ADC drugs (Adcetris, Padcev, Polivy, and Blenrep) carrying monomethyl auristatin E (MMAE, vedotin) and monomethyl auristatin F (MMAF, mafodotin) payloads have been approved for treatment of a number of cancers expressing antibody-specific antigens. More than 36 ADCs carrying a variety of pentapeptide analogues are undergoing preclinical and clinical developments. They are being evaluated in more than 200 human trials. A comprehensive review of the discovery, total synthesis of dolastatin 10 and new amino acids, SAR studies of dolastatin 10 and auristatins, conjugations to antibodies, and preclinical and clinical development of ADCs have been presented.


Prevalence of melanoma clinically resembling seborrheic keratosis: analysis of 9204 cases.
To estimate the prevalence of melanoma clinically mimicking seborrheic keratosis. Retrospective review of cases submitted for histological examination with a clinical diagnosis of seborrheic keratosis or with a differential diagnosis that included seborrheic keratosis. A tertiary medical care center-based dermatopathology laboratory serving academic dermatology clinics that have a busy pigmented lesion clinic. A total of 9204 consecutive pathology reports containing a diagnosis of seborrheic keratosis in the clinical information field were identified between the years 1992 and 2001 through a computer database search. Reports with a final histological diagnosis of melanoma were selected for further review and clinicopathological analysis. Histological diagnosis, which was correlated with the preoperative clinical diagnosis. Melanoma was identified in 61 cases (0.66%) submitted for histological examination with a clinical diagnosis that included seborrheic keratosis. Melanoma was in the clinical differential diagnosis of 31 cases (51%). The remaining lesions had a differential diagnosis of seborrheic keratosis vs melanocytic nevus (17 cases, 28%), basal cell carcinoma (7 cases, 12%), or a squamous proliferation (3 cases, 5%). In 3 cases (5%), seborrheic keratosis was the only clinical diagnosis. All histological types of melanoma were represented. Our results confirm that melanoma can mimic seborrheic keratosis. These data strongly support the current policy of submitting for histological examination all specimens that have been removed from patients.


Encapsulation of the ethylene inhibitor 1-Methylcyclopropene by cucurbit[6]uril.
1-Methylcyclopropene (1-MCP) is an excellent safe and commercially available ethylene antagonist for the preservation of horticultural products. However 1-MCP has to be stored in absorbents due to its gaseous and unstable characteristics. In this paper cucurbit[6]uril (CB[6]) was used as the absorbent to encapsulate 1-MCP, and the resultant inclusion complex was characterized by IR, powder X-ray diffraction, thermal analysis, and fluorescent spectra. The effects of encapsulation conditions on the formation of inclusion complex were also investigated. The amount of 1-MCP encapsulated by CB[6] was about 4.5% by weight when the initial concentration of 1-MCP, encapsulation temperature, CB[6] concentration, and encapsulation time were set at 75 mL/L, 20 °C, 30 mM, and 8 h, respectively. Furthermore, the release of 1-MCP from the complex can be realized with different solutions such as sodium bicarbonate, benzoic acid, and distilled water. CB[6] can be used as an excellent absorbent for encapsulation of 1-MCP.


[Expression of estrogen receptor-related receptor isoforms in endometrial carcinoma tissues and its clinical significance].
To investigate the role of estrogen receptor-related receptor (ERR), a subfamily of orphan receptors, in the tumorigenesis of endometrial carcinoma and to evaluate the clinical significance. A total of 46 cases of endometrial carcinoma tissues and 24 cases of normal endometrium tissues were collected. Semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to measure the expressions of ERR. All samples were classified into two groups according to ERalpha status. It was positively correlated between the ERR (alpha, beta, gamma) mRNA and protein expression (r = 0.462, P = 0.009; r = 0.689, P = 0.016 and r = 0.673, P = 0.001). The expression rate and level of ERRalpha mRNA in ERalpha-positive endometrial carcinoma (42%, 0.24 +/- 0.18) were lower than in normal endometrium (78%, 0.42 +/- 0.23; P = 0.019, P = 0.021). No significant difference was observed in the expression of ERRbeta mRNA between endometrial carcinoma (23%, 0.21 +/- 0.16) and normal endometrium (22%, 0.27 +/- 0.15; P > 0.05). In ERalpha-positive endometrial carcinoma, the expression level of ERRgamma mRNA (0.93 +/- 0.24) was higher than normal endometrium (0.72 +/- 0.21; P = 0.023). The numbers of patients of Federal International Gynecological Oncology (FIGO) stage II-IV and of deep myometrial invasion in ERRalpha mRNA positive endometrial carcinoma group were more than those in ERRalpha mRNA negative group (P = 0.017 and P = 0.033). ERRgamma mRNA positive patients had a lower occurrence of lymph metastases than negative patients (P = 0.021). ERR may be closely related with the tumorigenesis of endometrial carcinoma, similar to ER. ERRalpha may serve as a biomarker of poor prognosis and ERRgamma as a favorable biomarker in endometrial carcinoma.


Eco-Friendly Pavements Manufactured with Glass Waste: Physical and Mechanical Characterization and Its Applicability in Soil Stabilization.
The use of glass waste, which by its nature cannot be recycled, might be a viable alternative in the manufacture of cements and concrete that is also economical and environmentally friendly. This alternative can reduce landfill areas with this inert residue but also limit the use of raw materials employed in the manufacture of cement and concrete and, consequently, contribute to minimize the environmental impact generated by this activity. In this research, the feasibility of using a limestone-type material treated with a binder manufactured with micronized glass powder and basic reagents, in the preparation of a gravel-cement- or soil-cement-type material, was analyzed. For this purpose, the strength, compactability, structural capacity, resistance to the action of water, stiffness and durability of the material obtained were characterized. From the tests that were carried out and the results obtained, it can be concluded that the use of glass powder, with a particle size of 16 μm, is ideal for the production of a gravel-cement- or soil-cement-type material. This material could be used as an environmentally-friendly pavement, especially suitable for peri-urban roads and park roads, where it can be used without coating, or as a base layer or sub-base for road surfaces, with little cracking due to shrinkage.


Hyperbaric oxygen for late sequelae of carbon monoxide poisoning enhances neurological recovery: case report.
Neuropsychiatric sequelae have been reported in 15%-45% of survivors of carbon monoxide (CO) poisoning. Hyperbaric oxygen (HBO₂) therapy reduces the incidence of cognitive and neurological a dysfunction. The efficacy of providing HBO₂ beyond the first one to two days after initial insult is unknown. However, some evidence exists for the benefit of this treatment. We report on treating a patient 14 months after CO injury, who responded with markedly improved neurologic status. A 27-year-old scholar was found comatose due to CO poisoning (carboxyhemoglobin = 31.7%). He received five acute HBO₂ treatments. After discharge, he developed chorea, Parkinsonism, dystonia, memory loss, slowed processing speed and verbal fluency, leaving him disabled. After the patient reached a clinical plateau, HBO₂ was tried again at 90 minutes at 2.4 ATA plus air breaks. Neuropsychological testing was performed at baseline and after each 20 HBO₂ cycles, five of which were performed during the period from 14-22 months after CO exposure. After the first 20 treatments, Parkinsonism and dystonia improved. After 40 sessions, further improvements were seen on mental speed, verbal fluency, and fine motor movements. The outcome following 100 treatments was that the patient regained independence, including the ability to drive and to become gainfully employed. Our case calls into question the concept that HBO₂ therapy has no role during the chronic phase of CO brain injury. Randomized clinical trials should be considered to evaluate the therapeutic efficacy of HBO₂ in patients with neurological sequelae following CO injury.


Role of protein kinase C in caerulein induced expression of substance P and neurokinin-1-receptors in murine pancreatic acinar cells.
Substance P (SP) is involved in the pathophysiology of acute pancreatitis (AP) via binding to its high-affinity receptor, neurokinin-1-receptor (NK1R). An up-regulation of SP and NK1R expression was observed in experimental AP and in caerulein-stimulated pancreatic acinar cells. However, the mechanisms that lead to this up-regulation are not fully understood. In this study, we showed the role of protein kinase C (PKC) in caerulein-induced SP and NK1R production in isolated mouse pancreatic acinar cells. Caerulein (10(-7) M) stimulation rapidly activated the conventional PKC-α and novel PKC-δ as observed by the phosphorylation of these molecules. Pre-treatment of pancreatic acinar cells with Gö6976 (1-10 nM) and rottlerin (1-10 μM) inhibited PKC-α and PKC-δ phosphorylation, respectively, but not the other way round. At these concentrations used, PKC-α and PKC-δ inhibition reversed the caerulein-induced up-regulation of SP and NK1R, indicating an important role of PKCs in the modulation of SP and NK1R expression. Further experiments looking into signalling mechanisms showed that treatment of pancreatic acinar cells with both Gö6976 and rottlerin inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Inhibition of PKC-α or PKC-δ also affected caerulein-induced transcription factor activation, as represented by nuclear factor-κB and AP-1 DNA-binding activity. The findings in this study suggested that PKC is upstream of the mitogen-activated protein kinases and transcription factors, which then lead to the up-regulation of SP/NK1R expression in caerulein-treated mouse pancreatic acinar cells.


Apical and basolateral membrane conductances in the TBM cell line.
Cultured cell lines present several advantages over whole organ or ex vivo isolated epithelium for the physiological and biochemical study of epithelial transport. We have developed a new technique allowing for simultaneous intracellular and transepithelial electrophysiological measurements in the epithelium formed by a cultured cell line grown on thin collagen membranes. This technique was applied to the TBM 18/23 (toad bladder origin) cell line. The transepithelial and basolateral membrane potentials were -30 +/- 11 and -72 +/- 8 (SD) mV (n = 36), respectively. With the use of the effect of amiloride, which partially blocked the apical membrane conductance, and circuit analysis, the apical and basolateral membrane conductances were estimated to 0.7 +/- 0.1 and 2.8 +/- 0.4 mS/cm2, respectively. A sodium-selective conductive pathway was demonstrated in the apical membrane, and a barium-sensitive K(+)-selective conductance was shown to be present in the basolateral membrane. The basolateral membrane conductance was not modified by sudden inhibition of sodium transport by amiloride, but it was significantly reduced after a long-term decrease of Na+ transport. The cultured TBM cell line appears to be a convenient model to investigate the regulation of membrane ionic conductances in tight epithelia.


Enzyme Immobilized on Nanoporous Carbon Derived from Metal-Organic Framework: A New Support for Biodiesel Synthesis.
In this study, nanoporous carbon (NPC) derived from metal-organic framework was used as support for the immobilization of Burkholderia cepacia lipase. The decorated aluminum oxide within the mesoporous NPC improved the enzyme loading efficiency as well as the catalytic ability for the transesterification of soybean oil, thus making it a promising green and sustainable catalytic system for industrial application.


Fine-needle aspiration cytology of triple-negative basal-like breast cancer.
Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal-like (BL) and normal-like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine-needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC.


Optical image encryption based on a joint Fresnel transform correlator with double optical wedges.
An optical cryptosystem based on the joint Fresnel transform correlator (JFTC) with double optical wedges is designed. The designed cryptosystem retains the two major advantages of JTC-based optical cryptosystems. First, the encrypted image is real-valued and therefore is easier to record and transmit. Second, the encryption process is simplified, since it doesn't require accurate alignment of optical elements or the generation of the complex conjugate of the key. Also, the designed optical cryptosystem can produce a decrypted image with higher quality than a JTC-based optical cryptosystem, because the original encrypted image is divided by the Fresnel transform power distribution of the key mask to generate the new encrypted image, which significantly reduces the noise during the decryption process. Simulation results showed that the correlation coefficient of the decrypted image and the original image can reach as large as 0.9819 after denoising and adequately selecting half-central interval a and encrypted image width w. Another improvement relative to JTC-based optical cryptosystems is that the attack resistibility gets enhanced due to the nonlinearity of the encryption process as well as the additional key parameter a, which enlarges the key space.


Reaction time responses in parkinsonian and hemiparkinsonian patients.
Twenty-one normal subjects, 32 bilateral parkinsonian patients (BPs) and 29 hemiparkinsonian patients (HP) were submitted to separate or sequentially associated motor tasks that included simple reaction times (RT), choice RTs, directional RTs, and movement RTs. The results showed that simple RTs, directional RTs, and movement times (MT) were slower in BPs as compared to normal subjects; for choice RTs there was no difference. Response patterns were similar in normal controls and BPs. In both groups RTs became more prolonged as sequentially programmed operations increased. If movement occurred at the end of the sequence, they prolonged the RTs of the preceding operations, but MTs per se did not vary. In HPs the same results were observed on the "bad" hand side versus normal controls and versus the healthy side, but a significant statistical level was reached mainly when the "bad" hand was the right one.


Stable dispersions of silver nanoparticles in carbon dioxide with fluorine-free ligands.
Iso-stearic acid, a short, stubby compound with branched, methylated tails has been shown to have high solubility in carbon dioxide. Tail solvation by carbon dioxide makes iso-stearic acid a good choice for use as a ligand to sterically stabilize metallic nanoparticles. Iso-stearic acid coated silver nanoparticles have been stably dispersed in carbon dioxide with hexane cosolvent. Neat carbon dioxide has successfully dispersed iso-stearic acid coated silver nanoparticles that had been deposited on either quartz or polystyrene surfaces. These results are the first reports of sterically stabilized nanoparticles in carbon dioxide without the use of any fluorinated compounds.


Punicalagin ameliorates wear-particle-induced inflammatory bone destruction by bi-directional regulation of osteoblastic formation and osteoclastic resorption.
Periprosthetic osteolysis (PPO) and subsequent aseptic loosening are the main causes of implant failure and revision surgery. Emerging evidence has suggested that wear-particle-induced chronic inflammation, osteoblast inhibition and osteoclast formation at the biointerface of implant materials are responsible for PPO. Punicalagin (PCG), a polyphenolic compound molecularly extracted from pomegranate rinds, plays a critical role in antioxidant, anticancer and anti-inflammatory activities. However, whether PCG could attenuate chronic inflammation and bone destruction at sites of titanium (Ti)-particle-induced osteolysis remains to be determined. In this study, we explored the effect of PCG on Ti-particle-induced osteolysis in vivo and osteoblast and osteoclast differentiation in vitro. We found that PCG could relieve wear-particle-induced bone destruction in a murine calvarial osteolysis model by increasing bone formation activity and suppressing bone resorption activity. PCG treatment also reduced the Ti-particle-induced inflammatory response in vivo and vitro. In addition, we also observed that PCG promotes osteogenic differentiation of MC3T3-E1 cells under inflammatory conditions and inhibits RANKL-induced osteoclast formation of bone marrow-derived macrophages (BMMs). Meanwhile, the induction of the RANKL to OPG ratio was reversed by PCG treatment in vivo and in vitro, which demonstrated that PCG could also indirectly inhibit osteoclastogenesis. Collectively, our findings suggest that PCG represents a potential approach for the treatment of wear-particle-induced inflammatory osteolysis.


Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation.
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood. As the intestinal microbiota profoundly influences host behaviour, we sought to determine whether the altered gut microbiota associated with intestinal inflammation contributes to the development of behavioural abnormalities. Using the dextran sulphate sodium (DSS) model of colitis, we characterized intestinal inflammation, behaviour (elevated plus maze and tail suspension test) and the composition of the microbiota in male mice. Cecal contents from colitic mice were transferred into germ-free (GF) or antibiotic (Abx)-treated mice, and behaviour was characterized in recipient mice. Gene expression was measured using qPCR. DSS colitis was characterized by a significant reduction in body weight and an increase in colonic inflammatory markers. These changes were accompanied by increased anxiety-like behaviour, an altered gut microbiota composition, and increased central Tnf expression. Transfer of the cecal matter from colitic mice induced similar behavioural changes in both GF and Abx-treated recipient mice, with no signs of colonic or neuroinflammation. Upon characterization of the microbiota in donor and recipient mice, specific taxa were found to be associated with behavioural changes, notably members of the Lachnospiraceae family. Behavioural abnormalities associated with intestinal inflammation are transmissible via transfer of cecal matter, suggesting that alterations in the composition of the gut microbiota play a key role in driving behavioural changes in colitis.


Rapid serologic testing with immune-complex-dissociated HIV p24 antigen for early detection of HIV infection in neonates. Southern California Pediatric AIDS Consortium.
Serologic detection of human immunodeficiency virus (HIV) infection in neonates is complicated by the presence of immune complexes, consisting of passively transferred maternal antibodies and HIV antigens. A new, rapid assay has been designed to disrupt these immune complexes in order to permit the detection of a specific HIV antigen. We evaluated the efficacy of this assay in detecting HIV infection in neonates. We measured p24 antigen in blood samples from both infected and uninfected children of HIV-infected mothers. The samples were treated with glycine hydrochloride to dissociate the immune complexes, followed by neutralization with TRIS-hydrochloric acid. A commercial HIV p24 antigen assay was then used, with an optical density greater than 0.120 at a wavelength of 450 nm defined as indicating a positive result. Of eight cord-blood samples from neonates with proved HIV infection, five were positive for immune-complex-dissociated p24 antigen. For two other neonates the first postnatal sample, obtained on days 12 and 18, was positive. There was no follow-up sample for the eighth neonate. Of 22 uninfected neonates, 20 were negative on the cord-blood assay. Two neonates had positive cord-blood samples, but the first postnatal sample was negative. Thus, the tests with early postnatal samples identified the HIV-infection status correctly for all 29 children who could be evaluated. In a separate group of 78 children (median age, 188 weeks), the specificity of the test was 100 percent and the sensitivity 81 percent. The immune-complex-dissociated HIV p24 antigen assay is a rapid, simple serologic test that may be of value in diagnosing HIV infection in neonates born to HIV-infected women.


Differentiation of Dictyostelium discoideum in monolayer cultures and its modification by ionic conditions.
We have compared the pattern of enzyme expression in cyclic AMP-induced monolayer cultures of Dictyostelium discoideum with that found during normal development. We find that both the temporal and quantitative pattern of enzyme expression are initially similar in the two situations, although the developmental sequence is more protracted and terminal cell differentiation is delayed in the monolayer situation. We describe differentiation conditions that permit the expression of only one terminal phenotype, which may be useful for further biochemical studies. Enzyme accumulation patterns under these conditions indicate that UDP gal transferase is not required for stalk cell differentiation (i.e., it is a prespore enzyme). We have shown that, when cell monolayers are incubated with cAMP, the presence of a weak acid at low extracellular pH favors stalk-cell differentiation, while a weak base at high extracellular pH favors spore differentiation. Finally, we show that variations in the monovalent cation content of the buffer, or the addition of an ion transport inhibitor (scillaren), or an ionophore (valinomycin) all affect the ratio of stalk cells to spores. Taken together, these results suggest that intracellular H+ and/or other cations may play an important role in regulating differentiation of specific cell types in D. discoideum.


Reconstructing the Temporal Progression of Biological Data Using Cluster Spanning Trees.
Identifying the temporal progression of a set of biological samples is crucial for comprehending the dynamics of the underlying molecular interactions. It is often also a basic step in data denoising and synchronization. Finally, identifying the progression order is crucial for problems like cell lineage identification, disease progression, tumor classification, and epidemiology and thus impacts the spectrum of disciplines spanning basic biology, drug discovery, and public health. Current methods that attempt solving this problem, face difficulty when it is necessary to factor-in complex relationships within the data, such as grouping, partial ordering or bifurcating or multifurcating progressions. We propose the notion of cluster spanning trees (CST) that can model both linear as well as the aforementioned complex progression relationships in temporally evolving data. Through a number of experimental investigations involving synthetic data sets as well as data sets from the cell cycle, cellular differentiation, phenotypic screening, and genetic variation, we show that the proposed CST approach outperforms existing methods in reconstructing the temporal progression of the data.


Activities of daily living: reliability and validity of gross vs specific ratings.
The inter-rater reliability and criterion validity of gross vs specific ratings of activities of daily living (ADL) were compared. Forty-three physical therapy students rated 6 patients performing 16 ADL on videotape. With controls for tape order presentation and order of protocol use, specific ratings were found to be more reliable than gross ratings in terms of total scores, transfers, and personal hygiene activities. Dressing activities were found to be reliably rated on both protocols, but locomotion activities presented problems on both. In terms of criterion validity, both protocols significantly differentiated dependent, middle-range, and independent patients, but the gross ratings were significantly lower for dependent and middle-range patients than specific protocols. It was concluded that when activities can be broken down into independent task components, specific protocols are the assessment method of choice. When activities are made up of highly interdependent task components, a behaviorially anchored gross rating protocol may be more effective. Implications for further research are discussed.


Does public image of nurses matter?
The nursing profession is said to have long suffered from public stereotyping and from being closely associated with femininity and powerlessness. This descriptive correlational study was performed to identify the relationships between nurses' perception of common public stereotypes of their profession, nurses' self-concept, self-esteem, job satisfaction, and performance. Eighty registered nurses were invited to participate in this study by completing six types of questionnaires. The results suggest that nurses' perception of the public stereotyping of nursing is related to the development of their self-concept, collective self-esteem, and job satisfaction, all of which are associated with their performance. The results also indicate the importance of encouraging professional socialization and cultivation of positive, personal self-esteem to ward off the negative influences of public stereotypes on nursing practice. This study is tentative and requires further investigation with a more diverse sample.


Middle meatus anstrostomy: patency rates and risk factors.
Two hundred patients with chronic sinusitis were operated on using functional endoscopic sinus surgery (FESS) techniques. These patients were followed closely over 3 years. Patency of the endoscopic middle meatotomy was recorded using actuarial life-table methods. The overall patency rate of the endoscopic middle meatotomy was 93.55%, and the actuarial patency rate at 36 months was 87.47%. The presence of seasonal allergy with nasal polyps was the most important variable in predicting closure. Middle turbinectomy was the most important variable in predicting patency. Symptoms were evaluated by questionnaire at 1 year. Questionnaire data indicate that 96% of these patients are improved or asymptomatic.


An improved method for Organic Bound Tritium (OBT) determination in urine samples.
The Organic Bound Tritium (OBT) amount in the body may induce changes in the evaluation of the internal exposure to tritium, due to its different retention time relative to HTO. OBT measurements for urine are not performed routinely, mainly because of the lengthy work needed in preparation of the samples, when using the standard oxygen combustion method. A simpler and more rapid method based on liquid scintillation counting (LSC) was employed, and an evaluation was performed to check its suitability for urine samples. The principle of the proposed method is based on subtracting the LSC counts of the water phase sample (HTO) from the total activity of the urine sample (OBT+HTO). A good correlation was found between the results obtained when applying the proposed direct method and the Gold standard method. The minimum detectable activity when using this method was determined.


Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery.
Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery. Randomized, double-blind trial. Obstetric suite at a university-affiliated hospital. Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia. Patients were randomly assigned to receive either ephedrine (n = 29) in 10 mg intravenous (IV) bolus injections or phenylephrine (n = 31) in 80 microgram IV bolus injections to maintain systolic blood pressure (SBP) above 100 mmHg. Maternal venous, umbilical artery, and umbilical vein blood gases were measured, and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed. In the ephedrine group, umbilical artery pH was 7.28 +/- 0.01 (mean +/- SEM), umbilical artery partial pressure of carbon dioxide (PCO2) was 56.6 +/- 1.4 mmHg, and umbilical artery base deficit was 2.2 +/- 0.04 meq. In the phenylephrine group, umbilical artery pH was 7.32 +/- 0.01, umbilical artery PCO2 was 52.1 +/- 1.3 torr, and umbilical artery base deficit was 0.38 +/- 0.35 meq. There were significant differences between the groups in mean umbilical artery pH, PCO2, and base deficit, although all values obtained were within normal limits. There were no significant differences between the groups in the remaining acid-base values, neonatal Apgar scores, Early Neonatal Neurobehavior Scale scores, or frequency of maternal nausea and vomiting. Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension, and when used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, nonlaboring parturients.


Spin Reflection-Induced Field-Free Magnetization Switching in Perpendicularly Magnetized MgO/Pt/Co Heterostructures.
Field-free magnetization switching is critical towards practical, integrated spin-orbit torque (SOT)-driven magnetic random-access memory with perpendicular magnetic anisotropy. Our work proposes a technique to modulate the spin reflection and spin density of states within a heavy-metal Pt through interfacing with a dielectric MgO layer. We demonstrate tunability of the effective out-of-plane spin torque acting on the ferromagnetic Co layer, enabling current-induced SOT magnetization switching without the assistance of an external magnetic field. The influence of the MgO layer thickness on effective SOT efficiency shows saturation at 4 nm, while up to 80% of field-free magnetization switching ratio is achieved with the MgO between 5 and 8 nm. We analyze and attribute the complex interaction to spin reflection at the dielectric/heavy metal interface and spin scattering within the dielectric medium due to interfacial electric fields. Further, through substituting the dielectric with Ti or Pt, we confirm that the MgO layer is indeed responsible for the observed field-free magnetization switching mechanism.


A follow-up study on indoor 222Rn, 220Rn their decay product concentrations in a mineralised zone of Himachal Pradesh, India.
A follow-up study was taken up in a mineralised zone situated in Hamirpur district, Himachal Pradesh, India, to investigate high values of radon concentrations reported in past studies as well to update the old radon data based on bare SSNTD technique. In the present investigation, the concentrations of indoor radon, thoron and their decay products have been measured using the newly developed radon/thoron discriminating diffusion chamber with single entry face, direct radon and thoron progeny sensors (DRPS/DTPS), respectively. The measurements have been carried out in 75 dwellings of 14 different villages where the previous studies were carried out using bare SSNTD technique. It was observed that high values of earlier reported radon concentrations were mainly due to thoron interference in the Solid State Nuclear Track Detector (LR-115 type II) exposed in bare mode. Now, the average concentration values and the estimated annual inhalation dose in these villages have been found to be within the reference level as recommended by the ICRP. The annual average indoor radon and thoron concentrations observed in these dwellings have been found to vary from 44±12 to 157±73 Bq m(-3) and 44±11 to 240±125 Bq m(-3), respectively. The equilibrium equivalent concentrations of radon and thoron decay products have been observed to be in the range of 10 to 63 and 1 to 5 Bq m(-3), respectively.


A methodology for auto-monitoring of internal contamination by 131I in nuclear medicine workers.
The manipulation of 131I in Nuclear Medicine involves significant risks of internal contamination of the staff. In the event of an accidental contamination, or when the Radiological Protection Program includes routine individual monitoring of internal contamination, it is necessary to implement internal dose estimation through in vivo and in vitro bioassay techniques. Due to the huge extension of the Brazilian country, this type of monitoring becomes unfeasible if all measurements have to be performed at the institutes of the CNEN. Thus, if the Nuclear Medicine Centres (NMC) become able to conduct the monitoring of their employees, this skill would be of great significance. The methodology proposed in this work consists in a simple and inexpensive protocol for auto-monitoring the internal contamination by 131I, using the resources available at the NMC. In order to verify the influence of the phantom in the calibration factor for the measurement of 131I in thyroid, it was performed a comparison among a variety of phantoms commercially available, including the Neck-Thyroid Phantom developed in IRD. A protocol for performing in vivo and in vitro measurements by the NMC was established. The applicability of the individual monitoring techniques was also evaluated by comparing the detection limits with the derived limits associated with the annual dose limits for workers.


Contribution of chitinases to Listeria monocytogenes pathogenesis.
Listeria monocytogenes secretes two chitinases and one chitin binding protein. Mutants lacking chiA, chiB, or lmo2467 exhibited normal growth in cultured cells but were defective for growth in the livers and spleens of mice. Mammals lack chitin; thus, L. monocytogenes may have adapted chitinases to recognize alternative substrates to enhance pathogenesis.


Helping Basic Scientists Engage With Community Partners to Enrich and Accelerate Translational Research.
Engaging basic scientists in community-based translational research is challenging but has great potential for improving health. In 2009, The Rockefeller University Center for Clinical and Translational Science partnered with Clinical Directors Network, a practice-based research network (PBRN), to create a community-engaged research navigation (CEnR-Nav) program to foster research pairing basic science and community-driven scientific aims. The program is led by an academic navigator and a PBRN navigator. Through meetings and joint activities, the program facilitates basic science-community partnerships and the development and conduct of joint research protocols. From 2009-2014, 39 investigators pursued 44 preliminary projects through the CEnR-Nav program; 25 of those became 23 approved protocols and 2 substudies. They involved clinical scholar trainees, early-career physician-scientists, faculty, students, postdoctoral fellows, and others. Nineteen (of 25; 76%) identified community partners, of which 9 (47%) named them as coinvestigators. Nine (of 25; 36%) included T3-T4 translational aims. Seven (of 25; 28%) secured external funding, 11 (of 25; 44%) disseminated results through presentations or publications, and 5 (71%) of 7 projects publishing results included a community partner as a coauthor. Of projects with long-term navigator participation, 9 (of 19; 47%) incorporated T3-T4 aims and 7 (of 19; 37%) secured external funding. The CEnR-Nav program provides a model for successfully engaging basic scientists with communities to advance and accelerate translational science. This model's durability and generalizability have not been determined, but it achieves valuable short-term goals and facilitates scientifically meaningful community-academic partnerships.


Factors influencing nursing leadership effectiveness in Hong Kong.
Nursing education in Hong Kong has undergone major reform in recent years, similar to that in Australia and the United Kingdom (UK), involving the introduction of degree level preparation. Although there were some changes in the nursing education system, the reform was considered slow. While a combination of complex factors contributed to the reform, the effects of nurse leaders was instrumental in influencing policy development. This study investigated the factors that influenced the effectiveness of nursing leadership in the reform of nursing education in Hong Kong. A case study approach was used. Methods of data collection included document search and semi-structured interviews (n = 27). The time frame of the study extended from the first proposal of nursing degree programme in the year 1985 to 2000 by which 200 nursing degree places were secured. Situational variables that impacted on leadership effectiveness were categorized as barriers and facilitators. Barriers were related to nursing professional socialization in a health care system that was dominated by the medical profession. Facilitators were related to socio-politic-economical changes in the wider environment. This study suggests the importance of education, positive socialization and unity in promoting nursing leadership development.


Exploring patterns of seclusion use in Australian mental health services.
Seclusion has remained a common practice in mental health services. In Australia, recent mental health policy has reflected a desire to reduce (and, if possible, eliminate) the use of seclusion. The collection and analysis of data on the use of seclusion have been identified as an important component of the success of reduction initiatives. A cross-sectional design was used in the collection of inpatient unit data on seclusions that occurred in 11 mental health services in Australia over a 6-month period. During this time, there were 4,337 episodes of care. One or more seclusions occurred in 6.8% of episodes of care, with consumers being secluded, on average, 2.32 times and with 44% of them having been secluded more than once. The average length of the seclusions was 2 hours 52 minutes, with 51.4% of seclusions being less than 2 hours. These rates were lower than those reported in previous research studies. The practice of seclusion occurred more commonly on the first 2 days following admission, on weekdays than weekends, and between the hours of 9:00 a.m. and midnight. An understanding of seclusion data can provide fundamental information from which strategies to reduce seclusion can be developed.


Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson's disease-linked mutations.
Two missense mutations (Ala-30 --> Pro and Ala-53 --> Thr) in the gene encoding alpha-synuclein are associated with rare autosomal dominant forms of familial Parkinson's disease. In addition, alpha-synuclein is an abundant component of Lewy bodies in sporadic Parkinson's disease and diffuse Lewy body disease. However, the normal conformation of alpha-synuclein, its cellular localization in neurons, and the effects of the mutations remain to be determined. In the present study, we examine these questions using sensitive fluorescence resonance energy transfer techniques. Transient transfection of alpha-synuclein expression constructs into primary cortical neurons and counterstaining with the lipophilic fluorescent marker, DiI, demonstrates a close association between alpha-synuclein and cellular membranes. Both the N- and C-terminal regions of alpha-synuclein are tightly associated with membranes. A weak interaction also occurs between the N and C termini themselves. The Parkinson's disease-associated mutations have no effect on membrane interaction; however, the Ala-30 --> Pro mutation alters the three-dimensional conformation of alpha-synuclein, as measured by significantly increased fluorescence resonance energy transfer between the N and C termini.


Differential gene expression identified in Uigur women cervical squamous cell carcinoma by suppression subtractive hybridization.
Cervical cancer is one of the most common gynecological cancers worldwide. Over the past decade, much progress has been made in understanding the genetic changes associated with the development and progression of cervical cancer. However, the precise mechanisms of cervical carcinogenesis in Uigur women remain unclear. To screen differential gene expression in squamous cell carcinoma (SCC) of the cervix in Uigur women, suppressive subtractive hybridization (SSH) was performed on the cervical squamous cell carcinoma and corresponding normal cervical tissues of a Uigur patient. Thus we were be able to find the genes that are related with cervical tumors of Uigur women. A total of 300 samples were subject to DNA sequencing analysis and 46 genes were found to express differentially in tumors compared with normal tissues. Of the 46 genes, 24 genes were up-regulated whereas 22 genes were down-regulated in cervical tumors. The expression profiles of 5 of the 46 genes were further confirmed in 15 other Uigur patients by semi-quantitative reverse-transcription polymerase chain reaction. Our results revealed that ACADVL, CEBPB, IFITM1 and DNAJC9 are involved in cervical carcinogenesis.


Psychosocial characteristics of psychiatric inpatients at admissions and discharge: The Menninger Clinic Adult Outcomes Project.
The authors present a first look at the data from The Menninger Clinic Adult Outcomes Project. They provide descriptive data from 443 patients admitted to the Clinic between April 2008 and May 2009. Patients show significant improvement on a range of standardized measures from admission to discharge (effect sizes range from moderate to large, 0.31 to 1.44), and there are some differences among clinical programs within the hospital in the extent of change on some scales. A comparison of patients who did and did not complete discharge assessments showed minimal differences between groups on admissions variables. These results attest to the substantial impact of relatively long-term intensive inpatient treatment on improving clinical symptoms and functioning, but further studies are needed to determine the trajectory of change in the hospital and, most importantly, at follow-up.


Evaluation of Daphnid Grazing on Microscopic Zoosporic Fungi by Using Comparative Threshold Cycle Quantitative PCR.
Lethal parasitism of large phytoplankton by chytrids (microscopic zoosporic fungi) may play an important role in organic matter and nutrient cycling in aquatic environments by shunting carbon away from hosts and into much smaller zoospores, which are more readily consumed by zooplankton. This pathway provides a mechanism to more efficiently retain carbon within food webs and reduce export losses. However, challenges in accurate identification and quantification of chytrids have prevented a robust assessment of the relative importance of parasitism for carbon and energy flows within aquatic systems. The use of molecular techniques has greatly advanced our ability to detect small, nondescript microorganisms in aquatic environments in recent years, including chytrids. We used quantitative PCR (qPCR) to quantify the consumption of zoospores by Daphnia in laboratory experiments using a culture-based comparative threshold cycle (CT) method. We successfully quantified the reduction of zoospores in water samples during Daphnia grazing and confirmed the presence of chytrid DNA inside the daphnid gut. We demonstrate that comparative CT qPCR is a robust and effective method to quantify zoospores and evaluate zoospore grazing by zooplankton and will aid in better understanding how chytrids contribute to organic matter cycling and trophic energy transfer within food webs. The study of aquatic fungi is often complicated by the fact that they possess complex life cycles that include a variety of morphological forms. Studies that rely on morphological characteristics to quantify the abundances of all stages of the fungal life cycle face the challenge of correctly identifying and enumerating the nondescript zoospores. These zoospores, however, provide an important trophic link between large colonial phytoplankton and zooplankton: that is, once the carbon is liberated from phytoplankton into the parasitic zoospores, the latter are consumed by zooplankton and carbon is retained in the aquatic food web rather than exported from the system. This study provides a tool to quantify zoospores and evaluate the consumption of zoospores by zooplankton in order to further our understanding of their role in food web dynamics.


Supercritical fluid fractionation of fatty acid ethyl esters from butteroil.
Countercurrent supercritical fractionation of the fatty acid ethyl esters from butteroil has been investigated. The main objective of the present study was to obtain extracts rich in short- and medium-chain fatty acid ethyl esters. To that end, transesterification of the original butteroil was used to transform the triacylglycerols into the corresponding fatty acid ethyl esters. Then, several supercritical fluid extractions were carried out at pressures ranging from 8.9 to 18.6 MPa and at 2 different temperatures (48 and 60 degrees C). The flow ratio of CO2 to butteroil was 15. Composition and yield of short- and medium-chain fatty acid ethyl esters was evaluated at different extraction conditions. Extracts containing approximately 70% short- and medium-chain fatty acid ethyl esters were obtained at 101 bar and 60 degrees C, and can be used as starting material for the production of highly valuable functional lipids.


The Role of Religion in Buffering the Impact of Stressful Life Events on Depressive Symptoms in Patients with Depressive Episodes or Adjustment Disorder.
Most studies into the role of religiousness in relation to depression severity have mainly found an inverse relationship between greater religiousness and lower levels of depressive symptoms. There is reason to assume that religiousness has a buffering effect on the relationship between stressful life events and depressive symptoms. The aim of this study was to investigate the role of religiousness in moderating the impact of stressors on depressive symptoms. n = 348 patients with either a depressive episode or adjustment disorder were assessed at referral to the liaison psychiatry services in three Dublin hospitals and n = 132 patients were followed up six months later. We assessed depressive symptoms, life events, social support, and religiosity, and used hierarchical and multiple linear regression for data analysis. The interaction of organised religious activity and the amount of life events was significant (β = -0.19, p = 0.001) in the cross-sectional prediction of depressive symptoms while non-organised religious activity (β = -0.23, p = 0.001) and intrinsic religiousness (β = -0.15, p = 0.033) interacted significantly with life events in the longitudinal analysis. This study demonstrated that various dimensions of religiousness buffered the impact of life events on outcome.


Toroid moments in the momentum and angular momentum loss by a radiating arbitrary source.
In the context of experimental evidence concerning a nuclear toroid dipole, we briefly present here an exact but tedious calculation of the angular momentum loss, recoil force, and radiation intensity for an arbitrary source in terms of electric, magnetic, and toroid multipoles, thus emphasizing the importance of the latter in getting the results in closed forms, unbiased by approximations. Corrections to some familiar formulas from books, mostly on account of time varying toroid moments, are found and discussed.


β-Lactamase-Mediated Fragmentation: Historical Perspectives and Recent Advances in Diagnostics, Imaging, and Antibacterial Design.
The discovery of β-lactam (BL) antibiotics in the early 20th century represented a remarkable advancement in human medicine, allowing for the widespread treatment of infectious diseases that had plagued humanity throughout history. Yet, this triumph was followed closely by the emergence of β-lactamase (BLase), a bacterial weapon to destroy BLs. BLase production is a primary mechanism of resistance to BL antibiotics, and the spread of new homologues with expanded hydrolytic activity represents a pressing threat to global health. Nonetheless, researchers have developed strategies that take advantage of this defense mechanism, exploiting BLase activity in the creation of probes, diagnostic tools, and even novel antibiotics selective for resistant organisms. Early discoveries in the 1960s and 1970s demonstrating that certain BLs expel a leaving group upon BLase cleavage have spawned an entire field dedicated to employing this selective release mechanism, termed BLase-mediated fragmentation. Chemical probes have been developed for imaging and studying BLase-expressing organisms in the laboratory and diagnosing BL-resistant infections in the clinic. Perhaps most promising, new antibiotics have been developed that use BLase-mediated fragmentation to selectively release cytotoxic chemical "warheads" at the site of infection, reducing off-target effects and allowing for the repurposing of putative antibiotics against resistant organisms. This Review will provide some historical background to the emergence of this field and highlight some exciting recent reports that demonstrate the promise of this unique release mechanism.


Gene frequencies of human platelet antigens 1-5 in indigenous Australians in Western Australia.
The frequencies of human platelet antigen (HPA) systems vary between different racial groups; however, HPA frequency data for some racial groups are still incomplete. We report the distribution of HPA 1-5 systems in Australian Aborigines from a remote community in the north-west of Australia and compare our findings with HPA observed in a Western Australian blood donor population. Using a polymerase chain reaction (PCR) with sequence-specific primers, 185 indigenous Australians and 1000 Western Australian blood donors were genotyped for each of the HPA 1-5 systems. Comparison of gene frequencies of alleles from HPA-1, -2, -3 and -5 systems showed significant differences between Aboriginal people and Western Australian blood donors (P < 0.001). In particular, the frequency of HPA-3b (0.068) in the Australian Aboriginals, from this study, was one of the lowest reported, whilst the frequency of HPA-5b (0.246) was one of the highest for this allele. Gene frequencies were similar to those reported for central Australian Aborigines but with no other ethnic group. In conclusion, this study confirms significant differences in HPA distributions between indigenous Australians, Australian blood donors and other racial groups. These results indicate a higher potential risk of alloimmunization to HPA-1, -2 and -3 in Australian Aborigines receiving transfusion therapy from a Caucasian blood donor population, thereby having practical implications for transfusion and pregnancy risks in people of Aboriginal origin.


A method to differentiate chicken monocytes into macrophages with proinflammatory properties.
Macrophages are part of the first line of defense against invading pathogens. In mammals, the in vitro culture of macrophages from blood monocytes or bone marrow cells is well established, including culturing conditions to differentiate them towards M1 or M2-like macrophages. In chicken, monocyte-derived macrophages have been used in several studies, but there is no uniform protocol or actual characterization of these cells. Therefore, to generate proinflammatory M1-like macrophages, in this study blood monocytes were differentiated using GM-CSF for 4 days and characterized based on cell morphology, surface marker expression and cytokine expression response to TLRs stimulation at each (daily) time point. Cell morphology showed that one-day-cultured cells contained a mixture of cell populations, while the homogenous population of cells on day 3 and day 4 were flat and had a 'fried-egg' like shape, similar to human M1 macrophages. In addition, cell surface marker staining showed that 3 and 4- days-cultured cells expressed a high level of MRC1L-B (KUL01) and MHC-II. Furthermore, LPS stimulation of the cultured cells induced gene expression of the proinflammatory cytokines IL-1β, IL-6 and IL-8 after 3 days of culture. Finally, it was shown that day 3 macrophages were able to phagocytose avian pathogenic E. coli (APEC) and respond by nitric oxide production. Overall, our systematic characterization of the monocyte derived cells from blood showed that a 3-days culture was optimal to obtain pro-inflammatory M1 like macrophages, increasing our knowledge about chicken macrophage polarization and providing useful information for studies on chicken macrophage phenotypes.


Moral judgments recruit domain-general valuation mechanisms to integrate representations of probability and magnitude.
Many important moral decisions, particularly at the policy level, require the evaluation of choices involving outcomes of variable magnitude and probability. Many economic decisions involve the same problem. It is not known whether and to what extent these structurally isomorphic decisions rely on common neural mechanisms. Subjects undergoing fMRI evaluated the moral acceptability of sacrificing a single life to save a larger group of variable size and probability of dying without action. Paralleling research on economic decision making, the ventromedial prefrontal cortex and ventral striatum were specifically sensitive to the "expected moral value" of actions, i.e., the expected number of lives lost/saved. Likewise, the right anterior insula was specifically sensitive to outcome probability. Other regions tracked outcome certainty and individual differences in utilitarian tendency. The present results suggest that complex life-and-death moral decisions that affect others depend on neural circuitry adapted for more basic, self-interested decision making involving material rewards.


Simultaneous dynamic electromyographic proctography and cystometrography.
The rectum and bladder share a common origin and work in harmony; disturbance in one may lead to a similar problem in the other. The two have, however, not previously been investigated dynamically and simultaneously. A new system has been devised allowing dynamic integrated electromyographic proctography to be performed simultaneously with cystometrography in 41 patients (28 women and 13 men). Of 16 women with chronic constipation who underwent the combined study, ten were shown to have obstructed micturition. Eight of these ten women exhibited an inappropriate contraction of the puborectalis muscle during micturition, compared with one of the six with normal micturition (P = 0.02). Of the patients with obstructed micturition, seven of eight women with a rectocele also had anismus, compared with none of four women with a rectocele among those who were able to micturate normally (P = 0.02). Eight of the ten women with obstructed micturition thus had a proctological abnormality that explained the urological symptoms. Of 12 women with idiopathic faecal incontinence who underwent the combined study, eight were shown to have genuine stress incontinence of urine. In seven of these the severity was shown to be of type 2a or greater, indicating that pelvic floor dysfunction may be the causal factor of both rectal and urinary symptoms. The combined study shows abnormalities in one system that could explain similar symptoms in the other.


Mast cells and cell-to-cell interactions in airways.
Dog mastocytomas (anatomic and biochemical features comparable to normal dog and human mast cells) were used to study actions of mast cell mediators on several airway effector systems. We showed mastocytoma cell adherence to both cultured tracheal epithelial cells and tracheal tissue sections for greater than 48 h that was abolished completely by pretreatment of mast cells with proteases. This mast cell-epithelial cell adhesion-interaction reaction is probably mediated by a mast cell plasma membrane protein. Mast cell mediators stimulate short circuit current and ion flux across dog tracheal epithelia mounted in Ussing chambers. Pretreatment of epithelia with indomethacin blocks this effect, probably by inhibiting LTC4-induced activation of epithelial cyclooxygenases. Mastocytoma cells also increase secretion from cultured serous submucosal gland cells. Blockade of cyclooxygenase and lipoxygenase pathways in mastocytoma cells activated by calcium ionophore does not alter secretion of the serous cells induced by mastocytoma supernatant, but secretion induced by mastocytoma supernatant or purified mast cell chymase is markedly reduced by an inhibitor of chymase. These results suggest that mast cells can alter airway secretions not only by actions on ion flux in epithelial cells but also by actions on submucosal gland secretion; this latter action appears to be mediated by mast cell chymase. Finally, supernatants from mastocytoma cells stimulated by calcium ionophore greatly increase the sensitivity and magnitude of the contractile response of dog bronchial smooth muscle to histamine. These effects are blocked by an inhibitor of mast cell tryptase.(ABSTRACT TRUNCATED AT 250 WORDS)