Age-related alterations in alpha 1- and beta-adrenoceptors mediated responsiveness of rat aorta.
We have examined the responsiveness of alpha- and beta-adrenoceptors in aortae from 1.5, 3, 6 and 24 month old rats. The isometric contraction to phenylephrine was antagonised competitively by prazosin with a pA2 value of 9.45, suggesting that the receptor is an alpha 1-adrenoceptor. The potency of phenylephrine was significantly reduced in 24 months old as compared with all younger rats combined. The maximum contraction to phenylephrine was unaltered in 24 month old rats. The maximum contraction to potassium chloride was significantly less than that to phenylephrine only in 1.5 months old rats. In tissues contracted by potassium chloride, isoprenaline produced a marked relaxation in 1.5 months old animals, but there was a progressive loss with increasing age of the beta-adrenoceptor-mediated relaxation which was markedly reduced by 6 months and abolished in 24 months old. It is concluded that, in the rat aorta, there is a decrease in alpha 1-adrenoceptor responsiveness in senescence, and a loss of beta-adrenoceptor-mediated responses in maturation.


Concomitant Production of Erythritol and β-Carotene by Engineered Yarrowia lipolytica.
While the expansion of the erythritol production industry has resulted in unprecedented production of yeast cells, it also suffers from a lack of effective utilization. β-Carotene is a value-added compound that can be synthesized by engineered Yarrowia lipolytica. Here, we first evaluated the production performance of erythritol-producing yeast strains under two different morphologies and then successfully constructed a chassis with yeast-like morphology by deleting Mhy1 and Cla4 genes. Subsequently, β-carotene synthesis pathway genes, CarRA and CarB from Blakeslea trispora, were introduced to construct the β-carotene and erythritol coproducing Y. lipolytica strain ylmcc. The rate-limiting genes GGS1 and tHMG1 were overexpressed to increase the β-carotene yield by 45.32-fold compared with the strain ylmcc. However, increased β-carotene accumulation led to prolonged fermentation time; therefore, transporter engineering through overexpression of YTH1 and YTH3 genes was used to alleviate fermentation delays. Using batch fermentation in a 3 L bioreactor, this engineered Y. lipolytica strain produced erythritol with production, yield, and productivity values of 171 g/L, 0.56 g/g glucose, and 2.38 g/(L·h), respectively, with a concomitant β-carotene yield of 47.36 ± 0.06 mg/g DCW. The approach presented here improves the value of erythritol-producing cells and offers a low-cost technique to obtain hydrophobic terpenoids.


Reduction of steps in the preparation of motile sperm for intrauterine insemination does not reduce efficacy of the procedure: simplified one-step swim-up method versus classic swim-up.
Intrauterine insemination (IUI) is a valid treatment for infertility with a cumulative pregnancy rate of >40-90% after 3-10 treatment cycles. We studied the efficacy of a simplified method for motile sperm preparation for IUI. A prospective clinical trial was performed with 100 couples (male age 33-48 and female 28-37 years) with a 2-8 year history of primary infertility associated with slight oligozoospermia (16/100), oligomenorrhoea (32/100) or unknown (52/100). Motile sperm for IUI were prepared by: (A) the classic World Health Organization self-migration (swim-up) method which includes centrifugation, or (B) a simplified one-step swim-up procedure without centrifugation. Recombinant FSH was used for ovarian stimulation. Depending on the cause of infertility, patients were matched one-to-one at the time of IUI, so that when a total of 100 couples had been treated, 50/100 women received sperm prepared by method A and 50/100 by method B. A statistically significant correlation was found between the percentage motile sperm of the original semen sample and the percentage of motile sperm recovered by method A (r = 0.333, P < 0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P < 0.001) was found between the two methods. The simplified one-step swim-up method was as effective as the classic swim-up method, but the former was easier and more economical.


Blockade of Autocrine CCL5 Responses Inhibits Zika Virus Persistence and Spread in Human Brain Microvascular Endothelial Cells.
Zika virus (ZIKV) is a neurovirulent flavivirus that uniquely causes fetal microcephaly, is sexually transmitted, and persists in patients for up to 6 months. ZIKV persistently infects human brain microvascular endothelial cells (hBMECs) that form the blood-brain barrier (BBB) and enables viral spread to neuronal compartments. We found that CCL5, a chemokine with prosurvival effects on immune cells, was highly secreted by ZIKV-infected hBMECs. Although roles for CCL5 in endothelial cell (EC) survival remain unknown, the presence of the CCL5 receptors CCR3 and CCR5 on ECs suggested that CCL5 could promote ZIKV persistence in hBMECs. We found that exogenous CCL5 induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in hBMECs and that ERK1/2 cell survival signaling was similarly activated by ZIKV infection. Neutralizing antibodies to CCL5, CCR3, or CCR5 inhibited persistent ZIKV infection of hBMECs. While knockout (KO) of CCL5 failed to prevent ZIKV infection of hBMECs, at 3 days postinfection (dpi), we observed a >90% reduction in ZIKV-infected CCL5-KO hBMECs and a multilog reduction in ZIKV titers. In contrast, the addition of CCL5 to CCL5-KO hBMECs dose-dependently rescued ZIKV persistence in hBMECs. Inhibiting CCL5 responses using CCR3 (UCB35625) and CCR5 (maraviroc) receptor antagonists reduced the number of ZIKV-infected hBMECs and ZIKV titers (50% inhibitory concentrations [IC50s] of 2.5 to 12 μM), without cytotoxicity (50% cytotoxic concentration [CC50] of >80 μM). These findings demonstrate that ZIKV-induced CCL5 directs autocrine CCR3/CCR5 activation of ERK1/2 survival responses that are required for ZIKV to persistently infect hBMECs. Our results establish roles for CCL5 in ZIKV persistence and suggest the potential for CCL5 receptor antagonists to therapeutically inhibit ZIKV spread and neurovirulence. IMPORTANCE Our findings demonstrate that CCL5 is required for ZIKV to persistently infect human brain ECs that normally protect neuronal compartments. We demonstrate that ZIKV-elicited CCL5 secretion directs autocrine hBMEC activation of ERK1/2 survival pathways via CCR3/CCR5, and inhibiting CCL5/CCR3/CCR5 responses prevented ZIKV persistence and spread. Our findings demonstrate that ZIKV-directed CCL5 secretion promotes hBMEC survival and reveals an underlying mechanism of ZIKV pathogenesis and spread. We demonstrate that antagonists of CCR3/CCR5 inhibit ZIKV persistence in hBMECs and provide potential therapeutic approaches for preventing ZIKV persistence, spread, and neurovirulence.


Electronically Activated Organoboron Catalysts for Enantioselective Propargyl Addition to Trifluoromethyl Ketones.
A broadly applicable, practical, scalable, efficient and highly α- and enantioselective method for addition of a silyl-protected propargyl moiety to trifluoromethyl ketones has been developed. Reactions, promoted by 2.0 mol % of a catalyst that is derived in situ from a readily accessible aminophenol compound at ambient temperature, were complete after only 15 minutes at room temperature. The desired tertiary alcohols were isolated in up to 97 % yield and 98.5:1.5 enantiomeric ratio. Alkyl-, alkenyl-, alkynyl-, aryl- or heteroaryl-substituted trifluoromethyl ketones can be used. Utility is highlighted by application to a transformation that is relevant to enantioselective synthesis of BI 653048, a compound active against rheumatoid arthritis.


The discovery of biomarkers for type 2 diabetic nephropathy by serum proteome analysis.
Diabetic nephropathy (DN) is a serious kidney complication of diabetes, and constitutes the leading cause of end-stage renal disease. The earliest clinical evidence of DN is microalbuminuria, a term which refers to the appearance of small but abnormal amounts of albumin in the urine. However, screening methods for DN, such as biomarker assays, are yet to be developed for type 2 DN. In the present study, in an attempt to identify the biomarkers for initial diagnoses of type 2 DN, the protein profiles of human sera collected from 30 microalbuminuric type 2 diabetic patients were compared with those collected from 30 normoalbuminuric type 2 diabetic patients, via 2-DE. As a result, a total of 18 spots were determined to have different protein levels in the microalbuminuric patients. Twelve spots had lower protein levels of approximately 50%, and the other six had higher levels of approximately 100-300% as compared to the spots of normoalbuminuric patients. These spots were identified with ESI-Q-TOF (ESI-quadrupole-TOF) MS. Among the identified proteins, vitamin D-binding protein (DBP) and pigment epithelium-derived factor (PEDF) were verified by Western blotting. The results of this study indicate that the DBP may be employed as diagnostic and monitoring biomarkers of type 2 DN, contingent on further study into the matter.


The effect of trace elements on the immune response of rats with intact or injured immune system.
We studied the effect of a trace element combination (Béres Drop Plus; BDP) on the immune response of rats, with intact and with injured immune system. Rats were treated with different doses of BDP for 26 days. The immune system was injured by 7.0 Gy whole body gamma irradiation on the first day of BDP treatment. Rats were immunized on the 31st day of the BDP treatment with sheep red blood cells. In the spleen the cell count and the number of antibody producing cells were determined. In the serum the titre of hemolysin was tested. In rats with intact immune system all used doses of BDP induced elevation of the immune response. The moderate high doses were especially effective. In rats with injured immune system the effect was less. Only the 250 microliters/kg body weight dose could elevate the immune response, and the highest (500 microliters/kg) dose reduced the response.


Reduction of Benzonitriles via Osmium-Azavinylidene Intermediates Bearing Nucleophilic and Electrophilic Centers.
The reduction of the N≡C bond of benzonitriles promoted by OsH6(PiPr3)2 (1) has been studied. Complex 1 releases a H2 molecule and coordinates 2,6-dimethylbenzonitrile to afford the tetrahydride OsH4{κ1- N-(N≡CC6H3Me2)}(PiPr3)2 (2), which is thermally stable toward the insertion of the nitrile into one of the Os-H bonds. In contrast to 2,6-dimethylbenzonitrile, benzonitrile and 2-methylbenzonitrile undergo insertion, via Os(η2-N≡CR) intermediates, to give the azavinylidene derivatives OsH3(═N═CC6H4R)(PiPr3)2 [R = H (3) or Me (4)]. The analysis by means of computational tools (EDA-NOCV) of the bonding situation in these compounds suggests that the donor-acceptor nature of the osmium azavinylidene bond dominates over the mixed electron-sharing/donor-acceptor and pure electron-sharing bonding modes. The N atom is strongly nucleophilic, whereas one of the hydrides is electrophilic. In spite of the different nature of these centers, the migration of the latter to the N atom is kinetically prevented. However, the use of water as a proton shuttle allows hydride migration, as a consequence of a significant decrease in the activation barrier. The resulting phenylaldimine intermediates evolve by means of orthometalation to give OsH3{κ2- N, C-(NH═CHC6H3R)}(PiPr3)2 [R = H (5) or Me (6)]. The presence of electrophilic and nucleophilic centers in 3 confers upon it the ability to activate σ-bonds, including H2 and pinacolborane (HBpin). The reaction with the latter gives OsH3{κ2- N, C-[N(Bpin)═CHC6H4]}(PiPr3)2 (7).


Interpolative Separable Density Fitting through Centroidal Voronoi Tessellation with Applications to Hybrid Functional Electronic Structure Calculations.
The recently developed interpolative separable density fitting (ISDF) decomposition is a powerful way for compressing the redundant information in the set of orbital pairs and has been used to accelerate quantum chemistry calculations in a number of contexts. The key ingredient of the ISDF decomposition is to select a set of nonuniform grid points, so that the values of the orbital pairs evaluated at such grid points can be used to accurately interpolate those evaluated at all grid points. The set of nonuniform grid points, called the interpolation points, can be automatically selected by a QR factorization with column pivoting (QRCP) procedure. This is the computationally most expensive step in the construction of the ISDF decomposition. In this work, we propose a new approach to find the interpolation points based on the centroidal Voronoi tessellation (CVT) method, which offers a much less expensive alternative to the QRCP procedure when ISDF is used in the context of hybrid functional electronic structure calculations. The CVT method only uses information from the electron density and can be efficiently implemented using a K-Means algorithm. We find that this new method achieves comparable accuracy to the ISDF-QRCP method, at a cost that is negligible in the overall hybrid functional calculations. For instance, for a system containing 1000 silicon atoms simulated using the HSE06 hybrid functional on 2000 computational cores, the cost of the QRCP-based method for finding the interpolation points is 38.1 s, while the CVT procedure only takes 0.7 s. We also find that the ISDF-CVT method enhances the smoothness of the potential energy surface in the context of ab initio molecular dynamics (AIMD) simulations with hybrid functionals.


Correlation of fatigue with other disease related and psychosocial factors in patients with rheumatoid arthritis treated with tocilizumab: ACT-AXIS study.
To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ± 12.5 years, disease duration 8.7 ± 7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ± 4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ± 1.0 at baseline to 2.7 ± 1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ± 11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.


Metabolomics Uncovers the Regulatory Pathway of Acyl-homoserine Lactones Based Quorum Sensing in Anammox Consortia.
Acyl-homoserine lactones (AHLs)-mediated quorum sensing in bacterial communities have been extensively observed. However, the metabolic pathways regulated by AHLs in bacteria remain elusive. Here, we combined long-term reactor operation with microbiological and metabolomics analyses to explore the regulatory pathways for different AHLs in anammox consortia, which perform promising nitrogen removal for wastewater treatment. The results showed that no obvious shifts induced by exogenous AHLs occurred in the microbial community and, mainly, dosing AHLs induced changes in the metabolites. 3OC6-HSL, C6-HSL, and C8-HSL controlled the electron transport carriers that influence the bacterial activity. In contrast, only 3OC6-HSL regulated LysoPC(20:0) metabolism, which affected bacterial growth. AHLs mainly regulated the synthesis of the amino acids Ala, Val, and Glu and selectively regulated Asp and Leu to affect extracellular proteins. Simultaneously, all the AHLs regulated the ManNAc biosynthetic pathways, while OC6-HSL, OC8-HSL, and C6-HSL particularly enriched the UDP-GlcNAc pathway to promote exopolysaccharides, resulting in different aggregation levels of the anammox consortia. Our results not only provide the first metabolic insights into the means by which AHLs affect anammox consortia but also hint at potential strategies for overcoming the limitations of the long start-up period required for wastewater treatment by anammox processing.


A new genus and new species of Sciaenidae from the Gulf of Panama (Perciformes: Sciaenidae).
Paranebris bauchotae, a new genus and species of sciaenid from the Gulf of Panama is described from three specimens (138-212 mm SL). It is distinguished from all other sciaenids by having granulated tooth plates on the jaws and the premaxillary tooth plates that are exposed laterally of the lower jaw when the mouth is closed. The new genus shares the following characters with the New World genus Nebris: a thick fleshy and cartilage gap present between premaxillary bones where the ascending processes form an A-frame arch; gas bladder with a pair of long U-shaped appendages; and a thick, oval-shaped sagitta with deeply grooved caudal section of the sulcus. Paranebris bauchotae is distinct from all Nebris species in having a firmer interorbital skin and scale cover (spongy to the touch in Nebris), a larger eye (6-7 vs. 8-12 times in head length) and large ctenoid scales (vs. small and cycloid in Nebris).


Application of a diode-array detector in capillary electrophoresis.
In the last decade diode-array detection has proved to be extremely useful in high performance liquid chromatography in recording UV-visible spectra directly and on-line in the column effluent. In capillary electrophoresis (CE) only fast-scanning detectors with long scan times (up to 2 s) are commercially available. A home-made CE instrument with a diode-array detector (DAD) was built and compared with a commercial fast-scanning detector. It is shown that the fast-scanning detector is advantageous when less than eight wavelengths are monitored. Due to the high data collection rate the DAD is superior if high resolution UV-visible spectra are acquired or if several spectra of a narrow peak (usual peak width in CE below 5 s) are needed for peak purity control. It is shown that DAD detection can help to develop separation methods, to identify peaks according to their UV-visible spectra, and to check peak purity.


Clinical considerations of antidepressant prescribing for older patients.
Depression may affect up to 50% of people in older age groups. The increasing numbers of patients over 65 years of age may lead to higher prevalence rates of this debilitating condition. The diagnosis of depression in older patients is complex because symptoms may present as somatic concerns or anxiety. Comorbid conditions need to be investigated, evaluated and, if necessary, treated. Prescribing antidepressants to older patients requires consideration of the pharmacokinetic parameters of the medications used in this population, as these affect drug selection, duration of treatment, and suitability when comorbidity is present. This paper provides a review of current literature and makes recommendations for the pharmacological management of depression in older patients within the New Zealand context.


Prevalence of risk factors for residential fire and burn injuries in an American Indian community.
Fatality rates from residential fires are high among American Indians. Contact burns and scalds are also among the leading types of thermal injuries. Information about the prevalence of risk factors for burn injuries is required to design interventions aimed at reducing residential fire and burn injuries. The authors conducted a survey in July and August 1992 of 68 households located in a small American Indian community in Washington State to ascertain the prevalence of selected risk factors for residential fire and burn injuries. Nearly all households (96 percent) in the study had a smoke detector, and 95 percent of those tested were functioning. However, a high prevalence of other household characteristics associated with excess risk of residential fire and burn injuries was identified: 59 percent of households had at least one member who smoked, 25 percent had a member who smoked in bed, 38 percent had a member who drank alcohol and smoked at the same time, 46 percent used wood stoves as a heat source, and 15 percent of households were mobile homes. Thirteen percent of households had at least one fire during the previous 3 years, and the incidence of burns due to all causes and requiring medical treatment was 1.5 per 100 persons per year. Hot water temperature was measured to determine the potential risk for scald burns, and 48 percent of households had a maximum hot water temperature of 130 degrees or more Fahrenheit. Such surveys can guide intervention strategies to reduce residential fire and burn injuries in American Indian communities.


Malignant myoepithelioma of the breast. Case report with immunohistochemical study.
Malignant myoepitheliomas of the breast are rare. We report a case of spindle cell malignant myoepithelioma studied by light microscopy and immunohistochemistry. The malignant myoepithelial cells stained positively for cytokeratins, smooth muscle actin and vimentin, but not for epithelial membrane antigen. The tumor showed a focal positivity for S100 protein. A short review of the morphology and immunohistochemistry of cases reported in the international literature is given in a table. Morphologically malignant myoepitheliomas can be subdivided into spindle cell malignant myoepitheliomas and malignant adenomyoepitheliomas.


Spatial summation in subregions of simple-cell receptive fields in cat striate cortex as a function of slit length.
Spatial summation along the optimum stimulus orientation in subregions of simple-cell receptive fields in cat striate cortex was studied quantitatively by measuring the response to stationary light slits of variable length. Before summation analysis, the cell's discharge field was mapped by flashing a test slit on and off in a sequence of positions through the receptive field. A static activation procedure was used to determine the extension of subregions of the receptive field where light stimulation increased (enhancement) or decreased (suppression) the firing rate. An activation slit in the optimum orientation was positioned in the most responsive position of the discharge field and the effects of a parallel test slit, in a series of broadside positions, were assessed from the changes induced in the discharge elicited by the activation slit. Length-response curves for on and off responses were made by positioning a test slit in the respective subregions of the discharge field. The activation procedure was used to make length-response curves for suppression. A test slit of variable length was positioned in a suppression region defined by the activation profiles and an activation slit of fixed length was centred in the most responsive discharge field position. Length summation was found for all cells, both with respect to on and off responses, and suppression. The curves for on and off responses had a maximum value beyond which the response declined or levelled off, but some cells had a secondary, more shallow increase beyond an initial, steeply rising part. Similar properties were found for summation of suppression except that the effects were opposite in sign. Curves made for both on and off regions in the same cell often differed in shape. Such differences were also found when length-response curves made in different suppression regions of the same cell were compared. The various length-summation functions were explained by a model presuming that simple-cell receptive fields consist of partially overlapping non-concentric excitatory and inhibitory fields. This arrangement would also explain why length-response curves in various subregions often had different shapes.


A review of current salt marsh management issues in Florida.
For the past decade, salt marsh management in Florida has been a central issue in attempts to reconcile mosquito control and natural resource interests. Progress has been made in trying to maintain effective mosquito control while protecting and enhancing salt marsh resources primarily due to: 1) efforts by the Florida Coordinating Council on Mosquito Control and its Subcommittee on Managed Marshes, which are committees comprised of agencies responsible for wetlands resources, those mandated to provide mosquito control, and research institutions; and 2) funding of research to investigate ecosystem effects of marsh management techniques. Research and management experience have demonstrated that Rotational Impoundment Management (RIM) and rotary ditching can provide ecologically sound source reduction benefits. Salt marsh ownership, management of state lands and mariculture remain controversial salt marsh management issues.


Effective variables to control the fill factor of organic photovoltaic cells.
Effective cell design variables having a large impact on the fill factor (FF) of organic photovoltaic cells (OPVCs) were systematically identified using a general device structure of ITO/PEDOT:PSS/P3HT + PCBM/LiF/Al. The results show that the characteristic properties of the organic layer, such as morphology and thickness, the regioregularity of the conjugated polymer, and the two interfaces between the electrodes and the blend layer have a large influence on the FF by affecting the series resistance (R(s)) and the shunt resistance (R(sh)). The systematic investigation described in this contribution provides a comprehensive understanding of the correlation between the device variables and R(s) and R(sh) and a way to control FF, which is critically important to achieving a high-performance OPVC.


Threshold and stability results for an epidemic model with an age-structured meeting rate.
This paper examines threshold and stability results for simple mathematical models for the transmission of infectious diseases with permanent natural immunity. Examples of such diseases are measles, chicken-pox, hepatitis, and mumps. An important feature of this work is the introduction of an age structure into the population amongst whom the disease is spreading and, in particular, the realization of the fact that the contact rate itself may depend on age. Equilibrium and stability analyses are performed on these models. These results are in part directed towards establishing conditions sufficient for the existence of a nonzero equilibrium disease level to be possible. Conjectures about the existence of a nonzero solution to a set of partial integrodifferential equations are examined. These conditions determine the circumstances under which the disease will persist. Particular emphasis is devoted to the case where the meeting rate depends on age.


Oculodentodigital dysplasia with massive brain calcification and a new mutation of GJA1 gene.
Oculodentodigital dysplasia (ODDD) [MIM 164200] is a rare disorder caused by mutations in the gap junction alpha 1 (GJA1) gene encoding for connexin 43 (Cx43). Typical signs include type III syndactyly, microphtalmia, microdontia, and neurological disturbances. We report a 59-year-old man having clinical symptoms and signs suggestive of ODDD, with some rarely reported features, that is the presence of gross calcifications of basal ganglia and cerebellar nuclei. Mutation analysis of GJA1 gene identified an unreported heterozygous missense mutation [NM_000165.3:c.124 G>C;p.(Glu42Gln)], which may be thought to alter the brain microvessels leading to massive calcifications, as in primary familial brain calcification.


GLOBAL PHYLOGEOGRAPHY OF THE LOGGERHEAD TURTLE (CARETTA CARETTA) AS INDICATED BY MITOCHONDRIAL DNA HAPLOTYPES.
Restriction-site analyses of mitochondrial DNA (mtDNA) from the loggerhead sea turtle (Caretta caretta) reveal substantial phylogeographic structure among major nesting populations in the Atlantic, Indian, and Pacific oceans and the Mediterranean sea. Based on 176 samples from eight nesting populations, most breeding colonies were distinguished from other assayed nesting locations by diagnostic and often fixed restriction-site differences, indicating a strong propensity for natal homing by nesting females. Phylogenetic analyses revealed two distinctive matrilines in the loggerhead turtle that differ by a mean estimated sequence divergence p = 0.009, a value similar in magnitude to the deepest intraspecific mtDNA node (p = 0.007) reported in a global survey of the green sea turtle Chelonia mydas. In contrast to the green turtle, where a fundamental phylogenetic split distinguished turtles in the Atlantic Ocean and the Mediterranean Sea from those in the Indian and Pacific oceans, genotypes representing the two primary loggerhead mtDNA lineages were observed in both Atlantic-Mediterranean and Indian-Pacific samples. We attribute this aspect of phylogeographic structure in Caretta caretta to recent interoceanic gene flow, probably mediated by the ability of this temperate-adapted species to utilize habitats around southern Africa. These results demonstrate how differences in the ecology and geographic ranges of marine turtle species can influence their comparative global population structures.


[Clay ratio as a tracer to assess the origin of soil-derived dust].
The objectives of this research are to characterise the mineralogy of soil-derived dust in Northern China and to set up the mineralogical signature to trace their origin. Mineral composition of aerosol particles is investigated at five sites (Aksu, Dunhuang, Yulin, Tongliao and Changwu) during the intensive field campaign period of ACE-Asia. The results show that the Kaolinite (K) to Chlorite (C) ratio is sensitive to the regional origin of Asian dust. Western source areas (represent by Aksu) displayed the lowest K/ C ratio of 0.3 (in average), while it was found that to increase up to 0.70 (in average) as moving towards north source areas (represent by Yulin). By studying transported dust in a depositional area representative of the Chinese Loess Plateau, the usefulness of the K/C ratio to retrieve the origin of the dust by associating it with back air-mass trajectories is checked. Compared the mineralogical data between Asian dust and Sahara dust, it is shown that K/C ratio is also a good signature to identify the source areas on the global scale.


Rate and predictors of low serum ferritin levels among healthy parturient women in Enugu, Nigeria.
Low serum ferritin levels signify low iron stores and this could predispose to iron deficiency anemia. To determine the rate and predictors of low serum ferritin levels during the puerperium in Enugu, Southeast Nigeria. A hospital-based prospective longitudinal study involving parturient women who delivered singleton fetuses at term. Venous blood samples were collected to determine the serum ferritin concentration at 48 hours and 6 weeks postpartum. Data analysis involved descriptive and inferential statistics at 95% confidence interval (CI) using Statistical Package for Social Sciences (SPSS) computer software version 20.0. Two-hundred and two women who carried singleton pregnancies to term were studied. The mean serum ferritin levels at 48 hours and 6 weeks were 27.82±18.41 µg/L and 36.12±21.53 µg/L, respectively. Forty-eight hours postdelivery, 29.2% had low ferritin levels and this decreased to 12.4% at 6 weeks postpartum. There was a significant positive correlation between the serum ferritin level at 48 hours postdelivery and the serum ferritin level at 6 weeks postpartum (r=0.89, P<0.001). Predictors of the low ferritin level at 6 weeks included age <20 years (odds ratio [OR] =0.70, 95% CI =0.53, 0.93), multiparity (OR =63.7, 95% CI =3.18, 127.5), anemia at 48 hours postpartum (OR =61.7, 95% CI =13.27, 116.6), a low ferritin level at 48 hours (OR =78.1, 95% CI =8.8, 108.3), and intake of antenatal hematinics for <3 months (OR =0.04, 95% CI =0.01, 0.20). There was a significant occurrence of low ferritin levels during the puerperium in the study centers, and this was associated mainly with pregnancy and delivery factors. Efforts to improve the iron stores in parturient women could benefit from early booking and compliance with antenatal hematinics and optimizing hemoglobin and iron levels before delivery.


The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences.
Viral infection outcomes are sex biased, with males generally more susceptible than females. Paradoxically, the numbers of antiviral natural killer (NK) cells are increased in males. We demonstrate that while numbers of NK cells are increased in male mice, they display decreased effector function compared to females in mice and humans. These differences were not solely dependent on gonadal hormones, because they persisted in gonadectomized mice. Kdm6a (which encodes the protein UTX), an epigenetic regulator that escapes X inactivation, was lower in male NK cells, while NK cell-intrinsic UTX deficiency in female mice increased NK cell numbers and reduced effector responses. Furthermore, mice with NK cell-intrinsic UTX deficiency showed increased lethality to mouse cytomegalovirus. Integrative multi-omics analysis revealed a critical role for UTX in regulating chromatin accessibility and gene expression critical for NK cell homeostasis and effector function. Collectively, these data implicate UTX as a critical molecular determinant of sex differences in NK cells.


Application of penalized linear regression methods to the selection of environmental enteropathy biomarkers.
Environmental Enteropathy (EE) is a subclinical condition caused by constant fecal-oral contamination and resulting in blunting of intestinal villi and intestinal inflammation. Of primary interest in the clinical research is to evaluate the association between non-invasive EE biomarkers and malnutrition in a cohort of Bangladeshi children. The challenges are that the number of biomarkers/covariates is relatively large, and some of them are highly correlated. Many variable selection methods are available in the literature, but which are most appropriate for EE biomarker selection remains unclear. In this study, different variable selection approaches were applied and the performance of these methods was assessed numerically through simulation studies, assuming the correlations among covariates were similar to those in the Bangladesh cohort. The suggested methods from simulations were applied to the Bangladesh cohort to select the most relevant biomarkers for the growth response, and bootstrapping methods were used to evaluate the consistency of selection results. Through simulation studies, SCAD (Smoothly Clipped Absolute Deviation), Adaptive LASSO (Least Absolute Shrinkage and Selection Operator) and MCP (Minimax Concave Penalty) are the suggested variable selection methods, compared to traditional stepwise regression method. In the Bangladesh data, predictors such as mother weight, height-for-age z-score (HAZ) at week 18, and inflammation markers (Myeloperoxidase (MPO) at week 12 and soluable CD14 at week 18) are informative biomarkers associated with children's growth. Penalized linear regression methods are plausible alternatives to traditional variable selection methods, and the suggested methods are applicable to other biomedical studies. The selected early-stage biomarkers offer a potential explanation for the burden of malnutrition problems in low-income countries, allow early identification of infants at risk, and suggest pathways for intervention. This study was retrospectively registered with ClinicalTrials.gov, number NCT01375647, on June 3, 2011.


New records of Synallactes virgulasolida Massin Hendrickx, 2010 (Echinodermata: Holothuroidea) from the eastern Pacific.
Specimens of the sea cucumber Synallactes virgulasolida were obtained during sampling operations off western Mexico. Based on a total of 190 specimens and on additional records available in the Scripps Institution of Oceanography collections, new geographical (southern California to Chile) and bathymetric (712‒1300 m) distributions are provided. SEM photographs of ossicles are provided for the first time for this species. New ecological data associated with the presence of this species are also provided: 4.17‒5.81 °C, 0.15‒0.48 ml O2/l, and in 34.40‒34.48 ups. The species occurs in a wide variety of sediments with an organic carbon content of 17.93‒52.02 mg/g (1.79-5.20 % of organic matter) and is occasionally very dense (up to 170.32 orgs/ha). All Mexican records correspond to a bathymetric fringe located below the Oxygen Minimum Zone, thus indicating that S. virgulasolida is able to tolerate hypoxic conditions.


Characterizing bone tunnel placement in medial ulnar collateral ligament reconstruction using patient-specific 3-dimensional computed tomography modeling.
Medial ulnar collateral ligament (MUCL) reconstruction is successful in restoring valgus elbow stability, but variability in bone tunnel characteristics exists among surgical techniques. Tunnel parameters such as diameter, drill angle, and starting location in MUCL reconstruction affect tunnel length and bone bridge size between tunnels. Descriptive laboratory study. Three-dimensional models were created from elbow computed tomography scans of 10 throwing athletes and analyzed using Mimics (Materialise) software. The MUCL reconstructions were simulated on each elbow with 3 techniques: Jobe, humeral docking, and DANE TJ. Humeral central tunnels were modified by diameter, medial-lateral epicondylar starting point, and angle with respect to the humeral axis. Ulnar tunnels were varied by diameter and angle with respect to the ulnar axis. Humeral tunnel length, humeral and ulnar bone bridge sizes, and ulnar tunnel aperture and distance from the articular surface of the olecranon were measured. Comparisons were made using 1- and 2-way analysis of variance and Student-Newman-Keuls multiple comparison tests. Mean central humeral tunnel length varied significantly by starting point and angulation of the tunnel both in sagittal and coronal planes, ranging from 14.2 ± 2.3 mm to 25.5 ± 4.3 mm (P < .05). Mean bone bridge size between humeral exit tunnels ranged from 9.0 ± 2.5 mm to 15.1 ± 3.1 mm, varying by central humeral tunnel orientation and exit tunnel diameter (P < .05). Bone bridge size between ulnar tunnels with the Jobe and docking techniques averaged 6.7 ± 0.9 mm (3.2-mm tunnels) and 6.4 ± 0.8 mm (3.5-mm tunnels), respectively. Angle of ulnar tunnels affected distance from the articular surface with the Jobe and docking techniques (P < .0001) and affected tunnel aperture size with the interference screw technique (P < .0001). Humeral and ulnar tunnel angles, starting points, and diameters affect tunnel length, distance from the articular surface, and bone bridge size in MUCL reconstructions. Maximal humeral tunnel length is achieved by starting central or lateral to the midpoint of the epicondyle, angulated 30° to the humeral axis in the sagittal plane and 15° in the coronal plane. A reasonable goal tunnel depth should range from 15 to 20 mm. Ulnar tunnels should be placed on the anterior and posterior aspects of the sublime tubercle, directed away from the joint to minimize the likelihood of breaching the articular cartilage. A bone bridge of 6 to 8 mm between these tunnels can be reasonably achieved. Tunnels with the ulnar interference screw fixation technique should also be directed away from the joint but at an angle more perpendicular than 45° to minimize tunnel aperture size. Regardless of angle of the tunnel drilled for the ulnar interference screw employed in the DANE TJ technique, the tunnel length is sufficient to fully contain a 15-mm screw. Computer models can guide MUCL reconstruction technique by indicating tunnel placement for maximizing the bone bridge and tunnel length.


A radiological study of fractures of acrylic cement in relation to the stem of a femoral head prosthesis.
The incidence and prognostic significance of fractures of acrylic cement related to the stem of a femoral head prosthesis in total hip replacement are examined. These fractures are demonstrated when the cement has been rendered radio-opaque by the addition of barium sulphate. One and a half percent of the radiographs of 6,649 patients showed these fractures, which were sometimes associated with subsidence of the prosthesis. Fracture of the cement was usually evident at the six-month post-operative review, if it occurred at all. This radiological complication was devoid of symptoms in the majority of cases and tended to occur in patients with excellent functional recovery. In a minority of patients pain in the thigh during the first six months seemed likely to be explained by this fracture. Slight subsidence of the prosthesis in the cement bed appeared to result in a new and final position of stability. The prognosis was very good; only when separation of the fracture exceeded about 4 millimetres was the prognosis doubtful, in which case a chronic deep infection might be suspected. Possible mechanical and structural causes of fracture of the cement are discussed.


Use of life support in acutely admitted ICU patients. An international cohort study.
Use of life support in intensive care unit (ICU) patients has been associated with increased risk of poor outcome. The prognostic importance of the duration of support is less studied. We assessed the use of life support and the association between its duration and 90-day mortality in a contemporary cohort of acutely admitted adult ICU patients. We performed a post-hoc analysis of the SUP-ICU 7-day inception cohort study (n = 1034), which was conducted in 97 ICUs in 11 countries. We included patients with an ICU stay of 3 days or more. We assessed the use of life support during the first 3 days in ICU and the crude and adjusted association between its duration and 90-day mortality using logistic regression analyses. We included 690 patients; their 90-day mortality was 23%. During the first 3 days in ICU mechanical ventilation was used in 65%, vasopressors/inotropes in 57% and renal replacement therapy in 13%. Renal replacement therapy for 3 days or more was associated with a higher 90-day mortality as compared with 1 day of renal replacement therapy [odds ratio 6.5 (95% confidence interval 1.3 to 32.8)]. For mechanical ventilation and vasopressors/inotropes the odds ratios were 2.2 [0.9 to 5.3] and 1.2 [0.5 to 2.6], respectively. Among acutely admitted adult ICU patients, a higher number of days of renal replacement therapy in the initial ICU stay were associated with increased risk of death within 90 days. We did not observe such an association for mechanical ventilation or vasopressor/inotropic therapy.


Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors - Hyogo Sleep Cardio-Autonomic Atherosclerosis study.
Brain-derived neurotrophic factor (BDNF) has been shown to have protective effects against cardiovascular diseases and death through neural and non-neural pathways via tropomyosin-related kinase B signaling. However, it is not known whether plasma BDNF concentration is a predictor of chronic kidney disease (CKD). This study was conducted as a prospective cohort study as part of the Hyogo Sleep Cardio-Autonomic Atherosclerosis. We measured plasma BDNF concentration in 324 patients without CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m2, and with cardiovascular risk factors. As potential confounders, sleep condition, nocturnal hypertension, and autonomic function were quantitatively examined. The patients were followed for a median 37 months (range 2-59 months) and occurrence of CKD was noted. Plasma BDNF concentration was significantly and independently associated with CKD development, which occurred in 38 patients (11.7%). Kaplan-Meier analysis revealed that patients with reduced plasma BDNF concentration exhibited a significantly (p = 0.029) greater number of CKD events as compared to those with a higher concentration. Moreover, comparisons of key subgroups showed that the risk of CKD in association with low plasma BDNF concentration was more prominent in patients with a greater reduction of nocturnal systolic blood pressure, better movement index, higher standard deviations of the NN(RR) interval or average NN(RR) interval for each 5-minute period, and without past cardiovascular disease events, smoking habit, or albuminuria. Plasma BDNF concentration is an independent predictor for development of CKD in patients with cardiovascular risk factors.


Long noncoding RNA CCAT2 promotes breast tumor growth by regulating the Wnt signaling pathway.
In addition to protein-coding genes, the human genome makes a large amount of noncoding RNAs, including microRNAs and long noncoding RNAs (lncRNAs). Emerging evidence indicates that lncRNAs could have a critical role in the regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. The lncRNA CCAT2 is dysregulated in several cancers such as colon cancer, non-small cell lung cancer, esophageal squamous cell carcinoma, gastric cancer, and breast cancer; however, the contributions of CCAT2 to breast cancer remain largely unknown. In the current paper, we first confirmed the high expression level of CCAT2 in breast cancer tissues and breast cancer cell lines by reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay, and we further analyzed the relationship between CCAT2 expression and clinical prognostic factors. Also, the biological function of CCAT2 was explored and the results showed silencing of CCAT2 could suppress cell growth in vitro and tumor formation in vivo. Finally, our results revealed that the abnormal expression of CCAT2 could influence the Wnt signaling pathway. In conclusion, lncRNA CCAT2 might be considered as a novel molecule involved in breast cancer development, which provides a potential therapeutic target for breast cancer.


Collimation for imaging the myocardium. II.
Line-source response functions and modulation transfer functions (MTF) were used to compare the spatial resolutions obtained with an Anger camera system and four different nuclides used as myocardial-imaging agents: 99mTc, 123I, 201Tl, and 43K. The measurements were made with a low-energy converging collimator (LECY, a medium-energy converging collimator (MEC), and a pinhole collimator. The MTF values for 99mTc were very similar for all three collimator types, although the LEC collimator gave slightly higher values at hgih spatial frequencies and had 40% greater sensitivity. Iodine-123 was satisfactorily imaged only with the MEC and pinhole collimators, which in turn yielded MTF values comparable to those measured for 99mTc. Thallium-201 produced MTF curves that were similar for the MEC and pinhole collimators; the curve for th LEC collimator was slightly poorer. All three MTF curves for 201 Tl were inferior to those of 99mTc. For imaging with 43K, only the pinhole collimator provided marginally acceptable spatial resolution.


Reconstruction of the cervical spine following anterior vertebral body resection: a mechanical analysis of a canine experimental model.
In some quadriplegic patients whose acute spinal injury consists of a vertebral body fracture with bony retropulsion anteriorly and ligamentous damage posteriorly, it is appropriate to perform a decompression of the injured spinal cord by excision of the fractured body. Reconstruction of such a spine to achieve immediate and ultimate stability can be quite difficult. This is a report of mechanical testing using a canine in vitro experimental model to simulate different general types of reconstruction systems applicable to the spine destabilized as above. The results explain some of the previously noted failures of the traditional anterior strut grafting procedures. In addition, one of the reconstruction systems tested (anterior and posterior tension bands compressing an anterior strut graft into place) appeared to have sufficient immediate stability to eliminate the need for a halo-vest in the postoperative period. If such a reconstruction system were to prove clinically applicable, it would be quite beneficial to the quadriplegic patient in his rehabilitation.


ERF108 from Poncirus trifoliata (L.) Raf. functions in cold tolerance by modulating raffinose synthesis through transcriptional regulation of PtrRafS.
Ethylene-responsive factors (ERFs) are plant-specific transcription factors involved in cold stress response, and raffinose is known to accumulate in plants exposed to cold. However, it remains elusive whether ERFs function in cold tolerance by modulating raffinose synthesis. Here, we identified a cold-responsive PtrERF108 from trifoliate orange (Poncirus trifoliata (L.) Raf.), a cold-tolerant plant closely related to citrus. PtrERF108 is localized in the nucleus and has transcriptional activation activity. Overexpression of PtrERF108 conferred enhanced cold tolerance of transgenic lemon, whereas virus-induced gene silencing (VIGS)-mediated knockdown of PtrERF108 in trifoliate orange greatly elevated cold sensitivity. Transcriptome profiling showed that PtrERF108 overexpression caused extensive reprogramming of genes associated with signaling transduction, physiological processes and metabolic pathways. Among them, a raffinose synthase (RafS)-encoding gene, PtrRafS, was confirmed as a direct target of PtrERF108. RafS activity and raffinose content were significantly increased in PtrERF108-overexpressing transgenic plants, but prominently decreased in the VIGS plants under cold conditions. Meanwhile, exogenous replenishment of raffinose could recover the cold tolerance of PtrERF108-silenced plants, whereas VIGS-mediated knockdown of PtrRafS resulted in cold-sensitive phenotype. Taken together, the current results demonstrate that PtrERF108 plays a positive role in cold tolerance by modulation of raffinose synthesis via regulating PtrRafS. Our findings reveal a new transcriptional module composed of ERF108-RafS underlying cold-induced raffinose accumulation in plants.


Optical implementation of a space-time-trellis code for enhancing the tolerance of systems to polarization-dependent loss.
We propose a space-time coding scheme designed to increase the tolerance of fiber-optic communications systems to polarization-dependent loss (PDL). A notable increase in the tolerable amount of average link PDL is achieved without affecting the complexity of the overall optical communications link. Other advantages include seamless integration with the broadly deployed blind equalization modules relying on the constant modulus algorithm.


Charge Transport in Dendrimer Melts Using Multiscale Modeling Simulation.
In this article, we present a theoretical calculation of the charge carrier mobility in two different dendrimeric melt systems (dendritic phenylazomethine with a triphenyl amine core and dendritic carbazole with cyclic phenylazomethine as the core), which have recently been reported1 to increase the efficiency of dye-sensitized solar cells by interface modification. Our mobility calculation, which is a combination of molecular dynamics simulation, first-principles calculation, and kinetic Monte Carlo simulation, leads to mobilities that are in quantitative agreement with available experimental data. We also show how the mobility depends on dendrimer generation. Furthermore, we examine the variation of mobility with an external electric field and external reorganization energy. Physical mechanisms behind the observed electric field and generation dependencies of mobility are also explored.


Volumetric changes and graft stability after lateral window sinus floor augmentation: A randomized clinical trial.
The present investigation compared the stability and volumetric changes of two different grafting material used for lateral window sinus floor augmentation (LWSFA). Sixteen patients with a total 20 maxillary sinuses in need of LWSFA were included in the present study. The sinuses were grafted with either 100% anorganic bovine bone mineral (ABBM) alone (Group 1) or a mixture (0.8:1 ratio) of ABBM and mineralized cortical allograft (MCA) (Group 2). Cone beam computer tomography (CBCT) was obtained pre-operatively, and at 2-weeks, and 6-months after LWSFA to perform linear measurements including lateral window dimensions, sinus anatomy, residual bone height/thickness (RBH/RBT), and Schneiderian membrane thickness (SMT), among others. Three-dimensional segmentation analysis was used to evaluate changes of bone graft volume/height (GV/GH). A total of 10 sinuses per group were included in the analysis. No statistically significant difference was found in between groups regarding mean reduction of GV (Group 1: 14.87% ± 16.60%, Group 2: 18.06% ± 9.81%, p = 0.33). Among the linear measurements, only SMT revealed a significant increase after 2-weeks more pronounce in Group 1 (8.70 mm) when compared with Group 2 (5.70 mm) with plausible effect upon LWSFA outcomes. Sinus width showed weak positive correlation with GH reduction after 6 months. This study demonstrated that both ABBM alone and ABBM + MCA represent suitable alternatives for LWSFA with adequate graft stability as they revealed similar volumetric and linear dimensional changes 6 months postoperatively.


Reliability and repeatability of the motor and sensory examination of the international standards for neurological classification of spinal cord injury.
To determine the reliability and repeatability of the motor and sensory examination of the International Standards for Classification of Spinal Cord Injury (SCI) in trained examiners. Sixteen examiners (8 physicians, 8 physical therapists) with clinical SCI experience and 16 patients participated in a reliability study in preparation for a clinical trial involving individuals with acute SCI. After a training session on the standards, each examiner evaluated 3 patients for motor, light touch (LT), and pin prick (PP). The following day, 15 examiners reevaluated one patient. Interrater reliability was determined using intraclass correlation coefficients (1-way, random effects model). Intrarater reliability was determined using a 2-way random effects model. Repeatability was determined using the method of Bland and Altman. Patients were classified as complete tetraplegia (n = 5), incomplete tetraplegia (n = 5), complete paraplegia (n = 5), and incomplete paraplegia (n = 1). Overall, inter-rater reliability was high: motor = 0.97, LT = 0.96, PP = 0.88. Repeatability values were small in patients with complete SCI (motor < 2 points, sensory < 7 points) but large for patients with incomplete SCI. Intra-rater reliability values were > or = 0.98 for patients with complete SCI. The summed scores for motor, LT, and PP in subjects with complete SCI have high inter-rater reliability and small repeatability values. These measures are appropriately reliable for use in clinical trials involving serial neurological examinations with multiple examiners. Further research in subjects with incomplete SCI is needed to determine whether repeatability is acceptably small.


Risk groups and other target groups - preliminary ECDC guidance for developing influenza vaccination recommendations for the season 2010-11.
Providing guidance on risk and target groups for seasonal influenza immunisation is difficult for the 2010-11 season since there is no experience with the new influenza A(H1N1) virus in its seasonal form. Arguments exist for offering immunisation to people with chronic illness and older people, and also for other risk and target groups including pregnant women. A more rigorous approach is being developed to produce annual evidence-based guidance on risk and target groups for influenza vaccination.


[Central hemodynamics of antihypertensive agents. Studies on co-dergocrinmesylate].
The haemodynamic effects of a three-week-treatment with 4-8 mg co-dergocrinmesylate (Hydergin spezial) were investigated in 14 hypertensive patients with a mean age of 58 years and reduced ventricular function (exertional dyspnoea, enlarged cardiac opacity). Blood pressure values at rest and during physical exercise were reduced significantly. Marked cardiac relief was induced manifesting as decrease of enddiastolic and endsystolic volumes and at the same time as an increase of ejection fraction. Cardiac output remained largely constant, lowering of blood pressure was exclusively due to alteration of peripheral total vascular resistance. Cardiac frequency decreased significantly. There was no evidence of negative inotropic effects. Systolic wall tension as the main therapeutic target decreased at rest and during ergometry by 20% and 25%, respectively. Renal perfusion increased slightly, but significantly, in all patients.


Projection of lung cancer mortality in Japan.
According to the National Vital Statistics data, age-standardized mortality rates (ASRs) of lung cancer have shown slightly declining trends in Japan for both men and women. In order to evaluate whether this tendency will continue, a Bayesian age-period-cohort (APC) model was applied using the National Vital Statistics data from 1952 to 2001. In the projection, a Gaussian autoregressive prior model was applied to smooth age, period, and cohort effects from its 2 immediate predecessors by extrapolation. Posterior distributions from which we drew inferences on mortality rates were derived from 15,000 iterations using 5000 burn-in iterations. We defined the median of the iterated values as the overall summary mortality rate of the iterated results. Our results suggest that the number of deaths due to lung cancer will double for men and women during the next 3 decades due to the aging of the baby-boomer generation (individuals who were born between 1947 and 1951). Currently declining trends in some age groups will reverse and start to increase again in the next decades. However, for recent birth cohorts, the results of the projection varied according to whether the data set included early age group mortality or not. Lung cancer mortality in the future depends on the risk factors engaged in by today's young people, especially smoking. Strong promotion of anti-smoking measures and careful surveillance for lung cancer are needed.


Multimeric nature of voltage-gated proton channels.
Voltage-gated potassium channels are comprised of four subunits, and each subunit has a pore domain and a voltage-sensing domain (VSD). The four pore domains assemble to form one single central pore, and the four individual VSDs control the gate of the pore. Recently, a family of voltage-gated proton channels, such as H(V) or voltage sensor only protein (VSOP), was discovered that contain a single VSD but no pore domain. It has been assumed that VSOP channels are monomeric and contain a single VSD that functions as both the VSD and the pore domain. It remains unclear, however, how a protein that contains only a VSD and no pore domain can conduct ions. Using fluorescence measurements and immunoprecipitation techniques, we show here that VSOP channels are expressed as multimeric channels. Further, FRET experiments on constructs with covalently linked subunits show that VSOP channels are dimers. Truncation of the cytoplasmic regions of VSOP reduced the dimerization, suggesting that the dimerization is caused mainly by cytoplasmic protein-protein interactions. However, these N terminus- and C terminus-deleted channels displayed large proton currents. Therefore, we conclude that even though VSOP channels are expressed mainly as dimers in the cell membrane, single VSOP subunits could function independently as proton channels.


Development of pig embryos by nuclear transfer of cultured fibroblast cells.
Pig fibroblast cells were transferred to enucleated oocytes by micromanipulation and electrofusion. The donor cells used for nuclear transfer were synchronized in presumptive G0 by serum starvation. In the first experiment, nuclear transfer was performed with fibroblasts that had either a smooth or a rough surface. A significant difference (p < 0.05) in the percentage of chromosome condensation (39.5%, 15/38 and 16.6%, 5/30) and nuclear formation (36.8%, 14/38 and 16.3%, 8/49) was found between the reconstructed embryos derived from the cells with smooth surface and with rough surfaces, respectively. The percentage of chromosome condensation (42.5%, 17/40 and 19.6%, 11/56) and nuclear formation (38.3%, 23/60 and 18.8%, 9/48) were higher (p < 0.05) in reconstructed embryos derived from small (15 microm) donor cells compared to large donor cells (20 microm), respectively. The percentage nuclei at 3 different time points (3, 6, and 9 hours in culture medium) was higher (p = 0.003) in the reconstructed embryos activated by thimerosal and dithiothreitol (20%, 36%, and 41.3%) compared to those without activation treatment (0%, 11.8%, and 22.2%). In addition, there was an increased percentage with nuclei as the time in culture increased from 3 to 9 hours (p = 0.029). The percentages of chromosome condensation (34.6%; 9/26) and nuclear formation (33.3%; 9/27) in nuclear transfer embryos were similar. The rate of blastocysts/morulae development (14.0%; 6/43) was low. However, 2 cavitated embryos (presumptive blastocysts) with 14 and 11 nuclei and 1 morula with 8 nuclei were obtained. This together with the above evidence indicate that the nuclei from pig fibroblast cells can be partially reprogrammed, which suggests that transfer of nuclei from fibroblast cells to in vitro matured oocytes resulting in production of identical or genetically altered pigs may be possible.


Participatory Work Flow Analysis prior to Implementation of EPR: A Method to Discover Needs for Change.
We need to know how clinicians' use their paper based medical records to secure a local participation in the implementation process of Electronic Patient Record (EPR). In what way their use of paper based medical records is related to, or dependent on, other people and artifacts. The research presented in this paper was done as part of a work flow analysis of the particular sequence of doing rounds at two distinct hospital departments, a thoracic surgical and a cardiology department. It was designed to develop a method that would let the hospital clinicians obtain knowledge on the daily use of the paper based medical records during rounds and thus make use of their local knowledge to start a discussion on changes in organization and knowledge before EPR can be successfully implemented.We are grateful to the following clinicians, Cathrine H. Foss, MD. Pauline Schrødder, MD. Morten Smerup MD and Niels Henrik Stålsen, MD and the medical director Børge H. Jensen, MD, Skejby Sygehus, Aarhus University Hospital for sharing their knowledge with us.The aim was to investigate how paper based medical records are currently used at two wards.


Causal attribution and illness perception: a cross-sectional study in Mexican patients with psychosis.
Health psychology researchers have begun to focus greater attention on people's beliefs about health/illness since these beliefs can clearly affect behavior. This cross-sectional study aimed at (1) identifying the most common factors psychotic patients attribute their illness to and (2) assessing the association between causal attribution and illness perception (cognitive, emotional, and comprehensibility dimensions). Sixty-two patients (56.5% females) who had been treated for psychosis at a public psychiatric hospital in Mexico answered the Angermeyer and Klusmann Illness Attribution Scale and the Brief Illness Perception Questionnaire. Results showed that most patients attributed psychosis onset to social factors and that attribution to their personality might have an overwhelmingly negative effect on their lives. Acknowledging psychotic patient attributional beliefs and considering them in clinical practice could improve treatment efficacy and overall recovery success. This is particularly important in psychosis, since symptoms are often severe and/or persistent and require long-term treatment.


Cardio-protective effects of Corocalm on acute myocardial ischemia/reperfusion injury in rats.
To investigate the cardio-protective effects of Corocalm on acute myocardial ischemia in rats, and to explore its possible therapeutic mechanisms. The acute ischemic model was prepared by ligating the left anterior descending (LAD) coronary artery in rats. The animals were divided into 6 groups, 8 in each group. The sham operated group underwent heart exposure without ligation and were treated with normal saline 3 ml/kg, while the other 5 groups, the model groups, consisted of acceptable acute ischemic model rats and were also treated with normal saline, with the Guanxin Capsule (GXC) group treated with refined GXC, 600 mg/kg, the low and high dose Corocalm groups treated with 85 mg/kg and 340 mg/kg of Corocalm respectively, and the Diltiazem group, treated with Diltiazem 5 mg/kg, with all the tested drugs prepared with normal saline into equal volume (3 ml/kg) and administrated once via duodenum 10 min before ligation. Myocardial infarction area was determined by the quantitative histological assay with nitroblue tetrazolium (N-BT) stain. And the levels of creatine phosphokinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) content, and the activity of superoxide dismutase (SOD) in serum were measured by biochemical assay and spectrophotometry respectively. Besides, the blood viscosity in another 50 rats was determined, who received for 7 successive days oral administration with different concentration of Corocalm or aspirin. It showed that low and high dose Corocalm could significantly reduce the infarction area, inhibit the increase of serum CK, LDH activity and MDA content, and enhance the SOD activity after ischemia/reperfusion. The whole blood viscosity at different shear rates in rats treated with high dose Corocalm was significantly lower than those treated with normal saline (P < 0.05). Corocalm has favourable protective effects on heart in ischemic condition, the effect of which might be through its actions in inhibiting CK and LDH activity, scavenging oxygen free radicals, and lowering blood viscosity.


Improved Metabolic Models for E. coli and Mycoplasma genitalium from GlobalFit, an Algorithm That Simultaneously Matches Growth and Non-Growth Data Sets.
Constraint-based metabolic modeling methods such as Flux Balance Analysis (FBA) are routinely used to predict the effects of genetic changes and to design strains with desired metabolic properties. The major bottleneck in modeling genome-scale metabolic systems is the establishment and manual curation of reliable stoichiometric models. Initial reconstructions are typically refined through comparisons to experimental growth data from gene knockouts or nutrient environments. Existing methods iteratively correct one erroneous model prediction at a time, resulting in accumulating network changes that are often not globally optimal. We present GlobalFit, a bi-level optimization method that finds a globally optimal network, by identifying the minimal set of network changes needed to correctly predict all experimentally observed growth and non-growth cases simultaneously. When applied to the genome-scale metabolic model of Mycoplasma genitalium, GlobalFit decreases unexplained gene knockout phenotypes by 79%, increasing accuracy from 87.3% (according to the current state-of-the-art) to 97.3%. While currently available computers do not allow a global optimization of the much larger metabolic network of E. coli, the main strengths of GlobalFit are already played out when considering only one growth and one non-growth case simultaneously. Application of a corresponding strategy halves the number of unexplained cases for the already highly curated E. coli model, increasing accuracy from 90.8% to 95.4%.


Resorptive clearance and transepithelial potential difference in capsaicin-treated F344 rats.
The long-term effects of substance P (SP) depletion on epithelial integrity were assessed by measurements of airway transepithelial potential difference (PD) and resorptive clearance. Both techniques are highly sensitive to differences in epithelial permeability. PD (mV) was assayed with a KCl-saturated agar bridge technique in the lower trachea of Fischer 344 rats depleted of SP by neonatal capsaicin treatment. Capsaicin treatment is known to ablate a subpopulation of primary afferent fibers containing SP. Resorptive clearance (clearance in 1 h) was measured with 99mTc-labeled diethylenetriaminepentaacetic acid administered as a 100-microliters (100 microCi) bolus. Depletion of SP by neonatal treatment with capsaicin resulted in a highly significant increase in resorptive clearance (P less than 0.001). There was also a significant difference in PD in the lower trachea, the values being less negative for the capsaicin-treated rats (P less than 0.005). The increase in resorptive clearance may reflect the leakiness of the epithelial membrane, as also suggested by the decrease in PD. Aside from its known involvement as a neurotransmitter in neurogenic inflammation, SP may, under normal physiological conditions, have an additional role in the maintenance of epithelial barrier function.


Women and the opioid crisis: historical context and public health solutions.
Driven by a legitimate but overly opioid-focused response to pain, the United States is currently experiencing an opioid crisis, a crisis with parallels to the first opioid epidemic at the turn of the 20th century. Women, particularly white reproductive-age women, are increasingly the face of the opioid crisis. Given the penetration of opioid misuse and addiction across all income and insurance strata, any provider who cares for women needs to be prepared to assess and evaluate opioid use, misuse, and addiction. Although responsible opioid prescribing is essential, treatment capacity must be expanded and be inclusive of the unique needs of women. However, the public and public health response to the opioid crisis must include rolling back the war on drugs. The continued criminalization of the public health issue of drug use and the medical condition of addiction is unethical, ineffective, and inhumane.


Computer simulations of atherosclerotic plaque growth in coronary arteries.
A three dimensional mathematical model with a linear plaque growth function was developed to investigate the geometrical adaptation of atherosclerotic plaques in coronary arteries and study the influences of flow wall shear stress (WSS), blood viscosity and the inlet flow rate on the growth of atherosclerotic plaques using computational plaque growth simulations. The simulation results indicated that the plaque wall thickness at the neck of the stenosis increased at a decreasing rate in the atherosclerosis progression. The simulation results also showed a strong dependence of the plaque wall thickness increase on the blood viscosity and the inlet flow rate. The progression rate in a coronary artery was lower with a higher inlet velocity flow rate and higher with a smaller value of the blood viscosity.


Reducing sow confinement during farrowing and in early lactation increases piglet mortality.
The aim of this study was to investigate the effect of sow confinement and nonconfinement during parturition and early lactation on the performance of sows and piglets prior to weaning. Sows and their litters were housed in either a conventional farrowing crate (control; 1.7 × 2.4 m) or a swing-sided pen (2.8 × 2.15 m). Sows housed in the swing-sided pen had the crate open (open) or closed (closed) during farrowing and opened on d 3 (LAC3) or 7 (LAC7) of lactation. Data are means ± SEM. The numbers of total and live-born piglets were not different between treatments and averaged 13.1 ± 0.4 and 12.3 ± 0.2 piglets/litter, respectively. Sows housed in a farrowing crate had a greater ( = 0.03) number of stillborn piglets compared with open sows from pens (1.1 ± 0.2 vs. 0.6 ± 0.1 piglets/litter, respectively). Live-born piglet mortality before litter equalization on d 1 was greater ( < 0.01) for open sows compared with closed and control sows (1.6 ± 0.2 vs. 0.9 ± 0.2 vs. 1.1 ± 0.1 piglets/litter, respectively) and was largely explained by an increase in the incidence of piglets overlain ( < 0.01) in the open compared to closed and control sows (1.3 ± 0.1 vs. 0.5 ± 0.1 vs. 0.8 ± 0.1 piglets/litter, respectively). Overlay mortality between d 3 and 7 of lactation was greater ( = 0.03) in LAC3 sows compared to LAC7 and control sows (0.4 ± 0.1 vs. 0.2 ± 0.1 vs. 0.2 ± 0.1 piglets/litter, respectively). Treatment did not affect either the incidence or cause of piglet mortality after d 7 of lactation ( > 0.05). Total live-born piglet mortality from birth until weaning for the control, closedLAC7, closedLAC3, openLAC7, and openLAC3 was 1.86 ± 0.19, 1.95 ± 0.23, 2.10 ± 0.39, 2.45 ± 0.27, and 3.74 ± 0.48, piglets/litter, respectively. Total live-born piglet mortality from birth until weaning was greater in the openLAC3 and openLAC7 treatments compared to control ( < 0.01), and openLAC3 was also greater than openLAC7, closedLAC3, and closedLAC7 ( < 0.01). The current data indicated that reducing sow confinement during parturition decreased stillborn number but increased live-born piglet mortality compared to a farrowing crate, and removing confinement on d 3 of lactation further increased total piglet mortality compared to removing sow confinement on d 7 of lactation in sows that farrowed open. Sows that were confined during farrowing and until d 3 or 7 of lactation in a swing-sided pen had a similar piglet mortality compared to those in a farrowing crate.


Exploration of eosinopenia as a diagnostic parameter to differentiate sepsis from systemic inflammatory response syndrome: Results from an observational study.
Initial differentiation of sepsis from systemic inflammatory response syndrome (SIRS) is of prime importance for early institution of appropriate treatment. This study aimed to compare the differential diagnostic efficacy of absolute eosinophil count (AEC - a routinely available economic marker) with total leukocyte count (TLC) and procalcitonin (PCT - a costly marker available only in specialized settings). In this prospective observational study, 170 patients of sepsis (severe sepsis = 125; SIRS = 45) were enrolled. AEC, TLC, and PCT were measured in the blood of all patients at the time of admission and data analyzed statistically. Median AEC was 0 cells/mm(3) in both SIRS and sepsis. TLC and PCT levels were significantly higher (P < 0.001) in culture negative, culture positive, and overall sepsis groups in comparison to SIRS group. At a cutoff of < 50 cells/mm(3), AEC demonstrated a sensitivity and specificity of 23% and 68%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TLC were 57%, 71%, 85%, 37% and of PCT were 82.4%, 82.2%, 93%, and 63%, respectively with area under curve of 0.455 for AEC, 0.640 for TLC, 0.908 for PCT. This study suggests that eosinopenia is not a reliable diagnostic tool to differentiate sepsis from SIRS. PCT and TLC are better differential diagnostic biomarkers.


Electrical properties and mechanical stability of anchoring groups for single-molecule electronics.
We report on an experimental investigation of transport through single molecules, trapped between two gold nano-electrodes fabricated with the mechanically controlled break junction (MCBJ) technique. The four molecules studied share the same core structure, namely oligo(phenylene ethynylene) (OPE3), while having different aurophilic anchoring groups: thiol (SAc), methyl sulfide (SMe), pyridyl (Py) and amine (NH2). The focus of this paper is on the combined characterization of the electrical and mechanical properties determined by the anchoring groups. From conductance histograms we find that thiol anchored molecules provide the highest conductance; a single-level model fit to current-voltage characteristics suggests that SAc groups exhibit a higher electronic coupling to the electrodes, together with better level alignment than the other three groups. An analysis of the mechanical stability, recording the lifetime in a self-breaking method, shows that Py and SAc yield the most stable junctions while SMe form short-lived junctions. Density functional theory combined with non-equlibrium Green's function calculations help in elucidating the experimental findings.


Postoperative Pyoderma Gangrenosum in Children: The Case Report of a 13-Year-Old Boy With Pyoderma Gangrenosum After Hip Reconstruction Surgery and a Review of the Literature.
Postoperative pyoderma gangrenosum (PG) is a neutrophilic dermatosis and pathergic reaction at surgical sites. Reports of children with postoperative PG are rare in the literature. We report the case of a 13-year-old boy without any known preexisting illnesses, who developed severe systemic response and wound deterioration after elective hip reconstruction surgery. The working diagnosis of necrotizing fasciitis was later determined to be postoperative PG. The patient was successfully treated by the systemic application of corticosteroids. Postoperative PG is a very rare complication after surgery, especially in children. If mistaken for necrotizing fasciitis, it can substantially mutilate a patient because PG is worsened by surgical debridement. It can be treated successfully only by corticosteroids and other immunosuppressive drugs. Level IV-this is a case report.


Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity.
A robust gonadotropin-releasing hormone (GnRH) surge is a prerequisite signal for the luteinizing hormone (LH) surge that triggers ovulation. In rodents, the GnRH surge is initiated by elevated estradiol and a diurnal switch in estrogen action from negative to positive feedback. The ability of constant estradiol treatment to induce daily LH surges was tested in adult mice that were ovariectomized (OVX) or OVX and treated with estradiol implants (OVX+E). LH in OVX mice showed no time-of-day difference. In contrast, OVX+E mice showed a large LH surge (8- to 124-fold relative to the a.m.) in p.m. samples on d 2-5 post-OVX+E. Targeted extracellular recordings were used to examine changes in firing activity of GnRH neurons in brain slices. There was no time-of-day difference in cells from OVX mice. In contrast, OVX+E cells recorded in the p.m. showed an increased mean firing rate and instantaneous firing frequency, which could increase GnRH release, and decreased duration of quiescence between bouts of firing, possibly reflecting increased pulse frequency, compared with cells recorded in the a.m. In the a.m., OVX+E cells showed changes in GnRH neuron firing reflecting negative feedback compared with OVX cells, whereas in the p.m., OVX+E cells exhibited changes suggesting positive feedback. These data indicate that differences in pattern and level of individual GnRH neuron firing may reflect the switch in estradiol action and underlie GnRH surge generation. The persistence of altered GnRH neuron activity in slices indicates that this approach can be used to study the neurobiological mechanisms of surge generation.


Arnica compositum, Hekla lava and Acidum Nitricum Together are Superior to Arnica compositum Alone in the Local Treatment of Symptomatic Calcific Periarthritis of the Shoulder: A Pilot Study.
To evaluate the usefulness of Arnica compositum (AC) + Acidum nitricum (AN) + Hekla lava (HL) ointment in Emergency Medicine Department (EMD) as alternative nonpharmacological local treatment of patients with symptomatic calcific periarthritis of the shoulder (CPS) and to compare the effectiveness of this mixture against AC ointment alone. A series of 41 consecutive patients (20 women, 19 men, median age 49 years, range 25-80 years) with non-traumatic painful unilateral CPS were randomly assigned to receive local treatment with AC+AN+HL ointment mixture (Group A, cases, N=21) or AC ointment alone (Group B, controls, N=20). The radiological Gartner classification of the CPS, and the quantification of pre- and post-treatment pain intensity using a Visual Analogue Scale (VAS) were obtained. The orthopedic evaluation of Shoulder Motion (SM) was also performed. The use of painkillers was reported as a number of doses needed. Age, gender distribution, Gartner type, main calcification size, baseline VAS (VAS-0) and degree of SM did not differ (p=NS) between Groups. After 3-day therapy, the reduction of pain in Group A (4.5±2.5) was superior to that observed in Group B (2.7±2.6) (p =0.03). The same result was observed in the improvement of SM in Group A (69.4±24.9) than in Group B (51.1±21.1) (p =0.015). No local or general adverse effects were noted. The number of doses of paracetamol was similar, but Group A patients used less ibuprofen (p =0.007). Local administration of the AC+AN+HL ointment mixture, which in our pilot study was superior to AC alone, could be safely suggested as an alternative uneventful treatment of patients with CPS.


Accounting for Range Uncertainties in the Optimization of Combined Proton-Photon Treatments Via Stochastic Optimization.
Proton treatment slots are a limited resource. Combined proton-photon treatments, in which most fractions are delivered with photons and only a few with protons, may represent a practical solution to optimize the allocation of proton resources over the patient population. We demonstrate how a limited number of proton fractions can be optimally used in multimodality treatments and address the issue of the robustness of combined treatments against proton range uncertainties. Combined proton-photon treatments are planned by simultaneously optimizing intensity modulated radiation therapy and proton therapy plans while accounting for the fractionation effect through the biologically effective dose model. The method was investigated for different tumor sites (a spinal metastasis, a sacral chordoma, and an atypical meningioma) in which organs at risk (OARs) were located within or near the tumor. Stochastic optimization was applied to mitigate range uncertainties. In optimal combinations, proton and photon fractions deliver similar doses to OARs overlaying the target volume to protect these dose-limiting normal tissues through fractionation. Meanwhile, parts of the tumor are hypofractionated with protons. Thus, the total dose delivered with photons is reduced compared with simple combinations in which each modality delivers the prescribed dose per fraction to the target volume. The benefit of optimal combinations persists when range errors are accounted for via stochastic optimization. Limited proton resources are optimally used in combined treatments if parts of the tumor are hypofractionated with protons and near-uniform fractionation is maintained in serial OARs. Proton range uncertainties can be efficiently accounted for through stochastic optimization and are not an obstacle for clinical application.


Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD.
Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD. We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively. Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in RUNX1 were positively correlated with the CBCL scores, and DNA methylation in MYO1G correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in GFI1 correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of RUNX1 methylation levels with the CBCL score. The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models. This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy.


Long-standing malignant pancreatic carcinoid treated with octreotide.
A male presented with a metastatic, plasma serotonin-secreting (high 5-HIAA in urine), malignant pancreatic carcinoid with a carcinoid-like syndrome, and was assessed using ultrasounds (US), computerized tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) and Octreoscan; he sequentially received chemotherapy, interferon and octreotide, with long-term, 12-year survival after diagnosis. Given this unusual case, the second reported in our country, the overall literature is reviewed.


NADPH oxidase NOX5-S and nuclear factor κB1 mediate acid-induced microsomal prostaglandin E synthase-1 expression in Barrett's esophageal adenocarcinoma cells.
The mechanisms of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not known. Cycloxygenase-2 (COX-2)-derived prostaglandin E₂ (PGE₂) has been shown to be important in esophageal tumorigenesis. We have shown that COX-2 mediates acid-induced PGE₂ production. The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known. We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells. Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA. Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation. Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor κB (NF-κB) in vivo activation reporter plasmid pNF-κB-Luc. Knockdown of NF-κB1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE₂ production. Two novel NF-κB binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter. We conclude that mPGES1 mediates acid-induced increase in PGE₂ production and cell proliferation. Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-κB1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA.


Effects of Supplementation with Dried Neem Leaf Extract on Lipid Peroxidation and Antioxidant Enzyme mRNA Expression in the Pectoralis Major Muscle of Broiler Chickens.
This study was conducted to evaluate the effects of dietary supplementation of dried neem (Azadirachta indica) leaf extract (DNE) on lipid peroxidation and the expression of genes encoding mRNAs in antioxidant enzymes in the pectoralis major muscle of chickens. A total of 24 male broiler chickens (ROSS308) were divided into three groups (n=8) at 21 days of age. The control group of chickens was fed a basal diet, and the remaining two groups of chickens were fed a basal diet supplemented with DNE at a concentration of 0.5% or 2.0% until 35 days of age. Growth performance (body weight, weight gain, feed intake, and feed conversion ratio) and tissue weights did not differ among the three groups. The 2.0% DNE-supplemented diet decreased the muscle malondialdehyde content, a marker of lipid peroxidation, and drip loss compared to the control chickens. In addition, the expression of genes encoding mRNAs of antioxidant enzymes (i.e., Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, glutathione peroxidase 7, and catalase) were higher in the pectoralis major muscle of chickens fed the 2.0% DNE-supplemented diet than in the control chickens. Therefore, DNE supplementation increased the expression of genes encoding mRNAs in antioxidant enzymes and reduced lipid peroxidation and drip loss in the pectoralis major muscle of broiler chickens.


Tolerant Staphylococcus aureus causing vertebral osteomyelitis.
Vertebral osteomyelitis due to Staphylococcus aureus was suppressed by not cured by optimal therapy with nafcillin sodium; cure eventually was achieved by treatment with cefazolin sodium and gentamicin sulfate. This is vivo result correlated with in vitro observations that showed that the infecting organism was inhibited but not killed by prolonged incubation with nafcillin or cefazolin; killing was readily achieved in vitro by adding subinhibitory concentrations of gentamicin. Bacterial tolerance in this case appeared to be responsible for the failure of vertebral osteomyelitis to be cured by accepted therapy with beta-lactam antibiotics.


Fast Preparation of Porous MnO/C Microspheres as Anode Materials for Lithium-Ion Batteries.
Porous MnO/C microspheres have been successfully fabricated by a fast co-precipitation method in a T-shaped microchannel reactor. The structures, compositions, and electrochemical performances of the obtained MnO/C microspheres are characterized by X-ray diffraction, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller analysis, charge-discharge testing, cyclic voltammograms, and electrochemical impedance spectra. Experimental results reveal that the as-prepared MnO/C, with a specific surface area of 96.66 m²·g-1 and average pore size of 24.37 nm, exhibits excellent electrochemical performance, with a discharge capacity of 655.4 mAh·g-1 after cycling 50 times at 1 C and capacities of 808.3, 743.7, 642.6, 450.1, and 803.1 mAh·g-1 at 0.2, 0.5, 1, 2, and 0.2 C, respectively. Moreover, the controlled method of using a microchannel reactor, which can produce larger specific surface area porous MnO/C with improved cycling performance by shortening lithium-ion diffusion distances, can be easily applied in real production on a large scale.


Biochar applications for treating potentially toxic elements (PTEs) contaminated soils and water: a review.
Environmental pollution with potentially toxic elements (PTEs) has become one of the critical and pressing issues worldwide. Although these pollutants occur naturally in the environment, their concentrations are continuously increasing, probably as a consequence of anthropic activities. They are very toxic even at very low concentrations and hence cause undesirable ecological impacts. Thus, the cleanup of polluted soils and water has become an obligation to ensure the safe handling of the available natural resources. Several remediation technologies can be followed to attain successful remediation, i.e., chemical, physical, and biological procedures; yet many of these techniques are expensive and/or may have negative impacts on the surroundings. Recycling agricultural wastes still represents the most promising economical, safe, and successful approach to achieving a healthy and sustainable environment. Briefly, biochar acts as an efficient biosorbent for many PTEs in soils and waters. Furthermore, biochar can considerably reduce concentrations of herbicides in solutions. This review article explains the main reasons for the increasing levels of potentially toxic elements in the environment and their negative impacts on the ecosystem. Moreover, it briefly describes the advantages and disadvantages of using conventional methods for soil and water remediation then clarifies the reasons for using biochar in the clean-up practice of polluted soils and waters, either solely or in combination with other methods such as phytoremediation and soil washing technologies to attain more efficient remediation protocols for the removal of some PTEs, e.g., Cr and As from soils and water.


Including indoor offgassed emissions in the life cycle inventories of wood products.
Volatile organic compounds (VOCs) that negatively affect human health are emitted from wood products used indoors. However, the existing life cycle inventories of these products only document the emissions occurring during production and disposal phases. Consequently, the life cycle assessment (LCA) of indoor wooden products conducted using these inventories neglect the use-phase impacts from exposure to offgassed VOCs and therefore underestimate the product's total environmental impact. This study demonstrates a methodology to calculate the use phase inventory and the corresponding human health impacts resulting from indoor use of any VOC emitting product. For the five most commonly used types of boards used in indoor wood products, the mass of each VOC emitted into the indoor compartment over their service life was calculated by statistically analyzing data from 50 published chamber testing studies. Uncertainty was assessed using Monte Carlo simulations. The calculated inventory data were used in a case study to calculate and compare the health impacts of five different wooden floorings made of above materials. The results show that the use-phase human-toxicity impacts are an order of magnitude higher than those occurring during the rest of the flooring's life cycle. The factors influencing the offgassing of VOCs from wood products and measures to reduce exposure are discussed.


Case report: Case series featuring anastomotic colonic adenocarcinoma following jejunoileal bypass requiring oncologic resection and jejunoileal bypass reversal.
Like all surgical fields, bariatric surgery has evolved immensely, so much so that previous procedures are now obsolete. For instance, the jejunoileal bypass has fallen out of favor after severe metabolic consequences resulted in prolonged morbidity and even mortality. Despite this, several patients persevered long enough to develop other pathology, such as cancer. This progression has been validated in animal models but not human patients. Nonetheless, contemporary surgeons may encounter situations where they must resect and re-establish intestinal continuity in patients with this antiquated anatomy. When faced with this scenario, the question of whether or not the previously bypassed small bowel can be safely reunited plagues the surgeon remains unanswered. Unfortunately, the literature does not effectively answer this question, even anecdotally through case reports or series. Therefore, we share our experience with three patients who developed colon cancer following jejunoileal bypass and subsequently underwent oncologic resection with simultaneous reversal of their jejunoileal bypasses.


Cardiac troponins in renal failure - time for an optimistic consensus?
Elevated cardiac troponin concentrations are now accepted as the gold standard biochemical markers for the diagnosis of myocardial damage in patients with unstable coronary syndromes, having also a demonstrated value in early risk stratification and in adopting different therapeutic strategies. The specificity and sensitivity of cardiac troponins for diagnosis of acute coronary diseases in renal failure have been a point of confusion over the past decade, mainly because of moderate elevations of these cardiac biomarkers, commonly observed in patients with chronic renal dysfunction and without any significant myocardial damage. This review discusses the cardiac troponins, their biochemistry, their currently accepted cut-off values and their real significance in chronic renal failure (CRF), concluding that troponins maintain their diagnostic and prognostic values in patients with CRF, being predictive not only of cardiovascular mortality but also of general mortality in this patient group.


Limitation on prepulse level for cone-guided fast-ignition inertial confinement fusion.
The viability of fast-ignition (FI) inertial confinement fusion hinges on the efficient transfer of laser energy to the compressed fuel via multi-MeV electrons. Preformed plasma due to the laser prepulse strongly influences ultraintense laser plasma interactions and hot electron generation in the hollow cone of an FI target. We induced a prepulse and consequent preplasma in copper cone targets and measured the energy deposition zone of the main pulse by imaging the emitted K_{alpha} radiation. Simulation of the radiation hydrodynamics of the preplasma and particle in cell modeling of the main pulse interaction agree well with the measured deposition zones and provide an insight into the energy deposition mechanism and electron distribution. It was demonstrated that a under these conditions a 100 mJ prepulse eliminates the forward going component of approximately 2-4 MeV electrons.