Direct and indirect effect of predators on Anopheles gambiae sensu stricto.
The increased insecticides resistance by vectors and the ecological harm imposed by insecticides to beneficial organisms drawback mosquitoes chemical control efforts. Biological control would reduce insecticides tolerance and yet biodiversity friend. The predatory and non-predatory effects of Gambusia affinis and Carassius auratus on gravid Anopheles gambiae sensu strict and larvae survivorship were assessed. In determining predation rate, a single starved predator was exposed to third instar larvae of An. gambiae s.s. in different densities 20, 60 and 100. Six replicates in each of the densities for both predators, G. affinis and C. auratus, were set up. The larvae densities were monitored in every 12 and 24 h. In assessing indirect effects: An. gambiae s.s. first instar larvae of three densities 20, 60 and 100 were reared in water from a predator habitat and water from non-predator habitat. Larvae were monitored until they emerged to adults where larval survivorship and sex ratio (Female to total emerged mosquitoes) of the emerged adult from both water habitats were determined. Oviposition preference: twenty gravid females of An. gambiae s.s. were provided with three oviposition choices, one containing water from predator habitat without a predator, the second with water from a predator with a predator and the third with water from non-predatory habitat. The number of eggs laid on each container was counted daily. There were 20 replicates for each predator, G. affinis and C. auratus. Survivorship of An. gambiae s.s. larvae reared in water from non-predator habitat was higher than those reared in water from the predator habitats. Many males emerged in water from non-predatory water habitats while more females emerged from predator's habitats water. More eggs laid in tap water than in water from predator habitat and water from predator habitat with live predator. In 24 h, a starved C. auratus and G. affinis were able to consume 100% of the 3rd instar larvae. The findings from this study suggest that G. affinis and C. auratus may be useful in regulating mosquito populations in favour of beneficial insects. However, a small scale trial shall be needed in complex food chain system to ascertain the observed predation and kairomones effects.


Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients.
Fifty-one renal allograft recipients (15-62 years old, mean: 37 years) were monitored for 2.5-6.5 years (average: 4.3 years) after surgery by using magnetic resonance imaging (MRI) to find (i) initial signs of osteonecrosis of the femoral head (ONF), (ii) the presence of bone marrow edema as an initial sign of ONF, (iii) any changes of MRI patterns, and (iv) the relationship between these MRI findings and prognosis. MRI was performed preoperatively (baseline), and whenever possible during the 6-9th week, 12-16th week, 12th month, and yearly thereafter. T1- and T2-weighted images were obtained by using a spin echo technique. Abnormalities were first detected on MRI of 23 femoral heads in 13 patients between 6 weeks and 12 months. All lesions first showed a low intensity band on T1-weighted images and a high intensity band on T2-weighted images. No symptoms or diffuse patterns, such as bone marrow edema, preceded the appearance of the band pattern. After the 12th month, no new abnormal findings on MRI were detected. The lesions were classified into Type A, B, or C, according to the location. 12 of the 16 Type C femoral head lesions, which extend beyond the medial two thirds of the weight-bearing portion of the acetabulum, became symptomatic 7-14 months after transplantation and then progressed to collapse. Bone marrow edema appeared with radiological collapse and symptoms. With the exception of five lesions in three patients who failed to be MR imaged until 12 months postoperatively, all lesions were first detected on MRI within 16 weeks after transplantation. We therefore postulate that the ischemic event that causes ONF will have occurred within 12 weeks after transplantation, considering the time lag of reparative reaction to the dead bone.


Afferents of the mouse linear nucleus.
The linear nucleus (Li) was identified in 1978 from its projections to the cerebellum. However, there is no systematic study of its connections with other areas of the central nervous system possibly due to the challenge of injecting retrograde tracers into this nucleus. The present study examines its afferents from some nuclei involved in motor and cardiovascular control with anterograde tracer injections. BDA injections into the central amygdaloid nucleus result in labeled fibers to the ipsilateral Li. Bilateral projections with an ipsilateral dominance were observed after injections in a) jointly the paralemniscal nucleus, the noradrenergic group 7/ Köllike -Fuse nucleus/subcoeruleus nucleus, b) the gigantocellular reticular nucleus, c) and the solitary nucleus/the parvicellular/intermediate reticular nucleus. Retrogradely labeled neurons were observed in Li after BDA injections into all these nuclei except the central amygdaloid and the paralemniscal nuclei. Our results suggest that Li is involved in a variety of physiological functions apart from motor and balance control it may exert via its cerebellar projections.


Regulation of Ca2+ release from sarcoplasmic reticulum in skeletal muscles.
Ca2+ release from skeletal sarcoplasmic reticulum (SR) could be regulated by at least three mechanisms: 1) Ca2+, 2) calmodulin, and 3) Ca2+/calmodulin-dependent phosphorylation. Bell-shaped Ca(2+)-dependence of Ca2+ release from both actively- and passively-loaded SR vesicles suggest that opening and closing of the Ca2+ release channel could be regulated by [Ca2+o]. The time- and concentration-dependent inhibition of Ca2+ release from skeletal SR by calmodulin was also studied using passively-Ca2+ loaded SR vesicles. Up to 50% of Ca2+ release was inhibited by calmodulin (0.01-0.5 microM); this inhibition required 5-15 min preincubation time. The hypothesis that Ca2+/calmodulin-dependent phosphorylation of a 60 kDa protein regulates Ca2+ release from skeletal SR was tested by stopped-flow fluorometry using passively-Ca2+-loaded SR vesicles. Approximately 80% of the initial rates of Ca(2+)-induced Ca2+ release was inhibited by the phosphorylation within 2 min of incubation of the SR with Mg-ATP and calmodulin. We identified two types of 60 kDa phosphoproteins in the rabbit skeletal SR, which was distinguished by solubility of the protein in CHAPS. The CHAPS-soluble 60 kDa phosphoprotein was purified by column chromatography on DEAE-Sephacel, heparin-agarose, and hydroxylapatite. Analyses of the purified protein indicate that the CHAPS-soluble 60 kDa protein is an isoform of phosphoglucomutase (PGM). cDNAs encoding isoforms of PGM were cloned and sequenced using synthetic oligonucleotides. Two types of PGM isoforms (Type I and Type II) were identified. The translated amino acid sequences show that Type II isoform is SR-form.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanics and remodelling of cell packings in epithelia.
Epithelia are sheets of cells that are dynamically remodelled by cell division and cell death during development. Here we describe the cell shapes and packings as networks of polygons: stable and stationary network configurations obey force balance and are represented as local minima of a potential function. We characterize the physical properties of this vertex model, including the set of ground states, and the energetics of topological rearrangements. We furthermore discuss a quasistatic description of cell division that allows us to study the mechanics and dynamics of tissue remodelling during growth. The biophysics of cells and their rearrangements can account for the morphology of cell packings observed in experiments.


Adolescent sleep patterns are associated with the selection of positive and negative emotional situations.
Poor sleep in youth is a risk factor for experiencing increased negative emotions and decreased positive emotions, which can contribute to the development of later emotional disorders. Understanding of specific processes that produce sleep-related alterations in emotion is limited, although preliminary studies suggest changes in the ability to appropriately regulate or control emotions as one mechanism. The current study builds on this research by examining the relationship between adolescent sleep patterns and a previously unexplored emotion regulation strategy: situation selection. Situation selection strategies are implemented prior to the onset of an emotional experience via decisions to approach rewarding/positive situations or avoid unwanted/negative situations. Fifty-four healthy adolescents (ages 13-17 years) completed 1 week of actigraphy and assessments of situation selection using: (a) trait-based questionnaires; (b) daily reports; and (c) an experimental lab task where participants were given the option to watch various emotional video clips of their choice. Greater variability in sleep timing was associated with less avoidance of negative emotional situations, and a longer sleep-onset latency was associated with more avoidance of negative emotional situations. Greater variability in nightly sleep patterns was also associated with decreased tendencies to select positive emotional situations as assessed by trait questionnaires, daily reports, and the lab-based task, but only for boys. These findings add to a growing body of research on sleep and emotional experience, and provide further support for the importance of intra-individual variability of sleep patterns in youth.


Hymenobacter properus sp. nov., Hymenobacter ruricola sp. nov., and Hymenobacter jeongseonensis sp. nov., three new species isolated from mountain and beach soil in South Korea.
Three Gram-stain-negative, aerobic, circular, convex, red-colored and rod-shaped bacterial strains, designated BT439T, BT662T and BT683T were obtained from soil collected in South Korea. The phylogenetic analysis based on 16S rRNA gene sequences of the strains revealed a distinct lineage within the genus Hymenobacter. The complete genome sequence of strains BT439T, BT662T and BT683T is 5,542,738 bp, 5,964,541 bp, and 5,192,601 bp size, respectively. All three strains were found to have MK-7 as the major respiratory quinone. The major polar lipids of strains BT439T and BT662T were identified as phosphatidylethanolamine, aminophospholipids and amino lipids. Strain BT683T contained phosphatidylethanolamine. The major cellular fatty acids of strain BT439T were iso-C15:0, summed feature 3 (C16:1 ω6c/C16:1 ω7c) and anteiso-C15:0; strain BT662T possessed iso-C15:0 and summed feature 3 (C16:1 ω6c/C16:1 ω7c); strain BT683T were summed feature 3 (C16:1 ω6c/C16:1 ω7c), C16:1 ω5c, iso-C15:0 and anteiso-C15:0. Based on the polyphasic analysis, strains BT439T, BT662T and BT683T can be suggested as three novel bacterial species within the genus Hymenobacter and the proposed names are Hymenobacter properus sp. nov., Hymenobacter ruricola sp. nov. and Hymenobacter jeongseonensis sp. nov., respectively. The type strain of Hymenobacter properus is BT439T (= KCTC 72900T = NBRC 114849T), Hymenobacter ruricola is BT662T (= KACC 21966T = NBRC 114855T) and the type strain of Hymenobacter jeongseonensis is BT683T (= KACC 22013T = NBRC xxxxxT).


Discovery of a novel series of substituted quinolines acting as anticancer agents and selective EGFR blocker: Molecular docking study.
A Ta2O5-anchored-piperidine-4-carboxylic acid (PPCA) nanoparticle has been synthesized and characterized. It was then used as a highly effective nanocatalyst for the synthesis of quinolin-2(1H)-one derivatives through CO bond functionalization. The special advantage of this heterogeneous solid catalyst is the reusability of the catalyst for up to five cycles without any noticeable reduction in product yields. In comparison, healthy reaction profiles, wide substrate scope, excellent yields and easy workup conditions are the notable highlights of this approach. All the compounds were tested for their anticancer activity against MCF-7 (human breast), HepG2 (human liver), HCT116 (human colorectal), and PC-3 (human prostate) cancer cell lines with the MTT assay. All the compounds were shown to have moderate to good inhibitory effects on tested cancer cell lines. Besides, compounds 5b, 5c and 5d showed good selectivity against epidermal growth factor receptor-tyrosine kinase (EGFR-TK). Molecular docking results showed that active compounds showed a good affinity towards EGFR kinase (PDB ID: 6V6O) by forming two hydrogen bonds with Cys-797 and Tyr-801. All the compounds were screened for computational ADMET and Lipinski analysis.


The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase.
The ubiquitin-proteasome pathway is an important regulatory system for the lifetime of inducible nitric-oxide synthase (iNOS), a high-output isoform compared to neuronal NOS (nNOS) and endothelial NOS (eNOS), to prevent overproduction of NO that could trigger detrimental effects such as cytotoxicity. Two E3 ubiquitin ligases, Elongin B/C-Cullin-5-SPRY domain- and SOCS box-containing protein [ECS(SPSB)] and the C-terminus of Hsp70-interacting protein (CHIP), recently have been reported to target iNOS for proteasomal degradation. However, the significance of each E3 ubiquitin ligase for the proteasomal degradation of iNOS remains to be determined. Here, we show that ECS(SPSB) specifically interacted with iNOS, but not nNOS and eNOS, and induced the subcellular redistribution of iNOS from dense regions to diffused expression as well as the ubiquitination and proteasomal degradation of iNOS, whereas CHIP neither interacted with iNOS nor had any effects on the subcellular localization, ubiquitination, and proteasomal degradation of iNOS. These results differ from previous reports. Furthermore, the lifetime of the iNOS(N27A) mutant, a form of iNOS that does not bind to ECS(SPSB), was substantially extended in macrophages. These results demonstrate that ECS(SPSB), but not CHIP, is the master regulator of the iNOS lifetime.


Familial herpes simplex infection associated with activation of the complement system.
A patient with severe recurrent herpes infection was evaluated for immunologic analysis including a profile of complement components. The peripheral blood lymphocytes from the patient responded by proliferation to herpes simplex antigen but failed to produce leukocyte migration inhibition factor. Herpes simplex antibody titers increased during active infection. Total hemolytic complement (TCH50), the third (C3), fifth (C5), sixth (C6) and seventh (C7) components of complement, and factor B were dramatically reduced; the first (C1), second (C2) and fourth (C4) components of complement were within normal limits. In family members with a history of recurrent herpes simplex, one or more of the later complement components (C5, C6 or C7) was reduced. This study demonstrates the activation of complement in these serums via the alternative pathway.


Action's influence on spatial perception: resolution and a mystery.
Despite the impression that perception of spatial layout including distance, slant, and size is objective and geometrically accurate, spatial perception is influenced by a perceiver's ability to act. Hills appear steeper when the perceiver is fatigued, and balls appear faster when they are harder to block. The same environment looks different when the perceiver is better able to act than when actions are constrained. Claims of action's influence on spatial perception have been met with much controversy, and spurred many experiments designed to explore alternative explanations. In at least one case, these alternative explanations have failed to account for action's effect, thereby leading to the conclusion that the potential for action can truly influence spatial perception. The mystery remains, however, as to how action exerts its influence.


Phase II study of trifluridine/tipiracil (TAS-102) therapy in elderly patients with colorectal cancer (T-CORE1401): geriatric assessment tools and plasma drug concentrations as possible predictive biomarkers.
The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1-5 and 8-12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9-4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7-8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network).


Dynamic protein conformations preferentially drive energy transfer along the active chain of the photosystem II reaction centre.
One longstanding puzzle concerning photosystem II, a core component of photosynthesis, is that only one of the two symmetric branches in its reaction centre is active in electron transfer. To investigate the effect of the photosystem II environment on the preferential selection of the energy transfer pathway (a prerequisite for electron transfer), we have constructed an exciton model via extensive molecular dynamics simulations and quantum mechanics/molecular mechanics calculations based on a recent X-ray structure. Our results suggest that it is essential to take into account an ensemble of protein conformations to accurately compute the site energies. We identify the cofactor CLA606 of active chain as the most probable site for the energy excitation. We further pinpoint a number of charged protein residues that collectively lower the CLA606 site energy. Our work provides insights into the understanding of molecular mechanisms of the core machinery of the green-plant photosynthesis.


Effect of heat-moisture treatment on the physicochemical properties and digestibility of proso millet flour and starch.
Proso millet flour (PMF) and starch (PMS) were subjected to heat-moisture treatment (HMT) at 25 % moisture content and 110 °C for 4 h. The effects of HMT on physicochemical and structural properties and in vitro digestibility of PMF and PMS were analyzed. After HMT, SEM showed aggregation and damage to the surface of starch granules, while CLSM showed proteins wrapped around the granules. The amylopectin chain length distribution (CLD) remained unchanged in PMF and PMS after HMT, indicating intact covalent bonds between glucose units. HMT decreased the swelling power, solubility, viscosity of the paste, and gelatinization enthalpy and increased the pasting temperature and gelatinization temperature of PMF and PMS. HMT changed the XRD pattern of PMF from A to A + V type starches, whereas that of PMS remained unchanged. FTIR study showed an increase in the degree of short-range molecular order of PMF and PMS after HMT. In vitro digestibility evaluation showed that the rapidly (RDS) and slowly digestible starch (SDS) contents of PMF and PMS increased, whereas the resistant starch (RS) content decreased after HMT. HMT flour and starch have suitable properties for use in a wide range of food products, from canned to frozen, as well as non-food products.


Influence of different kinds of incinerators on PCDD/Fs: a case study of emission and formation pathway.
Few studies focused on the emission of polychlorinated-ρ-dibenzodioxins and dibenzofurans (PCDD/F) from different kinds of waste incinerators. This study was conducted in a full-scale MSW incineration plant to investigate the influence of different incinerator types on PCDD/F. Experimental results indicated that the 2,3,7,8-PCDD/F concentration in the inlet gas of the air pollution control system (APCS) in the studied fluidized bed was higher (2.03 ng I-TEQ/Nm3) than that of the grate (0.77 ng I-TEQ/Nm3). But gas in the outlet of APCS from both incinerators had an approximate concentration, lower than the Chinese emission limit of 0.1 ng I-TEQ/Nm3. Similar distribution patterns were observed for 2,3,7,8-PCDD/Fs, as well as 136 PCDD/F congeners. Specifically, OCDD and 1,2,3,4,6,7,8-HpCDD were major isomer constituents for 2,3,7,8-PCDD/F isomers. In terms of formation pathways, a similar formation mechanism was observed based on fingerprint characteristics of 136 PCDD/F congeners. De novo synthesis was the dominating formation pathway for both incinerators. Meanwhile, DD/DF chlorination was another contributor to PCDD/F formation, which in the fluidized bed was higher. In addition, little correlation (0.009 < R2 < 0.533) between conventional pollutants (HCl, CO, PM) and PCDD/Fs was found, suggesting little high-temperature synthesis observed and verifying the dominance of de novo synthesis.


Forefoot joint damage, pain and disability in rheumatoid arthritis patients with foot complaints: the role of plantar pressure and gait characteristics.
To assess (i) the relationship between forefoot joint damage and foot function (expressed as gait and pressure parameters), (ii) the relationship between foot function and pain, and (iii) the relationship between foot function and disability in patients with foot complaints secondary to rheumatoid arthritis (RA). Sixty-two patients with RA-related foot complaints were included. Measurements of joint damage, gait characteristics, plantar pressure, pain and disability were obtained. Data were analysed using descriptive and correlational techniques. s. Joint damage on radiographs of the forefoot correlated significantly with forefoot pressure (r = 0.296, P = 0.020). Further investigation of the metatarsophalangeal joints (MTPs) showed joint damage to correlate significantly with peak pressure and pressure-time integral (PTI) of MTP1 and MTP4. A significant correlation between PTI under the forefoot and barefoot pain was found (r = 0.290, P = 0.022). Gait parameters (total contact time and the duration of heel loading) and disability, measured with the Foot Function Index, were significantly correlated (r = 0.315, P = 0.013 and r = 0.266, P = 0.037, respectively). Forefoot joint damage in the rheumatoid foot is related to increased pressure under the forefoot, especially pressure under the first and fourth MTP joints. High forefoot pressure is associated with pain during barefoot walking. A prolonged stance phase and delayed heel lift are related to disability in daily activities.


Different forms of nitrogen application affect metabolite patterns in grapevine leaves and the sensory of wine.
The quality of grapevine berries, must and wine is influenced by environmental and viticultural inputs and their complex interactions. Aroma and flavour are decisive for quality and are mainly determined by primary and secondary metabolites. In particular, phenolic compounds contribute to berry and wine quality. The influence of various nitrogen forms on i) the composition of phenolic compounds in leaves and wine and; ii) the resulting wine quality were studied in a vineyard system. Must and wine quality was evaluated by chemical analysis and sensory testing. Metabolomic profiling was also performed. Aroma and sensory profile were significantly changed by the application of nitrogen in contrast to no nitrogen fertilisation. The levels of 33 metabolites in leaves and 55 metabolites in wine were significantly changed altered by fertilisation with the various nitrogen forms. In leaves, more metabolites were increased by the use of calcium nitrate or ammonium but were decreased by the use of urea. In terms of wine, the used nitrogen forms decreased more metabolites compared with no fertilisation.


The identification of a structurally important cysteine residue in the glycerol dehydrogenase from Bacillus stearothermophilus.
Evidence is presented to demonstrate that the Zn2+ metallo-enzyme glycerol dehydrogenase from the thermophile Bacillus stearothermophilus has one cysteine residue per subunit which is only available for reaction with thiol reagents in the metal-depleted form of the enzyme. Modification of the metal-depleted enzyme by methyl methanethiosulphonate prevents the reactivation of the enzyme by Zn2+ ions and induces dissociation of the oligomer into subunits. The rate of reaction of the cysteine residue with the thiol reagent DTNB is limited by a factor other than reagent concentration and it is proposed that the reagent only reacts with the cysteine residue in dissociated monomers. The enzyme has been labelled at the single cysteine residue by radioactive iodo[2-3H]acetic acid. Two radiolabelled peptides have been isolated and sequenced; one peptide is a component of the other. Spectroscopic evidence suggests that the cysteine residue is not involved in ligation of the essential metal ion. Chemical modification studies using the reagent diethylpyrocarbonate have suggested that two histidines are involved in the ligation of the metal.


Facile fabrication of ferroelectric poly(vinylidene fluoride) thin films with pure γ phase.
A simple heating-cooling procedure is employed to make pure polar γ-PVDF thin films. By controlling the relaxation state of the crystals, pure γ crystals are induced by two kinds of mechanism including self-seeding and self-nucleation upon cooling within 30 min. The methodology paves a new way for PVDF homopolymers in flexible ferroelectric device applications.


Addressing pressures on health services in Belo Horizonte, Brazil through community-based care for poor older people: a qualitative study.
In low and middle-income countries, there is growing interest in managing pressures on health services through community interventions for older people. Evidence on the effects of such interventions is scarce. We draw on qualitative data to examine these effects for a specific scheme, Programa Maior Cuidado (PMC) in the Brazilian city of Belo Horizonte. Building on quantitative findings reported elsewhere, we use qualitative data to develop and test theories of change. These include data from 50 meetings with policymakers, managers and staff in 30 health centres and social assistance posts. Data collection was embedded in key informant interaction and knowledge coproduction. Data include participant and non-participant observation, focus groups and semi-structured interviews with key informants, as well as older people and carers from seven families. The data reveal three theories of change. Theory 1 is PMC maintains older people's health which reduces their need for inpatient or outpatient care. We find strong evidence to support this, through effects on use of medication, chronic disease management and risk prevention. Theory 2 is PMC promotes timely intervention by anticipating health problems, thus reducing demand for emergency and acute care. We find some evidence for this, but it was limited by limited availability of timely treatment or referral beyond PMC. Theory 3 is PMC facilitates hospital discharge. We find limited evidence for this, reflecting a lack of formal liaison between PMC and hospitals. Schemes like PMC have potential to reduce pressures on health service utilisation by older people, if they are well articulated with wider health services. Medical Research Council, Newton Fund and Brazilian Council of State Funding Agencies.


Sex differences in concentrations of exhaled nitric oxide and plasma nitrate.
Nitric oxide (NO) is generally considered as an endogenous vasoprotective agent. Various studies indicate that the female sex hormone estradiol, that contributes to the well known gender differences in cardiovascular disease, may enhance NO-production. Thus we studied sex differences in NO-generation by measuring single breath NO-exhalation and plasma levels of nitrate (NO3), the stable endmetabolite of NO. In this observational trial 22 male and 21 female volunteers, 19 to 38 years of age, were studied on 3 days at weekly intervals. Median concentrations of NO were 20 parts per billion (95% CI: 16 to 32 ppb) in women and 34 ppb (95% CI: 31 to 58 ppb) in men. The median plasma concentrations of NO3 were 14 microM/L (95% CI: 11 to 23 microM/L) in women and 27 microM/L (95% CI: 24 to 47 microM/L) in men. Thus, men exhaled 59% more NO (p < 0.001) and had 99% higher NO3 levels than women (p < 0.0001). Even when exhaled NO concentrations were corrected for body weight, men exhaled 50% more NO than women (p = 0.024). No significant changes in measured endpoints were seen during the menstrual cycle (p > 0.05) in women. In view of the diversity of NO-actions, the finding of marked sex differences in NO-production is basic to the elucidation of gender differences in a number of (patho)-physiologic conditions.


The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors.
Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents.


Primary viscocanalostomy for juvenile open-angle glaucoma.
To evaluate the efficacy and safety of primary viscocanalostomy for medically uncontrolled juvenile open-angle glaucoma (JOAG). Prospective, noncomparative, interventional case-series study. The study included 20 eyes of 20 consecutive patients with medically uncontrolled JOAG who were treated by viscocanalostomy at one institution. No surgical or laser procedure preceded viscocanalostomy. Surgical outcome was defined as an overall success by the following criteria: no visual field deterioration, no optic-neuropathy progression, postoperative intraocular pressure IOP < or =20 mm Hg, and IOP reduction > or =30% compared with baseline values with or without medication. When medications were not required, success was defined as complete. Cases that did not fulfill the aforementioned criteria and cases in which a surgical revision or further goniopuncture was performed were defined as a failure. Gender distribution was similar. Fourteen eyes belonged to the white race; five eyes belonged to the black race, and one eye belonged to Arab ethnicity. Mean age (+/-SD) at operation was 33.77 +/- 6.16 years, with the mean preoperative IOP (+/-SD) at 22.9 +/- 4.77 mm Hg. Thirty-six months after operation, 16 cases (80%) were considered an overall success. In 11 cases (55%), success was complete. Four cases (20%) were considered failures. No serious complications were documented either during or after operation. In two cases (10%), we documented a spontaneously reabsorbed microhyphema. Trabeculo-Descemet-membrane microperforation occurred in two cases (10%). In two other cases (10%), Trabeculo-Descemet-membrane perforation occurred and was accompanied by iris prolapse that needed peripheral iridectomy. Primary viscocanalostomy can efficiently and safely reduce intraocular pressure in cases of medically uncontrolled JOAG and provide a rational alternative to conventional surgical modalities.


Effect of acute ethanol administration on the subcellular distribution of iron in rat liver and cerebellum.
An acute ethanol load (50 mmol/kg, i.p.) produced altogether a decrease in the non-heme iron content of the serum and an increase in the iron content in liver and cerebellum. Subcellular fractionation studies indicated that the non-heme iron accumulated by the liver, 4 hr after the ethanol load, was recovered in light mitochondria, microsomes and cytosol, and that iron accumulated by the cerebellum was localized in heavy mitochondria, light mitochondria, microsomes and cytosol. The low molecular weight chelatable (LMWC) iron content as well as the percentage of total non-heme iron represented by LMWC-iron were increased in the cytosol of liver and cerebellum after the ethanol load. These results suggest that an acute ethanol load induces (i) a shift in the distribution between circulating and tissular non-heme iron; (ii) an increase in the cytosolic LMWC-iron which, by favouring the biosynthesis of reactive free radicals, may contribute to lipid peroxidation in liver and cerebellum.


Molecular Detection of Oncogenic Gene Rearrangements.
Oncogenic gene rearrangements have been exponentially significant for clinical management of cancer, from diagnosis to therapy and disease monitoring. Testing algorithms should be created with caution, and sample type, accessibility to testing method, turnaround time, and economic aspects should be taken into consideration. Herein, different molecular technologies for detecting these gene rearrangements are discussed and the benefits and limitations of each method are highlighted.


Orthorhombic Cobalt Ditelluride with Te Vacancy Defects Anchoring on Elastic MXene Enables Efficient Potassium-Ion Storage.
The fast and reversible potassiation/depotassiation of anode materials remains an elusive yet intriguing goal. Herein, a class of the P-doping-induced orthorhombic CoTe2 nanowires with Te vacancy defects supported on MXene (o-P-CoTe2 /MXene) is designed and prepared, taking advantage of the synergistic effects of the conductive o-P-CoTe2 arrays with rich Te vacancy defects and the elastic MXene sheets with self-autoadjustable function. Consequently, the o-P-CoTe2 /MXene superstructure exhibits boosted potassium-storage performance, in terms of high reversible capacity (373.7 mAh g-1 at 0.2 A g-1 after 200 cycles), remarkable rate capability (168.2 mAh g-1 at 20 A g-1 ), and outstanding long-term cyclability (0.011% capacity decay per cycle over 2000 cycles at 2 A g-1 ), representing the best performance in transition-metal-dichalcogenides-based anodes to date. Impressively, the flexible full battery with o-P-CoTe2 /MXene anode achieves a satisfying energy density of 275 Wh kg-1 and high bending stability. The kinetics analysis and first-principles calculations reveal superior pseudocapacitive property, high electronic conductivity, and favorable K+ ion adsorption and diffusion capability, corroborating fast K+ ion storage. Especially, ex situ characterizations confirm o-P-CoTe2 /MXene undergoes reversible evolutions of initially proceeding with the K+ ion insertion, followed by the conversion reaction mechanism.


Association between ultrapocessed food and chronic kidney disease.
The modern diet is closely linked to the consumption of processed foods, causing an increase in the intake of salt, simple sugars, phosphorus and added potassium. This excess intake is associated with an increased risk of obesity, diabetes, hypertension and chronic kidney disease (CKD). CKD, which according to data from the ENRICA study affects 15% of the population, magnifies its impact due to the higher prevalence of diabetes and hypertension and due to limitations in the management of sodium and phosphorus. The intake of these products far exceeds the established recommendations, assuming 72% of total sodium, 25%-35% of phosphorus, 12%-18% of potassium and exceeding 10% of the caloric intake in simple sugars. Measures are necessary to reduce their contribution through nutritional advice, labeling review, education campaigns on healthy habits, fees and institutional actions that involve food safety agencies, industry, distribution and scientific societies.


Circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/SLC7A11 by miR-770-5p.
Diabetes nephropathy (DN) is one of the major complications in diabetes. With the improvement of people's living standards in China in recent years, the incidence of diabetes has become the main cause of end-stage renal disease. However, how and whether circ ASAP2 could mediate DN remain poorly understood. This study aimed to determine the function and its biological mechanism of circ ASAP2 on inflammation and ferroptosis of DN. C57BL/6 mice were fed with a high-fat diet and injected with streptozotocin. Human renal glomerular endothelial cells stimulated with 20 mmol/L D-glucose. In mice model DN, circular ASAP2 expression level was down-regulated, and miR-770-5p expression level was up-regulated. Moreover, the inhibition of ASAP2 aggravated diabetic nephropathy in mice model. The inhibition of ASAP2 promoted inflammation and oxidative stress to aggravate renal injury in mice model. Circular ASAP2 was reducing inflammation and oxidative stress in vitro model. The inhibition of ASAP2 promoted ferroptosis in model of DN. CASAP2 suppressed miR-770-5p in DN. Additionally, miR-770-5p aggravated diabetic nephropathy in mice model. MiR-770-5p promoted inflammation and oxidative stress to aggravate renal injury in mice model. MiR-770-5p was increasing inflammation and oxidative stress in vitro model. Circular ASAP2 induced SLC7A11 expression in model of DN through SOX2 by miR-770-5p. These results suggest that circ ASAP2 decreased inflammation and ferroptosis in DN through SOX2/SLC7A11 by miR-770-5p, which might serve as a target for improving the role of ferroptosis in DN.


The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population.
Recently, tremendous prominence has been given to the investigation of the effect of different research processes as part of the Cancer Moonshot. More than half a century ago, the National Cancer Institute (NCI) established a network of publicly funded cancer cooperative research groups to systematically evaluate new treatments for efficacy and safety. To examine the extent to which positive NCI-sponsored cancer treatment trials have benefited patients with cancer in the US population. This investigation used study data from SWOG, an NCI-sponsored network cooperative research group. All treatment trials during SWOG's 60-year history (1956-2016) were identified for which the new, experimental therapy provided a statistically significant improvement in overall survival. It was assumed that the new, proven treatments from these trials established new standards for cancer care in the treatment community. Twenty-three positive SWOG treatment trials were identified from a variety of different disease settings. This study estimated population life-years gained from the 23 treatment trials through 2015 by mapping the effect of the new treatments onto the US cancer population using an area under the Kaplan-Meier survival curve approach that combined trial-specific hazard function and hazard ratio results, along with Surveillance, Epidemiology, and End Results program and life table data. Calculations were age adjusted. The US dollar return on investment was estimated as the ratio of the total investment by the NCI in the treatment trial program divided by the estimate of life-years gained. In total, 12 361 patients were enrolled to the 23 positive trials from 1965 to 2012. The study estimated that 3.34 million (95% confidence limit, 2.39-4.15 million) life-years were gained from these 23 trials through 2015. Estimates were greater than 2 million life-years gained under most model simulations. The US dollar return on investment was $125 per life-year gained. SWOG treatment trials have had a substantial impact on population survival for patients with cancer over 60 years. The NCI's investment in its cancer cooperative group research program has provided exceptional value and benefit to the American public through its research programs generating positive cancer treatment trials. clinicaltrials.gov Identifiers: NCT00004001, NCT00075764, and NCT00644228.


Practical Considerations for Using RNA Sequencing in Management of B-Lymphoblastic Leukemia: Malaysia-Singapore Acute Lymphoblastic Leukemia 2020 Implementation Strategy.
Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients.


Differential response to 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in non-small cell lung cancer cells with distinct oncogene mutations.
We previously demonstrated that non-small cell lung cancer (NSCLC) cells and primary human lung tumors aberrantly express the vitamin D3-catabolizing enzyme, CYP24, and that CYP24 restricts transcriptional regulation and growth control by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in NSCLC cells. To ascertain the basis for CYP24 dysregulation, we assembled a panel of cell lines that represent distinct molecular classes of lung cancer: cell lines were selected which harbored mutually exclusive mutations in either the K-ras or the Epidermal Growth Factor Receptor (EGFR) genes. We observed that K-ras mutant lines displayed a basal vitamin D receptor (VDR)(low)CYP24(high) phenotype, whereas EGFR mutant lines had a VDR(high)CYP24(low) phenotype. A mutation-associated difference in CYP24 expression was also observed in clinical specimens. Specifically, K-ras mutation was associated with a median 4.2-fold increase in CYP24 mRNA expression (p=4.8×10(-7)) compared to EGFR mutation in a series of 147 primary lung adenocarcinoma cases. Because of their differential basal expression of VDR and CYP24, we hypothesized that NSCLC cells with an EGFR mutation would be more responsive to 1,25(OH)2D3 treatment than those with a K-ras mutation. To test this, we measured the ability of 1,25(OH)2D3 to increase reporter gene activity, induce transcription of endogenous target genes, and suppress colony formation. In each assay, the extent of 1,25(OH)2D3 response was greater in EGFR mutation-positive HCC827 and H1975 cells than in K-ras mutation-positive A549 and 128.88T cells. We subsequently examined the effect of combining 1,25(OH)2D3 with erlotinib, which is used clinically in the treatment of EGFR mutation-positive NSCLC. 1,25(OH)2D3/erlotinib combination resulted in significantly greater growth inhibition than either single agent in both the erlotinib-sensitive HCC827 cell line and the erlotinib-resistant H1975 cell line. These data are the first to suggest that EGFR mutations may identify a lung cancer subset which remains responsive to and is likely to benefit from 1,25(OH)2D3 administration. This article is part of a Special Issue entitled 'Vitamin D Workshop'.


Assessing the biodegradation of polycyclic aromatic hydrocarbons and laccase production by new fungus Trematophoma sp. UTMC 5003.
Environmental pollution caused by petroleum compounds has become a global concern. The aim of this study was to evaluate the indigenous fungal isolates in Iran for biodegradation of crude oil pollutants. In order to isolate fungal strains, the soil samples were enriched in minimal salts medium (MSM) with 1% crude oil and then the crude oil degradation was measured by total petroleum hydrocarbon (TPH) assay. The degradation of hydrocarbons compounds was also analysed by FT-IR and HPLC, and the activity of peroxidase enzyme and biosurfactant production were also measured. We isolated 40 fungal strains and selected the isolate G-05 with 70% degradation ability of petroleum hydrocarbons as a premium isolate after 15 days. Residual crude oil analysis with FT-IR spectrophotometry and HPLC showed that G-05 is able to degrade 90 and 100% of aliphatic compounds and some polycyclic aromatic hydrocarbons (PAH), respectively. Evaluation of enzymatic activity showed that this isolate can produce 4 U L-1 of Laccase enzyme for oil removal; it is capable of producing biosurfactant and reducing the surface tension of the medium to 25.95 ± 0.1 m Nm-1. This strain was identified as a member of Trematophoma genus and the obtained results showed that this strain is a highly potent strain in bioremediation of soils contaminated by crude oil.


Influences of irrigation and fertilization on soil N cycle and losses from wheat-maize cropping system in northern China.
Excess of water irrigation and fertilizer consumption by crops has resulted in high soil nitrogen (N) losses and underground water contamination not only in China but worldwide. This study explored the effects of soil N input, soil N output, as well as the effect of different irrigation and N- fertilizer managements on residual N. For this, two consecutive years of winter wheat (Triticum aestivum L.) -summer maize (Zea mays L.) rotation was conducted with: N applied at 0 kg N ha-1 yr-1, 420 kg N ha-1 yr-1 and 600 kg N ha-1 yr-1 under fertigation (DN0, DN420, DN600), and N applied at 0 kg N ha-1 yr-1 and 600 kg N ha-1 yr-1 under flood irrigation (FN0, FN600). The results demonstrated that low irrigation water consumption resulted in a 57.2% lower of irrigation-N input (p < 0.05) in DN600 when compared to FN600, especially in a rainy year like 2015-2016. For N output, no significant difference was found with all N treatments. Soil gaseous N losses were highly correlated with fertilization (p < 0.001) and were reduced by 23.6%-41.7% when fertilizer N was decreased by 30%. Soil N leaching was highly affected by irrigation and a higher reduction was observed under saving irrigation (reduced by 33.9%-57.3%) than under optimized fertilization (reduced by 23.6%-50.7%). The net N surplus was significantly increased with N application rate but was not affected by irrigation treatments. Under the same N level (600 kg N ha-1 yr-1), fertigation increased the Total Nitrogen (TN) stock by 17.5% (0-100 cm) as compared to flood irrigation. These results highlighted the importance to further reduction of soil N losses under optimized fertilization and irrigation combined with N stabilizers or balanced- N fertilization for future agriculture development.


Correlation of spinopelvic parameters with functional outcomes in surgically managed cases of lumbar spinal tuberculosis- A retrospective study.
The advanced stage of vertebral involvement in spinal tuberculosis (STB) can cause vertebral body collapse, which leads to kyphotic deformity and paraplegia in severe cases. Surgery is indicated in patients having disabling back pain, progressive neurological deficit, and instability in spine despite conservative management. The derangement of lumbar parameters, especially the loss of lumbar lordosis has been found to cause functional deterioration in patients. With the current evidences in place, this study was done to evaluate the correlation between the restoration of lumbar lordosis, pelvic parameters, and functional outcome when posterior only approach was used to manage the lumbar STB. Active Tuberculosis of lumbar vertebra (L1-S1) confirmed by radiology (X-ray, MRI) and histopathological examination were included. All the cases scheduled for surgery underwent radiographs, CT scan, and MRI scans. Lumbar lordosis and other pelvic parameters were calculated on X-rays. VAS scores and ODI scores were documented during the follow-up to assess functional well-being. A total of 33 (22 M:11 F) patients were included in the study. The mean lumbar lordosis pre-operatively was -22.84 ± 11.19° which was corrected to -37.03 ± 9.02° (p < 0.05) post-operatively. The pelvic tilt pre-operatively was 25.33 ± 6.75° which was corrected to 19.63 ± 5.84° (p < 0.05) post-operatively. The mean ODI improved from 84.33 ± 11.84 to 26.93 ± 8.74 (p < 0.05) at the final follow-up. The mean VAS score pre-operatively was 8.06 ± 1.27 which improved to 2.45 ± 0.93 (p < 0.05) in the post-operative period. The study found a strong negative correlation between ODI scores and lumbar lordosis and a strong positive correlation between pelvic tilt and ODI scores. But the correlation needs to be further studied and evaluated by a well-constructed study especially with a control group treated conservatively.


Primary transoral robotic surgery +/- adjuvant therapy for oropharyngeal squamous cell carcinoma-A large observational single-centre series from the United Kingdom.
To analyse the oncological outcomes following primary Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). Observational case series. Tertiary centre; first TORS practice to commence in the UK. All consecutive patients undergoing primary TORS with curative intent, with or without adjuvant treatment. Descriptive analysis of patient and tumour pathology variables. Survival outcomes: Overall, Disease-Specific, Progression-Free and Locoregional control. The cohort comprised of 120 patients undergoing TORS with minimum 12-month follow-up data and the following characteristics: mean age 58 years, 91 males (76%), 78 tonsil (65%) and 34 base of tongue primaries (28%), 89% HPV-related OPSCC. The surgical pathology revealed 14 (12%) with positive margins, 19 (16%) had close margins <2mm and 31% with extranodal extension. The treatment was as follows: 39 (33%) treated with TORS alone, 50 (42%) received adjuvant radiotherapy and 31 (26%) received adjuvant radiotherapy with chemotherapy. There were 15 recurrences. Estimated survival for all patients at 3 years (95% CI): overall 85% (78-92), disease-specific 90% (85-96), progression-free 86% (79-92) and locoregional control 90% (84-96). The equivalent survival figures for the HPV-related cases alone were as follows: overall 88% (82-94), disease-specific 93% (87-98), progression-free 88% (81-95) and locoregional control 92% (87-98). Whilst TORS has become a common practice in the management of OPSCC in the UK, these are the first reported oncological outcomes. For selected patients, TORS with or without adjuvant therapy is an appropriate treatment modality.


Practice patterns and outcomes of hemophagocytic lymphohistiocytosis in adults: a 2-decade provincial retrospective review.
Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous, life-threatening clinical syndrome. There are scarce data on the quality of care in HLH or data comparing treatment patterns and outcomes between different triggers. We aimed to examine quality-of-care indicators and outcomes in adults with various HLH triggers. In this multi-centre retrospective cohort study of adult HLH in the province of Alberta, Canada (1999-2019), we examined quality indicators including diagnostic testing, time to diagnosis and treatment and trigger identification. We also compared treatment regimens and outcomes across HLH triggers. Logistic regression was used to identify predictors of etoposide use. Overall survival (OS) was estimated using the Kaplan-Meier method. We identified 97 patients; 66 (68%) were male. Triggers included malignancy (36%), infection (35%), autoimmune disease (21%) and idiopathic/others (8%). Specialized tests such as sCD25 (53%) and natural killer degranulation assay (19%) were under-performed, as were testing for infectious triggers. Etoposide was administered in only 33 (34%). Neutropenia, hyperbilirubinemia and hyperferritinemia, but not age, sex and comorbidities, were significant predictors of etoposide use. At median follow-up of 32 months, median OS was 18.8 months. Worse OS was seen in malignancy-associated and idiopathic HLH (log-rank P < 0.001). Our study showed low rates of specialized testing such as sCD25 and a low rate of etoposide use. Development of a standardized provincial protocol has the potential to improve quality of care in adult HLH.


A systematic survey of conformational states in β1 and β4 integrins using negative-stain electron microscopy.
Structural analyses of β2 and β3 integrins have revealed that they generally assume a compact bent conformation in the resting state and undergo a global conformational transition involving extension during upregulation of ligand affinity, collectively called the 'switchblade model'. This hypothesis, however, has not been extensively tested for other classes of integrins. We prepared a set of recombinant integrin ectodomain fragments including αvβ3, α2β1, α3β1, α5β1, α6β1 and α6β4, and used negative-stain electron microscopy to examine their structures under various conditions. In contrast to αvβ3 integrin, which exhibited a severely bent conformation in low-affinity 5 mM Ca2+ conditions, all β1 integrin heterodimers displayed a mixed population of half-bent to fully extended conformations. Moreover, they did not undergo significant conformational change upon activation by Mn2+ Integrin α6β4 was even more resistant to conformational regulation, showing a completely extended structure regardless of the buffer conditions. These results suggest that the mechanisms of conformational regulation of integrins are more diverse and complex than previously thought, requiring more experimental scrutiny for each integrin subfamily member.


Hereditary hypertrophic neuropathy in the trembler mouse. Part 1. Histopathological studies: light microscopy.
The Trembler mouse suffers from a dominantly inherited chronic hypertrophic neuropathy. Quantitative light-microscopic studies have been performed on Trembler peripheral nerves from birth to adulthood, and compared with the findings in age-matched control mice. Teased fibres of Trembler nerves contained virtually no myelin, nodes of Ranvier were difficult to identify, and supernumerary Schwann cells were prominent. Results of quantitative studies performed on the dorsal root ganglia and spinal cord of Trembler mice did not differ from those in controls. The density of myelinated fibres in the case of Tremblers was reduced at all ages when compared with controls, and there was a predominant loss of large diameter fibres.


Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for the treatment of esophageal squamous cell carcinoma: a propensity score-matched study from the National Cancer Center in China.
The optimal mode of neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC) has not been well characterized. Our study compared neoadjuvant chemotherapy (NCT) with neoadjuvant chemoradiotherapy (NCRT) for patients with ESCC. Data from ESCC patients receiving NCRT or NCT combined with esophagectomy between 2010 and 2018 from the National Cancer Center in China were retrospectively collected. Long-term survival, pathological response, and perioperative mortality and morbidity were compared between the NCRT and NCT groups. A Cox proportional hazards model and propensity score matching (PSM) were used to minimize bias due to potential confounding. Out of 327 eligible patients with ESCC in our study, 90 patients were identified in each group by PSM. The complete pathologic response (pCR) rate in the NCRT group was markedly higher than that in the NCT group (before PSM: 35.1% vs. 6.0%; after PSM: 38.9% vs. 5.6%; both P < 0.001). The rates of 30-day or 90-day mortality were comparable between the two groups, but the NCRT group had a longer postoperative hospital stay (P < 0.001 before PSM and P = 0.012 after PSM) and more postoperative complications (P < 0.001 before PSM and P = 0.014 after PSM), especially, anastomotic leaks (P = 0.001 before PSM and P = 0.013 after PSM). No significant differences in 5-year overall survival (OS) (P = 0.439) or 5-year relapse-free survival (RFS) (P = 0.611) were noted between unmatched groups, but the trend favored NCRT in the propensity score-matched group (77.3% vs. 61.3%; hazard ratio [HR] 1.57; 95% confidence interval [CI] 0.86-2.87; P = 0.141 for OS, and 77.8% vs. 60.5%; HR 1.72; 95% CI 0.95-3.11; P = 0.073 for RFS). Multivariate analysis showed that only ypT and ypN stages were independent predictors of OS before and after PSM (both P < 0.05). There was no difference in survival between the NCT and NCRT groups, although a trend favored NCRT related to the significantly higher pCR rates. Prospective head-to-head clinical trials to compare these two types of neoadjuvant therapies in ESCC are warranted.


Regulation of gluconeogenesis by glucocorticoids.
1. Regulation of gluconeogenic substrate supply and modulation of the gluconeogenic pathway in the liver are both important in the control of gluconeogenesis by glucocorticoids. 2. Adrenal deficiency decreases the release of gluconeogenic and other amino acids from skeletal muscle during starvation. The effect is reversed by glucocorticoid replacement. The changes in amino acid release are accompanied by similar alterations in tissue amino acid levels and are not explained by alterations in net protein breakdown. Glucocorticoids do not alter protein catabolism and cause a small inhibition of protein synthesis. The biochemical alterations underlying the changes in amino acid metabolism induced by these steroids remain to be elucidated. Glucocorticoids may also regulate the supply of gluconeogenic substrates through permissive effects on the lipolytic action of catecholamines and other hormones in adipose tissue and on the glycogenolytic action of catecholamines on skeletal muscle. 3. Glucocorticoids are required for the increases in gluconeogenesis in starvation and diabetes. Part of their action is exerted directly on the liver and appears to involve modulation of P-enlopyruvate carboxykinase levels. Glucocorticoids increase the synthesis of this enzyme apparently through effects at the level of transcription. 4. Glucocorticoids exert permissive effects on the stimulation of gluconeogenesis in the liver by glucagon and epinephrine. The steroids are not required for cAMP generation or protein kinase activation by these hormones, but appear to act by maintaining the responsiveness of certain enzymes to the effects of the cAMP and alpha-adrenergic systems. It is proposed that this involves the maintenance of a normal intracellular ionic environment.


Trends in mortality and life expectancy in Fiji over 20 years.
Fiji, a Pacific Island nation of 884,887 (2017 census), has experienced a prolonged epidemiological transition. This study examines trends in mortality and life expectancy (LE) in Fiji by sex and ethnicity over 1996-2017, with comparisons to published estimates. Trends in infant mortality rates (IMR), under-5 mortality (U5M), adult mortality (probability of dying), LE (at birth) and directly age-standardised death rates (DASRs) by sex and ethnicity, are calculated (with 95% confidence limits) using unit death records from the Fiji Ministry of Health and Medical Services. The LE gap between populations, or within populations over time, is examined using decomposition by age. Period trends are assessed for statistical significance using linear regression. Over 1996-98 to 2014-17: IMR and U5M for i-Taukei and Fijians of Indian descent declined; U5M decline for i-Taukei (24.6 to 20.1/1000 live births) was significant (p = 0.016). Mortality (15-59 years) for i-Taukei males was unchanged at 27% but declined for Indians 33 to 30% (p = 0.101). Mortality for i-Taukei females increased 22 to 24% (p = 0.011) but declined for Indians 20 to 18% (p = 0.240). DASRs 1996-2017 were lower for i-Taukei (9.3 to 8.2/1000 population) than Indian males (10.6 to 9.8/1000). DASRs declined for i-Taukei (both sexes, p < 0.05), and for Indians (both sexes, p > 0.05). Over 22 years, LE at birth increased by 1 year or less (p = 0.030 in male i-Taukei). In 2014-17, LE (years) for males was: i-Taukei 64.9, Indians 63.5; and females: i-Taukei 67.0 and Indians 68.2. Mortality changes in most 5-year age groups increased or decreased the LE gap less than 10 weeks over 22 years. Compared to international agency reports, 2014-17 empirical LE estimates (males 64.7, females 67.8) were lower, as was IMR. Based on empirical data, LE in Fiji has minimally improved over 1996-2017, and is lower than some international agencies report. Adult mortality was higher in Indian than i-Taukei men, and higher in i-Taukei than Indian women. Exclusion of stillbirths resulted in IMRs lower than previously reported. Differing mortality trends in subgroups highlight the need to collect census and health data by ethnicity and sex, to monitor health outcomes and inform resource allocation.


Xenobiotic metabolism of bank vole (Myodes glareolus) exposed to PCDDs.
Previous studies in bank vole (Myodes glareolus) and field vole (Microtus agrestis) living at the old sawmill area contaminated by chlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) showed that these two relatively close species have a significant difference in their body burden of PCDD/Fs, bank voles having significantly higher concentrations. The aim of this study was to clarify more comprehensively the basic xenobiotic metabolism in wild bank voles and examine whether PCDD exposure would affect xenobiotic metabolism in bank voles more generally. The activity of cytochrome P450 enzymes was studied by fluorometric analyzes as well as by the aid of an earlier developed N-in-one CYP-selective activity cocktail, and immunoblotting assay. Several CYP-associated activities were considerably and statistically significantly elevated in the liver of animals living in the contaminated area. Increases in several CYP1A- and CYP2A/B-associated activities are probably due to the exposure to variable dioxin- and PCB-class inducers. The results of this comprehensive screening seemed to be in agreement with the existing knowledge of CYP enzyme induction by dioxin-like substances.


[Double-blind study on the anti-inflammatory effect of indomethacin after surgical removal of lower wisdom teeth].
The use of indomethacin (Amuno, Indocid) to prevent postoperative complications following oral surgery was checked in double blind tests. Impacted and half-impacted lower third molars from 100 patients were surgically removed; 50 were given indomethacin orally and 50 were given a placebo. Postoperative body temperature and pain were recorded on the first and second days after surgery. Trismus and cheek swelling were also measured.


A Comprehensive Study of the Quality of Fat-Tailed Sheep Carcasses in Greece.
Sheep farming in Greece is focused on milk production. Meat is considered a by-product and consists mainly light carcasses of undefined quality. The main challenge of the sector is to ensure sustainability, and hence efforts are towards efficient use of available resources, including undervalued carcasses of local fat-tailed sheep. The objective here was twofold: (i) to assess the carcass quality of fat-tailed sheep slaughtered at different live weights and (ii) to compare them with carcasses from thin-tailed sheep. In total, 146 fat-tailed and 97 thin-tailed dairy sheep were used. They belonged to five live-weight categories (LWC), representing 25%, 35%, 50%, 70% and 100% of mature body weight. Carcass length/weight/yield/pH and wither height were recorded. Muscle fiber minimum Feret's diameter and meat color/tenderness/moisture/lipid and protein content were determined. Sex and LWC differences in fat-tailed sheep were assessed. Parametric and non-parametric tests were used to compare with thin-tailed sheep, considering the effects of LWC, sex and their interactions with sheep population (fat-tailed/thin-tailed). Most traits were significantly different (p < 0.05) between groups of fat-tailed sheep. Carcass yield of fat-tailed sheep was significantly higher compared to thin-tailed (p < 0.01). Interactions of sheep population with LWC or sex affected wither height, carcass pH, meat color and tenderness (p < 0.05). Fat-tailed sheep meat quality is equal or higher compared to thin-tailed. Finishing weights corresponding to 50 and 70% LWC may improve capitalization of fat-tailed carcasses.


Prevalence and spatial concordance of visual field deterioration in fellow eyes of glaucoma patients.
To examine the prevalence of visual field deterioration in contralateral eyes of patients with worsening open-angle glaucoma and to evaluate the spatial concordance of visual field deterioration between both eyes. One hundred sixteen open-angle glaucoma patients who underwent 8 or more visual field examinations over ≥ 6 years of follow-up were included. The rates of the fast and slow components of visual field decay for each of 52 visual field test locations were calculated with point-wise exponential regression analysis. The spatial concordance of visual field deterioration in contralateral eyes was evaluated with a concordance ratio (calculated as the number of overlapping locations divided by the total number of deteriorating locations) and by comparing the rate of decay in corresponding modified glaucoma hemifield test clusters. The average visual field mean deviation (± standard deviation [SD]) was -8.5 (± 6.4) dB and the mean (± SD) follow-up time was 9.0 (± 1.6) years. Sixty-three patients had mild damage, 23 had moderate damage, and 30 had severe damage. The mean concordance ratio (± SD) was 0.46 (± 0.32) for the mild group, 0.33 (± 0.27) for the moderate group, and 0.35 (± 0.21) for the severe group. Thirty-one patients (27%) had deterioration in concordant locations (p < 0.05). Visual field deterioration was greater in the superior hemifield than the inferior hemifield (p < 0.05) when evaluated with both the concordance ratio and modified glaucoma hemifield test cluster analysis methods. There is only fair spatial concordance with regard to visual field deterioration between the both eyes of an individual. We conclude that testing algorithms taking advantage of inter-eye spatial concordance would not be particularly advantageous in the early detection of glaucomatous deterioration.


Alternative splicing is a developmental switch for hTERT expression.
Telomere length control is critical for cellular lifespan and tumor suppression. Telomerase is transiently activated in the inner cell mass of the developing blastocyst to reset telomere reserves. Its silencing upon differentiation leads to gradual telomere shortening in somatic cells. Here, we report that transcriptional regulation through cis-regulatory elements only partially accounts for telomerase activation in pluripotent cells. Instead, developmental control of telomerase is primarily driven by an alternative splicing event, centered around hTERT exon 2. Skipping of exon 2 triggers hTERT mRNA decay in differentiated cells, and conversely, its retention promotes telomerase accumulation in pluripotent cells. We identify SON as a regulator of exon 2 alternative splicing and report a patient carrying a SON mutation and suffering from insufficient telomerase and short telomeres. In summary, our study highlights a critical role for hTERT alternative splicing in the developmental regulation of telomerase and implicates defective splicing in telomere biology disorders.


Nanosecond difference-frequency generation in orientation-patterned gallium phosphide.
We report a tunable, single-pass, pulsed nanosecond difference-frequency generation (DFG) source based on the new semiconductor nonlinear material, orientation-patterned gallium phosphide (OP-GaP). The DFG source is realized by mixing the output signal of a nanosecond OPO tunable over 1723-1827 nm with the input pump pulses of the same OPO at 1064 nm in an OP-GaP crystal, resulting in tunable generation over 233 nm in the mid-infrared from 2548 to 2781 nm. Using a 40-mm-long crystal, we have produced ∼14 mW of average DFG output power at 2719 nm for a pump power of 5 W and signal power of 1 W at 80 kHz repetition rate. To the best of our knowledge, this is the first single-pass nanosecond DFG source based on OP-GaP. The DFG output beam has a TEM00 spatial mode profile and exhibits passive power stability better than 1.7% rms over 1.4 h at 2774 nm, compared to 1.6% and 0.1% rms for the signal and pump, respectively. The OP-GaP crystal is recorded to have a temperature acceptance bandwidth of 17.7°C.


N-[(11)C]-methyl-hydroxyfasudil is a potential biomarker of cardiac hypertrophy.
Pathologic cardiac hypertrophy is one of the leading causes of sudden death from cardiac disease and involves a complex network of bio-signaling mechanisms. To date, the clinical detection and pathologic progression of hypertrophy remains elusive. Here we tested whether imaging Rho kinase activity would serve an accurate proxy for detecting hypertrophy. Specifically, we examine the use of the N-[(11)C]-methylated derivative of hydroxyfasudil, a Rho kinase inhibitor, as a biomarker for accurate identification of cardiomyocyte hypertrophy. Both transformed and primary neonatal cardiomyocytes were treated with isoproterenol to induce β-adrenergic receptor stimulation and hypertrophy. Phenotypic hypertrophy was verified using cytochemical evaluation of cell and nuclear size. Western blot and activity assays were used to detect ERK 1/2 mTOR and Rho kinase activation. N-[(11)C]-methyl-hydroxyfasudil binding was verified using in vitro binding assays with isoproterenol stimulated cells. Isoproterenol induced a rapid and distinct activation of ERK 1/2, mTOR and Rho kinase with negligible cytotoxicity. Subsequent expansion in cell and nuclear size that is typically associated with hypertrophy was also observed. Enhanced retention of N-[(11)C]-methyl-hydroxyfasudil observed after ISO-induced Rho kinase activation in hypertrophic cells was prevented by pre-treatment with unlabeled hydroxyfasudil. N-[(11)C]-methyl-hydroxyfasudil is able to measure increased Rho kinase activity via specific binding in hypertrophied cardiomyocytes and demonstrates the potential for molecular imaging of altered Rho kinase activity in diseases such as cardiac hypertrophy.


[Distribution dynamics of dermatophytosis in Azerbaijan].
The study deals with the problem of the dermatophytosis in Azerbaijan, with regard to their etiologic and epidemiologic aspects. The information from 2004-2006 was obtained from official statistical report of Ministry of Health of Azerbaijan. From the data collected, the changes in cases of dermatophytosis were observed. The majority of cases were athlete's foot. In 2004 here were 294 cases of athlete's foot per year in Baku and 3042 in the rest of the country. The diseases declined and in 2005 there were 152 cases of athlete's foot in Baku per year and 1962 in the rest of the country; in 2006 - 197 cases of athlete's foot and 2092 cases in the rest of the country per year. The cases of dermatophytosis in Azerbaijan showed a tendency to decline. In 2004 the frequency of dermatophytosis was 48% of all cases of dermatological pathology; in 2005 the indices declined up to 17,7% of cases; in 2006 up to 14,3% cases.


Anatomical study of the anterior interosseous nerve.
The aim of this study is to investigate the location of nerves that innervate the flexor digitorum profundus (FDP), the flexor pollicis longus (FPL) and the pronator quadratus muscles. It also investigates the change in nerve location with hand movement. We studied 30 adult cadavers (17 males and 13 females) with a mean age of 69.5 years (range: 60-95 years). The reference line was from the humeral epicondylar line to the styloid process line of both the radius and ulnar bones. This study measured the anterior interosseous nerve (AIN) branch outpoint and the innervated muscle nerve entry point to the muscle belly. It also examines nerve position changes as related to making a fist. The reference line mean distance was 24.1 ± 1.2 cm. The median nerve branched into the AIN at 18.0 ± 4.0%. We found the most densely distributed section of the nerves' entry point to the muscle belly to be at a distance of 30% to 40% for the FDP and from 30% to 40% for the FPL. Except for the FPL, the nerve branch outpoints and the FDP moved by 3.0%, depending upon hand movements. The results of this study show that it will be necessary to consider the anatomy of the nerve location as it enters the muscle belly as well as how it changes with movement.


Clinical assessment of heart chamber size and valve motion during cardiopulmonary resuscitation by two-dimensional echocardiography.
It has been generally accepted that enhanced blood flow during closed-chest CPR is generated from compression of the heart between the sternum and the spine. To visualize the heart during closed-chest massage, we performed two-dimensional echocardiography (2DE) during resuscitation efforts in four patients who had cardiac arrest. 2DE analysis showed that (1) the LV internal dimensions did not change appreciably with chest compression; (2) the mitral and aortic valves were open simultaneously during the compression phase; (3) blood flow into the right heart, as evidenced by saline bubble contrast, occurred during the relaxation phase; and (4) compression of the right ventricle and LA occurred in varying amounts in all patients. We conclude that stroke volume from the heart during CPR does not result from compression of the LV. Rather, CPR-induced improved cardiocirculatory dynamics appear to be principally the result of changes in intrathoracic pressure created by sternal compression.


Imaging of Acquired Skull Base Cerebrospinal Fluid Leaks.
Acquired skull base cerebrospinal fluid (CSF) leaks can result from trauma, tumors, iatrogenic causes, or may be spontaneous. Spontaneous skull base CSF leaks are likely a manifestation of underlying idiopathic intracranial hypertension. The initial assessment of rhinorrhea or otorrhea which is suspected to be due to an acquired skull base CSF leak requires integration of clinical assessment and biochemical confirmation of CSF. Imaging with high-resolution CT is performed to locate osseous defects, while high-resolution T2w MRI may detect CSF traversing the dura and bony skull base. When leaks are multiple or if samples of fluid cannot be obtained for testing, then recourse to invasive cisternography may be necessary.


Antibiotic prophylaxis for selected gynecologic surgeries.
Antibiotic prophylaxis for surgery is commonly used and is recommended by multiple organizations. To critically review gynecology-specific data regarding surgical antibiotic prophylaxis in selected benign gynecologic surgeries. MEDLINE and Cochrane databases were searched from inception to July 2010. Randomized controlled trials of benign vaginal, cervical, transcervical, abdominal, or laparoscopic procedures other than hysterectomy comparing prophylactic antibiotic use with placebo or with another antibiotic. Outcomes of interest were postoperative infections, additional treatments, and adverse events. In total, 19 trials met the inclusion criteria. Studies were individually assessed for methodologic quality, then grouped by procedure and evaluated for evidence quality. There was no difference in infectious outcome for loop electrosurgical excision, hysteroscopic ablation, or laparoscopy, although evidence quality was poor. Fair evidence supports antibiotic prophylaxis for suction curettage or laparotomy. There were insufficient data regarding vaginal surgery prophylaxis. Antibiotic prophylaxis may be beneficial in first-trimester suction curettage and laparotomy. No advantage was found for loop electrosurgical excision, hysteroscopy, or laparoscopic gynecologic surgery. Newer procedures and vaginal surgery lack research and merit study.


Quality of drinking water and high incidence rate of esophageal cancer in Golestan province of Iran: a probable link.
Golestan province in north Iran is known to be a high-risk area for esophageal cancer (EC). Of a long list of multiple risk factors, this study focuses on a possible link between the epidemiologic patterns of EC and the anomalous concentration of some ions and elements in the drinking water sources. A total of 183 samples from 45 villages covering a wide range of EC mortality rates are collected and analyzed. The results demonstrate that NO(3)(-), SO(4)(2-), Sb, and Sr exceed the recommended maximum concentration level (MCL) in drinking water. This is more prominent in the villages with high esophageal cancer mortality rate, suggesting a possible link between EC incidence and water quality. Se concentration in drinking water increases from low to the high EC areas, a finding contrary to the expected trend. It is concluded that Se deficiency does not play a major role in the etiology of EC in the Golestan province. The statistical results obtained from Mann-Whitney and Kruskal-Wallis tests along with cluster analysis are consistent with the observed trend of EC mortality rate in Golestan province.


Radiogenomics study to predict the nuclear grade of renal clear cell carcinoma.
To develop models based on radiomics and genomics for predicting the histopathologic nuclear grade with localized clear cell renal cell carcinoma (ccRCC) and to assess whether macro-radiomics models can predict the microscopic pathological changes. In this multi-institutional retrospective study, a computerized tomography (CT) radiomic model for nuclear grade prediction was developed. Utilizing a genomics analysis cohort, nuclear grade-associated gene modules were identified, and a gene model was constructed based on top 30 hub mRNA to predict the nuclear grade. Using a radiogenomic development cohort, biological pathways were enriched by hub genes and a radiogenomic map was created. The four-features-based SVM model predicted nuclear grade with an area under the curve (AUC) score of 0.94 in validation sets, while a five-gene-based model predicted nuclear grade with an AUC of 0.73 in the genomics analysis cohort. A total of five gene modules were identified to be associated with the nuclear grade. Radiomic features were only associated with 271 out of 603 genes in five gene modules and eight top 30 hub genes. Differences existed in the enrichment pathway between associated and un-associated with radiomic features, which were associated with two genes of five-gene signatures in the mRNA model. The CT radiomics models exhibited higher predictive performance than mRNA models. The association between radiomic features and mRNA related to nuclear grade is not universal.


Anti-metastatic effect of methylprednisolone targeting vascular endothelial cells under surgical stress.
Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.


Enhanced red blood cell distribution width to platelet ratio is a predictor of mortality in patients with sepsis: a propensity score matching analysis based on the MIMIC-IV database.
To explore the association between dynamic changes in red blood cell distribution width to platelet count ratio (RPR) during hospitalisation and short-term mortality in patients with sepsis. A retrospective cohort study using propensity score matching. Intensive care units (ICUs) of Beth Israel Deaconess Medical Center. A total of 8731 adult patients with sepsis were included in the study. The patients were identified from the ICU of the Medical Information Mart for Intensive Care database. The observed group included patients who experienced an increase in RPR of more than 30% during the first week of ICU admission, whereas the control group included the rest. Using propensity score matching, a matched control group was created. The primary outcome was 28-day mortality, and the length of hospital stay and in-hospital mortality were the secondary outcomes. The difference was evident in 28-day mortality between the two groups (85.8% vs 74.5%, p<0.001, Kaplan-Meier analysis, and HR=1.896, 95% CI=1.659 to 2.168, p<0.001, Cox regression). In the secondary outcomes, there was a significant difference in in-hospital mortality (p<0.001). In addition, the study discovered that the observed groups had a significantly longer hospital stay (p<0.001). Meanwhile, the results of subgroup analyses were consistent with those of the primary analyses. In patients with sepsis, a significantly increased RPR is positively associated with the short-term death rate. Continuous RPR monitoring could be a valuable measure for predicting short-term mortality in patients with sepsis.


Use of Dorsal Nasal Flap in Combination With Nasolabial Perforator Propeller Flap for Reconstruction of Nasal Skin Defects of Medium to Large Size; A Simpler Alternative to Frontal Flap.
Nasal reconstruction is one of the most challenging procedures in plastic surgery. To get optimal aesthetic and functional results, the surgeon should know all the options well. Forehead flap is the gold standard technique for closure of medium to large defects of the nose. Although it provides a very good color and texture match, it may become a difficult option in patients with poor condition. The aim of this study was to define a simpler technique for nasal reconstruction using combined local flaps.Twelve patients, operated using a dorsal nasal flap combined with a nasolabial perforator propeller flap, were presented in the study. Properties of the patients, defect size and locations, and complications were evaluated.The mean size of the reconstructed defects was 10.1 cm2. No flap loss was observed. Venous congestion was the most common complication and resolved spontaneously in all cases. Two cases had partial distal necrosis, which also healed spontaneously.Closure was achieved successfully in all cases with a medium to large nasal defect using a combined dorsal nasal flap and nasolabial perforator propeller flap. This method can be used as an alternative to forehead flap.


SCAR makers and multiplex PCR-based rapid molecular typing of Lentinula edodes strains.
Lentinula edodes is the second most important cultivated mushroom worldwide, the most commercial strains have been identified only through traditional phenotypic analysis. In this study, a simple rapid PCR-based molecular method was developed for distinguishing commercial strains of L. edodes by developing specific sequence characterized amplified region (SCAR) markers and establishing multiplex PCR assays with the SCAR primers. Derived from the randomly amplified polymorphic DNA (RAPD) and sequence-related amplified polymorphism (SRAP) techniques, 10 informative SCAR markers were generated from 10 polymorphic RAPD and SRAP bands. The differences in SCAR phenotypes among different strains made these SCAR markers potentially useful to characterize 6 strains and identify them from other studied strains. Moreover, different SCAR phenotypes also made the other 17 studied strains to be divided into four distinguishable groups. The multiplex PCR assays were further established for the joint use of some SCAR markers efficiently. Compared with some identification methods reported previously, the special feature of this new molecular method is technically rapid and convenient in the practical use and suitable for analyzing large numbers of samples. Thus, the simple rapid PCR-based molecular method can be used as a helpful assistant tool for the lentinula industry. To our knowledge, this study is the first to describe a development of a new SCAR maker-based multiplex PCR assay for rapid molecular typing of edible mushroom.


The effects of eccentric hamstring exercise training in young female handball players.
The multidimensional role of hamstring muscle group strength in athletic performance and injury prevention is well documented, and nordic hamstring exercise (NHE) is a popular method for the development of hamstring strength. Our aim was to examine the EMG characteristics of the eccentric NHE as well as the effects of long-term eccentric NHE training on muscle strength and vertical jump performance in 10- to 11-year-old female handball players. Players from the same handball team were randomly assigned to an eccentric NHE training (13 players) or a control group (10 players). Both groups continued their regular handball training routine, but the NHE group performed additional eccentric NHE exercises once or twice a week, with progressively increasing volume, over 20 weeks. To test training effects, countermovement jump (CMJ) height, eccentric hamstring impulse, peak torque, and angle of peak torque were evaluated before, during and after the training period. In the pre-exercise test, EMG activity of the medial and lateral hamstring muscle was also assessed during NHE. Hamstring activities ranged between 98 and 129%. Lateral hamstring activity was greater than medial only in the right leg during NHE. Eccentric hamstring impulse improved in both legs at 10 weeks in both groups. Then, at 20 weeks, it remained unchanged in the NHE but decreased in controls. A similar adaptation was seen in eccentric hamstring torque, without change in the optimum knee angle. CMJ height improved only in the NHE. It is concluded that NHE activates the hamstring musculature effectively, and a favourable mechanical adaptation to long-term NHE exercise in girls can be triggered as early as 11 years of age.


Pulmonary acinar adenocarcinoma in a captive lioness (Panthera leo).
Neoplasms in wild felids are more frequently observed in captive animals, of which clinicopathological features of pulmonary tumors are not commonly described. This study aimed to describe the clinical and pathological aspects of a case of diffuse pulmonary acinar adenocarcinoma in a 23-year-old, captive lioness with clinical history of dyspnea, progressive weight loss and inappetence. At necropsy, the lungs were mildly pale, moderately firm, and the pleural surface was diffusely irregular with multifocal to coalescent, grey to white areas. No masses or superficial nodules were detected, but, on the cut surface, there were numerous, spherical, firm, white to yellow areas up to 0.5 cm in diameter affecting all pulmonary lobes. Histologically, in the lungs, there were extensive, non-delineated areas of neoplastic proliferation of columnar, ciliated epithelial cells arranged in irregular tubuloacinar structures. Immunohistochemical analysis revealed immunolabeling of neoplastic cells for pan-cytokeratin and thyroid transcription factor-1. Napsin-A exhibited only scarce and scattered immunolabeling in the neoplastic cells. The gross, histologic and immunohistochemical findings confirmed the final diagnosis of primary diffuse pulmonary adenocarcinoma.


Long-term outcomes of pediatric ocular myasthenia gravis.
To review the presenting signs, therapeutic interventions, and clinical outcomes of purely ocular myasthenia gravis in a preadolescent population treated primarily with pyridostigmine bromide. Retrospective case series. Twenty-one consecutive patients younger than 12 years with purely ocular myasthenia gravis at initial presentation. The clinical charts were reviewed retrospectively. Time to generalization, stabilization, or resolution; prism cover test results; and visual acuity. Median age at onset was 26 months. The mean duration of follow-up was 6.5 years (range, 2-15). Presenting signs included ptosis (95%), strabismus (76%), limitation of ductions (17%), and Cogan's lid twitch (76%). The most common form of strabismus was exotropia. Pyridostigmine monotherapy was the initial treatment for all patients. Corticosteroids were added to the therapy for 6 patients. Generalization to systemic disease occurred in 3 patients. Two of those required intravenous immunoglobulin and thymectomy. Complete resolution off of medical therapy occurred in 4 patients. All patients had stabilization of the ocular motor deficits regardless of treatment. Eleven patients were treated for amblyopia; 2 had residual amblyopia. Ocular myasthenia in preadolescent children generally presents before age 5 and is clinically distinguished from the disease as it affects adults. Although the presenting signs of strabismus, ptosis, and Cogan's lid twitch are common in children or adults, the response to treatment and eventual outcomes differ. Most children can be safely treated with pyridostigmine alone. Generalization to systemic disease occurs at a much lower rate than in adults. Ocular manifestations stabilize in all children and completely resolve in some.


A Flexible peptide tether controls accessibility of a unique C-terminal RNA-binding domain in leucyl-tRNA synthetases.
A unique C-terminal domain extension is required by most leucyl-tRNA synthetases (LeuRS) for aminoacylation. In one exception, the enzymatic activity of yeast mitochondrial LeuRS is actually impeded by its own C-terminal domain. It was proposed that the yeast mitochondrial LeuRS has compromised its aminoacylation activity to some extent and adapted its C terminus for a second role in RNA splicing, which is also essential. X-ray crystal structures of the LeuRS-tRNA complex show that the 60 residue C-terminal domain is tethered to the main body of the enzyme via a flexible peptide linker and allows interactions with the tRNA(Leu) elbow. We hypothesized that this short peptide linker would facilitate rigid body movement of the C-terminal domain as LeuRS transitions between an aminoacylation and editing complex or, in the case of yeast mitochondrial LeuRS, an RNA splicing complex. The roles of the C-terminal linker peptide for Escherichia coli and yeast mitochondrial LeuRS were investigated via deletion mutagenesis as well as by introducing chimeric swaps. Deletions within the C-terminal linker of E. coli LeuRS determined that its length, rather than its sequence, was critical to aminoacylation and editing activities. Although deletions in the yeast mitochondrial LeuRS peptide linker destabilized the protein in general, more stable chimeric enzymes that contained an E. coli LeuRS C-terminal domain showed that shortening its tether stimulated aminoacylation activity. This suggested that limiting C-terminal domain accessibility to tRNA(Leu) facilitates its role in protein synthesis and may be a unique adaptation of yeast mitochondrial LeuRS that accommodates its second function in RNA splicing.


Sexual assault.
Sexual assault is a problem that permeates all socioeconomic classes and impacts hundreds of thousands in the United States and millions worldwide. Most victims do not report the assault; those that do often present to an emergency department. Care must encompass the patients' physical and emotional needs. Providers must be cognizant regarding handling of evidence and possible legal ramifications. This article discusses the emergency medicine approach to history taking, physical examination, evidence collection, chain of custody, psychological and medical treatment, and appropriate follow-up. Special circumstances discussed include intimate partner violence, male examinations, pediatric examinations, suspect examinations, and drug-facilitated assaults.


In vitro inhibition of the activation of the human complement and coagulation systems by chloroquine.
The ability of chloroquine to inhibit the activation of the complement and coagulation systems was investigated. The activation of the classical pathway of complement by antibody coated sheep erythrocytes and aggregated IgG was blocked by chloroquine. Similarly, it prevented normal rabbit erythrocytes and zymosan from activating the the alternative pathway of complement. The activation of C3 by immune complexes of different solubilities also was inhibited by this drug. In addition, it abrogated the clotting of plasma by calcium chloride and thrombin. This effect could be reversed by the addition of excess thrombin but not of calcium chloride. It is suggested that the inhibition of these two important phlogistic mediator systems of inflammation may contribute to the anti-inflammatory property of chloroquine.


Metastatic nonseminomatous germ cell tumors of the testis: results of elective and salvage surgery for patients with residual retroperitoneal masses.
A mass may persist in the para-aortic region after patients undergo chemotherapy for metastatic, nonseminomatous germ cell tumor of the testis (NSGCT). Retroperitoneal lymphadenectomy removes the mass, which may contain residual active malignancy, and allows histologic assessment of the effectiveness of the chemotherapy. Whereas some have favored early, elective removal of such masses, others have chosen to observe them, reserving salvage surgery for patients who experience disease recurrence. A retrospective analysis was undertaken to define the outcome in these two groups of patients. After receiving chemotherapy for metastatic NSGCT, 442 men underwent lymphadenectomy for residual masses (measuring > or = 1 cm in greatest dimension) between 1976 and 1999, inclusive. Three hundred thirty men underwent elective surgery within 3 months of the completion of chemotherapy, and 112 men underwent salvage surgery after receiving reinduction chemotherapy for tumor recurrence. The residual mass was removed completely in 87% and 72% of patients in the elective and salvage lymphadenectomy groups, respectively; was removed with difficulty and possibly incompletely in 9% and 21% of patients, respectively; and was definitely removed incompletely in 4% and 7% of patients, respectively. The operative mortality rate was 0.9% in the elective surgery group and 1.8% in the salvage surgery group. There was malignant teratoma, undifferentiated in 8.5% of patients in the elective surgery group and in 49% of patients in the salvage surgery group (P < 0.001). Differentiated teratoma and necrosis/fibrosis were present in 66.0% and 25.4% of patients in the elective surgery group, respectively, and in 38.4% and 12.5% of patients in the salvage surgery group, respectively. The authors were unable to produce a clinically useful model to predict the presence of necrosis/fibrosis only in either group. The 5-year recurrence free and overall survival rates were 83% and 89%, respectively, in the elective surgery group and 62% and 56%, respectively, in the salvage surgery group. For the salvage surgery group, the completeness of surgical excision and the presence of undifferentiated teratoma were of overriding importance for overall survival. A variety of other patient-related, tumor-related, and surgery-related factors also were significant in the final model for the elective surgery group. The current results demonstrate the low level of morbidity that can be obtained, even in the salvage surgery group, and the importance of complete surgical resection in this setting. Because it is not possible to predict with sufficient accuracy which patients will have favorable pathology (necrosis/fibrosis), the authors continue to recommend elective surgery for all suitable men with residual masses after they receive first-line chemotherapy.


A geographical analysis of drunken drivers.
The "nearest-neighbor" spatial approach proved a useful tool in defining the geographic distribution pattern of persons arrested for drunken driving.