[Isolation of a PHA producing strain with butyric acid as the carbon source and its shaking-flask fermentation character].
A bacterial strain,WD-3,with high polyhydroxyalkanoates (PHA) yield was isolated from activated sludge. Its fermentation characters including the effects of C:N ratio, pH,fermentation time on the PHA production were also primary studied. The results showed that the optimal C/N ratio and pH were 35 and 7.0, respectively. PHA accumulation increased rapidly during the stable growth stage. The maximum PHA yield was 3.01 g x L(-), the strain accumulated PHA up to 45.4% of its cellular dry weight, and the proportion of PHV occupied one-third of the PHA production. Analysis of its 16S rRNA sequence showed that strain WD-3 belongs to Enterobacter.


Effects of dexamethasone on central and peripheral ACTH systems in the rat.
To investigate the simultaneous effects of dexamethasone on peripheral and central adrenocorticotropic hormone (ACTH) systems, rats were treated with dexamethasone or saline for 4 days. Pituitary, plasma, hypothalamus and cerebrospinal fluid (CSF) were then collected and analyzed for ACTH immunoreactivity. Additionally, hypothalamic tissue extracts were analyzed for corticotropin-releasing hormone (CRH) immunoreactivity. Dexamethasone significantly lowered peripheral levels of ACTH as measured in pituitary and plasma. Hypothalamic ACTH content significantly increased while CSF ACTH significantly decreased with dexamethasone treatment. Hypothalamic CRH concentrations showed a small but statistically insignificant decrease. These results suggest that prolonged exposure to dexamethasone affects central as well as peripheral ACTH activity, corroborate our previous findings in rhesus monkeys of decreased CSF ACTH in response to prolonged dexamethasone treatment, suggest that dexamethasone may inhibit the release of ACTH from hypothalamic neurons into the CSF, and provide evidence that the effect of dexamethasone on pituitary ACTH content is of greater magnitude than its effect on hypothalamic CRH.


Size restriction is required for proper functioning of a bipartite begomovirus AC4 protein.
Many geminiviruses including members of the genus Begomovirus produce a protein known as C4 or AC4. Whereas C4/AC4 typically consists of over 80 amino acid residues, a few are much shorter. The significance of these shorter C4/AC4 proteins in viral infection and why the virus maintains their abbreviated length is not yet understood. The AC4 of the begomovirus tomato leaf curl Hsinchu virus (ToLCHsV) contains only 65 amino acids, but it extends to 96 amino acids when the natural termination codon is replaced with a normal codon. We discovered that both interrupting and extending AC4 were harmful to ToLCHsV. The extended AC4 (EAC4) also showed a lower ability to promote the infection of the heterologous virus potato virus X than the wildtype AC4. When the wildtype AC4 was fused with yellow fluorescent protein (AC4-YFP), it was predominantly found in chloroplasts, whereas EAC4-YFP was mainly localized to the cell periphery. These results suggest that ToLCHsV's AC4 protein is important for viral infection, and the virus may benefit from its abbreviated length because it may lead to chloroplast localization.


Characteristics of physiological data during asymmetric gait of healthy subjects using a two-belt treadmill.
Mobile rehabilitation systems for patients with gait disorder are being developed. Safety functions to prevent patients from falling are considered during product development; however, few studies have been conducted on systems that have been prevalidated for healthy adults prior to application to patients. This study analyzed the characteristics of lower extremity muscles and foot pressure in healthy adults during unbalanced walking with differences in the speed of left and right speed using a two-belt treadmill. Twenty subjects performed gait motions with a difference in the weight support conditions (0% and 30%) and the left and right lower limb speeds (1-3 km/h). Each subject's muscular activities and foot pressure signals were collected. The gait patterns of the faster side exhibit similar characteristics to the paralyzed leg, and the slower side is similar to the non-paralyzed leg. Weight-supporting healthy subjects showed asymmetric gait patterns, similar to hemiplegic patients, because of the difference in the speed of the left and right side. The quantitative results can be used to develop a training protocol for two-belt treadmills with differently controlled left and right speeds for gait rehabilitation in hemiplegic patients.


A new species and new record of the commensal genus Alcyonosyllis Glasby & Watson, 2001 and a new species of Parahaplosyllis Hartmann-Schröder, 1990, (Annelida: Syllidae: Syllinae) from Philippines Islands.
A new species of Alcyonosyllis (Annelida: Syllidae), A. aidae n.sp. is described from Luzón island, Philippines, associated with the alcyonacean Dendronephthya sp. (Nephthydae). This is the sixth known species of this genus living in the Indo-Pacific region. The new species differs from other Alcyonosyllis in having long and slender cirri with the first pair of dorsal cirri slightly thicker than remaining, bidentate chaetae with distal tooth larger than proximal one, and a distinct colour pattern, with a median longitudinal, slender reddish line, and two wider lateral bands, giving a tri-lineate appearance. A new report of the recently described species, A. hinterkircheri, previously known only from an area close to Bohol, in Philippines, is also included, being the first report of this species in Luzón Island. A new species of the genus Parahaplosyllis Hartmann-Schröder, 1990, is also described. Up to now, only the type species of the genus was known, from New South Wales, Australia; this is the second known species of this genus. It differs from P. brevicirra Hartmann-Schröder, 1990 by having unidentate dorsal simple chaetae (instead of bidentate ones as in P. brevicirra), ventral simple chaeta with shorter and less curved basal spur, more distinctly articulated dorsal cirri, with a long distal article, and a shorter proventricle. Finally, new different types of stolons are described for both genera.


LSD1 mediated changes in the local redox environment during the DNA damage response.
The redox state of the cell can be affected by many cellular conditions. In this study we show that detectable reactive oxygen species (ROS) are also generated in response to DNA damage by the chromatin remodeling factor and monoamine oxidase LSD1/KDM1A. This raised the possibility that the localized generation of hydrogen peroxide produced by LSD1 may affect the function of proximally located DNA repair proteins. The two major pathways for repair of DNA double-strand breaks (DSBs) are homologous recombination (HR) and non-homologous end joining (NHEJ). Cells were exposed to low levels of ectopic H2O2, DNA breaks generated by laser light, and recruitment kinetics of NHEJ protein Ku80 to DNA damage sites determined. Ku80 recruitment to damage sites was significantly decreased in cells pretreated with H2O2 while HR end binding protein Nbs1 was increased. This suggests that the DNA repair pathway choice has the potential to be modulated by the local redox state. This has implications for chemotherapeutic approaches involving generating DNA damage to target actively dividing cancer cells, which may be more or less effective dependent on the redox state of the targeted cells and the predominant repair pathway required to repair the type of DNA damage generated.


Diversity of the transcriptional regulation of the pch gene cluster in two indigenous p-cresol-degradative strains of Pseudomonas fluorescens.
p-Cresol methylhydroxylase (PCMH), a key enzyme responsible for the catabolism of p-cresol via the protocatechuate ortho pathway, was used as a tool to characterize catabolic differences between phenol- and p-cresol-degrading Pseudomonas fluore-scens strains PC18 and PC24. Although both strains catabolize p-cresol using PCMH, different whole-cell kinetic parameters for this compound were revealed. Affinity for the substrate and the specific growth rate were higher in PC18, whereas maximum p-cresol tolerance was higher in PC24. In addition, PCMH of strain PC18 was induced during growth on phenol. In both strains, the pchACXF operon, which encodes p-hydroxybenzaldehyde dehydrogenase and PCMH, was sequenced. Transcriptional regulation of these operons by PchR, a putative sigma(54)-dependent regulator, was shown. Although the promoters of these operons resembled sigma(54)-controlled promoters, they differed from the consensus sequence by having T instead of C at position -12. Complementation assays confirmed that the amino acid sequence differences of the PchR regulators between the two strains studied led to different effector-binding capabilities of these proteins: (1) phenol was a more efficient effector for PchR of PC18 than p-cresol, (2) phenol did not activate the regulator of PC24, and (3) both regulators responded similarly to p-cresol.


Poroviscoelastic cartilage properties in the mouse from indentation.
A method for fitting parameters in a poroviscoelastic (PVE) model of articular cartilage in the mouse is presented. Indentation is performed using two different sized indenters and then these data are fitted using a PVE finite element program and parameter extraction algorithm. Data from a smaller indenter, a 15 mum diameter flat-ended 60 deg cone, is first used to fit the viscoelastic (VE) parameters, on the basis that for this tip size the gel diffusion time (approximate time constant of the poroelastic (PE) response) is of the order of 0.1 s, so that the PE response is negligible. These parameters are then used to fit the data from a second 170 mum diameter flat-ended 60 deg cone for the PE parameters, using the VE parameters extracted from the data from the 15 mum tip. Data from tests on five different mouse tibial plateaus are presented and fitted. Parameter variation studies for the larger indenter show that for this case the VE and PE time responses overlap in time, necessitating the use of both models.


Tumor-penetrating peptide fused to a pro-apoptotic peptide facilitates effective gastric cancer therapy.
KLA (sequence, KLAKLAKKLAKLAK) is a peptide which leads to programmed cell death by disrupting the mitochondrial membrane. However, low penetration in tumors greatly limits its application and efficacy. To develop a KLA-based cancer therapy, KLA-iRGD, a recombinant protein was constructed. It consists of the KLA peptide and iRGD (CRGDKGPDC), a tumor-homing peptide with high penetration into tumor tissue and cells. The conjugated KLA exhibits pro-apoptotic activity to prevent the growth of a tumor once it is inside the cell. Once KLA-iRGD is internalized in cultured tumor cells, via the activation of the receptor neuropilin-1, it spreads extensively throughout the mass of the tumor. The recombinant KLA-iRGD protein showed antitumor activity in vivo in mice and in vitro in tumor cell lines. Repeated treatment with KLA-iRGD greatly prevented tumor growth, resulting in a considerable reduction in tumor volume. According to our data, KLA-iRGD may serve as a potential anticancer agent with limited systemic toxicity and high selectivity for the treatment of MKN45 gastric cancer, which may lead to the enhancement of new targeted anticancer agents.


Differential effects of transforming growth factor-beta on the expression of collagenase-1 and collagenase-3 in human fibroblasts.
Collagenase-3 (MMP-13) is a matrix metalloproteinase (MMP) originally identified in breast carcinomas which is also produced at significant levels during fetal ossification and in arthritic processes. In this work, we have found that transforming growth factor beta1 (TGF-beta1), a growth factor widely assumed to be inhibitory for MMPs, strongly induces collagenase-3 expression in human KMST fibroblasts. In contrast, this growth factor down-regulated the expression in these cells of collagenase-1 (MMP-1), an enzyme highly related to collagenase-3 in terms of structure and enzymatic properties. The positive effect of TGF-beta1 on collagenase-3 expression was dose- and time-dependent, but independent of the effects of this growth factor on cell proliferation rate. Analysis of the signal transduction mechanisms underlying the up-regulating effect of TGF-beta1 on collagenase-3 expression demonstrated that this growth factor acts through a signaling pathway involving protein kinase C and tyrosine kinase activities. Functional analysis of the collagenase-3 gene promoter region revealed that the inductive effect of TGF-beta1 is partially mediated by an AP-1 site. Comparative analysis with the promoter region of the collagenase-1 gene which contains an AP-1 site at equivalent position, confirmed that TGF-beta1 did not have any effect on CAT activity levels of this promoter. Finally, by using electrophoretic mobility shift assays and antibody supershift analysis, we propose that c-Fos, c-Jun, and JunD may play major roles in the collagenase-3 activation by TGF-beta1 in human fibroblasts.


Increased high-level gentamicin resistance in invasive Enterococcus faecium is associated with aac(6')Ie-aph(2″)Ia-encoding transferable megaplasmids hosted by major hospital-adapted lineages.
Gentamicin is important in synergistic bactericidal therapy with cell wall agents for severe enterococcal infections. During 2003-2008, a 10-fold increase in the prevalence of high-level gentamicin resistance (HLGR), to above 50%, in blood culture isolates of Enterococcus faecium, was reported by the Norwegian Surveillance System for Antimicrobial Resistance. A representative national collection of invasive E. faecium isolates (n = 99) from 2008 was examined by a multilevel approach. Genotyping revealed a polyclonal population dominated by major hospital-associated lineages (mainly ST203, ST17, ST18, ST202 and ST192). The presence of aac(6')-Ie-aph(2″)-Ia, encoding the bi-functional aminoglycoside-modifying enzyme, was found in 98% of HLGR isolates (56/57). Furthermore, a significantly higher prevalence of potential virulence genes, toxin-antitoxin loci as well as pRE25 and pRUM type replicons was demonstrated in isolates belonging to major hospital-associated lineages compared to other sequence types. Megaplasmids of pLG1 replicon type (200-330 kb) were present in 90% of the isolates. Co-hybridization analyses revealed genetic linkage of aac(6')-Ie-aph(2″)-Ia to this replicon type. Transfer of HLGR-encoding plasmids was restricted to E. faecium. In conclusion, the increased prevalence of HLGR in invasive E. faecium in Norway is associated with hospital-adapted genetic lineages carrying aac(6')-Ie-aph(2″)-Ia-encoding transferable megaplasmids of the pLG1 replicon type.


Differential somatic cell count-A novel method for routine mastitis screening in the frame of Dairy Herd Improvement testing programs.
Somatic cell count (SCC) is used as key indicator in mastitis screening programs typically applied in the frame of Dairy Herd Improvement (DHI) testing programs. However, mastitis is still causing tremendous economic losses to the dairy industry. Hence, new biomarkers are needed that can be used for enhanced management of mastitis on dairy farms. Besides the determination of SCC, differentiation of cells has been described to be beneficial for a more definite description of the actual udder health status of dairy cows. The aim of this study was to develop a new method for rapid and simultaneous determination of SCC and a new parameter, differential somatic cell count (DSCC), in individual cow milk samples using flow cytometry. The method is sought to be applied in central milk testing laboratories, so that existing DHI infrastructures can be used. The DSCC represents the combined proportion of polymorphonuclear leukocytes (PMN) and lymphocytes expressed in percentage. The proportion of macrophages can be calculated by subtracting DSCC from 100%. Our research revealed increasing proportions of PMN, but decreasing proportions of macrophages as SCC increased. However, lymphocytes occurred fairly constantly with low proportions across the entire SCC range. Hence, the DSCC parameter reflects the antidromic trend of PMN and macrophages. Fluorescence microscopy was used to evaluate the specificity of the new Foss DSCC method in terms of DSCC and a high correlation was found. Apart from that, the accuracy of cell differentiation using the Foss DSCC method was confirmed in a cell sorting trial. Total SCC could be determined equally well using the new method as compared with existing methods. The new method was further proven to be robust toward a range of method and milk-sample-related factors. In an initial field trial, regular DHI samples of a local dairy herd were analyzed. The DSCC values occurred in a broad range from 34 to 79% in samples with <400,000 cells/mL. Higher DSCC values (53-89%) were found in samples with >400,000 cells/mL. In conclusion, the new Foss DSCC method allows reliable, repeatable, fast, robust, and accurate determination of both DSCC and SCC at low cost. This, in turn, provides more accurate information on the actual udder health status of dairy cows. The practical application of DSCC in the frame of DHI testing programs, however, needs further investigation.


Differential Effects of Early Energy and Protein Inadequacies on the Outcome of Critically Ill Patients.
Differential effects of energy and protein inadequacies of intensive care unit (ICU) patients in first 72 hours are unknown. We included all adult patients receiving mechanical ventilation (MV) > 72 hours between August 2012 and December 2014. Energy and protein doses were 25 kcal/kg/day and 1.5 g/kg/day, respectively. We used multivariable Cox regression analysis for 28-day mortality and competing risks regression analysis for post-ICU length of stay (LOS) in hospital survivors. In 421 patients (male 63.4%, mean age 62 ± 15.1 years) the energy and protein adequacies at 72 hours were 70% and 56%, respectively. Non-survivors by day 28 were started on feeding significantly later (median, 14.13 (5.48-33.78) versus 9.25 (5.45-16.58) hours, P = .003) and received lower energy (mean, 0.57 ± 0.36 versus 0.76 ± 0.29, P < 0.001) and protein (median, 0.51 (0.13-0.74) versus 0.61 (0.40-0.84), P < 0.001) adequacies at day 7 (same effect seen at 72 hours, P < 0.001). Higher energy adequacy at 72 hours was associated with lower mortality (hazard ratio [HR], 0.39 (95% CI 0.20-0.75), P = 0.004); the lowest mortality was seen between 61% and 70% energy adequacies. No such association was seen with protein adequacy. In 280 hospital survivors, higher energy adequacy at 72 hours (subdistribution HR 1.63; 95% CI, 1.06-2.50, P = 0.025) was significantly associated with shorter post-ICU LOS. No such effect was seen with protein adequacy. Higher energy but not protein adequacy at 72 hours of MV was associated with improved patient-centric outcomes.


Assessment of the Ocular Response Analyzer as an Instrument for Measurement of Intraocular Pressure and Corneal Biomechanics.
The purpose of this study is to provide better understanding of the Ocular Response Analyzer (ORA) and how reliable it is to produce intraocular pressure (IOP) measurements that are free of the effects of corneal stiffness parameters, and stiffness estimates that are independent of IOP. A numerical parametric study that closely represents the in-vivo conditions of the human eye and the ORA procedure was conducted to determine the correlation coefficient r(2) between ORA output and the values of true IOP and a number of stiffness parameters, namely corneal thickness, curvature and age. For the purpose of this exercise, the ORA output was put in the form k1P1+k2P2 where k1 and k2 were variables and P1 and P2 were ORA's measured applanation pressures. Two separate clinical datasets involving Moorfields Eye Hospital, London and the University of New South Wales, Sydney participants, respectively, were used to validate the numerical results. The numerical study results show a strong association between (k1P1 + k2P2) and the true IOP over a wide range of k1 and k2 values apart from a narrow region approximately extending from (k1 = +2, k2 = -2) to (k1 = -2, k2 = +2). On the other hand, (k1· P1 + k2· P2) was found to have a strong association with CCT, R and age (the stiffness parameters) over the same narrow region, beyond which the association was weak. Similar trends were found with the two clinical datasets. The results of this study show the potential of the ORA to provide reliable IOP measurements with weak dependence on the cornea's stiffness parameters and the considerably reduced reliability in producing stiffness estimates that are unaffected by IOP values.


Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) often acquires multi-drug resistance and is involved in many cases of disease in hospitals. We investigated natural substances directly effective against MRSA or that influence antibiotic resistance. Aloe-emodin, an anthraquinone, and several licorice flavonoids showed potent antibacterial effects against MRSA. Like some hydrolysable tannins (corilagin and tellimagrandin I) and a tea polyphenol [(-)-epicatechin gallate], the licorice flavonoid licoricidin also restored the effects of oxacillin, a beta-lactam antibiotic against MRSA. Further study revealed that theasinensin A, a polyphenol formed from (-)-epigallocatechin gallate, proanthocyanidins obtained from fruits of Zizyphus jujuba var. inermis, and polymeric proanthocyanidins from fruit peels of Zanthoxylum piperitum also suppressed the antibiotic resistance of MRSA.


Enhancing toxicity test performance by using a statistical criterion.
Aquatic toxicity tests are laboratory experiments that measure the biological effect (e.g., growth, survival, reproduction) of effluents, receiving waters, or storm water on aquatic organisms. These toxicity tests must be performed using the best laboratory practices, and every effort must be made to enhance repeatability of the test method. We evaluated the generated reference toxicant test data for insurance of a level of quality assurance for tests over time within a laboratory and among laboratories. We recommend the reporting and evaluation of the percent minimum significant difference (PMSD) value for all toxicity test results. The minimum significant difference (MSD) represents the smallest difference between the control mean and a treatment mean that leads to the statistical rejection of the null hypothesis (i.e., no toxicity) at each concentration of the toxicity test dilution series. The MSD provides an indication of within-test variability, and smaller values of MSD are associated with increased power to detect a toxic effect. We recommend upper and lower PMSD bounds for each test method in order to minimize within-test variability and increase statistical power. To ensure that PMSD does not exceed an upper bound, testing laboratories may need to increase replication, decrease variability among replicates, or increase the control mean performance.


Geographic Distribution and Temporal Trends of HIV-1 Subtypes through Heterosexual Transmission in China: A Systematic Review and Meta-Analysis.
Background: Heterosexual transmission (HST) has become the current predominant transmission pathways of the HIV-1 epidemic in China. The aim of this study was to explore the geographic and dynamic change of HIV-1 subtypes through HST in China from published studies. Methods: Several electronic databases were searched to identify the studies, and the overall prevalence of HIV-1 subtypes was estimated by a meta-analysis method. Subgroup analysis was conducted by study region and time period. Publication bias was evaluated using Egger's test. The χ² test was used to evaluate the proportion differences among subgroups. Sensitivity analysis was carried out to assess the stability of the overall prevalence estimates. Results: 42 studies were included in our final analysis. The overall prevalence of CRF01_AE was 46.34% (95% CI: 40.56-52.17%), CRF07_BC was 19.16% (95% CI: 15.02-23.66%), B/B' was 13.25% (95% CI: 9.68-17.25%), CRF08_BC was 10.61% (95% CI: 7.08-14.70%), and C was 4.29% (95% CI: 1.85-7.48%). In subgroup analysis, the prevalence of CRF01_AE and CRF07_BC increased, while the prevalence of B/B' decreased over time, whereby the prevalence of CRF07_BC and CRF08_BC have exceeded that of B/B' since 2010. A significant higher prevalence of CRF01_AE was found in the South provinces, CRF07_BC in East provinces, CRF08_BC and C in Southwest provinces, and B/B' in North provinces. Conclusions: The HIV-1 prevalent strains have evolved into complicated and diverse subtypes, and the proportion of HIV-1 subtypes through HST has changed constantly in different regions and periods in China. This highlights the urgent need to vigorously strengthen the prevention and control of the HIV-1 epidemic.


Validation of the taxon Ixodes aragaoi Fonseca (Acari: Ixodidae) based on morphological and molecular data.
The species Ixodes aragaoi Fonseca was described as Ixodes ricinus aragaoi, and later placed in synonymy with Ixodes affinis. However, this synonymy was rejected and the subspecies was elevated to species, and named as I. aragaoi. Some researchers did not consider the validity of I. aragaoi and maintained the synonymy proposed until 1998 when I. aragaoi was revalidated, and it was suggested that Ixodes pararicinus could be a synonym. The aim of this study was to confirm the taxonomic validity of I. aragaoi by means of redescription of adults and molecular analysis. Morphological studies were performed by optical and scanning electron microscopy; types of I. aragaoi were compared with those of I. pararicinus from Argentina, and also with material of I. pararicinus from Uruguay and I. affinis from the United States. Mitochondrial 16S rDNA sequences were obtained for determining phylogenetic relationships based on maximum parsimony. Morphological and molecular differences between I. aragaoi, I. pararicinus from Argentina, and I. affinis confirm the validity of the first each of these species. The morphological similarities of I. pararicinus from Uruguay with I. aragaoi, and the small distance of nucleotide sequences between them, confirm that the Uruguayan ticks are in fact I. aragaoi and expand the geographical distribution of this species. Based on the specimens of Ixodes examined in the present study, from the same locality of the types of I. ricinus rochensis in Uruguay, we agree with the synonymy of this subspecies with I. aragaoi as previously reported. Finally, our analyses indicate that both I. aragaoi and Ixodes fuscipes, another South American tick species, belong to the I. ricinus complex, currently composed of 19 species.


Comparative efficacy of hypnotics in young and middle-aged adults with insomnia: a systematic review and network meta-analysis.
Insomnia is highly prevalent in modern society. However, the hierarchical selection of hypnotics in young and middle-aged adults with insomnia remains unclear. We aimed to compare the efficacy and daytime drowsiness associated with different hypnotics for treating insomnia in young and middle-aged adults. We searched Embase, PubMed, Cochrane Library, and ProQuest Dissertations and Theses A&I databases from inception until December 15, 2021. We also manually searched reference lists and relevant publications. The literature search, data collection, and risk of bias evaluation were all carried out separately by pairs of reviewers. We included randomized control trials (RCTs) that compared hypnotics approved by the Food and Drug Administration. The R and Stata software were both used to perform the meta-analysis. In total, 117 RCTs comprising 22,508 participants with the age of 18 to 65 years were included. Assessment of the efficacy of the hypnotics and adverse events (drowsiness) revealed that zolpidem improved all objective sleep parameters (oTST, oSOL, oWASO, and oSE), zopiclone increased oTST and oSE and reduced oSOL, and daridorexant increased oTST and reduced oWASO. Regarding subjective sleep outcomes, zolpidem exhibited beneficial effects on sTST, sSOL, and sWASO. Zaleplon reduced sSOL, and zopiclone was the recommended hypnotic for improving SQ. Zolpidem was associated with drowsiness effect (odds ratio = 1.82; 95% confidence interval = 1.25 to 2.65). The results of sensitivity analysis remained unchanged after the exclusion of studies reporting long-term effects. Zolpidem is recommended for managing sleep-onset insomnia and sleep maintenance insomnia but should be used with caution because of daytime drowsiness effects. Daridorexant is recommended as a promising agent for managing sleep maintenance insomnia.


Intermolecular interactions and photogeneration of free radicals in metal-free tetrasulphophthalocyanine-tryptophan systems.
Complex formation between free-base tetrasulphophthalocyanine (TSPC) and tryptophan (Trp) in solutions of high dielectric constant was studied using absorption/emission spectroscopy. ESR experiments demonstrated dye/substrate electron or hydrogen atom transfer reactions during illumination, competing with superoxide radical generation. To discriminate between the well-known Trp photodynamic (1O2 mediated) oxidation and other reactions, Fe(III)-EDTA was added to initiate the Haber-Weiss reaction. The TSPC/Trp complex showed an enhanced ability to reduce Fe(III)-EDTA. Spin-trapping experiments and the SOD and catalase-independent formation of 2-deoxyribose/thiobarbituric acid products imply involvement of a photoinduced Haber-Weiss reaction with generation of Trp-peroxyl and Trp-alkoxy radicals as intermediates, followed by formation of Trp carbon-centred radical(s).


Accurate modeling and evaluation of microstructures in complex materials.
Accurate characterization of heterogeneous materials is of great importance for different fields of science and engineering. Such a goal can be achieved through imaging. Acquiring three- or two-dimensional images under different conditions is not, however, always plausible. On the other hand, accurate characterization of complex and multiphase materials requires various digital images (I) under different conditions. An ensemble method is presented that can take one single (or a set of) I(s) and stochastically produce several similar models of the given disordered material. The method is based on a successive calculating of a conditional probability by which the initial stochastic models are produced. Then, a graph formulation is utilized for removing unrealistic structures. A distance transform function for the Is with highly connected microstructure and long-range features is considered which results in a new I that is more informative. Reproduction of the I is also considered through a histogram matching approach in an iterative framework. Such an iterative algorithm avoids reproduction of unrealistic structures. Furthermore, a multiscale approach, based on pyramid representation of the large Is, is presented that can produce materials with millions of pixels in a matter of seconds. Finally, the nonstationary systems-those for which the distribution of data varies spatially-are studied using two different methods. The method is tested on several complex and large examples of microstructures. The produced results are all in excellent agreement with the utilized Is and the similarities are quantified using various correlation functions.


Enzyme patterns of dermatophytes.
Exoenzymes produced by common dermatophytes, in addition to their ability to cause cutaneous inflammation, are thought to contribute to fungal spread. To investigate the patterns of enzymes released by common dermatophytes as well as Scopulariopsis brevicaulis, the fungi were grown in liquid media containing either hair, stratum corneum, neopeptone or lipids, or in RPMI medium. Enzymes recovered from the culture supernatants were compared using the Api-zyme test. As a result, the widest range of enzymes was seen in protein-containing media, with a maximum of 13 enzymes stimulated by growth on hair. Dermatophytes in all protein media produced high levels of alkaline phosphatase, esterases and leucine arylamidase. In these media the highest total enzymatic activity was released by Microsporum canis, whereas the lowest was released by Epidermophyton floccosum. Although RPMI broth stimulated luxuriant growth of all species, recovery was limited to a maximum of six enzymes. In lipid medium E. floccosum and M. canis failed to grow. When comparing the various nutrients, Scopulariopsis released fewer enzymes than the dermatophytes and only minor quantities of alkaline phosphatase. We conclude that alkaline phosphatase, esterases and leucine arylamidase may be important for the parasitic growth of dermatophytes. The total enzymatic activity of dermatophytes appears to be correlated with the intensity of cutaneous inflammation. Furthermore, enzyme measurements may be helpful for species identification.


The mitochondrial genome of a sea anemone Bolocera sp. exhibits novel genetic structures potentially involved in adaptation to the deep-sea environment.
The deep sea is one of the most extensive ecosystems on earth. Organisms living there survive in an extremely harsh environment, and their mitochondrial energy metabolism might be a result of evolution. As one of the most important organelles, mitochondria generate energy through energy metabolism and play an important role in almost all biological activities. In this study, the mitogenome of a deep-sea sea anemone (Bolocera sp.) was sequenced and characterized. Like other metazoans, it contained 13 energy pathway protein-coding genes and two ribosomal RNAs. However, it also exhibited some unique features: just two transfer RNA genes, two group I introns, two transposon-like noncanonical open reading frames (ORFs), and a control region-like (CR-like) element. All of the mitochondrial genes were coded by the same strand (the H-strand). The genetic order and orientation were identical to those of most sequenced actiniarians. Phylogenetic analyses showed that this species was closely related to Bolocera tuediae. Positive selection analysis showed that three residues (31 L and 42 N in ATP6, 570 S in ND5) of Bolocera sp. were positively selected sites. By comparing these features with those of shallow sea anemone species, we deduced that these novel gene features may influence the activity of mitochondrial genes. This study may provide some clues regarding the adaptation of Bolocera sp. to the deep-sea environment.


Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease.
Periodontal disease is primarily associated with bacterial infection such as dental plaque. Dental plaque, an oral biofilm harboring a complex microbial community, can cause various inflammatory reactions in periodontal tissue. In many cases, the local bacterial invasion and host-mediated immune responses lead to severe alveolar bone destruction. To date, plaque control, non-surgical, and surgical interventions have been the conventional periodontal treatment modalities. Although adjuvant therapies including antibiotics or supplements have accompanied these procedures, their usage has been limited by antibiotic resistance, as well as their partial effectiveness. Therefore, new strategies are needed to control local inflammation in the periodontium and host immune responses. In recent years, target molecules that modulate microbial signaling mechanisms, host inflammatory substances, and bone immune responses have received considerable attention by researchers. In this review, we introduce three approaches that suggest a way forward for the development of new treatments for periodontal disease; (1) quorum quenching using quorum sensing inhibitors, (2) inflammasome targeting, and (3) use of FDA-approved anabolic agents, including Teriparatide and sclerostin antibody.


Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and Suppresses Tumor Growth on Xenografts Tumor Animal Model.
Saponins are natural compounds and possess the most promising anti-cancer function. Here, a saponin gleditsia saponin C (GSC), extracted from gleditsiae fructus abnormalis, could induce apoptosis of lung tumor cell line A549 via caspase dependent cascade and this effect could be prevented by the caspase inhibitors. In addition, GSC induced cell death companied with an increase ratio of Bax:Bcl-2 and inhibition of ERK and Akt signaling pathways. Meanwhile, GSC suppressed TNFα inducing NF-κB activation and increased the susceptibility of lung cancer cell to TNFα induced apoptosis. Furthermore, on mouse xenograft model, GSC significantly suppressed tumor growth and induced cancer cell apoptosis, which validated the anti-tumor effect of GSC. Based on these results, GSC might be a promising drug candidate of anti-lung cancer for its potential clinical applications.


Feeding behavior, life history, and virus transmission ability of Bemisia tabaci Mediterranean species (Hemiptera: Aleyrodidae) under elevated CO2.
The continuous rise of CO2 concentrations in the atmosphere is reducing plant nutritional quality for herbivores and indirectly affects their performance. The whitefly (Bemisia tabaci, Gennadius) is a major worldwide pest of agricultural crops causing significant yield losses. This study investigated the plant-mediated indirect effects of elevated CO2 on the feeding behavior and life history of B. tabaci Mediterranean species. Eggplants were grown under elevated and ambient CO2 concentrations for 3 weeks after which plants were either used to monitor the feeding behavior of whiteflies using the Electrical Penetration Graph technique or to examine fecundity and fertility of whiteflies. Plant leaf carbon, nitrogen, phenols and protein contents were also analyzed for each treatment. Bemisia tabaci feeding on plants exposed to elevated CO2 showed a longer phloem ingestion and greater fertility compared to those exposed to ambient CO2 suggesting that B. tabaci is capable of compensating for the plant nutritional deficit. Additionally, this study looked at the transmission of the virus Tomato yellow leaf curl virus (Begomovirus) by B. tabaci exposing source and receptor tomato plants to ambient or elevated CO2 levels before or after virus transmission tests. Results indicate that B. tabaci transmitted the virus at the same rate independent of the CO2 levels and plant treatment. Therefore, we conclude that B. tabaci Mediterranean species prevails over the difficulties that changes in CO2 concentrations may cause and it is predicted that under future climate change conditions, B. tabaci would continue to be considered a serious threat for agriculture worldwide.


Impact of diabetes duration and degree of carotid artery stenosis on major adverse cardiovascular events: a single-center, retrospective, observational cohort study.
We aimed to investigate the impact of diabetes duration and carotid artery stenosis (CAS) on the occurrence of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) without clinical cardiovascular disease. A total of 2006 patients with T2DM, without clinical cardiovascular disease, aged >50 years, and who underwent baseline carotid Doppler ultrasound screening with regular follow-ups at the outpatient clinic of our diabetes center, were stratified into four subgroups according to diabetes duration and CAS degree. The primary outcomes included the occurrence of MACE, defined as fatal or nonfatal stroke and myocardial infarction, and all-cause mortality. The difference in the MACE incidence was significantly greater in patients with a longer diabetes duration (≥10 years) and significant CAS (50-69% luminal narrowing) (p < 0.001). Analysis of individual MACE components indicated a trend towards an increased incidence of stroke (p < 0.001), parallel to a longer diabetes duration and significant CAS. In contrast, the risk of myocardial infarction was significantly higher in patients with a diabetes duration <10 years and significant CAS (p = 0.039). Multivariate regression analysis showed that patients with both a longer diabetes duration and significant CAS demonstrated additive and very high risks of MACE (hazard ratio [HR], 2.07; 95% confidence interval [CI] 1.17-3.66; p = 0.012) and stroke (HR, 3.38; 95% CI 1.54-7.44; p = 0.002). The risk of MACE is significantly greater in patients with T2DM, without clinical cardiovascular disease, who have both a longer diabetes duration and significant CAS, compared with those who have a shorter duration and/or nonsignificant CAS.


Patterns of Use of Human Papillomavirus and Other Adolescent Vaccines in the United States.
The purpose of the study was to describe the patterns of use of universally recommended adolescent vaccines in the United States. We identified 11-year-olds using the MarketScan insurance claims database (2009-2014). Human papillomavirus (HPV), tetanus-diphtheria-acellular pertussis (Tdap), and meningococcal (MenACWY) vaccination claims were identified using diagnosis and procedure codes. Generalized linear models estimated vaccination incidence rates and correlates of adolescent vaccination and timely vaccination. Among 1,691,223 adolescents, receipt of Tdap (52.1%) and MenACWY (45.8%) vaccinations exceeded receipt of HPV vaccination (18.4%). While both sexes had similar Tdap and MenACWY vaccination proportions, girls received HPV vaccination more frequently than boys (21.9% vs. 15.1%). Adolescents received HPV vaccination later (mean age: 11.8 years) than Tdap or MenACWY vaccination (mean age: 11.2 years for both). Half of vaccinated adolescents received Tdap and MenACWY vaccination only; however, coadministration with HPV vaccine increased with birth cohort. Western adolescents had the highest incidence rates of HPV vaccination, and Southern adolescents had the lowest. Rural adolescents were less likely than urban adolescents to receive each vaccination except in the Northeast, where they were more likely to receive HPV vaccination (incidence rate ratio: 1.09, 95% confidence interval: 1.2005-1.13). Timely HPV vaccination was associated with female sex, urbanicity, Western residence, and later birth cohort. HPV vaccination occurred later than Tdap or MenACWY vaccination and was less frequent in boys and rural adolescents. Girls, Western and urban residents, and younger birth cohorts were more likely to receive timely HPV vaccination. Vaccine coadministration increased over time and may encourage timely and complete vaccination coverage.


Deoxypodophyllotoxin suppresses tumor vasculature in HUVECs by promoting cytoskeleton remodeling through LKB1-AMPK dependent Rho A activatio.
Angiogenesis plays a critical role in the growth and metastasis of tumors, which makes it an attractive target for anti-tumor drug development. Deoxypodophyllotoxin (DPT), a natural product isolated from Anthriscus sylvestris, inhibits cell proliferation and migration in various cancer cell types. Our previous studies indicate that DPT possesses both anti-angiogenic and vascular-disrupting activities. Although the RhoA/ RhoA kinase (ROCK) signaling pathway is implicated in DPT-stimulated cytoskeleton remodeling and tumor vasculature suppressing, the detailed mechanisms by which DPT mediates these effects are poorly understood. In the current study, we found that DPT promotes cytoskeleton remodeling in human umbilical vein endothelial cells (HUVECs) via stimulation of AMP-activated protein kinase (AMPK) and that this effect is abolished by either treatment with a selective AMPK inhibitor or knockdown. Moreover, the cellular levels of LKB1, a kinase upstream of AMPK, were enhanced following DPT exposure. DPT-induced activation of AMPK in tumor vasculature effect was also verified by transgenic zebrafish (VEGFR2:GFP), Matrigel plug assay, and xenograft model in nude mice. The present findings may lay the groundwork for a novel therapeutic approach in treating cancer.


Modelling the effect of contact formation on electron transfer in single-molecule device.
The electric properties of single-molecule devices are very sensitive to details of contact formation between the molecule and the metallic electrodes. However the factors that control the electron transfer through the molecule in these devices, corresponding to slightly different molecule-metal attachments, are not well understood. In this work, we used a self-consistent molecular dynamics method to study the effect of symmetric and asymmetric contact realizations on electron transfer between two metallic electrodes through a spatially symmetric conjugated molecule. Our results showed that both symmetric and asymmetric electron transfer, with respect to voltage inversion, can be obtained with the same molecule in agreement with the experiments. Besides, a central factor determining the asymmetric electron transfer through a symmetric molecule, caused by the asymmetric contact realization, is the oscillation of the entire molecule between both electrodes and its distortion.


A glycosyltransferase gene signature to detect pancreatic ductal adenocarcinoma patients with poor prognosis.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an important heterogeneity, reflected by different clinical outcomes and chemoresistance. During carcinogenesis, tumor cells display aberrant glycosylated structures, synthetized by deregulated glycosyltransferases, supporting the tumor progression. In this study, we aimed to determine whether PDAC could be stratified through their glycosyltransferase expression profiles better than the current binary classification (basal-like and classical) in order to improve detection of patients with poor prognosis. Bioinformatic analysis of 169 glycosyltransferase RNA sequencing data were performed for 74 patient-derived xenografts (PDX) of resected and unresectable tumors. The Australian cohort of International Cancer Genome Consortium and the microarray dataset from Puleo patient's cohort were used as independent validation datasets. New PDAC stratification based on glycosyltransferase expression profile allowed to distinguish different groups of patients with distinct clinical outcome (p-value = 0.007). A combination of 19 glycosyltransferases differentially expressed in PDX defined a glyco-signature, whose prognostic value was validated on datasets including resected whole tumor tissues. The glyco-signature was able to discriminate three clusters of PDAC patients on the validation cohorts, two clusters displaying a short overall survival compared to one cluster having a better prognosis. Both poor prognostic clusters having different glyco-profiles in Puleo patient's cohort were correlated with stroma activated or desmoplastic subtypes corresponding to distinct microenvironment features (p-value < 0.0001). Besides, differential expression and enrichment analyses revealed deregulated functional pathways specific to different clusters. This study identifies a glyco-signature relevant for a prognostic use, potentially applicable to resected and unresectable PDAC. Furthermore, it provides new potential therapeutic targets. This work was supported by INCa (Grants number 2018-078 and 2018-079), Fondation ARC (Grant number ARCPJA32020070002326), Cancéropôle PACA, DGOS (labelization SIRIC, Grant number 6038), Amidex Foundation and Ligue Nationale Contre le Cancer and by institutional fundings from INSERM and the Aix-Marseille Université.


Delayed Diagnosis of Duodenal Metastasis From Primary Lung Adenocarcinoma: A Case Report.
The incidence of lung cancer metastasizing to the duodenum is rare, and its clinical presentation is still not fully understood due to its low frequency. It can be asymptomatic or present symptomatically in various ways. Here, we present the case of a 63-year-old female with an unusual case of duodenal metastasis from pulmonary adenocarcinoma, presenting with a new-onset seizure complicated by a fracture from a post-ictal fall. The diagnosis of anemia secondary to duodenal metastasis from lung cancer was delayed due to this sequence of events. The patient was ultimately found to have a circumferential mass in the third portion of the duodenum on esophagogastroduodenoscopy, which was found to be consistent with metastatic pulmonary adenocarcinoma on pathological examination.


Improving professional health literacy in hospitals: study protocol of a participatory codesign and implementation study.
In connection with a hospital stay, patients have to make important health-related decisions. They need to find, understand, assess and apply health-related information, and therefore, require health literacy. Adequately responding to the needs of patients requires promoting the communication skills of healthcare professionals within healthcare organisations. Health-literate healthcare organisations can provide an environment strengthening professionals' and patients' health literacy. When developing health-literate healthcare organisations, it has to be considered that implementing organisational change is typically challenging. In this study, a communication concept based on previously evaluated communication training is codesigned, implemented and evaluated in four clinical departments of a university hospital. In a codesign phase, focus group interviews among employees and patients as well as a workshop series with employees and hospital management are used to tailor the communication concept to the clinical departments and to patients' needs. Also, representatives responsible for the topic of health literacy are established among employees. The communication concept is implemented over a 12-month period; outcomes studied are health literacy on the organisational and patient levels. Longitudinal survey data acquired from a control cohort prior to the implementation phase are compared with data of an intervention cohort after the implementation phase. Moreover, survey data from healthcare professionals before and after the implementation are compared. For formative evaluation, healthcare professionals are interviewed in focus groups. The study protocol was approved by the Ethics Committee of the Medical Faculty of the University of Oldenburg and is in accordance with the Declaration of Helsinki. Study participants are asked to provide written informed consent. The results are disseminated via direct communication within the hospital, publications and conference presentations. If the intervention turns out to be successful, the intervention and implementation strategies will be made available to other hospitals. DRKS00019830.


Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.
To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.


Altered economic decision-making in abstinent heroin addicts: Evidence from the ultimatum game.
The development and persistence of drug addiction has been suggested to involve decision-making deficits. The Ultimatum Game is a widely used economic decision-making paradigm that illustrates the tension between financial self-interest and fairness motives. The behavior of responders in the Ultimatum Game has been associated with emotional reactions and cognitive control abilities, both of which are dysregulated in drug addicts. In this study, we investigated whether this economic decision-making process that involves considerations of social norms is affected by heroin addiction. Heroin addicts (n=17) and demographically matched healthy control subjects (n=18) were recruited to play the part of responders in the Ultimatum Game, during which they decided to accept or reject the monetary offers proposed by strangers. The offers were manipulated by varying the stake sizes and fairness scales. The rejection rates of all of the offer categories, response times, fairness judgments, and impulsivity were compared between heroin addicts and healthy controls. Compared with healthy subjects, the rejection rates of most unfair offers in the Ultimatum Game were significantly higher under low-offer-size conditions among heroin addicts. In contrast, the most unfair offers were more likely to be accepted by heroin addicts in the high-offer-size condition than by healthy subjects. The ratings of unfairness were equal in both conditions although the rejection rates were different. Heroin addicts had higher scores on BIS attentional/cognitive impulsivity and non-planning impulsivity, but not in motor impulsivity. Rejection rates to most unfair offers under low-offer-size conditions significantly correlated with score on BIS non-planning impulsivity and total score of impulsivity. Heroin addicts differentially responded under different stake-level conditions in the Ultimatum Game, with emotional impulses in low-offer-size conditions and selfish motives in the face of high monetary reward. These findings indicate that Ultimatum Game may be associated with heroin addiction and provide a productive new target for enhancing treatment for heroin addiction.


Elevated androgen levels induce hyperinsulinemia through increase in Ins1 transcription in pancreatic beta cells in female rats.
Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test. DHT females had no change in islet number, size and beta cell proliferation/apoptosis but exhibited significant mitochondrial dysfunction (higher ADP/ATP ratio, decreased mtDNA copy number, increased reactive oxygen production and downregulation of mitochondrial biogenesis) and enhanced glucose-stimulated insulin secretion. Ins expression was increased in DHT islets. In vitro incubation of control islets with DHT dose dependently stimulated Ins transcription. Analysis of Ins1 gene revealed a putative androgen responsive element in the promoter. Chromatin-immunoprecipitation assays showed that androgen receptors bind to this element in response to DHT stimulation. Furthermore, reporter assays showed that the promoter element is highly responsive to androgens. Insulin-stimulated glucose uptake in skeletal muscle was decreased with associated decrease in IRβ expression in DHT females. Our studies identified a novel androgen-mediated mechanism for the control of Ins expression via transcriptional regulation providing a molecular mechanism linking elevated androgens and hyperinsulemia. Decreased IRβ expression in the skeletal muscles may contribute, in part, to glucose intolerance in this model.


[Leg-lengthening for length inequality].
32 patients (age range 1.5-22 years) were treated for leg-length discrepancy. 39 lengthening procedures were performed of which 36 involved gradual distraction, in 2 cases chondrodiasthesis was used, and 1 had 1-step elongation. Gradual distraction was done according to Ilizarov, including corticotomy and a 1-week delay before the initiation of distraction. In 33 cases Wagner's external fixator was used, in 2 Ilizarov frame and in 1 an orthofix fixator. There was complete clinical and radiologic union in all but 1 case. Significant correction of leg-length discrepancy and equalization of leg-length was achieved in most patients. In some growing patients over-correction was successfully achieved. The most prevalent complications were pin-site problems, axis deviation, joint subluxation and joint contractures. At latest follow-up most of these complications had disappeared. 91% of the patients either functioned normal or were only mildly limited.


Unique V gene usage by B-Ly1 cell lines, and a discordance between isotype switch commitment and variable region hypermutation.
We have previously described a series of Ly-1+ B cell lines obtained as spontaneous outgrowth cultures from mouse spleen cells (B-Ly1 cells). In this study, we report the variable region sequences utilized by independent cell lines derived from three mouse strains. Remarkably, V region utilization and junctional diversification were essentially identical in all three cell lines. These included: lambda 1 light chain; JH1; DSP2-7,8; and, a novel VH gene segement. The VH was highly homologous to CP4, a rare VH family previously found in a group of Ly-1 B cell-derived autoantibodies to bromelain-treated mouse red blood cells. The selective expression of this unusual lg species implies the action of distinctive molecular or immunophysiological processes in the outgrowth of B-Ly1 cell lines. Clarification of these factors may be relevant to understanding the peculiar biology of Ly-1 B cells in vivo. We have also evaluated switch-committed B-Ly1 clones to determine whether this phenotype is accompanied by variable region somatic mutation. However, no evidence for somatic mutation was observed in these induced clones. This may indicate that these two processes are independently regulated, despite their common concordance in vivo.


Rapid Identification and Drug Susceptibility Testing of Mycobacterium tuberculosis: Standard Operating Procedure for Non-Commercial Assays: Part 3: Colorimetric Redox Indicator Assay v1.3.12.
The previous two standard operating procedures (SOPs) related to the culture and drug susceptibility testing (DST) of Mycobacterium tuberculosis with the microscopic observation drug susceptibility assay (Part 1) and nitrate reductase assay (Part 2). The present SOP is devoted to a third non-commercial culture and DST method known as colorimetric redox indicator assay (CRI). As its name indicates, the CRI detects the ability of the M. tuberculosis to reduce the colored oxidation-reduction indicator when added to a liquid culture of M. tuberculosis, after exposing the growth to different anti-mycobacterial drugs. The change in the color of the indicator denotes the proportionate number of viable Mycobacteria in the medium. The identification and DST results can be obtained in 7-8 days. This SOP document has been developed through the culture and DST subgroup of the STOP tuberculosis (TB) Partnership New Diagnostic Working Group. It is intended for laboratories that would want to use or already use this rapid non-commercial method for culture identification and DST of M. tuberculosis, notably in resource-constraint settings in Asia and Africa.


[Principles of functioning of the complex of transcription initiation by RNA polymerase II].
This final review describes the general principle and mechanisms that underlie functioning of the machinery of transcription initiation by polymerase II in eukaryotes. The main models of transcription initiation, the module principle underlying the structure of the transcription complex, the regulation of transcription initiation, and the association between the nuclear architecture and transcription are discussed.


Current and future therapeutic strategies in NAFLD.
Non alcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and considered to be the commonest liver disorder in Western countries. It comprises a disease spectrum ranging from simple steatosis (fatty liver), through non-alcoholic steatohepatitis (NASH) to fat with fibrosis and ultimately cirrhosis. Simple steatosis is largely benign and non-progressive, whereas NASH, characterized by hepatocyte injury, inflammation and fibrosis can lead to cirrhosis, liver failure and hepatocellular carcinoma (HCC). NAFLD is strongly associated with obesity, insulin resistance, hypertension and dyslipidaemia and is now regarded as the liver manifestation of the metabolic syndrome. Rapid spread of the obesity 'pandemic' in adults and children, coupled with the realisation that the outcomes of obesity-related liver disease are not entirely benign, has led to rapid growth in clinical and basic studies in NAFLD over the past decade. These studies are now beginning to inform management strategies for patients with NAFLD.


EN FACE IMAGING OF RETINAL ARTERY MACROANEURYSMS USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.
To describe the advantages of en face view with swept-source optical coherence tomography in assessing the morphologic features of retinal arterial macroaneurysms, their consequences on adjacent retina, planning laser treatment, and evaluating its effects. Three eyes were treated for retinal arterial macroaneurysms and followed by swept-source optical coherence tomography in 2014-2015. En face images of the retina and choroid were obtained by EnView, a swept-source optical coherence tomography program. Retinal arterial macroaneurysms have a typical optical coherence tomography appearance. En face view allows delineation of the macroaneurysm wall, thrombotic components within the dilation, and lumen measurement. Hemorrhage, lipids, and fluids can be precisely described in terms of amount and extent over the macula and depth. This technique is also practical for planning focal laser treatment and determining its effects. En face swept-source optical coherence tomography is a rapid, noninvasive, high-resolution, promising technology, which allows excellent visualization of retinal arterial macroaneurysms and their consequences on surrounding tissues. It could make angiography with intravenous injection redundant in planning and assessing therapy.


[Surgery (TUR-P) as a recommended initial treatment modality for the presented case].
The pathophysiology of lower urinary tract dysfunction in the presented case comprised voiding dysfunction and overactive bladder. Two etiologies for voiding dysfunction in this case could be considered, bladder outlet obstruction due to benign prostatic hyperplasia (BPH) or detrusor underactivity. Prospected efficacies of pharmacological and surgical treatment (transurethral resection of prostate: TUR-P) for this case were compared based on a literature review. Alpha-1 blockers improve both voiding and storage symptoms in patients with BPH. However, improvement of maximum flow rate (Qmax) on uroflowmetry is limited within a small range and there is no evidence of significant reduction in residual urine volume. Alpha-1 blockers have no significant efficacy in improvement of objective measures in patients with detrusor underactivity. Although anticholinergics improve overactive bladder symptoms, they are contraindicated for patients with severe voiding dysfunction with residual urine. There is a lack of study on efficacy of apha-1 blocker administration combined with anticholinergics available in our hands for patients with BPH and overactive bladder. On the other hand, TUR-P brings remarkable improvement in voiding and storage symptoms, increase of flow rate and reduction of residual urine as a gold-standard surgical treatment for BPH. Urge incontinence and uninhibited detrusor contraction on cystometry reportedly disappeared in 60% of patients following TUR-P. TUR-P also improves subjective symptom and objective measures in patients with BPH and detrusor underactivity. Based on the literature review, surgery is recommended as a standard initial therapy for the presented patient with significant voiding dysfunction (Qmax 9.4 ml/sac and residual urine 72 ml).


Outcome of hepatitis B and C virus infection on graft function after renal transplantation.
Chronic liver disease resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is still a major concern in kidney recipients. It is unclear whether HCV antibody status and markers of HBV infection are associated with renal dysfunction. Thus, we designed a study to investigate the incidence of HBV and HCV infection after renal transplantation and whether these infections alter graft function. Fifty-eight patients who underwent renal transplantation participated in the study. Serum creatinine and aminotransferase levels were measured with standard automated analyzers. Anti-HCV antibodies were detected with an enzyme immunoassay, and a reverse transcriptase-polymerase chain reaction (RT-PCR) technique was used to test for HCV-RNA. Serological markers for HBV (HBsAg and anti-HBc antibody) were detected by enzyme immunoassay. All samples from patients who were seropositive for HBsAg or anti-HBc antibody were PCR-tested for HBV-DNA. A serum sample collected from living donors was tested for anti-HCV antibodies and serological markers for HBV. Serum creatinine and aminotransferase levels were also measured in living donors. Anti-HCV was not detected in serum samples of any cases before transplantation. However, 10 (17.2%) tested positive after transplantation. HCV-RNA was detected in 2 of the 10 patients (3.4% of all patients). None of the pretransplantation serum samples tested positive for HBsAg. However, anti-HBc antibody was identified in 8 (13.8%) of the 58 patients.. No HBV DNA was detected in serum samples of the patients with anti-HBc or HBsAg-positive. HBsAg was only detected in 1 (1.7%) recipient after transplantation. None of the 58 patients showed clinical signs or symptoms of renal dysfunction during the study period. Our data suggest that, neither HBV nor HCV infection appears to cause or contribute to renal dysfunction in the early period (1 year) after renal transplantation. Nevertheless, a long-term consequence of chronic HBV or HCV liver disease or graft loss is not impossible in renal transplant recipients.


CLUTCH SIZE AND EGG SIZE IN FREE-LIVING AND PARASITIC COPEPODS: A COMPARATIVE ANALYSIS.
The evolution of reproductive strategies and the trade-off between number and size of eggs were investigated in a comparative analysis of free-living and parasitic copepods. Data from 1038 copepod species were used to obtain family averages for 105 families; the phylogenetic relationships among these families include 94 branching events or 94 independent contrasts on which the analysis was based. Transition from a free-living existence to parasitism on invertebrates resulted in small increases in body size. Transition from parasitism on invertebrates to parasitism on fish was associated with greater increases in body size. After controlling for body size, a switch to fish hosts resulted in an increase in the number of eggs produced and a reduction in egg size. Among all contrasts, there was a negative relationship between changes in relative clutch size and changes in relative egg size, suggesting the existence of a trade-off between egg size and numbers. However, opposite changes in these measures of clutch size and egg size were not quite more frequent than expected by chance, therefore indicating that investments into egg numbers are not necessarily made at the expense of egg size, and vice versa. Latitude affected copepod body size, clutch size, and egg size, whereas the effects of freshwater colonization or size of the fish host were not significant. Comparative analyses at either the genus or species levels within given taxa of copepods parasitic on fish provided limited support for a trade-off between clutch size and egg size, but were hampered by the small number of independent phylogenetic contrasts available. From the family-level comparative analysis, it appears that the evolutionary transition from a free life to parasitism on invertebrates, and the transition from parasitism on invertebrates to parasitism on fish, have led to changes in life-history traits in response to the different selective pressures associated with the different modes of life.


Fluorescent self-assembled monolayers of umbelliferone: a relationship between contact angle and fluorescence.
Self-assembled monolayers (SAMs) that contain fluorophore units are nowadays widely used to tune surface properties and design new chemical sensor chips. It is well-known that the nature of the substrate may strongly interfere with the emission properties of the grafted molecules, but the organization of the monolayer may also have an important role. To study the influence of the SAM organization on the luminescence properties, we prepared different coumarin-based derivatives endowed with tethered chains of different lengths and elaborated the corresponding SAMs on glass slides. Besides SAM structural characterizations by atomic force microscopy and X-ray reflectivity, we carried out contact angle measurements and applied the Van Oss-Chaudhury-Good theory, which was rarely used previously for self-assembled monolayers. As expected, by increasing the tethered chain length, a higher surface coverage, a higher degree of organization, and a stronger molecular packing were observed. However, it appears to facilitate the self-quenching process, and thus, this strongly affects the fluorescent properties of the SAMs.


Cerebral cysticercosis by Taenia crassiceps in a domestic cat.
Cerebral cysticercosis by Taenia crassiceps was diagnosed in an adult female domestic shorthair cat. The animal was euthanized 6 weeks after the initial presentation with signs of vomiting, lethargy, and ataxia. The disease took an intermittent relapsing course with the neurological signs progressing eventually to recumbancy and coma. At necropsy, numerous cysticerci were found in the dilated left lateral ventricle and the adjacent brain parenchyma. The cysticerci were identified as metacestodes of T. crassiceps larvae based on size and morphology of the cysts; shape, number, and size of the rostellar hooks; and mode of proliferation, including endogenous and exogenous budding. Cerebral cysticercosis by T. crassiceps is rare in atypical intermediate hosts and has not been described in cats.


Role of N-acetyl galactosamine-4-SO4, a ligand of CD206 in HSV-induced mouse model of Behçet's disease.
CD206 is a macrophage mannose receptor involved in variety of autoimmune and inflammatory diseases. This study aimed to identify the pathogenic role of CD206 in a herpes simplex virus (HSV) induced Behçet's disease (BD) mouse model. CD206 positive cells were detected in peripheral blood mononuclear cells and quantified by flow cytometry. Levels of cytokines were measured by ELISA. CD206 was found to be down-regulated both in vitro (10-6M) and in vivo (200μg/mouse) after treatment with N-acetylgalactosamine (GalNAc), a ligand for CD206. The down-regulation of CD206 was correlated with improvement in BD symptoms. Colchicine (2μg/mouse) or pentoxifylline (400μg/mouse) treated mice displayed improvement in BD symptoms with fewer CD206 positive cells. The prevalence of CD206-positive cells differed between ligand-responsive and non-responsive BD mice. Inhibition of CD206 was associated with down-regulated serum level of interleukin-17 in GalNAc-treated BD mice. These results suggest that the expression of CD206 is correlated with HSV-induced BD symptoms in mice, implicating that CD206 might have a pathogenic role in BD.


Modeling the contrast-sensitivity functions of older adults.
To determine whether a parabolic template is a good description of the contrast-sensitivity functions (CSF's) exhibited by older adults, the curve-fitting method of Pelli et al. [J. Opt. Soc. Am. A 3(13), P56 (1986)] was applied to contrast-sensitivity data from 100 older subjects (ages 53-85 years). Although the method resulted in reasonable fits for most subjects, closer inspection revealed that this technique may be problematic. A significant number of observers had functions that were nonparabolic, and for many subjects the error tended to be concentrated at the peak of the CSF. In addition, in contrast to the study of Pelli et al., the peak contrast sensitivities of the subjects were only weakly related to Pelli-Robson contrast sensitivity and letter acuity. The data were also fitted with an asymmetric function of variable shape. Whereas this function provided a better fit to the nonparabolic CSF's, it resulted in inferior fits to most of the remaining data. These results demonstrate that the spatial CSF's of older adults cannot be described by a single parametric curve such as a parabola or a function of an exponential and that Pelli-Robson contrast sensitivity and letter acuity are not adequate predictors of their peak contrast sensitivities.


Implications of methylation patterns of cancer genes in salivary gland tumors.
We investigated the methylation status and protein expression of four tumor suppressor genes to determine their role in salivary gland tumorigenesis. We performed methylation-specific PCR and protein analyses of 29 normal salivary glands, 23 benign, and 79 malignant salivary gland neoplasms to determine the pattern and potential diagnostic and/or biological role of the RASSF1, RARbeta2, DAPK, and MGMT tumor suppressor gene methylation in these tumors. No methylation was detected in the normal tissues. Methylation occurred in 9 of 23 (39.1%) benign tumors; 3 (25.0%) pleomorphic adenomas and 6 (66.7%) Warthin's tumors at the MGMT, DAPK, or RASSF1 genes. Methylation occurred in 33 of 79 (41.8%) malignant tumors; 8 (30.8%) adenoid cystic carcinomas, 6 (33.3%) mucoepidermoid carcinomas, 6 (42.9%) acinic cell carcinomas, and 13 (62.0%) salivary duct carcinomas. RASSF1 and RARbeta2 represented 75.8% of methylation events occurring most frequently in salivary duct and acinic cell carcinomas. Overall, we found no significant correlation between protein expression and methylation status of individual genes, but observed low or absent protein expression in several methylated tumors. Significant correlations were found between methylation and aggressive malignant phenotypes (P = 0.0004) and age (P = 0.05). (a) Benign and malignant salivary tumors differed in the frequency and pattern of gene methylation; (b) high-grade carcinomas were significantly methylated compared with low-grade phenotypes; (c) RASSF1 and RARbeta2 were highly methylated in malignant tumors and can be targeted for therapy; and (d) methylation pattern may serve as a diagnostic and biological marker in assessing these tumors.


Malassezia otitis externa in the dog: the effect of heat-fixing otic exudate for cytological analysis.
This study was conducted on 32 dogs with Malassezia otitis externa to determine the effect of heat-fixing otic exudate on cytological analysis. Malassezia infection was confirmed by cytological examination of otic exudate. Otic discharge collected with cotton swabs was then rolled onto glass slides. One slide per dog was heat-fixed prior to staining; the other slide was not heat-fixed. The number of yeast in 10 oil-immersion fields (1000 x magnification) was counted for both slides from each dog. Heat-fixing did not systematically cause either increased or decreased numbers of Malassezia on cytology of otic exudate.


Multiple Salivary Cortisol Measurements Are a Useful Tool to Optimize Metyrapone Treatment in Patients with Cushing's Syndromes Treatment: Case Presentations.
Measuring salivary cortisol is both convenient and non-invasive for patients; however, its usefulness as a marker for monitoring medical therapy has not yet been established. The aim of this study was to assess the utility of multiple salivary cortisol measurements in patients with Cushing's syndrome (CS) during medical therapy. Six patients with CS (three with cortisol-secreting adrenocortical adenoma and three with ACTH-secreting pituitary adenoma) were recruited. Samples for morning serum cortisol, urinary free cortisol (UFC), and multiple salivary cortisol levels were collected before and during metyrapone treatment. The area under the curve (AUC) and mean value (MV) of daily salivary cortisol levels were calculated. In five out of six patients, UFC were normalized; however, multiple salivary cortisol measurements revealed an impaired diurnal cortisol rhythm in these patients. To verify the usefulness of multiple salivary cortisol measurements, we performed a prospective case study of a patient in whom the excess secretion of cortisol was not controlled (UFC 211 μg/day) with 2,250 mg/day in four divided doses of metyrapone. Multiple measurements of salivary cortisol revealed that cortisol levels elevated before the next administration. Accordingly, we shortened the interval by increasing the number of administration from four to five times per day, with a slight increment of daily dose of 2,500 mg. These optimizations resulted in a drastic improvement of diurnal pattern as well as UFC level (101 μg/day). Changes in both the MV and AUC of salivary cortisol levels were more correlated with those in UFC levels (Correlation coefficient 0.75, p = 0.007, and 0.70, p = 0.017) than those in the morning serum cortisol levels (0.42, p = 0.200), indicating that multiple salivary cortisol measurements reflect more precisely the excess secretion of cortisol. Our preliminary data suggest that multiple salivary cortisol measurements can be a useful tool to visualize the diurnal cortisol rhythm and to determine the dose and timing of metyrapone during the treatment in patients with CS.


Maternal and congenital toxoplasmosis in Mayotte: Prevalence, incidence and management.
Toxoplasmosis is an infection caused by an intracellular protozoan, Toxoplasma gondii. It is usually asymptomatic, but toxoplasmosis acquired during pregnancy can cause congenital toxoplasmosis, potentially resulting in fetal damage. Epidemiological information is lacking for toxoplasmosis in Mayotte (a French overseas territory). We evaluated (1) the prevalence of maternal toxoplasmosis, (2) the incidence of maternal and congenital toxoplasmosis, and (3) the management of congenital toxoplasmosis in Mayotte. We collected all the available data for toxoplasmosis serological screening during pregnancy and maternal and congenital cases of toxoplasmosis obtained between January 2017 and August 2019 at the central public laboratory of Mayotte (Mamoudzou). Using toxoplasmosis serological data from samples collected from 16,952 pregnant women we estimated the prevalence of toxoplasmosis in Mayotte at 67.19%. Minimum maternal toxoplasmosis incidence was estimated at 0.29% (49/16,952, 95% CI (0.0022-0.0038)), based on confirmed cases of maternal primary infection only. The estimated incidence of congenital toxoplasmosis was 0.09% (16/16,952, 95% CI (0.0005-0.0015). Missing data made it difficult to evaluate management, but follow-up was better for mothers with confirmed primary infection and their infants. The seroprevalence of toxoplasmosis among pregnant women and the incidence of toxoplasmosis are higher in Mayotte than in mainland France. There is a need to improve the antenatal toxoplasmosis screening and prevention programme, providing better information to physicians and the population, to improve management and epidemiological monitoring.


Mechanism of Fluorescence Switching in One ESIPT-Based Al(3+) Probe.
A recently synthesized Schiff base used as a probe for aluminum cations was studied with ab initio models. The primary reason for the lack of fluorescence in aprotic solvents was found to be the presence of an efficient conical intersection (CI) between the ground-states and the first singlet excited-states close to the Franck-Condon geometry. The excited-state pathway leading to this CI is barrierless but implies large amplitude motions, explaining why the fluorescence was observed in frozen acetonitrile matrix. Our calculations suggest that constraining the molecule by impending the rotation around the imino bond enables excited-state intramolecular proton transfer. A similar stiffening mechanism is responsible for the strong fluorescence turn-on after formation of complexes between Al(3+) cations and dehydrogenated Schiff base. Finally, the analysis of the possible fluorescence mechanisms in water indicates that the anion of 1 is the likely fluorescence source. Overall, this work allows one to disentangle the various origins of fluorescence switching in a probe.


Does the number of free nicotine patches given to smokers calling a quitline influence quit rates: results from a quasi-experimental study.
The offer of free nicotine replacement therapy (NRT) can be a cost-effective marketing strategy to induce smokers to call a telephone quitline for quitting assistance. However, the most cost-effective supply of free NRT to provide to smokers who call a quitline remains unknown. This study tests the hypothesis that smokers who call a telephone quitline and are given more free nicotine patches would report higher quit rates upon follow-up 12 months later. A quasi-experimental design was used to assess nicotine patch usage patterns and quit rates among five groups of smokers who called the New York State Smokers' Quitline (NYSSQL) between April 2003 and May 2006 and were mailed 2-, 4-, 6- or 8-week supplies of free nicotine patches. The study population included 2,442 adult (aged 18 years or older) current daily smokers of 10 or more cigarettes per day, who were willing to make a quit attempt, and reported no contraindications for using the nicotine patch. Outcome variables assessed included the percentage of smokers who reported that they had not smoked for at least 7-days at the time of a 12 months telephone follow-up survey, sustained quitting, delayed quitting and nicotine patch use. Quit rates measured at 12 months were higher for smokers in the groups who received either 2, 6, or 8 weeks of free patches. The lowest quit rate was observed among the group of Medicaid/uninsured smokers who were eligible to receive up to six weeks of free patches. The quit rate for the 4-week supply group did not differ significantly from the 6-week or 8-week groups. These patterns remained similar in an intent-to-treat analysis of 12-month quit rates and in an analysis of sustained quitting. No clear cut dose response relationship was observed between the number of free nicotine patches sent to smokers and smoking outcomes. Baseline differences in the characteristics of the groups compared could account for the null findings, and a more definitive randomized trial is warranted.


Vasculotoxic and Proinflammatory Effects of Plasma Heme: Cell Signaling and Cytoprotective Responses.
The proinfammatory vasculotoxic effects of intravascular hemolysis are modulated by plasma hemoglobin and heme clearance via the haptoglobin/CD163 system and the hemopexin/CD91 system, respectively, and detoxification through the heme oxygenase/ferritin system. However, sudden or excessive hemolysis can overwhelm these protective systems leading to heme interacting with cells of the vasculature. Heme presents a damage-associated molecular pattern to the innate immune system. Heme is an extracellular inflammatory signaling molecule with strict binding specificity for TLR4 on monocyte/macrophages, endothelial, and other cells. The resulting TLR4 signaling cascade rapidly leads to intracellular oxidative stress and an inflammatory response. Heme also induces a cytoprotective response that includes Nrf2 responsive genes such as heme oxygenase-1, ferritin, haptoglobin, hemopexin, and other antioxidant response genes. It is the balance between the pro-inflammatory/vasculotoxic effects of plasma hemoglobin/heme and the cytoprotective responses that ultimately determines the pathophysiologic outcome in patients.


Comparative study of safety and efficacy of synthetic surgical glue for mesh fixation in ventral rectopexy.
Ventral mesh rectopexy (VMR) is a surgical option to treat rectal prolapse with pelvic floor dysfunction (PFD). Using synthetic surgical glue to fix the mesh to the anterior rectal wall after ventral dissection could be advantageous in comparison with sutured or stapled fixation. This study aimed to evaluate the safety and efficacy of synthetic surgical glue for mesh fixation compared with suture mesh fixation in VMR. This observational cohort study is a retrospective analysis conducted in a University Hospital Pelvic Surgery Center. All consecutive female patients (n = 176) who underwent laparoscopic or laparotomic VMR between January 2009 and December 2014 were included. Two groups were defined based on mesh fixation technique of the rectal wall: VMR with synthetic glue (n = 66) and VMR with suture (n = 110). The recurrence-free survival after VMR was determined by Kaplan-Meier method and multivariate analysis by Cox regression. Short-term postoperative complications, postoperative symptom improvement, the need for complementary treatment postoperatively, and procedure length were evaluated. A total of 176 females patients (mean age, 58.6 ± 13.7 years) underwent VMR with synthetic mesh. Mean recurrence-free survivals after VMR were 17.16 (CI 95% 16.54-17.80) and 17.33 (CI 95% 16.89-17.77) months in the glue group and the suture group, respectively (p > 0.05). Cox regression identified an independent effect on the recurrence risk of the external rectal prolapse, alone, or in combination with other anatomical abnormalities (HR = 0.37; CI 95% 0.14-0.93; p = 0.03). There was no significant difference of short-term postoperative morbidity, procedure length, postoperative symptom improvement, or need for complementary treatment postoperatively between suture versus glue groups (all p > 0.05). Use of glue to fix the mesh in VMR was safe and had no impact on outcomes. External prolapse was the unique significant predictive factor for recurrence.


A cascaded enzyme-loaded Fe-hemoporfin framework for synergistic sonodynamic-starvation therapy of tumors.
Enzyme-loaded nanosystems with multimodal therapeutic functions have received increasing attention in the treatment of malignant tumors. Herein, we designed and prepared cascaded dual-enzyme-augmented Fe-hemoporfin framework nanosonosensitizers for synergistic sonodynamic-starvation therapy of tumors. Amorphous Fe-hemoporfin frameworks (FeHF) with an average size of ∼85 nm were synthesized by assembling the clinical drug hemoporfin with Fe3+ ions. Then, FeHF was used to load dual enzymes (glucose oxidase (GOx) and catalase (CAT)) and modified by PEGylated folic acid-conjugated lipids. The dual-enzyme loaded FeHF (FeHF-GOx/CAT) exhibited higher efficiency not only for glucose depletion but also for ultrasound (US)-triggered 1O2 generation than that of pure FeHF, resulting from the cascaded catalytic reaction from the dual-enzyme system. As observed by magnetic resonance imaging, the intravenously injected FeHF-GOx/CAT was accumulated within tumors. The FeHF-GOx/CAT + US exhibited the highest inhibition effect compared to the FeHF-CAT + US (only SDT) or FeHF-GOx/CAT (only starvation therapy), due to the synergistic effects of SDT and starvation therapy. Therefore, the cascaded dual-enzyme loading strategy can increase the SDT efficiency of FeHF, which may guide further works in the development of efficient nanosonosensitizers.


[Epidermoid cyst of the testis: a report of 2 cases].
We report two cases of intratesticular epidermoid cyst, one of which had ossification in the cyst. Two cases were treated by orchiectomy with high ligation of the cord under the diagnosis of testicular malignant tumor. Ultrasonographic examination revealed a well-defined solid mass with echogenic rim. The internal echo of the cysts were relatively homogeneous and almost similar to the surrounding normal testicular parenchyma in the echo level.


Photochemical Reaction of OCSe with ClF in Argon Matrix: A Light-Driven Formation of XC(O)SeY (X, Y = F or Cl) Species.
The photochemistry of OCSe with ClF trapped together in argon matrices at cryogenic temperatures has been explored and the first interhalogen representatives of the elusive XC(O)SeY family, namely syn-ClC(O)SeF, anti-ClC(O)SeF, syn-FC(O)SeCl, and anti-FC(O)SeCl, as well as the hitherto triatomic species ClSeF complexed by a CO molecule, were obtained. Both ClC(O)SeF conformers appear to be produced independently by photolysis of the respective precursors; while formation of both FC(O)SeCl structures is ruled by the presence of an angular molecular complex OCSe···Cl-F formed prior to photolysis. This latter photochemical pathway seems to favor the formation of the less stable anti-FC(O)SeCl structure instead of the more stable syn- one. With the aid of quantum chemical calculations, using ab initio, DFT, TDDFT, and CASSCF methods, the mechanism for this photochemical reaction is rationalized both in terms of radical processes as well as a photoinduced electron transfer occurring into the OCSe···Cl-F complex. Also a singlet-triplet conical intersection between anti and syn rotamers of the FC(O)SeCl molecule is theoretically explored.


Early signs of Sertoli and Leydig cell dysfunction in the abdominal testes of immature unilaterally cryptorchid rats.
Testicular descent was prevented unilaterally by cutting the gubernaculum testis of newborn rats. When 20 days old unilaterally cryptorchid rats were injected intraperitoneally with 2 micrograms bFSH per gram body weight and killed 6 h later when testicular testosterone (T) and oestradiol (E2) concentrations were determined. The increase in E2 was subnormal in abdominal testes. In 18-day-old unilaterally cryptorchid rats the efferent ducts were ligated bilaterally, and the rats were killed 48 h later. The weight increase, due to accumulation of seminiferous tubule fluid, was significantly greater in the abdominal testes. In contrast, the ABP content of the abdominal epididymis was subnormal in 20-day-old unilaterally cryptorchid rats. Unilateral orchidectomy was performed in 16-day-old unilaterally cryptorchid rats and at 20 days of age intratesticular T and E2, and plasma FSH and LH concentrations were determined and compared to that in 20-day-old control unilaterally cryptorchid rats. Removal of an abdominal testis resulted in increased plasma FSH and intratesticular E2, whereas plasma levels of LH and intratesticular levels of T were unaffected. Removal of a scrotal testis resulted in increased plasma FSH and LH coupled with increased intratesticular T and E2. Rats with a single abdominal testis had higher plasma FSH and LH and intratesticular T, but similar intratesticular E2, than rats with a single scrotal testis. It is concluded that Sertoli and Leydig cell function are influenced by cryptorchidism at a stage when the temperature difference, and the morphological differences between the testes are very discrete.


Time Perspective and Age: A Review of Age Associated Differences.
We investigate the relationship between age and the five dimensions of time perspective measured by the Zimbardo Time Perspective Inventory (ZTPI) (past negative, past positive, present hedonistic, present fatalistic, and future). Time perspective is related to well-being, decision-making, level of development, and many other psychological issues. Hence, the existence of a systematic relationship between time perspective and age should be considered in all studies for which time is a relevant variable. However, no specific research about this has been conducted. We collected 407 papers that referenced the ZTPI between 2001 and 2015. From those, 72 studies met our inclusion criteria. They included 29,815 participants from 19 countries whose age spans most phases of adulthood (from 13.5 to 75.5 years, mean 28.7). We analyzed these studies adapting meta-analytical techniques. We found that present hedonistic and past negative dimensions are negatively related to aging with partial eta squared effect sizes of roughly 0.15. Our results have implications for the design of studies related to time as our findings highlight the importance of taking into account the differences associated with age.


Relationship of Ras association domain family 1 methylation and K-ras mutation in primary non-small cell lung cancer.
Recently, several groups have reported that Ras association domain family 1 (RASSF1A) interacts with Ras and mediates Ras-dependent apoptosis. However, the mechanism by which RASSF1A plays a role as a tumor suppressor in human cancer is unclear. In this study, we investigated the relationship between the RASSF1A methylation and K-ras mutation and their effects on patient's survival in 242 primary non-small cell lung cancers (NSCLCs) to understand the role of RASSF1A in Ras-mediated oncogenic transformation. RASSF1A methylation was not found to be associated with the K-ras mutation in NSCLCs (P = 0.37). For patients with stage I adenocarcinoma, those with RASSF1A methylation and K-ras mutation had a poorer prognosis than those with either RASSF1A methylation or K-ras mutation (P = 0.001). In stage II-III adenocarcinoma patients, the median survival of those with RASSF1A methylation and K-ras mutation was 9 months, and this was poorer than that of those with either RASSF1A methylation or K-ras mutation (P = 0.001). The hazard of failure for those with RASSF1A methylation and K-ras mutation was approximately 2.94 times higher compared with that of those with neither K-ras mutation nor RASSF1A methylation (95% confidence interval = 1.67-9.42; P = 0.01). Our results suggest that RASSF1A methylation and K-ras mutation are not mutually exclusive in NSCLC. In addition, RASSF1A methylation, in combination with K-ras mutation, may have an adverse synergistic effect on patient's survival in NSCLCs.


Germ cell tumor arising in the basal ganglia in a female--case report.
Germ cell tumors in the basal ganglia are very rare in females. The authors report the case of a 12-year-old girl with such a tumor in the left basal ganglia. The tumor was subtotally removed and responded well to irradiation.


Risk factors for neuroleptic-induced movement disorders.
Chronic neuroleptic therapy may be associated with the development of diverse movement disorders including Tardive dyskinesia (TD), Parkinsonism, dystonia, and akathisia in a subset of schizophrenic patients. It is presently unknown why only a proportion of neuroleptic-treated patients develop these movement disorders. In the following communication, we present a series of studies which demonstrate that the development of these movement disorders may be facilitated by certain risk factors including disturbances in pineal melatonin functions, diabetes mellitus, cognitive deficits, suicidal behavior, and disturbances in the functions of the choroid plexus. Recognition of these biological factors may prove useful in: (a) further understanding of the pathophysiology of these disorders, and (b) identifying patients at risk for these movement disorders.


Poorly Controlled Congenital Hypothyroidism due to an Underlying Allgrove Syndrome.
Congenital hypothyroidism of thyroidal origin (CHT) is a common disorder in pediatric endocrinology practices, which can be difficult to manage. Elevated thyrotropin (TSH) concentrations are in the great majority of cases explained by poor compliance to levothyroxine therapy. Case description. We present a boy with CHT, with 2 heterozygous mutations in the TSH receptor gene, who showed persistently elevated TSH concentrations and psychomotor retardation, initially misinterpreted as malcompliance. At the age of 4 years, he was diagnosed with adrenal insufficiency, wherefore a broad diagnostic search was initiated. After the start of glucocorticoid replacement therapy, his TSH normalized and the levothyroxine could be lowered. At the age of 6 years, his TSH increased again, this time caused by malabsorption of levothyroxine due to esophageal achalasia. In retrospect, alacrima was also present and the diagnosis of Allgrove syndrome was genetically confirmed. The CHT was considered a separate disease entity. In case of persistently elevated TSH levels in children with CHT, causes other than noncompliance must be considered. Second, in establishing the cause of adrenal insufficiency, specific symptoms, such as alacrima, are easily overlooked. Third, Allgrove syndrome is a rare disorder, in which diagnostic delay can lead to potentially life-threatening complications.