Urodynamic findings in elderly males without prostatic complaints.
Previous evaluations of urodynamic testing in patients with prostatism have been impeded because of a lack of age-matched controls. In this study, 13 asymptomatic male volunteers, ages fifty-two to seventy years, underwent urodynamic testing which included uroflowmetry, water cystometry, and pressure flow study. Comparison of these data to those obtained with patients with prostatism revealed several important differences including maximum flow rate and minimum urethral resistance.


[PyH][{TpMo(μ(3)-S)4Cu3}4(μ(12)-I)]: a unique tetracubane cluster derived from the S-S bond cleavage and the iodide template effects and its enhanced NLO performances.
Reactions of [Et4N][TpMoS(S4)] with three equiv. of CuI in MeCN or in pyridine gave rise to one dicubane and one tetracubane anionic clusters, [Et4N]2[{TpMo(μ3-S)3Cu3I}2(μ-I){Cu(μ-I)2(μ4-I)2}] and [PyH][{TpMo(μ3-S)4Cu3}4(μ12-I)], and their third-order nonlinear optical (NLO) responses were greatly enhanced relative to that of the precursor.


Expression of Shewanella frigidimarina fatty acid metabolic genes in E. coli by CRISPR/cas9-coupled lambda Red recombineering.
To construct a clustered, regularly interspaced, short palindromic repeats (CRISPR)/cas9 system and use this system to obtain a recombinant Escherichia coli strain possessing the fatty acid metabolism genes from a lipid-rich marine bacterium. The fatty acid regulatory transcription factor (fadR), delta9 (Δ(9) desaturase) and acetyl-CoA carboxylase (acc) genes were cloned from Shewanella frigidimarina. The fatty acid regulatory transcription factor (fadD) and phosphoenolpyruvate carboxylase inactivated strains were used to construct the fadR/delta9 and acc knock-in strains, which are both markerless and "scar"-less, and identified the change in fatty acid composition in the recombinant strains. There was no change in fatty acid composition between the wild-type strain and recombinant strains. All strains had 11:0, 12:0, 13:0, 14:0, 15:0, 16:0, 17:1, 17:0 and 18:0 fatty acids, with 16:0 and 18:0 fatty acids being dominant. The total lipid content of each recombinant strain was higher than the wild-type strain, with a maximum of 13.1 %, nearly 5.3 % higher than wild-type strain. The CRISPR/cas9 system, in conjunction with λ-Red recombinases, can rapidly and efficiently edit the E. coli genome. The CRISPR/cas9 recombineering machinery can be modified to select biotechnologically-relevant bacteria other than E. coli.


Soy protein isolate/kappa-carrageenan/cellulose nanofibrils composite film incorporated with zenian essential oil-loaded MOFs for food packaging.
Edible films applied in food packaging must possess excellent inhibitory and mechanical properties. Protein-based films exhibit a high capacity for film formation and offer good gas barrier properties. However, they have weak mechanical and water barrier characteristics. The objective of this research was to develop active composite films based on reinforced soy protein isolate (SPI)/Kappa-carrageenan (K) with varying concentrations of bacterial cellulose nanofibrils (BCN). Increasing the BCN concentration improved the morphological, structural, mechanical, water vapor barrier, and moisture content properties. In comparison to the pure SPI film (S), the film with a high BCN concentration demonstrated a significant decrease in WS (22.98 ± 0.78 %), MC (21.72 ± 0.68 %), WVP (1.22 ± 0.14 g mm-1 S-1 Pa-1 10-10), and EAB (57.77 ± 5.25 %) properties. It should be emphasized that there was no significant alteration in the physicomechanical properties of the optimal film (SKB0.75) containing Zenian-loaded metal-organic frameworks (ZM). However, it substantially enhanced the thermal stability of this film, which can be attributed to the strong interfacial interactions between polymer chains and ZM. Furthermore, the ZM films inhibited the growth of pathogenic bacteria and increased the DPPH antioxidant activity. Thus, SKB0.75-ZM2 films can be utilized as practical components in food packaging.


Kinetic, spectroscopic, and molecular docking studies on the inhibition of membrane-bound polyphenol oxidase from Granny Smith apples (Malus domestica Borkh.).
We investigated the inhibitory effect and binding mechanism of four selected compounds (ascorbic acid, l-cysteine, glutathione, and citric acid) on membrane-bound polyphenol oxidases (mPPO) using spectroscopic and molecular docking techniques. Kinetic analysis demonstrated that these inhibitors reversibly inhibited the mPPO activity. Fluorescence spectroscopy revealed that the intrinsic fluorescence intensity of mPPO was quenched by inhibitors with a single class of the inhibition site on mPPO. Amino acid residues His 180, His 201, His 366, Cys 184, Glu 328, and Asn 333 were the important binding sites in the active center. These sites were identified using molecular docking techniques. Our findings suggested that the inhibitors were allosterically bound to the active center of mPPO through hydrogen bonds and ion contacts. This study provides new insights into the active site residues responsible for catalyzing mPPO and provides applicable information about the design of mPPO inhibitors.


Immune response to rabies vaccine in Alaskan dogs: failure to achieve a consistently protective antibody response.
Previous studies in Thailand and Tunisia have shown that one injection of dog pre-exposure rabies vaccine does not produce a lasting antibody titre in a significant group of animals. We therefore duplicated the Thai study in a small North American community using healthy, owned dogs. A tissue culture vaccine of known high antigenicity was given intramuscularly as one primary injection and antibody titres were determined by the rapid fluorescent focus inhibition test on days 14, 30, 60, 180 and 360. Titres were less than 0.5 i.u./mL in 27% of dogs bled at 2 months, 24% at 6 months, and in 33% one year after the primary vaccination. In rabies endemic regions, it may be hazardous to rely on the previous vaccine history of a biting dog when making post-exposure management decisions. A retrospective study of antibody levels in previously vaccinated dogs in North America also indicated that a single injection of vaccine often failed to result in adequate titres.


Parental monitoring, negotiated unsupervised time, and parental trust: the role of perceived parenting practices in adolescent health risk behaviors.
To compare two different parenting practices (parental monitoring and negotiated unsupervised time) and perceived parental trust in the reporting of health risk behaviors among adolescents. Data were derived from 692 adolescents in 9th and 10th grades (x = 15.7 years) enrolled in health education classes in six urban high schools. Students completed a self-administered paper-based survey that assessed adolescents' perceptions of the degree to which their parents monitor their whereabouts, are permitted to negotiate unsupervised time with their friends and trust them to make decisions. Using gender-specific multivariate logistic regression analyses, we examined the relative importance of parental monitoring, negotiated unsupervised time with peers, and parental trust in predicting reported sexual activity, sex-related protective actions (e.g., condom use, carrying protection) and substance use (alcohol, tobacco, and marijuana). For males and females, increased negotiated unsupervised time was strongly associated with increased risk behavior (e.g., sexual activity, alcohol and marijuana use) but also sex-related protective actions. In males, high parental monitoring was associated with less alcohol use and consistent condom use. Parental monitoring had no affect on female behavior. Perceived parental trust served as a protective factor against sexual activity, tobacco, and marijuana use in females, and alcohol use in males. Although monitoring is an important practice for parents of older adolescents, managing their behavior through negotiation of unsupervised time may have mixed results leading to increased experimentation with sexuality and substances, but perhaps in a more responsible way. Trust established between an adolescent female and her parents continues to be a strong deterrent for risky behaviors but appears to have little effect on behaviors of adolescent males.


Temperature and moisture effect on spore emission in the fungal biofiltration of hydrophobic VOCs.
The effect of temperature and moisture on the elimination capacity (EC), CO(2) production and spore emission by Fusarium solani was studied in biofilters packed with vermiculite and fed with n- pentane. Three temperatures (15, 25 and 35°C) were tested and the highest average EC (64 g m(-3) h(-1)) and lower emission of spores (2.0 × 10(3) CFU m(-3) air) were obtained at 25°C. The effect of moisture content of the packing material indicates that the highest EC (65 g m(-3) h(-1)) was obtained at 50 % moisture. However, lowest emission (1.3 × 10(3) CFU m(-3) air) was obtained at 80 % moisture. Furthermore, the results show that a slight decrease in spore emission was found with increasing moisture content. In all cases, the depletion of the nitrogen source in the biofilter induced the sporulation, a decay of the EC and increased spore emission.


Do olfactory behaviour and marking responses of Konik polski stallions to faeces from conspecifics of either sex differ?
The aim of the study was to assess whether adult stallions differentiate their olfactory and marking behaviour towards the excreta of their potential male rivals and mares. Four Konik polski stallions were individually exposed simultaneously to their own and each others' faeces as well as faeces of mares in oestrus vs. dioestrus. Five series of 30min observation sessions were conducted in a round pen each on two consecutive days from March to July, totaling in 5h observation per stallion. Stallions sniffed and displayed flehmen reaction towards mares' faeces significantly longer (P<0.01) than towards stallions' faeces. No significant differences were found in marking by defecations upon stallions' vs. mares' faeces. The stallions urinated exclusively on mares' faeces. Sniffing, flehmen, defecations and urinations performed towards faeces of mares in oestrus vs. dioestrus did not differ significantly. The results showed that stallions differentiate their olfactory behaviour towards excreta of conspecifics of different sex but perhaps not towards faeces of females in different reproductive status. This for the first time establishes that stallions exhibit different marking behaviour upon stallions' vs. mares' faeces. It is hypothesized that marking of other stallions' faeces by defecation may advertise presence of the stallion, whereas marking of mares' faeces by urination may serve to mask the presence of a mare to prevent potential rivals from locating the mare in an area where mares' faeces are found.


Borate complexes of x-ray iodinated contrast agents: characterization and sorption studies for their removal from aqueous media.
Iodinated contrast media (ICM) are persistent and ubiquitous water pollutants. Because of their high water solubility and biochemical stability, their phase-separation and recovery from the aquatic environment is very difficult. Here, borate was chosen as a complexing agent of the two diagnostic aids iomeprol and iopamidol in order to provide them with a negative charge and to fix the resulting adducts on Dowex 1X4 ion exchangers. A systematic characterization study of the complex by means of capillary zone electrophoresis and 11B NMR revealed that iomeprol and iopamidol interact with borate anions in aqueous solutions giving a 1:1 single-charged adduct and that the association constant at 25 °C for both contrast agents is highest at pH 10.5. These findings allowed the proper calibration of experimental parameters for further batch adsorption-desorption trials, where the two ICM were shown to be almost completely removed from the water phase and released from the solid sorbents in mild conditions, enabling the recovery of functional resin.


Metabolic adaptations during extreme anoxia in the turtle heart and their implications for ischemia-reperfusion injury.
ATP depletion and succinate accumulation during ischemia lead to oxidative damage to mammalian organs upon reperfusion. In contrast, freshwater turtles survive weeks of anoxia at low temperatures without suffering from oxidative damage upon reoxygenation, but the mechanisms are unclear. To determine how turtles survive prolonged anoxia, we measured ~80 metabolites in hearts from cold-acclimated (5 °C) turtles exposed to 9 days anoxia and compared the results with those for normoxic turtles (25 °C) and mouse hearts exposed to 30 min of ischemia. In turtles, ATP and ADP decreased to new steady-state levels during fasting and cold-acclimation and further with anoxia, but disappeared within 30 min of ischemia in mouse hearts. High NADH/NAD+ ratios were associated with succinate accumulation in both anoxic turtles and ischemic mouse hearts. However, succinate concentrations and succinate/fumarate ratios were lower in turtle than in mouse heart, limiting the driving force for production of reactive oxygen species (ROS) upon reoxygenation in turtles. Furthermore, we show production of ROS from succinate is prevented by re-synthesis of ATP from ADP. Thus, maintenance of an ATP/ADP pool and low succinate accumulation likely protects turtle hearts from anoxia/reoxygenation injury and suggests metabolic interventions as a therapeutic approach to limit ischemia/reperfusion injury in mammals.


Proteomics to identify resistance factors in corn-a review.
The host resistance strategy for eliminating aflatoxins from corn has been advanced by the discovery of natural resistance traits such as proteins. This progress was aided by the development of a rapid laboratory-based kernel screening assay (KSA) used to separate resistant from susceptible seed, and for investigating kernel resistance.A. flavus GUS transformants have also been used, in conjunction with the KSA, to assess the amount of fungal growth in kernels and compare it with aflatoxin accumulation. Several proteins associated with resistance (RAPs) have been identified using 1 D PAGE. However, proteomics is now being used to further the discovery of RAPs. This methodology has led to the identification of stress-related RAPs as well as other antifungals. Characterization studies being conducted, including RNAi gene silencing experiments, may confirm roles for RAPs in host resistance.


Fennoscandian tree-ring anatomy shows a warmer modern than medieval climate.
Earth system models and various climate proxy sources indicate global warming is unprecedented during at least the Common Era1. However, tree-ring proxies often estimate temperatures during the Medieval Climate Anomaly (950-1250 CE) that are similar to, or exceed, those recorded for the past century2,3, in contrast to simulation experiments at regional scales4. This not only calls into question the reliability of models and proxies but also contributes to uncertainty in future climate projections5. Here we show that the current climate of the Fennoscandian Peninsula is substantially warmer than that of the medieval period. This highlights the dominant role of anthropogenic forcing in climate warming even at the regional scale, thereby reconciling inconsistencies between reconstructions and model simulations. We used an annually resolved 1,170-year-long tree-ring record that relies exclusively on tracheid anatomical measurements from Pinus sylvestris trees, providing high-fidelity measurements of instrumental temperature variability during the warm season. We therefore call for the construction of more such millennia-long records to further improve our understanding and reduce uncertainties around historical and future climate change at inter-regional and eventually global scales.


MetaComp: comprehensive analysis software for comparative meta-omics including comparative metagenomics.
During the past decade, the development of high throughput nucleic sequencing and mass spectrometry analysis techniques have enabled the characterization of microbial communities through metagenomics, metatranscriptomics, metaproteomics and metabolomics data. To reveal the diversity of microbial communities and interactions between living conditions and microbes, it is necessary to introduce comparative analysis based upon integration of all four types of data mentioned above. Comparative meta-omics, especially comparative metageomics, has been established as a routine process to highlight the significant differences in taxon composition and functional gene abundance among microbiota samples. Meanwhile, biologists are increasingly concerning about the correlations between meta-omics features and environmental factors, which may further decipher the adaptation strategy of a microbial community. We developed a graphical comprehensive analysis software named MetaComp comprising a series of statistical analysis approaches with visualized results for metagenomics and other meta-omics data comparison. This software is capable to read files generated by a variety of upstream programs. After data loading, analyses such as multivariate statistics, hypothesis testing of two-sample, multi-sample as well as two-group sample and a novel function-regression analysis of environmental factors are offered. Here, regression analysis regards meta-omic features as independent variable and environmental factors as dependent variables. Moreover, MetaComp is capable to automatically choose an appropriate two-group sample test based upon the traits of input abundance profiles. We further evaluate the performance of its choice, and exhibit applications for metagenomics, metaproteomics and metabolomics samples. MetaComp, an integrative software capable for applying to all meta-omics data, originally distills the influence of living environment on microbial community by regression analysis. Moreover, since the automatically chosen two-group sample test is verified to be outperformed, MetaComp is friendly to users without adequate statistical training. These improvements are aiming to overcome the new challenges under big data era for all meta-omics data. MetaComp is available at: http://cqb.pku.edu.cn/ZhuLab/MetaComp/ and https://github.com/pzhaipku/MetaComp/ .


Anchoring cobalt molybdenum nickel alloy nanoparticles on molybdenum dioxide nanosheets as efficient and stable self-supported catalyst for overall water splitting at high current density.
Developing bifunctional electrocatalysts with efficient and stable catalytic performance at high current density to improve the productivity of water splitting is important for relieving the environmental pollution and energy crisis. Herein, the Ni4Mo and Co3Mo alloy nanoparticles were anchored on MoO2 nanosheets (H-NMO/CMO/CF-450) by annealing the NiMoO4/CoMoO4/CF (CF: self-made cobalt foam) under Ar/H2 atmosphere. Benefitting from the nanosheets structure, synergistic effect of the alloys, existence of oxygen vacancy and the cobalt foam with smaller pore sizes as conductive substrate, the self-supported H-NMO/CMO/CF-450 catalyst demonstrates outstanding electrocatalytic performance, which delivers small overpotential of 87 (270) mV at 100 (1000) mA·cm-2 for HER and 281 (336) mV at 100 (500) mA·cm-2 for OER in 1 M KOH. Meanwhile, the H-NMO/CMO/CF-450 catalyst is used as working electrodes for overall water splitting, which just require 1.46 V @ 10 mA·cm-2 and 1.71 V @ 100 mA·cm-2, respectively. More importantly, the H-NMO/CMO/CF-450 catalyst can stabilize for 300 h at 100 mA·cm-2 in both HER and OER. This research provides an idea for the preparation of stable and efficient catalysts at high current density.


On the functional significance of retrieval mode: Task switching disrupts the recollection of conceptual stimulus information from episodic memory.
Episodic memory retrieval is assumed to be associated with the tonic cognitive state of retrieval mode. Despite extensive research into the neurophysiological correlates of retrieval mode, as of yet, relatively little is known about its functional significance. The present event-related potential (ERP) study was aimed at examining the impact of retrieval mode on the specificity of memory content retrieved in the course of familiarity and recollection processes. In two experiments, participants performed a recognition memory inclusion task in which they had to distinguish identically repeated and re-colored versions of study items from new items. In Experiment 1, participants had to alternate between the episodic memory task and a semantic task requiring a natural/artificial decision. In Experiment 2, the two tasks were instead performed in separate blocks. ERPs locked to the preparatory cues in the test phases indicated that participants did not establish retrieval mode on switch trials in Experiment 1. In the absence of retrieval mode, neither type of studied item elicited ERP correlates of familiarity-based retrieval (FN400). Recollection-related late positive complex (LPC) old/new effects emerged only for identically repeated but not for conceptually identical but perceptually changed versions of study items. With blocked retrieval in Experiment 2, both types of old items instead elicited equivalent FN400 and LPC old/new effects. The LPC data indicate that retrieval mode may play an important role in the successful recollection of conceptual stimulus information. The FN400 results additionally suggest that task switching may have a detrimental effect on familiarity-based memory retrieval.


Proton translocation mechanism and energetics in the light-driven pump bacteriorhodopsin.
In spite of many still unsolved problems, the mechanism and energetics of the light-driven proton transport are now basically understood. Energy captured during photoexcitation, and retained in the form of bond rotations and strains of the retinal, is transformed into directed changes in the pKa values of vectorially arranged proton transfer groups. The framework for the spatial and temporal organization of these changes is provided by the protein near the retinal Schiff base. The transport is completed by proton transfer among three essential groups in three domains lying roughly parallel with the membrane plane (Fig. 1): (a) the anionic D85 that is included in a complex of residues on the extracellular side containing also R82, D212, Y57 and bound water; (b) the protonated Schiff base; and (c) the protonated D96 that is included in a complex of residues on the cytoplasmic side containing also R227, T46, S226, and bound water. Other neighboring polar groups and water bound elsewhere which play a role in the transport do so either by further influencing the pKa values of the three protonable groups, or by providing passive pathways for proton transfer. The Schiff base proton, destabilized after photoexcitation, is transferred to the low pKa group D85 located on the extracellular side. The access of the deprotonated Schiff base then changes to the cytoplasmic side (the 'reprotonation switch') and its proton affinity increases. Finally, the proton of the high pKa group D96, with access to the cytoplasmic side, is destabilized by a protein conformational change through rearrangement of R227, T46, S226 and bound water, and becomes transferred to the Schiff base. As shown schematically in Fig. 3, these internal events are coupled to proton release and uptake at the two aqueous surfaces. The charge of the extracellular hydrogen-bonded complex is redistributed upon protonation of D85, and if the pH is above the pKa of the complex a proton is released to the bulk. After reprotonation of the Schiff base the pKa of the cytoplasmic hydrogen-bonded complex is raised well above the pH, and D96 regains a proton from the bulk. If the pH is lower than the pKa of the extracellular complex the proton release is delayed until the end of the photocycle. In either sequence there is net transfer of a proton from the cytoplasmic to the extracellular phase. The transfer of excess free energy from the chromophore to the protein, and finally to the transported proton, is described by a characteristic thermodynamic cycle.(ABSTRACT TRUNCATED AT 400 WORDS)


Intratumoral tumor necrosis factor induction and tumor growth suppression by ONO-4007, a low-toxicity lipid A analog.
ONO-4007 is a lipid A analog with low toxicity. The antitumor activity and tumor necrosis factor (TNF)-inducing activity of ONO-4007 were compared with those of lipopolysaccharide (LPS) in WKAH rats bearing KDH-8 hepatoma cells. Weekly injections of ONO-4007 (3 and 10 mg/kg i.v.) suppressed tumor growth, but LPS (0.01 and 0.1 mg/kg i.v.) did not. A single injection of ONO-4007 (3 and 10 mg/kg i.v.) into tumor-bearing rats induced higher levels of endogenous TNF production in tumor tissues than LPS (0.001, 0.01 and 0.1 mg/kg i.v.). Repeated injections of LPS caused a reduction of TNF production in tumor tissues, whereas the reduction by ONO-4007 was less remarkable than that by LPS. Intratumoral injections of anti-rat TNF-alpha antibody attenuated the antitumor effect of ONO-4007. The antitumor effect of ONO-4007 is more pronounced than that of LPS and the effect is mediated by TNF produced in tumor tissues.


High-field imaging of neurodegenerative diseases.
High-field magnetic resonance (MR) imaging is showing potential for imaging of neurodegenerative diseases. 7 T MR imaging is beginning to be used in a clinical research setting and the theoretical benefits of higher signal-to-noise ratio, sensitivity to iron, improved MR angiography, and increased spectral resolution in spectroscopy are being confirmed. Despite the limited number of studies to date, initial results in patients with multiple sclerosis, Alzheimer disease, and Huntington disease show promising additional features in contrast that may help the diagnosis of these disorders.


Laparoscopic Upper Colpectomy for VAIN III after Previous Total Hysterectomy.
To demonstrate the feasibility of laparoscopic upper colpectomy for the treatment of vaginal intraepithelial neoplasia (VAIN) after previous total hysterectomy. Stepwise demonstration of the technique with narrated video footage. In 2014, our patient aged 60 years underwent a routine smear that reported severe dyskaryosis. This was treated with large loop excision of the transformation zone. Histopathology confirmed cervical intraepithelial neoplasia II, with positive ectocervical margins. The patient was counseled for both repeat large loop excision of the transformation zone and hysterectomy, opting for definitive surgery. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed in January 2015, completely excising the residual cervical intraepithelial neoplasiaII. A vault smear was performed in October 2015, reporting further severe dyskaryosis. The patient subsequently underwent examination under anesthesia and multiple upper vaginal mapping biopsies-identifying extensive VAIN III. The case was successfully managed by a laparoscopic upper colpectomy. When determining the area of VAIN to be excised, it can be useful to place a vaginal marker stitch; however, we chose to perform a colposcopy and apply acetic acid to help delineate the extent of the VAIN, immediately before laparoscopy. The right-sided pelvic sidewall dissection proved more extensive owing to the disease burden on that side. No intra- or postoperative complications occurred. The final histopathology confirmed a 65 × 35 × 8-mm upper colpectomy specimen with VAIN III and clear surgical margins. The patient has since had a normal vault smear and no recurrence to date. We highlight the importance of gaining early retroperitoneal access and developing the lateral pelvic spaces to identify the ureters and gain vascular control of the pelvis. We demonstrate an approach to safely developing the posthysterectomy vesicovaginal plane, with the aid of bladder filling. We used a McCartney tube (Kebomed UK, Cullompton, Devon) to facilitate colpotomy and closed the vagina using a laparoscopic suturing technique. We believe laparoscopic upper colpectomy offers definitive management of VAIN-a condition that otherwise has a propensity for recurrence and is hence often associated with multiple vaginal excisional procedures.


Granulomatosis with polyangiitis presenting as an orbital inflammatory pseudotumor: a case report.
Granulomatosis with polyangiitis is a systemic inflammatory disease that often presents with necrosis, granuloma formation and vasculitis of small- to medium-sized vessels. Affected patients usually present with disease of the upper respiratory tract, lungs and kidneys, but this disease has been reported to involve almost any organ. We report the case of a patient with ocular manifestations of granulomatosis with polyangiitis after the remission of renal and auditory manifestations. An 81-year-old Japanese woman had a four-year history of biopsy-proven antineutrophil cytoplasmic antibody-related glomerulonephritis that had been treated with oral prednisolone and was in serological remission. She had also recovered from a one-year history of complete hearing loss immediately following the steroid treatment for glomerulonephritis. She gradually experienced right eye visual disturbance and exophthalmos over a two-month period. Radiographic and histopathological findings revealed an orbital inflammatory pseudotumor. The administration of prednisolone completely restored her right eye visual acuity and eye movement after two weeks. Considering this case retrospectively, our patient had an orbital inflammatory pseudotumor caused by granulomatosis with polyangiitis including a medical history of reversible hearing loss, although her glomerulonephritis had remitted with an undetectable level of specific antineutrophil cytoplasmic antibody. In this patient, hearing loss and visual loss occurred at different times during the course of treatment of granulomatosis with polyangiitis. Clinicians should consider a differential diagnosis of granulomatosis with polyangiitis in patients with treatable hearing and visual loss.


Assignments of 1H and 13C NMR spectral data for ondansetron and its two novel metabolites, 1-hydroxy-ondansetron diastereoisomers.
Assignments of 1H and 13C NMR chemical shifts were made by means of heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments for ondansetron, and by means of 1H-1H correlation spectroscopy (1H-1H COSY) and two-dimensional nuclear Overhauser effect spectroscopy (NOESY) experiments for two novel metabolites (M1 and M2) of ondansetron. These two metabolites were isolated for the first time from Mucor circinelloides.


Effect of allergen-specific immunotherapy on interleukin-4, interleukin-5 and interferon-gamma mRNA expression in the nasal mucosa of rats with allergic rhinitis.
To elucidate the mechanism of immunotherapy, we tested the effect of ovalbumin and ovalbumin-pullulan conjugate immunotherapy on the expression of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) mRNA in the nasal mucosa of sensitized rats. Forty-five rats were injected with ovalbumin intraperitoneally on three consecutive days and later were exposed to ovalbumin aerosol. The rats were injected intradermally, on six consecutive days, with saline, ovalbumin or ovalbumin-pullulan conjugate. Later, nasal mucosa was obtained and reverse transcription-polymerase chain reaction (RT-PCR) was performed. Nasal responses and specific immunoglobulin E (IgE) were measured. Although the immunotherapy significantly decreased nasal airway resistance, dye leakage and histamine content in nasal irrigation after allergen challenge, no significant difference was found in IL-4 and IL-5 mRNA expression or in specific IgE level among the three groups. We conclude that in this allergic model, the improvement of nasal responses after immunotherapy was the result of a mechanism other than decrease of T-helper 2 (Th2) cytokines.


The phlebotomine sand flies fauna in Parque Estadual do Rio Doce, Minas Gerais, Brazil.
Phlebotomine sand flies are dipterans of the family Psychodidae. They are very important to veterinary medicine because some species are vectors of infective forms of Leishmania spp., the etiological agents of leishmaniasis. The Parque Estadual do Rio Doce is located in an area with constant reports of cases of leishmaniasis. In order to better understanding the phlebotamine sand fly fauna of the park, the present work was undertaken with the goal of analyzing phlebotomine sand flies collected there, verifying their seasonality and correlating their presence with forest and/or anthropic areas. To analyze the fauna of phlebotomine sand flies, HP-type, model CDC light traps were distributed along the Juquita trail of PERD. Twelve traps were installed between September 2012 and February 2014, and captured specimens were identified to species. A total of 1993 phlebotomine sand flies of 30 species were captured. The most abundant species were Pressatia choti, Psychodopygus davisi and Nyssomyia intermedia. The high number of Nyssomyia intermedia captured drew attention because they are considered one of the vectors of the infective Leishmania braziliensis present at PERD. No seasonality was observed in the occurrence of phlebotomine sand flies captured at PERD. The number of captured specimens of vector species, and the distance of traps from the forest boarder, were negatively correlated, showing that these vectors (Nyssomyia intermedia, Nyssomyia whitmani and Migonemyia migonei) were less common inside the forest area and that attention should be drawn to other potential vector species in the forest. These results can contribute to leishmaniasis prevention strategies directed at the visitors and professionals at or near PERD. The finding of the presence of Leishmania vectors in the park area must be given attention, since disease transmission can threaten people who visit PERD and its surroundings. Therefore, information on the prevention of leishmaniasis needs to be provided to all people who go there.


A Bayesian multivariate approach to estimating the prevalence of a superordinate category of disorders.
Epidemiological research plays an important role in public health, facilitated by the meta-analytic aggregation of epidemiological trials into a single, more powerful estimate. This form of aggregation is complicated when estimating the prevalence of a superordinate category of disorders (e.g., "any anxiety disorder," "any cardiac disorder") because epidemiological studies rarely include all of the disorders selected to define the superordinate category. In this paper, we suggest that estimating the prevalence of a superordinate category based on studies with differing operationalization of that category (in the form of different disorders measured) is both common and ill-advised. Our objective is to provide a better approach. We propose a multivariate method using individual disorder prevalences to produce a fully Bayesian estimate of the probability of having one or more of those disorders. We validate this approach using a recent case study and parameter recovery simulations. Our approach produced less biased and more reliable estimates than other common approaches, which were at times highly biased. Although our approach entails additional effort (e.g., contacting authors for individual participant data), the improved accuracy of the prevalence estimates obtained is significant and therefore recommended.


Neocortical death in infants: behavioral, neurologic, and electroencephalographic characteristics.
Neocortical death is a form of the persistent vegetative state characterized by the maintenance of sleep/wakeful cycles and spontaneous respirations and the lack of cognitive function. It is difficult to diagnose in neonates and young infants because their cognitive skills are limited by inexperience and by immaturity of the central nervous system. Because neocortical death has not been described previously for this age group, we report the neurologic, behavioral, electroencephalographic, and computed tomographic characteristics of three infants who survived in the persistent vegetative state following severe brain injury. Each infant appeared to exhibit some complex behaviors, including interaction with the environment and the examiners, although the electroencephalograms documented no electrical activity of cerebral origin. Computed tomography revealed extensive destruction of the cerebral hemispheres. Infants and newborns with a history suggesting brain injury and with the neurologic and behavioral characteristics described here should be evaluated with serial electroencephalograms and computed tomography to diagnose the syndrome of neocortical death.


Frenectomy for improvement of a problematic conventional maxillary complete denture in an elderly patient: a case report.
Maxillary labial and buccal frena are considered as normal anatomic structures in the oral cavity. However, they may exist intraorally as a thick broad fibrous attachment and/or become located near the crest of the residual ridge, thus interfering with proper denture border extension resulting in inferior denture stability, retention and overall patient satisfaction. This case report highlights the importance of clinical examination and treatment planning which may mandate preprosthetic surgery prior to fabrication of a new conventional complete denture. Adequate patient satisfaction with conventional complete dentures can be significantly increased after frenectomy.


Sternal Resection and Reconstruction for Solitary Plasmacytoma of the Sternum: Case Report.
A 63-year-old patient was admitted with a sternal fracture and mass. On evaluation, most of the body of the sternum had been destroyed by a tumor. Radical resection of the sternum was performed and part of the major pectoral muscles adherent to the sternal tumor was also resected. The chest wall defect was reconstructed with mesh, bone cement, and a titanium rib plate system. Reconstruction with this method seemed to be an appropriate procedure to prevent instability of the chest wall.


Endovascular exclusion of abdominal aortic pathology in patients with concomitant malignancy.
The advent of endoluminal aortic repair has gained increasing popularity as an alternative to traditional open surgery in the setting of multiple comorbid disease states. This study analyzes a single center experience of excluding aortic disease in patients with concomitant malignancy. As part of a Federal Drug Administration FDA-approved trial, 318 patients underwent aortic stent-graft repair between June 1996 and February 2001. During that period five patients with advanced-stage neoplasia were treated. Endovascular management of symptomatic abdominal aortic aneurysms (AAA) with a mean diameter of 7.8 cm (range, 6-10 cm), was performed in four patients. In the fifth patient, a custom-made aortic prosthesis was utilized to exclude a paraanastamotic abdominal aneurysm (PAAA) from a previous open AAA repair. Malignancies included esophageal, lung, renal, prostate, and urinary bladder cancers. A mean follow-up of 10.1 months was available. Successful endoluminal repair was accomplished in all five patients with minimal in-hospital morbidity. Mean length of stay was 3.4 days. There were no device-related mortalities and no persistent endoleaks detected for the duration of follow-up. Aneurysm sac enlargement was not seen in any of the patients and complete resolution of the PAAA was noted at one year. Exclusion of AAA and other aortic pathology in patients with an associated malignancy can be performed with a relatively low procedure-related morbidity and mortality. In this population, stent-graft repair remains an individualized option with a multidisciplinary team necessary to explore this therapeutic approach.


Correlation of the lumbar dural sac dimension with the spread of spinal anesthesia in elderly female patients: A prospective observational study.
To test a hypothesis that the dural sac dimension would be correlated with the spinal block level, we evaluated the correlation between the lumbar dural sac dimension and the spread of spinal anesthesia in elderly women. In 40 women over the age of 65 years, the lumbar dural sac dimensions were measured at the L2-L3, L3-L4, L4-L5, and L5-S1 intervertebral spaces using ultrasonography in the lateral decubitus position, followed by the administration of spinal anesthesia. The correlation coefficients were analyzed for the lumbar dural sac dimension at each intervertebral level, peak sensory block level, peak motor block, time to peak sensory and peak motor blockade, durations of sensory and motor blockade, and patient characteristics. We subsequently analyzed the partial correlations between the lumbar dural sac dimension and the outcomes of spinal anesthesia, while adjusting for age, body mass index, and waist circumference. Peak sensory block level was inversely correlated with each lumbar sac dimension: L2-L3 (ρ = -0.37, P = .029), L3-L4 (ρ = -0.57, P < .001), L4-L5 (ρ = -0.65, P < .001), and L5-S1 (ρ = -0.49, P = .002) intervertebral spaces. Partial correlation analysis with adjustment for age, body mass index, and waist circumference revealed inverse correlations between the lumbar dural sac dimension at the following intervertebral spaces and peak sensory block level: L3-L4 (r = -.52, P = .003), L4-L5 (r = -.76, P < .001), and L5-S1 (r = -.65, P < .001). Outcomes of ultrasonographic investigation revealed an inverse correlation between the lumbar dural sac dimension and peak sensory block level in elderly women.


Effect of lyso-phosphatidylcholine and Schnurri-3 on osteogenic transdifferentiation of vascular smooth muscle cells to calcifying vascular cells in 3D culture.
In vitro cell culture is a widely used technique for investigating a range of processes such as stem cell behavior, regenerative medicine, tissue engineering, and drug discovery. Conventional cell culture is performed in Petri dishes or flasks where cells typically attach to a flat glass or plastic surface as a cell monolayer. However, 2D cell monolayers do not provide a satisfactory representation of in vivo conditions. A 3D culture could be a much better system for representing the conditions that prevail in vivo. To simulate 3D conditions, vascular smooth muscle cells (VSMCs) were loaded with gold-polyvmer-iron oxide hydrogel, enabling levitation of the cells by using spatially varying magnetic fields. These magnetically levitated 3D cultures appeared as freely suspended, clustered cells which proliferated 3-4 times faster than cells in conventional 2D cultures. When the levitated cells were treated with 10nM lysophosphatidylcholine (LPC), for 3days, cell clusters exhibited translucent extensions/rods 60-80μm wide and 200-250μm long. When 0.5μg/μl Schnurri-3 was added to the culture containing LPC, these extensions were smaller or absent. When excited with 590-650nm light, these extensions emitted intrinsic fluorescence at >667nm. When the 3D cultures were treated with a fluorescent probe specific for calcium hydroxyapatite (FITC-HABP-19), the cell extensions/rods emitted intensely at 518nm, the λmax for FITC emission. Pellets of cells treated with LPC were more enriched in calcium, phosphate, and glycosaminoglycans than cells treated with LPC and Schnurri-3. In 3D cultures, VSMCs grow more rapidly and form larger calcification clusters than cells in 2D cultures. Transdifferentiation of VSMC into calcifying vascular cells is enhanced by LPC and attenuated by Schnurri-3. The formation of calcified structures in 3D VSMC cultures suggests that similar structures may be formed in vivo.


Cost comparison of endoscopic stenting vs surgical treatment for unresectable cholangiocarcinoma.
Total lifetime costs of endoscopic vs surgical treatment for obstructive jaundice due to cholangiocarcinoma are difficult to assess. The purpose of this study was to compare total costs in these two groups, including all treatment and retreatments. This retrospective study identified patients with biopsy-proven cholangiocarcinoma treated this decade with either endoscopic biliary stenting or surgical biliary-enteric bypass with or without resection. Outcomes and hospital charges were recorded. Ten matched control patients were compared from each group. Costs included those for cost of repeat endoscopy in the endoscopic group and for the management of recurrent obstructive jaundice in the surgical group. The groups were similar in age and gender ratio. The surgical approach was frequently for cure; therefore, surgical patients were by and large at an earlier stage of their disease than those in the endoscopic group. Mean survival for the endoscopic group was 19 months vs 16.5 months for the surgical group. The median total lifetime cost for surgical therapy was $60,986 vs $24,251 for endoscopic therapy. Endoscopic therapy is an effective palliative therapy for unresectable cholangiocarcinoma. Endoscopic therapy for this entity costs significantly less than surgical treatment. The cost benefit of endoscopic stenting over standard surgical bypass in the management of patients with unresectable cholangiocarcinoma, when considered along with its minimally invasive approach, makes this the procedure of choice for palliative therapy.


Boswellic acids target the human immune system-modulating antimicrobial peptide LL-37.
The antimicrobial peptide LL-37 is the sole member of the human cathelicidin family with immune system-modulating properties and roles in autoimmune disease development. Small molecules able to interact with LL-37 and to modulate its functions have not been described yet. Boswellic acids (BAs) are pentacyclic triterpene acids that are bioactive principles of frankincense extracts used as anti-inflammatory remedies. Although various anti-inflammatory modes of action have been proposed for BAs, the pharmacological profile of these compounds is still incompletely understood. Here, we describe the identification of human LL-37 as functional target of BAs. In unbiased target fishing experiments using immobilized BAs as bait and human neutrophils as target source, LL-37 was identified as binding partner assisted by MALDI-TOF mass spectrometry. Thermal stability experiments using circular dichroism spectroscopy confirm direct interaction between BAs and LL-37. Of interest, this binding of BAs resulted in an inhibition of the functionality of LL-37. Thus, the LPS-neutralizing properties of isolated LL-37 were inhibited by 3-O-acetyl-β-BA (Aβ-BA) and 3-O-acetyl-11-keto-β-BA (AKβ-BA) in a cell-free limulus amoebocyte lysate assay with EC50=0.2 and 0.8 μM, respectively. Also, LL-37 activity was inhibited by these BAs in LL-37-enriched supernatants of stimulated neutrophils or human plasma derived from stimulated human whole blood. Together, we reveal BAs as inhibitors of LL-37, which might be a relevant mechanism underlying the anti-inflammatory properties of BAs and suggests BAs as suitable chemical tools or potential agents for intervention with LL-37 and related disorders.


Effects of Partially Defatted Hermetia illucens Meal in Rainbow Trout Diet on Hepatic Methionine Metabolism.
This study investigated, for the first time, the effects of replacement of fishmeal (FM) with insect meal from Hermetia illucens (HI) on the transcript levels of three genes involved in methionine (Met) metabolism in rainbow trout (Oncorhynchus mykiss) liver. Two target genes-betaine-homocysteine S-methyltransferase (BHMT) and S-adenosylhomocysteine hydrolase (SAHH)-are involved in Met resynthesis and the third one-cystathionine β synthase (CBS)-is involved in net Met loss (taurine synthesis). We also investigated the levels of two Met metabolites involved in the maintenance of methyl groups and homocysteine homeostasis in the hepatic tissue: S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). Three diets were formulated, an FM-based diet (HI0) and two diets in which 25% (HI25) and 50% (HI50) of FM was replaced with HI larvae meal. A 78-day feeding trial involved 360 rainbow trout with 178.9 ± 9.81 g initial average weight. Dietary replacement of up to 50% of FM with HI larvae meal, without any Met supplementation, did not negatively affect rainbow trout growth parameters and hepatic Met metabolism. In particular, Met availability from the insect-based diets directly modulated the transcript levels of two out of three target genes (CBS, SAHH) to maintain an optimal level of one-carbon metabolic substrates, i.e., the SAM:SAH ratio in the hepatic tissue.


Targeting Non-Replicating Mycobacterium tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review).
Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations-isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.


Neurofibromatosis 1 in childhood.
Neurofibromatosis 1 (NF1) is an autosomal-dominant disorder with an incidence of approximately 1 in 3,000. The cardinal features of the disorder are cafe au lait spots, axillary freckling, cutaneous neurofibromas, and iris hamartomas (Lisch nodules). Common complications include learning disability, scoliosis, and optic gliomas. Other complications (e.g., peripheral nerve malignancy, bony deformities, and epilepsy) are individually rare. The mainstay of care for patients with NF1 is anticipatory guidance, and the early detection and symptomatic treatment of disease complications. Counseling of patients and their families should provide a realistic overview of possible disease complications, while emphasizing that most individuals with NF1 lead healthy and productive lives. The gene for NF1 has been identified, and future cell biology research will focus on understanding the pathogenetic mechanisms that underly the diverse manifestations of the disorder.


Influence of tumor necrosis on treatment sensitivity and long-term survival in nasopharyngeal carcinoma.
To assess the impact of tumor necrosis on treatment sensitivity and long-term survival in patients with nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiation therapy (IMRT). In total, 757 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients were treated using IMRT; 93.7% patients with stage T3-T4/N1-N3 disease also received cisplatin-based chemotherapy. The incidence rates of tumor necrosis in primary tumor, retropharyngeal lymph nodes, neck lymph nodes, and total tumor were 2%, 17.7%, 21.5%, and 31.4%. Overall, 40.8% patients with necrosis of the total tumor achieved complete response (CR) and 54.7% patients without tumor necrosis achieved CR at the end of treatment (χ2 = 12.728, P < 0.001). The estimated 7-year overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS), and loco-regional relapse-free survival (LRRFS) for patients with tumor necrosis and without tumor necrosis of the total tumor were 68.5% vs. 88.4%, 70.5% vs. 88.1%, 77.6% vs. 90.6%, and 85.9% vs. 91.3%, respectively (all P < 0.001). Multivariate analyses indicated that necrosis of the total tumor was an independent predictor of OS, FFS, DMFS, and LRRFS. The impact of lymph node necrosis on long-term survival was similar to that of necrosis of the total tumor. ROC curves verified that inclusion of lymph node necrosis improved the predictive value of the current N classification criteria (P = 0.006). Tumor necrosis served as a predictor of treatment sensitivity and poor prognosis for patients with NPC. Lymph node necrosis significantly improved the prognostic value of the current N classification criteria for NPC.


Inactivation of catalase by phenylhydrazine. Formation of a stable aryl-iron heme complex.
Catalase promotes the H2O2-dependent oxidation of phenylhydrazine to benzene but simultaneously is subject to a pseudo-first order inactivation process. Each inactivation event is subtended by catalytic turnover of three molecules of phenylhydrazine and 52 molecules of H2O2. The dimethyl ester of N-phenylprotoporphyrin IX is extracted with acidic methanol from the inactivated enzyme, but the prosthetic heme with a phenyl sigma-bonded to the iron atom is obtained by gentle extraction with 2-butanone. The absolute chirality of N-ethylprotoporphyrin IX isolated from catalase inactivated with ethylhydrazine confirms that the prosthetic heme has the same chiral orientation in the active site as it does in hemoglobin. The known inactivation of methemoglobin by phenylhydrazine is shown to depend on H2O2 but not oxygen. The results demonstrate that the H2O2-dependent oxidation of phenylhydrazine by catalase and other hemoproteins results in sigma-coordination of a phenyl residue to the prosthetic heme iron. This process may play a role not only in phenylhydrazine-mediated erythrocyte lysis but also in the activation of guanylate cyclase.


Prognostic factors in chronic subdural hematoma: results from a monocentric consecutive surgical series of 605 patients.
The study of age-related diseases like chronic subdural hematoma (CSDH) is of high interest, considered the general ageing of the population. This investigation aimed to identify the main clinical characteristics of CSDH patients, to evaluate the impact of the disease on quality of life, its treatment and comorbidities/complications and to compare our data with other surgical series published over the past 5 years. A retrospective cohort study including all consecutive patients operated for CSDH between January 1, 2006 and December 31, 2013 at the Unit of Neurosurgery of our hospital was carried out. 605 patients were included in the study (66.0% male, mean age 77.5±10.5 years). History of brain trauma was reported in 65.6%. Common comorbidities were hypertension (59.0%), cardiopathies (36.0%), and previous stroke (23.6%). Clotting and coagulation alterations were present in 27.2% and 17.0%, respectively. In 24.0% of cases, the hematoma was bilateral. 17.3% had more than one surgery. Length of stay was of 14.8±10.1 days. Baseline Karnofsky Performance Score (KPS), presurgical KPS, and KPS at discharge were 87.7±14.9, 64.9 ±19.8 and 76.7±27.2, respectively. A complete recovery was observed in 62.9% of patients. Mortality rate during hospitalization was 7.4%. The knowledge of clinical and surgical factors which might impact on the clinical outcomes could help to better manage patients with CSDH, which represents a surgically "simple" but, indeed, not trivial disease.


Prior knowledge facilitates low homologous protein secondary structure prediction with DSM distillation.
Protein secondary structure prediction (PSSP) is one of the fundamental and challenging problems in the field of computational biology. Accurate PSSP relies on sufficient homologous protein sequences to build the multiple sequence alignment (MSA). Unfortunately, many proteins lack homologous sequences, which results in the low quality of MSA and poor performance. In this article, we propose the novel dynamic scoring matrix (DSM)-Distil to tackle this issue, which takes advantage of the pretrained BERT and exploits the knowledge distillation on the newly designed DSM features. Specifically, we propose the DSM to replace the widely used profile and PSSM (position-specific scoring matrix) features. DSM could automatically dig for the suitable feature for each residue, based on the original profile. Namely, DSM-Distil not only could adapt to the low homologous proteins but also is compatible with high homologous ones. Thanks to the dynamic property, DSM could adapt to the input data much better and achieve higher performance. Moreover, to compensate for low-quality MSA, we propose to generate the pseudo-DSM from a pretrained BERT model and aggregate it with the original DSM by adaptive residue-wise fusion, which helps to build richer and more complete input features. In addition, we propose to supervise the learning of low-quality DSM features using high-quality ones. To achieve this, a novel teacher-student model is designed to distill the knowledge from proteins with high homologous sequences to that of low ones. Combining all the proposed methods, our model achieves the new state-of-the-art performance for low homologous proteins. Compared with the previous state-of-the-art method 'Bagging', DSM-Distil achieves an improvement about 5% and 7.3% improvement for proteins with MSA count ≤30 and extremely low homologous cases, respectively. We also compare DSM-Distil with Alphafold2 which is a state-of-the-art framework for protein structure prediction. DSM-Distil outperforms Alphafold2 by 4.1% on extremely low-quality MSA on 8-state secondary structure prediction. Moreover, we release a large-scale up-to-date test dataset BC40 for low-quality MSA structure prediction evaluation. BC40 dataset: https://drive.google.com/drive/folders/15vwRoOjAkhhwfjDk6-YoKGf4JzZXIMC. HardCase dataset: https://drive.google.com/drive/folders/1BvduOr2b7cObUHy6GuEWk-aUkKJgzTUv. Code: https://github.com/qinwang-ai/DSM-Distil.


A personal reflection on the issues surrounding the use of euphemisms following sudden death.
This paper uses Driscoll's (1994) model of reflection to review the care given to a family who encountered sudden bereavement in a coronary care unit. As a result of using euphemisms to describe and break bad news, the author experienced feelings of guilt and inadequacy. Implications for nurse education in the area of sudden death and bereavement are discussed, with a focus on the need to include the sensitive use of interpersonal skills necessary to provide comfort and support to the suddenly bereaved.


Ultrasound accelerates pickling of reduced-sodium salted duck eggs: An insight into the effect on physicochemical, textural and structural properties.
In this work, high-intensity ultrasound (HIU) was used to accelerate the pickling of the reduced-sodium salted duck eggs (RSSDE). Meanwhile, it was evidenced that HIU treatment was also helpful to improve the overall quality of RSSDE. When the optimized HIU at 80 W was used, it resulted in favorably higher hardness (1.83 N), springiness (4.20 mm), and chewiness (4.83 mJ) of RSSDE whites, while the lowest hardness (1.12 N) of RSSDE yolks. The average particle size of RSSDE whites was significantly reduced (230.37 nm, 7.14%) as well. Apart from that, the absolute zeta potential and hydrophobicity were increased to -8.63 mV by 14.30% and 164.70 μg by 3.12%, respectively, attributed to the destruction of protein aggregation by cavitation effects. The oil exudation showed an obvious rising during the 14 days of the salting. HIU treatment at 80 W destroyed the emulsification state of lipid droplets and led to higher oil exudation (39.30%). The structural analysis of RSSDE proteins revealed marked alterations following HIU, with a reduction in α-helix and an increase in β-turn and random coil. The highest r-value reached 1.32 after HIU treatment at 80 W, which was attributed to the exposure of both tyrosine and tryptophan residues caused by the hydrophobic rearrangement of RSSDE protein. Scanning electron microscopy revealed that HIU altered the architecture of RSSDE proteins, resulting in more irregular pores. This work proved that HIU was a promising tool to shorten the salting period of RSSDE with much better quality.


The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target.
Targeted drugs have changed cancer treatment but are often ineffective in the long term against solid tumours, largely because of the activation of heterogeneous oncogenic pathways. A central common signalling mechanism in many of these pathways is proline-directed phosphorylation, which is regulated by many kinases and phosphatases. The structure and function of these phosphorylated proteins are further controlled by a single proline isomerase: PIN1. PIN1 is overactivated in cancers and it promotes cancer and cancer stem cells by disrupting the balance of oncogenes and tumour suppressors. This Review discusses the roles of PIN1 in cancer and the potential of PIN1 inhibitors to restore this balance.


Outcomes and special techniques for treatment of penile amputation injury.
Management of severe penile trauma presents great challenges for reconstructive urologists since these injuries vary from abrasions to total emasculation. A review of our case experience with penile amputation is presented, emphasizing techniques used to salvage or reconstruct the most difficult of penile injury cases. A total of 13 patients with penile amputation injury referred to us between 2007 and 2016 were analyzed. Mean age at surgery was 16 years (ranged from 4 to 29 years). Etiology of penile amputation (partial or total) combined with management and outcomes were evaluated. Management included different surgical procedures with the aim to achieve good functional and esthetical outcomes. Postoperative questionnaire was used for assessment of patient's overall satisfaction. Follow-up ranged from 13 to 182 months (mean 53). Causes of penile injury were iatrogenic trauma (8), self-amputation (2), electrocution (1), intentional sexual assault (1) and mother's hair strangulation (1). Outcome criteria including aesthetic appearance, urinary function and ability to engage in satisfactory coitus, were noted in 11 cases (85%). Two cases with ensuing complications relating to the total phalloplasty required additional treatment due to urethral fistula. Severe penile injuries should be treated on a case by case basis utilizing the most propitious techniques. We respectfully propose that the needs of such patients are best served by referral centers with extensive experience.


Photoreactions of furocoumarins with biomolecules.
Recent aspects of the photoreactions of linear and angular furocoumarins with DNA and related compounds, including [2 + 2] cycloaddition to pyrimidine bases, covalent attachment to the osidic moiety of adenine nucleosides and photodynamic effects, are surveyed. Reactions of photoexcited furocoumarins with proteins and unsaturated lipids and the possible biological roles of the resulting adducts are also presented and discussed.


The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure.
Limited information is available on the balance state of pro- and anti-inflammatory cytokines in patients with recurrent implantation failure (RIF). This study assessed the pro- and anti-inflammatory cytokines in plasma of 34 patients with RIF, compared with those of 25 women with a successful pregnancy in the first IVF/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycle. The IFN-γ, IL-1β, IL-6 and IL-4 concentrations were higher, whereas the TGF-β1 concentration was lower in the RIF group compared with the control group. Furthermore, the ratios of pro-inflammatory and anti-inflammatory cytokines IFN-γ/IL-4, IFN-γ/IL-10, IFN-γ/TGF-β1, IL-6/IL-10, IL-6/TGF-β1, IL-1β/TGF-β1 and TNF-α/TGF-β1 were higher in the RIF group (all P < 0.01). The results suggested a shift toward a pro-inflammatory state in peripheral blood of the patients with RIF.


[Recommendation for a systematic solution of documenting findings in obstetrical and gynecologic ultrasound diagnosis].
Ultrasonic findings in a women's clinic are very heterogeneous. In their totality they will be unmethodical very quick. Therefore we decided to organize four separate card indexes: 1. gynaecologic findings; 2. breast diagnostics; 3. supervision of pregnancy and look for fetal malformations; 4. single findings in pregnancy.--Each card index does not exceed 2000 to 3000 patients by appropriate actualization. A filing card for supervision of pregnancy and systemic detection of fetal malformations is created.


Preparation of a Novel Phosphorus-Nitrogen Containing Novolac Curing Agent for Epoxy Resin and flame-retardancy of its cured epoxy resin.
In this study, DICY (dicyandiamide)-containing novolac (NN) was first prepared, and then DOPO (9,10-Dihydro-9-oxa-10-phosphaphenanthrene-10-oxide) was introduced to react with the unsaturated bonds from DICY to obtain a novel phosphorus-nitrogen-containing novolac resin (PNN), which was used as a curing agent for epoxy resins. The curing condition was confirmed by a non-isothermal curing kinetics study. The thermal stability and flame retardancy of the cured epoxy resin system were studied by thermogravimetric analysis (TGA), limited oxygen index (LOI) measurement, UL-94 test and cone calorimeter. The morphology of the burned chard residues was observed by Scanning electron microscopy (SEM). The results show that epoxy resin cured by the prepared PNN curing system presents excellent flame retardancy. The cured resin system, which contains only 1.31wt% phosphorus and 2.48wt% nitrogen, can achieve UL 94 V-0 rating.


Experimental autoimmune encephalomyelitis as a testing paradigm for adjuvants and vaccines.
Experimental autoimmune encephalomyelitis (EAE) is an experimental model for multiple sclerosis. EAE can be induced by inoculation with central nervous system (CNS) proteins or peptides emulsified in complete Freund's adjuvant. Protection from EAE, enhancement of EAE or subclinical priming for EAE can occur as a result of either live viral infection or DNA immunization with molecular mimics of CNS proteins or peptides. Here we review the published data describing modulation of EAE through administration of various CNS proteins/peptides introduced via live virus or plasmid DNA and modulation of EAE through choice of adjuvant (immunostimulating agents).


Speech-language pathology and dysphagia in multiple sclerosis.
Dysarthria occurs in approximately 40% of all patients with MS. When speech and voice disturbances do occur, they usually present as a spastic-ataxic dysarthria with disorders of voice intensity, voice quality, articulation, and intonation. While language disturbances such as aphasia, auditory agnosia, anomia, dysgraphia, and dyslexia are very rare in MS, cognitive deficits and swallowing disorders are common. Treating dysarthria, dysphagia, and cognitive deficits in MS patients is effective for reestablishing functional daily activities. The types, severity, and rates of deterioration in MS are highly variable; complete restoration to normal functioning is therefore not always expected. For these reasons, careful documentation of clinical-treatment outcomes and the factors influencing these outcomes should be regularly collected and reported.


Fat Decisions: Leptin Regulates Bone versus Fat in the Marrow.
Leptin is an adipocyte-derived hormone involved in energy sensing. In this issue of Cell Stem Cell, Yue et al. (2016) show that leptin is a physiologic signal that acts directly on Leptin-Receptor-expressing mesenchymal stromal cells in adult bone marrow to influence their lineage allocation in vivo, inhibiting bone formation and inducing marrow adipogenesis.


High frequency of human leukocyte antigen class II DRB1*1602 haplotype in Greek patients with myelodysplastic syndrome and of DRB1*1501 in the low-risk subgroup.
Myelodysplastic syndromes (MDS) comprise a heterogenous group of clonal hematopoietic disorders in which the immune-mediated pathogenetic mechanisms are under investigation. Overrepresentation of human leukocyte antigen (HLA)-DR2 and its serologic split HLA-DR15 has been associated with low-risk MDS in certain ethnic groups and has been proposed as a predictive factor for a favorable response to immunomodulatory treatment. Because the HLA-DRB1*15 haplotype does not predominate in the Greek population, we investigated the frequency of HLA-DRB1 alleles among 114 patients of Greek origin suffering from various types of MDS: 36 refractory anemia (RA), 24 refractory anemia with ringed sideroblasts (RARS), 19 refractory anemia with excess of blasts (RAEB), 14 refractory anemia with excess of blasts in transformation (RAEB-t), 14 chronic myelomonocytic leukemia, and 7 hypoplastic MDS patients. HLA-DRB1 molecular typing was performed with polymerase chain reaction-sequence specific oligonucleotides and results were compared with that from a previously reported control Greek population. HLA-DRB1*1602 was the only allele that was significantly overrepresented in Greek MDS patients as a whole, whereas HLA-DRB1*1501 allele frequency was significantly higher in Greek patients with low-risk myelodysplasia. Our results suggest the possible value of HLA-DR15 and HLA-DR16 as determinants for immunomodulatory interventions, at least for Greek patients with low-risk MDS.


The role of the central nervous system in the pathogenesis of polycystic ovary syndrome.
This article reviews the master gland concept and the hypothalamic-pituitary-ovarian axis with respect to embryological development and maturation through normal puberty. Intrinsic function and extrinsic modulation of the pulse generator are discussed. The neuroendocrine disturbances evident in polycystic ovary syndrome (PCOS) are reviewed and put into the context of the recent consensus definition of the syndrome. Modern theories are presented addressing a significant role for neuroendocrine dysfunction during pubertal maturation in the aetiology of PCOS.


Quality of life in endometrial cancer survivors by grade of disease.
Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, with overall incidence increasing, particularly high-grade disease. There is sparse information regarding quality of life (QOL) in EC survivors with a focus on grade of disease. A total of 259 women with EC diagnosed between 2016 and 2020 were identified via the Metropolitan Detroit Cancer Surveillance System and consented to enroll in the Detroit Research on Cancer Survivors cohort study (if African American, n = 138) or completed the baseline interview (if non-Hispanic white, n = 121). Each respondent provided information about their health history, educational attainment, health behaviors, and demographics. The Functional Assessment of Cancer Therapy-General (FACT-G) and Endometrial-specific (FACT-En) were used to assess QOL. Women diagnosed with high-grade (n = 112) and low-grade (n = 147) EC participated in this study. EC survivors with high-grade disease reported significantly lower QOL compared to survivors with low-grade disease (85 vs. 91, respectively, p value = 0.025) as assessed by the FACT-G. This difference was driven by lower physical and functional subscales among women with high-grade disease compared to those with low-grade disease (p value = 0.016 and p = 0.028, respectively). Interestingly, EC-specific QOL measures, as assessed by the FACT-En, did not differ by grade. Grade of disease impacts QOL in EC survivors, as well as socioeconomic, psychological, and physical factors. Most of these factors are amenable to interventions and should be assessed in patients after an EC diagnosis.


Nerve Growth Factor is a Potential Treated Target in Tg(SOD1*G93A)1Gur Mice.
Nerve growth factor (NGF) is a protective factor of neural cells; the possible relationship between the NGF and the pathogenesis of amyotrophic lateral sclerosis (ALS) hasn't been completely known. In this study, we observed and analyzed the expression and distribution of NGF, as well as the possible relationship between the NGF expression and distribution and the neural cell death in both SOD1 wild-type (WT) and Tg(SOD1*G93A)1Gur (TG) mice applying the fluorescence immunohistochemistry method. The results showed that the expression and distribution of NGF in the anterior horn (AH), the lateral horn (LH), and the surrounding central canal (CC) significantly increased at the supper early stage of ALS (Pre-onset stage) and the early stage (Onset stage), but the NGF expression and distribution in the AH, the LH, and the surrounding CC significantly reduced at the progression stage. The astrocyte, neuron, and oligodendrocyte produced the NGF and the neural precursor cells (NPCs) produced the NGF. The neural cell death gradually increased accompanying with the reduction of NGF expression and distribution. Our data suggested that the NGF was a protective factor of neural cells, because the neural cells in the AH, the LH, and the surrounding CC produced more NGF at the supper early and early stage of ALS; moreover, the NPCs produced the NGF. It implied that the NGF exerted the protective effect of neural cells, prevented from the neural cell death and aroused the potential of self-repair in the development of ALS.


Transcriptomic and phenotypic analyses suggest a network between the transcriptional regulators HrcA and sigmaB in Listeria monocytogenes.
Listeria monocytogenes HrcA and CtsR negatively regulate class I and III stress response genes, respectively, while sigma(B) positively regulates the transcription of class II stress response genes. To define the HrcA regulon and identify interactions between HrcA, CtsR, and sigma(B), we characterized newly generated L. monocytogenes DeltahrcA, DeltactsR DeltahrcA, and DeltahrcA DeltasigB strains, along with previously described DeltasigB, DeltactsR, and DeltactsR DeltasigB strains, using phenotypic assays (i.e., heat resistance, acid resistance, and invasion of human intestinal epithelial cells) and performed whole-genome transcriptome analysis of the DeltahrcA strain. The hrcA and sigB deletions had significant effects on heat resistance. While the hrcA deletion had no significant effect on acid resistance or invasion efficiency in Caco-2 cells, a linear regression model revealed a significant (P = 0.0493) effect of interactions between the hrcA deletion and the ctsR deletion on invasiveness. Microarray-based transcriptome analyses and promoter searches identified (i) 25 HrcA-repressed genes, including two operons (the groESL and dnaK operons, both confirmed as HrcA regulated by quantitative real-time PCR) and one gene directly repressed by HrcA, and (ii) 36 genes that showed lower transcript levels in the DeltahrcA strain and thus appear to be indirectly upregulated by HrcA. A number of genes were found to be coregulated by either HrcA and CtsR (2 genes), HrcA and sigma(B) (31 genes), or all three regulators (5 genes, e.g., gadCB). Combined with previous evidence that sigma(B) appears to directly regulate hrcA transcription, our data suggest that HrcA and sigma(B), as well as CtsR, form a regulatory network that contributes to the transcription of a number of L. monocytogenes genes.


A new device for suction-assisted lipectomy: a flexible cannula.
A new type of cannula, "Flex," has been designed for suction-assisted lipectomy. It is flexible, permitting easy access to areas distant from the skin incision. Flex is best characterized by one word: Bend.


Efforts to advance underwater noise management in Canada: Introduction to the Marine Pollution Bulletin Special Issue.
This introduction to a special issue on approaches to managing underwater noise in Canada provides a brief overview of recent efforts to better understand and reduce anthropogenic underwater noise. Recent programs have aimed to increase understanding of anthropogenic noise in the habitats of highly endangered whales and have supported management actions such as vessel slow downs. Technical workshops have advanced the development of quiet ship design and associated technologies. Collaborative research examined noise levels in the St. Lawrence Estuary and the Arctic Ocean. Efforts to better manage noise have gone beyond shipping: enhanced mitigation measures have been put in place for naval exercises near habitats used by southern resident killer whales, while other work has focused on the identification of appropriate metrics for measuring noise. To coordinate and advance these and other efforts, the Government of Canada is developing a national Ocean Noise Strategy.


Effects of abnormal temperature and starvation on the internal defense system of the schistosome-transmitting snail Biomphalaria glabrata.
Climate change may affect the internal defense system (IDS) of freshwater snails, and as a result their capacity to transmit disease. We examined effects of short-term exposure to supra- and sub-optimal temperatures or starvation on 3 parameters of the IDS of the schistosome-resistant Salvador strain of Biomphalaria glabrata - hemocyte concentrations, cell division in the amebocyte-producing organ (APO), and resistance to infection with Schistosoma mansoni. Adult snails were exposed to 1 of 3 temperatures, 20°C, 27°C (controls), or 33°C, for 1 or 2weeks, with food. A fourth group was maintained at 27°C, but without food. Compared to the controls, starved snails had significantly higher hemocyte counts at both 1 and 2weeks, although mitotic activity in the APO was significantly lower at both time periods. Exposure to 20°C or 33°C for 1 or 2weeks did not affect hemocyte numbers. However, APO mitotic activity in snails exposed to 20°C was significantly higher at both 1 and 2weeks, whereas mitotic activity in snails exposed to 33°C was significantly lower at 1week but normal at 2weeks. None of the treatments altered the resistance phenotype of Salvador snails. In a follow-up experiment, exposure to 33°C for 4-5h, a treatment previously reported to both induce expression of heat shock proteins (Hsps) and abrogate resistance to infection, caused immediate upregulation of Hsp 70 and Hsp 90 expression, but did not alter resistance, and Hsp expression levels returned to baseline after 2weeks at 33°C. Results of this study indicate that abnormal environmental conditions can have both stimulatory and inhibitory effects on the IDS in adult B. glabrata, and that some degree of acclimation to abnormal temperatures may occur.


Brain serotonergic activity and plasma amino acid levels in genetically obese Zucker rats.
In order to test the hypothesis that serotonergic activity is abnormal in the brains of genetically obese Zucker rats, levels of serotonin (5-HT); its amino acid precursor, tryptophan (Trp), and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were measured in eight brain regions in groups of obese and non-obese male rats. Plasma albumin levels as well as levels of amino acids and related compounds in plasma and in a cortical sample were also determined in the same animals. While Trp was lower in several brain regions of the obese animals, the only region showing a depressed level of 5-HT in the obese group was the mesencephalon. Obese animals also had a lower amount of 5-HIAA in the diencephalon, but no other differences were significant. Both elevations and depressions were observed in cortical amino acid levels in obese animals. The level of plasma albumin was increased in the obese group. Free Trp was decreased in the plasma of obese rats while levels of other amino acids (methionine, leucine, isoleucine, valine and phenylalanine) which compete with Trp for transport across the blood-brain barrier were elevated. Thus the combination of lower plasma free Trp and increased levels of competitive amino acids appears to contribute to decreased levels of Trp in the brain of genetically obese rats.


Spontaneous production of a C-type RNA virus in a cell line derived from rat glioma.
The spontaneous production of a rat C-type RNA virus (ACV) in a cultured cell line (AC cells) established from a chemically induced rat glioma was studied. The characteristics of ACV were: morphology typical of C-type RNA virus; buoyant density of 1.15 g/ml in a sucrose density gradient; RNA directed DNA polymerase activity; viral core with a density of 1.28 to 1.30 g/ml; 70S RNA with dimer structure; and structural protein composed of mainly four polypeptides. Kinetical analysis of DNA-DNA hybridization revealed that DNA sequences homologous to DNA transcripts of RNA of ACV were present in rat cells. RNA directed DNA polymerase of ACV partially cross-reacted with antiserum to the polymerase of Rauscher murine leukemia virus. These data suggest that ACV is an endogenous C-type RNA virus of rat origin.


Blockade of T-type calcium channels prevents tonic-clonic seizures in a maximal electroshock seizure model.
T-type (Cav3) calcium channels play important roles in neuronal excitability, both in normal and pathological activities of the brain. In particular, they contribute to hyper-excitability disorders such as epilepsy. Here we have characterized the anticonvulsant properties of TTA-A2, a selective T-type channel blocker, in mouse. Using the maximal electroshock seizure (MES) as a model of tonic-clonic generalized seizures, we report that mice treated with TTA-A2 (0.3 mg/kg and higher doses) were significantly protected against tonic seizures. Although no major change in Local Field Potential (LFP) pattern was observed during the MES seizure, analysis of the late post-ictal period revealed a significant increase in the delta frequency power in animals treated with TTA-A2. Similar results were obtained for Cav3.1-/- mice, which were less prone to develop tonic seizures in the MES test, but not for Cav3.2-/- mice. Analysis of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and c-Fos expression revealed a rapid and elevated neuronal activation in the hippocampus following MES clonic seizures, which was unchanged in TTA-A2 treated animals. Overall, our data indicate that TTA-A2 is a potent anticonvulsant and that the Cav3.1 isoform plays a prominent role in mediating TTA-A2 tonic seizure protection.


Retained efficacy of ivermectin against cyathostomins in Swedish horse establishments practicing selective anthelmintic treatment.
Cyathostominae are ubiquitous to grazing horses and regarded the most prevalent internal parasite in the horse. Unfortunately, decades of indiscriminate use of anthelmintic drugs have resulted in the development of resistance in cyathostomins to all currently available drug groups, the most recent being a documented lack of efficacy to the macrocyclic lactones (ML). In vivo determination of anthelmintic resistance in horses most often utilises the faecal egg count reduction test (FECRT). Further, a shortened egg reappearance period (ERP) can indicate a change in response to the applied treatment and suggest an upcoming reduction of efficacy. Although both true resistance as demonstrated by the FECRT and shorter ERPs after ML treatment have now been shown in cyathostomins worldwide, the efficacy of ML as regards to cyathostomins in Sweden is currently unknown. The aim of the present study was therefore to determine FECRTs and ERPs after ivermectin (IVM) treatment in Swedish horses. Sixteen equestrian establishments with a minimum of six horses excreting at least 150 eggs per gram faeces (EPG) at screening were selected. For each establishment, FECRTs and ERPs were determined by collecting faecal samples prior to and 14 days after IVM treatment (200 µg/kg), and thereafter at weekly intervals for a total of eight weeks. All participants responded to a questionnaire detailing pasture management methods and anthelmintic routines.Questionnaire results showed that the majority of establishments (69%) only treated horses with anthelmintic drugs if indicated by faecal diagnostics and all of the establishments had a mean FECRT exceeding 99.0% and ERPs ranging from six to over eight weeks. The ERP was shown to increase with age as young individuals were shown to excrete cyathostomin eggs earlier after treatment compared with older horses (R = 0.21, p = 0.015). Riding schools, stud farms and those declaring not to use separate summer and winter paddocks had significantly shorter ERPs (p <0.01).In conclusion, retained ERPs and no confirmed resistance to IVM were found in Swedish equine establishments practising selective anthelmintic treatment, and supports the use of selective deworming regimens as a means of reducing the risk of anthelmintic resistance development.


Directing macrocyclic architecture using iron(III)-, gallium(III)-, or zirconium(IV)-assisted ring closure of linear dimeric endo-hydroxamic acid ligands.
Dimeric hydroxamic acid macrocycles are a subclass of bacterial siderophores produced for iron acquisition. Limited yields from natural sources provides the impetus to develop synthetic routes to improve access to these compounds, which have potential utility in metal ion binding applications in the environment and medicine. This work has examined the role of metal ions in forming pre-complexes with linear endo-hydroxamic acid (endo-HXA) ligands bearing terminal amine and carboxylic acid groups optimally configured for in situ ring closure reactions. The 1:1 reaction between Fe(III) and the dimeric endo-HXA ligand 5-((5-(5-((5-aminopentyl)(hydroxy)amino)-5-oxopentanamido)pentyl)(hydroxy)amino)-5-oxopentanoic acid (PPH-PPH) (1) formed the pre-complex (PC) [Fe(PP-PP)-PC]+ with in situ amide coupling generating the macrocycle (MC) [Fe(PP)2-MC]+ and, following Fe(III) removal, the apo-macrocycle 1,13-dihydroxy-1,7,13,19-tetraazacyclotetracosane-2,6,14,18-tetraone (PPH)2-MC (2). The 1:2 reaction system between Fe(III) and the monomeric endo-HXA ligand 5-((5-aminopentyl)(hydroxy)amino)-5-oxopentanoic acid (PPH) gave significantly less [Fe(PP)2-MC]+ than the former system, due to the requirement to form two rather than one amide bond(s). The 1:1 Ga(III):1 system yielded [Ga(PP-PP)-PC]+ and [Ga(PP)2-MC]+. Neither [Zr(PP-PP)-PC]2+ nor [Zr(PP)2-MC]2+ was detected in the 1:1 Zr(IV):1 system. Instead, the Zr(IV) system showed the formation of a 1:2 Zr(IV):1 pre-complex [Zr(PP-PP)2-PC], which following in situ amide bond forming chemistry, generated two Zr(IV) macrocyclic complexes with distinct architectures: a dimer-of-dimers complex [Zr((PP)2)2-MC] and an end-to-end macrocycle [Zr(PP)4-MC]. The formation of [Fe(PP)2-MC]+, [Ga(PP)2-MC]+ or [Zr((PP)2)2-MC] was confirmed from reconstitution experiments with 2. The work has shown that the choice of metal ion in metal-assisted ring closure reactions directs the assembly of macrocyclic complexes with distinct architectures.


Staphylococcus aureus bacteremia and endocarditis associated with a removable infected intravenous device.
Records of 21 patients with Staphylococcus aureus bacteremia associated with a removable infected intravenous device were reviewed. Sixteen patients had a peripheral intravenous catheter, four had a central venous catheter and one had a transvenous cardiac pacer. The duration of the indwelling intravenous device in situ prior to the detection of infection ranged from two to 11 (mean 5.2) days. The infected intravenous device was promptly removed as soon as bacteremia was suspected. Endocarditis was diagnosed in eight patients: in two patients an aortic murmur developed; in two the diagnosis was made clinically and was confirmed at necropsy (one mitral and one aortic); in four the diagnosis was made at necropsy (two tricuspid and two atrial wall). In patients with Staph. aureus bacteremia associated with a removable infected intravenous device, the risk of endocarditis developing was significant.


Implication of leumorphin in inhibitory control of vasopressin secretion in conscious rats.
The effects of leumorphin, a kappa-agonist derived from proenkephalin B (neoendorphin and dynorphin precursor), on vasopressin secretion were studied under basal and stimulated conditions in conscious, unrestrained rats. Intracerebroventricular injection of leumorphin (60 or 600 pmol) significantly inhibited basal vasopressin secretion. The vasopressin response induced by intracerebroventricular injection of angiotensin II (100 pmol) was significantly suppressed, in a dose-dependent fashion, by the simultaneous intracerebroventricular injection of leumorphin (6, 60, or 600 pmol). Intravenous pretreatment with naloxone (0.5 mg/kg body weight) diminished the inhibitory action of leumorphin (60 pmol) on vasopressin secretion. Moreover, naloxone (0.5 mg/kg body weight) prolonged the vasopressin secretion induced by intracerebroventricular injection of angiotensin II (100 pmol). These results indicate that leumorphin possesses a potent inhibitory effect on vasopressin secretion and that, alone or in combination with other endogenous opioid peptides, it plays an important role in the control of vasopressin secretion.


Editor's Choice - Comparison of Outcomes for Major Contemporary Endograft Devices Used for Endovascular Repair of Intact Abdominal Aortic Aneurysms.
To compare rates of mortality, rupture, and secondary intervention following endovascular repair (EVAR) of intact abdominal aortic aneurysms (AAA) using contemporary endograft devices from three major manufacturers. This was a retrospective cohort study using linked clinical registry (Australasian Vascular Audit) and all payer administrative data. Patients undergoing EVAR for intact AAA between 2010 and 2019 in New South Wales, Australia were identified. Rates of all cause death, secondary rupture, and secondary intervention (subsequent aneurysm repair; other secondary aortic intervention) were compared for patients treated with Cook, Medtronic, and Gore standard devices. Inverse probability of treatment weighted proportional hazards and competing risk regression were used to adjust for patient, clinical, and aneurysm characteristics, using Cook as the referent device. This study identified 2 874 eligible EVAR patients, with a median follow up of 4.1 (maximum 9.5) years. Mortality rates were similar for patients receiving different devices (ranging between 7.0 and 7.3 per 100 person years). There was no statistically significant difference between devices in secondary rupture rates, which ranged between 0.4 and 0.5 per 100 person years. Patients receiving Medtronic and Gore devices tended to have higher crude rates of subsequent aneurysm repair (1.5 per 100 person years) than patients receiving Cook devices (0.8 per 100 person years). This finding remained in the adjusted analysis, but was only statistically significant for Medtronic devices (HR 1.57, 95% CI 1.02 - 2.47; HR 1.73, 95% CI 0.94 - 3.18, respectively). Major endograft devices have similar overall long term safety profiles. However, there may be differences in rates of secondary intervention for some devices. This may reflect endograft durability, or patient selection for different devices based on aneurysm anatomy. Continuous comparative assessments are needed to guide evidence for treatment decisions across the range of available devices.


Composite SOSM controller for path tracking control of agricultural tractors subject to wheel slip.
In the work, the path tracking control methods are developed for autonomous agricultural tractors subject to wheel slip constraints by using second-order sliding mode (SOSM) and finite-time disturbance observer (FDOB) techniques. First of all, the path tracking error dynamics derived from the kinematic model is given and applied to controller design. In order to deal with the inevitable chattering problem existing in the conventional first-order sliding mode (FOSM) controller, a SOSM controller is constructed by regarding the controller derivative as the new control law, which means that the practical control law can be seen as an integration of the SOSM controller. Through a combination of the FDOB and the designed SOSM controller, the composite path tracking controller is further constructed to avoid high control gains in the designed SOSM controller. The strict Lyapunov stability analysis is carried out to ensure that the sliding variable can be finite-time stabilized to the origin under the proposed control algorithms. Finally, the comparative simulation results confirm that the developed guidance laws can achieve good tracking performance and strong robustness even in the presence of slipping effects.


The financial burden of sickle cell disease on households in Ekiti, Southwest Nigeria.
Studies on economic impact of sickle cell disease (SCD) are scanty despite its being common among children in developing countries who are mostly Africans. To determine the financial burden of SCD on households in Ado Ekiti, Southwest Nigeria. A longitudinal and descriptive study of household expenditures on care of 111 children with SCD managed at the pediatric hematology unit of the Ekiti State University Teaching Hospital was conducted between January and December 2014. There were 64 male and 47 female children involved, aged between 15 and 180 months. They were from 111 households, out of which only eight (7.2%) were enrolled under the National Health Insurance Scheme. The number of admissions and outpatients' consultations ranged from 1 to 5 and 1 to 10 per child, respectively. Malaria, vaso-occlusive crisis, and severe anemia were the leading comorbidities. The monthly household income ranged between ₦12,500 and ₦330,000 (US$76 and US$2,000) with a median of ₦55,000 (US$333), and health expenditure ranged between ₦2,500 and ₦215,000 (US$15 and US$1,303) with a mean of ₦39,554±35,479 (US$240±215). Parents of 63 children lost between 1 and 48 working days due to their children's ill health. Parents of 23 children took loans ranging between ₦6,500 and ₦150,000 (US$39 and US$909) to offset hospital bills. The percentage of family income spent as health expenditure on each child ranged from 0.38 to 34.4. Catastrophic health expenditure (when the health expenditure >10% of family income) occurred in 23 (20.7%) households. Parents who took loan to offset hospital bills, low social class, and patients who took ill during the study period significantly had higher odds for catastrophic health expenditure (95% confidence interval [CI] 5.399-87.176, P=0.000; 95% CI 2.322-47.310, P=0.002; and 95% CI 1.128-29.694, P=0.035, respectively). SCD poses enormous financial burden on parents and households.


Antimicrobial potential of four Lactobacillus strains isolated from breast milk.
The antimicrobial potential of four lactobacilli (Lactobacillus salivarius CECT5713, Lactobacillus gasseri CECT5714, L. gasseri CECT5715 and Lactobacillus fermentum CECT5716), isolated from fresh human breast milk, was evaluated in this study and compared with Lactobacillus coryniformis CECT5711, a reuterin-producing strain isolated from an artisan goat's cheese. Agar diffusion tests, competitive adhesion assays and mucin expression assays were carried out in order to value the antibacterial properties of the lactobacilli strains. The antibacterial capability of the strains was tested in vivo by using a murine infection model with Salmonella choleraesuis. The results revealed that all the strains studied, displayed antibacterial properties against pathogenic bacteria. However, the antibacterial potential varied among the lactobacilli tested and, in fact, L. salivarius CECT5713 showed not only the best in vitro antibacterial activity, but also the highest protective effect against a Salmonella strain in the murine infection model. The four breast-milk lactobacilli, and particularly L. salivarius CECT5713, possess potent antibacterial activities that result in a higher protection against S. choleraesuis CECT4155 in a mouse infection model. These results suggest that lactobacilli from breast milk could contribute to an anti-infective protection in neonates and would be excellent candidates for the development of infant probiotic products.


Inhibition of PDGF beta-receptor tyrosine phosphorylation and its downstream intracellular signal transduction in rat aortic vascular smooth muscle cells by kaempferol.
Kaempferol, a flavonoid present in human diet and plants, has been known to show cardiovascular protection via its anti-oxidant activity. In this study, we have investigated the effect of kaempferol on the proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Kaempferol significantly inhibited 50 ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation and [3H]-thymidine incorporation into DNA at concentrations of 5, 20 and 50 microM without any cytotoxicity. Kaempferol also inhibited the c-fos mRNA expression induced by PDGF-BB concentration-dependently. In addition, consistent with the inhibition of cell proliferation and c-fos mRNA expression, kaempferol inhibited the PDGF beta-receptor (Rbeta) phosphorylation in a concentration-dependent manner. Accordingly, the downstream signal transductions of PDGF-Rbeta such as ERK1/2, Akt and PLC-gamma1 phosphorylation were also inhibited by kaempferol in the same pattern. These findings suggest that, in addition to its anti-oxidant activity, the cardiovascular protective effect of kaempferol may be mediated, at least in part, by the suppression of VSMC proliferation, which is due to the inhibition of PDGF-Rbeta tyrosine phosphorylation and its downstream intracellular signal transduction.


Heterologous complementation studies in Escherichia coli with the Hyp accessory protein machinery from Chloroflexi provide insight into [NiFe]-hydrogenase large subunit recognition by the HypC protein family.
Six Hyp maturation proteins (HypABCDEF) are conserved in micro-organisms that synthesize [NiFe]-hydrogenases (Hyd). Of these, the HypC chaperones interact directly with the apo-form of the catalytically active large subunit of Hyd enzymes and are believed to transfer the Fe(CN)2CO moiety of the bimetallic cofactor from the Hyp machinery to this large subunit. In E. coli, HypC is specifically required for maturation of Hyd-3 while its paralogue, HybG, is specifically required for Hyd-2 maturation; either HypC or HybG can mature Hyd-1. In this study, we demonstrate that the products of the hypABFCDE operon from the deeply branching hydrogen-dependent and obligate organohalide-respiring bacterium Dehalococcoides mccartyi strain CBDB1 were capable of maturing and assembling active Hyd-1, Hyd-2 and Hyd-3 in an E. coli hyp mutant. Maturation of Hyd-1 was less efficient, presumably because HypB of E. coli was necessary to restore optimal enzyme activity. In a reciprocal maturation study, the highly O2-sensitive H2-uptake HupLS [NiFe]-hydrogenase from D. mccartyi CBDB1 was also synthesized in an active form in E. coli. Together, these findings indicated that HypC from D. mccartyi CBDB1 exhibits promiscuity in its large subunit interaction in E. coli. Based on these findings, we generated amino acid variants of E. coli HybG capable of partial recovery of Hyd-3-dependent H2 production in a hypC hybG double null mutant. Together, these findings identify amino acid regions in HypC accessory proteins that specify interaction with the large subunits of hydrogenase and demonstrate functional compatibility of Hyp accessory protein machineries.