Stereochemical determination of carbon partitioning between photosynthesis and photorespiration in C3 plants: use of (3R)-D-[3-3H1, 3-14C]glyceric acid.
When (3R)-D-[3-3H1,3-14C]glyceric acid is supplied in tracer amounts to illuminated tobacco leaf discs, the acid penetrates to the chloroplasts without loss of 3H, and is phosphorylated there. Subsequent metabolism associated with the reductive photosynthetic cycle fully conserves 3H. Oxidation of ribulose bisphosphate (RuBP) by RuBP carboxylase-oxygenase (EC 184.108.40.206) results in the formation of (2R)-[2-3H1, 14C]glycolic acid which, on oxidation by glycolate oxidase (EC 18.104.22.168), releases 3H to water. Loss of 3H from the combined photosynthetic and photorespiratory systems is, therefore, associated with the oxidative photorespiratory loop. Assuming steady-state conditions and a basic metabolic model, the fraction of RuBP oxidized and the photorespiratory carbon flux relative to gross or net CO2 fixation can be calculated from the fraction of supplied 3H retained in the triose phosphates exported from the chloroplasts. This retention can be determined from the 3H:14C ratio for glucose obtained from isolated sucrose. The dependence of 3H retention upon O2 and CO2 concentrations can be deduced by assuming simple competitive kinetics for RuBP carboxylase-oxygenase. The experimental results confirmed the stereochemical assumptions made. Under conditions of negligible photorespiration 3H retention was essentially complete. The change in 3H retention with O2 and CO2 concentrations were investigated. For leaf discs (upper surface up) in normal air, it was estimated that 39% of the RuBP was oxidized, 32% of the fixed CO2 was photorespired, and the photorespiration rate was 46% of the net photosynthetic CO2 fixation rate. These are minimal estimates, as it is assumed that the only source of photorespired CO2 is glycine decarboxylation.


Geochemistry and Mineralogy of Western Australian Salt Lake Sediments: Implications for Meridiani Planum on Mars.
Hypersaline lakes are characteristic for Western Australia and display a rare combination of geochemical and mineralogical properties that make these lakes potential analogues for past conditions on Mars. In our study, we focused on the geochemistry and mineralogy of Lake Orr and Lake Whurr. While both lakes are poor in organic carbon (<1%), the sediments' pH values differ and range from 3.8 to 4.8 in Lake Orr and from 5.4 to 6.3 in Lake Whurr sediments. Lake Whurr sediments were dominated by orange and red sediment zones in which the main Fe minerals were identified as hematite, goethite, and tentatively jarosite and pyrite. Lake Orr was dominated by brownish and blackish sediments where the main Fe minerals were goethite and another paramagnetic Fe(III)-phase that could not be identified. Furthermore, a likely secondary Fe(II)-phase was observed in Lake Orr sediments. The mineralogy of these two salt lakes in the sampling area is strongly influenced by events such as flooding, evaporation, and desiccation, processes that explain at least to some extent the observed differences between Lake Orr and Lake Whurr. The iron mineralogy of Lake Whurr sediments and the high salinity make this lake a suitable analogue for Meridiani Planum on Mars, and in particular the tentative identification of pyrite in Lake Whurr sediments has implications for the interpretation of the Fe mineralogy of Meridiani Planum sediments. Western Australia-Salt lakes-Jarosite-Hematite-Pyrite-Mars analogue. Astrobiology 16, 525-538.


Cancer stem cell-driven efficacy of trastuzumab (Herceptin): towards a reclassification of clinically HER2-positive breast carcinomas.
Clinically HER2+ (cHER2+) breast cancer (BC) can no longer be considered a single BC disease entity in terms of trastuzumab responsiveness. Here we propose a framework for predicting the response of cHER2+ to trastuzumab that integrates the molecular distinctions of intrinsic BC subtypes with recent knowledge on cancer stem cell (CSC) biology. First, we consider that two interchangeable populations of epithelial-like, aldehyde dehydrogenase (ALDH)-expressing and mesenchymal-like, CD44+CD24-/low CSCs can be found in significantly different proportions across all intrinsic BC subtypes. Second, we overlap all the intrinsic subtypes across cHER2+ BC to obtain a continuum of mixed phenotypes in which one extreme exhibits a high identity with ALDH+ CSCs and the other extreme exhibits a high preponderance of CD44+CD24-/low CSCs. The differential enrichment of trastuzumab-responsive ALDH+ CSCs versus trastuzumab-refractory CD44+CD24-/low CSCs can explain both the clinical behavior and the primary efficacy of trastuzumab in each molecular subtype of cHER2+ (i.e., HER2-enriched/cHER2+, luminal A/cHER2+, luminal B/cHER2+, basal/cHER2+, and claudin-low/cHER2+). The intrinsic plasticity determining the epigenetic ability of cHER2+ tumors to switch between epithelial and mesenchymal CSC states will vary across the continuum of mixed phenotypes, thus dictating their intratumoral heterogeneity and, hence, their evolutionary response to trastuzumab. Because CD44+CD24-/low mesenchymal-like CSCs distinctively possess a highly endocytic activity, the otherwise irrelevant HER2 can open the door to a type of "Trojan horse" approach by employing antibody-drug conjugates such as T-DM1, which will allow a rapid and CSC-targeted delivery of cytotoxic drugs to therapeutically manage trastuzumab-unresponsive basal/cHER2+ BC. Contrary to the current dichotomous model used clinically, our model proposes that a reclassification of cHER2+ tumors based on the spectrum of molecular BC subtypes might inform on their CSC-determined sensitivity to trastuzumab, thus providing a better delineation of the predictive value of cHER2+ in BC by incorporating CSCs-driven intra-tumor heterogeneity into clinical decisions.


[A case of cerebral arteriovenous malformation with accidental migration of a microcatheter during endovascular procedure].
This is a report of a case of cerebral arteriovenous malformation with accidental breakaway of a microcatheter during endovascular embolization. A 25-year-old female suddenly suffered severe headache. CT scan demonstrated intraventricular hemorrhage, and the angiogram revealed right parieto-occipital AVM. We performed endovascular embolization using a flow-directed microcatheter (1.5F BALT MAGIC catheter) 2 weeks after onset, and the microcatheter broke accidentally and a fragment of the soft tip migrated to the distal posterior cerebral artery during the procedure. Although we tried to retrieve the catheter using several retrieval devices, we failed. Two days after the procedure we undertook surgical treatment. The migrated catheter was recognized in a small feeding artery which was stretched tightly, so retrieval was very risky. Using hemoclips for trapping the part of the catheter which remained in the feeder, we were able to retrieve it by cutting the feeder. Flow-directed microcatheters are very usefull in endovascular procedures, but it is necessary to handle them carefully in accord with sufficient knowledge of their use and handling methods.


International exchange of emergency phase information and assessments: an aid to national/international decision makers.
This paper discusses a collaborative project (1) to demonstrate the feasibility and benefit of a system seeking early review, in a 'quasi peer review' mode, of nuclear accident plume and dose assessment predictions by four major international nuclear accident emergency response systems before release of calculations to respective national authorities followed by (2) sharing these results with responsible national/international authorities, (3) development of an affordable/accessible system to distribute results to countries without prediction capabilities and (4) utilisation for exercises and collaboration studies. The project exploits Internet browser technology and low-cost PC hardware, incorporates an Internet node, with access control, for depositing a minimal set of XML-based graphics files for presentation in an identical map format. Side-by-side viewing and televideo conferencing will permit rapid evaluation, data elaboration and recalculation (if necessary) and should produce strong consensus among decision makers. Successful completion affords easy utilisation by national/international organisations and non-nuclear states at risk of trans-boundary incursion.


Development of Human Breast Milk Microbiota-Associated Mice as a Method to Identify Breast Milk Bacteria Capable of Colonizing Gut.
Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium, Staphylococcus, Lactobacillus, and Escherichia/Shigella. Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium, Prevotella, Roseburia, Ruminococcus, and Bacteroides, was 0.01-1% in the milk inoculum and 0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.


Recent biological applications of heterocyclic hybrids containing s-triazine scaffold.
s-Triazine possesses an auspicious status in the field of drug discovery and development owing to its presence in many naturally occurring compounds as well as commercially available drugs like enasidenib, gedatolisib, bimiralisib, atrazine, indaziflam, and triaziflam. Easy, cost-effective, and efficient access to its derivatives in addition to their splendid biological activities such as anticancer, anti-inflammatory, antiviral, anticonvulsant, anti-tubercular, antidiabetic, antimicrobial, makes it an attractive heterocyclic nucleus in the field of medicinal chemistry. Other than the direct access of its derivatives from simple commercially available starting materials like amidine, the s-triazine derivatives have also been obtained starting from an inexpensive commercially available 2,4,6-trichloro-1,3,5-triazine (TCT) commonly known as cyanuric chloride. Owing to the high reactivity and the possibility of sequential substitution of TCT, a variety of biologically active heterocyclic scaffolds have been installed on this nucleus in order to have more potent compounds. These s-triazine-based heterocyclic hybrids have been reported to show enhanced biological activities in recent years. Therefore, it is important to summarize and highlight recent examples of these hybrids which is imperative to attract the attention of the drug development community.


CAL2 monoclonal antibody is a rapid and sensitive assay for the detection of calreticulin mutations in essential thrombocythemia patients.
Calreticulin (CALR) mutations are detected in the majority of JAK2 wild type patients with essential thrombocythemia (ET). Unlike JAK2V617F and MPL point mutations, CALR mutations are highly heterogeneous, with several types of indels being reported so far. CAL2 is a monoclonal antibody specifically recognizing the C-neoterminal peptide derived from all the frameshift mutations of CALR. We retrospectively analysed 172 ET patients diagnosed at our Institution from 1980 to 2015. In JAK2V617F- and MPLW515K/L-wild type patients CALR mutations were searched on peripheral blood and CAL2 immunostaining was performed on bone marrow. In addition, bone marrow biopsies were histologically reviewed for megakaryocytic features. Thirty-one patients (18%) were CALR-mutated. Concordance between molecular and immunohistological detection of CALR mutations was near complete, albeit a single patient was found to be positive by molecular tests only. Two patterns were defined in CAL2-positive bone marrow samples, characterized by staining of almost only megakaryocytes (pattern A: 41%) or staining of megakaryocytes and ≥ 2% small non megakaryocytic elements (pattern B: 59%), at least partially being myeloid precursors. Pattern B biopsies had higher cellularity and number of megakaryocytes compared to pattern A samples. In this series, CAL2 allowed rapid and cost-efficient identification of CALR-mutated ET patients. The biological significance of different staining pattern should be confirmed in wider and independent series.


Endoscopic mucosal resection of a solitary metastatic tumor in the stomach: a case report.
Endoscopic mucosal resection (EMR) is increasingly being utilized in the management of early gastric cancer. Metastatic cancer of the stomach is uncommon. We report a case of solitary gastric metastasis from renal cell carcinoma (RCC) that was successfully excised with EMR. A 71-year-old man presented with iron deficiency anemia, he had undergone a radical nephrectomy for RCC 3 years previously. Upper gastrointestinal endoscopy revealed a malignant-appearing 10 × 12 mm polyp in the stomach. Histopathology of the biopsy revealed that it was a metastasis from RCC, confirmed by immunohistochemistry with Vimentin and CAM 5.2 positivity. Computed tomography and bone scanning revealed no other metastases. Simultaneous laparoscopy and upper gastrointestinal endoscopy revealed that the lesion was localized to the gastric mucosa. EMR of the tumor en bloc was performed successfully. Histology confirmed a complete excision. He had an uneventful postoperative course and is well 15 months after surgery, without any tumor recurrence.


The trends and constructive ambiguity in international agreements on intellectual property and pharmaceutical affairs: Implications for domestic legislations in low- and middle-income countries.
The purpose of this study is to analyse the trends in international agreements including Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), Korea-United States Free Trade Agreements, and Trans-Pacific Partnership Agreements on intellectual property and pharmaceutical affairs with the updated framework. The study also assesses constructive ambiguity in international agreements, which might affect the implementation process through interpretation and domestic legislations. Five flexibility clauses and three TRIPS-plus provisions were selected, and presence of constructive ambiguity in the agreements was analysed to draw actual trends in international agreements. Flexibility provisions excluding compulsory licensing were not noticeably changed, and TRIPS-plus provisions including data exclusivity and patent linkage were expanded in scope or newly appeared, respectively. The clause regarding compulsory licensing, extension of the patent term, data exclusivity, and patent linkage showed unclear definitions or the lack of adequate explanations. With constructive ambiguity in those clauses, a country who wants to join international agreements in the near future could amend domestic legislations to minimise the detrimental effect of international agreements on access to medicines.


Perioperative and long-term outcomes after pancreaticoduodenectomy in elderly patients 80 years of age and older.
Although a pancreaticoduodenectomy (PD) has been recently regarded as a safe surgical procedure at high-volume centers, the efficacy of PD for patients 80 years of age and older is controversial. The aim of this study was to evaluate the perioperative and long-term outcomes following PD in patients 80 years of age and older. Elderly patients 80 years of age and older who underwent PD between 2001 and 2009 were identified. The perioperative and long-term outcomes were compared with patients younger than 80 years of age. Of 561 total patients, 22 patients (3.9 %) were 80 years of age or older. Mortality occurred in one patient (4.5 %). Postoperative major complications (Clavien-Dindo classification ≥ grade III) occurred in six patients (27.3 %) in this group, which was significantly higher than in patients younger than 80 years of age (P = 0.008). The survival of the elderly patients undergoing PD for pancreatic cancer was significantly shorter than that for the same patient group with other diseases (median survival, 13 versus 82 months; P = 0.014). Only one elderly patient with pancreatic cancer survived more than 3 years. PD for pancreatic cancer in patients aged 80 and older should be carefully selected, because it is associated with a higher incidence of severe postoperative complications and a small change of long-term survival.


Assessing the Robustness of Mixture Models to Measurement Noninvariance.
Recent work reframes direct effects of covariates on items in mixture models as differential item functioning (DIF) and shows that, when present in the data but omitted from the fitted latent class model, DIF can lead to overextraction of classes. However, less is known about the effects of DIF on model performance-including parameter bias, classification accuracy, and distortion of class-specific response profiles-once the correct number of classes is chosen. First, we replicate and extend prior findings relating DIF to class enumeration using a comprehensive simulation study. In a second simulation study using the same parameters, we show that, while the performance of LCA is robust to the misspecification of DIF effects, it is degraded when DIF is omitted entirely. Moreover, the robustness of LCA to omitted DIF differs widely based on the degree of class separation. Finally, simulation results are contextualized by an empirical example.


Identification and characterisation of two extracellular proteases of Streptococcus mutans.
Streptococcus mutans was shown to produce two extracellular proteases capable of degrading both gelatin and collagen-like substrates. These enzymes have molecular masses of 52 and 50 kDa when analysed by SDS-PAGE. Both enzymes were inhibited by EDTA, but not by a range of other inhibitors with different specificities, indicating that they are metalloproteases. The activity of EDTA-inactivated enzymes could be restored by the addition of manganese and zinc. The identical inhibition and restoration profiles of the two enzymes suggest that one of the proteases may be a degradation product of the other.


Redox-active ligand-induced homolytic bond activation.
Coordination of the novel redox-active phosphine-appended aminophenol pincer ligand (PNO(H2) ) to Pd(II) generates a paramagnetic complex with a persistent ligand-centered radical. The complex undergoes fully reversible single-electron oxidation and reduction. Homolytic bond activation of diphenyldisulfide by the single-electron reduced species leads to a ligand-based mixed-valent dinuclear palladium complex with a single bridging thiolate ligand. Mechanistic investigations support an unprecedented intramolecular ligand-to-disulfide single-electron transfer process to induce homolytic SS cleavage, thereby releasing a thiyl (sulfanyl) radical. This could be a new strategy for small-molecule bond activation.


Use of helium nanodroplets for assembly, transport, and surface deposition of large molecular and atomic clusters.
The utility of continuous beam of helium droplets for assembly, transport, and surface deposition of metal and molecular clusters is studied. Clusters of propyne having from about 10 to 10(4) molecules were obtained via sequential pickup of molecules by He droplets with average sizes in the range of 10(4)-10(7) atoms. The maximum attainable flux of the propyne molecules carried by He droplets was found to be in the range of (5-15)x10(15) molecules sr(-1) s(-1), being larger in larger droplets. The size of the clusters and the flux of the transported species are ultimately limited by the evaporative extinction of the entire helium droplet upon capture of particles. It is shown that the attenuation of the He droplet beam in the process of the cluster growth can be used in order to obtain the average size and the binding energy of the clusters. Furthermore, we used He droplets for assembling and surface deposition of gold and silver clusters having about 500 atoms. Typical deposition rate of metal atoms of about 3 x 10(15) atoms sr(-1) s(-1) is comparable to or larger than obtained with other beam deposition techniques. We propose that doping of He droplets by Au and Ag atoms in two separate pickup chambers leads to formation of the bimetal clusters having core-shell structure.


[Myomectomy by vaginal route].
Myomectomy by vaginal route is the least invasive of all methods for myoma removal. Compared to classical, abdominal myomectomy, it has numerous advantages, especially in cases of fundal and posterior wall myomas, but still it is relatively rarely performed. This study provides an analysis of operative and postoperative course of patients subjected to myomectomy by vaginal route in the period from 01/01/2003 to 01/11/2005 as well as the corresponding control group of patients which had undergone classical, abdominal myomectomy. The study points out to significance and advantages of application of surgical technique for removal of myoma through the posterior wall of the vagina as opposed to classical, abdominal myomectomy. Transvaginal myomectomy eliminates trauma of laparotomy, intraoperative blood loss is reduced, postoperative complications are down to minimum, postoperative recovery is shorter, and so is the number of days spent in hospital. Thus, by performing this type of surgery, a positive cost-benefit effect is obtained not only for the patient but for health authorities as well.


UHPLC-MS/MS phenolic profiling and in vitro antioxidant activities of Inula graveolens (L.) Desf.
Inula graveolens (L.) Desf. is an annual aromatic herb which has various uses on alternative medicine in many region of the world. In this study, antioxidant activities of ethanol and water extracts of the plant leaves were determined by in vitro DPPH method and phenolic composition of the plant sample was determined by LC-MS/MS analysis. The results showed that chlorogenic acid, quinic acid, hyperoside, protocatechuic acid and quercetin were the major phenolic compounds among the 27 standard compounds. The significant antioxidant capacity of the plant might be related with the high abundance of phenolic compounds.


Miniaturized USB-powered multi-channel module for gamma spectroscopy and imaging.
LAILA is a miniaturized eight-channel electronic readout system for compact γ-ray detectors, combining high-resolution spectroscopy capability with position sensitivity. Compactness is achieved by the combination of a novel CMOS front-end ASIC (Application-Specific Integrated Circuit) for analog processing of a large signal current from Silicon PhotoMultiplier (SiPM) solid-state photodetectors, with a microcontroller-based data acquisition system. The adoption of automatic gain regulation in the gated-integrator stage of the ASIC offers an 84 dB dynamic range, combining single-photon sensitivity with an extended input photon energy range (20 keV-4 MeV, using 30 μm-cell SiPMs). Using this module with properly merged 144 SiPM pixels coupled to a 3 in.-thick lanthanum bromide scintillation crystal, a 3% energy resolution at 662 keV and 1 cm spatial resolution in the estimation of the interaction coordinates are experimentally demonstrated in this work.


Antinucleosome autoantibodies bind directly to cell lines in vitro and via the FcgammaRIIB receptor to B lymphocytes in vivo: a role for immune complexes in interactions between antinucleosome IgG2a and B cells of BXSB lupus mice.
The initial novel observation of this study was that most B cells of male BXSB lupus mice bear surface IgG2a(b) of extrinsic origin. To define the surface antigen, we here examine three (NZBxBXSB)F1-derived IgG2a(b) monoclonal antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and an early target of autoimmunity in systemic lupus erythematosus. Their tentative dissociation constant (K(d)) for soluble nuc particles was approximately 7 x 10(-10) m. The mAbs bound more weakly to both H2A-H2B-DNA and H3-H4-DNA complexes, and in immunoblot they stained all four core histones. The mAbs detected a surface antigen on all cell lines examined, present on viable cells. When stripped of nuc, and in the presence of DNase I, their binding to cell lines improved. Heparin displaced the antigen from the cell surface. In vivo, the three mAbs stained B cells of several BALB/c mice clearly stronger than the isotype control; this differential staining was significantly reduced in FcgammaRIIB-deficient mice. The results indicate that the three mAbs recognize (a) planted antigen on viable cultured cells and (b) soluble autoantigen in vivo, leading to immune complexes that bind to FcgammaRIIB. Further experiments demonstrated that antinuc IgG2a could be eluted from splenocytes of a male BXSB lupus mouse. Hence, at least part of the extrinsic IgG2a(b) found on BXSB B cells may represent FcgammaRIIB-bound nuc-IgG2a(b) complexes.


Erythropoiesis-independent effects of iron in chronic kidney disease.
Chronic kidney disease (CKD) leads to alterations of iron metabolism, which contribute to the development of anemia and necessitates iron supplementation in patients with CKD. Elevated hepcidin accounts for a significant iron redistribution in CKD. Recent data indicate that these alterations in iron homeostasis coupled with therapeutic iron supplementation have pleiotropic effects on many organ systems in patients with CKD, far beyond the traditional hematologic effects of iron; these include effects of iron on inflammation, oxidative stress, kidney fibrosis, cardiovascular disease, CKD-mineral and bone disorder, and skeletal growth in children. The effects of iron supplementation appear to be largely dependent on the route of administration and on the specific iron preparation. Iron-based phosphate binders exemplify the opportunity for using iron for both traditional (anemia) and novel (hyperphosphatemia) indications. Further optimization of iron therapy in patients with CKD may inform new approaches to the treatment of CKD complications and potentially allow modification of disease progression.


Development of HPLC/fluorescence detection method for chiral resolution of dansylated benzimidazoles derivatives.
The development of high performance liquid chromatography method on amylose-based stationary phase (Chiralpak AD) with n-hexane-2-propanol (90:10, v/v) as mobile phase allowed the enantioseparation of non-dansylated and dansylated benzimidazole derivatives, prepared from potent-AMPK activators, to be achieved. Using both fluorescence and ultraviolet detection, limits of detection and quantification were determined. Fluorescence detection seems to be the most appropriate technique since the first enantiomer of dansylated benzimidazole 8 eluted with a limit of quantification of 2.25 nm. The quantification limit was improved 10-fold by fluorescence detection compared with a previous report describing mass spectrometry detection. Linearity and repeatability parameters were validated. These lower limits obtained by fluorescence detection, associated with good resolution observed for the dansylated derivatives, make this chiral methodology convenient for the use of these fluorescent potent-AMPK activators as probes to elucidate their cellular localization and their mechanism of action.


Bilateral Cubital Lymphoma and Mycobacteriosis in a Salmon-Crested Cockatoo (Cacatua moluccensis).
A 32-year-old male salmon-crested cockatoo (Cacatua moluccensis) was diagnosed by cytology with bilateral cubital lymphoma and mycobacteriosis. Polymerase chain reaction assay testing confirmed Mycobacterium genavense. This patient was subsequently humanely euthanized. Postmortem histopathology confirmed both diagnoses with findings of multicentric lymphoma, acid-fast bacilli, and severe degenerative changes in all synovial joints examined. Immunohistochemical staining for paired box protein 5 of the cubital mass was positive for a high percentage of B-cell lymphocytes, consistent with B-cell lymphoma. This unusual case of two major diseases presenting concurrently in one patient raises the question of whether the pathogenesis could have an interdependent relationship. Mycobacteriosis, severe degenerative joint changes, or both may have stimulated lymphocytes, eventually leading to lymphoma. Additional screening and monitoring for comorbidities may be advised if 1 of these diseases are diagnosed in companion avian species.


Moving outside the board room: A proof-of-concept study on the impact of walking while negotiating.
Negotiation is a consequential activity that can exacerbate power differentials, especially for women. While traditional contexts can prime stereotypical gender roles and promote conditions that lead to performance differences, these can be mitigated by context shifts. This proof-of-concept study explores whether an easy-to-apply context shift, moving from seated indoors to walking outside, can help improve the quality of negotiated interactions. Here we examine walking's effects on negotiation and relational outcomes as well as experienced emotions, moderated by gender. Same-gender pairs were randomly assigned to either sitting or walking as either candidate or recruiter negotiating a job offer. Eighty-one pairs of graduate students or community members participated: sitting pairs: 27 women, 14 men; walking pairs: 23 women, 17 men. Participants negotiated either while seated (across from each other) or walking (side by side along a path). We measured: negotiation performance (total points) and outcome equity (difference between negotiating party points); subjective outcomes of positive emotions, negative emotions, mutual liking, and mutual trust. With mixed effects models, we tested main effects of condition, gender, and interaction of condition x gender. Relative to sitting, walking was associated with: increased outcome equality for women, but decreased for men (B = 3799.1, SE = 1679.9, p = .027); decreased negative emotions, more for women than men (IRR = .83, 95% CI:[.69,1.00], p = .046); and greater mutual liking for both genders (W = 591.5, p-value = 0.027). No significant effects were found for negotiation point totals, positive emotions, or mutual trust. This study provides a foundation for investigating easy-to-implement changes that can mitigate stereotyped performance differences in negotiation.


Pricing the urban cooling benefits of solar panel deployment in Sydney, Australia.
Cities import energy, which in combination with their typically high solar absorption and low moisture availability generates the urban heat island effect (UHI). The UHI, combined with human-induced warming, makes our densely populated cities particularly vulnerable to climate change. We examine the utility of solar photovoltaic (PV) system deployment on urban rooftops to reduce the UHI, and we price one potential value of this impact. The installation of PV systems over Sydney, Australia reduces summer maximum temperatures by up to 1 °C because the need to import energy is offset by local generation. This offset has a direct environmental benefit, cooling local maximum temperatures, but also a direct economic value in the energy generated. The indirect benefit associated with the temperature changes is between net AUD$230,000 and $3,380,000 depending on the intensity of PV systems deployment. Therefore, even very large PV installations will not offset global warming, but could generate enough energy to negate the need to import energy, and thereby reduce air temperatures. The energy produced, and the benefits of cooling beyond local PV installation sites, would reduce the vulnerability of urban populations and infrastructure to temperature extremes.


Exercise and the Development of the Artificial Pancreas: One of the More Difficult Series of Hurdles.
Regular physical activity (PA) promotes numerous health benefits for people living with type 1 diabetes (T1D). However, PA also complicates blood glucose control. Factors affecting blood glucose fluctuations during PA include activity type, intensity and duration as well as the amount of insulin and food in the body at the time of the activity. To maintain equilibrium with blood glucose concentrations during PA, the rate of glucose appearance (Ra) to disappearance (Rd) in the bloodstream must be balanced. In nondiabetics, there is a rise in glucagon and a reduction in insulin release at the onset of mild to moderate aerobic PA. During intense aerobic -anaerobic work, insulin release first decreases and then rises rapidly in early recovery to offset a more dramatic increase in counterregulatory hormones and metabolites. An "exercise smart" artificial pancreas (AP) must be capable of sensing glucose and perhaps other physiological responses to various types and intensities of PA. The emergence of this new technology may benefit active persons with T1D who are prone to hypo and hyperglycemia.


Small fenestra stapedotomy for otosclerosis in a Canadian teaching centre.
This study reports the results of 112 primary stapedotomies and 13 revision stapedotomies performed by the senior author. Retrospective case review of all primary and revision stapedotomies performed at University Hospital between 1994 and 1999. All patients in this series had otosclerosis and underwent stapedotomy using a 0.6-mm diameter platinum wire/Teflon piston prosthesis. The air-bone gap was calculated as the difference between the preoperative boneconduction and the postoperative air-conduction thresholds. The average follow-up time post-stapedotomy to audiometric testing was approximately 2.5 months. An average air-bone gap closure at 500, 1000, and 2000 Hz to 10 dB or less was used as the criterion for success. The effects of stapedotomy on speech reception thresholds (SRTs), speech discrimination scores (SDSs), and airconduction thresholds are also reported. In primary stapedotomy, an air-bone gap closure of 10 dB or less was achieved in 85.7% of patients. A significant hearing gain was achieved at all frequencies (250-8000 Hz), with the greatest benefit being achieved at the lower frequencies. The SRT was significantly improved post-stapedotomy by an average of 26.7 dB, and no significant change was found in the SDS. In revision stapedotomy, 38.5% of patients had a significant hearing gain at 250 to 4000 Hz. The SRT was significantly improved postoperatively by an average of 12.7 dB, and no significant change was found in SDS. Overall complication rates were similar to other series with two cases of partial hearing loss (1.6%), one incus fracture (0.8%), one large tympanic membrane perforation (0.8%), and one perilymphatic fistula (0.8%), which was successfully repaired. No patients in this series experienced complete sensorineural hearing loss, facial nerve injury, worsened tinnitus, or reparative granuloma. The results of this study are comparable to other similar studies examining the use of stapedotomy in patients with otosclerosis. The high success rate and low incidence of serious complications support stapedotomy, without a laser but with resident involvement, as a highly effective treatment for otosclerosis.


Effects of angiotensin converting enzyme inhibitors MK 421, SA 446 and captopril on renal prostaglandin E and kinins in conscious normotensive rats.
Angiotensin converting enzyme inhibition by MK 421, SA 446 or captopril (6 mg/kg/day ip) for up to 6 days induced significant fall in systolic blood pressure and plasma angiotensin II concentration. The hypotensive effect was greater in sodium depleted rats than in sodium repleted rats. The hypotensive effect was also accompanied by increased excretion of urinary prostaglandin E2, however the levels of urinary prostaglandin E2 in sodium repleted rats were not different from those in sodium depleted rats. Urinary kinin excretion was increased during infusion of MK 421, SA 446 or captopril in sodium depleted rats, whereas no significant change was found in sodium repleted rats. Thus the present results suggest that renal prostaglandin E system may not be essential for the hypotensive effect of these inhibitors. In addition, the greater hypotensive effect of these inhibitors in sodium depleted rats may be in part due to stimulated renal kinin system.


Conserved and nonconserved proteins for meiotic DNA breakage and repair in yeasts.
During meiosis DNA double-strand breaks initiate recombination in the distantly related budding and fission yeasts and perhaps in most eukaryotes. Repair of broken meiotic DNA is essential for formation of viable gametes. We report here distinct but overlapping sets of proteins in these yeasts required for formation and repair of double-strand breaks. Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts. DNA breakage required the S. pombe midmeiosis transcription factor Mei4, but the structurally unrelated midmeiosis transcription factor Ndt80 is not required for breakage in S. cerevisiae. Rhp51, Swi5, and Rad22 + Rti1 were required for full levels of DNA repair in S. pombe, as are the related S. cerevisiae proteins Rad51, Sae3, and Rad52. Dmc1 was not required for repair in S. pombe, but its homolog Dmc1 is required in the well-studied strain SK1 of S. cerevisiae. Additional proteins required in one yeast have no obvious homologs in the other yeast. The occurrence of conserved and nonconserved proteins indicates potential diversity in the mechanism of meiotic recombination and divergence of the machinery during the evolution of eukaryotes.


[Iatrogenic "metalloma" (titanoma) caused by implant failure in "metal-backed" patellar joint surface replacement].
Patellofemoral problems frequently provide the cause for revisions after total knee replacements (TKR). Problems with metal-backed patellae, in particular, have been reported on in the past, with a failure rate of 33%. As a result of implant failure, there is an increase of polyethylene and metallic wear, which eventually leads to a synovialitis and metallosis. We report a case of a iatrogenic induced metallosis of the knee joint resulting from failure of a metal-backed patella component with the formation of a substantial pseudotumor within the popliteal fossa. Intraoperatively, a browny-grey, knotted and hard structure was to be seen, which histologically imposed as a hyalinated scar tissue with black particular deposits. Energy dispersive X-ray microanalysis showed a high level of titanium within the intra- and extracellular deposits. In differential diagnosis these findings were postulated as "metalloma" (titanoma). In cases of periprosthetic pseudotumors, particular those with implant failure, a iatrogenic-induced metalloma should be considered.


Accuracy of serum beta-human chorionic gonadotropin cutoff values at 42 and 49 days' gestation.
The accuracy of serum beta-human chorionic gonadotropin levels as cutoff values for estimating gestational age was studied. A database was created using information from previously performed research studies, which allowed entry of women both less than and greater than 49 days' gestation, involving medical abortion. Serum beta-human chorionic gonadotropin determinations and vaginal ultrasonography were performed in all studies before treatment. A total of 574 women had data available for analysis. A receiver operating characteristic curve was created to evaluate the predictive value of potential beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation. Appropriate serum beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation were 23,745 mIU/mL (sensitivity, 96%; specificity, 91%; positive predictive value, 68%; negative predictive value, 99%) and 71,160 mIU/mL (sensitivity, 95%; specificity, 62%; positive predictive value, 76%; negative predictive value, 91%), respectively. Under 42 days' gestation, the serum beta-human chorionic gonadotropin-time relationship appears to be linear, with a greater diversity of individual values after 42 days. Serum beta-human chorionic gonadotropin values can be used with reasonable accuracy to screen for a gestational age up to 49 days' gestation.


Biogenic amines in striatum of rats that had been treated with ethanol, and their brains later stored in different temperatures.
The purpose of this study was to investigate how ethanol pretreatment and storage temperatures of brain striatum affect levels of biogenic amines in this tissue. Adult Wistar male rats were injected with 25% ethanol (5.0 g/kg i.p.) while the control rats were administered i.p. with the same volume of saline. Two hours later the rats were decapitated, their brains removed, and the striatum separated. Each striatum was divided into three parts: one part was immediately frozen on dry ice and kept at -70 degrees C; a second fragment was kept in a household refrigerator (+4 degrees C); and the third fragment was kept at +22 degrees C. Twenty-four hours later, levels of DA, DOPAC, HVA, 3-MT, 5-HT, and 5-HIAA in the striatum were assayed by HPLC/ED. Immediately after decapitation; ethanol levels were assayed in the serum of ethanol-pretreated and saline-pretreated rats using gas chromatography. Our results indicate that levels of striatal DA, DOPAC, and HVA in saline-pretreated rats decreased significantly when the storage temperature of the striatum was raised from -70 degrees C, through +4 degrees C, to +22 degrees C, while levels of striatal 5-HT and 5-HIAA remained constant within the temperature range tested and levels of 3-MT fluctuated. In ethanol-pretreated rats, striatal levels of DOPAC, HVA, and 5-HIAA were increased in all three storage temperatures, while levels of DA, 5-HT, and 3-MT were decreased in those temperatures. Those decreases were most profound in striatal samples kept at +22 degrees C. We conclude that concern about possible interactions between drugs and biogenic amines should be exercised.


[Prevention of atherosclerosis by estrogen substitution?].
Epidemiological, experimental and clinical data verify that the risk of cardiovascular diseases is increased by a long-term estrogen deficiency. This is, among other things, caused by alterations of lipid metabolism (e.g., rise in total cholesterol and LDL-cholesterol, decrease in HDL-cholesterol) due to the estrogen dificit which are involved in an accelerated development of atherosclerosis. If there is an estrogen deficiency, an elevated serum level of cholesterol or LDL-cholesterol can be reduced and the HDL-cholesterol level can be increased by an adequate estrogen replacement therapy, i.e., treatment with an estrogen and progestogen the type and dose of which are adjusted to the clinical picture. When the present knowledge about the physiological and pathological pathways is weighed and the epidemiological data are critically valued - whereby the extent and duration of the stage of estrogen deficit has to be regarded as an important criterion -, it can be assumed that an estrogen therapy prevents a premature atherosclerosis and coronary heart disease provided that they are related to an estrogen deficiency. The differences in the degree of estrogen deficit and the symptoms as well as in the pharmacological and pharmacodynamic peculiarities if the individual women render it necessary to adjust individually the estrogen therapy, to avoid overdosing and to pay attention to risk factors. Therefore, an undifferentiated treatment with estrogens (e.g. estrogen for every woman) does not appear to be appropriate.


Textbook executive. The skills and knowledge that all healthcare execs need to master can now be found in one big directory.
What makes a good healthcare executive? According to the Health Leadership Alliance--a coalition of healthcare management, IT and nurse organizations--certain skills and knowledge are prerequisites for executive-wannabes. Pamela Thompson, left, CEO of the American Organization of Nurse Executives, says a full directory of those skills, recently compiled by the alliance, reflects the "current needs of healthcare.


What can we learn from randomized clinical trials about the construct validity of self-report measures of mindfulness? A meta-analysis.
Because they provide data on responsiveness to experimental manipulation, clinical trials involving mindfulness-based interventions are a source of evidence for the construct validity of self-report measures of mindfulness. Within-group and between-group changes in mindfulness were examined from randomized clinical trials comparing mindfulness interventions to other bona fide treatment comparison conditions or waitlist control conditions. We also examined changes in clinical outcomes and the magnitude of these changes relative to changes in mindfulness. We included 69 published studies representing 55 unique samples (n = 4,743). Self-report mindfulness measures showed relatively larger gains in mindfulness intervention conditions vis-à-vis waitlist comparison conditions at both post-treatment (effect size [ES] = 0.52, 95% CI [0.40, 0.64]) and follow-up (ES = 0.52 [0.20, 0.84]), although the effect at follow-up diminished to non-significance in a trim-and-fill analysis intended to account for publication bias (ES = 0.35 [-0.03, 0.72]). Measures of mindfulness also showed relatively larger gains in mindfulness intervention conditions vis-à-vis bona fide comparison conditions, but only at post-treatment (ES = 0.25 [0.11, 0.38], 0.10 [-0.08, 0.28], at post-treatment and follow-up, respectively). All three conditions (mindfulness, bona fide, waitlist) showed relatively larger improvements on measures of clinical outcomes than measures of mindfulness, with the exception of waitlist conditions for which this effect was no longer significant at follow-up. Taken together, findings provide partial support for the unique responsiveness of mindfulness self-report measures to interventions that include promotion of mindfulness meditation practice.


Photoelectron Spectroscopy of BiAu(-) and BiBO(-): Further Evidence of the Analogy between Au and Boronyl.
Boronyl (BO) is a monovalent σ radical with a B≡O triple bond. Its chemistry has remained relatively unknown, though analogy has been established for BO with monovalent atoms, such as H or Au. Here we report a photoelectron spectroscopic study of BiAu(-) and BiBO(-), showing further evidence of the analogy between Au and BO. The photoelectron spectra of BiAu(-) and BiBO(-) are found to be similar, suggesting that they possess similar electronic structure and chemical bonding. The electron affinities of BiAu and BiBO are measured to be 1.38(4) and 1.84(3) eV, respectively. The ground states of both BiAu and BiBO are shown to be a triplet (X (3)Σ(-)). In addition, vibrational structures are resolved in the spectra of BiBO(-). Two vibrational frequencies at 320(30) and 1860(50) cm(-1) are measured for the ground state of BiBO, corresponding to the Bi-B and B-O stretching modes, respectively. The low-lying electronic excited states of BiAu and BiBO are also found to be similar: their first four excited states are A (1)Δ, B (1)Σ(+), C (3)Π, and D (1)Π, with excitation energies at 0.71, 1.29, 2.54, and 2.67 eV for BiAu and 0.63, 1.26, 3.68, and 3.82 eV for BiBO, respectively, above the (3)Σ(-) ground state. Weak photoelectron features related to two-electron detachment transitions are also observed for both anions because of strong electron correlation effects in the ground state of the anions.


Hsa-miR-181a-5p, hsa-miR-182-5p, and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response.
Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. However, a low number of patients with long-term treatment-free remission (TFR) were observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months, with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for CML. Next Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at the molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real-time RT-qPCR in triplicate. Hsa-miR-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation. The down-regulation was consistent with decreased amounts of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with the substantial presence of BCR-ABL1 in CML patients treated with TKIs at the molecular response. Therefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.


Differences between sprint tests under laboratory and actual cycling conditions.
The aim of this study was to compare the maximal power output (POpeak) and force-velocity relationships in sprint cycling obtained from a laboratory protocol and from a field test during actual cycling locomotion. Seven male competitive cyclists performed 6 sprints (3 in the seated position and 3 in the standing position) on an ergo-trainer (Tacx, Netherlands) and 6 sprints during actual cycling locomotion in a gymnasium. The bicycle was equipped with the SRM Training System (Schoberer Rad Messtechnik, Germany) to measure (200 Hz) the power output (PO, W), the pedalling cadence (rpm), and the velocity (kmxh-1). From these measurements, the maximal force on the pedal (Fmax), the theoretical maximal force (Fo, N) and the theoretical maximal pedalling cadence (V0, rpm) were determined. During each sprint test the lateral bicycle oscillations were measured from a video analysis. During standing and seated sprints in the gymnasium, Fo and Fmax were significantly higher (p<0.05) compared with sprints on the ergo-trainer (+12% and +32%, respectively). The POpeak during sprints in seated and standing positions in the gymnasium was significantly (p<0.05) lower (-4%) and higher (+6%) respectively, compared with the ergo-trainer. For standing position in the gymnasium the kinematics analysis indicated a 24 degrees mean lateral bicycle oscillation compared with 0 degrees on the ergo trainer. The results of this study indicate that POpeak, Fo, and time to obtain POpeak were different between laboratory and actual cycling conditions. To obtain a valid estimation of the maximal power output, it is necessary to perform sprint tests during actual cycling locomotion. Thus, in the laboratory, it is advisable to use a cycle ergometer that enables natural lateral oscillations.


Recruitment and organization of ESCRT-0 and ubiquitinated cargo via condensation.
The general mechanisms by which ESCRTs (Endosomal Sorting Complexes Required for Transport) are specifically recruited to various membranes, and how ESCRT subunits are spatially organized remain central questions in cell biology. At the endosome and lysosomes, ubiquitination of membrane proteins triggers ESCRT-mediated substrate recognition and degradation. Using the yeast lysosome/vacuole, we define the principles by which substrate engagement by ESCRTs occurs at this organelle. We find that multivalent interactions between ESCRT-0 and polyubiquitin are critical for substrate recognition at yeast vacuoles, with a lower-valency requirement for cargo engagement at endosomes. Direct recruitment of ESCRT-0 induces dynamic foci on the vacuole membrane and forms fluid condensates in vitro with polyubiquitin. We propose that self-assembly of early ESCRTs induces condensation, an initial step in ESCRT assembly/nucleation at membranes. This property can be tuned specifically at various organelles by modulating the number of binding interactions.


Rapid Screening Using Pathomorphologic Interpretation to Detect BRAFV600E Mutation and Microsatellite Instability in Colorectal Cancer.
Rapid decision-making is essential in precision medicine for initiating molecular targeted therapy for patients with cancer. This study aimed to extract pathomorphologic features that enable the accurate prediction of genetic abnormalities in cancer from hematoxylin and eosin images using deep learning (DL). A total of 1,657 images (one representative image per patient) of thin formalin-fixed, paraffin-embedded tissue sections from either primary or metastatic tumors with next-generation sequencing-confirmed genetic abnormalities-including BRAFV600E and KRAS mutations, and microsatellite instability high (MSI-H)-that are directly relevant to therapeutic strategies for advanced colorectal cancer were obtained from the nationwide SCRUM-Japan GI-SCREEN project. The images were divided into three groups of 986, 248, and 423 images to create one training and two validation cohorts, respectively. Pathomorphologic feature-prediction DL models were first developed on the basis of pathomorphologic features. Subsequently, gene-prediction DL models were constructed for all possible combinations of pathomorphologic features that enabled the prediction of gene abnormalities based on images filtered by the combination of pathomorphologic feature-prediction models. High accuracies were achieved, with AUCs > 0.90 and 0.80 for 12 and 27, respectively, of 33 analyzed pathomorphologic features, with high AUCs being yielded for both BRAFV600E (0.851 and 0.859) and MSI-H (0.923 and 0.862). These findings show that novel next-generation pathology methods can predict genetic abnormalities without the need for standard-of-care gene tests, and this novel next-generation pathology method can be applied for colorectal cancer treatment planning in the near future.


BDNF and Cortisol in the Diagnosis of Cocaine-Induced Depression.
Major depressive disorder (MDD) and cocaine use disorder (CUD) are related with disability and high mortality rates. The assessment and treatment of psychiatric comorbidity is challenging due to its high prevalence and its clinical severity, mostly due to suicide rates and the presence of medical comorbidities. The aim of this study is to investigate differences in brain derived neurotrophic factor (BDNF) and cortisol plasmatic levels in patients diagnosed with CUD-primary-MDD and CUD-induced-MDD and also to compare them to a sample of MDD patients (without cocaine use), a sample of CUD (without MDD), and a group of healthy controls (HC) after a stress challenge. A total of 46 subjects were included: MDD (n = 6), CUD (n = 15), CUD-primary-MDD (n = 16), CUD-induced-MDD (n = 9), and 21 HC. Psychiatric comorbidity was assessed with the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders IV (PRISM-IV), and depression severity was measured with the Hamilton Depression Rating Scale (HDRS). Patients were administered the Trier Social Stress Test (TSST) before and after the biological measures, including BDNF, and cortisol levels were obtained. After the TSST, Cohen's d values between CUD-primary-MDD and CUD-induced-MDD increased in each assessment from 0.19 post-TSST to 2.04 post-90-TSST. Pairwise differences among CUD-induced-MDD and both MDD and HC groups had also a large effect size value in post-30-TSST and post-90-TSST. In the case of the BDNF concentrations, CUD-primary-MDD and CUD-induced-MDD in post-90-TSST (12,627.27 ± 5488.09 vs.17,144.84 ± 6581.06, respectively) had a large effect size (0.77). Results suggest a different pathogenesis for CUD-induced-MDD with higher levels of cortisol and BDNF compared with CUD-primary-MDD. Such variations should imply different approaches in treatment.


Tofacitinib in Steroid-Refractory Acute Severe Ulcerative Colitis: A Retrospective Analysis.
Steroid-refractory acute severe ulcerative colitis (ASUC) patients are at the highest risk of colectomy. Among the available options, cyclosporine and infliximab have similar efficacy but infliximab is a costly drug and cyclosporine has multiple side effects like kidney injury, neurotoxicity, and dyselectrolytemia. Surgical management is often associated with higher morbidity. Newer oral small molecules like Janus kinase inhibitors are the ideal molecules to bridge the gap. Tofacitinib has already been extensively evaluated in patients with moderate to severe UC; however, data on ASUC treated by tofacitinib are limited. We retrospectively analyzed the data of patients with ASUC who were admitted to our hospital's luminal gastroenterology unit between January 2021 and July 2023. Patients with ASUC who were managed with tofacitinib were included in the study. Eight patients with ASUC were identified who did not respond to intravenous hydrocortisone and were treated with tofacitinib. The mean age was 39 ± 15 years and 87.5% were female. The median duration of illness was 24 months (interquartile range (IQR): 12-120 months). Seven of eight patients (87.5%) responded to oral tofacitinib 10 mg twice a day by the fifth day of treatment. The median follow-up period was six months (IQR: 1-12 months). One patient required colectomy and one patient had varicella zoster reactivation requiring treatment discontinuation. Tofacitinib is an attractive alternative to the currently available salvage therapy for steroid-refractory ASUC; however, long-term efficacy and risk remain to be explored.


Increased IL-17-expressing γδ T cells in seborrhoeic dermatitis-like lesions of the Mpzl3 knockout mice.
Seborrhoeic Dermatitis (SD) is a common inflammatory skin disorder, but its molecular pathogenesis remains elusive. Previously, we have established the Mpzl3 knockout (-/-) mice as a model for SD. In this study, we focused on early phases of skin inflammation and determined the cytokine profiles and identified immune cell types in the lesional skin in the Mpzl3 -/- mice. Using flow cytometry, we detected a significant increase of CD45+ leucocytes, CD3+ T lymphocytes and especially γδ T cells but not αβ T cells in the lesional skin compared to control. We also detected high levels of IL-17 and determined that the γδ T cells were a major contributing source. CD3+ and γδ T cell localization in the skin was verified by indirect immunofluorescent staining. Since neither γδ T cells nor IL-17 had been implicated in SD, our study provides novel insights into the role of MPZL3 in the pathogenesis of SD-like skin inflammation.


Occupational exposure of personnel operating military radio equipment: measurements and simulation.
Technical literature provides numerous studies concerning radiofrequency exposure measurements for various radio communication devices, but there are few studies related to exposure of personnel operating military radio equipment. In order to evaluate exposure and identify cases when safety requirements are not entirely met, both measurements and simulations are needed for accurate results. Moreover, given the technical characteristics of the radio devices used in the military, personnel mainly operate in the near-field region so both measurements and simulation becomes more complex. Measurements were made in situ using a broadband personal exposimeter equipped with two isotropic probes for both electric and magnetic components of the field. The experiment was designed for three different operating frequencies of the same radio equipment, while simulations were made in FEKO software using hybrid numerical methods to solve complex electromagnetic field problems. The paper aims to discuss the comparative results of the measurements and simulation, as well as comparing them to reference levels specified in military or civilian radiofrequency exposure standards.


Current status of medical technology.
Medical Technology (MT) provides innovative instrumentation and methods designed for the purpose of improving prevention, diagnostics, therapy and rehabilitation. MT rooting in science, engineering and the biosciences is characterized by its inter- and transdisciplinarity. The current status of MT is described emphasizing the five aspects: (1) review of milestones, (2) the impact of MT on the health care system, (3) the economic significance of MT, (4) the financial resources dedicated to research and development in MT, and (5) the challenges for education and training in MT. The material used is a government issued survey on the situation of MT in Germany, data of health care authorities and congress reports from World Conference on Medical Physics and Biomedical Engineering 2005. The following fields of MT have emerged in recent years and will dominate future development: BioMEMOS, imaging technology, minimally invasive surgery, computer assisted diagnosis, therapy and treatment monitoring, e-health/telemedicine/ networking, and medical engineering for regenerative medicine. Development of MT is driven by the following facts, (1) early and individualized diagnosis enables better treatment, (2) MT enhances cost effectiveness in health care, (3) MT is an economic factor based on fast innovation cycles, a roughly 50% export share and a 6% growth rate in turnover during the last 10 years. A downward tendency of the domestic MT market is a challenge for appropriate measures in improving both the economic and the academic infrastructure, in particular by targeted actions to support research and education. The impact of MT on prevention, diagnostics, therapy and rehabilitation is significant and still increasing. Due to a wide spreading in all medical areas, the high innovation rate, and the potential to improve health care, MT is considered one of the key technologies even in the future.


Retrospective cross-sectional study of 34 cases of pernicious anemia at Mohammed V Military Training Hospital, Morocco.
pernicious anemia is an autoimmune disease characterized by atrophic gastritis due to malabsorption of vitamin B12. Certain oral manifestations, such as Hunter´s glossitis and burning mouth syndrome, may precede the onset of this anemia. The aim of this study is to describe the clinical presentation, para-clinical aspects, the treatment, and the evolution of the pernicious anemia (PA) after treatment. retrospective study conducted at the Department of Haematology and Internal Medicine B of the Mohammed V Military Training Hospital in Rabat between January 2009 and December 2018. Thirty-four patients were enrolled with vitamin B12 deficiency, non-regenerative macrocytic anemia, a positive anti-intrinsic factor antibody and anti-parietal cell antibody and a histological diagnosis of atrophic gastritis in the presence or not of Helicobacter pylori. The qualitative variables were expressed in numbers and percentages, and the quantitative variables in mean and standard deviation. Multivariate analysis used the Fischer test; it was considered significant for a p < 0.05 value. thirty-four cases were studied; the population study consists of 56% (n=19) of men and 44% (n=15) of women. The average age was 54.88± 9.14. The clinical manifestations of pernicious anemia are dominated by megaloblastic anemia 85.3% (n=29), followed by digestive 58.8%(n=20) and oral 55.9% (n=19) signs. Neurological manifestations were rarely found in 41% (n=14). Hunter´s glossitis 37% (n=7), stomatodynia 11% (n=2) were the most common oral manifestations accompanying pernicious anemia. The evolution was favorable in 79.4% (n=27) patients under substitution therapy with vitamin B12. dentists´ involvement in the diagnosis of pernicious anemia is based on changes in oral mucous membranes, which have been reported in 55.9% of all patients. These oral changes may occur in the absence of symptomatic anemia.


Occupational Stress and Professional Quality of Life Among Community Health Nurses During the COVID-19 Pandemic.
Purpose: This study aimed to identify the correlation between occupational stress and professional quality of life (Pro-QOL) among community nurses during the pandemic COVID-19. Design: This study was conducted with a correlational design of 120 community health nurses. The research sample was obtained using a nonprobability purposive sampling technique following the research inclusion criteria. Expanded Nursing Stress Scale and Pro-QOL were used in this study. The research hypothesis: there is a correlation between occupational stress and the Pro-QOL of community health nurses. Methods: Pearson's correlation coefficient was used to analyze the correlation between occupational stress and Pro-QOL. Findings: The results of correlation analysis showed that there was a statistically significant positive correlation between occupational stress and Pro-QOL. Despite being in a difficult situation due to the pandemic and vulnerable to occupational stress, nurses significantly had high compassion satisfaction. Conclusions: Occupational stress affects nurses' Pro-QOL, it can be considered for public healthcare organizations to promote healthcare workers' well-being. Mobilizing the existing workforce, changing work patterns, support from colleagues and supervisors, clear communication of directives, and precautionary measures can reduce psychiatric symptoms.


[Qianlie Jiedu capsule combined with rufloxacin for chronic prostatitis: a randomized double-blind controlled clinical trial].
Few double-blind controlled trials have been reported on Chinese patent medicines for the treatment of chronic prostatitis. The purpose of this study was to investigate the therapeutic efficacy of Qianlie Jiedu Capsule for chronic prostatitis (CP) by the randomized double-blind controlled method. Eighty CP patients were equally randomized into an experimental and a control group, the former treated with Qianlie Jiedu Capsule + Rufloxacin, and the latter given placebo + Rufloxacin, both for 4 weeks. All the patients were evaluated by NIH-CPSI and EPS examination before and after the medication. After 4-week treatment, the total score of NIH-CPSI and the scores of pain, voiding symptoms and quality of life were significantly decreased in both groups compared with the baseline (P < 0.05), so did the leukocyte count in EPS (P < 0.05). And the experimental group showed significant drops in the above scores as compared with the control (P < 0.05), except in the leukocyte count in EPS (P > 0.05). Qianlie Jiedu Capsule combined with Rufloxacin is highly effective for CP by relieving pain and voiding symptoms,decreasing the leukocyte count in EPS and improving the life quality of the patients.


Highly persistent and effective prime/boost regimens against tuberculosis that use a multivalent modified vaccine virus Ankara-based tuberculosis vaccine with interleukin-15 as a molecular adjuvant.
Novel immunization strategies are needed to enhance the global control of tuberculosis (TB). In this study, we assessed the immunizing activity of a recombinant modified vaccinia Ankara (MVA) construct (MVA/IL-15/5Mtb) which overexpresses five Mycobacterium tuberculosis antigens (antigen 85A, antigen 85B, ESAT6, HSP60, and Mtb39), as well as the molecular adjuvant interleukin-15 (IL-15). Homologous prime/boost studies showed that the MVA/IL-15/5Mtb vaccine induced moderate but highly persistent protective immune responses for at least 16 months after the initial vaccination and that the interval between the prime and boost did not significantly alter vaccine-induced antituberculosis protective immunity. At 16 months, when the Mycobacterium bovis BCG and MVA/IL-15/5Mtb vaccine-induced protection was essentially equivalent, the protective responses after a tuberculous challenge were associated with elevated levels of gamma interferon (IFN-gamma), IL-17F, Cxcl9, and Cxcl10. To amplify the immunizing potential of the MVA/IL-15/5Mtb vaccine, a heterologous prime/boost regimen was tested using an ESAT6-antigen 85B (E6-85) fusion protein formulated in dimethyldiotacylammonium bromide/monophosphoryl lipid A (DDA/MPL) adjuvant as the priming vaccine and the MVA/IL-15/5Mtb recombinant virus as the boosting agent. When MVA/IL-15/5Mtb vaccine boosting was done at 2 or 6 months following the final fusion protein injections, the prime/boost regimen evoked protective responses against an aerogenic M. tuberculosis challenge which was equivalent to that induced by BCG immunization. Long-term memory after immunization with the E6-85-MVA/IL-15/5Mtb combination regimen was associated with the induction of monofunctional CD4 and CD8 IFN-gamma-producing T cells and multifunctional CD4 and CD8 T cells expressing IFN-gamma/tumor necrosis factor alpha (TNF-alpha), TNF-alpha/IL-2, and IFN-gamma/TNF-alpha/IL-2. In contrast, BCG-induced protection was characterized by fewer CD4 and CD8 monofunctional T cells expressing IFN-gamma and only IFN-gamma/TNF-alpha and IFN-gamma/TNF-alpha/IL-2 expressing multifunctional T (MFT) cells. Taken together, these results suggest that a heterologous prime/boost protocol using an MVA-based tuberculosis vaccines to boost after priming with TB protein/adjuvant preparations should be considered when designing long-lived TB immunization strategies.


Effects of electric and magnetic fields on nocturnal melatonin concentrations in dairy cows.
Sixteen multiparous, pregnant, lactating Holstein cows (weighing 600 +/- 50 kg, at 184.8 +/- 52 d of lactation, and at 101.9 +/- 43 d of gestation) were confined to wooden metabolism cages and exposed to a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 microT. The trial was conducted using a switchback statistical design. Cows were divided into two sequence groups of 8 cows each. One sequence group was exposed for three periods of 28 d each. The electric and magnetic fields were off during the first period, on during the second period, and off during the final period. The second sequence group was exposed for three periods also, but the activity of the fields was reversed (on during the first period, off during the second period, and on during the third period). On d 25 of each exposure period, blood samples were obtained every 0.5 h for 14 h starting at 1700 h to determine melatonin concentration. Nocturnal melatonin concentrations did not show any variation that could be attributed to exposure to electric and magnetic fields.


Curvature-mediated programming of liquid crystal microflows.
Despite the recognized role of liquid crystal microfluidics in generating programmable, self-organized and guided flow properties, to date, the flow behavior of LCs within curved channels remains unexplored. Using experiments and numerical simulations, we demonstrate that the curvature of microscale conduits allow programming of liquid crystal (LC) flows. Focusing on a nematic LC flowing through U- and L-shaped channels - two simple yet fundamental curved flow paths - with rectangular cross-section, our results reveal that the curvature of flow path can trigger transverse flow-induced director gradients. The emergent director field feeds back into the flow field, ultimately leading to LC flows controlled by the channel curvature. This curvature-mediated flow control, identified by polarizing optical microscopy and supported by the nematofluidic solutions, offers concepts in LC microfluidic valves, wherein the throughput distribution is determined by the Ericksen number and variations in local curvature. Finally, this work leverages curvature to amplify (suppress) LC transport through flow-aligned (homeotropic) regions emerging within channels with bends, in a programmable manner. Our results demonstrating the dependence of the dynamic flow-director coupling on the local curvature will have far-reaching ramifications in advancing the understanding of LC-based passive and active biological systems under real life geometrical constraints.


Amino acid metabolism and protein synthesis in a pyrithiamine-requiring Staphylococcus aureus mutant.
1. Amino acid metabolism and protein synthesis in a Staphylococcus aureus mutant strain that requires pyrithiamine for optimum growth were studied and compared with those in the thiamine-requiring parent S. aureus. 2. The mutant strain utilized amino acids at a higher rate than did the parent strain. The utilization of glutamic acid, serine and glycine was much stimulated in the mutant strain. 3. The rate of oxidation of glutamic acid, aspartic acid, isoleucine and glycine was higher in the mutant strain. 4. The mutant strain contained serine, glycine, tyrosine, glutamic acid, aspartic acid, arginine and histidine as free amino acids, whereas the parent strain possessed lysine, arginine, histidine, aspartic acid and glutamic acid. 5. The mutant strain possessed slightly higher glutamate-oxalo-acetate transaminase activity, whereas the activities of glutamate-pyruvate transaminase were similar in both strains. 6. The incorporation of (14)C from [2-(14)C]-acetate into individual amino acids of the cell protein was greater in the mutant strain. 7. The incorporation of (14)C-labelled amino acids into the cell proteins of the mutant strain was not much different from that in the parent strain. 8. Induction of beta-d-galactosidase in the mutant strain did not occur, whereas induction of this enzyme is possible in the parent strain. Thiamine or pyrithiamine has no direct effect on the induction of beta-d-galactosidase.


Evaluation of a Ferromagnetic Marker Technology for Intraoperative Localization of Nonpalpable Breast Lesions.
The purpose of this study was to evaluate the magnetic occult lesion localization instrument (MOLLI) system that involves implantation of a small, ferromagnetic marker to guide surgical excision of nonpalpable breast lesions. Characterization of the system was undertaken as part of what is, to our knowledge, the first study to assess the MOLLI system. The MOLLI system consists of a handheld probe that can detect the position and distance of an implanted magnetic marker. The system presents the surgeon with an accurate assessment of lesion location and depth measurement for precise 3D localization. The marker is implanted under ultrasound or mammographic guidance at any time before the surgical procedure and requires no special precautions. Experimental analysis focused on characterization of the following aspects of the MOLLI system: visualization of the marker under imaging, 3D detection of the magnetic marker, spatial resolution of the probe to detect markers placed in close proximity, and the effect of signal interference on system performance. The MOLLI system can reliably detect mean (± SD) marker depths up to 53 ± 8.56 mm from the probe. Bracketing large lesions or localizing multiple lesions can be accomplished by placing markers as close as 10 mm apart, at depths of up to 42 mm. The biologically inert MOLLI marker is readily visible under ultrasound and mammographic guidance, and it is differentiable from radiologic clips. The effect of surgical instruments on MOLLI functioning is minimal and does not impact system accuracy or reliability. The MOLLI system offers an accurate and efficient alternative lesion localization method for nonpalpable breast lesions.


Effects of Funnelliformis mosseae inoculation on alleviating atrazine damage in Canna indica L. var. flava Roxb.
Atrazine residue in the environment continually damages plants and therefore requires immediate attention and effective development of methods for its decontamination. The effects of Funnelliformis mosseae inoculation on growth and physiology in atrazine-treated Canna indica L. var. flava Roxb. were investigated. At atrazine concentrations up to 15 mg L-1, the growth of C. indica plants were negatively affected. Inoculation with F. mosseae alleviated the atrazine inhibition of plant growth and biomass. Furthermore, the chlorophyll content and root function increased under F. mosseae inoculation, and the oxidative stress of malondialdehyde, peroxidase, and superoxide dismutase activities induced by atrazine were also alleviated by F. mosseae inoculation. The removal rate of atrazine by untreated C. indica was significant, with removal rates of 20.5-55.3% by the end of a 14-day experiment; however, F. mosseae inoculation increased the removal rate to 35.6-75.1%. In conclusion, F. mosseae inoculation can alleviate the damage induced by atrazine in C. indica. Accordingly, C. indica inoculated with F. mosseae has excellent potential to be used in phytoremediation in habitats polluted by high atrazine concentrations.


Safety of Benazepril in 400 Azotemic and 110 Non-Azotemic Client-Owned Cats (2001-2012).
This retrospective study examined cats after initiation of benazepril therapy to determine the frequency of systemic hypotension or elevations in serum creatinine and/or potassium. Medical records review identified azotemic and non-azotemic cats prescribed benazepril. Blood pressure was recorded at the first available time after initiation of therapy. No cats experienced documented systolic systemic hypotension (<90 mmHg). Serum creatinine, and potassium when available, were recorded at baseline and in time windows after initiation of treatment: 1-30 days and 31-60 days. Blood chemistry results were screened for hyperkalemia (≥6.0 mEq/L). During the first 2 mo after starting benazepril therapy, there was a low incidence (3.7%) and clinically insignificant magnitude of hyperkalemia. Serum creatinine increases of greater than 30% from baseline were noted. This change was found in 11.0% of cats during the first 30 days of therapy and in 13.7% of cats from days 31-60 after initiation of therapy. The long-term survival of the cats that had >30% increases in creatinine from baseline was not statistically different from the survival of those that did not experience these increases, which suggests this finding may not be a reason to discontinue therapy. Benazepril appeared safe in a heterogeneous population of cats.


Perioperative pain relief.
Perioperative pain relief has taken on a new dimension in recent years; that of helping to prevent chronic pain after surgery. Knowledge of pain mechanisms, the importance of both peripheral and central sensitisation and descending inhibitory and facilitatory pathways from the midbrain to spinal cord, have advanced our understanding of how pain may persist after surgery. There is advancing knowledge about the up-regulation and down-regulation of opioid receptors, opioid tolerance and hyperalgesia, and its similarities to neuropathic pain.


[Cystic hygroma: 2 case reports and review of the literature].
Cystic hygroma, an infrequent malformation of the lymphatic system (5 cases per 1000 abortions with CRL greater than 3 cm), was observed in 2 cases which prompted the present study. The Authors also present a brief review of the literature on this topic. After reviewing the hypothetic pathogenesis of the lymphatic obstruction which underlines this pathology, the paper focuses on the association of hygroma and anatomical and chromosomic alterations. The various anatomopathological and echographical findings are then described. Special attention is drawn to the diagnosis of cystic hygroma, after which the two case studies are illustrated. The prognosis of this pathology is pessimistic and the patient and specialist have to choose between immediate abortion or waiting for the inevitable outcome of gestation.


Impact of factor rotation on Q-methodology analysis.
The Varimax and manual rotations are commonly used for factor rotation in Q-methodology; however, their effects on the results may not be well known. In this article we investigate the impact of different factor rotation techniques in Q-methodology, specifically how the factors and their distinguishing statements might be affected. We applied three factor rotation techniques including Varimax, Equamax, and Quartimax rotations on two exemplary datasets and compared the results based on the number of Q-sorts loaded on each factor, number of distinguishing statements for each factor, and changes in the number of distinguishing statements. We also estimated the Pearson correlation between the extracted factors based on rotation techniques. This analysis shows that factors can change substantially from one rotation to another. For instance, there was only 3 common distinguishing statements between Factor 1 of no-rotation of Dataset 1 and its matched factor from Varimax rotation. Even for 3 common statements, the factor scores were quite different from no-rotation to Varimax rotation. This analysis shows that the effects of factor rotation on emerging factors are complex. The changes are usually substantial such that the rotated factors might be quite different from the original factors.


Unraveling the hypoxia modulating potential of VEGF family genes in pan-cancer.
Tumor hypoxia, oxygen deprivation state, occurs in most cancers and promotes angiogenesis, enhancing the potential for metastasis. The vascular endothelial growth factor (VEGF) family genes play crucial roles in tumorigenesis by promoting angiogenesis. To investigate the malignant processes triggered by hypoxia-induced angiogenesis across pan-cancers, we comprehensively analyzed the relationships between the expression of VEGF family genes and hypoxic microenvironment based on integrated bioinformatics methods. Our results suggest that the expression of VEGF family genes differs significantly among various cancers, highlighting their heterogeneity effect on human cancers. Across the 33 cancers, VEGFB and VEGFD showed the highest and lowest expression levels, respectively. The survival analysis showed that VEGFA and placental growth factor (PGF) were correlated with poor prognosis in many cancers, including kidney renal cell and liver hepatocellular carcinoma. VEGFC expression was positively correlated with glioma and stomach cancer. VEGFA and PGF showed distinct positive correlations with hypoxia scores in most cancers, indicating a potential correlation with tumor aggressiveness. The expression of miRNAs targeting VEGF family genes, including hsa-miR-130b-5p and hsa-miR-940, was positively correlated with hypoxia. In immune subtypes analysis, VEGFC was highly expressed in C3 (inflammatory) and C6 (transforming growth factor β dominant) across various cancers, indicating its potential role as a tumor promotor. VEGFC expression exhibited positive correlations with immune infiltration scores, suggesting low tumor purity. High expression of VEGFA and VEGFC showed favorable responses to various drugs, including BLU-667, which abrogates RET signaling, an oncogenic driver in liver and thyroid cancers. Our findings suggest potential roles of VEGF family genes in malignant processes related with hypoxia-induced angiogenesis.


An FGM decomposition-based fuzzy MCDM method for selecting smart technology applications to support mobile health care during and after the COVID-19 pandemic.
In a fuzzy multicriteria decision-making (MCDM) problem, a decision maker may have differing viewpoints on the relative priorities of criteria. However, traditional methods merge these viewpoints into a single one, which leads to an unrepresentative decision-making result. Several recent methods identify the multiple viewpoints of a decision maker by decomposing the decision maker's fuzzy judgment matrix into several symmetric fuzzy subjudgment matrices, which is an inflexible strategy. To enhance flexibility, this study proposed a fuzzy geometric mean (FGM) decomposition-based fuzzy MCDM method in which FGM is applied to decompose a fuzzy judgment matrix into several fuzzy subjudgment matrices that can be asymmetric. These fuzzy subjudgment matrices are diverse and more consistent than the original fuzzy judgment matrix. The proposed methodology was applied to select the best choice from a group of smart technology applications for supporting mobile health care during and after the COVID-19 pandemic. According to the experimental results, the proposed methodology provided a novel approach to decomposing fuzzy judgment matrices and produced more diverse fuzzy subjudgment matrices.


Hox gene expression, AV-1 antigen expression, and cartilage pattern formation in chick recombinant limb buds.
A recombinant limb bud composed of dissociated and reaggregated mesenchyme and an ectodermal jacket develops a limblike structure with bifurcated and segmented cartilage. We compared the cartilage structure formed from recombinants that were composed of mesenchymal cells derived from the limb bud progress zone at various stages. In the case of recombinants containing distal mesenchyme of early-stage limb buds (stage 18 or 20), long and thick cartilage structures were formed in the proximal region, and segmented digitlike structures were formed in the distal region. On the contrary, in the case of recombinants containing distal mesenchyme of late-stage limb buds (stage 25 or 27), only poorly developed cartilage structures were formed. Next, we analyzed expression patterns of the position-specific genes HoxA11, A13 and D12 and the position-specific antigen AV-1 protein in recombinants containing distal mesenchyme of stage 20 limb buds (stage 20 recombinants) or stage 25 limb buds (stage 25 recombinants). In stage 20 recombinants, HoxA11 was expressed throughout the mesenchyme, but HoxA13 was expressed only in the distal half of the mesenchyme. In stage 25 recombinants, HoxA13 was expressed throughout the mesenchyme, but HoxA11 was only faintly expressed. The expression pattern of HoxD12 was similar to that of HoxA13 in both stage 20 and stage 25 recombinants, and no asymmetric expression pattern, which is observed in normal limb buds, was detected. AV-1 antigen was expressed in the core region of stage 20 recombinants, and anteroposterior asymmetry, which is observed in the anterior-ventral-distal region of normal limb buds, was not found. No AV-1 expression was observed in stage 25 recombinants. These results suggest that the mesenchyme in recombinants shows spatially controlled gene/protein expressions along the proximodistal axis, and that these differences in gene/protein expressions may affect cartilage pattern formation in recombinants.


Intraoperative monitoring with stimulus-evoked electromyography during placement of iliosacral screws. An initial clinical study.
A consecutive series of twenty-seven patients who had thirty acute unstable (type-C) fractures of the pelvic ring was studied prospectively to evaluate the use of stimulus-evoked electromyography to decrease the risk of iatrogenic nerve-root injury during the insertion of iliosacral screws. A prerequisite for inclusion in the study was a normal neurological status preoperatively; somatosensory evoked potentials were monitored to further document the neurological status both before and after insertion of the screw or screws. A total of fifty-one iliosacral screws were inserted, and a current threshold of more than eight milliamperes was selected as the level that indicated that the drill-bit was a safe distance from the nerve root. Four of the fifty-one screws were redirected because of information obtained with stimulus-evoked electromyography. Postoperatively, all patients had a normal neurological status. Computerized tomography, although not accurate for detailed measurements, demonstrated that all of the screws were in a safe, intraosseous position. Monitoring with stimulus-evoked electromyography appears to provide reliable data and may decrease the risk of iatrogenic injury to the nerve roots during operations on the pelvic ring.


Synthesis, molecular docking, ADMET, and evaluation of the anxiolytic effect in adult zebrafish of synthetic chalcone (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one: An in vivo and in silico approach.
Anxiety disorders represent the complex interaction between biological, psychological, temperamental, and environmental factors; drugs available to treat anxiety such as benzodiazepines (BZDs) are associated with several unwanted side effects. Although there are useful treatments, there is still a need for more effective anxiolytics with better safety profiles than BZDs. Chalcones or 1,3-diphenyl-2-proper-1-ones can be an alternative since this class of compounds has shown therapeutic potential mainly due to interactions with GABAA receptors and serotonergic system. This study evaluated the anxiolytic potential of chalcone (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (C2OHPDA) in adult zebrafish (Danio rerio) (ZFa). Each animal (n = 6/group) was treated intraperitoneally (i.p.; 20 μL) with the chalcone (4, 20, and 40 mg/kg) and with the vehicle (DMSO 3%; 20 μL), being submitted to the tests of locomotor activity and 96-h acute toxicity. The light/dark test was also performed, and the serotonergic mechanism (5-HT) was evaluated through the antagonists of the 5-HTR1 , 5-HTR2A/2C , and 5-HTR3A/3B receptors. It was investigated the prediction of the chalcone's position and preferential orientation concerning its receptor, as well as the pharmacokinetic parameters (ADMET) involved in the process after administration. As a result, C2OHPDA was not toxic and reduced the locomotor activity of ZFa. Furthermore, chalcone demonstrated an anxiolytic effect on the central nervous system (CNS), mediated by the serotonergic system, with action on 5-HT2A and 5-HTR3A/3B receptors. The interaction of C2OHPDA with 5-HT2A R and 5-HT3A receptors was confirmed by molecular docking study, the affinity energy observed was -8.7 and -9.1 kcal/mol, respectively. Thus, this study adds new evidence and highlights that chalcone can potentially be used to develop compounds with anxiolytic properties.


A comprehensive analysis of flowering transition in Agapanthus praecox ssp. orientalis (Leighton) Leighton by using transcriptomic and proteomic techniques.
Comprehensive transcriptomic and proteomic analyses were performed to gain further understanding of the molecular mechanisms of floral initiation in Agapanthus praecox ssp. orientalis. Samples of stem apexes were collected at three different time points including the vegetative, induced, and reproductive period. A total of 374 transcript-derived fragments and 72 proteins showed significant differential expression between the samples. The largest proportion of the identified genes and proteins are involved in metabolism, followed by signal transduction, protein fate, cellular transport, and biogenesis of cellular components. A large number of these genes and proteins were upregulated during the induced and reproductive stages. Their expression profiles demonstrate that carbohydrate metabolism provides nutrients foundation for floral initiation in Agapanthus. Furthermore, a transcription factors GAI (GA insensitive protein) that negatively regulates gibberellin signaling, auxin receptor protein TIR1 (Transport inhibitor response 1), a key enzyme of ethylene biosynthesis SAMS (S-adenosylmethionine synthase), and ethylene receptor protein ETR were isolated and identified. Expression patterns of these proteins, in combination with the results of quantitative phytohormone and immunolocalization analyses, indicated that GA, indole-acetic acid (IAA), and ethylene regulate floral morphogenesis and flowering. In conclusion, these data provide novel insight into the early regulatory steps of flowering in Agapanthus.


A new sample preparation and separation combination for the precise, accurate, and simultaneous determination of uracil and dihydrouracil in human plasma by reversed-phase HPLC.
We have developed an efficient procedure and detection method using reversed-phase high-performance liquid chromatography for the simultaneous measurement of uracil and dihydrouracil in human plasma. The procedure, including chromatographic conditions and sample preparation, was optimized and validated. Optimization of the sample preparation included deproteinization, extraction, and cleanup. A new sample preparation method which resulted in an improved extraction yield of analytes and significantly reduced interference at low-wavelength UV detection was developed. The developed method was validated for specificity, linearity, limits of detection and quantitation, precision, and accuracy. All calibration curves showed excellent linear regression (R2 > 0.9990) within the testing range. The limit of detection for uracil and dihydrouracil was 2.5 and 5.0 ng/mL, respectively. The extraction yields were >94% for uracil and 91% for dihydrouracil. Intra- and interassay precision and accuracy for uracil and dihydrouracil were lower than 8% at all tested concentrations. The proposed method was successfully applied to measure plasma concentrations of uracil and dihydrouracil in colorectal cancer patients scheduled to receive fluoropyrimidine-based chemotherapy.


Retrospective evaluation of the effect of intravenous fluid administration on development of postoperative reflux in horses with colic (2004-2012): 194 horses.
To evaluate the role of intravenous fluid volume and electrolyte supplementation on the development of postoperative reflux (POR) in horses undergoing celiotomy for colic. Case-control study spanning 2004-2012 for horses undergoing celiotomy for colic. University teaching hospital. Sixty-seven client-owned horses >1 year of age with POR were each matched to 2 controls with similar surgical lesions that did not demonstrate POR. Survival was significantly lower in cases (65.7%) than controls (96.1%). Factors found to be associated with POR included decreased net fluid volume administered on day 1 postoperatively, increased age, and performing a resection and anastomosis. Mean time until onset of POR was 20.4 hours postoperatively. PCV was significantly higher immediately following surgery and at 24 hours postoperatively in horses that developed POR compared with matched controls. There was no association between electrolyte values at presentation or administration of potassium, calcium, or magnesium in the postoperative period and the subsequent development of reflux. In the perioperative period, IV fluid volume overload and electrolyte abnormalities were not contributing factors in the development of POR in this population of surgical colic patients. Close postoperative monitoring with consideration and correction of pre- and postoperative fluid deficits is recommended.


Hypertension in dialysis patients.
Hypertension is a major risk for cardiovascular complications in dialysis patients. The pathogenesis of hypertension is multifactorial and is not completely understood. Hypervolemia has always been considered a major pathogenetic factor. In addition, a disturbed hormone profile with an activated renin angiotensin system, increased catecholamine, vasopressin and endothelin, and perhaps decreased nitrous oxide activity seem to play a role in the high incidence of hypertension in dialysis patients. The influence of autonomic dysfunction on blood pressure control in hemodialysis patients is not clear. The frequent use of erythropoietin during the last decade may have contributed to the increased incidence of hypertension in the dialysis population. Data from the First Report on Dialysis and Transplant in Sicily showed that hypertension is the cause of end-stage renal disease in 8% of dialysis patients and that the incidence of hypertension, as a cause of end-stage renal disease, increased with age.


Percutaneous computed tomography-guided transdiscal low cervical cordotomy for cancer pain as a method to avoid sleep apnea.
Study of percutaneous computed tomography (CT)-guided transdiscal low cervical cordotomy undertaken to treat pain in cancer patients. At the Department of Neurosurgery, Ain Shams University, Cairo, Egypt, 8 cancer pain patients, with either impaired pulmonary function or a previous cordotomy on an opposite side (sleep apnea was a feared complication) that prevented the possibility of undergoing a C(1-2) cordotomy, underwent a percutaneous CT-guided transdiscal low cervical cordotomy (C(4-5) or C(5-6)) to treat cancer pain. Seven patients experienced initial improvement. One patient re-experienced pain within 2 weeks and 1 patient experienced no pain relief. In 6 patients in whom the cordotomy procedure was completed, satisfactory or complete pain relief, throughout a 6-month follow-up period was reported. In contrast, in 2 patients in whom the cordotomy was not completed there was no persistent pain relief. Percutaneous CT-guided cordotomy remains a successful procedure to control pain in cancer patients, and is an affordable viable option under circumstances where economic disadvantage is an overriding determinate.