Charge transfer complexes between pteridine substrates and the active center molybdenum of xanthine oxidase.
Anaerobic addition of lumazine (2,4-dihydroxypteridine) to xanthine oxidase leads to a rapid bleaching of the enzyme with concomitant formation of a long wave-length species with maximum absorbance at 650 nm. At the conclusion of the reaction there is a net increase in absorbance at wavelengths greater than 550 nm. A spectrally similar species is obtained when violapterin is added to dithionite-reduced enzyme. This long wavelength absorbance is not accompanied by an EPR signal characteristic of flavin neutral radical and it is produced equally well in flavin-free xanthine oxidase. Its production is eliminated by the inhibitors, cyanide and allopurinol, which react at the molybdenum center. We conclude that this new species is a charge transfer complex between Mo(IV) and the product of the reaction, violapterin (2,4,7-trihydroxypteridine). A similar, though less intense, absorbance at 650 nm is also obtained when lumazine is bound to the reduced enzyme. These Mo(IV)-pteridine charge transfer compounds are optically active and exhibit intense circular dichroism centered at 630 nm.


P53 regulates CCAAT/Enhancer binding protein β gene expression.
The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is implicated in diverse processes and diseases. Its two isoforms, namely liver-enriched activator protein (LAP) and liver-enriched inhibitor protein (LIP) are translated from the same mRNA. They share the same C-terminal DNA binding domain except LAP has an extra N-terminal activation domain. Probably due to its higher affinity for its DNA cognate sequences, LIP can inhibit LAP transcriptional activity even at substoichiometric levels. However, the regulatory mechanism of C/EBPβ gene expression and the LAP: LIP ratio is unclear. In this study, the C/EBPβ promoter sequence was scanned for conserved P53 response element (P53RE), and binding of P53 to the C/EBPβ promoter was tested by Electrophoretic Mobility Shift Assay (EMSA) and chromatin immunoprecipitation assay. P53 over-expression and dominant negative P53 expression plasmids were transfected into rat lung fibroblasts and tested for C/EBPβ gene transcription and expression. Western blot analysis was used to test the regulation of C/EBPβ LAP and LIP isoforms. Constructs containing the LAP 5'untranslated region (5'UTR) or the LIP 5'UTR region were used to test the importance of 5'UTR in the control of C/EBPβ LAP and LIP translation. The C/EBPβ promoter sequence was found to contain a conserved P53 response element (P53RE), which binds P53 as demonstrated by Electrophoresis Mobility Shift Assay and chromatin immunoprecipitation assays. P53 over-expression suppressed while dominant negative P53 stimulated C/EBPβ gene transcription and expression. Western blot analysis showed that P53 differentially regulated the translation of the C/EBPβ LAP and LIP isoforms through the regulation of eIF4E and eIF4E-BP1. Further studies with constructs containing the LAP 5'untranslated region (5'UTR) or the LIP 5'UTR region showed that the 5'UTR is important in differential control of C/EBPβ LAP and LIP translation. Analysis of the effects of P53 on C/EBPβ expression revealed a novel mechanism by which P53 could antagonize the effects of C/EBPβ on its target gene expression. For the first time, P53 is shown to be a repressor of C/EBPβ gene expression at both transcriptional and translational levels, with a differential effect in the magnitude of the effect on LAP vs. LIP isoforms.


An evaluation of a measure of the proportion of the treatment effect explained by a surrogate marker.
Time-dependent markers, such as CD4 and viral load, are potential surrogate markers in AIDS clinical trials. A critical issue with surrogate markers is whether changes in these markers explain the beneficial effect of treatment on the real end point of the clinical trial. A statistic to measure the proportion of the treatment effect explained by the surrogate is p(FGS) = 1 - gamma/alpha, where alpha is the treatment effect coefficient in a Cox model and gamma is the treatment effect coefficient from a time-dependent Cox model adjusted for the marker. In this article we evaluate the statistical properties of p(FGS). Using a Monte Carlo study we show that the statistic is not well calibrated, because it can fall outside the range zero to one, even in very large samples. In the simulation study we consider situations where the time-dependent marker is measured with error at a fixed number of times. We show that a method of fitting a time-dependent Cox model involving smoothing the marker reduces the bias in the estimate of p(FGS) compared with the standard method of using the current or last observed marker value. We also show that the estimate of p(FGS) has considerable variability and can have wide confidence intervals. We conclude that p(FGS) is only likely to be useful in large trials with a strong treatment effect. The methods are illustrated using CD4 counts from an AIDS clinical trial of zidovidine versus placebo.


Decreased expression of semaphorin 3D is associated with genesis and development in colorectal cancer.
Semaphorin 3D (SEMA3D) plays important roles in the genesis and progress of many cancers. However, the relationship between SEMA3D and colorectal cancer (CRC) remains unknown. The aim of this study was to investigate whether SEMA3D can be used as a predictive marker for the diagnosis, metastasis, and prognosis of CRC by assessing the expression of SEMA3D in the tissues and serum of CRC patients. Real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of SEMA3D mRNA in 100 CRC tissues and matched normal tissues. qPCR was also used to detect the expression of SEMA3D mRNA in the CRC cell line RKO. RKO cells were transfected with SEMA3D small-interring RNA (siRNA) to interfere with endogenous SEMA3D. The migratory ability of control and SEMA3D siRNA-transfected RKO cells was determined by transwell assays. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the levels of SEMA3D in the serum of 80 CRC patients and 100 normal healthy controls. The expression of SEMA3D in 215 CRC tissues was assessed using immunohistochemistry (IHC). Then, statistical analyses were adopted to assess SEMA3D protein levels and clinical pathological characteristics. The mRNA expression of SEMA3D was significantly lower in CRC tissues than in paired normal tissues (t = 5.027, P < 0.0001). Compared with normal healthy controls, the serum levels of SEMA3D were decreased significantly in CRC patients (t = 3.656, P = 0.0003). The expression of SEMA3D protein was linked to lymph node metastasis, and low expression led to lymph node metastasis (χ 2 = 8.415, P = 0.004). The expression of SEMA3D in CRC tissues was a favorable prognostic factor. Patients with a higher expression of SEMA3D experienced longer survival (P = 0.002, log-rank [Mantel-Cox]; Kaplan-Meier). In addition, multivariate Cox's proportional hazard model revealed that SEMA3D is an independent prognostic marker (hazard ratio [HR] 1.818, 95% CI 1.063-3.110, P = 0.029). Moreover, transwell assays showed that knocking down SEMA3D significantly increased RKO cell migration (t = 9.268, P = 0.0008). SEMA3D might function as a tumor suppressor during the formation and development of CRC. SEMA3D might become a predictive marker for the diagnosis, metastasis, and prognosis of CRC and provide a novel target for the prevention and treatment of CRC.


Erratum to: An approach to the research on ion and water properties in the interphase between the plasma membrane and bulk extracellular solution.
The article An approach to the research on ion and water properties in the interphase between the plasma membrane and bulk extracellular solution, written by Hiroshi Hibino, Madoka Takai, Hidenori Noguchi, Seishiro Sawamura, Yasufumi Takahashi, Hideki Sakai and Hitoshi Shiku, was originally published Online First without open access.


Características clínico-demográficas de pacientes recuperados de COVID-19 en una unidad de rehabilitación de tercer nivel.
To determine the clinical-demographic characteristics of patients recovered from COVID-19 in a third level rehabilitation service. A cross-sectional and descriptive study of recovered COVID-19 patients in a rehabilitation service was carried out. Demographic, personal pathological history, his work activity and COVID-19 were taken, as well as alterations after the disease. Descriptive statistics were performed. 186 files were collected. The mean age was 48.04 ± 11.32 years. Male predominance was found (65.6%). 50% of the patients were health workers. The most common previous pathological conditions were sedentary lifestyle (73.7%) and diabetes mellitus (29%). 43.5% presented grade 3 dyspnea according to the modified Medical Research Council scale. There was a high prevalence of neuromuscular involvement, predominantly peripheral neuropathy (48.4%) and dysautonomia (46.2%). It was possible to determine the clinical-demographic characteristics of patients recovered from COVID-19 in a third-level rehabilitation service, such as age, sex, type of work, previous pathological conditions (diabetes mellitus and arterial hypertension), body mass index, dyspnea, hospitalization, and post-illness disorders. Further investigation of COVID-19 is needed in the development of conditions to different systems.


Cyclic loading moves the peak stress to the cartilage surface in a biphasic model with isotropic solid phase properties.
Experimental indentation studies of articular cartilage have shown the initiation of fibrillation at the cartilage surface. To date, isotropic biphasic models have failed to support this observation. This study presents the results of applying cyclic loading to an isotropic biphasic cartilage indentation model using an FE based solution procedure. The model incorporated a contact dependent flow algorithm to prevent fluid movement across contacting regions. The results show that under the application of cyclic loading the location of key peak solid phase stresses move from the base of the cartilage layer to the surface and thus to the region of experimentally observed cartilage surface failures.


The evidence supporting the association between the use of pain scales and outcomes in hospitalized children: A systematic review.
Systematic use of pain intensity scales is considered a prerequisite for treatment of pain in hospitalized children, but already a decade ago, attention was called to the lack of robust evidence supporting the presumed positive association between their use and desired outcomes. To re-evaluate the evidence supporting the association between the use of pain scales and patient and process outcomes in hospitalized children. Systematic literature review. The online databases PubMed and Cumulative Index of Nursing and Allied Health Literature (CINAHL) were searched from inception to April 15, 2020. We performed single screening of all records followed by duplicate screening of full texts of interest with a disagreement procedure in place. Studies where the authors evaluated outcomes from the use of self-report or behavioral-based pain scales in children 0-18 years in a hospital setting were included. Emergency care settings were excluded. In a majority of the 32 included studies, complex interventions that included one or more pain scales were evaluated. Process outcomes (e.g., documentation) were most frequently studied. Interventions were commonly associated with improved documentation of pain assessment, while the effect on pain management documentation was inconsistent. However, improvements in process outcomes did not necessarily result in better patient outcomes. In regard to patient outcomes (e.g., pain intensity, side effects, or satisfaction with treatment), some authors reported reduced pain intensity on group level, but the effect on other functional outcomes, child and parent satisfaction, and aspects of safety were inconsistent. Methodological issues, e.g., weak study designs and small samples, biased the results, and it was not possible to determine how pain scales contributed to the overall effects since they were studied as part of complex interventions. Although both a theoretically founded understanding of pain and clinical experience suggest that the use of pain scales will make a difference for hospitalized children with pain, there is still limited evidence to support this notion. As pain scales have been almost exclusively studied as an aspect of complex interventions, research that determines the active ingredient(s) in a complex intervention and their joint and individual effects on outcomes that are meaningful for the child (for example reduced pain intensity or improved function) are urgently needed. Tweetable abstract: Limited #research supports association between use of pediatric #pain scales and patient outcomes @_randida @PainPearl.


Experiences of Japanese patients with colorectal cancer during the first six months after surgery.
To investigate the dynamic experience of patients who recently experienced the stressful situation of being diagnosed with colorectal cancer and undergoing surgery. A qualitative and inductive inquiry. General hospitals in Japan. 12 patients who had undergone colorectal cancer surgery and had been discharged in the previous six months. To inductively elicit the findings from patients' real experiences, interviews and qualitative analysis were used. Experience of patients with colorectal cancer. Three domains that symbolized experiences of patients with colorectal cancer during the first six months after surgery emerged: types of burdens, steps in accepting the cancer diagnosis, and way of living a normal life. Burdens included vulnerability, lack of control, asking for assistance or support, and a "why has this happened to me?" attitude. Way of living a normal life included resisting vulnerability, constructing a daily living routine, and asking for help. Although patients faced many and varied burdens, they were able to take several actions to gradually accept their cancer diagnoses and resume normal lives. Some of the patients were sincere and skillful in asking for help to live normal lives, but others found that difficult. The present findings are significant in helping nurses provide interventions to enable patients to make use of assistance or support.


Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer.
In the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC). To validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina. Retrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems. Reclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%). In this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.


Specific transfer of dipalmitoyl phosphatidylcholine in rabbit lung.
Liposomes were used as a tool to probe the specific transfer of dipalmitoyl phosphatidylcholine in rabbit lung. After incubation of liposomes with lung slices, lamellar bodies took up 30-50% more radioactively labeled dipalmitoyl phosphatidylcholine from egg yolk phosphatidylcholine liposomes than the labeled dioleoyl phosphatidylcholine, whereas mitochondria and microsomes took up both species at relatively equal rates. Furthermore, when 50% egg yolk phosphatidylcholine was replaced by dipalmitoyl phosphatidylcholine, the uptake of [1-14C]dipalmitoyl phosphatidylcholine by lamellar bodies was greatly reduced due to the isotope-dilution effect of the unlabeled dipalmitoyl species. This competitive uptake was not observed in mitochondria and microsomes. Similar results were also observed when liposomes were incubated with the cell-free homogenate. On the other hand, distearoyl or dioleoyl phosphatidylcholine did not compete with the uptake of [1-14C]dipalmitoyl phosphatidylcholine. These results suggest an intracellular specific transfer of dipalmitoyl phosphatidylcholine from liposomes to lamellar bodies, presumably by a specific transfer protein. When liposomes were labeled with [1-14C]dioleoyl phosphatidylcholine, the addition of unlabeled dioleoyl phosphatidylcholine up to 50% of total phosphatidylcholine concentration did not compete with the uptake of [1-14C]dioleoyl phosphatidylcholine in all fractions including lamellar bodies. This indicates that the intracellular uptake of liposomal dioleoyl phosphatidylcholine by lamellar bodies and other subcellular organelles was probably dominated by the fusion mechanism.


Memory reactivation in rats treated with the 5-HT1A agonist 8-OH-DPAT: a case of gone, but not forgotten.
The effect of various doses of the serotonin-1A agonist 8-OH-DPAT at training on 72-hr retention of passive avoidance was investigated in rats. Results indicated impaired retention, as measured by latency to avoid shock. However, when total time spent in the nonshock compartment at test was assessed, the performance of drug-treated subjects was not significantly different than that of control animals. It is suggested that although drug treatment produced initial retention impairment, the memory trace for the aversive event was reactivated (i.e., "reminder effect") when subjects entered the shock compartment at test. These data imply that pharmacological treatments, especially those that modulate serotonergic neurotransmission, that appear to disrupt learning per se may interrupt neural circuits involved in retrieval processes.


Joseph Henry Green (1791-1863): surgeon, philosopher and Coleridgean transcendentalist.
This article examines the life and work of the eminent surgeon and philosopher Joseph Henry Green. It details the influence on his literary output of his close friend Samuel Taylor Coleridge and shows the ways in which transcendental philosophy underpinned his scientific outlook.


What are hospital nurses' strengths and weaknesses in patient safety competence? Findings from three Korean hospitals.
To examine hospital nurses' patient safety competencies and the association between these competencies and safety climate. Cross-sectional questionnaire survey. Three teaching hospitals in Seoul, Korea. In total, 459 nurses from general adult nursing care units, intensive care units or operating rooms (response rate = 87.4%). Self-administered questionnaires were distributed to measure patient safety competency. Multiple regression analyses were performed to examine relationships between patient safety competency and safety climate. Patient safety competency scores ('teamwork', 'communication', 'managing safety risks', 'human and environmental factors', 'adverse event recognition' and 'safety culture' dimensions) and perceived safety climate. The mean patient safety competency score was 3.3 (SD = 0.4) out of 5.0; 396 nurses (86.3%) rated their competency as above average. Among subscales, 'managing safety risks' scores were the highest, and 'teamwork' scores were the lowest. Patient safety competency differed significantly by participants' age, educational level, clinical experience and position. Patient safety competency was higher in older nurses with master's or higher degrees and clinical experience of longer duration. Nurse managers' scores were higher than those of staff nurses. Safety climate was perceived as moderate. After adjusting for other individual and organizational characteristics, patient safety competency was positively associated with safety climate perception. Nurses' safety competency was rated as moderate. In particular, nurses lacked confidence in teamwork. Nurses with higher safety competency perceived safety climate more positively. Efforts emphasizing teamwork to enhance nurses' safety competency should be prioritized, thereby contributing to improvement of safety climates.


Iodosylbenzene and iodylbenzene adducts of cerium(IV) complexes bearing chelating oxygen ligands.
Reactions of [Ce(IV)(LOEt)2Cl2] (LOEt(-) = [Co(η(5)-C5H5){P(O)(OEt)2}3](-)) and [Ce(μ-O){N(Pr(i)2PO)2}4Cl2] with PhIO afford the λ3-iodane complexes [Ce(IV)(LOEt)2{OI(Cl)Ph}2] and [Ce{N(Pr(i)2PO)2}3{OI(Cl)Ph}], respectively, whereas that between [Ce(IV)(LOEt)2Cl2] and PhIO2 or excess PhIO yields the λ5-iodane adduct [Ce(IV)(LOEt)2{OI(O)ClPh}2]. The crystal structures of the Ce(IV)λ3- and λ5-iodane complexes have been determined and their oxo transfer reactivities have been investigated.


Expression of p53 in esophageal carcinoma with multiple areas unstained by iodine.
Esophageal squamous cell carcinoma is occasionally associated with multiple areas in the surrounding mucosa unstained with iodine. We examined 21 male patients with superficial esophageal carcinoma. Group 1 consisted of 4 cases of superficial esophageal carcinoma associated with multiple lesions that did not stain with iodine. Group 2 comprised 17 cases of a solitary tumor without major additional lesions in the mucosa. We assessed the correlation between clinicopathological factors, a history of tobacco and alcohol consumption, and p53 expression in the two groups. We found four cases (group 1) of superficial esophageal squamous cell carcinoma where there were a total of 10 satellite tumors in addition to the main tumor. These patients tended to have a higher daily consumption of tobacco and alcohol than those in group 2. Moreover in all these group 1 cases there was intraepithelial spread of the tumors and p53 overexpression in all of the main and additional tumors. We have found that higher tobacco and alcohol consumption are closely related to multiple lesions unstained by iodine and abnormal expression of the p53 gene.


The heterogeneous impacts of Sino-African trade relations on carbon intensity in Africa.
Studies on the environmental impacts of China-African trade relations are scarce. To fill the gap, this research examines the effects of Sino-African trade relations on carbon dioxide (CO2) emissions intensity in Africa, employing panel quantile regression for 39 African countries over the period of 1992-2015. The results indicate that imports have a negative and significant effect on CO2 emissions intensity across all quantile distributions, whereas exports have a positive and significant effect, except at the 25th and 35th quantiles. The findings also confirm the inverted U-shaped environmental Kuznets curve hypothesis, particularly for countries at higher emissions points. The study also demonstrates that urbanisation and energy intensity positively affect CO2 intensity, while the effect of foreign direct investment is negative and significant, confirming the pollution halo hypothesis. Finally, policy implications are presented based on the findings of the study.


The role of electromagnetic stimulation in the management of established non-union of long bone fractures: what is the evidence?
Non-union following long bone fractures is a cause of significant morbidity to the patient. The management of this condition has proved difficult for the orthopaedic surgeon. Much research has been carried out on the use of electromagnetic stimulation in the healing of non-union. The objective of this review is to determine what evidence exists to support electromagnetic stimulation in the management of established non-union of long bone fractures. A systematic search was carried out of the peer-reviewed English language literature to identify all studies investigating electromagnetic stimulation in the treatment of non-union of fractures of long bones. Three of the articles reviewed were randomised clinical trials. Forty-six other studies were also included in the review. There is a consensus that electromagnetic stimulation is an effective adjunct to conventional therapy when used in the management of non-union of long bone fractures.


Identification of photocatalytic degradation products of diazinon in TiO2 aqueous suspensions using GC/MS/MS and LC/MS with quadrupole time-of-flight mass spectrometry.
The photocatalytic degradation of the organophosphorus insecticide diazinon in aqueous suspensions has been studied by using titanium dioxide as a photocatalyst. The degradation of the insecticide was a fast process and included the formation of several intermediates that were identified using GC/ion-trap mass spectrometry with EI or CI in positive and negative ionization mode and HPLC/electrospray-QqTOF mass spectrometry. Since primarily hydroxy derivatives were identified in these aqueous suspensions, the mechanism of degradation was probably based on hydroxyl radical attack. The initial oxidative pathways of the degradation of diazinon involved the substitution of sulfur by oxygen on the Pz.dbnd6;S bond, cleavage of the pyrimidine ester bond, and oxidation of the isopropyl group. Exact mass measurements of the derivatives allowed the elemental formula of the molecules to be determined confidently. Similarities to the metabolic pathways occurring in living organisms were observed.


Suicide gene therapy in cancer and HIV-1 infection: An alternative to conventional treatments.
Suicide Gene Therapy (SGT) aims to introduce a gene encoding either a toxin or an enzyme making the targeted cell more sensitive to chemotherapy. SGT represents an alternative approach to combat pathologies where conventional treatments fail such as pancreatic cancer or the high-grade glioblastoma which are still desperately lethal. We review the possibility to use SGT to treat these cancers which have shown promising results in vitro and in preclinical trials. However, SGT has so far failed in phase III clinical trials thus further improvements are awaited. We can now take advantages of the many advances made in SGT for treating cancer to combat other pathologies such as HIV-1 infection. In the review we also discuss the feasibility to add SGT to the therapeutic arsenal used to cure HIV-1-infected patients. Indeed, preliminary results suggest that both productive and latently infected cells are targeted by the SGT. In the last section, we address the limitations of this approach and how we might improve it.


Reduction and fixation of jaw fractures using acrylic splints.
This paper proposes the criteria for application of acrylic splints in the treatment of various types of maxillofacial fractures. These were based mainly on the number of remaining teeth that are important for the restoration of occlusion. The acrylic splints studied consisted of intermaxillary, lingual and labiolingual types that hold a dental arch and a cap type that covers a dental arch. It was found that the intermaxillary type was best indicated for the loss of multiple teeth, the lingual type for the predicted intraversion of bone fragments and the labiolingual as well as cap types for the deciduous or mixed dentition. Clinical application based on the above standard, which was attempted in our 60 patients, produced successful results. In addition, the usefulness of these acrylic splints as an intraoral apparatus was discussed.


Deep learning-based 3D MRI contrast-enhanced synthesis from a 2D noncontrast T2Flair sequence.
Gadolinium-based contrast agents (GBCAs) have been successfully applied in magnetic resonance (MR) imaging to facilitate better lesion visualization. However, gadolinium deposition in the human brain raised widespread concerns recently. On the other hand, although high-resolution three-dimensional (3D) MR images are more desired for most existing medical image processing algorithms, their long scan duration and high acquiring costs make 2D MR images still much more common clinically. Therefore, developing alternative solutions for 3D contrast-enhanced MR image synthesis to replace GBCAs injection becomes an urgent requirement. This study proposed a deep learning framework that produces 3D isotropic full-contrast T2Flair images from 2D anisotropic noncontrast T2Flair image stacks. The super-resolution (SR) and contrast-enhanced (CE) synthesis tasks are completed in sequence by using an identical generative adversarial network (GAN) with the same techniques. To solve the problem that intramodality datasets from different scanners have specific combinations of orientations, contrasts, and resolutions, we conducted a region-based data augmentation technique on the fly during training to simulate various imaging protocols in the clinic. We further improved our network by introducing atrous spatial pyramid pooling, enhanced residual blocks, and deep supervision for better quantitative and qualitative results. Our proposed method achieved superior CE-synthesized performance in quantitative metrics and perceptual evaluation. In detail, the PSNR, structural-similarity-index, and AUC are 32.25 dB, 0.932, and 0.991 in the whole brain and 24.93 dB, 0.851, and 0.929 in tumor regions. The radiologists' evaluations confirmed that our proposed method has high confidence in the diagnosis. Analysis of the generalization ability showed that benefiting from the proposed data augmentation technique, our network can be applied to "unseen" datasets with slight drops in quantitative and qualitative results. Our work demonstrates the clinical potential of synthesizing diagnostic 3D isotropic CE brain MR images from a single 2D anisotropic noncontrast sequence.


Treatment of peripheral bronchopleural fistulas with endobronchial occlusion coils.
Persistent peripheral bronchopleural fistulas can be difficult to manage. Endoscopic plugging of involved bronchi has been accomplished in a number of ways. We have devised a method of permanently blocking small peripheral airways using Gianturco vascular occlusion coils placed endobronchially by modified angiographic techniques. This procedure has been applied in 5 cases of complicated parenchymal air leaks. Complete or substantial partial control was achieved in all cases. There were no complications.


Aldolase B inhibits metastasis through Ten-Eleven Translocation 1 and serves as a prognostic biomarker in hepatocellular carcinoma.
Downregulation of Aldolase B (ALDOB) has been reported in hepatocellular carcinoma. However, its clinical significance and its role in pathogenesis of HCC remain largely unknown. We analyzed the expression of ALDOB and its clinical features in a large cohort of 313 HCC patients using tissue microarray and immunohistochemistry. Moreover, the function of stably overexpressed ALDOB in HCC cells was explored in vitro and in vivo. Gene expression microarray analysis was performed on ALDOB-overexpressing SMMC7721 cells to elucidate its mechanism of action. ALDOB downregulation in HCC was significantly correlated with aggressive characteristics including absence of encapsulation, increased tumor size (>5 cm) and early recurrence. ALDOB downregulation was indicative of a shorter recurrence-free survival (RFS) and overall survival (OS) for all HCC patients and early-stage HCC patients (BCLC 0-A and TNM I stage patients). Multiple analyses revealed that ALDOB downregulation was an independent risk factor of RFS and OS. Stable expression of ALDOB in HCC cell lines reduced cell migration in vitro and inhibited lung metastasis, intrahepatic metastasis, and reduced circulating tumor cells in vivo. Mechanistically, we found that cells stably expressing ALDOB show elevated Ten-Eleven Translocation 1 (TET1) expression. Moreover, ALDOB expressing cells have higher levels of methylglyoxal than do control cells, which can upregulate TET1 expression. The downregulation of ALDOB could indicate a poor prognosis for HCC patients, and therefore, ALDOB might be considered a prognostic biomarker for HCC, especially at the early stage. In addition, ALDOB inhibits the invasive features of cell lines partly through TET1 expression.


Effects of Cd uptake, translocation and redistribution in different hybrid rice varieties on grain Cd concentration.
In order to identify the key transport process that determines the Cd concentration in brown rice, this study used 21 hybrid rice varieties as experimental materials and conducted field experiments in Qiyang (cadmium-contaminated site) and Yongding (low-cadmium site). Cd concentrations in 8 organs were measured, and bioconcentration factors and transfer factor were further calculated. The results showed that the Cd concentrations of the organs related to the xylem transport were as follows: root > node > stem > leaf sheath > leaf. In the phloem, the Cd concentrations were as follows: rachis > brown rice > rice husk. And the results of the correlation analysis found that Cd concentration between brown rice and root showed a significant positive correlation in Cd-contaminated site, but no significant correlation in low-cadmium site. Meanwhile, at both experimental sites, the Cd concentration of brown rice showed the most significant correlation with the phloem transfer factor from leaf and leaf sheath to brown rice. Principal Component Analysis (PCA) and stepwise regression analysis likewise found that Cd concentration in leaf and leaf sheath and their phloem transport of Cd to brown rice were significantly and positively correlated with Cd concentration in brown rice. The above results showed that the transport of leaf and leaf sheath to brown rice was a key process, and played a more important role in the accumulation of cadmium in brown rice than in root.


The effect of morphine on human neuromuscular transmission.
By utilizing high frequency nerve stimulation, we observed the effects of morphine sulphate, 0.5 mg.kg-1 on human neuromuscular transmission. Tetanic fade at 50, 100 and 200 hz did not change during the one hour period after infusion of morphine. Post-tetanic depression (PTD) of single twitch response increased progressively with time over the one-hour study period. This was most marked with the 100 and 200 hz tetanic frequencies. In contrast, control subjects displayed either no change, or a slight increase (post-tetanic facilitation; PTF), over a similar one-hour test period. We believe these results are best explained by a presynaptic action of morphine, whereby intraterminal mobilization of acetylcholine is impaired by the opiate narcotic drug.


The Ciliary Machinery Is Repurposed for T Cell Immune Synapse Trafficking of LCK.
Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a "regulatory arm" by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse.


"At least one" problem with "some" formal reasoning paradigms.
In formal reasoning, the quantifier "some" means "at least one and possibly all." In contrast, reasoners often pragmatically interpret "some" to mean "some, but not all" on both immediate-inference and Euler circle tasks. It is still unclear whether pragmatic interpretations can explain the high rates of errors normally observed on syllogistic reasoning tasks. To address this issue, we presented participants (reasoners) in the present experiments either standard quantifiers or clarified quantifiers designed to precisely articulate the quantifiers' logical interpretations. In Experiment 1, reasoners made significantly more logical responses and significantly fewer pragmatic responses on an immediate-inference task when presented with logically clarified as opposed to standard quantifiers. In Experiment 2, this finding was extended to a variant of the immediate-inference task in which reasoners were asked to deduce what followed from premises they were to assume to be false. In Experiment 3, we used a syllogistic reasoning task and observed that logically clarified premises reduced pragmatic and increased logical responses relative to standard ones, providing strong evidence that pragmatic responses can explain some aspects of the errors made in the syllogistic reasoning task. These findings suggest that standard quantifiers should be replaced with logically clarified quantifiers in teaching and in future research.


Community lifespan, niche expansion and the evolution of interspecific cooperation.
Microbes live in dense and diverse communities where they deploy many traits that promote the growth and survival of neighbouring species, all the while also competing for shared resources. Because microbial communities are highly dynamic, the costs and benefits of species interactions change over the growth cycle of a community. How mutualistic interactions evolve under such demographic and ecological conditions is still poorly understood. Here, we develop an eco-evolutionary model to explore how different forms of helping with distinct fitness effects (rate-enhancing and yield-enhancing) affect the multiple phases of community growth, and its consequences for the evolution of mutualisms. We specifically focus on a form of yield-enhancing trait in which cooperation augments the common pool of resources, termed niche expansion. We show that although mutualisms in which cooperation increases partners growth rate are generally favoured at early stages of community growth, niche expansion can evolve at later stages where densities are high. Further, we find that niche expansion can promote the evolution of reproductive restraint, in which a focal species adaptively reduces its own growth rate to increase the density of partner species. Our findings suggest that yield-enhancing mutualisms are more prevalent in stable habitats with a constant supply of resources, and where populations typically live at high densities. In general, our findings highlight the need to integrate different components of population growth in the analysis of mutualisms to understand the composition and function of microbial communities.


Ovarian torsion in utero diagnosed at 37 weeks of pregnancy: A case report.
Fetal ovarian masses are common abdominal anomalies in female fetuses, often diagnosed in the third trimester. Most masses are benign and tend to resolve spontaneously within a few months after birth, but larger masses may present complications such as torsion. A 21-year-old primagravid woman was noted to have a complex avascular solid mass in the fetal left pelvis, which was consistent with complex fetal left ovarian torsion. The patient underwent induction of labor at 39 weeks for possible intervention. The infant underwent surgery at 5 weeks of age and a torsed, necrotic ovary was discovered. The diagnosis of ovarian torsion in utero is rare, and prenatal and postnatal guidelines are needed on frequency of monitoring, timing of delivery, and postnatal follow-up.


Determinant factors in climbing ability: Influence of strength, anthropometry, and neuromuscular fatigue.
The goal of this study was to (i) assess the physical and anthropometric differences between three levels of climbers and (ii) predict climbing ability by using a multiple regression model. The participants were divided into novice (n = 15), skilled (n = 16), and elite (n = 10) climbers. Anthropometric characteristics such as height, weight, percentage of body fat and muscle, bi-acromial breath, arm span, and ape index were measured. General and specific strength were assessed through an arm jump test, a bench press test, and a hand and finger grip strength test in maximal and endurance conditions. All variables were combined into components via a principal component analysis (PCA) and the components used in a multiple regression analysis. The major finding of this study is that climbing ability is more related to specific rather than general strength. Only finger grip strength shows a higher level of initial strength between all samples while the arm jump test discriminates between climbers and non-climbers. The PCA reveals three components, labeled as training, muscle, and anthropometry, which together explain 64.22% of the variance. The regression model indicates that trainable variables explained 46% of the total variance in climbing ability, whereas anthropometry and muscle characteristics explain fewer than 4%.


Determining the area of influence of depression cone in the vicinity of lignite mine by means of triangle method and LANDSAT TM/ETM+ satellite images.
Problems with lowering of water table are common all over the world. Intensive pumping of water from aquifers for consumption, irrigation, industrial or mining purposes often causes groundwater depletion and results in the formation of cone of depression. This can severely decrease water pressure, even over vast areas, and can create severe problems such as degradation of agriculture or natural environment sometimes depriving people and animals of water supply. In this paper, the authors present a method for determining the area of influence of a groundwater depression cone resulting from prolonged drainage, by means of satellite images in optical, near infrared and thermal infrared bands from TM sensor (Thematic Mapper) and ETM+ sensor (Enhanced Thematic Mapper +) placed on Landsat 5 and Landsat 7 satellites. The research area was Szczercowska Valley (Pol. Kotlina Szczercowska), Central Poland, located within a range of influence of a groundwater drainage system of the lignite coal mine in Belchatow. It is the biggest lignite coal mine in Poland and one of the largest in Europe exerting an enormous impact on the environment. The main method of satellite data analysis for determining soil moisture, was the so-called triangle method. This method, based on TVDI (Temperature Vegetation Dryness Index) was supported by additional spatial analysis including ordinary kriging used in order to combine fragmentary information obtained from areas covered by meadows. The results obtained are encouraging and confirm the usefulness of the triangle method not only for soil moisture determination but also for assessment of the temporal and spatial changes in the area influenced by the groundwater depression cone. The range of impact of the groundwater depression cone determined by means of above-described remote sensing analysis shows good agreement with that determined by ground measurements. The developed satellite method is much faster and cheaper than in-situ measurements, and allows for systematic monitoring of the vast area in the vicinity of Belchatow lignite mine. Besides, this method could be useful as a helper in in-situ measurement allowing a significant reduction of the number of in-situ measurements by performing them only within problematic areas. Hence, the triangle method can be used as an effective supplement to field measurements. Although the research area is located in Poland, in the vicinity of lignite mine, the method of observation of depression cones provided in this study is universal and effective, and therefore could also be useful to an international audience.


e-Cigarettes and Oral Cancer: what do we know so far?
We aim to summarise the latest evidence to better inform OMFS practitioners about the deleterious effects of vaping on oral health and the risks of oral cancer, so they can better inform their patients. Current evidence suggests that e-cigarette use is not risk-free.


Separation of Escherichia coli from natural samples for identification of sources and microcosm inoculation.
Obtaining uncultured Escherichia coli from natural waters is an important step in the study of microbes in the environment, which are critical for bacterial decay and microbial source tracking. The quality of the samples used can influence the assays, because high contaminant concentrations, differing cell ages, and physiologic states can impair results. The proposed separation is based on a three-step filtration method applied to replicates of seven samples from a sewage plant affluent, collected in different periods. Aliquots of the leachate were inoculated into microcosms, aiming to observe the cultivability of the cells. The assay resulted in colimetry values ranging between 104 and 105 cells. In the leachate, averages of 1.05% of total coliforms and 1.10% of Escherichia coli were recovered from original samples. Although enduring unfavorable temperatures, salinities, and nutritional conditions, the inoculated microcosm populations grew approximately 310 times after 24 h. The final leachate contained cultivable cells in appropriate physiological states and quantities for inoculum in microcosm sets. The bacteria obtained from the leachate were also appropriate for surveys of microbial source tracking, because, in the developed procedure, organisms were separated from contaminants, while cell concentrations were sufficient for inocula.


The control of 5-hydroxytryptamine and dopamine synthesis in the brain: a theoretical approach.
The transport of the eight amino acids (phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, histidine and methionine) using the large neutral amino acid transporter of the blood-brain barrier (BBB) has been calculated using published kinetic data. The fate of the amino acids has been followed from blood to interstitial space, to cell and through metabolism which included, for tyrosine and tryptophan, the hydroxylases. The system was analysed in terms of flux control coefficients. Since the summation theorem did not hold, the system clearly behaved as a non-homogeneous system. At physiological levels of these eight amino acids, the largest contribution to the control of the flux of tyrosine is given by the hydroxylase step, followed by the diffusional component of the transport across the BBB. For tryptophan it is the hydroxylase step, followed by the carrier-mediated transport across the BBB. For the other amino acids it is the metabolism, followed by the diffusional component of the BBB transport. These parameters for tyrosine and tryptophan were determined at increased levels of blood phenylalanine, tyrosine or histidine. The flux through tryptophan hydroxylase can be affected by high blood levels of tyrosine and histidine to values also observed in hyperphenylalaninaemia. Since hypertyrosinaemia (type II) and hyperhistidinaemia are not associated with mental retardation, it is concluded that interference with transport across the BBB of tyrosine and tryptophan, as well as the flux through tryptophan hydroxylase leading to the synthesis of 5-hydroxytryptamine, do not contribute to the cause of permanent brain dysfunction in hyperphenylalaninaemia. It can be calculated that addition of tyrosine to the diet to raise the blood tyrosine level in phenylketonuria patients may have a beneficial effect for the synthesis of neurotransmitters derived from tyrosine.


Clinical inquiry: does brief physician counseling promote weight loss?
In some cases, it may. While physician counseling alone isn't more effective for weight loss than usual care, counseling (adults) as part of a multidisciplinary intervention may promote modest (2-3 kg) weight loss over 1 year.


Development and Validation of a Clinical Score to Predict Neurological Outcomes in Patients With Out-of-Hospital Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.
Extracorporeal cardiopulmonary resuscitation (ECPR) is expected to improve the neurological outcomes of patients with refractory cardiac arrest; however, it is invasive, expensive, and requires substantial human resources. The ability to predict neurological outcomes would assist in patient selection for ECPR. To develop and validate a prediction model for neurological outcomes of patients with out-of-hospital cardiac arrest with shockable rhythm treated with ECPR. This prognostic study analyzed data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multi-institutional nationwide cohort study that included 87 emergency departments in Japan. All adult patients with out-of-hospital cardiac arrest and shockable rhythm who were treated with ECPR between June 2014 and December 2017 were included. Patients were randomly assigned to the development and validation cohorts based on the institutions. The analysis was conducted between November 2019 and August 2020. Age (<65 years), time from call to hospital arrival (≤25 minutes), initial cardiac rhythm on hospital arrival (shockable), and initial pH value (≥7.0). The primary outcome was 1-month survival with favorable neurological outcome, defined by Cerebral Performance Category 1 or 2. In the development cohort, a simple scoring system was developed to predict this outcome using a logistic regression model. The diagnostic ability and calibration of the scoring system were assessed in the validation cohort. A total of 916 patients were included, 458 in the development cohort (median [interquartile range {IQR}] age, 61 [47-69] years, 377 [82.3%] men) and 458 in the validation cohort (median [IQR] age, 60 [49-68] years; 393 [85.8%] men). The cohorts had the same proportion of favorable neurological outcome (57 patients [12.4%]). The prediction scoring system was developed, attributing a score of 1 for each clinical predictor. Patients were divided into 4 groups, corresponding to their scores on the prediction model, as follows: very low probability (score 0), low probability (score 1), middle probability (score 2), and high probability (score 3-4) of good neurological outcome. The mean predicted probabilities in the groups stratified by score were as follows: very low, 1.6% (95% CI, 1.6%-1.6%); low, 4.4% (95% CI, 4.2%-4.6%); middle, 12.5% (95% CI, 12.1%-12.8%); and high, 30.8% (95% CI, 29.1%-32.5%). In the validation cohort, the C statistic of the scoring system was 0.724 (95% CI, 0.652-0.786). The predicted probability was evaluated as well calibrated to the observed favorable outcome in both cohorts by visual assessment of the calibration plot. In this study, the scoring system had good discrimination and calibration performance to predict favorable neurological outcomes of patients with out-of-hospital cardiac arrest and shockable rhythm who were treated with ECPR.


Choanal atresia and associated multiple anomalies.
Seventeen unrelated patients with multiple anomalies of unknown etiology were identified by the presence of choanal atresia. A regularly recurring pattern of associated features involving mental retardation, postnatal growth deficiency, hypogenitalism (males), small ears, cardiac defects, micrognathia, postnatal microcephaly, and ocular coloboma was identified. Choanal atresia when accompanied by multiple anomalies of unknown etiology has a serious prognosis with a predictable pattern of associated defects.


Intracerebral haemorrhage as first manifestation of pseudoxanthoma elasticum.
Pseudoxanthoma elasticum (PXE), a rare inherited, progressive connective tissue disorder, is an uncommon cause of ischemic stroke, mostly due to arterial occlusive small vessel disease. Intracranial haemorrhage rarely occurs in PXE. We report a patient with cerebral bleeding as the first manifestation of PXE, which has not been described before. This atypical presentation led to delayed diagnosis, which was not made until 3 years after the haemorrhage. PXE is a rare but noteworthy cause of ischemic and haemorrhagic stroke and should be considered in young patients lacking vascular risk factors.


Targeting collagen damage for sustained in situ antimicrobial activities.
Antimicrobial peptides (AMPs) are promising anti-infective drugs, but their use is restricted by their short-term retention at the infection site, non-targeted uptake, and adverse effects on normal tissues. Since infection often follows an injury (e.g., in a wound bed), directly immobilizing AMPs to the damaged collagenous matrix of the injured tissues may help overcome these limitations by transforming the extracellular matrix microenvironment of the infection site into a natural reservoir of AMPs for sustained in situ release. Here, we developed and demonstrated an AMP-delivery strategy by conjugating a dimeric construct of AMP Feleucin-K3 (Flc) and a collagen hybridizing peptide (CHP), which enabled selective and prolonged anchoring of the Flc-CHP conjugate to the damaged and denatured collagen in the infected wounds in vitro and in vivo. We found that the dimeric Flc and CHP conjugate design preserved the potent and broad-spectrum antimicrobial activities of Flc while significantly enhancing and extending its antimicrobial efficacy in vivo and facilitating tissue repair in a rat wound healing model. Because collagen damage is ubiquitous in almost all injuries and infections, our strategy of targeting collagen damage may open up new avenues for antimicrobial treatments in a range of infected tissues.


Analysis of Average Telomere Length in Human Telomeric Protein Knockout Cells Generated by CRISPR/Cas9.
Telomeres play an important role in ensuring the integrity of the genome. Telomere shortening can lead to loss of genetic information and trigger DNA damage responses. Cultured mammalian cells have served as critical model systems for studying the function of telomere binding proteins and telomerase. Tremendous heterogeneity can be observed both between species and within a single cell population. Recent advances in genome editing (such as the development of the CRISPR/Cas9 platform) have further enabled researchers to carry out loss-of-function analysis of how disrupting key players in telomere maintenance affects telomere length regulation. Here we describe the steps to be carried out in order to analyze the average length of telomeres in CRISPR-engineered human knockout (KO) cells (TRF analysis).


Membrane fouling control in membrane bioreactors (MBRs) using granular materials.
Membrane fouling is considered the major limitation of membrane bioreactors (MBRs). This paper provides an overview on fouling mitigation in MBRs using granular materials. Adsorbents addition extends filtration period, improves critical flux as well as sludge properties (increased flocs size, reduced soluble EPS, improved dewaterability). However, determination of optimal dosages of adsorbents is needed to balance cost savings from fouling mitigation versus cost of adsorbents and sludge handling. The abrasion from granular media reduces cake layer formation, extends membrane filtration period, increases flux (∼20-30%), and reduces aeration intensity by 50%. Finding appropriate aeration intensity and optimum dose for different media is critical for full-scale application. Granular sludge substantially reduces fouling in MBRs; but, optimal operational conditions for long-term granule stability are required. Quorum quenching (QQ) mitigates biofouling (energy savings ∼27-40%). Cost savings from QQ need assessment against the production and application of QQ approaches.


Repeated stereotactic radiosurgery for patients with progressive brain metastases.
In the present study we have evaluated the efficacy and toxicity of repeated stereotactic radiosurgery (SRS) in patients with recurrent/progressive brain metastases. Between March 2006 and October 2014, 43 patients (21 men and 22 women) with 47 lesions received a second course of SRS given in three daily fractions of 7-8 Gy. With a follow-up study of 19 months, the 1- and 2-year survival rates from repeated SRS were 37 and 20%, respectively, and the 1- and 2-year local control rates were 70 and 60%, respectively. Actuarial local control was significantly better for breast and lung metastases as compared with melanoma metastases; specifically, 1-year local control rates were 38% for melanoma, 78% for breast carcinoma and 73% for non-small cell lung cancer (NSCLC) metastases (p = 0.01). The cause of death was progressive systemic disease in 25 patients and progressive brain disease in 11 patients. Stable extracranial disease (p = 0.01) and Karnofsky performance status (KPS; p = 0.03) were predictive of longer survival. Radiologic changes suggestive of brain radionecrosis were observed in 9 (19%) out of 47 lesions, with an actuarial risk of 34% at 12 months. Neurological deficits (RTOG Grade 2 or 3) associated with brain necrosis occurred in 14% of patients. In conclusion, a second course of SRS given in three daily fractions is a feasible treatment for selected patients with recurrent/progressive brain metastases. Further studies are needed to explore the efficacy and safety of different dose-fractionation schedules, especially in patients with melanoma or large metastases.


Increased inflammasome-activated pyroptosis mediated by caspase-1 in Rasmussen's encephalitis.
Rasmussen's encephalitis (RE) is a rare, progressive disease characterized by unilateral cerebral hemisphere atrophy. Studies showed that inflammatory response and overexpressed chemokines were present in RE patients. The present study aims to determine whether caspase-1- mediated neuronal pyroptosis occurred in RE. Immunohistochemistry and Western blotting analysis were used to examine the expression of Gasdermin D (GSDMD), NOD-like receptor protein 1 (NLRP1), NOD-like receptor protein 3 (NLRP3), caspase-1, and pro-caspase-1 in RE and control cortical specimens (n = 14). Perilesional tissue specimens from six focal cortical dysplasia (FCD) cases were used as controls. Double staining showed the colocalization of GSDMD, NLRP1, NLRP3 and caspase-1. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the amount of interleukin (IL)-1β and IL-18 in RE cortical specimens. Compared with the control cortex, we found higher GSDMD expression in the cytoplasm of neurons in RE cortex but no detectable expression in astrocytes and microglia. Further analysis revealed that NLRP1, NLRP3, caspase-1 and its precursor pro-caspase-1 were also upregulated in the RE, and predominantly localized in the cytoplasm of the neurons. In addition, significantly higher levels of IL-1β and IL-18 were present in the RE group compared with the control group. Our results suggest that pyroptosis represents an important pathway for neuronal loss in the pathological processes associated with RE, and that targeting the canonical inflammasome pathway of pyroptosis may provide potential therapeutic value for RE.


Upper gastrointestinal fiberoptic endoscopy in pediatric patients.
One hundred and forty-two pediatric patients between age 1 month and 20 years had 163 endoscopic procedures. Of 66 with chronic abdominal pain, 21 had a source identified endoscopically that was seen in only 15 by esophagogram and upper gastrointestinal series. Of 31 with nausea, vomiting, dysphagia, and/or odynophagia and retrosternal pain, endoscopy demonstrated the source in 19 patients and radiographic studies in 14. Of 34 with hematemesis and/or melena, 26 had a bleeding site identified endoscopically but only 4 of 28 had an identified source by radiographic studies. Duodenal and gastric ulcers and hemorrhagic gastritis were the commonest cases of upper gastrointestinal bleeding and organically of chronic adbominal pain. Functional abdominal pain was the commonest cause of chronic abdominal pain in those endoscoped. Foreign bodies were removed from the esophagus and stomach of 6 patients and dislodged in 2 others. Caustic ingestion was recognized in the esophagus and stomach of 2 patients who did not have mouth burns. The GIF-P2-prototype with four-way tip control and ability to retroflex 180 degree up, 60 degree down, and 100 degree right and left was superior to GIF-P1 and CF-P-prototype for visualization of the entire esophagus, stomach, duodenal bulb, and postbulbar area in patients less than 10 years old. Visualization of the duodenal bulb was possible in 28 of 29 pediatric patients, and of the postbulbar area in 25 of 26 in whom it was attempted. Infants who weighed as little as 3 to 5 kg were successfully examined. Retroflexion was possible in 29 of 30 to see the fundus and cardioesophageal junction. Patients older than 10 years were better examined with the GIF-D because of its increased ability to transmit light. Sedation for the school-age child with 0.5 to 1.0 mg per kg of diazepam and 1 to 2 mg per kg of meperidine given intravenously provides excellent sedation in most instances. General anesthesia is preferable for the preschooler and infant. Minor complications occurred in 2 patients who received less than adequate sedation and in 1 patient with general anesthesia.


Functional expression of eukaryotic cytochrome P450s in yeast.
Cytochrome P450 enzymes (P450s) are a superfamily of heme-thiolate proteins widely existing in various organisms. Due to their key roles in secondary metabolism, degradation of xenobiotics, and carcinogenesis, there is a great demand to heterologously express and obtain a sufficient amount of active eukaryotic P450s. However, most eukaryotic P450s are endoplasmic reticulum-localized membrane proteins, which is the biggest challenge for functional expression to high levels. Furthermore, the functions of P450s require the cooperation of cytochrome P450 reductases for electron transfer. Great efforts have been devoted to the heterologous expression of eukaryotic P450s, and yeasts, particularly Saccharomyces cerevisiae are frequently considered as the first expression systems to be tested for this challenging purpose. This review discusses the strategies for improving the expression and activity of eukaryotic P450s in yeasts, followed by examples of P450s involved in biosynthetic pathway engineering.


Low back pain as the presenting symptom of renal artery aneurysm. A case report.
Hypertension of recent onset in a 29-year-old woman was associated with low pain radiating to the right groin. Angiography showed the presence of a large aneurysm of the right renal artery. Resection of the aneurysm and nephrectomy cured the hypertension.


Caudal dysplasia, femoral hypoplasia-unusual facies syndrome and absent radius: a new association in infant of diabetic mother?
The Caudal dysplasia syndrome (CDS) and the femoral hypoplasia-unusual facies syndrome (FHUFS) have been reported to be more frequent among infants of diabetic mothers (IDMs). Infact, uncontrolled maternal diabetes is the most common cause of both the syndromes. Till now, there is no case report to suggest absent radius as a manifestation of IDMs. The authors report a rare case of newborn, who presented with features compatible with both CDS and FHUFS with an additional feature of absent radius, which is not reported in the literature so far. The possibility that all these features represent different manifestations of the same disorder is discussed here.


Usefulness of postoperative ventriculography and intracranial pressure monitoring following endoscopic third ventriculostomy.
The authors sought to determine whether the insertion of an external ventricular drain (EVD) at the time of surgery to monitor intracranial pressure (ICP) and ventriculography done within the first day following an endoscopic third ventriculostomy (ETV) is of benefit in postoperative patient management. Following IRB approval, ETV procedures done by the senior author between January 1, 2007, and December 31, 2016, were reviewed. Included in a consecutive fashion were all patients who underwent an ETV with placement of an external ventricular drain (EVD) that was preceded preoperatively by an MRI or CT study and followed by a contrast CT ventriculogram within the first postoperative day. Identified were 72 patients who met the above criteria; however, technical ventriculography failure occurred in 4 (6%) and were eliminated from the analysis. Of the remaining 68 patients, contrasted CSF was seen in the basal cisterns/subarachnoid spaces (SAS) in 66 (97%) indicating a patent ETV and absent in 2 (3%) indicating a non-patent ETV. Of the 66 patients with a patent ETV, 34 (52%) patients were discharged on postoperative days 1 (8), 2 (13), and 3 (13) as their ICPs were not elevated and their clinical symptoms normal. EVDs placed at the time of the ETV recorded raised ICP > 20 cm H2O in 17/68 (25%) patients for 1 or more days, all of whom had a patent ETV. Because of persistently elevated ICP requiring CSF drainage for control, 4 of these patients were shunted on postoperative days 5, 6, 6, and 10 and 3 with prolonged elevated ICP for 5, 6, and 11 days postoperatively were not shunted as their ICP and symptoms progressively normalized. The remaining 17/68 (25%) patients did not have a postoperative ICP > 20 cm H2O; 14 were discharged after resolution of symptoms and other clinical factors, 1 was shunted on postoperative day 3 due to persistent symptoms and a consistently large volume of CSF drainage, and 2 had a non-patent ETV with 1 undergoing shunt placement and the other discharged because of the absence of symptoms. The sensitivity of ventriculography was only 13%; however, the specificity was 98% and the accuracy 88%. After reviewing this series, the continued use of a postoperative EVD appears appropriate as the risk is low and it provides ventricular access to control ICP, thereby, improving patients' safety and reducing the need for CSF shunting on an urgent/emergent basis should the ETV prove to be unsuccessful. From our limited series, the usefulness of a 1-day postoperative ETV ventriculogram is less clear and would need confirmation with additional studies.


Local immunity and Ostertagia circumcincta: changes in the gastric lymph of immune sheep after a challenge infection.
Immunity to Ostertagia circumcincta was demonstrated in 5 previously infected sheep which were killed 10 days after challenge with 50 000 larvae. This immunity was expressed as a reduction in the number as well as the degree of development of the surviving parasites compared with those found in 6 control sheep. Gastric lymph was sampled from the immune group from 2 days before till 10 days after challenge and a secondary local immune response was detected. The main features of this response were a large increase in cell output in the lymph, especially in lymphoblasts and IgA-containing cells, which reached a peak on day 4 or 5, followed by a ten-fold increase in IgA immunoglobulin and IgA anti-worm antibody which reached a peak 7 or 8 days after challenge. The timing of these events suggested that the cellular, but not the IgA, response could have been involved in a putative mechanism which caused arrested development, although both components could have been implicated in mechanisms which may have caused expulsion of developing larvae.


Research on the mechanism of drug-drug interaction between salvianolate injection and aspirin based on the metabolic enzyme and PK-PD model: study protocol for a PK-PD trial.
Coronary heart disease (CHD) is a common cardiovascular disease accounting for 10-20% mortality by heart disease worldwide. The gold standard treatment to manage CHD is aspirin, which may prevent myocardial infarction and sudden death; however, long-term use of aspirin may increase its side effects. Currently, more and more clinicians are exploring different approaches to use the right combination of medicine to enhance the efficacy and reduce side effects. Salvianolate can significantly inhibit the aggregation and activation of platelets in patients with CHD; however, its optimum combination with western medicine is not established or supported by clinical trial results. This trial is a prospectively planned, open-labeled, parallel-grouped, single-centered clinical trial with aggregated pharmacodynamics-pharmacokinetics (PK-PD) data. All treatment courses will last for 10 days and blood sample will be acquired before administration on days 8, 9, and 10, and after administration at 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h on day 10. This trial uses PK-PD modeling to provide a description of the concentration-effect relationship and an estimate of pharmacological potency of the medicine. The primary outcome will be changes in aspirin esterase and catechol-o-methyltransferase (COMT) activity at different blood concentrations to determine the PK-PD characteristics of the combination of salvianolate and aspirin, followed by analysis of the correlation between exposure level and pharmacodynamic index of the medicines. This trial will aim to evaluate the relationship between changes in the pharmacokinetics and therapeutic effect index in the combined use of salvianolate and aspirin. It also discusses the possible mechanism of medicine combination in the treatment for CHD and provides an experimental basis for a clinically rational medicine combination. ClinicalTrials.gov, NCT03306550 . Registered on 9 October 2017. ClinicalTrials.gov https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007D8H&selectaction=Edit&uid=U0003QY8&ts=2&cx=oiuc9g.


Respiratory bronchiolitis: radiographic and CT findings in a pathologically proven case.
A small number of cases of cigarette-smoking-associated respiratory bronchiolitis (RB) with positive findings on the chest radiograph have been reported in the literature. High-resolution computed tomography (HRCT) findings are available in even fewer cases. We describe the case of an asymptomatic female smoker presenting with a reticulomicronodular infiltrate on a routine chest radiograph. High-resolution CT was characterized by ground-glass opacities and centrilobular micronodules with an upper lobe predominance. Surgical biopsy revealed peribronchiolar lesions, with accumulation of brown pigmented macrophages in the lumen of alveolar and bronchiolar lumen, consistent with the pathologic diagnosis of RB.


Concomitant Increase of OX40 and FOXP3 transcripts in peripheral blood of patients with breast cancer.
Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. To evaluate FOXP3 and OX40 transcripts in the peripheral blood mononuclear cells of women with breast cancer. Blood samples from 40 women with histologically-confirmed infiltrating ductal carcinoma of the breast and 40 healthy volunteer women without a history of malignancy or autoimmune disorders were collected. The abundance of FOXP3 and OX40 gene transcripts were determined by quantitative real-time PCR (qRT-PCR). There was a significant positive correlation between FOXP3 and OX40 gene expression in women with breast cancer in a stage dependent manner. This finding emphasizes the importance of T-regs as predominant targets for breast cancer immunotherapy.


Gelatin-bacterial cellulose composite sponges thermally cross-linked with glucose for tissue engineering applications.
Freeze-drying and thermal cross-linking techniques were used to prepare gelatin-bacterial cellulose (GB) composite sponges for potential application as scaffolds in tissue engineering. To avoid the use of toxic and costly cross-linking agents, glucose was used to cross-link the gelatin via the Maillard reaction. The effects of the weight ratio of gelatin to bacterial cellulose (BC) and the cross-linking conditions (temperature and duration) on the GB sponges were examined. An open and highly interconnected porous structure was attained for the GB sponge with a gelatin:BC weight ratio of 25:75 that was cross-linked at 140°C for 3h. Its high porosity, good swelling properties, good structural stability in water, non-toxicity and good biocompatibility against Vero cell are promising for its application as a scaffold for tissue engineering.


Marked increase of fibrin gel permeability with very low dose ASA treatment.
Previous data from our group show that acetylsalicylic acid (ASA), especially at low dose, alters the network structure of fibrin, rendering it more porous. The present study was performed to extend the dose-response curve for effects of ASA on fibrinogen clotting properties and to examine the variability of these effects during a 24-h dose interval. Fifteen healthy volunteers received ASA 37.5 mg daily (low dose) for 10 days and, after an interval of 2 weeks, 320 mg daily (medium dose) for 7 days, followed by a single bolus dose of 640 mg (high dose). The plasma fibrinogen concentrations were determined and the permeability of fibrin gels (Ks) was assayed with a recently modified flow measurement technique. Three-dimensional (3D) structure of the fibrin network was studied by confocal microscopy. ASA therapy did not influence fibrinogen concentrations. Compared to baseline, Ks levels were increased by 21% and 31% in samples during medium and high dose ASA treatment (p<0.01) and, even more markedly, by 44% (p<0.0001) with very low dose ASA treatment (p<0.01, compared to the higher doses). The effects of ASA on fibrin gel permeability were stable over a 24-h dose interval. During ASA treatment, thicker fibrin fibers and larger network pores with irregular structure were observed by confocal microscopy. Acetylation of lysine residues in the fibrinogen molecule may explain the alterations in its clotting property, resulting in altered fibrin gel permeability. The mechanism(s) behind the greater increase in fibrin gel permeability and alterations in 3D structure of the fibrin network observed, and why this phenomenon is more pronounced at low compared to intermediate or high ASA doses, deserve further investigations.


Sewage sludge ash to phosphorus fertiliser: variables influencing heavy metal removal during thermochemical treatment.
The aim of this study was to improve the removal of heavy metals from sewage sludge ash by a thermochemical process. The resulting detoxified ash was intended for use as a raw material rich in phosphorus (P) for inorganic fertiliser production. The thermochemical treatment was performed in a rotary kiln where the evaporation of relevant heavy metals was enhanced by additives. The four variables investigated for process optimisation were treatment temperature, type of additive (KCl, MgCl(2)) and its amount, as well as type of reactor (directly or indirectly heated rotary kiln). The removal rates of Cd, Cr, Cu, Ni, Pb, Zn and of Ca, P and Cl were investigated. The best overall removal efficiency for Cd, Cu, Pb and Zn could be found for the indirectly heated system. The type of additive was critical, since MgCl(2) favours Zn- over Cu-removal, while KCl acts conversely. The use of MgCl(2) caused less particle abrasion from the pellets in the kiln than KCl. In the case of the additive KCl, liquid KCl - temporarily formed in the pellets - acted as a barrier to heavy metal evaporation as long as treatment temperatures were not sufficiently high to enhance its reaction or evaporation.


ROCK inhibition produces anxiety-related behaviors in mice.
The role of Rho/Rho-associated kinase (ROCK) in regulating dendritic and axonal morphology during development has gained much attention. Very little is known, however, about the role of the Rho/ROCK pathway in emotional behavior. To investigate the role of ROCK in emotional behaviors. We examined how the ROCK inhibitor Y27632 affects the performance of mice on three behavioral tests that measure anxiety-related behaviors. In the elevated plus-maze test, Y27632 (10 nmol, intracerebroventricular) induced a significant decrease in the percentage of time spent in the open arms and in the percentage of entries into open arms. In the fear conditioning test, Y27632-treated mice froze significantly more often and longer than did saline-treated mice. In the hole-board test, Y27632 significantly suppressed head-dipping behavior in Y27632-treated mice than in saline-treated mice. On the other hand, Y27632 did not produce on spontaneous alteration performance in the Y-maze test. These results indicate that ROCK inhibition increased anxiety-related behaviors. Our findings suggest that the ROCK pathway is involved in the expression of anxiety- and fear-related behaviors. Furthermore, we propose that if the Rho/ROCK pathway plays an important role in mediating anxiety-related behaviors in humans, it may prove to be a novel system for anxiolytics to target.


Xylanases from marine microorganisms: A brief overview on scope, sources, features and potential applications.
Global economic growth often leads to depletion of raw materials and generation of greenhouse gases, as industry manufactures goods at ever increasing levels to keep up with the demand. The currently implemented production processes mostly rely on non-renewable resources, they suffer from high energy consumption, and generate waste that often has a negative environmental impact. Eco-friendly production methods are therefore intensely searched for. Among them, enzyme-based processes are appealing, because of their high substrate and reaction specificity and the relatively mild operation conditions required by these catalysts. In addition, renewable raw materials that allow sustainable production processes are also widely explored. Marine xylanases, which catalyze the hydrolysis of xylan, the major component of lignocellulose, are promising biocatalysts. Since they are produced by microorganisms that thrive in a wide variety of environmental conditions, the enzymes may be active at widely different ranges of pH, temperature, and salt concentrations. These properties are important for their successful application in various industrial processes, such as production of bioethanol, bleaching of paper and pulp, and in the food and feed sector. The present work gives a brief overview of marine sources of xylanases, their classification and features, and of the potential applications of these marine enzymes, especially in sustainable processes in the scope of circular economy.


The entorhinal cortex and a delayed non-matching-to-place task in mice: emphasis on preoperative training and presentation procedure.
This study examined the effects of ibotenate lesions of the entorhinal cortex (EC) on performance of a spatial recognition memory task, the delayed non-matching-to-place task (DNMTP), varying in level of difficulty according to the number of interpolated arm visits between sample-place presentation and subsequent recognition in mice. Results of experiment 1, designed to test the rate of acquisition of the task, showed that experimental animals were impaired in the basic non-matching task. However, with further training they were able to learn the task. Impairments were also observed when the amount of interpolating information inserted was gradually increased, and then all problem difficulties were pseudorandomly tested. There was no measurable recovery of function over time when the animals were retested on the task approximately 1 month later. Experiment 2 showed that the animals that received extensive training on the task prior to lesions of the EC were only transiently impaired in the DNMTP task. These data suggest that the EC plays an important role in acquisition rather than retention of the spatial recognition memory task.


T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.
The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8+ T cell response to the highly effective YF-17D vaccine. We discover that these A2/LLW-specific CD8+ T cells are highly biased for the TCR α chain TRAV12-2. This bias is already present in A2/LLW-specific naïve T cells before vaccination with YF-17D. Using CD8+ T cell clones, we show that TRAV12-2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline-encoded complementarity determining region (CDR) 1α loop of TRAV12-2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T-cell responses specific for the A2/LLW epitope.


High-purity isolation of anthocyanins mixtures from fruits and vegetables--a novel solid-phase extraction method using mixed mode cation-exchange chromatography.
Research on biological activity of anthocyanins requires the availability of high purity materials. However, current methods to isolate anthocyanins or anthocyanin mixtures are tedious and expensive or insufficient for complete isolation. We applied a novel cation-exchange/reversed-phase combination solid-phase extraction (SPE) technique, and optimized the use of water/organic buffer mobile phases to selectively separate anthocyanins. Crude extracts of various representative anthocyanin sources were purified with this technique and compared to 3 commonly used SPE techniques: C(18), HLB, and LH-20. Purified anthocyanin fractions were analyzed with high performance liquid chromatography (HPLC) coupled to photodiode array (PDA) and mass spectrometry (MS) detectors and by Fourier transform infrared (FT-IR) spectroscopy. The UV-visible chromatograms quantitatively demonstrated that our novel technique achieved significantly higher (P<0.05) anthocyanin purity than the C(18) cartridge, the next best method, for 11 of the 12 anthocyanin sources tested. Among them, eight were purified to greater than 99% purity (based on UV-visible chromatograms). The new method efficiently removed non-anthocyanin phenolics. MS and FT-IR results semi-quantitatively confirmed extensive reduction of impurities. Due to strong ionic interaction, our sorbent capacity was superior to others, resulting in the highest throughput and least use of organic solvents. This new methodology for isolation of anthocyanin mixtures drastically increased purity and efficiency while maintaining excellent recovery rate and low cost. The availability of high purity anthocyanin mixtures will facilitate anthocyanin studies and promote the application of anthocyanins in the food and nutraceutical industries.


Safe usage of cosmetics in Bangladesh: a quality perspective based on microbiological attributes.
The present review attempted to emphasize on the microbiological quality of the commonly used cosmetics item by the majority of the Bangladeshi community. The abundance of contaminating microorganisms has been quantitatively discussed and the possible health risk has been focused upon usage of these items. Only a very few research efforts have been conducted on the cosmetic items in Bangladesh so far. The microbiological contamination aspects have been portrayed in this review using the information collected from a substantial number of cosmetic items which were earlier subjected to extensive microbiological and biochemical analyses. The prevalence of bacteria, fungi and the specific pathogenic microorganisms has been discussed based on research so far locally conducted on the finished items sold in markets, especially within the Dhaka metropolis. The laboratory scale experiments revealed the presence of enormous number of bacteria, actinomycetes and fungi within the commonly used cosmetics. Conversely, the anti-bacterial activity was noticed in some of the products which might be in favor of the user safety. The prevalence of pathogenic microorganisms in the cosmetic items certainly raises a substantial public health issue. The necessity of the routine microbiological testing of the commonly used cosmetic items as well as the legislative measures to mitigate the contamination problem is thus of great significance.


The modern Dental Cast Reference Collection from the University of Coimbra, Portugal.
Identified skeletal and skull collections are centrepiece for research in biological anthropology. However, until recently, the same relevance has not been placed on dental cast collections. This perspective evolved, mainly, with the research on population variation and human identification through dental characteristics. While dental collections exist throughout the world, their reports and documentation are scarce in the literature. This work aims to present the new Dental Cast Reference Collection - University of Coimbra (DCRC - UC) housed in the Laboratory of Prehistory of the Department of Life Sciences of the University of Coimbra (Portugal). The modern dental cast collection (DCRC - UC) was created in 2016 for teaching and research purposes. The casts were obtained from volunteers who answered a brief questionnaire (sex, age, nationality, previous orthodontic and dental data) after informed consent. The collection includes the dental casts of 90 adult individuals of both sexes: 69 females and 21 males. The volunteers were students, teachers and visiting researchers of the Department of Life Sciences of the University of Coimbra. Age ranges from 17 to 49 years, including individuals of Portuguese (n = 79) and non-Portuguese nationality (n = 11). Lastly, the strategy of the conservation and storage conditions of the casts are underlined, a vital aspect of this working collection, emphasizing its protection while also allowing it to function as a usable resource. Currently, the addition of new individuals to the dental cast collection is paused due to the COVID-19 pandemic, however the future work and expected expansion will require new logistic solutions. The DCRC - UC is an invaluable resource to both research and teaching activities.


Epidemiology and outcomes of allergic bronchopulmonary aspergillosis in the elderly.
The prevalence and outcomes of allergic bronchopulmonary aspergillosis (ABPA) in the elderly remain unknown. We reviewed our database to identify the proportion of subjects diagnosed with ABPA at ≥60 years of age (ABPA-elderly). We compared the clinical features, treatment and outcomes of ABPA-elderly versus the non-elderly (ABPA diagnosed at <60 years of age). Between 2007 and 2019, we encountered 810 ABPA subjects with a mean age of 34.9 years (49.4% women). Of these, 43 (5.3%) were aged ≥60 years (ABPA-elderly). There was a trend towards lower median (interquartile range [IQR]) serum total IgE (4900 [2659-10000] vs. 7156 [23360-11963] IU/mL; P = .06) and Aspergillus fumigatus-specific IgE (12.3 [4.8-29.6] vs. 22.4 [7.7-41.5] kUA/L; P = .06) in the elderly than the non-elderly. Eosinophil counts were similar in the two groups. The median [IQR] number of segments involved by bronchiectasis (5 [2-9] vs. 7 [4-11]) was significantly lower in the ABPA-elderly (P = .001). The proportion of subjects experiencing ABPA exacerbations was significantly (P = .047) lower in the elderly (25.6%) vs. the non-elderly (40.8%). There was also a tendency towards a lower mean number of exacerbations in the elderly (155 vs. 208 exacerbation per 1000 person-years) than the non-elderly (P = .09). There was also a trend towards longer mean time to first exacerbation in the ABPA-elderly than the non-elderly (1612 vs. 1159 days). ABPA was uncommon in the elderly. The bronchiectasis is less extensive with a trend towards lower immunological severity and fewer exacerbations in the elderly than the non-elderly subjects with ABPA.


Further studies on the electrophoretic pattern of albumin in diabetic sera.
Human sera from normal subjects and diabetic patients were electrophoresed in an urea-containing gel; polyacrylamide gel and cellulose acetate membrane. In polyacrylamide gel, normal serum exhibited the fast migrating Band 2 and the slower migrating albumin Bands 4 and 5 after overnight fasting and also after glucose administration. In diabetic serum Bands 4 and 5 did not appear before or after glucose administration in low mercaptoethanol gel which abnormality resembled the pattern in C57BL/KsJ-db/db mice. In high mercaptoethanol gel, about half of the diabetic sera exhibit a delay in appearance of Bands 4 and 5, i.e., Bands 4 and 5 were not observed 30--60 min after glucose administration, which seems to resemble the pattern in C57BL/6J-ob/ob mice. Conditions of electrophoresis in urea-submerged cellulose acetate membrane (species of buffer systems, pH, ion concentration, mercaptoethanol, ethylene-diaminetetraacetic acid, Ca2+ ion, urea concentration, etc.) were observed in relation to albumin sub-separation. At pH 8.6 with barbital buffer, albumin separated into two bands, and at pH 10.6 with glycine buffer, albumin separated into four bands. Almost all diabetic sera (ca. 80%) exhibited different electrophoretic patterns from that of normal serum.


Mandibular fracture in single-humped camels.
To report the causes and classification of mandibular fractures in dromedary camels and outcome after treatment. Single-humped camels (n = 116) with mandibular fracture. At admission, cause, site, classification, and radiography of mandibular fractures were recorded. Factors affecting fracture healing were analyzed. Biting was the main cause of mandibular fractures in camels, which occurred more commonly in older males (P = .001) than in females. Open fractures were more common than closed ones (92.2% versus 7.8%, P = .0001) and single fractures were more frequent (82%) than multiple and comminuted fractures (18%; P = .001). Fractures were treated by interdental wiring (91.2%) or U-shaped aluminum bar (8.8%) and healing occurred in most (83.2%) fractures. In dromedary camels, mandibular fracture is most commonly caused by bites and can be successfully repaired by interdental wiring or a U-bar technique with good outcome.


Identification of direct competition for, and indirect influences on, striatal muscarinic cholinergic receptors: in vivo [3H]quinuclidinyl benzilate binding in rats.
[3H]Quinuclidinyl benzilate (QNB) binds to specific muscarinic receptors of rat striatum, in vivo. The binding is saturable and displaceable by muscarinic drugs. Clozapine and thioridazine are unique antipsychotic agents with low liability for extrapyramidal side-effects, and both displaced ONB, while several other neuroleptics did not. In addition to this apparent direct competition for cholinergic receptors, morphine and amphetamine increased ONB binding by indirect influences on muscarinic receptors. In vivo QNB binding not only confirms in vitro findings, but it also detects indirect, probably transsynaptic, alterations of muscarinic cholinergic receptor dynamics.


The impact of multidisciplinary team conferences in urologic cancer in a tertiary hospital.
Multidisciplinary team (MDT) conferences are currently the standard of care in cancer patients' management. Despite evidence supporting benefits to the majority of malignancies, a paucity of data exists examining the impact in urinary and male genital cancers. This study aims to evaluate the impact of MDT conferences in urologic cancer practice. Clinical plans discussed in urologic MDT conferences in Centro Hospitalar Universitário de Lisboa Central between January 2019 and December 2019 were retrospectively analysed. Clinical plans were categorized as accepted, changed, rejected (cases that had to be re-presented to the MDT because of insufficient staging or administrative issues) or no plan. MDT conferences' impact was assessed according to type of consultation, referral medical specialty and primary tumour type. 710 clinical plans were discussed at the MDT conferences. 61.8% were accepted, 10.6% were changed, 16.5% were rejected and 11.1% of cases referred to MDT discussion had no defined clinical plan. First consultations had a higher rate of accepted clinical plans (63.4%) versus subsequent consultations (56.4%). Referrals by the urology specialty had the highest rate of acceptances (64.3%). On the stratification by primary tumour site, testicular cancer had the highest acceptance rate (70.3%), whereas bladder cancer had the lowest (47.8%). MDT conferences had an important impact in the management of 38.2% of cases. Therefore, all patients with urologic malignancies should be referred to MDT review to ensure optimal clinical care.


Knockdown of lncRNA HCG11 suppresses cell progression in ovarian cancer by modulating miR-144-3p/PBX3.
LncRNA HCG11 has been confirmed to act as a crucial role in several human cancers. Nevertheless, to our knowledge, the function of HCG11 on the progression of ovarian cancer (OC) has not been studied. This article is designed to explore the mechanism and role of HCG11 in the tumorigenesis and development of OC. RT-qPCR analysis was applied to detect the expression of HCG11, miR-144-3p and PBX3 in OC tissues and cell lines. MTT assay and transwell assay were opted to measure the cell viability of OC cells. The protein expression level of PBX3 was measured by Western blot assay. Dual-Luciferase reporter assay was carried out to assess the correlation between HCG11, miR-144-3p and PBX3. The upregulated of HCG11 was observed in OC tissues and OC cell lines. Moreover, miR-144-3p was down expressed in OC tissues and cell lines. Functionally, the knockdown of HCG11 prevented cell viability of SKOV3 cells, while miR-144-3p inhibitor abrogated the suppressor on cell progression. Furthermore, PBX3 was verified to be a target gene of miR-144-3p. In addition, PBX3 knockdown prevented the cell progression of SKOV3 cells. These data displayed that the knockdown of HCG11 prevented cell progression in OC by sponging miR-144-3p and downregulating PBX3. All results revealed that HCG11 can be a potential therapeutic target for OC therapy.


Value of contrast-enhanced ultrasound using perflubutane microbubbles for diagnosing liver fibrosis and cirrhosis in rats.
We determined the ability of contrast-enhanced ultrasound (CEUS) using perflubutane microbubbles to diagnose liver fibrosis and cirrhosis in rats using histology as the reference standard. Fibrosis was induced by oral administration of carbon tetrachloride to 32 Wistar rats. Features with baseline ultrasound (US) and enhancement level of liver and spleen with CEUS were obtained. In the post-vascular phase of CEUS, images of normal livers (n = 5) were significantly brighter than images of fibrotic (n = 6) and cirrhotic livers (n = 13) by quantitative analysis (all p < 0.05). The contrast between livers and spleens in rats with cirrhosis was quantitatively greater than that in normal rats and rats with fibrosis (all p < 0.05). Compared with US, CEUS improved sensitivity from 63% to 84% and accuracy from 71% to 88%. Specificity was 100% for both. The increased value of CEUS in diagnosing liver fibrosis and cirrhosis in rats supports its evaluation in clinical trials.


Animal experimentation in snake venom research and in vitro alternatives.
Current experimental techniques used in snake venom research (with and without the use of animals) are reviewed. The emphasis is on the reduction of the use of animals in the development of antivenoms for the clinical treatment of snakebite. Diagnostic and research techniques for the major pathologies of envenoming are described and those using animals are contrasted with non-sentient methods where possible. In particular, LD50 and ED50 assays using animals (in vivo) and fertilised eggs (in vivo, non-sentient) are compared as well as in vitro procedures (ELISA and haemolytic test) for ED50 estimations. The social context of antivenom production, supply and demand is outlined together with the consequent tension between the benefits derived and the increase in opposition to experiments on animals. Stringent regulations governing the use of animals, limited research funds and public pressure all focus the need for progress towards non-animal, or non-sentient, research methods. Some achievements are noted but success is hampered by lack of detailed knowledge of the many constituents of venom which have to be assessed as a whole rather than individually. The only way to evaluate the net pathological effect of venom is to use a living system, usually a rodent, and similarly, the efficacy of antivenoms is also measured in vivo. The pre-clinical testing of antivenoms in animals is therefore a legal requirement in many countries and is strictly monitored by government authorities. New technologies applied to the characterisation of individual venom proteins should enable novel in vitro assays to be designed thus reducing the number of animals required. In the meantime, the principles of Reduce, Refine and Replace relating to animals in research are increasingly endorsed by those working in the field and the many agencies regulating ethical and research policy.


Insomnia.
Insomnia is a symptom requiring medical investigation and the elimination of external and physical causes. Anxiety and/or depression have been shown to be present in most of the patients complaining of inability to sleep. Antidepressant medication with sedating potential is very effective in patients with depressive symptoms when most of the dose is given at bed-time. Most of the sedative-hypnotic drugs disturb the qualitative aspects of sleep and many rapidly produce tolerance. Flurazepam has been shown to be the drug of choice for purely symptomatic insomnia. Except in very transient situational stresses, a psychotherapeutic relationship to investigate the causes of the insomnia may be the most important aspect of the treatment program.