Efficient hydrogen evolution in transition metal dichalcogenides via a simple one-step hydrazine reaction.
Hydrogen evolution reaction is catalysed efficiently with precious metals, such as platinum; however, transition metal dichalcogenides have recently emerged as a promising class of materials for electrocatalysis, but these materials still have low activity and durability when compared with precious metals. Here we report a simple one-step scalable approach, where MoOx/MoS2 core-shell nanowires and molybdenum disulfide sheets are exposed to dilute aqueous hydrazine at room temperature, which results in marked improvement in electrocatalytic performance. The nanowires exhibit ∼100 mV improvement in overpotential following exposure to dilute hydrazine, while also showing a 10-fold increase in current density and a significant change in Tafel slope. In situ electrical, gate-dependent measurements and spectroscopic investigations reveal that hydrazine acts as an electron dopant in molybdenum disulfide, increasing its conductivity, while also reducing the MoOx core in the core-shell nanowires, which leads to improved electrocatalytic performance.


Clinical phenotyping in sarcoidosis using cluster analysis.
Most phenotyping paradigms in sarcoidosis are based on expert opinion; however, no paradigm has been widely adopted because of the subjectivity in classification. We hypothesized that cluster analysis could be performed on common clinical variables to define more objective sarcoidosis phenotypes. We performed a retrospective cohort study of 554 sarcoidosis cases to identify distinct phenotypes of sarcoidosis based on 29 clinical features. Model-based clustering was performed using the VarSelLCM R package and the Integrated Completed Likelihood (ICL) criteria were used to estimate number of clusters. To identify features associated with cluster membership, features were ranked based on variable importance scores from the VarSelLCM model, and additional univariate tests (Fisher's exact test and one-way ANOVA) were performed using q-values correcting for multiple testing. The Wasfi severity score was also compared between clusters. Cluster analysis resulted in 6 sarcoidosis phenotypes. Salient characteristics for each cluster are as follows: Phenotype (1) supranormal lung function and majority Scadding stage 2/3; phenotype (2) supranormal lung function and majority Scadding stage 0/1; phenotype (3) normal lung function and split Scadding stages between 0/1 and 2/3; phenotype (4) obstructive lung function and majority Scadding stage 2/3; phenotype (5) restrictive lung function and majority Scadding stage 2/3; phenotype (6) mixed obstructive and restrictive lung function and mostly Scadding stage 4. Although there were differences in the percentages, all Scadding stages were encompassed by all of the phenotypes, except for phenotype 1, in which none were Scadding stage 4. Clusters 4, 5, 6 were significantly more likely to have ever been on immunosuppressive treatment and had higher Wasfi disease severity scores. Cluster analysis produced 6 sarcoidosis phenotypes that demonstrated less severe and severe phenotypes. Phenotypes 1, 2, 3 have less lung function abnormalities, a lower percentage on immunosuppressive treatment and lower Wasfi severity scores. Phenotypes 4, 5, 6 were characterized by lung function abnormalities, more parenchymal abnormalities, an increased percentage on immunosuppressive treatment and higher Wasfi severity scores. These data support using cluster analysis as an objective and clinically useful way to phenotype sarcoidosis subjects and to empower clinicians to identify those with more severe disease versus those who have less severe disease, independent of Scadding stage.


Contrasting pressure-support ventilation and helium-oxygen during exercise in severe COPD.
Helium-oxygen mixtures and pressure-support ventilation have been used to unload the respiratory muscles and increase exercise tolerance in COPD. Considering the different characteristics of these techniques, we hypothesized that helium-oxygen would be more effective in reducing exercise-induced dynamic hyperinflation than pressure-support. We also hypothesized that patients would experience greater increases in respiratory rate and minute ventilation with helium-oxygen than with pressure-support. The hypotheses were tested in ten patients with severe COPD (FEV(1) = 28 ± 3% predicted [mean ± SE]) during constant-load cycling (80% maximal workrate) while breathing 30% oxygen-alone, helium-oxygen, and pressure-support in randomized order. As hypothesized, helium-oxygen had greater impact on dynamic hyperinflation than did pressure-support (end-exercise; p = 0.03). For the most part of exercise, respiratory rate and minute ventilation were greater with helium-oxygen than with pressure-support (p ≤ 0.008). During the initial phases of exercise, helium-oxygen caused less rib-cage muscle recruitment than did pressure-support (p < 0.03), and after the start of exercise it caused greater reduction in inspiratory reserve volume (p ≤ 0.02). Despite these different responses, helium-oxygen and pressure-support caused similar increases in exercise duration (oxygen-alone: 6.9 ± 0.8 min; helium-oxygen: 10.7 ± 1.4 min; pressure-support: 11.2 ± 1.6 min; p = 0.003) and similar decreases in inspiratory effort (esophageal pressure-time product), respiratory drive, pulmonary resistance, dyspnea and leg effort (p < 0.03). In conclusion, helium-oxygen reduced exercise-induced dynamic hyperinflation by improving the relationship between hyperinflation and minute ventilation. In contrast, pressure-support reduced hyperinflation solely as a result of lowering ventilation. Helium-oxygen was more effective in reducing exercise-induced dynamic hyperinflation in severe COPD, and was associated with greater increases in respiratory rate and minute ventilation than pressure-support.


Direct Probing of Dispersion Quality of ZrO2 Nanoparticles Coated by Polyelectrolyte at Different Concentrated Suspensions.
This study reports useful application of the electrokinetic sonic amplitude (ESA) technique in combination with rheometry and electron microscopy techniques for direct probing the stability of low and high-concentrated zirconia (ZrO2) nanosuspensions in the presence of an alkali-free anionic polyelectrolyte dispersant Dolapix CE64. A comparative study of the electrokinetic characteristics and the rheological behavior of concentrated ZrO2 nanosuspensions has been done. Good agreement was obtained from relationship between the electrokinetic characteristics (zeta potential, ESA signal), viscosity, and its pH dependence for each concentrated ZrO2 nanosuspension with different dispersant concentration in the range of 0.9-1.5 mass%. A nanoscale colloidal hypothesis is proposed to illustrate that the addition of different amounts of dispersant influences on both the stability and the electrokinetic and rheological properties of concentrated ZrO2 nanosuspensions. It is found that an optimum amount of 1.4 mass% dispersant at the inherent pH (>9.2) can be attached fully onto the nanoparticles with sufficient electrosteric dispersion effects, suitable for casting applications. Supplementary scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM) analyses followed by colorization effect were taken to verify the visible interaction between dispersant and nanoparticles surfaces. SEM and HR-TEM images proved the existence of visible coverage of dispersant on the surface of individual nanoparticles and showed that thin polyelectrolyte layers were physically bound onto the particles' surfaces. This study will be of interest to materials scientists and engineers who are dealing with dispersion technology, nanoparticle surface treatments, functionalization, characterization, and application of bio/nanoparticle suspensions at various concentrations using different types of polymers.


Adhesion and cohesion in structures containing suspended microscopic polymeric films.
This paper presents a novel technique for the characterization of adhesion and cohesion in suspended micro-scale polymeric films. The technique involves push-out testing with probes that are fabricated using focused ion beam techniques. The underlying stresses associated with different probe tip sizes were computed using a finite element model. The critical force for failure of the film substrate interface is used to evaluate adhesion, while the critical force for penetration of the film determines cohesion. When testing a standard material, polycarbonate, a shear strength of approximately 70 MPa was calculated using the Mohr-Coulomb theory. This value was shown to be in agreement with the results in the literature. The technique was also applied to the measurement of adhesion and cohesion in a model drug-eluting stent (the Nevo™ Sirolimus Eluting Coronary Stent) containing suspended microscopic polymeric films in metallic Co-Cr alloy reservoirs. The cohesive strength of the formulation was found to be comparable with that of plastics such as those produced by reaction injection molding and high-density polyethylene.


Narcotic agonist and antagonist potencies of a homologous series of N-alkyl-norketobemidones measured by the guinea-pig ileum and mouse vas deferens methods.
The narcotic agonist and antagonist potencies of the series of N-alkyl-norketobemidones from norketobemidone to decylnorketo-bemidone have been determined. The values obtained in the electrically stimulated preparations of the guinea-pig ileum and the mouse vas deferens are closely correlated. The agonist potencies observed in the guinea-pig ileum agree well with those found in the mouse hot-plate test (Oh-ishi & May) and those obtained by determining the inhibition of naloxone binding in brain homogenates (Wilson, Rogers, Pert & Snyder). The antagonist potencies in the guinea-pig ileum and, to a lesser extent, those in the mouse vas deferens agree with the values obtained in the morphine-dependent monkey.


Caregivers' predispositions and perceived organizational expectations for the provision of social support to nursing home residents.
This article presents the results of an investigation of caregivers' provision of supportive communication to nursing home residents. Five primary conclusions are drawn from the data: (a) Caregivers value providing affective over instrumental support; (b) caregivers believe they place more importance on supportive communication than their organizations; (c) role conflict is emotionally exhausting, but does not affect caregivers' self-evaluations or perceptions of residents; (d) caregivers' depersonalization of patients is related to their desire to communicate instrumental support; and (e) caregivers feel more accomplished when they believe their organization values supportive communication with patients. The implications of these findings for social support, caregivers' burnout, and nursing homes are discussed.


[Do electrostatic interactions determine glycation of hyaluronidase derivatives with N-acethylhexosamines?].
Glycation of native hyaluronidase and its chondroitin sulfate modified form was studied with N-acethylglucosamine, N-acethylgalactosamine and their mixture, as well as hyaluronan fragments (n = 0-4) and their mixture. The modified form of hyaluronidase exhibited higher inactivation than native enzyme. The chondroitin sulfate modification of hyaluronidase altered its surface electrostatic potential, but this effect was not crucial for inactivation of hyaluronidase derivatives. The observed picture of the glycation action on hyaluronidase derivatives was opposite for glycation with mono- and di-saccharides. Such results give us the informative enzyme test for in vivo system in order to determine the dominant type of glycation agents in bloodstream and its origin.


Establishment and clinical application of SARS-CoV-2 catch column.
A certain number of patients with coronavirus disease 2019 (COVID-19), particularly those who test positive for SARS-CoV-2 in the serum, are hospitalized. Further, some even die. We examined the effect of blood adsorption therapy using columns that can eliminate SARS-CoV-2 on the improvement of the prognosis of severe COVID-19 patients. This study enrolled seven patients receiving mechanical ventilation. The patients received viral adsorption therapy using SARS-catch column for 3 days. The SARS-catch column was developed by immobilizing a specific peptide, designed based on the sequence of human angiotensin-converting enzyme 2 (hACE2), to an endotoxin adsorption column (PMX). In total, eight types of SARS-CoV-2-catch (SCC) candidate peptides were developed. Then, a clinical study on the effects of blood adsorption therapy using the SARS-catch column in patients with severe COVID-19 was performed, and the data in the present study were compared with historical data of severe COVID-19 patients. Among all SCC candidate peptides, SCC-4N had the best adsorption activity against SARS-CoV-2. The SARS-catch column using SCC-4N removed 65% more SARS-CoV-2 than PMX. Compared with historical data, the weaning time from mechanical ventilation was faster in the present study. In addition, the rate of negative blood viral load in the present study was higher than that in the historical data. The timely treatment with virus adsorption therapy may eliminate serum SARS-CoV-2 and improve the prognosis of patients with severe COVID-19. However, large-scale studies must be performed in the future to further assess the finding of this study (jRCTs052200134).


A minimally invasive approach to the infected aorta with novel endovascular use of biocomposite antibiotic material.
We have presented the case of a symptomatic, primarily infected aortic pseudoaneurysm treated with endovascular stent graft exclusion and adjunctive use of a long-acting biocomposite antibiotic material injected directly into the pseudoaneurysm sac. We have described preparation of the biocomposite antibiotic material and the catheter-directed delivery technique in detail. Although the use of long-acting antibiotic materials such as antibiotic beads has been well described when performing open surgery in an infected field, the application of these materials in endovascular procedures has been less certain. The techniques we have described have the potential to promote field sterilization in a minimally invasive manner for patients with aortic infections who could be poor candidates for open surgery.


Silica nano supra-assembly for the targeted delivery of therapeutic cargo to overcome chemoresistance in cancer.
Cancer cells become resistant over the period to chemotherapeutic drugs and pose a challenging impediment for oncologists in providing effective treatment. Nanomedicine allows to overcome chemoresistance and is the focus of our investigation. Silica nanostructures have been highlighted as an interesting drug delivery platform in vitro and in vivo applications. Here we show the validity of nanomedicine approach for targeted chemotherapeutic cargo delivery to overcome chemoresistance in cancer cells both in vitro and in vivo. For demonstrating the concept, we functionalised ∼100 nm long porous silica nanoparticles (∼20 nm diameter ordered pore structure) by conjugating anticancer drug, cytochrome c enzyme and dual-function anticancer aptamer AS1411 in single supra-assembled nanocargos. The supra-assembly on the porous silica nanostructure allows for a high loading of catalytic enzyme cytochrome c, anticancer drug and aptamer. The silica supra-assembly is characterized by transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area analysis. Conjugation of cargoes has been monitored at each step by UV-vis and Fluorescence spectroscopy. Finally, the constructed supra-assembled nanocarrier tested on chemoresistance colon cancer (HCT116) cells. A pH-responsive, intracellular theranostic cargo delivery has been achieved and the triple action of the nanocargo made an efficient killing of drug resistance colon cancer cells in vitro (∼ 92% cell death) through triplex therapy effects by supressing the P-glycoprotein (P-gp) level. Furthermore, in vivo animal toxicity studies demonstrated, the supra-assembled nanocargos have encouraging safety index to be used in cancer therapy and drug delivery applications.


Anisotropic material behaviours of soft tissues in human trachea: an experimental study.
Human trachea is a multi-component structure composed of cartilage, trachealis muscle, mucosa and submucosa membrane and adventitial membrane. Its mechanical properties are essential for an accurate prediction of tracheal deformation, which has a significant clinic relevance. Efforts have been made in quantifying the material behaviour of tracheal cartilage and trachealis muscle. However, the material behaviours of other components have been least investigated. Three human cadaveric trachea specimens were used in this study. Trachealis muscle, mucosa and submucosa membrane and adventitia membrane were excised to perform the uniaxial test in axial and circumferential directions. In total, 72 tissue strips were prepared and tested. Tangent modulus was used to quantified the stiffness of each tissue strip at various stretch levels. The obtained results indicated that all types of tracheal soft tissues were highly non-linear and anisotropic. Trachealis muscle in the circumferential direction had the most excellent extensibility; and the adventitial collagen membrane in the circumferential direction was the stiffest. This study is helpful in understanding the material behaviour of trachea. Obtained results can be used for computational and analytic modelling to quantify the tracheal deformation.


Determination of defect densities from spatiotemporally resolved optical-laser induced damage measurements.
A procedure is developed to retrieve defect densities of optical coatings and surfaces from spatiotemporally resolved optical-laser induced damage (STEREO-LID) measurements. In STEREO-LID, the temporal onset and location of nanosecond laser damage initiation is measured for each excitation event. The power of STEREO-LID relative to traditional damage tests resulting in damage probabilities is characterized with LID data from Monte Carlo simulations.


Polymerization Properties of n-Butyl Cyanoacrylate Mixed with Ethiodized Oil in the Lymphatic System: In Vivo Investigation in a Rabbit Model.
To evaluate the polymerization properties of a mixture of n-butyl cyanoacrylate (nBCA) and ethiodized oil in the lymphatic system using an animal model. Nineteen male Japanese White rabbits underwent 28 lymphatic embolization procedures under fluoroscopic guidance using manually injected mixtures of nBCA and ethiodized oil at ratios of 1:2 (nBCA density of 33%), 1:4 (20%), 1:6 (14%), and 1:8 (11%) via the popliteal lymph node. The time required for polymerization and the distance traveled by the mixture were evaluated and compared among the groups using the Kruskal-Wallis test. Histopathologic intergroup comparisons and time-course changes were also evaluated using embolized lymph nodes. Among 23 successful procedures, the mean polymerization times were 14 ± 3, 88 ± 93, 331 ± 292, and 932 seconds ± 540 and the mean distances traveled were 13 ± 10, 31 ± 44, 85 ± 89, and 108 mm ± 35 in the 33% (n = 5), 20% (n = 6), 14% (n = 6), and 11% (n = 6) groups, respectively. The 11% group demonstrated a significantly longer polymerization time than the 33%, 20%, and 14% groups and distance traveled than the 33% group. Pathologically, the embolized lymph nodes showed inflammatory changes and massive necrosis regardless of the nBCA density. Polymerization times and distances traveled were increased when nBCA was diluted with increasing quantitites of ethiodized oil in this rabbit model of lymphatic embolization. These relationships should be considered when dilution is prescribed for clinical use.


The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma.
To determine whether the addition of metronomic chemotherapy improved outcome for dogs with splenic haemangiosarcoma treated with splenectomy and adjuvant maximum tolerated dose chemotherapy. Medical records were examined retrospectively for dogs with splenic haemangiosarcoma that had undergone splenectomy followed by anthracycline-based chemotherapy. Thirty-nine dogs underwent splenectomy followed by maximum tolerated dose chemotherapy with an anthracycline, cyclophosphamide, or both (Group 1). Twenty-two dogs underwent splenectomy followed by adjuvant maximum tolerated dose chemotherapy with an anthracycline, cyclophosphamide, or both, plus metronomic chemotherapy (Group 2). Dogs in both groups were further separated into those treated with either maximum tolerated dose anthracycline or maximum tolerated dose anthracycline and cyclophosphamide. Median progression-free survival was 165 days and median overall survival time was 180 days in Group 1. Median progression-free survival was 185 days and median overall survival time was 212 days in Group 2. In both groups, the overall survival was shorter in dogs that had received maximum tolerated dose cyclophosphamide. The addition of metronomic to maximum tolerated dose chemotherapy protocols does not appear to improve outcome in dogs with splenic haemangiosarcoma treated with splenectomy and maximum tolerated dose chemotherapy.


Potentiating interactions between medullary serotonin and thyrotropin-releasing hormone-induced gastric erosions in rats.
The central interaction between 5-HT and exogenous and endogenous thyrotropin-releasing hormone (TRH)-induced gastric lesions was investigated in conscious rats. Intracisternal injection (i.c.) of the TRH analog, RX 77368, (2.5 nmol) in indomethacin (2 mg/kg, i.p.)-treated rats produced 1.4 +/- 0.1% of gastric corpus mucosal lesions which were aggravated by 30 and 208% by simultaneous i.c. injection 5-HT at 10 and 100 nmol, respectively, whereas i.v. 5-HT (100 nmol) had no effect. The 5-HT2/1c antagonist, ketanserin, given i.c. at 10 or 100 nmol reduced by 44 and 76%, respectively, cold restraint stress-induced 3.4 +/- 0.6% gastric lesions in indomethacin-pretreated rats whereas, when given i.v. (100 nmol), it was inactive. Ketanserin or 5-HT (100 nmol, i.c.) alone did not modify the gastric mucosa. The present data suggest a potentiating interaction between endogenous 5-HT and TRH which has implication in the understanding of medullary mechanisms involved in gastric lesion formation induced by cold restraint.


Competence profile of an in-house educator of professionals providing elderly care (ComPro project).
The main goal of the study, conducted within the multicenter ComPro project (Competence Profiles for Learning Supporters in Elderly Care) and funded by the Leonardo da Vinci Programme in 2006-2008, was to define the competences profile of a person responsible for the inhouse education of professionals caring for the elderly persons in social care institutions. The qualitative (3 focus group interviews) and quantitative (the KODE®X questionnaire) approach was used to study opinions of 106 care professionals and 39 managers in social care institutions, and 35 teachers in vocational schools for workers in social care about desired competences of an in-house educator. The factor analysis with Varimax rotation performed separately for each group of surveyed professionals showed 4 factors in each, which had different components with the highest correlation rates. In the managers group--factor 1 correlated most with communication and organisational competences; among care professionals--with professional knowledge and their job specific skills; among teachers--with social and didactical competences. The most expected competences were different in each position, what may reflect the need of creation of a job description and a post of an in-house educator in social care institutions.


Neural tumours of the neck presenting as thyroid nodules: a report of three cases.
Neural tumours of the neck may at times secondarily involve the thyroid and manifest clinically as thyroid nodules. On cytological evaluation these nodules may be confused with other spindle lesions of the thyroid. We report two cases of schwannoma and one case of a malignant peripheral nerve sheath tumour (MPNST) of the neck, which presented as thyroid nodules and evaluate the role of cytology in identifying these tumours. The thyroid nodules in all the three cases were sampled by the non-aspiration technique using a 23-gauge needle. Both alcohol-fixed and air-dried smears were prepared and stained by the Papanicolaou and May-Grünwald-Giemsa stains. Cytology smears and histology sections from the resected specimens were reviewed, and the findings noted. Both the cases of schwannoma were correctly identified on cytology while the case of MPNST could only be typed as a spindle cell tumour. However, on cytology it was not possible to state whether the tumours were thyroidal or extrathyroidal in origin. Schwannomas of the neck are easily identifiable on cytology compared with MPNST. However, cytology alone is not helpful in identifying the origin of these tumours. As primary neural tumours of the thyroid are rare, the possibility of a soft tissue neural tumour extending into the thyroid should always be ruled out while evaluating these cases.


Is there protective haplotype of dysbindin gene (DTNBP1) 3 polymorphisms for major depressive disorder.
Dysbindin gene has been repeatedly associated with psychiatric disorders and schizophrenia in particular. This study aimed to investigate the variants of dysbindin gene in major depressive disorder (MDD). One hundred and eighty eight patients with MDD and 350 controls were investigated for 4 variants within the dysbindin gene (rs3213207 A/G, rs1011313 C/T, rs760761 C/T, and rs2619522 A/C). Haplotype analyses revealed a significant association with MDD (p=0.0007, protective A-C-T-A and A-C-C-C haplotypes), in particular the effect was due to the rs760761 (C/T) and rs2619522 (A/C) haplotype (p=0.000026). These results suggest a protective effect of some dysbindin gene haplotypes on the development of MDD. Coupled with previous findings on schizophrenia, our finding suggests that dysbindin gene variants may have a role in the susceptibility to MDD. Adequately powered further studies in different ethnic groups are warranted.


Postmastectomy locoregional recurrence and distant metastasis in breast carcinoma patients.
The aim of this study was to investigate predictive factors related to distant recurrence (DR) and to determine whether an association exists between locoregional recurrence (LRR) and DR in 956 patients. The multivariate time-dependent Cox regression analysis showed that tumor size (>2 cm vs <or=2 cm; p<0.0001; Hazard Ratio [HR], 3.7; 95% Confidence Interval [CI], 2.2-6.0), pN status (pN(2/3) vs pN(1); p<0.0001; HR, 2.3; 95%CI, 1.7-3.1), lymphatic vascular involvement (yes vs no; p=0.001; HR, 1.7; 95%CI, 1.2-2.3) and LRR (yes vs no; p=0.001; HR, dependent on time) were the important prognostic factors for DR. This study confirms a time-dependent association between LRR and DR. A DR occurred immediately after LRR is strongly associated with the LRR, but this association decreases over time, and therefore, a DR occurred lately after LRR is, possibly, not related to this LRR.


CCR 20th Anniversary Commentary: Setting the Stage for Nanoparticle Albumin-Bound Paclitaxel-How Far Science Has Come.
In this phase I pharmacokinetic study of ABI-007, which was published in the May 1, 2002, issue of Clinical Cancer Research, Ibrahim and colleagues provided the framework needed for subsequent studies to confirm the benefits of ABI-007 over solvent-based formulations. Since the study's publication, experiments have highlighted the importance of drug-delivery systems, the immune system in cancer biology, and immunoregulatory properties of taxane compounds.


[Magnetic resonance imaging in juvenile idiopathic arthritis: peculiarities of imaging children].
The term juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of arthritides with no known cause that begin before the age of 16 years and persist for at least 6 weeks. In recent decades, imaging techniques have acquired a fundamental role in the diagnosis and follow-up of JIA, owing to the unification of the different criteria for classification, which has strengthened the research in this field, and to the development of disease-modifying antirheumatic drugs. In this article, we briefly explain what JIA is. Moreover, we describe the role and limitations of plain-film radiography, ultrasonography, and magnetic resonance imaging (MRI). Finally, we review the MRI protocol and findings, and we comment on the differential diagnosis.


Partial trisomy 1q syndrome.
Six cases of partial trisomy 1q, including four cases from the literature and our own two observations are summarized with respect to their clinical symptoms. Distinct similarities of the external aspect and of internal malformations allow the delineation of a syndrome of partial trisomy 1q.


Resetting of the rat circadian clock after a shift in the light/dark cycle depends on the photoperiod.
Adjustment of the circadian clock to shifts in the light/dark (LD) cycle was assessed from the rat pineal N-acetyltransferase (NAT) rhythm which is controlled by a pacemaker in the suprachiasmatic nucleus of the hypothalamus. Re-entrainment to an 8-h delay in the LD cycle took more than 3 days in rats maintained under a regime with 18 h of light and 6 h of darkness per day (LD 18:6) whereas it was completed within 3 days in those maintained under LD 12:12. Re-entrainment to an advance in the LD cycle proceeded through a transient diminution or almost disappearance of the NAT rhythm amplitude following a 5-h, 3-h and even a mere 2-h advance shift under LD 18:6, whereas no such diminution occurred under LD 12:12 even after a 5-h advance shift. Altogether, the data indicate that resetting of the circadian clock after shifts in the LD cycle depends on the photoperiod.


Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax.
Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA) in human cutaneous anthrax cases. Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] = 0.9982; slope = 0.9186; intercept = 0.1108). The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.


Primary and Secondary Variants of Callous-Unemotional Traits in Early and Middle Childhood: Distinction, Evaluation and Empathic Differences.
Current literature demonstrates the relevance of considering two variants of CU traits based on high or low levels of anxiety. However, there is limited information about these variants in young community samples. The current study used cluster analyses to investigate the primary and the secondary variants of CU traits in two samples of children: preschool (N = 107; Mage = 4.95, SD = 0.62) and school-age (N = 153; Mage = 7.49, SD = 1.11). The identified clusters were compared on empathic dimensions, aggressive behavior and criteria from the "with limited prosocial emotions" specifier from the DSM-V. The primary variant was identified as early as preschool age while the secondary variant was only identified in the school-age sample. In this latter sample, the two variants did not differ on assessed variables, except for aggressive behavior. Despite the similarities between the two variants, these results suggest distinct developmental trajectories.


The current state of active third stage management to prevent postpartum hemorrhage: a cross-sectional study.
To investigate the implementation of the International Confederation of Midwives/International Federation of Gynecology and Obstetrics (ICM/FIGO) guideline on active third stage management in vaginal deliveries in daily clinical practice. Observational, cross-sectional study. One tertiary and one teaching hospital in the Netherlands. Women undergoing vaginal deliveries. A case record form was completed after every vaginal delivery. Primary outcome was adequate guideline adherence, defined as initial administration of 10 IU oxytocin, performance of controlled cord traction and uterine massage. Adequate guideline adherence was a priori estimated to be 10%. With a sample size of 600, i.e. 300 women per hospital, the standard error of the resulting percentage would be less than 2% for each hospital. Six hundred and twenty six women were included. Guideline adherence was adequately performed in 48% of vaginal deliveries. Oxytocin was administered after birth in 98% of deliveries and in 80% the correct dose was used. Controlled cord traction was performed in 63% and uterine massage in 93%; however, the latter was performed as advised (at least eight times) in only 8%. The amount of blood loss was not associated with the use of either 5 or 10 IU oxytocin (p = 0.818). Controlled cord traction and uterine massage were more frequently performed when blood loss exceeded 500 mL (p < 0.001). Active third stage management according to the ICM/FIGO guideline is adequately performed in only 48% of all vaginal deliveries. Results of this study call for training programs to increase adherence to the ICM/FIGO guideline.


Smartphone based visual and quantitative assays on upconversional paper sensor.
The integration of smartphone with paper sensors recently has been gain increasing attentions because of the achievement of quantitative and rapid analysis. However, smartphone based upconversional paper sensors have been restricted by the lack of effective methods to acquire luminescence signals on test paper. Herein, by the virtue of 3D printing technology, we exploited an auxiliary reusable device, which orderly assembled a 980nm mini-laser, optical filter and mini-cavity together, for digitally imaging the luminescence variations on test paper and quantitative analyzing pesticide thiram by smartphone. In detail, copper ions decorated NaYF4:Yb/Tm upconversion nanoparticles were fixed onto filter paper to form test paper, and the blue luminescence on it would be quenched after additions of thiram through luminescence resonance energy transfer mechanism. These variations could be monitored by the smartphone camera, and then the blue channel intensities of obtained colored images were calculated to quantify amounts of thiram through a self-written Android program installed on the smartphone, offering a reliable and accurate detection limit of 0.1μM for the system. This work provides an initial demonstration of integrating upconversion nanosensors with smartphone digital imaging for point-of-care analysis on a paper-based platform.


The Synergistic Effect of Iodide and Sodium Nitrite on the Corrosion Inhibition of Mild Steel in Bicarbonate-Chloride Solution.
The effect of potassium iodide (KI) and sodium nitrite (NaNO₂ inhibitor on the corrosion inhibition of mild steel in chloride bicarbonate solution has been studied using electrochemical techniques. Potentiodynamic polarisation data suggest that, when used in combination, KI and NaNO₂ function together to inhibit reactions at both the anode and the cathode, but predominantly anodic. KI/NO₂- concentration ratios varied from 2:1 to 2:5; inhibition efficiency was optimized for a ratio of 1:1. The surface morphology and corrosion products were analysed using scanning electron microscopy (SEM) and X-ray diffractometry (XRD). The latter shows that the addition of I- to NO₂ facilitates the formation of a passivating oxide (γ-Fe₂O₃) as compared to NO₂- alone, decreasing the rate of metal dissolution observed in electrochemical testing. The synergistic effect of KI/NO₂- inhibition was enhanced under the dynamic conditions associated with testing in a rotating disc electrode.


The mental health of non-commissioned soldiers deployed to Boko-Haram zones in Nigeria: Examining the roles of rank and other armed service characteristics.
This study examined the roles of rank and its interaction with armed service characteristics, including combat exposure, frequency of deployments, and length of service on psychological distress among non-commissioned military officers (NCOs). A cross-sectional sample of 256 NCOs (Meanage = 34.10 ± 7.33) of the Nigerian Army deployed to fight Boko Haram in North-East, Nigeria, participated in the study. Data were collected using self-report instruments and analyzed using multiple linear regression. The ranks of corporal and lance corporal/private (LCP) were associated with greater psychological distress than the sergeants. However, corporals had higher psychological distress than sergeants and LCPs. Rank accounted for almost twice the variances in psychological distress more than other service characteristics. LCPs had adverse mental health at increased service length than sergeants and corporals. Also, LCPs were more vulnerable to stress at higher combat experience than the corporals. Other factors may be inherent in rank effect on psychological distress beyond combat experience, deployments, and service length. Nevertheless, these service characteristics are important in the rank effect on psychological distress. Identifying relevant combat-related structural problems may additionally explain the association of rank with psychological distress beyond combat experience, deployments, and service length among NCOs.


On the organization of receptive fields of retinal spot detectors projecting to the fish tectum: Analogies with the local edge detectors in frogs and mammals.
Responses of ON- and OFF-ganglion cells (GCs) were recorded extracellularly from their axon terminals in the medial sublamina of tectal retino-recipient layer of immobilized cyprinid fish (goldfish and carp). These units were recorded deeper than direction selective (DS) ones and at the same depth where responses of orientation selective (OS) GCs were recorded. Prominent responses of these units are evoked by small contrast spots flickering within or moving across their visual field. They are not selective either to the direction of motion or to the orientation of stimuli and are not characterized by any spontaneous spike activity. We refer to these fish GCs as spot detectors (SDs) by analogy with the frog SD. Receptive fields (RFs) of SDs are organized concentrically: the excitatory center (about 4.5°) is surrounded by opponent periphery. Study of interactions in the RF has shown that inhibitory influences are generated already inside the central RF area. This fact suggests that RFs of SDs cannot be defined as homogeneous sensory zone driven by a linear mechanism of response generation. Physiological properties of fish SDs are compared with the properties of frog SDs and analogous mammalian retinal GCs-local edge detectors (LEDs). The potential role of the SDs in visually guided fish behavior is discussed.


Resveratrol Increases Anti-Proliferative Activity of Bestatin Through Downregulating P-Glycoprotein Expression Via Inhibiting PI3K/Akt/mTOR Pathway in K562/ADR Cells.
Multidrug resistance (MDR) is a major obstacle in the clinical therapy of hematological malignancies. P-glycoprotein (P-gp) overexpression results in reduction of intracellular drug concentration with a consequence that the cytotoxicity of anti-tumor drugs is decreased, which leads to MDR in K562/ADR cells. In this study, we found that resveratrol enhanced the anti-proliferative activity of bestatin in K562/ADR cells. Co-treatment with resveratrol, IC50 values of bestatin in K562/ADR cells significantly decreased and activation of caspase-3 and caspase-8 increased, which indicated that resveratrol potentiated bestatin-induced apoptosis. Resveratrol increased the intracellular concentration of bestatin through inhibiting P-gp function and downregulating P-gp expression at mRNA and protein levels, which increased anti-proliferative activity of bestatin in K562/ADR cells. Resveratrol decreased the phosphorylation of Akt and mTOR but did not affect the phosphorylations of JNK or ERK1/2. These results demonstrated that resveratrol could increase the anti-proliferative activity of bestatin through downregulating P-gp expression via suppressing the PI3K/Akt/mTOR signaling pathway.


Suramin inhibits binding and degradation of platelet-derived growth factor in arterial smooth muscle cells but does not interfere with autocrine stimulation of DNA synthesis.
During in vitro culture arterial smooth muscle cells of adult rats are able to produce a platelet-derived growth factor (PDGF)-like protein and to promote their own growth in an autocrine manner. Here, this process has been studied using suramin, a polyanionic drug that has been reported to interfere with the cellular binding of several growth factors. Our results indicate that suramin speeds up the transition of the cells from a contractile to a synthetic phenotype early in primary culture. It inhibits the binding of PDGF to the cells, displaces PDGF bound to the cell surface, and slows down the degradation of PDGF internalized by the cells. It reduces the specific activities of the lysosomal enzymes acid phosphatase, beta-N-acetylglucosaminidase and beta-glucuronidase, and gives rise to an accumulation of lysosomes with myelin-like inclusions. It blocks PDGF- and serum-induced DNA synthesis and cellular proliferation in secondary cultures, but lacks a distinct inhibitory effect on DNA synthesis in primary cultures under serum-free conditions. The results suggest that the PDGF-like protein produced by the smooth muscle cells under the latter conditions may bind to its receptor and exert its autocrine effect intracellularly, without prior release into the pericellular space.


Salivary Gland Ultrasonography as a Diagnostic Tool for Secondary Sjögren Syndrome in Rheumatoid Arthritis.
To assess salivary gland ultrasonography (US) as a diagnostic tool for secondary Sjögren syndrome (sSS) in patients with rheumatoid arthritis (RA). Salivary gland US images from 30 patients with RA were graded using a validated semiquantitative scoring system. Sicca symptoms, oral health, and RA disease activity were assessed. US changes consistent with SS were found in 40% of patients. Patients with higher US scores had more sicca symptoms as well as higher RA activity and poorer oral health. Salivary gland US may aid the diagnosis of sSS in patients with RA.


Variation in microbiologic profiles among pregnant women with bacterial vaginosis.
The purpose of this study was to determine if clinical findings and sociodemographic variables among bacterial vaginosis (BV)-positive pregnant women are associated with different microbiologic profiles. Pregnant women were assessed for BV by Nugent criteria. BV+ women were separated into 6 mutually exclusive microbiologic groups. In unadjusted analyses, we compared (1) sociodemographic and behavioral characteristics, and (2) 3 clinical characteristics among BV+ women with and without Mobiluncus (M+ vs M-). Unadjusted data were analyzed using the chi-square test. Multiple logistic regression was used to assess the likelihood of having clinical signs of BV in women with and without Mobiluncus spp while controlling for confounders. A total of 1756 BV+ pregnant women were followed. The M+ group (n=702) was significantly more likely than the M- group (n=1054) to be non-Hispanic black (80.9% vs 66.2%; P < .0001), older than 21 years (61.7% vs 48.7%; P < .0001), and to have had more than 3 lifetime sexual partners (66.4% vs 54.9%; P < .0001). The M+ group was also more likely to have clue cells on wet mount (63.9% vs 47.2%; P < .0001) and a positive amine odor after addition of KOH (57.2% vs 45.0%; P=.001). There was no difference in other demographic variables or physician diagnosis of abnormal vaginal discharge. In the adjusted analyses for each clinical outcome, all findings were consistent with the unadjusted analyses. BV+ pregnant women with Mobiluncus spp are more likely to have clue cells present on wet mount, a positive amine odor after KOH preparation, and to be older, non-Hispanic black, and have had more lifetime sexual partners compared to BV+ women without any Mobiluncus species.


Interactions between the amino-terminal domain of p56lck and cytoplasmic domains of CD4 and CD8 alpha in yeast.
The interactions between CD4 or CD8 and p56lck were tested using the two-hybrid protein interaction system in yeast. Plasmid constructs were created which fuse the cytoplasmic domains of either CD4 or CD8 alpha to the DNA-binding protein LexA, and the unique amino-terminal domain of p56lck fused to a transcriptional activation domain. These constructs were transfected into yeast bearing lacZ and LEU2 reporter genes controlled by upstream LexA operator sequences. Yeast transfectants bearing either CD4 or CD8 alpha hybrid proteins in combination with the amino terminal p56lck hybrid protein exhibited increased beta-galactosidase activity and growth on leucine-deficient medium, indicating interactions between these protein domains. Quantitation of reporter activation indicated that the interaction of p56lck with CD8 alpha is at least 18-fold weaker than the interaction with CD4 in this assay. This reduced interactive capacity is apparently not due to competition by CD8 alpha interacting with itself, since homotypic or heterotypic interactions between CD8 alpha and/or CD4 could not be detected. Truncation and point mutants demonstrated that the interactions of p56lck with CD4 or CD8 alpha were dependent on the integrity of a pair of cysteines on each protein. The results indicate that these interactions do not require any additional proteins. Additionally, expression of the entire p56lck molecule as a hybrid with LexA resulted in dramatic reduction in the growth of yeast. Though the two-hybrid system is a powerful tool for examining protein interactions, this result indicates potential limitations in studying full-length src family tyrosine kinases in yeast.


Tumor-targeted nanoflowers regulate glutamine metabolism and amplify oxidative stress for synergistic therapy.
We designed and synthesized tumor-targeted nanoflowers to inhibit glutamine metabolism and amplify oxidative stress, which could synergistically suppress tumor growth.


Low preoperative psoas muscle mass index is a risk factor for distal cholangiocarcinoma recurrence after pancreatoduodenectomy: a retrospective analysis.
This study aimed to investigate whether preoperative muscle mass is associated with the recurrence of distal cholangiocarcinoma after pancreatoduodenectomy (PD). We retrospectively examined 88 patients who had undergone PD for distal cholangiocarcinoma. The preoperative psoas muscle mass index (PMI) was measured using computed tomography as an index of muscle mass. We performed multivariate analysis of factors influencing early recurrence and developed a prognostic survival model using independent risk factors for recurrence. The cut-off PMI values for recurrence within 1 year of surgery, determined from the receiver operating characteristic curve, were 5.90 cm2/m2 in males and 3.98 cm2/m2 in females. Multivariate analysis of effects associated with early recurrence within 1 year indicated that low PMI (odds ratio [OR] 9.322; 95% confidence interval [CI] 2.832 - 30.678; p = 0.0002) and lymph node metastasis (OR 5.474; 95% CI 1.620 - 18.497; p = 0.0062) were independent risk factors, and the median recurrence-free survival (RFS) of the low and high PMI groups were 21.6 and 81.0 months, respectively (p = 0.0214). The median RFS for zero, one, and two risk factors of low PMI and lymph node metastasis were as follows: zero variables, median not reached; one variable, 15.3 months; two variables: 6 months. Low preoperative PMI may be a risk factor for distal cholangiocarcinoma recurrence after PD. The Institutional Review Board of St. Marianna University School of Medicine approved this study prior to commencement of data collection and analysis on October 9, 2020 (IRB no. 5006) and waived the informed consent requirement.


Expression of microRNA-150 and its Target Gene IGF2BP1 in Human Osteosarcoma and their Clinical Implications.
Previous study revealed that microRNA (miR)-150 might function as a tumor suppressor in osteosarcoma partially by targeting Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1). The aim of this study was to investigate the clinical significance of miR-150-IGF2BP1 axis in human osteosarcoma which remains unclear. At first, expression levels of miR-150, and IGF2BP1 mRNA and protein in 20 osteosarcoma and matched adjacent noncancerous tissues were respectively detected by quantitative real-time PCR and western blot analyses. Then, subcellular localization and expression pattern of IGF2BP1 protein in 100 osteosarcoma tissues were examined by immunohistochemistry. Associations of miR-150/IGF2BP1 expression with various clinicopathological features and patients' prognosis were also statistically evaluated. As a result, miR-150 expression was significantly decreased, while IGF2BP1 mRNA and protein expression were dramatically increased in osteosarcoma tissues compared to matched adjacent noncancerous tissues (all P < 0.001). Immunostaining of IGF2BP1 protein was localized in cytoplasm of tumor cells in osteosarcoma tissues. Statistically, low miR-150 expression and/or high IGF2BP1 protein immunoreactive score were all significantly associated with high tumor grade, presence of metastasis and recurrence, as well as poor response to chemotherapy (all P < 0.05). Moreover, miR-150, IGF2BP1 and combined miR-150/IGF2BP1 expressions were all identified as independent prognostic factors for overall and disease-free survivals of osteosarcoma patients (all P < 0.05). In conclusion, our data suggest that miR-150 and its downstream target IGF2BP1 may be a crucial axis for the development, progression and patients' prognosis of ostesarcoma. The newly identified miR-150/IGF2BP1 axis might be a novel potential therapeutic target for osteosarcoma treatment.


Effects of CPAP on energy expenditure in obese obstructive sleep apnoea patients: A pilot study.
We conducted a placebo-controlled crossover pilot study investigating the effects of 2 mo of active and sham continuous positive airway pressure (CPAP) on energy expenditure (EE) via whole-room indirect calorimetry in three obese obstructive sleep apnoea (OSA) patients. Total 24-h (active: 2970 ± 254 kcal/d, sham: 2705 ± 217 kcal/d; p = 0.015) and mean sleeping (active: 1.60 ± 0.20 kcal/min; sham: 1.47 ± 0.17 kcal/min; p = 0.038) EE were significantly increased after active vs. sham CPAP. Findings suggest that CPAP may correct a hypoxia-related adaptive decrease in thermogenesis.


Rapid heat production associated with excitation of electric organs of the electric eel.
By constructing a new type of thermal detector, rapid production of heat was demonstrated during the rising phase of the action potential of the eel electric organs evoked by direct electric stimulation. Following the indirect (synapse-mediated) action potential of the organs, the existence of very large and variable production of heat of unknown origin was revealed.


Congenital becker nevus with lichen planus.
We report an interesting and rare association of congenital Becker nevus with lichen planus occurring in an 11-year-old boy. Both conditions were confirmed histopathologically.


Kidney xenotransplantation: Future clinical reality or science fiction?
There is a global shortage of organs for transplantation and despite many governments making significant changes to their organ donation systems, there are not enough kidneys available to meet the demand. This has led scientists and clinicians to explore alternative means of meeting this organ shortfall. One of the alternatives to human organ transplantation is xenotransplantation, which is the transplantation of organs, tissues, or cells between different species. The resurgence of interest in xenotransplantation and recent scientific breakthroughs suggest that genetically engineered pigs may soon present a realistic alternative as sources of kidneys for clinical transplantation. It is therefore important for healthcare professionals to understand what is involved in xenotransplantation and its future implications for their clinical practices. First, we explore the insufficiency of different organ donation systems to meet the kidney shortage. Second, we provide a background and a summary of the progress made so far in xenotransplantation research. Third, we discuss some of the scientific, technological, ethical, and public health issues associated with xenotransplantation. Finally, we summarize the literature on the attitudes of healthcare professionals toward xenotransplantation.


Pain Recognition in Ferrets.
Recognition and accurate assessment of the severity of pain can be challenging in ferrets as they are unable to verbally communicate, and often hide their pain. Pain assessment relies on the assessment of behavioral, physiologic, and other clinical parameters that serve as indirect indicators of pain. Assessment of physiologic and clinical parameters requires handling, which results in changes in these parameters. Behavioral parameters can be assessed less invasively by observing the patient. Due to their nonspecificity, correct interpretation may be challenging. Just as in other species, a grimace scale seems to be the most helpful tool in recognizing pain in ferrets.


Prodrugs as self-assembled hydrogels: a new paradigm for biomaterials.
Prodrug-based self-assembled hydrogels represent a new class of active biomaterials that can be harnessed for medical applications, in particular the design of stimuli responsive drug delivery devices. In this approach, a promoiety is chemically conjugated to a known-drug to generate an amphiphilic prodrug that is capable of forming self-assembled hydrogels. Prodrug-based self-assembled hydrogels are advantageous as they alter the solubility of the drug, enhance drug loading, and eliminate the use of harmful excipients. In addition, self-assembled prodrug hydrogels can be designed to undergo controlled drug release or tailored degradation in response to biological cues. Herein we review the development of prodrug-based self-assembled hydrogels as an emerging class of biomaterials that overcome several common limitations encountered in conventional drug delivery.


The application of lectins to the characterization and isolation of mammalian cell populations.
Mammalian cells invariably contain a vast array of glycosylated moieties, both inside the cell and on the cell surface. There is an increasing awareness of the utility of these carbohydrates in delineating the phenotype or function of many populations of cells. To this end lectins are extremely useful reagents. Lectins are carbohydrate-binding proteins and glycoproteins of non-immune origin derived from numerous plants and animals. A wide variety of lectins with many distinct carbohydrate specificities have been isolated. Historically the most common laboratory techniques utilizing lectins have been agglutination, mitogen stimulation, and fluorescence techniques. Recent advances in the development and conjugation procedure for labels and matrices have led to the creation of numerous novel lectin-based assays. Lectins are currently used not only to identify cells with specified carbohydrate groups, but also to quantitate the carbohydrate groups or to isolate the carbohydrate-bearing cells or structures.


Application of 3-D computer graphics for facial reconstruction and comparison with sculpting techniques.
Facial reconstruction has until now been carried out by the sculpting technique. This method involves building a face with clay or other suitable material on to a skull or its cast, taking into account appropriate facial thickness measurements together with information provided by anthropologists such as approximate age, sex, race and other individual idiosyncrasies. A method for facial reconstruction is presented using 3-D computer graphics and is compared with the manual technique. The computer method involves initially digitising a skull using a laser scanner and video camera interfaced to a computer. A face, from a data bank which has previously digitised facial surfaces, is then placed over the skull in the form of a mask and the skin thickness is altered to conform with the underlying skull. The advantage of the computer method is its speed and flexibility. We have shown that the computer method for reconstructing a face is feasible and furthermore has the advantage over the manual technique of speed and flexibility. Nevertheless, the technique is far from perfect. Further facial thickness data needs collecting and the method requires evaluation using both known control skulls and later unknown remains.


Partial purification and characterization of hepatocyte proliferation stimulatory factor from liver of rats treated with D-galactosamine.
The partial purification and characterization of a hepatocyte proliferation stimulatory factor (HPSF) isolated from the liver of D-galactosamine-treated rats are described. The HPSF was a heat-labile, acid-stable and trypsin-sensitive protein. The partially purified HPSF stimulated DNA synthesis and increased the labeling index of parenchymal hepatocytes at 5 micrograms/ml and maximally at 50 micrograms/ml. The effect of HPSF in stimulating DNA synthesis was synergistic with that of insulin plus epidermal growth factor (EGF). The HPSF was scarcely detected in normal rat liver. The results obtained indicate that this HPSF is distinct from insulin, multiplication-stimulating activity (MSA), EGF and other hepatocyte growth factors previously reported, and suggest a plausible role for HPSF in the regeneration of liver tissue following hepatotoxic damage.


Targeting erbB receptors.
Our work is concerned with the origins and therapy of human cancers. Members of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, also known as erbB or HER receptors, are over expressed and/or activated in many types of human tumors and represent important therapeutic targets in cancer therapy. Studies from our laboratory identified targeted therapy as a way to treat cancer. Rational therapeutics targeting and disabling erbB receptors have been developed to reverse the malignant properties of tumors. Reversal of the malignant phenotype, best seen with disabling the HER2 receptors using monoclonal antibodies is a distinct process from that seen with blocking of ligand binding to cognate receptors as has been done for EGFr receptors. Here we review the mechanisms of action deduced from a number of approaches developed in our laboratory and elsewhere, including monoclonal antibodies, peptide mimetics, recombinant proteins and small molecules. The biochemical and biological principles which have been uncovered during these studies of disabling HER2 homomeric or HER2-EGFr heteromeric receptors will help the development of novel and more efficient therapeutics targeting erbB family receptors.


[Clinical and pathological significance of carotid siphon calcification observed on bone condition of brain CT].
On plain brain computed tomography (CT), it is difficult to evaluate stenosis of internal carotid artery (ICA) because ICA is surrounded by structures, even though we can observe calcification of carotid siphon in some patients by using bone condition. However the pathologic significance has not been well known. We studied the pathologic significance of carotid siphon calcification observed on bone condition of brain CT. A total of 112 patients who were diagnosed or suspected as cerebrovascular diseases were registered. We classified the calcification into four levels (none, mild, moderate, severe) based on the degree of calcification. Then we compared it with the degree of stenosis of carotid siphon seen on brain magnetic resonance angiography (MRA) and with max intima-medial thickness (IMT) from common carotid artery (CCA) to ICA on carotid ultrasonography. The mean +/- standard deviation of max IMT to none, mild, moderate and severe in the degree of calcification were 1.03 +/- 0.64 (0.4-2.8), 1.65 +/- 0.83 (0.5-4.1), 2.03 +/- 0.83 (0.8-4.1) and 2.81 +/- 1.15 (0.7-6.5) mm, respectively. The calcification on brain CT significantly correlated with the degree of stenosis on brain MRA and with max IMT on carotid ultrasonography. The calcification of carotid siphon on bone condition of brain CT correlated with stenosis of the same portion and atherosclerosis of CCA bifurcation. Recently, on DICOM viewer, clinicians can convert plain condition into bone condition on brain CT due to popularization of PACS. We should pay attention to calcification of carotid siphon in patients with ischemic cerebrovascular diseases because we can estimate the atherosclerosis of both carotid siphon and CCA bifurcation easily and immediately.


The germ cell nuclear factor (GCNF).
The germ cell nuclear factor (GCNF), which is also known as RTR (retinoid receptor-related testis-associated receptor) is a member of the nuclear receptor superfamily. As a natural ligand remains to be discovered, GCNF is referred to as an orphan receptor. Owing to GCNF's unique features and its distant relation to any other known nuclear receptor it has been classified as the only member of the subgroup six and designated NR6A1 by the Receptor Nomenclature Committee (Duarte et al., 2002: Nucleic Acids Res 30: 364-368). To date, GCNF has been cloned from distinct vertebrate species, including zebrafish, Xenopus laevis, mouse, rat, and human. Cloning and characterization of the gene, domain organization and DNA binding properties of the protein, as well as the differential expression of mRNA splice variants or the protein during development and in the adult animal have been comprehensively reviewed by others (Greschik and Schüle, 1998: J Mol Med 76:800-810; Cooney et al., 1999: Am Zool 39:796-806). In this minireview I focus on the pleiotropic function of GCNF in embryogenesis and germ cell differentiation, and discuss novel concepts about its putative role in neurogenesis.


A multi-step approach for tongue image classification in patients with diabetes.
In China, diabetes is a common, high-incidence chronic disease. Diabetes has become a severe public health problem. However, the current diagnosis and treatment methods are difficult to control the progress of diabetes. Traditional Chinese Medicine (TCM) has become an option for the treatment of diabetes due to its low cost, good curative effect, and good accessibility. Based on the tongue images data to realize the fine classification of the diabetic population, provide a diagnostic basis for the formulation of individualized treatment plans for diabetes, ensure the accuracy and consistency of the TCM diagnosis, and promote the objective and standardized development of TCM diagnosis. We use the TFDA-1 tongue examination instrument to collect the tongue images of the subjects. Tongue Diagnosis Analysis System (TDAS) is used to extract the TDAS features of the tongue images. Vector Quantized Variational Autoencoder (VQ-VAE) extracts VQ-VAE features from tongue images. Based on VQ-VAE features, K-means clustering tongue images. TDAS features are used to describe the differences between clusters. Vision Transformer (ViT) combined with Grad-weighted Class Activation Mapping (Grad-CAM) is used to verify the clustering results and calculate positioning diagnostic information. Based on VQ-VAE features, K-means divides the diabetic population into 4 clusters with clear boundaries. The silhouette, calinski harabasz, and davies bouldin scores are 0.391, 673.256, and 0.809, respectively. Cluster 1 had the highest Tongue Body L (TB-L) and Tongue Coating L (TC-L) and the lowest Tongue Coating Angular second moment (TC-ASM), with a pale red tongue and white coating. Cluster 2 had the highest TC-b with a yellow tongue coating. Cluster 3 had the highest TB-a with a red tongue. Group 4 had the lowest TB-L, TC-L, and TB-b and the highest Per-all with a purple tongue and the largest tongue coating area. ViT verifies the clustering results of K-means, the highest Top-1 Classification Accuracy (CA) is 87.8%, and the average CA is 84.4%. The study organically combined unsupervised learning, self-supervised learning, and supervised learning and designed a complete diabetic tongue image classification method. This method does not rely on human intervention, makes decisions based entirely on tongue image data, and achieves state-of-the-art results. Our research will help TCM deeply participate in the individualized treatment of diabetes and provide new ideas for promoting the standardization of TCM diagnosis.


Spontaneous closure of traumatic macular hole.
Macular hole formation is a well-known complication following ocular trauma. Less commonly recognised is the spontaneous closure of such holes. A 27-year-old man presented with a history of blunt trauma to his left eye. Eye evaluation showed conjunctival laceration, diffuse retinal oedema and multiple retinal haemorrhages in that eye. A month later, he developed a full thickness macular hole. Two months later, there was spontaneous complete closure of the full-thickness macular hole in the left eye as confirmed on optical coherence tomography. Spontaneous closure of hole is not uncommon. Observation for a period of up to 12 months is a reasonable management option. Macular hole surgery for traumatic macular holes may be delayed in such cases.


Killing two bugs with one stone: a perspective for targeting multiple pest species by incorporating reproductive interference into sterile insect technique.
The sterile insect technique is an environmentally friendly method to control and even eradicate agricultural and veterinary insect pests without using chemical pesticides in excess. However, the continuous production and release of sterile insects is economically costly and eradication programs using sterile insects have not always been successful owing to the incomplete mating ability of the sterile insects. Here we focus on the theory and empirical findings of interspecific negative mating interaction, known as reproductive interference, to develop a more cost-effective and value-added pest management program. We suggest that sterile insects can be used for simultaneous control of both wild-type conspecifics and closely related pest species by taking advantage of the fact that, when species recognition abilities are incomplete, courtship and mating are often misdirected toward heterospecies. This new approach might help mitigate economic damage and human health crises caused by pest insects. © 2018 Society of Chemical Industry.


Are there differences in LDL-C target value attainment in Austrian federal states? Yes!
Low density lipoprotein (LDL-C) levels determine the cardiovascular risk. Previous studies indicated an LDL-C target attainment of around 50%, but no Austrian wide analysis on results for the federal states was available. We therefore sought to detect potential differences. Open-label, non-interventional, longitudinal study, registered: www.clinicaltrials.gov NCT 01381679. In all, 746 statin treated patients not at LDL-C goal received intensified therapy for 12 months. The sample was split into nine subgroups, representing the federal states of Austria.We detected an east-west gradient for baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1-57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%). Univariate ANCOVA retrieved significant differences within the states (Upper Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the capacity of intensified lipid lowering therapy applied in practice was as high as -42% as compared to previous standard therapy (additional LDL-C reduction after switch from baseline therapy in Vorarlberg).


The effect of continuous enteral tube feeding on various nutritional parameters in patients with disseminated malignant melanoma during intensive chemotherapy.
In a prospective study the effect of continuous enteral tube feeding was evaluated on various nutritional parameters in patients with disseminated malignant melanoma during 13 chemotherapy courses employing bleomycin, DTIC, vindesine and actinomycin D. The patients received a quantity of calories according to their pretreatment intake, but complete metabolic equilibrium could not be obtained during chemotherapy. Although the weight/height index remained unchanged, a decrease of serum albumin and prealbumin level occurred during all 13 treatment courses. Transferrin level decreased during 11 of these courses and cholinesterase level during 12. Triceps skinfold thickness and arm muscle circumference diminished equally. Serum prealbumin was the first nutritional parameter to fall during chemotherapy and seems to be a very sensitive indicator of the occurrence of nutritional imbalance. The plasma vitamin C level was low before treatment while during treatment both vitamin C and vitamin A level fell quickly even though the nutritional intake of these vitamins was adequate. We conclude that continuous enteral tube feeding, which is a feasible method of feeding, can to some extent fulfill the nutritional needs of patients treated with intensive chemotherapy.


Lysophosphatidic acid increased infarct size in the early stage of cerebral ischemia-reperfusion with increased BBB permeability.
We investigated whether exogenous lysophosphatidic acid (LPA), a phospholipid extracellular signaling molecule, would increase infarct size and blood-brain barrier (BBB) disruption during the early stage of cerebral ischemia-reperfusion, and whether it works through Akt-mTOR-S6K1 intracellular signaling. Rats were given either vehicle or LPA 1 mg/kg iv three times during reperfusion after one hour of middle cerebral artery (MCA) occlusion. In another group, prior to administration of LPA, 30 mg/kg of PF-4708671, an S6K1 inhibitor, was injected. After one hour of MCA occlusion and two hours of reperfusion the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to measure the degree of BBB disruption. At the same time, the size of infarct was determined and western blot analysis was performed to determine the levels of phosphorylated Akt (p-Akt) and phosphorylated S6 (pS6). LPA increased the Ki in the ischemic-reperfused cortex (+43%) when compared with Control rats and PF-4708671 pretreatment prevented the increase of Ki by LPA. LPA increased the percentage of cortical infarct out of total cortical area (+36%) and PF-4708671 pretreatment prevented the increase of the infarct size. Exogenous LPA did not significantly change the levels of p-Akt as well as pS6 in the ischemic-reperfused cortex. Our data demonstrate that the increase in BBB disruption could be one of the reasons of the increased infarct size by LPA. S6K1 may not be the major target of LPA. A decrease of LPA during early cerebral ischemia-reperfusion might be beneficial for neuronal survival.


The influence of time structure on prediction motion in visual and auditory modalities.
Usually people can estimate the correct position of a moving object even when it temporarily moves behind an occlusion. Studies have been performed on this type of occluded motion with prediction motion (PM) tasks in the laboratory. Previous publications have emphasized that people could use mental imagery or apply an oculomotor system to estimate the arrival of a moving stimulus at the target place. Nevertheless, these two ways cannot account for the performance difference under a different set of conditions. Our study tested the role of time structure in a time-to-collision (TTC) task using visual and auditory modalities. In the visual condition, the moving red bar travelled from left to right and was invisible during the entire course but flashed at the initial and the occluded points. The auditory condition and visual condition were alike, except that the flashes in the visual condition were changed to clicks at the initial and the occluded points. The results illustrated that participants' performance was better in the equal time structure condition. The comparison between the two sense modalities demonstrated a similar tendency, which suggested there could be common cognitive processes between visual and auditory modalities when participants took advantage of temporal cues to judge TTC.


Nuclei of stroma: site of highest estrogen concentration in human benign prostatic hyperplasia.
In an earlier publication we found significantly more estrogen receptor-positive cases in the stroma if compared with the epithelium of human benign prostatic hyperplasia (BPH). We were therefore interested to find out whether this preferential assay of estrogen receptor in stroma is reflected by a higher estrogen content in this tissue fraction. Estradiol (E2) and estrone (E1) were measured by RIA in whole BPH tissue, stroma, and epithelium as well as in the nuclear fraction of stroma and epithelium. For comparison, E2 and E1 were measured in blood also. The main results are as follows: 1) In all BPH samples the E2 (26.0 +/- 3.5 (SEM) pg/g (n = 20)) and E1 (53.5 +/- 7.4 (14)) content was significantly higher than in the corresponding plasma (E2: 17.5 +/- 2.3 pg/ml (11); E1: 26.5 +/- 4.4(7)), the mean ratio of E2/E1 was 0.52 and 0.69 for BPH and plasma, respectively; 2) in stroma significantly more E2 (53.6 +/- 7.8 fmol/mg DNA (18)) and E1 (55.9 +/- 8.4 (12)) were measured than in epithelium (E2: 15.7 +/- 1.9 (16); E1: 20.7 +/- 3.2 (13)); 3) in nuclei of stroma significantly higher E2 (38.0 +/- 5.3 fmol/mg DNA (20)) and E1 (19.2 +/- 4.8 (14)) concentrations were present than in epithelium (E2: 6.8 +/- 3.1 (19); E1: 2.5 +/- 0.5 (13)), the mean ratio of E2/E1 for the nuclear fractions of stroma (2.3) and epithelium (2.7) increased dramatically if compared with the respective ratio in whole BPH tissue. In conclusion, there is a distinct accumulation of estrogens in the nuclei of stroma, E2 concentration being significantly higher than E1. These data support the hypothesis that E2 could play a preferential role in stimulating the growth of the BPH stroma.


Insights into the effects of operating parameters on sulfate reduction performance and microbial pathways in the anaerobic sequencing batch reactor.
Sulfate-reducing bacteria (SRB)-based anaerobic process has aroused wide concern in the treatment of sulfate-containing wastewater. Chemical oxygen demand-to-sulfate ratio (COD/SO42-) and HRT are two key factors that affect not only the anaerobic treatment performance but also the activity of SRB. In this study, an anaerobic sequencing batch reactor was constructed, and the effects of different operating parameters (COD/SO42-, HRT) on the relationship of sulfate (SO42-) reduction performance, microbial communities, and metabolic pathways were comprehensively investigated. The results indicated that the SO42- removal rates could achieve above 95% under different operating parameters. Bioinformatics analysis revealed that microbial community changed with reactor operation. At the genus level, the enrichment of Propionicclava and Peptoclostridium contributed to the establishment of a homotrophic relationship with Desulfobulbus, the dominant SRB in the reactor, which indicated that they took vital part in maintaining the structural and functional stability of the bacterial community under different operating parameters. In particular, an increasing trend of the relative abundance of functional genes encoding dissimilatory sulfate reduction was detected with the increase of COD/SO42-, which indicated high SO42- reduction potentials. This knowledge will help to reveal the mechanism of the effect of operating parameters on the anaerobic sulfate removal process, thus providing effective guidance for the targeted regulation of anaerobic sequencing batch bioreactors treating SO42--containing wastewater.


Characterization of in vitro metabolism of focal adhesion kinase inhibitors by LC/MS/MS.
Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is critically involved in cell migration, spreading and proliferation at the early step of various cancers. Small molecule inhibitors of FAK are effective to inhibit its activation in the process of tumor formation in cell. To better understand biotransformation of FAK inhibitors, this work has investigated in vitro phase I metabolism of inhibitors (namely PF-573228, PF-562271 and PF-03814735) by rat liver microsomes model. Using liquid chromatography - quadrupole time of flight mass spectrometry and tandem mass spectrometry (LC/Q-TOF/MS and MS/MS), three metabolites of PF-573228 and PF-562271 were observed and characterized, respectively. These in vitro metabolites were reported for the first time. The structures and fragmentation patterns of these metabolites were elucidated, and phase I metabolic pathways for FAK inhibitors were proposed. The main metabolic pathways of PF-573228 were hydroxylation, dehydrogenation and N-dealkylation. For PF-562271, they were hydroxylation and dehydrogenation. Hydroxylation was observed as the primary metabolism for PF-0381473.


Discovery of novel Quinazoline-based KRAS G12C inhibitors as potential anticancer agents.
A series of novel quinazoline analogs were designed and synthesized based on ARS-1620 and LLK-10 (a KRAS inhibitor reported by us recently) as KRAS G12C inhibitors with a 5-nitrofuran-2-carboxylic acid warhead. Most of the newly synthesized compounds exhibited antiproliferative activities similar to or better than ARS-1620 and LLK-10. Among them, compound KS-19 showed the highest activity (IC50 = 460 ∼ 870 nM) and reasonable selectivity (3 to 27-fold) for inhibiting the proliferation of KRAS G12C-mutated cells (NCI-H358 and NCI-H23) over other KRAS mutant (e.g. G13D, G12D, G12S, G12V, WT) cancer cells. ITC, KRAS-GTP pull-down assay and western blot analysis demonstrated that KS-19 could bind to KRAS G12C protein with high affinity (KD = 97 nM), thus decreasing the active form of KRAS G12C (KRAS G12C-GTP) and phosphorylated Erk, and leading to NCI-H358 tumor cell apoptosis. In addition, KS-19 was able to suppress the formation of NCI-H358 and NCI-H23 tumor colonies in a dose-dependent manner. Moreover, in vivo efficacy studies indicated that KS-19 (40 mg/kg) was effective in suppressing tumor growth in nude mice bearing NCI-H358 tumor xenografts with a TGI (tumor growth inhibition) of 47 %, comparable to that of ARS-1620 (50 %). Lastly, KS-19 possessed a benign toxicity profile without causing bone marrow suppression and any obvious morphological abnormalities in major organs of mice. Collectively, these results suggest that KS-19 represents a novel inhibitor of KRAS G12C worthy of further investigation as a potential anticancer agent.


Is 11C-choline Positron Emission Tomography/Computed Tomography Accurate to Detect Nodal Relapses of Prostate Cancer After Biochemical Recurrence? A Multicentric Study Based on Pathologic Confirmation from Salvage Lymphadenectomy.
A 11C-choline positron emission tomography/computed tomography (PET/CT) scan is used for restaging prostate cancer (PCa) patients with biochemical recurrence (BCR). Only a few reports have focused on the correlation between PET/CT and nodal relapse location at pathologic examination. To assess the accuracy of PET/CT in predicting the site of nodal relapses in patients undergoing pelvic and/or retroperitoneal salvage lymph node dissection (sLND). Multicentric retrospective study including 106 patients with BCR of PCa after radical treatment; all patients but six had a PET/CT showing at least one nodal recurrence and received sLND. PET/CT results were compared with histologic findings and analyzed in terms of sensitivity, specificity, and accuracy. Multivariable regression analyses were performed. Overall sensitivity, specificity, negative and positive predictive value, and accuracy of PET/CT for disease location were 61.6%, 79.3%, 66.3%, 75.7%, and 70.2%, respectively. Sensitivity was 75.5% in the lower pelvis with 69.8% specificity. The retroperitoneal region had high specificity (94.7%) but a relatively low sensitivity (58.3%). The sLNDs did not find any positive nodes in 16 patients (15%). According to regression analyses, discriminative accuracy of PET/CT was 70.4% and improved with an increased number of dissected nodes and prostate-specific antigen doubling time <12 mo. Limitations include retrospective design and lack of a standardized sLND template followed for all patients. The ability of PET/CT to detect nodal relapses is limited by a high false-positive rate, particularly in the iliac-obturator region and, more alarmingly, a high false-negative rate in the common iliac, sacral, and retroperitoneal regions. An extended template including pelvic and retroperitoneal regions should be adopted when sLND is planned for curative intent. The 11C-choline positron emission tomography/computed tomography scan is a commonly used tool to restage prostate cancer patients with biochemical recurrence, showing an overall per patient accuracy >80%; however, its ability to detect the site of nodal relapses remains suboptimal.


Cloning and stress-responding expression analysis of malonyl CoA-acyl carrier protein transacylase gene of Nannochloropsis gaditana.
Malonyl CoA-acyl carrier protein transacylase (MCAT, E188.8.131.52) is closely associated with the FASII pathway of fatty acid biosynthesis. However, the information about microalgal MCAT is scarce. In this study, a MCAT gene was isolated from Nannochloropsis gaditana with its deduced protein (NgMCAT) characterized with bioinformatic tools. The abundance of the NgMCAT transcript under different environmental conditions was determined with real-time quantitative PCR. Results showed that the open reading frame (ORF) of NgMCAT was 1059 bp in length, which encoded 352 amino acid residues. The abundance of NgMCAT transcript reached the maximum (5.17-fold) at 6h when sodium nitrate was limited, and reached the maximum (4.25-fold) at 12h at low temperature (15°C). The abundance of NgMCAT transcript fluctuated at high temperature (35°C) when the concentration of nitrate and sodium chloride exceeded 150 mg/L and 62 g/L, respectively. In addition, some components of fatty acid that changed with the expression of NgMCAT were also observed.


Paediatric traumatic brain injury.
To provide a summary of recent developments in the field of paediatric traumatic brain injury (TBI). The epidemiology of paediatric TBI with falling rates of severe TBI, and increasing presentations of apparently minor TBI. There is growing interest in the pathophysiology and outcomes of concussion in children, and detection of 'significant' injury, arising from concern about risks of long-term chronic traumatic encephalopathy. The role of decompressive craniectomy in children is still clarifying. Paediatric TBI remains a major public health issue.


Size-dependent cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles toward HeLa cells.
In this study, we investigated and reported the cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles (SNPs) with different sizes. Using confocal laser scanning microscope (CLSM), flow cytometry (FCM), and graphite furnace atomic absorption spectrometry (GFAAS), the qualitative and quantitative experimental results showed that the cellular uptake of SNPs toward HeLa cells is size-dependent. To further examine the uptake process, three different inhibitors including sucrose, Filipin III, and Cytochalasin D (Cyt D) were introduced to pretreat the HeLa cells. It appeared that the largest SNPs (SNPs-307.6) take an energy-dependent uptake pathway (clathrin dependent and caveolin independent) while that for the medium size SNPs-167.8 involves clathrin and caveolin dependent endocytosis. In contrast, the smallest SNPs (SNPs-55.6) follow not only energy required clathrin and caveolin dependent endocytosis but also an energy independent pathway to efficiently enter the cells. Moreover, the cellular uptake efficiency of SNPs, which also show excellent biocompatibility, is size-dependent in the order of 55.6>167.8>307.6 nm. This knowledge is fundamentally important and will facilitate more development of size-defined SNPs as the transporters for various purposes.


[Panhypopituitarism revealing metastasis of small-cell lung carcinoma associated with sarcoidosis].
Pituitary metastasis and sarcoidosis are two causes of pituitary stalk thickening. Their association has been described ago three decades. In this setting, we report a case of panhypopituitarism revealing pituitary metastasis from a small-cell lung carcinoma associated with sarcoidosis. A 49 year-old smoking patient with type 2 diabetes was admitted for acute adrenal failure with polyuria polydipsia syndrome and a pituitary tumor syndrome. Hormone explorations confirmed anterior pituitary insufficiency. Water restriction revealed central diabetes insipidus. The hypothalamic-pituitary MRI revealed a 1-cm sellar mass with nodular thickening of the stalk. The chest radiograph showed a heterogeneous opacity in the left lung. The thoraco-abdominal scan demonstrated a mass in the left lung highly suggestive of malignancy and many enlarged mediastinal nodes, hepatic nodules, and hypertrophy of the left adrenal. Bronchoscopy was performed three times and showed infiltration of the left bronchial tree but histological examination of the bronchial biopsies was negative for all samples. Ultrasound-guided biopsy of the liver was achieved and histology demonstrated sarcoidosis. The diagnosis of sarcoidosis was incompatible with the deterioration of the patient's general status. Subsequent radiographic explorations showed an increase in the size of the tumor mass and histological evaluation of a scan-guided trans-thoracic biopsy demonstrated small-cell carcinoma. Small-cell lung carcinoma is the most common cancer with pituitary metastasis. The proposed link between sarcoidosis and malignancy has remained controversial but has not been proven false.


Accuracy of remote chest X-ray interpretation using Google Glass technology.
We sought to explore the accuracy of remote chest X-ray reading using hands-free, wearable technology (Google Glass, Google, Mountain View, California). We compared interpretation of twelve chest X-rays with 23 major cardiopulmonary findings by faculty and fellows from cardiology, radiology, and pulmonary-critical care via: (1) viewing the chest X-ray image on the Google Glass screen; (2) viewing a photograph of the chest X-ray taken using Google Glass and interpreted on a mobile device; (3) viewing the original chest X-ray on a desktop computer screen. One point was given for identification of each correct finding and a subjective rating of user experience was recorded. Fifteen physicians (5 faculty and 10 fellows) participated. The average chest X-ray reading score (maximum 23 points) as viewed through the Google Glass, Google Glass photograph on a mobile device, and the original X-ray viewed on a desktop computer was 14.1±2.2, 18.5±1.5 and 21.3±1.7, respectively (p<0.0001 between Google Glass and mobile device, p<0.0001 between Google Glass and desktop computer and p=0.0004 between mobile device and desktop computer). Of 15 physicians, 11 (73.3%) felt confident in detecting findings using the photograph taken by Google Glass as viewed on a mobile device. Remote chest X-ray interpretation using hands-free, wearable technology (Google Glass) is less accurate than interpretation using a desktop computer or a mobile device, suggesting that further technical improvements are needed before widespread application of this novel technology.


Decrease in serum potassium concentration during epidural anaesthesia.
A mean decrease in the arterial serum potassium concentration (S-K) of 0.40 mmol/l (range 0-1.0) was found in 45 elderly men who were studied before and after induction of epidural anaesthesia (using mepivacaine 2% with adrenaline). The decrease was similar in patients who received acetated Ringer solution or dextran 40 in normal saline as intravenous fluid supplementation. No difference in S-K change was found between patients with a normal (less than 115 mumol/l) or elevated serum creatinine concentration. The decrease in S-K prevailed at the end of surgery except in patients with an elevated serum creatinine. Corrections of S-K for changes in arterial blood pH and rectal temperature during induction of anaesthesia did not explain the decrease in S-K. Correlations of clinical parameters such as the extension of anaesthesia, amount of intravenous fluid given and blood pressure changes gave conflicting results. A smaller decrease or no change in S-K was usually seen in arterial (n = 7) and venous (n = 7) samples when no intravenous fluid was given, as well as in venous samples when acetated Ringer solution was given (n = 6).


Tunable vicinal, geminal diphosphorylation and C-N bond phosphorylation of enaminones toward divergent phosphorylated ketone derivatives.
This paper reports the trifunctionalization reactions of tertiary enaminones in the fashion of selective gem- and vicinal diphosphorylation, leading to the tunable synthesis of α,α- and α,β-diphosphoryl ketones. In addition, the C-N bond phosphorylation with improved substrate tolerance has been achieved.


Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial.
Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables. In this randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). Patients had confirmed HR+ and HER2- locally recurrent inoperable or metastatic breast cancer and had received at least one previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting and two to four previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival (previously reported and not included in this analysis), and secondary endpoints included overall survival, objective response rate (ORR), and patient-reported outcomes. Overall survival was assessed using stratified log-rank tests and Cox regression. Trop-2 expression was assessed in tumour tissue by immunohistochemistry. In the statistical testing hierarchy, ORR and patient-reported outcomes were tested sequentially if overall survival was significant. This study is registered with ClinicalTrials.gov, NCT03901339. At the data cutoff date of July 1, 2022, 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group. With a 12·5-month (IQR 6·4-18·8) median follow-up, 390 deaths occurred among 543 patients. Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0-15·7] vs 11·2 months [10·1-12·7]; hazard ratio [HR] 0·79, 95% CI 0·65-0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups. ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients vs 38 [14%]; odds ratio 1·63 [95% CI 1·03-2·56]; p=0·035), as was time to deterioration of global health status and quality of life (median 4·3 months vs 3·0 months; HR 0·75 [0·61-0·92]; p=0·0059) and fatigue (median 2·2 months vs 1·4 months; HR 0·73 [0·60-0·89]; p=0·0021). The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. Sacituzumab govitecan demonstrated statistically significant and clinically meaningful benefit over chemotherapy, with a 3·2-month median overall survival improvement and a manageable safety profile. These data support sacituzumab govitecan as a new treatment option for patients with pretreated, endocrine-resistant HR+ and HER2- metastatic breast cancer. Gilead Sciences.


Permissible value for vanadium in allitic udic ferrisols based on physiological responses of green Chinese cabbage and soil microbes.
Greenhouse experiments were conducted to study the permissible value of vanadium (V) based on the growth and physiological responses of green Chinese cabbage (Brassica chinensis L.), and effects of V on microbial biomass carbon (MBC) and enzyme activities in allitic udic ferrisols were also studied. The results showed that biomass of cabbage grown on soil treated with 133 mg V kg(-1) significantly decreased by 25.1% compared with the control (P < 0.05). Vanadium concentrations in leaves and roots increased with increasing soil V concentration. Contents of vitamin C (Vc) increased by 10.3%, while that of soluble sugar in leaves significantly decreased by 54.0% when soil V concentration was 133 mg kg(-1), respectively. The uptake of essential nutrient elements by cabbage was disturbed when soil V concentration exceeded 253 mg kg(-1). Soil MBC was significantly stimulated by 15.5%, while dehydrogenase activity significantly decreased by 62.8% and urease activity slightly changed at treatment of 133 mg V kg(-1) as compared with the control, respectively. Therefore, the permissible value of V in allitic udic ferrisols is proposed as 130 mg kg(-1).


On-line monitoring of total sugar during kombucha fermentation process by near-infrared spectroscopy: Comparison of linear and non-linear multiple calibration methods.
Kombucha is widely recognized for its health benefits, and it facilitates high-quality transformation and utilization of tea during the fermentation process. Implementing on-line monitoring for the kombucha production process is crucial to promote the valuable utilization of low-quality tea residue. Near-infrared (NIR) spectroscopy, together with partial least squares (PLS), backpropagation neural network (BPANN), and their combination (PLS-BPANN), were utilized in this study to monitor the total sugar of kombucha. In all, 16 mathematical models were constructed and assessed. The results demonstrate that the PLS-BPANN model is superior to all others, with a determination coefficient (R2p) of 0.9437 and a root mean square error of prediction (RMSEP) of 0.8600 g/L and a good verification effect. The results suggest that NIR coupled with PLS-BPANN can be used as a non-destructive and on-line technique to monitor total sugar changes.


Biosynthesis of the O-glycosidically linked oligosaccharide chains of fetuin. Indications for an alpha-N-acetylgalactosaminide alpha 2 leads to 6 sialyltransferase with a narrow acceptor specificity in fetal calf liver.
Fetal calf liver microsomes were found to be capable of sialylating 14C-galactosylated ovine submaxillary asialomucin. The main oligosaccharide product chain could be obtained by beta-elimination under reductive conditions and was identified as NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAcol (where GalNAcol represents N-acetylgalactosaminitol) by means of high performance liquid chromatography (HPLC) analysis and methylation. The branched trisaccharide Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)-GalNAcol and the disaccharide NeuAc alpha 2 leads to 6GalNAcol were not formed. Very similar results were obtained when asialofetuin and antifreeze glycoprotein were used as an acceptor. When 3H-sialylated antifreeze glycoprotein ([3H]NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc-protein) was incubated with fetal calf liver microsomes and CMP-[14C]NeuAc, a reduced tetrasaccharide could be isolated. The structure of this product chain appeared to be [3H]NeuAc alpha 2 leads to 3Gal beta 1 leads to 3([14C]NeuAc alpha 2 leads to 6)GalNAcol, as established by means of HPLC analysis, specific enzymatic degradation with Newcastle disease virus neuraminidase, and periodate oxidation. These data indicate that fetal calf liver contains two sialyltransferases involved in the biosynthesis of the O-linked bisialotetrasaccharide chain. The first enzyme is a beta-galactoside alpha 2 leads to 3 sialyltransferase which converts Gal beta 1 leads to 3 GalNAc chains to the substrate for the second enzyme, a (NeuAc alpha 2 leads to 3Gal beta 1 leads to 3)GalNAc-protein alpha 2 leads to 6 sialyltransferase. The latter enzyme does not sialylate GalNAc or Gal beta 1 leads to 3GalNAc units but is capable of transferring sialic acid to C-6 of GalNAc in NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc trisaccharide side chains, thereby dictating a strictly ordered sequence of sialylation of the Gal beta 1 leads to 3 GalNAc units in fetal calf liver.