Toxoplasmosis in sheep. I. Effect of a killed vaccine on lambing losses caused by experimental challenge with Toxoplasma gondii.
A total of 50 two-tooth ewes were immunized pre-tupping using a killed vaccine of disintegrated Toxoplasma tachyzoites with Freunds incomplete adjuvant. At mid-pregnancy, the ewes were challenged intravenously with 1 x 10(4) live T. gondii tachyzoites. There was no difference in the lambing percentage between ewes vaccinated once and unvaccinated ewes. The lambing percentage for ewes vaccinated twice was significantly lower (p<0.05 normal score) than unvaccinated ewes. The serological response to vaccination and challenge was measured by the Toxoplasma dye test. The level of dye test antibodies at the time of challenge suggests that effective immunity to Toxoplasma n abortion is not dependent on dye test antibody titre. These results suggest that a killed vaccine would Toxoplasma on fertility and lambing performance in not be an effective tool to estimate the effects of commercial flocks.


Pathogenicity ofAeromonas hydrophila in red leg disease in frogs.
Endotoxin and hemolysin fromAeromonas hydrophila A(3) were studied to understand the pathogenicity of the organism. Neither the endotoxin nor the hemolysin alone produced typical red leg disease symptoms or death in frogs, even at a very high dosage of 8,000 μg; however, endotoxin and hemolysin together did. Further, histamine-stressed frogs died from hemolysin but not endotoxin. Hemolytic activity of hemolysin increased in cells that were preincubated with endotoxin. Results point to the conclusion that red leg disease in frogs represents a complex interaction between endotoxin and hemolysin and that stress-producing factors other than the endotoxin might trigger disease production.


A severe case of co-infection with Enterovirus 71 and vaccine-derived Poliovirus type II.
Enterovirus 71 (EV71) is often identified as the primary pathogen that directly leads to severe cases of HFMD, whereas the association between other enteroviruses and EV71 infection remains largely unclear. Here we report a rare case of a 5-year-old boy co-infected with EV71 and vaccine-derived Poliovirus (VDPV) type II, which were identified based on PCR and sequence analysis results and clinical symptoms and were characterized on CT. We determined that the EV71 strain belongs to the C4 subtype, and the VDPV II strain was closely genetically related to the reference Sabin type II strain. This report may improved our understanding of the clinical significance of the associations between clinical signs and the infectious properties of the involved pathogens.


Percutaneous recanalization and dilatation of a thrombotically occluded superior vena cava in a patient with a peritoneovenous shunt.
A superior vena cava syndrome developed in a patient with liver cirrhosis 6 months after implantation of a peritoneovenous shunt. Local fibrinolytic therapy resulted only in a transient improvement of clinical symptoms. Persistent patency of the superior vena cava and shunt function was regained only after percutaneous recanalization and balloon dilatation of the thrombotically occluded caval vein.


Bilateral temporalis muscle hypertrophy: a case report.
Although masseteric hypertrophy is common and can be accompanied by temporalis hypertrophy, temporalis hypertrophy by itself is an exceptional finding. A patient, a chronic bruxer who was receiving psychiatric care and psychotherapeutic medications, complained of moderate discomfort and swelling in both temporal areas. It is believed that the patient's long-term stress-related sleeping problem was causing her bruxism. Of great interest was the fact that chronic bruxing had resulted in the rare occurrence of temporalis muscle hypertrophy without a coexisting masseteric hypertrophy.


Aging and otitis media as sources of variance in the rat auditory brainstem response.
Auditory brainstem response (ABR) latencies were examined in normal female Sprague-Dawley rats at 6 months of age and in 10-12 month old animals which tested positive for Mycoplasma pulmonis, a frequently implicated pathogen in otitis media. Significant differences in the peak latencies of Waves I, II and IIIn were found between the two age groups. A significant age by intensity interaction effect was also identified for Waves II and IIIn. Since the age-related effects observed in Wave I were similarly reflected in Waves II and IIIn, it was concluded that the group differences were due to alterations of the auditory periphery and not to changes in the central auditory system.


Gas chromatography-full scan mass spectrometry determination of traces of chemical warfare agents and their impurities in air samples by inlet based thermal desorption of sorbent tubes.
A sensitive gas chromatography-mass spectrometry (GC-MS) based analytical method was developed for detection of the chemical warfare agents (CWA) and related compounds in air/vapor samples. The method uses a Tenax TA packed GC liner as an air/vapor sampling tube and Programmable Temperature-Vaporization (PTV) GC inlet as the thermal desorber. This approach eliminates secondary focusing step and allows transfer of desorbed analytes as sharp bands directly to the head of GC column. Use of a Peltier element for rapid cooling eliminates need for an external coolant. Minimal logistic and hardware needs make the method relatively inexpensive and especially suitable for a mobile laboratory. The limits of detection (LODs) of 0.8-2.9ng on tube for selected nerve and blister agents were achieved in the full scan MS mode. Simple derivatization method applied for detection of Lewisites 1 and 2 did not affect simultaneous analysis of other agents. The method was extensively evaluated with authentic CWA during the field trainings of the inspectors from the Organization for the Prohibition of Chemical Weapons (OPCW). The environmental area and personal samples were collected for a semi-quantitative determination of averaged airborne CWA concentration levels.


SSP: Early prediction of sepsis using fully connected LSTM-CNN model.
Sepsis is a life-threatening condition that occurs due to the body's reaction to infections, and it is a leading cause of morbidity and mortality in hospitals. Early prediction of sepsis onset facilitates early interventions that promote the survival of suspected patients. However, reliable and intelligent systems for predicting sepsis are scarce. This paper presents a novel technique called Smart Sepsis Predictor (SSP) to predict sepsis onset in patients admitted to an intensive care unit (ICU). SSP is a deep neural network architecture that encompasses long short-term memory (LSTM), convolutional, and fully connected layers to achieve early prediction of sepsis. SSP can work in two modes; Mode 1 uses demographic data and vital signs, and Mode 2 uses laboratory test results in addition to demographic data and vital signs. To evaluate SSP, we have used the 2019 PhysioNet/CinC Challenge dataset, which includes the records of 40,366 patients admitted to the ICU. To compare SSP with existing state-of-the-art methods, we have measured the accuracy of the SSP in 4-, 8-, and 12-h prediction windows using publicly available data. Our results show that the SSP performance in Mode 1 and Mode 2 is much higher than existing methods, achieving an area under the receiver operating characteristic curve (AUROC) of 0.89 and 0.92, 0.88 and 0.87, and 0.86 and 0.84 for 4 h, 8 h, and 12 h before sepsis onset, respectively. Using ICU data, sepsis onset can be predicted up to 12 h in advance. Our findings offer an early solution for mitigating the risk of sepsis onset.


Ophthalmic Presentation of Undiagnosed Sinonasal Masses.
To evaluate clinical features of patients who first present with orbital symptoms and signs due to undiagnosed sinonasal pathology. Retrospective chart review for patients seen at Moorfields Eye Hospital between 1969 and 2020. Patient demographics and clinical features were reviewed. Four hundred and forty-eight patients (250 males; 56%) presented to ophthalmologists with undiagnosed sinonasal pathologies, the patients attending at an average age of 47 years and having first symptoms at an average age of 46 years. The commonest presenting symptoms were proptosis (153 patients; 34%), orbital ache or pain (133; 31%), periorbital swelling (130; 29%), and diplopia (98; 22%). Eighty-seven patients (20%) had a corrected acuity of 6/18 or worse, and 66 (16%) had an ipsilateral relative afferent pupillary defect. There was 2.3 mm relative exophthalmos (median 2 mm; range 0-17 mm) in patients with unilateral disease, an orbital mass was palpable in 218 patients (49%), ocular movements were reduced in 252/448 (56%), and nonaxial displacement of the globe was recorded in 296/424 (74%). The commonest pathologies were sinus mucoceles (38%), sinus carcinoma (11%), and granulomatous polyangiitis (10%). Multivariate regression analysis of mass lesions identified periorbital pain (odds ratio, 6.0; 95% confidence interval, 1.7-21.5; P = 0.005) and reduced motility (odds ratio, 3.2; 95% confidence interval, 1.1-9.0; P = 0.03) as features most predictive for undiagnosed sinonasal malignancy. This study describes a large group of patients in whom unknown midfacial masses presented initially to the ophthalmologist: Mucoceles and sinonasal malignancy were the commonest lesions, and nonaxial globe displacement-particularly inferolateral, lateral, or upward-is commonly associated with sinonasal pathology. Pain and reduced ocular movements significantly favor a malignant, rather than benign, tumor.


Wikipedia, friend or foe regarding information on diabetic retinopathy? A content analysis in the world's leading 19 languages.
To compare the completeness and quality of information about diabetic retinopathy on Wikipedia in the world's leading spoken languages in 2020. An observational, descriptive, cross-sectional study. The information on diabetic retinopathy obtained from the free encyclopedia Wikipedia® was assessed in languages with one hundred million or more total speakers. The term "diabetic retinopathy" was accessed in the corresponding Wikipedia entry in English, while the "more languages" function gives access to other languages. The information on the sites was collected by three ophthalmologist observers. A database was created with the most important subtopics for the education of patients with diabetic retinopathy in any of its classifications, based on a 25-question survey. The results were stratified on a scale from 0 to 4. A confirming correlation was found in the statistical analysis among the observers. No language achieved the label "excellent"; 2 languages were rated as "fair "; 4 languages qualified as "substandard"; and 7 languages were scored as "poor." No information could be found in five languages. As would be expected, the quality of content is variable across different languages. However, if anyone can edit Wikipedia, health professionals can do so as well to improve the quality and quantity of information for patients.


[Role of mitogen-activated protein kinase (MAPK) in the sporadic renal cell carcinoma].
Only on the basis of the involvement of the vhl suppressor gene in the cases of renal cell carcinomas (RCC), the involvement of the signaling pathway between the pVHL and the Hypoxia inducible factor 1, alpha (HIF-1α) has been evaluated because of the need to find new diagnostic and prognostic and response to drugs markers. The overexpression of HIF-1α confers better prognosis in clear cell type RCC (ccRCC). Furthermore, HIF-1α regulates other genes, specifically that of the carbon anhydrase IX (CA-IX), whose overexpression is practically only of the ccRCC and its determination is useful for this subtype. However, the involvement of the CA-IX has not been demonstrated in the prognosis or in the response to immunomodulators or antiangiogenics. Therefore, it is necessary to make a global evaluation of all this pathway: pVHL → HIF-1α → CA-IX, and even the analysis of other proteins and signaling pathways that also control the HIF-1α activity. In the latter case, the MAPK are critical in the HIF-1α activation, there being evidence on the experimental level of the control on its activity. although its clinical role as a biomarkers has not been established. Although the role of the MAPK in the phenomena of resistance to conventional chemotherapy and radiotherapy has been demonstrated, it has not been demonstrated in response to sorafenib, an important piece of information if we consider that it is an inhibitor of several protein kinases. Recently, it has been observed that the MAPK may be involved in the responses to different therapies, included those based on tyrosine kinase inhibitors. The confirmation of these data would suppose an explanation of the variation observed between patients who, with the same functional alteration of the vhl gene, have a different biological, clinical behavior and better selection of non-surgical therapies.


Static or Dynamic Navigation for Implant Placement-Choosing the Method of Guidance.
The purpose of the present report is to contrast and compare 2 methods of dental implant placement. One method uses computed tomography data for computer-aided design and computer-aided manufacturing to generate static guides for implant placement. The second method is a dynamic navigation system that uses a stereo vision computer triangulation setup to guide implant placement. A review of the published data was performed to provide evidence-based material to compare each method. Finally, the indications for each type of method are discussed.


Field measurement and evaluation of noise and vibrations induced by bridge cranes in full-scale over-track buildings.
Over-track buildings have been increasingly favored in the construction of metro depots and freight depots in China in the last decade due to advantages of intensive utilization of land resources and high-profits. However, due to the relatively heavy transportation mass and high-operating frequency of bridge cranes, over-track buildings are often complained by occupants for annoying noise and vibrations. So far this issue is rarely concerned and the characteristics of noise and vibrations under bridge crane loading remain unclear. In this study, field measurements of two full-scale over-track buildings, including a seven-story building over a metro depot and a three-story building over a freight depot, were conducted. Vibration characteristics of both the structure and the bridge crane were obtained. The transmission of vibrations from bridge crane system to the over-track building was obtained by transfer function (TF) of vibration from the column bracket towards the outdoor platform or building floors. The structure-borne noise inside the building was also captured and evaluated. The effect of bridge crane operational parameters (loading capacity and running velocity) and structural dynamic properties (non-structural components) on system responses was further discussed. Results show that the bridge crane-induced vibrations are comparable to the levels of train-induced vibrations. Besides, both buildings tested in this study suffer from unacceptable structure-borne noise, although the building vibration is acceptable. We recommend to carefully examining design of new over-track buildings to avoid annoying indoor noise and improve the living or working environment of occupants. It is demonstrated that vibrations of over-track buildings are more sensitive to running velocity than load capacity of bridge crane. It could be expected that the future increase of velocity will worsen the noise and vibration environment of over-track buildings. Furthermore, it is seen that non-structural components would remarkably affect dynamic responses of the building.


Statistical optimization of adsorption processes for removal of 2,4-dichlorophenol by activated carbon derived from oil palm empty fruit bunches.
The adsorption capacity of activated carbon produced from oil palm empty fruit bunches through removal of 2,4-dichlorophenol from aqueous solution was carried out in the laboratory. The activated carbon was produced by thermal activation of activation time with 30 min at 800 degrees C. The adsorption process conditions were determined with the statistical optimization followed by central composite design. A developed polynomial model for operating conditions of adsorption process indicated that the optimum conditions for maximum adsorption of phenolic compound were: agitation rate of 100 r/min, contact time of 8 h, initial adsorbate concentration of 250 mg/L and pH 4. Adsorption isotherms were conducted to evaluate biosorption process. Langmuir isotherm was more favorable (R2 = 0.93) for removal of 2,4-dichlorophenol by the activated carbon rather than Freundlich isotherm (R2 = 0.88).


Behavioral response and dynamics of Eisenia fetida hemocytes exposed to environmentally relevant concentration of sulfentrazone.
Although the toxicity of the pesticide sulfentrazone in some aquatic organisms is known, its effects on edaphic organisms such as earthworms remain completely unknown. Thus, we aimed at evaluating the behavior and immune response of Eisenia fetida exposed to sulfentrazone at environmentally relevant concentrations (EC). E. fetida representatives exposed to this contaminant (for 48 h) were divided in the following groups: environmental concentration (EC1x: 318 ng sulfentrazone/g of dry weight soil) and EC100x (concentration 100 times higher than in EC1x). Based on the avoidance test results, earthworms responded to this pesticide and proved the toxicity of sulfentrazone. The observed immune response induction was expressed by increased granulocytes presenting phagocytic vacuoles and agglomerations/encapsulations, mainly in animals belonging to groups EC1x and EC100x. However, the reduced frequency of plasmocytes in these animals' hemolymphs suggested that the phagocytic immune response was not efficient to assure 100% survival. Our study is the first to report sulfentrazone toxicity in an edaphic organism, at environmental concentration.


Phacoemulsification and intraocular lens implantation in nanophthalmic eyes: report of a medium-size series.
To evaluate the outcomes in nanophthalmic eyes that had phacoemulsification and intraocular lens (IOL) implantation. Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. Six nanophthalmic eyes of 4 patients had uneventful phacoemulsification and posterior chamber IOL implantation with a retrobulbar or peribulbar block. All operations were performed by 1 surgeon. Patients ranged in age from 41 to 70 years. The visual acuity remained stable or improved in all 6 eyes. Glaucoma control was maintained or improved in 5 eyes. The results indicate that small-incision cataract surgery, although challenging, is safe and diminishes the need for prophylactic sclerotomies in these high-risk eyes.


Ultra-performance liquid chromatography-tandem mass spectrometry: a novel challenge in multiresidue pesticide analysis in food.
Potential of ultra-performance liquid chromatography (UPLC) separation strategy coupled with tandem (in space) mass spectrometric detection (MS/MS) in multiresidue pesticide analysis was critically assessed. Performance parameters such as number of theoretical plates, height of theoretical plate, peak symmetry and peak capacity were measured/calculated on the basis of data generated by analysis of apple extracts containing 17 (semi)polar pesticides representing various classes of active ingredients of widely used crop protective preparations. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) procedure provided improved chromatographic parameters resulting in significantly increased sample throughput including lower solvent consumption and lower limits of quantitation (LOQs) for most of target analytes compared to common method employing conventional high-performance liquid chromatography (HPLC) separation.


Enhanced monocyte binding to human cytomegalovirus-infected syncytiotrophoblast results in increased apoptosis via the release of tumour necrosis factor alpha.
We have shown that monocytes bound to intercellular adhesion molecules (ICAM-1) on syncytialized placental trophoblasts (ST) induce trophoblast apoptosis, and that ST infection by human cytomegalovirus (HCMV) up-regulates ICAM-1. We hypothesize that the focal loss of trophoblast seen in HCMV-infected placenta is mediated by increased adherence of monocytes at sites of infection. We find that ST cultures (differentiated from primary cytotrophoblasts) increase monocyte binding when infected with HCMV. Monocyte adhesion was inhibited by antibodies to ICAM-1 and its ligand leukocyte function-associated molecule (LFA-1) on monocytes. When co-cultured with adhering monocytes, infected ST cultures had higher levels of apoptosis than infected cultures alone. Although trophoblast apoptosis clustered around adhering monocytes, it occurred only in non-infected cells. Blocking monocyte binding with ICAM-1 and LFA-1 antibodies reduced the rate of apoptosis to that of the infected culture. Co-cultures incubated with TNFalpha antibody and EGF inhibited both monocyte- and HCMV-induced apoptosis but did not block binding. We conclude that HCMV stimulates ST culture expression of ICAM-1, which binds to LFA-1 on monocytes that release TNFalpha, thereby inducing apoptosis of neighbouring uninfected trophoblasts. The above data indicates that trophoblast loss associated with HCMV infection can be caused by increased monocyte adhesion to ST.


The mechanism by which monoamine oxidase inhibitors give rise to a non-calcium-dependent component in the depolarization-induced release of 5-HT from rat brain synaptosomes.
1. The effects of the monoamine oxidase inhibitors pargyline and nialamide on the Ca2+-dependency of [3H]-5-hydroxytryptamine release from superfused rat brain synaptosomes has been studied in order to evaluate the discrepancies that have occasionally been observed in studying transmitter release by in vivo and in vitro techniques. 2. The application of K+ pulses of low concentration (12.5-20 mM) caused an essentially Ca2+-dependent release of [3H]-5-HT. However, at K+ concentrations above 30 mM, a small non-Ca2+-dependent component appeared. 3. At high concentrations of K+ (30-55 mM), nialamide (18 microM) or pargyline (7 microM) increased the amount of [3H]-5-HT released which could be accounted for by an increase in the non-Ca2+-dependent component of release. 4. The elevation of the non-Ca2+-dependent component of release caused by the monoamine oxidase inhibitors was totally abolished by the inhibitors of the plasma membrane 5-HT carrier, chlomipramine (500 nM), citalopram (50 nM) and fluoxetine (1 microM). 5. The results suggest that the non-Ca2+-dependent component of release seen with high depolarizing concentrations of K+, particularly in the presence of monoamine oxidase inhibitors, is caused by the efflux of [3H]-5-HT through the plasma membrane carrier which seems to be activated during depolarization. 6. The significance of these findings to the physiological in vivo situation, and to the use of in vitro preparations in the study of transmitter release is discussed.


alpha-Mercaptopropionyl-glycine influence on the in vitro proliferative response of human lymphocytes.
The effect of alpha-mercaptopropinyl-glycine on the in vitro proliferative response of healthy subjects' lymphocytes was studied. Low doses of the drug enhanced spontaneous lymphocyte blastigenesis but had no effect on the PHA-induced blastic response. With increasing concentrations of alpha-mercaptopropionyl-glycine inhibition of 3H-thymidine incorporation was found in unstimulated as well as in PHA stimulated lymphocytes.


Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival.
The presence of steroid receptors (82 tumors) and aromatase activity (39 tumors) in ovarian carcinomas was correlated with patient survival. No statistically significant correlation was found between the presence or absence of estrogen receptors (ER, 56.1%), progesterone receptors (PR, 57.3%), androgen receptors (AR, 91.5%), or aromatase activity (33.3%) and survival. However, high levels of PR were associated with better survival (P less than 0.05). Furthermore, there was a tendency for patients with advanced disease and PR-positive tumors to have better survival than those with advanced disease and PR-negative tumors (P = 0.13). Patients with tumors that did not contain any of the receptors and those in which ER and AR were absent, or in which PR and AR were absent, had poor survival. It is concluded that receptor status, especially of PR, may be of prognostic importance and that status of receptors and aromatase activity may become useful in selecting ovarian cancer patients for endocrine therapy.


Semi-supervised calibration of noisy event risk (SCANER) with electronic health records.
Electronic health records (EHR), containing detailed longitudinal clinical information on a large number of patients and covering broad patient populations, open opportunities for comprehensive predictive modeling of disease progression and treatment response. However, since EHRs were originally constructed for administrative purposes not for research, in the EHR-linked studies, it is often not feasible to capture reliable information for analytical variables, especially in the survival setting, when both accurate event status and event times are needed for model building. For example, progression-free survival (PFS), a commonly used survival outcome for cancer patients, often involves complex information embedded in free-text clinical notes and cannot be extracted reliably. Proxies of PFS time such as time to the first mention of progression in the notes are at best good approximations to the true event time. This leads to difficulty in efficiently estimating event rates for an EHR patient cohort. Estimating survival rates based on error-prone outcome definitions can lead to biased results and hamper the power in the downstream analysis. On the other hand, extracting accurate event time information via manual annotation is time and resource intensive. The objective of this study is to develop a calibrated survival rate estimator using noisy outcomes from EHR data. In this paper, we propose a two-stage semi-supervised calibration of noisy event rate (SCANER) estimator that can effectively overcome censoring induced dependency and attains more robust performance (i.e., not sensitive to misspecification of the imputation model) by fully utilizing both a small-labeled set of gold-standard survival outcomes annotated via manual chart review and a set of proxy features automatically captured via EHR in the unlabeled set. We validate the SCANER estimator by estimating the PFS rates for a virtual cohort of lung cancer patients from one large tertiary care center and the ICU-free survival rates for COVID patients from two large tertiary care centers. In terms of survival rate estimates, the SCANER had very similar point estimates compared to the complete-case Kaplan Meier estimator. On the other hand, other benchmark methods for comparison, which fail to account for the induced dependency between event time and the censoring time conditioning on surrogate outcomes, produced biased results across all three case studies. In terms of standard errors, the SCANER estimator was more efficient than the KM estimator, with up to 50% efficiency gain. The SCANER estimator achieves more efficient, robust, and accurate survival rate estimates compared to existing approaches. This promising new approach can also improve the resolution (i.e., granularity of event time) by using labels conditioning on multiple surrogates, particularly among less common or poorly coded conditions.


Particular aspects of thyroid function development in the postnatal rat with special reference to interrelationships between mother and young.
Previous data have demonstrated that thyroid gland thyroxine secretion rate in suckling rats is high and correlated with the hormonal needs of the young. Non-hormonal iodine metabolism is more elevated in the young than in the adult. The object of the present work was to measure rates of iodine transfer in 10-day old families of rats equilibrated with 125I or not. Reciprocal iodine exchange between mother and young occurred in such a way that the dam recovered about 60 p. 100 of the iodine lost in the milk. Moreover, a large store of extrathyroidal iodine was constituted in the young, particularly in the pelt.


Dynamics of first-order phase transitions in multicomponent systems: a new theoretical approach.
In the theoretical description of nucleation-growth processes, currently Gibbs's classical thermodynamic theory of heterogeneous systems is predominantly employed for the description of the properties of the clusters. However, Gibbs's approach does not make it possible to describe, in general, the properties of critical clusters (determining the rate of nucleation) in a sufficiently correct way. Moreover, Gibbs's approach is restricted by its applicability to thermodynamic equilibrium states exclusively. For this reason, it does not give a theoretically founded prescription for a determination of the possible states of clusters of sub- and supercritical sizes in dependence on supersaturation and size of the clusters. In order to overcome these shortcomings, in recent years a generalization of Gibbs's classical approach has been developed and employed for the description of nucleation processes. This generalization of Gibbs' classical method leads, for a variety of different applications, to dependencies of the work of critical cluster formation on supersaturation, which are qualitatively and widely even quantitatively in agreement with density-functional computations. The theoretical methods and results are summarized in the first part of the present paper. They are then extended for the first time to a description of processes of growth of single clusters and ensembles of clusters. In order to fulfill this task, a new method for determination of the parameters of sub- and supercritical clusters is developed. It turns out as the result of the analysis that a variety of thermodynamic and kinetic parameters, determining cluster growth, become dependent on cluster size as well. The results are illustrated for a model system (segregation in regular solutions) and applied to the interpretation of experimental results on segregation processes in solutions and crystallization processes in glass-forming melts. It is shown that the newly developed approach resolves a variety of problems in the interpretation of experimental data on the kinetics of phase formation processes which could not be given a satisfactory explanation so far.


Utility of unipolar recordings for complex Wolff-Parkinson-White ablation.
Radiofrequency ablation has been shown to be a safe and effective treatment strategy for the management of symptomatic patients with Wolff-Parkinson-White syndrome. It is supported by a success rate of 95% and a recurrence rate of less than 5%. However, ablation of accessory pathways can be challenging at times. The causes for failure can be grouped into three categories - unusual location of the pathway, technical difficulties in delivering the ablation and localization error [1]. In this case report we are reporting a case of a young male who presented to us with symptomatic Wolff-Parkinson-White syndrome with two failed prior ablations at another institution. This case illustrates the importance of knowing accurate localization and course of the accessory pathway by utilizing the unipolar and bipolar electrograms simultaneously during radiofrequency ablation.


The effects of amplitude-spectrum statistics on foveal and peripheral discrimination of changes in natural images, and a multi-resolution model.
Psychophysical thresholds were measured for discriminating small changes in spatial features of naturalistic scenes (morph sequences), for foveal and peripheral vision, and under M-scaling. Sensitivity was greatest for scenes with near natural Fourier amplitude slope, perhaps implying that human vision is optimised for natural scene statistics. A low-level model calculated differences in local contrast between pairs of images within a few spatial frequency channels with bandwidth like neurons in V1. The model was "customised" to each observer's contrast sensitivity function for sinusoidal gratings, and it could replicate the "U-shaped" relationships between discrimination threshold and spectral slope, and many differences between picture sets and observers. A single-channel model and an ideal-observer analysis both failed to capture the U-shape.


4D CT image acquisition errors in SBRT of liver identified using correlation.
In the AAPM Report 80, the imaging modality of 4D CT and respiration-correlated CT was declared a "promising solution for obtaining high-quality CT data in the presence of respiratory motion". To gather anatomically correct data over time, the existence of correlation between the internal organ movement and an external surrogate has to be assumed. For the in-house evaluation of such correlation, we retrospectively analyzed 21 four-dimensional computer tomography (4D CT) scans of five patients, out of which the artifacts experienced in three patients are shown here. To provide context and a baseline for the analysis of patient motion, a real-tissue liver phantom was used with a solid water block and liver tissue. The superior-inferior motion of fiducials in phantom and patients was correlated to the recorded anterior-posterior motion of an external surrogate marker on the chest. The use of a solid water block yielded a measurable correlation coefficient of 0.98 or better using a sinusoidal animation pattern. With sinusoidally-animated liver tissue, the minimum correlation observed was 0.96. Comparing this to retrospective patient data, we found three cases of a change in the correlation coefficient, or simply a low correlation. The source of this low correlation was investigated by careful examination of the breathing traces and the CT-phase assignments used to reconstruct the datasets. Consequences of nonregular breathing are elaborated on. We demonstrate the impact of wrong phase assignments and missing image information in the 4D CT phase sampling processes. We also show how daily patient-based correlation analysis can indicate changes in breathing traces, which can be significant enough to decrease, or completely eliminate, previously existing correlation.


A case report of primary multiple hydatid cysts of psoas muscle: An exceptional location.
The psoas muscle localization is even more exceptional when they are multiple. The clinical and radiological features were often misleading. This case report aimed to highlight the difficulties of radiological diagnosis and the dilemma of choosing the best operative approach. A 27 year-old-men with no past medical history has been consulted for right down abdominal quadrant pain. Physical examination revealed a painless abdominal mass. An abdominal CT Scan concluded with the presence of two multisectional cystic lesions. The first cystic lesion had an exophytic development, and the second cystic lesion was in the posterior and lateral sides of the psoas muscle. The hemaglutinin reaction and the Western blot were positive. A laparotomy was done. The exploration objective is a first psoas muscle hydatid cyst of 5 cm with an exophytic development just behind the vermiform appendix with a second hydatid cyst of 15 cm. The puncturing and aspiration of the cystic fluid bring a clear hydatid fluid. Parasitic sterilization was performed by injecting a scoliosis solution, hypertonic serum, into the cystic lesion. After ten minutes, we resected the two cystic lesions' protruding dome. We have aspirated the fluid and all the daughter hydatid cysts from the two hydatid cysts. The postoperative follow-up was uneventful. The primary hydatid cyst of the psoas muscle often causes a problem of its hydatid nature. Surgery remains the only curative treatment. It avoids the risk of complications such as peritoneal rupture, which can modify the surgical therapeutic strategy.


The immune response to Echinococcus granulosus: sequential histological observations of lymphoreticular and connective tissues during early murine infection.
This paper describes the organ weight changes and the early (0 to 56 days) histological and ultrastructural changes in the lymphoid structures and injection sites after subcutaneous infection of Balb/c mice with Echinococcus granulosus protoscolices (psc). Local lymph nodes enlarged markedly, reaching maximal weight 5 to 14 days after infection (pi). Expansion of the thymus-dependent areas of draining lymph nodes was first recognized at 3 days pi and reached a maximum between 14 and 21 days pi. Lymphoproliferation within B-cell-dependent areas was less extensive and of shorter duration. Comparable, but diminished, changes were seen in contralateral lymph nodes and spleen. Lymphoid cell depletion was observed in T-dependent areas of lymphoid organs by 56 days pi. Local inflammatory reactions to psc, at the site of injection, were intense, involving neutrophils, eosinophils, macrophages and mast cells. Viable psc were present until at least 6 weeks pi. The central role of the T-lymphocyte in recognition of, and response, to E. granulosus psc is discussed.


Purification and characterization of two transcribed repetitive DNA fractions from the pigeon genome.
Two fractions of the repeats belonging to intermediate frequency repetitive DNA were isolated from the total pigeon nuclear DNA fragmented to about 450 nucleotides. One fraction was designated as "rare repeats" (repetition frequency about 35 per haploid genome) and another termed as "moderate repeats" (repetition frequency about 2500 per haploid genome). The rare repeats, which constitute about 7% of the total DNA, include at least 75% of the repetitive DNA sequences transcribed into the high molecular fraction (greater than 45S) of HnRNA in erythroid cells. These repeats have properties compatible with the characteristics of the class of low frequency interspersed DNA found in genomes of many other Metazoan species. The moderate repeats contribute only about 10-20% of the total repetitive DNA copies present in greater than 45S HnRNA and differ from the rare repeats in some other properties.--The possible role of the rare repeats in the genome is discussed.


Facilitated water transport in cyanobacterium Synechococcus sp. PCC 7942 studied by phycobilisome-sensitized chlorophyll a fluorescence.
Water transport across plant cell membranes is difficult to measure. We present here a model assay, based on chlorophyll (Chl) a fluorometry, with which net water transport across the cell membrane of freshwater cyanobacterium Synechococcus sp. PCC7942 (S7942) can be followed kinetically with millisecond-time resolution. In cyanobacteria, the phycobilisome (PBS)-sensitized Chl a fluorescence increases when cells expand (e.g., in hypo-osmotic suspension) and decreases when cells contract (e.g., in hyper-osmotic suspension). The osmotically-induced Chl a fluorescence changes are proportional to the reciprocal of the suspension osmolality (DeltaF proportional, variant Osm-1; Papageorgiou GC and Alygizaki-Zorba A (1997) Biochim Biophys Acta 1335: 1-4). In our model assay, S7942 cells were loaded with NaCl (passively penetrating solute) and shrunk in hyper-osmotic glycine betaine (nonpenetrating solute). Upon injecting these cells into hypo-osmotic medium, the PBS-sensitized Chl a fluorescence rose to a maximum due to the osmotically-driven water uptake. The rise of Chl a fluorescence (water uptake) was partially inhibited by HgCl2, at micromolar concentrations. Arrhenius plots of the water uptake rates gave activation energies of EA=4.9 kcal mol-1, in the absence of HgCl2, and EA=11.9 kcal mol-1 in its presence. These results satisfy the usual criteria for facilitated water transport through protein water pores of plasma membranes (aquaporins), namely sensitivity to Hg2+ ions and low activation energy.


Digestion of killed Paracoccidioides brasiliensis by neutrophils.
We previously described an in vitro assay showing that neutrophils (PMNs) from patients with paracoccidioidomycosis (PARA) have a specific digestive deficiency against suspensions of live Paracoccidioides brasiliensis. We now report that this defect is equally detectable against autoclaved, but not Amphotericin B-killed P. brasiliensis. The use of autoclaved suspensions facilitates the use of our in vitro assay. It might allow the development of an in vitro intradermal test for digestion of fungi. Differential digestive ability of phagocytes against live (or autoclaved) and Amphotericin-B killed fungi is of conceptual interest. It may be relevant in understanding therapeutic effect of Amphotericin B.


Benzodiazepine-like substances and hepatic encephalopathy : implications for treatment.
Hepatic encephalopathy is a neuropsychiatric syndrome that can complicate acute and chronic liver disease. Recent research has focused on the role benzodiazepine-like substances play in the pathogenesis of this disorder. It has been proposed that potentiation of the action of the neuroinhibitory transmitter γr-aminobutyric acid (GABA) through the binding of endogenous benzodiazepine agonists to the benzodiazepine receptor binding site accounts for the clinical and biochemical features of this condition.Increased levels of endogenous benzodiazepine-like substances have been noted in animal models of hepatic encephalopathy. In human studies, levels of these substances of up to 10 times those found in the body fluids of nonencephalopathic controls have been reported. The existence of such markedly elevated levels cannot be satisfactorily explained with reference to possible pharmaceutical or dietary origins.Further support for the role of benzodiazepines in the mediation of hepatic encephalopathy comes from the therapeutic effect reported after administration of the benzodiazepine receptor antagonist flumazenil. Improvements in the severity of hepatic encephalopathy have been documented in rats with fulminant hepatic failure given flumazenil, although results have been inconsistent according to the dose of flumazenil used and the procedure employed to induce the encephalopathy. Transient, but distinct, improvements in the grade of hepatic encephalopathy have also been documented in several human studies. In a placebo-controlled study involving patients with mild hepatic encephalopathy, a low dose of flumazenil (0.2 mg/kg) resulted in a significant improvement in reaction time.Research now needs to identify whether the beneficial effect of flumazenil is due to its antagonistic or inverse agonistic properties, and also to clarify the mechanisms by which the differential response to the drug in animal models of fulminant hepatic failure is mediated.


Background features of endometrial carcinoma on ThinPrep cytology.
Conventional smear screening has had little impact on the detection of endometrial carcinoma. Recent studies on liquid-based preparations show promise with increased detection rates of endometrial lesions. The purpose of this 2-yr retrospective study (February 1, 2002-February 29, 2004) was to evaluate the background features on ThinPrep slide preparations from endometrial carcinomas. During this period, 20 (0.06%) cases were diagnosed as adenocarcinoma, of which 15 (75%) showed endometrial carcinoma on cervical or vaginal biopsy. Classic tumor diathesis was present on the slides in 8 (53%) of the cases, the majority of which were from high-grade tumors. In 1 (7%) case, the tumor diathesis consisted of precipitated protein in a watery background. Tumor diathesis was absent in 6 (40%) of the cases, the majority of which were low-grade lesions. Background features on ThinPrep Pap tests from patients with endometrial features range from classic tumor diathesis to clean; findings dependent on the histologic type and grade of the tumor and the extent of the disease process.


Psychiatric referrals in a neuropsychiatric centre.
Consecutive new cases were screened to identify those referred by other specialties. The referred cases were compared with a randomly selected control group from the non referred cases. Referred cases constituted 16.4% of all the clinic new cases but the demographic characteristics were similar to those of the other clinic cases. Functional somatic complaints were significantly more often (p less than 0.01) reported by the referred cases. Depressive and anxiety symptoms were also significantly more often observed in the referred group (p less than 0.01). Most of the referred cases had identifiable psychiatric problems which could be managed in an out-patient setting. Studies on referral patterns and modes of clinical presentation are useful in planning and organising consultation liaison services in general and specialist centres.


Super-efficient removal and adsorption mechanism of anionic dyes from water by magnetic amino acid-functionalized diatomite/yttrium alginate hybrid beads as an eco-friendly composite.
The development of eco-friendly, large-capacity and easy-to-separate adsorbent materials has always been the focus and difficulty of adsorption technology in wastewater treatment applications based on the characteristics of dye wastewater. Therefore, in this study, a green magnetic glycine(Gly)-functionalized diatomite(Dia)/yttrium alginate (Y-SA) hybrid bead composite (Dia-Gly-Y-SA@Fe3O4) was synthesized by the droplet polymerization, and characterized by various modern analytical techniques. The adsorption performance and adsorption mechanism of the composite were evaluated and elucidated by the removal of anionic dyes direct Blue 106 (DB 106), Congo red (CR) and direct red 13 (DR 13) from water. The results show that the composite is a macroparticle gelpolymer with an average particle size of about 1.5 mm, flower-like fold surface structure, abundant porosity and sensitive magnetic response, and displays ultrastrong adsorption ability for three dyes. The adsorption equilibrium of each dye can be reached quickly within 30 min, and the removal efficiency is more than 95% at pH 2.0 and decreases slightly with pH up to 9.0. The adsorption processes could be explained by the Pseudo-second-order rate equation well. All isotherm data fitted the Langmuir model well, and the maximum adsorption capacities were 1635, 2359 and 1165 mg/g for DB 106, CR and DR 13 at 298 K, respectively. The ultrastrong adsorption performance was due to the multisite interaction of physicochemical action and various hydrogen bonds between hybrid beads and dye anions. As a cost-effective magnetic macroparticle adsorbent prepared by natural ingredients, Dia-Gly-Y-SA@Fe3O4 composite exhibits much more stronger adsorption efficiency, better collectability and no secondary pollution than powder Dia, and would have a good application prospect for the purification of anionic dye wastewater with a wide pH range.


Can COVID-19 pandemic change plastic contamination? The Case study of seven watercourses in the metropolitan city of Milan (N. Italy).
The more or less extensive lockdowns, quarantines, smart working and the closure of numerous recreational or personal care activities due to the COVID-19 pandemic have not only heavily changed the habits and behaviors of all of us, but have also had consequences on the release of some types of pollutants. The aim of this study was to evaluate the possible changes due to the indirect effects of the pandemic in the contamination of plastic mixtures sampled in 9 sites of the main watercourses of the metropolitan city of Milan (N. Italy), which is one of the major industrialized and urbanized areas in Italy. To achieve this goal, we carried out two sampling campaigns, the first one carried out in November 2019, before the arrival of the SARS-CoV-2 virus in Italy, the second in November 2020, during a severe regional lockdown that coincided with other restrictions imposed at the national level. The main results showed a difference in contamination of plastics between the two samplings, not so much due to a quantitative variation, but certainly qualitative. We obtained non-homogeneous data with respect to changes in the number of plastics sampled in the different waterbodies, while it was evident that the plastics' contamination has shifted from a primary and industrial origin to one due to a secondary origin of the sampled plastics, linked especially to the fragmentation of common use objects, or deriving from synthetic garments.


Identification by MRI.
A semi-skeletted water-lodged corpse was supposed to be an 82-year-old missed man. Fifteen years ago this person underwent an operation of a trimalleolar fracture of the left ankle joint. Conventional X-ray photograms of the left ankle joint of the water-lodged corpse showed no evidence of an operation. A T-1 weighted spin-echo sequence revealed the entire aspect of the osteosynthesis as documented in the previously performed post-operative X-ray photograms.


The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson's Disease.
Patients with Parkinson's Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson's Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93), SNCA_A53T_rs104893877 (8.21, 2.26-36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10), and ZNF184_rs9468199 (1.89, 1.08-3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78). The ML algorithms led to similar results. The predictive models were highly specific (95-99%) but lacked sensitivity (9-39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.


Tanshinones inhibit mast cell degranulation by interfering with IgE receptor-mediated tyrosine phosphorylation of PLCgamma2 and MAPK.
Recently we have isolated four active components from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) responsible for the anti-allergic activities. In this study, the molecular mechanism of action of tanshinones for the inhibition of mast cell degranulation was investigated by testing their effects on the signaling components of the high affinity IgE receptor FcepsilonRI. Activation of FcepsilonRI produced immediate tyrosine phosphorylation of Syk, mitogen-activated protein kinase extracellular signal-regulated kinase, ERK1/ERK2 (p44, p42), and phospholipase Cgamma2 (PLCgamma2). 5,16-Dihydrotanshinone-I possessed the strongest inhibitory effects on mast cell degranulation and markedly reduced FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma2. This suggests that tanshinones possibly exert their anti-allergic activities by affecting FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma2. Abbreviations. FcepsilonRI:high affinity IgE receptor ERK:extracellular signal regulated kinase PLC: phospholipase C


Validation of CARE Scale-7 in treatment-seeking patients with chronic pain: measurement of sex invariance.
Social and interpersonal factors impact the trajectory of chronic pain. We previously developed and validated a 2-factor, 7-item measure to assess interpersonal factors, including relationship guilt and worry and difficulty prioritizing self-care in chronic pain. Here, we confirm the factor structure and examine the sex invariance of the two-factor structure of the CARE Scale-7. Data were collected as part of routine clinical care at a tertiary pain clinic using the Collaborative Health Outcomes Information Registry. Patient participants (67% women) were predominantly middle-aged (M = 50.9 years, SD = 17.8), married (55.2%), and White/non-Hispanic (55.7%). Data included demographics, pain characteristics, CARE Scale-7, pain catastrophizing, and Patient-Reported Outcomes Measurement Information System psychological and physical function measures. Confirmatory factor analysis was conducted to validate the factor structure of the CARE Scale, and a stepwise approach to measurement invariances by sex examined configural, metric, and scalar invariance. Internal consistency of the scale items ensured suitability for factor analyses. Confirmatory factor analysis findings revealed an overall good fit of the 2-factor model among males and females and that CARE Scale-7 is in fact sex invariant. Finally, CARE Scale-7 showed convergent validity with pain-related outcomes. The CARE Scale is the first validated instrument to assess self-care in both sexes among patients with chronic pain. The subscale of difficulty prioritizing self-care emerged as a potentially unique factor that should be integrated in clinical assessment. CARE Scale may facilitate standardized measurement in research and clinical contexts, which may inform a comprehensive treatment focus that integrates individualized self-care planning.


Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs.
This study was designed to investigate the chronic cardiotoxic potential of SM-5887 and a possible deteriorating effect of SM-5887 on low-grade cardiotoxicity pre-induced by doxorubicin in beagle dogs. In the chronic treatment, beagle dogs of each sex were given intravenously once every 3 weeks, either a sublethal dose of doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg). The experiment was terminated 3 weeks after the ninth dosing. Animals which received over six courses of doxorubicin demonstrated the electrocardiogram (ECG) changes, decrease of blood pressure and high-grade histopathological cardiomyopathy, while animals which were terminally sacrificed after the SM-5887 administration did not show any changes in ECG, blood pressure and histopathological examinations. To examine a possibly deteriorating cardiotoxic effect of SM-5887, low-grade cardiomyopathy was induced in dogs by four courses of doxorubicin (1.5 mg/kg). Nine weeks after pre-treatment, dogs were given four courses of either doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg) once every 3 weeks. The low-grade cardiotoxic changes were enhanced by the additional doxorubicin treatment. On the contrary, the SM-5887 treatment did not progress the grade of cardiomyopathy. In conclusion, SM-5887 does not have any potential of chronic cardiotoxicity and deteriorating effect on doxorubicin-induced cardiotoxicity in dogs.


eBooks: A Novel Approach to Education and Training Offering Savings and Resources.
eBooks can be an essential tool in bringing in technology-enriched education, just-in-time resources, and enduring material for staff in the health care setting. eBooks provide the most relevant information and can serve as the central hub for links to important documents, such as policies and/or video demonstrations. The use of eBooks will improve training and educational efficiency and can result in cost savings and improvements in standardized clinical practice. [J Contin Educ Nurs. 2023;54(9):394-397.].


Glucocorticoids decreased Cx43 expression in osteonecrosis of femoral head: The effect on proliferation and osteogenic differentiation of rat BMSCs.
Glucocorticoid (GC)-induced osteonecrosis of the femoral head (GC-ONFH) is considered as one of the most serious side effects of long-term or over-dose steroid therapy. However, the underlying cause mechanisms are still not fully investigated. We firstly established a rat model of GC-ONFH and injected lipopolysaccharide (LPS) and methylprednisolone (MPS). We found that the expressions of Cx43, Runx2, ALP and COLⅠ were more decreased than the normal group. Secondly, the isolated rat bone marrow stem cells (BMSCs) were treated with dexamethasone (Dex) in vitro, and the expressions of Cx43, Runx2, ALP and COLⅠ were decreased significantly. Moreover, the results of immunofluorescence staining, alizarin red staining, EdU assay and CCK8 showed that the osteogenic differentiation and the proliferation capacity of BMSCs were decreased after induced by Dex. A plasmid of lentivirus-mediated Cx43 (Lv-Cx43) gene overexpression was established to investigate the function of Cx43 in BMSCs under the Dex treatment. Findings demonstrated that the proliferation and osteogenic differentiation abilities were enhanced after Lv-Cx43 transfected to BMSCs, and these beneficial effects of Lv-Cx43 were significantly blocked when PD988059 (an inhibitor of ERK1/2) was used. In conclusion, the overexpression of Cx43 could promote the proliferation and osteogenic differentiation of BMSCs via activating the ERK1/2 signalling pathway, which provide a basic evidence for further study on the detailed function of Cx43 in GC-ONFH.


Many-body correlations in one-dimensional optical lattices with alkaline-earth(-like) atoms.
We explore the rich nature of correlations in the ground state of ultracold atoms trapped in state-dependent optical lattices. In particular, we consider interacting fermionic ytterbium or strontium atoms, realizing a two-orbital Hubbard model with two spin components. We analyze the model in one-dimensional setting with the experimentally relevant hierarchy of tunneling and interaction amplitudes by means of exact diagonalization and matrix product states approaches, and study the correlation functions in density, spin, and orbital sectors as functions of variable densities of atoms in the ground and metastable excited states. We show that in certain ranges of densities these atomic systems demonstrate strong density-wave, ferro- and antiferromagnetic, as well as antiferroorbital correlations.


Obstructive jaundice due to intracholedochal blood clot: an unusual early presentation of primary hepatic carcinoma.
We report a case of early presentation of a hepatocellular carcinoma with obstructive jaundice, due to obstruction of the common bile duct by a blood clot. The possibility of preoperative diagnosis, the surgical treatment and the postoperative outcome are discussed.


Computer simulation as a tool for clinical trial design.
Use of a computer simulation technique as a tool for optimising the design of a clinical trial is described. One of several aspects of trial design facilitated by use of the technique is the estimation of the number of patients required in the trial. The simulation tool provides the basis for structured and disciplined discussion of all the issues to be considered in designing a trial. Copies of the simulation program are available from the author.


An ambient air quality evaluation model based on improved evidence theory.
It is significant to evaluate the air quality scientifically for the management of air pollution. As an air quality comprehensive evaluation problem, its uncertainty can be effectively addressed by the Dempster-Shafer (D-S) evidence theory. However, there is not enough research on air quality comprehensive assessment using D-S theory. Aiming at the counterintuitive fusion results of the D-S combination rule in the field of comprehensive decision, an improved evidence theory with evidence weight and evidence decision credibility (here namely DCre-Weight method) is proposed, and it is used to comprehensively evaluate air quality. First, this method determines the weights of evidence by the entropy weight method and introduces the decision credibility by calculating the dispersion of different evidence decisions. An algorithm case shows that the credibility of fusion results is improved and the uncertainty is well expressed. It can make reasonable fusion results and solve the problems of D-S. Then, the air quality evaluation model based on improved evidence theory (here namely the DCreWeight model) is proposed. Finally, according to the hourly air pollution data in Xi'an from June 1, 2014, to May 1, 2016, comparisons are made with the D-S, other improved methods of evidence theory, and a recent fuzzy synthetic evaluation method to validate the effectiveness of the model. Under the national AQCI standard, the MAE and RMSE of the DCreWeight model are 1.02 and 1.17. Under the national AQI standard, the DCreWeight model has the minimal MAE, RMSE, and maximal index of agreement, which validated the superiority of the DCreWeight model. Therefore, the DCreWeight model can comprehensively evaluate air quality. It can provide a scientific basis for relevant departments to prevent and control air pollution.


Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer.
KRAS mutations, which occur in approximately 25% of lung adenocarcinoma cases, represent a major unmet clinical need in thoracic oncology. Preclinical studies have demonstrated that KRAS mutant NSCLC cell lines and xenografts with additional alterations in either TP53 or CDKN2A (INK4A/ARF) loci are sensitive to focal adhesion kinase (FAK) inhibition. Defactinib (VS-6063) is a selective oral inhibitor of FAK. Patients with previously treated advanced KRAS mutant NSCLC were prospectively assigned to one of four molecularly defined cohorts based on the presence or absence of TP53 or CDKN2A alterations and received treatment with defactinib 400 mg orally BID until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at 12 weeks. Fifty-five patients were enrolled. Mean age was 62 years; 51% were female. The median number of prior lines of therapy was 4 (range 1-8). Fifteen (28%) patients met the 12-week PFS endpoint, with one patient achieving a partial response. Median PFS was 45 days. Clinical efficacy did not correlate with TP53 or CDKN2A status. The most common adverse events were fatigue, gastrointestinal, and increased bilirubin, and were generally grade 1 or 2 in severity. In heavily pretreated patients with KRAS mutant NSCLC, defactinib monotherapy demonstrated modest clinical activity. Efficacy was not associated with TP53 and CDKN2A status. Defactinib was generally well tolerated.


Synthesis and biological evaluation of paclitaxel and vorinostat co-prodrugs for overcoming drug resistance in cancer therapy in vitro.
Paclitaxel (PTX) is the first-line treatment drug for breast cancer. However, drug resistance after a course of treatment and low selectivity restricted its clinical utility sometimes. In this study, we successfully bound PTX and vorinostat (SAHA) to form co-prodrugs based on the synergistic anticancer effects. The PTX-SAHA co-prodrugs were conjugated by glycine (1a) and succinic acid (1b) respectively and the former has shown better activity in cytotoxicity, cell cycle arrest and western-blot experiments. Therefore, 1a was further prepared to nanomicelles with mPEG2000-PLA1750 as the carrier by using thin film method. PTX-SAHA co-prodrug nanomicelles were spherical with a particle size of 20-100 nm. In vitro drug release test showed 1a nanomicelles had sustained release effect, which could reduce the resistance of PTX. In vitro cytotoxicity was evaluated by SRB assay in HCT-116 cells, MCF-7 cells and drug-resistant MCF-7/ADR cells. The results showed 1a nanomicelles had comparable or even better cytotoxicity than PTX especially in the MCF-7/ADR cells. All the results suggested that PTX-SAHA co-prodrug nanomicelles were promising treatment for PTX resistance cancer.


Subcutaneous implantable defibrillator in dextrocardia secondary to Lobectomy.
Knowledge of anatomy is vital preimplant to screen the patient for the subcutaneous implantable defibrillator (S-ICD), particularly those who have previously had thoracic surgery. X-ray screening in these patients is highly recommended.


The mediator role of psychological morbidity on sleep and health behaviors in adolescents.
This study examined the mediation role of psychological morbidity, defined in this study as depression/anxiety, in the relationship between excessive daytime sleepiness and sleep quality, and between sleep habits and health behaviors, in adolescents. A total of 272 students, between 12 and 18 years old, underwent a psychological protocol assessing excessive daytime sleepiness, sleep quality, sleep habits, health behavior, and psychological morbidity. Psychological morbidity was not associated with the relationship between excessive daytime sleepiness and sleep quality, but was associated, with statistical significance, in the relationship between sleep habits and health behaviors. These results emphasize the role of psychological morbidity in adolescent health behaviors. Analyzing the symptoms of depression and anxiety in pediatric patients may help in a more accurate diagnosis, especially in relation to sleep problems and health behaviors.


Characterization of a novel natural tetracenomycin reveals crucial role of 4-hydroxy group in ribosome binding.
The aromatic polyketides tetracenomycins were recently found to be potent inhibitors of protein synthesis. Their binding site is located in a unique locus within the tunnel of the large ribosomal subunit. Here we report the isolation and structure elucidation of a novel natural tetracenomycin congener - O4-Me-tetracenomycin C (O4-Me-TcmC). This compound is isomeric to tetracenomycin X (TcmX), however, in contrast to TcmX, O4-Me-TcmC exhibited no antimicrobial activity and was unable to inhibit protein synthesis in vitro. Structural alignment of tetracenomycins to the binding locus from cryo-EM TcmX-70S ribosome data revealed the crucial role of the 4-hydroxyl group. These findings are important for further development of semi-synthetic tetracenomycins as potential antibacterials.


Apolipoprotein B mRNA-editing, catalytic polypeptide cytidine deaminases and retroviral restriction.
Apolipoprotein B (apo B) messenger RNA (mRNA)-editing, catalytic polypeptide (APOBEC) cytidine deaminases (CDAs), which can insert mutations into DNA and/or RNA as a result of their ability to deaminate cytidine (C) to uridine (U), originated from a branch of the zinc-dependent deaminase superfamily at the beginning of vertebrate radiation. The ability of mammalian CDAs encoded by the APOBEC3 genes to restrict a broad number of endogenous retroelements and exogenous retroviruses, including human immunodeficiency virus-1, is well established. Furthermore, APOBEC1 from a variety of mammalian species, which mediates the C-to-U deamination of apo B mRNA, a protein involved in lipid transport, also has a role in controlling mobile elements. A large portion of the mammalian genome is derived from ancient transposable elements. Retroelements, transported by an intracellular copy-and-paste process involving an RNA intermediate, constitute the majority of these mobile genetic elements. Endogenous retroviruses are long-terminal repeat (LTR)-type retroelements that account for approximately 10% of human and murine genomic DNA. Non-LTR members are present in extremely high copy numbers, with approximately 40% of the human and murine genomes consisting of long-interspersed nuclear element-1 (L1). These L1 elements modify mammalian genomes not only through insertions but also by the indirect replication of non-autonomous retrotransposons. As expected, vertebrate intrinsic immunity has evolved to support a balance between retroelement insertions that cause deleterious gene disruptions and those that confer beneficial genetic diversity. This review discusses the current understanding of the mechanism of action of APOBEC CDAs and their role in controlling retroviruses and retroelements.


Emergency-department accesses in home care paediatric patients: Occurrence and risks of use in a six-year retrospective investigation in Northern Italy.
To assess the determinants of ED use in paediatric patients enrolled in an Integrated Paediatric Home Care (IPHC) program. A retrospective study was conducted using administrative databases on a cohort of patients enrolled in an IPHC program between January 1st, 2012, and December 31st, 2017, in Northern Italy. ED visits that occurred during the IPHC program were considered. Data were collected considering sociodemographic, clinical and organizational variables. A multivariable stepwise logistic regression analysis was performed. The dependent variable to identify possible associations was ED visit. A total of 463 ED visits occurred in 465 children, with an incidence rate of 1. The risk of ED visits significantly increased among children involved in the IPHC program after hospital discharge (OR 1.94). Additionally, the risk of ED visits increased significantly as the duration of IPHC increased (OR 5.80 between 101 and 200 days, to OR 7.84 between 201 and 300 days, OR 12.54 between 301 and 400 days and OR 18.67 to more than 400 days). The overall results represent a practical perspective to contribute improving both the service quality of IPHC and reducing low acuity and improper ED use.


From GTP and G proteins to TRPC channels: a personal account.
By serendipity and good fortune, as a postdoctoral fellow in 1967, I landed at the right place at the right time, as I was allowed to investigate the mechanism by which hormones activate the enzyme adenylyl cyclase (then adenyl cyclase) in Martin Rodbell's Laboratory at the NIH in Bethesda, Maryland. The work uncovered first, the existence of receptors separate from the enzyme and then, the existence of transduction mechanisms requiring guanosine-5'-triphosphate (GTP) and Mg(2+). With my laboratory colleagues first and postdoctoral fellows after leaving NIH, I participated in the development of the field "signal transduction by G proteins," uncovered by molecular cloning several G-protein-coupled receptors (GPCRs) and became interested in both the molecular makeup of voltage-gated Ca channels and Ca2+ homeostasis downstream of activation of phospholipase C (PLC) by the Gq/11 signaling pathway. We were able to confirm the hypothesis that there would be mammalian homologues of the Drosophila "transient receptor potential" channel and discovered the existence of six of the seven mammalian genes, now called transient receptor potential canonical (TRPC) channels. In the present article, I summarize from a bird's eye view of what I feel were key findings along this path, not only from my laboratory but also from many others, that allowed for the present knowledge of cell signaling involving G proteins to evolve. Towards the end, I summarize roles of TRPC channels in health and disease.


Contraceptive and sexual practices among single women with an unplanned pregnancy: partner influences.
Data from an urban obstetrics clinic on 291 unmarried women with a current unplanned pregnancy show that women with only one partner in the past year are older and are more likely to use the most effective contraceptive methods than are women who have more than one partner. Women with only one partner are also more likely to be solely responsible for decision-making about the choice of contraceptive methods, and are not as likely to use drugs in conjunction with sex. However, women with one partner are also less likely than others to use condoms or to protect in some other way against sexually transmitted diseases or the human immunodeficiency virus.


Rapid ejaculation: a review of conceptual, etiological, and treatment issues.
A man's ability to control the timing of his ejaculation is a key aspect of his and his partner's sexual pleasure. This paper reviews the available clinical and experimental literature on rapid ejaculation (RE) highlighting methodological weaknesses common to research in the area. The numerous operational definitions of RE are reviewed. Inconsistencies among these definitions have led to difficulties in comparing studies. Empirical support for existing theories regarding the etiology of RE are reviewed. None has clear empirical support as being causally related to RE. The success of therapeutic interventions for RE are evaluated. The active ingredient(s) of therapeutic interventions for RE and the mechanisms by which they work have yet to be identified. Further, these treatments are far from universally successful, suggesting a need for additional approaches. A multivariate approach to operationalizing RE based on both ejaculatory latency and perceived control is proposed. This approach would also facilitate the understanding of both etiological and treatment issues.


Early postoperative calcium levels as predictors of hypocalcemia.
Early, safe postoperative hospital discharge has become a priority in the current environment of cost containment and managed care. One determinant for this following operations of the thyroid or parathyroid glands is a stable postoperative calcium level. This study sought to determine whether early postoperative calcium levels could safely predict hypocalcemia following operations of the thyroid or parathyroid glands. A retrospective chart review of 197 patients undergoing such operations was undertaken. The study population was divided into patients undergoing parathyroid exploration with removal of one or more glands for parathyroid disease ("parathyroid" group) and patients undergoing bilateral thyroid operations ("nonparathyroid" group). Postoperative calcium levels were plotted as a function of time, and the slope between the first two postoperative calcium levels examined. A positive slope predicted normocalcemia in 100% of "nonparathyroid" and 90% of "parathyroid" surgeries. A negative slope was predictive in its magnitude. The nonparathyroid patients who developed postoperative hypocalcemia had an average slope significantly more negative (-0.84% change/h) than patients remaining normocalcemic (-0.49% change/h) (P = .03). Similarly, the parathyroid patients who became hypocalcemic had an average initial slope nearly twice as negative (-1.4% change/h) as patients remaining normocalcemic (-0.78% change/h) (P = .005). These results indicate that an initial upsloping postoperative calcium curve based on two early postoperative calcium measurements is strongly predictive of a stable postoperative calcium level, and a steeply downsloping initial calcium curve is worrisome for eventual hypocalcemia.


Quantitative analysis of the capillary network of aged APPswe/PS1dE9 transgenic mice.
A combination of immunohistochemical and stereological techniques were used to investigate the capillary network in the cerebral cortex of 18-month-old APPswe/PS1dE9 transgenic (Tg) mice and control littermates. Data regarding total capillary length, segment number, diffusion radius, and pericyte number are presented. The total length was 60 meters and there was a one-to-one relationship between the number of capillary segments and pericytes in both groups. Significant differences were not observed in the Tg and wild-type controls indicating that the Alzheimer's-like amyloidosis produced in this Tg mouse has a minimal affect on the structural integrity of the cerebral capillary network.


Value of color Doppler estimation of regurgitant volume in patients with chronic aortic insufficiency.
We studied 16 patients with chronic aortic insufficiency to compare a method for measuring regurgitant volume with color Doppler flow mapping to stroke count ratio determined by radionuclide ventriculography and to ventricular volumes assessed by two-dimensional echocardiography. A real-time color flow map of the left ventricular was obtained from an apical two- and five-chamber view and the maximal mosaic pattern of diastolic turbulent flow was planimetered as a reflection of the maximal regurgitant volume using biplane Simpson's rule. The maximal Doppler regurgitant volume evaluated by color Doppler flow mapping correlated with the stroke count ratio measured by scintigraphy (r = 0.86, SEE = 11 cc). There were significant relationships between maximal regurgitant volume measured by color Doppler and echocardiographic left ventricular end-diastolic volume (r = 0.88), left ventricular end-systolic volume (r = 0.77), and left ventricular mass (r = 0.71). Patients with larger regurgitant volumes tended to have a larger left ventricular end-diastolic volume-to-mass ratio (r = 0.56). Thus maximal aortic regurgitant volume can be estimated noninvasively with color Doppler flow mapping. The measurement appears to relate to left ventricular morphologic changes occurring in this condition and it may prove to be useful in assessing patients with chronic aortic insufficiency and in determining their long-term management.


Effect of forest management choices on carbon sequestration and biodiversity at national scale.
Forest management methods and harvest intensities influence wood production, carbon sequestration and biodiversity. We devised different management scenarios by means of stakeholder analysis and incorporated them in the forest growth simulator PREBAS. To analyse impacts of harvest intensity, we used constraints on total harvest: business as usual, low harvest, intensive harvest and no harvest. We carried out simulations on a wall-to-wall grid in Finland until 2050. Our objectives were to (1) test how the management scenarios differed in their projections, (2) analyse the potential wood production, carbon sequestration and biodiversity under the different harvest levels, and (3) compare different options of allocating the scenarios and protected areas. Harvest level was key to carbon stocks and fluxes regardless of management actions and moderate changes in proportion of strictly protected forest. In contrast, biodiversity was more dependent on other management variables than harvesting levels, and relatively independent of carbon stocks and fluxes.


Regulation of estrogen-dependent and estrogen-independent levels of progesterone receptor in hamster vagina and uterus.
It is generally accepted that progesterone action is mediated in target cells through a specific, intracellular receptor protein. Since various progesterone target tissues respond differently to progesterone action, it may be postulated that such differences result from variations in: (1) the physicochemical properties; (2) the regulation, and/or (3) the intracellular response of the progesterone receptor (Rp) complex. A previous report demonstrated similar physicochemical properties of hamster vaginal and uterine Rp [1]. Our objective in this report was to analyze the regulation of estrogen-independent (ID-Rp) and estrogen-dependent (D-Rp) populations of receptor in different tissues of the lower reproductive tract of the golden hamster. In untreated ovariectomized animals, a basal level of (ID-Rp) was detected in endometrium, myometrium and vagina. Thus, each compartment contained a significant quantity of Rp which was maintained in the absence of continued estrogen support. Following 3 days of estradiol (E2) administration, the level of nuclear estrogen receptor increased and was related quantitatively to the amount of cytoplasmic Rp produced in these tissues. Maximal weight and D-Rp responses in endometrium, myometrium and vagina were obtained with 10-100 micrograms E2 per 100 g BW. The weight response of these tissues was due primarily to cellular proliferation in the endometrium; cellular hypertrophy in the myometrium; and cellular proliferation with concomitant nuclear pyknosis in the vagina. Although the morphological response of these tissues to estrogen action is quite different, the present study reveals no differences in the regulation of ID-Rp and D-Rp levels in these particular compartments. Furthermore, our results demonstrate a relationship between DNA content and ID-Rp and D-Rp levels in target tissues of the lower reproductive tract.


A novel approach for quantitative peptides analysis by selected electron transfer reaction monitoring.
Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with selective reaction monitoring (SRM) is a selective and sensitive method for quantitation of peptides. SRM is achieved via MS/MS utilizing collision-induced dissociation (CID) while monitoring unique precursor-product ion transitions. Low-energy CID tandem mass spectrometry has been, by far, the most common method used to dissociate peptide ions for sequence analysis. However, collisional scattering of product ions in CID results in decreased intensity of the primary product ion. The lower intensity of the targeted product ion can lead to a reduction in the sensitivity of a quantitative method that uses SRM. Electron transfer dissociation (ETD) is a fragmentation method that is complementary to CID. During the ETD reaction for doubly protonated peptides ([M+2H](2+)), there is a significant shift toward nondissociative electron transfer (ET) product species ([M+2H](+)). We utilized that particular defect in ETD to develop a new quantitative method for monitoring the transition of unique precursors ([M+2H](2+)) to charge-reduced ions ([M+2H](+)). We refer to this method as selective electron transfer reaction monitoring (SETRM). In ESI-MS, trypsin-digested peptides tend to generate doubly protonated peptide precursors. We found that SETRM was more suitable than SRM for these doubly charged tryptic peptides with nano-LC-MS/MS. The quantitative capabilities of SETRM provide a more sensitive way of performing quantitative experiments using the same instrument, thereby improving the application of electron transfer dissociation in proteomics.


Light-activated composite resin as an adjunct to the fabrication of fixed partial denture prosthesis.
A technique that permits characterization of provisional restorations with bonding procedures is described. On completion, a glaze of unfilled resin is added to ensure a smooth, nonporous, biologically compatible restoration. Shade tabs are custom stained for dental laboratory use.


Case of lens-induced uveitis associated with supernormal flicker ERG amplitudes after cataract surgery.
To report our findings in a case of lens fragment-induced uveitis associated with supernormal flicker electroretinograms (ERGs) twenty months after the cataract surgery. This is an observational case report. Full-field flicker ERGs were recorded with the RETeval system. Optical coherence tomography (OCT) and slit-lamp biomicroscopy were used to assess the uveitis during the follow-up period. A 70-year-old man, who had undergone cataract surgery 20 months earlier, visited our hospital with a complaint of decreased vision in his right eye. Slit-lamp biomicroscopy revealed corneal edema and a lens fragment was detected in the inferior part of the anterior chamber. OCT showed cystoid macular edema, and flicker ERGs showed a marked increase in the amplitude and a delay in the implicit time in the right eye. These abnormalities of the flicker ERGs improved gradually after the removal of lens fragment and application of topical anti-inflammatory medications. Our case of lens-induced uveitis had supernormal flicker ERG amplitudes. Clinicians should be aware that eyes with uveitis can have larger-than-normal ERG amplitudes.


[Association of cytotoxic T lymphocyte antigen-4 gene polymorphisms with susceptibility to breast cancer].
To investigate the association between the CTLA-4 promoter-1722(T/C) and 3' untranslated region CT60(G/A) polymorphisms and the risk of breast cancer in Han women of northeast China. 328 patients with breast cancer and 327 healthy people as control were genotyped for -1722 and CT60 polymorphism using polymerase chain reaction and restriction fragment length polymorphism. The frequency of the G allele at the CT60 site in breast cancer patients was statistically higher than that in control(28.7% vs 23.5%, P=0.0352, OR=1.30, 95% CI=1.02-1.67). The frequency of -1722C-CT60A haplotype in control was significantly higher than that in breast cancer patients(P=0.0283, OR=0.77, 95% CI=0.97-0.61). However, the distribution of genotypes at -1722 site was not significantly different between breast cancer patients and control. The polymorphism of -1722T/C and CT60G/A may be related to the development of breast cancer in Han women of northern China.


Science Policy in Canada.
The formation and current state of science policy in Canada are analyzed. Attention to this topic is explained by the fact that the country is a member of the G7 of the leading industrialized countries, although its population is only 0.5% and its GDP is about 2% of the global numbers. By international standards, Canada is not a leader in scientific and technological advance, its specificity being that, with relatively low R&D spending, it occupies leading positions in terms of indicators such as the number of scientific publications in international databases and the number of Nobel laureates (in the last 13 years alone, seven Canadian scientists have become Nobel prizewinners). Canadian affiliation makes up 3.6% of articles published in peer-reviewed journals worldwide. The evolution of the mechanisms of government support for science in Canada is traced, and current practices are summarized. The strengths and weaknesses of the Canadian model of organization of science are identified. This experience may be of interest to Russia.


Tardive dyskinesia treated with pimozide.
We have investigated the action of pimozide in tardive dyskinesia induced by prolonged administration of phenothiazines. Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage (mean 18.8 mg/day) for 6 weeks. There was no deterioration in the therapeutic action of pimozide over this time. Parkinsonism and sedation were the main adverse effects. They were corrected by reduction of the dose of pimozide, but often recurred so that further adjustments of dosage were necessary. Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased.


Clustering patterns in polysubstance mortality in the United States in 2017: a multiple correspondence analysis of death certificate data.
The main goal of this analysis was to identify mortality patterns apparent when many drug classes are analyzed together. The Drug Involved Mortality database is a registry of drug terms mentioned on death certificates of all drug-related deaths in the United States. Means of total number of drugs involved and percentages of specific drug combinations were calculated. Dimensionality reduction using multiple correspondence analysis and hierarchical clustering identified clusters of drugs listed on death certificates. An average of 2.4 specific drugs were listed on death certificates in 2017. For 9 of the top 10 drugs involved, over 80% of deaths involved at least one other drug. As expected, opioid drugs and psychostimulants clustered together, but other psychoactive substances (non-opioid analgesics, sedatives, antidepressants, antipsychotics) clustered together into multi-class groups. Other drugs (e.g., acetaminophen, oxymorphone) were frequently involved in polysubstance death, but did not cluster with any other specific drug. Deaths involving illicit drugs listed fewer drugs than deaths involving prescription drugs. While individual drug substances might contribute to many deaths (e.g., fentanyl), polysubstance mortality is more common than single substance mortality. Multidimensional analyses integrating all drugs involved are useful to identify uncommon patterns of overdose and changing trends.


A novel empirical method for quickly estimating the charge-transfer state of fullerene-donor derivatives.
Herein, a convenient equivalent conjugated electron number technique is put forward to set up a numerical relationship between the electron number and HOMO even before molecules are synthesized, especially used for quickly predicting the charge-transfer state of C60-donor derivatives. It provides a method for designing fullerene conjugates with different excited-state properties.


Insulin injection in the fetal rat: accelerated intrauterine growth and altered fetal and neonatal glucose homeostasis.
Fetal hyperinsulinemia is a well-known correlate of accelerated fetal growth; the consequences of fetal hyperinsulinemia upon fetal and neonatal glucoregulation are less well understood. We injected rat fetuses of a litter on day 18 of gestation with either 5 units of long acting insulin (I) or 154 mmol/L NaCl. Twelve hours after injection, the wet and dry mass of total body and liver of I fetuses significantly exceeded that of controls. At birth (day 21.5), newborn I pups weighed 5.86 +/- .08 g, and controls, 5.48 +/- .05 g, (P less than .001). On day 18, within one hour of injection, fetal plasma insulin concentrations were significantly elevated and remained so for 24 hours. Mothers of I fetuses had significant elevations of plasma insulin at 1, 3, and 6 hours, and they developed transient hypoglycemia. Plasma glucose concentrations in I fetuses were significantly diminished at 1, 3, and 6 hours and then achieved control levels by 12 hours. Fetal hypoglycemia resulted from an apparent direct effect of insulin upon fetal tissue and from the maternal hypoglycemia. Hypoglycemic I fetuses demonstrated a sluggish alpha-cell response; they failed to increase plasma glucagon one hour after insulin injection. Values were significantly increased three hours after injection. At birth, I pups became hypoglycemic relative to controls. This was, in part, due to their significantly elevated plasma insulin concentrations at 120 and 240 minutes (120 minutes, 43.8 +/- 8 v 17.5 +/- 6 microU/mL, P less than .001). Plasma glucagon was significantly increased in I pups at 240 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)


Transient and chronic neurological complications of fast neutron radiation for adenocarcinoma of the prostate.
The records of 132 patients participating in clinical trials using fast neutron (n = 94), mixed neutron and photon (n = 16), or conventional photon (n = 22) irradiation for primary management of prostatic cancer were retrospectively reviewed to assess treatment-related neurological complications. With a median follow-up of 14 months (range 1 to 101 months), 31/132 patients (26 neutron, 3 mixed beam, 2 photon) have experienced either sciatica beginning during or shortly after treatment, or diminished bladder or bowel continence that developed at a median time of 6.5 months following treatment. Sciatica responded to oral steroids and was usually self-limited, whereas sphincter dysfunction appears to be permanent. Pre-treatment risk factors for complications included a history of hypertension, diabetes, cigarette smoking or peripheral vascular disease, with 81% of affected patients having one or more risk factors compared with 55% of unaffected patients (p = 0.01). Seven patients have moderate (5) or severe (2) residual problems, all in the cohorts receiving neutrons (6/7) or mixed beam therapy (1/7).


Efficacy and tolerability of levocabastine and azelastine nasal sprays for the treatment of allergic rhinitis.
Levocabastine and azelastine are currently the only antihistamines available as nasal sprays for the topical therapy of seasonal allergic rhinitis. The present study was undertaken to compare the onset of action, efficacy and tolerability of these two agents in a total of 242 patients with this condition. This was an international, multicentre, open-label, randomized, parallel-group trial with 123 patients treated with levocabastine (0.5 mg/ml, two puffs per nostril twice daily) and 119 with azelastine (1 mg/ml, one puff per nostril twice daily). Onset of action was comparable for the two drugs with over 50% of patients in each group reporting significant symptomatic relief within 30 min of administration of the first dose of study medication. Therapeutic efficacy was also found to be comparable in the two groups with no statistically significant intergroup differences reported for any of the parameters evaluated, although assessments of global therapeutic efficacy revealed a trend favouring levocabastine. Levocabastine appeared to be better tolerated than azelastine (p = 0.06), with the incidence of the most common adverse experiences, application site reactions and taste disturbances, significantly higher on azelastine than with levocabastine (5% versus 1%; p = 0.05 and 5% versus 0%; p = 0.01, respectively). In conclusion, levocabastine nasal spray appears to be at least as effective as, but better tolerated than, azelastine nasal spray for the treatment of seasonal allergic rhinitis.


Protease inhibitors in rheumatoid synovial fluid. Analyses of electrophoretic homogeneity and protease inhibitory capacity.
Paired plasma and synovial fluids from 17 patients with seropositive rheumatoid arthritis were examined for electrophoretic homogeneity/heterogeneity and enzymic inhibitory capacity of the protease inhibitors. The high degree of saturation (approximately 90%) of the polyvalent protease inhibitor alpha 2-macroglobulin in the rheumatoid synovial fluid contrasts sharply with the low saturation of alpha 1-anti-trypsin. The inhibitory reactivity of the non-complexed fraction of both of these dominating antiproteases was retained (approximately 85-90%). Thus, a selective inactivation of synovial alpha 1-antitrypsin could not be demonstrated. alpha 1-Anti-chymotrypsin revealed electrophoretic homogeneity in all synovial fluids. Electrophoretic heterogeneity of the plasmin inhibitor antiplasmin was detected in the majority of synovial fluids indicating plasmin activation. The existence of a protease-antiprotease imbalance in the rheumatoid joint was indicated by the high degree of saturation of alpha 2-macroglobulin and a cleavage of C3 in rheumatoid synovial fluids.


The social benefits of WEEE re-use schemes. A cost benefit analysis for PCs in Spain.
One goal of the new European legislation set out in WEEE Directive 2012/19/UE is the promotion of WEEE re-use schemes. However, some authors are rather sceptical about the contribution of WEEE re-use schemes to improve resource efficiency. In order to evaluate and to design adequate policy instruments, some authors recommend the cost-benefit analysis (CBA) as a compulsory first step. In this context, the main contribution of this paper is to enlarge the empirical literature by providing a CBA of re-use schemes versus recycling processes of PCs. The analysis is made for Spain by quantifying in monetary terms the social damages of environmental impacts such as climate change, human toxicity, particulate matter formation, metal depletion, etc. Our results suggest that promoting re-use against recycling (and consequently the need for manufacturing a new PC from raw materials) may reduce environmental costs by 45.20€ per PC. Those social benefits are mainly generated in the re-use preparation process and distribution activities, whereas the re-use scenario displays a worse performance in energy consumption. The difference in the distribution stage during the second life cycle originates from the fact that the ready to re-use product is produced locally, while the brand new product is manufactured and distributed from abroad, mainly Asia. These results provide valuable information to policymakers and think tanks willing to design support schemes for re-use over recycling operations.


Building resilient supply chains in uncertain times: a comparative study of EU and ASEAN approaches to supply chain resilience.
Amid rising uncertainty in the global economy and unprecedented economic disruption caused by the COVID-19 pandemic, the concept of supply chain resilience has gained increasing popularity in ASEAN and the EU. However, by comparing their paths to resilient supply chains, this article argues that while both organizations regard resilience as a departure from past doctrines of pure economic efficiency, each has a different understanding of and approach to supply chain resilience. While for ASEAN, supply chain resilience is meant to reconcile inward- and outward-looking dimensions to support ASEAN competitiveness, within the EU, resilience is associated with the search for strategic autonomy with an internal focus. Despite these differences, both groups regard sustainability and digital transformation as crucial components of supply chain resilience, which they see as a way to enhance their economic cooperation and strategic partnership.


Higher plasma somatomedin A (biological) and C (immunological) levels with sc than with im growth hormone replacement therapy.
In a short-term cross-over study the effect of daily sc human growth hormone was compared with that of thrice weekly im treatment. At the end of each 6-week treatment period the 10 growth hormone deficient children were admitted to hospital for evaluation of diurnal plasma levels of hormones and intermediary metabolites. Somatomedin A as well as C levels were higher in 9 of 10 children after sc than after im growth hormone therapy. This may be the basis for previous observations of improved growth after change to sc treatment.