Preoperative data-based deep learning model for predicting postoperative survival in pancreatic cancer patients.
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis even after curative resection. A deep learning-based stratification of postoperative survival in the preoperative setting may aid the treatment decisions for improving prognosis. This study was aimed to develop a deep learning model based on preoperative data for predicting postoperative survival. The patients who underwent surgery for PDAC between January 2014 and May 2015. Clinical data-based machine learning models and computed tomography (CT) data-based deep learning models were developed separately, and ensemble learning was utilized to combine two models. The primary outcomes were the prediction of 2-year overall survival (OS) and 1-year recurrence-free survival (RFS). The model's performance was measured by area under the receiver operating curve (AUC) and was compared with that of American Joint Committee on Cancer (AJCC) 8th stage. The median OS and RFS were 23 and 10 months in training dataset (n = 229), and 22 and 11 months in test dataset (n = 53), respectively. The AUC of the ensemble model for predicting 2-year OS and 1-year RFS in the test dataset was 0.76 and 0.74, respectively. The performance of the ensemble model was comparable to that of the AJCC in predicting 2-year OS (AUC, 0.67; P = 0.35) and superior to the AJCC in predicting 1-year RFS (AUC, 0.54; P = 0.049). Our ensemble model based on routine preoperative variables showed good performance for predicting prognosis for PDAC patients after surgery.


Efficient and high accuracy 3-D OCT angiography motion correction in pathology.
We describe a novel method for non-rigid 3-D motion correction of orthogonally raster-scanned optical coherence tomography angiography volumes. This is the first approach that aligns predominantly axial structural features such as retinal layers as well as transverse angiographic vascular features in a joint optimization. Combined with orthogonal scanning and favorization of kinematically more plausible displacements, subpixel alignment and micrometer-scale distortion correction is achieved in all 3 dimensions. As no specific structures are segmented, the method is by design robust to pathologic changes. Furthermore, the method is designed for highly parallel implementation and short runtime, allowing its integration into clinical workflow even for high density or wide-field scans. We evaluated the algorithm with metrics related to clinically relevant features in an extensive quantitative evaluation based on 204 volumetric scans of 17 subjects, including patients with diverse pathologies and healthy controls. Using this method, we achieve state-of-the-art axial motion correction and show significant advances in both transverse co-alignment and distortion correction, especially in the subgroup with pathology.


Possible mechanism of abrupt jump in winter surface air temperature in the late 1980s over the Northern Hemisphere.
Possible cause of an abrupt warming in winter mean surface air temperature in the midlatitudes of the Northern Hemisphere in the late 1980s is investigated using observation and reanalysis data. To determine the timing of abrupt warming, we use a regime shift index based on detection of the largest significant differences between the mean values of two contiguous periods. Results show that the abrupt warming occurred in association with a regime shift after the 1980's in which the zonal mean sea level pressure (SLP) is significantly increased (decreased) at the latitude 25-35°N (60-70°N), in the form of north-south dipole-like SLP anomaly spanning the subtropics and high latitude. The dipole SLP anomaly can be attributed to a northward expansion of Hadley cell, a poleward broadening and intensification of the Ferrel cell, coupled with a collapse of polar cell. During the abrupt warming, strong anomalous southerly warm advection at the surface was induced by an enhanced and expanded Ferrel circulation, in association with a northward and downward shift of maximum center of northward eddy heat flux over the midlatitudes. An intensification of polar jet subsequent to regime shift may be instrumental in sustaining the warming up to more than 5 years.


A cohort study examining the relationship among housing status, patient characteristics, and retention among individuals enrolled in low-barrier-to-treatment-access methadone maintenance treatment.
Few studies have directly compared patient characteristics and retention among those enrolled in methadone maintenance treatment (MMT) based on housing status. Low-barrier-to-treatment-access programs may be particularly effective at attracting patients experiencing homelessness into MMT; however, the literature on retention in such settings is limited. We performed a retrospective chart review of 488 consecutive patients enrolled from April to October 2017 at low-barrier-to-treatment-access MMT programs in southern New England. Patients completed measures of demographics, social isolation, trauma, chronic pain, smoking behavior, and psychiatric distress. The study investigated associations between housing status and correlates with chi-square and Mann-Whitney U tests while controlling the False Discovery Rate. A two-sample log-rank test examined the relationship between retention and housing status. The study further scrutinized this association by regressing retention on all covariates using a Cox proportional hazards model. Forty-six patients (9.4%) reported experiencing homelessness and 442 (90.6%) reported being housed. Thirty-seven percent of patients self-identified as female and 20% as non-white. Compared to patients who were housed, those experiencing homelessness had lower rates of recent employment; higher rates of social isolation, trauma, current chronic pain, and recent cannabis use; and higher overall psychiatric distress (all p < 0.01). At one year, overall retention was 51.8%, and retention was 32.6% in the unhoused group and 53.8% in the housed group. A significant negative association occurred between retention and housing status (p = 0.006). After regressing on all covariates, homelessness was associated with a 69% increase in one-year treatment discontinuation (HR = 1.69 for homelessness, CI = 1.14-2.50). Patients entering MMT experiencing homelessness have multiple clinical vulnerabilities and are at increased risk for 12-month MMT discontinuation. Low-barrier-to-treatment-access MMT programs are an important venue for identifying and addressing vulnerabilities associated with homelessness.


Compact 3D printed module for fluorescence and label-free imaging using evanescent excitation.
Total internal reflection fluorescence (TIRF) microscopy is widely used for selective excitation and high-resolution imaging of fluorophores, and more recently label-free nanosized objects, with high vertical confinement near a liquid-solid interface. Traditionally, high numerical aperture objectives (>1.4) are used to simultaneously generate evanescent waves and collect fluorescence emission signals which limits their use to small area imaging (<0.1 mm2). Objective-based TIRFs are also expensive as they require dichroic mirrors and efficient notch filters to prevent specular reflection within the objective lenses. We have developed a compact 3D module called cTIRF that can generate evanescent waves in microscope glass slides via a planar waveguide illumination. The module can be attached as a fixture to any existing optical microscope, converting it into a TIRF and enabling high signal-to-noise ratio (SNR) fluorescence imaging using any magnification objective. As the incidence optics is perpendicular to the detector, label-free evanescent scattering-based imaging of submicron objects can also be performed without using emission filters. SNR is significantly enhanced in this case as compared to cTIRF alone, as seen through our model experiments performed on latex beads and mammalian cells. Extreme flexibility and the low cost of our approach makes it scalable for limited resource settings.


Atrioventricular septal defect with separate right and left atrioventricular valvar orifices in a patient with foetal hydantoin syndrome.
The teratogenic properties of phenytoin, including cardiac malformations, have been previously documented. We report one patient with foetal hydantoin syndrome and atrioventricular septal defect with common atrioventricular junction but separate right and left atrioventricular valves, an association that has not been described, to the best of our knowledge.


Saposin D solubilizes anionic phospholipid-containing membranes.
Saposin (Sap) D is a late endosomal/lysosomal small protein, generated together with three other similar proteins, Sap A, B, and C, from the common precursor, prosaposin. Although the functions of saposins such as Sap B and C are well known (Sap B promotes the hydrolysis of sulfatides and Sap C that of glucosylceramide), neither the physiological function nor the mechanism of action of Sap D are yet fully understood. We previously found that a dramatic increase of Sap D superficial hydrophobicity, occurring at the low pH values characteristic of the late endosomal/lysosomal environment, triggers the interaction of the saposin with anionic phospholipid-containing vesicles. We have presently found that, upon lipid binding, Sap D solubilizes the membranes, as shown by the clearance of the vesicles turbidity. The results of gel filtration, density gradient centrifugation, and negative staining electron microscopy demonstrate that this effect is due to the transformation of large vesicles to smaller particles. The solubilizing effect of Sap D is highly dependent on pH, the lipid/saposin ratio, and the presence of anionic phospholipids; small variations in each of these conditions markedly influences the activity of Sap D. The present study documents the interaction of Sap D with membranes as a complex process. Anionic phospholipids attract Sap D from the medium; when the concentration of the saposin on the lipid surface reaches a critical value, the membrane breaks down into recombinant small particles enriched in anionic phospholipids. Our results suggest that the role played by Sap D is more general than promoting sphingolipid degradation, e.g. the saposin might also be a key mediator of the solubilization of intralysosomal/late endosomal anionic phospholipid-containing membranes.


Spectroscopic and Computational Characterization of 2-Aza-1,3-butadiene, a Molecule of Astrochemical Significance.
Being N-substituted unsaturated species, azabutadienes are molecules of potential relevance in astrochemistry, ranging from the interstellar medium to Titan's atmosphere. 2-Azabutadiene and butadiene share a similar conjugated π system, thus allowing investigation of the effects of heteroatom substitution. More interestingly, 2-azabutadiene can be used to proxy the abundance of interstellar butadiene. To enable future astronomical searches, the rotational spectrum of 2-azabutadiene has been investigated up to 330 GHz. The experimental work has been supported and guided by accurate computational characterization of the molecular structure, energetics, and spectroscopic properties of the two possible forms, trans and gauche. The trans species, more stable by about 7 kJ/mol than gauche-2-azabutadiene, has been experimentally observed, and its rotational and centrifugal distortion constants have been obtained with remarkable accuracy, while theoretical estimates of the spectroscopic parameters are reported for gauche-2-azabutadiene.


Big tobacco focuses on the facts to hide the truth: an algorithmic exploration of courtroom tropes and taboos.
To use methods from computational linguistics to identify differences in the rhetorical strategies deployed by defence versus plaintiffs' lawyers in cigarette litigation. From 318 closing arguments in 159 Engle progeny trials (2008-2016) archived in the Truth Tobacco Industry Documents, we calculated frequency scores and Mann-Whitney Rho scores of plaintiffs versus defence corpora to discover 'tropes' (terms used disproportionately by one side) and 'taboos' (terms scrupulously avoided by one side or the other). Defence attorneys seek to place the smoker on trial, using his or her friends and family members to demonstrate that he or she must have been fully aware of the harms caused by smoking. We show that 'free choice,' 'common knowledge' and 'personal responsibility' remain key strategies in cigarette litigation, but algorithmic analysis allows us to understand how such strategies can be deployed without actually using these expressions. Industry attorneys rarely mention personal responsibility, for example, but invoke that concept indirectly, by talking about 'decisions' made by the individual smoker and 'risks' they assumed. Quantitative analysis can reveal heretofore hidden patterns in courtroom rhetoric, including the weaponisation of pronouns and the systematic avoidance of certain terms, such as 'profits' or 'customer.' While cigarette makers use words that focus on the individual smoker, attorneys for the plaintiffs refocus agency onto the industry. We show how even seemingly trivial parts of speech-like pronouns-along with references to family members or words like 'truth' and 'facts' have been weaponised for use in litigation.


The dental health of adults in an integrated urban development in Addis Ababa, Ethiopia.
Two hundred and forty-three Ethiopian adults (18 years-old and over) were examined for caries, periodontal disease, malocclusions and enamel opacities. These adults were the parents of children cared for by an independent charitable organisation, the Ethiopian Gemini Trust. The prevalence of dental caries was generally low with a mean DMFT for the sample of 2.7 (+/- 0.2) and a mean DMFS of 6.7 (+/- 0.6), although one adult had a DMFS of 62. A high proportion of the adults (83.5 per cent) had calculus, but only 2 per cent had deep pocketing. Twenty-three per cent of the adults had a malocclusion and for 6 per cent of these this was moderate to severe. The most prevalent enamel defects were hypoplasias and diffuse opacities with 22 per cent of adults having one or more index teeth affected. Access to dental services was virtually non-existent as judged by the clinical status of these adults.


Transcranial Doppler series part II: performing a transcranial Doppler.
Because of its portability, low cost, and quick, noninvasive nature, transcranial Doppler (TCD) has become a widely utilized exam to evaluate the basal cerebral arteries for various disease processes. The test is considered a "blind" and very difficult study by most vascular labs. Neurologists commonly order TCD, so the performance of it is slowly being adopted by neurodiagnostic labs. To perform a quality TCD, the technologist must be extremely skilled. The technologist must know where to place and how to angle the probe in order to insonate the vessels and must be familiar with the TCD equipment. The technologist should also have an understanding of what each vessel's waveform should look like under normal circumstances.


A Prospective Longitudinal Clinical Trial Evaluating the Preservation of the Peri-implant Hard and Soft Tissues.
This prospective longitudinal clinical trial aimed to evaluate the success of a bone-level implant with an integrated platform-switched connection by assessing peri-implant soft tissue and marginal bone level. Twenty-six patients were treated in two different centers with implants placed in healed partially edentulous ridges. Implant success rate and marginal bone level were evaluated with photographs, radiographs, and clinical measurements, with a 6-month postloading follow-up. The esthetic appearance of the photographed peri-implant soft tissue was evaluated at 6 months via the Pink Esthetic Score applied by two calibrated operators. All of the implants except for one placed in the mandible demonstrated successful osseointegration, resulting in a success rate of 97.8% at the 6-month follow-up. Compared to historical controls, no detectable differences in peri-implant marginal bone loss or esthetic outcome were seen.


Epidemiology of Treatment-Resistant Depression in the United States.
Background: The prevalence of treatment-resistant depression (TRD) among patients with pharmaceutically treated depression (PTD) varies greatly in publications. The aim of this study is to estimate the prevalence of TRD using 2 large claims databases in the US. Methods: This cross-sectional study used data from the Humana and Optum databases. Patients aged ≥ 18 years who had at least 1 diagnosis of major depressive disorder (ICD-10-CM codes: F32.xx, F33.xx) and 1 antidepressant prescription filled in 2018 were identified as having PTD. Among patients with PTD, TRD was defined as experiencing failure of treatment with at least 2 antidepressants with ≥ 4 weeks of adequate treatment. We estimated the age- and gender-standardized prevalence of TRD and then used logistic regression to investigate if TRD risk varies by age, sex, race, and geographic region. Finally, we described the timeline of TRD development in incident PTD patients. Results: We identified 296,055 and 277,941 patients with PTD in the Humana and Optum databases, among whom 17,640 (6.0%) and 16,131 (5.8%) had TRD. After age and sex standardization, TRD prevalence among PTD patients was 6.8% in Humana vs 5.8% in Optum. Females, middle-aged adults, and White patients had higher risk of TRD. The median time from index antidepressant use to TRD was about 6 months in incident PTD patients. Conclusions: The prevalence of TRD among patients with PTD was similar in the 2 databases. TRD prevalence varies by sex, race, and age, with a higher prevalence in females, White patients, and those in the age group of 45-64 years. However, the absolute differences were small.


Tissue-specific kinase expression and activity regulate flux through the pyruvate dehydrogenase complex.
The pyruvate dehydrogenase complex (PDC) is a multienzyme assembly that converts pyruvate to acetyl-CoA. As pyruvate and acetyl-CoA play central roles in cellular metabolism, understanding PDC regulation is pivotal to understanding the larger metabolic network. The activity of mammalian PDC is regulated through reversible phosphorylation governed by at least four isozymes of pyruvate dehydrogenase kinase (PDK). Deciphering which kinase regulates PDC in organisms at specific times or places has been challenging. In this study, we analyzed mouse strains carrying targeted mutations of individual isozymes to explore their role in regulating PDC activity. Analysis of protein content of PDK isozymes in major metabolic tissues revealed that PDK1 and PDK2 were ubiquitously expressed, whereas PDK3 and PDK4 displayed a rather limited tissue distribution. Measurement of kinase activity showed that PDK1 is the principal isozyme regulating hepatic PDC. PDK2 was largely responsible for inactivation of PDC in tissues of muscle origin and brown adipose tissue (BAT). PDK3 was the principal kinase regulating pyruvate dehydrogenase activity in kidney and brain. In a well-fed state, the tissue levels of PDK4 protein were fairly low. In most tissues tested, PDK4 ablation had little effect on the overall rates of inactivation of PDC in kinase reaction. Taken together, these data strongly suggest that the activity of PDC is regulated by different isozymes in different tissues. Furthermore, it appears that the overall flux through PDC in a given tissue largely reflects the properties of the PDK isozyme that is principally responsible for the regulation of PDC activity in that tissue.


Cardiovascular disease and kidney transplantation‑evaluation of potential transplant recipient.
Cardiovascular evaluation of a potential kidney transplant recipient remains controversial. The burning issue is the lack of clear guidelines as well as the fact that patients with a low probability of cardiovascular disease undergo numerous unnecessary screening procedures and false‑positive results are common. In general, the standard procedure involves clinical data collection, physical examination, electrocardiography, chest‑X ray, measurement of the lipid profile and fasting glycemia, cardiac ultrasonography, followed by coronary angiography. An exercise tolerance test is not recommended because it has low sensitivity and is difficult to perform and interpret. Cardiac ultrasonography should be performed after a hemodialysis session to avoid an effect on hypervolemia. All noninvasive diagnostic imaging and isotope tests are usually of limited value and, to a large extent, are facility- and operator‑dependent. Coronary angiography should be considered in patients with positive exercise tolerance test results and a history of acute coronary syndrome, unstable coronary artery disease, and high cardiovascular risk. However, a decision regarding therapy, ie, percutaneous coronary intervention, stenting (type of stent), or coronary artery bypass grafting should be made during the meeting of a cardiac team. The guidelines also discuss cardiac contraindications to kidney transplantation. It should be stressed that a patient scheduled for a kidney transplant is sick at the time of evaluation and that his or her condition may change after several years on the waiting list. Therefore, cardiac reevaluation may be needed. Preemptive transplantation as well as short dialysis therapy before transplantation (<6 months) are associated with better patient and graft survival and thus with lower incidence of cardiovascular complications and better quality of life. The current review discusses the available guidelines on the evaluation of the potential kidney transplant recipient.


Dermatologic diagnoses in the perianal area.
Perianal dermatosis can encompass lesions from benign eczematous processes to advanced malignancies. It is important for the colorectal surgeon to be able to distinguish common problems from more serious pathology. This article covers nonsexually transmitted diseases occurring in the intergluteal fold and perianal region. These include inflammatory dermatoses, bacterial and fungal infections, and other disease processes.


Immunoscintigraphy in the follow up of patients with ovarian cancer.
Our case series concerns eight patients affected by epithelial cancer of the ovary. The immune scintigraphical examination with B 72.3-I-131 monoclonal antibody was carried out as a follow-up after surgical therapy with chemo- and/or radio-therapy. The results were compared with traditional diagnostic methods (CT, pelvic echography etc.). The immunoscintigraphy confirmed the presence of local relapses in seven patients, correlating positively with the results of conventional enquiries. The conclusions, although relating to a limited number of cases, are satisfactory and seem to indicate important diagnostic possibilities to the end of follow-up in patients affected by ovarian cancer.


Low pH is required for avian sarcoma and leukosis virus Env-dependent viral penetration into the cytosol and not for viral uncoating.
A novel entry mechanism has been proposed for the avian sarcoma and leukosis virus (ASLV), whereby interaction with specific cell surface receptors activates or primes the viral envelope glycoprotein (Env), rendering it sensitive to subsequent low-pH-dependent fusion triggering in acidic intracellular organelles. However, ASLV fusion seems to proceed to a lipid mixing stage at neutral pH, leading to the suggestion that low pH might instead be required for a later stage of viral entry such as uncoating (L. J. Earp, S. E. Delos, R. C. Netter, P. Bates, and J. M. White. J. Virol. 77:3058-3066, 2003). To address this possibility, hybrid virus particles were generated with the core of human immunodeficiency virus type 1 (HIV-1), a known pH-independent virus, and with subgroups A or B ASLV Env proteins. Infection of cells by these pseudotyped virions was blocked by lysosomotropic agents, as judged by inhibition of HIV-1 DNA synthesis. Furthermore, by using HIV-1 cores that contain a Vpr-beta-lactamase fusion protein (Vpr-BlaM) to monitor viral penetration into the cytosol, we demonstrated that virions bearing ASLV Env, but not HIV-1 Env, enter the cytosol in a low-pH-dependent manner. This effect was independent of the presence of the cytoplasmic tail of ASLV Env. These studies provide strong support for the model, indicating that low pH is required for ASLV Env-dependent viral penetration into the cytosol and not for viral uncoating.


Cyanide-resistant Respiration in Freshly Cut Potato Slices.
Treating intact white potato (Solanum tuberosum L.) tuber with ethylene in air or O(2) made it possible to obtain freshly cut slices which exhibit cyanide-resistant respiration. The cyanide-resistant path requires induction in whole tubers. The data also indicate that high O(2) concentration is necessary for the full development of cyanide-resistant respiration.


Sensitization to the psychosis-inducing effects of cocaine compared with measures of cocaine craving and cue reactivity.
A previous study has suggested that sensitization to the psychosis-inducing effects of cocaine may be a marker of vulnerability to relapse in cocaine addiction. In this report, cocaine-dependent subjects participating in a study on naturally occurring and cue-induced cocaine craving were interviewed about prior experience of cocaine-induced psychosis and the degree to which this effect had become more frequent or severe or had occurred at lower cumulative doses. Sensitization to cocaine-induced psychosis was negatively correlated with baseline measures of drug dependence severity and indices of cocaine craving over the preceding 24 hours but not with measures of cocaine cue reactivity.


Adult plant resistance-related gene expression in 'Camp Remy' wheat inoculated with Puccinia striiformis.
The French wheat variety 'Camp Remy' (CR) possesses a durable, adult plant resistance to yellow rust (YR), caused by the pathogen Puccinia striiformis. Using cDNA-AFLP on different sets of heterogeneous inbred families (HIFs) derived from the cross CR x Récital, we compared gene expression profiles during one seedling and two adult developmental stages following inoculation with P. striiformis. Transcripts differentially expressed in response to YR infection were isolated and cloned. Sequence analysis of the resultant clones revealed several classes of putative genes, including those related to resistance/defence responses, transcription and signal transduction, and primary metabolism. The expression profiles of seven selected genes were obtained using real-time PCR in CR leaves at the same three stages of development. The results confirmed the stage-specific expression of the genes at one or two specific stages in response to P. striiformis infection and demonstrated that CR modifies the expression of some resistance/defence-related genes during its transition from the seedling to adult growth stages. These results provided the first clue to understand the molecular basis of quantitative trait loci for adult plant resistance to YR and connect it with durability.


Hemisphere differences in accessing lexical knowledge of Chinese characters.
The lateralisation of lexical knowledge of Chinese characters is investigated in this study. Three experiments were conducted in which stimuli were presented unilaterally to a visual field for recognition tests. The orthographic similarity of two alternative items for choice in Experiment 1 was manipulated, and the results showed an LVF advantage effect for legal characters in the visually similar condition and a more prominent LVF than RVF character-superiority effect. The phonological similarity of two alternative items for choice was manipulated in Experiment 2. The results showed a prominent RVF advantage effect and a significant phonological similarity effect in the RVF. In Experiment 3, the semantic similarity was manipulated, and the semantic similarity effect was observed in the RVF. These results suggest hemisphere asymmetries in accessing lexical knowledge of Chinese characters.


Occurrence and phylogenetic analysis of Pseudanabaena sp. producing 2-methylisoborneol in drinking water source of South Korea.
We investigated the abundance of Pseudanabaena species and the concentration of the monoterpene 2-methylisoborneol (2-MIB) from July to October at three sampling sites in South Korea. To identify the main cause of 2-MIB occurrence in drinking water source, we characterized and performed a phylogenetic analysis of the 2-MIB synthase gene. Pseudanabaena was the dominant cyanobacterium (68%-100%) among the samples. At all three sampling sites, a strong positive correlation was detected between 2-MIB concentrations and Pseudanabaena cell numbers. A phylogenetic analysis of 222 MIB sequences isolated from the water samples showed that all of the clones were affiliated with the Pseudanabaena MIB synthase gene, demonstrating that the 2-MIB in the Han River drinking water source was produced by Pseudanabaena sp. Using a clone of the 2-MIB gene, network-based analysis and unweighted pair group method with arithmetic mean analysis were used to examine temporal and spatial variation in the 2-MIB concentration and Pseudanabaena abundance. The network analysis showed greater temporal than spatial similarity among the 2-MIB gene clones. Together, our results demonstrate that Pseudanabaena was the main producer of 2-MIB. These findings provide important information for odour management in drinking water source.


Effect of in vivo exposure to insulin on glucose metabolism in rat aorta.
The effect of administration of insulin in vivo on accumulation of [14C]glucose carbon in rat aorta in vitro was studied. Insulin was injected intravenously in a tail vein 5-60 min before the rats were killed and the accumulation of [14C]glucose was determined after incubation for 30-120 min in 5.6 mM [14C]glucose. When determined 30 min after injection of insulin (4 U kg-1) the aortic [14C]glucose incorporation was significantly increased when an incubation period of 120 min was used, while no significant effect was found after incubation for 30 or 60 min. In subsequent experiments an incubation time of 120 min was used. The aortic [14C]glucose accumulation was not increased when determined 5 or 60 min after injection of insulin (4 U kg-1). Injection of insulin (2 U kg-1) 5 or 30 min before the rats were killed had no effect on the aortic [14C]glucose accumulation but it had a pronounced effect on [14C]glucose accumulation in rat diaphragm. Serum insulin determined 30 min after injection of insulin (2 U kg-1) was 731 +/- 58 mU-1 and in saline-treated control rats 37 +/- 3 mU l-1. These results suggest that the glucose metabolism of vascular smooth muscle has a low sensitivity to the immediate effects of insulin.


Gut Microbiological Disorders Reduce Semen Utilization Rate in Duroc Boars.
Although rising evidence suggests that the gut microbiota is closely related to host health, the effects of gut microbiota on male fertility are still rarely explored. This study was to investigate the gut microbiota composition and function, fecal short-chain fatty acids (SCFA), intestinal permeability, and systemic inflammatory status of Duroc boar with high (H group, 100%) and low (L group, <80%) semen utilization rate. Fecal samples, analyzed by 16S ribosomal RNA gene sequencing, displayed taxonomic and functional changes between boars with high and low semen utilization rates. For the gut microbiota composition of the boars, four genera were different between the two groups. The [Ruminococcus] and Sphingobium were enriched in L group boars, then negatively correlated with the semen utilization rate. While RFN20 and Paludibacter were enhanced in the H group, only RFN20 showed a significantly positive correlation with the semen utilization rate of boars. In addition, changes in the metabolic function of the gut microbiota of the two groups were found, including altered branched-chain fatty acid (BCFA) production. Significant increases in plasma endotoxin, zonulin, diamine oxidase, and lipocalin-2 levels were observed in boars with low semen utilization, and also, a similar trend in IL-6 and TNF-α was found. However, the concentration of IL-10 in plasma of boars with high semen utilization rate showed an increasing tendency. These results indicated increased intestinal permeability and systemic inflammation in boars with low semen utilization. Data showed that the composition and functions of gut microbiota varied between boars with high or low semen utilization rates, while the semen utilization rate is notably correlated with the gut microbiota composition, intestinal permeability, and inflammatory status of the boar.


Genomic approaches for investigating mechanisms of genotoxicity.
The current genetic toxicity testing battery enables an accurate and effective detection of genotoxicity associated with exposure to chemicals. However, the interpretation of the data in light of the relevant risk to humans is often difficult due to limited insight into underlying genotoxic mechanisms. Thus, the development of experimental approaches capable of differentiating genotoxic mechanisms is expected to facilitate risk assessment. Recent progress in science and technology has enabled the investigation of the stress response associated with chemical exposure at the genomic level. For instance, gene expression profile analysis, transcriptomics, was proposed as a tool for evaluating toxic mechanisms. In addition, the advancement in genetic tools has allowed the study of stress response on a functional level, functional genomics. This review will outline a number of recent developments in genomic analyses of genotoxic stress response and provide a perspective on their application in genetic toxicology.


Anthropometric Profile, Serum Leptin, Antioxidant Vitamins, LEPR Q223R Polymorphism and Cardiovascular Risk Factors in Adolescents.
Cardiovascular disease (CVD) risk factors, such as bad eating habits, are typical in adolescence and lead to the consumption of meals that are not always sufficient in vitamins A, E, β-carotene, excess calories and elevated serum leptin levels. The purpose of this research is to study the relationship between vitamin A deficiency (VAD), β-carotene deficiency (βcD), vitamin E deficiency (VED) and to explore the association of leptin receptor Q223R polymorphisms with obesity and other risk factors for CVD. Method: This observational study included 237 adolescents recruited from Adolescents Reference Center, Brazil. It was collected: socioeconomic and clinical data, laboratory and molecular samples. Results: The average age was 14.93 ± 2.18 years, 66.2 % were girls, 38.0 % had high levels of total cholesterol (TC) between 10-14 years Triceps (TSF) and subscapular skinfolds (SSF) measurements were inversely correlated with VAD. There was also an association between VAD, βcD and high triglyceride (TG) levels. Adolescents with the RR genotype presented a trend toward higher levels of body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), TC, TG, low density lipoprotein (LDLC), leptin and low levels of high-density lipoprotein (HDL-c). Conclusion: The girls had higher levels of leptin than boys. Abdominal fat, βcD and VED were observed in adolescents with VAD. Individuals with RR genotype have drawn attention to cardiovascular risk factors such as high rate of LDLC and reduced rate of HDLc. Thus, it is possible that individuals with this genotype may be more susceptible to the presence of cardiovascular risk factors.


Introduction of a three-dimensional anthropometry of the viscerocranium. Part I: measurement of craniofacial development and establishment of standard values and growth functions.
The analysis of lateral cephalograms is based on many vague landmarks that vary intra- and inter-individually. Exposure to radiation and high-quality equipment are essential, while identical object positioning is almost impossible. Anthropometry as presented in the literature is time consuming and cannot reproduce cranial three-dimensionality. Poor landmark definitions and resilience of the soft tissue foster systematic measurement errors. We used few easily detectable and accessible landmarks that are closely related to underlying bone. The distances measured were visualized three-dimensionally. Measurements from 540 volunteers were reconstructed. Reliability was assessed through repeated measurements. Corresponding distances were measured in lateral cephalograms taken the same day. The age- and sex-related mean values and 95%-percentiles were visualized as growth functions. The intra-individual relative error in anthropometry was 3.7%, in roentgenocephalometry 0.9%. The inter-individual error was 5.8% for anthropometry and 3.6% for roentgenocephalometry. Applied anthropometry as described in the paper is reliable and valid for measuring craniofacial growth, arriving at a diagnosis and 'monitoring' treatment results. The relative measurement error in anthropometry appear to be smaller than the systematic magnification and distortion found in lateral cephalograms.


Epigenetics as an answer to Darwin's "special difficulty".
Epigenetic modifications produce distinct phenotypes from the same genome through genome-wide transcriptional control. Recently, DNA methylation in honeybees and histone modifications in ants were found to assist the formation of caste phenotypes during development and adulthood. This insight allows us to revisit one of Darwin's greatest challenges to his natural selection theory; the derivation of multiple forms of sterile workers within eusocial species. Differential feeding of larvae creates two distinct developmental paths between queens and workers, with workers further refined by pheromone cues. Flexible epigenetic control provides a mechanism to interpret the milieu of social cues that create distinct worker sub-caste phenotypes. Recent findings suggest a distinct use for DNA methylation before and after adult emergence. Further, a comparison of genes that are differentially methylated and transcriptionally altered upon pheromone signaling suggests that epigenetics can play a key role in mediating pheromone signals to derive sub-caste phenotypes. Epigenetic modifications may provide a molecular mechanism to Darwin's "special difficulty" and explain the emergence of multiple sub-phenotypes among sterile individuals.


Tree-rings reveal two strong solar proton events in 7176 and 5259 BCE.
The Sun sporadically produces eruptive events leading to intense fluxes of solar energetic particles (SEPs) that dramatically disrupt the near-Earth radiation environment. Such events have been directly studied for the last decades but little is known about the occurrence and magnitude of rare, extreme SEP events. Presently, a few events that produced measurable signals in cosmogenic radionuclides such as 14C, 10Be and 36Cl have been found. Analyzing annual 14C concentrations in tree-rings from Switzerland, Germany, Ireland, Russia, and the USA we discovered two spikes in atmospheric 14C occurring in 7176 and 5259 BCE. The ~2% increases of atmospheric 14C recorded for both events exceed all previously known 14C peaks but after correction for the geomagnetic field, they are comparable to the largest event of this type discovered so far at 775 CE. These strong events serve as accurate time markers for the synchronization with floating tree-ring and ice core records and provide critical information on the previous occurrence of extreme solar events which may threaten modern infrastructure.


Role of radiation therapy and radiopharmaceuticals in bone metastases.
Bone metastases remain the most common cause of cancer-related pain. Palliative radiotherapy and radiopharmaceuticals are effective for symptom control, but continue to be underutilized. We review recent literature for the treatment of bone metastases and spinal cord compression, and address new developments in the prevention of adverse effects secondary to radiotherapy. Evidence continues to mount in support of the efficacy of short-course radiation schedules. Emerging data support the use of single fractions. While radiotherapy is relatively nontoxic, pain flare can be a distressing side effect. Recent reports suggest that traditional and more innovative radiopharmaceuticals are well tolerated, with effects comparable with external beam radiation and the added advantage of addressing multiple, widespread painful sites simultaneously. There is an urgent need for more randomized controlled trials in the radiotherapy of complicated bone metastases, such as the settings of spinal cord compression and neuropathic pain. Additional study of radiopharmaceuticals as adjuvants to external beam radiotherapy would also serve to further elucidate the optimal treatment for these patients.


Expression of cellular prion protein on platelets from patients with gray platelet or Hermansky-Pudlak syndrome and the protein's association with alpha-granules.
The cellular prion protein (PrPc) is a membrane glycoprotein expressed on many human cells including platelets. We investigated the cellular localization of platelet PrPc. In resting platelets most PrPc was localized inside the cells. The correlation of PrPc and P-selectin surface up-regulation after platelet activation suggested its association with alpha-granules. This was confirmed by normal expression of PrPc on Hermansky-Pudlak syndrome platelets, which lack dense granules, and failure of gray platelet syndrome platelets, which lack alpha-granules, to up-regulate PrPc. Our results warrant further studies on the role of platelet PrPc in the transmission of prion diseases by blood transfusion.


Relation between peripheral vascular endothelial function and coronary flow reserve in patients with chest pain and normal coronary angiogram.
To evaluate the relation between peripheral vascular endothelial function and coronary flow reserve (CFR), we assessed flow mediated dilation (FMD) of brachial artery and the intima-media thickness (IMT) of the carotid artery in 32 subjects (mean age 58+/-9 years, M/F=9:23 ) with chest pain and normal coronary angiogram. The subjects were divided into 2 groups according to CFR >or=2.1 or <2.1 measured with transthoracic echocardiography in distal left anterior descending coronary artery. We found % FMD was decreased in the group with CFR <2.1 than those of CFR >or=2.1 and CFR was correlated with peripheral FMD. However, IMT was not different between two groups. These results suggest that microvascular dysfunction is primarily related to endothelial dysfunction rather than advanced atherosclerosis and because it is a generalized process that involves the whole arteries, the measurement of brachial FMD can be a useful diagnostic tool to evaluate microvascular dysfunction in patients with chest pain and normal coronary angiogram.


1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent.
We and others have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibits cell proliferation and increases secretion of prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human prostate cancer cell line. The present study was designed to investigate the possible interactions between 1,25-(OH)2D3 and androgens in the regulation of LNCaP cellular function. LNCaP cell growth was dose-dependently inhibited by 1,25-(OH)2D3 (60% inhibition at 10 nM) when cells were cultured in medium supplemented with FBS (FBS medium). 1,25-(OH)2D3-treated cells showed a 5-fold increase in PSA secretion, similar to the increase seen in dihydrotestosterone (DHT)-treated cells. In combination, 1,25-(OH)2D3 and DHT synergistically enhanced PSA secretion 22-fold. This synergistic effect was even greater when cells were cultured in medium supplemented with charcoal-stripped serum (CSS medium), where endogenous steroids are substantially depleted. Under these conditions, 1,25-(OH)2D3 and DHT together stimulated PSA secretion up to 50-fold over the untreated control. Radioligand binding assays and Western blot analyses showed that the androgen receptor (AR) content was increased significantly by 1,25-(OH)2D3 at 48 h. Furthermore, the steady-state mRNA level of AR was up-regulated approximately 2-fold by 1,25-(OH)2D3 at 24 h. When cells were grown in CSS medium, 1,25-(OH)2D3 alone no longer inhibited cell growth or induced PSA secretion. Titration experiments revealed that the addition of DHT at 1 nM to the medium restored the antiproliferative activity of 1,25-(OH)2D3. Conversely, an antiandrogen, Casodex, completely blocked 1,25-(OH)2D3 antiproliferative and PSA stimulation activities when cells were cultured in FBS medium. In conclusion, these results demonstrate that the antiproliferative and PSA induction activities of 1,25-(OH)2D3 in LNCaP cells are dependent upon androgen action and that AR up-regulation by 1,25-(OH)2D3 likely contributes to the synergistic actions of 1,25-(OH)2D3 and DHT in these cells.


Predictors of Effective Self-care Interventions Among Jordanians With Heart Failure.
Jordanians are more at risk for heart failure now than in years prior. However, there are few studies addressing heart failure self-care in Jordanians. Identifying predictors that promote heart failure self-care among Jordanian patients is crucial in providing comprehensive care. This study aimed to identify predictors of self-care behaviors among Jordanians with heart failure. A cross-sectional study with a convenience sample of 300 Jordanian patients was performed in an educational hospital in the north of Jordan. Differences in the level of self-care between selected sociodemographic and clinical variables were identified using univariate statistics, and multiple regression was used to adjust estimates for covariates. The predictors of self-care were insomnia (p ≤ .001) and marital status (p = .018). Identifying factors influencing self-care can assist with addressing the causes of insomnia to ensure effective treatment, providing patients with social support, and eventually promoting heart failure self-care.


Optical effects of shock front on nose-mounted optics.
The density discontinuity in a shock wave of a vehicle in supersonic flight may affect the performance of optical systems behind the shock. These effects are evaluated for nose mounted f/2 optics under Mach 1.5 conditions. The optical conditions of the shock are included as an optical element in a computer ray trace program that computes modulation transfer function. Comparison of MTF results, both with and without the shock in the system, provides an indication of the performance degradation due to the shock.


Bone-lengthening for symbrachydactyly of the hand with the technique of callus distraction.
Bone-lengthening in the hand and foot is a relatively new application for distraction osteogenesis. We present the operative treatment and postoperative outcome for four patients with M ller type-D symbrachydactyly of the hand who underwent metacarpal lengthening with use of a distraction device to establish pinch function. Four patients who underwent distraction osteogenesis for the treatment of congenital symbrachydactyly of the hand were evaluated over a thirteen-year period. The nondominant right hand was treated in two patients, and the nondominant left hand was treated in the other two. The patients included three boys and one girl; all patients had the operation between the ages of five and eleven years. Distraction osteogenesis was performed on the fifth metacarpal in one patient and on the fourth and fifth metacarpals in the remaining three, in whom both bones were lengthened simultaneously with use of a single device. Postoperative bone elongation was analyzed with radiographs made at the time of removal of the distractor. The sensory function of the treated fingers and any growth disturbance of the distracted bones were evaluated. The mean duration of distraction was 37.3 days (range, thirty-two to forty-nine days), and the distractor was removed at a mean of eighty-four days after surgery. The bones were lengthened by a mean of 22.3 mm (81.6% of their original length) at a rate of 0.6 mm/day. Pinch function was improved in all patients. On the basis of our limited experience, we found that distraction osteogenesis of the metacarpals was an effective technique for the establishment of pinch function. We also found that an intramedullary Kirschner wire could maintain the alignment of the osteotomized bone. Although distraction requires a longer treatment period, it is apparently more effective than bone-grafting in terms of achieving adequate bone length. Simultaneous lengthening of two metacarpals also was found to be an effective technique.


Eudragit® RL as a stabilizer for supersaturation and a substrate for nanocrystal formation.
In order to optimize supersaturation levels and avoid early drug precipitation, Eudragit® RL was tested as a carrier in solid dispersions, either alone or in combination with a hydrophilic polymer (PVP K25). In vitro dissolution performance of the spray dried solid dispersions was tested. The phase behavior of the produced solid dispersions was analyzed as well as dissolution precipitates. In case of weak acid model compounds (indomethacin and naproxen), the incorporation of Eudragit® RL resulted in a prolongation of supersaturation. A combination of PVP and Eudragit® RL led to high and stable drug concentrations. Eudragit® RL was only suited as a carrier in combination with higher drug loadings. Phase behavior analysis of the produced solid dispersions showed that Eudragit® RL could form glass solutions, and precipitate analysis showed that these drug-polymer combinations remained amorphous after in vitro dissolution for 24h. Surprisingly, indomethacin and naproxen also formed nanocrystals in presence of Eudragit® RL. These nanocrystals were formed by a dynamic interplay of dissolution, sorption and desorption. A charge interaction between anionic drugs and a cationic polymer provided a high driving force for sorption, which was necessary for nanocrystal formation and supersaturation stabilization.


CDC's Flu on Call Simulation: Testing a National Helpline for Use During an Influenza Pandemic.
During an influenza pandemic, healthcare facilities are likely to be filled to capacity, leading to delays in seeing a provider and obtaining treatment. Flu on Call is a collaborative effort between the US Centers for Disease Control and Prevention and partners to develop a toll-free telephone helpline to reduce the burden on healthcare facilities and improve access to antivirals for people who are ill during an influenza pandemic. This study tested the feasibility of Flu on Call during a 1-day simulation using a severe pandemic scenario. Trained volunteer actors placed calls to the helpline using prepared scripts that were precoded for an expected outcome ("disposition") of the call. Scripts represented callers who were ill, those calling for someone else who was ill, and callers who were only seeking information. Information specialists and medical professionals managed the calls. Results demonstrated that Flu on Call may effectively assist callers during a pandemic, increase access to antiviral prescriptions, and direct patients to the appropriate level of care. Overall, 84% of calls exactly matched the expected call disposition; few calls (2%) were undermanaged (eg, the caller was ill but not transferred to a medical professional or received advice from the medical professional that was less intensive than what was warranted). Callers indicated a high level of satisfaction (83% reported their needs were met). Because of the high volume of calls that may be received during a severe pandemic, the Flu on Call platform should evolve to include additional triage channels (eg, through internet, chat, and/or text access).


Studies on pp60src and associated kinase activity in regressing tumors induced by Rous sarcoma virus.
Rous sarcoma virus induced chicken tumors usually grow progressively for several weeks and then regress. pp60src kinase activity was reduced in cultured tumor cells which derived from regressing sarcomas by 60-75% as compared to progressively-growing neoplasms. We have demonstrated the presence of inhibitory activity to pp60src kinase activity in extracts of regressing tumor cells. Such extracts were able to reduced by 60% the level of kinase activity found in progressively-growing tumors, as measured in a IgG phosphorylation assay. Immunoprecipitation analyses of membrane or cytosol fractions did not reveal any significant differences between these two types of tumor cells in distribution of pp60src. The pp60src kinase of progressively-growing tumor cells was more sensitive than that of "regressor" cells to inhibition by P1, P4 di-(adenosine-5') tetraphosphate (Ap4 A) and to heat inactivation. These results suggest that the reduction of pp60src kinase activity in regressing neoplasms might be due to the presence of inhibitors in such cells, but that the basal levels of activity which remain are relatively resistant to further perturbation by heat and/or chemical antagonists.


RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2.
The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.


[Circadian rhythm of parasympathetic nervous function in asthmatic children].
We examined the circadian rhythm of parasympathetic nervous function in asthmatic children. The subjects were 80 patients with asthma (mild 54 patients, moderate 15 patients and severe 11 patients) and 90 individuals in healthy children. All the patients underwent 24-electrocardiography in normal condition. We measured the %RR50 for hour and analyzed the rhythm using the single cosine fitting method, comparing the values of the Amplitude, the MESOR and the Acrophase in terms of the therapy and also the severity of asthma. Circadian rhythm disappeared in 9 of the 80 asthmatic children and was observed in all the individuals in the healthy children. The value of MESOR was lower in the asthmatic children than in the healthy children. There was no significant difference between the different severity or therapies in each group. In some asthmatic children, the circadian rhythm of parasympathetic nervous function disappeared, the parasympathetic nervous function was low in remission. It is suggested that the disorder of biologic rhythm is related to the pathogenesis of asthma.


Acidic Urine Is Associated With Poor Prognosis of Upper Tract Urothelial Carcinoma.
To assess the prognostic role of acidic urine (low urine pH) in upper tract urothelial cancer (UTUC). We reviewed patients enrolled in Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Upper Tract Urothelial Cancer (SUPER-UC-UTUC) who underwent surgical resection from March 2016 to December 2020 in Seoul National University Hospital (SNUH). Patients with non-urothelial cancer or those who are in condition at end-stage renal disease were excluded. Acidic urine was defined as urine pH ≤ 5.5. A total of 293 patients with a mean age of 70.7 ± 9.5 years were enrolled in this study. Pre-operative laboratory results showed a mean estimated glomerular filtration rate (eGFR) of 64.1 ± 19.2 mL/min/1.73m2 and a mean urine pH of 5.86 ± 0.66. Patients were subdivided into low (pH ≤ 5.5) and high (pH > 5.5) urine pH for comparison. As a result, all variables were comparable except for the T stage, which was significantly higher in the low urine pH group (p = 0.017). Cox regression analysis was performed to assess the clinical impact of acidic urine on patient survival. Multivariate Cox regression analysis revealed that tumor multifocality (HR 2.07, p = 0.015), higher T stage (HR 1.54, p = 0.036), lymphovascular invasion (HR 1.69, p = 0.033), eGFR < 60 mL/min per 1.73 m2 (HR 1.56, p = 0.017), and acidic urine (HR 1.63, p < 0.01) independently decreased disease-free survival (DFS), while multifocality (HR 9.50, p < 0.01), higher T stage (HR 9.51, p = 0.001) and acidic urine (HR 10.36, p = 0.004) independently reduced the overall survival (OS). Acidic urine is independently associated with reduced DFS and OS in UTUC. Acidic urine contributing to acidic environment may promote acquisition of agressive behavior of UTUC.


Peptide Agonists and Antagonists with Potential Application in Neurological Disorders.
Peptides are usually used to investigate regulatory networks and protein function. They can also be used in therapeutic research: They are employed both to identify and later to validate therapeutical target and in drug discovery processes. Their development enables the identification of several protein surfaces as crucial therapeutic targets and to promote the discovery of small drugs specific for these molecular interfaces. This review was developed through the research of online content and patents related to natural and de novo designed peptides in neurological diseases studies. The effects of natural and derived peptides and/or peptidomimetic on models of neurodegenerative diseases and other neurological disorders were discussed. Many peptides are frequently identified as receptor antagonists, inhibitors of protein-protein interactions and several of them and/or peptide-derived compounds are commercial drugs or in clinical trials. Thus, peptide research could play a crucial role in the identification of protein ligands. Despite these favorable properties, they present low bioavailability and metabolic stability respect with traditional drugs. New synthetic strategies for limiting metabolic degradation and alternative routes of administration have been conceived to enlarge the number of peptide-based drugs in preclinical phases. Peptide-based drug discovery is an important option to address common therapeutic challenges including human neurological diseases.


Continuous flow nanoparticle concentration using alternating current-electroosmotic flow.
Achieving real-time detection of environmental pathogens such as viruses and bacterial spores requires detectors with both rapid action and a suitable detection threshold. However, most biosensors have detection limits of an order of magnitude or more above the potential infection threshold, limiting their usefulness. This can be improved through the use of automated sample preparation techniques such as preconcentration. In this paper, we describe the use of AC electroosmosis to concentrate nanoparticles from a continuous flow. Electrodes at an optimized angle across a flow cell, and energized by a 1 kHz signal, were used to push nanoparticles to one side of a flow cell, and to extract the resulting stream with a high particle concentration from that side of the flow cell. A simple model of the behavior of particles in the flow cell has been developed, which shows good agreement with experimental results. The method indicates potential for higher concentration factors through cascading devices.


Beneficial effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy.
A prospective study on the vasodilatory effect of prostaglandin E1 on blood flow to the gastric tube after esophagectomy is reported. Twelve patients with thoracic esophageal cancer who underwent esophagectomy were enrolled in this study. In all patients, the esophagogastrostomy was performed in the cervical region, and the stomach was used for reconstruction. Immediately after the creation of the gastric tube, baseline blood flow was measured at the oral end, in the center, and at the pyloric ring of the gastric tube using a laser Doppler flowmeter. The prostaglandin E1 group (n = 6) was then infused with prostaglandin E1 until postoperative day 2; the control group (n = 6) received saline. At +5 minutes and +40 minutes after administration, blood flow was again measured at the same three sites. The control group did not show a significant increase of blood flow to any site over time. For the prostaglandin E1 group, blood flow at +40 minutes increased from the baseline measurements significantly at a rate of 63%, 39%, and 36%, respectively. Prostaglandin E1 has a characteristic vasodilating effect on the area of impaired microcirculation of the gastric tube, thereby increasing blood flow to the affected area.


Synthesis and Anti-HCV Activities of 18β-Glycyrrhetinic Acid Derivatives and Their In-Silico ADMET Analysis.
Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18β-Glycyrrhetinic acid (GA) is the main active metabolite of GL. Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate the structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for a promising lead compound for further identification of anti-HCV terpenoid candidates. GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis was performed via "pkCSM" and "SwissADME" platforms. Eighteen GA derivatives were synthesized, and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with an IC50 value of 0.79 μM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed that the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidates.


An evaluation of a computer-imaging program to prepare women for chemotherapy-related alopecia.
This study was conducted to evaluate a computer program named Help with Adjustment to Alopecia by Image Recovery (HAAIR) that was developed to provide educational support and reduce distress in women with hair loss following chemotherapy. Forty-five women who had been diagnosed with cancer and anticipated alopecia following treatment were randomly assigned to either the Imagining group (IG) or Standardized Care group (SCG). Patients in the IG used a computer-imaging program that created the patient's image on a screen to simulate baldness and use of wigs whereas patients in the SCG were directed to a resource room at the Cancer Center established for women with chemotherapy-related alopecia. Assessment data using the Brief Symptom Inventory, Importance of Hair Questionnaire, and the Brief Cope were completed at baseline (T1), before chemotherapy and hair loss, following hair loss (T2), and 3 months follow-up (T3). All women were able to successfully use the touch screen computerized-imaging program and reported that using the computer was a positive, helpful experience, thus establishing acceptability and usability. Women in both the IG and the SCG group showed significantly lower hair loss distress scores at T2 after hair loss than at T1 with T3 distress scores increasing in the SCG and decreasing in the IG. Those with avoidance coping reported more distress. This evaluation demonstrates that the HAAIR program is a patient-endorsed educational and supportive complement to care for women facing chemotherapy-related alopecia.


Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.
Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.


Simultaneous determination of ezetimibe and simvastatin in pharmaceutical preparations by MEKC.
A micellar electrokinetic capillary chromatography method was developed and validated for the simultaneous determination of ezetimibe and simvastatin in pharmaceutical preparations. The influence of buffer concentration, buffer pH, sodium dodecyl sulphate (SDS) concentration, organic modifier, capillary temperature, applied voltage, and injection time was investigated, and the method validation studies were performed. The optimum separation for these analytes was achieved in less than 10 min at 30 degrees C with a fused-silica capillary column (56 cm x 50 microm i.d.) and a 25mM borate buffer at pH 9.0 containing 25mM SDS and 10% (v/v) acetonitrile. The samples were injected hydrodynamically for 3 s at 50 mbar, and the applied voltage was +30.0 kV. Detection wavelength was set at 238 nm. Diflunisal was used as internal standard. The method was suitably validated with respect to stability, specificity, linearity, limits of detection and quantification, accuracy, precision, and robustness. The limits of detection and quantification were 1.0 and 2.0 microg/mL for both ezetimibe and simvastatin, respectively. The method developed was successfully applied to the simultaneous determination of ezetimibe and simvastatin in pharmaceutical preparations.


Clonidine reduces blood pressure and heart rate oscillations in hypertensive patients.
Short-term fluctuations in blood pressure (BP) and heart rate (HR) were analyzed in a group of eight men with essential hypertension. Indirect finger BP was measured by a Finapres device. Analog-to-digital conversion of the BP was used to determine systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) and HR every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm. The effects of an oral dose of clonidine (150 micrograms) were studied in a double-blind, crossover, placebo-controlled study. Clonidine markedly reduced the variability of BP and HR after 90 min as indicated by a reduction in the standard deviations of BP by 36.7% for SAP, 21.0% for DAP, 22.1% for MAP, and 26.0% for HR. At this time clonidine reduced the average BP by 19.7 mm Hg for SAP, 10.6 mm Hg for DAP, 16.0 mm Hg for MAP, and 1.0 beat/min for HR. Spectral profiles of BP and HR illustrated the alterations in the spontaneous oscillations underlying the standard deviation changes. Clonidine dramatically reduced the amplitude of BP and HR oscillations in the mid-frequency region 66-129 mHz, which depends on the activity of the autonomic nervous system. We suggest that an increased sensitivity of the baroreflex is responsible for the apparent better control of BP and HR with clonidine.


Replication of Streptococcus equi subspecies zooepidemicus infection in swine.
Streptococcus equi subspecies zooepidemicus (SEZ) is a commensal bacterium of horses and causes infections in mammalian species, including humans. Historically, virulent strains of SEZ caused high mortality in pigs in China and Indonesia, while disease in the U.S. was infrequent. More recently, high mortality events in sows were attributed to SEZ in North America. The SEZ isolates from these mortality events have high genetic similarity to an isolate from an outbreak in China. Taken together, this may indicate SEZ is an emerging threat to swine health. To generate a disease model and evaluate the susceptibility of healthy, conventionally raised pigs to SEZ, we challenged sows and five-month-old pigs with an isolate from a 2019 mortality event. Pigs were challenged with a genetically similar guinea pig isolate or genetically distinct horse isolate to evaluate comparative virulence. The swine isolate caused severe systemic disease in challenged pigs with 100 % mortality. Disease manifestation in sows was similar to field reports: lethargy/depression, fever, reluctance to rise, and high mortality. The guinea pig isolate also caused severe systemic disease; however, most five-month-old pigs recovered. In contrast, the horse isolate did not cause disease and was readily cleared from the respiratory tract. In conclusion, we were able to replicate disease reported in the field. The results indicate differences in virulence between isolates, with the highest virulence associated with the swine isolate. Additionally, we generated a challenge model that can be used in future research to evaluate virulence factors and disease prevention strategies.


Astigmatism and toric intraocular lenses.
The article reviews some of the basic optics of astigmatism and the correction of astigmatism with cylindric lenses. A simple model of the conoid of Sturm is demonstrated, and an ideal position for the conoid is postulated. The orientation of the conoid shows that leaving patients with some simple myopic "against-the-rule" astigmatism is beneficial to near work, whereas "with-the-rule" astigmatism is beneficial for distant viewing. Surgeons should be less aggressive with patients with with-the-rule and against-the-rule astigmatism and more aggressive with oblique astigmatism. The toric intraocular lens (IOL) should be positioned on axis or, if slightly off axis, err on the side away from the vertical or horizontal meridian so that the resultant cylinder is more vertical or horizontal. Clinically significant rotation of the toric IOL occurs in a few cases, but these can be easily rerotated. Rerotation should be done between the first and second weeks after primary implantation.


Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system.
The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses using the forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) in mice. Our results revealed that intra-peritoneal (i.p.) injection of ketamine (5 and 10 mg/kg), a non-competitive NMDA antagonist, dose-dependently produced antidepressant-like effect in the FST. Moreover, i.p. administration of both CB1 and CB2 receptor drugs: ACPA (1 mg/kg; CB1 receptor agonist), AM251 (1 mg/kg; CB1 receptor antagonist), GP1a (2 mg/kg; CB2 receptor agonist) and AM630 (0.5 mg/kg; CB2 receptor antagonist) exhibited antidepressant action. Interestingly, the concomitant administration of ineffective doses of ketamine and cannabinoid receptor antagonists provoked the antidepressant-like effects as compared to control group. It should be considered, all above mentioned doses of drugs could not change locomotor activity in the OFT. It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.


Subcellular localization of the barley stripe mosaic virus triple gene block proteins.
Barley stripe mosaic virus (BSMV) spreads from cell to cell through the coordinated actions of three triple gene block (TGB) proteins (TGB1, TGB2, and TGB3) arranged in overlapping open reading frames (ORFs). Our previous studies (D. M. Lawrence and A. O. Jackson, J. Virol. 75:8712-8723, 2001; D. M. Lawrence and A. O. Jackson, Mol. Plant Pathol. 2:65-75, 2001) have shown that each of these proteins is required for cell-to-cell movement in monocot and dicot hosts. We recently found (H.-S. Lim, J. N. Bragg, U. Ganesan, D. M. Lawrence, J. Yu, M. Isogai, J. Hammond, and A. O. Jackson, J. Virol. 82:4991-5006, 2008) that TGB1 engages in homologous interactions leading to the formation of a ribonucleoprotein complex containing viral genomic and messenger RNAs, and we have also demonstrated that TGB3 functions in heterologous interactions with TGB1 and TGB2. We have now used Agrobacterium tumefaciens-mediated protein expression in Nicotiana benthamiana leaf cells and site-specific mutagenesis to determine how TGB protein interactions influence their subcellular localization and virus spread. Confocal microscopy revealed that the TGB3 protein localizes at the cell wall (CW) in close association with plasmodesmata and that the deletion or mutagenesis of a single amino acid at the immediate C terminus can affect CW targeting. TGB3 also directed the localization of TGB2 from the endoplasmic reticulum to the CW, and this targeting was shown to be dependent on interactions between the TGB2 and TGB3 proteins. The optimal localization of the TGB1 protein at the CW also required TGB2 and TGB3 interactions, but in this context, site-specific TGB1 helicase motif mutants varied in their localization patterns. The results suggest that the ability of TGB1 to engage in homologous binding interactions is not essential for targeting to the CW. However, the relative expression levels of TGB2 and TGB3 influenced the cytosolic and CW distributions of TGB1 and TGB2. Moreover, in both cases, localization at the CW was optimal at the 10:1 TGB2-to-TGB3 ratios occurring in virus infections, and mutations reducing CW localization had corresponding effects on BSMV movement phenotypes. These data support a model whereby TGB protein interactions function in the subcellular targeting of movement protein complexes and the ability of BSMV to move from cell to cell.


Ion collision crosssection measurements in quadrupole ion traps using a time-frequency analysis method.
In this study, a method for measuring ion collision crosssections (CCSs) was proposed through time-frequency analysis of ion trajectories in quadrupole ion traps. A linear ion trap with added high-order electric fields was designed and simulated. With the presence of high-order electric fields and ion-neutral collisions, ion secular motion frequency within the quadrupole ion trap will be a function of ion motion amplitude, thus a function of time and ion CCS. A direct relationship was then established between ion CCS and ion motion frequency with respect to time, which could be obtained through time-frequency analysis of ion trajectories (or ion motion induced image currents). To confirm the proposed theory, realistic ion trajectory simulations were performed, where the CCSs of bradykinin, angiotensin I and II, and ubiquitin ions were calculated from simulated ion trajectories. As an example, differentiation of isomeric ubiquitin ions was also demonstrated in the simulations.


Spatiotemporal Profiles of Proprioception Processed by the Masseter Muscle Spindles in Rat Cerebral Cortex: An Optical Imaging Study.
Muscle spindles in the jaw-closing muscles, which are innervated by trigeminal mesencephalic neurons (MesV neurons), control the strength of occlusion and the position of the mandible. The mechanisms underlying cortical processing of proprioceptive information are critical to understanding how sensory information from the masticatory muscles regulates orofacial motor function. However, these mechanisms are mostly unknown. The present study aimed to identify the regions that process proprioception of the jaw-closing muscles using in vivo optical imaging with a voltage-sensitive dye in rats under urethane anesthesia. First, jaw opening that was produced by mechanically pulling down the mandible evoked an optical response, which reflects neural excitation, in two cortical regions: the most rostroventral part of the primary somatosensory cortex (S1) and the border between the ventral part of the secondary somatosensory cortex (S2) and the insular oral region (IOR). The kinetics of the optical signal, including the latency, amplitude, rise time, decay time and half duration, in the S1 region for the response with the largest amplitude were comparable to those in the region with the largest response in S2/IOR. Second, we visualized the regions responding to electrical stimulation of the masseter nerve, which activates both motor efferent fibers and somatosensory afferent fibers, including those that transmit nociceptive and proprioceptive information. Masseter nerve stimulation initially excited the rostral part of the S2/IOR region, and an adjacent region responded to jaw opening. The caudal part of the region showing the maximum response overlapped with the region responding to jaw opening, whereas the rostral part overlapped with the region responding to electrical stimulation of the maxillary and mandibular molar pulps. These findings suggest that proprioception of the masseter is processed in S1 and S2/IOR. Other sensory information, such as nociception, is processed in a region that is adjacent to these pulpal regions and is located in the rostral part of S2/IOR, which receives nociceptive inputs from the molar pulps. The spatial proximity of these regions may be associated with the mechanisms by which masseter muscle pain is incorrectly perceived as dental pain.


Expression of the mature and the pro-form of human sterol carrier protein 2 in Escherichia coli alters bacterial lipids.
Sterol carrier protein 2 (SCP2) is a protein that is believed to be involved in the intracellular transport of cholesterol and phospholipids. Expression in mammalian COS cells of a cDNA encoding SCP2 revealed that the mature protein is synthesized as a pro-form containing a 20-residue amino-terminal leader sequence. The function of this presequence is currently not known, and pro-SCP2 is generally not detected in tissues. In order to obtain large quantities of pro-SCP2 as well as the mature form of human SCP2, Escherichia coli expression plasmids were constructed. Both proteins were produced in high yield (10-30% of the total cell protein) and were found in the supernatant fraction after cell lysis. Recombinant human SCP2 and pro-SCP2 were purified to homogeneity by acid precipitation followed by ion-exchange chromatography. Both recombinant human SCP2 and pro-SCP2 had sterol exchange activity similar to that seen with SCP2 purified from rat liver. In addition, the lipid content of SCP2- and pro-SCP2-producing E. coli was analyzed. Acidic lipids were significantly increased in the transfected cells. Specifically, fatty acids were increased 2-3-fold, phosphatidylglycerol was increased 2-fold, and lipid A was increased 3-4-fold, while neutral lipids were decreased 2-3-fold as compared to control cells. This alteration of the lipid composition of E. coli expressing SCP2 or pro-SCP2 is consistent with the proposed role for SCP2 in intracellular lipid movement.


Chromosome analysis by spectral karyotyping of spermatozoa from an oligoasthenozoospermic carrier of a 10; 21 reciprocal translocation.
Cytogenetic analysis of germ-line cells prior to intracytoplasmic sperm injection (ICSI) treatment is thought to be necessary for infertile males with an identified chromosomal abnormality. We analyzed the chromosomal karyotype of human spermatozoa from an oligoasthenozoospermic carrier of a reciprocal translocation t(10; 21). Cytogenetic analysis of 39 spermatozoa was performed by spectral karyotyping (SKY) and by ICSI into mouse oocytes. The motile morphologically normal spermatozoa were injected into mouse oocytes. Of these spermatozoa, 38 (97.4%) were activated. Twenty-one (53.8%) of the activated oocytes formed two pronuclei. Metaphase chromosome spreads from 13 spermatozoa were analyzed. Only one spermatozoon was normal and 2 spermatozoa exhibited balanced translocation. Nine and one spermatozoa showed abnormalities related and unrelated to the translocation, respectively. The numbers of normal/balanced spermatozoa were lower than those in previous reports analyzing reciprocal translocations using a previously described technique involving penetrated golden hamster oocytes. After genetic counseling with the carrier and his partner, ICSI treatment was performed. Healthy female and male infants were delivered at 37 weeks gestation via a Caesarean section. The female infant was a carrier of the reciprocal translocation and the male infant was confirmed normal on prenatal diagnosis at 16 weeks gestation. For genetic counseling prior to ICSI treatment, the incidence of unbalanced type spermatozoa after swim-up or Percoll gradient treatment should be investigated and discussed with couples having fertility problems related to oligozoospermia autosomal structural abnormalities.


Protein Bodies from the Endosperm of Castor Bean: Subfractionation, Protein Components, Lectins, and Changes during Germination.
Protein bodies from the storage endosperm of dry castor bean (Ricinus communis L.) were isolated by successive nonaqueous linear density gradient centrifugation. The isolated protein bodies were lysed by the addition of water, and the various structural components of the organelles were separated by sucrose gradient centrifugation. The matrix protein remained at the top of the gradient while the membrane, the crystalloids, and the globoids migrated to densities 1.15 g/cm(3), 1.30 g/cm(3), and > 1.46 g/cm(3), respectively. The protein of the protein bodies was distributed evenly between the crystalloids and the matrix, and little protein was present in the globoids or the membrane.The proteins of the protein bodies were resolved into protein components of diverse molecular weights in sodium dodecyl sulfate-acrylamide gel electrophoresis. The protein components of the organelle matrix were distinct from those of the crystalloids. Whereas the matrix proteins had very diverse molecular weights, the crystalloid proteins were mainly composed of several proteins with molecular weights between 50,000 and 60,000 daltons. Also, the matrix proteins were soluble in water while the crystalloid proteins were insoluble in water but soluble in salt solution, thus representing albumins and globulins, respectively. Two of the matrix proteins with molecular weights approximately 120,000 and 65,000 daltons were identified as the phytohemagglutimin and the toxic protein ricin, respectively.During germination, the crystalloid proteins served as the storage protein and went through rapid degradation with smaller polypeptides formed as intermediates. In contrast, the proteins of the matrix under-went a much slower degradation during the same period and did not appear to be storage protein.


Chemotherapy Effectiveness and Prognosis of Gastric Cancer Influenced by PTPN11 Polymorphisms.
Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.


Clinical, hematologic, hemostatic, and serum biochemical findings related to survival in Arabian horses with colic.
The efficacy of clinical examinations, and hematologic, hemostatic, and serum biochemical assessments to determine appropriate early medical or surgical therapy in Arabian horses with colic have not been well-described. We aimed to evaluate clinical and hematologic findings, coagulation-fibrinolytic parameters, and organ dysfunction markers in association with survival in horses with colic. Seventeen Arabian horses with colic and ten healthy horses were enrolled. After clinical examinations, including heart rates (HRs), capillary refill times (CRTs), abdominal sounds, rectal palpations, and nasogastric (NG) reflux assessments in both healthy and diseased horses, blood samples were collected and hematologic parameters, coagulation indices such as the prothrombin time (PT), activated partial thromboplastin time (APTT), plasma d-dimer (PDD), platelet count, fibrinogen, and hepatorenal biomarkers were measured. Based on the outcomes, horses with colic were divided into survival (10) and nonsurvival (7) groups, and all mentioned parameters were compared with the control group horses. Unlike HRs, CRTs, and abdominal sounds, rectal palpations (57.1%) and NG reflux (28.6%) findings were least sensitive in being able to determine survival. At least three of the five coagulation indices were significantly abnormal (prolonged PT, increased PDD, and decreased plasma fibrinogen) in 71.4% of the horses in the nonsurvival group compared with the control and survival groups. Significantly increased urea, creatinine, and bilirubin levels, and AST activities were also observed in the survival group compared with the control and nonsurvival groups. The combination of prolonged PT, increased PDD, and hypofibrinogenemia could be a reliable predictor of survival in horses with colic. The significant renal and hepatic dysfunctions in nonsurviving horses with colic appeared to be consistent with disseminated intravascular coagulation (DIC) and a grave prognosis.


Pediatric Epstein-Barr virus-associated encephalitis: 10-year review.
Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been documented, including encephalitis, aseptic meningitis, transverse myelitis, and Guillain-Barré syndrome. These manifestations can occur alone or coincidentally with the clinical picture of infectious mononucleosis. Since 1994, The Hospital for Sick Children has maintained a prospective registry of all children admitted with acute encephalitis. This report summarizes all cases of Epstein-Barr virus-associated encephalitis compiled from 1994 to 2003. Twenty-one (6%) of 216 children, median age 13 years (range 3-17 years), in the Encephalitis Registry were identified as having evidence of Epstein-Barr virus infection. This evidence consisted of convincing Epstein-Barr virus serology and/or positive cerebrospinal fluid polymerase chain reaction (PCR). One patient had symptoms of classic infectious mononucleosis; all others had a nonspecific prodrome, including fever (n = 17; 81%) and headache (n = 14; 66%). Slightly less than half (n = 10; 48%) had seizures and often had electroencephalograms showing a slow background (n = 12; 57%). Many demonstrated cerebrospinal fluid pleocytosis (n = 17; 81%), and 71% (n = 15) had abnormal magnetic resonance imaging findings. Two patients died, 2 suffered mild deficits, and 16 were neurologically normal at follow-up. Most patients with Epstein-Barr virus encephalitis do not show typical symptoms of infectious mononucleosis. Establishing a diagnosis of Epstein-Barr virus encephalitis can be difficult, and, consequently, a combination of serologic and molecular techniques should be used when investigating a child with acute encephalitis. Most children make full recoveries, but residual neurologic sequelae and even death can and do occur.


Development of a Strategy for Enhancing the Biomass Growth and Lipid Accumulation of Chlorella sp. UJ-3 Using Magnetic Fe3O4 Nanoparticles.
In this study, magnetic Fe3O4 nanoparticles (NPs) were used as an effective enhancer to increase the biomass and total lipid production of Chlorella sp. UJ-3. It was found that the biomass of algal cells increased significantly when they were exposed to low concentrations of Fe3O4 NPs (20 mg/L), while the best total lipid content of algal cells was achieved when they were exposed to high concentrations of Fe3O4 NPs (100 mg/L). Therefore, we established a strategy to promote the growth and lipid accumulation of microalgae by initially exposing the algal cells to low concentrations of Fe3O4 NPs and then treating them with an increased concentration of Fe3O4 NPs after 12 days of culture. For this strategy, the biomass and total lipid production of algal cells increased by 50% and 108.7%, respectively, compared to the untreated control. The increase in lipid production and change in the fatty acid composition of Chlorella cells were found to help them to cope with the increased number of reactive oxygen species produced due to oxidative stress in alga cells after the addition of Fe3O4 NPs. This study provided a highly efficient way to improve the lipid production of microalgae using nanoparticles.


Protein synthesis, amino acid uptake, and pools during isoproterenol-induced hypertrophy of the rat heart and tibialis muscle.
Chronic administration of isoproterenol (ISO) produces hypertrophy of the rat heart and tibialis muscle. With doses of 0.1, 0.3, and 0.6 mg/kg, hypertrophy of the heart is significantly by the 3rd day of treatment. Maximum cardiac enlargement attained with doses of 0.3 and 0.6 mg/kg occurs after 21 days and averages 40% above control values. ISO increases tibialis muscle weight by 15%. Incorporation of 14C-labeled amino acids into total heart and tibialis muscle protein is stimulated by ISO. Maximum stimulation occurs 2-3 h after the fifth daily injection of ISO. The stimulation of incorporation is greater during the first few days of treatment and decreases gradually thereafter. A single injection of ISO decreases the total amino acid concentration of the serum, heart and tibialis muscle whereas the rate of amino acid uptake by the heart and tibialis muscle is increased by ISO. The production of hypertrophy of the heart and tibialis muscle in diabetic or castrated animals by ISO suggests that insulin and testosterone are not essential in the mechanism of ISO-induced hypertrophy.


Parasitic Helminths in Snakes from The Global Legal Trade.
In recent years, the demand for snakes imported from different countries around the world has increased in Slovakia. However, such snakes can be infected with a wide variety of parasites. We have been focused on monitoring the prevalence of parasitic helminths of snakes imported to Slovakia. From 2015 to 2020, 205 samples were collected. We examined faecal samples of 185 live snakes, and a parasitological autopsy was performed on 20 carcasses. Out of a total of 205 snakes, parasitic helminths were found in 44 individuals (21.46 %). Coprological examination of live snakes confirmed positivity for the presence of helminths in 38 snakes (20.54 %). Through parasitological autopsy of all the dead snakes, we found helminths or their eggs in 6 carcasses (30.00 %). The genera of helminths found in the positive snakes were: Ophiotaenia spp., Kapsulotaenia spp., Strongyloides spp., Rhabdias spp., Ophidascaris spp., Ascaridia spp., f. Heterakidae, Kalicephalus spp., Capillaria spp., order Oxyurida and stages of the plerocercoid of an unidentifi ed species of tapeworm in the subcutaneous tissue.


Identification of membrane protein associated with sucrose transport into cells of developing soybean cotyledons.
The photolyzable sucrose derivative 6'-deoxy-6'-(4-azido-2-hydroxy)-benzamidosucrose (6'-HABS), competitively inhibited the influx of [(14)C] sucrose into protoplasts from developing soybean (Glycine max L. Merr cv Wye) cotyledons. Photolysis of (125)I-labeled 6'-HABS in the presence of 10 millimolar dithiothreitol and microsomal preparations from developing soybean cotyledons led to label incorporation into a moderately abundant membrane protein with an apparent molecular mass of about 62 kilodalton (kD) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 62 kD protein was partially protected from labeling by the inclusion of 100 millimolar sucrose in the photolysis medium and also by the inclusion of 10 millimolar phenyl alpha-d-thioglucopyranoside. Glucose, raffinose, or phenyl alpha-d-3-deoxy-3-fluoroglucopyranoside did not afford even partial protection from labeling. When the photolyzable moiety of 6'-HABS was attached to 6-deoxy-6-aminoglucose and (125)I labeled, the resulting photoprobe did not label the 62 kD protein above background. The labeled protein at 62 kD is therefore apparently a specific, sucrose binding protein. Sucrose influx into cotlyedons of less than 25 milligrams fresh weight (approximately 10 days after flowering) occurred by passive processes, but metabolically dependent uptake became dominant over the next 5 to 7 days of development. Both the Coomassie staining protein at 62 kD and label incorporation at that position in analysis of membrane proteins appeared concomitant with the onset of active sucrose influx. Polyclonal antibodies to the purified 62 kD protein bound specifically to a protein in the plasmalemma of thin sections prepared from cotyledons and density stained with colloidal gold-protein A. The results suggest that the 62 kD membrane protein is associated with sucrose transport and may be the plasmalemma sucrose transporter.


Autoradiographic Distribution of Muscarinic Acetylcholine Receptor Subtypes in Rat Cochlear Nucleus.
The cochlear nucleus (CN) receives cholinergic inputs primarily from centrifugal pathways. There is evidence that the effects of these cholinergic inputs may be mediated mainly by muscarinic acetylcholine receptors. We used 1-[N-methyl-3H]scopolamine (NMS) to study muscarinic receptor binding in the rat CN autoradiographically. To determine which muscarinic receptor subtypes participate in the binding, we included competition assays using the unlabeled subtype-preferential ligands pirenzepine, AF-DX 116, 4-DAMP, HHSiD, and tropicamide to compete with [3H]NMS for binding. Our results suggest that NMS binding density in the CN is about a tenth of that in the facial nucleus. Inside the CN, the highest binding was found in granular regions, followed in order by the dorsal CN (DCN) fusiform soma layer, the DCN molecular layer, the DCN deep layer, the anteroventral CN (AVCN) and posteroventral CN (PVCN). Binding in the interstitial nucleus (auditory nerve root) was similar to background. The results of the competition assays suggest that the M2 receptor subtype predominates in VCN, M4 in the DCN fusiform soma layer, and both subtypes in DCN molecular and deep layers. M4 and M3 subtypes predominated in the granular region of AVCN, while M1 and M2 were more prominent in the granular region of PVCN. The results show similarities to those obtained with pharmacological and immunohistochemical methods, but also some discrepancies. The different distributions of the different muscarinic receptor subtypes suggest that the effects of cholinergic inputs may differ among CN subregions, in agreement with in vivo pharmacological results. Overall, the centrifugal cholinergic influences on information processing in the CN may especially involve M2 and M4 receptors.