Modulation of acute immune complex-mediated tissue injury by the presence of polyionic substances.
Considerable attention has been focused on the role of electrostatic charge in the pathogenesis of immune complex-mediated tissue injury. The authors have examined the ability of cationic (histone, polyhistidine, polyarginine) and anionic (polyanetholsulfonate) polyelectrolytes to modulate acute immune complex-mediated tissue injury. Tissue injury elicited in rats by the reversed dermal Arthus reaction was increased 26-43% by addition of polyelectrolytes to antibody prior to its intradermal injection. Kinetic studies using 111In-labeled neutrophils indicated that the enhanced tissue injury was not the result of increased influx of neutrophils. Infusion of polyethylene glycol-conjugated superoxide dismutase prior to induction of the Arthus reaction resulted in 40-68% suppression of tissue injury. Concomitant in vitro functional studies (enzyme secretion, O-2 and H2O2 generation, and chemiluminescence) of rat neutrophils demonstrated that addition of polyelectrolytes to preformed immune complexes (IgG-bovine serum albumin) resulted in marked increases in O-2, H2O2, and chemiluminescence, but no increases in enzyme secretion, compared with neutrophils stimulated with immune complexes alone. The cationic polyelectrolytes did not alter the capacity of preformed immune complexes to activate complement in vitro. These studies suggest that both cationic and anionic polyelectrolytes can increase the pathogenic potential of immune complexes and that this modulation is, at least in part, mediated by enhanced generation of toxic oxygen-derived metabolites by neutrophils.


Juvenile dermatomyositis presenting with periorbital edema.
Juvenile dermatomyositis is a rare disease that affects the skin and muscles. It often presents with a classic heliotrope eyelid rash. We present a case of juvenile dermatomyositis presenting with significant bilateral periorbital edema, with its complete resolution after systemic antiinflammatory therapy.


MDR1A deficiency restrains tumor growth in murine colitis-associated carcinogenesis.
Patients with Ulcerative Colitis (UC) have an increased risk to develop colitis-associated colorectal cancer (CAC). Here, we found that protein expression of ABCB1 (ATP Binding Cassette Subfamily B Member 1) / MDR1 (multidrug resistance 1) was diminished in the intestinal mucosa of patients with active UC with or without CAC, but not in non-UC patients with sporadic colon cancer. We investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine model for CAC (AOM/DSS). Mice deficient in MDR1A (MDR1A KO) showed enhanced intratumoral inflammation and cellular damage, which were associated with reduced colonic tumor size and decreased degree of dysplasia, when compared to wild-type (WT). Increased cell injury correlated with reduced capacity for growth of MDR1A KO tumor spheroids cultured ex-vivo. Gene expression analysis by microarray demonstrated that MDR1A deficiency shaped the inflammatory response towards an anti-tumorigenic microenvironment by downregulating genes known to be important mediators of cancer progression (PTGS2 (COX2), EREG, IL-11). MDR1A KO tumors showed increased gene expression of TNFSF10 (TRAIL), a known inducer of cancer cell death, and CCL12, a strong trigger of B cell chemotaxis. Abundant B220+ B lymphocyte infiltrates with interspersed CD138+ plasma cells were recruited to the MDR1A KO tumor microenvironment, concomitant with high levels of immunoglobulin light chain genes. In contrast, MDR1A deficiency in RAG2 KO mice that lack both B and T cells aggravated colonic tumor progression. MDR1A KO CD19+ B cells, but not WT CD19+ B cells, suppressed growth of colonic tumor-derived spheroids from AOM/DSS-WT mice in an ex-vivo co-culture system, implying that B-cell regulated immune responses contributed to delayed tumor development in MDR1A deficiency. In conclusion, we provide first evidence that loss of ABCB1/MDR1 function may represent an essential tumor-suppressive host defense mechanism in CAC.


Chronic disease burden predicts food insecurity among older adults.
Increased out-of-pocket health-care expenditures may exert budget pressure on low-income households that leads to food insecurity. The objective of the present study was to examine whether older adults with higher chronic disease burden are at increased risk of food insecurity. Secondary analysis of the 2013 Health and Retirement Study (HRS) Health Care and Nutrition Study (HCNS) linked to the 2012 nationally representative HRS. USA. Respondents of the 2013 HRS HCNS with household incomes <300 % of the federal poverty line (n 3552). Chronic disease burden was categorized by number of concurrent chronic conditions (0-1, 2-4, ≥5 conditions), with multiple chronic conditions (MCC) defined as ≥2 conditions. The prevalence of food insecurity was 27·8 %. Compared with those having 0-1 conditions, respondents with MCC were significantly more likely to report food insecurity, with the adjusted odds ratio for those with 2-4 conditions being 2·12 (95 % CI 1·45, 3·09) and for those with ≥5 conditions being 3·64 (95 % CI 2·47, 5·37). A heavy chronic disease burden likely exerts substantial pressure on the household budgets of older adults, creating an increased risk for food insecurity. Given the high prevalence of food insecurity among older adults, screening those with MCC for food insecurity in the clinical setting may be warranted in order to refer to community food resources.


The gametogenic cycle of Leguminaia whaetleyi (Lea, 1862) in lake Gölbaşı, Turkey (Bivalvia: Unionidae).
The gonadal structure and cycle of the Leguminaia whaetleyi is described for the first time indicating that 5% of this species is simultaneous hermaphrodite. A total of 420 individuals were collected in monthly samples from October 2008 to September 2009 in Gölbaşı Lake, Turkey. Calculation of the condition index and histological examination of the gonads showed that gametogenesis began in January. Spawning occurred between May and August with one maximum peak in July. Annual maximum oocytes size peaked in July. The population consisted of simultaneous hermaphrodite individuals. Sex ratio of L. whaetleyi was significantly different from the expected 1:1 ratio (P< 0.05), and also female biased sex ratio was recorded. In hermaphrodite specimens, male and female follicles were mixed in the visceral mass but can be clearly distinguished by light microscopy study. L. whaetleyi appears to be a dioecious species in which 25 specimens were simultaneous hermaphrodite and under certain environmental conditions may be capable of self-fertilization. This suggests that detailed studies on sex ratio of L. whaetleyi may be helpful in understanding unionid phylogeny.


Characterization of new bisphenol a metabolites produced by CD1 mice liver microsomes and S9 fractions.
Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA) is a widely used industrial chemical resulting in occupational and consumer exposure. BPA possesses weak estrogenomimetic activity and can be cytotoxic, though the underlying mechanisms of its toxicity toward cells are not completely understood. The metabolism of BPA by CD1 mice liver microsomal and S9 fractions was investigated. Nine metabolites were isolated and characterized using HPLC and mass spectrometry. Many of these metabolites were characterized for the first time in mammals, namely isopropyl-hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers. Most of these metabolites apparently share a common metabolic pathway, for which considerable evidence supports the hypothesis of the production of a reactive intermediate, and also helps explain BPA cytotoxicity.


Specific gonadotrophin-releasing hormone analogue binding predominantly in human luteinized follicular aspirates and not in human pre-ovulatory follicles.
In an attempt to resolve the apparent controversy in the observed effects of gonadotrophin-releasing hormone (GnRH) analogues on the ovary, conventional binding studies were conducted with a GnRH agonist and an antagonist in various ovarian tissues to demonstrate possible GnRH receptor binding. In human luteinized granulosa cells derived from unstimulated in-vitro fertilization cycles, high affinity receptor binding was present in 17 out of 24 patients, while binding was not observed in any of the six pre-ovulatory follicles removed during abdominal surgery. Apparently contradictory observations on the direct ovarian effects of GnRH analogues may be the result of the intermittent presence of high affinity GnRH receptors. Our observations indicate that in the human, high affinity ovarian GnRH receptors are present predominantly in ovarian tissue after the luteinizing hormone surge. We also propose the possibility of regulation and activation of a human follicular GnRH receptor in the ovary as a physiological process which may be influenced pharmacologically.


Unsupervised learning techniques reveal heterogeneity in memory CD8+ T cell differentiation following acute, chronic and latent viral infections.
CD8+ T lymphocytes are critical for the control of gammaherpesvirus latency. To determine how memory CD8+ T cells generated during latency differ from those primed during acute or chronic viral infection, we adoptively transferred naive P14 CD8+ T cells into uninfected recipients, and examined surface proteins, cytokines and transcription factors following infection with the Armstrong (acute) or Clone 13 (chronic) strains of lymphocytic choriomeningitis virus (LCMV), or murine gammaherpesvirus 68 (MHV68) expressing the LCMV epitope DbGP33-41. By performing k-means clustering and generating self organizing maps (SOM), we observed increased short-lived effector-like, CD27lo CD62Llo and Bcl-6lo CD8+ T cells following latent infection. In addition, we found that memory CD8+ T cells from latent primed mice underwent less expansion following adoptive transfer and antigen rechallenge. Data from cluster models were combined and visualized by principal component analysis (PCA) demonstrating memory CD8+ T cells from latent infection occupy an intermediate differentiation space.


ORIGINS OF GENOTYPIC VARIATION IN NORTH AMERICAN DANDELIONS INFERRED FROM RIBOSOMAL DNA AND CHLOROPLAST DNA RESTRICTION ENZYME ANALYSIS.
Restriction enzyme analysis of ribosomal DNA (rDNA) and chloroplast DNA (cpDNA) is used to assess the relative contribution of hybridization and mutation as sources of genotypic variation in weedy asexual dandelions, with focus on the dandelion flora of North America. Of 318 North American dandelions surveyed, 145 rDNA-cpDNA clones are detected. The combined rDNA-cpDNA genotypes show that most of the polymorphic rDNA and cpDNA restriction sites or lengths in these plants are also present in weedy asexual dandelions collected from natural populations in Europe and in asexual and diploid taxa (microspecies) chosen to represent diverse Eurasian members of the genus. However, of 222 combined rDNA-cpDNA genotypes found in 427 asexual plants surveyed, only 9 genotypes are found in both North American and Eurasian dandelions. Two rDNA and three cpDNA characters are unique to individual plants in North America and are consistent with mutational origins of genotypic variation in asexual lineages. But the array of genotypic diversity, characterized by different combinations of the rDNA and cpDNA characters, show that multiple hybridization events are a more important source of genotypic variation than mutation in the asexual polyploids. The rDNA and cpDNA data also indicate polyphyletic origin of several asexual Taraxacum taxa.


Kinematic and biomimetic assessment of a hydraulic ankle/foot in level ground and camber walking.
Improved walking comfort has been linked with better bio-mimicking of the prosthetic ankle. This study investigated if a hydraulic ankle/foot can provide enough motion in both the sagittal and frontal planes during level and camber walking and if the hydraulic ankle/foot better mimics the biological ankle moment pattern compared with a fixed ankle/foot device. Five active male unilateral trans-femoral amputees performed level ground walking at normal and fast speeds and 2.5° camber walking in both directions using their own prostheses fitted with an "Echelon" hydraulic ankle/foot and an "Esprit" fixed ankle/foot. Ankle angles and the Trend Symmetry Index of the ankle moments were compared between prostheses and walking conditions. Significant differences between prostheses were found in the stance plantarflexion and dorsiflexion peaks with a greater range of motion being reached with the Echelon foot. The Echelon foot also showed significantly improved bio-mimicry of the ankle resistance moment in all walking conditions, either compared with the intact side of the same subject or with the "normal" mean curve from non-amputees. During camber walking, both types of ankle/foot devices showed similar changes in the frontal plane ankle angles. Results from a questionnaire showed the subjects were more satisfied with Echelon foot.


Relationship between follicle-stimulating hormone levels at the beginning of the human menstrual cycle, length of the follicular phase and excreted estrogens: the FREEDOM study.
Although reproductive aging has been separately related to elevated FSH and shorter follicular phase (FP), the direct association between both parameters has not been investigated. Also, the exact effects of increased FSH on estrogen production are yet to be established.A large database of daily urinary concentrations of FSH, LH, and estrone 3-glucuronide (E1G) from 37 regularly menstruating women (median 11 cycles per patient) was used. Initial FSH levels (iFSH) were estimated as the mean value of d 1-5. The day of E1G take-off (ETO) was determined by an algorithm, and accordingly, the FP was divided into early (d 1 to ETO) and late (ETO+1 to LH peak). FP maximum and integrated E1G were calculated. Subjects were distributed according to their mean iFSH into three categories (</=5, >5 to 10, and >10 IU/liter). There was a gradual decrease in FP length with increasing category (15.2 +/- 3.8, 14.1 +/- 3.6, and 13 +/- 2.6 d, respectively; P < 0.0001). A similar effect occurred in early FP (7.5 +/- 4, 6.4 +/- 3.7, and 5.4 +/- 2.7; P < 0.0001); in contrast, late FP was unaffected (7.7 +/- 2.1, 7.7 +/- 2.1, and 7.6 +/- 2.4; P = 0.86). No consistent increase in E1G was found with advancing iFSH category; however, women with mean initial LH higher than 6 IU/liter had significantly elevated maximum (P < 0.0001) and integrated (P = 0.002) E1G.FP length decreases in parallel with increasing iFSH, with a selective effect on the early FP. Increased FSH does not affect E1G; however, elevated initial LH level was related to higher E1G.


Mirabegron: a safety review.
Mirabegron is being developed as a new treatment for the management of overactive bladder (OAB). It is an orally active drug that works by activating the β(3)-adrenoceptor with a better safety profile than antimuscarinic drugs. However, long-term adverse effects are not yet completely investigated. The following article reviews the pharmacology and efficacy of mirabegron by analyzing the tolerability findings in the data available from several Phase II placebo-controlled clinical trials conducted with an active comparator. We aim to provide familiarity with the metabolic pathway responsible for disposition of mirabegron which makes it likely to produce pharmacokinetic interactions with other drugs, as although mirabegron is generally well tolerated, its potential to cause drug interactions may limit its use in some patients. Mirabegron is a β(3)-adrenoceptor agonist developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile for OAB patients with advanced age and cognitive deficit. It has been well tolerated with significant efficacy in reducing the number of incontinence episodes and mean micturition frequency. The most commonly reported toxic effects of mirabegron are gastrointestinal adverse events and headache.


Alkyl- and alkenylresorcinols of wheat grains and their chemotaxonomic significance.
Resorcinolic lipid contents and homologue compositions in extracts isolated from soft winter, soft spring and hard (durum) wheat grains were evaluated by both instrumental and chromatography means. Resorcinol concentrations determined in wheat were diverse and varied in samples harvested within two consecutive vegetative years, whereas their homologue profiles were found to be rather invariable. The predominant alkylresorcinols identified in wheat grains were saturated 1,3-dihydroxy-5-n-heneicosylbenzene and 1,3-dihydroxy-5-n-nonadecylbenzene. 1,3-Dihydroxy-5-n-heptadecylbenzene and 1,3-dihydroxy-5-n-tricosylbenzene were also determined, whereas 1,3-dihydroxy-5-n-pentadecylbenzene and 1,3-dihydroxy-5-n-pentacosylbenzene were present in these extracts only in spurious amounts. Furthermore, our results show that alk(en)ylresorcinols may be useful as chemotaxonomic markers for a distinction between soft and hard wheat plants. Cluster analysis with Ward's amalgamation algorithm and five different distance linkage types clearly discriminated particular wheats into species- and cultivar-specific clusters, whereas the use of principal component analysis allowed us to specify, which of the variables analysed were decisive. This approach may be useful for both plant breeders and taxonomists to classify wheat species/cultivars.


Pharmacokinetics of cefpodoxime proxetil in healthy young and elderly volunteers.
The influence of age on the pharmacokinetics of cefpodoxime was evaluated in 12 elderly (ages 65-85 years) and 12 weight- and sex-matched young (ages 20-33 years) subjects, each of whom received two cefpodoxime proxetil 200-mg tablets every 12 hours for 14.5 days. Serial blood samples and urine were collected after the first dose on day 1, after the morning dose on day 8, and after the last (morning) dose on day 15. Plasma and urine samples were assayed for cefpodoxime concentrations using HPLC methods. Within each age group, mean pharmacokinetic parameters determined on day 1 were similar to corresponding values on days 8 and 15, indicating that cefpodoxime does not accumulate after twice-daily dosing of cefpodoxime proxetil. Based on this result, parameters were pooled across days in each age group. No significant differences were observed between healthy and elderly volunteers in area under the plasma concentration-time curve for the 12-hour dosing interval, peak plasma concentration, or time to peak concentration. Mean urinary excretion and renal clearance of cefpodoxime were significantly lower in elderly subjects. Differences in renal clearance were attributed to the corresponding age-related reduction that was noted in creatinine clearance values, whereas the lower urinary excretion of cefpodoxime probably reflected slightly reduced systemic drug absorption in the elderly. Differences in these parameters between groups were less than 30%, and were unlikely to be of clinical importance. The data indicate that dose adjustment of cefpodoxime in elderly subjects having normal (age-adjusted) creatinine clearance values is not required.


Nanotechnology-General Aspects: A Chemical Reduction Approach to the Synthesis of Nanoparticles.
The role of nanotechnology is increasingly important in our society. Through it, scientists are acquiring the ability to understand the structure and properties of materials and manipulate them at the scale of atoms and molecules. Nanomaterials are at the forefront of the rapidly growing field of nanotechnology. The synthesis of nanostructured materials, especially metallic nanoparticles, has attracted tremendous interest over the past decade due to their unique properties, making these materials excellent and indispensable in many areas of human activity. These special properties can be attributed to the small size and large specific surface area of nanoparticles, which are very different from those of bulk materials. Nanoparticles of different sizes and shapes are needed for many applications, so a variety of protocols are required to produce monodisperse nanoparticles with controlled morphology. The purpose of this review is firstly to introduce the reader to the basic aspects related to the field of nanotechnology and, secondly, to discuss metallic nanoparticles in greater detail. This article explains the basic concepts of nanotechnology, introduces methods for synthesizing nanoparticles, and describes their types, properties, and possible applications. Of many methods proposed for the synthesis of metal nanoparticles, a chemical reduction is usually preferred because it is easy to perform, cost-effective, efficient, and also allows control of the structural parameters through optimization of the synthesis conditions. Therefore, a chemical reduction method is discussed in more detail-each factor needed for the synthesis of nanoparticles by chemical reduction is described in detail, i.e., metal precursors, solvents, reducing agents, and stabilizers. The methods that are used to characterize nanomaterials are described. Finally, based on the available literature collection, it is shown how changing the synthesis parameters/methods affects the final characteristics of nanoparticles.


Feline model of acute nipah virus infection and protection with a soluble glycoprotein-based subunit vaccine.
Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID(50)) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID(50) of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.


Comorbidity indices: a call for the integration of physical and mental health.
Comorbidity indices are commonly used in health services research as a measure of, or as a control for, the severity of a person's medical state. Currently, there is not a comorbidity index for mental health diagnoses, despite the fact that almost half of Americans have a diagnosable mental health condition at least once in their lifetime. This commentary calls for the integration of mental and behavioral health in comorbidity indices to appropriately account for the role of mental health in overall morbidity and mortality.


Application of Magnetic Resonance DTI Technique in Evaluating the Effect of Postoperative Exercise Rehabilitation.
Magnetic resonance diffusion tensor imaging (DTI) is a new kind of magnetic resonance imaging technology. Its imaging principle is to distinguish different pathological tissues according to the movement of water molecules, which is higher than regular magnetic resonance diffusion-weighted imaging. Magnetic resonance diffusion tensor imaging has exact utility price in medical analysis and sickness evaluation. However, there are few researches on the utility of diffusion tensor imaging in the rehabilitation comparison of patients. This paper explores the utility of magnetic resonance DTI science in evaluating the impact of postoperative patients' exercising rehabilitation. Taking stroke patients as an example, through giving patients rehabilitation training method, using magnetic resonance DTI technology, the motor function rehabilitation of patients was evaluated, and FA changes of the affected side and healthy side and Fugl-Meyer score of two groups of patients before and after rehabilitation were observed. The software outcomes exhibit that, in the contrast of rehabilitation therapy impact of motor feature in sufferers with cerebral infarction, the use of magnetic resonance DTI technological know-how gives a foundation for clinicians to deeply apprehend the CST involvement of patients, which helps to scientifically evaluate the effect and quality of limb motor rehabilitation training of patients and provides a basis for disease treatment.


[Research progress on biofilm formation by Bacillus subtilis- a review ].
Biofilm is a prevalent lifestyle in nature and closely related to the life and production of humans. Bacillus subtilis is an important industrial strain and a good model for biofilm research. Combined with our current studies, we reviewed significant progress on biofilm formation by Bacillus subtilis, including main process, characteristics of biofilm formation, research models, and regulatory pathway for biofilm formation. In addition, further research focuses are addressed.


The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.
Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.


Phenotypic diversity of Xanthomonas sp. mangiferaeindicae.
Carbohydrate utilization profiles by means of the API (Appareils et Procédés d'Identification) system and sensitivity to antibiotics and heavy metal salts of 68 Xanthomonas sp. mangiferaeindicae strains isolated in nine countries from mango (Mangifera indica L.) and other genera of the Anacardiaceae were examined to assess the variability of the taxon. The strains could be separated into 10 groups according to Ward clustering. Apigmented strains isolated from the pepper tree [syn. Brazilian pepper] (Schinus terebenthifolius Raddi) could not be clearly differentiated from most apigmented strains isolated from mango. Yellow-pigmented strains isolated from mango in Brazil and Reunion Island, apigmented strains isolated from mango in Brazil and from ambarella in the French West Indies, clustered in distinct groups. The results are consistent with those of other studies, based on isozyme analysis of esterase, phosphoglucomutase and superoxide dismutase, and hrp-RFLP analysis; they indicate the need for a comprehensive taxonomic evaluation of xanthomonads associated with Anacardiaceae.


Comparison of borderline personality subcategories to schizophrenic and affective disorders.
This clinical research report identified 4 subcategories of the hospitalized borderline personality disorder: developmental, affective disorder, attentional deficit/learning disabled, and organic. Developmental and affective disorder subcategories are predominantly composed of females, while males are overly represented in the attentional deficit/learning disabilities subcategory . Comparison of the borderline patients with schizophrenic and affective disorder control groups supports the hypothesis that the borderline personality disorder is a diagnostic entity distinct from schizophrenia, but perhaps not from affective disorders.


Dynamic perfusion analysis in acute ischemic stroke: A comparative study of two different softwares.
In clinical practice, decisions often must be made rapidly; therefore, automated software is useful for diagnostic support. Perfusion computed tomography and follow-up evaluation of perfusion data are valuable tools for selecting the optimal recanalization therapy in patients with acute ischemic stroke. This study aimed to compare commercially available software used to evaluate stroke patients prior to thrombectomy. The performance of Olea Sphere (OlS) software vs. CT Neuro Perfusion from Syngo (Sy), as well as the electronic Alberta Stroke Program Early Computed Tomography Score (e-ASPECTS) software vs. an experienced radiologist, were compared using descriptive statistics including significance analysis, Spearman's correlation, and the Bland-Altman agreement analysis. For this purpose, 43 data sets of patients with stroke symptoms related to the middle cerebral artery territory were retrospectively post-processed with both tools and analyzed. The automatic e-ASPECTS showed high agreement with an expert rater assessment of the ASPECTS. Using OlS and Sy, we compared the parameters for the ischemic core (relative cerebral blood flow), Time to maximum (Tmax) for the penumbra, and the relative mismatch between these two values. Overall, both software tools achieved good agreement, and their respective values correlated well with each other. However, OlS predicted significantly smaller infarct core volumes compared with Sy. Although the absolute values have a certain degree of variation, both software programs have good agreement with each other.


Potential causes of medication errors: perceptions of Serbian nurses.
The aim of this study was to identify the most common contributing factors to medication errors in everyday practice of Serbian nurses. Nurses have the key role in medication, and it is very important that they understand why errors occur. This research study was a cross-sectional study in five healthcare institutions. The sample was 965 nurses. A specially designed questionnaire was used as the research instrument. The most dominant contributing factor of medication errors was insufficient number of nurses. Interestingly other dominant factors given in literature were not recognized in this research study. The study results confirm that the recommendations we find in literature cannot be simply copied and implemented into the existing system, but can be used as a starting point for further research. The obtained data were compared with the studies of the countries with different healthcare systems and different educational structures of nurses. The results of the study imply that healthcare institutions have to take the initiative and the responsibility for teaching safe medication use during formal education, as well as in clearly planned programmes of continuous education for nurses. To reduce errors to the least possible level, it is important that nurses clearly define what an error is and recognize the causes and the importance of reporting and analysing them. Systemic practices are required in the health system in Serbia and the culture of patients' safety accepted as the common goal and imperative of everyday practice.


A model combining excess and relative mortality for population-based studies.
Considering expected mortality provides an attractive approach to analyse mortality of population-based cohorts of patients presenting with a chronic disease. Two classes of methods are available: either modelling the excess mortality using an additive hazard model or modelling the relative mortality using a multiplicative hazard model. Because these two models are informative to look for factors associated with mortality related to a chronic disease, we developed an alternative model modelling both the excess and the relative mortality. We generalised Andersen and Vaeth's model to fit covariates and obtain directly an estimation of the Excess Mortality Ratio and Relative Mortality Ratio for each covariate. We assessed the performances of the combined model by using simulations, and it appeared satisfactorily. We illustrate the combined model by data collected in patients presenting with end-stage renal disease and treated by dialysis. The combined model offers the possibility of performing pure additive and multiplicative models and thus to compare their log-likelihoods. The combined model appears useful to select one of these pure models or to conclude to the need of modelling both excess and relative mortality. In this latter case, our model enabled better describing the effect of covariates on the excess and relative mortality.


Expression of the maize proteinase inhibitor (mpi) gene in rice plants enhances resistance against the striped stem borer (Chilo suppressalis): effects on larval growth and insect gut proteinases.
The maize proteinase inhibitor (mpi) gene was introduced into two elite japonica rice varieties. Both constitutive expression of the mpi gene driven by the maize ubiquitin 1 promoter and wound-inducible expression of the mpi gene driven by its own promoter resulted in the accumulation of MPI protein in the transgenic plants. No effect on plant phenotype was observed in mpi-expressing lines. The stability of transgene expression through successive generations of mpi rice lines (up to the T(4) generation) and the production of functional MPI protein were confirmed. Expression of the mpi gene in rice enhanced resistance to the striped stem borer (Chilo suppressalis), one of the most important pests of rice. In addition, transgenic mpi plants were evaluated in terms of their effects on the growth of C. suppressalis larvae and the insect digestive proteolytic system. An important dose-dependent reduction of larval weight of C. suppressalis larvae fed on mpi rice, compared with larvae fed on untransformed rice plants, was observed. Analysis of the digestive proteolytic activity from the gut of C. suppressalis demonstrated that larvae adapted to mpi transgene expression by increasing the complement of digestive proteolytic activity: the serine and cysteine endoproteinases as well as the exopeptidases leucine aminopeptidase and carboxypeptidases A and B. However, the induction of such proteolytic activity did not prevent the deleterious effects of MPI on larval growth. The introduction of the mpi gene into rice plants can thus be considered as a promising strategy to protect rice plants against striped stem borer.


PSMA-targeted stably linked "dendrimer-glutamate urea-methotrexate" as a prostate cancer therapeutic.
One of the important criteria for achieving efficient nanoparticle-based targeted drug delivery is that the drug is not prematurely released at off-target sites. Here we report the preclinical evaluation of a serum-stable dendrimer-based drug conjugate capable of actively targeting into prostate cancer (PC) cells, delivered through the prostate-specific membrane antigen (PSMA). Multiple molecules of PSMA-binding small molecule glutamate urea (GLA; targeting agent) and the drug methotrexate (MTX) were conjugated to generation 5 PAMAM dendrimer (G5) through Cu-free "click" chemistry. The GLA was conjugated through a stable amide bond, and the MTX was conjugated either through ester (Es)- or amide (Am)-coupling, to generate G5-GLA(m)-(Es)MTX(n) and G5-GLA(m)-(Am)MTX(n), respectively. In serum-containing medium, free MTX was slowly released from "G5-GLA(m)-(Es)MTX(n)", with ~8% MTX released from the dendrimer in 72 h, whereas the MTX on G5-GLA(m)-(Am)MTX(n) was completely stable. The G5-GLA(m)-(Am)MTX(n) bound and internalized into PSMA-expressing LNCaP cells, but not into PSMA-negative PC3 cells. The conjugate-inhibited recombinant dihydrofolate reductase and induced potent cytotoxicity in the LNCaP cells, but not in the PC3 cells. Similar to the action of free GLA, stable amide-linked dendrimer-GLA was capable of inhibiting the enzyme N-acetylated α-linked acidic dipeptidase (NAALADase) activity of PSMA. The G5-GLA(m)-MTX(n) may serve as a serum-stable nanoparticle conjugate to specifically and effectively target and treat PSMA-overexpressing prostate tumors.


Projective identification in Othello and Verdi's Otello.
In this paper I explore how projective identification is depicted in Shakespeare's Othello (1603-4 [2006]) and in Verdi's Otello (1887). Both the play and the opera can be seen as studies in projection - in the evacuation into others of feelings that the subject finds unbearable, such as envious and jealous exclusion or unbearable sexual excitement. The essential issue is the same in both the play and the opera, which is that the very sight of love between Othello and Desdemona, or of contentment in anyone's mind, drives Iago mad with envy and jealousy, which he has to expel and project into others, particularly into Othello, who is susceptible to this attack because of his own narcissistic vulnerability. I take two episodes, which appear in both the play and the opera, to explore in detail how projective identification is represented both verbally and musically. I suggest that music, and words used musically, are particularly suited to conveying complex inter- and intra-personal processes such as projective identification.


Primary safety results from the LEADLESS Observational Study.
A prospective, single-arm, multicentre, post-market study was conducted to confirm the short-term safety of the Nanostim™ leadless pacemaker (LP). In this study, we report the primary results of the LEADLESS Observational Study. Subjects meeting VVIR pacemaker indications were enrolled and followed up after successful LP implantation, prior to discharge and post-implantation at 90 days, 180 days, and every 6 months thereafter for the assessment of adverse events. The primary safety endpoint was evaluated in terms of freedom from serious adverse device effects (SADEs) at 6 months in 300 subjects. Data for all enrolled subjects were also presented. A total of 470 subjects were enrolled (75.8 ± 13.1 years, 62.8% male). The study paused in April 2014 following the occurrence of perforation events that led to changes in the protocol and investigator training. Freedom from SADEs, evaluated in 300 subjects enrolled post-pause, was 94.6% (95% confidence interval 91.0-97.2%) and demonstrated non-inferiority to a performance goal of 86% (P < 0.0001). Eighteen SADEs were observed in 16 (5.3%) subjects. The most frequently occurring events were cardiac perforation (1.3%), device dislodgement (0.3%), and vascular complications (1.3%). In the 470 subjects, 34 similar SADEs were observed in 31 (6.6%) subjects. After stratifying the results in relation to the study pause, there was a statistically significant difference in the final LP location (septum vs. apex) (P < 0.0001) and the number of repositioning attempts (<2 vs. ≥2) (P = 0.05) and a decreasing trend in the rates of cardiac perforation and device dislodgement. The primary safety endpoint at 6 months was successfully met for the Nanostim LP. The occurrence of cardiac perforation and device dislodgement declined after changes following the study pause.


The Impact of Comprehensive Pre-visit Preparation on Patient Engagement and Quality of Care in a Population of Underserved Patients with Diabetes: Evidence from the Care Management Medical Home Center Model.
This study evaluated the impact of pre-visit preparation, a key component of Patient-Centered Medical Home guidelines, on compliance with recommended tests and screenings in a diabetic patient population receiving care in Federally Qualified Health Centers in Miami-Dade County. The pre-visit preparation consisted of a pre-visit phone call to review patient compliance with recommended tests and screenings, provide encouragement for self-care goal setting, answer patient questions, assure referrals and tests were scheduled, and notify an in-center patient care team about which services are required at the upcoming visit. Aggregated data from 7 health centers and a cohort analysis of 7491 patients showed significantly higher compliance among those who were successfully contacted prior to the visit compared to those who were not successfully contacted at 24 months for all compliance measures included in the study. These results included a 28.8 percentage point difference in compliance with HbA1c testing, a 14.6 percentage point difference in influenza immunization, a 27.7 percentage point difference in diabetic foot exam compliance, and a 33.2 percentage point difference in compliance with annual low-density lipoprotein testing. After 24 months, the patient no-show rate decreased by 6.8 percentage points (from 20.7% to 14.0%) among contacted patients and by 5.5 percentage points (from 20.7% to 15.2%) among patients who were not contacted. Study results suggest that proactive pre-visit preparation may be a key strategy for primary care practices to improve areas critical for chronic disease management, such as patient engagement, appointments kept, and compliance with recommended screenings, tests, and services. (Population Health Management 2016;19:171-177).


Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in diabetic patients: A meta-analysis.
Dipeptidyl peptidase-4 inhibitors (DPP-4is) improve glucose control in patients with type 2 diabetes mellitus (DM); however, only few studies were properly designed to evaluate their cardiovascular (CV) effects. The purpose of this study was to assess the impact of DPP-4i treatment on CV morbidity and mortality. Randomized clinical trials enrolling more than 200 patients, comparing DPP-4 versus placebo or active treatments in patients with DM and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of heart failure (HF) were included in the analysis. Ninety-four trials enrolling 85,224 patients (median follow-up=29weeks) were included in the analysis. Compared to control, treatment with DPP-4i did not affect all-cause and CV mortality, as well as stroke, in the short and long terms (< and >=29weeks, respectively). DPP-4i reduced the risk of MI in the short (RR: 0.584 [95% CI: 0.361 to 0.943]; p=0.028), but not in the long term. Additionally, long-term treatment with DPP-4 was associated with a 15.8% increased risk of HF (RR: 1.158 [CI: 1.011 to 1.326]; p=0.034). No heterogeneity among studies or publication bias was detected. DPP4is do not affect all cause- and CV-mortality and stroke in diabetic patients; the reduction in MI observed with short-term treatment does not persist in the long term. Long-term use of DPP-4i in diabetic patients is associated with increased risk of HF.


Feeding Behavioral Assessment in Children with Cleft Lip and/or Palate and Parental Responses to Behavior Problems.
Children with cleft lip and/or palate frequently experience feeding difficulties that may place them at risk of malnutrition. Parents' negative response to these problems is associated with development of problematic behaviors in the child. This study aimed to investigate feeding behavior in children with cleft lip and/or palate and parental responses to these problems. A total of 120 parents of children (aged 6 months to 6 years) with cleft lip and/or palate were recruited from the Cleft Lip and Palate Clinic in Isfahan University of Medical Sciences, Isfahan, Iran, who gave consent and completed a two-part questionnaire through interviews. Part A of the questionnaire consisted of 25 items that evaluate children's feeding behavior during mealtimes and part B consists of 18 items that assess parental response (strategies, feelings, and anxiety) to these problems. Independent t-test showed a significant difference in the mean score of feeding behavior in mothers (P = 0.020) and parental responses in fathers (P = 0.030). The Pearson correlation coefficient showed an inverse correlation between behavioral feeding score and children's interval (P = 0.008, r = -0.381) and direct correlation between parental response and feeding behavioral difficulties (P = 0.003, r = 0.428). With regards to the results representing appropriate feeding behaviors in children with cleft lip and/or palate, it is suggested that feeding be avioral assessment is an essential nursing and nonmedical intervention for all children.


beta-hydroxy-beta-methylbutyrate (HMB) kinetics and the influence of glucose ingestion in humans.
The dietary supplement, beta-hydroxy-beta-methylbutyrate (HMB), has been shown to decrease muscle proteolysis during the stress of exercise and disease. The aim of this investigation was to determine the time course kinetics of HMB and to determine whether oral glucose ingestion alters the kinetics. In Study 1, eight males (32 +/- 10 yrs) participated in two randomize trials: 1) oral ingestion of 1g of HMB with water in capsule form (HMB), and 2) placebo. Blood samples were obtained prior to ingestion of treatment and at 30, 60, 90, 120, 150, and 180 min for the measurement of plasma HMB. Additional blood samples were obtained at 6, 9, and 12 hr. Urine was collected prior to ingestion and at 3, 6, 9, and 12 h for the measurement of urinary HMB. In Study 2, eight males (25 +/- 6 yrs) followed the same study design and testing procedure as for Study 1. Treatments were 1) modified glucose tolerance test (75 g glucose) (GLU), 2) oral ingestion of 3 g of HMB with water (HMB), and 3) ingestion of 3 g of HMB with 75 g of glucose (HMB+GLU). Blood samples were analyzed for insulin, glucose, and HMB. Additional blood samples were obtained at 24h and 36h for the measurement of HMB. Additional urine samples were collected at 24h and 36h. In Study 1, plasma HMB peaked at 120 nmol/ml at 2.0 +/- 0.4 hr in HMB trial. Half-life was 2.37 +/- 0.1 hr. Following the consumption of 1g of HMB, approximately 14% of the HMB consumed accumulated in the urine. In Study 2, plasma glucose and insulin levels were significantly greater in GLU and HMB+GLU treated subjects compared to HMB treated subject at minutes 30, 60 and 90. Plasma HMB peaked at 487.9 +/- 19.0 nmol/ml at 1.0 +/- 0.1 hr in the HMB treated subjects and at 352.1 +/- 15.3 nmol/ml at 1.94 +/- 0.2 hr when subjects consumed HMB+GLU. The time to reach peak was different (P <0.001) between HMB and HMB+GLU. The plasma HMB half-life was less (P = 0.08) 2.38 +/- 0.1 hr in HMB trial compared to 2.69 +/- 0.2 hr in HMB+GLU trial. Area under the plasma HMB curve during the first 3 hr was less (P = 0.002) in the HMB+GLU trial compared to the HMB trial. From 3 h through 36 h the area under the HMB curve tended to be less (P = 0.106) for the HMB+GLU compared to the HMB alone. HMB accumulation in the urine as well as the area under the curve were similar with both HMB (94875.8 +/- 15159.5 nmol/36 hrs) and HMB+GLU (80678.2 +/- 3863.1 nmol/36 hrs). The percentage of the HMB dose that accumulates in the urine was 27% for HMB+GLU and 29% for HMB alone. In conclusion, HMB plasma levels peak within 60 to 120 min depending on the amount of HMB consumed and whether glucose is consumed with HMB. The plasma half-life is approximately 2.5 hr. Plasma HMB reaches baseline levels at approximately 9 hr following ingestion. However, 70 to 85% of the ingested oral HMB is retained in the body for further metabolism.


Role of biomarkers in early infectious complications after lung transplantation.
Infections and primary graft dysfunction are devastating complications in the immediate postoperative period following lung transplantation. Nowadays, reliable diagnostic tools are not available. Biomarkers could improve early infection diagnosis. Multicentre prospective observational study that included all centres authorized to perform lung transplantation in Spain. Lung infection and/or primary graft dysfunction presentation during study period (first postoperative week) was determined. Biomarkers were measured on ICU admission and daily till ICU discharge or for the following 6 consecutive postoperative days. We included 233 patients. Median PCT levels were significantly lower in patients with no infection than in patients with Infection on all follow up days. PCT levels were similar for PGD grades 1 and 2 and increased significantly in grade 3. CRP levels were similar in all groups, and no significant differences were observed at any study time point. In the absence of PGD grade 3, PCT levels above median (0.50 ng/ml on admission or 1.17 ng/ml on day 1) were significantly associated with more than two- and three-fold increase in the risk of infection (adjusted Odds Ratio 2.37, 95% confidence interval 1.06 to 5.30 and 3.44, 95% confidence interval 1.52 to 7.78, respectively). In the absence of severe primary graft dysfunction, procalcitonin can be useful in detecting infections during the first postoperative week. PGD grade 3 significantly increases PCT levels and interferes with the capacity of PCT as a marker of infection. PCT was superior to CRP in the diagnosis of infection during the study period.


Isolation and characterization of a pancreatic elastase from plasma of patients with acute pancreatitis.
1. An elastase-like enzyme in plasma of patients with acute pancreatitis was purified by DEAE-cellulose column chromatography and polyacrylamide-gel disc electrophoresis. 2. In this way 0.24 mg of purified enzyme with a specific activity of 3.94 succinyl-L-alanyl-L-alanyl-L-alanyl-p-nitroanilide units/mg of protein was obtained from 10 ml of plasma. 3. The purified material was homogeneous as ascertained by sodium dodecyl sulphate/polyacrylamide-gel disc electrophoresis and had an apparent molecular weight of 24 000 as measured by gel filtration on Sephadex G-100. 4. This enzyme hydrolysed denatured casein and Congo Red-elastin as well as succinyl-L-alanyl-L-alanyl-L-alanyl-p-nitroanilide. Its amidolytic activity was inhibited by soya bean trypsin inhibitor, but not by aprotinin. 5. Although the enzyme was immunologically similar to elastase 2, its kinetic properties and substrate specificity were apparently different. 6. We propose that an elastase-like enzyme, probably different from elastase 1 or elastase 2, is liberated from the pancreas into blood during acute pancreatitis and becomes combined with alpha 2-macroglobulin.


Validity of tympanometry in the diagnosis of middle ear effusion.
A group of 266 children (515 ears), ranging in age from 5 months to 11 years, was studied. These children were candidates for the insertion of ventilation tubes, or adenoidectomy and/or tonsillectomy with myringotomy. Before surgery, tympanometry was performed. The surgical and tympanometric findings were compared afterwards. Two different tympanometers were used (GSI-27A and TYMP-85TT). This study showed a comparable validity of these two tympanometers. The sensitivity and specificity of tympanometry in the age group of 5 months to 2 years did not show a significant difference from that in the age group of 2-12 years. Otoscopy has limited value for the diagnosis of middle ear effusion in this age group.


Reference values for local arterial stiffness. Part A: carotid artery.
Non-invasive measures of common carotid artery properties, such as diameter and distension, and pulse pressure, have been widely used to determine carotid artery distensibility coefficient - a measure of carotid stiffness (stiffness ∼1/distensibility coefficient). Carotid stiffness has been associated with incident cardiovascular disease (CVD) and may therefore be a useful intermediate marker for CVD. We aimed to establish age and sex-specific reference intervals of carotid stiffness. We combined data on 22 708 individuals (age range 15-99 years, 54% men) from 24 research centres worldwide. Individuals without CVD and established cardiovascular risk factors constituted a healthy sub-population (n = 3601, 48% men) and were used to establish sex-specific equations for percentiles of carotid distensibility coefficient across age. In the sub-population without CVD and treatment (n = 12 906, 52% men), carotid distensibility coefficient Z-scores based on these percentile equations were independently and negatively associated, in men and women, respectively, with diabetes {-0.28 [95% confidence interval (CI) -0.41; -0.15] and -0.27 (-0.43; -0.12)}, mean arterial pressure [-0.26 (-0.29; -0.24) and -0.32 (-0.35; -0.29)], total-to-high-density lipoprotein cholesterol ratio [-0.05 (-0.09; -0.02) and -0.05 (-0.11; 0.01)] and BMI [-0.06 (-0.09; -0.04) and -0.05 (-0.08; -0.02)], whereas these were positively associated with smoking [0.30 (0.24; 0.36) and 0.24 (0.18; 0.31)]. We estimated age and sex-specific percentiles of carotid stiffness in a healthy population and assessed the association between cardiovascular risk factors and carotid distensibility coefficient Z-scores, which enables comparison of carotid stiffness values between (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures.


Filaroides hirthi: hyperinfective lungworm infection in immunosuppressed dogs.
Filaroides hirthi is a pulmonary parasite found primarily in beagle dogs. The modes of transmission and the life cycle of this parasite have been described recently, and the possibility of an autoinfectious cycle has been suggested. In this paper, we report two cases of experimentally immunosuppressed beagles (4 mg/day of prednisolone for over four months) in which massive disseminated F. hirthi infections developed. Large numbers of F. hirthi adults were present in the lungs, and larvae were found in lungs, mesenteric nodes, intestinal walls, and liver. While only minimal cellular responses were associated with the adult worms, a conspicuous mononuclear cell reaction was found around the larvae in the tissues. Since our dogs were caged to minimize contact with their own feces, we suggest that autoinfection took place in these dogs. Heavy worm burdens probably were reached because the reduced immune responses against the larva facilitated their successful penetration of the intestinal wall and their recirculation within the host.


When to Compound Medications for Veterinary Patients.
This article serves as a brief discussion about some of the restrictions applicable to compounding medications for veterinary patients based on U. S. Food and Drug Administration compliance policy guidelines and provides a brief summary of when it is appropriate to compound medications for veterinary patients.


Socioeconomic implications of pediatric cervical methicillin-resistant Staphylococcus aureus infections.
To study cervical methicillin-resistant Staphylococcus aureus (MRSA) infections using a national database with the goal of providing normative data and identifying variations in resource utilization. Retrospective review using a pediatric national data set (Kids' Inpatient Database 2009). Inclusion criteria were admissions with International Classification of Diseases, Ninth Revision, Clinical Modification, codes for both MRSA and specific neck and pharyngeal infections. There were 26,829 admissions with MRSA; 3571 included a head and neck infection. The mean (SE) age at admission was 7.72 (0.20) years. Most patients (65.0%) were in the lower 2 socioeconomic quartiles; the most common payer was Medicaid (53.3%). The mean total charge per admission was $20,442. The mean (SE) length of stay (LOS) was 4.39 (0.15) days; there were significant differences among age (P < .001) and racial (P < .001) groups. A total of 1671 children underwent at least 1 surgical drainage procedure; there were statistically significant differences among racial (P < .001), age (P < .001), and socioeconomic (P = .048) groups. There were no regional variations in resource utilization when LOS, number of procedures, and total hospital charges were compared. Cervical MRSA infections have a large socioeconomic impact across the nation. There are differences among the various races in resource utilization. Younger children have longer hospitalizations, are more likely to need surgery, and require more intubations. Children from the lowest socioeconomic group require surgery more frequently, but their LOS is not statistically different when compared with the other 3 groups. Knowledge of such characteristics for cervical MRSA infections in children can facilitate targeted clinical interventions to improve care of affected populations.


Teratogenicity of 5-azacytidine in the Sprague-Dawley rat.
5-Azacytidine (5-aza), a chemical that is incorporated into DNA and RNA with consequent alterations in the expression of mammalian genes, was administered to pregnant Sprague-Dawley rats on single days during gestation. Doses of 0.5, 1, and 2 mg/kg were given by intraperitoneal injection on d 9, 10, 11, or 12. Dams were killed on d 20 of gestation and fetuses were examined for both external and skeletal defects. 5-Azacytidine affected development on all days tested. The compound was embryolethal, caused reductions in fetal weight, and had profound effects on morphological development. Digit and limb anomalies, exencephaly, micrognathia, gastroschisis, and various rib defects were observed and related to the day of exposure.


Lack of universality in decaying magnetohydrodynamic turbulence.
Using computations of three-dimensional magnetohydrodynamic (MHD) turbulence with a Taylor-Green flow, whose inherent time-independent symmetries are implemented numerically, and in the absence of either a forcing function or an imposed uniform magnetic field, we show that three different inertial ranges for the energy spectrum may emerge for three different initial magnetic fields, the selecting parameter being the ratio of nonlinear eddy to Alfvén time. Equivalent computational grids range from 128(3) to 2048(3) points with a unit magnetic Prandtl number and a Taylor Reynolds number of up to 1500 at the peak of dissipation. We also show a convergence of our results with Reynolds number. Our study is consistent with previous findings of a variety of energy spectra in MHD turbulence by studies performed in the presence of both a forcing term with a given correlation time and a strong, uniform magnetic field. However, in contrast to the previous studies, here the ratio of characteristic time scales can only be ascribed to the intrinsic nonlinear dynamics of the paradigmatic flows under study.


Depression as a Comorbid Condition: A Descriptive Comparative Study.
Studies analyzing depressive symptoms across chronic disease populations are limited. Our descriptive comparison investigation included two studies on life-limiting conditions: Human Immunodeficiency Virus (HIV) and breast cancer. In both, depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). We found a mean depression score of 18.1 (± 11.8) overall (N = 243). Over half (54%) reported clinically significant depressive symptoms (CES-D ≥ 16); 26% reported severe depressive symptoms (CES-D > 24). Disease and years of education were predictors of depressive symptoms. Persons living with breast cancer showed significantly worse depressive symptoms than persons living with HIV (p < 0.0001). After adjusting for disease, fewer years of education predicted worse depressive symptoms (p < 0.0001). This study demonstrated common determinants of depressive symptoms in both disease populations, suggesting that underlying conditions known to be predictors of depression could be assessed to identify those at higher risk for depression.


[Studies on chemical constituents from the root of Coriaria nepalensis wall (Coriaria sinica Maxim)].
The root of Coriaria nepalensis Wall (Coriaria sinica Maxim) is a Chinese herbal medicine and has been used to treat numbness, toothache due to wind and heat, phlegm-retention syndrome, traumatic injury and acute conjunctivitis. Nine compounds were isolated from the root of Coriaria nepalensis Wall and they were identified as braylin (I), norbraylin (II), dihydrocoriamyrtin (III), coriamyrtin (IV), tutin (V), coriatin (VI), apotutin (VII), hydroxycoriatin (VIII) and gallic acid (IX) on the basis of their physicochemical properties and IR, UV, MS, 1HNMR, 13CNMR data. I, II were isolated from the title plant for the first time; III was obtained from plant origin for the first time, and VII, VIII were new compounds.


Death, democracy and public ethical choice.
The Danish Council of Ethics...believed that the brain-death criterion should not be accepted without public education and debate. Following the introduction of a spectrum of educational and related activites, a Gallup poll found that 98% of the survey population was aware of the debate over brain-vs-heart criteria and that 80% favoured the adoption of a supplemental brain-death standard... This raises the fundamental question of decisionmaking in pluralist democratic societies, of the limits of democratic involvement in such choices, and of the role of bodies like the Danish Council of Ethics... It must be part of the mission of a governmental bioethical body to use its peculiar expertise to teach and to lead -- to build a popular consensus out of confusion. But in doing so, such a Commission will be steering a dangerous course....


Cryptogenic liver disease in the United States: further evidence for non-A, non-B, and non-C hepatitis.
Since the advent of anti-hepatitis C virus (HCV)-testing, the current worldwide prevalence of cryptogenic cirrhosis is essentially unknown. 1) determine if serum HCV RNA testing by the polymerase chain reaction (PCR) enhances the diagnostic yield for HCV in patients with anti-HCV-negative cryptogenic liver disease and 2) further define the epidemiology of patients with indeterminate causes of chronic hepatitis and cirrhosis. We reviewed the records of 567 patients with chronic liver disease who were evaluated over a 3-yr period. A definite etiology for liver disease was established in all but 28 patients (4.9%). Histology was available in 20 patients. Twenty-one of the 28 patients were female (mean age, 52 yr). Thirteen patients (46%) had a history of previous blood transfusion, and one patient was a health care worker. Histology revealed CAH/cirrhosis in 17 patients, CPH in one patient, and no diagnosis in two patients. Five additional patients had clinically advanced cirrhosis. None of the 28 patients with cryptogenic chronic liver disease was HCV RNA positive by PCR. 1) Approximately 5% of patients with chronic hepatitis/cirrhosis remain cryptogenic despite the addition of HCV RNA testing. 2) PCR does not improve the diagnostic yield in this population. 3) Nearly half of the patients with presumed cryptogenic cirrhosis have been transfused, supporting the hypothesis of a non-A, non-B, and non-C hepatitis virus. 4) Screening donor blood for serum ALT may still be necessary to further reduce posttransfusion hepatitis.


[Drug resistance of enterohemorrhagic Escherichia coli O157 and a possible relation of plasmids to the drug-resistance].
Antimicrobial susceptibility was examined using 89 enterohemorrhagic Escherichia coli O157 isolates obtained from diarrhea patients in Aichi Prefecture, Japan between June 1996 and June 1997. Among the 89 isolates, 15 (16.9%) were found to be resistant to 6 of 9 antibiotics examined. These 6 antibiotics were ampicillin (ABPC), cefaloridine (CER), chloramphenicol (CP), kanamycin (KM), streptomycin (SM), and tetracycline (TC). Among the 15 drug-resistant isolates, 7 were resistant to 4 drugs (ABPC, CER, SM, TC), 3 were resistant to 3 (ABPC and 2 of CER, SM, TC), 2 were resistant to 2 (SM, TC), one each to KM or SM. Another isolate showed resistance to 5 drugs (ABPC, CP, KM, SM, TC). Selected 13 drug-sensitive and selected 12 multi-drug resistant isolates were tested for the presence of plasmids. All of the drug-sensitive isolates had 54 MDa plasmid and the majority (8/13) had 2.0 MDa plasmids, whereas; all of the drug-resistant isolates except one (1/12) had 54 MDa plasmid and the majority had 8.0 MDa (9/12) and 4.2 MDa (11/12) plasmids. The first transformation test revealed that plasmids of 8.0 MDa (3/4) and 46 MDa (1/4) were transferred to a donor cell with ABPC resistance. 54 MDa plasmid was transferred to a donor cell with both of ABPC and TC resistance. In the second transformation test, only the 8.0 MDa plasmid was confirmed to be transferred to a donor cell with ABPC resistance. Accordingly, it was indicated that the ABPC resistant gene was carried on 8.0 MDa plasmid, and it was suggested that resistant genes for ABPC and TC, and ABPC were carried on 54 MDa, and on 46 MDa plasmids, respectively.


Phenelzine as a stimulant drug antagonist: a preliminary report.
Phenelzine administration, monitored via a pharmacy-controlled program, was employed in 38 subjects over a 6-month period to prevent amphetamine-type drug abuse, in much the same manner as disulfiram programs are employed against alcohol abuse. Advantages of the program were apparent, with a majority of subjects abstaining during the enforced phenelzine trial. Subjects generally made use of this abstinent period to benefit from a variety of psychotherapeutic modes, and demonstrated enhanced job and school performance and improved marital relationships. Results based on subject and observer reports, reports from dispensing pharmacies, and random urinalyses for drugs were encouraging. However, the study was uncontrolled and observational, and thus results are merely suggestive at present. Potential dangers as well as benefits of administering phenelzine to such a population are discussed.


Glia activation of eukaryotic translation initiation factor 4e-binding protein 1 in temporal lobe epilepsy.
This study was aimed to investigate whether 4e-binding protein 1 is activated during temporal lobe epileptogenesis. We used the hippocampus of patients with refractory temporal lobe epilepsy (TLE), diagnosed with hippocampal sclerosis (HS) or non-HS, to examine the distribution of phospho-4e-binding protein 1 (p4EBP1) by immunohistochemical staining (n=3-5). We also examined p4EBP1 in the kainic acid (KA)-induced mouse model of TLE before and after anticonvulsant treatment (n=3 per group). The results showed that the hippocampus of both patients with HS and KA mouse model displayed significantly upregulated p4EBP1 immunoreactivity in glial fibrillary acidic protein-positive astrocytes in hippocampus. Quantitative results showed that there is a 5.9-fold upregulation in the number of p4EBP1+glia-like cells in TLE group than control group (P<0.05). However, treatment with lamotrigine failed to suppress spontaneous seizures and did not affect the astrocytic distribution of p4EBP1 (P=0.73). Taken together, we investigated the spatiotemporal expression of p4EBP1 in the sclerotic hippocampus of both patients and a KA-induced mouse model and found glia activation of 4e-binding protein 1 in TLE. Our findings suggest that the upregulation of p4EBP1 in astrocytes may play a critical role in the pathogenesis of TLE.


[Determination of glyoxalate and oxalate by capillary zone electrophoresis].
A method for the simultaneous determination of glyoxalate and oxalate by capillary zone electrophoresis (CZE) was developed. The influences of type, concentration and pH of the running buffer, and the applied voltage on separation were investigated. Glyoxalate and oxalate were separated within 11 min under the conditions of 20 mmol/L borax-5.5 mmol/L potassium hydrogen phthalate (pH 9.0), applied voltage of 20 kV, and detected wavelength of 212 nm. The calibration curves of glyoxalate and oxalate showed good linearity in the ranges of 0.8 -20 g/L and 1.2-20 g/L, respectively. The correlation coefficients were 0.999 3 and 0.997 5, respectively. The limits of detection for glyoxalate and oxalate were 0.2 and 0.4 g/L (S/N = 3), respectively. The average recoveries at three spiked levels were 98.3%-102.5% with acceptable relative standard deviations of 0.35%-0.61%. This method is simple, low cost and high performance. The method was successfully used for the determination of glyoxalate and oxalate in real samples, and the assay results were satisfactory.


Two distinct classes of degenerative change are independently linked to clinical progression in mild cognitive impairment.
We previously demonstrated 2 statistically distinct factors of degeneration in Alzheimer's disease: one strongly related to white matter damage and age interpreted as "age- and vascular-related", and the other related to cortical atrophy thought to represent "neurodegenerative changes associated with Alzheimer's disease". Those factors are now replicated in a distinct cross-sectional data set of 364 participants from the Alzheimer's Disease Neuroimaging Initiative and their interpretation is improved using correlations with CSF biomarkers. Furthermore, we now show that changes in both factors over 2 years are independently associated with decline in Mini-Mental State Examination score in a longitudinal subset of 116 individuals with mild cognitive impairment. Progression in the "age- and vascular-related" factor was greater for individuals with 2 APOE ε4 alleles and linked to a greater attributable change in Mini-Mental State Examination than the "neurodegenerative" factor. These results suggest benefits of targeting white matter and vascular health to complement interventions focused on the neurodegenerative aspect of the disease, even in individuals with little discernable vascular comorbidity.


The Negative Effects of Feces-Associated Microorganisms on the Fitness of the Stored Product Mite Tyrophagus putrescentiae.
Feces have been suggested as a major source of microorganisms for recolonization of the gut of stored product mites via coprophagy. The mites can host microorganisms that decrease their fitness, but their transmission is not known. To address the role of fecal microbiota on mite fitness, we performed an experimental study in which the surfaces of mite (Tyrophagus putrescentiae) eggs were sterilized. Mites eggs (15 per experimental box) were then hatched and grown on feedstock with and without feces. These experiments were conducted with four distinct T. putrescentiae populations (5L, 5K, 5N, and 5P), and mite population density after 21 day of cultivation was used to assess mite fitness and the impact of fecal microbiota on fitness. Population density was not affected by the presence of feces in two of the cultures (5L and 5K), while significant effects of feces were observed in the other cultures (5N and 5P). Mite culture microbial communities were analyzed using cultivation-independent next-generation amplicon sequencing of microbial 16S and 18S ribosomal RNA (rRNA) genes in the fitness influenced populations (5N and 5P). Several microbial taxa were associated with fecal treatments and reduced mite fitness, including Staphylococcus and Bartonella-like bacteria, and the fungal genera Yamadazyma, Candida, and Aspergillus. Although coprophagy is the transmission route mites used to obtain beneficial gut bacteria such as Bartonella-like organisms, the results of this study demonstrate that fecal-associated microorganisms can have negative effects on some populations of T. putrescentiae fitness, and this may counteract the positive effects of gut symbiont acquisition.


Analysis of Suicide Notes: An experience in Eskişehir City.
It is estimated that a million people around the world die by suicide each year. It has been reported that a note was left in 5%-43% of the suicides. In this study, it we aimed to evaluate and discuss suicide notes in our city which is situated in Western Anatolia and where several universities are located. All forensic deaths in Eskişehir in 10-year period between 2001 and 2011 were evaluated. Forensic investigation files were assessed. After investigation, Out of 399 cases, 168 (42.1%) cases, who were determined to have left a suicide letter, telephone message (sms) or message via social network sites, were included in the scope of the study. It was found that 95 (56.5%) of all cases had left a suicide letter, 69 (41.1%) cases had sent a telephone message to a person or more than one person, 4 (2.4%) cases had written notes about suicide and death in social networking sites. A suicide note is an important finding in suicide cases to clarify the case. However, the note should be confirmed by investigation to be accepted as evidence.


Gastric heterotopia of the anus: report of two rare cases and review of the literature.
Heterotopic gastric mucosa is an extremely rare occurrence in the anorectal region, with 41 reported cases till date. Of these, in only nine cases the heterotopic tissue has been found to be located within 2 cm of the dentate line. We report two cases of gastric heterotopia in the anus - one, in a 55-year-old man; and the other, in a 35-year-old woman. Sigmoidoscopy showed presence of a single sessile anal polyp in the first patient and hemorrhoid in the other. Pathologic examination of the biopsy specimens revealed fundic-type gastric mucosa in both the cases. Both the patients had complete resolution of symptoms after the excision. We present these cases to highlight the significance of recognizing this unusual histologic entity. To the best of our knowledge, the second case represents the first reported description of gastric heterotopia in association with hemorrhoid.


A Case of Anti-Ma2 Encephalitis Presenting with Pendular Torsional Nystagmus.
Antibodies against the neuronal protein Ma2 have been reported in a peculiar form of paraneoplastic encephalitis with prominent involvement of the limbic, brainstem, and diencephalic structures and usually associated with germ cell testicular, lung, or breast cancer. The diagnosis is frequently challenged by atypical clinical manifestations including parkinsonism, sleep disturbances, hypothalamic-pituitary dysfunctions, and motor neuron-like syndrome. In recent years, the advent of monoclonal antibodies targeting immune checkpoints has deeply changed the treatment of different tumors, especially melanoma and lung cancer. However, given their nature, an increasing number of neurological immune-related adverse events, including ocular motor abnormalities, have been described. Here, we report a woman with advanced non-small cell lung cancer treated with anti-PD-L1 durvalumab, presenting with an isolated pendular torsional nystagmus, in association with anti-Ma2 antibodies. This peculiar case widens our knowledge on the clinical presentation of anti-Ma2 encephalitis associated with checkpoint inhibitors.


Controversies in iron management.
Iron therapy is required in hemodialysis patients receiving erythropoietic stimulators in order to achieve the target hemoglobin in the most efficient way. While oral iron has been disappointing in this regard, parenteral iron has been widely used, despite a significant incidence of severe side effects when iron dextran is used. The recent availability of a more effective form of oral iron (heme-iron), and safer forms of parenteral iron (iron sucrose and iron gluconate) has made iron management in this population simpler. Many questions remain, however, about the use, efficacy, and safety of these compounds in hemodialysis patients. Current literature was reviewed and combined with the authors' clinical experience to address a number of current questions regarding the use of iron in hemodialysis patients. Although oral non-heme iron is infrequently sufficient to maintain iron stores in hemodialysis patients, recent studies suggest that heme-iron may be more useful in this regard. Heme-iron is absorbed to a greater extent than non-heme iron, and is better tolerated. Small studies have shown that when heme-iron is administered, less parenteral iron and lower doses of erythropoietin (EPO) are needed to maintain target hemoglobin. Current evidence suggests that both iron sucrose and iron gluconate are safer than iron dextran, and the latter should only be used in extraordinary circumstances. While in vitro studies have demonstrated some differences in the effects of iron sucrose and iron gluconate on cellular toxicity, the clinical importance of these has not been determined. Both compounds can be used safely for repletion and maintenance therapy, and doses of up to 300 mg of either are generally well tolerated when such higher doses are needed, as in peritoneal dialysis (PD) patients or chronic kidney disease (CKD) patients not on dialysis. A number of questions remain regarding the appropriate use, efficacy, and potential toxicity of iron therapy in dialysis patients. Further prospective research should address the myriad questions raised in this review.


Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles.
Functional interaction between neurons and glia is an exciting field that has expanded tremendously during the past decade. Such partnership has multiple impacts on neuronal activity and survival. Indeed, numerous findings indicate that glial cells interact tightly with neurons in physiological as well as pathological situations. One typical feature of glial cells is their high expression level of gap junction protein subunits, named connexins (Cxs), thus the membrane channels they form may contribute to neuroglial interaction that impacts neuronal activity and survival. While the participation of gap junction channels in neuroglial interactions has been regularly reviewed in the past, the other channel function of Cxs, i.e., hemichannels located at the cell surface, has only recently received attention. Gap junction channels provide the basis for a unique direct cell-to-cell communication, whereas Cx hemichannels allow the exchange of ions and signaling molecules between the cytoplasm and the extracellular medium, thus supporting autocrine and paracrine communication through a process referred to as "gliotransmission," as well as uptake and release of metabolites. More recently, another family of proteins, termed pannexins (Panxs), has been identified. These proteins share similar membrane topology but no sequence homology with Cxs. They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels. Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs) in glia. In the present review, we update and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglial interactions in brain health and disease.


Risk Factors for Loss to Follow-Up in the Lower Extremity Limb Salvage Population.
Limb salvage for chronic lower extremity wounds requires long-term care best delivered by specialized multidisciplinary centers. This optimizes function, reduces amputation rates, and improves mortality. These centers may be limited to urban/academic settings, making access and appropriate follow-up challenging. Therefore, the authors hypothesize that both system- and patient-related factors put this population at exceedingly high risk for loss to follow-up. Records were reviewed retrospectively for 200 new patients seen at the Georgetown Center for Wound Healing in 2013. The primary outcome was loss to follow-up, defined as three consecutive missed appointments despite explicit documentation indicating the need for return visits. Demographic, clinical, and geographic data were compared. Multivariate logistic regression analysis for loss to follow-up status controlled for variables found significant in the bivariate analysis. Spatial dependency was evaluated using variograms. Over a 6.5-year-period, 49.5 percent of patients followed were lost to follow-up. Male sex and increased driving distance to the limb salvage center were risk factors for loss to follow-up. Wound-specific characteristics including ankle and knee/thigh location were also associated with higher rates of loss to follow-up. There was no spatial dependency or discrete clustering of at-risk patients. This study is the first of its kind to investigate the demographic and clinical characteristics that predispose chronic lower extremity wound patients to loss to follow-up. These findings inform stakeholders of the high rates of loss to follow-up and support decentralized specialty care, in the form of telemedicine, satellite facilities, and/or dedicated case managers. Future work will focus on targeting vulnerable populations through focused interventions to reduce patient and system burden. Risk, III.


Cholecystectomy among Patients Admitted to the Department of Surgery in a Tertiary Care Centre: A Descriptive Cross-sectional Study.
Cholecystectomy refers to the surgical removal of the gallbladder. It is indicated in acute cholecystitis, and other complications of gallstones like cholecystitis, pancreatitis and bile duct obstruction, the presence of gallbladder trauma, and gallbladder cancer. The aim of this study was to find out the prevalence of cholecystectomy among patients admitted to the Department of Surgery in a tertiary care centre. A descriptive cross-sectional study was conducted among patients admitted to the Department of Surgery of a tertiary care centre. Data from 1 July 2021 to 1 July 2022 were collected between 10 February 2023 to 20 February 2023 from the hospital records. Ethical approval was taken from the Institutional Review Committee of the same institute (Reference number: 630/2079/80). Convenience sampling method was used. Documents and medical records of the cholecystectomy patients were assessed for personal data, medical history was extracted and analysed using Microsoft Excel 2016. Point estimate and 95% Confidence Interval were calculated. Among 2452 patients admitted to the Department of Surgery, 894 (36.46%) (34.46-38.26, 95% Confidence Interval) underwent cholecystectomy. The prevalence of cholecystectomy in our study was found to be similar to other studies done in similar settings. cholecystectomy; cholelithiasis; Nepal; prevalence.


Musculoskeletal symptoms of the upper extremities and the neck: a cross-sectional study on prevalence and symptom-predicting factors at visual display terminal (VDT) workstations.
The aim of this study was to determine the prevalence and the predictors of musculoskeletal symptoms in the upper extremities and neck at visual display terminal (VDT) workstations. In a cross-sectional study 1,065 employees working at VDT > 1 h/d completed a standardised questionnaire. Workstation conditions were documented in a standardised checklist, and a subgroup of 82 employees underwent a physical examination. Using the Nordic Questionnaire, the 12-month prevalence of symptoms of the neck, shoulder region, hand/wrist, or elbow/lower arm was 55%, 38%, 21%, and 15% respectively. The duration of VDT work had a significant impact on the frequency of neck symptoms in employees performing such work > 6 h/d. With regard to musculoskeletal symptoms of the upper extremities, preventive measures at VDT workstations should be focused on neck and shoulder symptoms (e.g. ergonomic measures, breaks to avoid sitting over long periods).


Perceptual span in schizophrenia and affective disorders.
Perceptual span was assessed in schizophrenic, bipolar affective disorder-manic, bipolar affective disorder-depressed, and nonpsychotic inpatients. Both schizophrenics and manics processed less information than depressives, and did not differ from each other. This suggests that reduced span may be a concomitant of psychoses characterized by distractibility and thought disorder, rather than a trait specific to schizophrenia.


Effect of Fenton process as a pretreatment in the phytoremediation of metronidazole by Scirpus lacustris.
The present study evaluated the effect of the Fenton process as pretreatment for metronidazole (MNZ) removal coupled with a phytoremediation system using Scirpus lacustris as macrophyte. Initial concentrations of 0.5, 5, 10, 15, and 20 mg MNZ/L were studied in batch cultures. Results obtained in the MNZ removal by phytoremediation showed efficiencies of 93 ± 2%, 81 ± 4%, 85 ± 1%, 84 ± 2%, and 87 ± 6%, respectively. The metronidazole pretreated by the Fenton process and subsequently fed to the phytoremediation system increased the removal efficiencies up to 93 ± 3%, 99 ± 1%, 99 ± 4%, 94 ± 2%, and 94 ± 3%, respectively. Individual studies with Scirpus lacustris in touch with metronidazole displayed relative growth rates of 0.02-0.04 d-1, showing the not toxic effect of the antibiotic on the macrophyte growth. On the other hand, the BMG kinetic model best describes the removal of MNZ by phytoremediation. Finally, applying the Fenton process as a pretreatment makes the MNZ more assimilable for the phytoremediation system, converting the integration of Fenton with the phytoremediation like other attractive technology to be considered in removing emerging compounds.


[Cardiopulmonary diversion in minimally invasive heart surgery].
Cardiac surgery has evolved greatly in the last pears. New techniques for the treatment of cardiac patients, such as minimally invasive heart surgery, off-pump coronary surgery, limited or port access surgery, video-assisted and robotic cardiac surgery have been developed. Technology provides new instruments, such as heart stabilizers for off-pump coronary surgery, ventricular support devices or direct coronary bypass perfusion systems, all of them with the main goal of maintaining the patient's hemodynamics. Minimally invasive heart surgery contributes to a faster recovery and less suffering, and decreases costs. The perfusionist is involved in all these new techniques, the future is a challenge, he she must learn to use all these new devices without forgetting the human sede of his her specialty.


Probing the hexosamine biosynthetic pathway in human tumor cells by multitargeted tandem mass spectrometry.
Cancer progression is accompanied by increases in glucose and glutamine metabolism, providing the carbon and nitrogen required in downstream anabolic pathways. Fructose-6P, glutamine, and acetyl-CoA are central metabolites and substrates of the hexosamine biosynthesis pathway (HBP) to UDP-N-acetylglucosamine (UDP-GlcNAc), an essential high-energy donor for protein glycosylation. Golgi and cytosolic glycosylation pathways are sensitive to UDP-GlcNAc levels, which in turn regulates metabolic homeostasis in a poorly understood manner. To study the hexosamine biosynthesis pathway in cancer cells, we developed a targeted approach for cellular metabolomics profiling by liquid chromatography-tandem mass spectrometry. Human cervical (HeLa) and prostate cancer (PC-3) cell lines were cultured in medium with increasing concentrations of glucose, glutamine, or GlcNAc to perturb the metabolic network. Principal component analysis indicated trends that were further analyzed as individual metabolites and pathways. HeLa cell metabolism was predominantly glycolytic, while PC-3 cells showed a greater dependency on extracellular glutamine. In both cell lines, UDP-GlcNAc levels declined with glucose but not glutamine starvation, whereas glutamine abundance increased UDP-GlcNAc levels 2-3-fold. GlcNAc supplementation increased UDP-GlcNAc 4-8-fold in both HeLa and PC-3 cells. GlcNAc supplementation in HeLa cells induced nonmonotonic changes in NADH/NAD+, NADPH/NADP+, reactive oxygen species, and reduced/oxidized glutathione. In PC-3 cells, GlcNAc supplementation also increased glucose and glutamine uptake and catabolism. Our results suggest that stimulation of the HBP in cancer cells regulates metabolism and redox potential, which might be exploited to target cancer cells.


Soluble CD22 as a tumor marker for hairy cell leukemia.
CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22(+)/CD25(-) disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.


Importance of airborne contamination during dressing of beef and lamb carcasses.
Carcasses along slaughter lines were exposed to normal slaughterhouse air or ultraclean air provided from a unit fitted with a HEPA filter. In cattle slaughterhouses, aerobic viable counts were measured by sponging the brisket at the end of the line to determine whether the slaughterhouse air had led to contamination of the carcasses. Furthermore, a replica cattle carcass with settle plates attached was exposed to similar conditions. The greatest contamination of the plates occurred at the hide puller (P < 0.01). The use of ultraclean air reduced the deposition of organisms onto settle plates (P < 0.01). The airborne route contributed to contamination in cattle slaughterhouses, but other vectors were more important. Further study of contamination of the brisket, at the time that it was first exposed, showed that knives transfer contamination from the hide. The use of ultraclean air at this position showed that the airborne route was a contributor to contamination (P < 0.1), but it was not the greatest vector. In lamb slaughterhouses, the highest counts on settle plates were found at the fleece puller (P < 0.05). The highest counts on the lamb carcasses were found on the brisket exposed from the start of the line to just after the fleece puller (P < 0.05). There was no clear relationship between the measured counts and the concentration of organisms in the air, indicating that the airborne route in lamb slaughterhouses contributes less to carcass contamination than do the surface contacts.


Thermal stability of trimeric light-harvesting chlorophyll a/b complex (LHCIIb) in liposomes of thylakoid lipids.
The major light-harvesting chlorophyll a/b complex (LHCIIb) of photosystem (PS) II functions by harvesting light energy and by limiting and balancing the energy flow directed towards the PSI and PSII reaction centers. The complex is predominantly trimeric; however, the monomeric form may play a role in one or several of the regulatory functions of LHCIIb. In this work the dissociation temperature was measured of trimeric LHCIIb isolated from Pisum thylakoids and inserted into liposomes made of various combinations of thylakoid lipids at various protein densities. Dissociation was measured by monitoring a trimer-specific circular dichroism signal in the visible range. The LHCIIb density in the membrane significantly affected the trimer dissociation temperature ranging from 70 degrees C at an LHCIIb concentration comparable to or higher than the one in thylakoid grana, to 65 degrees C at the density estimated in stromal lamellae. Omitting one thylakoid lipid from the liposomes had virtually no effect on the thermal trimer stability in most cases except when digalactosyl diacylglycerol (DGDG) was omitted which caused a drop in the apparent dissociation temperature by 2 degrees C. In liposomes containing only one lipid species, DGDG and, even more so, monogalactosyl diacylglycerol (MGDG) increased the thermal stability of LHCIIb trimers whereas phosphatidyl diacylglycerol (PG) significantly decreased it. The lateral pressure exerted by the non-bilayer lipid MGDG did not significantly influence LHCII trimer stability.


Facile provision of CuO-Kaolin nanocomposite for boosted sonocatalytic removal of Cr(VI) from hydrous media.
Nowadays, nanoscale materials have been widely applied in the removal of contaminants from the water system. Reduction of Cr(VI) (as a poisonous species) to Cr(III) (as a slight toxic species) was performed using CuO-Kaolin with ultrasound (US) irradiation. The CuO-Kaolin nanocomposite was synthesized via a facile co-precipitation method. Then X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscope and Energy dispersive X-ray spectroscopy analyses were performed to identify the structural features of CuO-Kaolin. The role of influential parameters for the reduction of Cr(VI) was investigated in sonocatalytic advanced oxidation system. About 89.35% of Cr(VI) was removed via US/CuO-Kaolin process after 90 min at optimum conditions (pH = 3, sonocatalyst dosage = 1 g L-1 and [Cr (VI)]0 = 20 mg L-1). This outstanding result was due to the synergistic effect of the increased electron delivery to conduction band on CuO-Kaolin nanocomposite and the increased reactive surface region of nanoparticles by sonication. The presence of H2O2 as an amplifier improved the removal efficiency of Cr(VI) from 89.35% to 100% after 20 min. Kinetic experimental results were well described by a pseudo-first-order kinetic model. Desorption experiments showed excellent stability of sonocatalyst during the reaction and maintenance of the catalytic activity up to 10 sequential cycles.


RFE-UNet: Remote Feature Exploration with Local Learning for Medical Image Segmentation.
Although convolutional neural networks (CNNs) have produced great achievements in various fields, many scholars are still exploring better network models, since CNNs have an inherent limitation-that is, the remote modeling ability of convolutional kernels is limited. On the contrary, the transformer has been applied by many scholars to the field of vision, and although it has a strong global modeling capability, its close-range modeling capability is mediocre. While the foreground information to be segmented in medical images is usually clustered in a small interval in the image, the distance between different categories of foreground information is uncertain. Therefore, in order to obtain a perfect medical segmentation prediction graph, the network should not only have a strong learning ability for local details, but also have a certain distance modeling ability. To solve these problems, a remote feature exploration (RFE) module is proposed in this paper. The most important feature of this module is that remote elements can be used to assist in the generation of local features. In addition, in order to better verify the feasibility of the innovation in this paper, a new multi-organ segmentation dataset (MOD) was manually created. While both the MOD and Synapse datasets label eight categories of organs, there are some images in the Synapse dataset that label only a few categories of organs. The proposed method achieved 79.77% and 75.12% DSC on the Synapse and MOD datasets, respectively. Meanwhile, the HD95 (mm) scores were 21.75 on Synapse and 7.43 on the MOD dataset.


TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway.
Hypertrophy of the ligamentum flavum (LF) is one of the key pathomechanisms of lumbar spinal stenosis (LSS). Transforming growth factor (TGF)-β1 is abundantly expressed in hypertrophied degenerative LF tissues from LSS. However, the molecular mechanisms underling the association between TGF-β1 and LF hypertrophy have not yet been fully elucidated. In this study, we investigated the important role of the mitogen-activated protein kinase (MAPK) pathway in the pathogenesis of LSS by analyzing the expression of connective tissue growth factor (CTGF) and extracellular matrix (ECM) components (collagen I and collagen III) in TGF-β1-treated LF cells. Cell growth assay revealed that TGF-β1, in association with CTGF, enhanced the the proliferation of LF cells, and we found that TGF-β1 also elevated CTGF expression and subsequently enhanced the mRNA expression of collagen I and collagen III. The increased mRNA expression levels of CTGF, collagen I and collagen III were abolished by p38 inhibitors. Both immunofluorescence imaging and western blot analysis of p38 and p-p38 revealed the increased expression and phosphorylation of p38. Silencing the expression of p38 by siRNA in LF cells decreased the protein expression of p38, p-p38 and CTGF, as well as the mRNA expression of CTGF, collagen I and collagen III. Taken together, our findings indicate that TGF-β1, in association with the increased expression of CTGF, contribute to the homeostasis of the ECM and to the hypertrophy of LF through the p38 MAPK pathway.