Evaluation of the effects of histone deacetylase inhibitors on cells from canine cancer cell lines.
To determine whether exposure of canine cancer cells to histone deacetylase (HDAC) inhibitors S(+)-N-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)benzamide (OSU-HDAC42) or suberoylanilide hydroxamic acid (SAHA) results in increased histone acetylation and decreased cell viability and whether any changes in viability involve induction of apoptosis or alterations in progression of the cell cycle. 9 canine cancer cell lines. Cells from 9 canine cancer cell lines were treated with dimethyl sulfoxide vehicle, OSU-HDAC42, or SAHA, then assays of cell viability were performed. Histone acetylation was assessed by use of western blot analysis. Apoptosis was assessed via ELISA to detect fragmentation of cytoplasmic nucleosomal DNA and western blot analysis to detect cleavage of caspase 3. Cell cycle analysis was performed by use of propidium iodide staining and flow cytometry. RESULTS-Concentrations of OSU-HDAC42 and SAHA required to achieve 50% inhibition of cell viability (IC(50)) were reached in cells of 6 and 4 canine cancer cell lines, respectively, and ranged from approximately 0.4 to 1.3 microM for OSU-HDAC42 and 0.6 to 4.8 microM for SAHA. Cells from T-cell lymphoma, mast cell tumor, osteosarcoma, and histiocytic sarcoma lines were most sensitive to HDAC inhibition, with IC(50)s of < 1 microM for OSU-HDAC42 and < 5 microM for SAHA. Induction of apoptosis was indicated via cleavage of caspase 3 and increases in cytoplasmic nucleosomes and the subG(1) cell population. Micromolar concentrations of HDAC inhibitors OSU-HDAC42 and SAHA induced histone acetylation, cytotoxicity, and apoptosis in canine cancer cells. In general, OSU-HDAC42 was more potent than SAHA.


Anemia: determining the cause.
Anemia is a common finding in small animal practice; however, the multitude of potential causes can make determining the underlying diagnosis a challenging and frustrating endeavor. With a basic understanding of red blood cell production and a systematic diagnostic approach, clinicians should be able to clearly define the cause of anemia in most cases.


Efficacy of Transcutaneous Electrical Nerve Stimulation and Interferential Current on Tactile Acuity of Individuals With Nonspecific Chronic Low Back Pain.
Transcutaneous electrical nerve stimulation (TENS) and interferential currents (IFC) are pain electrotherapies with questioned efficacy. Studies of their effects on tactile acuity of individuals with nonspecific chronic low back pain (NSCLBP) are limited, hence, this study. Thirty-three individuals with NSCLBP randomly allocated into three groups completed this study. Data collected from participants included age, gender, and anthropometric characteristics of height, weight, body mass index, and percentage body fat measured with standard instruments. Also, participants' tactile acuity, pain intensity, and disability were assessed before and after interventions with digital caliper, numerical pain rating scale, and Roland-Morris Disability Questionnaire, respectively. Interventions consisted of stretching, strengthening, and stabilization exercises to all three groups in addition of TENS to group 1 and IFC to group 2, respectively, for five weeks. Descriptive statistics of mean and standard deviation summarized the data. Inferential statistics of paired t-test, independent t-test, and analysis of variance tested the level of significance among variables at p ≤ 0.05. Tactile acuity was significantly (p < 0.05) increased after TENS intervention only, while pain intensity was significantly (p < 0.05) reduced after the three interventions. The result showed no gender difference in tactile acuity values among the participants. TENS increases the tactile acuity of individuals with NSCLBP, whereas IFC demonstrated no significant change in tactile acuity.


A preliminary study of the changes in the direct-acting mutagenicities of several nitropolycyclic aromatic hydrocarbons after exposure under sunlight.
Five commercially available nitropolyclyclic aromatic hydrocarbons (nitro-PAH), namely, 4-nitrobiphenyl, 2-nitrofluorene, 9-nitroanthracene, 1-nitropyrene, and 2,7-dinitrofluorene, were exposed under restricted sunlight in the open air. The direct-acting mutagenicities of the samples after an exposure of 45 days were measured in order to compare them with those of the original samples in the Ames Salmonella typhimurium bioassay. It was found that the mutagenicities of some nitro-PAH do not change significantly while the mutagenicities of others increase or decrease after exposure. A preliminary study of nitro-PAH reaction products after exposure using GC, GC/MS, and FT-IR is also reported.


Zero temperature phase diagram of the square-shoulder system.
Particles that interact via a square-shoulder potential, consisting of an impenetrable hard core with an adjacent, repulsive, steplike corona, are able to self-organize in a surprisingly rich variety of rather unconventional ordered, three-dimensional structures. Using optimization strategies that are based on ideas of genetic algorithms, we encounter, as we systematically increase the pressure, the following archetypes of aggregates: low-symmetry cluster and columnar phases, followed by lamellar particle arrangements, until at high pressure values compact, high-symmetry lattices emerge. These structures are characterized in the isobaric-isothermal ensemble as configurations of minimum Gibbs free energy. Based on simple considerations, i.e., basically minimizing the number of overlapping coronas while maximizing at the same time the density, the sequence of emerging structures can easily be understood. In contrast to a previous contribution [G. J. Pauschenwein and G. Kahl, Soft Matter 4, 1396 (2008)], we present here a systematic investigation of this phenomenon, considering a short, an intermediate, and a large shoulder width.


[The detection of antibodies to HCV F protein with immune enzyme analysis using synthetic peptide.]
Alternative reading frame encoding a single protein known as protein F or core + 1 / ARFP is located in the core region of the hepatitis C virus (HCV) genome. The presence of antibodies to the F protein of HCV in the serum of patients with chronic hepatitis C indicates the expression of this protein in vivo. In this study, to determine antibodies to the F protein of HCV in serum samples the methodology of the enzyme immunoassay (ELISA) was developed using the synthetic peptide F10 corresponding to the antigenic determinant of the F protein of the HCV subtype 1b. The immunogenicity and immunochemical specificity of synthetic F10 peptide has been demonstrated in laboratory animals (mice).


Genetic effects of chronic treatment with cathinone in mice.
The mutagenicity of (-)-cathinone has been evaluated in the germ cells of male albino mice using a dominant lethal test. An aqueous solution of cathinone was administered orally at doses of 5, 20 or 40 mg/kg body wt, respectively to three different groups of male mice for a period of six weeks. After treatment, each male was allowed to mate with two different groups of three females each, on two consecutive weeks. These females were necropsied on the 17th day after mating. The number of implants in each female and the ratio of live and dead embryos was determined. The results of this study showed that treatment of male mice over a period of 6 weeks produced a dose-dependent reduction in fertility with total sterility at a dose of 40 mg/kg body wt. Cathinone also induced dose-dependent post-implantation loss during the first week following treatment. However, no dominant lethality was detected during the second week of mating.


Seroepidemiologic studies on Babesia caballi and Babesia equi infections in Japan.
Antibodies to Babesia caballi and Babesia equi were examined on a total of 2,019 horse serum samples that had been collected in 1971-1973 by the National Institute of Animal Health by enzyme-linked immunosorbent assay (ELISA) using recombinant proteins and by Western-blot analysis. Based on the criterion for positivity by ELISA, 5.4% (109/2,019) and 2.2% (44/2,019) had antibodies against B. caballi and B. equi, respectively. The ELISA-positive sera were further examined by Western blot; 30/109 for B. caballi and 2/ 44 for B. equi were positive for native B. caballi or B. equi, but none of them was seropositive for both infections. Based on the results of this study, further investigations should be required to survey horses that have arrived in Japan relatively recently and tick vectors of equine Babesia using ELISA with some recombinant protein, a parasite detection method in an in vitro culture of equine Babesia, and PCR testing.


Are Uric Acid Levels Different from Healthy Subjects in Bipolar Affective Disorder and Schizophrenia?: Relationship Between Clinical Improvement and Episode Severity in Male Patients.
Purinergic system dysfunction has been shown both in patients with bipolar disorder (BD) and those with schizophrenia. The aim of this study was to evaluate whether uric acid levels in male BD patients with manic episode and schizophrenia patients with psychotic relapse differ from healthy male subjects. Secondly to assess whether uric acid levels in both patient groups correlate with episode severity and if a decrease in uric acid levels correlate with clinical improvement. A total of 55 BD patients with manic episode and 59 schizophrenic patients with psychotic relapse were evaluated at baseline and at weeks 1, 2, 3 using the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS), and their plasma uric acid levels were measured. 60 age-matched healthy males without history of any previous or current psychiatric diagnosis and treatment constituted the control group. In order to determine plasma uric acid levels, blood samples were centrifuged at 3000 × g for 15 minutes, stored at -80°C and measured in milligrams per deciliter. Uric acid levels in both patient groups with manic episode and psychotic relapse were found higher than in healthy controls (f=6.122, p=.027). The difference between repeated measurements of uric acid levels in BD patient group was found to be between baseline and first week measurements (after Bonferroni correction) (p<.001). No correlation was found between YMRS and PANSS scores and uric acid levels at 4 assessment times. Uric acid levels in male BD and schizophrenia patients with manic episode and psychotic relapse were similar with each other, and higher than in healthy males. No correlation was found between uric acid levels and episode severity in both groups. However, for patients with BD, a decrease in uric acid levels between baseline and first week seems to be correlated with clinical improvement.


Lectin-like effect of Echis coloratus Venom on human and mouse lymphocytes.
Echis coloratus venom (ECV) treated human and mouse lymphocytes were examined for synthesizing activities and morphologic alterations. RNA, DNA and protein synthesis were markedly inhibited. Human cells were less affected than mouse lymphocytes. No mitogenic activity was observed. Transmission (TEM) and scanning electron microscopy (SEM) revealed membranal damage in all types of lymphocytes and a considerable degree of agglutination. Human lymphocytes showed concentration of the microvilli at one pole of the cell. This phenomenon was considered as a capping effect. The action of ECV may be compared with the effect of the nonmitogenic lectin RCAII, known to penetrate the cells by endocytosis and to inhibit their protein synthesis.


Immune activation decreases sperm viability in both sexes and influences female sperm storage.
All animals are under the constant threat of pathogenic infection. However, little is known regarding the influence of acute infection on sperm viability, particularly in female insects. This information is crucial for our understanding of mating and immune system coevolution, considering that females store sperm and serve as the site of sperm competition. Using the fruitfly, Drosophila melanogaster, we examined the influence of infection on sperm viability and storage. Twenty-four hours after haemocoel inoculation with a pathogen mimic (peptidoglycan, PGN) both sexes exhibited reduced sperm viability, indicating that systemic immune activation played a significant role in gamete survival. Surprisingly, sperm death did not appear to result from a reproductive-immune system trade-off, considering that sperm survived 24 h in vitro once removed from their somatic resources. Instead, our results are most consistent with death owing to immune effector collateral damage. We also examined the potential for sexually transmitted pathogens to influence sperm storage. Females mated with 'infected' males (created by dipping genitalia into a PGN solution) exhibited a higher proportion of empty sperm stores 48 h after mating compared to their controls. Remarkably, these data indicate that females may increase their fitness by removing 'infected' ejaculates from storage over time.


Effects of Chitosan and Cellulose Derivatives on Sodium Carboxymethyl Cellulose-Based Films: A Study of Rheological Properties of Film-Forming Solutions.
Bio-based packaging materials and efficient drug delivery systems have garnered attention in recent years. Among the soluble cellulose derivatives, carboxymethyl cellulose (CMC) stands out as a promising candidate due to its biocompatibility, biodegradability, and wide resources. However, CMC-based films have limited mechanical properties, which hinders their widespread application. This paper aims to address this issue by exploring the molecular interactions between CMC and various additives with different molecular structures, using the rheological method. The additives include O-carboxymethylated chitosan (O-CMCh), N-2-hydroxypropyl-3-trimethylammonium-O-carboxymethyl chitosan (HTCMCh), hydroxypropyltrimethyl ammonium chloride chitosan (HACC), cellulose nanocrystals (CNC), and cellulose nanofibers (CNF). By investigating the rheological properties of film-forming solutions, we aimed to elucidate the influencing mechanisms of the additives on CMC-based films at the molecular level. Various factors affecting rheological properties, such as molecular structure, additive concentration, and temperature, were examined. The results revealed that the interactions between CMC and the additives were dependent on the charge of the additives. Electrostatic interactions were observed for HACC and HTCMCh, while O-CMCh, CNC, and CNF primarily interacted through hydrogen bonds. Based on these rheological properties, several systems were selected to prepare the films, which exhibited excellent transparency, wettability, mechanical properties, biodegradability, and absence of cytotoxicity. The desirable characteristics of these selected films demonstrated the strong biocompatibility between CMC and chitosan and cellulose derivatives. This study offers insights into the preparation of CMC-based food packaging materials with specific properties.


Carotid artery intima-media thickness and cognition in cardiovascular disease.
Increased carotid artery intima-media thickness (IMT) is a non-invasive marker of systemic arterial disease. Increased IMT has been associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. Given evidence of a relationship between cardiovascular health and attention-executive-psychomotor functioning, the purpose of this study was to examine IMT in relation to neuropsychological test performance in patients with a variety of cardiovascular diagnoses. One hundred and nine participants, ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of the left common carotid artery. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and measures of language, memory, visual-spatial abilities and attention-executive-psychomotor functioning was modeled using hierarchical linear regression analyses adjusted for age, education, sex, cardiovascular risk, current systolic blood pressure, and history of coronary artery disease (CAD). Increased IMT was associated with significantly lower performance in the attention-executive-psychomotor domain (IMT beta=-0.26, p<.01), independent of age, education, sex, cardiovascular risk, current systolic blood pressure, and CAD (F(10,100)=3.61, p<.001). IMT was not significantly related to language, memory, or visual-spatial abilities. Our findings suggest that, in patients with cardiovascular disease, IMT may be associated with the integrity of frontal subcortical networks responsible for attention-executive-psychomotor performance. Future studies are needed to clarify the mechanisms by which IMT affects cognition and examine potential interactions between increased IMT and other measures of cardiovascular health such as blood pressure variability, cardiac systolic performance, and systemic perfusion.


The influence of formulation components on the aerosolisation properties of spray-dried powders.
Dry powders suitable for inhalation containing beta-estradiol, leucine as a dispersibility enhancer and lactose as a bulking agent were prepared by spray-drying from aqueous ethanol formulations. The influence of formulation components on the characteristics of the resultant spray-dried powders was examined through the use of a range of ethanol concentrations (10-50% v/v) in the solvent used to prepare the initial formulations. Additionally, the amount of leucine required to act as a dispersibility enhancer was investigated by varying the amount of leucine added to the formulation prior to spray-drying. Following spray-drying, resultant powders were characterised using scanning electron microscopy, laser diffraction and tapped density measurements, and the aerosolisation performance determined using Twin Stage Impinger and Andersen Cascade Impactor analysis. We demonstrate that selection of appropriate solvent systems and leucine concentration allows the preparation of spray-dried powders that display enhanced aerosolisation properties, and would be predicted to exhibit high deposition in the lower regions of the respiratory tract.


Differential expression of SUC genes: a question of bases.
Non-coding nucleotide sequences located 5' upstream of the transcriptional start site play an essential role in gene expression as they contain binding sites for transcription and regulatory factors. The yeast SUC gene family is a useful model to study the influence that nucleotide exchanges within the promoter regions have on their expression, since (i) these genes, regulated by glucose repression, are differentially transcribed (invertase activity produced by distinct SUC genes may show variations of about 10-fold); and (ii) promoter sequences of SUC3, SUC4, SUC5 and SUC7 are more than 99% homologous, showing only six base exchanges among all of them. Comparison of these nucleotide exchanges with the expression of each SUC gene (located either on chromosomes or on multicopy and centromeric plasmids) points out that naturally occurring base exchanges as few as one nucleotide modification (G to A transition at position -497 relative to the translational start site, C to T transition at position -460 and insertion/deletion of a T at positions -590, -586 and -435) may have a strong effect on gene expression.


Discovery of microRNAs during early spermatogenesis in chicken.
Spermatogenesis is a complex process that involves many elements. However, until now, little is known at the molecular level about spermatogenesis in poultry. Here we investigated microRNAs and their target genes that may be involved in germ cell development and spermatogonial in chicken. We used next-generation sequencing to analyze miRNA expression profiles in three types of germline cells: primordial germ cells (PGCs), spermatogonial stem cells (SSCs), and spermatogonia (Sp) during early stage of spermatogenesis. After validated the candidate miRNAs and corresponding genes' expression in three types of cells, we found 15 miRNAs that were enriched 21 target genes that may be involved in spermatogenesis. Among the enriched miRNAs, miR-202-5p/3p were up-regulated in the Sp library and down-regulated in the PGCs library. Through RT-qPCR and Dual-Luciferase reporter assay, we confirmed that miR-202-5p bind to LIMK2 and involved in germ cell development. Collectively, we firstly discover the novel miRNAs, like miR-202-5p, and its related genes and pathways, expressed during the early spermatogonial stage in chicken, which will provide new clues for deciphering the molecular mechanism of the miRNAs regulating germline stem cell differentiation and spermatogenesis in chicken.


The APC I1307K allele conveys a significant increased risk for cancer.
This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ∼ 6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non-colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non-carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk (OR 2.53). Further studies are needed to evaluate its use for specific cancer types-particularly in males. Female carriers have better prognosis and increased lifespan.


Behavioral and neural correlates to multisensory detection of sick humans.
Throughout human evolution, infectious diseases have been a primary cause of death. Detection of subtle cues indicating sickness and avoidance of sick conspecifics would therefore be an adaptive way of coping with an environment fraught with pathogens. This study determines how humans perceive and integrate early cues of sickness in conspecifics sampled just hours after the induction of immune system activation, and the underlying neural mechanisms for this detection. In a double-blind placebo-controlled crossover design, the immune system in 22 sample donors was transiently activated with an endotoxin injection [lipopolysaccharide (LPS)]. Facial photographs and body odor samples were taken from the same donors when "sick" (LPS-injected) and when "healthy" (saline-injected) and subsequently were presented to a separate group of participants (n = 30) who rated their liking of the presented person during fMRI scanning. Faces were less socially desirable when sick, and sick body odors tended to lower liking of the faces. Sickness status presented by odor and facial photograph resulted in increased neural activation of odor- and face-perception networks, respectively. A superadditive effect of olfactory-visual integration of sickness cues was found in the intraparietal sulcus, which was functionally connected to core areas of multisensory integration in the superior temporal sulcus and orbitofrontal cortex. Taken together, the results outline a disease-avoidance model in which neural mechanisms involved in the detection of disease cues and multisensory integration are vital parts.


Characterization of Spatial Learning and Sickness Responses in Aging Rats Following Recurrent Lipopolysaccharide Administration.
Infections in older individuals can result in cognitive function decline, yet research is limited on how recurrent infections affect cognitive responses. Activation of the immune system results in sickness responses mediated by cytokines. This pilot study examined effects of a model of recurrent infection in aged, male Brown Norway rats on sickness responses, including spatial learning, and cytokine levels. To model initial and recurrent infection, 300 μg/kg lipopolysaccharide (LPS) or saline was administered 1/day for 2 consecutive days during 2 weeks separated by 16 days. Testing occurred for 6 days during each LPS injection week using the Morris water maze, a measure used to evaluate spatial learning. Directional heading error (DHE) and swim time latency served as spatial learning indices. Retention tests and probe trials assessed memory. Plasma cytokine levels were assessed 5 and 24 hr after each LPS injection during Week 2. While food intake and weight decreased significantly in LPS-injected rats compared to controls during Week 1, both displayed increased DHE. Despite exhibiting lessened sickness behaviors during Week 2, experimental animals still displayed spatial learning deficits. Probe trials revealed memory deficits in LPS-injected animals. Interleukin 6 level was higher in the experimental group 5 and 24 hr after LPS injection on Day 1 compared to Day 2 and higher in the experimental compared to the control group at 5 hr on Day 1. Cognitive effects were dissociated from metabolic effects in aged rats, with recurring LPS exposure resulting in persistent cognitive impairment despite decreased sickness responses. Further research with older individuals is warranted.


Glioma angiogenesis is boosted by ELK3 activating the HIF-1[Formula: see text]/VEGF-A signaling axis.
Clinical studies have shown that first-line use of anti-angiogenetic therapy can prolong progression-free survival but little progress has been made in extending the overall survival of the patients. We explored the role of ELK3 in glioma angiogenesis to improve and design more efficacious therapies. A tissue microarray and immunohistochemistry analysis were used to determine the expression of ELK3 protein in 400 glioma patients. Cell proliferation, metastasis, cell cycle, and apoptosis were monitored in U87 and U251 cells using CCK-8, EdU, transwell assays, and flow cytometry. A tube-formation assay, a rat aorta ring sprouting assay, and a matrigel plug assay were performed to examine the antiangiogenic activity of ELK3. An ELISA, Western blot, and correlation analysis of the CGGA dataset were used to detect the association between ELK3 and VEGF-A or ELK3 and HIF-1[Formula: see text]. Besides, orthotopic transplantation in nude mice and histopathological and immunological analysis of in vitro tumors were used to explore the effect of ELK3 on tumor progression and median survival. ELK3 was upregulated in glioma tissues and associated with a poor prognosis. In vitro, ELK3 promoted cell proliferation and cell cycle progression, induced metastasis, and suppressed apoptosis. Then, silencing ELK3 inhibited VEGF-A expression and secretion by facilitating HIF-1[Formula: see text] degradation via ubiquitination. Finally, knockdown ELK3 inhibited tumor progression and angiogenesis in vitro and in vivo, as well as prolonged nude mice's median survival. Our findings first evidenced that ELK3 is crucial for glioma because it promotes angiogenesis by activating the HIF-1[Formula: see text]/VEGF-A signaling axis. Therefore, we suggest that ELK3 is a prognostic marker with a great potential for glioma angiogenesis and ELK3-targeted therapeutic strategies might hold promise in improving the efficacy of anti-angiogenic therapies.


Dynamics of Deoxynivalenol and Nivalenol Glucosylation in Wheat Cultivars Infected with Fusarium culmorum in Field Conditions─A 3 Year Study (2018-2020).
Fusarium head blight (FHB) caused by pathogenic species of Fusarium fungi is one of the most important diseases of cereal plants and a factor contributing to losses in plant production. The growth of FHB-associated species is often accompanied by biosynthesis of secondary metabolites─mycotoxins, which serve as a virulence factor. The aim of the study was to evaluate the ratios between deoxynivalenol (DON) and nivalenol (NIV) and their derivatives in the ears of six cultivars of winter wheat with varying resistance to FHB, taking into account a range of factors (weather conditions, location, cultivar, and year) after inoculation with Fusarium culmorum, during a 3 year field experiment, 2018-2020. The presence of toxins in the ears was measured within 21 days of inoculation. The toxins were found in the ears as soon as on the third day from the start of the experiment, whereas relative humidity higher than 80% was a decisive factor for FHB incidence. All wheat cultivars showed the ability to biotransform DON and NIV present in the ears to glucosides, that is, deoxynivalenol-3-glucoside (DON-3G) and nivalenol-3-glucoside (NIV-3G). The levels of these metabolites showed significant correlation with the levels of their basic analogues. In most cases, higher levels of DON and NIV in wheat ears and higher levels of their metabolites were observed, but the relative levels of DON-3G/DON and NIV-3G/NIV at relatively high levels of toxins were lower compared to the ear samples with relatively low toxin levels. The presented results are the first studies, which systematically correlate a variety of wheat cultivars with their extent to glucosylate trichothecenes.


Bridging the gap between interviewer and interviewee: developing an interview guide for individual interviews by means of a focus group.
In developing an interview guide, pre-existing knowledge about the research topic is essential. In a recent study, we were interested in exploring the experiences of weight changes among women treated for breast cancer using individual interviews. However, to develop an interview guide for the individual interviews that covered relevant thematic and dynamic dimensions, we found existing literature insufficient. Thus, we turned our attention to the benefit of the focus group method. This study aims to discuss how a focus group prior to individual interviews may contribute in developing the thematic dimension and translating the dynamic dimension of an interview guide into everyday language. We conducted one focus group interview of five women treated for breast cancer with experiences in weight changes. Data were analysed using content and conversation analysis and discussed with relevant literature on interview guide development. The study is approved by the Danish Data Protection Agency (2008-58-0028) and follows the ethical guidelines for qualitative research. Data generation and analysis resulted in themes for the thematic dimension, as well as three dynamic areas to consider in the individual interviews to bridge the gap between the interviewer and the interviewee. The dynamic areas are as follows: The use of words, images and metaphors - a shield and self-protection, Multiple meanings to explore and Staying close to the everyday language. The analysis made us more familiar with the content and meaning of weight changes among breast cancer survivors. Furthermore, it provided images and metaphors, multiple meanings and a sense of the women's everyday language that calls for an open interview frame to be used in subsequent individual interviews.


A Study of Elderly Suicide Attempters Admitted to an Inpatient Psychiatric Unit.
The authors distinguish demographic and clinical characteristics of elderly suicide attempters admitted to an inpatient psychiatric unit within 4 weeks of a suicide attempt. Of 560 patients admitted, 28 (5%) were recent attempters, 32 (6%) had a past history of suicide attempt, and 500 (89%) were nonattempters. Of the 28 recent attempters, 21 (75%) were diagnosed with a mood disorder, 4 (14%) with an organic mental disorder, and 3 (11%) with other mental disorders. Among the nonattempters, the distribution among the three diagnostic categories was 188 (38%), 251 (50%), and 61 (12%), respectively. Of 166 patients with a diagnosis of major depression, 18 (11%) were recent attempters, 14 (8%) were past attempters, and 134 (71%) were nonattempters. Recent attempts were significantly associated with alcohol abuse. This study confirms earlier reports of high rates of major depression in elderly attempters.


Clinical laboratory applications of monoclonal antibodies.
Monoclonal antibody (MAb) technology is well recognized as a significant development for producing specific serologic reagents to a wide variety of antigens in unlimited amounts. These reagents have provided the means for developing a number of highly specific and reproducible immunological assays for rapid and accurate diagnosis of an extensive list of diseases, including infectious diseases. The impact that MAbs have had in characterizing infectious disease pathogens, as well as their current and future applications for use in clinical microbiology laboratories, is reviewed. In addition, the advantages (and disadvantages) of the use of MAbs in a number of immunoassays, such as particle agglutination, radioimmunoassays, enzyme-linked immunosorbent assays, immunofluorescent-antibody assays, and immunohistology, are explored, including the use of these reagents in novel test system assays. Also, nucleic acid probe technology is compared with the use of MAbs from the perspective of their respective applications in the diagnosis of infectious disease agents. There is no question that hybridoma technology has the potential to alter significantly the methods currently used in most clinical microbiology laboratories.


[Current status of external quality assessment of syphilis test in Korea].
Current status of external quality assessment (EQA) of laboratory tests for syphilis in Korea was analyzed to find out the problems that should be improved in the future. Based on the data from the external quality assessment program performed twice a year by the Immunoserology Subcommittee of the Korean Association of Quality Assurance for Clinical Laboratory from the year 2004 to 2006, discordance rates were analyzed according to the test method and commercial kit used. Among the laboratories participating in the EQA program for syphilis test, about 90% of them used non-treponemal tests and about 55% treponemal tests. The non-treponemal tests included RPR (rapid plasma reagin) and VDRL tests used in 88% (363/412) and 11% (45/412), respectively, of the laboratories. The discordance rates were 2.2% for RPR test and 3.6% for VDRL. For the treponemal tests, Treponema pallidum hemagglutination assay (TPHA) was used in 60-76% and Immunochromatography assay (ICA) in about 30% of the laboratories in 2006. A high discordance rate of over 10% was reported in both TPHA and in ICA methods, possibly due to a low titer (1:1 in VDRL) of EQA samples in 2005. Analysis of the accumulated data from year 2004 to 2006 showed that the discordance rates of TPHA, ICA, and FTA-ABS were 4.6%, 3.7%, and 2.7%, respectively. For syphilis tests, RPR test, TPHA, and ICA are mainly used in Korea. A high discordance rate is still reported in TPHA and ICA, especially when testing samples with a low titer. Further analysis of data and education of laboratory personnel are needed for the improvement of the EQA program.


Nitrate tolerance aggravates postischemic myocardial apoptosis and impairs cardiac functional recovery after ischemia.
This study examined the effects of nitrate tolerance (NT) on myocardial ischemia reperfusion (MI/R) injury and elucidated the potential mechanisms involved. Furthermore, the effects of GSH on postischemic myocardial apoptosis in NT rats were investigated. Male Sprague-Dawley rats were randomized to receive nitroglycerin (60 microg/kg/h) or saline for 12 h followed by 40 min of MI and 4 h of reperfusion. Myocardial apoptosis, infarct size, nitrotyrosine formation, plasma CK and LDH activity, and cardiac function were determined. MI/R resulted in significant apoptotic cell death, which was further increased in animals with NT. In addition, NT further increased plasma CK and LDH activity, enlarged infarct size, and impaired cardiac functional recovery after ischemia. Myocardial nitrotyrosine, a footprint for cytotoxic reactive nitrogen species formation, was further enhanced in the NT heart after MI/R. Treatment of NT animals with exogenous GSH inhibited nitrotyrosine formation, reduced apoptosis, decreased infarct size, and improved cardiac functional recovery. Our results demonstrate that nitrate tolerance markedly enhances MI/R injury and that increased peroxynitrite formation likely plays a role in this pathologic process. In addition, our results suggest that GSH could decrease peroxynitrite formation and reduce MI/R injury in nitrate tolerant hearts.


Improving links between literature and biological data with text mining: a case study with GEO, PDB and MEDLINE.
High-throughput experiments and bioinformatics techniques are creating an exploding volume of data that are becoming overwhelming to keep track of for biologists and researchers who need to access, analyze and process existing data. Much of the available data are being deposited in specialized databases, such as the Gene Expression Omnibus (GEO) for microarrays or the Protein Data Bank (PDB) for protein structures and coordinates. Data sets are also being described by their authors in publications archived in literature databases such as MEDLINE and PubMed Central. Currently, the curation of links between biological databases and the literature mainly relies on manual labour, which makes it a time-consuming and daunting task. Herein, we analysed the current state of link curation between GEO, PDB and MEDLINE. We found that the link curation is heterogeneous depending on the sources and databases involved, and that overlap between sources is low, <50% for PDB and GEO. Furthermore, we showed that text-mining tools can automatically provide valuable evidence to help curators broaden the scope of articles and database entries that they review. As a result, we made recommendations to improve the coverage of curated links, as well as the consistency of information available from different databases while maintaining high-quality curation. Database URLs: http://www.ncbi.nlm.nih.gov/PubMed, http://www.ncbi.nlm.nih.gov/geo/, http://www.rcsb.org/pdb/


Risk of hepatitis C virus infection in injecting and noninjecting drug users receiving opioid substitution therapy.
Hepatitis C virus (HCV) is the most common viral infection among illicit drug users in the world. Although intervention of needle and syringe program and opioid substitution therapy had engaged to prevent HCV infection, the prevalence of HCV infection does not seem to decline. The aim of this study was to estimate the risk of HCV infection in injecting drug users (IDUs) and noninjecting drug users (NIDUs) receiving opioid substitution therapy. We recruited 1179 heroin-dependent patients (age: 20-66 years) under opioid substitution therapy from 2012 to 2015 in a Psychiatric Center, Southern Taiwan. The data of HCV, hepatitis B virus and HIV infection and liver biochemical examination were obtained. We used multivariate logistic regression analysis to predict the risk of HCV infection. There were 93.1% of IDUs and 68.1% of NIDUs positive for HCV infection. In IDUs, HIV infection, age of heroin initiation, duration and dose of heroin use, frequency of detoxification, and number of criminal conviction were significantly associated with HCV infection. In NIDUs, snort/sniff heroin exhibited a significantly increased risk of HCV infection. Intravenous injecting (odds ratio [OR] = 23.10, 95% CI = 8.04-66.40, p < 0.001), intravenous injecting combined snort/sniff (OR = 12.95, 95% CI = 3.90-42.97, p < 0.001), and snort/sniff (OR = 4.14, 95% CI = 1.30-13.18, p = 0.016) were significantly associated with increased risk of HCV infection compared with smoking. The trend was significant (p for trend <0.001). In Taiwan, IDUs had harmful characteristics compared with NIDUs and both had extremely high prevalence of HCV infection. We provided evidence that snort/sniff is a possible way of leak in HCV infection despite needle-syringes supplement program been provided. Opioid substitution therapy program should include HCV assessment and treatment in the new direct-acting antiviral therapy era.


Effect of abomasal butyrate infusion on net nutrient flux across the portal-drained viscera and liver of growing lambs.
The purpose of this experiment was to determine if supplying butyrate to the postruminal gastrointestinal tract of growing lambs alters blood flow and nutrient flux across the portal-drained viscera (PDV) and hepatic tissues. Polled Dorset wether lambs ( = 10; initial BW = 55 ± 3.3 kg) had catheters surgically implanted into the portal vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta. A cannula was placed in the abomasum to deliver the treatment. Lambs were fed a pelleted ration once daily consisting of 69.7% dehydrated alfalfa, 30.0% ground corn, and 0.3% salt at 1.3 × NE requirement. The experimental design was a crossover balanced in time, so that each lamb received both treatments. Treatments consisted of either a pulse dose infusion of butyrate (buffered solution) to supply butyrate (10 mg/kg BW) or a buffered saline solution (1 mL/kg BW) once daily at the time of feeding. On d 14 of the treatment period, nutrient fluxes were measured using para-aminohippuric acid as a blood flow marker. Blood samples were collected from the aorta, portal vein, and hepatic vein every hour for 9 h beginning at 30 min prior to treatment/feeding. There was a tendency for a treatment × time interaction ( = 0.05) for portal vein blood flow, indicating that blood flow began to decrease earlier postprandial in lambs receiving butyrate. The butyrate treatment tended to increase the uptake of O ( = 0.07) and increased the uptake of glucose ( = 0.002), glutamate ( = 0.04), and glutamine ( = 0.02) by the PDV. There was a treatment × time interaction ( < 0.01) for flux of acetate, propionate, butyrate, isobutyrate, and valerate across the PDV. The interaction was mainly due to an earlier postprandial peak and associated decrease in the flux rate of the VFA. The alteration in timing of the postprandial peak of VFA flux was also observed in hepatic fluxes of VFA. It appears that supplying butyrate to the postruminal tissues through an abomasal cannula increases glucose, glutamate, and glutamine metabolism by the PDV.


[Anomalous origin of the right coronary artery from pulmonary trunk in an 11 year old girl - a case report].
A case of 11 year old girl with the anomalous origin of the right coronary artery from pulmonary trunk is presented. Initially the patient was treated conservatively, however, after demonstrating myocardial ischaemia during SPECT, she was selected for surgical treatment.


Ablation of non functioning renal allograft by embolization: a valid alternative to graft nephrectomy?
Removal of transplant for the treatment of graft intolerance syndrome (GIS) is an invasive procedure with high risk, often performed in patients with poor general conditions. Renal allograft embolization is a recent alternative treatment to surgical nephrectomy. The aim of this study was to evaluate the efficacy and safety of allograft embolization in a series of patients with GIS. The study included 12 patients (9 males and 3 females) with irreversible renal graft rejection and GIS. All patients were in hemodialysis and they have not responded to medical treatment. Infection was ruled out by blood and urine cultures. The embolization was performed using polyvinyl alcohol particles and steel coils. Vascular access was obtained via femoral artery puncture in all the patients. Before starting embolization at the puncture site local anaesthesia was performed. Eleven of the twelve procedures were technically successful, but in one patient a second treatment was necessary, after a month, for the presence of collateral perirenal circulation caused hematuria. There were no major complications and the mean hospital stay was 5 days. The graft embolization is a simple, safe and effective technique that permits non-surgical ablation of a non-functioning renal allograft in a significant number of patients.


Maternal mortality in the Nordic countries 1970-1979.
There are approximately 400,000 births plus legal abortions in the five Nordic countries annually. During the 1970s the number of maternal deaths ranged from 14 to 33 per year, the overall mean rate being 7.2 per 100,000 births. The rates declined somewhat from 1972 onwards, but otherwise there was no demonstrable change in frequency with time. Mortality rose steeply with increasing maternal age, with a rate of 28.5 for mothers over 35. The two most frequent causes of death were pre-eclampsia/eclampsia and hemorrhage, comprising 17.0 and 14.2% of the total, respectively. Legal abortion carried less risk of death than did pregnancy continuing to birth. Among the countries, Denmark and Sweden had the lowest average maternal mortality rates. The distribution of causes showed a predominance of abortion and thrombosis in Finland, and of hemorrhage and infection in Norway, but neither singular causes nor age-specific birth distributions can explain inter-country differences.


[Changes in 25-hydroxyvitamin D3 level in children with Henoch-Schönlein purpura].
To examine the changes in 25-hydroxyvitamin D3 [25-(OH)D3] level in children with Henoch-Schönlein purpura (HSP) and its clinical significance. A total of 92 HSP children were included in this study, and were divided into HSP nephritis (HSPN) group (31 cases) and HSP group (61 cases) based on the presence or absence of HSPN. Alternatively, the patients were divided into purpura alone group (22 cases), purpura with joint symptoms group (joint symptom group, 24 cases), purpura with gastrointestinal symptoms group (gastrointestinal symptom group, 20 cases), and purpura with joint and gastrointestinal symptoms (mixed group, 26 cases) based on their clinical symptoms. In addition, 42 healthy children were selected as healthy control group. The level of 25-(OH)D3 in each group was measured using enzyme-linked immunoassay. The 25-(OH)D3 level in the HSP and HSPN groups was significantly lower than that in the healthy control group (P<0.05), and the 25-(OH)D3 level in the HSPN group was significantly lower than that in the HSP group (P<0.05). Although there was no significant difference in the 25-(OH)D3 level between the joint symptom, gastrointestinal symptom, and mixed groups (P=0.22), the 25-(OH)D3 level in the three groups was all significantly lower than that in the purpura alone group (P<0.05). The level of 25-(OH)D3 is reduced in children with HSP, particularly those with HSPN or with joint and gastrointestinal symptoms. Therefore, the reduction in 25-(OH)D3 level may serve as a predictor of whether HSP is associated with other impairments.


Sustainable Capture: Concepts for Managing Stream-Aquifer Systems.
Most surface water bodies (i.e., streams, lakes, etc.) are connected to the groundwater system to some degree so that changes to surface water bodies (either diversions or importations) can change flows in aquifer systems, and pumping from an aquifer can reduce discharge to, or induce additional recharge from streams, springs, and lakes. The timescales of these interactions are often very long (decades), making sustainable management of these systems difficult if relying only on observations of system responses. Instead, management scenarios are often analyzed based on numerical modeling. In this paper we propose a framework and metrics that can be used to relate the Theis concepts of capture to sustainable measures of stream-aquifer systems. We introduce four concepts: Sustainable Capture Fractions, Sustainable Capture Thresholds, Capture Efficiency, and Sustainable Groundwater Storage that can be used as the basis for developing metrics for sustainable management of stream-aquifer systems. We demonstrate their utility on a hypothetical stream-aquifer system where pumping captures both streamflow and discharge to phreatophytes at different amounts based on pumping location. In particular, Capture Efficiency (CE) can be easily understood by both scientists and non-scientist alike, and readily identifies vulnerabilities to sustainable stream-aquifer management when its value exceeds 100%.


The transport of alpha(1A)-adrenergic receptor with 33-nm step size in live cells.
We used the technique of single particle tracking (SPT) with high tempo-spatial resolution to efficiently explore the route and mechanism for the transport of alpha(1A)-adrenergic receptor (alpha(1A)-AR) in real time in living cells. We found that the initial transport of alpha(1A)-AR in cells depended on actin filaments with the velocity of 0.2 microm/s and exhibited discrete 33-nm steps. It was noted that the step size, the rate constant, and the velocities were in accordance with the character of single myosin in vitro, implying that while transporting each endosome myosins did not work in the "tug-of-war" mode and that they did not adopt the strategy to boost up transporting speed by working coordinately. These results provided insight into the mechanism of GPCR transport in vivo.


Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity.
Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.


[Fetal biometry: review and application of sex determination].
Diagnostic ultrasound was introduced in the practice of obstetrics through its ability to measure accurately the biparietal (DBP) diameter of the foetus. The development of bidimensional and grey tone images expanded the possibility of fetal biometry. One of its most important uses is the estimation of gestational age. A knowledge of foetal age is necessary to interpret the results of most of the investigations currently performed during pregnancy. Different fetal dimensions increase with age at different rates according to the period of gestation. During the embryonic period, the crown-rump length gives a very good estimation of age within 4-6 days for twice the standard deviation. Later on, because of the curvature of the fetus, the age is estimated with the DBP. The accuracy diminishes with the slowing down of fetal growth, from 12 weeks onwards, when twice the standard deviation of the age estimate may be as long as 2 weeks. When DBP is no longer reliable in determining age, femur length is measured being more reliable for that purpose at least till 24 weeks. A very early assessment of foetal age reduces the risk of errors in estimating the duration of pregnancy and is important to detect early growth retardation (IUGR); this is usually symmetric, i.e. affecting all fetal parts (versus asymmetrical or late IUGR where trunk growth is first involved). Fetal weight can be estimated by fetal parts measurements. A formula was derived as long as twenty years ago but not all authorities agree on any measuring technique as evidenced by the many different formulas proposed--a sign that no very satisfactory one yet exists.(ABSTRACT TRUNCATED AT 250 WORDS)


Network Pharmacology Analysis and Experimental Validation to Explore the Anti-inflammatory Mechanism of Asiatic Acid on Alcoholic Steatohepatitis.
The mechanism of action of asiatic acid (AA) on alcoholic steatohepatitis (ASH) was investigated using network pharmacology and experiments. Through data retrieval, network construction, and enrichment analysis, the potential mechanism of AA in the treatment of alcoholic steatohepatitis was explored. Animal and cell models were established in this study. Animal Model. The mouse model was divided into six groups: normal group; model group; low, medium, and high AA group; and silibinin-positive group. Cell Model. An in vitro inflammatory model of RAW264.7 cells was established by alcohol stimulation. Compared with the model group, the low, medium, and high AA group showed decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (T-CHO). The inflammatory factor tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) in a dose-dependent manner were decreased. In addition, hematoxylin-eosin staining showed that liver tissue damage and inflammatory cell infiltration in mice were significantly reduced with increasing doses. Further, oil red staining showed that lipid accumulation in hepatocytes in the low, medium, and high AA group was significantly reduced, with increasing dose. In addition, in the cellular model, real-time reverse transcriptase-polymerase chain reaction (Real-Time RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that AA could alleviate alcohol-induced cellular inflammation, while western blot and immunofluorescence results showed that AA might alleviate alcohol-induced cellular inflammation by inhibiting the nuclear factor-κB (NF-κB) pathway. This study provides multiple lines of evidence that asiatic acid may alleviate alcoholic hepatitis in mice by modulating the NF-κB pathway.


What proportion of people with migraine report postdromal symptoms? A systematic review and meta-analysis of observational studies.
Postdromal symptoms, following headache resolution, are said to constitute a distinct phase of the migraine attack. We question the evidence for this, with regard both to the nature of such symptoms and to how often they are reported to occur. We searched the Pubmed and Embase databases for relevant articles from their inception until 25 May 2023. We included observational studies recording the proportions of participants with migraine reporting one or more postdromal symptoms or specific individual symptoms. Two reviewers independently screened studies for relevance (agreeing on those to be included), extracted data and assessed risk of bias. Data were analyzed using random-effects meta-analysis to establish the proportions of those with migraine reporting one or more postdromal symptoms, whether among the general population or patients in clinic-based samples. Large majorities of participants in either case reported postdromal symptoms: 97% in the only population-based study, and a mean of 86% (95% CI: 71-94%) in four clinic-based studies. The most commonly reported specific symptoms were fatigue (52%; 95% CI: 44-60%), concentration difficulties (35%; 95% CI: 14-65%) and mood changes (29%; 95% CI: 9-64%), none of these being clearly described. These estimates could not be considered reliable: they were subject to substantial study heterogeneity, none of the studies applied International Classification of Headache Disorders definitions of postdromal symptoms, and all had high risk of bias. Postdromal symptoms in migraine appear to be very commonly reported, but the data are unreliable with regard both to their nature and to how often they occur. Further studies are needed to conclude that they constitute a distinct phase of migraine.


Measurement of cognitive performance in computer programming concept acquisition: interactive effects of visual metaphors and the cognitive style construct.
An innovative research program was devised to investigate the interactive effect of instructional strategies enhanced with text-plus-textual metaphors or text-plus-graphical metaphors, and cognitive style on the acquisition of programming concepts. The Cognitive Styles Analysis (CSA) program (Riding,1991) was used to establish the participants' cognitive style. The QUEST Interactive Test Analysis System (Adams and Khoo,1996) provided the cognitive performance measuring tool, which ensured an absence of error measurement in the programming knowledge testing instruments. Therefore, reliability of the instrumentation was assured through the calibration techniques utilized by the QUEST estimate; providing predictability of the research design. A means analysis of the QUEST data, using the Cohen (1977) approach to size effect and statistical power further quantified the significance of the findings. The experimental methodology adopted for this research links the disciplines of instructional science, cognitive psychology, and objective measurement to provide reliable mechanisms for beneficial use in the evaluation of cognitive performance by the education, training and development sectors. Furthermore, the research outcomes will be of interest to educators, cognitive psychologists, communications engineers, and computer scientists specializing in computer-human interactions.


Role of Dispersion Interactions in Endohedral TM@(ZnS)12 Structures.
II-VI semiconducting materials are gaining attention due to their optoelectronic properties. Moreover, the addition of transition metals, TMs, might give them magnetic properties. The location and distance of the TM are crucial in determining such magnetic properties. In this work, we focus on small hollow (ZnS)12 nanoclusters doped with TMs. Because (ZnS)12 is a cage-like spheroid, the cavity inside the structure allows for the design of endohedral compounds resembling those of C60. Previous studies theoretically predicted that the first-row TM(ZnS)12 endohedral compounds were thermodynamically unstable compared to the surface compounds, where the TM atom is located at the surface of the cluster. The transition states connecting both structure families were calculated, and the estimated lifetimes of these compounds were predicted to be markedly small. However, in such works dispersion effects were not taken into account. Here, in order to check for the influence of dispersion on the possible stabilization of the desired TM(ZnS)12 endohedrally doped clusters, several functionals are tested and compare to MP2. It is found that the dispersion effects play a very important role in determining the location of the metals, especially in those TMs with the 4s3d shell half-filled or completely filled. In addition, a complete family of TM doped (ZnS)12 nanoclusters is explored using ab initio molecular dynamics simulations and local minima optimizations that could guide the experimental synthesis of such compounds. From the magnetic point of view, the Cr(7S)@(ZnS)12 compound is the most interesting case, since the endohedral isomer is predicted to be the global minimum. Moreover, molecular dynamics simulations show that when the Cr atom is located at the surface of the cluster, it spontaneously migrates toward the center of the cavity at room temperature.


Evaluation of the Effect of Porcelain Laminate Thickness on Degree of Conversion of Light Cure and Dual Cure Resin Cements Using FTIR.
Increasing the thickness of the veneering porcelain may affect the polymerization of resin cements. Incomplete polymerization of resin cements can lead to compromised quality of restoration and decrease the longevity of indirect restorations. This study sought to assess the effect of IPS Empress porcelain thickness on the degree of conversion of light-cure and dual-cure resin cements using Fourier transform infrared spectroscopy. In this experimental study, IPS Empress porcelain discs (A2 shade) with 10mm diameter and 0.5, 1 and 1.5 mm thicknesses were fabricated. Choice2 (Bisco, USA) and Nexus3 (Kerr, USA) resin cements were light cured through the three porcelain thicknesses in two groups of 3 samples using a LED light-curing unit (LEDemetron II; Kerr, USA). The control group samples were cured individually with no porcelain disc. The degree of conversion of resin cements was determined using FTIR (Bruker; Equinox55, Germany). The data were analyzed using Dunn's test. The degree of conversion (in percent) beneath the 0.5, 1.5 and 2 mm thicknesses of IPS Empress was 68.67±0.88, 71.06±0.94 and 72.51±0.41 for Choice2 resin cement and 69.60±2.12, 69.64±1.63 and 69.24±2.12 for Nexus3, respectively. Porcelain thickness and type of resin cement had no significant effect on degree of conversion (p≥ 0.05). It seems that increasing the porcelain thickness by up to 1.5 mm has no adverse effect on degree of conversion of both dual cure and light cure resin cements evaluated in this study.


Method development and validation for the simultaneous determination of four coumarins in Saussurea superba by capillary zone electrophoresis.
A capillary zone electrophoretic method has been developed for the determination of four coumarins--skimmin, scopolin, scopoletin, and umbelliferone-in Saussurea superba with UV detection at 254 nm. The capillary temperature was kept constant at 25 degrees C. Effects of buffer pH, electrolyte concentration, organic modifier, and applied voltage on migration behavior were studied systematically. The optimum conditions for separation were achieved by using 30 mM borate buffer at pH 9.02 containing 15% (v/v) methanol as the electrolyte and 25 kV as the applied voltage. For all analytes a good linear regression relationship (r > 0.999) was obtained between peak area and concentration over a relatively wide range. The method was validated for repeatability, precision, and accuracy. The validated method was successfully applied to the simultaneous determination of the four analytes in S. superba.


Normative data for the personal report of confidence as a speaker.
Normative data for the Personal Report of Confidence as a Speaker (PRCS; Paul, 1966), a measure of public-speaking anxiety, were collected by administering the PRCS to 1109 college students. PRCS scores were examined in relation to gender, race, age, and grade-point average. No significant between-group differences were found. The findings indicate that levels of public-speaking anxiety are generally constant across gender, race, and age. Normative data for all scores across Caucasian and African-American subjects are presented.


K+ and Cl- contribute to resting membrane conductance of cultured porcine endocardial endothelial cells.
The conventional whole cell patch-clamp technique was used to measure the resting membrane conductance and membrane currents of single, nonstimulated, cultured endocardial endothelial cells of the porcine right ventricle in different ionic conditions. All cells displayed the barium-sensitive, inwardly rectifying potassium (K+) current (I(Ki)). In 65% of the cells, I(Ki) was the predominant membrane current. The mean zero-current potential (V0) was -61.0 +/- 12.5 mV (+/- SD, n = 45). In 35% of the cells, I(Ki) was superposed on an outwardly rectifying (OR) current. V0 of these cells was more depolarized (-33.5 +/- 22.0 mV, n = 26). High intracellular Cl- (122 instead of 52 mmol/l) activated or increased the OR current and shifted V0 in the direction of the equilibrium potential for Cl-. In cells displaying the OR current, V0 was dependent on extracellular Cl-, indicating the contribution of an OR Cl- current in setting V0. At low intracellular Cl- (6 instead of 52 mmol/l), the OR current was decreased and V0 shifted in the direction of the equilibrium potential for K+. In cells not displaying the OR current, V0 was dependent on extracellular K+ but not on Cl-, indicating major permeability to K+ in these conditions. Block of the OR current by the Cl(-)-channel blockers anthracene-9-carboxylic acid (1 mmol/l), flufenamic acid (100-500 micromol/l), and Zn2+ (100-200 micromol/l) provided further evidence for the anionic nature of the OR current. After inhibition of I(Ki) and the OR Cl- current, a third current component was observed in 50% of the cells. The pharmacology and voltage dependence of this current suggested the presence of Ca2+-activated K+ channels in endocardial endothelial cells. We concluded that the resting membrane conductance of nonstimulated endocardial endothelial cells is mainly determined by the combined activity of inwardly rectifying K+, OR Cl-, and Ca2+-activated K+ channels.


Dose-plasma concentration--effect relationship of felodipine in essential hypertension: a review.
Calcium antagonists demonstrate a close relationship between plasma drug level and effect on blood pressure (BP). Thus, the intensity and duration of action can be influenced by dose and disposition. Felodipine has a dose-related effect on diastolic BP whether given alone or with a beta-blocker. The latter combination reduces adverse effects and improves tolerability, particularly at higher (20 mg/day) doses of felodipine. Felodipine 5 or 10 mg/day in an extended release formulation could be predicted to lower BP throughout a 24-h period. The results of formal prospective clinical trials confirm the predictions and indicate that felodipine can be used as a once-daily agent in essential hypertension.


Relative amplitude noise transfer function of an Yb3+-doped fiber amplifier chain.
In this work we measure the frequency dependent transfer function of the amplitude noise for both the seed and pump power in an Yb3+-doped fiber amplifier chain. In particular, the relative intensity noise transfer function of this amplifier chain in the frequency range of 10 Hz - 100 kHz has been investigated. It is shown that the pump power noise of the pre-amplifier stages is transformed into seed power noise for the next amplification stage. Crucially, the seed power noise in the frequency range of interest is strongly damped by the main-amplifier. This, however, does not happen for the pump power noise. Thus, the noise of the pump of the last amplifier stage is the factor with the strongest impact on the overall noise level of the system. Finally, useful guidelines to minimize the output amplitude noise of an Yb3+-doped fiber amplifier chain are given.


Anthocyanin pigment stability of Cornus mas-Macrocarpa under treatment with pH and some organic acids.
The use of colors in food industry is essential for the creation of new products or their improvement. As an important pigment group, anthocyanin could be used as a natural coloring pigment in foods. This study aims at exploring strategies that result in color stability of anthocyanin in pear-shaped variety of blueberry (Cornus mas-Macrocarpa). In this study, the effects of different pH values (1, 2, 3, 4) as well as various concentrations (0, 120, 240, 480, 960 mg/L) of five copigments, including tannic, caffeic, benzoic, and coumaric acids, on anthocyanin copigment complexes (ratio 1:1) were investigated. The studied copigments were tannic, caffeic, benzoic, and coumaric acids. Anthocyanin was influenced by the highest concentration of 960 mg/L copigment in the presence of different pHs. Five groups were considered, one of which contained anthocyanin without copigment and the rest consisted of copigments. To evaluate the response of copigmentation through spectrophotometer, absorbance from samples was measured after 30 min of adding copigment to anthocyanin in the range of 450-600 nm wavelengths. The results showed that caffeic acid possessed the greatest anthocyanin stability compared to other copigments and it was the best copigment. An increase in the concentrations of copigments led to a higher level of anthocyanin stability and changes in hyperchromic and bathochromic. Moreover, the results revealed that the strongest hyperchromic effect for all organic acids was observed in pH 2, and the strongest bathochromic changes were observed in pH 4.


Obtaining ready-to-eat blue corn expanded snacks with anthocyanins using an extrusion process and response surface methodology.
Extrusion is an alternative technology for the production of nixtamalized products. The aim of this study was to obtain an expanded nixtamalized snack with whole blue corn and using the extrusion process, to preserve the highest possible total anthocyanin content, intense blue/purple coloration (color b) and the highest expansion index. A central composite experimental design was used. The extrusion process factors were: feed moisture (FM, 15%-23%), calcium hydroxide concentration (CHC, 0%-0.25%) and final extruder temperature (T, 110-150 °C). The chemical and physical properties evaluated in the extrudates were moisture content (MC, %), total anthocyanins (TA, mg·kg(-1)), pH, color (L, a, b) and expansion index (EI). ANOVA and surface response methodology were applied to evaluate the effects of the extrusion factors. FM and T significantly affected the response variables. An optimization step was performed by overlaying three contour plots to predict the best combination region. The extrudates were obtained under the following optimum factors: FM (%) = 16.94, CHC (%) = 0.095 and T (°C) = 141.89. The predicted extrusion processing factors were highly accurate, yielding an expanded nixtamalized snack with 158.87 mg·kg(-1) TA (estimated: 160 mg·kg(-1)), an EI of 3.19 (estimated: 2.66), and color parameter b of -0.44 (estimated: 0.10).


A novel transcriptional regulator of L-arabinose utilization in human gut bacteria.
Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR-DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.


Chalcone epoxide intermediates in the syntheses of lignin-related phenylcoumarans.
Compounds (2R*,3S*)-1-(3,4-dimethoxyphenyl)-3-{3-methoxy-2-[(2R*)-tetrahydropyran-2-yloxy]phenyl}-2,3-epoxy-1-propanone, C23H26O7, (I), and trans-1-(3,4-dimethoxyphenyl)-3-[3-methoxy-2-(methoxymethoxy)phenyl]-2,3-epoxy-1-propanone, C20H22O7, (II), were obtained on epoxidation of chalcones. The stereochemistries of (I) and (II) were elucidated. In both compounds, the substituents on the oxirane ring are trans-oriented. Compound (I) was obtained together with a diastereometric form that differs from (I) with respect to the configuration of the asymmetric C atom in the tetrahydropyran group. The geometries of the substituted oxirane rings of (I) and (II) are very similar. The hydrogen-bonding patterns, mediated via weak C-H...O interactions, differ considerably. The crystal structures of (I) and (II) are compared with those of related chalcone epoxides. The conversion of (I) and (II) into lignin-related phenylcoumarans is discussed.


Fe-based double perovskite with Zn doping for enhanced electrochemical performance as intermediate-temperature solid oxide fuel cell cathode material.
This study aims to investigate the implications of transition-metal Zn doping at the B-site on the crystal structure, average thermal expansion coefficient (TEC), electrocatalytic activity, and electrochemical performance of LaBaFe2O5+δ by preparing LaBaFe2-xZnxO5+δ (x = 0, 0.05, 0.1, 0.15, 0.2, LBFZx). The X-ray diffraction (XRD) results show that Zn2+ doping does not change the crystal structure, the unit cell volume increases, and the lattice expands. The X-ray photoelectron spectroscopy (XPS) and mineral titration results show that the oxygen vacancy concentration and Fe4+ content gradually increase with the increase in doping amount. TEC decreases with the increase in Zn2+ doping amount, and the TEC of LBFZ0.2 is 11.4 × 10-6 K-1 at 30-750 °C. The conductivity has the best value of 103 S cm-1 at the doping amount of x = 0.1. The scanning electron microscopy (SEM) images demonstrate that the electrolyte CGO(Gd0.1Ce0.9O1.95) becomes denser after high-temperature calcination, and the cathode material is well attached to the electrolyte. The electrochemical impedance analysis shows that Zn2+ doping at the B-site can reduce the (Rp) polarization resistance, and the Rp value of the symmetric cell with LaBaFe1.8Zn0.2O5+δ as cathode at 800 °C is 0.014 Ω cm2. The peak power density (PPD) value of the anode-supported single cell is 453 mW cm-2, which shows excellent electrochemical performance.


[Opposite trends in the incidence of gonorrhea and syphilis in the East Bohemian Region - 30 years of surveillance].
The epidemiology of selected sexually transmitted diseases in the Czech Republic has been carefully evaluated for many years. Data from 1981-2011 for eastern Bohemia shows a sharp decrease in the incidence of gonorrhea in 1993-1994 and a very low incidence thereafter with a slightly higher prevalence in males. However, syphilis and genitourinary infections with Chlamydia trachomatis show entirely opposite trends. Also, for the similar number of diagnostic tests performed, Chlamydia had a 10 fold higher rate of positive results. This underscores the changing epidemiology of sexually transmitted infections (STI) and necessity for adapting the reporting algorithms accordingly.


County hospitals and regional medical care in Texas: an analysis of out-of-county costs.
The current system of regional medical service delivery in Texas places large demands on the state's urban public hospitals. To assess the nature and scope of such demands, we examined financial data from five of the state's largest public hospital districts. During fiscal year 2002, these hospitals reported 103,381 encounters with out-of-county patients, resulting in 66 million dollars in unreimbursed costs. Given the current economic outlook, Texas requires a more effective regional model that centralizes tertiary care, disperses primary and secondary care, and preserves key public health goods.


Identification and quantification of phenolic compounds in berry skin, pulp, and seeds in 13 grapevine varieties grown in Serbia.
Phenolic profile of 13 grapevine varieties was determined, with respect to three different parts of berries: skin, seed and pulp. Identification and quantification of the phenols was done using ultra-high performance liquid chromatography (UHPLC) coupled with a diode array detector and a triple-quadrupole mass spectrometer. The most abundant phenols in grape seeds were found to be flavan-3-ols, most of which are gallocatechin gallate and catechin. The skins were characterized mostly by flavonols, i.e. quercetin and myricetin. Characterization of anthocyanins in the berry skin by UHPLC coupled with Linear Trap Quadrupole and OrbiTrap mass analyzer revealed a total of twenty derivatives of malvidin, delphinidin, petunidin, cyanidin, and peonidin. To the extent of our knowledge this is the first work that shows the presence of malvidin 3,5-O-dihexoside in the berry skin of 'Merlot', 'Cabernet Franc', 'Shiraz' 'Sangiovese', 'Pinot Noir' and 'Prokupac', untypical for Vitis vinifera Linneo species.


CRISPR-Cas9-Mediated Intersectional Knockout of Glycogen Synthase Kinase 3β in D2 Receptor-Expressing Medial Prefrontal Cortex Neurons Reveals Contributions to Emotional Regulation.
Glycogen synthase kinase 3β (GSK3β) activity is regulated by dopamine D2 receptor signaling and can be inhibited by psychoactive drugs in a D2 receptor-dependent manner. However, GSK3β is ubiquitously expressed in the brain, and D2 receptor-expressing cells are distributed as a mosaic in multiple cortical regions. This complicates the interrogation of GSK3β functions in cortical D2 cells in a circuit-defined manner using conventional animal models. We used a CRISPR-Cas9-mediated intersectional approach to achieve targeted deletion of GSK3β in D2-expressing neurons of the adult medial prefrontal cortex (mPFC). Isolation and analysis of ribosome-associated RNA specifically from mPFC D2 neurons lacking GSK3β demonstrated large-scale translatome alterations. Deletion of GSK3β in mPFC D2 neurons revealed its contribution to anxiety-related, cognitive, and social behaviors. Our results underscore the viability of an intersectional knockout approach to study functions of a ubiquitous gene in a network-defined fashion while uncovering the contribution of GSK3β expressed in mPFC D2 neurons in the regulation of behavioral dimensions related to mood and emotions. This advances our understanding of GSK3β action at a brain circuit level and can potentially lead to the development of circuit selective therapeutics.


Regulation of firearm dealers in the United States: an analysis of state law and opportunities for improvement.
Firearms were associated with 30, 136 deaths in the United States in 2003. Most guns are initially sold to the public through a network of retail dealers. Licensed firearm dealers are an important source of guns for criminals and gun traffickers. Just one percent of licensed dealers were responsible for more than half of all guns traced to crime. Federal law makes it difficult for ATF to inspect and revoke the licenses of problem gun dealers. State licensing systems, however, are a greatly under-explored opportunity for firearm dealer oversight. We identify and categorize these state systems to identify opportunities for interventions to prevent problem dealers from supplying guns to criminals, juveniles, or gun traffickers. Just seventeen states license gun dealers. Twenty-three states permit routine inspections of dealers but only two mandate that those inspections occur on a regular basis. Twenty-six states impose record-keeping requirements for gun sales. Only thirteen states require some form of store security measures to minimize firearm theft. We conclude with recommendations for a comprehensive system of state licensing and oversight of gun dealers. Our findings can be useful for the coalition of more than fifty U.S. mayors that recently announced it would work together to combat illegal gun trafficking.


Molecular interactions underlying the unusually high adenosine affinity of a novel Trypanosoma brucei nucleoside transporter.
Trypanosoma brucei encodes a relatively high number of genes of the equilibrative nucleoside transporter (ENT) family. We report here the cloning and in-depth characterization of one T. brucei brucei ENT member, TbNT9/AT-D. This transporter was expressed in Saccharomyces cerevisiae and displayed a uniquely high affinity for adenosine (Km = 0.068 +/- 0.013 microM), as well as broader selectivity for other purine nucleosides in the low micromolar range, but was not inhibited by nucleobases or pyrimidines. This selectivity profile is consistent with the P1 transport activity observed previously in procyclic and long-slender bloodstream T. brucei, apart from the 40-fold higher affinity for adenosine than for inosine. We found that, like the previously investigated P1 activity of long/slender bloodstream trypanosomes, the 3'-hydroxy, 5'-hydroxy, N3, and N7 functional groups contribute to transporter binding. In addition, we show that the 6-position amine group of adenosine, but not the inosine 6-keto group, makes a major contribution to binding (DeltaG0 = 12 kJ/mol), explaining the different Km values of the purine nucleosides. We further found that P1 activity in procyclic and long-slender trypanosomes is pharmacologically distinct, and we identified the main gene encoding this activity in procyclic cells as NT10/AT-B. The presence of multiple P1-type nucleoside transport activities in T. brucei brucei facilitates the development of nucleoside-based treatments for African trypanosomiasis and would delay the onset of uptake-related drug resistance to such therapy. We show that both TbNT9/AT-D and NT10/AT-B transport a range of potentially therapeutic nucleoside analogs.


Slow Release of Plant Volatiles Using Sol-Gel Dispensers.
The black citrus aphid, also known as the tea aphid, (Toxoptera aurantii Boyer) attacks economically important crops, including tea (Camellia sinensis (L.) O. Kuntze). In the current study, silica sol-gel formulations were screened to find one that could carry and release C. sinensis plant volatiles to lure black citrus aphids in a greenhouse. The common plant volatile trans-2-hexen-1-al was used as a model molecule to screen for suitable sol-gel formulations. A zNose (Electronic Sensor Technology, Newbury Park, CA) transportable gas chromatograph was used to continuously monitor the volatile emissions. A sol-gel formulation containing tetramethyl orthosilicate and methyltrimethoxysilane in an 8:2 (vol:vol) ratio was selected to develop a slow-release dispenser. The half-life of trans-2-hexen-1-al in the sol-gel dispenser increased slightly with the volume of this compound in the dispenser. Ten different volatiles were tested in the sol-gel dispenser. Alcohols of 6-10 carbons had the longest half-lives (3.01-3.77 d), while esters of 6-12 carbons had the shortest (1.53-2.28 d). Release of these volatiles from the dispensers could not be detected by the zNose after 16 d (cis-3-hexenyl acetate) to 26 d (3,7-dimethylocta-1,6-dien-3-ol). In greenhouse experiments, trans-2-hexen-1-al and cis-3-hexen-1-ol released from the sol-gel dispensers attracted aphids for ≍17 d, and release of these volatiles could not be detected by the zNose after ≍24 d. The sol-gel dispensers performed adequately for the slow release of plant volatiles to trap aphids in the greenhouse.


Assessment of Addiction Medicine Training in Family Medicine Residency Programs: A CERA Study.
Substance use disorder (SUD) is a widespread problem but physicians may feel inadequately prepared to provide addiction care. We sought to assess current addiction medicine curricula in US family medicine residencies (FMRs) and evaluate barriers to improving or implementing addiction medicine curricula. Questions regarding addiction medicine training were added to the December 2015 Council of Academic Family Medicine Educational Research Alliance (CERA) survey to US FMR program directors to evaluate each FMR's curriculum, potential workforce production, perceived barriers to improving or implementing curricula and faculty training in addiction medicine. Of 461 FMR directors, 227 (49.2%) responded; 28.6% reported a required addiction medicine curricula. Regional variations of having a required curriculum ranged from 41.3% in the Northeast to 20.0% in the South (P=0.07). Of residencies, 31.2% had at least one graduate obtain a buprenorphine prescription waiver in the past year and 8.6% had at least one graduate pursue an addiction medicine fellowship in the past 5 years. Lack of faculty expertise was the most commonly cited barrier to having a curriculum, with only 36.2% of programs having at least one buprenorphine waivered faculty member, 9.4% an addiction medicine board certified faculty, and 5.5% a fellowship trained faculty. Few FMRs have addiction medicine curricula and most graduates do not seek additional training. Multifaceted efforts, including developing model national curricula, training existing faculty, and recruiting addiction trained faculty, may improve addiction medicine training in family medicine residencies to better address the growing SUD epidemic.


Bacterial cyanogenesis: impact on biotic interactions.
The ability of bacteria to influence organisms that they associate with via metabolite production is one of the hallmarks of microbial interactions. One metabolite of interest is the metabolic poison cyanide. Production of this metabolite is an unique characteristic of certain bacteria that inhabit a wide array of habitats ranging from the human body to the rhizosphere. This review focuses on four targets of cyanogenic bacteria: the human lung, plant pathogens, plants and invertebrates. For a number of cyanogenic bacteria, the contribution of cyanide to the interaction has been rigorously tested using mutants altered in cyanide production. Both deleterious and stimulatory effects of cyanogenic bacteria on other organisms have been documented. In addition, the HCN synthase-encoding gene cluster hcnABC has served as a marker of cyanogenic capability in the soil environment revealing both genetic diversity at this locus and regulatory influences by other organisms. The pervasive nature of cyanogenesis in a number of different ecological contexts encourages exploration of this bacterial ability and its possible optimization for improving human health, crop production and pest control.


Emerging epidemic diseases of frogs in Britain are dependent on the source of ranavirus agent and the route of exposure.
A series of transmission studies was conducted to investigate the aetiology, or aetiologies, of emerging fatal epidemic disease syndromes affecting the common frog (Rana temporaria) in Britain. The syndromes, characterized by skin ulceration or systemic haemorrhages, were induced upon exposure to lesion homogenates or cultured ranavirus. The re-isolation of ranavirus from experimentally affected frogs fulfilled Koch's postulates. Aeromonas hydrophila, previously associated with similar lesions, was not significant to disease development. Unexpectedly, disease outcomes were influenced by both the source of agent and the route of exposure, indicating that different ranaviruses with different tissue tropisms and pathogeneses (possibly similar to quasi-species in RNA virus populations) are circulating in the British common frog population. Our findings confirm that ranavirus disease has emerged as an important cause of amphibian mortality in Britain.


Coexistence of diffuse large B-cell lymphoma, acute myeloid leukemia, and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient: A case report.
The Coexistence of myeloid and lymphoid malignancies is rare. Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies. Synchronous diagnoses of diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in the same patient have not been reported. Here we report one such case. An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL. The bone marrow and peripheral blood contained two groups of cells. One group of cells fulfilled the criteria of AML, and the other revealed the features of small B lymphocytic proliferative disorder, which we considered LPL/WM. Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells, including ATM deletion, CCND1 amplification, mutations of MYD88 (L265P) and TP53, WT1 overexpression, and fusion gene of BIRC2-ARAP1, as well as complex chromosomal abnormalities. The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis. The coexistence of DLBCL, AML, and untreated LPL/WM in the same patient is extremely rare, which probably results from multiple steps of genetic abnormalities. Asymptomatic LPL/WM might have occurred first, then myelodysplastic syndrome-related AML developed, and finally aggressive DLBCL arose. Therefore, medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.


Brønsted acid-catalyzed cascade cycloisomerization of enynes via acetylene cations and sp3-hybridized C-H bond activation.
A novel Brønsted acid-catalyzed cascade cycloisomerization of cyclic and acyclic enynes via acetylene cation cyclization followed by cleavage of the entirely inactive C(sp(3))-H bond is described. The reaction proceeds efficiently under mild conditions to afford various tri- and bicyclic compounds in good to high yields.


Identification and validation of PCSK9 as a prognostic and immune-related influencing factor in tumorigenesis: a pan-cancer analysis.
Proprotein convertase subtilisin/kexin-9 (PCSK9) has been primarily studied in the cardiovascular field however, its role in cancer pathophysiology remains incompletely defined. Recently, a pivotal role for PCSK9 in cancer immunotherapy was proposed based on the finding that PCSK9 inhibition was associated with enhancing the antigen presentation efficacy of target programmed cell death-1 (PD-1). Herein, we provide results of a comprehensive pan-cancer analysis of PCSK9 that assessed its prognostic and immunological functions in cancer. Using a variety of available online cancer-related databases including TIMER, cBioPortal, and GEPIA, we identified the abnormal expression of PCSK9 and its potential clinical associations in diverse cancer types including liver, brain and lung. We also validated its role in progression-free survival (PFS) and immune infiltration in neuroblastoma. Overall, the pan-cancer survival analysis revealed an association between dysregulated PCSK9 and poor clinical outcomes in various cancer types. Specifically, PCSK9 was extensively genetically altered across most cancer types and was consistently found in different tumor types and substages when compared with adjacent normal tissues. Thus, aberrant DNA methylation may be responsible for PCSK9 expression in many cancer types. Focusing on liver hepatocellular carcinoma (LIHC), we found that PCSK9 expression correlated with clinicopathological characteristics following stratified prognostic analyses. PCSK9 expression was significantly associated with immune infiltrate since specific markers of CD8+ T cells, macrophage polarization, and exhausted T cells exhibited different PCSK9-related immune infiltration patterns in LIHC and lung squamous cell carcinoma. In addition, PCSK9 was connected with resistance of drugs such as erlotinib and docetaxel. Finally, we validated PCSK9 expression in clinical neuroblastoma samples and concluded that PCSK9 appeared to correlate with a poor PFS and natural killer cell infiltration in neuroblastoma patients. PCSK9 could serve as a robust prognostic pan-cancer biomarker given its correlation with immune infiltrates in different cancer types, thus potentially highlighting a new direction for targeted clinical therapy of cancers.


Periodic DFT Calculations-Review of Applications in the Pharmaceutical Sciences.
In the introduction to this review the complex chemistry of solid-state pharmaceutical compounds is summarized. It is also explained why the density functional theory (DFT) periodic calculations became recently so popular in studying the solid APIs (active pharmaceutical ingredients). Further, the most popular programs enabling DFT periodic calculations are presented and compared. Subsequently, on the large number of examples, the applications of such calculations in pharmaceutical sciences are discussed. The mentioned topics include, among others, validation of the experimentally obtained crystal structures and crystal structure prediction, insight into crystallization and solvation processes, development of new polymorph synthesis ways, and formulation techniques as well as application of the periodic DFT calculations in the drug analysis.


Atom Interferometric Imaging of Differential Potentials Using an Atom Laser.
Interferometry is a prime technique for modern precision measurements. Atoms, unlike light, have significant interactions with electric, magnetic, and gravitational fields, making their use in interferometric applications particularly versatile. Here, we demonstrate atom interferometry to image optical and magnetic potential landscapes over an area exceeding 240 μm×600 μm. The differential potentials employed in our experiments generate phase imprints in an atom laser that are made visible through a Ramsey pulse sequence. We further demonstrate how advanced pulse sequences can enhance desired imaging features, e.g., to image steep potential gradients. A theoretical discussion is presented that provides a semiclassical analysis and matching numerics.


Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria.
Biofilms are surface-attached groups of microbial cells encased in an extracellular matrix that are significantly less susceptible to antimicrobial agents than non-adherent, planktonic cells. Biofilm-based infections are, as a result, extremely difficult to cure. A wide range of molecular mechanisms contribute to the high degree of recalcitrance that is characteristic of biofilm communities. These mechanisms include, among others, interaction of antimicrobials with biofilm matrix components, reduced growth rates and the various actions of specific genetic determinants of antibiotic resistance and tolerance. Alone, each of these mechanisms only partially accounts for the increased antimicrobial recalcitrance observed in biofilms. Acting in concert, however, these defences help to ensure the survival of biofilm cells in the face of even the most aggressive antimicrobial treatment regimens. This review summarises both historical and recent scientific data in support of the known biofilm resistance and tolerance mechanisms. Additionally, suggestions for future work in the field are provided.


Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor.
A high resolution structure of alpha-conotoxin EI has been determined by (1)H NMR spectroscopy and molecular modeling. alpha-Conotoxin EI has the same disulfide framework as alpha 4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the alpha 3/5 and alpha A conotoxins. The unique binding preference of alpha-conotoxin EI to the alpha(1)/delta subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various alpha-conotoxins possessing distinct receptor subtype specificities. Structural comparison of alpha-conotoxin EI with the gamma-subunit favoring alpha-conotoxin GI suggests that the Torpedo delta-subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven alpha-conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is approximately 20 A (height) x 20 A (width) x 15 A (thickness).


Feasibility and Acceptability of a Group Music Intervention in Memory Care Communities.
Music-based interventions have been shown to reduce behavioral expressions among persons with dementia. The goal of this study was to examine the feasibility and acceptability of a group music intervention to reduce agitation. Two memory care communities were recruited to participate in this single-arm mixed-methods study. The group music intervention program included a total of 12 sessions delivered over 4 weeks. Agitation was assessed quantitatively at weeks 0, 2, and 4. Qualitative interviews of memory care staff were conducted post-intervention. Data were analyzed using linear mixed-effects models and qualitative content analysis. The study sample (N = 19) had a mean age of 82.74, and 73.7% were female. The great majority of participants completed the intervention and 63.2% experienced a reduction in agitation, suggesting that the intervention is feasible and acceptable in memory care and may be efficacious. Future research should evaluate the efficacy of the intervention in a randomized controlled trial.