Genetic variability and individual assignment of Chinese indigenous sheep populations (Ovis aries) using microsatellites.
The purpose of this study was to assess the genetic characteristics of six breeds of Chinese local sheep using 19 microsatellite loci and to effectively validate statistical methods for individual assignment based on informative microsatellites. All the six breeds deviated from Hardy-Weinberg equilibrium expectations, while the majority of markers complied. The polymorphism information content (PIC) of overall loci for the six populations ranged from 0.283 (SRCRSP5) to 0.852 (OarVH72). Tibetan sheep were the most diverse population with the highest mean allelic richness (6.895), while Ujmuqin (UQ) harboured the lowest allelic richness (6.000). The F-statistics for the six populations were F(IS) = -0.172, F(IT) = -0.082 and F(ST) = 0.077, respectively. Furthermore, the pair-wise F(IS) revealed a moderate genetic differentiation among populations (P < 0.01), indicating that all breeds can be considered genetically independent entities. The lowest genetic differentiation was between Tengchong (TC) and UQ (F(ST) = 0.041), and the highest one was between TC and Fat-tailed Han (F(ST) = 0.111). In comparing the three statistical models, we note that the seven microsatellite loci (MAF65, OarJMP58, SRCRSP9, MCM140, OarAE129, BM8125 and SRCRSP5) commonly used for individual assignment will ensure a powerful detection of individual origin, with accuracy up to 91.87%, when the likelihood-based method is used. Overall, these findings shed light onto the genetic characteristics of Chinese indigenous sheep and offer a set of microsatellite loci that is simple, economic and highly informative for individual assignment of Chinese sheep.


Effect of soluble interleukin-6 receptor alpha and interleukin-6 secreted by polymorphonuclear leukocytes on tumor necrosis factor-alpha expression and its production by peripheral blood mononuclear cells.
It has recently been shown that soluble interleukin-6 receptor (sIL-6R) alone or complexed with interleukin (IL)-6, besides their regulatory role in a wide variety of both normal and abnormal biologic reactions mediated by IL-6, could be an effective stimulator of the cell function. The key question of the present study is whether the sIL-6Ralpha or sIL-6R with IL-6 released by polymorphonuclear leukocytes (PMN) can influence cytokine secretion such as tumor necrosis factor-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC), which together with PMN develop the inflammatory and immune response of a host. Cells were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 1 h at 37 degrees C in 5% CO(2). After incubation, the culture supernatant of PMN was removed and was added to PBMC. The PBMC were cultured for 1 h at 37 degrees C in the same conditions. In the culture supernatants and lysates of PMN, we examined the concentrations of sIL-6R by enzyme-linked immunosorbent assay (ELISA). TNF-alpha was measured at both protein and mRNA levels. Protein levels were determined by ELISA. To examine TNF-alpha mRNA expression, we isolated mRNA from PBMC after culture, using TRIZOL Reagent. The quantity of mRNA TNF-alpha was determined by the Quantikine mRNA assay. The results obtained revealed that sIL-6R with IL-6 secreted by PMN may play a regulatory role in the immune response by modulating the TNF-alpha expression and its production by PBMC. This may have a significant influence on an early phase of the inflammation and other reactions mediated by TNF-alpha.


[Simultant laparoscopic operations for biliary calculi disease and hernia of the anterior abdominal wall].
The results of treatment of patients, in whom biliocalculous disease and hernia of anterior abdominal wall were diagnosed, were analyzed. The main aspects of diagnosis and prognosis of simultant operations in such patients, some technical procedures of operative interventions were depicted. Indications for performance of simultant completely laparoscopic and simultant laparoscopic combined operations in these patients were determined.


Structural variations, the regulatory landscape of the genome and their alteration in human disease.
High-throughput genomic technologies are revolutionizing human genetics. So far the focus has been on the 1.5% of the genome, which is coding, in spite of the fact that the great majority of genomic variants fall outside the coding regions. Recent efforts to annotate the non-coding sequence show that over 80% of the genome is biochemically active. The genome is divided into regulatory domains consisting of sequence regions that enhance and/or silence the expression of nearby genes and are, in some cases, separated by boundaries with insulator activity. In this paper, we review the recent advances in the identification of variations that influence gene regulation and their consequences for human disease. We hypothesize that structural variations outside of the coding genome can interfere with normal gene regulation by disrupting the regulatory landscape. Therefore, the regulatory landscape of the genome has also to be taken into consideration when investigating the pathology of human disease.


Detecting Immune Response to Therapies Targeting PDL1 and BRAF by Using Ferumoxytol MRI and Macrin in Anaplastic Thyroid Cancer.
Background Anaplastic thyroid cancer (ATC) is aggressive with a poor prognosis, partly because of the immunosuppressive microenvironment created by tumor-associated macrophages (TAMs). Purpose To understand the relationship between TAM infiltration, tumor vascularization, and corresponding drug delivery by using ferumoxytol-enhanced MRI and macrin in an ATC mouse model. Materials and Methods ATC tumors were generated in 6-8-week-old female B6129SF1/J mice through intrathyroid injection to model orthotopic tumors, or intravenously to model hematogenous metastasis, and prospectively enrolled randomly into treatment cohorts (n = 94 total; August 1, 2018, to January 15, 2020). Mice were treated with vehicle or combined serine/threonine-protein kinase B-Raf (BRAF) kinase inhibitor (BRAFi) and anti-PDL1 antibody (aPDL1). A subset was cotreated with therapies, including an approximately 70-nm model drug delivery nanoparticle (DDNP) to target TAM, and an antibody-neutralizing colony stimulating factor 1 receptor (CSF1R). Imaging was performed at the macroscopic level with ferumoxytol-MRI and microscopically with macrin. Genetically engineered BrafV600E/WT p53-null allografts were used and complemented by a GFP-transgenic derivative and human xenografts. Tumor-bearing organs were processed by using tissue clearing and imaged with confocal microscopy and MRI. Two-tailed Wilcoxon tests were used for comparison (≥five per group). Results TAM levels were higher in orthotopic thyroid tumors compared with pulmonary metastatic lesions by 79% ± 23 (standard deviation; P < .001). These findings were concordant with ferumoxytol MRI, which showed 136% ± 88 higher uptake in thyroid lesions (P = .02) compared with lung lesions. BRAFi and aPDL1 combination therapy resulted in higher tumor DDNP delivery by 39% ± 14 in pulmonary lesions (P = .004). Compared with the untreated group, tumors following BRAFi, aPDL1, and CSF1R-blocking antibody combination therapy did not show greater levels of TAM or DDNP (P = .82). Conclusion In a mouse model of anaplastic thyroid cancer, ferumoxytol MRI showed 136% ± 88 greater uptake in orthotopic thyroid tumors compared with pulmonary lesions, which reflected high vascularization and greater tumor-associated macrophage (TAM) levels. Serine/threonine-protein kinase B-Raf inhibitor and anti-programmed death ligand 1 antibody elicited higher local TAM levels and 43% ± 20 greater therapeutic nanoparticle delivery but not higher vascularization in pulmonary tumors. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Luker in this issue.


Safety of dried whole cell Euglena gracilis as a novel food pursuant to Regulation (EU) 2015/2283.
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of dried whole cell Euglena gracilis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. E. gracilis is a single-cell microalga which occurs widely in nature and is commonly found in freshwater habitats. The NF, the dried biomass of E. gracilis, is produced by fermentation and its major constituent (> 50%) is a β-glucan polysaccharide. The applicant proposed to use the NF in food supplements, in foods for total diet replacement for weight control and as a food ingredient added to a number of food products. The target population proposed by the applicant is the general population, except for food supplements and for foods for total diet replacement for which the target population is the general population from 12 months of age onwards. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS)-status with the qualification 'for production purposes only', which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e. 3,300 mg NF/kg body weight, considered as the no observed adverse effect level (NOAEL). The margins of exposure between this dose and the high (95th percentile) intake estimates, range from 33 for infants to 192 for adults. The Panel considers that in view of the QPS status of the source of the NF, supported by the compositional data and lack of toxicity observed in the 90-day study, the margins of exposure are sufficient. The Panel considers that the NF, i.e. dried whole cell Euglena gracilis, is safe at the proposed uses and use levels.


Seminal vesicle biopsies in the preoperative staging of prostatic cancer.
Twenty-five patients with localized prostate cancer underwent seminal vesicle biopsies before radical prostatectomy. A transrectal probe of 7 MHz, a 18-gauge needle and a biopsy gun were used. The preoperative biopsy established the absence of seminal vesicle invasion in 89% of cases. When the seminal vesicles are positive at biopsy, capsular penetration is observed in 100% of the cases and lymph node positivity in 50%. When seminal vesicles are negative at biopsy and the prostate-specific antigen level is less than 20 ng/ml (n less than 2.5), capsular penetration of greater than 1 cm is absent in 100% of cases and lymph nodes are positive in only 7% of cases. Biopsy of the seminal vesicle, as an outpatient procedure, improves the preoperative staging of prostate cancer before radical prostatectomy: negative biopsies are good predictors of the absence of lymph node invasion.


A fractal model of HIV transmission on complex socio-geographic networks. Part 2: spread from a ghettoized 'core group' into a 'general population'.
"Study of the initial stages of HIV transmission along a 'sociogeographic network'--a large, complex, spatially focused social network with possibly fractal geometry--is extended to include interaction between a low-dimensional ghettoized 'core group' within which the disease spreads very rapidly and a higher dimensional, more loosely structured 'general population' in which spread is relatively slow. A mathematical modeling exercise suggests that contextually modulated interaction between them can be highly nonlinear and may greatly increase the initial rate of disease transmission within the general population. This work contributes to a growing body of literature which suggests that programs to control HIV infection within the majority heterosexual population of the United States will fail spectacularly without particular focus on the coupled physical and social stabilization and rehabilitation of the urban ghettoes of marginalized populations which are the present, and rapidly expanding, disease epicenters. Evidence suggests their continued disintegration can both increase disease rates within the epicenters and increase the coupling between core groups and general populations by creating large numbers of spatially or economically displaced refugees."


Influence of acoustic masking noise in fMRI of the auditory cortex during phonetic discrimination.
The application of functional magnetic resonance imaging (fMRI) to study activation of auditory cortex suffers from one significant confounding factor, namely, that of the acoustic noise generated by the gradient system, which is an integral part of the imaging process. Earlier work has shown that it is indeed possible to distinguish cortical activation resulting from presentation of auditory stimuli despite the presence of background noise from the gradient system. The influence of acoustic noise from the gradient system of the MRI scanner on the blood oxygen level-dependent (BOLD) response during functional activation of the auditory cortex has been investigated in six healthy subjects with no hearing difficulties. Experiments were performed using gradient-echo echoplanar imaging (EPI) and a verbal, auditory discrimination paradigm, presented in a block-wise manner, in which carefully aligned consonant-vowel syllables were presented at a rate of 1 Hz. For each volunteer the experiment was repeated three times with all parameters fixed, except slice number, which was 4, 16, or 64. The positioning of the central four slices in each experiment was common. Thus, the fraction of TR during which the stimulus is on but no imaging is being performed, varies from almost zero, in the case of 64 slices, to over 8 seconds, in the case of four slices. Only the central four slices were of interest; additional slices simply generated acoustic noise and were discarded. During the four-slice experiment, all subjects showed a robust BOLD response in the superior temporal gyrus covering the primary and secondary auditory cortex. The spatial extent and the z-scores of the activated regions decreased with longer duration of gradient noise from the scanner. For a phonetic discrimination task, the results indicate that presentation of the stimulus during periods free from scanner noise leads to a more pronounced BOLD response.


Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer's Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation.
The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer's disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD. Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice. Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons. In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1 β (IL-1 β ) intracerebroventricularly into mice expressing human ACT, human tau, or both transgenes. It was found that the hyperphosphorylation of tau in ACT and ACT/htau mice after IL-1 β injection correlated with increased phosphorylation of c-Jun N-terminal kinase (JNK). We verified the involvement of JNK in ACT-induced tau phosphorylation by utilizing JNK inhibitors in cultured primary neurons treated with ACT, and we found that the inhibitor showed complete prevention of ACT-induced tau phosphorylation. These results indicate that JNK is one of the major kinases involved in the ACT-mediated tau hyperphosphorylation and suggest that inhibitors of this kinase may protect against inflammation-induced tau hyperphosphorylation and neurodegeneration associated with AD.


Design and evaluation of short-term monitoring campaigns for long-term air pollution exposure assessment.
Short-term mobile monitoring campaigns to estimate long-term air pollution levels are becoming increasingly common. Still, many campaigns have not conducted temporally-balanced sampling, and few have looked at the implications of such study designs for epidemiologic exposure assessment. We carried out a simulation study using fixed-site air quality monitors to better understand how different short-term monitoring designs impact the resulting exposure surfaces. We used Monte Carlo resampling to simulate three archetypal short-term monitoring sampling designs using oxides of nitrogen (NOx) monitoring data from 69 regulatory sites in California: a year-around Balanced Design that sampled during all seasons of the year, days of the week, and all or various hours of the day; a temporally reduced Rush Hours Design; and a temporally reduced Business Hours Design. We evaluated the performance of each design's land use regression prediction model. The Balanced Design consistently yielded the most accurate annual averages; while the reduced Rush Hours and Business Hours Designs generally produced more biased results. A temporally-balanced sampling design is crucial for short-term campaigns such as mobile monitoring aiming to assess long-term exposure in epidemiologic cohorts. Short-term monitoring campaigns to assess long-term air pollution trends are increasingly common, though they rarely conduct temporally balanced sampling. We show that this approach produces biased annual average exposure estimates that can be improved by collecting temporally-balanced samples.


Bilateral bifid mandibular canal: a case report using cone beam computed tomography.
The mandibular canal (MC) originates in the mandibular foramen and runs bilaterally through the mandibular ramus and body, ending in the mental foramen. One of the most common anatomical variations is bifid MC, the configurations of which have been classified into four categories and sub-categories. The prevalence of these variations depends on the imaging method used. Studies carried out in panoramic X-rays and cone beam computed tomography (CBCT) show prevalences varying between 1% and 20%. In this case report we present the finding of a bilateral bifid MC by CBCT examination; we describe its location and morphological characteristics. The variation found was a type 1 bilateral bifid MC, which consists in an accessory canal originating from a single mandibular foramen and extending to the third molar or its immediate surroundings. In this report we discuss the importance of detecting these anatomical variations, as well as their implications in clinical practice.


Evolutionary implications of primate endogenous retroviruses.
Endogenous DNA sequences related to retroviruses are probably present in all primates. By using approaches based on the polymerase chain reaction, two separate studies have revealed the evolutionary history of some of these sequences. In the first study, a retrovirus-like reverse transcriptase (RT) sequence homologous to that of Baboon endogenous virus (BaEV) has been identified in both Old World monkeys and African apes, but not in humans or Asian apes. This RT sequence is highly conserved at the amino acid level, but not the nucleotide level, in the baboon, African green monkey, Java macaque, chimpanzee, and gorilla. The patterns of nucleotide substitution indicate functional conservation and suggest that this RT sequence was present in the primate germline before apes and Old World monkeys diverged about 30 million years ago. In the second study, a comparison of endogenous proviral DNAs and their adjacent sequences has been used to analyze the evolutionary history of three previously reported human endogenous retroviruses, HERV-E(4.14), HERV-R(3), and HERV-Ia. It is shown that these retroviruses have also been resident in the primate line since before the ape-Old World monkey divergence. The implications of the presence of functionally conserved RT genes in the germlines of primates, and the potential for using integration sites as tools for analyzing phylogenetic relationships among primates and their retroviruses, are discussed.


Activity and nature of plasminogen activators associated with the casein micelle.
In fresh milk, plasminogen, the zymogen form of plasmin (PL), is the predominant form. Therefore, plasminogen activators (PA) can contribute significantly to PL activity in milk. Both tissue-type PA (tPA) and urokinase-type PA (uPA) exist in milk; however, contradictory findings have been reported for which type of PA is most closely associated with the casein micelles. Little is known about the factors that might lead to variations in the individual activities of the PA. The objective of this work was therefore to investigate possible factors that might affect the association of tPA and uPA with the casein micelle and their activities thereafter. Plasminogen activators were isolated from milk samples with different somatic cell counts following 2 different isolation protocols. Determination of uPA, tPA, and PL activities was carried out quantitatively following chromogenic assays using 2 different substrates, and qualitatively using specialized sodium dodecyl sulfate-PAGE. Different isolation methods and conditions led to differences in uPA, tPA, and PL activities. Urokinase-type PA activity was significantly higher in PA fractions isolated from milk with high somatic cell counts than from milk with low somatic cell counts. Activity results indicated that in pasteurized milk uPA could dissociate from the somatic cells and bind to casein. Moreover, a high level of PL in isolated PA fractions contributed to significantly enhanced PA activities. Overall, results confirmed the association of both uPA and tPA with the casein micelle; however, their amounts, activities, and molecular weights varied based on the nature of the milk and methods of separation, with uPA being the PA with greater potential to affect plasminogen activation in milk.


Evaluation of Arizona Health Care Cost Containment System, 1984-85.
In this article, we describe the evaluation of the Arizona Health Care Cost Containment System (AHCCCS), Arizona's alternative to the acute care portion of Medicaid. We provide an assessment of implementation of the program's innovative features during its second 18 months of operation, from April 1984 through September 1985. Included in the evaluation are assessments of the administration of the program, provider relations, eligibility, enrollment and marketing, information systems, quality assurance and member satisfaction activities, the relationship of the county governments to AHCCCS, the competitive bidding process, and the plans and their financial status.


Detecting the tipping points in a three-state model of complex diseases by temporal differential networks.
The progression of complex diseases, such as diabetes and cancer, is generally a nonlinear process with three stages, i.e., normal state, pre-disease state, and disease state, where the pre-disease state is a critical state or tipping point immediately preceding the disease state. Traditional biomarkers aim to identify a disease state by exploiting the information of differential expressions for the observed molecules, but may fail to detect a pre-disease state because there are generally little significant differences between the normal and pre-disease states. Thus, it is challenging to signal the pre-disease state, which actually implies the disease prediction. In this work, by exploiting the information of differential associations among the observed molecules between the normal and pre-disease states, we propose a temporal differential network based computational method to accurately signal the pre-disease state or predict the occurrence of severe disease. The theoretical foundation of this work is the quantification of the critical state using dynamical network biomarkers. Considering that there is one stationary Markov process before reaching the tipping point, a novel index, inconsistency score (I-score), is proposed to quantitatively measure the change of the stationary processes from the normal state so as to detect the onset of pre-disease state. In other words, a drastic increase of I-score implies the high inconsistency with the preceding stable state and thus signals the upcoming critical transition. This approach is applied to the simulated and real datasets of three diseases, which demonstrates the effectiveness of our method for predicting the deterioration into disease states. Both functional analysis and pathway enrichment also validate the computational results from the perspectives of both molecules and networks. At the molecular network level, this method provides a computational way of unravelling the underlying mechanism of the dynamical progression when a biological system is near the tipping point, and thus detecting the early-warning signal of the imminent critical transition, which may help to achieve timely intervention. Moreover, the rewiring of differential networks effectively extracts discriminatively interpretable features, and systematically demonstrates the dynamical change of a biological system.


Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain.
By acting in the central nervous system, circulating insulin may regulate food intake and body weight. We have previously shown that the kinetics of insulin uptake from plasma into cerebrospinal fluid (CSF) can best be explained by passage through an intermediate compartment. To determine if transport kinetics into this compartment were consistent with an insulin receptor-mediated transport process, we subjected overnight fasted, anesthetized dogs to euglycemic intravenous insulin infusions for 90 min over a wide range of plasma insulin levels (69-5,064 microU/ml) (n = 10). Plasma and CSF samples were collected over 8 h for determination of immunoreactive insulin levels, and the kinetics of insulin uptake from plasma into CSF were analyzed using a compartmental model with three components (plasma-->intermediate compartment-->CSF). By sampling frequently during rapid changes of plasma and CSF insulin levels, we were able to precisely estimate three parameters (average standard deviation 14%) characterizing the uptake of insulin from plasma, through the intermediate compartment and into CSF (k1k2); insulin entry into CSF and insulin clearance from the intermediate compartment (k2 + k3); and insulin clearance from CSF (k4). At physiologic plasma insulin levels (80 +/- 7.4 microU/ml), k1k2 was determined to be 10.7 x 10(-6) +/- 1.3 x 10(-6) min-2. With increasing plasma levels, however, k1k2 decreased progressively, being reduced sevenfold at supraphysiologic levels (5,064 microU/ml). The apparent KM of this saturation curve was 742 microU/ml (approximately 5 nM). In contrast, the rate constants for insulin removal from the intermediate compartment and from CSF did not vary with plasma insulin (k2 + k3 = 0.011 +/- 0.0019 min-1 and k4 = 0.046 +/- 0.021 min-1). We conclude that delivery of plasma insulin into the central nervous system is saturable, and is likely facilitated by an insulin-receptor mediated transport process.


Effects of cell cycle dependent histone H1 phosphorylation on chromatin structure and chromatin replication.
We have reconstituted salt-treated SV40 minichromosomes with differentially phosphorylated forms of histone H1 extracted from either G0-, S- or M-phase cells. Sedimentation studies revealed a clear difference between minichromosomes reconstituted with S-phase histone H1 compared with histone H1 from G0- or M-phase cells, indicating that the phosphorylation state of histone H1 has a direct effect on chromatin structure. Using reconstituted minichromosomes as substrate in the SV40 in vitro replication system, we measured a higher replication efficiency for SV40 minichromosomes reconstituted with S-phase histone H1 compared with G0- or M-phase histone H1. These data indicate that the chromatin structure induced by the phosphorylation of histone H1 influences the replication efficiency of SV40 minichromosomes in vitro.


[Hsp70-H22 tumor antigen peptide complex activated dendritic cell in the induction of antitumor immunity].
To investigate the feasibility of reduction in tumor antigen peptide dose by dendritic cell (DC)-presenting so as to elucidate the characteristics of modifying DC by heat shock protein (Hsp70) and antigen peptide. Antigen peptide bound to Hsp70 was used to modify DC in vitro. The metabolism of the modified DC and the cytokine secreted thereby was determined. Then the activation of lymphocytes by the modified DC and Hsp70-H22 peptide was tested. The cytotoxicity of the activated lymphocytes to H22 tumor cells and the inhibition of tumor in mice by DC injection and Hsp70-H22 peptide was tested. 0.15 micro g of H22 peptide bound to Hsp70 could mature 2 x 10(5) DC. 4 x 10(3) matured DC could activate 2 x 10(6) lymphocytes. The same amount of lymphocyte could be activated to produce similar cytotoxicity to tumor cells by either DC modified by 0.003 micro g of peptides bound with Hsp70 or by direct stimulation with 0.15 micro g of peptides bound to Hsp70. The dose of peptide could be reduced to 1/50 if the modified DC injection was used instead of direct Hsp70-peptide injection. Peptide from the normal hepatocytes, if bound to Hsp70, could not mature DC, nor could it activate lymphocytes through DC. The dose of Hsp70-H22 peptides can be reduced significantly by DC-presenting to activate lymphocytes. Peptides from normal cells, being unable to activate the lymphocytes by either Hsp70-presenting or DC-presenting, have little to offer in the induction of autoimmunity.


Aggressive rectal lymphoma of large granular lymphocytes with the histologic feature of an angiocentric growth pattern.
The authors report an unusual large cell lymphoma of the rectum composed of large granular lymphocytes (LGL) with histologic characteristics of an angiocentric growth pattern. Immunophenotyping showed that most of the tumor cells were CD3-, CD4-, CD8+, CD16+, CD56+, and CD57-. Fine structural analysis of the tumor cells found substantial numbers of electron-dense granules. Genotypic investigation showed a germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene. The clinical course was aggressive, with rapid dissemination to the lungs, liver, and subcutis. The lesion was resistant to chemotherapy. There was, however, no evidence for peripheral blood or bone marrow involvement. This case report demonstrates the need for continued inquiry into the possible association of LGL with angiocentric lymphoproliferative lesions and gut-associated T-lymphocyte lesions.


Drug-dependent antibodies with immune hemolytic anemia in AIDS patients.
We studied the presence of drug-dependent antibodies (D-DAbs) in 53 patients with AIDS who developed immune hemolytic anemia (IHA). We examined sera and eluates for the presence of D-DAbs. Drug antibodies were detected in 43.4 percent (23/53) of the patients with IHA. Antibodies to more than one drug were detected in 60.8 percent (14/23) of patients with drug-induced IHA (D-IHA). The DAT was positive by RBC-bound IgG in eight patients, RBC-bound IgG/C3d in nine, IgG/IgA in three, IgG/IgA/C3d in two, and one patient had RBC-bound C3d only. No drug-independent antibodies were detected. Our study demonstrates that patients with AIDS commonly develop D-DAbs. D-IHA should be included in the differential diagnosis of a falling Hb in AIDS patients receiving drugs.


Development and validation of the numeracy understanding in Medicine Instrument short form.
Health numeracy can be defined as the ability to understand and use numeric information and quantitative concepts in the context of health. The authors previously reported the development of the Numeracy Understanding in Medicine Instrument (NUMi), a 20-item test developed using item response theory. The authors now report the development and validation of a short form of the NUMi. Item statistics were used to identify a subset of 8 items representing a range of difficulty and content areas. Internal reliability was evaluated with Cronbach's alpha. Divergent and convergent validity was assessed by comparing scores of the S-NUMI with existing measures of education, print and numeric health literacy, mathematic achievement, cognitive reasoning, and the original NUMi. The 8-item scale had adequate reliability (α=.72) and was strongly correlated to the 20-item NUMi (α=.92). S-NUMi scores were strongly correlated with the Lipkus Expanded Health Numeracy Scale (α=.62), the Wide Range of Achievement Test-Mathematics (α=.72), and the Wonderlic Cognitive Ability Test (α=.76). Moderate correlation was found with education level (α=.58) and print literacy as measured by the Test of Functional Health Literacy in Adults (α=.49). Results show that the short form of the NUMi is a reliable and valid measure of health numeracy feasible for use in clinical and research settings.


Characterization of Non-O157 Shiga Toxin-Producing Escherichia coli Cultured from Cattle Farms in Xinjiang Uygur Autonomous Region, China, During 2016-2017.
Most outbreaks of Shiga toxin-producing Escherichia coli (STEC) are attributed to consumption of contaminated foodstuffs including beef and dairy products. In this study, we evaluated the prevalence of non-O157 STEC cultured from beef and dairy cattle and collected in Xinjiang Uygur Autonomous Region in China. Results identified 67 non-O157 STEC recovered from the 793 samples including beef cattle (10.28%, 43/418) and dairy cattle (6.40%, 24/375). A total of 67 non-O157 STEC was sequenced allowing for in silico analyses of their serotypes, virulence genes, and identification of the corresponding multilocus sequence types (STs). Twenty-one O serogroups and nine H serotypes were identified and the dominant serotype identified was O22:H8. One stx1 subtype (stx1a) and four stx2 subtypes (2a, 2b, 2c, and 2d) were found in the 67 non-O157 STEC isolates. The results revealed that stx1a+stx2a-positive STEC isolates were predominant (32.83%, 22/67), followed by stx1a+stx2d (29.85%, 20/67) and stx2a alone (17.91%, 12/67). Non-O157 STEC isolates carried virulence genes ehxA (98.51%), subA (53.73%), and cdtB (17.91%). Of the four adherence-associated genes tested, eaeA was absent, whereas lpfA and iha were present in 67 and 55 non-O157 STEC isolates, respectively. The STEC isolates were divided into 48 pulsed-field gel electrophoresis patterns and 10 STs, and ST446 (O22:H8) was the dominant clone (22.38%). Our results revealed that there was a high genetic diversity among non-O157 STEC isolated from beef and dairy cattle, some of which have potential to cause human diseases.


The geographic distribution of physicians revisited.
While there is debate over whether the U.S. is training too many physicians, many seem to agree that physicians are geographically maldistributed, with too few in rural areas. Official definitions of shortage areas assume the market for physician services is based on county boundaries. We wished to ascertain how the picture of a possible shortage changes using alternative measures of geographic access. We measure geographic access by the number of full-time equivalent physicians serving a community divided by the expected number of patients (possibly both from within the community and outside) receiving care from those physicians. Moreover, we wished to determine how the geographic distribution of physicians had changed since previous studies, in light of the large increase in physician numbers. Cross-sectional data analyses of alternative measures of geographic access to physicians in 23 states with low physician-population ratios. Between 1979 and 1999, the number of physicians doubled in the sample states. Although most specialties experienced greater diffusion everywhere, smaller specialties had not yet diffused to the smallest towns. Multiple measures of geographic access, including physician-to-population ratios, average distance traveled to the nearest physician, and projected average caseload per physician, confirm that residents of metropolitan areas have better geographic access to physicians. Physician-to-population ratios exhibit the largest degree of geographic disparity, but ratios in rural counties adjacent to metropolitan areas are smaller than in those not adjacent to metropolitan areas. Distance-traveled and caseload models that allow patients to cross county lines show less disparity and indicate that residents of isolated rural counties have less access than those living in counties adjacent to metropolitan areas. Geographic access to physicians has continued to improve over the past two decades, although some smaller specialties have not diffused to the most rural areas. While substantial variation in the supply of physicians across communities remains, current measures of geographic access to physicians overstate the extent of maldistribution and yield an incorrect ranking of areas according to geographic accessibility of physicians.


Quality and reporting of guidelines on the diagnosis and management of dystonia.
The quality of clinical practice guidelines on dystonia has not yet been assessed. Our aim was to appraise the methodological quality of guidelines worldwide and to analyze the consistency of their recommendations. We searched for clinical practice guidelines on dystonia diagnosis/treatment in the National Guideline Clearinghouse, PubMed, National Institute for Health and Care Excellence, Guidelines International Network and Web of Science databases. We also searched for guidelines on homepages of international neurological societies. We asked for guidelines from every Management Committee member of the BM1101 Action of the Cooperation between Science and Technology European framework and every member of the International Parkinson and Movement Disorders Society with special interest in dystonia. Fifteen guidelines were evaluated. Among guidelines on treatment, only one from the American Academy of Neurology could be considered as high quality. Among guidelines on diagnosis and therapy, the guideline from the European Federation of Neurological Societies was recommended by the appraisers. Clinical applicability and reports of editorial independence were the greatest shortcomings. The rigor of development was poor and stakeholder involvement was also incomplete in most guidelines. Discrepancies among recommendations may result from the weight given to consensus statements and expert opinions due to the lack of evidence, as well as inaccuracy of disease classification. The quality of appraised guidelines was low. It is necessary to improve the quality of guidelines on dystonia, and the applied terminology of dystonia also needs to be standardized.


Sodium Selenite Modulates IDO1/Kynurenine, TLR4, NF-κB and Bcl2/Bax Pathway and Mitigates Acetic Acid-Induced Colitis in Rat.
Colitis is a main presentation of inflammatory bowel disease (IBD) and yet, has no definitive cure. Currently, corticosteroids, anti-tumor necrosis factor (anti-TNF) agents and 5-aminosalicylic acid derivatives are prescribed for management of colitis. Except their failure rate, they are not always tolerated because of their severe adverse effects. Additive formulas with fewer adverse effects may improve the treatment of colitis. In this study, colitis was induced with intra-rectal injection of three concentrations of acetic acid (4, 6 and 8 v/v). Each group received sodium selenite (0.5 mg/kg) or saline, gavaged on days 0 and 1 for treatment. Two days after induction of colitis, rats were sacrificed and the end part of their colons were resected for macroscopic and microscopic evaluation and molecular measurement. Sodium selenite improved macroscopic and microscopic view of the colon, decreased cryptitis, crypt abscess and inflammatory cells infiltration and partly maintained mucosal structure. Sodium selenite markedly reduced tissue levels of malondialdehyde (MDA), TNF-α and interferon γ (INF-γ) and decreased myeloperoxidase (MPO) activity. Treatment with sodium selenite also significantly downregulated IL17, IL22, indoleamine 2,3-dioxygenase (IDO1), and kynurenine levels. Western blotting revealed that sodium selenite prevented apoptosis by increasing bcl2/Bax ratio. Furthermore, our findings showed that sodium selenite significantly downregulated the upstream inflammatory molecules such as nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) in colitis. These findings show that sodium selenite alleviates inflammatory response and oxidative stress and protects against colitis.


Differences in health-related quality of life between three clusters of physical activity, sitting time, depression, anxiety, and stress.
Physical inactivity, sitting behaviour, and mental health problems are detrimental to health-related quality of life but typically are considered as independent determinants. This study tested how these factors clustered together as profiles of subgroups of people and whether the clusters differed as a function of physical and mental health-related quality of life. In 2012, Australian adults (N =1,014) self-reported their physical and mental health-related quality of life, physical activity, sitting time, depression, anxiety, and stress using a web-based survey. Cluster analysis was used to identify subgroups of health behaviour and mental health profiles, and ANOVA was used to test for between-cluster differences in health-related quality of life. Three subgroups were identified: people with higher psychological stress (n =13%), people with higher amounts of sitting time (n =45%), and people with lower amounts of sitting time (n =42%). There were no differences in mental health-related quality of life between subgroups; however people represented by the subgroup of higher amounts of sitting time had significantly lower physical health-related quality of life than the other two subgroups, F(2, 1011) =10.04, p < .01. Interventions should consider that (1) physical activity, sitting time, and psychological distress are aspects of multifaceted behavioural-psychological profiles, and (2) reductions of sitting time may have major impacts for physical health-related quality of life.


Tunneled lumbar drain. Technical note.
The authors report a simple and rapid procedure for tunneling a lumbar drain subcutaneously to facilitate chronic cerebrospinal fluid (CSF) drainage. A standard lumbar puncture (LP) is performed with a large-bore Tuohy needle (14- to 16-gauge), the drainage catheter is advanced into the subarachnoid space, and the needle is removed. The free Tuohy needle is then passed from a lateral position and brought out through the initial LP site. The free catheter is fed through the needle, and the needle is removed. The drain is attached to an external drainage bag in the usual manner. The authors have found this method particularly useful in some skull base and spinal surgical applications in which longer term continuous CSF drainage is desired.


[Qualitative and quantitative analysis on crocins in fruits of Gardenia species].
The aim of this study was to compare crocins in the fruit of Gardenia jasminoides and Gardenia jasminoides var. radicans. Acchrom XCharge C_(18) column(4.6 mm×250 mm, 5 μm) was used for separation, with mobile phase of acetonitrile and 0.1% formic acid for gradient elution. The detection wavelength was set at 440 nm with a flow rate of 1.0 mL·min~(-1), and the column temperature was 30 ℃. The high performance liquid chromatography(HPLC) fingerprint of crocin in Gardenia species was established by testing 20 batches of G. jasminoides and 8 batches of G. jasminoides var. radicans samples from different sources, and UHPLC-ESI-Orbitrap-MS/MS technology and reference substances were used to predict and identify the common peaks. The results showed that 20 common chromatographic peaks from the samples were selected and the structures of 16 common peaks were predicted by mass spectrum. Four common peaks(crocin Ⅰ, Ⅱ, Ⅲ, and Ⅳ) were identified by the comparison with reference substances. The content of crocin Ⅰ, Ⅱ, Ⅲ, and Ⅳ was determined simultaneously under the same chromatographic condition, and both the system suitability and the methodological investigation results met the requirements of content determination. The relative similarity of HPLC fingerprint of 28 samples to the reference fingerprint was above 0.98. The results of cluster analysis(CA) showed that G. jasminoides and G. jasminoides var. radicans were separately grouped into one group. In the 20 batches of G. jasminoides, the content of crocin Ⅰ, Ⅱ, Ⅳ, and Ⅲ was between 3.58-9.58, 0.230-1.452, 0.014 5-0.135, and 0.301-1.12 mg·g~(-1), respectively, and the total content was between 4.12-12.25 mg·g~(-1). In the 8 batches of G. jasminoides var. radicans, the content of crocin Ⅰ, Ⅱ, Ⅳ, and Ⅲ was between 5.84-11.48, 0.308-0.898, 0.010 6-0.025 5, and 0.675-1.34 mg·g~(-1), respectively, and the total content was between 6.97-13.72 mg·g~(-1). The existing results showed that there is a certain similarity between G. jasminoides and G. jasminoides var. radicans in the composition of crocin, which needs further proved by more batches of samples. The method established in this paper provides references for the quality control of G. jasminoides, G. jasminoides var. radicans, and related products.


MiR-381 functions as a tumor suppressor in colorectal cancer by targeting Twist1.
MiR-381 has been reported to be dysregulated in several human cancers. However, the function and mechanism of miR-381 in colorectal cancer (CRC) remains unclear. In the present study, the miR-381 expression was assessed in a cohort of 113 CRC specimens using real-time quantitative polymerase chain reaction (RTq-PCR), which demonstrated that miR-381 was significantly downregulated in CRC and correlated with distant metastasis and tumor, node, and metastasis (TNM) stage. Functional study revealed that restoration of miR-381 significantly inhibited the invasion, migration, and epithelial-mesenchymal transition (EMT) of CRC cells. Luciferase reporter assay validated that Twist1, an important EMT inducer, was a direct target of miR-381, and rescued Twist1 attenuated the function of miR-381 in CRC cells. Correlation analysis also revealed an inverse correlation between miR-381 and Twist1 expression levels in CRC specimens. Taken together, our results highlight the significance of miR-381/Twist1 interaction in the development and progression of CRC, and suggest that restoration of miR-381 may be a potential therapeutic strategy for the patients with CRC.


Dietary polyunsaturated fatty acids and aging modulate glutathione-related antioxidants in rat liver.
The effects of dietary polyunsaturated fatty acids (PUFA) on the age-dependent changes in liver glutathione antioxidant system were investigated in male Wistar rats fed diets supplying either balanced amounts of linoleic acid and alpha-linolenic acids (control) or deficient in alpha-linolenic acid [n-3) deficient]. The animals were studied at the age of 6 or 24 mo. Glutathione antioxidative metabolism was markedly affected by aging. Cytosolic concentration of reduced glutathione (GSH) was lower (P < 0.01), whereas that of oxidized glutathione (GSSG) as well as the GSSG:GSH ratio were greater (P<0.001) in the 24-mo-old as compared with the 6-mo-old rats, regardless of the diet. Glutathione peroxidase activities were lower (P < 0.001) in 24-mo-old rats, though more markedly in those fed the control diet. The lipid composition of rat liver microsomal membranes was strongly modified by both diet and aging. The age-related changes mainly involved the polyunsaturated fatty acids. These results suggest that the nature of dietary PUFA and not only their degree of unsaturation affects the cellular glutathione-dependent antioxidant system and thus may modify the age-related changes in metabolic reactions.


Evaluation of 5-year imatinib treatment of 458 patients with CP-CML in routine clinical practice and prognostic impact of different BCR-ABL cutoff levels.
We evaluated responses to the treatment and long-term outcomes of chronic myeloid leukemia patients treated with imatinib as first-line treatment in routine clinical setting from two countries with centralized tyrosine kinase inhibitors (TKIs) treatment. We assessed prognostic significance of European LeukemiaNet (ELN) 2006- and 2009-defined responses and the prognostic value of molecular responses at defined time points on 5-year survivals. Among the cumulative rates of incidence of hematologic, cytogenetic, and molecular responses and all important survival parameters, we evaluated the prognostic significance of different BCR-ABL transcript-level ratios (≤1%; >1%-≤10%; >10%) at 3, 6, 12, and 18 months (n = 199). The ELN optimal response criteria and their predictive role were significantly beneficial for event-free survival at all given time points. We found significant improvement in survivals of patients with BCR-ABL lower than 10% in the 6th and 12th months. Significantly better outcome was found in patients who achieved major molecular response (MMR) in the 12th month. The cumulative incidences of complete cytogenetic response (CCyR) and MMR were significantly associated with the molecular response in the 3rd month. The ELN response criteria and their predictive role were helpful at given time points; however, the 2009 definition did not significantly alter the prognostic accuracy compared with that of the 2006 definition. The significant value was observed for cytogenetic responses at the 6th and 12th month. Moreover, progression-free and event-free survivals were improved with MMR at the 12th month.


Antibacterial agents in renal failure.
This article provides background information on the pharmacokinetics of antimicrobial agents in patients with normal and impaired renal function. Tables are provided to allow quick determination of appropriate dosages for varying degrees of renal failure. Specific mention is made of aminoglycoside dosing, dosage adjustment in dialysis, and antibiotic toxicity in renal failure.


Human Trafficking ICD-10 Code Utilization in Pediatric Tertiary Care Centers Within the United States.
Human trafficking is a global public health issue that affects pediatric patients widely. The International Labor Organization estimates children comprise approximately 25% of the identified trafficked persons globally, with domestic estimates including over 2000 children a year. Trafficked children experience a broad range of health consequences leading to interface with healthcare systems during their exploitation. In June 2018, International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) released diagnostic codes for human trafficking. To use a large, multicenter database of US pediatric hospitalizations to describe the utilization of the ICD-10-CM codes related to child trafficking, as well as the demographic and clinical characteristics of these children. This study was descriptive in nature. Encounters using data from the Pediatric Health Information System database (PHIS) with ICD-10-CM codes indicating trafficking from June 1, 2018 to March 1st, 2020 were included in the study cohort, with data collection continuing for 30 days after first hospital encounter, until March 31st, 2020. Patients 19 years old and younger were included. Condition-specific prevalence as well as demographic and clinical characteristics for patient encounters were analyzed. Study subjects were followed for 30 days after first hospital encounter to describe healthcare utilization patterns. During the study period, 0.005% (n = 293) of patient encounters in the PHIS database were identified as trafficked children. The children of our cohort were mostly female (90%), non-Hispanic Black (38%), and had public insurance (59%). Nearly two-thirds of patients (n = 190) had a documented mental health disorder at the initial encounter, with 32.1% classified as the principal diagnosis. Our cohort had a 30-day hospital inpatient, overnight observation, or emergency department readmission rate of 16% (n = 48). Our study demonstrates a low utilization of human trafficking ICD-10-CM codes in academic children's health centers, with code usage predominantly assigned to Non-Hispanic Black teenage girls. As comparison, in 2019 the National Human Trafficking Hotline identified 2,582 trafficked US children in a single year. These results suggest widespread under-recognition of child trafficking in health care settings, including the intensive care unit, in addition to racial and socioeconomic disparities amongst trafficked children.


Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone.
Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proinflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl(+/+)) and MBL-deficient (Mbl(-/-)) mice were exposed to ozone (0.3 ppm) for up to 72 h, and bronchoalveolar lavage fluid was examined for inflammatory markers. Mean numbers of eosinophils and neutrophils and levels of the neutrophil attractants C-X-C motif chemokines 2 [Cxcl2 (major intrinsic protein 2)] and 5 [Cxcl5 (limb expression, LIX)] in the bronchoalveolar lavage fluid were significantly lower in Mbl(-/-) than Mbl(+/+) mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in transcript response profiles and networks at baseline [e.g., nuclear factor erythroid-related factor 2 (NRF2)-mediated oxidative stress response] and after exposure (e.g., humoral immune response) between Mbl(+/+) and Mbl(-/-) mice. The microarray data were further analyzed to discover several informative differential response patterns and subsequent gene sets, including the antimicrobial response and the inflammatory response. We also used the lists of gene transcripts to search the LINCS L1000CDS(2) data sets to identify agents that are predicted to perturb ozone-induced changes in gene transcripts and inflammation. These novel findings demonstrate that targeted deletion of Mbl caused differential levels of inflammation-related gene sets at baseline and after exposure to ozone and significantly reduced pulmonary inflammation, thus indicating an important innate immunomodulatory role of the gene in this model.


Contrast-enhanced spectral mammography in recalls from the Dutch breast cancer screening program: validation of results in a large multireader, multicase study.
Contrast-enhanced spectral mammography (CESM) is a promising problem-solving tool in women referred from a breast cancer screening program. We aimed to study the validity of preliminary results of CESM using a larger panel of radiologists with different levels of CESM experience. All women referred from the Dutch breast cancer screening program were eligible for CESM. 199 consecutive cases were viewed by ten radiologists. Four had extensive CESM experience, three had no CESM experience but were experienced breast radiologists, and three were residents. All readers provided a BI-RADS score for the low-energy CESM images first, after which the score could be adjusted when viewing the entire CESM exam. BI-RADS 1-3 were considered benign and BI-RADS 4-5 malignant. With this cutoff, we calculated sensitivity, specificity and area under the ROC curve. CESM increased diagnostic accuracy in all readers. The performance for all readers using CESM was: sensitivity 96.9 % (+3.9 %), specificity 69.7 % (+33.8 %) and area under the ROC curve 0.833 (+0.188). CESM is superior to conventional mammography, with excellent problem-solving capabilities in women referred from the breast cancer screening program. Previous results were confirmed even in a larger panel of readers with varying CESM experience. • CESM is consistently superior to conventional mammography • CESM increases diagnostic accuracy regardless of a reader's experience • CESM is an excellent problem-solving tool in recalls from screening programs.


Assessment of historical exposures to talc at a mining and milling facility.
The purpose of this study was to develop an estimate of exposure to respirable dust for all job categories and all years in a retrospective follow-up study of worker mortality in a talc mining and milling facility. All jobs were assigned to work areas that were considered to have similar exposure profiles. Uniform exposure time periods during which non-random, deterministic variables were thought to be constant were identified and an experienced rater assigned categorical exposure scores to each work area/time period. These scores and measured baseline respirable dust concentrations were used to calculate the estimated job area/year concentrations for each work area/time period. Estimates were compared to available historical measurements. The estimated exposures ranged from 1.7 to 0.1 mg/m(3) and displayed a decreasing trend over time. When compared with measured exposures, the estimated exposures had a correlation coefficient of 0.55 with an average difference of 0.01 mg/m(3) and a range of 0.60 to -0.48 mg/m(3). The estimates were considered to be acceptable for determining relative ranking of subjects according to cumulative exposure.


Extraction, Enrichment, and LC-MSn-Based Characterization of Phlorotannins and Related Phenolics from the Brown Seaweed, Ascophyllum nodosum.
Phenolic components from the edible brown seaweed, Ascophyllum nodosum, have been associated with considerable antioxidant activity but also bioactivities related to human health. This study aims to select and identify the main phlorotannin components from this seaweed which have been previously associated with potential health benefits. Methods to enrich phenolic components then further select phlorotannin components from ethanolic extracts of Ascophyllum nodosum were applied. The composition and phenolic diversity of these extracts were defined using data dependent liquid chromatography mass spectroscopic (LC-MSn) techniques. A series of phlorotannin oligomers with apparent degree of polymerization (DP) from 10 to 31 were enriched by solid phase extraction and could be selected by fractionation on Sephadex LH-20. Evidence was also obtained for the presence of dibenzodioxin linked phlorotannins as well as sulphated phlorotannins and phenolic acids. As well as diversity in molecular size, there was evidence for potential isomers at each DP. MS2 fragmentation analyses strongly suggested that the phlorotannins contained ether linked phloroglucinol units and were most likely fucophlorethols and MS3 data suggested that the isomers may result from branching within the chain. Therefore, application of these LC-MSn techniques provided further information on the structural diversity of the phlorotannins from Ascophyllum, which could be correlated against their reported bioactivities and could be further applied to phlorotannins from different seaweed species.


A Case of COVID-19 With Memory Impairment and Delayed Presentation as Stroke.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen with remarkable properties of multisystem involvement and numerous complications. The coronavirus disease of 2019 (COVID-19) presenting as stroke is becoming more common. Herein, we describe an unusual case of COVID-19 in a patient who initially presented with myalgia, fatigue, loss of taste and smell, and non-specific memory impairment. Two months after infection with SARS-CoV-2, the patient presented with acute onset of right-sided weakness, sensory loss, and worsening cognitive impairment. Reverse transcription-polymerase chain reaction was performed to detect the SARS-CoV-2 virus, and the results were positive at the time of initial infection as well as during the current admission. Neuroimaging suggested a subacute ischemic infarct in the middle cerebral artery. The patient was re-tested for SARS-CoV-2 and found to be positive, but the cycle threshold was high (40.4) along with a positive test for immunoglobulin-G (IgG) for SARS-CoV-2. This report highlights a unique case of stroke-related to COVID-19 infection in a middle-aged woman with otherwise mild symptomatic illness. The patient had a chronic ischemic stroke with delayed presentation two months after the initial symptomatic viral infection. This case underscores the importance of neurological assessment as well as timely evaluation of patients presenting with COVID-19 and any neurological concerns to recognize stroke as a complication of COVID-19 promptly.


Farnesyltransferase--new insights into the zinc-coordination sphere paradigm: evidence for a carboxylate-shift mechanism.
Despite the enormous interest that has been devoted to the study of farnesyltransferase, many questions concerning its catalytic mechanism remain unanswered. In particular, several doubts exist on the structure of the active-site zinc coordination sphere, more precisely on the nature of the fourth ligand, which is displaced during the catalytic reaction by a peptide thiolate. From available crystallographic structures, and mainly from x-ray absorption fine structure data, two possible alternatives emerge: a tightly zinc-bound water molecule or an almost symmetrical bidentate aspartate residue (Asp-297beta). In this study, high-level theoretical calculations, with different-sized active site models, were used to elucidate this aspect. Our results demonstrate that both coordination alternatives lie in a notably close energetic proximity, even though the bidentate hypothesis has a somewhat lower energy. The Gibbs reaction and activation energies for the mono-bidentate conversion, as well as the structure for the corresponding transition state, were also determined. Globally, these results indicate that at room temperature the mono-bidentate conversion is reversible and very fast, and that probably both states exist in equilibrium, which suggests that a carboxylate-shift mechanism may have a key role in the farnesylation process by assisting the coordination/displacement of ligands to the zinc ion, thereby controlling the enzyme activity. Based on this equilibrium hypothesis, an explanation for the existing contradictions between the crystallographic and x-ray absorption fine structure results is proposed.


Tracking historical sources of polycyclic aromatic compounds (PACs) in dated lake sediment cores near in-situ bitumen operations of Cold Lake, Alberta.
Most bitumen in the Alberta oil sands (Canada) is extracted by thermal in-situ recovery. Despite the widespread use of in-situ bitumen extraction, little information is available on the release of petroleum hydrocarbons by this method to adjacent land and water. Here we analyzed the composition and abundance of parent and alkylated polycyclic aromatic compounds (PACs) in 11 radiometrically-dated lake sediment cores collected near in-situ operations at Cold Lake Alberta to assess potential petroleum contamination sources to surrounding lakes over the past century. Like open-pit mining areas, alkylated PACs in Cold Lake sediments were elevated compared to unsubstituted parent PACs and increased coeval with the onset of bitumen extraction in the area. Diagnostic ratios and pyrogenic indices showed that PAC sources to these lake sediments were dominantly pyrogenic, likely from historic forest fires, however they shifted to more petrogenic sources coeval with expanding oil sands extraction at Cold Lake. PACs in sediment from regional lakes are weakly correlated to their proximity to in-situ oil wells, once corrected for lake area. These results suggest that in-situ operations, via diesel-fueled vehicular emissions and the combustion of natural gas for steam generation, are a source of PACs to nearby lakes, but PACs did not exceed Canadian sediment quality guidelines for the protection of aquatic life.


Personal, Social and Cultural Predictors of Intention to Misuse Prescription Stimulants among Medical Students: A Test of the Theory of Triadic Influence.
The misuse of prescription stimulants among students has been identified as a public health problem. To date, most research has focused on individual-level determinants of stimulant misuse, making research on the socio-cultural context of students' misuse a priority. This study aims to test the applicability of the Theory of Triadic Influence, capturing three influence streams (personal, social and cultural) and three causational levels (ultimate, distal and proximal). A questionnaire on stimulant misuse was distributed among all bachelor's and master's students from the five Flemish medical faculties. In total, 3159 students participated (48.99% response rate). Data were analyzed using structural equation modeling. Multiple personal (i.e., fear of failure, procrastination, self-perceived ADHD, sensation-seeking, academic stress, controllability), social (i.e., living situation, peer endorsement, social norm) and cultural (i.e., competitive study-environment, financial worries, positive and negative expectancies, attitude) factors were identified as risk factors of misuse intention. The strongest ultimate to distal pathway was found between self-perceived ADHD and positive expectancies, meaning that students who believed they have ADHD, although not diagnosed, were more likely to have positive expectancies about stimulants. Moreover, the strongest distal to proximal pathways were found between expectancies and attitudes toward stimulant misuse (i.e., more positive and fewer negative expectancies were associated with more favorable attitudes). Finally, attitudes were most strongly related to misuse intention. The current study shows that the TTI is an important framework to understand the risk factors of stimulant misuse among medical students. This study offers a strong basis for prevention initiatives.


Pathological identification of HER2-low breast cancer: Tips, tricks, and troubleshooting for the optimal test.
The introduction of novel anti-HER2 antibody-drug conjugates (ADC) for the treatment of HER2-low breast cancers has transformed the traditional dichotomy of HER2 status to an expanded spectrum. However, the identification of HER2-low (i.e., immunohistochemistry (IHC) score 1 + or IHC score 2+, without gene amplification) tumors is challenged by methodological and analytical variables that might influence the sensitivity and reproducibility of HER2 testing. To open all possible therapeutic opportunities for HER2-low breast cancer patients the implementation of more accurate and reproducible testing strategies is mandatory. Here, we provide an overview of the existing barriers that may trouble HER2-low identification in breast cancer and discuss practical solutions that could enhance HER-low assessment.


Interleukin-1 expression by neutrophils in rheumatoid arthritis.
To determine if neutrophils from blood and synovial fluid of patients with rheumatoid arthritis and other joint arthropathies express interleukin-1 beta mRNA. RNA was isolated from neutrophils from patient and control blood, and synovial fluid of patients, probed in northern blots, and quantified by densitometry. It was also isolated and analysed from control blood neutrophils after incubation in vitro with granulocyte macrophage colony stimulating factor (GM-CSF). Neutrophils from the synovial fluid of patients with rheumatoid arthritis contained low levels of mRNA for interleukin-1 beta--between 0.1 and 2% of those observed during stimulation of control neutrophils with GM-CSF for one hour. Higher levels (4-40% of the maximal GM-CSF values) were observed in blood neutrophils from patients with rheumatoid arthritis. Neutrophils contribute to the cytokine network in rheumatoid arthritis. In some circumstances, activation of transcription may occur within the circulation of these patients.


Plasmodium falciparum.
Plasmodium falciparum is a protozoan parasite that causes the most severe form of human malaria. Five other Plasmodium species can also infect humans - P. vivax, P. malariae, P. ovale curtisi, P. ovale wallikeri and P. knowlesi - but P. falciparum is the most prevalent Plasmodium species in the African region, where 90% of all malaria occurs, and it is this species that causes the great majority of malaria deaths. These were reported by the WHO at 438 000 in 2015 from an estimated 214 million cases; importantly, however, figures for the global burden of malaria tend to have wide margins of error due to poor and inaccurate reporting. In this Perspective, features of P. falciparum that are unique among human malaria parasites are highlighted, and current issues surrounding the control and treatment of this major human pathogen are discussed.


Rehabilitation of reading in older individuals with macular degeneration: a review of effective training programs.
Macular degeneration (MD) is the most common cause of visual impairment among older adults. It severely affects reading performance. People with MD have to rely on peripheral vision for reading. In this review, we considered several training programs that aim to improve peripheral reading, with a focus on eccentric viewing, oculomotor control, or perceptual learning. There was no strong support in favor of one particular training method for rehabilitation of reading in MD, but there is evidence that older individuals with MD can be trained to improve reading performance, even within limited time.


Internet based clinical trial protocols -- as applied to a study of warfarin pharmacogenetics.
To describe and evaluate the use of an Internet-based study protocol in a multicentre study of genetic risk factors in anticoagulant treatment. A web-based study protocol, similar to existing anticoagulation medical record systems, was developed for entry of clinical data. It was also supplied with a separate interface for study monitoring. Measures were taken to assure the confidentiality of transferred data. In addition, software modifications were made to enable automated transfer of clinical data from an existing medical record system to the study database. The system has been in use since March 2002, and at present 39 centres have included 909 patients with a dropout rate of 2.8%. The need for education of participating clinicians has been satisfactorily provided for by means of written instructions and telephone support. Our study demonstrates the usability of Internet-based data acquisition techniques in a full-scale multicentre clinical trial. The main advantages of such a protocol are automated data validation and standardization, fast data transfer independent of geographical distance, user feedback, synchronization of protocol updates and automatic data formatting facilitating statistical analyses. Safety and accessibility are possibly cumbersome areas and should be addressed duly.


Trends and determinants of early initiation of breastfeeding and exclusive breastfeeding in Ethiopia from 2000 to 2016.
At the national level in Ethiopia, there is limited knowledge of trends and factors associated with early initiation of breastfeeding and exclusive breastfeeding (EBF), particularly during the Millenium Development Goal (MDG) era (2000-2015). The study aimed to examine the trends and determinants of early initiation of breastfeeding and EBF in Ethiopia between 2000 and 2016. Using the Ethiopia Demographic and Health Survey (EDHS) data for the years: 2000 (n = 3680), 2005 (n = 3528), 2011 (n = 4037) and 2016 (n = 3861), trends in early initiation of breastfeeding and EBF were estimated. Multivariate logistic regression models that adjusted for confounders, sampling weight, clustering and stratification were used to examine the association between socioeconomic, demographic, health service and community level factors with early initiation of breastfeeding and EBF from 2000 to 2016. The prevalence of early initiation of breastfeeding increased from 48.8% in 2000 to 75.7% in 2016 in Ethiopia. Improvement in EBF prevalence was not statistically significant (from 54.5% in 2000 to 59.9% in 2016). Over the study period, informal maternal employment (Adjusted Odds Ratio [aOR] 0.75; 95% Confidence Interval [CI] 0.68, 0.83), frequent antenatal care visits (aOR 0.74; 95% CI 0.65, 0.85), and cesarean birthing (aOR 0.22; 95% CI 0.17, 0.30) were associated with delayed initiation of breastfeeding. Birthing in the health facility (aOR 1.35; 95% CI 1.05, 1.75) and residing in the metropolis region (aOR 1.95; 95% CI 1.65, 2.32) were associated with timely initiation of breastfeeding. In a similar period, informally employed mothers (aOR 1.37; 95% CI 1.15, 1.63) and those with six or more family size (aOR 1.46; 95% CI 1.10, 1.93) were more likely to exclusively breastfeed their babies. Early initiation of breastfeeding improved in Ethiopia during the MDG era but it is still below the national target; progress in EBF remained slow. To improve breastfeeding outcomes and meet the global breastfeeding targets in Ethiopia, infant feeding efforts should focus on improving key modifiable factors, including place and mode of birthing and socioeconomic status of mothers.


[Screening for attention deficit hyperactivity disorder in adult patients in primary care].
AIMS. To estimate the proportion of adult patients in primary care with a positive screening test for attention deficit hyper-activity disorder (ADHD) and to analyse their characteristics. PATIENTS AND METHODS. A cross-sectional descriptive study was performed in nine primary care clinics in the province of Tarragona. The sample consisted of 432 consecutive patients in primary care who visited for any reason, with ages ranging from 18 to 55 years. Screening for ADHD was carried out by means of the Adult ADHD Self-Report Scale (ASRS). Data about functional impact (Sheehan Disability Inventory) were obtained and a review of the patient records provided data concerning psychiatric comorbidity and the consumption of psychopharmaceuticals. RESULTS. The percentage of positive results in the screening tests was 19.9% (95% CI = 16.4-23.9%). Taking into account the sensitivity and specificity of the ASRS, the 'real' prevalence was estimated to be 12.5% (95% CI = 8.2-16.8%). None of these patients were diagnosed or treated for ADHD. Positive screening tests are associated with occupational, social and familial dysfunction, and greater perceived stress. There is also a higher level of comorbidity with affective disorders and substance abuse, as well as greater use of psychopharmaceuticals. CONCLUSIONS. Screening for ADHD in adult patients in primary care gives rise to a notably high proportion of positive screening test results, which suggests that there could be a significant prevalence of patients with ADHD. These data contrast with the absence of this diagnosis in the patient records. Further research is needed to determine the usefulness of the diagnosis of ADHD and the possible role that must be played by primary care.


Carotid intima-media thickness--a potential predictor for rupture risk of intracranial aneurysms.
Individual assessment of rupture risk of cerebral aneurysms is challenging, and increased knowledge of predictors for aneurysm rupture is needed. Smoking and hypertension are shared risk factors for atherosclerotic disease and cerebral aneurysms, and patients with atherosclerosis have an increased prevalence of intracranial aneurysms. Carotid ultrasound with evaluation of intima-media thickness (IMT) is a non-invasive, safe, rapid, well-validated and reproducible technique for quantification of subclinical atherosclerosis and assessment of cardio- and cerebrovascular risk. Increased IMT is associated with elevated risk for ischemic stroke and myocardial infarction, but sparse data exist on carotid ultrasound findings in patients with intracranial aneurysms. The purpose of this study was to investigate carotid IMT in patients with unruptured intracranial aneurysms (UIA) and aneurysmal subarachnoid hemorrhage (aSAH), and to assess if IMT might be associated with aneurysm rupture risk. Patients treated for saccular aneurysms (UIA and aSAH) from February 2011 to August 2012 were included. Standardized high resolution B-mode ultrasound assessment of carotid arteries was done after aneurysm treatment, and traditional vascular risk factors were recorded. Healthy partners of young patients with ischemic stroke were used as controls. 69 patients treated for UIA (n=28) and aSAH (n=41) were compared with 80 controls. Mean IMT was higher in patients with aSAH (0·79 mm) than patients with UIA (0·65 mm) and controls (0·63 mm). Multiple multinomial regression analysis comparing aSAH, UIA and control groups demonstrated that IMT was the only variable predicative of aSAH compared to UIA. According to the multiple regression model, the probability of having aSAH compared to non-rupture increased by 62% for each 0·10 mm increment of mean IMT (RRR=1·62, P=0·017). Taking into account only patients harboring intracranial aneurysms, simple binary logistic regression was then applied to the UIA and aSAH groups. According to this model the risk of belonging to the aSAH group increased with higher mean IMT values (OR=1·40 per 0·10 mm increase of mean IMT, P=0·024). There is an association between IMT and intracranial aneurysm rupture status at the time of aneurysm treatment. Carotid IMT can be a potential predictor of aneurysm rupture. IMT may thus be a possible adjunct in the risk assessment of aneurysm rupture, and a helpful tool in patient risk stratification and counseling.


Cellular signaling in the bladder.
Embryologically, the urinary bladder is formed from endodermally derived epithelial cells and mesenchymal cells from the urogenital sinus and allantois. Experimentally, we have shown that bladder mesenchyme differentiates into bladder smooth muscle via an unknown signaling mechanism that originates from the urothelium. It is hypothesized that this signaling between the cellular types, occurs via growth factors. Evidence supporting this hypothesis is that a number of known growth factors, such as TGF beta 2 and 3, KGF and TGF alpha, as well as their receptors are regulated as a function of bladder development and are also modulated during experimental bladder outlet obstruction. Furthermore, growth factors most likely affect extracellular matrix degradative proteins which play a role in bladder remodeling during development, as well as in partial outlet obstruction. There is certainly impressive cellular communication that occurs during development and also occurs postnatally; such as during bladder injury. We have recently shown that KGF is directly responsible for the proliferation of urothelium during bladder injury. This normally quiescent cell, which in humans turns over once every six months to a year when injured, has the incredible ability to immediately proliferate covering the exposed areas of bladder muscle and submucosa. This proliferation is due to the direct effects of KGF, a classic paracrine growth factor which is secreted by the stromal compartment of the bladder and acts directly on the urothelium which harbors the receptor. The bladder also has an uncanny ability to regenerate. In a model to study the basic science behind bladder regeneration, a partial cystectomy was performed and an acellular tissue matrix devoid of all cellular elements was sutured to the defect. Within four days, the urothelium completely covered the acellular matrix, and within two weeks native smooth muscle was seen streaming into the acellular matrix in association with a new epithelium. It is hypothesized that cellular interactions between the epithelium and the mesenchyme, as we have shown in bladder differentiation, are encouraging the new growth of smooth muscle. For the bladder to be a safe and effective storage chamber the ideal cellular lining should be urothelium. Cells from the gastrointestinal are not optimal for this purpose since they either secrete or absorb electrolytes. We believe that the cellular interactions that occur between the urothelium and the foreign intestinal stroma will in time change the phenotype of the urothelium. Newer strategies for bladder replacement which take into account cellular signaling are critical for our young patients with neurogenic bladder disorders.


Role of octreotide in the prevention of postoperative complications following pancreatic resection.
Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.


Primary health services in Ecuador: comparative costs, quality, and equity of care in Ministry of Health and rural social security facilities.
This study of costs, quality and financial equity of primary health services in Ecuador, based on 1985 data, examines three assumptions, common in international health, concerning Ministry of Health (MOH) and Social Security (SS) programs. The assumptions are that MOH services are less costly than SS services, that they are of lower quality than SS services, and that MOH programs are more equitable in terms of the distribution of funds available for PHC among different population groups. Full costs of a range of primary health services were estimated by standard accounting techniques for 15 typical health care establishments, 8 operated by the MOH and 7 by the rural SS program (RSSP), serving rural and peri-urban populations in the two major geographical regions of Ecuador. Consistent with the conventional premise, MOH average costs were much lower than RSSP costs for several important types of services, especially those provided by physicians. Little difference was found for dental care. The lower MOH physician service costs appeared to be attributable primarily to lower personnel compensation (only partially offset by lesser productivity) and to greater economies of scope. Several measures of the quality of care were applied, with varying results. Based on staff differences and patterns of expenditures on resource inputs, notably drugs, RSSP quality appeared higher, as assumed. However, contrary to expectation, a questionnaire assessment of staff knowledge and procedures favored the MOH for quality. Program equity was judged in terms of per capita budgeted expenditures (additional measures, such as the likelihood of receiving necessary care, would have required household survey data beyond the scope of this program-based study). The results support the assumption of greater MOH financial equity, as its program reveals less variation in budgeted expenditures between different population groups covered. Additional evidence of equity, using other indicators, would be helpful in future research. The paper's findings have policy implications not only for Ecuador's health sector but also for policy-makers in other countries at similar levels of socioeconomic development. These implications are spelled out in order to guide officials wrestling with issues of efficiency, quality, and equity as they search for the best use of scarce resources to promote health.


Ice hockey players using a weighted implement when training on the ice: a randomized control trial.
The purpose of this study was to investigate the potential for improving hockey players'performance using a weighted implement on the ice. Forty-eight players were tested using a grip strength dynamometer They also were assessed on their abilities to stick-handle. The participants were randomly placed into a control or research group. The conditioning drills were performed for 10-15 min 3 days/week for 6 weeks. Use of the weighted implement resulted in a significantly enhanced grip strength endurance and stick-handling ability (p < .05). Using weighted implements prior to a regular ice hockey training session may be of benefit to young hockey players to enhance their grip strength endurance and stick-handling abilities.


A Gibberellin-Deficient Brassica Mutant-rosette.
A single-gene mutant (rosette [ros/ros]) in which shoot growth and development are inhibited was identified from a rapid cycling line of Brassica rapa (syn campestris). Relative to normal plants, the mutant germinated slowly, had delayed or incomplete floral development, and reduced leaf, petiole, and internode growth. The exogenous application of GA(3) by foliar spray or directly to the shoot tip of rosette resulted in rapid flowering, bolting (shoot elongation), and viable seed production. Shoots of rosette contained endogenous levels of total gibberellin (GA)-like substances (;Tan-ginbozu' dwarf rice assay) of about one-tenth of that of the normal rapid-cycling line of B. rapa which consisted almost entirely of a very nonpolar, GA-like substance which yielded GA(1) and GA(3) upon mild acid hydrolysis. In a normal rapid-cycling B. rapa line, the nonpolar putative GA(1) and GA(3) conjugates were present, but additionally, free GA(1) and GA(3) were abundant and identified by gas chromatography-mass spectrometry-selected ion monitoring. The quantities of free GA(1) and GA(3) in the normal line and in rosette were quantified by GC-MS-SIM using [(2)H(2)]GA(1) as an internal standard. Fourteen-day-old rosette and normal seedlings contained 5.3 and 23.2 ng GA(1) per plant, respectively. At day 21 the rosette plants contained 7.7 and 26.1 nanograms per plant of GA(1) and GA(3), while normal plants contained 31.1 and 251.5 nanograms per plant, respectively. Thus, normal plants contained from four to ten times higher levels of total GA-like substances, GA(1), or GA(3), than rosette. The ros allele results in reduced GA level, yielding the rosette phenotype whose delayed germination and flowering, and reduced shoot growth responses indicate a probable role for endogenous GA(1) and GA(3) in the regulation of these processes in Brassica.


Colossal Permittivity and Low Dielectric Loss of Thermal Oxidation Single-Crystalline Si Wafers.
In this work, thin SiO₂ insulating layers were generated on the top and bottom surfaces of single-crystalline silicon plates (n type) by thermal oxidation to obtain an insulator/semiconductor/insulator (ISI) multilayer structure. X-ray diffraction (XRD) pattern and scanning electron microscope (SEM) pictures implied that all of the synthesized SiO₂ layers were amorphous. By controlling the thermal oxidation times, we obtained SiO₂ layers with various thicknesses. The dielectric properties of silicon plates with different thicknesses of SiO₂ layers (different thermal oxidation times) were measured. The dielectric properties of all of the single-crystalline silicon plates improved greatly after thermal oxidation. The dielectric constant of the silicon plates with SiO₂ layers was approximately 10⁴, which was approximately three orders more than that of the intrinsic single-crystalline silicon plate (11.9). Furthermore, both high permittivity and low dielectric loss (0.02) were simultaneously achieved in the single-crystalline silicon plates after thermal oxidation (ISI structure).


Temperament profile in patients with central serous chorioretinopathy: a case-control study.
To assess temperament in patients with central serous chorioretinopathy (CSCR) compared to healthy controls. A total of 32 patients diagnosed with acute CSCR and 30 healthy controls matched by age and sex were assessed with the self-report Cloninger's Temperament and Character Inventory. Central serous chorioretinopathy was diagnosed based on fluorescein angiography and spectral optical coherence tomography. Significantly higher mean scores of harm avoidance in patients with CSCR were found. Differences also were noted in subscales of novelty-seeking and reward dependence. The patients with CSCR demonstrated less exploratory behaviors, higher risk avoidance, restraint, and low extravagance. They were more quick-tempered, disorganized, and easily frustrated, with a tendency to avoid negative and potentially harmful stimuli, less tolerance to frustration, higher level of insecurity, and higher level of anticipatory anxiety.


Conceptual and methodological aspects of relations between discrimination and health in epidemiological studies.
This article addresses conceptual and methodological aspects of the relations between discrimination and health from an epidemiological perspective. Definitions of discrimination and related constructs are reviewed, and the main theories underlying their association with health are presented. Scales developed to assess discrimination are discussed, in conjunction with a new instrument, devised to operationalize the concept in Brazilian epidemiological surveys. As a relatively unpredictable and uncontrollable source of psychosocial stress, discrimination has been consistently associated with adverse health outcomes and behaviors, particularly mental disorders, smoking, and alcohol use. However, progress in the area depends partly on dealing with aspects related to the assessment of the phenomenon, such as the definition of a construct map and simultaneous measurement of different types of discrimination. Research involving these aspects will enhance our understanding of discrimination and its health consequences, thus increasing our ability to reduce its social occurrence.


Ultrafast Evolution of B2E2g - X2E1g Conical Intersection of Benzene Cations by Strong Field Ionization-Photo Fragmentation.
Benzene cation is a prototypical complex system that exhibits ultrafast conical intersections of different electronic states located close to the Franck-Condon region, yet little information is available about the dynamics of the cationic excited states. Here we utilize femtosecond time-resolved strong field ionization-photo fragmentation (SFI-PF) method to prepare and probe the electronic states of benzene cations. The transient of both the parent ion and the daughter ions are obtained, which present distinct behaviors at different pulse energies of the SFI laser. The results provide the first experimental evidence of B2E2g-X2E1g ultrafast relaxation of benzene cation, which occurs in about 250-270 fs. Our study should pave the way to revealing the ultrafast photochemistry of complex molecular cations.


Comparative Analysis of Proteomes of a Number of Nosocomial Pathogens by KEGG Modules and KEGG Pathways.
Nosocomial (hospital-acquired) infections remain a serious challenge for health systems. The reason for this lies not only in the local imperfection of medical practices and protocols. The frequency of infection with antibiotic-resistant strains of bacteria is growing every year, both in developed and developing countries. In this work, a pangenome and comparative analysis of 201 genomes of Staphylococcus aureus, Enterobacter spp., Pseudomonas aeruginosa, and Mycoplasma spp. was performed on the basis of high-level functional annotations-KEGG pathways and KEGG modules. The first three organisms are serious nosocomial pathogens, often exhibiting multidrug resistance. Analysis of KEGG modules revealed methicillin resistance in 25% of S. aureus strains and resistance to carbapenems in 21% of Enterobacter spp. strains. P. aeruginosa has a wide range of unique efflux systems. One hundred percent of the analyzed strains have at least two drug resistance systems, and 75% of the strains have seven. Each of the organisms has a characteristic set of metabolic features, whose impact on drug resistance can be considered in future studies. Comparing the genomes of nosocomial pathogens with each other and with Mycoplasma genomes can expand our understanding of the versatility of certain metabolic features and mechanisms of drug resistance.


[In vivo studies of the main functional systems in the heteronemertean pilidium larva].
There is performed in vivo morphological study of the White Sea heteronemerteans belonging to the type of pilidium pyramidale (conussoidale). Based on the layer-by-layer microshooting with subsequent computer processing, development of the pilidium digestive, nervous, and muscle systems is described from the stage following at once the gastrula to the premetamorphose larva. Peculiarities of structural organization of the main functional systems are revealed depending on the larva size and the stage of formation of imaginal discs. It is first shown that even in the not completely formed pilidium, neurons are located not only in integuments and wall of the digestive tract, but also in the depth of cupola along the central muscle retractor. Their processes are distributed between the main body parts and organs by seeming to perform connections of the apical organ and central muscle retractor with the digestive tract, blades, and the nerve plexus of the cupola wall. In the digestive tract between pharynx and stomach in the formed pilidium, the sphincter is first revealed. It has been shown that in the course of larva development, the non-orderly arranged and poorly developed muscle fibers gradually form in the blade the fan-like, whereas in the cupola wall, the net-like structure.


Quantitation of serum 25(OH)D2 and 25(OH)D3 concentrations by liquid chromatography tandem mass spectrometry in patients with diabetes mellitus.
Vitamin D has been considered to regulate calcium and phosphorus homeostasis and to preserve skeletal integrity. Serum 25-hydroxyvitamin D (25(OH)D) is the best indicator of vitamin D levels. The association of serum 25(OH)D deficiency with increased risk of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) is controversial. We investigated serum 25(OH)D2 and 25(OH)D3 levels in diabetes patients by using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum 25(OH)D2 and 25(OH)D3 levels were measured with liquid chromatography tandem mass spectrometry in electrospray ionization positive mode. Chromatograms were separated using an ACE5 C18 column on a gradient of methanol. The total 25(OH)D levels were calculated as the sum of 25(OH)D3 and 25(OH)D2 levels. A total of 56 patients with T1DM and 41 patients with T2DM were enrolled in this study. There were 42 and 28 non-diabetic, age-matched volunteers who participated as the T1DM controls and the T2DM controls, respectively. The total 25(OH)D levels were lowest in the 21-40 age group. The levels of both 25(OH)D3 and the total 25(OH)D were significantly higher in the T1DM and T2DM groups than in the controls (p < 0.01 in T1DM and p < 0.05 in T2DM group, respectively). The 25(OH)D2 levels were only significantly higher in T1DM patients than in the controls. The percentages of vitamin D deficiency (total 25(OH)D less than 20 ng/mL) in the T1DM, T2DM, the T1DM controls and the T2DM controls were 7.1%, 0%, 14.3% and 3.6%, respectively. The percentages of vitamin D insufficiency (total 25(OH)D less than 30 ng/mL) in the T1DM, T2DM, the T1DM controls and the T2DM controls were 26.8%, 7.3%, 54.8% and 17.9%, respectively. The percentages of vitamin D deficiency and insufficiency were significantly lower in the T1DM patients than in the T1DM controls (p < 0.01). In the present study, both type 1 and type 2 diabetes patients had higher serum 25(OH)D levels and lower percentages of vitamin D deficiency/insufficiency.


Sharing pro-marijuana messaging on social media: The moderating role of legislation.
ObjectivesThis study investigates whether recreational marijuana legislation and perceived social norms (descriptive and injunctive) affect college students' propensity to share pro-marijuana messages. We examine which referent group (close friends, typical student, parents) most influence those norms. Participants: A sample of 343 college students participated in the study. Of these students, 214 were from Washington State, where recreational marijuana is legal, and 129 were from Wyoming, where recreational marijuana is illegal. Method: Data, from an online survey, were analyzed through PROCESS analyses. Results: College students in Washington State who believed a typical peer would want them to share pro-marijuana messaging were marginally more likely to share pro-marijuana messages than their counterparts in Wyoming. However, among students who thought a typical peer would not approve of them sharing pro-marijuana messaging, the opposite pattern emerged. Conclusion: Restrictive recreational marijuana legislation does not uniformly abate related message sharing on social media.