Vasopressin-Independent Regulation of Aquaporin-2 by Tamoxifen in Kidney Collecting Ducts.
Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective estrogen receptor modulator, attenuates the downregulation of AQP2 in lithium-induced nephrogenic diabetes insipidus (NDI). In this study, we investigated the AVP-independent regulation of AQP2 by TAM and the therapeutic effect of TAM on the dysregulation of AQP2 and impaired urinary concentration in a unilateral ureteral obstruction (UUO) model. Primary cultured inner medullary collecting duct (IMCD) cells from kidneys of male Sprague-Dawley rats were treated with TAM. Rats subjected to 7 days of UUO were treated with TAM by oral gavage. Changes of intracellular trafficking and expression of AQP2 were evaluated by quantitative PCR, Western blotting, and immunohistochemistry. TAM induced AQP2 protein expression and intracellular trafficking in primary cultured IMCD cells, which were independent of the vasopressin V2 receptor (V2R) and cAMP activation, the critical pathways involved in AVP-stimulated regulation of AQP2. TAM attenuated the downregulation of AQP2 in TGF-β treated IMCD cells and IMCD suspensions prepared from UUO rats. TAM administration in vivo attenuated the downregulation of AQP2, associated with an improvement of urinary concentration in UUO rats. In addition, TAM increased CaMKII expression, suggesting that calmodulin signaling pathway is likely to be involved in the TAM-mediated AQP2 regulation. In conclusion, TAM is involved in AQP2 regulation in a vasopressin-independent manner and improves urinary concentration by attenuating the downregulation of AQP2 and maintaining intracellular trafficking in UUO.


Does improved access to diagnostic imaging results reduce hospital length of stay? A retrospective study.
One year after the introduction of Information and Communication Technology (ICT) to support diagnostic imaging at our hospital, clinicians had faster and better access to radiology reports and images; direct access to Computed Tomography (CT) reports in the Electronic Medical Record (EMR) was particularly popular. The objective of this study was to determine whether improvements in radiology reporting and clinical access to diagnostic imaging information one year after the ICT introduction were associated with a reduction in the length of patients' hospital stays (LOS). Data describing hospital stays and diagnostic imaging were collected retrospectively from the EMR during periods of equal duration before and one year after the introduction of ICT. The post-ICT period was chosen because of the documented improvement in clinical access to radiology results during that period. The data set was randomly split into an exploratory part used to establish the hypotheses, and a confirmatory part. The data was used to compare the pre-ICT and post-ICT status, but also to compare differences between groups. There was no general reduction in LOS one year after ICT introduction. However, there was a 25% reduction for one group - patients with CT scans. This group was heterogeneous, covering 445 different primary discharge diagnoses. Analyses of subgroups were performed to reduce the impact of this divergence. Our results did not indicate that improved access to radiology results reduced the patients' LOS. There was, however, a significant reduction in LOS for patients undergoing CT scans. Given the clinicians' interest in CT reports and the results of the subgroup analyses, it is likely that improved access to CT reports contributed to this reduction.


Low-dose ultraviolet radiation selectively degrades chromophore-rich extracellular matrix components.
Photoageing of human skin due to chronic exposure to ultraviolet radiation (UVR) is characterized histologically by extensive remodelling of the dermal elastic fibre system. Whilst enzymatic pathways are thought to play a major role in mediating extracellular matrix (ECM) degeneration in UV-exposed skin, the substrate specificity of UVR-up-regulated and activated matrix metalloproteinases (MMPs) is low. It is unclear, therefore, how such cell-mediated mechanisms alone could be responsible for the reported selective degradation of elastic fibre components such as fibrillin-1 and fibulin-5 during the early stages of photoageing. Here we use atomic force microscopy (AFM) and scanning transmission electron microscopy (STEM) to demonstrate that physiologically attainable doses (20-100 mJ/cm(2)) of direct UV-B radiation can induce profound, dose-dependent, changes in the structure of, and mass distribution within, isolated fibrillin microfibrils. Furthermore, using reducing and native PAGE in combination with AFM, we show that, whilst exposure to low-dose UV-B radiation significantly alters the macromolecular and quaternary structures of both UV chromophore (Cys, His, Phe, Trp and Tyr)-rich fibrillin microfibrils (fibrillin-1, 21.0%) and fibronectin dimers (fibronectin, 12.9%), similar doses have no detectable effect on UV chromophore-poor type I collagen monomers (2.2%). Analysis of the published primary amino acid sequences of 49 dermal ECM components demonstrates that most elastic fibre-associated proteins, but crucially neither elastin nor members of the collagen family, are rich in UV chromophores. We suggest, therefore, that the amino acid composition of elastic fibre-associated proteins [including the fibrillins, fibulins, latent TGFbeta binding proteins (LTBPs) and the lysyl oxidase family of enzymes (LOK/LOXLs)] may predispose them to direct degradation by UVR. As a consequence, this selective acellular photochemical pathway may play an important role in initiating and/or exacerbating cell-mediated ECM remodelling in UVR-exposed skin.


Relationship between ionized and total magnesium in serum.
The relationship between the concentration of ionized magnesium and total magnesium was investigated. Ionized magnesium was determined by an ion-selective electrode (Microlyte 6, KONE) and the result was adjusted to pH 7.4. Total magnesium concentration was measured by flame atomic absorption spectrometry. Total and ionized magnesium were only closely related in marked hypermagnesaemia (> 1.2 mmol/L), but correlation was poor in samples with slightly elevated total concentration or in hypomagnesaemia (< 0.65 mmol/L). The relationship was dependent on protein concentration. The agreement between total and ionized magnesium was acceptable in normoproteinaemia, but in hypoproteinaemia (< 40 g/L) total magnesium concentration was classified in 35% of the samples as below or within the reference interval, whereas the pertinent ionized magnesium concentration was normal or elevated, instead. Studies on paraproteinaemic sera clearly demonstrated that albumin concentration is most important for the size of the protein bound fraction.


Comparing hemodynamic and glycemic response to local anesthesia with epinephrine and without epinephrine in patients undergoing tooth extractions.
Lignocaine with epinephrine as local anesthetic (LA) provides hemostasis and decreases the risk of systemic toxicity. The purpose of the present study was to investigate and compare the response of lignocaine with and without epinephrine to evaluate hemodynamic and metabolic response in normotensive and type II controlled diabetic patients. A total of 50 patients (25 healthy and 25 controlled type II diabetics) undergoing multiple tooth extractions (age group of 20-80 years) were included in this prospective, randomised, clinical study. On their first visit, the patients were given 2% lignocaine HCl with 1:200,000 epinephrine, and 2% lignocaine HCl was given on the second visit, to carry out tooth extractions. Blood pressure (BP), pulse rate, oxygen saturation, and blood glucose estimations were done at definite intervals (before, immediately after, and 20 min after the administration of LA) on both the visits. The increase in blood glucose concentration following the administration of 2% lignocaine HCl with 1:200,000 epinephrine was statistically significant (P < 0.05) in controlled diabetic patients. Statistically significant variability in diastolic BP (DBP) was also noted in controlled diabetic patients. Both systolic BP and DBPs were statistically significantly elevated after the administration of 2% lignocaine HCl. 2% lignocaine HCl with 1:200,000 epinephrine in type II diabetics and 2% lignocaine HCl should be used with caution in normotensive as well as type II controlled diabetic patients.


Antibiotic treatment of metritis in dairy cows-A meta-analysis.
The objective of this meta-analysis was to assess the efficacy of the treatment of bovine metritis with common antibiotic and nonantibiotic treatment options. Acute puerperal metritis, a systemic and potentially painful illness with rectal temperature >39.5°C and signs of toxemia due to an infection of the uterus, occurs within 21 d after parturition. Because of the infectious nature, antibiotics are considered beneficial for the treatment of acute puerperal metritis. Each use of an antimicrobial drug, however, is associated with selective pressure for eventual emergence of resistant bacteria. The 23 trials evaluated in the course of a previously conducted systematic review were the basis for meta-analytic investigations. Selected trials were screened regarding their eligibility for the following investigations: (1) comparison of different antibiotic treatments with respect to metritis prevalence at time of re-examination, (2) efficacy of ceftiofur treatment with respect to metritis prevalence at time of re-examination, (3) comparison of efficacy of antibiotic versus nonantibiotic drugs with respect to metritis prevalence at time of re-examination, and (4) equivalence assessment of treatment effects on reproductive performance measures. Where at least 3 trials had investigated the same outcome variable and met the inclusion criteria (inclusion of a control or reference group diagnosed with metritis; reporting means and standard deviation in case of continuous data), meta-analytic investigations were carried out. Due to a shortage of comparable studies, we could not conduct investigations (1) and (3). Ceftiofur treatment of 828 metritic cows was associated with a decrease in the prevalence of metritis following treatment in comparison to 804 untreated cows. In conclusion, meta-analytic investigations uncovered a need for more high-quality studies. Furthermore, a positive effect of the most commonly used antibiotic drug, ceftiofur, for the treatment of bovine metritis could be shown. A comparison with other antibiotic or nonantibiotic treatment options could not be made.


A counterfactual approach to bias and effect modification in terms of response types.
The counterfactual approach provides a clear and coherent framework to think about a variety of important concepts related to causation. Meanwhile, directed acyclic graphs have been used as causal diagrams in epidemiologic research to visually summarize hypothetical relations among variables of interest, providing a clear understanding of underlying causal structures of bias and effect modification. In this study, the authors aim to further clarify the concepts of bias (confounding bias and selection bias) and effect modification in the counterfactual framework. The authors show how theoretical data frequencies can be described by using unobservable response types both in observational studies and in randomized controlled trials. By using the descriptions of data frequencies, the authors show epidemiologic measures in terms of response types, demonstrating significant distinctions between association measures and effect measures. These descriptions also demonstrate sufficient conditions to estimate effect measures in observational studies. To illustrate the ideas, the authors show how directed acyclic graphs can be extended by integrating response types and observed variables. This study shows a hitherto unrecognized sufficient condition to estimate effect measures in observational studies by adjusting for confounding bias. The present findings would provide a further understanding of the assumption of conditional exchangeability, clarifying the link between the assumptions for making causal inferences in observational studies and the counterfactual approach. The extension of directed acyclic graphs using response types maintains the integrity of the original directed acyclic graphs, which allows one to understand the underlying causal structure discussed in this study. The present findings highlight that analytic adjustment for confounders in observational studies has consequences quite different from those of physical control in randomized controlled trials. In particular, the present findings would be of great use when demonstrating the inherent distinctions between observational studies and randomized controlled trials.


Ciliary activity of cultured rabbit tracheal epithelium: beat pattern and metachrony.
The beat pattern of rabbit tracheal cilia has been investigated using high-speed cine photography and scanning electron microscopy, on cultured epithelia of known orientation. The cilia normally rest in the position reached at the end of the effective stroke, the ciliary tips pointing towards the oropharynx. Each beat begins with a recovery (or preparative) stroke in which a bend is propagated up the cilium causing the cilium to rotate backwards in a clockwise sweep, as viewed from above. At the end of its recovery stroke the cilium progresses immediately into the effective (or power) stroke, which is almost planar and in a cephalad direction. The active cilium describes an arc of almost 110 degrees before reaching the rest stage. This beat pattern is not significantly altered over an increase in frequency from 13-29 Hz; the relative duration of the 2 active phases of the beat remain similar over this range. Metachronal waves exist in the form of short erratic areas of coordinated beating which travel only short distances. Within each area, the non-planar recovery strokes initiate an antilaeoplectic wave of activity which recruits inactive cilia to extent the wave. As cilia perform their effective strokes, adjacent cilia in the plane of beating move in an antiplectic sequence. This pattern of coordination is related to the pattern of beat of the cilia and their distribution on the epithelium.


Patients' health as a predictor of physician and patient behavior in medical visits. A synthesis of four studies.
Although some patient characteristics are known to be related to physician and patient communication in medical encounters, very little is known about the impact of patients' health status on communication processes. The authors assess relations of patients' physical and emotional health status to verbal and nonverbal communication between physicians and patients in four original studies, and combine results across the four studies using meta-analytic procedures. In four original studies of routine outpatient visits (consisting of more than 250 physicians and more than 1,300 patients), health status was measured and audiotape or videotape records were coded for verbal content and nonverbal cues indicating task-related behavior and affective reactions on the part of both the physician and the patient. Both physical and mental health data were obtained, using physicians and/or patients as sources; in two studies, physicians' satisfaction with the visit also was measured. All available background characteristics for both physicians and patients were controlled via partial correlations. The meta-analytic procedures used were the unweighted and weighted (by sample size) average partial correlations, the combined P across studies (Stouffer method), and the test of effect size heterogeneity. Physicians showed signs of negative response to sicker or more emotionally distressed patients, both in their behavior and in their ratings of satisfaction with the visit. Sicker patients also behaved more negatively than healthier patients. However, physicians also engaged in a variety of positive and professionally appropriate behaviors with the sicker or more distressed patients. This mixed pattern of responses is discussed in terms of alternative frameworks: the physician's goals, reciprocation of affect, and ambivalence on the part of the physician. The patient's health status appears to influence physician-patient communication. In clinical practice, increased attention by physicians to their own and their patients' behavior may enhance diagnosis and prevent misunderstandings.


[Alkaloid production in the fungus Penicillium sizovae].
The dynamics of production of agroclavine-I and epoxyagroclavine-I, the basic components of the Penicillium sizovae alkaloid fraction, was being studied. The biosynthesis of alkaloids occurs in two stages coinciding in time with the growth phases. The culture studied is shown to have a considerably higher content of extracellular alkaloids than that of the mycelium. When the culture is grown on a medium with mannitol and succinic acid, separate consumption of carbon sources is observed. The alkaloid production in P. sizovae occurs in the presence of high residual concentrations of phosphorus in the medium.


Surficial gains and subsoil losses of soil carbon and nitrogen during secondary forest development.
Reforestation of formerly cultivated land is widely understood to accumulate above- and belowground detrital organic matter pools, including soil organic matter. However, during 40 years of study of reforestation in the subtropical southeastern USA, repeated observations of above- and belowground carbon documented that significant gains in soil organic matter (SOM) in surface soils (0-7.5 cm) were offset by significant SOM losses in subsoils (35-60 cm). Here, we extended the observation period in this long-term experiment by an additional decade, and used soil fractionation and stable isotopes and radioisotopes to explore changes in soil organic carbon and soil nitrogen that accompanied nearly 50 years of loblolly pine secondary forest development. We observed that accumulations of mineral soil C and N from 0 to 7.5 cm were almost entirely due to accumulations of light-fraction SOM. Meanwhile, losses of soil C and N from mineral soils at 35 to 60 cm were from SOM associated with silt and clay-sized particles. Isotopic signatures showed relatively large accumulations of forest-derived carbon in surface soils, and little to no accumulation of forest-derived carbon in subsoils. We argue that the land use change from old field to secondary forest drove biogeochemical and hydrological changes throughout the soil profile that enhanced microbial activity and SOM decomposition in subsoils. However, when the pine stands aged and began to transition to mixed pines and hardwoods, demands on soil organic matter for nutrients to support aboveground growth eased due to pine mortality, and subsoil organic matter levels stabilized. This study emphasizes the importance of long-term experiments and deep measurements when characterizing soil C and N responses to land use change and the remarkable paucity of such long-term soil data deeper than 30 cm.


An Elicitation Study to Understand Young Adults' Beliefs About Seeking Health Information From Social Media Influencers.
Social media influencers increasingly make health recommendations on social media. Research on influencer health messaging is mixed in that some studies show it can result in misleading or harmful health information, and others demonstrate it can lead to beneficial behavioral outcomes. However, there is little research on young adults' beliefs about following health guidance from influencers. Guided by the reasoned action approach, this study examined young adults' attitudes, normative beliefs, and control in seeking health information from social media influencers using focus groups (n = 31). Results suggest that young adults obtain health information from influencers and perceive them as a source of health education. Several barriers to getting health information from influencers were mentioned, including sponsorship, lack of credibility, and perceived normative pressure to critically analyze influencer content from peers and family. Practical and theoretical implications for future research are discussed.


[Outcome quality of psychosomatic rehabilitation: goal attainment scaling on the basis of a structured catalogue of therapy goals].
Within the scope of a multicenter study regarding the outcome quality of inpatient psychosomatic rehabilitation a structured catalogue of therapy goals (SZK, strukturierter Therapiezielkatalog) was developed. The catalogue contains 89 predetermined therapy goals as well as the option to formulate further goals in own words. The SZK is available both as a patient and as a therapist version. At the beginning of treatment up to five primary objectives are chosen from the list. At the end of treatment and at the 1-year follow-up the level of achievement of objectives is assessed. Moreover the SZK contains the option to mark goals as not relevant any more and to add goals which came up during the treatment and to evaluate them regarding the level of achievement. The study on hand asks for empirical identification of the target structure. Furthermore, reliability and validity of the calculated measures of goal attainment are analysed. As the most important finding the SZK turns out to be a practical and economical assessment instrument for goal-oriented evaluation.


Histamine H(3) receptor (H(3)R) antagonists and inverse agonists in the treatment of sleep disorders.
After the discovery and characterization of the H(3)R and H(4)R receptors, they have become widely anticipated as potential therapeutic agents in the treatment of sleep disorders. In preliminary studies, histamine H(3) receptor (H(3)R) antagonists and inverse agonists have demonstrated promise in the treatment of sleep disorders associated with excessive daytime sleepiness. This review article summarizes the current research in this area and characteristics of H(3)R and H(3)R antagonists and inverse agonists in development.


Lymphocytic vasculitis mimicking aggressive multifocal cerebral neoplasm: mr imaging and MR spectroscopic appearance.
We present a case of multifocal enhancing lesions confined to the right cerebral hemisphere that mimicked diffuse neoplasm. MR spectroscopy revealed not only minimal elevation of the choline peak, but also marked elevation of the glutamate and glutamine peaks, findings that are more suggestive of an inflammatory process. Biopsy showed lymphocytic vasculitis, a rare variant of primary angiitis of the CNS. Following appropriate medical therapy, MR imaging demonstrated complete resolution of the lesions.


Genetic modeling of primary tooth emergence: a study of Australian twins.
The aim of this study was to quantify contributions of genetic and environmental factors to variation in timing of emergence of the primary teeth in a sample of monozygotic and dizygotic twins, using univariate model-fitting approaches. The sample comprised 94 pairs of monozygotic twins and 125 pairs of dizygous twins, all of European ancestry, aged from 2-6 years. Tooth emergence timing was based on parental report, with a subset of data validated by clinical assessment. Heritability estimates for tooth emergence timing were generally high, around 90%, however estimates for the lower right lateral incisor and the lower canines were around 50%. These findings confirm a strong genetic influence on observed variation in the timing of emergence of the human primary teeth.


Dealing with the gray zones in the management of gastric cancer: The consensus statement of the İstanbul Group.
The geographical location and differences in tumor biology significantly change the management of gastric cancer. The prevalence of gastric cancer ranks fifth and sixth among men and women, respectively, in Turkey. The international guidelines from the Eastern and Western countries fail to manage a considerable amount of inconclusive issues in the management of gastric cancer. The uncertainties lead to significant heterogeneities in clinical practice, lack of homogeneous data collection, and subsequently, diverse outcomes. The physicians who are professionally involved in the management of gastric cancer at two institutions in Istanbul, Turkey, organized a consensus meeting to address current problems and plan feasible, logical, measurable, and collective solutions in their clinical practice for this challenging disease. The evidence-based data and current guidelines were reviewed. The gray zones in the management of gastric cancer were determined in the first session of this consensus meeting. The second session was constructed to discuss, vote, and ratify the ultimate decisions. The identification of the T stage, the esophagogastric area, imaging algorithm for proper staging and follow-up, timing and patient selection for neoadjuvant treatment, and management of advanced and metastatic disease have been accepted as the major issues in the management of gastric cancer. The recommendations are presented with the percentage of supporting votes in the results section with related data.


Impact of UGT1A9 Polymorphism on Mycophenolic Acid Pharmacokinetic Parameters in Stable Renal Transplant Patients.
There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil (MMF) among transplanted patients. Some studies have shown that single nucleotide polymorphisms (SNPs) of the Uridine Diphosphate Glucuronosyl Transferase1A9 (UGT1A9) are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran. Blood samples were taken from 40 de novo stable Iranian renal transplant patients taking 2 g MMF daily with SrCr≤1.4 mg/dL with at least 3 months history of transplantation. Appropriate PCR and HPLC methods were used for the determination of SNPs and their impact on MPA pharmacokinetics. T-275A polymorphism occurred in 15% of patients, UGT1A9*3 occurred in 2.5% of patients. Carriers of T-275A polymorphism had significant lower MPA AUC 0-12 in comparison with non-carriers or wild type (73.3±17.8 g/h/mL vs. 110.8±31.1 μg/h/mL, p = 0.006). There was no significant difference in AUC 6-12 between the two groups although carriers of T-275A SNP had lower MPA AUC 6-12 (22.4±4.5 μg/h/mL vs. 26.8±10.2 μg/h/mL, p = 0.24). Cmax was lower in the carriers of (20.2±9.0 μg/mL vs. 37.2±12.5 μg/mL, p=0.004). There was no significant difference in C0 between two groups. (3.0±1.2 μg/mL vs. 3.9±1.6 μg/mL, p = 0.1). This study in Iranian stable transplanted patients shows that carriers of T-275A polymorphism had significantly lower MPA exposure compared to non-carriers.


Membrane-anchored beta 2-microglobulin stabilizes a highly receptive state of MHC class I molecules.
The magnitude of response elicited by CTL-inducing vaccines correlates with the density of MHC class I (MHC-I)-peptide complexes formed on the APC membrane. The MHC-I L chain, beta2-microglobulin (beta2m), governs complex stability. We reasoned that genetically converting beta2m into an integral membrane protein should exert a marked stabilizing effect on the resulting MHC-I molecules and enhance vaccine efficacy. In the present study, we show that expression of membranal human beta2m (hbeta2m) in mouse RMA-S cells elevates MHC-I thermal stability. RMA-S transfectants bind an exogenous peptide at concentrations 10(4)- to 10(6)-fold lower than parental RMA-S, as detected by complex-specific Abs and by T cell activation. Moreover, saturation of the transfectants' MHC-I by exogenous peptide occurs within 1 min, as compared with approximately 1 h required for parental cells. At saturation, however, level of peptide bound by modified cells is only 3- to 5-fold higher. Expression of native hbeta2m only results in marginal effect on the binding profile. Soluble beta2m has no effect on the accelerated kinetics, but the kinetics of transfectants parallel that of parental cells in the presence of Abs to hbeta2m. Ab inhibition and coimmunoprecipitation analyses suggest that both prolonged persistence of peptide-receptive H chain/beta2m heterodimers and fast heterodimer formation via lateral diffusion may contribute to stabilization. In vivo, peptide-loaded transfectants are considerably superior to parental cells in suppressing tumor growth. Our findings support the role of an allosteric mechanism in determining ternary MHC-I complex stability and propose membranal beta2m as a novel scaffold for CTL induction.


Efficacy of Psychosocial Interventions for People with Multiple Sclerosis: A Meta-Analysis of Specific Treatment Effects.
Psychosocial interventions are often used as an adjunct to the medical management of multiple sclerosis (MS). However, the efficacy of such approaches for a range of psychosocial indications remains unclear. To determine the efficacy of psychosocial therapies for people with MS (PwMS). We searched 6 electronic databases (Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, and Clinicaltrials.gov) until April 21, 2016, for randomized controlled trials reporting the effect of psychological interventions for depressive symptoms, anxiety, pain, fatigue, or health-related quality of life (HRQoL) in PwMS. The search yielded 356 articles with 13 included studies (n = 1,617). Benefits of psychological interventions were found for depressive symptoms (Cohen's d = 0.281), anxiety (d = 0.285), fatigue (d = 0.228), and mental (d = 0.398) and total HRQoL (d = 0.444), but not physical HRQoL. There were insufficient studies to meta-analyze posttreatment outcomes for pain. Interventions were more effective for HRQoL for patients with relapsing-remitting MS and when treatment doses were larger. Cognitive behavioral therapy (CBT) was not efficacious for PwMS when considered alone. Psychosocial interventions have a significant, positive impact across a range of outcomes for PwMS with small, yet consistent, effect sizes. There was some indication that CBT was less efficacious than other interventions. However, this may be due to smaller treatment doses in CBT studies.


Accuracy of breeding values in small genotyped populations using different sources of external information-A simulation study.
Genetically linked small and large dairy cattle populations were simulated to test the effect of different sources of information from foreign populations on the accuracy of predicting breeding values for young animals in a small population. A large dairy cattle population (PL) with >20 generations was simulated, and a small subpopulation (PS) with 3 generations was formed as a related population, including phenotypes and genomic information. Predicted breeding values for young animals in the small population were calculated using BLUP and single-step genomic BLUP (ssGBLUP) in 4 different scenarios: (S1) 3,166 phenotypes, 22,855 pedigree animals, and 1,000 to 6,000 genotypes for PS; (S2) S1 plus genomic estimated breeding value (GEBV) for 4,475 sires from PL as external information; (S3) S1 plus 221,580 phenotypes, 402,829 pedigree animals, and 53,558 genotypes for PL; and (S4) single nucleotide polymorphism (SNP) effects calculated based on PL data. The ability to predict true breeding value was assessed in the youngest third of the genotyped animals in the small population. When data only from the small population were used and 1,000 animals were genotyped, the accuracy of GEBV was only 1 point greater than the estimated breeding value accuracy (0.32 vs. 0.31). Adding external GEBV for sires from PL did not considerably increase accuracy (0.33 vs. 0.32 in S1). Combining phenotypes, pedigree, and genotypes for PS and PL was beneficial for predicting accuracy of GEBV in the small population, and the prediction accuracy of GEBV in this scenario was 0.38 compared with 0.31 from estimated breeding values. When SNP effects from PL were used to predict GEBV for young genotyped animals from PS, accuracy was greatest (0.56). With 6,000 genotyped animal in PS, accuracy was greatest (0.61) with the combined populations. In a small population with few genotypes, the highest accuracy of evaluation may be obtained by using SNP effects derived from a related large population.


A microcolumnar structure of monkey cerebral cortex revealed by immunocytochemical studies of double bouquet cell axons.
Immunocytochemical methods were used to study 28,000 mol. wt calbindin and tachykinin immunoreactivity in the monkey cerebral cortex. Calbindin and tachykinin immunoreactivity give rise to a generally different pattern of staining of cell bodies and terminal-like puncta. However, the staining of long, vertically-oriented bundles of processes--identical to classical double bouquet cell axonal arborizations--is the most prominent feature of the pattern of both calbindin- and tachykinin-immunoreactive staining. These bundles form a widespread and regular columnar system descending from layer II to layers III-V. The bundles are most evident in layer III where, in tangential sections, they have a density of 7-15 bundles/10,000 microns 2 with a center-to-center spacing of 15-30 microns. The distribution of immunoreactive bundles through the cortex is not homogeneous; somatic sensory, auditory, and visual areas display a large number of calbindin-immunoreactive bundles while tachykinin-immunoreactive bundles are only numerous in the auditory areas and in area 18 of the visual cortex. In the motor cortex (area 4) few or no immunoreactive bundles are visualized with either antibody. Correlative light and electron microscope analysis of tachykinin immunoreactive bundles in the primary auditory cortex shows that the tachykinin-positive axons of the bundles form symmetrical synaptic contacts with dendritic shafts (57%) and spines (43%). Frequently, several immunoreactive boutons that arise from the same fiber are seen climbing along the surfaces of vertically-oriented, non-immunoreactive processes which include myelinated and unmyelinated axons and probably glial processes. The same ultrastructural features and a similar synaptic distribution were found in a previous study [DeFelipe et al. (1989) Brain Res. 503, 49-54] of calbindin-positive bundles in the somatic sensory cortex (areas 3a and 1). Despite the virtually identical morphological features of tachykinin- and calbindin-immunoreactive bundles, colocalization studies demonstrate little coexistence of the two antigens in somata and none in the axonal bundles of double bouquet cells. These data suggest that the double bouquet cell is a chemically heterogeneous, but ubiquitous morphological type of cortical interneuron, whose uniquely bundled axonal system, which is probably GABAergic, imposes a fundamental microcolumnar organization upon the cerebral cortex.


Determining the effect of implementing an educational package on quality of life among patients with chronic obstructive pulmonary disease referring to teaching hospitals affiliated with Ilam University of Medical Sciences in 2016.
Nowadays, pulmonary diseases have become one of the most important causes of mortality in the world. In this regard, the present study was aimed at examining the effect of implementing an educational package on quality of life (QoL) among patients with chronic obstructive pulmonary disease (COPD) referring to teaching hospitals affiliated with Ilam University of Medical Sciences. The present study was an interventional clinical trial in which the participants were randomly assigned into an intervention group and a control group. The statistical population included all COPD patients who had referred to the teaching hospitals affiliated with Ilam University of Medical Sciences. Sixty patients were selected by a convenience sampling method out of the whole patients who had referred to Shahid Mostafa Khomeini Hospital in Ilam. Afterward, they were randomly assigned into an intervention group and a control group (each including 30 patients). The collected data were analyzed using descriptive statistics; Chi-square test, independent and paired samples t-test, and correlational tests at a significance level of 0.05. The results of the present study showed that as a result of the educational package, the intervention patients had a significantly higher QoL than the control patients (P = 0.001). The results also showed that implementing the educational package had a significant effect on QoL among the intervention patients in dimensions of physical function, mental health, social status, playing physical role, playing emotional role, physical pains, general health, and energy and vitality (P = 0.001). Based on the results of the present study, it can be concluded that collaborative education is a significant issue in health and treatment, and different dimensions of QoL can be enhanced by an appropriate educational program.


Ferromagnetic insulating substrate for magnetic proximity studies: LaCoO3thin film.
Ferromagnetic insulators (FMIs) are intriguing not only due to their rare nature, but also due to their potential applications in spintronics and various electronic devices. One of its key promising applications is based on an FMI-induced magnetic proximity effect, which can impose an effective time-reversal symmetry breaking on the target ultrathin layer to realize novel emergent phenomena. Here, we conduct systematic studies on thin film LaCoO3, an insulator known to be ferromagnet under tensile strain, with varying thicknesses, to establish it as an FMI platform to be integrated in heterostructures. The optimal thickness of the LaCoO3layer, providing a smooth surface and robust ferromagnetism with large remanence, is determined. A heterostructure consisting of an ultrathin target layer (2 uc SrRuO3), the LaCoO3FMI layer, and the La0.5Sr0.5CoO3conducting layer has been fabricated and the angle-resolved photoemission spectroscopy measurement on the multi-layer system demonstrates a sharp Fermi edge and a well-defined Fermi surface without the charging effect. This demonstrates the feasibility of the proposed heterostructure using LaCoO3thin film as the FMI layer, and further lays a groundwork to investigate the magnetic proximity induced phases in quantum materials.


Keratinocyte expression of MMP3 enhances differentiation and prevents tumor establishment.
Matrix metalloproteinase (MMP)-3 is induced by multiple cell types in the skin during processes involved in both normal and pathological tissue remodeling. We previously demonstrated that MMP3-null animals have an increased sensitivity to the development of squamous cell carcinoma, suggesting that overall, MMP3 has a protective role in squamous cell carcinoma. However, not all cellular responses affected by a loss of MMP3 are tumor-protective, and tumor expression of MMP3 is co-incident with an invasive tumor phenotype. Transgenic mice were generated with MMP3 targeted to keratinocytes to examine the biological role of tumor-produced MMP3. Overexpression of MMP3 reduced tumor multiplicity in response to chemically induced squamous cell carcinoma. Vascular density was increased with MMP3 overexpression; however, other cellular processes, including tumor growth and leukocyte infiltration, were unaffected. In accordance with the change in tumor multiplicity, SP-1 murine papilloma cell lines that were generated to stably express MMP3 lost the capacity to establish palpable tumors following orthotopic injection into immunocompromised mice. Analysis of epidermal biopsies taken at 1 to 2 weeks postinjection revealed that these MMP3-expressing Sp-1 lines had reduced levels of proliferation and pronounced differentiation. These same cells demonstrated an increased ability to differentiate in vitro, an effect that was inhibited by broad-spectrum MMP and selective MMP3 inhibition. These studies suggest that keratinocyte expression of MMP3 promotes cellular differentiation, impeding tumor establishment during tumorigenesis.


Menopause and hormone replacement therapy: the 2017 Recommendations of the Italian Menopause Society.
Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.


Screening for treponemal infection by a new enzyme immunoassay.
A new enzyme immunoassay (EIA, Captia Syphilis-G) for detecting IgG antibodies against Treponema pallidum was evaluated as a screening test for syphilis. When serum samples were tested at a dilution of 1 in 20 (EIA20), the overall agreement between the IgG EIA and serological status based on the T pallidum haemagglutination assay (TPHA) and the fluorescent treponemal antibody absorption (FTA-ABS) test was 99.2% (1310/1321). The sensitivity of the EIA20 was 98.4% (60/61) and the specificity 99.3% (1251/1260). Discrimination between patients with and without treponemal infection was good: the mean EIA20 absorbance ratios (patient/mean low titre positive control results) were 0.49 for antibody negative patients, 3.30 for patients with positive Venereal Diseases Research Laboratory (VDRL) test and TPHA results, and 1.77 for patients with negative VDRL but positive TPHA results. The cut off point for excluding treponemal infection was taken as 0.9. Specimens with ratios of more than 0.9 should be confirmed by the FTA-ABS test and evaluated for specific IgM antibodies to treponemes. When serum samples were tested at a 1 in 50 dilution (EIA50) the sensitivity was lower (80.3%) but the specificity was absolute. The reduction in sensitivity correlated with low absorbance ratios in the patients who were VDRL negative and TPHA positive. The screening performance of the IgG EIA20 is thus comparable with that provided by a combination of the VDRL test and TPHA. The potential for automation makes the EIA an attractive alternative, particularly in larger centres. Alternatively, the test can be performed at a 1 in 50 dilution (EIA50), at which level it is ideally suited for confirming the treponemal status of antibodies in serum samples preselected by positive cardiolipin antigen screening test results.


[Degradation of diazepam in aqueous solution. Simulation essay by action of diluted hydrogen peroxide].
The mild oxidation of diazepam by hydrogen peroxide in neutral medium at room temperature in daylight is reported. The oxidation product has been isolated and purified and its purity determined by thin layer chromatography. It has been identified by spectroscopy, chiefly by infrared and mass spectroscopy. Finally it has been compared, by high pressure liquid chromatography, to the product from an aqueous diazepam solution placed 6 months at room temperature in daylight.


LIBS using dual- and ultra-short laser pulses.
Pre-ablation dual-pulse LIBS enhancement data for copper, brass and steel using ns laser excitation are reported. Although large enhancements are observed for all samples, the magnitude of the enhancement is matrix dependent. Whereas all of the dual-pulse studies used ns laser excitation we see interesting effects when using ps and fs laser excitation for single-pulse LIBS. LIBS spectra of copper using 1.3 ps and 140 fs laser pulses show much lower background signals compared to ns pulse excitation. Also, the atomic emission decays much more rapidly with time. Because of relatively low backgrounds when using ps and fs pulses, non-gated detection of LIBS is shown to be very effective. The plasma dissipates quickly enough using ps and fs laser pulses, that high pulse rates, up to 1,000 Hz, are effective for increasing the LIBS signal, for a given measurement time. Finally, a simple near-collinear dual-pulse fiber-optic LIBS probe is shown to be useful for enhanced LIBS measurements.


Promoter hypermethylation and inactivation of O(6)-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines.
The purpose of this study was to characterize the role of DNA hypermethylation in the loss of expression of O(6)-methylguanine-DNA methyltransferase (MGMT) during the development of esophageal squamous cell carcinoma (ESCC) and to investigate its reactivation in cell lines. Samples were collected from Linzhou City of the Henan province in northern China, a high-risk area of this disease. The hypermethylation of promoter CpG islands of the MGMT gene was examined by methylation-specific PCR in ESCC and neighboring non-tumorous tissues, as well as in laser capture microdissected samples with normal epithelium, basal cell hyperplasia (BCH), and dysplasia (DYS). The MGMT mRNA and protein expression were determined with RT-PCR and immunohistochemistry, respectively. Five of 17 (29%) normal, 10 of 20 (50%) BCH, 8 of 12 (67%) DYS, and 13 of 18 (72%) ESCC samples had DNA hypermethylation in the MGMT promoter region, showing a gradual increase with the progression of carcinogenesis. The frequency of the loss of MGMT mRNA and protein expression progressively decreased from normal to BCH, DYS, and ESCC, and it was highly correlated with MGMT promoter hypermethylation according to Fisher's exact tests. When each individual sample was considered, good concordance between DNA hypermethylation and the loss of expression of MGMT was also observed. In samples from the same patient, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, treatment with a DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine partially reversed the CpG hypermethylation status and restored mRNA expression of the MGMT gene. Similar reactivation of MGMT gene by dietary polyphenols, (-)-epigallocatechin-3-gallate and genistein, has also been observed. The results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing in the development of ESCC, and this epigenetic event may be prevented or reversed by these polyphenols for the prevention of carcinogenesis.


The role of intuition.
"Intuition," as used by the modern mathematician, means an accumulation of attitudes (including beliefs and opinions) derived from experience, both individual and cultural. It is closely associated with mathematical knowledge, which forms the basis of intuition. This knowledge contributes to the growth of intuition and is in turn increased by new conceptual materials suggested by intuition. The major role of intuition is to provide a conceptual foundation that suggests the directions which new research should take. The opinion of the individual mathematician regarding existence of mathematical concepts (number, geometric notions, and the like) are provided by this intuition; these opinions are frequently so firmly held as to merit the appellation "Platonic." The role of intuition in research is to provide the "educated guess," which may prove to be true or false; but in either case, progress cannot be made without it and even a false guess may lead to progress. Thus intuition also plays a major role in the evolution of mathematical concepts. The advance of mathematical knowledge periodically reveals flaws in cultural intuition; these result in "crises," the solution of which result in a more mature intuition. The ultimate basis of modern mathematics is thus mathematical intuition. and it is in this sense that the Intuitionistic doctrine of Brouwer and his followers is correct. Modern instructional methods recognize this role of intuition by replacing the "do this, do that" mode of teaching by a "what should be done next?" attitude which appeals to the intuitive background already developed. It is in this way that understanding and appreciation of new mathematical knowledge may be properly instilled in the student.


Multivariate Analysis and Statistics in Pharmaceutical Process Research and Development.
The application of statistics in pharmaceutical process research and development has evolved significantly over the past decades, motivated in part by the introduction of the Quality by Design paradigm, a landmark change in regulatory expectations for the level of scientific understanding associated with the manufacturing process. Today, statistical methods are increasingly applied to accelerate the characterization and optimization of new drugs created via numerous unit operations well known to the chemical engineering discipline. We offer here a review of the maturity in the implementation of design of experiment techniques, the increased incorporation of latent variable methods in process and material characterization, and the adoption of Bayesian methodology for process risk assessment.


Hydrological regimes and water quality variations in the Yangtze River basin from 1998 to 2018.
Understanding the long-term variations in basins that undergo large-scale hydroelectric projects is crucial for effective dam operation and watershed management. In this study, comprehensive analyses were conducted on a dataset spanning over 20 years (1998-2018) of hydrological regime and physicochemical parameters from the Yangtze River basin to evaluate the potential impacts of the Three Gorges Dam. Water level significantly increased from 128.75±58.18 m in 2002 to 136.78±55.05 m in 2005, and the mean flow velocity significantly decreased from 2004 to 2010. However, no significant change in the flow was observed in the basin. Meanwhile, remarkable fluctuations in physicochemical parameters, including dissolved oxygen, chemical oxygen demand, conductivity, hardness, and alkalinity, were mainly observed during impoundment (2003-2009). After that, the above parameters tended to stabilize, and some even returned to their original levels. The dam's retention effect significantly reduced the suspended solids (SS) in both up- and downstream, to only one-third of the pre-operation level. And total phosphorus and chemical oxygen demand also significantly decreased with the decline of SS. Particularly, ammonium also showed a significant downward trend, with the up- and downstream of the dam falling by 36.8 % and 26.1 %, respectively. However, the increasing total nitrogen (7.5 % and 20.0 % up- and downstream of the dam, respectively) still threatened the water quality of the basin, especially in the estuaries. Additionally, the significant decline in dissolved oxygen downstream (from 8.53±1.08 mg/L to 8.11±1.36 mg/L) also exacerbated the hypoxia in the Yangtze River estuary. The results demonstrated the long-term impact of the construction of the Three Gorges Dam on the environmental elements of the Yangtze River basin, which provides reference data and guidance for the construction of big dams in major rivers in the future.


The murine Fc receptor for immunoglobulin: purification, partial amino acid sequence, and isolation of cDNA clones.
The murine Fc receptor for IgG (Fc gamma R) was purified to homogeneity by immunoaffinity chromatography from detergent lysates of the macrophage cell line J774. Microsequencing of intact protein yielded a single amino-terminal sequence, which was confirmed and extended to 20 residues by the isolation of an overlapping peptide. The isolation of additional proteolytic fragments obtained by using Staphylococcus aureus V8 protease, cyanogen bromide, and lysine C proteinase, facilitated sequence analysis of a total of 119 amino acid residues. Codon usage charts were used to construct oligonucleotide probes based on the amino acid sequences of three nonoverlapping peptides. These probes were used to screen a cDNA library derived from the WEHI-3B myelomonocytic cell line, and a single cDNA clone (pFc24) to which all three probes hybridized was isolated. This clone, containing a 1.02-kilobase cDNA insert, has been characterized by restriction mapping and partial DNA sequencing, and it has been shown to encode the Fc gamma R. The sequence at the 5' end of the clone contained the coding information for the amino-terminal sequence of the Fc gamma R as well as a putative 13-amino acid signal sequence. The 3' end of the clone encoded a peptide identified in purified receptor preparations. Thus, the presence of coding information at the 5' and 3' ends of this clone suggests that full-length Fc receptor cDNA spans greater than 1 kilobase.


Women of the American Otological Society.
To describe the history of women in the American Otological Society (AOS). Biographies of the early women of the AOS were compiled through review of the AOS transactions, their published scholarship, newspaper articles, and memorials. Interviews were conducted with the only two women to have led the society and also with former colleagues and family members of pioneering AOS women members who are no longer with us. The evolving gender composition of the society over time was researched from AOS membership lists and compared with data on surgical workforce composition from multiple sources such as the Association of American Medical Colleges, Accreditation Council for Graduate Medical Education, American Medical Association, and the American Academy of Otolaryngology-Head and Neck Surgery. Although American women specialized in otology as far back as 1895, the first woman to be invited to join the AOS as Associate member in 1961 was Dorothy Wolff, PhD. The first female full member was otologic surgeon LaVonne Bergstrom, M.D., who was elected in 1977, 109 years after the foundation of the Society. As of 2017, only two women have served as AOS President. The first was Aina Julianna Gulya, M.D., who took office during the 133rd year in 2001. At the time of the sesquicentennial (2017), 7.5% of AOS members are women including three of eight who serve on the AOS Council. This compares with 15.8% of women among the otolaryngology workforce and a growing 10.9% representation among those who have earned subcertification in neurotology. Gender disparities remain in the AOS, but both participation and scholarly contributions by women in otology have grown substantially since the society's inception 150 years ago, and particularly in the 21st century. Increasing the presence of women in leadership provides role models and mentorship for the future.


Species and size diversity in protective services offered by coral guard-crabs.
Coral guard-crabs in the genus Trapezia are well-documented defenders of their pocilloporid coral hosts against coral predators such as the Crown-of-Thorns seastar (Acanthaster planci complex). The objectives of this study were to examine the protective services of six species of Trapezia against corallivory, and the extent of functional diversity among these Trapezia species. Studies conducted in Mo'orea, French Polynesia showed the Trapezia-coral mutualism protected the host corals from multiple predators through functional diversity in the assemblage of crab symbionts. Species differed in their defensive efficacy, but species within similar size classes shared similar abilities. Smaller-size Trapezia species, which were previously thought to be ineffective guards, play important defensive roles against small corallivores. We also measured the benefits of this mutualism to corals in the midst of an Acanthaster outbreak that reduced the live coral cover on the fore reef to less than 4%. The mutualism may positively affect the reef coral demography and potential for recovery during adverse predation events through shelter of multiple species of small corals near the host coral. Our results show that while functional diversity is supported within the genus, some Trapezia species may be functionally equivalent within the same size class, decreasing the threat of gaps in coral protection caused by absence or replacement of any single Trapezia species.


Diagnostic value of routine pre-operative investigations used in combination in the diagnosis of periprosthetic joint infection.
The primary aim of this study was to assess the diagnostic accuracy of joint aspiration culture, serum C-reactive protein (CRP) and serum erythrocyte sedimentation rate (ESR), individually, and in combination for the diagnosis of periprosthetic joint infection (PJI). A consecutive patient series with pre-operative inflammatory marker levels, an aspiration culture of either hip or knee arthroplasty and intra-operative culture samples from subsequent revision surgery was compiled. This retrospective patient cohort analysis included 128 aspiration. The data were analysed to compare pre-operative aspiration cultures, serum ESR and CRP levels to the chosen gold standard for PJI diagnosis of intra-operative culture samples. A diagnostic algorithm was created using the above tests combined with clinical suspicion index. The values that had the highest sensitivity and specificity of predicting PJI were >5 for CRP and >16 for ESR. CRP used individually had the highest sensitivity and negative predictive value (NPV) of any test (75.0% and 75.9%, respectively). ESR + aspirate had the highest specificity and positive predictive value (PPV), of 100% for both. Using all three tests together the specificity and PPV were higher than the test individual values (95.3% and 85.0% respectively). Based on subgroup analyses the combination of ESR or CRP plus joint aspiration has superior PPV compared to individual tests. ESR and CRP had the highest NPV when used in isolation. An algorithm has been developed to guide clinical diagnosis.


Investigating the Agreement Between Cardiovascular Disease Risk Calculators Among People Diagnosed With Schizophrenia.
Background: People diagnosed with schizophrenia have a much reduced life expectancy compared to the general population, and a more than doubled risk of dying from cardiovascular disease (CVD). Existing CVD risk calculators can be used to detect people with an elevated predicted risk of CVD to inform interventions to reduce risk. Aims: This study aimed to compare four different risk calculators for 10-year predicted CVD risk in a sample of people with schizophrenia. Methods: Thirty participants with a diagnosis of schizophrenia spectrum disorders living within Greater Manchester, United Kingdom took part. Ten-year predicted cardiovascular risk scores were calculated using four different models: QRISK3, Framingham, PRIMROSE BMI, and PRIMROSE lipid. Risk estimates and classified risk categories were compared. Results: QRISK3 identified 11 (39%) as having >10% risk of a CV event within 10 years, 4 (14%) of whom exceeded 20%. The Framingham model identified 4 (14%) as exceeding 10%, none of whom exceeded 20%. PRIMROSE risk calculators identified no participants as having >10% risk of a CV event within 10 years. Pairwise concordance correlation coefficients between types of model ranged 0.22-0.77. Mean (± SD) age was 40 (± 10) years but QRISK3's mean "Heart age" was 58 (± 14) years. Conclusion: Risk calculators generate differing predicted CVD risk scores for patients with schizophrenia. Using one risk calculator might yield different recommended monitoring and treatment plans compared to another. Clinicians should therefore take into account other patient-related factors, such as patients' preferences and other underlying physical conditions when making treatment decisions.


Trends in Ultra-Processed Food Purchases from 1984 to 2016 in Mexican Households.
Global trade agreements have shaped the food system in ways that alter the availability, accessibility, affordability, and desirability of ready-to-eat foods. We assessed the time trends of ultra-processed foods purchases in Mexican households from 1984 to 2016. Cross-sectional data from 15 rounds of the National Income and Expenditure Survey (1984, 1989, 1992, 1994, 1996, 1998, 2000, 2002, 2004, 2006, 2008, 2010, 2012, 2014 and 2016) were analyzed. Food and beverage purchases collected in a daily record instrument (over seven days) were classified according to their degree of processing according to the NOVA food framework: (1) Unprocessed or minimally processed foods; (2) processed culinary ingredients; (3) processed foods; and (4) ultra-processed foods. From 1984 to 2016, the total daily energy purchased decreased from 2428.8 to 1875.4 kcal/Adult Equivalent/day, there was a decrease of unprocessed or minimally processed foods (from 69.8% to 61.4% kcal) and processed culinary ingredients (from 14.0% to 9.0% kcal), and an increase of processed foods (from 5.7% to 6.5% kcal) and ultra-processed foods (from 10.5% to 23.1% kcal). Given that ultra-processed foods purchases have doubled in the last three decades and unprocessed or minimally processed foods purchased have gradually declined, future strategies should promote the consumption of unprocessed or minimally processed foods, and discourage ultra-processed foods availability and accessibility in Mexico.


Voltage Rollercoaster Filtering of Low-Mass Contaminants During Native Protein Analysis.
Intact protein mass spectrometry (MS) via electrospray-based methods is often degraded by low-mass contaminants, which can suppress the spectral quality of the analyte of interest via space-charge effects. Consequently, selective removal of contaminants by their mobilities would benefit native MS if achieved without additional hardware and before the mass analyzer regions used for selection, analyte readout, or tandem MS. Here, we use the high-pressure multipole within the source of an Orbitrap Tribrid as the foundation for a coarse ion filter. Using this method, we show complete filtration of 2 mM polyethylene glycol (PEG-1000) during native MS of SILu mAb antibody present at a 200× lower concentration. We also show the generality of the process by rescuing 10 μM tetrameric pyruvate kinase from 2 mM PEG-1000, asserting this voltage rollercoaster filtering (VRF) method for use in native MS as an efficient alternative to conventional purification methods.


Fabrication of calcium phosphate films for coating on titanium substrates heated up to 773 K by RF magnetron sputtering and their evaluations.
Calcium phosphate films were fabricated on titanium substrates heated up to 773 K using radiofrequency (RF) magnetron sputtering. The deposition rate, phase and preferred orientation of the calcium phosphate films were studied. Immersion tests for the films were conducted using Hanks' solution and PBS(-), and the surface reactions on the specimens coated with the calcium phosphate films were investigated. The bonding strength between the coating films and the titanium substrates before and after the immersion tests was evaluated; the bonding strength decreased after the immersion tests. The alkaline phosphatase (ALP) activity of SaOS-2 cells on a titanium plate coated with a calcium phosphate film was examined by conducting a culture test. Calcium phosphate coating increased the ALP activity of SaOS-2 cells cultured for 3 and 7 days. Titanium cylinders were coated with an amorphous calcium phosphate film and implanted into the mandibles of beagle dogs. An increase in the extent of bone-implant contact for the coated titanium cylinders was confirmed 8 to 12 weeks after implantation and compared with the case for uncoated titanium cylinders.


Awareness of bird flu amongst young college students.
To assess the awareness among students about the disease, their attitude during the outbreak, along with their perceptions about treatment, and severity of disease. A cross sectional study was conducted among 220 intermediate students. The data was collected through a self filled questionnaire after taking verbal consent. The variables included in this study were age, gender and department (medical/non-medical). A total of 220 students participated with mean age of 17 +/- 1 year. There were 132 (61%) males and 84 (39%) females. The students were divided into pre-medical 110 (50%) and non-premedical 110 (50%). About 211 (96%) students said that they had heard about bird flu but only 86 (39%) correctly identified it as a disease of birds and humans both. One hundred and fifty-four (70%) participants said that virus causes it and the most common source of knowledge was media (T.V) by 153 (70%) followed by newspaper 113 (51%) respondents. Flu like symptoms were identified by 77 (35%) and 160 (73%) considered birds to human as the most likely route of transmission. Regarding vaccine, 133 (70%) replied that it is not available and 80 (41%) said that there is a treatment for the disease. About 143 (73%) thought that it is life-threatening. According to 105 (48%) the suitable preventive measure taken by the government would be to kill susceptible chickens. The awareness regarding bird flu was quite low among students. As bird flu is a world wide public health problem therefore increasing awareness would be a solution to avoid its spread and complications.


Lennox-Gastaut Syndrome: A State of the Art Review.
Lennox-Gastaut syndrome (LGS) is a severe age-dependent epileptic encephalopathy usually with onset between 1 and 8 years of age. Functional neuroimaging studies recently introduced the concept of Lennox-Gastaut as "secondary network epilepsy" resulting from dysfunctions of a complex system involving both cortical and subcortical structures (default-mode network, corticoreticular connections, and thalamus). These dysfunctions are produced by different disorders including hypoxic-ischemic encephalopathies, meningoencephalitis, cortical malformations, neurocutaneous disorders, or tumors. The list of etiologies was expanded to pathogenic copy number variants at whole-genome array comparative genomic hybridization associated with late-onset cases or pathogenic mutations involving genes, such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2. Various clinical trials demonstrated the usefulness of different drugs (including rufinamide, clobazam, lamotrigine, topiramate, or felbamate), ketogenic diet, resective surgery, corpus callosotomy, and vagus nerve stimulation in the treatment of epileptic manifestations. The outcome of LGS often remains disappointing regarding seizure control or cognitive functioning. The realization of animal models, which are still lacking, and the full comprehension of molecular mechanisms involved in epileptogenesis and cognitive impairment would give a relevant support to further improvements in therapeutic strategies for LGS patients.


Prospective Randomized Trial Comparing Transperitoneal Versus Extraperitoneal Laparoscopic Aortic Lymphadenectomy for Surgical Staging of Endometrial and Ovarian Cancer: The STELLA Trial.
There is an ongoing debate on which approach, transperitoneal or extraperitoneal, is superior for the performance of laparoscopic aortic lymphadenectomy (LPA-LND) for the surgical staging of gynecologic cancer. A prospective randomized trial (STELLA trial) was designed to compare the perioperative outcomes and node retrieval of extraperitoneal versus transperitoneal aortic lymphadenectomy by laparoscopy or robot-assisted laparoscopy. Patients with endometrial or ovarian carcinoma requiring aortic lymphadenectomy for surgical staging were randomized to an extraperitoneal or transperitoneal approach by laparoscopy or robot-assisted laparoscopy between June 2012 and July 2014. A total of 60 patients were entered into the study, 48 with endometrial cancer (80 %) and 12 with ovarian cancer (20 %). Thirty-one patients (51.6 %) were randomly assigned to the extraperitoneal group and 29 to the transperitoneal group (48.3 %). The means LPA-LND operating time was 90 min in both group (p = 0.343). The mean (range) blood loss was 105 (10-400) mL for extraperitoneal versus 100 (5-1000) mL for transperitoneal group (p = 0.541). There were no differences in the number of collected lymph nodes between the two groups [median (range) for extraperitoneal 12 (4-41) vs. 13 (4-29) for transperitoneal (p = 0.719)]. The extraperitoneal and transperitoneal approaches for laparoscopic and robotic aortic lymphadenectomy provide similar perioperative outcomes and nodal yields. The STELLA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT01810874.


Cardiac Output Measurements in Septic Patients: Comparing the Accuracy of USCOM to PiCCO.
USCOM is an ultrasound-based method which has been accepted for noninvasive hemodynamic monitoring in various clinical conditions (USCOM, Ultrasonic cardiac output monitoring). The present study aimed at comparing the accuracy of the USCOM device with that of the thermodilution technique in patients with septicemia. We conducted a prospective observational study in a medical but noncardiological ICU of a university hospital. Septic adult patients (median age 55 years, median SAPS-II-Score 43 points) on mechanical ventilation and catecholamine support were monitored with USCOM and PiCCO (n = 70). Seventy paired left-sided CO measurements (transaortic access = CO(US-A)) were obtained. The mean CO(US-A) were 6.55 l/min (±2.19) versus CO(PiCCO) 6.5 l/min (±2.18). The correlation coefficient was r = 0.89. Comparison by Bland-Altman analysis revealed a bias of -0.36 l/min (±0.99 l/min) leading to a mean percentage error of 29%. USCOM is a feasible and rapid method to evaluate CO in septic patients. USCOM does reliably represent CO values as compared to the reference technique based on thermodilution (PiCCO). It seems to be appropriate in situations where CO measurements are most pertinent to patient management.


[Toxicological evaluation of gamma ray-treated fresh fish in an experiment on rats].
The effect of fish treated with gamma-beams on the animal body on the whole and on some organs and tissues was studied in chronic experiments on 4 generations of Wistar rats of both sexes. The animals' status was evaluated according to the rats' appearance, behavior, and the time-course of changes in the body weight. In rats of the basic generation, the rate of tumor occurrence and tumor sites were also examined. Morphological and biochemical investigations were carried out over time, namely after 4, 8, 12 and 17 months. The measurements were taken of blood serum and liver proteins, blood sulfhydryl groups and hemoglobin, ascorbic acid in the liver and adrenals, as well as of the activity of AST, ALT and cholinesterase in the blood serum and in the liver. In the majority of cases, the findings obtained in experimental animals did not differ from those in controls.


EEG beta desynchronization during hand goal-directed action observation in newborn monkeys and its relation to the emergence of hand motor skills.
Previous developmental research suggests that motor experience supports the development of action perception across the lifespan. However, it is still unknown when the neural mechanisms underlying action-perception coupling emerge in infancy. The goal of this study was to examine the neural correlates of action perception during the emergence of grasping abilities in newborn rhesus macaques. Neural activity, recorded via electroencephalogram (EEG), while monkeys observed grasping actions, mimed actions and means-end movements during the first (W1) and second week (W2) of life was measured. Event-related desynchronization (ERD) during action observation was computed from the EEG in the alpha and beta bands, two components of the sensorimotor mu rhythm associated with activity of the mirror neuron system (MNS). Results revealed age-related changes in the beta band, but not the alpha band, over anterior electrodes, with greater desynchronization at W2 than W1 for the observation of grasping actions. Additionally, desynchronization to observed grasping actions at W2 was associated with infants' motor skills - measured by a separate behavioral task - such that more grasping attempts were associated to greater beta ERD. These findings suggest the emergence of an early action-perception system, that relies on motor experience, shortly after birth.


Methodology for antithrombotic and thrombolytic therapy guideline development: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th Edition).
The American College of Chest Physicians (ACCP) invited a panel of experts, researchers, information scientists, and guideline methodologists to develop the eighth edition of ACCP evidence-based guidelines on antithrombotic and thrombolytic therapy. The process began with guideline authors specifying the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible articles, including methodologic criteria, for each recommendation. The McMaster University Evidence-Based Practice Center, in collaboration with the guideline authors and methodologists, developed strategies and executed systematic searches for evidence. The resulting guidelines are organized in chapters that present a clear link between the evidence and the resulting recommendations. The panel identified questions in which resource allocation issues were particularly important and obtained input from consultants with expertise in economic analysis for these issues. Authors paid careful attention to the quality of underlying evidence and the balance between risks and benefits, both reflected in grades of recommendations. For recommendations that are particularly sensitive to underlying values and preferences, the panel made explicit the values underlying the recommendations. Thus, the process of making recommendations for the ACCP guidelines included explicit definition of questions, transparent eligibility criteria for including studies, comprehensive searches and methodologic assessment of studies, and specification of values and preferences and resource implications underlying recommendations where particularly relevant. In combination with our previous practice of grading recommendations according to their strength and the methodologic quality of the supporting studies, these methods establish our guideline methodology as evidence based.


An Anesthesiologist's Perspective on the History of Basic Airway Management: The "Progressive" Era, 1904 to 1960.
This third installment of the history of basic airway management discusses the transitional-"progressive"-years of anesthesia from 1904 to 1960. During these 56 yr, airway management was provided primarily by basic techniques with or without the use of a face mask. Airway maneuvers were inherited from the artisanal era: head extension and mandibular advancement. The most common maneuver was head extension, also used in bronchoscopy and laryngoscopy. Basic airway management success was essential for traditional inhalation anesthesia (ether, chloroform) and for the use of the new anesthetic agents (cyclopropane, halothane) and intravenous drugs (thiopental, curare, succinylcholine). By the end of the era, the superiority of intermittent positive pressure ventilation to spontaneous ventilation in anesthesia and negative pressure ventilation in resuscitation had been demonstrated and accepted, and the implementation of endotracheal intubation as a routine technique was underway.


Maturation-related changes in the expression of Fc gamma RII and Fc gamma RIII on mouse mast cells derived in vitro and in vivo.
The expression and function of Fc gamma RII and Fc gamma RIII on three mouse mast cell populations that differ in maturity as assessed by secretory granule constituents were analyzed by cellular and immunochemical approaches. As quantified by flow cytometric analysis of the binding of the rat 2.4G2 anti-Fc gamma RII/III mAb, mouse serosal mast cells (SMC) purified from the peritoneal cavity expressed more receptors per cell than did mouse IL-3-dependent, bone marrow culture-derived mast cells (BMMC), which are progenitors of SMC. Coculture of BMMC with mouse 3T3 fibroblasts for 2 wk, which alters the secretory granule composition toward that of SMC, also increased receptor epitope expression to a level equivalent to that of SMC. As assessed by rosette assays with mouse mAb to SRBC, all three mast cell populations bound IgG1, IgG2a, and IgG2b, essentially all binding was inhibited by 2.4G2 antibody, and greater quantities of the antibody were required to block immune adherence by cocultured mast cells and SMC as compared with BMMC. Immunoprecipitation and SDS-PAGE analysis of Fc gamma RII and Fc gamma RIII from BMMC, cocultured mast cells, and SMC that were surface radiolabeled with Na125I revealed predominant native forms of 62, 57, and 56 kDa, respectively, and an additional surface form of 43 kDa in SMC. Removal of N-linked carbohydrate from immunoprecipitates demonstrated that BMMC expressed peptide cores of 38 kDa (Fc gamma RII-1 gene product) and 31 kDa (Fc gamma RII-2 gene product), and barely detectable amounts of a 28-kDa (Fc gamma RIII gene product) core. The expression of all three was increased by coculture with 3T3 fibroblasts, consistent with the increased expression of their common epitope by cytofluorographic analysis. SMC expressed primarily the Fc gamma RII-1 and some Fc gamma RIII gene product. Thus, the three populations of mast cells express different amounts and ratios of the Fc gamma RII and Fc gamma RIII gene products, and maturation of BMMC during coculture with fibroblasts in vitro and in the peritoneal cavity in vivo augments cell-surface expression of the receptors and immune adherence function.


Associations of plasma renin with 10-year cardiovascular mortality, sudden cardiac death, and death due to heart failure.
Renin is the key regulator of the renin-angiotensin-aldosterone system. Previous studies have reported conflicting results on the relation of plasma renin with fatal cardiovascular events. This study in a large cohort of patients sought to evaluate the association between plasma renin concentration (PRC) and cardiovascular mortality after long-term follow-up of almost 10 years. Plasma renin concentration [median: 11.4 (6.0-24.6) pg/mL] was measured in 3303 patients (mean age: 62.7 ± 10.6 years; 30.3% women) referred to coronary angiography. After a median follow-up of 9.9 years, 554 participants (16.8%) with PRC measurement at baseline had died due to fatal cardiovascular events. Multivariable-adjusted Cox analysis revealed that when compared with participants in the lowest PRC quartile, those in the highest quartile were at increased risk of cardiovascular mortality (hazard ratio: 1.79, 95% CI 1.28-2.48). Analyses of specific causes of cardiovascular death showed that for each standard deviation increase in log-PRC there was a 22% (P = 0.006) increase in risk of sudden cardiac death and a 23% (P = 0.033) greater risk of death due to heart failure. The association of PRC with cardiovascular mortality remained stable after adjustment for established cardiovascular risk factors, ongoing antihypertensive medication, immunoreactive angiotensin II, and aldosterone levels. Age, N-terminal pro-B-type natriuretic peptide levels, coronary artery disease, the use of angiotensin-converting enzyme-inhibitors, beta-blockers, diuretics, and kidney function were important effect modifiers. Plasma renin concentration is associated with long-term cardiovascular mortality in patients referred to coronary angiography. Further intervention studies should determine whether renin is a potential therapeutic target or only a marker of mortality risk in various cardiovascular risk groups.


Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and retrovirus infections.
The acyclic nucleoside phosphonates [HPMPC: cidofovir, Vistide; PMEA: adefovir dipivoxil, Hepsera; and PMPA: tenofovir, Viread] have proven to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections, for example, cidofovir against herpesvirus [herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus type 6, 7 and 8), polyoma-, papilloma-, adeno- and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus and orf) infections; adefovir against herpesvirus, hepadnavirus [human hepatitis B virus] and retrovirus [HIV type-1 and 2, simian immunodeficiency virus and feline immunodeficiency virus] infections; and tenofovir against both hepadna- and retrovirus infections. Cidofovir has been officially approved for the treatment of cytomegalovirus retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) for the treatment of HIV infections (i.e., AIDS) and adefovir dipivoxil for the treatment of chronic hepatitis B.


Artificial intelligence in cardiology.
Decision-making is complex in modern medicine and should ideally be based on available data, structured knowledge and proper interpretation in the context of an individual patient. Automated algorithms, also termed artificial intelligence that are able to extract meaningful patterns from data collections and build decisions upon identified patterns may be useful assistants in clinical decision-making processes. In this article, artificial intelligence-based studies in clinical cardiology are reviewed. The text also touches on the ethical issues and speculates on the future roles of automated algorithms versus clinicians in cardiology and medicine in general.


Epigallocatechin-3-gallate reduces the proliferation of benign prostatic hyperplasia cells via regulation of focal adhesions.
Benign prostatic hyperplasia (BPH) is the most common urological disease that is characterized by the excessive growth of prostatic epithelial and stromal cells. Pharmacological therapy for BPH has limited use due to the many side effects so there is a need for new agents including natural compounds such as epigallocatechin-3-gallate (EGCG). This study was undertaken to assess the role of EGCG, suppressing the formation of BPH by reducing inflammation and oxidative stress, in cytoskeleton organization and ECM interactions via focal adhesions. We performed MTT assay to investigate cell viability of BPH-1 cells, wound healing assay to examine cell migration, immunofluorescence assay for F-actin organization and paxillin distribution and finally immunoblotting to investigate focal adhesion protein levels in the presence and absence of EGCG. We found that EGCG inhibits cell proliferation at the concentration of 89.12μM, 21.2μM and 2.39μM for 24, 48 and 72h, respectively as well as inhibitory effects of EGCG on BPH-1 cell migration were observed in a wound healing assay. Furthermore, it was determined by immunofluorescence labeling that EGCG disrupts F-actin organization and reduces paxillin distribution. Additionally, EGCG decreases the activation of FAK (Focal Adhesion Kinase) and the levels of paxillin, RhoA (Ras homolog gene family, member A), Cdc42 (cell division cycle 42) and PAK1 (p21 protein-activated kinase 1) in a dose-dependent manner. For the first time, by this study, we found evidence that BPH-1 cell proliferation could be inhibited with EGCG through the disruption of cytoskeleton organization and ECM interactions. Consequently, EGCG might be useful in the prevention and treatment of diseases characterized by excessive cell proliferation such as BPH.


Statin Adverse Events in Primary Prevention: Between Randomized Trials and Observational Studies.
Considerable debate exists regarding who might benefit from statins for primary prevention. Statins have wide pleotropic effects, which contribute to their efficacy in lowering cardiovascular disease but may also result in adverse events (AEs). Caveats in identifying AEs in randomized controlled trials (RCTs) include the lack of a standardized definition of statin-associated AEs, the differences in properties of different statins, the selectivity of RCTs in choosing their participants, the presence of high rate of nonadherence/withdrawal from trials and other concerns related to study design and conflict of interest. Caveats in identifying or overestimating AEs in observational studies include failure to identify baseline confounders, ascertainment bias, confounding by indication and healthy user bias. Statin use in observational studies may be a surrogate marker for higher socioeconomic standards, access to health care or use of other preventive services. Integrating evidence from both RCTs and observational studies is of paramount importance for appropriate patient-centered decision.


Folate supplementation in pregnancy.
Folate depletion may result in anaemia during pregnancy. The objective of this review was to assess the effects of folate supplementation in pregnancy on haematological and biochemical parameters and measures of pregnancy outcome. This review did not address the role of periconceptual folate supplementation to diminish the risk of fetal malformation. A comprehensive electronic search included that of the Cochrane Pregnancy and Childbirth Group trials register. Acceptably controlled trials of folate supplementation compared with placebo or no treatment to pregnant women with normal haemoglobin levels. Trial quality was assessed. Study authors were contacted for additional information when necessary. Twenty-one studies were included. The trials varied in quality. Compared to placebo or no supplementation, folate supplementation was associated with increased or maintained serum folate levels (odds ratio 0.18, 95% confidence interval 0.13 to 0.24) and red cell folate levels (odds ratio 0.18, 95% confidence interval 0.09 to 0.38). Folate supplementation was associated with a reduction in the proportion of women with low haemoglobin level in late pregnancy (odds ratio 0.61, 95% confidence interval 0.52 to 0.71) and megaloblastic erythropoiesis (odds ratio 0.65, 95% confidence interval 0.45 to 0.95). Apart from a possible reduction in the incidence of low birthweight, folate supplementation appears to have no measurable effect on any other substantive measures of pregnancy outcome. Folate supplementation during pregnancy appears to improve haemoglobin levels and folate status. There is not enough evidence to evaluate whether folate supplementation has any effect, beneficial or harmful, on clinical outcomes for mother and baby.


Uranium Mining and Norm in North America-Some Perspectives on Occupational Radiation Exposure.
All soils and rocks contain naturally occurring radioactive materials (NORM). Many ores and raw materials contain relatively elevated levels of natural radionuclides, and processing such materials can further increase the concentrations of naturally occurring radionuclides. In the U.S., these materials are sometimes referred to as technologically-enhanced naturally occurring radioactive materials (TENORM). Examples of NORM minerals include uranium ores, monazite (a source of rare earth minerals), and phosphate rock used to produce phosphate fertilizer. The processing of these materials has the potential to result in above-background radiation exposure to workers. Following a brief review of the sources and potential for worker exposure from NORM in these varied industries, this paper will then present an overview of uranium mining and recovery in North America, including discussion on the mining methods currently being used for both conventional (underground, open pit) and in situ leach (ISL), also referred to as In Situ Recovery (ISR), and the production of NORM materials and wastes associated with these uranium recovery methods. The radiological composition of the NORM products and wastes produced and recent data on radiological exposures received by workers in the North American uranium recovery industry are then described. The paper also identifies the responsible government agencies in the U.S. and Canada assigned the authority to regulate and control occupational exposure from these NORM materials.


Establishment of a rapid and effective plate chromogenic assay for screening of Aspergillus species with high β-fructofuranosidase activity for fructooligosaccharides production.
Fructooligosaccharides (FOS) are commonly regarded as prebiotics and used as components of functional foods. Currently, the industrial sucrose-to-FOS biotransformation is mainly carried out using the microbial-derived β-fructofuranosidases with transglycosylation activity as catalysts. Evaluation of the ability of a microorganism to produce β-fructofuranosidase is commonly conducted by measuring enzyme activity. However, the traditional method requires several steps to identify strains with high β-fructofuranosidase activity, which is not suitable for high-throughput screening. To facilitate screening of a large number of microbial cultures, this study developed a plate chromogenic assay method based on the glucose oxidase (GOD) - peroxidase (POD) bienzymatic system for screening of β-fructofuranosidase-producing fungal strains and predicting their potential to produce FOS. This method used the amount of glucose released from sucrose as indicator to form clear pink halos around the microbial colonies with β-fructofuranosidase activity. Cultivation conditions for the plate assay were optimized as cultivation time 5 h and spore inoculum concentration 108/ml. Moreover, the method was applied to screening of an Aspergillus niger ATCC 20611 mutant library. The mutant A11 displaying the largest pink halo was screened out and its β-fructofuranosidase activity was determined to be 1.65 fold than that of the parental strain. Thin layer chromatography (TLC) assay further indicated that A11 with the largest halo possessed the highest FOS synthesis ability. These results demonstrated the potential of this plate chromogyenic assay method in the rapid and effective identification of excellent FOS producers from a large number of strain samples.


Amygdala volume in schizophrenia: post-mortem study and review of magnetic resonance imaging findings.
Claims that schizophrenia is a disease of the limbic system have been strengthened by meta-analyses of magnetic resonance imaging (MRI) studies finding reduced hippocampus and amygdala volumes. Some post-mortem studies do not find these abnormalities. To assess the volume of the amygdala in a series of brains post-mortem. Amygdala volume was estimated using point-counting in both hemispheres of the brains of 10 male and 8 female patients with schizophrenia, and a comparison group of 9 males and 9 females. No significant reduction of amygdala volume was found. Significant volume reduction of the amygdala is not a consistent feature of schizophrenia; findings from early MRI studies using coarse delineation methods may introduce bias to subsequent meta-analyses.


Occurrence and spontaneous remission of Graves' hyperthyroidism preceded by painless thyroiditis.
A 45-year-old woman was referred to our hospital because of discomfort in the cervical region. Laboratory findings revealed thyrotoxicosis with positive TSH receptor antibodies, but acute inflammatory data were absent. After three weeks the thyroid hormone levels spontaneously decreased to hypothyroid levels, and thyroidal radioactive iodine uptake (RAIU) was below normal. A needle-biopsy specimen of the thyroid gland obtained two months later showed diffuse lymphocytic thyroiditis, and she was therefore diagnosed as having had painless thyroiditis. Two months after returning to euthyroidism, a second thyrotoxicosis developed. TSH receptor antibodies remained positive, but RAIU was slightly above normal, indicating Graves' hyperthyroidism. Treatment with antithyroidal drugs was commenced but was soon discontinued due to an allergic reaction. Although only beta-adrenergic antagonist was administered for treating the thyrotoxicosis, thyroid function was gradually normalized in parallel with the reduction in TSH receptor antibody. In this case, painless thyroiditis would be followed by Graves' disease and subsequent spontaneous remission.


Effect of converting enzyme inhibition on glucocorticoid hypertension in the rat.
The renin-angiotensin system was evaluated by inhibition of converting enzyme (CEI) and by testing sensitivity to angiotensin II (AII) in sodium-depleted rats made hypertensive by methylprednisolone (MP), 20 mg/kg im. During a 2-wk period blood pressure rose 38 +/- 4 mmHg (P less than 0.001) in MP and 3 +/- 4 mmHg in controls. After pentobarbital anesthesia, intra-arterial pressure and dose-response curves to AII were determined, before and after SQ14225 (d-3-mercapto-2-methylpropranoyl-l-proline) (1 mg/kg iv). CEI reduced pressure significantly in both MP and controls, although the decrease was smaller in the former (P less than 0.05). Pressor responses to AII were nearly identical in MP and controls and were enhanced to a similar extent by CEI. Ganglionic blockade with pentolinium tartrate, given after CEI, did reduce the pressure in both groups to equal levels. Responses to AII after pentolinium were similar to those obtained after CEI alone. These results indicate that the renin component of glucocorticoid hypertension during sodium deficiency is smaller than that of the normotensive controls. No evidence of glucocorticoid-induced vascular hypersensitivity to AII was detected in this model of experimental hypertension.


Different domains of Sgs1 are required for mitotic and meiotic functions.
The SGS1 of Saccharomyces cerevisiae is a homologue for human Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson's syndrome causative genes. Disruptants of SGS1 show high sensitivity to methyl methanesulfonate (MMS) and hydroxyurea, and hyper recombination phenotypes including interchromosomal homologous recombination in mitotic growth. In addition, sgs1 disruptants show poor sporulation and a reduced level of meiotic recombination as assayed by return-to-growth. We examined domains of Sgs1 required for mitotic and meiotic functions of Sgs1 by transfecting variously mutated SGS1 into sgs1 disruptants. The N-terminal 1-401 amino acid region was required for complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations of sgs1 disruptants in mitotic growth and for complementation of poor sporulation and of reduced meiotic recombination. Although the N-terminal 1-125 amino acid region was absolutely required for the complementation of MMS sensitivity and suppression of hyper heteroallelic recombinations in mitotic growth, it was dispensable for the meiotic functions. In contrast, the highly acidic region (400-596 amino acid) was dispensable for the mitotic functions but a deletion of this region affected the meiotic functions. The C-terminal 1271-1350 amino acid region containing a HRDC (helicase and RNaseD C-terminal) domain was dispensable for the mitotic and meiotic functions. Although DNA helicase activity of Sgs1 was not required for Sgs1 to complement the meiotic functions, a deletion of helicase motifs III-IV (842-1046 amino acid) abolished the complementing activity of Sgs1, indicating that a structurally intact helicase domain is necessary for Sgs1 to fulfill its meiotic functions.


Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: complications, aneurysm sac occlusion, reabsorption, recurrence, and jailed branch modification at follow-up.
The purpose of this study is to present the authors' medium-term results, with special emphasis on complications, occlusion rate of the aneurysm sac (digital subtraction angiography [DSA] and MRI), and the fate of cortical branches and perforating arteries covered ("jailed") by the flow diverter (FD) stent. Between January 2010 and September 2017, 29 patients (14 female) with 30 aneurysms were treated with an FD stent. Twenty-one aneurysms were at the middle cerebral artery bifurcation, 8 were in the anterior communicating artery region, and 1 was a pericallosal artery bifurcation. Thirty-five cortical branches were covered. A single FD stent was used in all patients. Symptomatic and asymptomatic periprocedural and delayed complications were reported. DSA and MRI controls were analyzed to evaluate modification of the aneurysm sac and jailed branches. Permanent morbidity was 3.4% (1/29), due to a jailed branch occlusion, with a modified Rankin Scale (mRS) score of 2 at the last follow-up. Mortality and permanent complication with poor prognosis (mRS score > 2) rates were 0%. The mean follow-up time for DSA and MRI (mean ± SD) was 21 ± 14.5 months (range 3-66 months) and 19 ± 16 months (range 3-41 months), respectively. The mean time to aneurysm sac occlusion (available for 24 patients), including stable remodeling, was 11.8 ± 6 months (median 13, range 3-27 months). The overall occlusion rate was 82.1% (23/28), and it was 91.7% (22/24) in the group of patients with at least 2 DSA control sequences. One recanalization occurred at 41 months posttreatment. At the time of publication, at the latest follow-up, 7 (20%) of 35 covered branches were occluded, 18 (51.4%) showed a decreased caliber, and the remaining 10 (28.5%) were unchanged. MRI T2-weighted sequences showed complete sac reabsorption in 7/29 aneurysms (24.1%), and the remaining lesions were either smaller (55.2%) or unchanged (17.2%). MRI revealed asymptomatic and symptomatic ischemic events in perforator territories in 7/28 (25%) and 4/28 (14.3%) patients, respectively, which were reversible within 24 hours. Flow diversion of bifurcation aneurysms is feasible, with low rates of permanent morbidity and mortality and high occlusion rates; however, recurrence may occur. Caliber reduction and asymptomatic occlusion of covered cortical branches as well as silent perforator stroke are common. Ischemic complications may occur with no identified predictable factors. MRI controls should be required in all patients to evaluate silent ischemic lesions and aneurysm sac reabsorption over time.