How different are robust and gracile capuchin monkeys? An argument for the use of sapajus and cebus.
Capuchin monkey behavior has been the focus of increasing numbers of captive and field studies in recent years, clarifying behavioral and ecological differences between the two morphological types: the gracile and the robust capuchins (also referred to as untufted and tufted). Studies have tended to focus on the gracile species Cebus capucinus (fewer data are available for C. albifrons, C. olivaceus, and C. kaapori) and on Cebus apella, a name that has encompassed all of the robust capuchins since the 1960s. As a result, it is difficult to ascertain the variation within either gracile or robust types. The phylogenetic relationships between gracile and robust capuchins have also, until now, remained obscure. Recent studies have suggested two independent Pliocene radiations of capuchins stemming from a common ancestor in the Late Miocene, about 6.2 millions of years ago (Ma). The present-day gracile capuchins most likely originated in the Amazon, and the robust capuchins in the Atlantic Forest to the southeast. Sympatry between the two types is explained by a recent expansion of robust capuchins into the Amazon (ca. 400,000 years ago). Morphological data also support a division of capuchins into the same two distinct groups, and we propose the division of capuchin monkeys into two genera, Sapajus Kerr, 1792, for robust capuchins and Cebus Erxleben, 1777, for gracile capuchins, based on a review of extensive morphological, genetic, behavioral, ecological, and biogeographic evidence.


Using agricultural metadata: a novel investigation of trends in sowing date in on-farm research trials using the Online Farm Trials database.
Background: A growing ability and interest in the collection of data, together with the development and adoption of the FAIR guiding principles, has increased the amount of data available in many disciplines. This has given rise to an urgent need for robust metadata. Within the Australian grains industry, data from over thousands of on-farm research trials (Trial Projects) have been made available via the Online Farm Trials (OFT) website. OFT Trial Project metadata were developed as filters to refine front-end database searches, but could also be used as a dataset to investigate trends in metadata elements. Australian grains crops are being sown earlier, but whether on-farm research trials reflect this change is currently unknown. Methods: We investigated whether OFT Trial Project metadata could be used to detect trends in sowing dates of on-farm crop research trials across Australia, testing the hypothesis that research trials are being sown earlier in line with local farming practices. The investigation included 15 autumn-sown, winter crop species listed in the database, with trial records from 1993 to 2019. Results: Our analyses showed that (i) OFT Trial Project metadata can be used as a dataset to detect trends in sowing date; and (ii) cropping research trials are being sown earlier in Victoria and Western Australia, but no trend exists within the other states. Discussion/Conclusion: Our findings show that OFT Trial Project metadata can be used to detect trends in crop sowing date, suggesting that metadata could also be used to detect trends in other metadata elements such as harvest date. Because OFT is a national database of research trials, further assessment of metadata may uncover important agronomic, cultural or economic trends within or across the Australian cropping regions. New information could then be used to lead practice change and increase productivity within the Australian grains industry.


[Detection of endocrine pathology in children in a rural locale and the organization of their care].
As a result of the examination of 14500 children, living in the Rostov Region, data have been obtained, characterizing the level and nature of endocrine disturbance in rural children, being evaluated from such aspects as the individual physical and sexual development. Endocrine disease in the rural children (116.2 +/- 3.2%) does not exceed these abnormalities observed among the town children. The prevalence of endocrine diseases increases from 90.3 +/- 5.1% in the children, ranging in age from birth to 7 years old, to 143.2 +/- 5.3% in the schoolchildren. Girls are more often developing obesity (t = 4.2) and endocrine abnormalities (t = 4.6), whereas boys are suffering from delay of the growth (t = 3.5) and sexual maturation. The standard glucose tolerance test, performed in the children at a high risk of diabetes mellitus (with aggravated heredity in regard to diabetes mellitus and obesity of the II, III and IV stages) has revealed intolerance in 59% of the children, of whom 2.2% had diabetic type curves. Based on the data on endocrine abnormalities, a mode of the organization structure for the children's endocrinological service was developed.


Altitude-dependent and -independent variations in Plasmodium falciparum prevalence in northeastern Tanzania.
Effective malaria control requires information about intensity of transmission across large areas and populations. Estimates based on entomological factors lack precision and are not cost-effective to obtain. We tested altitude and rainfall measurements as correlates of transmission intensity in different ecological settings. We conducted 2 cross-sectional surveys of approximately 12,000 people (1-45 years old) in 6 altitude transects (150-1800 m) in the Kilimanjaro and Tanga regions of Tanzania. Data were analyzed for associations with altitude and rainfall estimates by use of appropriate regression models. Plasmodium falciparum prevalence showed a negative relationship with altitude (19% and 21% decrease/100-m altitude increase, respectively, in children in Kilimanjaro and Tanga) and rainfall during the 3 months before the survey (46% decrease/100-mm rainfall increase in children in Kilimanjaro). Mean hemoglobin concentrations increased with altitude (0.05 and 0.09 g/dL/100-m altitude increase, respectively, in children in Kilimanjaro and Tanga) and rainfall (0.17 g/dL/100-mm rainfall increase in children and adults in Kilimanjaro). Altitude and rainfall were correlated with parasite prevalence and mean hemoglobin concentration; however, the relationship varied according to ecological setting. Climatological variables alone cannot predict malarial outcomes. Local variations in seasonality of malaria transmission--together with vector species composition, topography, host and parasite genetics, and socioeconomic factors--may influence malaria prevalence.


Factors associated with survival of epiploic foramen entrapment colic: a multicentre, international study.
Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area.


Overview: measles outbreak on a college campus.
Although the introduction of the measles vaccine in the United States in 1963 has led to a marked decrease in the incidence of measles (rubeola), this childhood exanthem has not been eliminated. Since 1983, increases in incidence have been observed. Outbreaks have occurred among previously immunized school and college-age students and unimmunized preschool children, infants, and babies. This article reports a measles outbreak at a state university in Texas and proposes a plan to develop immunity against measles to prevent future outbreaks at college and university campuses.


The chromosome 3p21.3-encoded gene, LIMD1, is a critical tumor suppressor involved in human lung cancer development.
Loss of heterozygosity (LOH) and homozygous deletions at chromosome 3p21.3 are common in both small and nonsmall cell lung cancers, indicating the likely presence of tumor suppressor genes (TSGs). Although genetic and epigenetic changes within this region have been identified, the functional significance of these changes has not been explored. Concurrent protein expression and genetic analyses of human lung tumors coupled with functional studies have not been done. Here, we show that expression of the 3p21.3 gene, LIMD1, is frequently down-regulated in human lung tumors. Loss of LIMD1 expression occurs through a combination of gene deletion, LOH, and epigenetic silencing of transcription without evidence for coding region mutations. Experimentally, LIMD1 is a bona fide TSG. Limd1(-/-) mice are predisposed to chemical-induced lung adenocarcinoma and genetic inactivation of Limd1 in mice heterozygous for oncogenic K-Ras(G12D) markedly increased tumor initiation, promotion, and mortality. Thus, we conclude that LIMD1 is a validated chromosome 3p21.3 tumor-suppressor gene involved in human lung cancer development. LIMD1 is a LIM domain containing adapter protein that localizes to E-cadherin cell-cell adhesive junctions, yet also translocates to the nucleus where it has been shown to function as an RB corepressor. As such, LIMD1 has the potential to communicate cell extrinsic or environmental cues with nuclear responses.


Ecotope-based entomological surveillance and molecular xenomonitoring of multidrug resistant malaria parasites in anopheles vectors.
The emergence and spread of multidrug resistant (MDR) malaria caused by Plasmodium falciparum or Plasmodium vivax have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease in vitro and in vivo susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in Anopheles vectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation of Anopheles vectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction, Plasmodium- and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence of Anopheles vectors carrying MDR P. vivax in infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notified P. vivax patients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria parasites in hotspots or suspected areas established in most endemic GMS countries implementing the National Malaria Control Programs, in addition to what is guided by the World Health Organization.


Neuropeptides related to [Arg8]vasopressin facilitates social recognition in rats.
The decrease of social investigations of adult rats during a second encounter session with the same juvenile was used as an index of social recognition or memory. Social recognition was present when the interexposure interval was 15 or 30 min, but not when this interval lasted 60 or 120 min. Animals treated with desglycinamide[Arg8]vasopressin (DGAVP) (6.0 micrograms.kg-1, SC) or [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8] (1.0 microgram.kg-1, SC), immediately after the first encounter, recognized the same juveniles still after 120 min, suggesting a facilitatory effect of these peptides on social recognition and that this effect of vasopressin is dissociated from the classical endocrine effects of this hormone. The decrease of social investigating behavior, in both placebo- and DGAVP-treated rats, was completely due to a decrease in anogenital exploration, indicating that the social recognition in rats is presumably based on odor cues from the anogenital part of the body.


The overall pattern of ocular dominance bands in cat visual cortex.
This study describes the overall arrangement of geniculocortical input representing the system of cortical ocular dominance bands in layer IV of striate cortex in the adult cat. The pattern of ocular dominance bands was revealed by transneuronal transport of the intraocularly injected tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Our data indicate that this procedure does not damage the retina and that it results in relatively uniform uptake and transport of the tracer. Using previously published techniques (Olavarria and Van Sluyters, 1983, 1985), both cortical hemispheres of each cat were unfolded, flattened and tangentially sectioned. Analysis of the WGA-HRP labeling patterns in these sections revealed a relatively continuous network of irregularly branching bands in layer IV of area 17 in both hemispheres. Because of a systematic difference in the level of interband labeling, ocular dominance bands appear less distinct in the hemisphere contralateral to the injected eye. There is also a tendency for interband labeling to be greater in cortical regions that represent the more peripheral aspects of the binocular portion of the visual field. The width of an individual ocular dominance band in the cat fluctuates, so that it appears to be made up of a series of uniformly sized, roughly circular beads of label. The diameter of these beads averages 667 micron, and preliminary counts indicate that there are 650-675 beads in each striate cortex. Contrary to earlier suggestions, in 4 out of 6 hemispheres analyzed quantitatively there was no tendency for ocular dominance bands to be oriented along a preferred axis in cat striate cortex, including an axis orthogonal to the border between areas 17 and 18. Ocular dominance bands in area 18 appear to be broader than those in area 17, and they seem to have a greater tendency to be oriented orthogonal to the 17/18 border than those in area 17. Compared with the ocular dominance pattern in monkey striate cortex, the ocular dominance pattern in the cat is much less regular. In general, cat ocular dominance bands appear to fluctuate more in width, to change direction more often, and to be less likely to run orthogonal to the 17/18 border. The greater regularity of the primate ocular dominance pattern may be related to differences in the way in which the visual hemifield is mapped onto the striate cortex in these 2 species.


The syndrome of a large drop in hematocrit in hospitalized patients: clinical features and gastrointestinal bleeding outcomes.
Hemoglobin/hematocrit decreases in hospitalized patients without evidence of obvious gastrointestinal (GI) bleeding are common and often attributed to GI lesions. We hypothesized that inpatients with hematocrit declines without clinically overt GI bleeding have distinct clinical features and hence aimed to evaluate this clinical syndrome. We evaluated consecutive GI consults for patients with a decrease (drop) in hematocrit. Patients with documented prior GI bleeding, melena, hematochezia, hematemesis, and melenemesis were excluded. Hematocrit drops were calculated from preconsult zenith and nadir values and identified as acute (within 7 days), intermediate (7-30 days), or remote (beyond 30 days) on the basis of the shortest time to a hematocrit drop of at least 6%. We identified 101 patients having hematocrit drops without clinical evidence of GI bleeding. Seventy-six patients (75%) had an acute drop in hematocrit with a mean decline of 9.5%, whereas the 25 patients with an intermediate or remote drop in hematocrit had a mean decline of 12.5%. Endoscopic evaluation was performed in 55 patients. Five patients (5%) had a lesion consistent with GI bleeding; identified lesions included ischemic colitis, duodenal ulcer, esophageal varices, and postsphincterotomy ulcer. In the remaining 96 patients, a clinical explanation for the hematocrit drop was identified in 56 patients (58%), most commonly attributed to sepsis/shock, volume shifts, and postprocedure bleeding. Hematocrit drops without visible GI bleeding were uncommonly caused by bleeding intestinal lesions, contrary to current dogma. Non-GI explanations for hematocrit drops were often identified, although the cause of hematocrit drop remained unexplained in many patients.


Assessment of synovial fluid and serum cytokine levels in children with septic arthritis.
Acute septic arthritis (ASA) is a common orthopedic infection of children which may produce devastating sequelae and chronic morbidity. Improved understanding of the intra-articular inflammatory response in ASA may identify cytokine targets with diagnostic or therapeutic potential, though no detailed investigations to this end have been performed. Given this, we used a multiplex cytokine assay for assessment of levels of 40 different cytokines in the synovial fluid and blood of children with ASA. Twelve children (8 controls undergoing orthopedic surgery for non-infectious conditions and 4 with ASA) were prospectively enrolled. Blood and synovial fluid were collected intraoperatively from each subject, and the levels of 40 cytokines were determined using a multiplex assay. Cytokines were organized by function and structure into 12 groups for analysis. The Benjamini-Hochberg method was used to control for type 1 errors, with an a priori false discovery rate of 10%. Subjects with ASA were younger than controls (mean age 8.0 vs 13.1 years, p=0.0400). Significant elevations were seen in interleukins (IL) with chemokine properties, IL-6 and those in the common-γ chain group in the blood and synovial fluid of children with ASA compared with controls, while significant elevations in 5 additional cytokine groups were seen in synovial fluid from children with ASA compared with controls, most notably IL-6 (median 8294.3 vs 10.7 pg/mL, p=0.0066). Our pilot study is the first to describe in detail the cytokine response in children with ASA, and highlights the need for additional study.


High-resolution melting analysis of the single nucleotide polymorphism hot-spot region in the rpoB gene as an indicator of reduced susceptibility to rifaximin in Clostridium difficile.
Clostridium difficile, a Gram-positive, spore-forming, anaerobic bacterium, is the main causative agent of hospital-acquired diarrhoea worldwide. In addition to metronidazole and vancomycin, rifaximin, a rifamycin derivative, is a promising antibiotic for the treatment of recurring C. difficile infections (CDI). However, exposure of C. difficile to this antibiotic has led to the development of rifaximin-resistance due to point mutations in the β-subunit of the RNA polymerase (rpoB) gene. In the present study, 348 C. difficile strains with known PCR-ribotypes were investigated for respective single nucleotide polymorphisms (SNPs) within the proposed rpoB hot-spot region by using high-resolution melting (HRM) analysis. This method allows the detection of SNPs by comparing the altered melting behaviour of dsDNA with that of wild-type DNA. Discrimination between wild-type and mutant strains was enhanced by creating heteroduplexes by mixing sample DNA with wild-type DNA, leading to characteristic melting curve shapes from samples containing SNPs in the respective rpoB section. In the present study, we were able to identify 16 different rpoB sequence-types (ST) by sequencing analysis of a 325 bp fragment. The 16 PCR STs displayed a total of 24 different SNPs. Fifteen of these 24 SNPs were located within the proposed 151 bp SNP hot-spot region, resulting in 11 different HRM curve profiles (CP). Eleven SNPs (seven of which were within the proposed hot-spot region) led to amino acid substitutions associated with reduced susceptibility to rifaximin and 13 SNPs (eight of which were within the hot-spot region) were synonymous. This investigation clearly demonstrates that HRM analysis of the proposed SNP hot-spot region in the rpoB gene of C. difficile is a fast and cost-effective method for the identification of C. difficile samples with reduced susceptibility to rifaximin and even allows simultaneous SNP subtyping of the respective C. difficile isolates.


Antimicrobial stewardship in rural and remote primary health care: a narrative review.
Antimicrobial resistance is an emerging problem worldwide and poses a significant threat to human health. Antimicrobial stewardship programmes are being implemented in health systems globally, primarily in hospitals, to address the growing threat of antimicrobial resistance. Despite the significance of primary health care services in providing health care to communities, antimicrobial stewardship programmes are not well established in this sector, especially in rural and remote settings. This narrative review aims to identify in rural and remote primary health care settings the (1) correlation of antimicrobial resistance with antibiotic prescribing and volume of antibiotic use, (2) appropriateness of antimicrobial prescribing, (3) risk factors associated with inappropriate use/prescribing of antibiotics, and (4) effective antimicrobial stewardship strategies. The international literature was searched for English only articles between 2000 and 2020 using specified keywords. Seven electronic databases were searched: Scopus, Cochrane, Embase, CINAHL, PubMed, Ovid Medline and Ovid Emcare. Publication screening and analysis were conducted using Joanna Briggs Institute systematic review tools. Fifty-one eligible articles were identified. Inappropriate and excessive antimicrobial prescribing and use directly led to increases in antimicrobial resistance. Increasing rurality of practice is associated with disproportionally higher rates of inappropriate prescribing compared to those in metropolitan areas. Physician knowledge, attitude and behaviour play important roles in mediating antimicrobial prescribing, with strong intrinsic and extrinsic influences including patient factors. Antimicrobial stewardship strategies in rural and remote primary health care settings focus on health care provider and patient education, clinician support systems, utility of antimicrobial resistance surveillance, and policy changes. Results of these interventions were generally positive with decreased antimicrobial resistance rates and improved appropriateness of antimicrobial prescribing. Inappropriate prescribing and excessive use of antimicrobials are an important contributor to the increasing resistance towards antimicrobial agents particularly in rural and remote primary health care. Antimicrobial stewardship programmes in the form of education, clinical support, surveillance, and policies have been mostly successful in reducing prescribing rates and inappropriate prescriptions. The narrative review highlighted the need for longer interventions to assess changes in antimicrobial resistance rates. The review also identified a lack of differentiation between rural and remote contexts and Indigenous health was inadequately addressed. Future research should have a greater focus on effective interventional components and patient perspectives.


Clinical and financial burden of hospitalised community-acquired pneumonia in patients with selected underlying comorbidities in England.
Hospitalised pneumonia may have long-term clinical and financial impact in adult patients with underlying comorbidities. We conducted a retrospective cohort study using the Hospital Episode Statistics (HES) database to determine the clinical and financial burden over 3 years of hospitalised community-acquired pneumonia (CAP) to England's National Health Service (NHS). Subjects were adults with six underlying comorbidities (chronic heart disease (CHD); chronic kidney disease (CKD); chronic liver disease (CLD); chronic respiratory disease (CRD); diabetes mellitus (DM) and post bone marrow transplant (post-BMT)) with an inpatient admission in 2012/2013. Patients with CAP in 2013/2014 were followed for 3 years and compared with similarly aged, propensity score-matched adults with the same comorbidity without CAP. The RR of hospital admissions increased after CAP, ranging from 1.08 (95% CI 1.04 to 1.12) for CKD to 1.38 (95% CI 1.35 to 1.40) for CRD. This increase was maintained for at least 2 years. Mean difference in hospital healthcare costs (£) was higher for CAP patients in 2013/2014; ranging from £1115 for DM to £8444 for BMT, and remained higher for 4/6 groups for 2 more years, ranging from £1907 (95% CI £1573 to £2240) for DM to £11 167 (95% CI £10 847 to £11 486) for CRD.) The OR for mortality was significantly higher for at least 3 years after CAP, ranging from 4.76 (95% CI 4.12 to 5.51, p<0.0001) for CLD to 7.50 (95%CI 4.71 to 11.92, p<0.0001) for BMT. For patients with selected underlying comorbidities, healthcare utilisation, costs and mortality increase for at least 3 years after being hospitalised CAP.


Differences in prescription rates and odds ratios of antidepressant drugs in relation to individual hormonal contraceptives: a nationwide population-based study with age-specific analyses.
To examine, among young women, the association of individual hormonal contraceptives, within two broad groupings, with antidepressant therapy. In a nationwide register-based study, we examined the prescription rates of antidepressant drugs in relation to individual combined hormonal and progestin-only contraceptives among Swedish women aged 16-31 years (N = 917,993). Drug data were obtained from the Swedish Prescribed Drug Register for the period 1 July 2005-30 June 2008. Data on the total population of women aged 16-31 in 2008 were obtained from the Total Population Register of Statistics Sweden. The proportion of women using both hormonal contraception and antidepressants, and odds ratios (ORs) for antidepressant use for hormonal contraceptive users versus non-users, were calculated, the latter by logistic regression, for each formulation. The highest antidepressant OR in all age groups, particularly in the 16-19 years age group, related to medroxyprogesterone-only, followed by etonogestrel-only, levonorgestrel-only and ethinylestradiol/norelgestromin formulations. Oral contraceptives containing ethinylestradiol combined with lynestrenol or drospirenone had considerably higher ORs than other pills. ORs significantly lower than 1 were observed when ethinylestradiol was combined with norethisterone, levonorgestrel or desogestrel. The association between use of hormonal contraceptives and antidepressant drugs varies considerably within both the combined hormonal contraceptive and the progestin-only groups.


A Descriptive Study of Objectively Measured Pokémon GO Playtime in College Students.
Since its debut in July 2016, Pokémon GO has been a wildly popular mobile gaming app. In contrast to many previous apps, Pokémon GO requires the user to be physically active. However, the extent to which Pokémon GO contributes to physical activity is unknown. Therefore, the purpose of this study was to investigate the physical activity profile of playing Pokémon GO for 60 minutes in recreationally active college students. College students (n=27, n=19 female) were fitted with an accelerometer, pedometer, and heart rate monitor to assess the activity demands during a 60-min bout of Pokémon GO. Troiano accelerometer cut points were utilized to estimate time spent in sedentary, light, moderate, and vigorous-intensity physical activity. Of the 60-min allotted playtime, accelerometry indicated 82% was achieved via moderate-to vigorous-intensity physical activity. Pedometer counts indicated approximately 6000-steps/100-steps/min, indicative of moderate-intensity physical activity. Heart rates were approximately 50% of age-predicted maximum, also indicative of moderate-intensity physical activity. The results of this study provide evidence that playing one hour of Pokémon GO can be an effective means of accumulating recommended levels of daily/weekly physical activity.


Signaling alterations in oral keratinocytes in response to shisha and crude tobacco extract.
Tobacco consumption in smoking and non-smoking forms has been consequential in the rise of oral cancer cases. Among different forms, epidemiological studies from Middle Eastern countries and rural parts of northern India have reported increasing association of oral cancer with waterpipe (hookah) smoking. However, molecular mechanisms and role played by waterpipe smoking in the onset of oral carcinogenesis remains unexplored. In this study, immortalized normal human oral keratinocytes were chronically treated with extracts of two varieties of waterpipe tobacco-crude tobacco and processed shisha. Phenotypic changes and molecular aberrations were examined using cell culture-based assays and mass spectrometry-based quantitative proteomic analysis, respectively. Bioinformatics analysis was utilized to analyze proteomics data and identify dysregulated pathways. Our data indicate that chronic treatment with waterpipe tobacco extracts increased proliferation, invasion, migration, and significant dysregulation of protein expression in oral keratinocytes. Altered expression of proteins involved in interferon signaling pathway were observed with both varieties of tobacco. Overexpression of cholesterol metabolism and vesicle-mediated transport proteins were identified exclusively in cells treated with crude tobacco extract. Bioinformatics analyses revealed different oncogenic response in oral cells based on the type of waterpipe tobacco used. This study may serve as a useful resource in understanding the early onset of oral cancer attributed to waterpipe smoking.


[The role of positron emission tomography with C18-Fluorodeoxyglucose in clinical oncology].
The study was concerned with evaluation of the diagnostic potential of positron emission tomography (PET) with 18-FDG in clinical oncology and elucidation of its role in assessing therapy effectiveness. The Ecat Exact 47 and Ecat Exat HR+ (Siemens) insatllations were used to examine 674 patients, with Whole Body protocol used in 585. PET with 18-FDG proved highly effective in diagnosing malignancies of the breast, lung, liver, pancreas, testis, brain and lymphoma as well as evaluating the efficacy of therapy.


Biases in Understanding Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder in Japan.
Recent research has shown high rates of comorbidity between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) and difficulties regarding differential diagnosis. Unlike those in Western countries, the Japanese ADHD prevalence rate is lower relative to that of ASD. This inconsistency could have occurred because of cultural diversities among professionals such as physicians. However, little is known about attitudes toward ADHD and ASD in non-Western cultural contexts. We conducted two experiments to identify biases in ASD and ADHD assessment. In Study 1, we examined attitudes toward these disorders in medical doctors and mental health professionals, using a web-based questionnaire. In Study 2, medical doctors and clinical psychologists assessed four fictional cases based on criteria for ADHD, ASD, oppositional defiant disorder, and disinhibited social engagement disorder (DSED). Diagnosis of ASD was considered more difficult relative to that of ADHD. Most participants assessed the fictional DSED case as ASD, rather than DSED or ADHD. The results provide evidence that Japanese professionals are more likely to attribute children's behavioral problems to ASD, relative to other disorders. Therefore, Japanese therapists could be more sensitive to and likely to diagnose ASD, relative to therapists in other countries. These findings suggest that cultural biases could influence clinicians' diagnosis of ADHD and ASD.


Interactions and Supramolecular Organization of Sulfonated Indigo and Thioindigo Dyes in Layered Hydroxide Hosts.
Supramolecularly organized host-guest systems have been synthesized by intercalating water-soluble forms of indigo (indigo carmine, IC) and thioindigo (thioindigo-5,5'-disulfonate, TIS) in zinc-aluminum-layered double hydroxides (LDHs) and zinc-layered hydroxide salts (LHSs) by coprecipitation routes. The colors of the isolated powders were dark blue for hybrids containing only IC, purplish blue or dark lilac for cointercalated samples containing both dyes, and ruby/wine for hybrids containing only TIS. The as-synthesized and thermally treated materials were characterized by Fourier transform infrared, Fourier transform Raman, and nuclear magnetic resonance spectroscopies, powder X-ray diffraction, scanning electron microscopy, and elemental and thermogravimetric analyses. The basal spacings found for IC-LDH, TIS-LDH, IC-LHS, and TIS-LHS materials were 21.9, 21.05, 18.95, and 21.00 Å, respectively, with intermediate spacings being observed for the cointercalated samples that either decreased (LDHs) or increased (LHSs) with increasing TIS content. UV-visible and fluorescence spectroscopies (steady-state and time-resolved) were used to probe the molecular distribution of the immobilized dyes. The presence of aggregates together with the monomer units is suggested for IC-LDH, whereas for TIS-LDH, IC-LHS, and TIS-LHS, the dyes are closer to the isolated situation. Accordingly, while emission from the powder H2TIS is strongly quenched, an increment in the emission of about 1 order of magnitude was observed for the TIS-LDH/LHS hybrids. Double-exponential fluorescence decays were obtained and associated with two monomer species interacting differently with cointercalated water molecules. The incorporation of both TIS and IC in the LDH and LHS hosts leads to an almost complete quenching of the fluorescence, pointing to a very efficient energy transfer process from (fluorescent) TIS to (nonfluorescent) IC.


Full Mouth Implant-supported Rehabilitation of a Patient with Ectodermal Dysplasia: Clinical Report and Literature Review.
The purpose of this case report is to present the clinical course of full mouth rehabilitation in an 1 8-year-old female patient with ectodermal dysplasia who was treated with implant-supported fixed partial dentures for the mandible and the maxilla. Fourteen dental implants (8 in the maxilla and 6 in the mandible) were placed simultaneously after full mouth extraction and alveoloplasty surgery. After 6 months of healing, prosthetic rehabilitation was started for screw-retained fixed partial dentures. The patient was followed for one year and a peri-implant maintenance regime established for six-month recalls. The patient was satisfied with the prosthesis both esthetically and functionally. Furthermore, the patient reported significant improvements in oral function and psychosocial activities. The use of dental implants to support full mouth prosthetic rehabilitation for adolescents with ectodermal dysplasia may provide a considerable improvement in function and esthetic compared to conventional removable prosthetic options. This has the potential to enhance the quality of life for these patients.


Hypertension in Oregon pesticide-formulating workers.
In a statewide survey of hypertension prevalence among pesticideformulating workers and controls in Oregon, we found no difference in mean systolic and diastolic blood pressure values but a modest excess of hypertension prevalence among chlorophenoxy herbicide workers which was largely explained by a greater constitutional predisposition to hypertension as estimated by positive family histories. Neither our study nor other published to date are adequate to allay the suspicion that chronic pesticide exposure may increase the risk of hypertension manifestation.


Monosymptomatic hypochondriacal psychoses: a diagnostic entity which may respond to pimozide.
Monosymptomatic hypochondriacal psychoses are akin to paranoia. Although presenting with a variety of delusional complaints in individual cases, the condition appears to represent a relatively dis crete diagnostic entity. It is less rare than usually thought, but those afflicted frequently to to the physical specialties, whose treatment does not benefit them. It is important to recognize the illness, since there is tentative evidence that it may respond to treatment with pimozide.


Financial considerations of operating room education: getting the most bang for your buck.
Health care costs now demand value for each dollar spent. Funding for perioperative educational activities is a very precious commodity and cannot be spent in a frivolous manner. The perioperative educator must ensure all resources are spent to gain the maximum benefit, and that the activity is purposeful with improvement in performance as the expectation. Through use of the formulas and information provided in this article, the perioperative educator will have an objective base to make decisions concerning allocation of funds and development of training programs. Considerations affecting the decision-making process are presented.


[Recent treatment perspectives in lipidology].
Clinical lipidology has gained its recognition with the publication of numerous clinical trials since the 4S study in 1994. Since that time statins have fully confirmed their promises and play now a crucial role in the battle against cardiovascular diseases. The last decade has been dominated by two demonstrations that apparently are discordant: (1) the lower the cholesterol level with the pharmacological intervention, the lower the risk of cardiovascular complications, arguing for the use of very efficacious cholesterol-lowering therapies; and (2) the cardiovascular protection provided by statins is present whatever the baseline cholesterol level, supporting the concept of pleiotropic effects of statins. As a consequence, statin treatment should be prescribed and intensified according to the high individual cardiovascular risk rather than because of the cholesterol level stricto sensu. Statin therapy should be completed by the addition of ezetimibe when LDL cholesterol level remains above target values or by the addition of fenofibrate when triglyceride levels are high and/or HDL cholesterol level is low. New pharmacological approaches aiming at further improving lipid profile, especially by targeting low HDL cholesterol levels, are currently in clinical development.


The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions.
The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. This was a retrospective, case-control study. We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.


Relationship between mortality and health care expenditure: Sustainable assessment of health care system.
Infant and maternal mortality are important indicators for assessing the quality of healthcare systems. The World Health Organization underscores the importance of proper health care system in reducing preventable mortality through early intervention. Early intervention includes availability, accessibility and affordability of health care systems for children and mothers. While there are several studies that assess the immediate and underlying drivers of child mortality, literature on the role of policy measures are limited and inconsistent. Thus, robust empirical analysis of the determinants of maternal and infant mortality remains inconclusive in the era of achieving the Sustainable Development Goals (SDG). Here, we examined the influence of health expenditure on infant and maternal deaths for the period 2000-2015 across 177 countries. Using panel Quantile Regression with bootstrapping, this study accounted for the 2007-2008 financial crisis in an empirical relationship between health outcome and health expenditure. We found a negative effect of health expenditure on mortality across all percentiles. Infant mortality rate declines between 0.19% - 1.45% while maternal mortality rate declines ranging from 0.09% - 1.91%. To attain the goal of ensuring healthy lives and wellbeing of all people (SDG 3), this study infers that health expenditure potentially reduces maternal and infant mortality across lower and middle income countries. We highlight the need for an enhanced health care expenditure, especially in developing countries to curb the levels of infant and maternal deaths.


Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management.
Comorbidities impact a large proportion of patients with chronic obstructive pulmonary disease (COPD), with over 80% of patients with COPD estimated to have at least one comorbid chronic condition. Guidelines for the treatment of COPD are just now incorporating comorbidities to their management recommendations of COPD, and it is becoming increasingly clear that multimorbidity as well as specific comorbidities have strong associations with mortality and clinical outcomes in COPD, including dyspnea, exercise capacity, quality of life, healthcare utilization, and exacerbation risk. Appropriately, there has been an increased focus upon describing the burden of comorbidity in the COPD population and incorporating this information into existing efforts to better understand the clinical and phenotypic heterogeneity of this group. In this article, we summarize existing knowledge about comorbidity burden and specific comorbidities in COPD, focusing on prevalence estimates, association with outcomes, and existing knowledge about treatment strategies.


Action of brown widow spider venom and botulinum toxin on the frog neuromuscular junction examined with the freeze-fracture technique.
1. Structural changes which normally accompany transmitter release at frog neuromuscular junctions are visualized with the freeze-fracture technique. The effects of brown widow spider venom and botulinum toxin were evaluated in terms of their ability to block or produce these structural changes. Changes produced by these neuropoisons were correlated with their known effects on neurotransmitter release. 3. Fusion of synaptic vesicles with the presynaptic plasmalemma, normally evoked by electrical stimulation, was abolished at neuromuscular junctions from frogs treated with botulinum toxin. 3. The concentration of large intramembranous particles in the presynaptic plasmalemma, an indication of the excess of synaptic vesicle fusion over recovery of synaptic vesicle membrane, was increased by treatment with brown widow spider venom, even in the presence of botulinum toxin. 4. When external calcium was present, sites of vesicle fusion induced by brown widow spider venom, as well as by electrical stimulation, were located mainly in the active zone. In the absence of external calcium, many plasmalemmal deformations, also though to be sites of vesicle fusion, were more evenly dispersed over the presynaptic surface of nerve terminals. 5. Botulinum toxin decreased the number of vesicle fusion sites in the active zone induced by spider venom in the presence of external calcium but had little effect on the number of fusion sites induced by spider venom in the absence of external calcium. 6. Nerve terminals soaked in a sodium-free Ringer solution were partially depleted of vesicles. Addition of spider venom to this Ringer did not cause additional depletion of vesicles. 7. Formation of cation-permeable channels in the presynaptic membrane could account for these effects of spider venom on the frog neuromuscular junction. Botulinum toxin blocks vesicle fusion by some means which is not yet understood.


Differences in the chemesthetic subqualities of capsaicin, ibuprofen, and olive oil.
Chemesthetic sensations elicited by ibuprofen, extra-virgin olive oil, and capsaicin were compared to quantify perceptual differences between known agonists of TRPA1 and TRPV1. Extra virgin olive oil contains a phenolic compound, oleocanthal, which is thought to share unique chemesthetic qualities with the nonsteroidal anti-inflammatory drug, ibuprofen. Pilot work suggested participants had difficulty distinguishing between multiple chemesthetic subqualities (e.g., burn, sting, itch, tickle, etc.) in a multiattribute rating task. Here, we assessed overall irritation via direct scaling, and a check all that apply task was used to collect information about chemesthetic subqualities over time. Replicated ratings were collected at discrete intervals using the generalized labeled magnitude scale to generate time-intensity curves; maximum intensity (Imax) and area under the curve were extracted for each participant. Intensity responses varied substantially across participants, and within a participant, the relationship was strongest between ibuprofen and olive oil. However, there were also positive, albeit weaker, correlations between capsaicin and ibuprofen and capsaicin and olive oil. The correlation found between olive oil and capsaicin may suggest the presence of unknown TRPV1 agonists in olive oil. This view was also supported by the qualitative data: capsaicin was described most often as burning and warm/hot, whereas ibuprofen was numbing and tickling. Olive oil shared characteristics with both capsaicin (warm/hot) and ibuprofen (tickle).


Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation.
Honokiol is a natural biphenolic compound extracted from traditional Chinese medicine Magnolia species, which have been known to display various biological effects including anti-cancer, anti-proliferative, anti-angiogenic, and anti-metastatic activities in cancer cells. Here, we found that honokiol sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of anti-apoptotic proteins survivin and c-FLIP. Ectopic expression of survivin and c-FLIP markedly abolished honokiol and TRAIL-induced apoptosis. Mechanistically, honokiol induced protein degradation of c-FLIP and survivin through STAMBPL1, a deubiquitinase. STAMBPL1 interacted with survivin and c-FLIP, resulted in reduction of ubiquitination. Knockdown of STAMBPL1 reduced survivin and c-FLIP protein levels, while overexpression of STAMBPL1 inhibited honokinol-induced survivin and c-FLIP degradation. Our findings provided that honokiol could overcome TRAIL resistance through survivin and c-FLIP degradation induced by inhibition of STAMBPL1 expression.


Reconstructed Metabolic Network Models Predict Flux-Level Metabolic Reprogramming in Glioblastoma.
Developments in genome scale metabolic modeling techniques and omics technologies have enabled the reconstruction of context-specific metabolic models. In this study, glioblastoma multiforme (GBM), one of the most common and aggressive malignant brain tumors, is investigated by mapping GBM gene expression data on the growth-implemented brain specific genome-scale metabolic network, and GBM-specific models are generated. The models are used to calculate metabolic flux distributions in the tumor cells. Metabolic phenotypes predicted by the GBM-specific metabolic models reconstructed in this work reflect the general metabolic reprogramming of GBM, reported both in in-vitro and in-vivo experiments. The computed flux profiles quantitatively predict that major sources of the acetyl-CoA and oxaloacetic acid pool used in TCA cycle are pyruvate dehydrogenase from glycolysis and anaplerotic flux from glutaminolysis, respectively. Also, our results, in accordance with recent studies, predict a contribution of oxidative phosphorylation to ATP pool via a slightly active TCA cycle in addition to the major contributor aerobic glycolysis. We verified our results by using different computational methods that incorporate transcriptome data with genome-scale models and by using different transcriptome datasets. Correct predictions of flux distributions in glycolysis, glutaminolysis, TCA cycle and lipid precursor metabolism validate the reconstructed models for further use in future to simulate more specific metabolic patterns for GBM.


Scanning Electron Microscopy of Second-Stage Juvenile Cephalic Morphology in Heterodera glycines Races.
Scanning electron microscopy (SEM) was used to compare juvenile cephalic morphology of the five described races of Heterodera glycines. Races 1, 2, 3, and 4 were obtained in the United States and race 5 was obtained from Japan. Differences in the gross morphology o f labial discs; ventral, dorsal and lateral lips; amphidial apertures; and fissures on the labial disc o f some specimens were observed. There was considerable interracial and intraracial variation which precluded separation o f juveniles of H. glycines races by SEM.


Bacterial and eukaryotic phosphoketolases: phylogeny, distribution and evolution.
Phosphoketolases (XFPs) are glycolytic enzymes present in several organisms belonging to the Eukarya and Bacteria domains. A total of 151 putative xfp genes were detected in 650 complete genomes available in public databases. Elimination of redundant sequences and pseudogenes rendered a final data set of 128 phosphoketolases, which was analyzed by phylogenetic methods. The distribution of xfp genes was uneven in most taxonomic groups, with the exception of the taxonomical division Lactobacillaceae, in which all the species studied harbored a putative xfp gene. Putative xfp genes were also present predominantly in Rhizobiales and Actinobacteria divisions, in which 23 out of 28 genomes and 23 out of 41 genomes contained at least one putative xfp homolog, respectively. Phylogenetic analyses showed clear discordance with the expected order of organismal descent even in groups where xfp is prevalent, such as Lactobacillaceae. The presence of putative paralogs in some organisms cannot account for these discrepancies; instead, these paralogs are most possibly xenologs. The results of the phylogenetic analyses, the distribution of xfp genes and the location of some xfp genes in plasmids are independent pieces of evidence that point to horizontal gene transfer as a major driving force in the evolution of phosphoketolases.


Expression and localization of cystic fibrosis transmembrane conductance regulator in human gingiva.
CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-activated chloride channel that regulates electrolyte and water transport. The present study investigated the expression and localization of CFTR in human gingiva and explored the possible association of CFTR with periodontal conditions. CFTR expression in gingival biopsies from five periodontally healthy subjects and ten subjects with chronic periodontitis and in the RHGE (reconstituted human gingival epithelia) was detected by immunohistochemistry, whereas its expression in gingival biopsies was analysed by immunofluorescence staining. CFTR mRNA was analysed by reverse transcription-PCR. CFTR mRNA was detected in human gingival epithelia and RHGE. CFTR protein was detected in gingival biopsies from both healthy subjects and individuals with periodontitis and in RHGE. In healthy subjects, CFTR expression was mainly confined to the granular and spinous layers of epithelia and localized on the cell membrane. In patients with periodontitis, CFTR was detected in all layers of epithelia and the underlying connective tissues. The mean CFTR expression levels in periodontitis patients were significantly higher than those in healthy subjects. The present study for the first time showed the expression and localization of CFTR in human gingival epithelia. Elevated CFTR expression in periodontitis subjects implies the possible involvement of CFTR in periodontal disease pathogenesis. Further study is warranted to confirm the present findings.


Prediction of Mortality and Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury.
Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI. Multicenter cohort study. 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays. Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay. (1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge. Four machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation. One developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both). The models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay. The reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models. Acute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.


Effect of temperature on mosquito olfaction.
Mosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues ( e.g. , host emitted odors, including CO 2 , and skin volatiles) play a central role in mediating host seeking behaviors. While mosquito olfaction can be impacted by many factors, such as the physiological state of the insect ( e.g. , age, reproductive state), the impact of environmental temperature on the olfactory system remains unknown. In this study, we quantified the behavioral responses of Aedes aegypti mosquitoes, vectors of dengue, yellow fever and Zika viruses, to host and plant related odors under different environmental temperatures.


FoxM1 promotes Wnt/β-catenin pathway activation and renal fibrosis via transcriptionally regulating multi-Wnts expressions.
The activation of Wnt/β-catenin pathway plays a pivotal role in promoting renal fibrosis. The activation of Wnt/β-catenin pathway relies on the binding of Wnts to Frizzled receptors on cell membrane. However, the factor regulating Wnts production remains unclear. Here, we demonstrated that transcriptional factor FoxM1 was significantly increased in obstructed kidneys and patients' kidneys with fibrosis. The up-regulation of FoxM1 mainly distributed in tubular epithelial cells. Pharmacological inhibition of FoxM1 down-regulated multi-Wnts elevation in UUO mice and attenuated renal fibrosis. In cultured renal tubular epithelial cells, overexpression of FoxM1 promoted 8 Wnts expression, while knock-down on FoxM1-suppressed multi-Wnts including Wnt1, Wnt2b and Wnt3 expression induced by Ang II. Chromatin immunoprecipitation PCR confirmed that FoxM1 bound to Wnt1, Wnt2b, Wnt3 promoters and luciferase assay further identified that the transcriptions of Wnt1, Wnt2b and Wnt3 were regulated by FoxM1. Thus, our findings show that multi-Wnt family members were regulated by transcriptional factor FoxM1. FoxM1 might be a key switch for activating β-catenin pathway and renal fibrosis. Therefore, FoxM1 might be a potential therapeutic target in manipulating renal fibrosis.


Is Caperatic Acid the Only Compound Responsible for Activity of Lichen Platismatia glauca within the Nervous System?
Lichens are a source of various biologically active compounds. However, the knowledge about them is still scarce, and their use in medicine is limited. This study aimed to investigate the therapeutic potential of the lichen Platismatia glauca and its major metabolite caperatic acid in regard to their potential application in the treatment of central nervous system diseases, especially neurodegenerative diseases and brain tumours, such as glioblastoma. First, we performed the phytochemical analysis of the tested P. glauca extracts based on FT-IR derivative spectroscopic and gas chromatographic results. Next the antioxidant properties were determined, and moderate anti-radical activity, strong chelating properties of Cu2+ and Fe2+ ions, and a mild effect on the antioxidant enzymes of the tested extracts and caperatic acid were proved. Subsequently, the influence of the tested extracts and caperatic acid on cholinergic transmission was determined by in vitro and in silico studies confirming that inhibitory effect on butyrylcholinesterase is stronger than against acetylcholinesterase. We also confirmed the anti-inflammatory properties of P. glauca extracts and caperatic acid using a COX-2 and hyaluronidase inhibition models. Moreover, our studies show the cytotoxic and pro-apoptotic activity of the P. glauca extracts against T98G and U-138 MG glioblastoma multiforme cell lines. In conclusion, it is possible to assume that P. glauca extracts and especially caperatic acid can be regarded as the source of the valuable substances to finding new therapies of central nervous system diseases.


Protective effects of Aronia melanocarpa juices either alone or combined with extracts from Rosa canina or Alchemilla vulgaris in a rat model of indomethacin-induced gastric ulcers.
The aim of the study was to investigate the effects of four Aronia melanocarpa-based juices in a rat model of indomethacin-induced gastric ulceration. THE JUICES WERE: AM1 and AM2 (produced from aronia fruits at 20 °C and 60 °C, respectively), AMRC (a mixture of AM2 with Rosa canina extract) and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were used. Each of the juices (10 ml/kg) was administered for 10 days. Indomethacin (30 mg/kg) was injected subcutaneously and after 4 h, the effects were estimated. Indomethacin caused heavy destructions of the gastric mucosa, increased the expression of Bax and decreased the expression of Bcl-2, induced a certain increase in lipid peroxidation and a slight decrease in gastric PGE2 content. The pretreatment with the juices reduced the severity of indomethacin-induced gastric lesions and antagonized the effects of indomethacin on apoptosis and lipid peroxidation. The highest was the protective effect of AMAV, the juice with the highest polyphenolic content. The protective effect of Aronia melanocarpa-based juices against indomethacin-induced gastric lesions could be attributed to their polyphenolic contents. The mechanism involved to the highest extent in the protective effect of the juices was the inhibition of apoptosis.


The role of laser-induced fluorescence in myocardial tissue characterization: an experimental in vitro study.
The fluorescence of tissue when stimulated by a laser beam is a well-known phenomenon. The resulting emission spectra depend on the biochemical and structural composition of the tissue. In this study, we examined the spectra of laser-induced fluorescence emitted by myocardial tissue. We used an argon-ion laser to stimulate the myocardium of 20 intact sheep hearts. For each spectral emission, we calculated the intensity in specific regions in order to characterize the spectra and to reveal intercavitary and intracavitary morphologic differences. The statistical analysis showed significant differences in the emission spectra intensity between atria and ventricles. The intensity was higher in the atria than in the ventricles (p < 0.001). The atrial emission spectra were morphologically different from those of the ventricles. There was no difference in the intensity or morphology of emission spectra within each chamber. All measurements showed good reproducibility after a short period of time. Laser-induced fluorescence of myocardial tissue seems to have the characteristics necessary for tissue recognition. This might prove useful in identifying cardiomyopathies and transplant rejection, as well as for myocardial mapping, assisting electrophysiologists in discovering fibrotic arrhythmogenic foci.


Lipid binding to the tail domain of vinculin: specificity and the role of the N and C termini.
Vinculin is a highly conserved and abundant cytoskeletal protein involved in linking the actin cytoskeleton to the cell membrane at sites of cellular adhesion. At these sites of adhesion, vinculin plays a role in physiological processes such as cell motility, migration, development, and wound healing. Loss of normal vinculin function has been associated with cancer phenotypes, cardiovascular disease, and lethal errors in embryogenesis. The tail domain of vinculin (Vt) binds to acidic phospholipids and has been proposed to play a role in vinculin activation and focal adhesion turnover. To better characterize Vt-lipid specificity, we conducted a series of lipid co-sedimentation experiments and find that Vt shows specific association with phosphatidylinositol 4,5-bisphosphate (PIP2), compared with phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), or phosphatidylinositol (PI) in the context of mixed lipid vesicles. The C terminus of Vt has been proposed to be important for PIP2 association, as various mutations and deletions within the C-terminal reduce PIP2 association. Lipid co-sedimentation and NMR analyses indicate that removal of the hydrophobic hairpin does not alter Vt structure or PIP2 association. However, more extensive deletions within the C-terminal introduce Vt structural perturbations and reduce PIP2 binding. Intriguingly, a significant increase in PIP2 binding was observed for multiple Vt variants that perturb interactions between the N-terminal strap and helix bundle, suggesting that a rearrangement of this N-terminal strap may be required for PIP2 binding.


Learning Nonparametric Relational Models by Conjugately Incorporating Node Information in a Network.
Relational model learning is useful for numerous practical applications. Many algorithms have been proposed in recent years to tackle this important yet challenging problem. Existing algorithms utilize only binary directional link data to recover hidden network structures. However, there exists far richer and more meaningful information in other parts of a network which one can (and should) exploit. The attributes associated with each node, for instance, contain crucial information to help practitioners understand the underlying relationships in a network. For this reason, in this paper, we propose two models and their solutions, namely the node-information involved mixed-membership model and the node-information involved latent-feature model, in an effort to systematically incorporate additional node information. To effectively achieve this aim, node information is used to generate individual sticks of a stickbreaking process. In this way, not only can we avoid the need to prespecify the number of communities beforehand, the algorithm also encourages that nodes exhibiting similar information have a higher chance of assigning the same community membership. Substantial efforts have been made toward achieving the appropriateness and efficiency of these models, including the use of conjugate priors. We evaluate our framework and its inference algorithms using real-world data sets, which show the generality and effectiveness of our models in capturing implicit network structures.


[Biological functions of the duplicated GGAA-motifs in various human promoter regions].
Transcription is one of the most fundamental cellular functions and is an enzyme-complex mediated reaction that converts DNA sequences into mRNA. TATA-box is known to be an important motif for transcription. However, there are majority of promoters that have no TATA-box. They are called as TATA-less promoters and possess other elements that determine the transcription start site (TSS) of the genes. Multiple protein factors including ETS family proteins are known to recognize and bind to the GGAA containing sequences. In addition, it has been reported that the ETS binding motifs play important roles in regulation of various promoters. Here, we propose that the duplication and multiplication of the GGAA motifs are responsible for the initiation of transcription from TATA-less promoters.


Effects of bradykinin on renal interstitial pressures and proximal tubule reabsorption.
Renal interstitial Starling forces have been postulated as the link between the peritubular microcirculation and fluid reabsorption by the proximal tubule. The renal vasodilator bradykinin was used as a tool to test this relationship in micropuncture studies in the rat. Bradykinin increased peritubular capillary and interstitial hydrostatic pressures and decreased peritubular and interstitial oncotic pressures. The balance of Starling forces in the interstitium (interstitial oncotic pressure minus interstitial hydrostatic pressure) was significantly decreased from 6.5 +/- 2.3 to -4.0 +/- 1.3 mmHg without a change in fluid reabsorption by the proximal tubule. We conclude that renal interstitial Starling forces do not regulate reabsorption by the superficial proximal tubule in the rat in response to bradykinin.


[Risk factors for myocardial remodeling at stage II-IV of chronic kidney disease].
To evaluate frequency and risk factors of development of left ventricular hypertrophy (LVH) of the heart in patients with chronic kidney disease (CKD) of stage II-IV. The trial enrolled 83 patients (42 - 51% males, 41 - 49% females, mean age 46.7 years) with stage II-IV CKD of non-diabetic origin. Glomerular filtration rate (GFR) estimated according to Cockroft-Goult formula was 37,7 ml/min (95% confidence interval from 33,9 do 41,4). Chronic renal failure duration averaged 2,7 years (95 % CI from 2.0 to 3.3). Arterial hypertension (AH) was diagnosed in 96% patients, hereditary predisposition to cardiovascular diseases - in 54%, obesity - in 60%. lipid disbolism - in 66%, anemia - in 34 % and hyperphosphatemia - in 45%; 40% patients smoked. Echocardiography was performed in all the patients. LVH was detected in 31 (37.3%) of 83 patients. With progression of renal failure, frequency of registration of LVH increased LVH onset was associated with conventional (age, AH, high level of total cholesterol) and renal (lowering of GFR, anemia, hyperphosphatemia) factors. Concentric remodeling, concentric LVH, eccentric LVH were detected in 31.3, 19.3 and 18.1% patients, respectively. Eccentric LVH developed more frequently under the influence of factors associated with renal failure (GFR, anemia, hyperphosphatemia, hypocalcemia). Concentric LVH was characterized with the highest systolic blood pressure. Patients with renal dysfunction develop LVH of different geometric model associated with both conventional and renal risk factors even at early stages of CKD.


Ownership and utilization of insecticide-treated nets (ITNs) for malaria control in Harari National Regional State, Eastern Ethiopia.
Insecticide-treated nets (ITNs) stood at center in the current efforts to prevent and control malaria at community and individual levels. Though ITNs are the most prominent measure for large-scale deployment in highly endemic areas their compliance in terms of ownership and usage needs attention. The aim of this study was therefore to determine the ownership and utilization pattern of ITNs in Harari Peoples National Regional state, Ethiopia. A community based cross-sectional study was conducted in Harari National Regional State from September to October, 2012. A total of 784 households were included from malarious areas. Data were collected by using structured questionnaires and observational checklist. About 57.9% of participants had at least one ITNs. The utilization of ITNs based on history of sleeping under net in the previous night was 73.3%. Regarding proper use of ITNs, 57.9% of respondents demonstrated proper hanging and tucking. Those households with secondary school education (AOR: 1.775(1.047, 3.009)), knowledge about ITNs use (AOR: 2.400(1.593, 3.615)) and knowledge of malaria transmission by bite of mosquito (AOR: 1.653(1.156, 2.365)) have more likely hood to own ITNs. ITNs Ownership was low as compared to the target by Federal ministry of Health of Ethiopia. Though utilization of ITNs was promising, there are still significant number of participants who demonstrate hanging and tucking improperly. Therefore, health bureau need to work towards increasing the distribution of ITNs per household and also provide health information through health extension workers to enhance regular and proper usage of the ITNs.


Rapid detection of human herpesvirus 8 DNA using loop-mediated isothermal amplification.
The reliability of a loop-mediated isothermal amplification (LAMP) method for the detection of human herpesvirus 8 (HHV-8) DNA was evaluated. Although LAMP products were produced with the DNA sample extracted from BCP-1 cells, LAMP products were not produced with the DNAs from seven other human herpesviruses. The detection limit of the HHV-8 LAMP method was 100 copies of target sequence/tube. To determine whether the HHV-8 LAMP method could be used to quantify viral DNA, threshold times, which are defined as the time (in s) it takes to reach the threshold turbidity level (0.1), were measured for the amplification of serial dilutions of a DNA plasmid containing the target sequence. The standard curve possessed a correlation coefficient of 0.9428 with a slope of -84.079 and y-intercept value of 1936.2. Additionally, an attempt was made to detect viral DNA in 17 specimens collected from Kaposi's sarcomas and two cell lines obtained from primary effusion lymphomas. HHV-8 DNA was detected in 14 of the 17 Kaposi's sarcoma tissue samples and both of the primary effusion lymphoma cell lines. Viral DNA was not detected in HHV-8 LAMP-negative samples using the real-time PCR method.


A bi-specific inhibitor targeting IL-17A and MMP-9 reduces invasion and motility in MDA-MB-231 cells.
The cytokine IL-17A is associated with the progression of various cancers, but little is known about the molecular cross-talk between IL-17A and other tumor-promoting factors. Previous studies have shown that the IL-17A-mediated invasion of breast cancer cells can be inhibited by selective antagonists of the matrix metalloproteinase 9 (MMP-9), suggesting that the cross-talk between IL-17A and MMP-9 may promote cancer invasiveness and metastasis. Here, we present a novel strategy for developing cancer therapeutics, based on the simultaneous binding and inhibition of both IL-17A and MMP-9. To this end, we use a bi-specific heterodimeric fusion protein, comprising a natural inhibitor of MMPs (N-TIMP2) fused with an engineered extracellular domain (V3) of the IL-17A receptor. We show that, as compared with the mono-specific inhibitors of IL-17A (V3) and MMP-9 (N-TIMP2), the engineered bi-specific fusion protein inhibits both MMP-9 activation and IL-17A-induced cytokine secretion from fibroblasts and exhibits a synergistic inhibition of both the migration and invasion of breast cancer cells. Our findings demonstrate, for the first time, that dual targeting of inflammatory (IL-17A) and extracellular matrix remodeling (MMP) pathways can potentially be used as a novel therapeutic approach against cancer. Moreover, the platform developed here for generating the bi-specific IL-17A/MMP-9 inhibitor can be utilized for generating bi-specific inhibitors for other cytokines and MMPs.


Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study.
Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.


[Molecular biology at the service of the daily medical virology. 1. Methodological principles].
Molecular biology techniques which can rapidly detect a few copy number of viral genome allow to obtain new parameters for the diagnosis, the prognosis, and the monitoring of viral diseases in addition to or in substitution for cell culture and antigen and antibody detection. The methods are based on the virus structural organization and on their replication into cells. They use the tools which have been developed to analyse nucleic acids. Molecular hybridization (dot-blot, southern-blot, liquid phase hybridization, in situ hybridization), enzymatic amplification (PCR, nested-PCR, RT-PCR, NASBA, bDNA, multiplex PCR), DNA and RNA quantification (quantitative PCR or RT-PCR, NASBA, bDNA) and genotyping (virus types, mutations, variant virus) are used. Nucleic acid extracts native or amplified with a reporter molecule (dUTP-biotin or dUTP-digoxigenin) are identified using gel electrophoresis followed by hybridization or using microwell capture hybridization assay and colorimetric immunoenzymatic or bioluminescence assays.


Compliance with antithrombotic guidelines in surgery patients in German hospitals: a multicenter study involving pharmacy interns.
Despite the existence of antithrombotic guidelines, there is low compliance with these guidelines in clinical practice. Until now pharmacy interns (PIs) have not been involved in this process. The objectives were to involve PIs to evaluate compliance with antithrombotic guidelines for VTE prophylaxis in surgery patients, and in cases of noncompliance to carry out pharmaceutical interventions. The study was conducted in 7 hospitals in Germany involving 27 PIs within the project "Pharmacy interns on the ward" (P-STAT 2). Pharmacy interns determined the thromboembolic risk, documented antithrombotic medication, and checked the compliance with current antithrombotic guidelines. A total of 6491 patients were enrolled; 5695 patients received antithrombotic prophylaxis. Antithrombotic guideline was followed in 77.5% patients. Many patients are not receiving appropriate VTE prophylaxis or heparin bridging regimen despite the fact that evidence-based antithrombotic guidelines are available. Pharmacy interns may play an important role in antithrombotic management.


[CE-marking in the dental profession].
In the present article the authors summarise the meaning and mechanism of CE-marking in the EU in general and its significance in the dental profession. Their goal was to increase the awareness of Hungarian dental professionals to issues of quality management in the European Union.


CRITICAL ILLUMINATION AND FLICKER FREQUENCY IN RELATED FISHES.
Flicker response curves have been obtained at 21.5 degrees C. for three genera of fresh water teleosts: Enneacanthus (sunfish), Xiphophorus (swordtail), Platypoecilius (Platy), by the determination of mean critical intensities for response at fixed flicker frequencies, and for a certain homogeneous group of backcross hybrids of swordtail x Platy (Black Helleri). The curves exhibit marked differences in form and proportions. The same type of analysis is applicable to each, however. A low intensity rod-governed section has added to it a more extensive cone portion. Each part is accurately described by the equation F = F(max.)/(1 + e(-p log(-p logI/I(i) ) )), where F = flicker frequency, I = associated mean critical intensity, and I(i) is the intensity at the inflection point of the sigmoid curve relating F to log I. There is no correlation between quantitative features of the rod and cone portions. Threshold intensities, p, I(i), and F(max.) are separately and independently determined. The hybrid Black Helleri show quantitative agreement with the Xiphophorus parental stock in the values of p for rods and cones, and in the cone F(max.); the rod F(max.) is very similar to that for the Platy stock; the general level of effective intensities is rather like that of the Platy form. This provides, among other things, a new kind of support for the duplicity doctrine. Various races of Platypoecilius maculatus, and P. variatus, give closely agreeing values of I(m) at different flicker frequencies; and two species of sunfish also agree. The effect of cross-breeding is thus not a superficial thing. It indicates the possibility of further genetic investigation. The variability of the critical intensity for response to flicker follows the rules previously found to hold for other forms. The variation is the expression of a property of the tested organism. It is shown that, on the assumption of a frequency distribution of receptor element thresholds as a function of log I, with fluctuation in the excitabilities of the marginally excited elements, it is to be expected that the dispersion of critical flicker frequencies in repeated measurements will pass through a maximum as log I is increased, whereas the dispersion of critical intensities will be proportional to I(m); and that the proportionality factor in the case of different organisms bears no relation to the form or position of the respective curves relating mean critical intensity to flicker frequency. These deductions agree with the experimental findings.


Teachers' experiences of adolescents' pain in everyday life: a qualitative study.
More adolescents report pain now than previously. In Norway, episodic pain problems have been reported by 60% of children and adolescents aged 8-18 years, with 21% reporting duration of pain of more than 3 months. Since adolescents spend much time at school, the attitude and behaviour of teachers play important roles regarding the experience of pain felt by adolescents in everyday life. Yet research on how teachers perceive the pain experienced by adolescents in a school setting is limited. We therefore seek to gain insight to teachers' classroom experiences with (1) adolescent's self-reported pain symptoms; (2) adolescents management of their pain and (3) how to help adolescents manage their pain. Teachers in 5 junior high schools in Norway representing municipalities in 3 rural areas and 2 cities. A qualitative study with an explorative design comprising 5 focus group interviews. Each group consisted of 3-8 junior high school teachers. A semistructured interview guide was used to cover the issues. The transcribed text was analysed with qualitative content analysis. 22 teachers participated (5 men, 17 women; age range 29-62 years) with teaching experience ranging from 3 to nearly 40 years. The main theme describing the experience of teachers with adolescents' pain in everyday life is that pain and management of pain is a social, physical and psychological interwoven phenomenon. Through empirical analyses, 3 subcategories emerged: (1) everyday pain--expressing strenuous life; (2) managing pain--escaping struggle and (3) strategies of teachers--support and normalisation. Teachers have a biopsychosocial understanding and approach to pain experienced by adolescents. This understanding influences the role of teachers as significant others in the lives of adolescents with regard to pain and management of their pain in a school setting.


Diagnostic utility of a modified forearm ischemic exercise test and technical issues relevant to exercise testing.
The sensitivity and specificity of a modified forearm ischemic test (FIT) are described in the diagnosis of glycogen storage disease, myoadenylate deaminase deficiency, and mitochondrial disease. FIT and muscle biopsy results were reviewed from 99 patients (glycogen storage disease [GSD], myoadenylate deaminase deficiency [AMPD], mitochondrial disease [MITO], miscellaneous neuromuscular disorders, and controls). The influence of catheter placement and an antecedent sugar bolus were also assessed in healthy young men. The FIT had a sensitivity of 1.00 and a specificity of 1.00 for a diagnosis of GSD, whereas the corresponding values were 1.00 and 0.37 for AMPD deficiency. A baseline lactate of >2.5 mmol/L provided the highest sensitivity (0.62) and specificity (1.00) for MITO disease. A baseline and +1 min sample provided optimal sensitivity and specificity for GSD and AMPD deficiency. Catheter placement in any vein other than the ipsilateral antecubital resulted in attenuated lactate responses (P < 0.0001). A pre-FIT sugar bolus did not alter the postexercise lactate or ammonia response. Thus, a modified FIT was helpful in the diagnosis of GSD and excluding AMPD deficiency, but not in the diagnosis of MITO disease. Catheter placement is critical to the interpretation of a FIT, whereas pretesting diet is less important.


Quantifying activities of daily living impairment in Parkinson's disease using the Functional Activities Questionnaire.
Cognitive-driven activity of daily living (ADL) impairment in Parkinson's disease (PD) is increasingly discussed as prodromal marker for dementia. Diagnostic properties of assessments for this specific ADL impairment are sparsely investigated in PD. The ability of the Functional Activities Questionnaire (FAQ) for differentiating between PD patients with normal cognition and with mild cognitive impairment (PD-MCI), according to informant and self-reports, was examined. Global cognitive function in groups with and without mild ADL impairment was compared according to different cut-offs. Multicenter data of 589 patients of an international cohort (CENTRE-PD) were analyzed. Analyses were run separately for informant-rated and self-rated FAQ. Receiver operating characteristic (ROC) analysis was conducted to define the optimal FAQ cut-off for PD-MCI (≥ 1), and groups were additionally split according to reported FAQ cut-offs for PD-MCI in the literature (≥ 3, ≥ 5). Binary logistic regressions examined the effect of the Montreal Cognitive Assessment (MoCA) score in PD patients with and without mild ADL impairment. Two hundred and twenty-five (38.2%) patients were classified as PD-MCI. For all three cut-off values, sensitivity was moderate to low (< 0.55), but specificity was moderately high (> 0.54) with a tendency of higher values for self-reported deficits. For the self-report, the cut-off ≥ 3 showed a significant effect of the MoCA (B = - 0.31, p = 0.003), where FAQ ≥ 3 patients had worse cognition. No effect for group differences based on informant ratings was detected. Our data argue that self-reported ADL impairments assessed by the FAQ show a relation to the severity of cognitive impairment in PD.


Is rosiglitazone use associated with an increase in intensive eye treatment in diabetic patients? A community based study.
To evaluate the effect of rosiglitazone on diabetic retinopathy in the usual care setting. Type 2 diabetic patients, aged over 40, who received rosiglitazone therapy for at least one year during the study period, were considered for the study group. All diabetic patients who had never received rosiglitazone or insulin were candidates for the control group. For each subject treated with rosiglitazone, up to five controls were randomly selected and matched on age, gender, and HbA1c%. We retrieved information about ophthalmologist visits, retinal argon laser therapy, vitrectomy and the date of the procedure. Time from the first rosiglitazone prescription to the first intervention was calculated. A total of 6689 subjects, 1304 in the rosiglitazone group and 5385 in the control group were followed for a median of 3.6 years. The baseline level of HbA1C% was slightly higher in the rosiglitazone group (9.2 versus 8.8). There were more ophthalmologist visits in the rosiglitazone group compared to the control group. 115/1304 (8.8%) patients in the study group had an event compared to 379/5385 (7.0%) control group (P = 0.027). HR for the study group was 1.3 (95% CI: 1.08-1.64) for any event compared to control group (P = 0.008). Rosiglitazone was associated with increased laser treatments and vitrectomy. Caution may be needed when treating diabetic patients with rosiglitazone.


Dietary energy density is associated with body mass index and waist circumference, but not with other metabolic risk factors, in free-living young Japanese women.
Little is known about the relation of dietary energy density (kilocalories per gram) to metabolic risk factors, particularly in young adults and non-Western populations. We examined the cross-sectional associations between dietary energy density and several metabolic risk factors in free-living young Japanese women. The subjects were 1136 female Japanese dietetic students 18-22 y of age. Dietary energy density was estimated based on foods only, using a self-administered diet history questionnaire; before the present analysis, this measurement was validated against 16-d weighed dietary records in 92 Japanese women 31-69 y of age (Pearson's correlation coefficient 0.52). Body height and weight, from which body mass index (BMI) was derived, waist circumference, and blood pressure were measured, and fasting blood samples were collected for biochemical measurements. Mean BMI was 21.3 kg/m(2) (standard deviation 2.7), mean waist circumference was 72.9 cm (standard deviation 7.1), and mean dietary energy density was 1.41 kcal/g (standard deviation 0.23). After adjustment for potential confounding factors, dietary energy density was positively associated with BMI (P for trend = 0.004). Dietary energy density also showed an independent and positive association with waist circumference (P for trend <0.0001). No significant associations were observed between dietary energy density and any of the other metabolic risk factors examined. Dietary energy density was independently and positively associated with BMI and waist circumference, but not with other metabolic risk factors, in free-living young Japanese women who are not only lean but whose dietary energy density is also low compared with Western populations.


Lifelong Exposure to PCBs in the Remote Norwegian Arctic Disrupts the Plasma Stress Metabolome in Arctic Charr.
Lake Ellasjøen on the remote Norwegian island of Bjørnøya is populated by Arctic charr (Salvelinus alpinus) having 20-fold higher body burdens of polychlorinated biphenyls (PCB) compared to charr from the neighboring Lake Laksvatn. This provides a natural setting to test the hypothesis that lifelong exposure to PCBs compromises the energy metabolism in this northernmost living salmonid. To test this, blood was sampled from charr from both lakes immediately after capture and following a 1 h handling and confinement stressor to assess possible differences in their energy metabolism and energy substrate mobilization, respectively. The plasma metabolome of charr was assessed by metabolite detection/separation with LC-MS. Plasma metabolite profiles revealed differences in key pathways involved in amino acid metabolism between charr from each lake, underscoring an impact of PCBs on energy metabolism in Arctic charr residing in Lake Ellasjøen. Subjecting charr from either lake to an acute stressor altered the plasma metabolite profiles and revealed distinct stress metabolome in Lake Ellasjøen charr, suggesting a reduced metabolic capacity. Taken together, lifelong exposure to PCBs in Ellasjøen charr disrupts the plasma metabolome, and may impair the adaptive metabolic response to stressors, leading to a reduced fitness.


Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI.
Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.


Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) patients are not routinely screened for depression and anxiety despite knowledge of an increased prevalence in people with chronic disease and negative effects on quality of life. Prevalence of anxiety and depression was assessed in IBD outpatients through retrospective chart review. The presence of anxiety and/or depression was determined using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 self-report questionnaires or by diagnosis through psychiatric interview. Patient demographics, disease characteristics, and medication information were also collected. Multivariable analysis was used to determine associations between patient factors and depression and anxiety. 327 patient charts were reviewed. Rates of depression and anxiety were found to be 25.8% and 21.2%, with 30.3% of patients suffering from depression and/or anxiety. Disease activity was found to be significantly associated with depression and/or anxiety (p = 0.01). Females were more likely to have anxiety (p = 0.01). A significant proportion of IBD patients suffer from depression and/or anxiety. The rates of these mental illnesses would justify screening and referral for psychiatric treatment in clinics treating this population. Patients with active disease are particularly at risk for anxiety and depression.


One Year Follow-Up of Taste-Related Reward Associations with Weight Loss Suggests a Critical Time to Mitigate Weight Regain Following Bariatric Surgery.
Weight regain is a concerning issue in bariatric patients. We previously demonstrated that taste-related reward processing was associated with six-month weight loss outcomes following Roux-en-Y gastric bypass (RYGB) but not vertical sleeve gastrectomy (VSG). Here, we assessed whether these taste factors persisted in predicting weight loss, and weight regain, at one year post-surgery. Adult women enrolled in a longitudinal study of taste preferences following bariatric surgery completed behavioral and neuroimaging assessments at one year post-surgery. RYGB produced better weight loss relative to VSG, with weight regain and greater weight loss variability observed from six months to one year post-VSG. Changes in liking for high fat at 2 weeks post-surgery from baseline remained a predictor of weight loss in RYGB, but other predictors did not persist. Average liking ratings rebounded to baseline and higher self-reported food cravings and dietary disinhibition correlated with poorer weight loss at one year post-surgery. Initial anatomical and metabolic changes resulting from RYGB that reset neural processing of reward stimuli in the mesolimbic pathway appear to be temporary and may be contingent upon post-operative eating behaviors returning to preoperative obesogenic tendencies. Six months post-surgery may be a critical window for implementing interventions to mitigate weight gain.