[The missions of the Occupational Diseases Fund. Under-claim and recognition of occupational lung cancer, in particular those related to asbestos].
The missions of the Occupational Diseases Fund are defined in application of the law regarding the insurance against occupational diseases. The workers covered by this law are granted several rights, such as a financial compensation in case of temporary or permanent disability, a further compensation if they have to be taken away from the risk in the workplace, the reimbursement of health care costs related to the occupational disease, or the payment of an annuity to the widow(er) if death is its ultimate consequence. Among the compensable diseases, we shall focus on lung cancer, and especially the one related to asbestos exposure. This type of cancer is clearly under-registrated in Belgium as in most countries of the European Union, leading to an insufficient number of cases entitled to compensation by our institution. In this instance, the insurance against occupational diseases and all related social advantages are hugely under-exploited in our country. It is our duty to increase doctors' awareness of the problem and spread accurate information to reverse this trend and provide occupational cancer cases with a legitimate compensation, in particular those related to asbestos. A wider knowledge of the occupational history of cancer patients, thanks to occupational physicians, and a better use of mineralogical analyses on lung samples, would improve this situation inacceptable on any level : medical, social or even human.


Molecular characterization of influenza A(H1N1)pdm09 viruses circulating at various geographical locations in India, 2017.
Influenza virological surveillance is an essential tool for the early detection of novel genetic variants of epidemiologic and clinical significance. This study was aimed to genetically characterize A(H1N1)pdm09 virus circulating in 2017 and to compare it with the global data. The regional/State Viral Research and Diagnostic Laboratories (VRDLs) provided influenza diagnosis for referred clinical samples and shared influenza A(H1N1)pdm09 positives with the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, India, for hemagglutinin (HA) gene phylogenetic analysis. Sites at Manipal, Jaipur and Dibrugarh performed the sequencing and shared the sequence data for analysis. The antiviral susceptibility of influenza viruses was assessed for known molecular marker H275Y at the ICMR-NIV, Pune. All the eight VRDLs had well-established influenza diagnostic facilities and showed increased activity of influenza A(H1N1)pdm09 during 2017. Phylogenetic analysis showed that the viruses from the different regions of the country were similar to A/Michigan/45/2015 strain which was the 2017-2018 recommended vaccine strain and were clustered with the globally circulating clade 6B.1 with signature mutations S84N, S162N and I216T. The clade 6B.1 showed further subgrouping with additional mutations S74R, S164T and I295V; however, there was no significant association between the presence of these mutations and severity of disease due to influenza. All the study viruses were sensitive to oseltamivir. During the study period, all the study sites reported globally circulating A/Michigan/45/2015 vaccine strain of influenza A(H1N1)pdm09 viruses and remained sensitive to oseltamivir. Further genetic and antigenic characterization of influenza viruses is recommended to address public health concerns.


Differences in Outpatient Health Care Utilization 12 Months after COVID-19 Infection by Race/Ethnicity and Community Social Vulnerability.
Ensuring access to high-quality outpatient care is an important strategy to improve COVID-19 outcomes, reduce social inequities, and prevent potentially expensive complications of disease. This study assesses the equity of health care response to COVID-19 by examining outpatient care utilization by factors at the individual and community levels in the 12 months prior to and following COVID-19 diagnosis. Employing a retrospective, observational cohort design, we analyzed electronic health record data from a sample of 11,326 adults diagnosed with COVID-19 between March and July 2020. We used two-part models to estimate changes in use of primary and specialty care by race/ethnicity and community social vulnerability in the year before and after COVID-19 diagnosis. Our findings showed that while overall probability and counts of primary and specialty care visits increased following a positive COVID-19 diagnosis, disparities in care utilization by race/ethnicity and living in a socially vulnerable community persisted in the year that followed. These findings reiterate the need for strategic approaches to improve access to and utilization of care among those diagnosed with COVID-19, especially for individuals who are traditionally undeserved by the health system. Our findings also highlight the importance of systematic approaches for addressing social inequity in health care.


Extracorporeal Membrane Oxygenation in Pregnancy: An Analysis of the Extracorporeal Life Support Organization Registry.
We examined data from the International Registry of the Extracorporeal Life Support Organization to identify risk factors for mortality in pregnant and peripartum patients receiving extracorporeal membrane oxygenation. Retrospective analysis. International Registry of Extracorporeal Life Support Organization. We collected de-identified data on all peripartum patients who needed extracorporeal membrane oxygenation between 1997 and 2017 using International Classification of Diseases, 9th and 10th Edition criteria. Our primary outcome measure was in-hospital mortality. We also collected data on demographics, preextracorporeal membrane oxygenation ventilator, hemodynamic and biochemical parameters, extracorporeal membrane oxygenation mode, duration, and complications. Initial bivariate analysis assessed potential associations between survival and various preextracorporeal membrane oxygenation as well as extracorporeal membrane oxygenation-related factors. Variables with p values of less than 0.1 were considered for logistic regression analysis which identified predictors of mortality. There were 280 peripartum patients who received extracorporeal membrane oxygenation. Overall maternal survival was 70%, with observed mortality for these patients decreasing over the 21-year time period. Multivariate regression identified extracorporeal cardiopulmonary resuscitation (odds ratio, 3.674; 95% CI, 1.425-9.473; overall p = 0.025), duration of extracorporeal membrane oxygenation (< 66 hr: odds ratio, 1; 66-128 hr: odds ratio, 0.281; 95% CI, 0.101-0.777; p = 0.014; 128-232 hr: odds ratio, 0.474; 95% CI, 0.191-1.174; p = 0.107; and > 232 hr: odds ratio, 1.084; 95% CI, 0.429-2.737; p = 0.864; overall p = 0.017), and renal complications on extracorporeal membrane oxygenation (odds ratio, 2.346; 95% CI, 1.203-4.572; p = 0.012) as significant risk factors for mortality. There was no statistically significant difference in mortality between venovenous versus venoarterial versus mixed group extracorporeal membrane oxygenation (23.9 vs 34.4 vs 29.4%; p = 0.2) or between pulmonary versus cardiac indications (1.634; 95% CI, 0.797-3.352; p = 0.18) for extracorporeal membrane oxygenation. On analysis of this multicenter database, pregnant and peripartum patients with refractory cardiac or respiratory failure supported on extracorporeal membrane oxygenation had survival rates of 70%. We identified preextracorporeal membrane oxygenation as well as extracorporeal membrane oxygenation-related factors that are associated with mortality.


Kinetics of hydrogen consumption by rumen fluid, anaerobic digestor sludge, and sediment.
Michaelis-Menten kinetic parameters for H(2) consumption by three methanogenic habitats were determined from progress curve and initial velocity experiments. The influences of mass transfer resistance, endogenous H(2) production, and growth on apparent parameter estimates were also investigated. Kinetic parameters could not be determined for undiluted rumen fluid and some digestor sludge from gas-phase measurements of H(2), since mass transfer of H(2) across the gas-liquid interface was rate limiting. However, accurate values were obtained once the samples were diluted. H(2) consumption by digestor sludge with a long retention time and by hypereutrophic lake sediment was not phase transfer limited. The K(m) values for H(2) uptake by these habitats were similar, with means of 5.8, 6.0, and 7.1 muM for rumen fluid, digestor sludge, and sediment, respectively. V(max) estimates suggested a ratio of activity of approximately 100 (rumen fluid):10 (sludge):1 (sediment); their ranges were as follows: rumen fluid, 14 to 28 mM h; Holt sludge, 0.7 to 4.3 mM h; and Wintergreen sediment, 0.13 to 0.49 mM h. The principles of phase transfer limitation, studied here for H(2), are the same for all gaseous substrates and products. The limitations and errors associated with gas phase determination of kinetic parameters were evaluated with a mathematical model that combined mass transport and Michaelis-Menten kinetics. Three criteria are described which can be used to evaluate the possibility that a phase transfer limitation exists. If it does not exist, (i) substrate consumption curves are Michaelis-Menten and not first order, (ii) the K(m) is independent of initial substrate concentration, and (iii) the K(m) is independent of biomass (V(max)) and remains constant with dilution of sample. Errors in the Michaelis-Menten kinetic parameters are caused by endogenously produced H(2), but they were <15% for rumen fluid and 10% for lake sediment and digestor sludge. Increases in V(max) during the course of progress curve experiments were not great enough to produce systematic deviations from Michaelis-Menten kinetics.


Effect of ozone treatment on microbial and quality alteration of onions during 2 months storage.
Storing and preserving onion using pesticides is common in Brebes District. The study determined the use of ozone to reduce microorganisms and to maintain the onion quality during months of post-harvesting. There were three chambers with 2.5 m3 in size, and with a capacity of 20 kg onion used for this study. Each chamber received different treatment for 2 months; chamber I: no treatment; chamber II: pesticide; chamber III: ozone. The ozone treatment maintained better temperature and humidity for preservation. Ozone treatment was also observed to maintain low level of mass damage (1.8%) as compared to control and pesticide (6.5% and 2.4%). The protein, ash, fat and vit B1 of onions were remained high in ozone-treated chamber. Total Plate Count (CFU/mL) and the Mold Yeast Count (colonies/mL) decreased on day 30 and 60 after pesticides and ozone treatment. This study showed the importance of ozone treatment to maintain better quality of onion after months of storage as compared to pesticide treatment. Therefore, ozone can be a potential use to replace the pesticide for preservation at post-harvesting.


Analysis of the genome structure of influenza A virus strains isolated during the epidemics of 1977-1980.
The genome structure of different A(H1N1) and A(H3N2) influenza virus strains isolated from 1977 to 1980 was analysed by electrophoresis of single-stranded RNA and of the double-stranded RNA obtained by hybridization with complementary RNA of the A/Stavropol 188/79 (H3N2) strain. The differences in genome structure are insignificant within the A(H1N1) subtype, and considerable (involving almost all the 8 RNA fragments) between the two A(H3N2) strains (A/Texas 1/77 and A/Stavropol 188/79). The great differences between the genomes of A(H1N1) and A(H3N2) strains do not exclude certain genetic relationships between these viruses.


Platform for in situ real-time measurement of protein-induced conformational changes of DNA.
A platform for in situ and real-time measurement of protein-induced conformational changes in dsDNA is presented. We combine electrical orientation of surface-bound dsDNA probes with an optical technique to measure the kinetics of DNA conformational changes. The sequence-specific Escherichia coli integration host factor is utilized to demonstrate protein-induced bending upon binding of integration host factor to dsDNA probes. The effects of probe surface density on binding/bending kinetics are investigated. The platform can accommodate individual spots of microarrayed dsDNA on individually controlled, lithographically designed electrodes, making it amenable for use as a high throughput assay.


Notch3 interactome analysis identified WWP2 as a negative regulator of Notch3 signaling in ovarian cancer.
The Notch3 signaling pathway is thought to play a critical role in cancer development, as evidenced by the Notch3 amplification and rearrangement observed in human cancers. However, the molecular mechanism by which Notch3 signaling contributes to tumorigenesis is largely unknown. In an effort to identify the molecular modulators of the Notch3 signaling pathway, we screened for Notch3-intracellular domain (N3-ICD) interacting proteins using a human proteome microarray. Pathway analysis of the Notch3 interactome demonstrated that ubiquitin C was the molecular hub of the top functional network, suggesting the involvement of ubiquitination in modulating Notch3 signaling. Thereby, we focused on functional characterization of an E3 ubiquitin-protein ligase, WWP2, a top candidate in the Notch3 interactome list. Co-immunoprecipitation experiments showed that WWP2 interacted with N3-ICD but not with intracellular domains from other Notch receptors. Wild-type WWP2 but not ligase-deficient mutant WWP2 increases mono-ubiquitination of the membrane-tethered Notch3 fragment, therefore attenuating Notch3 pathway activity in cancer cells and leading to cell cycle arrest. The mono-ubiquitination by WWP2 may target an endosomal/lysosomal degradation fate for Notch3 as suggested by the fact that the process could be suppressed by the endosomal/lysosomal inhibitor. Analysis of The Cancer Genome Atlas dataset showed that the majority of ovarian carcinomas harbored homozygous or heterozygous deletions in WWP2 locus, and there was an inverse correlation in the expression levels between WWP2 and Notch3 in ovarian carcinomas. Furthermore, ectopic expression of WWP2 decreased tumor development in a mouse xenograft model and suppressed the Notch3-induced phenotypes including increase in cancer stem cell-like cell population and platinum resistance. Taken together, our results provide evidence that WWP2 serves as a tumor suppressor by negatively regulating Notch3 signaling in ovarian cancer.


Modeling conditional dependence between diagnostic tests: a multiple latent variable model.
Applications of latent class analysis in diagnostic test studies have assumed that all tests are measuring a common binary latent variable, the true disease status. In this article we describe a new approach that recognizes that tests based on different biological phenomena measure different latent variables, which in turn measure the latent true disease status. This allows for adjustment of conditional dependence between tests within disease categories. The model further allows for the inclusion of measured covariates and unmeasured random effects affecting test performance within latent classes. We describe a Bayesian approach for model estimation and describe a new posterior predictive check for evaluating candidate models. The methods are motivated and illustrated by results from a study of diagnostic tests for Chlamydia trachomatis.


Influence of IL17A polymorphisms (rs2275913 and rs3748067) on the susceptibility to ulcerative colitis.
Interleukin-17A plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We investigated the association between ulcerative colitis (UC) and polymorphisms of IL17A, rs2275913 (-197 G > A), and rs3748067 (*1249 C > T). The study was performed in 475 healthy subjects (controls) and 202 with UC (UC cases), including 113 controls and 64 UC cases from previous study. We employed the multiplex PCR-SSCP method to detect gene polymorphisms. The minor allele frequency of rs2275913 was significantly higher but that of rs3748067 was significantly lower in UC cases than controls. The rs2275913 minor homozygote (AA) had an increased risk of the development of UC, whereas rs3748067 minor carrier (CT + TT) had decreased risks for the development of UC. When compared with LR group (rs2275913 GG + GA with rs3748067 CT + TT), HR group (rs2275913 AA with rs3748067 CC) had a more increased risk of the development of UC (OR, 3.38; p = 0.0007). The polymorphisms of IL17A were associated with the noncontinuous and pancolitis phenotypes of UC. Our results suggest that IL17A polymorphisms (both rs2275913 and rs3748067) influence the susceptibility to and pathophysiological features of UC, coordinately.


[Highly active analogs of opiate-like peptides historphin and kapporphin].
Analgetic activity of analogues of new opioid peptides historphine Tyr-Gly-Phe-Gly-Gly and capporphine Tyr-Ser-Phe-Gly-Gly was studied. Analogues of historphine Tyr-D-Ala-Phe-Gly-Gly and of capporphine Tyr-D-Ser-Phe-Gly-Gly exceeded 10(3)-fold the Leu-encephaline efficiency using a tail-jerk test and their derivatives containing amide group in the C-end position--10(4)-fold. All the four analogues increased the resistance period in the heat plate test. Naloxone removed or decreased the effect of these peptides studied. After repeated administration peptides Tyr-D-Ala-Phe-Gly-Gly-NH2 and Tyr-D-Ser-Phe-Gly-NH2 were similar in the activity to the most strong native opioid peptide desmorphine. Considering that analogues of historphine and capporphine exhibited high analgetic activity, they may be used as promising structures in more complicated modifications in order to produce highly effective analogues of opioid peptides.


Structural details of anthrax spores during stages of transformation into vegetative cells.
Moberly, Betty J. (The University of Michigan, Ann Arbor), F. Shafa, and Philipp Gerhardt. Structural details of anthrax spores during stages of transformation into vegetative cells. J. Bacteriol. 92:220-228. 1966.-Anthrax spores in stages of dormancy, activation, germination, and outgrowth into vegetative cells were examined in an electron microscope. The fine structure proved to be much like that observed in related species of Bacillus, except for a visible alteration after heat activation and clusters of vesicle-like bodies in the cytoplasm of vegetative cells.


Effect of priming polymorphonuclear leukocytes with cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF] and G-CSF) on the host resistance to Streptococcus pneumoniae in chinchillas infected with influenza A virus.
Patients infected with influenza A virus (IAV) are at increased risk for bacterial superinfections, and this occurs in association with depressed polymorphonuclear leukocyte (PMNL) function. Recently, we reported that in vitro exposure of human PMNL to granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses IAV-induced cell dysfunction. The present study used an established animal model of IAV infection to examine whether G-CSF and/or GM-CSF can overcome IAV-induced PMNL dysfunction and thereby prevent secondary infections. Preliminary studies determined a dosing schedule of these cytokines that caused significant priming of chinchilla PMNL. In subsequent studies, animals were inoculated intranasally with IAV (day 1) followed 3 days later by Streptococcus pneumoniae, and administered daily intraperitoneal injections with a cytokine or placebo on days 3 through 9. Animals had blood obtained on multiple occasions for PMNL studies, and were followed-up for evidence of pneumococcal disease. Both cytokines caused significant priming of the PMNL chemiluminescence response and this was associated with reversal of the IAV-induced PMNL dysfunction. However, neither cytokine decreased the incidence of pneumococcal disease.


Nocardioides aquiterrae sp. nov., isolated from groundwater in Korea.
A bacterial strain, GW-9T, which was isolated from groundwater in Korea, was subjected to a polyphasic taxonomic study using phenotypic characterization and phylogenetic and genetic methods. Phylogenetic analysis based on 16S rDNA sequences showed that strain GW-9T forms an evolutionary lineage within the radiation enclosing Nocardioides species and, in particular, a coherent cluster with Nocardioides pyridinolyticus. The cell-wall peptidoglycan type of strain GW-9T was based on LL-diaminopimelic acid as the diamino acid, indicating wall chemotype I. The predominant menaquinone was MK-8(H4). Strain GW-9T had a cellular fatty acid profile containing straight-chain, branched, unsaturated and 10-methyl fatty acids. The major fatty acid was iso-C(16:0). The DNA G+C content of strain GW-9T was 73 mol%. The 16S rDNA of strain GW-9T was 99.2% similar to that of the type strain of Nocardioides pyridinolyticus and 94.9-96.0% similar to sequences of the type strains of other Nocardioides species. Differences in phenotypic characteristics and genetic distinctiveness indicate that strain GW-9T is separate from previously described Nocardioides species. Therefore, on the basis of the data presented, a novel species of the genus Nocardioides, Nocardioides aquiterrae sp. nov., is proposed. The type strain is strain GW-9T (=KCCM 41647T=JCM 11813T).


A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression.
Even though all of the energy contained with the UV wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress immune responses to Ag introduced at distant nonirradiated sites. In addition, data from a number of laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinoctyes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets. Although IL-10 can influence Th1 cell activation by altering Ag presentation and suppressing IFN-gamma secretion, the major signal for the development of a Th2 response is IL-4. Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV-irradiated mice with anti-IL-4 blocked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prostaglandins released by irradiated keratinocytes induce serum IL-4 since treating UV-irradiated mice with a cyclooxygenase-2 inhibitor blocked its production. Moreover, we found that treating UV-irradiated mice with anti-IL-4 suppressed serum IL-10 levels. In addition, injecting normal mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV exposure activates a cytokine cascade (PGE2 --> IL-4 --> IL-10) that ultimately results in systemic immune suppression.


Insect insulin receptors: insights from sequence and caste expression analyses of two cloned hymenopteran insulin receptor cDNAs from the fire ant.
The insulin and insulin-like growth factor (IGF) signalling (IIS) pathway in the honey bee (Apis mellifera) is linked to reproductive division of labour and foraging behaviour. Two insulin receptor genes are present in the released genomes of other social hymenopterans. Limited information is available on the IIS pathway role in ants. The predicted insulin receptor sequences from the recently released draft genome of the fire ant Solenopsis invicta (Hymenoptera: Formicidae) are incomplete and biologically significant data are also lacking. To elucidate the role of the IIS pathway in the fire ant, two putative insulin receptors (SiInR-1 and SiInR-2) were cloned; the first InR cDNAs cloned from social insects. Analyses of putative post-translational modification sites in SiInRs revealed the potential for differential regulation. We investigated the transcriptional expression of both receptors at different developmental stages, castes and queen tissues. In last instar larvae and pharate pupae of workers and reproductive, transcriptional abundance of both receptors was negatively correlated with body size and nutritional status. The expression level of both receptors in different queen tissues appears to correlate with requirements for queen reproductive physiology and behaviours. This study contributes new information to the understanding of social insects because in fire ants juvenile hormone acts as a gonadotropin and workers are fully sterile, contrary to honey bees.


Multifactorial etiology and multifaceted prevention strategy of hepatocellular carcinoma.
In many Asian and African countries, hepatitis B virus (HBV) has been identified as a major causative agent of hepatocellular carcinoma (HCC). In these endemic areas, HBV infection also occurs early in life. An internationally collaborative study on universal immunization of newborns against HBV to prevent HCC was initiated in September 1983 and expanded later in the rural Qidong County of China, a prevalent area of both HBV infection and HCC. The 5-year follow-up data of the pilot phase of this controlled study have shown encouraging results. Over 98% of the newborns in local communities were vaccinated and over 97% of the vaccinees are being followed. The vaccination group with boosted 5-micrograms regimen showed significantly reduced HBsAg positive rate at 5 years, 2.5 vs. 12.5% of the nonvaccinated age-matched control. The anti-HBs level was also enhanced. The main study starting from the beginning of 1985 has been progressing according to schedule. Striking male preponderance and peak age shift to younger age of HCC in the high incidence area strongly points to the action of cofactors that may further increase the risk. Male preponderance was not observed in the animal models of HCC induced by hepadnaviruses. These phenomena were associated with increased exposure to aflatoxins as measured by urinary excretion of AFM1, as well as with a high prevalence of tobacco smoking and alcohol consumption among the Chinese males. The clarification of the etiological role of cofactors has important implications in the possible prevention of HCC among HBV carriers.


Factors associated with past HIV testing among men who have sex with men attending university in China: a cross-sectional study.
Background HIV prevalence has been rapidly increasing among men who have sex with men (MSM) attending university in China, but HIV testing rates remain suboptimal. The factors associated with past HIV testing in this population in Beijing, China, were investigated. This study used data from the baseline survey of an HIV intervention clinical trial among MSM who did not have a history of a positive HIV diagnosis. This analysis focused on the HIV testing experience in a subgroup of university student MSM participants. Log-binomial models were used to evaluate factors associated with past HIV testing. Of 375 university student MSM, the median age was 22 years; 89.3% were Han ethnic. Approximately half (50.4%, n = 189) had ever taken an HIV test before the survey. In a multivariable log-binomial model, older age (adjusted prevalence ratio (APR), 1.04; 95% confidence interval (CI), 1.02-1.06), had first sexual intercourse at age <18 years (APR, 1.35; 95% CI, 1.08-1.45) and knew someone living with HIV (APR, 1.33; 95% CI, 1.07-1.61) were associated with a higher likelihood of past testing. Self-reported barriers to taking a test included perceived low HIV risk, fear of a positive diagnosis, did not know where to get tested and fear of discrimination. Facilitators included anonymity in taking a test, confidentiality of testing results and availability of home-based and rapid testing. The HIV testing rate among university student MSM was low. Interventions should be implemented to address structural, institutional and individual barriers to HIV testing in this vulnerable population.


Hydrogen exchange kinetics of proteins in denaturants: a generalized two-process model.
The recent progress in measurements on the amide hydrogen exchange (HX) in proteins under varying denaturing conditions, both at equilibrium and in transient relaxation, necessitates the development of a unifying theory which quantitatively relates the HX rates to the conformational energetics of the proteins. We present here a comprehensive kinetic model for the site-specific HX of proteins under varying solvent denaturing conditions based on the two-state protein folding model. The generalized two-process model considers both conformational fluctuations and residual protections, respectively, within the folded and unfolded states of a protein, as well as a global kinetic folding-unfolding transition between the two states. The global transition can be either rapid or slow, depending on the solvent condition for the protein. This novel model is applicable to the traditional equilibrium HX measurements in both EX2 and EX1 regimes, and also the recently introduced transient pulse-labeling HX experiments. A set of simple analytical equations is provided for quantitative interpretation of experimental data. The model emphasizes the use of full time-course of bi-exponential HX kinetics, rather than fitting time-course data to single rate constants, to obtain quantitative information about fluctuating conformers within the folded and unfolded states of proteins. This HX kinetic model naturally unfolds into a simple two-state and two-stage kinetic interpretation for protein folding. It suggests that the various observed intermediates of a protein can be interpreted as dominant isomers of either the folded or the unfolded state under different solvent conditions. This simple, minimalist's view of protein folding is consistent with various recent experimental observations on folding kinetics by HX.


Comparison of Standard Automated Perimetry, Short-Wavelength Automated Perimetry, and Frequency-Doubling Technology Perimetry to Monitor Glaucoma Progression.
Detection of progression is paramount to the clinical management of glaucoma. Our goal is to compare the performance of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry in monitoring glaucoma progression.Longitudinal data of paired SAP, SWAP, and FDT from 113 eyes with primary open-angle glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. Data from all tests were expressed in comparable units by converting the sensitivity from decibels to unitless contrast sensitivity and by expressing sensitivity values in percent of mean normal based on an independent dataset of 207 healthy eyes with aging deterioration taken into consideration. Pointwise linear regression analysis was performed and 3 criteria (conservative, moderate, and liberal) were used to define progression and improvement. Global mean sensitivity (MS) was fitted with linear mixed models.No statistically significant difference in the proportion of progressing and improving eyes was observed across tests using the conservative criterion. Fewer eyes showed improvement on SAP compared to SWAP and FDT using the moderate criterion; and FDT detected less progressing eyes than SAP and SWAP using the liberal criterion. The agreement between these test types was poor. The linear mixed model showed a progressing trend of global MS overtime for SAP and SWAP, but not for FDT. The baseline estimate of SWAP MS was significantly lower than SAP MS by 21.59% of mean normal. FDT showed comparable estimation of baseline MS with SAP.SWAP and FDT do not appear to have significant benefits over SAP in monitoring glaucoma progression. SAP, SWAP, and FDT may, however, detect progression in different glaucoma eyes.


Lobomycosis in a Post-Covid 19 Patient: A Case Report and Review of Literature.
To document a case of lobomycosis and to discuss its epidemiology & diagnosis. A 53-year-old male presented with a history of nasal congestion, nasal discharge, and epistaxis following Covid 19 infection. On physical examination, there was necrotic slough in the nasal vestibule near the inferior turbinate. Scrapings and punch biopsy were taken from the lesion. Hematoxylin-eosin-stained sections showed necrotic and mucoid areas with mixed inflammatory cell infiltration and numerous budding yeasts 3- 7μm diameter in singles, and small clusters with single narrow based budding as well as multiple budding including sequential budding forming "chains of yeasts". A diagnosis of Lobomycosis was made. Yeasts of lobomycosis are often confused with other yeasts such as P. brasiliensis, Candida spp., B. dermatitidis, and Cryptococci, but characteristic 'sequential budding' with a 'chain of yeasts" aid in the final diagnosis. Demonstration of yeasts with characteristic chains either in tissue sections or in potassium hydroxide (KOH) preparation of scraped material, exudate, or exfoliative cytology is the mainstay in the diagnosis as the organisms are uncultivable in vitro in culture medium.


[Treatment of sudden deafness with the calcium antagonist nimodipine. Results of a comparative study].
In a prospective randomised clinical study on 80 patients with idiopathic sudden hearing loss the therapeutic value of nimodipine was evaluated. Nimodipine is a 4-5-dihydropyridine calcium antagonist with selective spasmolytic and vasodilatory properties on cerebral vessels. The mean improvement of hearing (250, 500, 1000, 2000, 4000 Hz) amounted to 16.5 +/- 11.3 dB as compared with 18.6 +/- 10.2 dB achieved by standard treatment with hydroxyethyl starch (HAES) and naftidrofuryl. The difference is not significant (p greater than 0.2). These results together with the low rate of side effects indicate nimodipine as a therapeutic alternative in cases of hypertension, cardiac failure and allergic predisposition. The possible role of spontaneous recovery on one side and of specific parameters such as rheologic abnormalities or type of audiogram are discussed. They are important for a more sophisticated therapeutic approach towards sudden hearing loss.


Oil body proteins sequentially accumulate throughout seed development in Brassica napus.
Despite the importance of seed oil bodies (OBs) as enclosed compartments for oil storage, little is known about lipid and protein accumulation in OBs during seed formation. OBs from rapeseed (Brassica napus) consist of a triacylglycerol (TAG) core surrounded by a phospholipid monolayer embedded with integral proteins which confer high stability to OBs in the mature dry seed. In the present study, we investigated lipid and protein accumulation patterns throughout seed development (from 5 to 65 days after pollination [DAP]) both in the whole seed and in purified OBs. Deposition of the major proteins (oleosins, caleosins and steroleosins) into OBs was assessed through (i) gene expression pattern, (ii) proteomics analysis, and (iii) protein immunodetection. For the first time, a sequential deposition of integral OB proteins was established. Accumulation of oleosins and caleosins was observed starting from early stages of seed development (12-17 DAP), while steroleosins accumulated later (~25 DAP) onwards.


Maximizing the Benefit of Quality Improvement Activities: A Spread of Innovations Model.
Many organizations struggle to efficiently and effectively spread improvement activities. This article presents findings from a model developed to standardize the sharing of innovative ideas within nursing at an academic medical center. Quality improvement activities were occurring in many nursing units but often did not spread beyond the originating unit. Challenges included variability in operationalizing initiatives, inconsistent understanding of project goals, and the lack of a dissemination process. The Spread of Innovations Model was developed to ensure structure and resources are in place to spread successful initiatives. The model uses Lean problem-solving and engages frontline nurses with senior leadership when spreading internally developed best practices. The model was piloted by spreading a catheter-associated urinary tract infection (CAUTI) prevention project throughout nursing. Using the model led to significantly decreased CAUTIs. Improvement efforts without a process for spreading can lead to inefficiencies and variable outcomes.


Relationship between 100% juice consumption and nutrient intake and weight of adolescents.
This study investigated the associations among 100% juice consumption, nutrient intake, and measures of weight in adolescents. A cross-sectional secondary analysis of data from adolescents aged 12 to 18 years (n = 3939) participating in the National Health and Nutrition Examination Survey 1999-2002 was conducted to assess nutrient and weight in categories of 100% juice consumption. Least square means and logistic regression analyses were generated, and were adjusted for gender, age, ethnicity, and energy intake. Analyses were Bonferroni corrected with an effective p value of .0125. Twenty-eight percent of adolescents (51% male, 42% Hispanic, 25% non-Hispanic white, 29% non-Hispanic black) consumed 100% juice the day of the recall. The mean amount of 100% juice consumed was 3.7 ounces (2.2% of energy intake). Compared with non-juice consumers, carbohydrate, fiber, vitamins C and B6, folate, potassium, copper, magnesium, and iron intakes of juice consumers were higher, and intakes of fat and saturated fatty acids were lower. Those consuming greater than 6 ounces of juice consumed more servings of fruit and less discretionary fat and added sugar than nonconsumers. No differences were found in weight by juice consumption group. In conclusion, when compared with non-juice consumers, adolescents consuming 100% juice did not show mean increased weight measures. Juice provided valuable nutrients, and consumption was associated with lower intakes of total fat, saturated fatty acids, discretionary fat, and added sugars and with higher intakes of whole fruit; however, consumption was not associated with decreased intake of milk, meat, or grains.


Comparison of esophageal motility in gastroesophageal reflux disease with and without globus sensation.
This study aimed to compare the esophageal motility between gastroesophageal reflux disease (GERD) patients with typical symptoms but without globus sensation and GERD patients only with globus symptoms. A total of 57 consecutive GERD patients diagnosed by endoscopy or by 24-hour pH monitoring between May 2013 and September 2015 were included retrospectively into the study. The patients were grouped based on the presence or absence of globus. Thirty patients presented with typical reflux symptoms but without globus were assigned to the typical GERD group and 27 patients only with globus symptom were assigned to the globus GERD group. All patients underwent esophageal high resolution manometry (HRM) and the differences in esophageal motility between the two groups were analyzed. The globus GERD group showed a significantly greater lower esophageal sphincter (LES) length, LES basal pressure and upper esophageal sphincter (UES) residual pressure than that of the typical GERD group (3.47 ± 0.76 vs. 2.65 ± 0.62 cm, 21.71 ± 9.68 vs. 16.04 ± 8.49 mmHg, 7.30 ± 4.42 vs. 4.12 ± 2.92 mmHg, all p < 0.05). There was no significant difference between the two groups in terms of the distal wave amplitude, mean wave duration, distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL), integrated relaxation pressure (IRP) and UES basal pressure. The incidence of esophageal dysmotility in the globus GERD group (33.3%) was higher than in the typical GERD group (23.3%). There was no significant difference in esophageal acid exposure of the non-erosive gastroesophageal reflux disease (NERD) patients between the two groups. Globus GERD patients have a higher UES residual pressure, longer LES length, higher LES basal pressure and greater esophageal dysmotility than typical GERD patients. HRM is useful in evaluating esophageal motility of GERD patients.


G protein beta3 subunit 825T allele is associated with depression in young, healthy subjects.
This study investigated the relationship between the G protein beta3 subunit 825T allele and depression in young, healthy subjects. 825T and 825C allele carriers were characterized among 190 healthy medical students. State depression was assessed by the Becks Depression Inventory, supplemented by subscales of the Freiburg Personality Inventory, and Questionnaire for Measuring Factors of Aggression which assess trait depression. Depression of homo- and heterozygous 825T allele carriers was compared to 825C allele carriers via multi-level statistical analysis. 825T allele carriers displayed higher levels of depression, as measured by each questionnaire. Regression analysis demonstrated that allele type was the single predictor of depression. The predictive capacity of the 825T allele in depression was further supported by odds-ratio analysis. We conclude that the G protein beta3 subunit 825T allele is predictive of depressive mood in a young, healthy population.


Identification of candidate cancer predisposing variants by performing whole-exome sequencing on index patients from BRCA1 and BRCA2-negative breast cancer families.
In the majority of familial breast cancer (BC) families, the etiology of the disease remains unresolved. To identify missing BC heritability resulting from relatively rare variants (minor allele frequency ≤ 1%), we have performed whole exome sequencing followed by variant analysis in a virtual panel of 492 cancer-associated genes on BC patients from BRCA1 and BRCA2 negative families with elevated BC risk. BC patients from 54 BRCA1 and BRCA2-negative families with elevated BC risk and 120 matched controls were considered for germline DNA whole exome sequencing. Rare variants identified in the exome and in a virtual panel of cancer-associated genes [492 genes associated with different types of (hereditary) cancer] were compared between BC patients and controls. Nonsense, frame-shift indels and splice-site variants (strong protein-damaging variants, called PDAVs later on) observed in BC patients within the genes of the panel, which we estimated to possess the highest probability to predispose to BC, were further validated using an alternative sequencing procedure. Exome- and cancer-associated gene panel-wide variant analysis show that there is no significant difference in the average number of rare variants found in BC patients compared to controls. However, the genes in the cancer-associated gene panel with nonsense variants were more than two-fold over-represented in women with BC and commonly involved in the DNA double-strand break repair process. Approximately 44% (24 of 54) of BC patients harbored 31 PDAVs, of which 11 were novel. These variants were found in genes associated with known or suspected BC predisposition (PALB2, BARD1, CHEK2, RAD51C and FANCA) or in predisposing genes linked to other cancer types but not well-studied in the context of familial BC (EXO1, RECQL4, CCNH, MUS81, TDP1, DCLRE1A, DCLRE1C, PDE11A and RINT1) and genes associated with different hereditary syndromes but not yet clearly associated with familial cancer syndromes (ABCC11, BBS10, CD96, CYP1A1, DHCR7, DNAH11, ESCO2, FLT4, HPS6, MYH8, NME8 and TTC8). Exome-wide, only a few genes appeared to be enriched for PDAVs in the familial BC patients compared to controls. We have identified a series of novel candidate BC predisposition variants/genes. These variants/genes should be further investigated in larger cohorts/case-control studies. Other studies including co-segregation analyses in affected families, locus-specific loss of heterozygosity and functional studies should shed further light on their relevance for BC risk.


[Effects of 3-hydroxypyridine and succinic acid derivates on the dynamics of vertebral/neurologic symptoms after the surgical treatment of disk herniations].
A study of 3-hydroxypiridine and succinic acid derivates (emoxipin, reamberin and mexidol) effects on the 14 week dynamics of vertebral/neurologic symptoms was performed in 136 patients after the surgical treatment of disk herniations. Data obtained demonstrated the reduction of severity of neurodystrophic and radicular syndromes without significant changes in dorsalgia, psychological maladaptation (PM) and disability scores (DS) during 3.5 months in patients treated with emoxipin (150 mg i.v., daily) for two weeks after the microdiscectomy. The two-week administration of reamberin (400 mg i.v., daily) led to the early attenuation of neuropathic pain. The reduction of sings of radicular compression and DS measured with the Roland-Morris questionnaire were delayed for 3 months. Mexidol (300 mg i.v., once a day during two weeks) demonstrated the highest efficacy. This drug attenuated radicular and neurodystrophic syndromes, nociceptive and neuropathic pain, reduced PM and DS measured with both the Roland-Morris and the Oswestry questionnaires during 14 weeks after the surgery.


A functional C5a anaphylatoxin receptor in a teleost species.
The anaphylatoxins are potent, complement-derived low m.w. proteins that bind to specific seven-transmembrane receptors to elicit and amplify a variety of inflammatory reactions. C5a is the most potent of these phlogistic peptides and is a strong chemoattractant for neutrophils and macrophages/monocytes. Although lower vertebrates possess complement systems that are believed to function similarly to those of mammals, anaphylatoxin receptors have not previously been characterized in any nonmammalian vertebrate. To study the functions of C5a in teleost fish, we generated recombinant C5a of the rainbow trout, Oncorhynchus mykiss (tC5a), and used fluoresceinated tC5a (tC5aF) and flow cytometry to identify the C5a receptor (C5aR) on trout leukocytes. Granulocytes/Macrophages present in cell suspensions of the head kidney (HKL), the main hemopoietic organ in teleosts, showed a univariate type of receptor expression, whereas those from the peripheral blood demonstrated either a low or high level of expression. The binding of tC5aF was inhibited by excess amounts of unlabeled tC5a or tC5a(desArg), demonstrating that sites other than the C-terminal of tC5a interact with the C5aR. Both tC5a and tC5a(desArg) were able to induce chemotactic responses in granulocytes in a concentration-dependent manner, but the desArg derivative was at least 10-fold less active. Homologous desensitization occurred after HKL were exposed to continuous or high concentrations of tC5a, with a loss of tC5aF binding and an 80% reduction in chemotactic responses toward tC5a. Pertussis toxin reduced the migration of HKL toward tC5a by 40%, suggesting only a partial involvement of pertussis toxin-sensitive G(i) proteins in tC5a-mediated chemotaxis.


Functional Domains of the Early Proteins and Experimental and Epidemiological Studies Suggest a Role for the Novel Human Polyomaviruses in Cancer.
As their name indicates, polyomaviruses (PyVs) can induce tumors. Mouse PyV, hamster PyV and raccoon PyV have been shown to cause tumors in their natural host. During the last 30 years, 15 PyVs have been isolated from humans. From these, Merkel cell PyV is classified as a Group 2A carcinogenic pathogen (probably carcinogenic to humans), whereas BKPyV and JCPyV are class 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer. Although the other PyVs recently detected in humans (referred to here as novel HPyV; nHPyV) share many common features with PyVs, including the viral oncoproteins large tumor antigen and small tumor antigen, as their role in cancer is questioned. This review discusses whether the nHPyVs may play a role in cancer based on predicted and experimentally proven functions of their early proteins in oncogenic processes. The functional domains that mediate the oncogenic properties of early proteins of known PyVs, that can cause cancer in their natural host or animal models, have been well characterized and we examined whether these functional domains are conserved in the early proteins of the nHPyVs and presented experimental evidence that these conserved domains are functional. Furthermore, we reviewed the literature describing the detection of nHPyV in human tumors.


Identification and characterization of two distinct truncated forms of gp130 and a soluble form of leukemia inhibitory factor receptor alpha-chain in normal human urine and plasma.
Leukemia inhibitory factor (LIF) is a polyfunctional cytokine known to require at least two distinct receptor components (LIF receptor alpha-chain and gp130) in order to form a high affinity, functional receptor complex. In this report, we present evidence that there are two distinct truncated forms of gp130 in normal human urine and plasma: a large form with a molecular weight of approximately 100, 000, which is similar to a previously described form of soluble gp130 in human serum, and a previously undescribed small form with a molecular weight of approximately 50,000. Using a panel of monoclonal antibodies raised against the extracellular domain of human gp130, we were able to show that the small form of the urinary gp130 probably contained only the hemopoietin domain. Both forms of gp130 bound LIF specifically and were capable of forming heterotrimeric complexes with soluble human LIF receptor alpha-chain in the presence of human LIF. In addition to the soluble forms of gp130, a soluble form of LIF receptor alpha-chain was also detected in human urine and plasma.


A Case of Lysosomal Acid Lipase Deficiency Confirmed by Response to Sebelipase Alfa Therapy.
Lysosomal acid lipase (LAL) deficiency, or cholesterol ester storage disease, is a disorder affecting the breakdown of cholesterol esters and triglycerides within lysosomes. Clinical findings include hepatomegaly, hepatic dysfunction, and dyslipidemia with a wide range of phenotypic variability and age of onset. The available clinical and molecular information of the patient presented herein was consistent with a diagnosis of LAL deficiency, but her LAL activity assay repeatedly showed normal or borderline low results. Her response to enzyme replacement therapy and demonstrable deficiency on a newer specific enzymatic assay ultimately confirmed her diagnosis of LAL deficiency.


The role of dietary long chain fatty acids in mitochondrial structure and function. Effects on rat cardiac mitochondrial respiration.
To evaluate the effect of dietary rapeseed oils on cardiac mitochondrial function and metabolic conservation of energy, male weanling rats derived from the Sprague-Dawley strain were fed three rations containing either 15% (w/w) soybean oil, low erucic acid rapeseed oil or a high erucic acid rapeseed oil. Cardiac mitochondria were isolated for measurement of mitochondrial respiratory functions. Pyruvate and malate plus malonate or succinate plus amytal, or alpha-ketoglutarate and malate plus malonate were utilized as substrates for oxidative phosphorylation. Net rates of state 3 oxygen uptake and therefore ATP synthesis were found to decline with chronic feeding of the 15% (w/w) oil containing diets. Significantly reduced ADP/O ratios were observed for groups fed high erucic acid rapeseed oil containing diets for 11 days. Decreased ADP/O ratios were also observed for groups fed high or low erucic acid rapeseed oils for 112 days. When pyruvate and malate plus malonate were utilized as substrates, reduced rates of ATP synthesis were observed after chronic feeding of high erucic acid rapeseed oil diets. Only prolonged feeding of low erucic acid rapeseed oils resulted in significant alterations in the efficiency of oxidative phosphorylation.


Roles and responsibilities in substance use prevention in the school setting: views among Finnish school personnel representatives.
This study explores the views of Finnish school personnel representatives regarding substance use prevention responsibilities. Twenty-two focus groups were conducted within the scope of a regional intervention study in 2019. Qualitative content analysis was performed. Focus group interviews were conducted in the school setting. Focus group participants included representatives for educational personnel and student welfare personnel working in basic education, general upper secondary education or vocational education settings. Views and experiences concerning roles and responsibilities in primary prevention of substance use. Findings highlight the need for intersectoral efforts and intra-school collaboration in primary prevention efforts, but also in mental health promotion - on which the informants placed great emphasis. The health promotion leadership in schools, structural guidelines and the school curriculum could both challenge and support school personnel in their roles. An increased need to focus on the early years of life and related responsibilities of the homes was emphasized, along with the need to place more emphasis on health education in the first years of basic education, and responsibilities related to early risk identification. The findings highlight a need to develop structures and role clarity among school personnel, which can advance further development of intra-school and inter-sectoral collaboration in primary substance use prevention and mental health promotion. In the Finnish context, the successful implementation of relevant legislation, which some school representatives view as unclear or contravening, could be further supported.Key pointsViews regarding responsibilities in primary substance use prevention in the school setting have been less researched in the Nordic countries:The importance of inter-sectoral and intra-school collaboration is emphasized among school personnel representatives, including the role of the homesPrimary prevention and mental health promotion responsibilities are viewed as less clear than secondary and tertiary prevention responsibilitiesStructural guidelines concerning e.g. confidentiality aspects and curriculum features can both support and challenge school representatives in their roles.


Enteral Sodium Chloride Supplementation and Fluid Balance in Children Receiving Diuretics.
The use of sodium chloride (NaCl) supplementation in children being prescribed diuretics is controversial due to concerns that supplementation could lead to fluid retention. This is a single-center retrospective study in which fluid balance and diuretic dosing was examined in children prescribed enteral NaCl supplements for hyponatremia while receiving loop diuretics. The aim of this study was to determine whether significant fluid retention occurred with the addition of NaCl. Fifty-five patients with 68 events were studied. The median age was 5.2 months, and 82% were hospitalized for cardiac disease. Daily fluid balance the seven days prior to NaCl supplementation was lower than the seven days after, with measurement of: median 17 mL/kg/day (7-26) vs. 22 mL/kg/day (13-35) (p = 0.0003). There was no change in patient weight after supplementation (p = 0.63). There was no difference in the median loop diuretic dose before and after supplementation, with the diuretic dose in furosemide equivalents of 3.2 mL/kg/day (2.3-4.4) vs. 3.2 mL/kg/day (2.2-4.7) (p = 0.50). There was no difference in the proportion of patients receiving thiazide diuretics after supplementation (56% before vs. 50% after (p = 0.10)). NaCl supplementation in children receiving loop diuretics increased calculated fluid balance, but weight was unchanged, and this was not associated with an increase in diuretic needs, suggesting clinicians did not consider the increase in fluid balance to be clinically significant.


Rationale for revisions to the definition of death and criteria for its determination in Canada.
Clarity regarding the biomedical definition of death and the criteria for its determination is critical to inform practices in clinical care, medical research, law, and organ donation. While best practices for death determination by neurologic criteria and circulatory criteria were previously outlined in Canadian medical guidelines, several issues have arisen to force their reappraisal. Ongoing scientific discovery, corresponding changes in medical practice, and legal and ethical challenges compel a comprehensive update. Accordingly, the A Brain-Based Definition of Death and Criteria for its Determination After Arrest of Neurologic or Circulatory Function in Canada project was undertaken to a develop a unified brain-based definition of death, and to establish criteria for its determination after devastating brain injury and/or circulatory arrest. Specifically, the project had three objectives: (1) to clarify that death is defined in terms of brain functions; (2) to clarify how a brain-based definition of death is articulated; and (3) to clarify the criteria for determining if the brain-based definition is met. The updated death determination guideline therefore defines death as the permanent cessation of brain function and describes corresponding circulatory and neurologic criteria to ascertain the permanent cessation of brain function. This article explores the challenges that prompted revisions to the biomedical definition of death and the criteria for its determination and outlines the rationales underpinning the project's three objectives. By clarifying that all death is defined in terms of brain function, the project seeks to align guidelines with contemporary medicolegal understandings of the biological basis of death.


Intendedness of pregnancies and preconception contraceptive use in women of Swedish and non-European origins seeking emergency care in early pregnancy.
Unintended pregnancies in Europe have been estimated to constitute 43% of all pregnancies, with the proportion in Sweden being unknown. In striving for equitable healthcare, increased knowledge about unintended pregnancies among women born outside Europe is needed. We aimed to estimate the proportion of unintended pregnancies in women born in Sweden compared with women born outside Europe in an unselected population seeking gynaecological emergency care in early pregnancy. Our secondary aim was to compare contraceptive use at the time of conception in unplanned pregnancies between women born in Sweden and women born outside Europe. Pregnant women seeking gynaecological emergency care in early pregnancy at a tertiary hospital were asked to fill out a questionnaire in their native language. The questionnaire contained questions from the London Measure of Unplanned Pregnancy (LMUP) and questions regarding sociodemographic data, gynaecological health and previous contraception. Of 180 pregnancies, 66 were unintended (36.7%) according to the LMUP. Among patients born in Sweden, 49/129 (38.0%) of the pregnancies were unintended compared with 17/51 (33.3%) among patients born outside Europe (p=0.56). 86% of participants with unintended pregnancy did not use any form of contraception during the month of conception, with no difference between women born in Sweden and those born outside Europe. Among women seeking gynaecological emergency care in early pregnancy, unintended pregnancies are common. Women with unintended pregnancies had low use of preconception contraceptives, which highlights a need for further interventions aimed at avoiding unintended pregnancies.


Effects of zinc and ferritin levels on parent and teacher reported symptom scores in attention deficit hyperactivity disorder.
It has been suggested that both low iron and zinc levels might be associated with Attention Deficit Hyperactivity Disorder (ADHD) symptoms. However, the association of zinc and iron levels with ADHD symptoms has not been investigated at the same time in a single sample. 118 subjects with ADHD (age = 7-14 years, mean = 9.8, median = 10) were included in the study. The relationship between age, gender, ferritin, zinc, hemoglobin, mean corpuscular volume and reticulosite distribution width and behavioral symptoms of children and adolescents with ADHD were investigated with multiple linear regression analysis. Results showed that subjects with lower zinc level had higher Conners Parent Rating Scale (CPRS) Total, Conduct Problems and Anxiety scores, indicating more severe problems. CPRS Hyperactivity score was associated both with zinc and ferritin levels. Conners Teacher Rating Scale (CTRS) scores were not significantly associated with zinc or ferritin levels. Results indicated that both low zinc and ferritin levels were associated with higher hyperactivity symptoms. Zinc level was also associated with anxiety and conduct problems. Since both zinc and iron are associated with dopamine metabolism, it can be speculated that low zinc and iron levels might be associated with more significant impairment in dopaminergic transmission in subjects with ADHD.


Pluripotency in avian species.
Pluripotency defines the ability of a cell to self-renew and to differentiate into all embryonic lineages both in vitro and in vivo. This definition was first established mainly with the mouse model and the establishment of mouse embryonic stem cells (ESCs) in the 1980's and extended later on to other species including non-human primates and humans. Similarly, chicken ESCs were derived and established in vitro from pregastrulating embryos leading to cells with unique properties at molecular, epigenetic and developmental levels. By comparing the properties of murine, mammalian and avian ESCs and of the more recently discovered induced pluripotential stem (iPS)-derived cells generated in all of these species, avian specificities start to emerge including specific molecular genes, epigenetic mark profiles and original developmental properties. Here, we present common, but also avian-specific elements that contribute to defining avian pluripotency.


Combining multi-site magnetic resonance imaging with machine learning predicts survival in pediatric brain tumors.
Brain tumors represent the highest cause of mortality in the pediatric oncological population. Diagnosis is commonly performed with magnetic resonance imaging. Survival biomarkers are challenging to identify due to the relatively low numbers of individual tumor types. 69 children with biopsy-confirmed brain tumors were recruited into this study. All participants had perfusion and diffusion weighted imaging performed at diagnosis. Imaging data were processed using conventional methods, and a Bayesian survival analysis performed. Unsupervised and supervised machine learning were performed with the survival features, to determine novel sub-groups related to survival. Sub-group analysis was undertaken to understand differences in imaging features. Survival analysis showed that a combination of diffusion and perfusion imaging were able to determine two novel sub-groups of brain tumors with different survival characteristics (p < 0.01), which were subsequently classified with high accuracy (98%) by a neural network. Analysis of high-grade tumors showed a marked difference in survival (p = 0.029) between the two clusters with high risk and low risk imaging features. This study has developed a novel model of survival for pediatric brain tumors. Tumor perfusion plays a key role in determining survival and should be considered as a high priority for future imaging protocols.


Relapsed/refractory thrombotic thrombocytopenic purpura treated with N-acetylcysteine: a case report.
Thrombotic thrombocytopenic purpura is a rare condition that presents with microangiopathic haemolytic anaemia, thrombocytopaenia, fever, renal impairment and neurological symptoms. Plasma exchange is a lifesaving treatment for this condition. However, some cases may be non-responsive to plasma exchange, or loss of response may occur. Treatment options for refractory cases include high-dose corticosteroids, rituximab, vincristine, cyclophosphamide, splenectomy, bortezomib and N-acetylcysteine. We present a refractory case of thrombotic thrombocytopenic purpura responding to the last of these therapies.


[Ways of economizing on homologous blood. Concepts of autologous blood transfusion].
Transfusion of homologous blood may be associated with various complications. In this review, the authors present concepts of prevention of homologous blood transfusion. Different autotransfusion techniques are discussed, i.e., predeposit of autologous blood, plasmapheresis, normovolaemic haemodilution, blood salvage with/without cell washing, postoperative blood salvage of drainage blood, anaesthesia and surgical techniques as well as drugs for minimizing blood loss. The third part of the essay deals with indications of each technique depending on the surgical field. The authors conclude with unanswered questions and problems of the future.


Habitat configurations shape the trophic and energetic dynamics of reef fishes in a tropical-temperate transition zone: implications under a warming future.
Understanding the extent to which species' traits mediate patterns of community assembly is key to predict the effect of natural and anthropogenic disturbances on ecosystem functioning. Here, we apply a trait-based community assembly framework to understand how four different habitat configurations (kelp forests, Sargassum spp. beds, hard corals, and turfs) shape the trophic and energetic dynamics of reef fish assemblages in a tropical-temperate transition zone. Specifically, we tested (i) the degree of trait divergence and convergence in each habitat, (ii) which traits explained variation in species' abundances, and (iii) differences in standing biomass (kg ha-1), secondary productivity (kg ha-1 day-1) and turnover (% day-1). Fish assemblages in coral and kelp habitats displayed greater evidence of trait convergence, while turf and Sargassum spp. habitats displayed a higher degree of trait divergence, a pattern that was mostly driven by traits related to resource use and thermal affinity. This filtering effect had an imprint on the trophic and energetic dynamics of reef fishes, with turf habitats supporting higher fish biomass and productivity. However, these gains were strongly dependent on trophic guild, with herbivores/detritivores disproportionately contributing to among-habitat differences. Despite these perceived overall gains, turnover was decoupled for fishes that act as conduit of energy to higher trophic levels (i.e. microinvertivores), with coral habitats displaying higher rates of fish biomass replenishment than turf despite their lower productivity. This has important implications for biodiversity conservation and fisheries management, questioning the long-term sustainability of ecological processes and fisheries yields in increasingly altered marine habitats.


Resistance to insect pests in wheat-rye and Aegilops speltoides Tausch translocation and substitution lines.
Various insect pests attack wheat (Triticum aestivum L.) that can cause significant grain yield losses to the crop. Farmers usually depend on pesticides, however, smallholder farmers often have limited and ill-timed access to control methods, including insecticides. Host plant resistance is an alternative to protect grain yield and reduce costs to farmers. Three of the most serious pests of wheat are Diuraphis noxia (Kurdjumov), Mayetiola destructor (Say), and Cephus pygmeaus L. These pests occur in most of the wheat growing areas. However, they are of high importance in North Africa and West Asia. The aim of this study was to evaluate a set of wheat-alien translocations for resistance against D. noxia, M. destructor and C. pygmeaus. Genotypes of this germplasm set have already been reported to carry resistance against certain wheat aphid species. Genotypes 1RSam.1AL and MA1S.1RLe(1B), displayed high levels of resistance against D. noxia and C. pygmeaus, respectively. While three genotypes showed resistance reaction against M. destructor: 1Re(1D), 7A.7S-L5, and 7A.7S-Gb5. Except for the resistant genotype to C. pygmeaus, the other four genotypes were previously reported to carry resistance against Sitobion avenae Fabricius, Rhopalosiphum padi L. and Schizaphis graminum (Rondani). These five wheat-alien translocations are currently being used in the bread-wheat breeding programs at CIMMYT and ICARDA to transfer the multiple pest resistance in elite germplasm.


Standardization Initiatives in the (eco)toxicogenomics domain: a review.
The purpose of this document is to provide readers with a resource of different ongoing standardization efforts within the 'omics' (genomic, proteomics, metabolomics) and related communities, with particular focus on toxicological and environmental applications. The review includes initiatives within the research community as well as in the regulatory arena. It addresses data management issues (format and reporting structures for the exchange of information) and database interoperability, highlighting key objectives, target audience and participants. A considerable amount of work still needs to be done and, ideally, collaboration should be optimized and duplication and incompatibility should be avoided where possible. The consequence of failing to deliver data standards is an escalation in the burden and cost of data management tasks.


[Intermediate metabolism and respiratory function in peritonitis].
During observations of 26 patients and in acute and chronic experiments on 31 dogs under conditions of peritonitis the author studied neurohumoral relations and the effect of hydrocortisone on the respiratory function. A conclusion is made on the vital importance of the consistent associated corrective neurohumoral therapy with cholinomimetics and corticosteroids in peritonitis.


Screening and Recording of Patients' Alcohol-use Habit by Clinicians in a Tertiary Accident and Emergency Unit in Ireland.
Alcohol is widely consumed in Ireland; more so in major urban centers. Alcohol-related problems account for a significant number of Accident and Emergency (A and E) department presentations in Ireland. As a result, the national alcohol policy calls on doctors to be proactive in screening for and addressing alcohol misuse. The aim of the following study is to determine if patients presenting to a tertiary North Dublin A and E were asked about their alcohol use habit and if it was recorded. This was a descriptive observational study involving the retrospective review of case-notes for all patients who were assessed at the A and E Department of a North Dublin general hospital over a 1 week period for screening about their alcohol use habit. Data was entered into and analyzed using Microsoft Excel. Only 17% (106/613) of the A and E attendees over the study period were asked about their alcohol use habit or had it recorded. No case-note examined documented use of alcohol screening instruments. This study has revealed an inadequacy of enquiry about alcohol use habit. In light of high rates of alcohol misuse in Ireland we suggest the need for improved enquiry/screening and recording of alcohol use among all patients attending A and E's.


Clinical immunoscintigraphy of recurrent ovarian cancer with indium 111-labeled B72.3 monoclonal antibody.
To prospectively evaluate the ability for immunoscintigraphy with monoclonal antibody CYT-103 labeled with indium 111 to detect tumor presence in 15 patients with ovarian cancer undergoing second-look surgery. Prospective, open-label, nonrandomized trial. Hospital-based nuclear medicine facility and operating room. Patients with previous ovarian cancer scheduled for second-look surgery. Correctness of prediction of immunoscintigraphy for presence or absence of ovarian cancer compared with serum CA 125 titer and computed tomography. Immunoscintigraphy, computed tomography, and serum CA 125 titer had respective sensitivities of 92%, 42%, and 42%; specificities of 67%, 100%, and 100%; accuracies of 87%, 53%, and 53%; and diagnostic values of 59%, 42%, and 42%. The full regional extent of recurrent tumor was correctly detected in 45% of patients by immunoscintigraphy and in none of the patients by computed tomography. Immunoscintigraphy detected miliary tumor in two of four patients and computed tomography, as expected, was unable to detect miliary disease. Recurrent ovarian cancer often presents as multiple small lesions throughout the abdominal cavity. In this subset of patients, immunoscintigraphy may be particularly well suited for detection of the presence of recurrent tumor.


Psychoeducation for psychotic patients.
Psychoeducation programs have been shown in the last two decades to significantly improve the post-hospital discharge care of individuals with schizophrenia by demonstrated effects on rehospitalization rates, compliance with medication and knowledge. The benefits of psychoeducation can be sustained for up to seven years although most studies have not shown such enduring benefit. Psychoeducation is a type of psychotherapeutic support that aims to provide broad and adequate information on psychotic disorders for both patients and their families. The purpose of the group psychoeducational program at the Psychiatric clinic in Olomouc is to familiarize patients with the core of the disorder, explain the part played by pharmacotherapy, teach recognition of the warning signs of relapse, to advise on communication problems within families, and finally the training of social skills. Patients perceive the program as meaningful and helpful in better understanding their lives.


[SOS-repair--60 years].
This review integrates 60 years of research on SOS-repair and SOS-mutagenesis in procaryotes and eucaryotes, from Jean Weigle experiment in 1953 year (mutagenesis of lambda bacteriophage in UV-irradiated bacteria) to the latest achievements in studying SOS-mutagenesis on all living organisms--Eukarya, Archaea and Bacteria. A key role in establishing of a biochemical basis for SOS-mutagenesis belonges to the finding in 1998-1999 years that specific error-prone DNA polymerases (PolV and others) catalysed translesion synthesis on damaged DNA. This review focuses on recent studies addressing the new models for SOS-induced mutagenesis in Escherichia coli and Home sapiens cells.


How Secure Are Two-Way Ping-Pong and LM05 QKD Protocols under a Man-in-the-Middle Attack?
We consider a man-in-the-middle attack on two-way quantum key distribution ping-pong and LM05 protocols in which an eavesdropper copies all messages in the message mode, while being undetectable in the mode. Under the attack there is therefore no disturbance in the message mode and the mutual information between the sender and the receiver is always constant and equal to one and messages copied by the eavesdropper are always genuine. An attack can only be detected in the control mode but the level of detection at which the protocol should be aborted is not defined. We examine steps of the protocol to evaluate its security and find that the protocol should be redesigned. We also compare it with the security of a one-way asymmetric BB84-like protocol in which one basis serves as the message mode and the other as the control mode but which does have the level of detection at which the protocol should be aborted defined.


Protein kinase C zeta transactivates hypoxia-inducible factor alpha by promoting its association with p300 in renal cancer.
Hydroxylation at an asparagine residue at the COOH-terminal activation domain of hypoxia-inducible factor (HIF)-1/2 alphas is essential for its inactivation under normoxic condition. To date, the mechanism by which HIF-alpha avoids the inhibitory effect of asparagine hydroxylase in renal cell carcinoma (RCC) in normoxia is undefined. We have shown herein that protein kinase C (PKC) zeta has an important role in HIF-alpha activation in RCC. By using dominant negative mutant and small interference RNA approaches, we have demonstrated that the association between HIF-alpha and p300 is modulated by PKCzeta. Moreover, a novel signaling pathway involving phosphatidylinositol 3'-kinase and PKCzeta has been shown to be responsible for the activation of HIF-alpha by inhibiting the mRNA expression of FIH-1 (factor inhibiting HIF-1) in RCC and thereby promoting the transcription of hypoxia-inducible genes such as vascular permeability factor/vascular endothelial growth factor.


Cholestasis is associated with preproenkephalin mRNA expression in the adult rat liver.
Cholestatic liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total opioid activity, and elevated plasma enkephalin concentrations. In contrast to the normal adult rat liver, preproenkephalin mRNA was detected by Northern blotting in livers of adult rats with cholestasis due to bile duct resection and not in the sham-resected controls. Preprodynorphin mRNA was not detected in livers of either group, while preproopiomelanocortin mRNA was found in very low levels in both groups. Preproenkephalin mRNA was not expressed in the livers of rats with acute hepatocellular necrosis induced by thioacetamide. Hybridization histochemistry of cholestatic livers demonstrated the presence of preproenkephalin mRNA primarily over cells in the periportal areas, some of which appeared to be proliferating bile ductular cells. Immunohistochemical staining of cholestatic liver indicated the production of at least Met-enkephalin in association with preproenkephalin gene expression. These findings suggest that the liver itself, by synthesizing enkephalins, contributes directly to the abnormalities of the opioid system reported in cholestasis.


[The response of the hepatitis C and hepatitis G viruses to treatment with recombinant interferon alfa-2b].
The efficacy of recombinant alfa-2b interferon therapy in C-virus (HCV) and G-virus (HGV) in children with chronic hepatitis C was evaluated. Fifteen patients, between 6 and 16 years of age and positive for HCV of which four were also infected with HGV, were treated with interferon (3 M three times a week for 6 months). The responders were treated for 12 months. HCV RNA, antibodies to HCV, HVC viral genome (expressed as 1000 copy equivalents of HCV genome = 1 keq), HGV RNA (RT/PCR, 5'NCR-NS5), and E2-HGV antibodies were determined before treatment and at 3 and 6 months in all patients and at 12-24 months in the responders. Four HCV patients (27%) with low viral load (mean 36 keg/ml) showed good results after interferon treatment and two of them (13%) with genotypes 1b and 3 according to Simmond's classification showed a maintained response. The four HGV children also showed the same good results and the RNA was negative without sero-conversion to anti-E2 after 12 months of interferon treatment. In the post-interferon treatment period, the HGV RNA appeared again in the serum in 3 of the 4 children. In the child with a maintained response, serum conversion to anti-E2 was not detected. 1) The current results, with only 13% of the patients reaching a sustained response, question the systematic treatment of all children affected with hepatitis C virus. Since the cost-benefit ratio is not yielding the expected results, such therapy may be reserved for patients with genotype other than 1b and a low level of viral genome. 2) HGV is sensitive to treatment with interferon, although the infection frequently appears again once the treatment is over.


Human brain temperature in vivo: lack of heating during color transcranial Doppler ultrasonography.
This study was undertaken to assess the effect of ultrasound on human brain temperature in vivo. The investigation consisted of direct recording of intracranial temperature during color transcranial Doppler (TCD) sonography in a neurosurgical patient. The temperature was recorded from 3 thermocouples. One was implanted together with an intracranial pressure sensor into a surgically reduced intraparenchymal hematoma, the second was placed within the subdural space close to the temporal acoustic window, and the third was located extracranially at the outer surface of the temporal bone. Tympanic temperatures were also measured to give an approximation of global brain temperature. A 2.5-MHz transducer was used, and the system settings were as follows: spatial peak temporal average intensity = 234 mW/cm2 in B-mode at a maximum power of 32.3 mW and 2132 mW/cm2 in Doppler mode at a maximum power of 149.3 mW. Neither increase in the intraparenchymal brain temperature nor increase in the temperature at the bone/soft tissue interface was observed during 30 minutes of insonation. The ipsilateral tympanic temperature increased by only 0.06 degree C, and this value may be regarded as a measure of the overall increase in brain temperature. Passive cooling effect produced by the transducer, which was at ambient temperature, was found to reach the brain surface and to surpass any possible heating caused by the ultrasound. The results indicate that no noticeable increases in human brain temperature occur in response to ultrasound emitted by a color TCD device at high transmitter power settings within the diagnostic range.


In vitro and in vivo bioequivalence of commercial prednisone tablets.
The purpose of the study was to examine the bioequivalence of five commercially available oral prednisone products. The in vivo study utilized 18 healthy males, each of whom was administered 20 mg of prednisone as a reference solution or as a tablet in a 6-week, six-way crossover design. Blood was collected and serum was assayed, using an HPLC procedure specific for prednisone and prednisolone. Mean pharmacokinetic parameters (t 1/2, ke, Cmax, tmax, and AUC) were determined. ANOVA was performed on the prednisone and prednisolone data (F-test, p less than 0.05) as well as Duncan's multiple range analysis. Dissolution tests were also performed on each of the five products in order to test the relationship between dissolution and bioequivalence among prednisone products. The in vitro study consisted of a standard USP dissolution test which included tablets from the same lots as the tablets used in the in vivo study. The data showed no statistical difference in any of the pharmacokinetic parameters among tableted products, subjects, or dosing periods in the study. There was also no statistical difference in the dissolution study among the five commercial tablet forms.


Should I be more concerned about patient care or the four-hour target?
UK emergency departments (EDs) are high-pressure environments focused on delivering care in the most efficient way to patients with a range of health problems. For many people EDs are the front door of the NHS and are a focus of significant media and political interest. People who attend EDs are often anxious and a main element of their concern is waiting time for treatment. In UK EDs the four-hour target is a main NHS target and a cornerstone of evaluating ED performance. There is ongoing debate about whether spending additional time in EDs affects patient care and outcomes, with some research showing increased mortality associated with longer stays and some showing no effect on mortality. Evidence suggests that patients are spending longer in UK EDs and it is possible that those who remain longer than four hours could have worse outcomes. This article identifies the effects of prolonged ED length of stay through a systematic literature review of data published since implementation of the four-hour target to measure the relationship between breaching the target and morbidity and mortality.


Identification of Patients with New-Onset Heart Failure and Reduced Ejection Fraction in Danish Administrative Registers.
In Danish administrative registers, ejection fraction (EF) is not recorded, which is a considerable limitation for correct subclassification of patients with heart failure (HF). We hypothesized that a diagnosis of HF combined with the recorded prescription of both renin-angiotensin system (RAS) inhibitors and beta- blockers (RASi+BB) within 120 days could identify patients with HF and reduced ejection fraction (EF ≤40%) (HFrEF). On two sites, we identified all patients with a first-time registration of HF as primary hospital discharge diagnosis (ICD-10: I50) between June 1, 2016, and May 31, 2018 in inpatient or outpatient settings. Patients were included if they survived the initial 120 days after discharge. Reviewing patient records, we identified patients with HFrEF, based on EF ≤ 40% and reported HF symptoms. We registered the use of RASi+BB at 120 days and calculated sensitivity, specificity and predictive values. A total of 704 consecutive patients with a primary diagnosis of HF were included, of whom 541 (77%) fulfilled the HFrEF criteria. Patients with HFrEF confirmed from patient records were younger (median age 73 compared to 79 years) and less frequently women (31% compared to 56%) compared to non-HFrEF patients. At baseline, 24 (4%) of HFrEF patients were treated with RASi+BB compared to 22 (14%) of non-HFrEF patients. At 120 days, 460 (85%) of HFrEF patients received RASi+BB as compared to 25 (15%) of non-HFrEF patients. This resulted in a positive predictive value of 95%, sensitivity of 85% and specificity of 85%. In Denmark, the ICD-10 HF diagnosis combined with recorded RASi+BB treatment by 120 days after discharge has high positive predictive value and can accurately be used to identify patients with HFrEF.


[Letters of condolence to the relatives of patients].
Most people who die in the Netherlands receive medical care during the final stage of their life. Since the 19th century, when a sombre prognosis was often the only medical intervention available, sophisticated diagnostic procedures and curative victories have forced elementary bedside manners into retreat. However, modern medicine is rediscovering its boundaries; the inevitability of death and the human tragedy of dying. The renewed interest in letters of condolence from doctors to the family of their deceased patients is an example of this. These letters provide the physician with an opportunity for worthy and effective behaviour under trying circumstances.


[Identification of occupational risks associated with diseases suspected to be of possible occupational origin seen in the National Health System].
In an earlier study, we identified 26 diseases of possible occupational origin, seen in different settings within the national health system in Catalonia. In this literature review we identify those occupational risk factors most strongly associated with these pathologies. After applying inclusion/exclusion criteria to 754 reviews, meta-analyses and/or practice guidelines, 37 articles remained that were rated for study quality by 3 reviewers. Of these, the 31 studies of highest quality were examined in depth, and summarised in a final table. Ergonomic risk factors (manual handling of materials, highly repetitive movements and awkward postures), especially for musculoskeletal disorders of the upper extremity, and exposures to chemical products and physical agents, were prominent. These results provide an additional resource for primary care physicians to assist them with the identification of possible occupational illness and to improve communication between the National Health Service and social security system.


Prevalence of essential tremor: door-to-door neurologic exams in Mersin Province, Turkey.
Estimates of the prevalence of essential tremor (ET) are probably low because screening questionnaires have been used. The authors estimated the prevalence of ET in Mersin Province, Turkey, in 2,253 individuals aged >or=40 years, all of whom were examined by study neurologists. There were 89 ET cases (prevalence = 4.0%, 95% CI = 3.2 to 4.8%). The prevalence of ET may be higher than previously estimated. This is important when defining the extent of the health care problem.


Alcohol consumption, illicit substances, and intimate partner violence in a sample of batterers in psychological treatment.
The purpose of this study is to analyze the alcohol and illicit substance consumption characteristics in a sample of 572 batterers in treatment by court order. The results indicate that the prevalence of alcohol consumption in the past year was 89.3%, whereas within illicit substances, the prevalences were higher for cannabis (27.8%), followed by cocaine 20.3%). In order to analyze the possible effect of consumption on levels of perpetration and victimization of partner-aggression, the sample was divided into 4 groups: nonconsumers (16.3%), alcohol consumers (58.6%), illicit drug consumers (3.5%), and consumers of alcohol and illicit drugs (21.7%), finding that the groups of nonconsumers and alcohol consumers presented the lowest level of perpetration of psychological, physical, and sexual aggression and of victimization of psychological and physical aggression, whereas the group of consumers of alcohol and illicit drugs presented the highest levels. The results reveal the need to assess substance consumption when designing intervention protocols with batterers.


[Effect of phenazepam and seduxen on the presence of histidase and urokinase in the blood].
Liver tissue specific enzymes histidase and urokinase were found in blood of 160 rats after intraperitoneal administration of phenazepam at the doses of 1.0 and 2.5 mg/200 g of body weight as well as of diazepam at the dose of 2.0 mg/200 g. Administration of products of diazepam enzymatic degradation caused also the liberation of these enzymes from liver tissue into blood.


Erianin: A phytoestrogen with therapeutic potential.
Erianin, a phytoestrogen with therapeutic potential, is one of the major active components of Dendrobll caulis. Erianin has a variety of pharmacological effects, such as anti-tumor, anti-inflammatory, anti-diabetic retinopathy, anti-psoriasis, and antibacterial effects. Especially, in regard to the anti-tumor effect of erianin, the underlying molecular mechanism has been partly clarified. In fact, the numerous pharmacological actions of erianin are complex and interrelated, mainly including ERK1/2, PI3K/Akt, JAK2/STAT3, HIF-1α/PD-L1, PPT1/mTOR, JNK/c-Jun, and p38 MAPK signal pathway. However, on account of the poor water solubility and the low bioavailability of erianin, greatly affected and limited its further development and application. And it is worthwhile and meaningful to explore more extensive pharmacological effects and mechanisms, clarify pharmacokinetics, and synthesize the derivatives of erianin. Conclusively, in this paper, the pharmacological effects of erianin and its mechanism, pharmacokinetics, and derivatives studies were reviewed, in order to provide a reference for the development and application of erianin.


The myth of masochism.
The personality disorder called "Masochism," which traditionally has been regarded as a preference for and pursuit of suffering is dynamically misconceived. There presently is no fundamental agreement on a diagnostic category for this personality disorder. There are aspects of what is called masochism, such as sexual arousal associated with pain, which have not been considered in this study. I feel that the essential nature of the pain in those designated as masochists is low self-esteem and that it develops in a childhood context of inadequate loving nurturance. I strongly believe that low self-esteem evolves from and is maintained by the competitive social milieu and a resultant personal functioning, which is diffusely competitive. The competitive activity is often associated unawarely with cynicism (Bonime, 1989). The gratification of victory substitutes for the gratifications of intimacy and growth, but is relatively brief, and although it produces some self acceptance, it is never enough to overcome the basic low feeling about oneself. Here was Marjorie, a woman who had miserably low self-esteem as a child, as low as being "just a crack in the door." As an adult, as shown in her dream, she felt like a woman full of shit that comes out involuntarily. She struggled to keep from being exposed as such and ached with humiliation or inwardly--and sometimes openly--raged when some distasteful quality or inadequacy showed or threatened to show. This pained person strove to overcome her sense of inadequacy as a person. She overcame it by succeeding in outdoing others according to her private, competitive standards. Her criteria of value were success in evoking signs of approval and sustaining herself while suffering, while "taking it." Her highest value was being able to take it, to suffer intensely without breaking. She was cynical and never sensed for long that she was genuinely regarded as an acceptable human being. She didn't believe in the existence of any genuine caring. She dreamt of an ecstatic evening dining, dancing, and having wonderful sex with "Bill" who she felt was an exceptional man. Later in the dream, she expected the same ecstasy the following evening with him. However, he said to her they couldn't go on because she was cruel. Almost always the prospect of an enjoyable situation "scared" her because it required her to abandon her protective cynicism, which made her a defeatable, exploitable target for the cynicism and competitiveness of others.(ABSTRACT TRUNCATED AT 400 WORDS)


Home Triad: A New Exploration of Home for People Living With Dementia Based on Lefebvre's Spatial Triad.
This article examines a novel theoretical framework, which we term Home Triad, for research and practice involving people living with dementia (PLWD). Most of the existing home-related research on PLWD focuses on interior modifications, home care interventions and models, place attachment, and/or institutional homelike environments. However, limited studies have examined the meaning of home from PLWD's perspective, and even fewer have simultaneously considered the individual experience of PLWD, the external power (e.g., the role of design), and their interaction dynamics in the meaning-making process. We developed home triad based on Lefebvre's spatial triad. Inspired by Chaudhury's home story structure, we conducted a life story analysis of a person living with dementia, "Kai," under four contexts-childhood home, neighborhood and city, daily routine, and attachment-within home triad. Home triad abstracts "home" with a dialectically interconnected relationship of the conceived, perceived, and lived home. Through PLWD's everyday life, the essence of home is primarily shaped by the interaction between their lived and perceived homes. However, a person's experiences of and participation in home living activities are also planned and/or regulated by different groups of people (caregivers, designers, and policymakers), who play important roles in the conceived home. Critically examining how PLWD's lived and perceived home is constrained or enabled through the conceived home deserves greater future research efforts. A systematic examination of the essence of home for PLWD using home triad can facilitate subsequent research and practice that promote PLWD's health, well-being, and quality of life.


Silent brain infarcts in 755 consecutive patients with a first-ever supratentorial ischemic stroke. Relationship with index-stroke subtype, vascular risk factors, and mortality.
We wanted to establish independent associations of various clinical variables, computed tomographic (CT) scan features, presenting stroke subtypes, and outcome with the presence of silent infarcts on CT. We studied 755 consecutive patients in a prospective registration of patients with first-ever supratentorial atherothrombotic, cardioembolic, or lacunar stroke or stroke of undetermined cause by multiple logistic regression analysis. Two hundred six patients (27%) with a first symptomatic territorial or small deep ischemic stroke had one or more silent infarcts on CT. Of all silent lesions, 169 (82%) were small and deep. Silent infarcts were significantly more strongly associated with a lacunar than atherothrombotic (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.02 to 2.47; P = .039) or cardioembolic (OR, 1.89; 95% CI, 1.2 to 2.99; P = .005) index stroke. Silent territorial lesions were more strongly associated with cardioembolic than with lacunar stroke but not with atherothrombotic stroke. In this respect, no differences were found between the atherothrombotic and undetermined-cause group. Advanced age and hypertension were the only risk factors that were significantly associated with silent infarcts (OR, 1.76; 95% CI, 1.14 to 2.71; P = .011; and OR, 1.58; 95% CI, 1.13 to 2.21; P = .007; respectively), mainly because of a strong independent association of these risk factors with silent small deep infarcts (OR, 1.75; 95% CI, 1.10 to 2.79; P = .018; and OR, 1.57; 95% CI, 1.09 to 2.24; P = .014; respectively). A cardioembolic source or atrial fibrillation in specific was not independently associated with any type or number of silent infarcts. Significant carotid stenosis (diameter reduction > 50%) was not significantly associated with any type of silent lesion. Initial severe handicap (Rankin Scale score > 3), 30-day case fatality rate, and 1-year mortality were not affected by the presence of silent infarcts. The strong association of silent small deep lesions with first symptomatic small deep infarcts suggests a common underlying mechanism (presumably small-vessel vasculopathy), whereas cardiogenic embolism and large-vessel thromboembolism are the most likely causes in both silent and first symptomatic territorial infarcts. Single or multiple silent infarcts do not predict a cardioembolic stroke mechanism in first symptomatic supratentorial brain infarcts. As silent infarcts do not predict the cause of carotid embolic stroke in first symptomatic brain infarcts, their presence should not influence the decision on carotid surgery. Silent infarcts do not affect the degree of initial handicap, 30-day case fatality, or 1-year mortality. The significance of silent infarcts for predicting possible future cognitive decline and risk of recurrent stroke deserves further study.