Critical advances in bridging personal health informatics and clinical informatics.
To provide a survey over significant developments in the area of linking personal health informatics and clinical informatics, to give insights into critical advances and to discuss open problems and opportunities in this area. A scoping review over the literature published in scientific journals and relevant conference proceedings in the intersection between personal health informatics and clinical informatics over the years 2010 and 2011 was performed. The publications analyzed are related to two main topics, namely "Sharing information and collaborating through personal health records, portals and social networks" and "Integration of personal health systems with clinical information systems". For the first topic, results are presented according to five different themes: "Patient expectations and attitudes", "Real use experiences", "Changes for care providers", "Barriers to adoption" and "Proposed technical infrastructures". For the second topic, two different themes were found, namely "Technical architectures and interoperability" and "Security, safety and privacy issues". Results show a number of gaps between the information needs of patients and the information care provider organizations provide to them as well as the lack of a trusted technical, ethical and regulatory framework regarding information sharing. Despite recent developments in the areas of personal health informatics and clinical informatics both fields have diverging needs. To support both clinical work processes and empower patients to effectively handle self-care, a number of issues remain unsolved. Open issues include privacy and confidentiality, including trusted sharing of health information and building collaborative environments between patients, their families and care providers. There are further challenges to meet around health and technology literacy as well as to overcome structural and organizational barriers. Frameworks for evaluating personal health informatics applications and pervasive health technology are needed to build up an evidence basis.


The Impact of Deviation of the Stun Shot from the Ideal Point on Motor Paralysis in Cattle.
The effect on motor paralysis of a deviation in the stun shot placement from the ideal point on cattle skulls was monitored in 627 bovine animals (271 bulls and 356 cows) stunned with a captive bolt during slaughter in a slaughterhouse. The number of animals that experienced motor paralysis and the necessary fall of the animal in the stunning box were recorded after the stun shot. Subsequently, the position of the stun shot was measured on the skull of the slaughtered cattle in relation to the ideal point on the skull, and at a deviation from the ideal point, the quadrant on the skull in which the bullet was located was determined. The results show that with the increasing distance of the placement of the stun shot from the ideal point on the skull, the incidence of failure to induce motor paralysis in cattle increases significantly (p < 0.01) from 2.4% (within 3 cm of deviation) to 72.2% (at deviations ˃ 7 cm). There was a significant increase in the failure to induce motor paralysis in bulls as well as in cows, but this was more frequent in bulls regardless of the magnitude of the deviation from the ideal point (with the exception of a distance greater than 7 cm where the chances of inducing motor paralysis in bulls and cows are equally low). The incidence of failure to induce motor paralysis in cattle was not dependent on the placement of a stun shot in various quadrants on the skull. With the increasing deviation in any direction from the ideal point, the likelihood of effective stunning of cattle decreases. The results are important from the animal welfare point of view of the slaughter of cattle, and demonstrate the necessity of optimum placement of the stunning shot on the bovine skull in order to achieve the successful motor paralysis of cattle during their stunning at the slaughterhouse.


Transactional models between personality and alcohol involvement: a further examination.
Although correlated changes between personality and alcohol involvement have been shown, the functional relation between these constructs is also of theoretical and clinical interest. Using bivariate latent difference score models, we examined transactional relations (i.e., personality predicting changes in alcohol involvement, which in turn predicts changes in personality) across two distinct but overlapping developmental time frames (i.e., across college and during young adulthood) using two large, prospective samples. Across college, there was some evidence that alcohol involvement predicted changes in personality; however, these findings were limited to models that included more proximal measures of alcohol use. When examined across a longer timeframe, we found no evidence that alcohol involvement significantly predicted changes in personality but found some evidence that personality predicted changes in alcohol use. We did find reliable evidence of correlated changes between personality and alcohol use, especially during emerging adulthood. The findings from our datasets highlight that the impact of alcohol involvement on personality change may be limited to shorter intervals during specific developmental time-frames and that the relation between changes in personality and alcohol involvement may be best viewed from a noncausal perspective.


OX2R-selective orexin agonism is sufficient to ameliorate cataplexy and sleep/wake fragmentation without inducing drug-seeking behavior in mouse model of narcolepsy.
Acquired loss of hypothalamic orexin (hypocretin)-producing neurons causes the chronic sleep disorder narcolepsy-cataplexy. Orexin replacement therapy using orexin receptor agonists is expected as a mechanistic treatment for narcolepsy. Orexins act on two receptor subtypes, OX1R and OX2R, the latter being more strongly implicated in sleep/wake regulation. However, it has been unclear whether the activation of only OX2R, or both OX1R and OX2R, is required to replace the endogenous orexin functions in the brain. In the present study, we examined whether the selective activation of OX2R is sufficient to rescue the phenotype of cataplexy and sleep/wake fragmentation in orexin knockout mice. Intracerebroventricular [Ala11, D-Leu15]-orexin-B, a peptidic OX2R-selective agonist, selectively activated OX2R-expressing histaminergic neurons in vivo, whereas intracerebroventricular orexin-A, an OX1R/OX2R non-selective agonist, additionally activated OX1R-positive noradrenergic neurons in vivo. Administration of [Ala11, D-Leu15]-orexin-B extended wake time, reduced state transition frequency between wake and NREM sleep, and reduced the number of cataplexy-like episodes, to the same degree as compared with orexin-A. Furthermore, intracerebroventricular orexin-A but not [Ala11, D-Leu15]-orexin-B induced drug-seeking behaviors in a dose-dependent manner in wild-type mice, suggesting that OX2R-selective agonism has a lower propensity for reinforcing/drug-seeking effects. Collectively, these findings provide a proof-of-concept for safer mechanistic treatment of narcolepsy-cataplexy through OX2R-selective agonism.


Quantitative versus qualitative estrogen and luteinizing hormone testing for personal fertility monitoring.
A new fertility monitor is now available that provides quantitative measurement of urinary hormones, but clinical use requires validation against an established fertility monitor that provides only qualitative results. Two fertility monitors were compared using daily first morning urine samples over 3 cycles of use in 21 women users with experience using a fertility monitor with the Marquette Method of Natural Family Planning. Women were aged 33.4 ± 5.5 years and had menstrual cycles ranging between 23 and 41 days. The quantitative Mira Monitor estimates of ovulation were highly correlated with the qualitative ClearBlue Fertility Monitor (CBFM) estimates of ovulation. Both monitors provided an accurate estimate of the fertile window. In this preliminary trial, the Mira monitor was shown to be effective at delineating the fertile window and ovulation. We demonstrated the feasibility of applying the Marquette Method algorithm with the use of the Mira monitor. Satisfaction differences between the two monitors did not reach statistical significance. We anticipate that quantitative fertility monitoring will give couples and health-care providers new and unprecedented insights into the menstrual cycle and fertility.


Deriving Effective Decision-Making Strategies of Prosthetists: Using Hidden Markov Modeling and Qualitative Analysis to Compare Experts and Novices.
This research focuses on studying the clinical decision-making strategies of expert and novice prosthetists for different case complexities. With an increasing global amputee population, there is an urgent need for improved amputee care. However, current prosthetic prescription standards are based on subjective expertise, making the process challenging for novices, specifically during complex patient cases. Hence, there is a need for studying the decision-making strategies of prosthetists. An interactive web-based survey was developed with two case studies of varying complexities. Navigation between survey pages and time spent were recorded for 28 participants including experts (n = 20) and novices (n = 8). Using these data, decision-making strategies, or patterns of decisions, during prosthetic prescription were derived using hidden Markov modeling. A qualitative analysis of participants' rationale regarding decisions was used to add a deep contextualized understanding of decision-making strategies derived from the quantitative analysis. Unique decision-making strategies were observed across expert and novice participants. Experts tended to focus on the personal details, activity level, and state of the residual limb prior to prescription, and this strategy was independent of case complexity. Novices tended to change strategies dependent upon case complexity, fixating on certain factors when case complexity was high. The decision-making strategies of experts stayed the same across the two cases, whereas the novices exhibited mixed strategies. By modeling the decision-making strategies of experts and novices, this study builds a foundation for development of an automated decision-support tool for prosthetic prescription, advancing novice training, and amputee care.


Management of secondary diabetes mellitus after total pancreatectomy in infancy.
We report five children who required total pancreatectomy in the neonatal period for life threatening hypoglycaemia. Subsequent diabetes was managed with once daily subcutaneous insulin, oral pancreatic extract, and a controlled carbohydrate diet. Daily home blood glucose profiles in four of these children were different from those of 14 C-peptide negative children with type 1 insulin dependent diabetes--in the pancreatectomy group there was less variation in blood glucose throughout the day with a fall after breakfast as against a rise after breakfast in the type 1 group. Hyperglycaemia (greater than 10 mmol/l) with or without ketonaemia was extremely rare in the pancreatectomy group. Despite neonatal convulsions, physical growth and development have been normal. Hypoglycaemia, usually after food refusal, has been a major problem. In addition, there have been considerable emotional and family disturbances despite the excellent metabolic control, which presumably reflect the cumulative difficulties in managing such young children with diabetes.


[Neurobiology of imprinting].
Imprinting is an example of learning and memory acquisition in infancy. In the case of precocial birds, such as geese, ducks, and chickens, the baby birds learn the characteristics of the first moving object that they see within a critical period, and they imprint on it and follow it around. We analyzed the neural basis of this behavior in order to understand the neural mechanism of learning and memory in infancy. Information pertaining to a visual imprinting stimulus is recognized and processed in the visual Wulst, a region that corresponds to the mammalian visual cortex. It is then transmitted to the posterior region of the telencephalon, followed by the core region of the hyperpallium densocellulare (HDCo), periventricular region of the hyperpallium densocellulare (HDPe), and finally, the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. Memory is stored in the IMM. After imprint training, plastic changes are observed in the visual Wulst as well as in the neurons of this circuit. HDCo cells, located at the center of this circuit, express N-methyl-D-aspartate (NMDA) receptors containing the NMDA receptor (NR) 2B subunit; the expression of this receptor increased after the imprint training. Inhibition of this receptor in the cells of the HDCo region leads to failure of imprinting and inactivation of this circuit. Thus, NMDA receptors bearing the NR2B subunit play a critical role in plastic changes in this circuit and in induction of imprinting.


[Diego de Cisneros and novo-Hispanic astrological and geographical medicine].
The collection of geographical information about the New World which was originated during the XVI century started being organized during the XVI century started being organized and explained, in the field of medicine, towards the end of the century and continued during the earliest decades of the following. Writers in the medical profession of these days are characterized by their interest, sometimes coexisting with or alternated with the outlooks of geography of illness and astrology. Diego Cisneros is a outstanding writer of a single place of valuable work so far Known, who was born in Madrid, became a doctor at Alcala de Henares and then arrive in New Spain in 1612. His book represents the incipient baroque of the time and is a valuable contribution to the Knowledge of geography and medicine and is also a piece of art work. It contains one of the first plans of the City of Mexico and its neighbouring sites drawn ina a typical baroque style. The scientific importance of the book consists of the clearcut separation between science and belief leading to assert the freedom of Mankind to put an end to medieval astrology which imprisoned the individual. Because of his leanings towards the Alcala School he upholds the idea of the utility of science and experience linked up to objective clinical observation. Cisneros contributes through his work to the unfolding of two significant processes in the history of national culture: one relates to identity and the other one to scientific community. These pages contain an analysis of the development of his work.


Parenting and depressive symptoms among adolescents in four Caribbean societies.
The strategies that parents use to guide and discipline their children may influence their emotional health. Relatively little research has been conducted examining the association of parenting practices to depressive symptoms among Caribbean adolescents. This project examines the association of parenting styles to levels of depressive symptoms among adolescents in Jamaica, the Bahamas, St. Kitts and Nevis, and St. Vincent. Adolescents attending grade ten of academic year 2006/2007 in Jamaica, the Bahamas, St. Vincent, and St. Kitts and Nevis were administered the Parenting Practices Scale along with the BDI-II. Authoritative, Authoritarian, Permissive and Neglectful parenting styles were created using a median split procedure of the monitoring and nurturance subscales of the Parenting Practices Scale. Multiple regression analyses were used to examine the relationships of parenting styles to depressive symptoms. A wide cross-section of tenth grade students in each nation was sampled (n = 1955; 278 from Jamaica, 217 from the Bahamas, 737 St. Kitts and Nevis, 716 from St. Vincent; 52.1% females, 45.6% males and 2.3% no gender reported; age 12 to 19 years, mean = 15.3 yrs, sd = .95 yrs). Nearly half (52.1%) of all adolescents reported mild to severe symptoms of depression with 29.1% reporting moderate to severe symptoms of depression. In general, authoritative and permissive parenting styles were both associated with lower levels of depressive symptoms in adolescents. However, the relationship of parenting styles to depression scores was not consistent across countries (p < .05). In contrast to previous research on Caribbean parenting, caregivers in this study used a mixture of different parenting styles with the two most popular styles being authoritative and neglectful parenting. There appears to be an association between parenting styles and depressive symptoms that is differentially manifested across the islands of Jamaica, the Bahamas, St. Kitts and Nevis and St. Vincent.


Bioconversion of glycerol for bioethanol production using isolated Escherichia coli ss1.
Bioconverting glycerol into various valuable products is one of glycerol's promising applications due to its high availability at low cost and the existence of many glycerol-utilizing microorganisms. Bioethanol and biohydrogen, which are types of renewable fuels, are two examples of bioconverted products. The objectives of this study were to evaluate ethanol production from different media by local microorganism isolates and compare the ethanol fermentation profile of the selected strains to use of glucose or glycerol as sole carbon sources. The ethanol fermentations by six isolates were evaluated after a preliminary screening process. Strain named SS1 produced the highest ethanol yield of 1.0 mol: 1.0 mol glycerol and was identified as Escherichia coli SS1 Also, this isolated strain showed a higher affinity to glycerol than glucose for bioethanol production.


Prevalence of hepatitis B and C viral co-infections among HIV-1 infected individuals in Nairobi, Kenya.
Hepatitis B virus (HBV) and Hepatitis C virus (HCV) co-infections among HIV-1 infected individuals are growing worldwide health problems characterized by lack of effective vaccines, need for expensive treatment, chronicity of morbidity and associated mortality. Their prevalence and distribution patterns continue to vary across geographical locations with high prevalence being detected among high risk populations. To determine the prevalence of HBV and HCV among HIV-1 infected individuals, blood samples were collected from consenting study subjects visiting comprehensive HIV clinics in Nairobi during the period between October and December 2009. Blood samples from volunteers were screened with ELISA tests for detecting HIV, HBV surface antigen (HBsAg) and anti-HCV antibodies. In a total of three (300) hundred infected individuals consisting of 129 (43%) males and 171 (57%) females 15.3% (46/300) were HIV-1 co-infected with either HBV or HCV or both, 10.3% (31/300) with HIV-1 and HCV and 6% (18/300) with HIV-1 and HBV infections. However, only three individuals (1%) were coinfected with the three viruses (HIV/HBV/HCV). Though, low levels of co-infection with all three viruses were reported, there could be higher prevalence rates than reported here especially among high risk populations.


Principles of electron wave front modulation with two miniature electron mirrors.
We have analyzed the possibilities of wave front shaping with miniature patterned electron mirrors through the WKB approximation. Based on this, we propose a microscopy scheme that uses two miniature electron mirrors on an auxiliary optical axis that is in parallel with the microscope axis. A design for this microscopy scheme is presented for which the two axes can be spatially separated by as little as 1 mm. We first provide a mathematical relationship between the electric potential and the accumulated phase modulation of the reflected electron wave front using the WKB approximation. Next, we derive the electric field in front of the mirror, as a function of a topographic or pixel wise excited mirror pattern. With this, we can relate the effect of a mirror pattern onto the near-field phase, or far field intensity distribution and use this to provide a first optical insight into the functioning of the patterned mirror. The equations can only be applied numerically, for which we provide a description of the relevant numerical methods. Finally, these methods are applied to find mirror patterns for controlled beam diffraction efficiency, beam mode conversion, and an arbitrary phase and amplitude distribution. The successful realization of the proposed methods would enable arbitrary shaping of the wave front without electron-matter interaction, and hence we coin the term virtual phase plate for this design. The design may also enable the experimental realization of a Mach-Zehnder interferometer for electrons, as well as interaction-free measurements of radiation sensitive specimen.


Desirable standards for laboratory tests if they are to fulfill medical needs.
Many strategies to define desirable standards for laboratory tests to fulfill medical needs have been proposed over the last three decades. Traditional approaches are based on reference (normal) values, opinions of clinicians, the state of the art, views of experts, data on biological variation, and assessment of the effect of error on clinical use. All these approaches have advantages and disadvantages, but the consensus of experts reached over a decade ago that imprecision desirably be less than one-half of the within-subject biological variation still seems to provide the best set of generally applicable performance standards. Desirable bias is less than one-quarter of the group (within-subject plus between-subject) biological variation. Recent proposals are either restatements of traditional recommendations, further empirical suggestions, or models based on assessment of clinical needs, and have not been widely accepted. Both old and new studies on clinical opinions, sought by using structured questionnaires containing clinical vignettes designed to seek views on the magnitude of significant change, are flawed in design, execution, and data analysis. Until clinicians are more aware of test-result variability and clinical chemists gain quantitative knowledge on the interpretation of test results, it will be difficult to set desirable standards that fulfill actual medical needs, except in a few well-defined screening situations.


Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment.
Leukocyte migration across endothelial cell borders (paracellular) and through endothelial cells (transcellular) appear to be distinct processes. During paracellular migration, membrane from a parajunctional reticulum of interconnected vesicles, the endothelial lateral border recycling compartment (LBRC), moves to surround the leukocyte in a kinesin-mediated, microtubule-dependent manner. We show that transcellular migration likewise requires targeted trafficking of LBRC membrane. We show that in addition to platelet/endothelial cell adhesion molecule (PECAM; CD31), CD99 and junctional adhesion molecule A (JAM-A), but apparently not vascular endothelial cell-specific cadherin (cadherin 5, CD144), are components of the LBRC. During transcellular migration, LBRC membrane invests the transmigrating leukocyte. Intracellular adhesion molecule 1 (ICAM-1) on the apical endothelial surface is enriched around adherent leukocytes. Depolymerization of microtubules has no effect on ICAM-1 enrichment but blocks targeted trafficking of LBRC membrane and transcellular migration by >90%. Similar to their effects on paracellular transmigration, antibodies against PECAM or CD99, but not JAM-A, block transcellular migration. We conclude that similar molecular mechanisms promote both para- and transcellular migration.


Managing Swedish forestry's impact on mercury in fish: Defining the impact and mitigation measures.
Inputs of anthropogenic mercury (Hg) to the environment have led to accumulation of Hg in terrestrial and aquatic ecosystems, contributing to fish Hg concentrations well above the European Union standards in large parts of Fennoscandia. Forestry operations have been reported to increase the concentrations and loads of Hg to surface waters by mobilizing Hg from the soil. This summary of available forestry effect studies reveals considerable variation in treatment effects on total Hg (THg) and methylmercury (MeHg) at different sites, varying from no effect up to manifold concentration increases, especially for the bioavailable MeHg fraction. Since Hg biomagnification depends on trophic structures, forestry impacts on nutrient flows will also influence the Hg in fish. From this, we conclude that recommendations for best management practices in Swedish forestry operations are appropriate from the perspective of mercury contamination. However, the complexity of defining effective policies needs to be recognized.


Effect of ascorbic acid concentrations, methods of cooling and freezing on Boer goat semen cryopreservation.
To improve the Boer goat semen quality during cryopreservation process, three experiments were carried out to investigate the effect of (i) different concentration of ascorbic acid supplementation (ii) rate of cooling with chilled semen characteristics and (iii) method of freezing on post-thaw Boer goat sperm using Tris-based extender. Ascorbic acid at 8.5 mg/ml improved the sperm parameters (motility, integrity of membrane and acrosome, morphology and viability), compared to control in cooled samples (p < 0.05). With regard to other concentrations and post-thawed parameters, ascorbic acid at 2.5-8.5 mg/ml led to higher percentages of sperm motility and integrities of membrane and acrosome when compared to control (p < 0.05). Slow cooling rises to higher percentages of sperm motility, acrosome integrity and viability, in comparison with fast cooling, in terms of cooled and frozen samples (p < 0.05). Programmable freezing method produced the higher percentages of sperm motility, integrities of membrane and acrosome and viability when compared to the freezing method of polystyrene box during goat sperm freezing (p < 0.05). In conclusion, chilled and post-thawed sperm quality of Boer goat was improved when a Tris-based extender supplemented with ascorbic acid was used at stages of different cooling rates and freezing methods.


Expression of growth factor mRNA in rabbit PVR model systems.
Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)


Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum.
The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.


Fabrication and characterization of amidoxime-functionalized silica decorated with copper: a catalytic assembly for rapid reduction of dyes.
In this study, amidoxime-functionalized silica decorated with copper (AFS-Cu) was fabricated and tested for its catalytic application. Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction were employed to characterize its structure and morphology. The application of AFS-Cu as a catalyst for the catalytic reduction of methylene blue (MB) in aqueous media using NaBH4 as reductant was evaluated. The ability to reuse as well as the effect of catalyst dose and pH of solution on the catalytic activity was investigated. The reduction of MB followed pseudo-first-order kinetics and the rate constant (k) was 0.6224 min-1. AFS-Cu was found to be a highly effective catalyst for MB reduction reaction and can be easily recovered and reused several times with no appreciable loss of catalytic activity.


Paenibacillus phoenicis sp. nov., isolated from the Phoenix Lander assembly facility and a subsurface molybdenum mine.
A novel Gram-positive, motile, endospore-forming, aerobic bacterium was isolated from the NASA Phoenix Lander assembly clean room that exhibits 100 % 16S rRNA gene sequence similarity to two strains isolated from a deep subsurface environment. All strains are rod-shaped, endospore-forming bacteria, whose endospores are resistant to UV radiation up to 500 J m(-2). A polyphasic taxonomic study including traditional phenotypic tests, fatty acid analysis, 16S rRNA gene sequencing and DNA-DNA hybridization analysis was performed to characterize these novel strains. The 16S rRNA gene sequencing convincingly grouped these novel strains within the genus Paenibacillus as a separate cluster from previously described species. The similarity of 16S rRNA gene sequences among the novel strains was identical but only 98.1 to 98.5 % with their nearest neighbours Paenibacillus barengoltzii ATCC BAA-1209(T) and Paenibacillus timonensis CIP 108005(T). The menaquinone MK-7 was dominant in these novel strains as shown in other species of the genus Paenibacillus. The DNA-DNA hybridization dissociation value was <45 % with the closest related species. The novel strains had DNA G+C contents of 51.9 to 52.8 mol%. Phenotypically, the novel strains can be readily differentiated from closely related species by the absence of urease and gelatinase and the production of acids from a variety of sugars including l-arabinose. The major fatty acid was anteiso-C(15 : 0) as seen in P. barengoltzii and P. timonensis whereas the proportion of C(16 : 0) was significantly different from the closely related species. Based on phylogenetic and phenotypic results, it was concluded that these strains represent a novel species of the genus Paenibacillus, for which the name Paenibacillus phoenicis sp. nov. is proposed. The type strain is 3PO2SA(T) ( = NRRL B-59348(T) = NBRC 106274(T)).


N400 brain responses to spoken phrases paired with photographs of scenes: implications for visual scene displays in AAC systems.
Augmentative and alternative communication (AAC) systems are often implemented for individuals whose speech cannot meet their full communication needs. One type of aided display is called a Visual Scene Display (VSD). VSDs consist of integrated scenes (such as photographs) in which language concepts are embedded. Often, the representations of concepts on VSDs are perceptually similar to their referents. Given this physical resemblance, one may ask how well VSDs support development of symbolic functioning. We used brain imaging techniques to examine whether matches and mismatches between the content of spoken messages and photographic images of scenes evoke neural activity similar to activity that occurs to spoken or written words. Electroencephalography (EEG) was recorded from 15 college students who were shown photographs paired with spoken phrases that were either matched or mismatched to the concepts embedded within each photograph. Of interest was the N400 component, a negative deflecting wave 400 ms post-stimulus that is considered to be an index of semantic functioning. An N400 response in the mismatched condition (but not the matched) would replicate brain responses to traditional linguistic symbols. An N400 was found, exclusively in the mismatched condition, suggesting that mismatches between spoken messages and VSD-type representations set the stage for the N400 in ways similar to traditional linguistic symbols.


Circumstances preceding suicide in U.S. soldiers: A qualitative analysis of narrative data.
To gain a better understanding of military suicide, we examined suicide narratives for 135 Soldiers extracted from two large-scale surveillance systems: the Department of Defense Suicide Event Report (DoDSER) and the Centers for Disease Control and Prevention's (CDC) National Violent Death Reporting System (NVDRS). Using coroner/medical examiner and law enforcement narratives captured in the NVDRS and mental health provider narrative data collected across multiple domains from the DoDSER, we examined circumstances surrounding military suicides using a qualitative content analysis approach. We identified five common proximal circumstances: (1) intimate partner relationship problems (63.0%); (2) mental health/substance abuse (51.9%); (3) military job-related (46.7%); (4) financial (17.8%); and (5) criminal/legal activity (16.3%). Evidence of premeditation was present in 37.0% of suicides. Decedents frequently struggled with multiple, high-stress problems and exhibited symptoms of coping and emotion regulation difficulties. Findings demonstrate potential points of intervention for suicide prevention strategies. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


An unusual presentation of secondary syphilis in a patient with human immunodeficiency virus infection. A case report and review of the literature.
Syphilis has been reported to assume unusual clinical appearances and to exhibit unusual courses in patients infected with the human immunodeficiency virus (HIV) type 1. We recently observed a distinct manifestation of syphilis in an HIV-infected patient with features not previously described. A 38-year-old HIV-seropositive homosexual man presented with fever, chills, malaise, and a cutaneous eruption consisting of indurated, shiny, erythematous plaques that were confluent on the face and scalp leading to alopecia and extreme tautness of the skin. Initial clinical diagnoses included lymphoreticular malignancy and infection. Although cultures yielded Staphylococcus aureus, a skin biopsy specimen was diagnostic of syphilis. This case demonstrates an unusual clinical manifestation of syphilis in a patient with HIV infection and emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of virtually any inflammatory cutaneous disorder in HIV-seropositive individuals.


Case report: Mafb promoter activity may define the alveolar macrophage dichotomy.
Cre-LoxP system has been widely used to induce recombination of floxed genes of interest. Currently available macrophage promoter-specific Cre recombinase mice strains have various limitations that warrants the testing of additional Cre strains. V-maf musculoaponeurotic fibrosarcoma oncogene family, protein b -Cre (Mafb-Cre) mice label macrophages in most organs such as spleen, small intestine, lung, bone marrow, and peritoneal cavity. However, whether Mafb-Cre recombinase targets the gene recombination in alveolar macrophage remains untested. Here, we utilized MafbCre/WTR26mTmG/WT strain that expresses mTOM protein in all the cells of mouse body except for those that express Mafb-Cre-regulated mEGFP. We performed fluorescent microscopy and flow cytometry to analyze mTOM and mEGFP expression in alveolar macrophages from MafbCre/WTR26mTmG/WT mice. Our analyses revealed that the Mafb-Cre is active in only ~40% of the alveolar macrophages in an age-independent manner. While Mafb- (mTOM+/mEGFP-) and Mafb+ (mEGFP+) alveolar macrophages exhibit comparable expression of CD11b and CD11c surface markers, the surface expression of MHCII is elevated in the Mafb+ (mEGFP+) macrophages. The bone marrow-derived macrophages from MafbCre/WTR26mTmG/WT mice are highly amenable to Cre-LoxP recombination in vitro. The bone marrow depletion and reconstitution experiment revealed that ~98% of alveolar macrophages from MafbCre/WTR26mTmG/WT → WT chimera are amenable to the Mafb-Cre-mediated recombination. Finally, the Th2 stimulation and ozone exposure to the MafbCre/WTR26mTmG/WT mice promote the Mafb-Cre-mediated recombination in alveolar macrophages. In conclusion, while the Mafb-/Mafb+ dichotomy thwarts the use of Mafb-Cre for the induction of floxed alleles in the entire alveolar macrophage population, this strain provides a unique tool to induce gene deletion in alveolar macrophages that encounter Th2 microenvironment in the lung airspaces.


Extinction training after cocaine self-administration induces glutamatergic plasticity to inhibit cocaine seeking.
Learning to inhibit drug seeking can be an important strategy for inhibiting relapse, and this can be modeled by extinguishing drug seeking in response to a drug-paired context. Rats were either extinguished or withdrawn without extinction training (abstinence) from cocaine self-administration, and measurements of postsynaptic density proteins in the core and shell subcompartments of the nucleus accumbens were compared with yoked-saline controls. Only extinguished rats had elevations of PSD-95, Homer1b/c, and Narp in the postsynaptic density of the core, whereas no proteins measured were altered in the postsynaptic density of the shell in either extinguished or abstinent rats. Using a biotinylation strategy, it was found that surface expression of mGluR5 was reduced only in the core of extinguished animals. Although both extinguished and abstinent animals showed a reduction in long-term potentiation elicited in the core by stimulating prefrontal cortex, blunted long-term depression was observed only in extinguished rats. These data indicate that the elevation in Homer1b/c in the core may have sequestered mGluR5 away from the membrane surface and that the loss of surface mGluR5 inhibits long-term depression. Accordingly, when Homer1c was overexpressed in the core of cocaine-naive rats with an adenoassociated virus, long-term depression was inhibited. This mechanism may contribute to the inhibition of cocaine seeking by extinction training because overexpression of Homer1c in the core also inhibited cue-induced reinstatement of cocaine seeking. These data identify a cellular mechanism that may contribute to extinction-induced inhibition of cocaine seeking.


Exploring the social and emotional representations used by students from the University of the Basque Country to face the first outbreak of COVID-19 pandemic.
In 2020, COVID-19, a new emerging infectious disease (EID), was spread throughout the world, including Europe. Spain, in particular, witnessed a significant outbreak of the pandemic. In consequence, all classes were cancelled and the Government declared a state of emergency, ordering the lockdown of the entire population from March to May. The aim of this research is to explore the impact of the COVID-19 outbreak on the representations of young university students from the University of the Basque Country and their emotional response when the crisis started. A free-association exercise was completed by 503 students from the University of the Basque Country (UPV/EHU) (Northern Spain). To analyze the content, the Reinert method was used with the Iramuteq software for lexical analysis. The results showed that students placed COVID-19 at a distance from the self, pointing out issues related to social response and disinformation, while showing concerns for self-related issues that are linked to negative emotions, academic consequences, and potentially close victims. The students' concerns were categorized at four main levels: the communicative-informative level, health-emotional level, community-social level, and academic level. All of this has created overwhelming feelings of nervousness, along with anger and emotional fatigue. These results indicate the necessity for universities to work from a holistic standpoint, not only in terms of responding to academic needs but also from psychological, communicative, social, health, and well-being perspectives.


Epimerization of green tea catechins during brewing does not affect the ability to poison human type II topoisomerases.
(-)-Epigallocatechin gallate (EGCG) is the most abundant and biologically active polyphenol in green tea (Camellia sinensis) leaves, and many of its cellular effects are consistent with its actions as a topoisomerase II poison. In contrast to genistein and several related bioflavonoids that act as interfacial poisons, EGCG was the first bioflavonoid shown to act as a covalent topoisomerase II poison. Although studies routinely examine the effects of dietary phytochemicals on enzyme and cellular systems, they often fail to consider that many compounds are altered during cooking or cellular metabolism. To this point, the majority of EGCG and related catechins in green tea leaves are epimerized during the brewing process. Epimerization inverts the stereochemistry of the bond that bridges the B- and C-rings and converts EGCG to (-)-gallocatechin gallate (GCG). Consequently, a significant proportion of EGCG that is ingested during the consumption of green tea is actually GCG. Therefore, the effects of GCG and related epimerized green tea catechins on human topoisomerase IIα and IIβ were characterized. GCG increased levels of DNA cleavage mediated by both enzyme isoforms with an activity that was similar to that of EGCG. GCG acted primarily by inhibiting the ability of topoisomerase IIα and IIβ to ligate cleaved DNA. Several lines of evidence indicate that GCG functions as a covalent topoisomerase II poison that adducts the enzyme. Finally, epimerization did not affect the reactivity of the chemical substituents (the three hydroxyl groups on the B-ring) that were required for enzyme poisoning. Thus, the activity of covalent topoisomerase II poisons appears to be less sensitive to stereochemical changes than interfacial poisons.


Examining supports and barriers to breastfeeding through a socio-ecological lens: a qualitative study.
Early breastfeeding cessation is a societal concern given its importance to the health of mother and child. More effective interventions are needed to increase breastfeeding duration. Prior to developing such interventions more research is needed to examine breastfeeding supports and barriers from the perspective of breastfeeding stakeholders. One such framework that can be utilized is the Socio-Ecological Model which stems from Urie Broffenbrenner's early theoretical frameworks (1973-1979). The purpose of this study was to examine supports and barriers to breastfeeding across environmental systems. A total of 49 representatives participated in a telephone interview in Nebraska, USA in 2019. Interviewees represented various levels of the model, based on their current breastfeeding experience (i.e., mother or significant other) or occupation. A direct content analysis was performed as well as a constant comparative analysis to determine differences between level representatives. At the Individual level, breastfeeding is a valued behavior, however, women are hindered by exhaustion, isolation, and the time commitment of breastfeeding. At the Interpersonal level, social media, peer-to-peer, and family were identified as supports for breastfeeding, however lack of familial support was also identified as a barrier. At the community level, participants were split between identifying cultural acceptance of breastfeeding as support or barrier. At the organizational level, hospitals had supportive breastfeeding friendly policies in place however lacked enough personnel with breastfeeding expertise. At the policy level, breastfeeding legislation is supportive, however, more specific breastfeeding legislation is needed to ensure workplace breastfeeding protections. Future efforts should target hospital-community partnerships, family-centered education, evidence-based social media strategies and improved breastfeeding legislation to ensure breastfeeding women receive effective support throughout their breastfeeding journey.


Co-existing feedback loops generate tissue-specific circadian rhythms.
Gene regulatory feedback loops generate autonomous circadian rhythms in mammalian tissues. The well-studied core clock network contains many negative and positive regulations. Multiple feedback loops have been discussed as primary rhythm generators but the design principles of the core clock and differences between tissues are still under debate. Here we use global optimization techniques to fit mathematical models to circadian gene expression profiles for different mammalian tissues. It turns out that for every investigated tissue multiple model parameter sets reproduce the experimental data. We extract for all model versions the most essential feedback loops and find auto-inhibitions of period and cryptochrome genes, Bmal1-Rev-erb-α loops, and repressilator motifs as possible rhythm generators. Interestingly, the essential feedback loops differ between tissues, pointing to specific design principles within the hierarchy of mammalian tissue clocks. Self-inhibitions of Per and Cry genes are characteristic for models of suprachiasmatic nucleus clocks, whereas in liver models many loops act in synergy and are connected by a repressilator motif. Tissue-specific use of a network of co-existing synergistic feedback loops could account for functional differences between organs.


High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells.
Epithelial-mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway.


Isotopic response after herpesvirus infection: an update.
The term postherpetic isotopic response describes the occurrence of a new, unrelated disease that appears at the same location as a previously healed herpetic infection. When dealing with the pathogenetic mechanism involved in the isotopic response, several possibilities should be considered: a viral origin, an immunologic origin, a vascular origin, and a neural origin. The aim of this article is to review and discuss the different pathogenetic mechanisms with particular attention to new information related to the possible neural origin of this abnormal response of the skin.


Patterns and Associations of Shoulder Motion, Strength, and Function in MARSOC Personnel Without History of Shoulder Injury.
Military personnel are at an increased risk of shoulder injuries due to training and deployment demands, however, there is a lack of information on the tactical athlete's upper extremity profile. Therefore, the purpose of this study was to examine shoulder musculoskeletal characteristics, including range of motion (ROM), strength, and function, and the relationships between these measures in Marine Corps Forces Special Operations Command (MARSOC) personnel without history of shoulder injury. Participants included 195 full-duty male MARSOC personnel (age: 25.38 ± 2.85 yr; height: 1.79 ± 0.06 m, mass: 82.79 ± 7.88 kg) without history of shoulder injury. Measurements of ROM, strength, and function were obtained bilaterally. Shoulder internal rotation (IR) and external rotation (ER) ROM were summed to calculate total arc of motion (ARC). Shoulder IR and ER strength were assessed using an isokinetic dynamometer. Function was evaluated with an explosive push-up. MARSOC personnel present with significantly increased ER ROM, and decreased IR ROM and ARC in their dominant shoulder. They demonstrated greater IR strength and peak force during the explosive push-up on the dominant side but no bilateral differences in average or peak rate were found. Correlation analyses suggest a weak inverse relationship between strength and ARC (r = -0.15 to -0.24). Positive relationships between strength and function were identified except for dominant IR strength and push-up variables. Those with the greatest ARC demonstrated significantly weaker IR and ER strength compared to those with less motion. MARSOC personnel demonstrate shoulder ROM and strength symmetry patterns similar to overhead athletes. Increased dominant shoulder strength does appear to translate to a bilateral functional performance, but overall performance may be limited by the weaker nondominant upper extremity. As ARC increases, IR and ER rotation strength decrease. Repetitive, increased loading of the dominant shoulder during functional movements and training may increase risk of chronic, overuse-type injuries, common to the military. Unilateral exercises and movement analysis should be incorporated to encourage proper development of bilateral shoulder strength, which may be particularly important in those with high ranges of ARC.


Mapping of the transcriptional initiation site of the herpes simplex virus type 1 ICP8 gene in infected and transfected cells.
The initiation site for transcription of the herpes simplex virus type 1 (HSV-1) gene encoding the major DNA-binding protein. ICP8, was mapped by nuclease S1 analysis of RNA-DNA hybrids. When RNA isolated from cells infected with HSV-1 was used, one major start site of ICP8 gene transcription was mapped at 89 base pairs to the right of the BstEII site at 0.409 map units. In cells transfected with a cloned ICP8 gene, the same major start site was detected either in the presence or absence of the immediate-early (alpha) genes encoding ICP4 or ICP0, which have been shown to stimulate ICP8 gene expression in transfected cells. Both ICP4 and ICP0 stimulated the accumulation of the ICP8 gene transcripts in the transient expression system, and their effects were synergistic. By comparison of the sequence of the putative promoter region of the ICP8 gene with the promoter of the HSV-1 TK gene, a significant similarity was detected between the three transcriptional regulatory signals of the TK gene and the upstream sequences of the ICP8 gene. Analysis of promoters of other delayed-early (beta) genes showed that they all contained regions of significant homology with the distal signals of the upstream sequences of the TK or ICP8 gene.


Increased sensitivity of monoamine release in the supraoptic nucleus in late pregnancy: region- and stimulus-dependent responses.
Oxytocin neurone activation at birth depends upon noradrenaline-mediated signals from the uterus via a brainstem pathway, as well as on factors within the supraoptic nucleus (SON), including oxytocin itself, and the system adapts during pregnancy to optimise the delivery process. We determined whether noradrenaline release in the SON in response to stimuli activating brainstem inputs or antidromically activating magnocellular neurones is enhanced at term pregnancy. Noradrenaline, serotonin and dopamine concentrations were measured in microdialysis samples collected from the dorsal and ventral SON before, during and after either i.v. cholecystokinin (CCK) or neural stalk stimulation in virgin and late pregnant rats. Each stimulus transiently increased noradrenaline and serotonin but not dopamine concentration in the dorsal SON, and responses were increased on days 21 and 22 of pregnancy compared to day 20 pregnant and virgin rats. Neural stalk stimulation induced sensitisation to subsequent stalk stimulation and so the responses in the dorsal SON were doubled; on day 22 of pregnancy, the area under the curve of monoamine concentration was 3.4-fold greater than in virgins, suggesting that adaptations perinatally enhance responsiveness. In conclusion, there are enhanced responses of noradrenaline and serotonin release in the SON that can generate very high, transient extracellular concentrations at term. This may be a consequence of neuroendocrine adaptations in late pregnancy and probably contributes to optimal oxytocin neurone activation during parturition.


Celiac Disease: Risk of Hepatitis B Infection.
The aim of our study was to assess the response to hepatitis B virus (HBV) vaccination and the risk of HBV infection in patients with celiac disease (CD). We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009-2014) to assess the rate of HBV vaccination, immune response, and HBV infection risk in patients with and without CD. We also determined the rate of HBV infection via retrospective analysis of two cohorts: patients seen at Mayo Clinic (1998-2021), and a stable longitudinally observed cohort, the Rochester Epidemiology Project (REP; 2010-2020). Based on the NHANES data, the rate of HBV infection in the United States was 0.33% (95% confidence interval 0.25-0.41). Of 93 patients with CD, 46 (49%) were vaccinated for HBV and of the remaining 19,422 without CD, 10,228 (53%) were vaccinated. Twenty-two (48%) vaccinated patients with CD had HBV immunity and 4405 (43.07%) vaccinated patients without CD had HBV immunity, which was not statistically different. In NHANES data, there were no cases of HBV infection in patients with CD. During the study period, 3568 patients with CD were seen at Mayo Clinic and 3918 patients with CD were identified using the REP database. Of those patients with CD, only four (0.11%) at Mayo Clinic and nine (0.23%) of the REP patients had HBV infection. The rate of HBV vaccination and immunity was similar in individuals with and without CD. Predictably, no increased risk of HBV infection was detected in CD patients. These results do not support screening and revaccination practice for HBV immunity in patients with CD within the United States.


MR imaging of parotid tumors: typical lesion characteristics in MR imaging improve discrimination between benign and malignant disease.
The surgical approach to parotid tumors is different for benign and malignant neoplasms, but the clinical symptoms do not correlate well with histology. Difficulties in tumor classification also arise in imaging modalities, in which sonography has the lowest and MR imaging, the highest accuracy. The purpose of this study was to review our experience using conventional MR imaging of the neck in the evaluation of parotid tumors and to evaluate which MR imaging findings are best able to predict malignant histology. Eighty-four consecutive patients (43 males, 41 females; median age, 56 years; range, 9-85 years) with parotid gland tumors who underwent MR imaging before surgery were prospectively included in the present study and retrospectively analyzed. Histology was available for all tumors. We analyzed the following MR imaging parameters: signal intensity, contrast enhancement, lesion margins (well-defined versus ill-defined), lesion location (deep/superficial lobe), growth pattern (focal, multifocal, or diffuse), and extension into neighboring structures, perineural spread, and lymphadenopathy. The 57 (68%) benign and 27 (32%) malignant tumors consisted of 29 pleomorphic adenomas, 17 Warthin tumors, 11 various benign tumors, 5 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas, 1 acinic cell carcinoma, 1 carcinoma ex pleomorphic adenoma, 9 metastases, and 8 various malignant neoplasms. Specific signs predictive of malignancy were the following: T2 hypointensity of the parotid tumor (P = .048), ill-defined margins (P = .001), diffuse growth (P = .012), infiltration of subcutaneous tissue (P = .0034), and lymphadenopathy (P = .012). Low signal intensity on T2-weighted images and postcontrast ill-defined margins of a parotid tumor are highly suggestive of malignancy.


Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia.
High hyperdiploid acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. The main driver event of this disease is a nonrandom aneuploidy consisting of gains of whole chromosomes but without overt evidence of chromosomal instability (CIN). Here, we investigated the frequency and severity of defective sister chromatid cohesion-a phenomenon related to CIN-in primary pediatric ALL. We found that a large proportion (86%) of hyperdiploid cases displayed aberrant cohesion, frequently severe, to compare with 49% of ETV6/RUNX1-positive ALL, which mostly displayed mild defects. In hyperdiploid ALL, cohesion defects were associated with increased chromosomal copy number heterogeneity, which could indicate increased CIN. Furthermore, cohesion defects correlated with RAD21 and NCAPG mRNA expression, suggesting a link to reduced cohesin and condensin levels in hyperdiploid ALL. Knockdown of RAD21 in an ALL cell line led to sister chromatid cohesion defects, aberrant mitoses, and increased heterogeneity in chromosomal copy numbers, similar to what was seen in primary hyperdiploid ALL. In summary, our study shows that aberrant sister chromatid cohesion is frequent but heterogeneous in pediatric high hyperdiploid ALL, ranging from mild to very severe defects, and possibly due to low cohesin or condensin levels. Cases with high levels of aberrant chromosome cohesion displayed increased chromosomal copy number heterogeneity, possibly indicative of increased CIN. These abnormalities may play a role in the clonal evolution of hyperdiploid pediatric ALL.


Teratogenic effects of amniotic sac puncture: a mouse model.
The possibility of an association between chorionic villus sampling (cvs) and limb abnormalities has prompted a review of the relevant experimental data. Although a vascular aetiology is favoured by many at present, the possibility exists that a proportion of cases may be caused by oligohydramnios secondary to inadvertent amniotic sac puncture. A mouse model of amniotic puncture syndrome has been developed to study the craniofacial and limb abnormalities produced by this procedure. Pregnant mice were anaesthetised and a laparotomy performed. One uterine horn was exteriorised, and the amniotic sacs punctured through the wall of the uterus with either a 21 gauge or a 25 gauge needle. The conceptuses in the contralateral uterine horn acted as controls. The mice were all killed on d 19 of pregnancy (day of finding a vaginal plug = d 1 of pregnancy) by cervical dislocation, and the morphological features of the embryos examined in detail. In a preliminary study, amniotic sac puncture was carried out on d 12, 13, 14, 15 or 16 of pregnancy, with either a 21 or a 25 gauge needle. Since the highest rates of palatal defects and limb deformities were observed following amniotic sac puncture using a 21 gauge needle, when this procedure was carried out on either d 13 or 14 of pregnancy, the main study was undertaken using a 21 gauge needle on these two days of pregnancy. Of 102 embryos in which amniotic sac puncture was carried out on d 13, 53% survived to d 19. Of the latter, 35% had a cleft palate, 61% had one or more morphologically abnormal limbs, and 43% had an abnormal tail. When amniotic sac puncture was carried out on d 14 of pregnancy, of 83 embryos subjected to this procedure, 81% survived to d 19. Of the latter, 27% had a cleft palate, 39% had one or more morphologically abnormal limbs, and 19% had an abnormal tail. In the controls, of 86 and 61 embryos isolated respectively from the d 13 and 14 mice, the survival rates were 97 and 90%, respectively. Palatal, limb and tail abnormalities were not observed in the control series. Tentative relationships are drawn between cvs and amniocentesis-associated abnormalities, the Robin sequence and their rodent phenocopies.


18FDG synthesis and supply: a journey from existing centralized to future decentralized models.
Positron emission tomography (PET) as the functional component of current hybrid imaging (like PET/ CT or PET/MRI) seems to dominate the horizon of medical imaging in coming decades. 18Flourodeoxyglucose (18FDG) is the most commonly used probe in oncology and also in cardiology and neurology around the globe. However, the major capital cost and exorbitant running expenditure of low to medium energy cyclotrons (about 20 MeV) and radiochemistry units are the seminal reasons of low number of cyclotrons but mushroom growth pattern of PET scanners. This fact and longer half-life of 18F (110 minutes) have paved the path of a centralized model in which 18FDG is produced by commercial PET radiopharmacies and the finished product (multi-dose vial with tungsten shielding) is dispensed to customers having only PET scanners. This indeed reduced the cost but has limitations of dependence upon timely arrival of daily shipments as delay caused by any reason results in cancellation or rescheduling of the PET procedures. In recent years, industry and academia have taken a step forward by producing low energy, table top cyclotrons with compact and automated radiochemistry units (Lab- on-Chip). This decentralized strategy enables the users to produce on-demand doses of PET probe themselves at reasonably low cost using an automated and user-friendly technology. This technological development would indeed provide a real impetus to the availability of complete set up of PET based molecular imaging at an affordable cost to the developing countries.


A prospective evaluation of the Button gastrostomy in children.
The Button gastrostomy has become popular for patients requiring long-term enteral feeding, because it is considered less irritating, more stable and more esthetically acceptable than the traditional tube gastrostomy. By a standardized questionnaire and personal interview, the authors evaluated prospectively the efficacy and complication rate in 19 children who had a Button gastrostomy inserted during a 6-month period. In 15 children the Button replaced a standard tube gastrostomy, and in 4 the Button was inserted surgically initially. Thirteen children had severe neurologic disabilities, and 6 required supplemental enteral feeding as part of the nutritional management of another chronic disease. In all 19 children, the Button was esthetically more acceptable and produced less skin irritation than the standard tube gastrostomy. All but one caregiver thought that the Button gastrostomy was preferable to a tube gastrostomy. This was especially apparent in the six neurologically normal children who were able to be more active and had an improved self-image. Cost analysis showed that, despite the higher initial cost of the Button, elimination of the need for frequent tube changes and hospital visits made it ultimately more cost effective than the standard tube gastrostomy. The authors conclude that the Button gastrostomy is a useful alternative to the standard tube gastrostomy in selected patients. Close long-term follow-up is extremely important to ensure a good result.


Egr1 signaling in prostate cancer.
Egr1 is a multifunctional transcription factor regulating a remarkable spectrum of cellular responses from survival to apoptosis, growth to growth arrest, differentiation to transformation, senescence as well as memory and learning effects. In prostate cancer, Egr1 levels are constitutively high and closely linked to cancer development and progression. This zinc-finger protein is a short-lived, immediate early growth response gene known to be induced by a large number of extracellular stimuli such as irradiation (all wavelengths tested), hypoxia, hyperoxia, chemotherapy agents, and more. Therefore the target genes that Egr1 regulates in prostate cancer cells play an important role in generating many of the cellular responses that characterize these cells. After Egr1 binds to its binding sites on gene promoters, specificity of response is determined by whether Egr1 transcriptionally up- or downregulates the target genes. Expression microarray analyses combined with binding data promise new ways to identify stage specific cancer markers, to aid in patient risk assessment and in therapeutic choices.


Nuclear Genetic Analysis of the Red Fox Across its Trans-Pacific Range.
The red fox (Vulpes vulpes) occurs on multiple continents in diverse habitats, making it an informative system for evolutionary genomic research. However, its phylogeography remains unclear. Previously, mitochondrial DNA and small numbers of nuclear loci provided discordant views. Both markers indicated deep divergence (~ 0.5 million years [MY]) between Eurasian and southern North American populations but differed in the apparent continental affinity of Alaskan red foxes, implying some degree of gene exchange during secondary contact (~0.1 MY). We assayed >173000 nuclear genomic sites in 52 red foxes, along with 2 Rueppell's foxes (Vulpes rueppellii) and a gray wolf (Canis lupus) using the Illumina CanineHD BeadChip. We obtained 5107 single nucleotide polymorphisms (SNPs) in the foxes. Consistent with the Afro-Eurasian origins of red foxes, genetic diversity was higher in Eurasian than North American samples. Phylogenetic trees indicated that Alaskan and southern North American red foxes formed a monophyletic group nested within the Eurasian clade. However, admixture models suggested Alaskan red foxes contained up to 40% Eurasian ancestry. We hypothesize that North American red foxes either hybridized with Eurasian foxes in Beringia at the start of the last glaciation or merged with a Beringian population after the last glaciation. Future work is needed to test between these scenarios and assess speciation.


High-throughput sequencing of the T-cell receptor repertoire: pitfalls and opportunities.
T-cell specificity is determined by the T-cell receptor, a heterodimeric protein coded for by an extremely diverse set of genes produced by imprecise somatic gene recombination. Massively parallel high-throughput sequencing allows millions of different T-cell receptor genes to be characterized from a single sample of blood or tissue. However, the extraordinary heterogeneity of the immune repertoire poses significant challenges for subsequent analysis of the data. We outline the major steps in processing of repertoire data, considering low-level processing of raw sequence files and high-level algorithms, which seek to extract biological or pathological information. The latest generation of bioinformatics tools allows millions of DNA sequences to be accurately and rapidly assigned to their respective variable V and J gene segments, and to reconstruct an almost error-free representation of the non-templated additions and deletions that occur. High-level processing can measure the diversity of the repertoire in different samples, quantify V and J usage and identify private and public T-cell receptors. Finally, we discuss the major challenge of linking T-cell receptor sequence to function, and specifically to antigen recognition. Sophisticated machine learning algorithms are being developed that can combine the paradoxical degeneracy and cross-reactivity of individual T-cell receptors with the specificity of the overall T-cell immune response. Computational analysis will provide the key to unlock the potential of the T-cell receptor repertoire to give insight into the fundamental biology of the adaptive immune system and to provide powerful biomarkers of disease.


Dark-field oxidative addition-based chemosensing: new bis-cyclometalated PtII complexes and phosphorescent detection of cyanogen halides.
Heavy metal complexes that are phosphorescent at room temperature are becoming increasingly important in materials chemistry, principally due to their use in phosphorescent organic light-emitting devices (OLEDs). Their use in optical sensory schemes, however, has not been heavily explored. Homoleptic bis-cyclometalated Pt(II) complexes are known to undergo oxidative addition with appropriate electrophiles (principally alkyl halides) by either thermal or photochemical activation. We have applied this general reaction scheme to the development of a phosphorescence-based sensing system for cyanogen halides. To carry out structure-property relationship studies, a series of previously unreported Pt(II) complexes was prepared. Most of the complexes (excluding those that incorporated substituents on the ligands that forced steric crowding in the square plane) were strongly orange-red phosphorescent (Phi = 0.2-0.3) in a room-temperature oxygen-free solution. These sterically demanding ligands also accelerated the addition of cyanogen bromide to these complexes but slowed the addition of methyl iodide, indicating that the oxidative addition mechanisms for these two electrophiles is different. The lack of solvent-polarity effect on the addition of BrCN suggests a radical mechanism. Oxidative addition of BrCN to the metal complexes in solution or dispersed in poly(methyl methacrylate) gave blue-shifted emissive Pt(IV) complexes. The blue-shifted products give a dark-field sensing scheme that is in sharp contrast to energy transfer-based sensing schemes, which have limited signal-to-noise because of the presence of lower-energy vibronic bands of the energy donor that can overlap with the emission of the acceptor.


Tics and Tourette syndrome in autism spectrum disorders.
Autism spectrum disorders (ASDs) are more frequently associated with tic disorders than expected by chance. Variable rates of comorbidity have been reported and common genetic and neurobiological factors are probably involved. The aim of this study was to determine the rate of tic disorders in a clinical sample (n = 105) of children and adolescents with ASDs and to describe the clinical characteristics of a group with comorbid ASDs and tics (n = 24). The overlap between tics and other repetitive movements and behaviors in ASDs was carefully assessed. Among individuals with ASDs, 22 percent presented tic disorders: 11 percent with Tourette disorder (TD), and 11 percent with chronic motor tics. All had various degrees of cognitive impairment. An association between the level of mental retardation and tic severity was found. It is concluded that the occurrence of tics in ASDs should not be overlooked and should be carefully evaluated.


In vivo macromolecule signals in rat brain 1 H-MR spectra at 9.4T: Parametrization, spline baseline estimation, and T2 relaxation times.
Reliable detection and fitting of macromolecules (MM) are crucial for accurate quantification of brain short-echo time (TE) 1 H-MR spectra. An experimentally acquired single MM spectrum is commonly used. Higher spectral resolution at ultra-high field (UHF) led to increased interest in using a parametrized MM spectrum together with flexible spline baselines to address unpredicted spectroscopic components. Herein, we aimed to: (1) implement an advanced methodological approach for post-processing, fitting, and parametrization of 9.4T rat brain MM spectra; (2) assess the concomitant impact of the LCModel baseline and MM model (ie, single vs parametrized); and (3) estimate the apparent T2 relaxation times for seven MM components. A single inversion recovery sequence combined with advanced AMARES prior knowledge was used to eliminate the metabolite residuals, fit, and parametrize 10 MM components directly from 9.4T rat brain in vivo 1 H-MR spectra at different TEs. Monte Carlo simulations were also used to assess the concomitant influence of parametrized MM and DKNTMN parameter in LCModel. A very stiff baseline (DKNTMN ≥ 1 ppm) in combination with a single MM spectrum led to deviations in metabolite concentrations. For some metabolites the parametrized MM showed deviations from the ground truth for all DKNTMN values. Adding prior knowledge on parametrized MM improved MM and metabolite quantification. The apparent T2 ranged between 12 and 24 ms for seven MM peaks. Moderate flexibility in the spline baseline was required for reliable quantification of real/experimental spectra based on in vivo and Monte Carlo data. Prior knowledge on parametrized MM improved MM and metabolite quantification.


Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen.
Recent concern about the safety of combined oral contraceptives (OCs) with third-generation progestagens prompted an examination of data from a population-based case-control study (Leiden Thrombophilia Study). We compared the risk of deep-vein thrombosis (DVT) during use of the newest OCs, containing a third-generation progestagen, with the risk of "older" products. We also investigated the influence of family history of thrombosis, previous pregnancy, age, and the thrombogenic factor V Leiden mutation. We selected 126 women with DVT and 159 controls aged 15-49 (mean age 34.9) and premenopausal and found, as compared with non-users, the highest age-adjusted relative risks to be that for an OC containing desogestrel and 30 micrograms ethinyloestradiol (relative risk [RR] 8.7, 95% CI 3.9-19.3). We found lower relative risks for all other types of OC, ranging from 2.2 to 3.8. In a direct comparison, users of the desogestrel-containing oral contraceptive had a 2.5-fold higher risk (95% CI 1.2-5.2) than users of all other OC types combined. The relative risk for the desogestrel-containing OC was similar among women with and without a family history--ie, preferential prescription because of family history cannot explain our findings. Nor could the excess risk be explained by previous pregnancy, and it was highest in the youngest age categories, where we would expect most new users. The age-adjusted RR for the desogestrel-containing contraceptive was 9.2 (3.9-21.4) among non-carriers of the factor V Leiden mutation and 6.0 (1.9-19.0) among carriers of the mutation. This latter risk is superimposed on the 8-fold increased risk of venous thrombosis for carriers of the factor V Leiden mutation. The risk of carriers using the desogestrel-containing OC as compared with noncarrier non-users will therefore be increased almost 50-fold. Use of low-dose OCs with a third-generation progestagen carries a higher risk of DVT than the previous generation of OCs. The absolute risk of DVT associated with these OCs seems to be especially high among carriers of the factor V Leiden mutation and among women with a family history of thrombosis. However, the higher risk associated with OC with a third-generation progestagen compared with previous generations was also present in women without factor V Leiden and with no family history.


Effects of reverberation on speech recognition in stationary and modulated noise by school-aged children and young adults.
The purpose of this study was to determine how combinations of reverberation and noise, typical of environments in many elementary school classrooms, affect normal-hearing school-aged children's speech recognition in stationary and amplitude-modulated noise, and to compare their performance with that of normal-hearing young adults. In addition, the magnitude of release from masking in the modulated noise relative to that in stationary noise was compared across age groups in nonreverberant and reverberant listening conditions. Last, for all noise and reverberation combinations the degree of change in predicted performance at 70% correct was obtained for all age groups using a best-fit cubic polynomial. Bamford-Kowal-Bench sentences and noise were convolved with binaural room impulse responses representing nonreverberant and reverberant environments to create test materials representative of both audiology clinics and school classroom environments. Speech recognition of 48 school-aged children and 12 adults was measured in speech-shaped and amplitude-modulated speech-shaped noise, in the following three virtual listening environments: nonreverberant, reverberant at 2 m, and reverberant at 6 m. Speech recognition decreased in the reverberant conditions and with decreasing age. Release from masking in modulated noise relative to stationary noise decreased with age and was reduced by reverberation. In the nonreverberant condition, participants showed similar amounts of masking release across ages. The slopes of performance-intensity functions increased with age, with the exception of the nonreverberant modulated masker condition. The slopes were steeper in the stationary masker conditions, where they also decreased with reverberation and distance. In the presence of a modulated masker, the slopes did not differ between the two reverberant conditions. The results of this study reveal systematic developmental changes in speech recognition in noisy and reverberant environments for elementary-school-aged children. The overall pattern suggests that younger children require better acoustic conditions to achieve sentence recognition equivalent to their older peers and adults. In addition, this is the first study to report a reduction of masking release in children as a result of reverberation. Results support the importance of minimizing noise and reverberation in classrooms, and highlight the need to incorporate noise and reverberation into audiological speech-recognition testing to improve predictions of performance in the real world.


Comparison between western blotting, immunohistochemical and ELISA assay for p185neu quantitation in breast cancer specimens.
The protein encoded by erbB2 oncogene was evaluated by three different methodological approaches (Western blotting, ELISA and immunohistochemistry) in 147 breast cancer specimens. A highly significant correlation was found between Western blotting and ELISA results (p < 0.001). The data from ELISA and Western blotting were categorized as negatives (-), low-overexpressing (+) and high-overexpressing (++). Immunohistochemical results were classified as (-) or (+) according to the absence or the presence of specific staining. Overall positive cases (+ and ++) were 42.2% by Western blotting and 51% by ELISA, while (++) cases were 23.8% and 25.2% respectively. Histochemical staining was found in 29.8% of cases. The two by two evaluation of the assays showed a close association (chi2, p < 0.0001). In particular, the comparison between both ELISA and Western blotting with immunohistochemistry showed concordance rates of 78.9% for ELISA and 83.1% for Western blotting considering the + and ++ cases as a single group. When only the ++ cases were considered as positive, the overall agreement rises to 93.3% and 89.1% respectively. From these preliminary data we conclude that p185 values obtained with the three evaluated methods are possibly superimposable. Nevertheless, the biochemical methods seem to identify an intermediate p185 expression group, whose clinical meaning should be investigated.


[Detection of polyamines by a new enzymatic differential assay. (4). Fundamental study on a new enzymatic differential assay of blood].
The enzymatic method for isolation and determination of urinary polyamines was modified to measure the polyamines in the blood. High recovery rates of polyamine in blood by enzymatic hydrolyzation were obtained, namely, 101.9 +/- 4.4% for diamine, 96.0 +/- 5.4% for spermidine and 104.1 +/- 3.3% for spermine. Furthermore excellent linearity was demonstrated. Within-run precision of polyamine in blood was excellent, namely, in C.V., 1.15% for Reaction 1, 2.11% for Reaction 2 and 2.79% for Reaction 3. This method was compared with high pressure liquid chromatography (HPLC), and a close correlation was demonstrated for all the fractions: diamine r = 0.8824, y = 1.367x+0.0417 (n = 15); spermidine r = 0.9878, y = 0.806x+5.218 (n = 15); spermine r = 0.9764, y = 1.068x-0.9195 (n = 15).


Modeling Modulation of the Tick Regulome in Response to Anaplasma phagocytophilum for the Identification of New Control Targets.
Ticks act as vectors of pathogens affecting human and animal health worldwide, and recent research has focused on the characterization of tick-pathogen interactions using omics technologies to identify new targets for developing novel control interventions. The regulome (transcription factors-target genes interactions) plays a critical role in cell response to pathogen infection. Therefore, the application of regulomics to tick-pathogen interactions would advance our understanding of these molecular interactions and contribute to the identification of novel control targets for the prevention and control of tick infestations and tick-borne diseases. However, limited information is available on the role of tick regulome in response to pathogen infection. In this study, we applied complementary in silico approaches to modeling how Anaplasma phagocytophilum infection modulates tick vector regulome. This proof-of-concept research provided support for the use of network analysis in the study of regulome response to infection, resulting in new information on tick-pathogen interactions and potential targets for developing interventions for the control of tick infestations and pathogen transmission. Deciphering the precise nature of circuits that shape the tick regulome in response to pathogen infection is an area of research that in the future will advance our knowledge of tick-pathogen interactions, and the identification of new antigens for the control of tick infestations and pathogen infection/transmission.


[Electrostimulation of the skeletal muscles in sanatorium rehabilitation of patients with myocardial infarction].
Passive physical training with ESMA device was used in rehabilitation of 81 men with complicated myocardial infarction treated in sanatorium Taraskul. The training had no negative clinical and hemodynamic reactions, increased exercise tolerance, reduced volume of heart chambers, aggravated neither arrhythmia nor autonomic imbalance. This method of physical training is recommended if standard rehabilitative programs are impossible.


The gynecologic contribution to intestinal obstruction in females.
This study was done to identify the cause of intestinal obstruction with particular emphasis on the gynecologic and perioperative related causes. All medical records from females with the discharge diagnosis "intestinal obstruction" from 1988 to 1991 at Columbia Presbyterian Medical Center were requested. The patient series consisted of the first 100 completed charts received. Forty-eight percent of those patients with intestinal obstruction had experienced a previous gynecologic or obstetric event that could account for the obstruction. Primarily, the gynecologist managed more than 20 percent of all female patients with intestinal obstruction. The most common causative factors contributing to intestinal obstruction were postoperative adhesions (59 percent) and tumor (17 percent). Fifty-six percent of the patients with intestinal obstruction associated with postoperative adhesions had a history of previous gynecologic and obstetric operation. Hysterectomy was the most common previously performed operation. In this series, cesarean section was less likely and myomectomy was more likely to cause subsequent intestinal obstruction than expected. Of 59 female patients with postoperative adhesions associated with intestinal obstruction, 31 had the original operative reports available for analysis. Eleven of these patients were taken to the operating room for management of the obstruction. In the nine patients who had surgical peritoneal closure in the original operation, the adhesions causing the obstruction were always to the site of reperitonealization. In the two patients in whom the peritoneum was left open, the adhesions causing obstruction were remote from the site of spontaneous reperitonealization. In an unselected patient series of intestinal obstruction, a history of previous gynecologic pathology is a significant factor contributing to the total number of instances of intestinal obstruction in females. Also, surgical peritoneal closure may result in an increase in the incidence of intestinal obstruction.


3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: one disease - many faces.
3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL. We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided. More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development. This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.


Cervical spondylosis: three-dimensional gradient-echo MR with magnetization transfer.
To compare a three-dimensional Fourier transform (3DFT) gradient-echo pulse sequence with magnetization transfer at a short echo time against standard 3DFT gradient-echo technique in the evaluation of cervical spondylosis, specifically addressing the effects of motion and susceptibility artifacts on the dimensions of the neural foramina and contrast at the cerebrospinal fluid (CSF)-spinal cord interface. Ten patients with clinically suspected cervical spondylosis were examined with axial MR imaging using both our standard 3DFT gradient-echo sequence and a 3DFT gradient-echo sequence with a short echo time plus magnetization transfer. Two neuroradiologists measured the transverse dimensions of 22 diseased neural foramina and graded the contrast at the CSF-spinal cord interface. Sixteen of 22 affected neural foramina were larger in the transverse dimension when the magnetization transfer technique was used than when the standard 3DFT gradient-echo sequence was used. In 9 of 10 patients superior contrast was seen at the CSF-spinal cord interface on images obtained with the magnetization transfer technique. In the cervical spine, 3DFT gradient-echo imaging with magnetization transfer improves contrast and sharpness of the CSF-spinal cord interface at short echo times. This results in less exaggeration of the neural foraminal stenosis as compared with that seen with standard 3DFT gradient-echo techniques owing to the diminished effects of motion and susceptibility artifacts.


Does Elevated Alcohol Consumption Delay the Diagnostic Assessment of Cognitive Impairment among Older Adults?
The time from symptom debut to assessment of cognitive impairment (TSA) is usually substantial, and many factors can influence the length of this interval. Our objective was to discern whether elevated alcohol consumption is associated with TSA. Alcohol consumption was measured among 3,236 older Norwegians assessed for cognitive impairment. Elevated consumption was defined as drinking 4-7 times a week. TSA was defined as the number of months between symptom debut and assessment. The association between alcohol consumption and TSA was examined with a multiple regression analysis controlled for sociodemographic and clinical covariates. Mean (SD) and median TSA were 34.8 (35.8) and 24.0 months, respectively. Elevated alcohol consumption was not associated with TSA. Longer TSA was associated with being male, having a high education level, being retired or unemployed, being single, having low scores on the Mini-Mental State Examination (MMSE) or Personal Activities of Daily Living (PADL), having high subsyndrome scores of depression or agitation on The Neuropsychiatric Inventory - Questionnaire (NPI-Q), or having a spouse/cohabitant as the designated next of kin. This study indicates that elevated alcohol consumption does not influence TSA. Possible explanations are discussed, but further research is needed to determine the effect of alcohol definitively. We did identify other novel characteristics associated with TSA which may be important in minimizing the risk of delayed cognitive assessments and should be kept in mind when considering assessment.


CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.
CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine. Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting.


[Roentgenoradionuclide study of the lymphatic system of the liver (development of the method and criteria for the evaluation of extravascular plasma flow)].
An attempt was made to develop an instrumental method for the evaluation of the extravascular plasma flow (lymph flow) of the liver. Ultrasonography of the liver does not give an opportunity to differentiate between different states including those accompanied by the excess lymph discharge into the liver. The results of intraparenchymal lymphography of the liver were analysed in patients with and without biliary and portal hypertension. The authors have singled out 11 criteria that make it possible to judge an elevated production of the lymph in the liver. This procedure possesses some instability of results due to the equipment, the doctor's experience and the number of attempts. A method of " radioangiolymphography " of the liver based on the administration of diffusing and nondiffusing radionuclides in the afferent vessels of the liver was worked out. Variation in the parameters of the radionuclide circulation seems to reflect significantly extrahepatic circulation in the liver and holds great promise for the use in hepatology.


Transition readiness among finnish adolescents with juvenile idiopathic arthritis.
With chronic diseases, the responsibility for care transfers to adult clinics at some point. Juvenile idiopathic arthritis (JIA) is the most common persistent rheumatic condition in children. A successful transition requires sufficient self-management skills to manage one´s chronic condition and all the tasks involved. In this study, we evaluated transition readiness in Finnish patients with JIA. We aimed to find practical tools to support a successful transition and to study the possible consequences of an unsuccessful transition. The usefulness of a specific questionnaire, which was administered to 83 JIA patients, was evaluated in this study. We also gathered information from their first adult clinic visit to assess the success of their transition and its relation to disease activity. In 55 (71%) patients, the transition was estimated to be successful. We were able to determine a cut-off score in the questionnaire for a successful transition: the best estimate for a successful transition is when the score is 24 or more. At the first adult clinic visit, an unsuccessful transition was evident in its effect on disease outcome. If the transition was defined as successful, the DAS28 was better. We found the questionnaire to be a useful tool for evaluating transition readiness. Determination of a successful transition helped us identify those adolescents who needed more profound support to improve their self-management skills and thus enhance their transition process. An unsuccessful transition was shown to negatively impact on disease outcomes.


[Diagnosis and management of central nervous system infections in pediatric cancer patients].
Infections of the central nervous system (CNS) are a common cause of neurological abnormalities in pediatric oncology patients apart from cancer disease of the CNS. Often symptoms do not present unequivocally, impeding a clear distinction from other differential diagnosis. Repeated neurological examinations of the patient allow selecting the necessary laboratory tests and imaging techniques. As delayed antiinfectious treatment is associated with high mortality and severe sequelae of survivors, patients do need empirical therapy using adequate doses until diagnostic results allow a more specific treatment. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of infections of the CNS in immunocompromised patients.