[Effects of a non-face-to-face behavioral intervention on poor sleepers and factors affecting improvement of sleep].
The purposes of this study were 1) to re-examine effects obtained from previous research of a non-face-to-face behavioral intervention in poorer sleepers and 2) to examine the factors impacting on improvement of sleep. The subjects were 178 poor sleepers who participated in an intervention for sleep improvement. The educational procedures comprised a minimal behavioral self-help package for one month that featured self- learning and self- monitoring of practical target habits for change. It was non face-to-face program conducted by only one member of staff. Subjects were asked to answer a questionnaire before and after the intervention. To reexamine the effects of this program found in our previous research, 9 sleep indices, sleep quality, and sleep-related behaviors were compared between before and after intervention. The sleep indices were total sleep time, sleep onset latency, sleep efficiency etc. Subjects were divided into an improvement group (n = 63) and a non-improvement group (n = 115) using a cutoff value for average change in sleep onset latency and sleep efficiency. After comparison of sleep and behavior between the two groups, logistic regression analysis was conducted to select parameters affecting improvement with this program. Total sleep time was significantly increased from 5.7 h to 6.1 h, sleep onset time decreased 18 minutes, and sleep efficiency improved 5.6 points. With 8 of 9 sleep-related behaviors, the proportion of subjects having an undesirable habit significantly decreased. The mean total number of desirable habit' changes was 2.63 in the improvement group and significantly higher than the 2.06 in the non-improvement group. Logistic regression analysis demonstrated that large sleep onset latency at baseline and beginning of regular exercise significantly affected the improvement of sleep in the subjects, after adjusting for all other parameters. The effects revealed by our previous research were reconfirmed. It is suggested that this program is more useful for persons having severe sleep onset difficulties, and regular exercise is particularly important in improvement of sleep. It is possible that even simple behavioral intervention is feasible with many subjects to improve sleep and related habits in poor sleepers.


A Novel Effector Protein of Apple Proliferation Phytoplasma Disrupts Cell Integrity of Nicotiana spp. Protoplasts.
Effector proteins play an important role in the virulence of plant pathogens such as phytoplasma, which are the causative agents of hundreds of different plant diseases. The plant hosts comprise economically relevant crops such as apples (Malus × domestica), which can be infected by 'Candidatus Phytoplasma mali' (P. mali), a highly genetically dynamic plant pathogen. As the result of the genetic and functional analyses in this study, a new putative P. mali effector protein was revealed. The so-called "Protein in Malus Expressed 2" (PME2), which is expressed in apples during P. mali infection but not in the insect vector, shows regional genetic differences. In a heterologous expression assay using Nicotiana benthamiana and Nicotiana occidentalis mesophyll protoplasts, translocation of both PME2 variants in the cell nucleus was observed. Overexpression of the effector protein affected cell integrity in Nicotiana spp. protoplasts, indicating a potential role of this protein in pathogenic virulence. Interestingly, the two genetic variants of PME2 differ regarding their potential to manipulate cell integrity. However, the exact function of PME2 during disease manifestation and symptom development remains to be further elucidated. Aside from the first description of the function of a novel effector of P. mali, the results of this study underline the necessity for a more comprehensive description and understanding of the genetic diversity of P. mali as an indispensable basis for a functional understanding of apple proliferation disease.


Owning the past, claiming the present: perspectives on the treatment of dissociative patients.
From the early 1990s there has been a growing awareness in Australia of dissociative processes and dissociative disorders. The objective in this paper is to provide a selective overview of the context and process of treatment based on the substantive dissociative disorders literature, ongoing clinical experience and research, and over 8 years as director of a trauma and dissociation unit at Belmont Hospital, Brisbane. The construct of individual selfhood is of direct relevance in illustrating the psychological damage sustained by patients who have relied on dissociative defences to survive, and in highlighting issues and areas that are a particular focus of informed treatment.


Nonpulmonary outcomes of asbestos exposure.
The adverse pulmonary effects of asbestos are well accepted in scientific circles. However, the extrapulmonary consequences of asbestos exposure are not as clearly defined. In this review the potential for asbestos to produce diseases of the peritoneum, immune, gastrointestinal (GIT), and reproductive systems are explored as evidenced in published, peer-reviewed literature. Several hundred epidemiological, in vivo, and in vitro publications analyzing the extrapulmonary effects of asbestos were used as sources to arrive at the conclusions and to establish areas needing further study. In order to be considered, each study had to monitor extrapulmonary outcomes following exposure to asbestos. The literature supports a strong association between asbestos exposure and peritoneal neoplasms. Correlations between asbestos exposure and immune-related disease are less conclusive; nevertheless, it was concluded from the combined autoimmune studies that there is a possibility for a higher-than-expected risk of systemic autoimmune disease among asbestos-exposed populations. In general, the GIT effects of asbestos exposure appear to be minimal, with the most likely outcome being development of stomach cancer. However, IARC recently concluded the evidence to support asbestos-induced stomach cancer to be "limited." The strongest evidence for reproductive disease due to asbestos is in regard to ovarian cancer. Unfortunately, effects on fertility and the developing fetus are under-studied. The possibility of other asbestos-induced health effects does exist. These include brain-related tumors, blood disorders due to the mutagenic and hemolytic properties of asbestos, and peritoneal fibrosis. It is clear from the literature that the adverse properties of asbestos are not confined to the pulmonary system.


Groshong catheter-related complications in children with cancer.
Children with cancer undergo intensive treatments requiring reliable vascular access. Central venous catheters (CVCs) reduce discomfort due to venipuncture and the risks of extravasations from chemotherapy administration. The aim of our retrospective study was to assess safety and complications of Groshong devices in children with cancer. One hundred ninety Groshong CVCs were placed in 166 children over a 5-year period. Early complications, and infectious and mechanical events were collected. The mean period of permanence of the CVCs was 330 days per patient (range 7-1,037). Of the febrile episodes, 36 (34.6%) were CVC-related, with an incidence rate of 0.56 per 1,000 CVC days. Severe neutropenia conditions most of all complicated CVC-related infectious events (94.4%) and Gram-negative bacteria were those most often isolated (55%). Twenty CVCs were affected by mechanical or thrombotic complications, with an incidence of 0.33 episodes per 1,000 CVC days. Mechanical complications led to CVC removal in 6 (3.1%) cases, while CVC-related infective episodes were responsible for 10 (5.2%) CVC removals. The long in situ duration of this device allowed it to be safely employed from the beginning to the end of the treatment period in most children.


A comprehensive genetic map of the mouse genome.
The availability of dense genetic linkage maps of mammalian genomes makes feasible a wide range of studies, including positional cloning of monogenic traits, genetic dissection of polygenic traits, construction of genome-wide physical maps, rapid marker-assisted construction of congenic strains, and evolutionary comparisons. We have been engaged for the past five years in a concerted effort to produce a dense genetic map of the laboratory mouse. Here we present the final report of this project. The map contains 7,377 genetic markers, consisting of 6,580 highly informative simple sequence length polymorphisms integrated with 797 restriction fragment length polymorphisms in mouse genes. The average spacing between markers is about 0.2 centimorgans or 400 kilobases.


Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction.
Conduction through separated myocyte bundles causes multipotential electrograms and reentrant ventricular tachycardia. We hypothesized that without initiating tachycardia, the reentry region could be detected by analysing the change in multipotential electrograms during two different activation sequences. During catheter mapping and ablation in 16 patients with ventricular tachycardia late after infarction ventricular electrograms were recorded from 1072 sites during atrial and right ventricular paced ventricular activation. Multipotential electrograms were present during both activation sequences at 285 (27%) sites, during atrial pacing only at 159 (15%) sites and during right ventricular pacing only at 152 (14%) sites. Sites with multipotential electrograms during both activation sequences were more often related to a ventricular tachycardia circuit isthmus (43%) as compared to sites where such electrograms were present during one activation sequence (20%). Multipotential electrograms with >2 low amplitude deflections and a >100 ms difference in duration between the two activation sequences were infrequent but highly predictive of the reentry circuit. Regions with fixed multipotentials consistent with conduction block might be useful guides for ablation approaches that target large regions of the infarct, but are not sufficiently specific to be the sole guide for focal ablation approaches.


Trapping liquids may bias the results of beetle diversity assessment.
Several different techniques and methods are used to capture and study beetles (Coleoptera). One option is the use of window traps with various trapping liquids. However, these liquids used in comparative studies may have a biasing effect on the results. The effectiveness of the frequently used liquid baits, involving beer, wine, vinegar, and water as the reference liquid, was compared in this study. Twenty-four traps were assigned to two habitat categories (sunny and shady) and four kinds of bait: beer, wine, vinegar, and water. During the study from June to July 2021, a total of 29,944 invertebrates were captured; of these, 3,931 individuals belonged to Coleoptera. A total of 3,825 beetles were identified, belonging to 120 species and 36 families. The most abundant family was Nitidulidae, with 3,297 adults (86% of the total). The number of arthropods differed only in the trapping liquid, and the captures were similar between beer and wine and between vinegar and water. The trapping liquid had a more significant effect on beetle abundance and species richness. In contrast, exposure had a significant effect only on the number of beetle species and a higher ratio of beetles was found in the shade. Beer and wine were very attractive and collected similar beetle communities. However, the diversity (Shannon's index) was low due to the high abundance of several species. Traps with vinegar and water collected a similar composition and species richness. After removing sap beetles (Nitidulidae) from all traps, a significant difference was still recorded between trapping liquids in the number of individuals and species, and their communities were much more similar. Thus, at high abundances of sap beetles, it is possible to exclude them from analyses and obtain more accurate data when assessing environmental variables. The results showed that the type of trapping liquids used can have substantial effects on abundance and species composition captured beetles in traps especially for beer and wine. The beer and wine in traps can significantly influence the subsequent biodiversity assessment. We recommend the use of trapping liquids without the baiting effect to correctly assess the effect of environmental variables on beetle richness and abundance.


Surgical approaches for double-outlet right ventricle or transposition of the great arteries associated with straddling atrioventricular valves.
The surgical management of patients with double-outlet right ventricle or transposition of the great arteries and straddling atrioventricular valves remains a subject of controversy. Biventricular repair has theoretic advantages because it establishes normal anatomy and physiology. In some instances, however, it seems to carry too high operative risk, and a univentricular heart repair is preferred. Since 1984, we have operated on 34 patients with double-outlet right ventricle (n = 15) or transposition of the great arteries (n = 19) with isolated straddling tricuspid valve (n = 17), isolated straddling mitral valve (n = 9), both mitral and tricuspid straddling (n = 2), or abnormal insertion of tricuspid (n = 7) or mitral (n = 2) chordae in the left ventricular outlet, precluding an adequate tunnel construction. Straddling was categorized according to the location of the papillary muscle insertion in the opposite ventricular chamber: type A, on the edge of the ventricular septal defect (n = 14); type B, on the opposite side of the ventricular septum away from the edge of the defect (n = 8); type C, on the free wall of the opposite ventricular chamber (n = 8). Abnormal chordal insertions were classified according to the location of their attachments around the edges of the defect. Three types of chordal distribution were identified: on the aortic conus, on the pulmonary conus crossing the ventricular septal defect, or around the defect closing it like a curtain. All but three patients had two ventricles of adequate size. Sixteen patients underwent palliation. Median age at the definitive operation was 6.5 months (range 1 to 130 months). Thirty patients underwent a biventricular repair and four had a univentricular repair. Biventricular repair was achieved by an arterial switch operation in 18 patients and by tunnel construction from the left ventricle to the aorta in 12. In isolated straddling of types A and B, the ventricular septal defect was closed by adjusting the septal patch on the ventricular side above the straddled papillary muscle. In type C, the patch was sewn over the papillary muscle by applying it on the septum. In double straddling, the ventricular septum was incised between the two papillary muscles, and an ellipsoid patch was used to reconstruct the septal defect, directing each subvalvular apparatus into its own ventricular chamber. When the abnormal chordae in the left outflow tract inserted on the aortic or pulmonary conus, the conus was incised and tailored to make a flap, leaving an unobstructed left ventricular outflow tract. In two patients the subvalvular apparatus was resected and reattached to the patch. Curtainlike chordae were a contraindication to biventricular repair in double-outlet right ventricle but not in transposition. There were four early deaths and one late death, all occurring in the group having biventricular repair. Death was due to myocardial ischemia (n = 1), right ventricular hypoplasia (n = 1), pulmonary hypertension (n = 1), and residual subaortic stenosis (n = 1). Two patients had moderate to severe postoperative atrioventricular valve incompetence, caused by a cleft in the mitral valve in one patient. Three patients were reoperated on for subaortic stenosis (n = 1), pulmonary stenosis (n = 1), and mitral regurgitation (n = 1). Mean follow-up of 30.7 +/- 19.4 months was achieved in the survivors. All but one patient (univentricular repair) were in New York Heart Association class I, without atrioventricular valve incompetence. Actuarial survival at 4 years was 85.3% +/- 3%. We conclude that straddling or abnormal distribution of chordae tendineae of the atrioventricular valves does not preclude biventricular repair in double-outlet right ventricle or transposition of the great arteries provided that the ventricles are of adequate size. Curtainlike abnormal tricuspid chordae remain a contraindication to biventricular repair in double-outlet right ventricle.


Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases.
The existence of a papillary lesion of the urinary bladder with a benign clinical course and recognizable morphologic features that merit the benign categorization "papilloma" has been controversial. The clinical aspects and histologic features of these lesions remain to be fully elucidated. We have studied the clinicopathologic features of 26 patients with urothelial papillomas and correlated them with outcome. Papillomas occurred in two distinct clinical settings: (1) de novo neoplasms (23/26) or (2) those occurring in patients with a known clinical history of bladder cancer ("secondary" papillomas; 3/26). Follow-up information was available in 14/23 of the de novo cases (mean = 39 mo) and in 3/3 secondary cases (mean = 24 mo). Patients with de novo papillomas had a mean age of 46 years; 16 were male and 7 were female. Twelve of 14 had a benign clinical course with no recurrences; 1 developed a recurrent papilloma at 3 years, and 1 developed a pT3a high-grade papillary urothelial carcinoma at 4 years. Patients with secondary papillomas had a mean age of 66 years; two were male and one was a female. One of these patients developed two additional recurrences, and two patients had no new recurrences. Morphologically, the papillary architecture ranged from a common simple, nonhierarchical arrangement to, infrequently, more complex anastomosing papillae with budding. The individual papillae ranged from small (most common), with scant stroma and slender fibrovascular cores, to large, with marked stromal edema and/or cystitis cystica-like urothelial invaginations. Common to all was a lining of normal-appearing urothelium without hyperplasia, maintenance of normal polarity, and frequent prominence of the umbrella cell layer. Overall, no patient with a diagnosis of papilloma died of disease; only one patient with a de novo lesion (7.0%) had a recurrent papilloma, and 1/14 (7.0%) progressed to a higher grade and stage of disease, although this patient was on immunosuppressive therapy secondary to a renal transplant. De novo urothelial papillomas occur in younger patients and usually have a benign course. Urothelial papillomas are histologically and probably biologically distinctive tumors and merit distinction from other higher risk papillary neoplasms of the urinary bladder.


Which socio-economic measures are associated with psychological distress for men and women? A cohort analysis.
There are contradictory results regarding whether there is a social gradient in common mental disorders or not, or if this relation differs for different indicators or by gender. We analysed the relation between various measures of socio-economic position and later psychological distress among men and women in a Swedish context. The study is based on data from the Northern Swedish Cohort (N = 1001, 93.5% response rate), a 27-year prospective study. Logistic regression was used to explore the relation between various indicators of socio-economic position at age 30 (occupation, education, financial strain, cash margin, unemployment and living primarily on social welfare or unemployment insurance) and psychological distress (age 42), controlling for earlier psychological distress (age 21) and parental occupational class. Register data were used to measure unemployment. All other variables were self-reported, and measured by a questionnaire. Financial strain and living on social welfare or unemployment insurance at age 30 were associated with psychological distress at age 42 for men and women. Poor cash margin and unemployment were only associated with psychological distress in women, after controlling for potential confounders. Low occupational class and low education were not significantly related to later psychological distress. The two most commonly used measures of socio-economic position, occupation and education, were not significantly associated with psychological distress while other, less studied measures were. This study highlights the importance of measuring socio-economic position in several ways when studying common mental disorders, as well as to take gender into account.


The sciatic nerve of the toad Xenopus laevis as a physiological model of the human cochlear nerve.
The response of single fibres of the human cochlear nerve to electrical stimulation by a cochlear implant has previously been inferred from the response of the cochlear nerve in other mammals. These experiments are hindered by stimulus artefact and the range of stimulus currents used is therefore much less than the perceptual dynamic range (from threshold to discomfort) of human subjects. We have investigated use of the sciatic nerve of the toad Xenopus laevis as a convenient physiological model of the human cochlear nerve. Use of this completely dissected nerve reduces the problems of stimulus artefact whilst maintaining the advantages of a physiological preparation. The validity of the model was assessed by measuring the refractory periods, excitation time-constant, and relative spread of single fibres using microelectrode recording. We have also investigated the response of nerve fibres to sinusoidal stimulation. Based on these measurements, we propose that the sciatic nerve may be a suitable model of the human cochlear nerve if the timescales of stimuli are decreased by a factor of about five to compensate for the slower dynamics of the sciatic nerve and if noise is added to the stimuli to compensate for the lower internal noise of sciatic nerve fibres.


A symposium on surgery for coronary artery disease. Patient selection and preoperative evaluation.
Patient selection based upon preoperative evaluation is a complex problem. In using a procedure with the tremenduous implications and applications seen in aortocoronary bypass grafting, excesses in enthusiasm and criticism are the rule rather than the exception. With patience and careful evaluation,,the correct place for the procedure will be found and, though it is not quite the panacea once claimed for patients with coronary artery disease, aortocoronary bypass surgery will remain an important and valuable therapeutic tool, perhaps the most significant development in cardiovascular treatment of the past decade.


Caregiving stress, immune function, and health: implications for research with parents of medically fragile children.
Caregiving stress has been associated with considerable demands imposed on parents responsible for the physical and emotional care of medically fragile children. With health care advances in medicine and technology, there are a growing number of children with chronic conditions and disabilities (i.e., the medically fragile) surviving longer and being cared for almost exclusively in the home by parents. The physical strains, financial constraints, emotional effects, and social isolation experienced by parents caring for children with such complex medical needs may ultimately impact their physical and emotional health. Stress associated with the caregiving of older adults has been shown to negatively impact on health and immune functioning with the potential for associated morbidity. Studies exploring the relationship of stress with biological markers of immune functioning in parents have not been widely conducted. Therefore, there is a great opportunity in parent-child health for researchers to investigate implications of stress on immune functioning and health outcomes in parents caring for medically fragile children at home. The purpose of this review article will be to provide an overview of the literature related to caregiving stress and immune functioning and to discuss implications for research in this area with parents of medically fragile children.


Nucleocapsid protein VP15 of White spot syndrome virus colocalizes with the nucleolar proteins nucleolin and fibrillarin.
The core nucleocapsid protein VP15 of White spot syndrome virus (WSSV) was shown to interact with DNA and predicted to be involved in the packaging of the WSSV genome. In the present study, we explored the colocalization of VP15 with several nuclear proteins in insect cells. The results showed that the VP15 completely colocalized with nucleolin and fibrillarin, suggesting that VP15 is a nucleolar localization protein and plays an important role in the life cycle of WSSV in host cells.


Clinical, radiographic, and genetic evaluation of a novel form of autosomal-dominant oligodontia.
A frameshift mutation recently identified within the paired domain of the transcription factor, PAX9, has been linked to a unique form of oligodontia in a single, multigenerational family (Stockton et al., 2000). We now describe the phenotypic and segregation analyses of this remarkable kindred, the initial approach taken to identify a candidate gene involved in this form of oligodontia, and the power of this single-family pedigree to generate significant linkage in a genome search. Of the 43 family members enrolled in this study, 21 individuals were affected with several congenitally missing permanent teeth. The pattern of inheritance of the oligodontia trait suggested the involvement of a single gene bearing a dominant mutation. To various degrees, affected members lacked permanent first, second, and third molars in all four quadrants. Several individuals with missing molars also lacked second premolars- most commonly, maxillary second premolars and mandibular central incisors. To the best of our knowledge, this pattern of non-syndromic, familial tooth agenesis has not been previously described in the literature. Since a missense mutation in the homeobox gene, MSX1, was previously linked to tooth agenesis in a single family lacking second premolars and third molars, we performed a mutational analysis of MSX1 by PCR. The absence of a mutation in exons 1 and 2 of MSX1 suggested that allelic mutations in the coding region of MSX1 are not associated with this phenotypically distinct form of oligodontia. Computer simulation of linkage analysis further proved that this pedigree alone was sufficient to generate a significant result for a total genome scan.


Stress-modulated collagen fiber remodeling in a human carotid bifurcation.
This work concerns with the implementation of a new stress-driven remodeling model for simulating the overall structure and mechanical behavior of a human carotid bifurcation. By means of an iterative finite element based procedure collagen fiber direction and maximal principal stresses are computed. We find that the predicted fibers' architecture at the cylindrical branches and at the apex of the bifurcation correlates well with histological observations. Some insights about the mechanical response of the sinus bulb and the bifurcation apex are revealed and discussed. The results are compared with other, isotropic and orthotropic, models available in the literature.


Quantitative risk assessment of African swine fever introduction into Spain by legal import of swine products.
African swine fever (ASF) is currently threatening the global swine industry. Its unstoppable global spread poses a serious risk to Spain, one of the world's leading producers. Over the past years, there has been an increased global burden of ASF not only in swine but also swine products. Unfortunately, many pigs are not diagnosed before slaughter and their products are used for human consumption. These ASF-contaminated products are only a source for new ASF outbreaks when they are consumed by domestic pigs or wild boar, which may happen either by swill feeding or landfill access. This study presents a quantitative stochastic risk assessment model for the introduction of ASF into Spain via the legal import of swine products, specifically pork and pork products. Entry assessment, exposure assessment, consequence assessment and risk estimation were carried out. The results suggest an annual probability of ASF introduction into Spain of 1.74 × 10-4, the highest risk being represented by Hungary, Portugal, and Poland. Monthly risk distribution is homogeneously distributed throughout the year. Illegal trade and pork product movement for own consumption (e.g., air and ship passenger luggage) have not been taken into account due to the lack of available, accredited data sources. This limitation may have influenced the model's outcomes and, the risk of introduction might be higher than that estimated. Nevertheless, the results presented herein would contribute to allocating resources to areas at higher risk, improving prevention and control strategies and, ultimately, would help reduce the risk of ASF introduction into Spain.


Antiviral agents in respiratory infections.
Viral respiratory illnesses are among the most common afflictions in the United States. Until recently, few agents were available to control these infections. Now, there are specific and nonspecific agents either to prevent or treat viral respiratory infections. For example, a better understanding of the pathogenesis of the common cold provided new insights into therapeutic intervention for that entity. In other instances (eg, influenza), the antiviral agent is so specific that there is a need for diagnostic information to guide therapy. Epidemiological clues, clinical symptoms, and some newer laboratory methods all contribute to the clinician's understanding of the cause of an individual respiratory illness and guide the choice of therapy. In other circumstances, information is being gradually developed that points toward the availability of a broad-spectrum antiviral drug with activity against at least five of the important respiratory viruses; its major limitation is that a cumbersome and expensive means of delivery to the patient is required. For such a drug to gain widespread use, a more practical method of delivery is necessary.


Parasitic manipulation or side effects? The effects of past Toxoplasma gondii and Borrelia spp. infections on human personality and cognitive performance are not mediated by impaired health.
Bacteria Borrelia burgdorferi s. l. and even more the protist Toxoplasma gondii Nicolle et Manceaux, 1908, are known to affect the behaviour and mental health of their animal and human hosts. Both pathogens infect a significant fraction of human population, both are neurotropic and survive in the host's body for a long time. While latent infections were thought to be clinically asymptomatic, recent studies suggest otherwise, revealing adverse effects on human health. It was hypothesised that the specific behavioural effects of these pathogens may be side effects of general health impairments in infected individuals. This hypothesis was tested using about one hour-long survey consisting of questionnaires and performance tests on a cohort of 7,762 members of the internet population. Results showed that individuals infected with T. gondii reported worse physical and mental health, and those infected with Borrelia spp. reported worse physical health than uninfected controls. Furthermore, infected and noninfected individuals differed in several personality traits, including conscientiousness, pathogen disgust, injury disgust, Machiavellianism, narcissism, tribalism, anti-authoritarianism, intelligence, reaction time, and precision. While the majority of behavioural effects associated with Borrelia infection were similar to those associated with Toxoplasma infection, some differences were observed, such as performance in the Stroop test. Path analyses and nonparametric partial Kendall correlation tests showed that these effects were not mediated by impaired health in infected individuals, contradicting the side effects hypothesis.


The CO 2 laser in omphalitis.
Over a period of 18 months, from January 1988 to June 1989, 8 patients with chronic omphalitis were treated in a Multi-Specialty Military Clinic, using a CO 2 laser. A significant decrease in periumbilical pain, elimination of the disturbing chronic discharge, and vaporization of the reactive granulation tissue were achieved, suggesting this technique as an attractive option in the treatment of chronic recidivant omphalitis.


[Role of children with chronic hepatitis in the intrafamilial spread of hepatitis B virus infection].
In order to evaluate the intrafamilial spread of hepatitis B virus (HBV) infection we studied the serological markers of HBV in 101 relatives of 35 children with chronic hepatitis B. Sixty per cent of relatives had markers of infection and 25% showed persistent HBs antigenemia. The high prevalence of HBeAg versus anti-HBe in chronically infected relatives suggests a close temporal relationship of the infection between adults and children. These results support the hypothesis that the child is the main carrier of HBV infection in his family.


Associations of body size and body composition with functional ability and quality of life in hemodialysis patients.
Modifiable factors, such as body size and body composition, could influence physical function and quality of life in patients undergoing maintenance hemodialysis (MHD). From January 2008 to June 2012, in body mass index (BMI), waist circumference (WC), and magnetic resonance imaging measurements of midthigh muscle area (MTMA) and intra-abdominal fat area (IAFA) were obtained at baseline in 105 MHD patients. Six-minute walk distances and physical and mental component scores (PCS and MCS) from the Short Form-12 questionnaire were obtained at baseline and 6 and 12 months. Separate mixed-effects regression models were used to relate baseline BMI, WC, and IAFA with baseline and the average of follow-up 6-minute walk distances and PCS and MCS after adjustment for baseline covariates and MTMA. for baseline covariates and baseline MTMA, each SD increase in baseline BMI was inversely associated with baseline (-31.5 m; 95% confidence interval [95% CI], -53.0 to -10.0 m) and follow-up (-36.9 m; 95% CI, -54.6 to -19.2 m) 6-minute walk distances. Results were similar for WC and IAFA. In each of these models, each SD increase in MTMA had a strong positive association with 6-minute walk distance. Adiposity measures were not associated with baseline or follow-up PCS and MCS. After adjustment for baseline BMI, each SD increase in baseline MTMA was associated with higher baseline PCS score (3.78; 95% CI, 0.73 to 6.82) and MCS (3.75; 95% CI, 0.44 to 7.05) but had weaker associations with follow-up PCS and MCS. Body size and composition are significantly associated with physical functioning and quality of life. Interventions that improve muscle mass and decrease obesity might improve these measures in patients undergoing MHD.


[The clinical and experimental evaluation of the pharmacological efficacy of the new antidiarrheal preparation ftorazol].
A clinical trial of the new antidiarrheal drug of antisecretory action fluorasol was studied with patients with salmonellosis and food toxic infections. 65 patients had moderate and 53 severe symptoms. It was established that fluorasol was superior to basic rehydration therapy in relieving diarrheal syndrome irrespective of severity of acute intestinal infections. Clinical effects on intoxication were not registered. Antidiarrheal activity of fluorasol was confirmed on the model of experimental diarrhea on isolated loops of the rat small intestine. Liquid secretion into the lumen of small intestinal isolated loops in the presence of fluorasol substance fell twofold compared to control loops.


Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5.
Inflammatory chemokines are often elevated in disease settings, where the largest group of CC-chemokines are the macrophage inflammatory proteins (MIP), which are promiscuous for the receptors CCR1 and CCR5. MIP chemokines, such as CCL3 and CCL5 are processed at the N terminus, which influences signaling in a highly diverse manner. Here, we investigate the signaling capacity of peptides corresponding to truncated N termini. These 3-10-residue peptides displayed weak potency but, surprisingly, retained their signaling on CCR1. In contrast, none of the peptides generated a signal on CCR5, but a CCL3-derived tetrapeptide was a positive modulator boosting the signal of several chemokine variants on CCR5. In conclusion, chemokine N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators.


Biphasic respiratory depression from neurolept anesthesia.
The recovery of patients following neurolept or fentanyl/nitrous oxide anesthesia is extremely variable due to variations in drug dosage, biotransformation and excretion idiosyncracies among individuals. The respiratory depressant effects of fentanyl or fentanyl/droperidol can far outlast the analgesic duration and can recur after having dissipated. The level of consciousness and the quality of breathing can be misleading indicators of complete recovery from neurolept anesthesia. Respiratory rate has been observed to return to control levels when simultaneous response to CO2 rebreathing was reduced and resting PeCO2 was increased. Naloxone can be used in dosages which will help ensure adequate ventilation without attenuating postoperative analgesia.


Molecular simulation of CO chemisorption on Co(0001) in presence of supercritical fluid solvent: A potential of mean force study.
For several decades, heterogeneous catalytic processes have been improved through utilizing supercritical fluids (SCFs) as solvents. While numerous experimental studies have been established across a range of chemistries, such as oxidation, pyrolysis, amination, and Fischer-Tropsch synthesis, still there is little fundamental, molecular-level information regarding the role of the SCF on elementary heterogeneous catalytic steps. In this study, the influence of hexane solvent on the adsorption of carbon monoxide on Co(0001), as the first step in the reaction mechanism of many processes involving syngas conversion, is probed. Simulations are performed at various bulk hexane densities, ranging from ideal gas conditions (no SCF hexane) to various near- and super-critical hexane densities. For this purpose, both density functional theory and molecular dynamics simulations are employed to determine the adsorption energy and free energy change during CO chemisorption. Potential of mean force calculations, utilizing umbrella sampling and the weighted histogram analysis method, provide the first commentary on SCF solvent effects on the energetic aspects of the chemisorption process. Simulation results indicate an enhanced stability of CO adsorption on the catalyst surface in the presence of supercritical hexane within the reduced pressure range of 1.0-1.5 at a constant temperature of 523 K. Furthermore, it is shown that the maximum stability of CO in the adsorbed state as a function of supercritical hexane density at 523 K nearly coincides with the maximum isothermal compressibility of bulk hexane at this temperature.


Effects of adrenalectomy and corticosterone administration on hypothalamic obesity in rats.
The present experiment was designed to assess the role of adrenal hormones in hypothalamic hyperphagia and obesity. Ventromedial hypothalamic (VMH) or sham lesions were produced either 15 days before or after adrenalectomy (ADX) or sham adrenalectomy in rats in a completely counterbalanced design (experiment 1). Body weight and food intake were recorded for 30 days after the second surgery. Adrenalectomy in obese VMH animals eliminated all excess weight gain and decreased food intake to below the level of all control groups. VMH lesions in ADX animals did not produce the characteristic weight gain associated with ventromedial hypothalamic damage, and this group was not significantly different from animals with sham lesions in body weight or food intake. In experiment 2, the administration of corticosterone resulted in a marked increase in the rate of weight gain in ADX-VMH animals, and the withdrawal of the hormones was followed by weight loss. It is concluded that adrenal glucocorticoid hormones are necessary for the development and maintenance of VMH hyperphagia and obesity.


MDSC and TGFβ Are Required for Facilitation of Tumor Growth in the Lungs of Mice Exposed to Carbon Nanotubes.
During the last decades, changes have been observed in the frequency of different histologic subtypes of lung cancer, one of the most common causes of morbidity and mortality, with a declining proportion of squamous cell carcinomas and an increasing proportion of adenocarcinomas, particularly in developed countries. This suggests the emergence of new etiologic factors and mechanisms, including those defining the lung microenvironment, promoting tumor growth. Assuming that the lung is the main portal of entry for broadly used nanomaterials and their established proinflammatory propensities, we hypothesized that nanomaterials may contribute to changes facilitating tumor growth. Here, we report that an acute exposure to single-walled carbon nanotubes (SWCNT) induces recruitment and accumulation of lung-associated myeloid-derived suppressor cells (MDSC) and MDSC-derived production of TGFβ, resulting in upregulated tumor burden in the lung. The production of TGFβ by MDSC requires their interaction with both SWCNT and tumor cells. We conclude that pulmonary exposure to SWCNT favors the formation of a niche that supports ingrowth of lung carcinoma in vivo via activation of TGFβ production by SWCNT-attracted and -presensitized MDSC.


Dorsal unpaired median neurones in the insect central nervous system: towards a better understanding of the ionic mechanisms underlying spontaneous electrical activity.
The efferent dorsal unpaired median (DUM) neurones, which include octopaminergic neurones, are among the most intensively studied neurones in the insect central nervous system. They differ from other insect neurones in generating endogenous spontaneous overshooting action potentials. The second half of the 1980s is certain to be considered a turning point in the study of the ion channels underlying the electrical activity of DUM neurones. Recent advances made using the patch-clamp technique have stimulated an increasing interest in the understanding of the biophysical properties of both voltage-dependent and voltage-independent ion channels. Patch-clamp studies of DUM neurones in cell culture demonstrate that these neurones express a wide variety of ion channels. At least five different types of K(+) channel have been identified: inward rectifier, delayed rectifier and A-like channels as well as Ca(2+)- and Na(+)-activated K(+) channels. Moreover, besides voltage-dependent Na(+) and Ca(2+)-sensitive Cl(-) channels, DUM neurones also express four types of Ca(2+) channel distinguished on the basis of their kinetics, voltage range of activation and pharmacological profile. Finally, two distinct resting Ca(2+) and Na(+) channels have been shown to be involved in maintaining the membrane potential and in regulating the firing pattern. In this review, we have also attempted critically to evaluate these existing ion channels with regard to their specific functions in the generation of the different phases of the spontaneous electrical activity of the DUM neurone.


Parenting to Reduce Child Screen Time: A Feasibility Pilot Study.
Excessive screen time has been associated with a multitude of child health problems. This pilot study examined the feasibility and preliminary outcome of a novel 1-session intervention designed to help parents reduce their child's screen time. Thirty-nine parents of 5- to 12-year-old children were randomized to the intervention (a combined didactics and hands-on approach focused on technology-specific parenting) or waitlist control group. The findings suggested that a sample could be recruited in a reasonable time (6 wk) at a reasonable cost, randomized, and retained at 6 weeks postintervention. Preliminary evidence suggested the intervention, which was implemented with fidelity, was associated with change in technology-specific parenting and 1 of 2 measures of child screen time. Parents reported satisfaction with the intervention and confidence in managing their child's screen time. The results of this pilot study suggest that this 1-session intervention is a promising approach to managing child screen time.


Muscle growth: To infinity and beyond?
Strength increases following training are thought to be influenced first by neural adaptions and second by large contributions from muscle growth. This is based largely on the idea that muscle growth is a slow process and that a plateau in muscle growth would substantially hinder long-term increases in strength. This Review examines the literature to determine the time course of skeletal muscle growth in the upper and lower body and to determine whether and when muscle growth plateaus. Studies were included if they had at least 3 muscle size time points, involved participants 18 years or older, and used a resistance training protocol. Muscle growth occurs sooner than had once been hypothesized, and this adaptation is specific to the muscle group. Furthermore, the available studies indicate that the muscle growth response will plateau, and additional growth is not likely to occur appreciably beyond this initial plateau. However, the current study durations are a limitation. Muscle Nerve 56: 1022-1030, 2017.


Last findings on dual inhibitors of abl and SRC tyrosine-kinases.
Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome that expresses the constitutively activated tyrosine kinase Bcr-Abl; this enzyme causes hyperproliferation of the stem cells and the consequent pathology of the disease. Targeted inhibitors of Bcr-Abl have antiproliferative effects on the leukemic cells and induce apoptosis, favouring a regression of the CML chronic phase, but in the successive blast crisis phase cancer cells frequently develop resistance to Bcr-Abl inhibitors. Src is a family of non-receptor tyrosine kinases, fundamental for cell development, growth, replication, adhesion, motility and is overexpressed in a wide number of human cancers. Recently it was demonstrated that Src is increased in hematopoietic cells expressing Bcr-Abl and is involved in the oncogenic pathway that causes CML. For this reason and also for the development of resistance to classical Bcr-Abl inhibitors, various dual Src/Abl inhibitors have been recently synthesized and tested. This mini review will be focused on the latest finding on this matter.


Field assessment of permethrin in the control of sheep headfly disease.
Three groups of sheep, gimmers, ewes with lambs and rams, were sprayed at fortnightly intervals from June to September 1980 with a 0.1 per cent emulsion of permethrin in an attempt to control damage caused by Hydrotaea irritans. Complete prevention of damage was not achieved but the number of sheep affected and the severity of lesions present in affected sheep was significantly reduced in comparison with untreated control groups. Permethrin treatment was also judged to be valuable in the management of rams with head wounds. Variation in susceptibility with age was noted, gimmers being the most severely affected and a breed variation was apparent in the rams which was related to the character of horn present.


Fetuin-A and its genetic association with cardiometabolic disease.
Fetuin-A acts as both an inhibitor of calcification and insulin signaling. Previous studies reported conflicting results on the association between fetuin-A and cardiometabolic diseases. We aim to provide further insights into the association between genetically predicted levels of fetuin-A and cardiometabolic diseases using a Mendelian randomization strategy. Genetic variants associated with fetuin-A and their effect sizes were obtained from previous genetic studies. A series of two-sample Mendelian randomization analyses in 412,444 unrelated individuals from the UK Biobank did not show evidence for an association of genetically predicted fetuin-A with any stroke, ischemic stroke, or myocardial infarction. We do find that increased levels of genetically predicted fetuin-A are associated with increased risk of type 2 diabetes (OR = 1.21, 95%CI 1.13-1.30, P = < 0.01). Furthermore, genetically predicted fetuin-A increases the risk of coronary artery disease in individuals with type 2 diabetes, but we did not find evidence for an association between genetically predicted fetuin-A and coronary artery disease in those without type 2 diabetes (P for interaction = 0.03). One SD increase in genetically predicted fetuin-A decreases risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men (P for interaction = < 0.01). Genetically predicted fetuin-A is associated with type 2 diabetes. Furthermore, type 2 diabetes status modifies the association of genetically predicted fetuin-A with coronary artery disease, indicating that fetuin-A increases risk in individuals with type 2 diabetes. Finally, higher genetically predicted fetuin-A reduces the risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men.


Refractory anaemia with excess of blasts as a terminal evolution of paroxysmal nocturnal haemoglobinuria. A case report with chromosomal analysis.
A 63-year-old man presented with paroxysmal nocturnal haemoglobinuria (PNH). After a 31 months' course of typical PNH the patient developed a type 1 (refractory anaemia) myelodysplastic syndrome (MDS) which subsequently evolved into type 5 (refractory anaemia with excess of blasts in transformation) myelodysplastic syndrome. At this time, bone marrow chromosomal analysis revealed a clonal pseudodiploidy (46 XY, -10, -16, -20, +3 markers) while phytohaemagglutinin-stimulated blood lymphocytes had a normal male karyotype. Both the acid haemolysis and thrombin tests remained positive throughout the course of the disease. This case report emphasizes the link between PNH and the myelodysplastic syndromes. Serial chromosomal analysis may help to define the myelodysplastic potential of PNH.


Which parameters describe the electrophysiological properties of successful slow pathway RF ablation in patients with common atrioventricular nodal reentrant tachycardia?
Atrioventricular nodal reentrant tachycardia (AVNRT) accounts for about 60% of the patients presenting with paroxysmal supraventricular tachycardia. The radiofrequency (RF) catheter ablation of the slow atrioventricular (AV) node pathway is the preferred therapeutic approach in patients with AV node reentrant tachycardia. The aim of our study was describe the electrophysiological properties of successful slow pathway RF ablation in patients with common atrioventricular nodal reentrant tachycardia. The study design was a retrospective analysis involving fifty consecutive patients (18 males; mean age of 39+/-22 years) who underwent slow pathway ablation because of AVNRT. Slow junctional beats with a cycle length longer than 550 ms were observed in 39 patients (79%); the presence of rapid junctional beats with a cycle length less than 550 ms was showed in 5 patients (10%). Moreover, in 32 of 50 patients (65%) duration of atrial electrogram more than 40 ms was noticed. Analyzing data reported, we found the statistically significant presence of slow junctional beats (p=0.001) and atrial electrogram >40 ms (p=0.05) in successful RF ablation procedures. In patients with AVNRT undergoing slow pathway ablation, the duration of atrial electrogram >40 ms and slow junctional beats with cycle length >550 ms during the application of RF energy describe the electrophysiological properties of successful slow pathway RF ablation.


Evidence for a regulatory loop between IFN-γ and IL-33 in skin inflammation.
Interleukin-33 has recently gained much attention due to its role in allergic responses. It has been shown to amplify Th2 responses and to act as a damage-associated molecular pattern. IL-33 acts on a broad range of cells and has been proposed to link innate and adaptive features of allergic responses. It was the aim of this study to investigate this property of IL-33 in the inflammatory response characterising atopic dermatitis (AD). We have analysed the response of skin-resident cells derived from patients with AD and healthy donors with regard to the expression of IL-33 and its receptor ST2. The functional impact of IL-33 on CD4+ T cells was investigated. Keratinocytes and dermal fibroblasts clearly differ in their regulation of IL-33. In fibroblasts, the concerted action of TNF-α and IL-1β was the strongest inducer, whereas IFN-γ is clearly the key molecule that upregulates IL-33 in keratinocytes with a more pronounced response of cells derived from patients with AD. Keratinocytes from patients with AD showed a markedly higher constitutive expression level of surface ST2. CD4+ T cells respond to IL-33. Unexpectedly, IL-33 failed to induce a significant secretion of IL-5 or IL-13. By contrast, high amounts of IFN-γ were detectable if IL-33 was added to the T-cell receptor-stimulated cells or in combination with IL-12. These results suggest that IL-33 and IFN-γ are closely interlinked in epidermal AD inflammation. IFN-γ induces IL-33 in keratinocytes and IL-33 acts on activated T cells to further increase the release of IFN-γ, therefore contributing to drive skin inflammation towards chronic responses.


Dysregulated Lipid Metabolism and Its Role in α-Synucleinopathy in Parkinson's Disease.
Parkinson's disease (PD) is the second most common neurodegenerative disease, the main pathological hallmark of which is the accumulation of α-synuclein (α-syn) and the formation of filamentous aggregates called Lewy bodies in the brainstem, limbic system, and cortical areas. Lipidomics is a newly emerging field which can provide fresh insights and new answers that will enhance our capacity for early diagnosis, tracking disease progression, predicting critical endpoints, and identifying risk in pre-symptomatic persons. In recent years, lipids have been implicated in many aspects of PD pathology. Biophysical and lipidomic studies have demonstrated that α-syn binds preferentially not only to specific lipid families but also to specific molecular species and that these lipid-protein complexes enhance its interaction with synaptic membranes, influence its oligomerization and aggregation, and interfere with the catalytic activity of cytoplasmic lipid enzymes and lysosomal lipases, thereby affecting lipid metabolism. The genetic link between aberrant lipid metabolism and PD is even more direct, with mutations in GBA and SMPD1 enhancing PD risk in humans and loss of GALC function increasing α-syn aggregation and accumulation in experimental murine models. Moreover, a number of lipidomic studies have reported PD-specific lipid alterations in both patient brains and plasma, including alterations in the lipid composition of lipid rafts in the frontal cortex. A further aspect of lipid dysregulation promoting PD pathogenesis is oxidative stress and inflammation, with proinflammatory lipid mediators such as platelet activating factors (PAFs) playing key roles in arbitrating the progressive neurodegeneration seen in PD linked to α-syn intracellular trafficking. Lastly, there are a number of genetic risk factors of PD which are involved in normal lipid metabolism and function. Genes such as PLA2G6 and SCARB2, which are involved in glycerophospholipid and sphingolipid metabolism either directly or indirectly are associated with risk of PD. This review seeks to describe these facets of metabolic lipid dysregulation as they relate to PD pathology and potential pathomechanisms involved in disease progression, while highlighting incongruous findings and gaps in knowledge that necessitate further research.


Antiangiogenic phytochemicals and medicinal herbs.
Medicinal herbs and their phytochemicals are potential novel leads for developing antiangiogenic drugs. This review aims to assess the current status of research with medicinal herbs and their phytochemicals for the development of antiangiogenic agents for cancer and other angiogenesis-related diseases including inflammation, diabetic retinopathy, endometriosis and obesity. Most studies reviewed have focused on vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR-2) signaling for endothelial response processes and have led to the identification of many potential antiangiogenic agents. Since human clinical trials with antiangiogenic modalities targeting VEGF/VEGFR-2 signaling have shown limited efficacy and occasional toxic side effects, screening strategies for herbal phytochemicals based on other signaling pathways important for cancer-endothelial and stromal crosstalks should be emphasized in the future.


Technical aspects of entrapped coronary guidewire retrieval using rotational atherectomy device: A case series.
This article highlights four unique cases where rotational atherectomy (RA Rotapro, Boston Scientific) was used to cut and retrieve an entrapped coronary guidewire with parts extending into the aorta We discuss the technique and step by step approach to the retrieval procedure. Three of four cases described a guide wire entrapment in the right coronary artery (RCA), and one in the left anterior descending artery via retrograde route. In all cases the guide wire was intact within the intracoronary segment. In Case 1, the guide wire (Runthrough; Terumo) was entrapped in an acute marginal branch during chronic total occlusion (CTO) percutaneous coronary intervention. In Case 2, a whisper wire (Abbott) was entrapped during re-wiring of the right posterolateral branch through stent struts, the traction on the wire caused severe malformation of distal and proximal stents requiring second staged procedure to complete revascularization of the RCA CTO. In Case 3, a Runthrough wire was entrapped between two layers of stents and fractured at the proximal point with filaments extending into descending aorta. And in Case 4, a Pilot 200 (Abbott) wire was entrapped retrograde in the subintimal space via saphenous vein graft connection by tying a knot at the distal tip of the wire. In all four cases RA was used to successfully cut and remove the entrapped guide wires. Rotablation technique appears to be a safe and effective strategy for the management of entrapped coronary guidewire when conventional strategies fail.


Management of Inflammatory Cardiac Masses.
Systemic rheumatologic and inflammatory disorders can affect almost any organ system, including the heart. The cardiac valves, conduction system, myocardium, endocardium, pericardium, and coronary arteries may be affected. Intracardiac masses may develop as part of the disease process or a consequence of their therapy, such as methotrexate-associated nodulosis. Optimal therapy in these cases is not known, since many patients are asymptomatic and the potential benefit of surgical excision must be weighed against its associated morbidity and mortality. Importantly, these inflammatory masses must be differentiated from thrombus, infection, and primary and metastatic tumors. We present three cases of inflammatory cardiac masses associated with rheumatoid arthritis and Wegener's granulomatosis, which were successfully treated conservatively, and propose a management algorithm. The benefits of such an approach must be individualized and weighed against the risks of systemic embolization, stroke and obstruction.


Infant meningoencephalitis caused by yellow fever vaccine virus transmitted via breastmilk.
To describe a case of infant meningoencephalitis that was probably caused by yellow fever vaccine virus transmitted via breastmilk. A 38-day old patient was admitted to hospital on May 23, 2009, with fever. On May 25, 2009, convulsive crises began. Cerebrospinal fluid (CSF) test results were suggestive of meningoencephalitis. The mother had been given a dose of yellow fever vaccine and the baby was on exclusive breastfeeding. The baby was discharged after the convulsive crises were controlled. Tests identified IgM antibodies specific for yellow fever in both serum and CSF. In 2009, the first case was confirmed of meningoencephalitis caused by the yellow fever vaccine virus transmitted via breastmilk. We describe a second case in which the vaccine virus was possibly the etiologic agent of meningoencephalitis. The Brazilian Ministry of Health now recommends delaying vaccination of nursing mothers until their children reach 6 months or providing them with guidance on alternative options to avoid the risk of transmission of the vaccine virus via breastmilk.


Can treating critically-ill haematological malignancy patients in a separate intensive care unit decrease intensive care unit mortality?
The aim of the study was to investigate whether treating haematological malignancy (HM) patients in a separate intensive care unit (ICU) would reduce ICU mortality. HM patients treated by the same ICU team in a general medical ICU (GM-ICU) and a separate haematology ICU (H-ICU) were included in this study. Patients' demographic characteristics and ICU data were recorded retrospectively. Differences in the ICU course and prognosis between these two groups were determined. A total of 251 patients (102 from GM-ICU, 149 from H-ICU) were included in this study. The disease severity and organ failure scores at ICU admission and underlying HMs were not different between the two groups. Patients waited longer for admission to GM- ICU. Therapeutic procedures were performed significantly more frequently in GM-ICU. ICU complications were not different between the groups. ICU mortality rates were higher in GM-ICU (59.8% vs 37.6%, p = 0.006). A separate ICU allocated for haematology patients will allow timely and rapid admission of HM patients to ICU. Thus, mortality rates of HM patients needing ICU care will decline.


Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta stimulate extracellular signal-regulated kinase 1/2 signaling by accelerating recycling through the endocytic recycling compartment.
We demonstrate that recycling through the endocytic recycling compartment (ERC) is an essential step in Fc epsilonRI-induced activation of extracellular signal-regulated kinase (ERK)1/2. We show that ERK1/2 acquires perinuclear localization and colocalizes with Rab 11 and internalized transferrin in Fc epsilonRI-activated cells. Moreover, a close correlation exists between the amount of ERC-localized ERK1/2 and the amount of phospho-ERK1/2 that resides in the nucleus. We further show that by activating phosphatidylinositol 4-kinase beta (PI4Kbeta) and increasing the cellular level of phosphatidylinositol(4) phosphate, neuronal calcium sensor-1 (NCS-1), a calmodulin-related protein, stimulates recycling and thereby enhances Fc epsilonRI-triggered activation and nuclear translocation of ERK1/2. Conversely, NCS-1 short hairpin RNA, a kinase dead (KD) mutant of PI4Kbeta (KD-PI4Kbeta), the pleckstrin homology (PH) domain of FAPP1 as well as RNA interference of synaptotagmin IX or monensin, which inhibit export from the ERC, abrogate Fc epsilonRI-induced activation of ERK1/2. Consistently, NCS-1 also enhances, whereas both KD-PI4Kbeta and FAPP1-PH domain inhibit, Fc epsilonRI-induced release of arachidonic acid/metabolites, a downstream target of ERK1/2 in mast cells. Together, our results demonstrate a novel role for NCS-1 and PI4Kbeta in regulating ERK1/2 signaling and inflammatory reactions in mast cells. Our results further identify the ERC as a crucial determinant in controlling ERK1/2 signaling.


The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification.
High polyamine (PA) levels and ornithine decarboxylase (ODC) overexpression are well-known phenomena in many aggressive cancer types. We analyzed the expression of ODC and ODC-activity regulating genes antizymes 1-3 (OAZ1-3) and antizyme inhibitors 1-2 (AZ-IN1-2) in human neuroblastoma (NB) tumors and correlated these with genetic and clinical features of NB. Since ODC is a known target gene of MYCN, the correlation between ODC and MYCN was of special interest. Data were obtained from Affymetrix micro-array analysis of 88 NB tumor samples. In addition, mRNA expression levels of ODC, OAZ2 and MYCN in a MYCN-inducible NB cell line were determined by quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). ODC mRNA expression in NB tumors was significantly predictive of decreased overall survival probability and correlated with several unfavorable clinical NB characteristics (all p < 0.005). Interestingly, high ODC mRNA expression also showed significant correlation with poor survival prognosis in Kaplan-Meier analyses stratified for patients without MYCN amplification, suggesting an additional role for ODC independent of MYCN. Conversely, high OAZ2 mRNA expression correlated with increased survival and with several favorable clinical NB characteristics (all p < 0.003). In addition, we provide first evidence of a role for MYCN-associated transcription factors MAD2 and MAD7 in ODC regulation. In NB cell cultures, ectopic overexpression of MYCN altered ODC but not OAZ2 mRNA levels. In conclusion, these data suggest that elevated ODC and low OAZ2 mRNA expression levels correlate with several unfavorable genetic and clinical features in NB, offering new insights into PA pathways and PA metabolism-targeting therapy in NB.


Model for the First NIH-funded Center of Excellence in End-of-Life Research.
Centers of excellence are widely acknowledged as a mechanism to promote scientific advances in a particular field of science, but until recently there have been no end-of-life or palliative care research centers funded by the National Institutes of Health (NIH). The purpose of this article is to describe aims, framework, and organizational structure of the first NIH-funded Center of Excellence on end-of-life research, the Center for End-of-Life Transition Research (CEoLTR), and the advances in end-of-life research that the CEoLTR will facilitate. The teams of researchers involved in the CEoLTR have grown impressively since it was funded in 2007. Collectively, the teams are on target to accomplish all of the original goals for this five year award.


Is there a general factor of prevalent psychopathology during adulthood?
The patterns of comorbidity among prevalent mental disorders in adults lead them to load on "externalizing," "distress," and "fears" factors. These factors are themselves robustly correlated, but little attention has been paid to this fact. As a first step in studying the implications of these interfactor correlations, we conducted confirmatory factor analyses on diagnoses of 11 prevalent Diagnostic and Statistical Manual of Mental Disorders (4th ed.) mental disorders in a nationally representative sample. A model specifying correlated externalizing, distress, and fears factors fit well, but an alternative model was tested in which a "general" bifactor was added to capture what these disorders share in common. There was a modest but significant improvement in fit for the bifactor model relative to the 3-factor oblique model, with all disorders loading strongly on the bifactor. Tests of external validity revealed that the fears, distress, and externalizing factors were differentially associated with measures of functioning and potential risk factors. Nonetheless, the general bifactor accounted for significant independent variance in future psychopathology, functioning, and other criteria over and above the fears, distress, and externalizing factors. These findings support the hypothesis that these prevalent forms of psychopathology have both important common and unique features. Future studies should determine whether this is because they share elements of their etiology and neurobiological mechanisms. If so, the existence of common features across diverse forms of prevalent psychopathology could have important implications for understanding the nature, etiology, and outcomes of psychopathology.


[Validation of a Hebrew translation of the Gastroparesis Cardinal Symptom Index (GCSI)].
Symptom checklists used in clinical research of gastroparesis have not been evaluated for reliability or validity. The Gastroparesis Cardinal Symptom Index (GCSI) is a reliable, validated measure whereby patients score three groups of symptoms: nausea/vomiting, postprandial fullness/early satiety and bloating. The purpose of this study was to translate the GCSI into Hebrew and then validate the language of the translation for use in future studies. The measure was first translated into Hebrew and then back-translated to English, followed by a comparison of the two versions. The English and Hebrew versions were then completed by 40 healthy bilingual volunteers, using a cross-over design, with half answering the English version first while the other half replied to the Hebrew version first. The internal consistency for both measures was moderate, the English slightly lower than the Hebrew (Cronbach's alpha 0.67 vs. 0.72). Intra-class correlation values were larger than 0.7 for all but one of the symptoms (item 3, "vomiting"), although a Wilcoxian signed-rank test found this correlation to be of borderline significance (z=-1.63, p=0.50). The Hebrew translation of the GCSI is valid for use in clinical research, although further psychometric testing is needed to test its value for this purpose. This manuscript describes the stages of measurement, translation and language validation, the difficulties that researches face and possible solutions when researches choose to use a measure which was developed in a different language.


Strength and anthropometric measures in identical and fraternal twins: no evidence of masculinization of females with male co-twins.
Sharing of intrauterine environment in twins of opposite sex has been hypothesized to result in masculinization of the female twin. We tested this hypothesis by comparing strength (maximum hand-grip pressure) and various anthropometric measures in a newly established survey panel comprising 4,314 middle-aged twins identified through a Danish population-based twin registry. Sex- and zygosity-specific mean values of handgrip strength, height, weight, body mass index, and waist circumference were highly comparable between fraternal twins of opposite sex and fraternal twins of same sex. Our results provide no support for the hypothesis of masculinization of female twins from opposite sex twin pairs.


Herpes simplex virus immediate-early ICP0 protein inhibits Toll-like receptor 2-dependent inflammatory responses and NF-kappaB signaling.
The discovery of the Toll-like receptors (TLRs) and their importance in the regulation of host responses to infection raised attention to the complex interplay between viral gene products and the host innate immune responses in determining the outcome of virus infection. Robust inflammatory cytokine responses are observed in herpes simplex virus (HSV)-infected animals and cells. Our studies have demonstrated that Toll-like receptor 2 (TLR2) activation by HSV results in NF-κB activation with concomitant inflammatory cytokine production and that TLR2 activation plays a critical role in HSV-induced pathology and mortality. Here we demonstrate that the HSV-1 immediate-early ICP0 protein reduces the TLR2-mediated inflammatory response to HSV 1 (HSV-1) infection. Expression of ICP0 alone is sufficient to block TLR2-driven responses to both viral and nonviral ligands at or downstream of the MyD88 adaptor and upstream of p65. ICP0 alone can also reduce the levels of MyD88 and Mal (TIRAP). In HSV-infected cells, the E3 ligase function of ICP0 and cellular proteasomal activity are required for the inhibitory activity. Our results argue for a model in which ICP0 promotes the degradation of TLR adaptor molecules and inhibition of the inflammatory response, much as it inhibits the interferon response by sequestration and degradation of interferon regulatory factor 3 (IRF-3).


Mosaic evolution in an asymmetrically feathered troodontid dinosaur with transitional features.
Asymmetrical feathers have been associated with flight capability but are also found in species that do not fly, and their appearance was a major event in feather evolution. Among non-avialan theropods, they are only known in microraptorine dromaeosaurids. Here we report a new troodontid, Jianianhualong tengi gen. et sp. nov., from the Lower Cretaceous Jehol Group of China, that has anatomical features that are transitional between long-armed basal troodontids and derived short-armed ones, shedding new light on troodontid character evolution. It indicates that troodontid feathering is similar to Archaeopteryx in having large arm and leg feathers as well as frond-like tail feathering, confirming that these feathering characteristics were widely present among basal paravians. Most significantly, the taxon has the earliest known asymmetrical troodontid feathers, suggesting that feather asymmetry was ancestral to Paraves. This taxon also displays a mosaic distribution of characters like Sinusonasus, another troodontid with transitional anatomical features.


Effects of isometric handgrip training on blood pressure among hypertensive patients seen within public primary healthcare: a randomized controlled trial.
Meta-analyses have demonstrated that isometric handgrip training (IHT) decreases blood pressure in hypertensive individuals. Nonetheless, most studies were conducted in laboratory settings and its effects in real-world settings remain unclear. To analyze the effects of IHT on office and ambulatory blood pressure in hypertensive patients attended within primary healthcare. Randomized controlled trial conducted in primary healthcare units within the Family Health Program, Petrolina, Pernambuco, Brazil. 63 hypertensive patients (30-79 years old; 70% female) were randomly allocated into IHT or control groups. IHT was performed three times per week (4 x 2 minutes at 30% of maximal voluntary contraction, one-minute rest between bouts, alternating the hands). Before and after the 12-week training period, office and ambulatory blood pressure and heart rate variability were obtained. The significance level was set at P < 0.05 (two-tailed testing) for all analyses. IHT significantly decreased office systolic blood pressure (IHT: 129 ± 4 versus 121 ± 3 mmHg, P < 0.05; control: 126 ± 4 versus 126 ± 3 mmHg, P > 0.05), whereas there was no effect on diastolic blood pressure (IHT: 83 ± 3 versus 79 ± 2 mmHg, P > 0.05; control: 81 ± 3 versus 77 ± 3 mmHg, P > 0.05). Heart rate variability and ambulatory blood pressure were not altered by the interventions (P > 0.05 for all). IHT reduced office systolic blood pressure in hypertensive patients attended within primary care. However, there were effects regarding diastolic blood pressure, ambulatory blood pressure or heart rate variability. NCT03216317.


Lipid composition of the liver oil of deep-sea sharks from the Chatham Rise, New Zealand.
Deep-sea sharks approach neutral buoyancy by means of a large liver that contains large amounts of low-density lipids, primarily squalene and diacyl glyceryl ether (DAGE). As an animal increases in size and matures sexually, many biochemical changes take place within the animal. It was hypothesized that maintenance of neutral buoyancy in deep-sea sharks involves fine-scale changes in the chemical composition of the liver oil as individual sharks grow and develop. To test this hypothesis, the lipid composition of liver oil for individuals of different size and sex of deep-sea sharks from the Chatham Rise, New Zealand was compared. The composition of liver oil varied within and among species. Several species contained large amounts of squalene and DAGE, whereas only traces of these lipids were present in other species. The amounts of squalene and DAGE in liver oil were inversely related, and squalene content tended to decrease as sharks increased in size. Species with high squalene levels (> 80%) in liver oil were not abundant on the Chatham Rise, although levels of DAGE (a lipid of increasing commercial interest) were elevated in many species. Maintenance of neutral buoyancy in deep-sea sharks appears to involve changes in the composition of low-density liver lipids as the sharks increase in size and mature.


Intrinsic Connectivity Network-Based Classification and Detection of Psychotic Symptoms in Youth With 22q11.2 Deletions.
22q11.2 Deletion syndrome (22q11DS) is a genetic disorder associated with numerous phenotypic consequences and is one of the greatest known risk factors for psychosis. We investigated intrinsic-connectivity-networks (ICNs) as potential biomarkers for patient and psychosis-risk status in 2 independent cohorts, UCLA (33 22q11DS-participants, 33 demographically matched controls), and Syracuse (28 22q11DS, 28 controls). After assessing group connectivity differences, ICNs from the UCLA cohort were used to train classifiers to distinguish cases from controls, and to predict psychosis risk status within 22q11DS; classifiers were subsequently tested on the Syracuse cohort. In both cohorts we observed significant hypoconnectivity in 22q11DS relative to controls within anterior cingulate (ACC)/precuneus, executive, default mode (DMN), posterior DMN, and salience networks. Of 12 ICN-derived classifiers tested in the Syracuse replication-cohort, the ACC/precuneus, DMN, and posterior DMN classifiers accurately distinguished between 22q11DS and controls. Within 22q11DS subjects, connectivity alterations within 4 networks predicted psychosis risk status for a given individual in both cohorts: the ACC/precuneus, DMN, left executive, and salience networks. Widespread within-network-hypoconnectivity in large-scale networks implicated in higher-order cognition may be a defining characteristic of 22q11DS during adolescence and early adulthood; furthermore, loss of coherence within these networks may be a valuable biomarker for individual prediction of psychosis-risk in 22q11DS.


Exploratory analysis of social cognition and neurocognition in individuals at clinical high risk for psychosis.
Neurocognition and social cognition are separate but related constructs known to be impaired in schizophrenia. The aim of this study was to extend the current knowledge of the relationship between social cognition and neurocognition in individuals at clinical high risk (CHR) of developing psychosis by examining, in a large sample, the associations between a wide range of neurocognitive tasks and social cognition. Participants included 136 young people at CHR. Specific domains within neurocognition and social cognition were compared using Spearman correlations. Results showed that poor theory of mind correlated with low ratings on a wide range of neurocognitive tasks. Facial affect was more often associated with low ratings on spatial working memory and attention. These results support a link between neurocognition and social cognition even at this early stage of potential psychosis, with indication that poorer performance on social cognition may be associated with deficits in attention and working memory. Understanding these early associations may have implications for early intervention.


Meta-analysis of the differential effects of habitat fragmentation and degradation on plant genetic diversity.
Genetic diversity is a key factor for population survival and evolution. However, anthropogenic habitat disturbance can erode it, making populations more prone to extinction. Aiming to assess the global effects of habitat disturbance on plant genetic variation, we conducted a meta-analysis based on 92 case studies obtained from published literature. We compared the effects of habitat fragmentation and degradation on plant allelic richness and gene diversity (equivalent to expected heterozygosity) and tested whether such changes are sensitive to different life-forms, life spans, mating systems, and commonness. Anthropogenic disturbance had a negative effect on allelic richness, but not on gene diversity. Habitat fragmentation had a negative effect on genetic variation, whereas habitat degradation had no effect. When we examined the individual effects in fragmented habitats, allelic richness and gene diversity decreased, but this decrease was strongly dependent on certain plant traits. Specifically, common long-lived trees and self-incompatible species were more susceptible to allelic richness loss. Conversely, gene diversity decreased in common short-lived species (herbs) with self-compatible reproduction. In a wider geographical context, tropical plant communities were more sensitive to allelic richness loss, whereas temperate plant communities were more sensitive to gene diversity loss. Our synthesis showed complex responses to habitat disturbance among plant species. In many cases, the absence of effects could be the result of the time elapsed since the disturbance event or reproductive systems favoring self-pollination, but attention must be paid to those plant species that are more susceptible to losing genetic diversity, and appropriate conservation should be actions taken.


Studies on the fluidity of milk lipids of mothers from three socioeconomic groups of West Bengal, India.
This study evaluated the fluid character of human milk by determining the mean melting points (MMP) of fatty acids of milk lipid of Bengali mothers. Fatty acid methyl esters were analyzed by gas liquid chromatography. MMPs were calculated from the fatty acid concentration (% w/w) and their molar mass. Phospholipid content of samples was also determined. The MMPs of milk lipid of higher income group (n = 48), medium income group (n = 57) and lower income group (n = 112) mothers were found to be 31.33°C ± 0.61, 36.86°C ± 0.64 and 35.11°C ± 0.65, respectively, which showed a significant correlation with the fatty acid composition, with P < 0.0001, 0.003, 0.0001, respectively. The average MMP of milk lipid (34.43°C ± 0.63) of these three groups was below the core body temperature (37.4°C) of human beings, which perhaps helps in maintaining the milk fluidity as well as lipid digestion in breastfed infants.


Tracking the apparent location of targets in interpolated motion.
Under appropriate conditions, a target moving in discrete steps can appear to move smoothly and continuously even within the portions of the path where no physical stimulus is present. We investigated the nature of this interpolated motion in attentive tracking displays as well as apparent motion. The results showed that the apparent location of the target moved smoothly through space between the two discrete locations and the judgements of interpolated motion for attentive tracking and apparent motion were comparable to those for continuous motion in both the perceived path and the precision of the judgements. There were few, if any, differences between judgements for real and interpolated motion. An alignment procedure showed that the smooth change in location judgements was real and not a consequence of averaging across discrete locations actually seen on each trial. We also found that the slowest alternation rate which supported accurate location judgements corresponded to a critical SOA of about 500 ms, similar to the longest SOA which supported a subjective impression of motion in the display. Deviations from a constant velocity which were shorter than 200 ms did not register in the judged motion path, suggesting a fairly long time constant for the integration of velocity information into the perceived motion. These results suggest a specialized motion analysis which provides an accurate, explicit model of the interpolated motion path.


Glucocorticoid receptor activation leads to up-regulation of adenosine A1 receptors and down-regulation of adenosine A2 responses in DDT1 MF-2 smooth muscle cells.
The effect of glucocorticoid treatment of DDT1 MF-2 smooth muscle cells on the signaling via two adenosine receptors with opposing actions on cAMP generation was examined. Treatment with dexamethasone caused a dose- and time-dependent increase in the number of adenosine A1 receptors but did not affect the KD or the proportions of receptors in high and low affinity states. The EC50 was 1 nM dexamethasone, and maximal response was achieved after 24 hr. The number of receptors was increased by approximately 50%. Other steroid hormones, including aldosterone, progesterone, testosterone, and estrogen, were much less effective, and addition of the glucocorticoid receptor antagonist RU 486 or the protein synthesis inhibitor cycloheximide prevented the up-regulation, showing that the effect was mediated via a glucocorticoid receptor-specific mechanism that involves protein synthesis. In dexamethasone-treated cells the A1 receptor agonist (-)-N6-phenylisopropyladenosine [(R)-PIA] was 3 times more potent as an inhibitor of cAMP formation induced by isoprenaline than in untreated cells. ADP ribosylation of inhibitory GTP-binding proteins by pertussis toxin completely prevented (R)-PIA from inhibiting cAMP accumulation. A further analysis of the different GTP-binding proteins, including the three Gi subtypes (Gi1, Gi2, and Gi3), revealed no quantitative or qualitative change after dexamethasone treatment. In addition, the adenosine A2 receptors were down-regulated, as indicated by the fact that the ability of the A2 receptor agonist 5'-N-ethylcarboxamidoadenosine to increase cAMP formation was decreased by 20-30% in dexamethasone-treated cells. In summary, we have shown that A1 and A2 receptors on the same cell are differentially regulated by glucocorticoids and that this has functional importance in the regulation of cAMP accumulation.


Towards open boundary molecular dynamics simulation of ionic liquids.
We extend the use of the adaptive resolution (AdResS) method in its grand canonical-like version (GC-AdResS) to the molecular dynamics simulation of 1,3-dimethylimidazolium chloride. We show that the partitioning of the total system in a subsystem of interest with atomistic details and a reservoir of coarse-grained particles leads to satisfactory results. The challenging aspect of this study, compared to previous AdResS simulations, is the presence of charged particles and the necessity of addressing the question about the minimal physical input needed to model the coarse-grained particles in the reservoir. We propose two different approaches and show that in both cases they are sufficient to capture the decisive physical characteristics that allow a valid system-reservoir coupling. The technically satisfactory results pave the way for the multiscale analysis of ionic liquids and truly open boundary molecular simulations.


Mutagenesis analysis of the murine leukemia virus matrix protein: identification of regions important for membrane localization and intracellular transport.
We have created two sets of substitution mutations in the Moloney murine leukemia virus (Mo-MuLV) matrix protein in order to identify domains involved in association with the plasma membrane and in incorporation of the viral envelope glycoproteins into virus particles. The first set of mutations was targeted at putative membrane-associating regions similar to those of the human immunodeficiency virus type 1 matrix protein, which include a polybasic region at the N terminus of the Mo-MuLV matrix protein and two regions predicted to form beta strands. The second set of mutations was created within hydrophobic residues to test for the production of virus particles lacking envelope proteins, with the speculation of an involvement of the membrane-spanning region of the envelope protein in incorporation into virus particles. We have found that mutation of the N-terminal polybasic region redirected virus assembly to the cytoplasm, and we show that tryptophan residues may also play a significant role in the intracellular transport of the matrix protein. In total, 21 mutants of the Mo-MuLV matrix protein were produced, but we did not observe any mutant virus particles lacking the envelope glycoproteins, suggesting that a direct interaction between the Mo-MuLV matrix protein and envelope proteins either may not exist or may occur through multiple redundant interactions.


Muscular phenotype description of abnormal THOC2 splicing.
Until recently, the disease known to be associated with THOC2 mutations was Intellectual developmental disorder, X-linked 12 (MIM300957). However, recently, fetal arthrogryposis multiplex congenita has been associated with a specific splice site mutation in the THOC2 gene. We report a family with the same splice site mutation in the THOC2 gene involved in fetal arthrogryposis as well. We provide the first description of the muscular phenotype of this disease which reveals the presence of cytoplasmic bodies. Our findings expand the clinical phenotype of THOC2 gene related defects.


Early mother-child dyadic pathways to childhood obesity risk: A conceptual model.
Understanding the emotional quality of the mother-child dyadic relationship and parent-child feeding interactions may further clarify early developmental pathways to eating behaviours and obesity risk. The quality of parent-child relationships fosters all aspects of child development but has not yet been extensively examined in relation to childhood weight gain. The aim of this paper is to propose a conceptual model, which outlines early mother-child dyadic pathways linking parent-child feeding interactions to child body mass index, where parent-child relationships have a central role. It maps out individual and dyadic mother-child factors (i.e., attachment, child temperament and maternal mental health) that influence the nature and quality of parent-child feeding interactions from infancy to toddlerhood. Our model bridges the gap between research fields by bringing together key maternal and child factors implicated in child development. Understanding early parent-child feeding interactional patterns and their influence on child self-regulation and eating behaviours may be relevant to multidisciplinary approaches toward preventing childhood obesity. High quality quantitative and observational data capturing meaningful parent, child and dyadic level interactions around food contexts, attachment security, maternal mental health, child temperament and self-regulation will help to inform new, aetiologically important, targets for preventative intervention.


Interrelation between MEPP amplitude and MEPP frequency in different regions along the frog neuromuscular junction.
Experiments were done to study the relationship between miniature endplate potential (MEPP) frequency and MEPP amplitude in different regions along the frog neuromuscular junction (NMJ). The position of the release site producing a MEPP and the amplitude of a MEPP at its release site were evaluated by using the spatial decay method after simultaneous intracellular recordings at each distal end of the NMJ. The NMJ was divided in 10 regions of equal length. It was found that MEPP amplitude and MEPP frequency are smaller in distal regions than in proximal ones. Moreover, we observed a logarithmic relationship between MEPP frequency of a given region and the mean MEPP amplitude of the same region. These results suggest that the probability to produce a MEPP and the quantity of neurotransmitter liberated are two synaptic functions controlled or affected by common mechanisms.


Community consultation for prehospital research: experiences of study coordinators and principal investigators.
To assess principal investigators' and study coordinators' views and experiences regarding community consultation in a multicenter trial of prehospital treatment for status epilepticus conducted under an exception from informed consent for research in emergency settings. Principal investigators and study coordinators at all 17 hubs for the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) were invited to complete a web-based survey regarding community consultation at their site for RAMPART. Major domains included 1) perceived goals of community consultation, 2) experiences with and views of community consultation methods used, 3) interactions with IRB regarding community consultation, and 4) general satisfaction and lessons learned. Descriptive statistics were tabulated for Likert scale data; relevant themes were reported for text-based data. Twenty-eight individuals (16 coordinators and 12 investigators) representing all 17 RAMPART hubs completed the survey. Respondents considered multiple community consultation goals to be important, with least support for the role of community consultation in altering study design. All sites used multiple methods (median = 5). The most widely used, and generally favored, method was attending previously scheduled meetings of existing groups. Respondents expressed frustration with low attendance and responsiveness at open public meetings. Coordinators and investigators in this trial viewed community consultation efforts as successful but reported real challenges generating public interest. Individuals with the condition under study were found to be more engaged and supportive of the trial. Respondents endorsed numerous potential goals of the community consultation process and often combined methods to achieve these goals.


Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.
DNA ends exposed after introduction of double-strand breaks (DSBs) undergo 5'-3' nucleolytic degradation to generate single-stranded DNA, the substrate for binding by the Rad51 protein to initiate homologous recombination. This process is poorly understood in eukaryotes, but several factors have been implicated, including the Mre11 complex (Mre11-Rad50-Xrs2/NBS1), Sae2/CtIP/Ctp1 and Exo1. Here we demonstrate that yeast Exo1 nuclease and Sgs1 helicase function in alternative pathways for DSB processing. Novel, partially resected intermediates accumulate in a double mutant lacking Exo1 and Sgs1, which are poor substrates for homologous recombination. The early processing step that generates partly resected intermediates is dependent on Sae2. When Sae2 is absent, in addition to Exo1 and Sgs1, unprocessed DSBs accumulate and homology-dependent repair fails. These results suggest a two-step mechanism for DSB processing during homologous recombination. First, the Mre11 complex and Sae2 remove a small oligonucleotide(s) from the DNA ends to form an early intermediate. Second, Exo1 and/or Sgs1 rapidly process this intermediate to generate extensive tracts of single-stranded DNA that serve as substrate for Rad51.


2,3-diamino-2,3-dideoxy-D-glucofuranurono-6,3-lactam from the hydrolysate of Pseudomonas aeruginosa P14 lipopolysaccharide.
An unknown amino sugar, U-7, which had been detected in the hydrolysate of the polysaccharide fraction (F-A) of Pseudomonas aeruginosa P14 lipopolysaccharide, was isolated from the hydrolysate of whole cells of this micro-organism and converted into the N-acetyl derivative (U-7NAc). On the basis of i.r.-absorption spectrometry, 13C-n.m.r. and 1H-n.m.r. spectroscopy and mass spectrometry, the structure of compound U-7NAc was identified as 2-acetamido-3-amino-2,3-dideoxyhexofuranurono-6,3-lactam. The configuration of compound U-7NAc was then unequivocally identified as 2-acetamido-3-amino-2,3-dideoxy-D-glucofuranurono-6,3-lactam by comparing the synthetic and natural compounds. Compound U-7 and synthetic 2,3-diamino-2,3-dideoxy-D-glucofuranurono-6,3-lactam showed the same behaviour on chromatography. G.l.c.--mass-spectral analyses of fraction F-A and synthetic 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid after methanolyses and trimethylsilylations showed the presence of the same derivative. It was concluded that the amino sugar U-7 was produced from the 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid residue present in fraction F-A.


[Microfilariae in vaginal exudates from Argentinian apes].
The finding of Dipetalonema gracile larves in vaginal content of capuchin monkeys (Cebus apella) was reported. The sizes of microfilarias, which did not present capsule, were 110-160 microns long and 4-5 microns wide. Microfilarias did not find in peripheral blood. Assuming that the cycle of this worm is not yet elucidated, the authors postulate that the presence of larves in the female genital tract could relate with venereal transmission.