Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis.
Endometriosis is a chronic gynecological disease, affecting up to 10% of reproductive-age women. The exact cause of the disease is unknown; however, it is a heritable condition affected by multiple genetic, epigenetic, and environmental factors. Previous studies reported variations in the epigenetic patterns of numerous genes known to be involved in the aberrant modulation of cell cycle steroidogenesis, abnormal hormonal, immune and inflammatory status in endometriosis, apoptosis, adhesion, angiogenesis, proliferation, immune and inflammatory processes, response to hypoxia, steroidogenic pathway and hormone signaling are involved in the pathogenesis of endometriosis. Accumulating evidence suggest that various epigenetic aberrations may contribute to the pathogenesis of endometriosis. Among them, DNA methyltransferases, histone deacetylators, and non-coding microRNAs demonstrate differential expression within endometriotic lesions and in the endometrium of patients with endometriosis. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may contribute to the discovery of a useful prognostic biomarker, which could aid in the future earlier detection, timely diagnosis, and initiation of a new approach to the treatment of endometriosis, as well as inform us about the effectiveness of treatment and the stage of the disease. As the etiology of endometriosis is highly complex and still far from being fully elucidated, the presented review focuses on different approaches to identify the genetic and epigenetic links of endometriosis and its pathogenesis.


Public reporting of antibiotic timing in patients with pneumonia: lessons from a flawed performance measure.
The administration of antibiotics within 4 hours to patients with community-acquired pneumonia has been criticized as a quality standard because it pressures clinicians to rapidly administer antibiotics despite diagnostic uncertainty at the time of patients' initial presentations. The measure was recently revised (to 6 hours) in response to this criticism. On the basis of the experience with the 4-hour rule, the authors make 5 recommendations for the development of future publicly reported quality measures. First, results from samples with known diagnoses should be extrapolated cautiously, if at all, to patients without a diagnosis. Second, for some measures, "bands" of performance may make more sense than "all-or-nothing" expectations. Third, representative end users of quality measures should participate in measure development. Fourth, quality measurement and reporting programs should build in mechanisms to reassess measures over time. Finally, biases, both financial and intellectual, that may influence quality measure development should be minimized. These steps will increase the probability that future quality measures will improve care without creating negative unintended consequences.


miRNAs: early prognostic biomarkers for Type 2 diabetes mellitus?
Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and is associated with peripheral insulin resistance. The currently used therapies aim to delay progression of T2DM. Their efficacy could drastically be improved if implemented at earlier stages. Classical diagnostic markers (blood glucose and HbA1C) are generally detected once metabolic imbalance has already set in. Therefore, development of biomarkers for early diagnosis would help identify individuals at risk for developing T2DM. Along with genetic predisposition, epigenetics also plays a major role in T2DM development. In this review, we discuss the potential role of early diagnostic markers such as circulating miRNAs, studies done so far and challenges to be considered while taking into account the novel role of miRNAs as prognostic biomarkers.


Tree species diversity increases soil microbial carbon use efficiency in a subtropical forest.
Plant communities strongly influence soil microbial communities and, in turn, soil carbon (C) cycling. Microbial carbon use efficiency (CUE) is an important parameter for predicting soil C accumulation, yet how plant and soil microbial community traits influence microbial CUE remains poorly understood. Here, we determined how soil microbial CUE is influenced by plant and soil microbial community traits, by studying a natural gradient of plant species diversity in a subtropical forest. Our results showed that microbial CUE increased with increasing tree species diversity, suggesting a correlation between plant community traits and soil C storage. The specific soil properties that explained the greatest variation in microbial CUE were associated with microbial communities (biomass, enzyme activities and the ratio of oligotrophic to copiotrophic taxa); there were weaker correlations with plant-input properties, soil chemistry and soil organic C quality and its mineral protection. Overall, high microbial CUE was associated with soil properties correlated with increased tree species diversity: higher substrate availability (simple SOM chemical structures and weak mineral organic associations) and high microbial growth rates despite increased community dominance by oligotrophic strategists. Our results point to a mechanism by which increased tree species diversity may increase the forest C sink by affecting carbon use with the soil microbial community.


[Cystic liver, an indication for liver transplantation or decompressive resection?].
In patients suffering from polycystic liver disease sclerosing therapy, decompressive hepatic resection and liver transplantation represent the main therapeutic options. Since 1987, 10 females with highly symptomatic polycystic liver disease underwent hepatic resection for decompression (five left lateral bisegmentectomies, one left hemihepatectomy, one right central and three bilateral atypical resections). Despite of a 0% lethality 3 patients developed complications, in two cases an abscess had to be drained and in one case a postoperatively increasing hepatic insufficiency required urgent liver transplantation. Patient's symptoms were remarkably improved in 8 cases, but only 6 patients had a long lasting benefit over years. One patient was resected a second time three years after the first operation and is free of symptoms for another five years. 6/96 the "European Liver Transplant Registry" has listed 81 patients after liver transplantation because of polycystic liver disease. 5-year survival is 78.2%. So liver transplantation offers a therapeutic alternative for patients severely suffering from symptoms or increasing hepatic insufficiency.


[Toxoplasmosis after antineoplastic therapy in non-Hodgkin lymphoma. Demand of preventive measures].
BACKGROUND. Toxoplasmosis is an opportunistic infection reported in several groups of inmunosupressed patients. It is considered uncommon in patients with lymphoproliferative disorders and in bone marrow transplant recipiets (BMT). Nevertheless, recent reviews have reported cases of cerebral and disseminated toxoplasmosis in BMT recipients, particularly among patients with IgG antibodies to Toxoplasma sp. prior to BMT and antineoplastic treatment. PATIENTS AND METHODS. Two cases of toxoplasmosis are reported of patients with non-Hodgkin lymphoma who did not have graft-versus-host-disease and with positive antitoxoplasma serologic response. In the first patient, the predominant clinical picture was febrile neutropenia without source, with good response to specific treatment for toxoplasmosis; in the second patient, and autologous BMT was performed and six months later the patient developed a retino-choroiditis by toxoplasmosis reactivation. CONCLUSIONS. The excessive morbidity and mortality associated with toxoplasmosis reactivations in lymphomyeloproliferative neoplasms with antineoplastic therapy and both allogenic and autologous BMT, demand preventive measures. The pretransplant serologic tests can be helpful in evaluating the potential risk of suffering a reactivation by Toxoplasma sp. and considering the administration of chemoprophylaxis in selected patients with positive serology.


The incidence of Ceutorhynchus species in winter oilseed rape in Lithuania.
Research on identification of Ceutorhynchus Species in winter oilseed rape was done during the vegetation seasons of 2010 and 2011. Weevils were sampled in using Moericke's type yellow water traps during the period from March to harvest of oilseed rape. Eleven species of weevils were identified: C. pallidactylus, C. obstrictus C. floralis C. napi, C. rapae, C. erysimi, C. sulcicollis, C. ruglosus, C. gallorheranus, C. pleurostigma and C. rusticus. The most common species were C. pallidactylus, C. obstrictus and C. floralis. During experimental period the first catches of C. pallidactylus were registered at the time when an average daily air temperature reached 8.4-9.2 degrees C and C. obstrictus--at the temperature 16.6-19.9 degrees C.


In vivo monitoring of topical therapy for acne with reflectance confocal microscopy.
Acne vulgaris is a common disease of the pilosebaceous unit. The aim of the study was to evaluate compartment-specific treatment action through the microscopic non-invasive imaging of skin changes. Mild-moderate acne patients, that were prescribed a topical anti-acne product, were followed by clinical and reflectance confocal microscopy (RCM) imaging every 14 days to 6 weeks. Mean and standard deviation of the scores were analyzed for each time point. After 2 weeks, the RCM count of papules/pustules and the RCM scores of exocytosis and dermal inflammation, decreased substantially. After 4 weeks, the RCM number of comedos was reduced. After 6 weeks, the number of regular follicles increased, while the infundibula with thickened bright border decreased significantly. The progressive reduction in the clinical scores was correlated with the improvement of the RCM parameters. RCM study of acne skin showed a different timing for inflammatory and hyperkeratotic components to achieve a significant reduction during topical therapy with the association of retinoid and antibacterial molecules. The microscopic changes observed showed the regularization of the skin and the improvement of acne related features. RCM may represent a useful tool for the objective assessment of treatment efficacy and individual response evaluation.


Assessing the gene space in draft genomes.
Genome sequencing projects have been initiated for a wide range of eukaryotes. A few projects have reached completion, but most exist as draft assemblies. As one of the main reasons to sequence a genome is to obtain its catalog of genes, an important question is how complete or completable the catalog is in unfinished genomes. To answer this question, we have identified a set of core eukaryotic genes (CEGs), that are extremely highly conserved and which we believe are present in low copy numbers in higher eukaryotes. From an analysis of a phylogenetically diverse set of eukaryotic genome assemblies, we found that the proportion of CEGs mapped in draft genomes provides a useful metric for describing the gene space, and complements the commonly used N50 length and x-fold coverage values.


Microporous organic materials from hydrophobic dipeptides.
In the last few years dipeptides with two hydrophobic residues (hydrophobic dipeptides) have emerged as an unexpected source of stable microporous organic materials. Supramolecular self-assembly of the rather small building blocks is dictated by stringent demands on the hydrogen-bond formation by the peptide main chains and the aggregation of hydrophobic entities in the side chains. A systematic survey of structures derived from single-crystal X-ray diffraction studies has revealed the existence of two large classes of structures, differing in the dimensionality of the hydrogen-bonding patterns in the crystals and the nature of the channels. The present review summarizes the structural properties of the microporous dipeptides and discusses their potential applications.


Examination of the frequency of upward and downward fluctuations in the pressure obtained from the cuff pressure-time curve by continuous measurement of endotracheal tube cuff pressure during thyroid surgery: a case series.
Few studies examined time-to-time changes of cuff pressure of an endotracheal tube during surgery. We retrospectively analyzed the changes of cuff pressure during thyroid surgery and examined its relationships with postoperative airway complications. Cuff pressure was initially adjusted at 26 cmH2O and continuously measured in 61 patients. The cuff pressure-time curve dynamically fluctuated, and exceeded 30 cmH2O in all patients, whereas decreased to ≤ 20 cmH20 in 42 (69%) patients. Ratio of the period with such an increase and decrease of cuff pressure to the total duration of surgery were 40% (28-66%) and 9% (0-21%), respectively (median, interquartile range). No patients showed symptoms of airway stenosis requiring treatment except one who developed recurrent laryngeal nerve palsy. No patients had lower respiratory tract infection. Cuff pressure dynamically fluctuated during thyroid surgery. Preventing an increase as well as decrease of cuff pressure is required.


Neurotoxicant-induced animal models of Parkinson's disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration.
The etiologic basis of Parkinson's disease (PD), the second most common age-related neurodegenerative disorder, is unknown. Recent epidemiological and experimental studies indicate that exposure to environmental agents, including a number of agricultural chemicals, may contribute to the pathogenesis of this disorder. Animal models are important tools in experimental medical science for studying the pathogenesis and therapeutic intervention strategies of human diseases. Since many human disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by neurotoxic agents. Recently, agricultural chemicals, when administrated systemically, have been shown to reproduce specific features of PD in rodents, thus opening new routes for the development of animal models for this disorder. In addition to a brief historical overview of the toxin-induced PD models, this study provides a detailed description of exiting models in which Parkinsonism is initiated via the exposure of animals to such agricultural chemicals as rotenone, paraquat, and maneb. Suggested neurotoxicity mechanisms of these chemicals are considered, and the major lessons learned from the analysis of pesticide-induced PD models are discussed.


[In vivo fluorescence spectroscopy of human skin: principles and application to penetration measurements].
The fluorescence properties of untreated human skin and the penetration of topically applied drugs were measured in vivo using a commercially available fluorescence spectrometer which was adapted to in vivo-measurements on skin by means of optical fibres and a remote viewing head. The intensity and characteristics of the intrinsic fluorescences of human skin and their dependences upon several parameters like pigmentation, water content of the skin or depth of the horny layer are shown. The principles of the penetration measurements based on the fluorescence of the skin or the fluorescence of the drug topically applied to the skin are described and measurements of the penetration of some drugs are reported.


[Study on regularity of drug use in Tibetan medicine treating hypertension based on multi-center clinical medical records and "prescription-property-efficacy-disease"].
This study aimed to explore the rule of Tibetan medicine in clinical treatment of hypertension( k Hrag-rLung-stod-vtshangs) and analyze the characteristics of its prescriptions. One hundred and thirty-seven cases of hypertension treated Tibetan medicine were collected. Data mining,Gephi,Cytoscape and other methods and software were used to analyze the characteristics of Tibetan medicine. The results showed that there were 44 cases of r Lung-type hypertension in clinical medical records,while 57 cases of k Hrag-type hypertension. There were 103 treatment prescriptions. The frequency of these prescriptions covered Twenty-five Yuganzi Pills( 96 times),Seventy Pearl Pills( 80 times),Eight Chenxiang Pills( 75 times),and Sanwei Ganlu Powder( 62 times),and they were highly correlated,with confidence greater than 95%. There were 332 prescriptions involved in the prescriptions which is core prescription medicines. This study first proposed the dosage analysis method of Tibetan medicine prescription medicines,and obtained the more dosage of Chebulae Fructus,Phyllanthi Fructus,Aucklandiae Radix,Aquilariae Lignum Resinatum and so on. The correlation analysis of the prescription medicines found that Carthami Flos,Myristicae Semen,Bambusae Concretio Silicea,Caryophylli Flos,Amomi Fructus Rotundus led by Tsaoko Fructus had a high correlation and a confidence greater than 75%. These herbs were guaranteed when Tibetan medicine was used in combination. The key drugs for protecting viscera and regulating the three gastric fires. The prescription is mainly cold,blunt,sparse and rough. Its efficacy focuses on the pathogenesis of blood fever,blood stickiness and venous blockage caused by heat,sharpness,odor and stickiness. It mainly treats Tibetan medicine diseases such as k Hrag-r Lung-stod-vtshangs and k Hrag-vpel( polyemia). It is suggested that Tibetan medicine has a three-in-one invisible treatment principle of " clearing blood-heat,opening vessel and regulating stomach-fire" in the treatment of hypertension,which attributed to both cardiovascular function and gastrointestinal metabolic function. This may be a significant and invisible knowledge of Tibetan medicine in the treatment of hypertension.


Extracellular vesicles and microRNAs in the regulation of cardiomyocyte differentiation and proliferation.
Cardiomyocyte differentiation and proliferation are essential processes for the regeneration of an injured heart. In recent years, there have been several reports highlighting the involvement of extracellular vesicles (EVs) in cardiomyocyte differentiation and proliferation. These EVs originate from mesenchymal stem cells, pluripotent stem cells, and heart constituting cells (cardiomyocytes, cardiac fibroblasts, cardiac progenitor cells, epicardium). Numerous reports also indicate the involvement of microRNAs (miRNAs) in cardiomyocyte differentiation and proliferation. Among them, miRNA-1, miRNA-133, and miRNA-499, recently demonstrated to promote cardiomyocyte differentiation, and miRNA-199, shown to promote cardiomyocyte proliferation, were found effective in various studies. MiRNA-132 and miRNA-133 have been identified as cargo in EVs and are reported to induce cardiomyocyte differentiation. Similarly, miRNA-30a, miRNA-100, miRNA-27a, miRNA-30e, miRNA-294 and miRNA-590 have also been identified as cargo in EVs and are shown to have a role in the promotion of cardiomyocyte proliferation. Regeneration of the heart by EVs or artificial nanoparticles containing functional miRNAs is expected in the future. In this review, we outline recent advancements in understanding the roles of EVs and miRNAs in cardiomyocyte differentiation and proliferation. Additionally, we explore the related challenges when utilizing EVs and miRNAs as a less risky approach to cardiac regeneration compared to cell transplantation.


Role of endovascular intervention in patients with diabetic foot ulcer and concomitant peripheral arterial disease.
The aim of this study was to evaluate wound healing, major amputation and mortality in patients with diabetic foot ulcer and peripheral arterial disease (PAD), and to compare the group decided to have an endovascular intervention with groups referred to conservative treatment or to those judged as unreconstructable. A retrospective two-year review of all patients with diabetic foot ulcers and PAD presented at an interdisciplinary diabetic foot round 2006-2007 at Malmö University Hospital, Sweden, was performed. Independent predictive factors of insufficient ulcer healing, amputation and mortality during follow-up were analysed according to treatment decisions at the diabetic foot round. A total of 135 limbs in 115 consecutive diabetic patients with foot ulcers were included. Median age was 73 years and 41% were women. During a median follow-up time of 17 months, 44% of the ulcers did not heal, 15% of the limbs underwent major amputation and 42% died. Ulcer depth with a Wagner grade ≥3 (hazard ratio [HR] 5.8; 95% confidence interval [CI] 2.6-12.9), CRP (HR 1.007; 95% CI 1.002-1.012, and impaired run-off (HR 3.0; 95% CI 1.03-8.9) were independent risk factors for incomplete wound healing. The three treatment decision groups: attempt for endovascular leg revascularization (N.=75), conservative (N.=42) and unreconstructable (N.=18) showed no significant difference in terms of wound healing, major amputation or death. Patients with diabetic foot ulcers and concomitant PAD are at high risk for limb loss and premature death. Ulcer depth, CRP and impaired run-off are independent risk factors for incomplete wound healing. There is an apparent need for prospective controlled studies to better define the role of endovascular therapy in this subset of diabetic foot ulcer patients.


The Northwestern University Triplet Study. II: Fourteen triplet pregnancies delivered between 1981 and 1986.
Fourteen triplet deliveries conducted between 1 January 1981 and 30 June 1986 at the principal teaching hospitals of Northwestern University Medical School are reviewed. Maternal demographic characteristics are listed, as are the obstetric outcomes, including mode of delivery, and the fetal outcome. The recent literature of triplet delivery is reviewed. The rate of triplet delivery in our study was 0.37 per 1,000 live births. About two-thirds of the pregnancies resulted from the use of fertility-inducing agents. Ultrasonic confirmation was available in all cases. The majority of women were delivered by cesarean section (85%). No consistent pattern of presentation was seen. The mean weight of all 42 infants was 1,779 g (+/- 594). Unlike-sex triplets accounted for most of the sets (77%). The mean 5-min Apgar score of all infants was 9 and had no association with the order of deliveries. The weight differences by sex regardless of birth order were clinically insignificant. Neonatal mortality was 2.3%.


Strategies for reducing racial and ethnic disparities in health.
This report is the fourth in a series of programs made possible by a grant to Grantmakers In Health (GIH) from The Commonwealth Fund to bring grantmakers together with experts in policy, practice, and research to exchange information and ideas about key health issues facing the nation. On May 18, 2000, GIH convened a select group of grantmakers along with officials from the U.S. Department of Health and Human Services and other experts in research and practice for an Issue Dialogue on racial and ethnic disparities in health. Intended to both share lessons learned and stimulate new ideas, the Issue Dialogue proved to be a rich, although difficult discussion about the conditions that give rise to health disparities. Among the ideas discussed were the interaction of race and socioeconomic status on health, environmental justice, and the complexities of working with different racial and ethnic groups. At the same time, the forum focused on what health funders can do to support the development of programs to improve the health of minorities. This Issue Brief brings together key points from the day's discussion with factual information on racial and ethnic disparities in health and grantmaker activities drawn from a background paper prepared for Dialogue participants.


[New approaches to lecture medicine--or: what can we learn from television?].
The development of new media and high-performance Internet connections do not stop in front of the auditorium. The classic teaching course is in direct competition with the new media that provide some excellent illustrated and animated educational videos and clips. In order to bring students back into the classroom, it is mandatory to make teaching more attractive. One can, as we shall show in the following contribution, use popular television series for successful teaching. This approach is accepted by the students with great interest and allows us to teach our students also in the field of rare diseases.


Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2. Evidence for a gene-gene interaction.
In four large pedigrees with heterozygous familial hypercholesterolemia (FH) genetically linked to the low density lipoprotein receptor locus, we have observed a strong interaction between the presence of FH and a single apolipoprotein (apo) E2 allele, resulting in a markedly increased prevalence of type III dyslipoproteinemia (DLPIII). DLPIII was defined by chemical criteria. None of the patients with DLPIII had tuberous or palmar xanthomas characteristic of classically defined type III hyperlipoproteinemia. After exclusion of four persons with apo E 2-2 phenotype, there were 89 FH patients and 110 non-FH subjects. Definite DLPIII (defined as a very low density lipoprotein [VLDL] cholesterol to plasma triglyceride ratio greater than 0.30 with plasma triglycerides greater than or equal to 150 mg/dl) was present in 26% of 43 FH patients with a single E2 allele compared with only 3.4% of 29 non-FH subjects with an E2 allele (p = 0.003). To further characterize this interaction we performed a two-way analysis of covariance, after adjustment for age, sex, and body mass index, to test for any interaction between FH and the apo E loci. There was a statistically significant interaction between FH and the presence of a single E2 allele for the ratio of VLDL cholesterol to plasma triglycerides and for a newly derived estimate of beta-VLDL cholesterol concentration. Estimated beta-VLDL cholesterol level was strongly correlated with age in the subgroup with FH and an E2 allele but not in other subgroups. There was no difference in estimated beta-VLDL cholesterol between sexes. Correlation between estimated beta-VLDL cholesterol level and body mass index in persons older than 18 years was of only marginal significance and of similar magnitude in persons with or without an apo E2 allele. Present knowledge suggests that beta-VLDLs are highly atherogenic; if so, then a sizable subset of FH patients having at least one apo E2 allele and DLPIII may be at increased risk for premature coronary heart disease.


Identification of Mycoplasma ovipneumoniae and Mycoplasma arginini in sheep with pneumonia in North East of Iran.
Pneumonia due to Mycoplasma infections can cause serious health problems and economic losses in small ruminants industry. The aim of this study was isolation and identification of Mycoplasmas in sheep naturally infected with pneumonia in Northeastern Iran. This study used histopathology, culture and polymerase chain reaction (PCR) to examine samples from 50 lungs of sheep naturally infected with Mycoplasmas. Grossly, irregular consolidation with lobular or lobar to diffuse pattern in the cranioventral to caudal lobes of affected lungs were observed. Histopathologically, bronchointerstitial pneumonia in 38 (76%), and purulent to fibrinopurulent bronchopneumonia in 12 (24%) affected sheep were diagnosed. DNA was extracted from lung tissue samples and replicated using genus and species specific primers for Mycoplasma. Mycoplasma growth was observed in 3 (6%) of a total of 50 lung samples. Genus-specific Mycoplasma DNA was identified by PCR in 12 (24%) of samples. Two (4%) and 7 (14%) samples of these 12 cases were positive for reaction with species-specific primers of Mycoplasma ovipneumoniae and Mycoplasma arginini, respectively. Our results showed that M. ovipneumoniae and M. arginini were the two agents that can be involved in inducing lung consolidation and pneumonia in sheep and PCR was more successful than the culture in detecting Mycoplasmas.


Identification of quantitative trait loci affecting body composition in a mouse intercross.
Gravimetric analysis and dual energy x-ray absorptiometry densitometry were used to determine lean, fat, and bone tissue traits in a F(2) mouse population from a C57BL/6J and CASA/Rk intercross (B6CASAF2). These traits were used in a linkage analysis to identify quantitative trait loci that affect body composition. Linkage mapping showed that body weight (BW) loci on proximal chromosome 2 occurred in the same region as body length, lean tissue mass, and bone mineral content and on chromosome 13 in the same region as lean tissue mass, bone mineral density, and bone mineral content. Fat-related loci occurring on mid-chromosome 2 near 60 cM, proximal chromosome 6, and mid-chromosome 10 were distinct from BW, lean tissue, and bone tissue loci. In B6CASAF2 females, heterozygotes and CASA/Rk homozygotes at the chromosome 6 locus marker had higher body fat percentages, and this locus was responsible for 11% of the variance for body fat percentage. Female heterozygotes and C57BL/6J homozygotes at the chromosome 15 locus marker had higher bone mineral densities, and this locus could explain 8% of that trait's variance. A survey of the literature did not reveal any previous reports of fat-specific loci in the chromosomal 10 region near 42 cM reported in this study. The results of this study indicate that BW and BMI have limited usefulness as phenotypes in linkage or association studies when used as obesity phenotypes.


SAN: Side Adapter Network for Open-Vocabulary Semantic Segmentation.
This article concentrates on open-vocabulary semantic segmentation, where a well optimized model is able to segment arbitrary categories that appear in an image. To achieve this goal, we present a novel framework termed Side Adapter Network, or SAN for short. Our design principles are three-fold: 1) Recent large-scale vision-language models (e.g. CLIP) show promising open-vocabulary image classification capability; it is training-economized to adapt a pre-trained CLIP model to open-vocabulary semantic segmentation. 2) Our SAN model should be both lightweight and effective in order to reduce the inference cost-to achieve this, we fuse the CLIP model's intermediate features to enhance the representation capability of the SAN model, and drive the CLIP model to focus on the informative areas of an image with the aid of the attention biases predicted by a side adapter network. 3) Our approach should empower mainstream segmentation architectures to have the capability of open-vocabulary segmentation-we present P-SAN and R-SAN, to support widely adopted pixel-wise segmentation and region-wise segmentation, respectively. Experimentally, our approach achieves state-of-the-art performance on 5 commonly used benchmarks while having much less trainable parameters and GFLOPs. For instance, our R-SAN outperforms previous best method OvSeg by +2.3 averaged mIoU across all benchmarks while using only 6% of trainable parameters and less than 1% of GFLOPs. In addition, we also conduct a comprehensive analysis of the open-vocabulary semantic segmentation datasets and verify the feasibility of transferring a well optimzied R-SAN model to video segmentation task.


Prospective effects of internalized stigma on same-sex relationship satisfaction: The mediating role of depressive symptoms and couple conflict.
Same-sex couples face unique minority stressors that affect relationship functioning, yet remarkably little research has examined the mechanisms by which individual and partner experiences of internalized stigma affect relationships over time. Using actor-partner interdependence models, the present study examined the effects of internalized stigma on relationship satisfaction, and whether depressive symptoms and couple conflict mediated these effects. Hypotheses were tested cross-sectionally and prospectively across a 5-year period. Participants were 330 same-sex couples (n = 660 individuals; Mage = 39.5 years, SD = 10.8) who were assessed annually over a 5-year period. There were 109 male couples, 216 female couples, and five couples in which one partner did not identify with these labels. There was a significant actor effect of internalized stigma on lower relationship satisfaction cross-sectionally and prospectively, and significant indirect actor-actor and actor-partner effects of internalized stigma on satisfaction via couple conflict cross-sectionally and prospectively. Finally, there was a cross-sectional indirect actor-actor effect of internalized stigma on relationship satisfaction via depressive symptoms, though depressive symptoms did not mediate any effects over time. These findings highlight the importance of considering both individual and interpersonal mediators of minority stress, particularly when investigating partner effects of minority stress on relationship satisfaction. Implications for research and clinical practice with same-sex couples are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The low-affinity neurotrophin receptor p75 regulates the function but not the selective survival of specific subpopulations of sensory neurons.
Mice with a targeted deletion of the low-affinity neurotrophin receptor p75 (p75-/-) exhibit a 50% loss of large- and small-diameter sensory neurons in the dorsal root ganglion. Using neurophysiological recording techniques, we now show that p75 is not required for the survival of specific, functionally defined subpopulations of sensory neurons. Rather, p75-/- mice exhibit losses of neurons that subserve nociceptive as well as non-nociceptive functions. The receptive properties of large myelinated afferent fibers were normal in p75-/- mice. However, the receptive properties of subpopulations of afferent fibers with thin myelinated or unmyelinated axons were strikingly impaired in mice lacking p75. Furthermore, the presence of p75 is required for normal mechanotransduction in C fibers and D-hair receptors and normal heat sensitivity in A-fiber nociceptors.


Mice deficient in cystathionine beta synthase display increased Dyrk1A and SAHH activities in brain.
Hyperhomocysteinemia is associated with brain disease. However, biological actions linking hyperhomocysteinemia to neuronal abnormalities are not well understood. We recently found a relationship between Dyrk1A protein expression, a serine/threonine kinase that might be responsible for cognitive functions in Down's syndrome, and hepatic S-adenosylhomocysteine hydrolase (SAHH) activity, which plays a key role in S-adenosylmethionine-dependent methylation reactions. Considering the role of methylation and Dyrk1A in cognitive functions, the aim of this study was to investigate the relationship between Dyrk1A and SAHH activity in brain of hyperhomocysteinemic mice. We found an increase in Dyrk1A protein expression and activity in brain of hyperhomocysteinemic mice, concomitant with an increased SAHH activity. The effect of overexpression of protein Dyrk1A on SAHH activity was confirmed in brain of Dyrk1A transgenic mice, and additionally we found a positive correlation between Dyrk1A and SAHH activity. These observations suggest a potential effect of Dyrk1A on brain phenotypes linked to hyperhomocysteinemia.


[Associative processes disorders in schizophrenia].
This paper tries to approach and systematize knowledge about the character of associative process disorders in schizophrenia. In considering schizophrenia as an illness composed of various symptoms which may lead to different clinical progress, the paper is mainly focused on disorganization of thinking and, consequently, speaking and communication disorders. Authors reviewed various concept of pathogenesis and course of associative process disorders in schizophrenic patients. Special attention was paid to a connectionist model of disturbed associations. This model originates from cognitive psychology and assumes that concepts are represented as networks in the mental lexicon. Following from this model, a hypothesis was presented, claiming that disturbed associations in schizophrenia may be related to abnormalities in semantic networks. Results of research, supporting this hypothesis, were referred. Moreover, authors tried to describe the relationship between associative processes disorders in schizophrenia and abnormalities in neurophysiological (event--related potentials) and neuropathological (MRI) examinations. At least hypotheses describing the role of neurotransmission disorders was presented.


Design, Synthesis, and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 Antagonist and Its Comparison to Available Small Molecular PD-L1 Inhibitors.
In search of a potent small molecular PD-L1 inhibitor, we designed and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile moiety. Ligand's performance was tested in vitro and compared side-by-side with a known PD-L1 antagonist with a proven bioactivity BMS1166. Subsequently, we modified both compounds to allow 18F labeling that could be used for PET imaging. Radiolabeling, which is used in drug development and diagnosis, was applied to investigate the properties of those ligands and test them against tissue sections with diverse expression levels of PD-L1. We confirmed biological activity toward hPD-L1 for this inhibitor, comparable with BMS1166, while holding enhanced pharmacological properties.


Synthetic Evolution of Colloidal Metal Halide Perovskite Nanocrystals.
Metal halide perovskite semiconductor nanocrystals have emerged as a lucrative class of materials for many optoelectronic applications. By leveraging the synthetic toolboxes developed from decades of research into more traditional semiconductor nanocrystals, remarkable progress has been made across these materials in terms of their structural, compositional, and optoelectronic control. Here, we review this progress in terms of their underlying formation stages, synthetic approaches, and postsynthetic treatment steps. This assessment highlights the rapidly maturing nature of the perovskite nanocrystal field, particularly with regard to their lead-based derivatives. It further demonstrates that significant challenges remain around precisely controlling their nucleation and growth processes. In going forward, a deeper understanding of the role of precursors and ligands will significantly bolster the versatility in the size, shape, composition, and functional properties of these exciting materials.


Aneurysm of the radial artery following blunt trauma to the wrist.
Aneurysms involving the distal radial artery are rare lesions which are usually secondary to penetrating trauma or iatrogenic injury. Blunt trauma is an extremely uncommon cause. In the absence of a history of penetrating vascular injury, a radial artery aneurysm may easily be misdiagnosed as a nonvascular mass such as a synovial cyst. A diagnostic approach to these lesions is discussed emphasizing the role of noninvasive studies in uncomplicated cases. Excision of the aneurysm is recommended. The decision to ligate or reconstruct the radial artery remains controversial.


Temperature sensitivity of proteoliposomes reconstituted from a mixture of scallop and rabbit sarcoplasmic reticulum Ca2+-ATPases.
We reconstituted proteoliposomes by mixing scallop and rabbit sarcoplasmic reticulum, SR, at different protein weight ratios, and investigated the effects of temperature on their Ca2+-transport activity. When proteoliposomes containing scallop and rabbit SR at a protein ratio of 1:1 were pre-incubated in the presence of Ca2+ at 39 degrees C for 10 min, the Ca2+-transport activity was almost completely lost, whereas the activity of proteoliposomes containing rabbit SR alone decreased only slightly. Essentially the same results were obtained for proteoliposomes reconstituted with Ca2+-ATPases partially purified from scallop and rabbit SR. The susceptibility of the reconstituted proteoliposomes to heat inactivation increased with an increase in the protein weight ratio of scallop to rabbit SR, the maximum being approached at a ratio higher than 1. When the scallop SR was thermally treated before reconstitution, the resulting vesicles showed as high Ca2+-transport activity as that of control vesicles reconstituted from rabbit SR alone. The former vesicles were not inactivated on further treatment at high temperature. In contrast, when the scallop SR was heated in EGTA before reconstitution of vesicles with rabbit SR, the Ca2+-transport activity of the vesicles was strongly inhibited by subsequent treatment at high temperature in the presence of Ca2+. These results can be easily explained if we assume that Ca2+ transport by the reconstituted vesicles can be catalyzed through a dimeric interaction between the scallop and rabbit Ca2+-ATPases in the membrane. Pre-incubation of these vesicles at 39 degrees C for 10 min in the presence of Ca2+ may destroy the dimeric interaction due to denaturation of the scallop Ca2+-ATPase.


Optimization of culture conditions for short-term maintenance, proliferation, and colony formation of porcine gonocytes.
Gonocytes give rise to spermatogonial stem cells, and thereby play an essential role in establishing spermatogenesis. Optimized culture conditions for gonocytes provide an opportunity for their study and in vitro manipulation for potential application in reproductive technologies. Using six experiments in a step-wise design, we examined the effects of several culture conditions on the maintenance, proliferation, and colony formation of porcine gonocytes. Testis cells from neonatal piglets were cultured for 7 d in DMEM supplemented with 10% fetal bovine serum. The examined culture conditions included using different cell seeding densities, gonocyte proportions, incubation temperatures, sampling strategies, and medium changing regimens. Confluency of cells was optimal (>90% by ~6 d) when 3.0 × 104 testis cells/cm2 containing ~40% gonocytes were used. Incubating the cells at 35 °C or 37 °C resulted in similar cell number and viability at confluency, but incubation at 35 °C resulted in a delayed confluency. In the first 2 d of culture, gonocytes remained mostly floating in the medium and gradually settled over the next 5 d. Consequently, not changing the medium for 7 d (as opposed to changing it every 2 d) led to a significant increase in the number of gonocyte colonies by reducing the loss of "floating gonocytes". We found that gonocytes require the presence of a critical minimum number of somatic cells for settlement, and can proliferate and form growing colonies even in a basic medium. Large numbers of viable gonocytes remain floating in the medium for several days. The optimized culture conditions in the present study included seeding with 3.0 × 104 testis cells/cm2 containing ~40% gonocytes, incubating at 37 °C, and without changing the medium in the first week, which can result in improved colony formation of porcine gonocytes.


Protein synthesis inhibitors of natural origin for CML therapy: semisynthetic homoharringtonine (Omacetaxine mepesuccinate).
Omacetaxine mepesuccinate is a drug approved in 2014 by FDA for the use in CML therapy in patients resistant to at least two thymidine kinase inhibitors (TKIs). It possesses unique mechanism of anticancer activity that is principally different from mechanism of activity of TKIs. Omacetaxine mepesuccinate inhibits protein translation through prevention of the initial elongation step of protein synthesis and its use benefits CML patients possessing the BCR-ABL oncogene. Because of the superior activity of Omacetaxine in patients who became resistant to therapy with TKIs, FDA decided on the accelerated approval of this drug taking its consideration not only its activity as such but also a favorable benefit-to-risk profile in patients included into clinical studies.


Evaluation of coercive measures in different psychiatric hospitals: the impact of institutional characteristics.
Epidemiological studies have demonstrated considerable differences in the use of coercive measures among psychiatric hospitals; however, the underlying reasons for these differences are largely unclear. We investigated to what extent these differences could be explained by institutional factors. Four psychiatric hospitals with identical responsibilities within the mental health care system, but with different inpatient care organizations, participated in this prospective observational study. We included all patients admitted over a period of 24 months who were affected by mechanical restraint, seclusion, or compulsory medication. In addition to the patterns of coercive measures, we investigated the effect of each hospital on the frequency of compulsory medication and the cumulative duration of mechanical restraint and seclusion, using multivariate binary logistic regression. To compare the two outcomes between hospitals, odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. Altogether, coercive measures were applied in 1542 cases, corresponding to an overall prevalence of 8%. The frequency and patterns of the modalities of coercive measures were different between hospitals, and the differences could be at least partially related to institutional characteristics. For the two hospitals that had no permanently locked wards, certain findings were particularly noticeable. In one of these hospitals, the probability of receiving compulsory medication was significantly higher compared with the other institutions (OR 1.9, CI 1.1-3.0 for patients < 65 years; OR 8.0, CI 3.1-20.7 for patients ≥65 years); in the other hospital, in patients younger than 65 years, the cumulative duration of restraint and seclusion was significantly longer compared with the other institutions (OR 2.6, CI 1.7-3.9). The findings are compatible with the hypothesis that more open settings are associated with a more extensive use of coercion. However, due to numerous influencing factors, these results should be interpreted with caution. In view of the relevance of this issue, further research is needed for a deeper understanding of the reasons underlying the differences among hospitals.


Pre-operative ultrasound for breast tumour measurements: is there potential for mismanagement?
The pre-operative size of breast tumour is the most important factor in determining feasibility of breast conserving surgery in operable breast cancer. Currently there is no consensus on the most accurate modality to measure tumour size. A prospective study of consecutive and unselected symptomatic patients with invasive breast cancer who had primary surgery between January 2006 and December 2007 was conducted. Patients with multi-focal and multi-centric tumours were excluded. The aim of this study was to find the correlation between histological size of invasive breast cancer and pre-operative tumour size as measured by ultrasound. Over this two year period, data for 192 patients was analysed for this study. The mean tumour diameter on ultrasound and histology was 19.5mm and 29 mm respectively. The difference between the means in the two modalities was found to be statistically significant (P<0.001).Ultrasound underestimates the true size of breast tumours as determined histologically. Inaccurate tumour size measurements may result in re-operations to achieve adequate margins.


Isolation and characterization of Micromonospora phage PhiHAU8 and development into a phasmid.
PhiHAU8, a temperate Micromonospora phage, which is capable of infecting Micromonospora sp. strains 40027 and A-M-01, was isolated. The PhiHAU8 virion has a polyhedral head and a flexible tail and has a small genome (ca. 42.5 kb) with double-stranded DNA and cohesive ends. PhiHAU8 was most stable at 4 degrees C in Difco nutrient broth within a pH range of 6 to 12. PhiHAU8 plaque formation on Micromonospora sp. strain 40027 was optimal with 32 mM Ca(2+) and 30 mM Mg(2+). A lysogen, LXH8, was isolated from turbid plaques, and a phasmid derivative that functions as a lambda cosmid vector in Escherichia coli and as a phage in Micromonospora sp. strain 40027 was constructed. Pulsed-field gel electrophoresis of AseI-digested total DNA showed that PhiHAU8 DNA integrates into the 500-kb AseI fragment of Micromonospora sp. strain 40027.


Keeping kidneys safe: the pharmacist's role in NSAID avoidance in high-risk patients.
To provide information on the role of pharmacists in nonsteroidal anti-inflammatory drug (NSAID) avoidance in high-risk patients. Nonprescription analgesics such as ibuprofen and naproxen are widely used by Americans. These nonsteroidal anti-inflammatory drugs (NSAIDs) are available in large quantities in pharmacies and also in wholesale stores, gas stations, and convenience stores. In addition, more than 111 million people use prescription NSAIDs each year, including many older Americans. NSAIDs may seem innocuous, but they carry a significant risk of disrupting blood flow to the kidneys and thus precipitating acute kidney injury (AKI). Episodes of AKI can lead to costly hospitalizations and long-term consequences such as new-onset chronic kidney disease (CKD) or more rapid progression of existing CKD. Most cases of NSAID-induced AKI can be avoided by recognizing high-risk patients and counseling them on appropriate use of these medications. Community pharmacy-based NSAID counseling and education at the point of prescription dispensing or nonprescription purchase could complement and augment NSAID-induced AKI education provided by other members of the health care team to high-risk patients. NSAID use is widespread and severely compromises effective renal perfusion in high-risk patients. The community pharmacist can play a pivotal role in NSAID avoidance education to prevent potential episodes of AKI that have long-term consequences for patients.


Acute effects of whole-body vibration on the motor function of patients with stroke: a randomized clinical trial.
The aim of this study was to investigate the acute effects of whole-body vibration on the motor function of patients with stroke. The present investigation was a randomized clinical trial studying 43 individuals with hemiparesis after stroke, with 33 subjects allocated to the intervention group and 10 subjects allocated to the control group. The intervention group was subjected to one session of vibration therapy (frequency of 50 Hz and amplitude of 2 mm) comprising four 1-min series with 1-min rest intervals between series in three body positions: bipedal stances with the knees flexed to 30 degrees and 90 degrees and a unipedal stance on the paretic limb. The analytical tests were as follows: simultaneous electromyography of the affected and unaffected tibialis anterior and rectus femoris muscles bilaterally in voluntary isometric contraction; the Six-Minute Walk Test; the Stair-Climb Test; and the Timed Get-Up-and-Go Test. The data were analyzed by independent and paired t tests and by analysis of covariance. There was no evidence of effects on the group and time interaction relative to variables affected side rectus femoris, unaffected side rectus femoris, affected side tibialis anterior, unaffected side tibialis anterior, and the Stair-Climb Test (P > 0.05). There was evidence of effects on the group interaction relative to variables Six-Minute Walk Test and Timed Get-Up-and-Go Test (P < 0.05). Whole-body vibration contributed little to improve the functional levels of stroke patients.


An integrated omics analysis reveals the gene expression profiles of maize, castor bean, and rapeseed for seed oil biosynthesis.
Seed storage lipids are valuable for human diet and for the sustainable development of mankind. In recent decades, many lipid metabolism genes and pathways have been identified, but the molecular mechanisms that underlie differences in seed oil biosynthesis in species with developed embryo and endosperm are not fully understood. We performed comparative genome and transcriptome analyses of castor bean and rapeseed, which have high seed oil contents, and maize, which has a low seed oil content. These results revealed the molecular underpinnings of the low seed oil content in maize. First of all, transcriptome analyses showed that more than 61% of the lipid- and carbohydrate-related genes were regulated in castor bean and rapeseed, but only 20.1% of the lipid-related genes and 22.5% of the carbohydrate-related genes were regulated in maize. Then, compared to castor bean and rapeseed, fewer lipid biosynthesis genes but more lipid metabolism genes were regulated in the maize embryo. More importantly, most maize genes encoding lipid-related transcription factors, triacylglycerol (TAG) biosynthetic enzymes, pentose phosphate pathway (PPP) and Calvin Cycle proteins were not regulated during seed oil synthesis, despite the presence of many homologs in the maize genome. Additionally, we observed differential regulation of vital oil biosynthetic enzymes and extremely high expression levels of oil biosynthetic genes in castor bean, which were consistent with the rapid accumulation of oil in castor bean developing seeds. Compared to high-oil seeds (castor bean and rapeseed), less oil biosynthetic genes were regulated during the seed development in low-oil seed (maize). These results shed light on molecular mechanisms of lipid biosynthesis in maize, castor bean, and rapeseed. They can provide information on key target genes that may be useful for future experimental manipulation of oil production in oil plants.


A retrospective study describing the characteristics of one Mental Health Trust's admissions under sections 47 and 48 of the Mental Health Act 1983.
Sections 47 and 48 of the Mental Health Act 1983 allow prisoners to be transferred from prison to an appropriate health-care setting in order to be treated. There is an awareness that delays exist when transferring prisoners to hospital. However, literature regarding the delay in returning these patients from hospital is limited. The admissions from prison to a Psychiatric Intensive Care Unit (PICU) in South West London were compared to non-offenders on the PICU in order to compare the average length of stay for both groups and the time taken for the discharge from PICU once felt clinically appropriate. The study also compared demographic profiles, reason for admissions, psychiatric diagnosis and index offences. Over six years, there were 18 admissions from prison to a PICU. The control group comprised 37 non-offenders admitted to the same PICU. On average the prison group took longer to be deemed clinically ready for discharge and, even once clinically ready, then took longer to be discharged. The average length of stay in PICU was 77.83 days for prisoners, and 16.46 days for non-offenders. All 55 admissions were between 1 January 2008 and 31 December 2014. The offender pathway and the difference in the length of stay between prisoners and non-offenders in a PICU warrants further exploration. Possible recommendations to reduce the length of stay of prisoners include improved information sharing between prisons and hospital, and clearer guidelines regarding the level of security required.


[In vitro pathogenicity of fungic formulation on nymphs and adults of Rhipicephalus sanguineus (Latreile, 1806) (Acari:Ixodidae)].
Rhipicephalus sanguineus is responsible for transmitting several pathogenic agents, such as: Babesia sp. and Ehrlichia sp.. This species is known as the brown dog tick and has wide geographical distribution. The purpose of this work was to evaluate the pathogenicity of biological formulations of Beauveria bassiana and Metarhizium anisopliae applied to the fed nymphs and adults of R. sanguineus under laboratory conditions. The following treatments were evaluated: control, distilled water with tween 80, emulsible concentrated, cellulose polymerized gel, fungus mixed with emulsible concentrated, fungus mixed with cellulose polymerized gel and fungus mixed with emulsible concentrated and cellulose polymerized gel. Each treatment was repeated ten times. The survival of fed nymphs and unfed adults was evaluated on the 5th, 10th, 15th and the 20th days after treatments. Significant differences were observed between the treatments (p<0.05). The treatment with M. anisopliae mixed with emulsible concentrated and cellulose polymerized gel showed the lower survival on the 15th and 20th days after treatment. We can conclude that the fungi formulation is harmful to fed nymphs and unfed adults of R. sanguineus in vitro, on this account it is suggested its use for the microbial control of this tick.


[Why complete or partial response can not be achieved by immunotherapy].
It has been shown that shrinkage of tumor mass can hardly be achieved by immunotherapy. However, this does not appear to indicate that the immunotherapy is ineffective in cancer treatment. Although chemotherapy can reduce a tumor mass by means of fractional kill of tumor cells and, thereby assure complete and partial responses, the cytocidal action of immunotherapy seems to be effected through constant number cell kill. When residual tumor cells in patients who underwent radical surgery are considered from a microscopic standpoint, it is suggested from the disease-free survival curve that the tumor burden is surely reduced logarithmically even in each class of patients who failed to respond to adjuvant chemotherapy. Moreover, there is a great possibility that these residual tumor cells will acquire a drug resistance. Therefore, even if the degree of cell kill potential of immunotherapy is so low that complete or partial response cannot be achieved, the role of immunotherapy in combined modality for cancer treatment is inevitably important.


Noise-aware dictionary-learning-based sparse representation framework for detection and removal of single and combined noises from ECG signal.
Automatic electrocardiogram (ECG) signal enhancement has become a crucial pre-processing step in most ECG signal analysis applications. In this Letter, the authors propose an automated noise-aware dictionary learning-based generalised ECG signal enhancement framework which can automatically learn the dictionaries based on the ECG noise type for effective representation of ECG signal and noises, and can reduce the computational load of sparse representation-based ECG enhancement system. The proposed framework consists of noise detection and identification, noise-aware dictionary learning, sparse signal decomposition and reconstruction. The noise detection and identification is performed based on the moving average filter, first-order difference, and temporal features such as number of turning points, maximum absolute amplitude, zerocrossings, and autocorrelation features. The representation dictionary is learned based on the type of noise identified in the previous stage. The proposed framework is evaluated using noise-free and noisy ECG signals. Results demonstrate that the proposed method can significantly reduce computational load as compared with conventional dictionary learning-based ECG denoising approaches. Further, comparative results show that the method outperforms existing methods in automatically removing noises such as baseline wanders, power-line interference, muscle artefacts and their combinations without distorting the morphological content of local waves of ECG signal.


An overview of the pharmacological properties and potential applications of natural monoterpenes.
Monoterpenes, the major components of essential oils, belong to the group of isoprenoids containing ten carbon atoms. Being widely distributed in the plant kingdom they are extensively used in cuisine and human health care products. Studies have shown that both natural monoterpenes and their synthetic derivatives are endowed with various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, antiarrhythmic, anti-aggregating, local anesthetic, antinociceptive, anti-inflammatory, antihistaminic and anti-spasmodic activities. Monoterpenes act also as regulators of growth, heat, transpiration, tumor inhibitors, inhibitors of oxidative phosphorylation, insect repellants, feline and canine attractants and antidiabetics. These interesting activities which might be potentially used not only in pharmaceutical, but also food and cosmetic industries are discussed below.


N-Oleoylethanolamine Reduces Inflammatory Cytokines and Adhesion Molecules in TNF-α-induced Human Umbilical Vein Endothelial Cells by Activating CB2 and PPAR-α.
Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Peroxisome proliferator-activated receptor-alpha (PPAR-α) and cannabinoid receptor 2 (CB2) crucially impact the modulation of inflammation. N-Oleoylethanolamine (OEA), a natural agonist of PPAR-α, can also up-regulate the expression of CB2 in human umbilical vein endothelial cells (HUVECs) and further shows an antiatherosclerotic effect. Our study was designed to determinate whether OEA could inhibit inflammation in HUVECs induced by tumor necrosis factor-α (TNF-α) and to identify the mechanism of OEA function. Interleukin-6 (IL-6), interleukin-8 (IL-8), vascular adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) levels were detected in HUVECs exposed to tumor necrosis factor-α in the presence of OEA. The results showed that OEA suppressed the expression of interleukin-6, interleukin-8, vascular adhesion molecule-1, and intercellular adhesion molecule-1 in a dose-dependent manner. OEA also enhanced CB2 and PPAR-α receptor expression, which contributed to its anti-inflammatory effect. OEA inhibited the nuclear factor-κB (NF-κB) pathway, and the effect of OEA on nuclear factor-κB was partly abolished when HUVECs were pretreated with either CB2 or PPAR-α antagonist. OEA attenuated tumor necrosis factor-α-induced inflammation in HUVECs by up-regulating the expression of CB2 and PPAR-α receptors. Furthermore, OEA suppresses the nuclear factor-κB pathway. These results suggest that OEA exerts anti-inflammatory and anti-adhesive effects on HUVECs.


The impact of early environmental interventions on structural plasticity of the axon initial segment in neocortex.
Plasticity of the axon initial segment (AIS) is a newly discovered type of structural plasticity that regulates cell excitability. AIS plasticity has been reported to happen during normal development of neocortex and also in a few pathological conditions involving disruption of the inhibition/excitation balance. Here we report on the impact of early environmental interventions on structural plasticity of AIS in the mouse neocortex. C57BL/6 mice were raised in standard or enriched environment (EE) from birth up to the time of experiments and were injected with saline or MK-801 [N-Methyl-D-Aspartate (NMDA) receptor antagonist, 1 mg/kg] on postnatal days (P) 6-10. We used Ankyrin G immunoreactivity to mark the AIS of cortical neurons in two sub-regions of frontal cortex (frontal association area, FrA and secondary motor cortex, M2) and in the secondary visual cortex (V2). In 1-month-old mice, the mean AIS length differed between three areas, with the shortest AISs being observed in V2. Postnatal MK-801 or EE led to shortening of AIS only in the frontal areas. However, exposure to EE restored AIS shortening induced by MK-801. Chronic postnatal MK-801 results in structural plasticity of AIS exclusive to the frontal cortex. EE may modify underlying neuronal mechanisms resulting in restoration of AIS length.


Effect of glucocorticoid therapy on long-term growth and development of children with bronchiolitis.
To explore the effect of glucocorticoid therapy on the growth and development of children with bronchiolitis. A total of 143 children with bronchiolitis who were treated with glucocorticoids from February 2017 to March 2018 were enrolled. The medical data were retrospectively collected, including height, weight, course of the disease, and diagnosis and treatment plan at initial admission. After three years of treatment, physical development indices were measured, growth and development were evaluated by Z-score, and related hematological parameters were measured, including osteocalcin, serum phosphorus, and insulin-like growth factor-1. As for the children with bronchiolitis, the incidence rates of growth retardation and obesity increased significantly after three years of glucocorticoid therapy (P<0.05). The children treated with glucocorticoids for ≥29 days showed a significantly higher incidence rate of obesity than those treated with glucocorticoids for <29 days (P<0.05), while nebulized glucocorticoid treatment had no effect on the growth and development (P>0.05). Compared with the children with growth retardation, the children with normal development had significantly higher levels of serum phosphorus and insulin-like growth factor-1 (P<0.05). Glucocorticoid therapy can adversely affect long-term growth and development in children with bronchiolitis.


Identification and characterization of a novel neural cell adhesion molecule (NCAM)-associated protein from quail myoblasts: relationship to myotube formation and induction of neurite-like protrusions.
We identified a novel neural cell adhesion molecule (NCAM)-associated protein, myogenesis-related and NCAM-associated protein (MYONAP), the expression of which increases during the formation of myotubes in quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells). MYONAP shares homology with PL48 in human cytotrophoblasts and KIAA0386 in human brain. Excess expression of MYONAP in presumptive QM-RSV myoblasts induced long protrusions like neurites in cooperation with microtubules. Suppression of MYONAP by antisense cDNA prevented myotubes from forming in spite of the expression of myogenin, creatine kinase, and myosin, and rendered myoblast membranes resistant to fusion. Yeast two-hybrid screening showed that MYONAP interacted with NCAM specifically. Deletion of the NCAM-associated domain resulted in a loss of the function that induces neurite-like protrusions to form and disturbed the elongation of microtubules. The results suggested that MYONAP influenced the functions of microtubules and was involved in the formation of myotubes via its interaction with NCAM.


[Experimental correlation study of lumbar spinal stenosis and knee joint degeneration].
To explore the correlation of lumbar stenosis and knee osteoarthritis by establishing a rabbit lumbar spinal stenosis model and observing the hind limb movement function and pathological change of articular cartilage of knee joint. A total of 36 healthy adult rabbits were randomly divided into model group and control group. In the model group, spinal canal was filled with bone pieces to make lumbar spinal stenosis; in the control group, sham operation was performed and materials were inserted into spinal canal. Movement function was evaluated by Tarlov method and pathological features were observed by Mankin's scores under light microscope at 4, 8 and 12 weeks. Early degenerative changes of knee cartilage were observed in the model group at 4 and 8 weeks post-operation. There were synovial hyperemia and hyperplasia, increased synovial fluid effusion and lightly-stained cartilage. The Mankin score was 3.3 - 4.5 and Tarlov score 3 - 4. Intermediate stage changes of osteoarthritis were found in the model group at 12 weeks post-operation, showing synovial hyperplasia, decreased synovial fluid, fissure in cartilage surface, tangled cartilage cells and unevenly stained matrix. The Mankins score was 7 - 9 and Tarlov score 2 - 3. Most of articular cartilage was normal in the control group with Mankin score of 0 - 1 and Tarlov score of 4. Lumbar stenosis may be correlated with knee joint degeneration.


Three cases of renal angiomyolipoma.
We report three non-typical cases of renal angiomyolipoma including clinical features, imaging examinations (with ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography) and histological findings. Microaneurysms observed by angiography were common to the three cases and were considered to be an important finding in the diagnosis of renal angiomyolipoma. Moreover, the short tau inversion recovery (STIR) method of MRI, which suppresses photon signals of fat, was considered to be useful for the diagnosis. Case 1 was accompanied by spontaneous rupture, Case 2 was difficult to diagnose because of little fat tissue and Case 3 revealed a very small tumor.


Tumors and tumor-like lesions in the genitalia of sows.
Of a total of 1445 sows, tumors were detected in the uterus of 11 animals and in the cervix/vagina of 1 animal. Tumor-like lesions were detected in the ovary of 56 animals. The incidence of tumors was higher than that mentioned in the literature, possibly because of the relatively high age of the sows (mean parity of 6.8) and the accuracy of investigation. Several tumors would not have been detected during routine slaughter examination. The uterine tumors were diagnosed as leiomyoma (6), fibroma (3), cyst-adenoma (1) and fibro-leiomyoma (1). The cervical/vaginal tumor appeared to be a fibroma. The ovarian lesions could not be satisfactorily classified. They consisted of connective tissue, blood vessels, and granulosa cells, which were present in variable quantities in different ovaries and in different sides of the same ovary. Sows with tumors were older than the mean determined age at slaughter (parity 6.8). Sows with uterine and cervical/vaginal tumors had a parity of 11.6; sows with ovarian lesions had a parity of 9.0. Sows with uterine- or a cervical/vaginal tumor were often slaughtered for infertility reasons.


X-Linked Agammaglobulinaemia: Outcomes in the modern era.
Colonel Ogden Bruton reported X-Linked Agammaglobulinaemia in 1952 and treated the child with replacement immunoglobulin therapy. Over 60years later, the treatment for XLA has largely remained unchanged. Replacement immunoglobulin lacks the isotypes IgA and IgM, leading to concerns that patients continue to experience recurrent sinopulmonary tract infections and be at increased risk of bronchiectasis. There is potential hope of earlier diagnosis with newborn screening, and a potential cure for these patients, in the form of gene therapy. However, it is first necessary to evaluate current management and outcomes to aid decisions regarding further research and clinical trials. This article reviews current management and outcomes of XLA, whilst identifying gaps in our knowledge base that may need answering before we proceed with novel diagnostic methods and treatment for XLA.


Perioperative and Anesthetic Considerations in Ebstein's Anomaly.
Ebstein's anomaly is a complex and heterogeneous form of congenital heart disease characterized by malformation and apical displacement of the tricuspid valve leaflets. Patients may present at any time from the neonatal period to adulthood with symptoms ranging from cardiac failure and cyanosis to paroxysmal arrhythmias. Depending on the timing of presentation, various surgical options are available for the management of symptomatic patients. This review will discuss the perioperative and anesthetic management of patients with Ebstein's anomaly with reference to the more common surgical approaches.


Bepridil versus nifedipine for ventricular tachycardia induced in the late postinfarction phase in conscious dogs.
The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyarrhythmias were studied by programmed electrical stimulation in 15 dogs, 4-8 days after myocardial infarction. Recordings from the infarcted and normal anterior wall of the left ventricle were obtained with an epicardial implanted 'composite' electrode. Bepridil (5 mg/kg) or nifedipine (0.025 mg/kg) were administered i.v. on different days and testing was repeated. Sustained ventricular tachycardia was prevented or significantly slowed by bepridil in 11/12 experiments compared with none of 9 experiments with nifedipine. Paradoxically, in 10/15 dogs nifedipine accelerated arrhythmias or even provoked ventricular fibrillation. Bepridil prolonged refractoriness of infarcted myocardium by 15 +/- 4% (mean +/- SD, p less than 0.01), which was greater than the increase it produced in the effective refractory period of normal tissue (9.0 +/- 3.8%) or QTc interval (11 +/- 5.5%). In contrast, nifedipine significantly shortened these parameters. Both drugs did not influence conduction in infarcted and normal zones as indicated by unchanged late potentials, QRS duration and normal-zone electrograms, respectively. The data indicate that the antiarrhythmic action of bepridil was predominantly related to the prolongation of ventricular refractoriness and repolarization (class III effects).


Rapid and quantitative detection of C-reactive protein based on quantum dots and immunofiltration assay.
Convenient and rapid immunofiltration assays (IFAs) enable on-site "yes" or "no" determination of disease markers. However, traditional IFAs are commonly qualitative or semi-quantitative and are very limited for the efficient testing of samples in field diagnostics. Here, we overcome these limitations by developing a quantum dots (QDs)-based fluorescent IFA for the quantitative detection of C-reactive proteins (CRP). CRP, the well-known diagnostic marker for acute viral and bacterial infections, was used as a model analyte to demonstrate performance and sensitivity of our developed QDs-based IFA. QDs capped with both polyethylene glycol (PEG) and glutathione were used as fluorescent labels for our IFAs. The presence of the surface PEG layer, which reduced the non-specific protein interactions, in conjunction with the inherent optical properties of QDs, resulted in lower background signal, increased sensitivity, and ability to detect CRP down to 0.79 mg/L with only 5 µL serum sample. In addition, the developed assay is simple, fast and can quantitatively detect CRP with a detection limit up to 200 mg/L. Clinical test results of our QD-based IFA are well correlated with the traditional latex enhance immune-agglutination aggregation. The proposed QD-based fluorescent IFA is very promising, and potentially will be adopted for multiplexed immunoassay and in field point-of-care test.


Associations between parents' and 12-year-old children's sport and vigorous activity: the role of self-esteem and athletic competence.
The aims of this study were to investigate parent-child physical activity (PA) associations and whether children's self-esteem or athletic competence mediates such associations. The study population comprised 1124 12-year-old children and their parents. Parents' PA was assessed using the Baecke questionnaire and a question about sport participation. Children's PA was assessed by questions about participation in sport and vigorous activities. The children's self-esteem and athletic competence were assessed by Harter's Self-Perception Profile for Adolescents. Parents' PA was strongly associated with their children's PA. With 2 active parents, the odds ratio for their children to participate in sport was 3.9 (95% CI = 2.2-6.9, girls) and 8.8 (95% CI = 4.3-18.0, boys) compared with having inactive parents. Athletic competence partly mediated these associations. The family is an important target for interventions to increase PA among children, and it might be important to consider ways to reinforce children's athletic competence.


Morphological and functional aspects of heart homograft adaptation to hamster cheek pouch. Spontaneous pulsatile activity and ultrastructure.
Atrial homografts from newborn hamsters, transplanted into cheek pouches of adult Syrian golden hamsters, were studied using intravital and electron microscopy. Half of the transplants survived up to 1 year, performing spontaneous pulsatile activity. The transplants could be influenced by beta-receptor activating or blocking substances applied intravenously to the host animal. For morphological analysis homografts were taken 3, 6, and 12 months after transplantation. Irregular arrangement of the myofibers occurred, and the T system was seen to be replaced by plasmalemmal and sub-plasmalemmal vesiculations. There was some evidence for hypoxia in the grafts. Dedifferentiation of atrial cardiocytes, somehow resembling smooth muscle cells, is discussed. Despite these morphological changes the specific contractile function of the grafts was preserved.


Could Values and Social Structures in Singapore Facilitate Attainment of Patient-Focused, Cultural, and Linguistic Competency Standards in a Patient-Centered Medical Home Pilot?
Primary care practices in the United States are transforming into patient-centered medical homes (PCMHs) at a rapid pace. Newer PCMH standards have emphasized culturally and linguistically appropriate services (CLAS), but at this time, only some states in the United States have proposed or passed cultural competency training for health care professionals. Other countries are moving to PCMH models. Singapore, a small, ethnically diverse island nation, has national values and social structures that emphasize cultural and linguistic cohesion. In this piece, we examine Singapore's first PCMH pilot with a national academic center and primary care practice group. Features such as common shared values, self-reliance, racial and religious harmony, patient experience surveillance, and incorporation of CLAS standards in routine health care transactions may predict success for the PCMH in Singapore, with some implications for the United States.


[Prevention of ischemic stroke in atrial fibrillation from the point of view of a neurologist. Standards and real clinical practice].
The article outlines aspects of the current state of the problem of the priority choice of an oral anticoagulant for indefinite prevention of stroke and systemic thromboembolism in patients with atrial fibrillation. The advantages of direct oral angicoagulants over warfarin are presented, as well as a comparative analysis of the individual characteristics of the main direct oral angicoagulants from the point of view of personification of preventive therapy in accordance with modern treatment standards. The efficacy and safety of oral anticoagulant therapy has been reviewed in terms of the net clinical benefit. Particular attention is paid to the age-related aspects of choosing an anticoagulant for indefinite prophylaxis; an assessment of anticoagulants is presented in accordance with the FORTA concept, which regulates the use of drugs in elderly patients. In conclusion, recommendations are formulated for the choice of an anticoagulant in patients with atrial fibrillation in the most common clinical situations. As a general rule, the choice of a particular drug should be individualized based on risk factors, tolerability, net clinical benefit, patient preference, potential adverse interactions, and other clinical characteristics.


Two hundred ninety-six cases of onychomycosis in children and teenagers: a 10-year laboratory survey.
There is still little data available about the epidemiology of childhood onychomycosis. Looking at our laboratory figures over a 10-year period provided us with some useful information. Nail keratin samples were taken by dermatologists from 21,557 patients with nail conditions, mainly in the Brussels region. The specimens were examined by direct microscopy and/or histology, and cultured on Sabouraud medium agar. Only patients less than 17 years of age were considered as children. Clinical information was gathered about age, sex, and the location of the infected nail. Nine hundred sixty-three of the samples were from children, and 296 of those children had proven onychomycosis. More than three-fourths of the cases were found in children more than 6 years old, and boys were more frequently affected than girls. Toenails were the predominant location of infection. Trichophyton rubrum was the main pathogen, followed by Candida spp. and Trichophyton interdigitale. One case was caused by Scopulariopsis spp. As in adults, onychomycosis is probably the main nail disease in children. After the age of 6 years, the presentation is very similar to that in adults: toenails are mostly involved, and T. rubrum, the main pathogen, is responsible for distal and lateral subungual onychomycosis.


Therapy in allergic rhinoconjunctivitis: new horizons.
Allergic Rhinitis (AR) is a common disease that impacts productivity and has significant patient morbidity. We have a variety of agents available for the treatment of AR, but numerous patients still lack good control of symptoms and some are tolerating undesired side effects. Surveys have shown 1/5 of patients with AR are not fully satisfied with their AR medications and almost 1/2 feel they receive insufficient attention from their physicians. Newer agents for the treatment of AR are in development, and an overview of some of these are presented here.


Long term follow up of clinical outcome between patellar resurfacing and nonresurfacing in total knee arthroplasty: Chinese experience.
The long term outcome of patellar resurfacing in Chinese has not been well described. This study evaluated more than 10-year clinical outcomes and survivorship of patellar resurfacing or nonresurfacing in total knee arthroplasty. From January 1993 to December 2002, 265 patients accepted total knee arthroplasty in Department of Orthopaedic Surgery, Peking Union Medical College Hospital. Among them, 226 patients (246 knees) were successfully followed up, with 176 knees for patellar resurfacing and 70 knees for nonresurfacing. The survivorship of total knee arthroplasty between two groups and the hospital for special surgery knee score (HSS), patellar score, patellar related complication and radiological results were studied at the latest follow-up. The HSS knee score increased from 55.9±12.2 preoperatively to 92.0±10.9 postoperatively for patellar resurfacing group and from 56.6±9.9 to 94.2±11.4 for nonresurfacing group after average 11.4-year follow-up. Patellar score increased from 13.93±2.42 preoperatively to 28.33±2.20 for resurfacing group and from 13.55±2.73 to 27.8±2.37 for nonresurfacing group. There was no statistically significant difference for both HSS score, patellar score between the two groups with higher rate of anterior knee pain for nonresurfacing group. Patellar nonresurfacing had higher lateral subluxation than resurfacing group according to radiological evaluation. Patients with rheumatoid arthritis had 5.5 fold patellar related complication than patients with osteoarthritis. The 10-year survival rate was not statistically significant different between the two groups (P = 0.12). There was no significant difference of long-term clinical outcome and survivorship between patellar resurfacing and nonresurfacing. Patellar nonresurfacing can be advisable during primary total knee arthroplasty especially in Chinese patients with osteoarthritis. Selective patellar resurfacing for patients with rheumatoid arthritis can achieve lower patella related complication.


Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.
To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-β=0.8, α=0.05, two-sided). The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.


Perceived needs of parents of critically ill children.
To identify the needs of parents of critically ill hospitalized children as perceived by the parents and critical care nurses, and to identify any differences between the two groups. Descriptive, comparative. Pediatric intensive care unit (PICU) in a Midwestern hospital. A nonprobability convenience sample of parents or primary caregivers of critically ill children (n = 21) and pediatric critical care nurses (n = 17). Critical Care Family Needs Inventory modified for pediatrics and demographic questionnaires. Information, assurance, and proximity to the critically ill child were identified as priority needs of the PCGs in this study. Significant differences on specific needs were identified between PCG/nurse matched pairs; however, no significant differences were found in total scores between the two groups by a two-tailed paired t test. This study supports the need to investigate interventions to better address parental needs of critically ill children. By consistent identification, prioritization, and incorporation of parental needs into the plan of care, nurses can assist the parents in the recognition and fulfillment of needs that have less perceived importance. Research-based interventions will facilitate improved parental adaptation to their child's critical hospitalization.


The role of cPLA2 in Methylglyoxal-induced cell apoptosis of HUVECs.
Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is mainly formed as a byproduct of glycolysis. Elevated MGO level is known to induce apoptosis of vascular endothelial cells, which is implicated with progression of atherosclerosis and diabetic complications. However, the underlying mechanisms have not been exhaustively investigated yet. Here, we further characterized the mechanisms how MGO induced apoptosis in human umbilical vein endothelial cells (HUVECs). Our data revealed that cytosolic phospholipase A2 (cPLA2) played an important role in MGO-induced cell apoptosis. It was found that MGO could increase both the activity and expression of cPLA2. Inhibition of cPLA2 by Pyrrophenone (PYR) or siRNA significantly attenuated the MGO-induced apoptosis. Additionally, MGO time-dependently decreased the phosphorylation of nuclear factor κB (NF-κB). Pretreatment of the cells with NF-κB inhibitor, BAY11-7082, further increased MGO-induced apoptosis of HUVECs, indicating that NF-κB played a survival role in this MGO-induced apoptosis. Furthermore, in the presence of si-cPLA2 or PYR, MGO no longer decreased NF-κB phosphorylation. Beyond that, the antioxidant N-acetyl cysteine (NAC) could reverse the changes of both cPLA2 and NF-κB caused by MGO. p38, the upstream of cPLA2, was also significantly phosphorylated by MGO. However, p38 inhibitor failed to reverse the apoptosis induced by MGO. This study gives an important insight into the downstream signaling mechanisms of MGO, cPLA2-NF-κB, in endothelial apoptosis.


[Glutathione peroxidase and glutathione reductase activity in the rat liver after the administration of sodium selenite].
Sodium selenite 24h after its single administration to rats causes an increase in the activity of glutathione peroxidase and glutathione reductase in the liver tissue. 6 h after the selenium administration the enzymes activity does not differ from the control. Doses of 0.15, 0.3, 0.5 and 1 mg of selenium per 1 kg of the animal weight were investigated. 0.3 mg proved to be the least effective dose. An increase in the enzyme activity after administering 0.5 mg of selenium is retained for 6 days and 14 days after it does not differ from the control. The liver relative weight 24 h after administration of 0.5 mg of selenium per 1 kg of animal weight proved to be higher but three days later it did not differ from the control. After administering selenium in a dose of 1 mg/kg the liver relative weight was higher for 6 days. Actinomycin D administered in a dose of 0.5 mg/kg simultaneously with selenite prevents the rise in the enzyme activity and relative weight of the liver caused only by a single injection of selenium in the same dose.


Ultrasonically diagnosed simple cysts of the liver.
In 26 patients simple cysts of the liver were diagnosed by ultrasonography. Half of the patients had no symptoms, and half presented with abdominal pain and a palpable mass; 14 patients with small cysts required no treatment. Nine patients were operated upon, while 3 patients with large cysts were treated exclusively by ultrasonically guided drainage. Further, ultrasonically guided drainage was successful in two patients with recurrences after surgical treatment. Patients with small asymptomatic cysts of the liver, incidentally diagnosed should be left without treatment. Ultrasonically guided puncture is advocated as the first treatment in patients with large symptomatic cysts.


Pharmacovigilance study of a regional intravenous immunoglobulin (II): evaluation and comparison of an improved pharmaceutical form.
Intravenous immunoglobulin (IVIG) therapy is an effective treatment in patients with different diseases. This product must comply with all the regulatory requirements established by the World Health Organization and the European Pharmacopoeia for clinical tolerance, therapeutic efficacy, and viral safety. Although IVIG are effective and safe products, in some patients they may cause adverse reactions. The aim of this study was to assess the clinical tolerance of two pharmaceutical forms (lyophilized and liquid) of Imunoglobulina G Endovenosa UNC (IVIG UNC), a regional IVIG preparation, and to compare the reported data. The pharmacovigilance reports of 149 infusions in 51 patients treated with lyophilized IVIG UNC and of 157 infusions in 53 patients treated with liquid IVIG UNC were statistically evaluated. Clinical tolerance was evaluated through the adverse reactions reported. Lyophilized IVIG UNC: adverse reactions were reported in 6.7 % of the total number of infusions. Of these reactions, 4.0 % were mild, 2.0 % were moderate, and 0.7 % severe. Liquid IVIG UNC: adverse reactions were reported in 3.2 % of the total number of infusions; of these, 1.3 % were mild, 1.9 % were moderate, and 0.0 % were severe. Statistical analysis showed no association between tolerance and the pharmaceutical form used (p > 0.05) and indicated similar tolerance for both preparations. Based on the results obtained, the excellent clinical tolerance of both pharmaceutical forms of IVIG UNC can be confirmed.


[A case of collagenous colitis with watery diarrhea due to lansoprazole use in an elderly woman].
We report a case of a 75-year-old woman with urgent watery diarrhea, occurring 5 to 8 times per day, which began after starting lansoprazole (30 mg/day) for erosive gastritis. Her chronic watery diarrhea persisted for over 2 years with mild weight loss. Colonoscopy was performed and biopsies showed collagenous colitis in her transverse colon. We therefore replaced lansoprazole with famotidine (20 mg/day). Within 3 days after the discontinuation of lansoprazole, her watery diarrhea resolved and she recovered, and reported normal feces. Increasing age and female gender are major risk factors for collagenous colitis. The differential diagnosis of collagenous colitis should include: 1) an appropriate clinical history, excluding other etiologies, 2) normal or near-normal endoscopic and/or radiographic findings, and 3) colonoscopic biopsy histopathologic findings consistent with collagenous colitis. The histopathologic findings of colonoscopic biopsy are important for diagnosis. However, because of the colonoscopic burden in elderly patients, we first recommend the discontinuation of medications suspected to cause collagenous colitis.


MEDI-528, an anti-IL-9 humanized antibody for the treatment of asthma.
In development by MedImmune LLC, under license from Genaera Corp, MEDI-528 is an injectable, humanized mAb against IL-9 for the potential treatment of asthma. In asthma, airway inflammation is usually adequately minimized with standard-of-care treatments, such as inhaled corticosteroids and leukotriene modifiers, but it is sometimes less responsive to such therapies and other anti-inflammatory approaches are required. Several T-helper cell type 2-derived cytokines, such as IL-4, -5, -9 and -13, play a major role in the development of disease pathogenic features in asthma, including airway eosinophilia, increased IgE production, mucus hypersecretion and airway hyperreactivity. As an IL-9 antagonist, MEDI-528 appears to inhibit a range of asthma pathogenic features in antigen-exposed mice. To date, clinical data are modest, although insufficient to judge the efficacy of the drug in humans, and larger and longer-term clinical trials are required. MEDI-528, along with other anticytokine therapies targeting different ILs, remains under investigation in early-phase trials for asthma. Time will tell if this form of therapy can be used as an add-on to less efficacious anti-inflammatory therapy or can replace the existing anti-inflammatory therapies in the treatment of asthma.


Entanglement and co-tunneling of two equivalent protons in hydrogen bond pairs.
A theoretical study is reported of a system of two identical symmetric hydrogen bonds, weakly coupled such that the two mobile protons can move either separately (stepwise) or together (concerted). It is modeled by two equivalent quartic potentials interacting through dipolar and quadrupolar coupling terms. The tunneling Hamiltonian has two imaginary modes (reaction coordinates) and a potential with a single maximum that may turn into a saddle-point of second order and two sets of (inequivalent) minima. Diagonalization is achieved via a modified Jacobi-Davidson algorithm. From this Hamiltonian the mechanism of proton transfer is derived. To find out whether the two protons move stepwise or concerted, a new tool is introduced, based on the distribution of the probability flux in the dividing plane of the transfer mode. While stepwise transfer dominates for very weak coupling, it is found that concerted transfer (co-tunneling) always occurs, even when the coupling vanishes since the symmetry of the Hamiltonian imposes permanent entanglement on the motions of the two protons. We quantify this entanglement and show that, for a wide range of parameters of interest, the lowest pair of states of the Hamiltonian represents a perfect example of highly entangled quantum states in continuous variables. The method is applied to the molecule porphycene for which the observed tunneling splitting is calculated in satisfactory agreement with experiment, and the mechanism of double-proton tunneling is found to be predominantly concerted. We show that, under normal conditions, when they are in the ground state, the two porphycene protons are highly entangled, which may have interesting applications. The treatment also identifies the conditions under which such a system can be handled by conventional one-instanton techniques.


Public perception as a barrier to introducing wood in rivers for restoration purposes.
Reintroduction of wood in rivers for restoration purposes is now recognized in a positive way by scientists. Nevertheless, the perception of wood in riverscapes is strongly affected by the socio-cultural environment. This cultural influence might explain why wood reintroduction is accepted and promoted in some regions of the world but not in others, despite the demonstrated ecological benefits. From an extensive student perception survey, we show that most of the groups from nine countries in the world considered riverscapes with wood to be less aesthetic, more dangerous, and needing more improvement than riverscapes without wood. By contrast, this way of thinking was not observed in Germany, Sweden, and Oregon (USA), where the first instances of wood reintroduction occurred.


Demineralized bone matrix-induced ectopic bone formation in rats: in vivo study with follow-up by magnetic resonance imaging, magnetic resonance angiography, and dual-energy X-ray absorptiometry.
The aim of this study was to further explore the use of magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and dual-energy X-ray absorptiometry (DEXA) to assess bone formation and blood circulation in a pedicled bone graft substitute. In 14 Wistar rats, initially 10 weeks old, heterogeneous demineralized femur bone matrix implants were wrapped in pedicled adductor thigh muscle flaps. One rat died after surgery. Subsequently, bone formation and maintenance of blood vessel functionality were evaluated in six rats 6 weeks postimplantation by means of in vivo MRI/MRA and postmortem histomorphometry. The other seven rats were left for 12 weeks, whereafter bone formation was evaluated by in vivo DEXA and postmortem histomorphometry. The results demonstrated that after 6 weeks bone formation was present in four of six animals, quantified as 42 (+/-35)% and 25 (+/-19)% by means of MRI and histomorphometry, respectively. MRA was able to show patency of the pedicles of these four rats only, which suggests that the lack of blood supply in the other two rats is the cause of the failure to form bone. In the 12-week group, histology showed increased bone formation without signs of osteolysis, which was quantified histomorphometrically to be as high as 48 (+/-15)%. DEXA failed to show bone formation. It is concluded that in vivo MRI proved to be a reliable method for monitoring ectopic bone formation in a rat model, whereas in vivo DEXA was unable to detect the implants. Furthermore, in vivo MRA proved to be a useful technique for studying the circulation of muscle flaps in this animal model.


Lasonolide A: structural revision and total synthesis.
The proposed structure of lasonolide A was synthesized employing radical cyclization reactions of beta-alkoxyacrylates for preparation of the tetrahydropyranyl units A and B, but the spectroscopic data did not match those of the natural product. Both enantiomers of a revised structure featuring 17E,25Z double bonds were synthesized, and the (-)-isomer was found to be the biologically active enantiomer.