Multiparameter evidence synthesis in epidemiology and medical decision-making.
Meta-analysis has been well-established for many years, but has been largely confined to pooling evidence on pair-wise contrasts. Broader forms of synthesis have also been described, apparently re-invented in disparate fields, each time taking different computational approaches. The potential value of Bayesian estimation of a joint posterior parameter distribution and simultaneously sampling from it for decision analysis has also been appreciated. However, applications have been relatively few in number, sometimes stylized, and presented mainly to a statistical methods audience. As a result, the potential for multiparameter evidence synthesis in both epidemiology and health technology assessment has remained largely unrecognized. The advent of flexible software for Bayesian Markov chain Monte Carlo in the shape of WinBUGS has the made these earlier strands of work more widely available. Researchers can now carry out synthesis at a realistic level of complexity. The Bristol programme has not only contributed to a growing body of literature on how to synthesize different evidence structures, but also on how to check the consistency of multiple information sources and how to use the resulting models to prioritize future research.


Functional expression of PHO1 to the Golgi and trans-Golgi network and its role in export of inorganic phosphate.
Arabidopsis thaliana PHO1 is primarily expressed in the root vascular cylinder and is involved in the transfer of inorganic phosphate (Pi) from roots to shoots. To analyze the role of PHO1 in transport of Pi, we have generated transgenic plants expressing PHO1 in ectopic A. thaliana tissues using an estradiol-inducible promoter. Leaves treated with estradiol showed strong PHO1 expression, leading to detectable accumulation of PHO1 protein. Estradiol-mediated induction of PHO1 in leaves from soil-grown plants, in leaves and roots of plants grown in liquid culture, or in leaf mesophyll protoplasts, was all accompanied by the specific release of Pi to the extracellular medium as early as 2-3 h after addition of estradiol. Net Pi export triggered by PHO1 induction was enhanced by high extracellular Pi and weakly inhibited by the proton-ionophore carbonyl cyanide m-chlorophenylhydrazone. Expression of a PHO1-GFP construct complementing the pho1 mutant revealed GFP expression in punctate structures in the pericycle cells but no fluorescence at the plasma membrane. When expressed in onion epidermal cells or in tobacco mesophyll cells, PHO1-GFP was associated with similar punctate structures that co-localized with the Golgi/trans-Golgi network and uncharacterized vesicles. However, PHO1-GFP could be partially relocated to the plasma membrane in leaves infiltrated with a high-phosphate solution. Together, these results show that PHO1 can trigger Pi export in ectopic plant cells, strongly indicating that PHO1 is itself a Pi exporter. Interestingly, PHO1-mediated Pi export was associated with its localization to the Golgi and trans-Golgi networks, revealing a role for these organelles in Pi transport.


A survey of DNA methylation across social insect species, life stages, and castes reveals abundant and caste-associated methylation in a primitively social wasp.
DNA methylation plays an important role in the epigenetic control of developmental and behavioral plasticity, with connections to the generation of striking phenotypic differences between castes (larger, reproductive queens and smaller, non-reproductive workers) in honeybees and ants. Here, we provide the first comparative investigation of caste- and life stage-associated DNA methylation in several species of bees and vespid wasps displaying different levels of social organization. Our results reveal moderate levels of DNA methylation in most bees and wasps, with no clear relationship to the level of sociality. Strikingly, primitively social Polistes dominula paper wasps show unusually high overall DNA methylation and caste-related differences in site-specific methylation. These results suggest DNA methylation may play a role in the regulation of behavioral and physiological differences in primitively social species with more flexible caste differences.


Funneling and frustration in the energy landscapes of some designed and simplified proteins.
We explore the similarities and differences between the energy landscapes of proteins that have been selected by nature and those of some proteins designed by humans. Natural proteins have evolved to function as well as fold, and this is a source of energetic frustration. The sequence of Top7, on the other hand, was designed with architecture alone in mind using only native state stability as the optimization criterion. Its topology had not previously been observed in nature. Experimental studies show that the folding kinetics of Top7 is more complex than the kinetics of folding of otherwise comparable naturally occurring proteins. In this paper, we use structure prediction tools, frustration analysis, and free energy profiles to illustrate the folding landscapes of Top7 and two other proteins designed by Takada. We use both perfectly funneled (structure-based) and predictive (transferable) models to gain insight into the role of topological versus energetic frustration in these systems and show how they differ from those found for natural proteins. We also study how robust the folding of these designs would be to the simplification of the sequences using fewer amino acid types. Simplification using a five amino acid type code results in comparable quality of structure prediction to the full sequence in some cases, while the two-letter simplification scheme dramatically reduces the quality of structure prediction.


Chromatin remodeling during sea urchin early development: molecular determinants for pronuclei formation and transcriptional activation.
Transcriptional activation of specific genes is initiated after fertilization by the interaction of specific transcription factors with its cognate sequences in the chromatin context, thereby leading to a concerted and coordinated program which determines early development. Remodeling of the sperm chromatin after fertilization is a fundamental event for transcriptional activation and expression of the paternally inherited genome. The transitions in chromosomal proteins, as well as the mechanisms that participate in these transitions, have been investigated only to a limited extent as compared to the signal transduction patterns that govern egg activation or the dynamics and structural changes accompanying sperm nuclear membrane dissociation-association following insemination. In this review, we will discuss the remodeling of sperm chromatin that follows fertilization. We will emphasize the transitions of chromosomal proteins, as well as the post-translational modifications associated with these transitions. The molecular mechanisms that may be participating in these events will also be analyzed. We will further discuss the mechanisms that govern chromatin remodeling and the role of specific transcription factors in the control of the transcriptional program during sea urchin early development.


Quantitative and qualitative evaluation of Campylobacter spp. contamination of turkey cecal contents and carcasses during and following the slaughtering process.
The present study aimed to document quantitatively and qualitatively the contamination by thermotolerant Campylobacter spp. of turkey samples during slaughtering. Four Campylobacter-positive turkey flocks were investigated at the slaughterhouse at three different stages: evisceration (cecal content), after carcass rinses but before chilling (neck skin), and after breast meat cut (meat). In each case, the studied flock was slaughtered first thing in the morning any given day of the week. The efficiency of cleaning and disinfecting operations was examined in the facility prior to processing the studied flock. For each flock, 90 samples were collected from cecal contents, neck skins, and meat pieces and checked quantitatively and qualitatively for Campylobacter. Identification of Campylobacter species was determined by PCR, and genetic patterns were determined by pulsed-field gel electrophoresis. Campylobacter contamination levels of ceca range from 2 to more than 7 Log CFU/g, while those of neck skin range from 0.5 to 3.5 Log CFU/g and those of meat range from 0.1 to 1.9 Log CFU/g. These differences in Campylobacter counts were not associated with a modification of Campylobacter species ratio; however, in the Campylobacter jejuni population, four genetic groups identified from the ceca were not recovered during slaughtering operations and two other genetic groups were only detected after chilling at the cutting stage of the breast meat. The present study suggests that the slaughtering process did not affect Campylobacter species populations; however, it might have influenced the strain population. Finally, the Campylobacter populations found on breast meat were similar to those isolated from the digestive tract of the birds.


Evaluation of the psychometric properties of the Beck Depression Inventory in a non-elderly adult sample of patients with generalized anxiety disorder.
Although the Beck Depression Inventory (BDI) is commonly administered across a wide range of psychological disorders, its psychometric properties have not yet been examined in a non-elderly (aged 59 years or younger) adult sample of patients with generalized anxiety disorder (GAD). Completed BDIs were obtained from 48 patients with GAD (mean age=31.85 years) and 41 nonanxious control participants (mean age=30.49 years). The BDI exhibited good internal consistency in the clinical sample. Patients obtained more extreme scores on the BDI than did control participants, and patients with a comorbid mood disorder obtained more extreme scores on the BDI than did patients without a comorbid mood disorder. Patients' BDI scores correlated significantly more strongly with a clinician-administered measure of depression than with self-report measures of generalized anxiety, worry, social anxiety, or anxiety sensitivity, but not more strongly than with a clinician-administered measure of anxiety. BDI scores correlated positively with self-reported disability and negatively with life satisfaction. Overall, the BDI demonstrated good psychometric properties in this non-elderly adult sample of patients with GAD.


The electronic structure of carbones revealed: insights from valence bond theory.
In this contribution, we studied the OC-C bond in carbon suboxide and related allene compounds using the valence bond method. The nature of this bond has been the subject of debate, whether it is a regular, electron sharing bond or a dative bond. We compared the nature of this bond in carbon suboxide with the gold-CO bond in Au(CO)2+, which is a typical dative bond, and we studied its charge-shift bond character. We found that the C-CO bond in carbon suboxide is unique in the sense that it cannot be assigned as either a dative or electron sharing bond, but it is an admixture of electron sharing and dative components, together with a high contribution of ionic character. These findings provide a clear basis for distinguishing the commonly found dative bonds between ligands and transition metals and the present case of what may be described as coordinative bonding to carbon.


Modification of flower architecture during early stages in the evolution of self-fertilization.
The evolution of selfing from outcrossing is characterized by a series of morphological changes to flowers culminating in the selfing syndrome. However, which morphological traits initiate increased self-pollination and which are accumulated after self-fertilization establishes is poorly understood. Because the expression of floral traits may depend on the conditions experienced by an individual during flower development, investigation of changes in mating system should also account for environmental and developmental factors. Here, early stages in the evolution of self-pollination are investigated by comparing floral traits among Brazilian populations of Eichhornia paniculata (Pontederiaceae), an annual aquatic that displays variation in selfing rates associated with the breakdown of tristyly to semi-homostyly. Thirty-one Brazilian populations under uniform glasshouse conditions were compared to investigate genetic and environmental influences on flower size and stigma-anther separation (herkogamy), two traits that commonly vary in association with transitions to selfing. Within-plant variation in herkogamy was also examined and plants grown under contrasting environmental conditions were compared to examine to what extent this trait exhibits phenotypic plasticity. In E. paniculata a reduction in herkogamy is the principal modification initiating the evolution of selfing. Significantly, reduced herkogamy was restricted to the mid-styled morph and occurred independently of flower size. Significant genetic variation for herkogamy was detected among populations and families, including genotypes exhibiting developmental instability of stamen position with bimodal distributions of herkogamy values. Cloned genets exposed to contrasting growth conditions demonstrated environmental control of herkogamy and genotypic differences in plasticity of this trait. The ability to modify herkogamy independently of other floral traits, genetic variation in the environmental sensitivity of herkogamy, and the production of modified and unmodified flowers within some individuals, reveal the potential for dynamic control of the mating system in a species that commonly confronts heterogeneous aquatic environments.


[Descriptive study of infectious ear disease in relation to summer].
A descriptive study was made of infectious ear disease (including diffuse otitis externa, otomycosis, acute-on-chronic otitis media, and superinfection of a radical mastoidectomy cavity) in relation to changes of weather and habits in summer. During the months of June, July, and August 1996, 179 patients were evaluated in the emergency room of the Alicante General University Hospital, Spain. Average patient age at presentation was 30.52 (+/- 20.08) years and 56% were men. The most frequent disease was diffuse otitis externa (78%) followed by acute-on-chronic otitis media (12%), otomycosis (8%), and superinfection of a radical mastoidectomy cavity (2%). The most frequently involved microorganisms were Pseudomonas aeruginosa in diffuse otitis externa, Aspergillus niger and Candida in otomycosis, Escherichia coli, Haemophilus influenzae, Proteus mirabilis, and Staphylococcus aureus in acute-on-chronic otitis media. Patients were treated by cleaning detritus and secretions, usually followed by topical antibiotics for a maximum period of one week.


A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.
The gene responsible for cystic fibrosis (CF) has recently been identified and is predicted to encode a protein of 1,480 amino acids called the CF transmembrane conductance regulator (CFTR). Several functional regions are thought to exist in the CFTR protein, including two areas for ATP-binding, termed nucleotide-binding folds (NBFs), a regulatory (R) region that has many possible sites for phosphorylation by protein kinases A and C, and two hydrophobic regions that probably interact with cell membranes. The most common CF gene mutation leads to omission of phenylalanine residue 508 in the putative first NBF, indicating that this region is functionally important. To determine whether other mutations occur in the NBFs of CFTR, we determined the nucleotide sequences of exons 9, 10, 11 and 12 (encoding the first NBF) and exons 20, 21 and 22 (encoding most of the second NBF) from 20 Caucasian and 18 American-black CF patients. One cluster of four mutations was discovered in a 30-base-pair region of exon 11. Three of these mutations cause amino-acid substitutions at residues that are highly conserved among the CFTR protein, the multiple-drug-resistance proteins and ATP-binding membrane-associated transport proteins. The fourth mutation creates a premature termination signal. These mutations reveal a functionally important region in the CFTR protein and provide further evidence that CFTR is a member of the family of ATP-dependent transport proteins.


[Production of the mutant E strain of Rickettsia prowazekii by mutagen exposure].
The possibility of obtaining the mutants of R. prowazekii, strain E, by exposing these organisms to the action of N-methyl-N-nitro-N-nitrosoguanidine was studied; this substance, used in doses of 5-10 micrograms, showed a mutagenic effect on rickettsiae suspended in physiological saline, after their exposure for 10-20 minutes at 37 degrees C. The mutants thus obtained proved to be resistant to erythromycin and rifampicin and were characterized by heterogeneity in the degree and stability of their antibiotic resistance. The effectiveness of selection was increased if mutagen-treated rickettsiae were selected after the first passage in chick embryos. The induced mutants differed from the original rickettsial strain by their lower infectiosity for chick embryos.


Modelling genetic and clinical heterogeneity in epithelial ovarian cancers.
The biology underlying early-stage epithelial ovarian cancer (EOC) development is poorly understood. Identifying biomarkers associated with early-stage disease could have a significant impact on reducing mortality. Here, we describe establishment of a three-dimensional (3D) in vitro genetic model of EOC initiation and early-stage neoplastic progression. Normal primary ovarian epithelial (POE) cells, immortalized using hTERT (immortalised ovarian epithelial [IOE] cells), were partially transformed by overexpressing the CMYC oncogene (IOE(CMYC) cells). Subsequent expression of mutant alleles of KRAS (KRAS(G12V)) or BRAF (BRAF(V600E)) created double-mutant lines (IOE(CMYC.KRAS) and IOE(CMYC.BRAF)). The transformed phenotype of IOE(CMYC) cells was further enhanced in concert with KRAS(G12V)/BRAF(V600E) expression, as in vitro analyses indicated that IOE(CMYC) cells had undergone morphological and phenotypic changes characteristic of neoplastic progression. When cultured as 3D spheroids, IOE cells underwent growth arrest, reminiscent of nonproliferative, unstimulated POE in vivo. In contrast, IOSE(CMYC+BRAF/KRAS) cells formed highly proliferative, poly-aggregate spheroid structures, showing increased expression of the Wilms tumour 1 tumourigenic marker and MIB1 proliferation marker. Transcriptomic analyses identified different gene expression profiles between the different cell lines and novel candidate genes (e.g. RGS4, CTGF and THBS1) that are somatically altered in EOCs. Gene expression signatures were compared with signatures from primary EOCs; tumours with IOE(CMYC) 'like' signatures were more likely to be high grade (P = 0.018); tumours with BRAF signatures were associated with improved relapse-free survival (P = 0.003). In conclusion, we have established in vitro 3D models of early-stage EOCs, which reflect genetic and phenotypic heterogeneity of the disease. Molecular genetic characteristics of these models correlated with molecular and clinical features of primary EOCs.


Pulmonary infiltrates in non-HIV immunocompromised patients: a diagnostic approach using non-invasive and bronchoscopic procedures.
The development of pulmonary infiltrates is a frequent life threatening complication in immunocompromised patients, requiring early diagnosis and specific treatment. In the present study non-invasive and bronchoscopic diagnostic techniques were applied in patients with different non-HIV immunocompromised conditions to determine the aetiology of the pulmonary infiltrates and to evaluate the impact of these methods on therapeutic decisions and outcome in this population. The non-invasive diagnostic methods included serological tests, blood antigen detection, and blood, nasopharyngeal wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic techniques included fibrobronchial aspirate (FBAS), protected specimen brush (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of pulmonary infiltrates were prospectively evaluated during a 30 month period in 52 solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT) recipients, 68 patients with haematological malignancies, and 27 patients requiring chronic treatment with corticosteroids and/or immunosuppressive drugs. An aetiological diagnosis was obtained in 162 (81%) of the 200 patients. The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non-infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral (20/125, 10%), and the most frequent pathogens were Aspergillus fumigatus (n=29), Staphylococcus aureus (n=17), and Pseudomonas aeruginosa (n=12). Among the non-infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were used; specifically, the diagnostic yield of blood cultures was 30/191 (16%); sputum cultures 27/88 (31%); NPW 9/50 (18%); and TBAS 35/55 (65%). Bronchoscopic techniques led to the diagnosis of pulmonary infiltrates in 59% of the cases in which they were used: FBAS 16/28 (57%), BAL 68/135 (51%), and PSB 30/125 (24%). The results obtained with the different techniques led to a change in antibiotic treatment in 93 cases (46%). Although changes in treatment did not have an impact on the overall mortality, patients with pulmonary infiltrates of an infectious aetiology in whom the change was made during the first 7 days had a better outcome (29% mortality) than those in whom treatment was changed later (71% mortality; p=0.001). Non-invasive and bronchoscopic procedures are useful techniques for the diagnosis of pulmonary infiltrates in immunocompromised patients. Bronchial aspirates (FBAS and TBAS) and BAL have the highest diagnostic yield and impact on therapeutic decisions.


Injectable ECM scaffolds for cardiac repair.
Injectable biomaterials have been developed as potential minimally invasive therapies for treating myocardial infarction (MI) and heart failure. Christman et al. first showed that the injection of a biomaterial alone into rat myocardium can improve cardiac function after MI (Christman et al. Tissue Eng 10:403-409, 2004). More recently, hydrogel forms of decellularized extracellular matrix (ECM) materials have shown substantial promise. Here we present the methods for fabricating an injectable cardiac specific ECM biomaterial shown to already have positive outcomes in small and large animal models for cardiac repair (Singelyn et al. Biomaterials 30:5409-5416, 2009; Singelyn et al. J Am Coll Cardiol 59:751-763, 2012; Seif-Naraghi et al. Sci Transl Med 5:173ra25, 2013). Also covered are the methods for the injection of a biomaterial into rat myocardium using a surgical approach through the diaphragm. Although the methods shown here are for injection of an acellular biomaterial, cells or other therapeutics could also be added to the injection for testing other regenerative medicine strategies.


Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial.
Observational data suggested that supplementation with vitamin D could reduce risk of infection, but trial data are inconsistent. We aimed to examine the effect of oral vitamin D supplementation on antibiotic use. We conducted a post hoc analysis of data from pilot D-Health, which is a randomized trial carried out in a general community setting between October 2010 and February 2012. A total of 644 Australian residents aged 60-84 y were randomly assigned to receive monthly doses of a placebo (n = 214) or 30,000 (n = 215) or 60,000 (n = 215) IU oral cholecalciferol for ≤12 mo. Antibiotics prescribed during the intervention period were ascertained by linkage with pharmacy records through the national health insurance scheme (Medicare Australia). People who were randomly assigned 60,000 IU cholecalciferol had nonsignificant 28% lower risk of having antibiotics prescribed at least once than did people in the placebo group (RR: 0.72; 95% CI: 0.48, 1.07). In analyses stratified by age, in subjects aged ≥70 y, there was a significant reduction in antibiotic use in the high-dose vitamin D compared with placebo groups (RR: 0.53; 95% CI: 0.32, 0.90), whereas there was no effect in participants aged <70 y (RR: 1.07; 95% CI: 0.58, 1.97) (P-interaction = 0.1). Although this study was a post hoc analysis and statistically nonsignificant, this trial lends some support to the hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with lower risk of infection, particularly in older adults. The trial was registered at the Australian New Zealand Clinical Trials Registry (anzctr.org.au) as ACTRN12609001063202.


Barriers and Facilitators for the Donation and Acceptance of Human Breast milk: A Scoping Review.
Human milk is the best source of nutrients for all infants. When a mother's own milk is unavailable, the World Health Organization suggests using donor human milk for premature neonates with or without medical complications. Exploring the barriers and facilitators for breast milk donation and its acceptability is essential for developing this intervention. A scoping review was conducted based on a methodological framework developed by Arksey and O'Malley (Int J Soc Res Methodol 8:19-32, 2005). A search was conducted in PubMed (NCBI), CINAHL (EBSCO), and Web of Science (Elsevier). A two-stage sequential screening process was adopted. Data extraction was done using a piloted data extraction form. We included 20 articles for narrative synthesis. Barriers and facilitators for donating and accepting breast milk were categorized under six themes: individual, family, community, workplace, health system, and policy-related. The common individual barriers were time requirements for BMD, personal dislike of the process, lack of knowledge, insufficient milk, negative opinions, and lack of information. Family stigma, negative rumors, less educated family members, and illness of a family member were identified as family-related barriers. Community-related barriers include cultural or religious unacceptable practices, societal taboos, and distance to milk banks. The major barriers identified in relation to the health system were lack of practical and psychological support, lack of information, storing and transportation issues, lack of knowledge among HCWs, and logistical challenges of creating a milk lab. The common work-related barriers were the lack of adequate time, philosophical objections, and incomprehension at returning to work. Policy-related barriers identified include the need for hygiene requirements, donation costs, and lack of standardized guidelines. Making the donation process faster, providing pick-up services for donors, and community education and male partner engagement regarding breast milk donation could help to boost the acceptability of breast milk donation.


Potential biomarkers of dichlorvos induced neuronal injury in rats.
The present study was designed to develop suitable biochemical markers of chronic dichlorvos exposure using rat as the animal model. Animals were exposed to dichlorvos (6 mg kg-1 (body weight) day-1) for 8 weeks and the activities of five potential markers were assayed. Acetylcholinesterase, assayed as an index of cholinergic function, was found to decrease in both haemolysate and brain tissue. Cytochrome oxidase, used as a marker of impaired energy metabolism, was also seen to decrease in platelets and brains of dichlorvos-treated animals. However, acid phosphatase, a lysosomal marker of tissue injury, was increased in both serum and brains of experimental animals. Chronic dichlorvos exposure also led to a decrease in the activity of glucose-6-phosphate dehydrogenase, which was assayed in brain as an index of oxidative stress. Dichlorvos administration did not affect 2', 3'-cyclic nucleotide phosphohydrolase. The present study therefore, indicates that apart from acetylcholinesterase, which is probably a non-specific marker of dichlorvos neurotoxicity, the levels of cytochrome oxidase, acid phosphatase and glucose-6-phosphate dehydrogenase may serve as useful determinants of dichlorvosinduced neuronal injury.


"The Florence Experience": A multimedia and multisensory guidebook for cultural towns inspired by Universal Design approach.
In order to plan a trip, tourists with disabilities need to gather and analyse a broad range of information concerning the features of the places and services with which they are going to interact. For these people, guidebooks may represent an important source of information for gaining prior knowledge about the various critical situations they may experience as tourists. Generally, disabled people find tourist information on dedicated communication tools; guidebooks for the disabled often provide information for wheelchair users only. The aim of the research project was to develop a mainstream guidebook with supplementary tourist information both for people with impaired vision and for people with reduced mobility. The communication project behind "The Florence Experience" guidebook is inspired by both the Universal Design approach and the Performance Design approach. This article describes a case study and provides suggestions for planning in similar situations. It is also part of a broader research project relating to the communication about urban spaces accessibility. The main outcome of the research project is a multimedia and multisensory bilingual guidebook (in Italian and English) that provides information in four separate coordinated forms: a paper-based guidebook, web pages, MP3 audio files, and portable tactile maps. Creating a guidebook for all is a tough challenge that requires a highly articulated vision and the cooperation of different fields of knowledge and skills. Despite the limits described in the paper, "The Florence Experience" guidebook is, in our opinion, a considerable step forward with respect to the majority of available guidebooks both because it is a unique information tool for disabled and non-disabled people and because, unlike the majority of the guidebooks for disabled people, it does not only consider the needs of wheelchair users.


Modulated interlayer charge transfer dynamics in a monolayer TMD/metal junction.
The performance of optoelectronic devices based on monolayer transition-metal dichalcogenide (mTMD) semiconductors is significantly affected by the contact at the mTMD-metal interface, which is dependent on interlayer interactions and coupling. Here, we report a systematic optical method to investigate the interlayer charge transfer and coupling in a mTMD-metal heterojunction. Giant photoluminescence (PL) quenching was observed in a monolayer MoS2/Pd (1L MoS2/Pd) junction which is mainly due to the efficient interlayer charge transfer between Pd and MoS2. 1L MoS2/Pd also exhibits an increase in the PL quenching factor (η) as the temperature decreases, due to a reduction of the interlayer spacing. Annealing experiments were also performed which supported interlayer charge transfer as the main mechanism for the increase of η. Moreover, a monolayer MoS2/Au (1L MoS2/Au) junction was fabricated for engineering the interlayer charge transfer. Interestingly, a narrowing effect of the full width at half maximum (FWHM) was encountered as the junctions changed from 1L MoS2/SiO2 → 1L MoS2/Au → 1L MoS2/Pd, possibly originating from a change of the doping level induced weakening of exciton-carrier scattering. Our results deepen the understanding of metal-semiconductor junctions for further exploring fundamental phenomena and enabling high-performance devices using mTMD-metal junctions.


Epithelial topology.
It is universally accepted that genetic control over basic aspects of cell and molecular biology is the primary organizing principle in development and homeostasis of living systems. However, instances do exist where important aspects of biological order arise without explicit genetic instruction, emerging instead from simple physical principles, stochastic processes, or the complex self-organizing interaction between random and seemingly unrelated parts. Being mostly resistant to direct genetic dissection, the analysis of such emergent processes falls into a grey area between mathematics, physics and molecular cell biology and therefore remains very poorly understood. We recently proposed a mathematical model predicting the emergence of a specific non-Gaussian distribution of polygonal cell shapes from the stochastic cell division process in epithelial cell sheets; this cell shape distribution appears to be conserved across a diverse set of animals and plants.1 The use of such topological models to study the process of cellular morphogenesis has a long history, starting almost a century ago, and many insights from those original works influence current experimental studies. Here we review current and past literature on this topic while exploring some new ideas on the origins and implications of topological order in proliferating epithelia.


[Dry bed training in nocturnal enuresis].
In order to determine the prevalence of bedwetting, in the period September 1987-June 1989 an investigation was conducted among 1882 pupils of 15 primary schools in a rural area of the Netherlands. The investigation coincided with the periodical medical examination for which all pupils of these groups were invited and for which over 99% reported. In addition to this epidemiological study, a study was made of the effect of dry bed training, as a part of youth health care, in 36 children with nocturnal enuresis. Of the children examined, 8% wet their beds at least once a week, boys twice as often as girls. The secondary form of nocturnal enuresis occurred mostly in those aged 7-8 (44%) and mostly after certain events such as start of the school year, family problems or hospitalization. The proportion of bedwetting children with a parent with a history of nocturnal enuresis in youth was large: 56%. Of the girls with nocturnal enuresis, 25% had had a urinary tract infection as against 0.4% of the control group. Nocturnal enuresis often caused emotional stress in child and parents. The success rate of the dry bed training was 86%. Most children were dry within two months; 32% had a--frequently transient--relapse. After six months, 75% of the children who had had dry bed training remained dry at night. Group dry bed training appears a suitable method for children with nocturnal enuresis from age 8 when other methods (including the pad and buzzer) are unsuccessful. The training is feasible outside hospital and is an appropriate part of the tasks of youth health care.


Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies on α(1A)-adrenergic receptor antagonists based on pharmacophore molecular alignment.
The α(1A)-adrenergic receptor (α(1A)-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α(1A)-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-oneout cross-validation correlation coefficients were q(2) (CoMFA) = 0.840 and q(2) (CoMSIA) = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r(2) (pred) (/CoMFA) = 0.694; r(2) (pred) (/CoMSIA) = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α(1A)-AR antagonists.


Development of improved adenosine deaminase retroviral vectors.
A series of adenosine deaminase (ADA) retroviral vectors were designed and constructed with the goal of improved performance over the PA317/LASN vector currently used in clinical trials. First, the bacterial selectable-marker neomycin phosphotransferase (neo) gene was removed to create a "simplified" vector. Second, the Moloney murine leukemia virus long terminal repeat (LTR) promoter used for ADA expression was replaced with either the myeloproliferative sarcoma virus (MPSV) or SL3-3 LTR. Supernatant from each ADA vector was used to transduce ADA-deficient (ADA-) B- and T-cell lines as well as primary peripheral blood mononuclear cells (PBMC) from an ADA- severe combined immunodeficiency patient. Total ADA enzyme activity and ADA activity per integrant in the transduced cells demonstrated that the MPSV LTR splicing vector design provided the highest level of ADA expression per cell. This ADA(MPSV) vector was then tested in packaging cell lines containing either the gibbon ape leukemia virus envelope (PG13 cells), the murine amphotropic envelope (FLYA13 cells), or the feline endogenous virus RD114 envelope (FLYRD18 cells). The results indicate that FLYRD18/ADA(MPSV), a simplified ADA retroviral vector with the MPSV LTR, provides a 17-fold-higher level of ADA expression in human lymphohematopoietic cells than the PA317/LASN vector currently in use.


Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence.
The aim was to evaluate changes of bone mineral density (BMD) and markers of bone turnover in healthy adolescents, and in adolescent users of combined oral contraceptives (COCs) with different ethinylestradiol (EE) contents. In this prospective crossover study, 56 healthy females (15-19.5 years) with desire to use hormonal contraception were randomized to COC with either 30 or 15 μg of EE in crossover design of 9-month intervention each in reverse order. Nonusers of the same age (n=28) served as controls. BMD at lumbar spine (LS), total femur, femoral neck, distal radius, and total body, and serum markers (N-propeptide of type I procollagen, and type I collagen C-telopeptide) were measured at baseline and after 9 and 18 months. In COC nonusers, BMD significantly increased at LS and radius, while markers decreased. In COC users, BMD did not increase, with the exception of LS BMD in the 30 μg COC group (P<0.05). In the crossover design, a difference between the low- and very low-dose COC users was found in LS BMD changes (P<0.05), where increase in BMD was more impaired in the 15 μg COC users. The skeletal effects of COC remained significant after adjustments for age and smoking status. Markers declined faster in COC users during the first period, while they remained stable or even increased during the second 9 months. Physiological acquisition of LS BMD during adolescent age may be prevented by use of COC, especially those containing very low dose of EE.


Laparoscopy-Assisted Transperitoneal Percutaneous Nephrolithotomy for the Treatment of Renal Stones in a Horseshoe Kidney.
The objective of this case report is to highlight treatment by LAT-PCNL in a patient with horseshoe kidney. A 51-year-man with hematuria presented to the emergency department with moderate abdominal pain starting 7 hrs ago. He did not report a history of previous urological disease. Renal stone and horseshoe kidney malformation were diagnosed based on the plain abdominal film, intravenous urogram (IVU), non-contrast computed tomography (CT-IVU), and ultrasound findings. Due to the larger stone bulk and renal malformation, it was not possible to perform extracorporeal shock wave lithotripsy (ESWL) monotherapy or ESWL sandwich therapy. Moreover, since percutaneous nephrolithotomy (PCNL) had some challenges and limitations due to high skin-to-stone distance, special anatomy, dispersion stones, and possible consequent internal organs injuries, we performed LAT-PCNL on our patient. We did not observe any perioperative complication. Postoperative control abdominal x-ray revealed only a medium ureteral stone that was extracted while removing the Double-J stent a month later. The patient was discharged on the third postoperative day with normal laboratory values. At 3-month follow-up, the patient was stone-free with normal renal function and renal ultrasonography. Laparoscopy-assisted transperitoneal PCNL seems to be a safe and minimally invasive technique that can be used as an alternative approach in the management of renal stones in special cases of horseshoe kidneys.


Archaeological, radiological, and biological evidence offer insight into Inca child sacrifice.
Examination of three frozen bodies, a 13-y-old girl and a girl and boy aged 4 to 5 y, separately entombed near the Andean summit of Volcán Llullaillaco, Argentina, sheds new light on human sacrifice as a central part of the Imperial Inca capacocha rite, described by chroniclers writing after the Spanish conquest. The high-resolution diachronic data presented here, obtained directly from scalp hair, implies escalating coca and alcohol ingestion in the lead-up to death. These data, combined with archaeological and radiological evidence, deepen our understanding of the circumstances and context of final placement on the mountain top. We argue that the individuals were treated differently according to their age, status, and ritual role. Finally, we relate our findings to questions of consent, coercion, and/or compliance, and the controversial issues of ideological justification and strategies of social control and political legitimation pursued by the expansionist Inca state before European contact.


Injurious effects of lysophosphatidylcholine on barrier properties of alveolar epithelium.
We studied the effects of lysophosphatidylcholine (lysoPC) on the barrier properties and the morphology of the alveolar-capillary membrane in isolated, fluid-filled hamster lungs continuously perfused. When instilled into the airspace at initial concentrations of 8-128 micrograms/ml, lysoPC causes dose-dependent increases in the permeability-surface area product of the alveolar epithelium for small (14C-sucrose, 342) and large (125I-neutral dextran, 70,000) solutes, with maximal values for each solute approximately 15 times control. Rapid whole-lung weight gains are caused by 128 micrograms lysoPC per milliliter, but each of the lower concentrations has no effect on net lung water balance. Electron-microscopic studies demonstrate that type I pneumonocytes are the lung cells most susceptible to lysoPC exposure, with cell swelling being the most prominent feature from low-dose exposure with more severe disruptive changes at the highest concentration tested. The effects of lysoPC are relatively specific, as several structurally related lipids have little or no effect at equivalent concentrations. Instillation of phospholipase A2 causes functional changes similar to those seen with lysoPC, presumably by generation of lysoPC from endogenous phospholipids. Studies employing a 14C-radiolabeled compound show that instilled lysoPC rapidly partitions into the lung lipid fraction where a major portion of the acyl group becomes incorporated into phosphatidylcholine. The amount of instilled lysoPC required to produce functional and morphological effects comprises only a few percent of total lung phospholipids. Since lysoPC is a normal component of lung phospholipids, severe lung dysfunction might result from minor abnormalities in the formation or degradation of this compound.


[Study of the latex agglutination reaction using a light-scattering method].
Light scattering techniques as a method for monitoring latex agglutination test were under study. The model system, employed in the studies, consisted of a suspension containing polystyrene latex microspheres with tetanus antitoxin immobilized on them (carrier particles) and antitetanus serum (3000 IU). The studies helped define approaches to the choice of the optimal conditions for monitoring the latex agglutination test. Light scattering method has proved to be highly sensitive, its sensitivity essentially surpassing that of slide tests and permitting the detection of early agglutination stages.


Supercomputing in medical imaging.
It is suggested that the diagnostic imaging department of the future will make extensive use of computer networks, mass storage devices, and sophisticated workstations at which humans and machines will interact, assisted by techniques of computer vision and artificial intelligence, to achieve integration of multimodality imaging information and expert medical knowledge. Recent developments in medical imaging are described, and manipulation, display, and analysis techniques that are likely to benefit from supercomputing are examined. The following image processing tasks are discussed; restoration of images; spatial and temporal image and image sequence analysis; image restoration; mathematical image reconstruction from projections; and three-dimensional image analysis. Current trends and future efforts are discussed.


Multiple reassortment and interspecies transmission events contribute to the diversity of feline, canine and feline/canine-like human group A rotavirus strains.
RNA-RNA hybridization assays and complete genome sequence analyses have shown that feline rotavirus (FRV) and canine rotavirus (CRV) strains display at least two distinct genotype constellations (genogroups), represented by the FRV strain RVA/Cat-tc/AUS/Cat97/1984/G3P[3] and the human rotavirus (HRV) strain RVA/Human-tc/JPN/AU-1/1982/G3P3[9], respectively. G3P[3] and G3P[9] strains have been detected sporadically in humans. The complete genomes of two CRV strains (RVA/Dog-tc/ITA/RV198-95/1995/G3P[3] and RVA/Dog-tc/ITA/RV52-96/1996/G3P[3]) and an unusual HRV strain (RVA/Human-tc/ITA/PA260-97/1997/G3P[3]) were determined to further elucidate the complex relationships among FRV, CRV and HRV strains. The CRV strains RV198-95 and RV52-96 were shown to possess a Cat97-like genotype constellation. However, 3 and 5 genes of RV198-95 and RV52-96, respectively, were found in distinct subclusters of the same genotypes, suggesting the occurrence of reassortment events among strains belonging to this FRV/CRV/HRV genogroup. Detailed phylogenetic analyses of the HRV strain PA260-97 showed that (i) 8 genome segments (VP3, VP4, VP6, VP7 and NSP2-5) clustered closely with RV198-95 and/or RV52-96; (ii) 2 genome segments (VP1 and VP2) were more closely related to HRV AU-1; and (iii) 1 genome segment (NSP1) was distantly related to any other established NSP1 genotypes and was ratified as a new NSP1 genotype, A15. These findings suggest that the human strain PA260-97 has a history of zoonotic transmission and is likely a reassortant among FRV/CRV strains from the Cat97 and AU-1-like genogroups. In addition, a potential third BA222-05-like genogroup of FRV and HRV strains should be recognized, consisting of rotavirus strains with a stable genetic genotype constellation of genes also partially related to bovine rotavirus (BRV) and bovine-like rotaviruses. The detailed phylogenetic analysis indicated that three major genotype constellations exist among FRV, CRV and feline/canine-like HRV strains, and that reassortment and interspecies transmission events contribute significantly to their wide genetic diversity.


The flight of the Passenger Pigeon: phylogenetics and biogeographic history of an extinct species.
The human-caused extinction of the Passenger Pigeon (Ectopistes migratorius) is one of the best known and documented of any bird. This event was particularly alarming because the Passenger Pigeon went from being one of the most numerous avian species in the world to extinct in a period of decades, when the last individual died in captivity in a Cincinnati Zoo in 1914. While a great deal of information exists on the likely direct and indirect causes of its demise, as well as information on life-history, the phylogenetic relationships of this species have been subject to considerable speculation. Here we use DNA sequences obtained from museum specimens to resolve the phylogenetic position of this species with respect to other pigeons and doves (Columbiformes). We show that the Passenger Pigeon is not related to the New World mourning doves (Zenaida) as many authors have suggested, but is the sister taxon of all other New World pigeons (Patagioenas). Biogeographic analysis suggests the Passenger Pigeon lineage may have colonized North America from Asia, and subsequently dispersed into South America, leading to a more extensive radiation of New World pigeons.


Effects of pH and salinity on the antimicrobial properties of clavanins.
Clavanins are histidine-rich, amidated alpha-helical antimicrobial peptides that were originally isolated from the leukocytes (hemocytes) of a tunicate, Styela clava. The activities of clavanin A amide and clavanin A acid against Escherichia coli, Listeria monocytogenes, and Candida albicans were substantially greater at pH 5.5 than at pH 7.4. In contrast, clavanin AK, a synthetic variant of clavanin A acid containing 4 histidine-->lysine substitutions exerted substantial activity at both pH 7.4 and pH 5.5. Each of these three clavanins permeabilized the outer and inner membranes of E. coli very effectively at pH 5.5, but only clavanin AK did so at pH 7.4. Unlike magainin 1 and cecropin P1, alpha-helical antimicrobial peptides from frog skin and porcine intestine, respectively, clavanins were broadly effective against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, as well as gram-negative organisms. Because clavanins exert substantial antimicrobial activity in 0.1 to 0.3 M NaCl, they provide templates for designing broad-spectrum peptide antibiotics intended to function in extracellular environments containing normal or elevated NaCl concentrations. The pH-dependent properties of histidine-rich antimicrobial peptides may allow the design of agents that would function selectively in acidic compartments, such as the gastric lumen, or within phagolysosomes.


Production of alpha-amylase with Aspergillus flavus on Amaranthus grains by solid-state fermentation.
The effects of the ingredients of the Rajgeera (Amaranthus paniculatas) medium designed for production by A. flavus was evaluated with the help of the fractional factorial method, 'The Plackett-Burman' design. Out of the fifteen medium components used in the design, four components, viz., corn steep liquor, ammonium hydrogen phosphate, sodium chloride and calcium chloride were selected based on the contrast coefficient values and further used as independent variables in the 'Box-Behnken' design. A polynomial multiple regression model was generated using the SPSS/PC + (version 7.5) statistical analysis package. Corn steep liquor, ammonium hydrogen phosphate, sodium chloride and calcium chloride contributed to the yield to the tune of 81.3% of which sodium chloride and calcium chloride affected the yield to the tune of 68.3%. The yield obtained from the optimized medium was 8 times that obtained from the original medium. Amaranthus paniculatas grains as a source of starch and carbon for production of alpha-amylase under solid-state fermentation has been studied for the first time.


Drug metabolism by the human fetus.
A review of the literature that pertains to drug biotransformation in human fetal tissues reveals that, in spite of several publications in this comparatively new area of research, only very limited definitive information is currently available. The large majority of the studies performed have dealt with the cytochrome P-450-dependent microsomal mono-oxygenase systems and for several of the common drug metabolising reactions, very little or no data are available at this time. Some of the more important data that have emerged include observations that important bioactivation reactions can be demonstrated in human fetal tissues obtained during the period of late embryogenesis (high susceptibility to chemical dysmorphogenesis) and that the human fetal adrenal gland possesses considerable capacity to catalyse several important oxidation-reduction reactions. From the data available to date, it would appear that, in most instances, the biotransformation of drugs in the human embryo and fetus would not affect maternal plasma concentrations significantly. From the viewpoint of parameters of the pharmacokinetics of parent drug (or other xenobiotic) substrates under steady-state conditions, human fetal drug metabolism probably is of little consequence in most cases, although exceptions may exist. Pharmacokinetic parameters observed after isolated exposure, however, are very likely to be affected, perhaps markedly, in some instances. The demonstrated capacity of human prenatal tissues and cells to generate reactive intermediary metabolites, including those that produce mutations, has attracted the greatest attention recently. This capacity may be associated with extremely important adverse reactions to drugs and other environmental chemicals. Such adverse responses include transplacental mutagenesis, carcinogenesis, dysmorphogenesis, and perhaps several other undesirable effects. Although far from conclusive, the data tend to suggest that humans and subhuman primates may be more vulnerable than the smaller common experimental animals to the toxic effects of foreign organic chemicals during prenatal life. These factors should be weighed whenever exposure of pregnant women to such agents (e.g. via drug administration) is contemplated.


Multi-input square iterative learning control with input rate limits and bounds.
We present a simple modification of the iterative learning control algorithm of Arimoto et al. (1984) for the case where the inputs are bounded and time-rate-limited. The Jacobian error condition for monotonicity of input-error, rather than output-error, norms, is specified, the latter being insufficient to assure convergence, as proved herein. To the best of our knowledge, these facts have not been previously pointed out in the iterative learning control literature. We present a new proof that the modified controller produces monotonically decreasing input error norms, with a norm that covers the entire time interval of a learning trial.


Paradoxical movement of the lower ribcage at rest and during exercise in COPD patients.
Paradoxical inward displacement of the costal margin during inspiration is observed in many chronic obstructive pulmonary disease patients at rest but its importance is unclear. The current authors studied 20 patients (forced expiratory volume in one second 32.6+/-11.7, functional residual capacity 186+/-32% predicted) and 10 healthy controls at rest and during symptom-limited incremental exercise. With optoelectronic plethysmography, the phase shift between pulmonary and abdominal ribcage volumes and the percentage of inspiratory time the ribcage compartments moved in opposite directions were quantified, using control data to define the normal range of movement. Eight patients showed lower ribcage inspiratory paradox at rest (P+), while 12 patients did not (P-). This was unrelated to resting lung function or exercise tolerance. Total end-expiratory chest wall volume (EEV(cw)) increased immediately when exercise began in P+ patients, but later in exercise in P- patients. This difference in EEV(cw) was mainly due to a greater increase of end-expiratory pulmonary ribcage volume in P+ patients. During exercise, dyspnoea increased similarly in the two groups, while leg effort increased more markedly in the patients without paradox. In conclusion, lower ribcage paradox at rest is reproducible and associated with early-onset hyperinflation of the chest wall and predominant dyspnoea at end-exercise. When paradox is absent, the sense of leg effort becomes a more important symptom limiting exercise.


The elucidation of phosphosugar stress response in Bacillus subtilis guides strain engineering for high N-acetylglucosamine production.
Bacillus subtilis is a preferred microbial host for the industrial production of nutraceuticals and a promising candidate for the synthesis of functional sugars, such as N-acetylglucosamine (GlcNAc). Previously, a GlcNAc-overproducer B. subtilis SFMI was constructed using glmS ribozyme dual-regulatory tool. Herein, we further engineered to enhance carbon flux from glucose towards GlcNAc synthesis. As a result, the increased flux towards GlcNAc synthesis triggered phosphosugar stress response, which caused abnormal cell growth. Unfortunately, the mechanism of phosphosugar stress response had not been elucidated in B. subtilis. To reveal the stress mechanism and overcome its negative effect in bioproduction, we performed comparative transcriptome analysis. The results indicate that cells slow glucose utilization by repression of glucose import and accelerate catabolic reactions of phosphosugar. To verify these results, we overexpressed the phosphatase YwpJ, which relieved phosphosugar stress and allowed us to identify the enzyme responsible for GlcNAc synthesis from GlcNAc 6-phosphate. In addition, the deletion of nagBB and murQ, responsible for GlcNAc precursor degradation, further improved GlcNAc synthesis. The best engineered strain, B. subtilis FMIP34, increased GlcNAc titer from 11.5 to 26.1 g/L in shake flasks and produced 87.5 g/L GlcNAc in 30-L fed-batch bioreactor. Our results not only elucidate, for the first time, the phosphosugar stress response mechanism in B. subtilis, but also demonstrate how the combination of rational metabolic engineering with novel insights into physiology and metabolism allows the construction of highly efficient microbial cell factories for the production of high-value chemicals.


Migraine and Central Sensitization: Clinical Features, Main Comorbidities and Therapeutic Perspectives.
Migraine is a very common neurologic disorder, characterized by recurrent attacks of severe headache, autonomic nervous system dysfunction and in some patients by an aura. Migraine is a very common neurologic disorder of neuro-vascular origin, being amongst the 20 most disabling diseases. Migraine attacks are characterized by severe headache, associated to autonomic nervous system dysfunction and in some patients by aura. Pathophysiology and Role of Central Sensitization: Abnormal neuronal excitability may subtend altered processing of sensory stimuli, leading to cortical spreading depression and trigeminal activation. A dysfunction of pain modulation enhances central sensitization phenomena, contributing to acute allodynia and headache persistence. The peculiarity of migraine pain facilitates the use of analgesics, and causes an adjunctive invalidating tendency toward drug over-use. Comorbidity: Chronic migraine patients are frequently affected by diffuse pain, framed in fibromyalgia diagnosis. This comorbidity seems to be supported by common pathophysiological mechanisms. It may aggravate migraine invalidity being worth of consideration for therapeutic management. Migraine Management: Acute and preventive treatments need to be tailored to single cases. Main comorbidity and factors facilitating central sensitization should be taken into account. The management of migraine patients should include a link between headache centers and general practitioner, in order to provide for a better patient information and treatment just at the onset of the disease. Despite its high epidemiologic impact, migraine is frequently underestimated and destined to evolve into chronic form and drugs abuse. A more focused attention to factors facilitating central sensitization and invalidating comorbidities, should reduce the global burden of the disease. migraine, pathophysiology, central sensitization, fibromyalgia comorbidity, acute and preventive therapy, patients - centered approach.


Imaging features of orbital myxosarcoma in dogs.
Myxomas and myxosarcomas are infiltrative connective tissue tumors of fibroblastic origin that can be distinguished by the presence of abundant mucinous stroma. This paper describes the clinical and imaging features of orbital myxosarcoma in five dogs and suggests a predilection for the orbit. The main clinical signs were slowly progressive exophthalmos with soft swelling of the pterygopalatine fossa, and in two dogs, of the periorbital area. No pain was associated with the eye or orbit but one dog had pain on opening the mouth. The dogs were imaged using combinations of ultrasonography, radiography, and magnetic resonance imaging. In four dogs, extensive fluid-filled cavities in the orbit and fascial planes were seen and in the fifth dog, the tumor appeared more solid with small, peripheral cystic areas. In all dogs, the lesion extended along fascial planes to involve the temporomandibular joint, with osteolysis demonstrable in two dogs. Fluid aspirated from the cystic areas was viscous and sticky, mimicking that from a salivary mucocoele. Myxomas and myxosarcomas are known to be infiltrative and not readily amenable to surgical removal but their clinical course seems to be slow, with a reasonable survival time with palliative treatment. In humans, a juxta-articular form is recognized in which a prominent feature is the presence of dilated, cyst-like spaces filled with mucinous material. It is postulated that orbital myxosarcoma in dogs may be similar to the juxta-articular form in man, and may arise from the temporomandibular joint.


Jaggery protects hepatorenal injury induced by acute exposure to carbon tetrachloride in Wistar rats.
In this study, we evaluated the protective activity of aqueous extract of jaggery against CCl4-induced hepatic-renal damage in rats. Jaggery was administered in one group at doses of 250, 500 and 750 mg/ kg body weight (bwt) (p.o., once only), and CCL4 was administered in another group at a dose of 1.5 ml/kg bwt (i.p., once only) to evaluate the protective effect of jaggery on induced oxidative damage in rats. Various blood and tissue biochemical studies were performed. The administration of toxicant significantly altered blood biochemical variables. Hepatic and renal lipid peroxidation (LPO) levels increased significantly, whereas considerable depletion was observed in reduced glutathione (GSH) level after intoxication. A remarkable decrease was observed in the activities of adenosine triphosphatase (ATPase) and glucose-6-phosphatase (G-6-Pase) after induction of toxicity. Treatment with extract at three different altered all measured biochemical variables, but greater hepatic-renal protection was observed at higher doses (750 mg/kg bwt) than at lower does (250 and 500 mg/kg bwt). Jaggery also reversed histopathological alterations. Thus, it may be concluded that jaggery can be used to reduce hepatic and renal damage and may serve as an alternative medicine in hepatic and renal etiology.


Understanding behavior in escalation situations.
Everyday observation reveals that both individuals and organizations often become overly committed to losing courses of action; in a sense, throwing good money after bad. More than 10 years of research on this escalation problem shows that persistence is associated with at least four major clases of determinants: project, psychological, social, and organizational variables. The influence of these four sets of variables evolves over time, forming a dynamic model of behavior in escalation situations.


Integrating dilution-based sequencing and population genotypes for single individual haplotyping.
Haplotype information is useful for many genetic analyses and haplotypes are usually inferred using computational approaches. Among such approaches, the importance of single individual haplotyping (SIH), which infers individual haplotypes from sequence fragments, has been increasing with the advent of novel sequencing techniques, such as dilution-based sequencing. These techniques could produce virtual long read fragments by separating DNA fragments into multiple low-concentration aliquots, sequencing and mapping each aliquot, and merging clustered short reads. Although these experimental techniques are sophisticated, they have the problem of producing chimeric fragments whose left and right parts match different chromosomes. In our previous research, we found that chimeric fragments significantly decrease the accuracy of SIH. Although chimeric fragments can be removed by using haplotypes which are determined from pedigree genotypes, pedigree genotypes are generally not available. The length of reads cluster and heterozygous calls were also used to detect chimeric fragments. Although some chimeric fragments will be removed with these features, considerable number of chimeric fragments will be undetected because of the dispersion of the length and the absence of SNPs in the overlapped regions. For these reasons, a general method to detect and remove chimeric fragments is needed. In this paper, we propose a general method to detect chimeric fragments. The basis of our method is that a chimeric fragment would correspond to an artificial recombinant haplotype and would differ from biological haplotypes. To detect differences from biological haplotypes, we integrated statistical phasing, which is a haplotype inference approach from population genotypes, into our method. We applied our method to two datasets and detected chimeric fragments with high AUC. AUC values of our method are higher than those of just using cluster length and heterozygous calls. We then used multiple SIH algorithm to compare the accuracy of SIH before and after removing the chimeric fragment candidates. The accuracy of assembled haplotypes increased significantly after removing chimeric fragment candidates. Our method is useful for detecting chimeric fragments and improving SIH accuracy. The Ruby script is available at https://sites.google.com/site/hmatsu1226/software/csp.


Progenitor cell sources for 3D bioprinting of lymphatic vessels and potential clinical application.
The lymphatic system maintains tissue fluid homeostasis and is involved in transport of nutrients and immunosurveillance. It also plays a pivotal role in both pathological and regenerative processes. Lymphatic development in the embryo occurs by polarization and proliferation of lymphatic endothelial cells from the lymph sacs, i.e. lymphangiogenesis. Alternatively, lymphvasculogenesis further contributes to the formation of lymphatic vessels. In adult tissues, lymphatic formation rarely occurs under physiological conditions, being restricted to pathological processes. In lymphvasculogenesis, progenitor cells seem to be a source of lymphatic vessels. Indeed, mesenchymal stem cells, adipose stem cells, endothelial progenitor cells and colony forming endothelial cells are able to promote lymphatic regeneration by different mechanisms, such as direct differentiation and paracrine effects. In this review, we summarize what is known on the diverse stem/ progenitor cell niches available for the lymphatic system, emphasizing the potential that these cells hold for lymphatic tissue engineering through 3D bioprinting and their translation to clinical application.


Growth characteristics, cytogenetic stability and virus susceptibility of cell lines from New Zealand rabbits.
We have initiated and established over 90 cell cultures from tissues of embroynic New Zealand rabbits. These cell lines show a very varied growth pattern when compared to cell lines initiated from human embryonic tissues. The type of medium used to grow the cells influences the chromosome stability of rabbit cells. Cultures initiated from kidney tissue rarely grow more than 10 passages unless the medium is supplemented with lactalbumin hydrolysate. In turn, analyses of metaphase chromosomes from the kidney cultures, revealed they were aneuploid as early as passages 15. Cultures established from skin and lung tissues will remain diploid at least 60 passages when grown on Eagle's Basal Medium supplemented with 10% fetal bovine serum. However, rarely do rabbit cell lines go into senescence.


Oral acyclovir prophylaxis of varicella after intimate contact.
Whether oral acyclovir (ACV) given in late incubation can prevent clinical varicella or not. Twenty-seven healthy infants and children susceptible to varicella received oral ACV (40 mg/kg daily in four divided doses) for 5 days, starting 9 or 11 days after exposure from the index case in the family (2 in the classroom). The clinical features were compared with 13 control children who did not receive ACV. Enzyme-linked immunoassay was used to detect varicella-zoster virus (VZV) antibody and, in follow-up immunologic studies, lymphocyte proliferative response was added. In some cases, blood culture and polymerase chain reaction with Southern hybridization were used for detection of viremia. Among the 27 children in the treatment group, two (7.4%) developed the disease and seroconversion was observed in 17 subjects (63%). Follow-up immunologic studies in 12 of these 17 seroconverted subjects 30 months later showed persistent cellular and/or humoral immunity to VZV. Only one subject, bled 11 days after exposure, had positive VZV DNA and blood culture for VZV. On the other hand 10 of 13 (77%) control subjects developed clinical varicella. Oral ACV administration to healthy susceptible subjects at the beginning of secondary viremia in the late incubation period (9 days after exposure) can effectively prevent or modify clinical varicella.


The alpha-amylase gene amyH of the moderate halophile Halomonas meridiana: cloning and molecular characterization.
Two types of Tn1732-induced mutants defective in extracellular amylase activity were isolated from the moderate halophile Halomonas meridiana DSM 5425. Type I mutants displayed amylase activity in the periplasm, and were unable to use any of the carbon sources tested, including starch and its hydrolysis product maltose. The type II mutant was affected in the gene responsible for the synthesis of the extracellular alpha-amylase. This gene (amyH) was isolated by functional complementation of mutant II and sequenced. The deduced protein (AmyH) showed a high degree of homology to a proposed family of alpha-amylases consisting of enzymes from Alteromonas (Pseudoalteromonas) haloplanktis, Thermomonospora curvata, streptomycetes, insects and mammals. AmyH contained the four highly conserved regions in amylases, as well as a high content of acidic amino acids. The amyH gene was functional in the moderate halophile Halomonas elongata and, when cloned in a multicopy vector, in Escherichia coli. AmyH is believed to be the first extracellular-amylase-encoding gene isolated from a moderate halophile, a group of extremophiles of great biotechnological potential. In addition, H. meridiana and H. elongata were able to secrete the thermostable alpha-amylase from Bacillus licheniformis, indicating that members of the genus Halomonas are good candidates for use as cell factories to produce heterologous extracellular enzymes.


Neuro-mesenchymal units control ILC2 and obesity via a brain-adipose circuit.
Signals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1-4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain-body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain-adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the β2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity.


A comparison of drug use and adjustment in urban adolescent children of substance abusers.
Children of alcoholics and other drug abusers are at elevated risk for substance abuse and other related psychosocial problems. Adolescents with a positive family history for drug abuse or alcoholism were compared to a similar group of low-SES, urban youth who were at risk for school failure but did not report any family history of substance abuse. A survey of depression, self-esteem, behavioral competence and dysfunction, and drug/alcohol use found that, overall, adolescents with a positive family history (FHP) for substance abuse exhibited more use of illicit drugs compared to those with a negative family history (FHN). There were also a greater number of FHP cases which fell into the clinical range on the psychosocial measures of behavioral dysfunction and depression compared to FHN youth. There were differential effects for boys versus girls, with FHP girls exhibiting a greater number of problem cases. Implications for substance abuse prevention with urban youth are discussed.


Pharmacological characterization of SR 48692 sensitive neurotensin receptor in human pancreatic cancer cells, MIA PaCa-2.
Previously, one type of human neurotensin receptor has been molecularly cloned. Recently, it has been proposed that a subtype of neurotensin receptor exists, which is not sensitive to newly synthesized neurotensin receptor antagonist SR 48692. In this study, we characterize the pharmacological properties of neurotensin receptor expressed in human pancreatic cancer cells, MIA PaCa-2. In binding studies with [3H]neurotensin, the data fit a model for a single population of high-affinity binding sites that are competitively antagonized by SR 48692. The rank order of the equilibrium dissociation rate constants for neurotensin(8-13), neurotensin, neuromedin N, [Ala11] neurotensin(8-13), and SR 48692 were similar to those found with the molecularly cloned human neurotensin receptors. Additionally, the intracellular calcium mobilization and the growth of MIA PaCa-2 cells induced by neurotensin receptor agonist were completely inhibited by SR 48692. In conclusion, our results showed that MIA PaCa-2 cells express functional and SR 48692-sensitive-type neurotensin receptors. It is suggested that the neurotensin receptor antagonist SR 48692 may be useful in the treatment of pancreatic cancers that possess this type of neurotensin receptor.


Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair.
Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca(2+) activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca(2+), AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing.


Discrepancies between the electronic medical record and website access to the prescription drug monitoring program.
The US opioid crisis has affected many patients across the age spectrum. Yet little has been reported on the effects of this crisis on cancer patients. Prescription drug monitoring programs have emerged as potential tools to mitigate risks of opioid prescribing, but they are not without limitations. We present a case of missing opioid prescriptions on EMR integrated PDMP versus the web based PDMP. A full review of PDMP integration is needed to identify gaps as these pose a significant patient safety issue.


Direct current stimulation-induced synaptic plasticity in the sensorimotor cortex: structure follows function.
Non-invasive direct current stimulation (DCS) of the brain induces functional plasticity in vitro and facilitates motor learning across species. The effect of DCS on structural synaptic plasticity is currently unknown. This study addresses the effects and the underlying mechanisms of anodal DCS on structural plasticity and morphology of dendritic spines in the sensorimotor cortex (M1/S1). A DCS electrode setup was combined with a chronic cranial window over M1/S1 in transgenic Thy1-GFP mice, to allow for in vivo 2-photon microscopy and simultaneous DCS. Contralateral electrical forepaw stimulation (eFS) was used to mimic the second synapse specific input, a previously shown requirement to induce functional plasticity by DCS. Changes in spine density and spine morphology were compared between DCS/eFS and sham, as well as two control conditions (sham-DCS/eFS, DCS/sham-eFS). Furthermore, the role of BDNF for stimulation-induced changes in spine density was assessed in heterozygous Thy1-GFP x BDNF+/- mice. Combined DCS/eFS rapidly increased spine density during stimulation and changes outlasted the intervention for 24 h. This effect was due to increased survival of original spines and a preferential formation of new spines after intervention. The latter were morphologically characterized by larger head sizes. The DCS-induced spine density increase was absent in mice with reduced BDNF expression. Previous findings of DCS-induced functional synaptic plasticity can be extended to structural plasticity in M1/S1 that similarly depends on a second synaptic input (eFS) and requires physiological BDNF expression. These findings show considerable parallels to motor learning-induced M1 spine dynamics.


Genetic and Chemical-Genetic Interactions Map Biogenesis and Permeability Determinants of the Outer Membrane of Escherichia coli.
Gram-negative bacteria are intrinsically resistant to many antibiotics due to their outer membrane barrier. Although the outer membrane has been studied for decades, there is much to uncover about the biology and permeability of this complex structure. Investigating synthetic genetic interactions can reveal a great deal of information about genetic function and pathway interconnectivity. Here, we performed synthetic genetic arrays (SGAs) in Escherichia coli by crossing a subset of gene deletion strains implicated in outer membrane permeability with nonessential gene and small RNA (sRNA) deletion collections. Some 155,400 double-deletion strains were grown on rich microbiological medium with and without subinhibitory concentrations of two antibiotics excluded by the outer membrane, vancomycin and rifampin, to probe both genetic interactions and permeability. The genetic interactions of interest were synthetic sick or lethal (SSL) gene deletions that were detrimental to the cell in combination but had a negligible impact on viability individually. On average, there were ∼30, ∼36, and ∼40 SSL interactions per gene under no-drug, rifampin, and vancomycin conditions, respectively; however, many of these involved frequent interactors. Our data sets have been compiled into an interactive database called the Outer Membrane Interaction (OMI) Explorer, where genetic interactions can be searched, visualized across the genome, compared between conditions, and enriched for gene ontology (GO) terms. A set of SSL interactions revealed connectivity and permeability links between enterobacterial common antigen (ECA) and lipopolysaccharide (LPS) of the outer membrane. This data set provides a novel platform to generate hypotheses about outer membrane biology and permeability.IMPORTANCE Gram-negative bacteria are a major concern for public health, particularly due to the rise of antibiotic resistance. It is important to understand the biology and permeability of the outer membrane of these bacteria in order to increase the efficacy of antibiotics that have difficulty penetrating this structure. Here, we studied the genetic interactions of a subset of outer membrane-related gene deletions in the model Gram-negative bacterium E. coli We systematically combined these mutants with 3,985 nonessential gene and small RNA deletion mutations in the genome. We examined the viability of these double-deletion strains and probed their permeability characteristics using two antibiotics that have difficulty crossing the outer membrane barrier. An understanding of the genetic basis for outer membrane integrity can assist in the development of new antibiotics with favorable permeability properties and the discovery of compounds capable of increasing outer membrane permeability to enhance the activity of existing antibiotics.


Bioactive glass serves as a substrate for maintenance of phenotype of nucleus pulposus cells of the intervertebral disc.
The objective of the study was to investigate the capability of bioactive glass 45S5 to serve as a substrate for nucleus pulposus cells in vitro. Nucleus pulposus cells were isolated from adult rabbit discs and seeded onto bioactive glass. At selected time intervals, the cells and glass were evaluated. We found that the cells rapidly attached to the substrate, colonizing it within 12 h. By 21 days, they had formed a lawn of cells over the glass substrate. DNA measurements showed a progressive increase in cell number with time. The phenotype was maintained; the cells expressed aggrecan, and collagen type II and I, but were negative for collagen type X. CD44, a cell-surface glycoprotein that binds hyaluronate, was also expressed by these cells. Electron dispersive X-ray analysis and Fourier transform infrared spectroscopy revealed calcium phosphate-rich layer formation on the substrate surface. The results of this study suggest that nucleus pulposus cell proliferation may be an anchorage dependent event, and that the cells use the calcium phosphate-rich layer to facilitate cell adhesion, and subsequent proliferation. These findings point to the importance of the conditioned bioactive glass as a substrate for nucleus pulposus cells.


[Objective assessment of the degree of ischaemia and efficacy of treatment in chronic arterial insufficiency of lower limbs].
Presented in the review is the data concerning contemporary criteria for assessing the degree of chronic lower limb ischaemia and quality of the treatment performed. Problems regarding objectivization of the degree of an ischaemic lesion of an extremity and assessment of quality of conservative treatment still remain unresolved. Currently, in the world practice along with instrumental methods (assessment of the ankle-brachial index) subjective criteria are mainly employed: assessment of pain-free walking distance or maximum distance walked. In order to work out appropriate regiments of conservative treatment and compare efficacy of various drugs for treatment of chronic lower limb ischaemia and, in particular, intermittent claudication, it is necessary to use objective criteria. Detailed consideration is hence given to the possibilities of using morphological, biochemical and histological criteria such as determination of vascular endothelial growth factor A (VEGF-A) in peripheral blood and determination of apoptosis markers (BNIP3) and hypoxia-inducible factor (HIF-1) in a biopsy sample of the gastrocnemius muscle of the ischaemized extremity.


Biodegradable, three-dimensional colorimetric fliers for environmental monitoring.
Recently reported winged microelectronic systems offer passive flight mechanisms as a dispersal strategy for purposes in environmental monitoring, population surveillance, pathogen tracking, and other applications. Initial studies indicate potential for technologies of this type, but advances in structural and responsive materials and in aerodynamically optimized geometries are necessary to improve the functionality and expand the modes of operation. Here, we introduce environmentally degradable materials as the basis of 3D fliers that allow remote, colorimetric assessments of multiple environmental parameters-pH, heavy metal concentrations, and ultraviolet exposure, along with humidity levels and temperature. Experimental and theoretical investigations of the aerodynamics of these systems reveal design considerations that include not only the geometries of the structures but also their mass distributions across a range of bioinspired designs. Preliminary field studies that rely on drones for deployment and for remote colorimetric analysis by machine learning interpretation of digital images illustrate scenarios for practical use.


Prevalence and risk factors for falls among community-dwelling adults in Riyadh area.
This study aimed to assess fall prevalence, identify related risk factors, and establish cut-off scores for fall risk measures among community-dwelling adults in Riyadh region of Saudi Arabia. A cross-sectional study was conducted in community, Riyadh city, Saudi Arabia. A sample of 276 Saudi citizens aged ≥40 years who were able to read and write in Arabic. Fall history and number of falls in the past 12 months were determined via self-reports. Variables assessed included demographic information, self-reported chronic diseases, depressive symptoms, and back pain severity. Participants were classified as either fallers (n = 28, 10.14%) or non-fallers. Fallers were more likely to have arthritis (odds ratio [OR]: 7.60, p = 0.001), back pain (OR: 5.22, p = 0.002), and higher depressive symptom scores (OR: 1.09, p = 0.013) than non-fallers. The number of reported falls was significantly associated with an elevated body mass index (incidence rate ratio [IRR]: 1.09, p = 0.045), arthritis (IRR: 8.74, p < 0.001), back pain (IRR: 4.08, p = 0.005), neurological diseases (IRR: 13.75, p < 0.007), and depressive symptoms (IRR: 1.08, p = 0.005). Cut-off scores predictive of falls associated with back pain and depressive symptoms were 1.5 (sensitivity: 0.61; specificity: 0.79; area under the curve [AUC]: 0.70) and 11.5 score (sensitivity: 0.57; specificity: 0.76; AUC: 0.66), respectively. The prevalence of falls was relatively low among the individuals considered in this study. Chronic conditions, back pain severity, and depressive symptoms were determined to be associated with falls among community-dwelling individuals in Saudi Arabia.


Stabilisation of hollow colloidal TiO2 particles by partial coating with evenly distributed lobes.
Photo-catalytically active crystalline TiO2 has attracted special attention due to its relevance for renewable energy and is typically obtained by the calcination of amorphous TiO2. However, stabilising hollow colloidal TiO2 particles against aggregation during calcination without compromising their photocatalytic activity poses two conflicting demands: to be stable their surface needs to be coated, while efficient photocatalysis requires an exposed TiO2 surface. Here, this incompatibility is resolved by partially coating TiO2 shells with evenly distributed 3-trimethoxysilyl propyl methacrylate (TPM) lobes. These lobes act both as steric barriers and surface charge enhancers that efficiently stabilise the TiO2 shells against aggregation during calcination. The morphology of the TPM lobes and their coverage, and the associated particle stability during the calcination-induced TiO2 crystallization, can be controlled by the pH and the contact angle between TPM and TiO2. The crystal structure and the grain size of the coated TiO2 shells are controlled by varying the calcination temperature, which allows tuning their photocatalytic activity. Finally, the durable photocatalytic activity over many usage cycles of the coated TiO2 compared to uncoated shells is demonstrated in a simple way by measuring the photo-degradation of a fluorescent dye. Our approach offers a general strategy for stabilising colloidal materials, without compromising access to their active surfaces.


Aortic valve replacement and concomitant coronary artery bypass: assessing the impact of multiple grafts.
The impact of multivessel coronary artery disease and multivessel coronary artery bypass grafting on outcomes after combined aortic valve replacement and coronary artery bypass grafting (AVR-CABG) has not been sufficiently evaluated. We retrospectively reviewed all patients who underwent AVR-CABG at our institution between January 2000 and December 2004. Patients with any previous or concomitant procedures were excluded. The Kaplan-Meier method was used to calculate survival and freedom from postoperative repeat revascularization. Predictors of mortality were determined by Cox regression analysis. The study cohort consisted of 233 AVR-CABG patients. Mean follow-up was 2.2 +/- 1.7 years with one patient lost to follow-up. Preoperative clinical characteristics were well-matched between patients who received one (n = 86), two (n = 81), or three or four (n = 66) bypass grafts. Operative mortality was 9.3%, 11.1%, and 7.6%, respectively (p = 0.76). Patients in all groups demonstrated significant improvement in New York Heart Association (NYHA) status (p < 0.01). Freedom from postoperative repeat revascularization for all patients after five years was 96.8% and did not differ among groups (p = 0.93). Five-year survival for each group was 63.6%, 72.4%, and 63.9%, respectively (p = 0.91). Emergent operation, ejection fraction less than 0.30, operative age greater than 65 years, NYHA class III/IV, and chronic obstructive pulmonary disease were significant predictors of mortality. The number of stenosed vessels, the number of bypass grafts, incomplete revascularization, and the presence of aortic stenosis or aortic insufficiency did not predict mortality. For patients undergoing AVR-CABG, the number of bypass grafts does not adversely affect survival. Rather, a patient's preoperative risk factors are a better predictor of outcome.


[Psychosocial aspects of dance and music of the Brazilian carnival].
In this paper the author analyses the rites of Carnival, a sociocultural phenomenon that has aroused the interest of sociologists and anthropologists through out the world. He emphasizes the importance of Carnival as a psychic stabilizing mechanism, responsible for the reduction of psychiatric cases observed during this period. He studies the origins of Brazilian culture, the peculiarities the meeting of the African folklore and mysticism with the European folklore has created, and also the results of such interaction. In tracing the origins of Carnival rites, the author points out the significant role played by the dynamic and contagious rhythm of the music, that generates an unrestrained atmosphere in which enthusiastic singing and dancing act as elements of catharsis, liberation, compensation and social integration.


RhoA inactivation enhances endothelial barrier function.
The modulation of endothelial barrier function is thought to be a function of contractile tension mediated by the cell cytoskeleton, which consists of actomyosin stress fibers (SF) linked to focal adhesions (FA). We tested this hypothesis by dissociating SF/FA with Clostridium botulinum exoenzyme C3 transferase (C3), an inhibitor of the small GTP-binding protein RhoA. Bovine pulmonary artery endothelial cell (EC) monolayers given C3, C3 + thrombin, thrombin, or no treatment were examined using a size-selective permeability assay and quantitative digital imaging measurements of SF/FA. C3 treatment disassembled SF/FA, stimulated diffuse myosin II immunostaining, and reduced the phosphotyrosine (PY) content of paxillin and 130- to 140-kDa proteins that included p125(FAK). C3-treated monolayers displayed a 60-85% decline in F-actin content and a 170-300% increase in EC surface area with enhanced endothelial barrier function. This activity correlated with reorganization of F-actin and PY protein(s) to beta-catenin-containing cell-cell junctions. Because C3 prevented the thrombin-induced formation of myosin ribbons, SF/FA, and the increased PY content of proteins, these characteristics were Rho dependent. Our data show that C3 inhibition of Rho proteins leads to cAMP-like characteristics of reduced SF/FA and enhanced endothelial barrier function.


A novel Creb family gene telomeric of HLA-DRA in the HLA complex.
cDNA selection was used to identify genes encoded by a 440-kb yeast artificial chromosome (YAC) clone that spanned from HLA-DRA to CYP21 in the HLA complex. An initially selected short cDNA was used to isolate a 2639-nucleotide, apparently full-length cDNA from a human tonsil library. This cDNA contained one extended open reading frame that predicted a protein of 700 amino acids with a basic region and a leucine zipper that is highly similar to members of the Creb/ATF subfamily. High-stringency Southern blotting of total human genomic DNA using this cDNA as the probe showed only a single locus that mapped to the selecting YAC clone. This gene, designated Creb-related protein (Creb-rp), is expressed ubiquitously and is evolutionarily conserved in mammals. It is located in the HLA Class III region 6-10 kb centromeric of the XB gene, which encodes a tenascin-like extracellular matrix protein. Homologous sequences are located in the Class II-Class III interval of the mouse H-2 complex. The amino acid sequence homology and general structural features of the predicted protein indicate that this gene encodes a general transcription factor belonging to the Creb/ATF subfamily of the bZip super-family.


Highly Selective Extraction of U(VI) from Solutions by Metal Organic Framework-Based Nanomaterials through Sorption, Photochemistry, and Electrochemistry Strategies.
With the rapid development of nuclear technology and peaceful utilization of nuclear energy, plentiful U(VI) not only is required to be extracted from solutions for a sustainable nuclear fuel supply but also is inevitably released into the surrounding environment to result in pollution and threaten human health. Thereby, realizing selective extraction of U(VI) from aqueous solutions is crucial for U(VI) pollution control and a sustainable nuclear industry. Metal organic frameworks (MOFs) have gained multidisciplinary attention due to their excellent properties including large specific surface areas, tunable pore structures, easy functionalization, etc. This Review comprehensively summarizes the research progress of MOFs and MOF-based materials on U(VI) removal from aqueous solutions by sorption, photocatalysis, electrocatalysis, membrane separation, etc. The efficient high extraction ability is dependent on the intrinsic properties of MOFs and the techniques used. The removal properties of MOF-based materials as adsorbents, photocatalysts, and electrocatalysts for U(VI) are discussed. Information about the interaction mechanisms between U(VI) and MOF-based materials are analyzed in-depth, including experiments, theoretical calculations, and advanced spectroscopy analysis. The removal properties for U(VI) of various MOF-based materials are assessed through different techniques. Finally, a summary and perspective on the direction and challenges of MOF-based materials and various pollutant removal technologies are proposed to provide some significant information on designing and fabricating MOF-based materials for environmental pollution management.


Sonographic assessment of the medial ulnar collateral ligament distal ulnar attachment.
The purpose of this study was to determine whether the long distal attachment of the medial ulnar collateral ligament (MUCL) can be delineated on sonography. We used 12 fresh-frozen cadaveric elbows for this study. We performed sonography of the elbow using a coronal-equivalent long-axis view of the MUCL. All sonographic examinations and measurements were performed by a board-certified, fellowship-trained musculoskeletal radiologist. Measurements were performed from the anteroinferior aspect of the medial epicondyle to the sublime tubercle and then from the sublime tubercle to the terminal fibers of the MUCL long ulnar attachment. We then measured the length of the MUCL from its attachment at the medial epicondyle of the humerus to the sublime tubercle and then from the sublime tubercle to the distal extent of its terminal fibers at the ulnar attachment with digital calipers. On sonography, the average length of the MUCL from its humeral attachment to the sublime tubercle (transarticular) was 19.6 mm. The average length of the ulnar attachment was 27.9 mm. The MUCL was thickest (mediolateral dimension) at its humeral attachment and tapered as it coursed distally along the ulnar attachment. The MUCL was clearly identified on sonography and in all anatomic specimens. On gross measurement, the average lengths of the transarticular portion of the MUCL and its ulnar footprint were 21.5 and 30.2 mm, respectively. We have successfully shown that the distal ulnar attachment of the MUCL can be visualized on high-resolution sonography. This preliminary work provides a framework for developing protocols for diagnosis of injuries to the distal ulnar collateral ligament.