Changes in Attitudes and Actual Practice of Oxygen Therapy in ICUs after Implementation of a Conservative Oxygenation Guideline.
Little is known to what extent attitudes of ICU clinicians are influenced by new insights and recommendations to be more conservative with oxygen therapy. Our aim was to investigate whether implementation of a conservative oxygenation guideline structurally changed self-reported attitudes and actual clinical practice. After the implementation of a conservative oxygen therapy guideline in 3 teaching hospitals in the Netherlands, ICU clinicians were surveyed regarding their attitudes toward oxygen therapy. The survey results were compared with survey results taken before the introduction of the new guideline. Arterial blood gas analysis data and ventilator settings were retrieved from all patients admitted to the participating ICUs in the studied period, and changes after implementing the guideline were assessed. In total, 180 ICU clinicians returned the survey. Compared to before implementation of a conservative oxygen guideline, more clinicians chose a preferred [Formula: see text] and an oxygen saturation measured from an arterial sample ([Formula: see text]) limit after implementation of the guideline. In general, clinicians reported a more conservative approach toward management of [Formula: see text] and less frequently increased the [Formula: see text]. In the period after the active implementation of the guideline, 5,840 subjects were admitted to the participating ICUs and 101,869 arterial blood gas analyses were retrieved. Actual practice changed with overall lower oxygenation levels (median [Formula: see text] 77.93 mm Hg, compared to 86.93 mm Hg before implementation) of arterial blood and a decrease of PEEP and [Formula: see text]. Implementing a conservative oxygenation guideline was an effective method that changed self-reported attitudes and actual clinical practice and improved adherence to conservative oxygenation targets in a short period of time.


Ultrahigh-Responsivity Photodetectors from Perovskite Nanowire Arrays for Sequentially Tunable Spectral Measurement.
Compared with polycrystalline films, single-crystalline methylammonium lead halide (MAPbX3, X = halogen) perovskite nanowires (NWs) with well-defined structure possess superior optoelectronic properties for optoelectronic applications. However, most of the prepared perovskite NWs exhibit properties below expectations due to poor crystalline quality and rough surfaces. It also remains a challenge to achieve aligned growth of single-crystalline perovskite NWs for integrated device applications. Here, we report a facile fluid-guided antisolvent vapor-assisted crystallization (FGAVC) method for large-scale fabrication of high-quality single-crystalline MAPb(I1-xBrx)3 (x = 0, 0.1, 0.2, 0.3, 0.4) NW arrays. The resultant perovskite NWs showed smooth surfaces due to slow crystallization process and moisture-isolated growth environment. Significantly, photodetectors made from the NW arrays exhibited outstanding performance in respect of ultrahigh responsivity of 12 500 A W-1, broad linear dynamic rang (LDR) of 150 dB, and robust stability. The responsivity represents the best value ever reported for perovskite-based photodetectors. Moreover, the spectral response of the MAPb(I1-xBrx)3 NW arrays could be sequentially tuned by varying the content of x = 0-0.4. On the basis of this feature, the NW arrays were monolithically integrated to form a unique system for directly measuring light wavelength. Our work would open a new avenue for the fabrication of high-performance, integrated optoelectronic devices from the perovskite NW arrays.


odNEAT: An Algorithm for Decentralised Online Evolution of Robotic Controllers.
Online evolution gives robots the capacity to learn new tasks and to adapt to changing environmental conditions during task execution. Previous approaches to online evolution of neural controllers are typically limited to the optimisation of weights in networks with a prespecified, fixed topology. In this article, we propose a novel approach to online learning in groups of autonomous robots called odNEAT. odNEAT is a distributed and decentralised neuroevolution algorithm that evolves both weights and network topology. We demonstrate odNEAT in three multirobot tasks: aggregation, integrated navigation and obstacle avoidance, and phototaxis. Results show that odNEAT approximates the performance of rtNEAT, an efficient centralised method, and outperforms IM-(μ + 1), a decentralised neuroevolution algorithm. Compared with rtNEAT and IM-(μ + 1), odNEAT's evolutionary dynamics lead to the synthesis of less complex neural controllers with superior generalisation capabilities. We show that robots executing odNEAT can display a high degree of fault tolerance as they are able to adapt and learn new behaviours in the presence of faults. We conclude with a series of ablation studies to analyse the impact of each algorithmic component on performance.


Identification of a new subset of lymph node stromal cells involved in regulating plasma cell homeostasis.
Antibody-secreting plasma cells (PCs) arise rapidly during adaptive immunity to control infections. The early PCs are retained within the reactive lymphoid organ where their localization and homeostasis rely on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by colocalizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRCs) that forms a dense meshwork throughout medullary cords of lymph nodes (LNs) where PCs reside. This medullary FRC type is shown to be anatomically, phenotypically, and functionally distinct from T zone FRCs, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRCs are the main cell type in contact with PCs guiding them in their migration. Medullary FRCs also represent a major local source of the PC survival factors IL-6, BAFF, and CXCL12, besides also producing APRIL. In vitro, medullary FRCs alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps in promoting the rapid development of humoral immunity, which is critical in limiting early pathogen spread.


Mouse Phenotype Database Integration Consortium: integration [corrected] of mouse phenome data resources.
Understanding the functions encoded in the mouse genome will be central to an understanding of the genetic basis of human disease. To achieve this it will be essential to be able to characterize the phenotypic consequences of variation and alterations in individual genes. Data on the phenotypes of mouse strains are currently held in a number of different forms (detailed descriptions of mouse lines, first-line phenotyping data on novel mutations, data on the normal features of inbred lines) at many sites worldwide. For the most efficient use of these data sets, we have initiated a process to develop standards for the description of phenotypes (using ontologies) and file formats for the description of phenotyping protocols and phenotype data sets. This process is ongoing and needs to be supported by the wider mouse genetics and phenotyping communities to succeed. We invite interested parties to contact us as we develop this process further.


Periodic health examination, 1999 update: 1. Detection, prevention and treatment of obesity. Canadian Task Force on Preventive Health Care.
(1) To evaluate the evidence relating to the effectiveness of methods to prevent and treat obesity, and (2) to provide recommendations for the prevention and treatment of obesity in adults aged 18 to 65 years and for the measurement of the body mass index (BMI) as part of a periodic health examination. In adults with obesity (BMI greater than 27) management options include weight reduction, prevention of further weight gain or no intervention. The long-term (more than 2 years) effectiveness of (a) methods to prevent obesity and (b) methods to treat obesity. MEDLINE was searched for articles published from 1966 to April 1998 that related to the prevention and treatment of obesity; additional articles were identified from the bibliographies of review articles and the listings of Current Contents. Selection criteria were used to limit the analysis to prospective studies with at least 2 years' follow-up. Health benefits of weight reduction were evaluated in terms of alleviation of symptoms, improved management of obesity-related diseases and a reduction in major clinical outcomes. The health risk of weight-reduction methods were briefly evaluated in terms of increased mortality and morbidity. The recommendations of this report reflect the commitment of the Canadian Task Force on Preventive Health Care to provide a structured, evidence-based appraisal of whether a manoeuvre should be part of a periodic health examination. (1) PREVENTION: There is insufficient evidence to recommend in favour of or against community-based obesity prevention programs; however, because of considerable health risks associated with obesity and the limited long-term effectiveness of weight-reduction methods, the prevention of obesity should be a high priority for health care providers (grade C recommendation). (2) TREATMENT: (a) For obese adults without obesity-related diseases, there is insufficient evidence to recommend in favour of or against weight-reduction therapy because of a lack of evidence supporting the long-term effectiveness of weight-reduction methods (grade C recommendation); (b) for obese adults with obesity-related diseases (e.g., diabetes mellitus, hypertension), weight reduction is recommended because it can alleviate symptoms and reduce drug therapy requirements, at least in the short term (grade B recommendation). (3) Detection: (a) for people without obesity-related diseases, there is insufficient evidence to recommend the inclusion or exclusion of BMI measurement as part of a periodic health examination, and therefore BMI measurement is left to the discretion of individual health care providers (grade C recommendation); (b) for people with obesity-related diseases, BMI measurement is recommended because weight reduction should be considered with a BMI of more than 27 (grade B recommendation). The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care. The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada.


Transient expressions of synthetic biology in plants.
Recent developments in transient expression methods have enabled the efficient delivery and expression of multiple genes within the same plant cell over a timescale of days. In some cases, the vectors deployed can be fine-tuned to allow differential expression of the various genes. This has opened the way to the deployment of transient expression for such applications as the production of macromolecular complexes and the analysis and manipulation of metabolic pathways. The ability to observe the effect of gene expression in a matter of days means that transient expression is becoming the method of choice for many plant-based synthetic biology applications.


Calculation of Elastic Bond Constants in Atomistic Strain Analysis.
Strain analysis has significance both for tailoring material properties and designing nanoscale devices. In particular, strain plays a vital role in engineering the growth thermodynamics and kinetics and is applicable for designing optoelectronic devices. In this paper, we present a methodology for establishing the relationship between elastic bond constants and measurable parameters, i.e., Poisson's ratio ν and systematic elastic constant K. At the atomistic level, this approach is within the framework of linear elastic theory and encompasses the neighbor interactions when an atom is introduced to stress. Departing from the force equilibrium equations, the relationships between ν, K, and spring constants are successfully established. Both the two-dimensional (2D) square lattice and common three-dimensional (3D) structures are taken into account in the procedure for facilitating, bridging the gap between structural complexity and numerical experiments. A new direction for understanding the physical phenomena in strain engineering is established.


Pyogenic hepatic abscess. Changing trends over 42 years.
The authors document changes in the etiology, diagnosis, bacteriology, treatment, and outcome of patients with pyogenic hepatic abscesses over the past 4 decades. Pyogenic hepatic abscess is a highly lethal problem. Over the past 2 decades, new roentgenographic methods, such as ultrasound, computed tomographic scanning, direct cholangiography, guided aspiration, and percutaneous drainage, have altered both the diagnosis and treatment of these patients. A more aggressive approach to the management of hepatobiliary and pancreatic neoplasms also has resulted in an increased incidence of this problem The records of 233 patients with pyogenic liver abscesses managed over a 42-year period were reviewed. Patients treated from 1952 to 1972 (n = 80) were compared with those seen from 1973 to 1993 (n = 153). From 1973 to 1993, the incidence increased from 13 to 20 per 100,000 hospital admissions (p < 0.01. Patients managed from 1973 to 1993 were more likely (p < 0.01) to have an underlying malignancy (52% vs. 28%) with most of these (81%) being a hepatobiliary or pancreatic cancer. The 1973 to 1993 patients were more likely (p < 0.05) to be infected with streptococcal (53% vs. 30%) or Pseudomonas (30% vs. 9%) species or to have mixed bacterial and fungal 26% vs. 1%) infections. The recent patients also were more likely (p < 0.05) to be managed by percutaneous abscess drainage (45% vs. 0%). Despite having more underlying problems, overall mortality decreased significantly (p < 0.01) from 65% (in 1952 to 1972 period) to 31% (in 1973 to 1993 period). The reduction was greatest for patients with multiple abscesses (88% vs. 44%; p < 0.05) with either a malignant or a benign biliary etiology (90% vs. 38%; p < 0.05). Mortality was increased (p < 0.02) in patients with mixed bacterial and fungal abscesses (50%). From 1973 to 1993, mortality was lower (p = 0.19) with open surgical as opposed to percutaneous abscess drainage (14% vs. 26%). Significant changes have occurred in the etiology, diagnosis, bacteriology, treatment, and outcome patients with pyogenic hepatic abscesses over the past 4 decades. However, mortality remains high, and proper management continues to be a challenge. Appropriate systemic antibiotics and fungal agents as well as adequate surgical, percutaneous, or biliary drainage are required for the best results.


Short-chain glucose polymer and anthracene-9-carboxylic acid inhibit water and electrolyte secretion induced by dibutyryl cyclic AMP in the small intestine.
Glucose-stimulated sodium absorption is the rationale for treatment with glucose-based oral rehydration solution in diarrhea. Concurrent treatment with pharmacological inhibitors, which specifically block chloride secretion, may be a useful adjunct to oral fluid therapy. To examine this hypothesis, the authors determined the intestinal water and ion transport rates in rat small intestine during the secretory phase induced by perfusion with N6-2'-0-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), 1.0 mmol/L. A marker (polyethylene glycol 4000) dilution technique was used to evaluate the antisecretory effects of a defined short-chain glucose polymer, D-glucose, and a chloride channel blocker, anthracene-9-carboxylic acid (A-9-C). The results showed that dbcAMP induced small intestinal water and chloride ion secretion rapidly and reliably. The 2.5% concentration of rice short glucose polymer (G2, 22.7%; G3, 28.2%; G4, 14.0%; G5, 16.6%; G6, 11.6%; G7-9, 6.9%) is a better carbohydrate than the 2.5% concentration of D-glucose in reversing secretion of water, chloride, and sodium ions induced by dbcAMP. The combination of A-9-C and the glucose polymer can reverse dbcAMP-induced intestinal secretion and produces significantly (P less than 0.05) better antisecretory effect on water, sodium, and chloride ions than D-glucose with A-9-C.


A systematic review and meta-analysis of failure to take history as a barrier of reporting child abuse by dentists in private and state clinics.
Since the symptoms of child abuse and neglect often manifest in the orofacial region, the dental team has a key role in identifying children subjected to abuse. This study was aimed to explore the prevalence of failure to take history as a barrier to reporting child abuse by dentist around the world. In this systematic review and meta-analysis, PubMed, Embase, Scopus, Google Scholar, ProQuest, Cochrane, and ISI databases were searched for the cross-sectional articles in English languages on barriers to reporting child abuse and lack of knowledge about referral procedures by dentists since 1985 using Medical Subject Headings (MeSH). The full-texts of all included articles were obtained and assessed for quality according to Newcastle-Ottawa Scale adapted for cross-sectional studies. The qualified articles were then studied thoroughly and results were extracted. Data were analyzed by Comprehensive Meta-Analysis software using meta-analysis and random effects model. Heterogeneity was determined by Q-test and I-square index. A total of 17 articles were included in the meta-analysis. The prevalence of lack of knowledge about referral procedures as a barrier was determined according to the meta-analysis of the number of relevant articles and was (55%, confidence interval: 0.48, 0.62). The analysis of various studies revealed lack of information about referral procedures as an important barrier to report child abuse by dentists.


Balancing "fidelity" and community context in the adaptation of asthma evidence-based interventions in the "real world".
The Merck Childhood Asthma Network (MCAN) initiative selected five sites (New York City, Puerto Rico, Chicago, Los Angeles, and Philadelphia) to engage in translational research to adapt evidence-based interventions (EBIs) to improve childhood asthma outcomes. The authors summarize the sites' experience by describing criteria defining the fidelity of translation, community contextual factors serving as barriers or enablers to fidelity, types of adaptation conducted, and strategies used to balance contextual factors and fidelity in developing a "best fit" for EBIs in the community. A conceptual model captures important structural and process-related factors and helps frame lessons learned. Site implementers and intervention developers reached consensus on qualitative rankings of the levels of fidelity of implementation for each of the EBI core components: low fidelity, adaptation (major vs. minor), or high fidelity. MCAN sites were successful in adapting core EBI components based on their understanding of structural and other contextual barriers and enhancers in their communities. Although the sites varied regarding both the EBI components they implemented and their respective levels of fidelity, all sites observed improvement in asthma outcomes. Our collective experiences of adapting and implementing asthma EBIs highlight many of the factors affecting translation of evidenced-based approaches to chronic disease management in real community settings.


First Report of Colletotrichum acutatum Causing Bitter Rot on Apple in Italy.
Italy could be considered the main apple-producing country in the European Union. Italian apple (Malus domestica L. Borkh.) production is estimated at approximately 2.1 million tons and encompasses a wide range of cultivars, harvested from August to November. Colletotrichum acutatum, which causes severe losses to strawberry production, was a regulated organism for all European countries until 2008, when it was removed from the EPPO quarantine pathogen list because of its wide distribution in strawberry-production areas. During the growing season of 2010, fungi were isolated from apple fruits exhibiting bitter rot symptoms after 4 months of storage in several packinghouses in the Emilia Romagna Region. The apples belonged to the Golden Delicious, Granny Smith, Pink Lady and Crisp Pink cultivars. Lesions on the fruit surface were circular and 1 to 3 cm in diameter. When lesions enlarged, they became sunken with relatively firm rotten tissues. The fungal fruiting structures, acervuli, were distributed sparsely or densely on old lesions, and under humid conditions, they discharged an orange conidial mass. Conidia observed with a light microscope appeared hyaline and fusiform, 8 to 16 × 2.5 to 4 μm, with two pointed ends or one rounded end. The fungal isolates were grown on potato dextrose agar (PDA) plates incubated at 25°C. After 7 days, colonies were white, becoming gray to pale orange, and when viewed from the reverse side, the color ranged from pink to reddish orange. Both cultural and morphological characteristics of the pathogen were similar to those described for C. acutatum J.H. Simmonds (3), which is responsible for bitter rot of apple (2). Koch's postulates were performed with one representative isolate from each host by artificial inoculation of 30 healthy apples from the cultivars listed above. Fruit surfaces were disinfected with 70% ethanol, wounded with a sterile needle, and then inoculated with 20 μl of a spore suspension (105 conidia ml-1) prepared from a 15-day-old culture on PDA. Inoculated fruits were sealed in a plastic bag and incubated at 25°C for 10 days. In 92% of fruits, symptoms appeared 10 days later, forming lesions with cream-to-salmon pink fruiting structures. The fungus was reisolated onto PDA from the lesions on the inoculated apples. After 7 days of incubation, the colonies and the morphology of conidia were the same as those of the original isolates. The tests were performed on all four cultivars with similar results. The PCR analysis, carried out using universal primers ITS1 and ITS4 (4) directly from single-spore-derived mycelium (1), resulted in an amplification product with 100% sequence homology with C. acutatum isolate AB626881 from GenBank database. Considering the results obtained, to our knowledge, this is the first report of C. acutatum in Italy causing bitter rot on apple. The disease is common in practically all countries where apples are commercially grown and since the losses could be severe under prolonged warm and wet weather conditions, C. acutatum could represent a serious issue for the Italian apple industry. References: (1) M. Iotti and A. Zambonelli. Mycol. Res. 110:60, 2006. (2) A. L. Jones et al. Plant Dis. 80:1294, 1996. (3) B. C. Sutton. Page 1 in: Colletotrichum: Biology, Pathology and Control. Brit. Soc. Plant Pathol. Oxon. UK 1992. (4) T. J. White et al. Page 315 in: PCR Protocols. A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.


Development of an engineered bioluminescent reporter phage for detection of bacterial blight of crucifers.
Bacterial blight, caused by the phytopathogen Pseudomonas cannabina pv. alisalensis, is an emerging disease afflicting important members of the Brassicaceae family. The disease is often misdiagnosed as pepper spot, a much less severe disease caused by the related pathogen Pseudomonas syringae pv. maculicola. We have developed a phage-based diagnostic that can both identify and detect the causative agent of bacterial blight and differentiate the two pathogens. A recombinant "light"-tagged reporter phage was generated by integrating bacterial luxAB genes encoding luciferase into the genome of P. cannabina pv. alisalensis phage PBSPCA1. The PBSPCA1::luxAB reporter phage is viable and stable and retains properties similar to those of the wild-type phage. PBSPCA1::luxAB rapidly and sensitively detects P. cannabina pv. alisalensis by conferring a bioluminescent signal response to cultured cells. Detection is dependent on cell viability. Other bacterial pathogens of Brassica species such as P. syringae pv. maculicola, Pseudomonas marginalis, Pectobacterium carotovorum, Xanthomonas campestris pv. campestris, and X. campestris pv. raphani either do not produce a response or produce significantly attenuated signals with the reporter phage. Importantly, the reporter phage detects P. cannabina pv. alisalensis on diseased plant specimens, indicating its potential for disease diagnosis.


Innovative ICU Solutions to Prevent and Reduce Delirium and Post-Intensive Care Unit Syndrome.
Delirium, the most common form of acute brain dysfunction affecting up to 80% of intensive care unit (ICU) patients, has been shown to predict long-term cognitive impairment, one of the domains in "Post-ICU Syndrome" (PICS). The ICU environment affects several potentially modifiable risk factors for delirium, such as disorientation and disruption, of the sleep-wake cycle. Innovative solutions aim to transform standard concepts of ICU room design to limit potential stressors, and utilizing the patient care space as a treatment tool, exerting positive, therapeutic effects. The main areas affected by most architectural and interior design modifications are sound environment, light control, floor planning, and room arrangement. Implementation of corresponding solutions is challenging considering the significant medical and technical demands of ICUs. This article discusses innovative concepts and promising approaches in ICU design that may be used to prevent stress and to support the healing process of patients, potentially limiting the impact of delirium and PICS.


The Prevalence and Long-Term Outcomes of Extreme Right versus Extreme Left Ventricular Hypertrophic Cardiomyopathy.
Extreme left ventricular hypertrophy (LVH) is a known risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM). Extreme right ventricular hypertrophy (RVH) is rare, and whether it is linked to a poor outcome is unknown. This study was designed to investigate differences between HCM patients with extreme RVH and those with extreme LVH. Among 2,413 HCM patients, 31 with extreme RVH (maximum right ventricular wall thickness ≥ 10 mm) and 194 with extreme LVH (maximum left ventricular wall thickness ≥ 30 mm) were investigated. The main clinical features and natural history were compared between the 2 groups. The prevalence of extreme RVH and extreme LVH was 1.3 and 8.0%, respectively. Patients with extreme RVH tended to be younger and female (p < 0.01). Cardiovascular-related mortality and morbidity within 10 years were significantly greater in the extreme RVH group (p < 0.05). Multivariate analysis demonstrated 3 independent predictors for cardiovascular mortality - extreme RVH, left ventricular end-diastolic dimension ≥ 50 mm, and age ≤ 18 years at baseline - and 2 for morbidity - extreme RVH and presyncope. Compared with extreme LVH, extreme RVH was quite uncommon in HCM and had a worse prognosis. A right ventricle examination should be performed in routine HCM evaluation.


Optical coherence tomography in diagnosing, differentiating and monitoring of choroidal nevi - 1 year observational study.
To assess the utility of the optical coherence tomography (OCT) in diagnosing, differentiating and monitoring of choroidal nevi situated in the posterior pole and optic disc area. 116 consecutive patients (65 women, 51 men) aged 27-95 years, with choroidal nevus were included to the research. Routine ophthalmoscopic evaluation and OCT using the Zeiss Stratus OCT as well as fundus photography were performed in each patient. The OCT was used to assess the structure of the retina overlying the choroidal nevus, the retinal pigment epithelium (RPE) - choriocapillaris complex, as well as the anterior portion of the choroidal lesion. In 31 patients due to suspected malignant melanoma fluorescein angiography and ultrasound were additionally performed. Follow-up OCT was done after 12 months in 51 out of 85 patients with characteristics of choroidal nevi, and after 6 and 12 months in 27 patients with "suspicious" lesion. The basal dimension of the lesion ranged from 0.5 mm to 12 mm (mean 2.75mm), mean thickness was 1.25 mm. The pigmented lesion did not affect visual acuity. In 85 patients the lesion was flat or slightly elevated, without secondary changes in the retina. In 31 patients additional changes in the retina were observed - most frequently subretinal fluid. Two patients were eventually diagnosed with malignant melanoma. The follow-up OCT did not show progression in neither patients without secondary changes nor those with risk factors of malignancy. Optical coherence tomography enables detailed evaluation of the retina overlying the pigmented lesion. Secondary changes in the retina need additional exams and strict observation. OCT could be an additional tool in the evaluation of treatment of malignant melanoma.


Family medicine training and practice in Malawi: History, progress, and the anticipated role of the family physician in the Malawian health system.
This article analyses the development and implementation of family medicine training and practice in Malawi, with special attention given to its current status and the projected role the trained family physician will be expected to play in the future. The general aim of the paper is to briefly review the role of family physicians in rural areas, as well as to discuss the history of family medicine training in Malawi. The idea of formal family medicine training and practice in Malawi started as early as 2001 but did not come to fruition until 2011, with the start of the undergraduate clerkship in the fourth year of medical school at the University Of Malawi College Of Medicine. This energy was followed by the launch of a postgraduate training programme in early 2015. The challenges encountered in this endeavour are also reviewed. The paper concludes by discussing the expected role a Malawian family physician will play in the local context, considering the key roles that family physicians play elsewhere in Africa.


Use of the International Classification of Functioning, Disability and Health (ICF) in social services for elderly in Sweden.
To examine the content of health information in acts of social services of elderly people in relation to the International Classification of Functioning, Disability and Health (ICF) and to describe the health information in the different parts of the acts according to the ICF. Health information of 25 acts from four municipalities was analysed and the concepts were linked to ICF codes, using the established coding rules. The health information consisted of 372 concepts, which were linked to 122 specific ICF codes. The concepts in the acts were mostly linked to the ICF component Activities and Participation, except for the current functioning concepts where the ICF component Body functions was the most frequent. The 3rd level was most frequent in Activities and Participation and in Environmental factors, and the 2nd level was most frequent in Body functions. The ICF covers the concepts and terms contained in the acts to a large extent. Furthermore, the results show that the ICF codes differ in the different parts of the acts. The ICF provides a coherent and structured documentation, which contributes to a legally secure assessment of assistance. The selection of ICF codes can be used in development of "code sets" for social services for elderly.


Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases. Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.


Transferability of the EST-SSRs developed on Nules clementine (Citrus clementina Hort ex Tan) to other Citrus species and their effectiveness for genetic mapping.
During the last decade, numerous microsatellite markers were developed for genotyping and to identify closely related plant genotypes. In citrus, previously developed microsatellite markers were arisen from genomic libraries and more often located in non coding DNA sequences. To optimize the use of these EST-SSRs as genetic markers in genome mapping programs and citrus systematic analysis, we have investigated their polymorphism related to the type (di or trinucleotide) or their position in the coding sequences. Among 11000 unigenes from a Clementine EST library, we have found at least one microsatellite sequence (repeated units size ranged from 2 to 6 nucleotides) in 1500 unigenes (13.6%). More than 95% of these SSRs were di or trinucleotides. If trinucleotide microsatellites were encountered trough all part of EST sequences, dinucleotide microsatellites were preferentially (50%) concentrated in the 5' 100th nucleotides. We assessed the polymorphism of 41 EST-SSR, by PCR amplification droved with flanking primers among ten Citrus species plus 3 from other genera. More than 90% of EST-SSR markers were polymorphic. Furthermore, dinucleotide microsatellite markers were more polymorphic than trinucleotide ones, probably related to their distribution that was more often located in the 5' UnTranslated Region (UTR). We obtained a good agreement of diversity relationships between the citrus species and relatives assessed with EST-SSR markers with the established taxonomy and phylogeny. To end, the heterozygosity of each genotype and all dual combinations were studied to evaluate the percentage of mappable markers. Higher values (> 45%) were observed for putative Citrus inter-specific hybrids (lime lemon, or sour orange) than for Citrus basic true species (mandarin, pummelo and citron) (<30%). Most favorable combinations for genome mapping were observed in those involving interspecific hybrid genotypes. Those gave higher levels of mappable markers (>70%) with a significant proportion suitable for synteny analysis. Fourty one new EST-SSR markers were produced and were available for citrus genetic studies. Whatever the position of the SSR in the ESTs the EST-SSR markers we developed are powerful to investigate genetic diversity and genome mapping in citrus.


Inula Viscosa Extracts Induces Telomere Shortening and Apoptosis in Cancer Cells and Overcome Drug Resistance.
Telomerase is activated in human papillomavirus (HPV) positive cervical cancer and targeting telomeres offers a novel anticancer therapeutic strategy. In this study, the telomere targeting properties, the cytotoxic as well as the pro-apoptotic effects of hexane (IV-HE) and dichloromethane (IV-DF) fractions from Inula viscosa L. extracts were investigated on human cervical HeLa and SiHa cancer cells. Our data demonstrate that IV-HE and IV-DF extracts were able to inhibit cell growth in HeLa and SiHa cells in a dose-dependent manner and studied resistant cell lines exhibited a resistance factor less than 2 when treated with the extracts. IV-HE and IV-DF extracts were able to inhibit telomerase activity and to induce telomere shortening as shown by telomeric repeat amplification protocol and TTAGGG telomere length assay, respectively. The sensitivity of fibroblasts to the extracts was increased when telomerase was expressed. Finally, IV-HE and IV-DF were able to induce apoptosis as evidenced by an increase in annexin-V labeling and caspase-3 activity. This study provides the first evidence that the IV-HE and IV-DF extracts from Inula viscosa L. target telomeres induce apoptosis and overcome drug resistance in tumor cells. Future studies will focus on the identification of the molecules involved in the anticancer activity.


In vitro characterization of a nineteenth-century therapy for smallpox.
In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections.


Identifying Research Priorities among Patients and Families of Children with Rheumatic Diseases Living in the United States.
To improve the quality and participation in pediatric rheumatology research, patient-prioritized studies should be emphasized. We collaborated with United States-based pediatric rheumatology advocacy organizations to survey patients and caregivers of children with rheumatic diseases to identify what research topics were most important to them. We conducted Web-based surveys and focus groups (FG) of patients and caregivers of children with juvenile myositis (JM), juvenile arthritis (JA), and childhood-onset systemic lupus erythematosus (cSLE). Surveys were emailed to listservs and posted to social media sites of JM, JA, and cSLE patient advocacy organizations. An initial survey asked open-ended questions about patient/caregiver research preferences. Responses were further characterized through FG. A final ranking survey asked respondents to rank from a list of research themes the 7 most important to them. There were 365 JM respondents, 44 JA respondents, and 32 cSLE respondents to the final ranking survey. The top research priority for JM was finding new treatments, and for JA and cSLE, the priority was understanding genetic/environmental etiology. The 3 prioritized research themes common across all disease groups were medication side effects, disease flare, and disease etiology. Patient-centered research prioritization is recognized as valuable in conducting high-quality research, yet there is a paucity of data describing patient/family preferences, especially in pediatrics. We used multimodal methodologies to assess current patient/caregiver research priorities to help frame the agenda for the pediatric rheumatology research community. Patients and caregivers from all surveyed disease groups prioritized the study of medication side effects, disease flares, and disease etiology.


Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial.
With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso. An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline. MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies. (ClinicalTrials.gov) NCT00354380.


Demonstration and partial characterization of the interferon-gamma receptor on human mononuclear phagocytes.
Radioiodinated recombinant human interferon-gamma (IFN gamma) bound to human monocytes, U937, and HL60 cells in a specific, saturable, and reversible manner. At 4 degrees C, the different cell types bound 3,000-7,000 molecules of IFN gamma, and binding was of comparable affinity (Ka = 4-12 X 10(8) M-1). No change in the receptor was observed after monocytes differentiated to macrophages or when the cell lines were pharmacologically induced to differentiate. The functional relevance of the receptor was validated by the demonstration that receptor occupancy correlated with induction of Fc receptors on U937. Binding studies using U937 permeabilized with digitonin showed that only 46% of the total receptor pool was expressed at the cell surface. The receptor appears to be a protein, since treatment of U937 with trypsin or pronase reduced 125I-IFN gamma binding by 87 and 95%, respectively. At 37 degrees C, ligand was internalized, since 32% of the cell-associated IFN gamma became resistant to trypsin stripping. Monocytes degraded 125I-IFN gamma into trichloroacetic acid-soluble counts at 37 degrees C but not at 4 degrees C, at an approximate rate of 5,000 molecules/cell per h. The receptor was partially characterized by SDS-polyacrylamide gel electrophoresis analysis of purified U937 membranes that had been incubated with 125I-IFN gamma. After cross-linking, the receptor-ligand complex migrated as a broad band that displayed an Mr of 104,000 +/- 18,000 at the top and 84,000 +/- 6,000 at the bottom. These results thereby define and partially characterize the IFN gamma receptor of human mononuclear phagocytes.


The evolution of social monogamy in mammals.
The evolution of social monogamy has intrigued biologists for over a century. Here, we show that the ancestral condition for all mammalian groups is of solitary individuals and that social monogamy is derived almost exclusively from this social system. The evolution of social monogamy does not appear to have been associated with a high risk of male infanticide, and paternal care is a consequence rather than a cause of social monogamy. Social monogamy has evolved in nonhuman mammals where breeding females are intolerant of each other and female density is low, suggesting that it represents a mating strategy that has developed where males are unable to defend access to multiple females.


Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study.
Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.


Living related versus deceased donor liver transplantation for maple syrup urine disease.
Maple syrup urine disease (MSUD) is an inherited disorder of branched chain ketoacid (BCKA) oxidation associated with episodic and chronic brain disease. Transplantation of liver from an unrelated deceased donor restores 9-13% whole-body BCKA oxidation capacity and stabilizes MSUD. Recent reports document encouraging short-term outcomes for MSUD patients who received a liver segment from mutation heterozygous living related donors (LRDT). To investigate effects of living related versus deceased unrelated grafts, we studied four Brazilian MSUD patients treated with LRDT who were followed for a mean 19 ± 12 postoperative months, and compared metabolic and clinical outcomes to 37 classical MSUD patients treated with deceased donor transplant. Patient and graft survival for LRDT were 100%. Three of 4 MSUD livers were successfully domino transplanted into non-MSUD subjects. Following LRDT, all subjects resumed a protein-unrestricted diet as mean plasma leucine decreased from 224 ± 306 μM to 143 ± 44 μM and allo-isoleucine decreased 91%. We observed no episodes of hyperleucinemia during 80 aggregate postoperative patient-months. Mean plasma leucine:isoleucine:valine concentration ratios were ~2:1:4 after deceased donor transplant compared to ~1:1:1.5 following LRDT, resulting in differences of predicted cerebral amino acid uptake. Mutant heterozygous liver segments effectively maintain steady-state BCAA and BCKA homeostasis on an unrestricted diet and during most catabolic states, but might have different metabolic effects than grafts from unrelated deceased donors. Neither living related nor deceased donor transplant affords complete protection from metabolic intoxication, but both strategies represent viable alternatives to nutritional management.


The impact of extended half-life versus conventional factor product on hemophilia caregiver burden.
Extended half-life factor products have reduced annualized bleeding rates in hemophilia patients. The impact of extended half-life versus conventional factor products on hemophilia caregiver burden has not been investigated. This study aimed to evaluate caregiver burden in extended half-life versus conventional factor products for hemophilia A and B. This cross-sectional web-based study of caregivers of people with hemophilia A or B was recruited from a panel research company and by word of mouth. Participants completed the Hemophilia Caregiver Impact measure, the PedsQL Family Impact Module (PedsQL), and the Work Productivity and Activity Impairment Questionnaire (WPAI). We also collected demographic, insurance coverage, and medical information related to the hemophilia patient(s). Burden differences were assessed using linear regression and matched cohort analyses. The sample (n = 448) included 49 people who were caring for people on extended half-life factor products. Worse caregiver burden was associated with more infusions per week and more bleeds in the past 6 months. Regression analyses suggested that caring for someone who is on a extended half-life factor product is associated with lower emotional impact (β = - 0.11, p < 0.05, Adjusted R2 = 0.06), and shows a trend association with lower practical impact (β = - 0.09, p < 0.10, Adjusted R2 = 0.05). The matched cohort analysis also revealed that people on extended half-life factor product had lower Emotional Impact and Practical Impact scores (t = - 2.95 and - 2.94, respectively, p < 0.05 in both cases). No differences were detected on the PedsQL or the WPAI. The reduced required frequency of factor product infusions of extended half-life factor products appears to reduce the emotional distress and practical burden of caregiving. Future work should evaluate the longitudinal impact.


Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma.
Pediatric ependymomas are enigmatic tumors, and their clinical management remains one of the more difficult in pediatric oncology. The identification of biological correlates of outcome and therapeutic targets remains a significant challenge in this disease. We therefore analyzed a panel of potential biological markers to determine optimal prognostic markers. We constructed a tissue microarray from 97 intracranial tumors from 74 patients (WHO grade II-III) and analyzed the candidate markers nucleolin, telomerase catalytic subunit (hTERT; antibody clone 44F12), survivin, Ki-67, and members of the receptor tyrosine kinase I (RTK-I) family by immunohistochemistry. Telomerase activity was determined using the in vitro-based telomere repeat amplification protocol assay, and telomere length was measured using the telomere restriction fragment assay. Primary tumors with low versus high nucleolin protein expression had a 5-year event-free survival of 74%+/-13% and 31%+/-7%, respectively. Multivariate analysis identified low nucleolin expression to be independently associated with a more favorable prognosis (hazard ratio=6.25; 95% confidence interval, 1.6-24.2; p=0.008). Ki-67 and survivin correlated with histological grade but not with outcome. Immunohistochemical detection of the RTK-I family did not correlate with grade or outcome. Telomerase activity was evident in 19 of 22 primary tumors, with telomere lengthening and/or maintenance occurring in five of seven recurrent cases. Low nucleolin expression was the single most important biological predictor of outcome in pediatric intracranial ependymoma. Furthermore, telomerase reactivation and maintenance of telomeric repeats appear necessary for childhood ependymoma progression. These findings require corroboration in a clinical trial setting.


Changes in the surface of Leptospira interrogans serovar grippotyphosa during in vitro cultivation.
Surface components of virulent and attenuated Leptospira interrogans serovar grippotyphosa were compared by using Triton X-114 solubilization and phase partitioning, immunoprecipitation of intact organisms, and freeze-fracture electron microscopy. Removal of the leptospiral outer membrane by using 0.1% Triton X-114 was demonstrated by whole-mount electron microscopy and by essentially complete solubilization of a lipopolysaccharidelike substance (LLS) from the outer membrane. Triton X-114 (0.1%) did not solubilize subsurface proteins, such as endoflagellar filaments or penicillin-binding proteins, which are markers for the periplasmic space and inner membrane, respectively. Triton X-114 solubilized material from both the virulent and attenuated strains, which partitioned into the hydrophobic, detergent phase, contained LLS and major proteins of 41 and 44 kDa, which were also immunoprecipitable from intact organisms. The virulent strain contained greater amounts of an LLS component with an apparent molecular mass of 30 kDa (R(f) = 0.57), whereas the attenuated strain contained larger amounts of an LLS component with an apparent molecular mass of 20 kDa (R(f) = 0.74). Differences in protein components between virulent and attenuated organisms were also detected; whereas the 41- and 44-kDa proteins were immunoprecipitated in equal amounts from both the virulent and attenuated strains, a 33-kDa protein was immunoprecipitated in significantly greater amounts from the attenuated strain. Quantitation of outer membrane particle density by freeze-fracture electron microscopy showed that both strains had a low transmembrane outer membrane protein content compared with that of typical gram-negative bacteria. The virulent and attenuated strains had 443 and 990 particles (P less than 0.000001) per micron, respectively, in the concave outer membrane fracture face. These findings suggest that in vitro cultivation of L. interrogans is accompanied by quantitative and qualitative changes in both LLS and outer membrane-associated proteins.


Homomorphic ZW chromosomes in a wild strawberry show distinctive recombination heterogeneity but a small sex-determining region.
Recombination in ancient, heteromorphic sex chromosomes is typically suppressed at the sex-determining region (SDR) and proportionally elevated in the pseudoautosomal region (PAR). However, little is known about recombination dynamics of young, homomorphic plant sex chromosomes. We examine male and female function in crosses and unrelated samples of the dioecious octoploid strawberry Fragaria chiloensis in order to map the small and recently evolved SDR controlling both traits and to examine recombination patterns on the incipient ZW chromosome. The SDR of this ZW system is located within a 280 kb window, in which the maternal recombination rate is lower than the paternal one. In contrast to the SDR, the maternal PAR recombination rate is much higher than the rates of the paternal PAR or autosomes, culminating in an elevated chromosome-wide rate. W-specific divergence is elevated within the SDR and a single polymorphism is observed in high species-wide linkage disequilibrium with sex. Selection for recombination suppression within the small SDR may be weak, but fluctuating sex ratios could favor elevated recombination in the PAR to remove deleterious mutations on the W. The recombination dynamics of this nascent sex chromosome with a modestly diverged SDR may be typical of other dioecious plants.


Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis.
Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis. Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression. Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients. Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.


Certainty Level of Water Delivery of the Required Quality by Water Supply Networks.
The security of water delivery of the required quality by water supply networks is identified with the concept of reliability. Therefore, a method of reliability evaluation of water distribution of the required quality was developed. The method is based on the probabilistic character of secondary water contamination in the water supply network. Data for the method are taken from monitoring of the water distribution system. The method takes into consideration the number and locations of individual measurement points and the results of the tests of water quality indicators at these points. The sets of measurement points and water quality indicators constitute a matrix research (observation) field in the model. The proposed method was implemented to assess the reliability of a water distribution process with respect to water with the required microbiological quality indicators in a real distribution system.


Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population.
To study the variation in CYP1A2 activity in relation to smoking, gender, age and CYP1A2 polymorphisms. CYP1A2 activity was determined by plasma paraxanthine:caffeine ratio (17X:137X) 4 h after the intake of a standardized cup of coffee in 146 Turkish healthy volunteers. Seven CYP1A2 polymorphisms (-3860G>A, -3113G>A, -2467del/T, -739T>G, -729C>T, -163C>A and 5347T>C) were analyzed. The 17X:137X ratios were increased in smokers (p < 0.0001) and tended to be higher in men both among nonsmokers (p = 0.051) and smokers (p = 0.064). Age-related differences were observed only among nonsmoking women (p = 0.024). The -163C>A polymorphism correlated with 17X:137X ratios only in smokers (p = 0.006). Furthermore, increased 17X:137X ratios were observed in CYP1A2 haplotype H4 (-3860G, -3113G, -2467del, -739T, -729C, -163A and 5347T) carriers in the overall study population (p = 0.026). Multiple regression analyses including smoking, gender, -163C>A genotype and age revealed a significant influence of smoking (p < 0.0001) and gender (p = 0.002) in the overall study population. However, in nonsmokers only the influence of gender remained significant (p = 0.021), while in smokers the influence of the -163C>A genotype held the statistical significance (p = 0.019). The influence of haplotype H4 remained significant (p = 0.028) in the overall study population in similar analyses. Smoking has the strongest impact on CYP1A2 activity, while gender and haplotype H4 showed marginal effects. The influence of the -163C>A polymorphism on CYP1A2 activity in smokers suggests an effect on the inducibility of the enzyme.


Risks of tubo-ovarian abscess in cases of endometrioma and assisted reproductive technologies are both under- and overreported.
To study possible associations among endometriosis, pelvic infectious disease, and ART. Retrospective cohort analysis over 4 consecutive years, based on medical records and insurance coding in a tertiary endometriosis reference center. Tertiary university-based reference center for endometriosis. We retrieved all charts carrying the diagnoses infectious process and endometriosis in 2009-2012. Each chart was individually analyzed for categorization of the infectious episode and determining whether ART had been performed. Hospitalization for acute infection in women with known endometriosis and possible past ART. Retrospective insurance codes-triggered chart analysis. Ten patients were admitted for an acute infection with fever, acute abdomen syndrome, elevated white blood cell count, and adnexal mass. Three women had oocyte retrieval, and an endometrioma was present 16, 57, and 102 days earlier. In one patient, the complication occurred 37 days after a cesarean section without prior ART. In the remaining six cases tubo-ovarian abscesses (TOAs) occurred spontaneously in endometriosis women who never had ART. Medical treatment succeeded in only two patients, and the remaining eight needed laparoscopic drainage. In 6 out of those 8 cases, laparoscopic drainage was a second-stage measure justified by failure to respond to antibiotic therapy. Our data indicate that some putative complications of ART and endometrioma may actually not be linked to ART, but rather constitute sporadic occurrences in endometriosis. Furthermore, TOAs occurring in women with endometriosis are best treated by early surgical drainage together with intravenous antibiotics.


Schooling affects the feeding success of Australian salmon (Arripis trutta) when preying on mysid swarms (Paramesopodopsis rufa).
When feeding on mysid swarms (Paramesopodopsis rufa), juvenile Australian salmon (Arripis trutta) had higher rates of successful attacks when foraging in a group of six fish (55% total advances) than when foraging alone (39% total advances). Six schooling fish had lower approach rates than solitary fish (25% and 37% of total advances, respectively). This result indicated that schooling fish were better at reducing the confusion effect of swarming prey, resulting in more efficient feeding. In larger areas, schools achieved higher rates of successful attacks (19 prey/fish in the large tank, compared with 11 prey/fish in the smaller tank). There was no influence on the feeding success of individual fish when changes were made to the number of prey presented to each fish. Nearest neighbour distances were smallest in the absence of prey, and increased with the introduction of prey and again in an attack sequence. Six fish schooled more cohesively than three fish, indicating increased benefits of schooling in larger groups that contribute to advanced vigilance and foraging techniques.


High-Risk Advanced Maternal Age and High Parity Pregnancy: Tackling a Neglected Need Through Formative Research and Action.
Pregnancy among women of advanced maternal age (those 35 years or older) or among women of high parity (those having had 5 or more births) is linked to maternal and infant mortality. Yet little is known about the drivers of these pregnancies as they are often neglected in existing family planning and reproductive health programs. To better understand the context in which advanced maternal age and high parity pregnancies occur and the acceptability of discussing associated pregnancy risks, the Health Communication Capacity Collaborative (HC3) conducted formative qualitative research between January and March 2015 on the perception and determinants of such pregnancies in rural and urban areas of Niger and Togo. We supplemented this research with secondary analyses of data from Demographic and Health Surveys and a 2014 Niger survey. Our formative research showed that urban Togolese participants demonstrated more knowledge about advanced maternal age and high parity pregnancy risks than did participants in Niger as a whole. We found that such pregnancies were generally seen as part of reproductive norms in situations where fertility rates remain exceptionally high, especially in Niger. Social, gender, and religious norms, including competition between co-wives, also drove women into high parity and advanced maternal age situations, particularly in Niger, highlighting the need to bring men and community and religious leaders into family planning conversations to increase acceptance. The study also provided important insights needed to address these high-risk pregnancies through culturally appropriate health communication interventions. A main insight was that providers often had incomplete information about advanced maternal age and high parity pregnancies and lacked communication skills, protocols, and tools to appropriately discuss such pregnancy risks with clients. HC3 used these and additional findings to create an Implementation Kit (I-Kit) for family planning and maternal and child health program managers with guidance and tangible tools to address advanced maternal age and high parity pregnancy through social and behavior change communication. The I-Kit includes health communication materials to engage women, men, decision makers, communities, health care providers, journalists, and others. In 2016 and 2017, one organization each in Niger and Togo piloted the I-Kit, integrated selected I-Kit tools into their unique programs, and documented their experiences. Both organizations credited the I-Kit with expanding the scope of their programs to now address advanced maternal age and high parity pregnancy and provided concrete suggestions for adapting the materials according to activity and intended audience.


Solid phase extraction in combination with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry for the detailed investigation of volatiles in South African red wines.
Comprehensive two-dimensional gas chromatography in combination with time-of-flight mass spectrometry (GC×GC-TOFMS) has been applied for the analysis of volatile compounds in three young South African red wines. In spite of the significant benefits offered by GC×GC-TOFMS for the separation and identification of volatiles in such a complex matrix, previous results utilizing headspace solid phase micro extraction (HS-SPME) demonstrated certain limitations. These were primarily associated with the choice of sample preparation technique, which failed to extract some influential semi-volatile wine constituents. Therefore, in the current report, we utilized solid phase extraction (SPE) in combination with GC×GC-TOFMS for the detailed investigation of particularly low-level semi-volatiles in South African wine. 214 compounds previously reported in grapes and related beverages were tentatively identified based on mass spectral data and retention indices, while 62 additional compounds were positively identified using authentic standards. The method proved particularly beneficial for the analysis of terpenes, lactones and volatile phenols, and allowed us to report the presence of numerous volatile compounds for the first time in Pinotage wines.


ATP driven structural changes of the bacterial Mre11:Rad50 catalytic head complex.
DNA double-strand breaks (DSBs) threaten genome stability in all kingdoms of life and are linked to cancerogenic chromosome aberrations in humans. The Mre11:Rad50 (MR) complex is an evolutionarily conserved complex of two Rad50 ATPases and a dimer of the Mre11 nuclease that senses and processes DSBs and tethers DNA for repair. ATP binding and hydrolysis by Rad50 is functionally coupled to DNA-binding and tethering, but also regulates Mre11's nuclease in processing DNA ends. To understand how ATP controls the interaction between Mre11 and Rad50, we determined the crystal structure of Thermotoga maritima (Tm) MR trapped in an ATP/ADP state. ATP binding to Rad50 induces a large structural change from an open form with accessible Mre11 nuclease sites into a closed form. Remarkably, the NBD dimer binds in the Mre11 DNA-binding cleft blocking Mre11's dsDNA-binding sites. An accompanying large swivel of the Rad50 coiled coil domains appears to prepare the coiled coils for DNA tethering. DNA-binding studies show that within the complex, Rad50 likely forms a dsDNA-binding site in response to ATP, while the Mre11 nuclease module retains a ssDNA-binding site. Our results suggest a possible mechanism for ATP-dependent DNA tethering and DSB processing by MR.


Deafness and HIV/AIDS: a systematic review of the literature.
A systematic review of the literature focused on empirical work on deafness and HIV/AIDS published during the past decade. The review reveals that deaf people are vulnerable to contracting HIV and might lack access to HIV/ AIDS information, testing and treatment. Three studies that were located through this review included prevalence data on disability and HIV. These indicated that deaf people are as likely, if not twice as likely, to be infected with HIV. The data also reveal that although some research has focused on HIV/AIDS knowledge among deaf people, this might not be the main area of concern in relation to HIV risk for this population. The available research more often points to increased instances of multiple partners, sexual abuse and earlier sexual debut, and, in some contexts, decreased use of condoms. These factors might explain increased risk of HIV infection for the deaf population. Additionally, the review elaborates on the geographical and methodological focuses of past research and identifies gaps, strengths and weaknesses in this body of literature.


Controlling medicine prices in Sudan: the challenge of the recently established medicines regulatory authority.
This study evaluated the capacity of the medicine pricing mechanism of the National Medicines and Poisons Board (NMPB), the medicine regulatory agency of Sudan, in controlling prices of imported medicines. The study was conducted between July and September 2008 and data on the 50 most sold medicines in 2007 were obtained from the records of the regulatory authority and pharmacies in Khartoum; 135 products were included. The cost and freight (C&F) prices of 23% of the selected medicines approved by NMPB were over 10 times the International Reference Price; 71% of these items were generics. The wholesale price of only 40% of the studied medicines was less than that approved by NMPB, while the retail price of 47% of medicines was less than that approved by the authority. The retail price of 11 of 12 originator medicines was equal to or more than their prices published in the British National Formulary. The price of the medicines distributed by Central Medical Supplies was about 2-fold their C&F price. The current pricing system is of limited benefit in controlling medicine prices in Sudan.


Wall shear stress and flow patterns in the ascending aorta in patients with bicuspid aortic valves differ significantly from tricuspid aortic valves: a prospective study.
We compared flow and wall shear stress (WSS) patterns in the ascending aorta of individuals with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) using four-dimensional cardiovascular magnetic resonance (4D-CMR). BAV are known to be associated with dilation and dissection of the ascending aorta. However, the cause of vessel disease in patients with BAVs is unknown. Inborn connective tissue disease and also dilation secondary to increased WSS because of altered blood flow patterns in the ascending aorta are discussed as causes for dilation of the aorta. WSS can be estimated non-invasively by 4D-CMR. Eighteen, otherwise, healthy individuals with functionally normal BAVs were compared prospectively with an age- and sex-matched control group of healthy individuals with TAV. Blood flow data were obtained by 4D-CMR visualization and WSS was calculated with specific software tools. Eighty-five per cent of the individuals with BAVs showed a high-grade helical flow pattern in the ascending aorta compared with 6% of the individuals with TAV. WSS in the ascending aorta was significantly altered in individuals with BAVs compared with TAV. WSS and flow patterns in the ascending aorta in patients with BAVs without concomitant valve or vessel disease are significantly different compared with TAV. The significantly higher shear forces may have an impact on the development of aortic dilation in patients with BAVs.


Effects of systemic and intravitreal TNF-α inhibition in experimental autoimmune uveoretinitis.
To investigate the effect of systemic or local TNF-α inhibition with etanercept on experimental autoimmune uveoretinitis (EAU). EAU was induced by immunizing B10.RIII mice with IRBPp161-180 or by adoptively transferring uveitogenic splenocytes. Mice received systemic or local treatment with etanercept in the afferent or efferent phase. For systemic treatment, mice were injected intraperitoneally. For local treatment, etanercept was injected intravitreally or subconjunctivally. Control mice received PBS. EAU scores were determined histologically. Splenic cells were assessed for [(3)H]thymidine incorporation. ELISA was performed to measure levels of cytokines produced by splenocytes. Vitreous cavity-associated immune deviation (VCAID) was induced by intravitreally injecting ovalbumin and evaluated by measuring DTH reaction. After systemic treatment with etanercept in the afferent phase, EAU disease scores, IRBP-specific cell proliferation, and production of Th1, Th2, and Th17 cytokines were reduced. EAU also improved after intravitreal etanercept treatment in the afferent phase, with unaltered IRBP-specific proliferation, reduced IFN-γ, but increased IL-6 and IL-10 secretion. VCAID induction was impaired after intravitreal etanercept treatment. No amelioration of EAU or reduction in IRBP-specific cell response was found after systemic or intravitreal treatment in the efferent phase or after subconjunctival treatment. After adoptive transfer, etanercept- and PBS-treated recipients showed similar disease severity and antigen-specific proliferation of splenocytes. It can be concluded that TNF-α participates mainly in the immunopathology in the induction phase of EAU. The mechanism of action underlying EAU improvement may be different for local and systemic etanercept treatment.


The Relationship Between Range of Motion and Injuries in Adolescent Dancers and Sportspersons: A Systematic Review.
Background: The frequent and intensive training and performance of pre-professional ballet dancers and sportspersons is offered at a time when young ballet dancers and young athletes may be vulnerable to injury due to the progress through adolescence and growth spurts. Hypothesis: There are changes in range of motion during the progress through adolescence and growth periods in dancers and sportspersons. These changes in ROM can be linked to the increase of injury. Objectives: The primary aim of this systematic review is to determine whether there are changes in ROM during the progress through adolescence and growth spurts in dancers and sportspersons. The secondary aim is to determine whether these changes can predict the risk of injuries for adolescent dancers and sportspersons. Search strategy: Pubmed, Cochrane Register of Controlled Trails (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), EBSCO Host databases: CINAHL Plus, MEDLINE, SPORTDiscus, Embase were searched using MeSH terms. Manual search in the Journal of Dance Medicine and Science and screening of the reference lists of identified studies and reviews was conducted. Selection criteria: Studies included adolescent dancers and sportspersons, aged 8-18, both sexes, growth spurt related to changes in ROM and injury incidence. Data collection and analysis: Search strategy was performed in the flow diagram of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently appraised each included study using Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) for methodological quality of the included studies. For data extraction, the following information was systematically extracted: first author and year of publication, study design, participants (sample size of mean age), age, maturation (if assessed), intervention, outcome(s), and some notes of each study. For evaluation of the risk of bias and precision the Research Triangle Institute Item Bank (RTI-IB) is included. Main results: Seven observational studies met the inclusion criteria of this current review. The results of this review suggest that there are changes in ROM during the progress through adolescence and growth spurts in dancers and sportspersons. These changes may lead to an increase in injury incidence. Conclusion: There is evidence linking to changes in ROM during the progress through adolescence and growth spurts in dancers and sportspersons. These changes in ROM may be related to injury incidence.


Long-term exposure to residential green and blue spaces and anxiety and depression in adults: A cross-sectional study.
Although exposure to natural outdoor environments has been consistently associated with improved perceived general health, available evidence on a protective association between this exposure and specific mental health disorders such as depression and anxiety is still limited. The aim of this study was to evaluate the effects of long-term exposure to residential green and blue spaces on anxiety and depression and intake of related medication. Additionally, we aimed to explore potential mediators and effect modifiers of this association. The study was based on an existing adult cohort (ALFA - Alzheimer and Families) and includes 958 adult participants from Barcelona recruited in 2013-2014. For each participant residential green and blue exposure indicators [surrounding greenness (NDVI), amount of green (land-cover) and access to major green spaces and blue spaces] were generated for different buffers (100m, 300m and 500m). Participants reported their history of doctor-diagnosed anxiety and depressive disorders and intake of related medication. Logistic regression models were applied to assess the corresponding associations. Increasing surrounding greenness was associated with reduced odds of self-reported history of benzodiazepines [e.g. Odds ratio - OR (95%CI) = 0.62 (0.43, 0.89) for 1-interquartile range (IQR) increase in NDVI in a 300m buffer] and access to major green spaces was associated with self-reported history of depression [OR (95%CI) = 0.18 (0.06, 0.58)]. No statistically significant associations were observed with blue spaces. Air pollution (between 0.8% and 29.6%) and noise (between 2.2% and 5.3%) mediated a proportion of the associations observed, whereas physical activity and social support played a minor role. Our findings suggest a potential protective role of green spaces on mental health (depression and anxiety) in adults, but further studies, especially longitudinal studies, are needed to provide further evidence of these benefits and of the mediation role of exposures like air pollution and noise.


Genes responsive to low-intensity pulsed ultrasound in MC3T3-E1 preosteoblast cells.
Although low-intensity pulsed ultrasound (LIPUS) has been shown to enhance bone fracture healing, the underlying mechanism of LIPUS remains to be fully elucidated. Here, to better understand the molecular mechanism underlying cellular responses to LIPUS, we investigated gene expression profiles in mouse MC3T3-E1 preosteoblast cells exposed to LIPUS using high-density oligonucleotide microarrays and computational gene expression analysis tools. Although treatment of the cells with a single 20-min LIPUS (1.5 MHz, 30 mW/cm(2)) did not affect the cell growth or alkaline phosphatase activity, the treatment significantly increased the mRNA level of Bglap. Microarray analysis demonstrated that 38 genes were upregulated and 37 genes were downregulated by 1.5-fold or more in the cells at 24-h post-treatment. Ingenuity pathway analysis demonstrated that the gene network U (up) contained many upregulated genes that were mainly associated with bone morphology in the category of biological functions of skeletal and muscular system development and function. Moreover, the biological function of the gene network D (down), which contained downregulated genes, was associated with gene expression, the cell cycle and connective tissue development and function. These results should help to further clarify the molecular basis of the mechanisms of the LIPUS response in osteoblast cells.


Selection strength and hitchhiking around two anti-malarial resistance genes.
Neutral mutations may hitchhike to high frequency when they are situated close to sites under positive selection, generating local reductions in genetic diversity. This process is thought to be an important determinant of levels of genomic variation in natural populations. The size of genome regions affected by genetic hitchhiking is expected to be dependent on the strength of selection, but there is little empirical data supporting this prediction. Here, we compare microsatellite variation around two drug resistance genes (chloroquine resistance transporter (pfcrt), chromosome 7, and dihydrofolate reductase (dhfr), chromosome 4) in malaria parasite populations exposed to strong (Thailand) or weak selection (Laos) by anti-malarial drugs. In each population, we examined the point mutations underlying resistance and length variation at 22 (chromosome 4) or 25 (chromosome 7) microsatellite markers across these chromosomes. All parasites from Thailand carried the K76T mutation in pfcrt conferring resistance to chloroquine (CQ) and 2-4 mutations in dhfr conferring resistance to pyrimethamine. By contrast, we found both wild-type and resistant alleles at both genes in Laos. There were dramatic differences in the extent of hitchhiking in the two countries. The size of genome regions affected was smaller in Laos than in Thailand. We observed significant reduction in variation relative to sensitive parasites for 34-64 kb (2-4 cM) in Laos on chromosome 4, compared with 98-137 kb (6-8 cM) in Thailand. Similarly, on chromosome 7, we observed reduced variation for 34-69 kb (2-4 cM) around pfcrt in Laos, but for 195-268 kb (11-16 cM) in Thailand. Reduction in genetic variation was also less extreme in Laos than in Thailand. Most loci were monomorphic in a 12 kb region surrounding both genes on resistant chromosomes from Thailand, whereas in Laos, even loci immediately proximal to selective sites showed some variation on resistant chromosomes. Finally, linkage disequilibrium (LD) decayed more rapidly around resistant pfcrt and dhfr alleles from Laos than from Thailand. These results demonstrate that different realizations of the same selective sweeps may vary considerably in size and shape, in a manner broadly consistent with selection history. From a practical perspective, genomic regions containing resistance genes may be most effectively located by genome-wide association in populations exposed to strong drug selection. However, the lower levels of LD surrounding resistance alleles in populations under weak selection may simplify identification of functional mutations.


In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease.
Immunological reactions have a key role in health and disease and are complex events characterized by coordinated cell trafficking to specific locations throughout the body. Clarification of these cell-trafficking events is crucial for improving our understanding of how immune reactions are initiated, controlled and recalled. As we discuss here, an emerging modality for revealing cell trafficking is bioluminescence imaging, which harnesses the light-emitting properties of enzymes such as luciferase for quantification of cells and uses low-light imaging systems. This strategy could be useful for the study of a wide range of biological processes, such as the pathophysiology of graft-versus-host and graft-versus-leukaemia reactions.


Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial.
Emtricitabine is a new, once-daily nucleoside reverse transcriptase inhibitor (NRTI) with potent activity against human immunodeficiency virus (HIV). To assess the efficacy and safety of emtricitabine as compared with stavudine when used with a background regimen of didanosine and efavirenz. Randomized, double-blind, double-dummy study conducted at 101 research clinics in North America, Latin America, and Europe. The first patient was enrolled on August 21, 2000; no investigator or patient was unblinded until the last patient randomized completed the week 48 visit on October 24, 2002. Analyses were based on data collected in a double-blind setting with a median follow-up of 60 weeks. Patients were 571 antiretroviral-naive, HIV-1-infected adults aged 18 years or older with viral load levels greater than or equal to 5000 copies/mL. Receipt of either 200 mg of emtricitabine once daily (plus stavudine placebo twice daily) (n = 286) or stavudine at standard doses twice daily (plus emtricitabine placebo once daily) (n = 285) plus open-label didanosine and efavirenz, once daily. Persistent virological response, defined as achieving and maintaining viral load at or below the limit of assay quantification (< or =400 or 50 copies/mL). At the interim analysis on June 14, 2002, when the last patient randomized completed 24 weeks of double-blind treatment (median follow-up time of 42 weeks), patients in the emtricitabine group had a higher probability of a persistent virological response < or =50 copies/mL vs the stavudine group (85% vs 76%, P =.005). This was associated with a higher mean CD4 cell count change from baseline for the emtricitabine group (156 cells/ microL vs 119 cells/microL, P =.01 [of note, there was no statistical difference at 48 weeks [P =.15], although a sensitivity analysis, using an intent-to-treat population with the last CD4 cell count observation carried forward to week 48 showed a difference [P =.02]]). The independent data and safety monitoring board recommended offering open-label emtricitabine based on the interim analysis. The probability of persistent virological response < or =50 copies/mL through week 60 was 76% for the emtricitabine group vs 54% for the stavudine group (P<.001). The probability of virological failure through week 60 was 4% in the emtricitabine group and 12% in the stavudine group (P<.001). Patients in the stavudine group had a greater probability of an adverse event that led to study drug discontinuation through week 60 than did those in the emtricitabine group (15% vs 7%, P =.005). Once-daily emtricitabine appeared to demonstrate greater virological efficacy, durability of response, and tolerability compared with twice-daily stavudine when used with once-daily didanosine and efavirenz.


Holographic opto-fluidic microscopy.
Over the last decade microfluidics has created a versatile platform that has significantly advanced the ways in which micro-scale organisms and objects are controlled, processed and investigated, by improving the cost, compactness and throughput aspects of analysis. Microfluidics has also expanded into optics to create reconfigurable and flexible optical devices such as reconfigurable lenses, lasers, waveguides, switches, and on-chip microscopes. Here we present a new opto-fluidic microscopy modality, i.e., Holographic Opto-fluidic Microscopy (HOM), based on lensless holographic imaging. This imaging modality complements the miniaturization provided by microfluidics and would allow the integration of microscopy into existing on-chip microfluidic devices with various functionalities. Our imaging modality utilizes partially coherent in-line holography and pixel super-resolution to create high-resolution amplitude and phase images of the objects flowing within micro-fluidic channels, which we demonstrate by imaging C. elegans, Giardia lamblia, and Mulberry pollen. HOM does not involve complicated fabrication processes or precise alignment, nor does it require a highly uniform flow of objects within microfluidic channels.


Early interaction of adeno-associated virus serotype 8 vector with the host immune system following intramuscular delivery results in weak but detectable lymphocyte and dendritic cell transduction.
Following in vivo recombinant adeno-associated virus (rAAV)-based gene transfer, adaptive immune responses specific to the vector or the transgene product have emerged as a potential roadblock to successful clinical translation. The occurrence of such responses depends on several parameters, including the route of vector administration as well as the viral serotype and the genome configuration, either self-complementary (sc) or single-stranded (ss). These parameters influence rAAV vector-associated immunity by modulating the crosstalk between the vector and the host immune system, including vector ability to interact or even transduce lymphoid tissues in general and antigen-presenting cells (APCs) in particular. Little is known about immune cell populations that are targeted in vivo by rAAV vectors. Moreover, the transduction of dendritic cells is still controversial and not directly demonstrated. Here, we show that intramuscular administration of an sc rAAV8 vector in the mouse leads to a rapid distribution of viral genomes in the lymphoid tissues that is associated with transgene expression. Transduced cells were detected in follicular areas of the spleen and the draining lymph nodes. In addition to B and T lymphocytes, transduced professional APCs were detected although at very low frequency. In addition, viral genomes and transgene transcripts were also detected in these cell populations after ss rAAV8 vector administration. Although the functional significance of those observations needs further explorations, our results highlight an early and intricate interaction between the rAAV vector upon its in vivo delivery and the host immune system.


Utility of negative oral contrast (milk with 4% fat) in PET-CT studies.
The aim of this study was to evaluate whether low-attenuation oral contrast agent (milk with 4% fat) in PET-CT gastrointestinal studies(GIT) improves the diagnostic accuracy. Traditional high-contrast oral agents like iodine solutions, and barium suspensions which due to overcorrection problems in PET-CT interpretation lowers the accuracy of diagnosis. Traditional low-attenuation oral contrast agents are water, air, fat containing agents used with 12.5% corn oil and polyethylene glycol. Volumen is a 0.1% barium suspension and has found favor in visualization of mural features as well as for GIT distension. Milk with 4% fat content has also been tested out in radiological studies and found to be as effective as Volumen. As the former is more easily available, palatable, and acceptable especially, by children it needed to be tested in the visualization of the GIT in the PET-CT scenario. Total of 112 patients were divided into 3 groups. Group I: No intervention (18 subjects) Group II: Water (55 subjects): All these patients had 500-750 ml of water 5-10 min before PET examination. Group III: Milk (39 subjects) 500 ml of milk (4% fat content with no additives) was given 40-45 min after 18F-Fluorodeoxyglucose (FDG) injection and another 500 ml 5 min before scan was started. For patients intolerant to milk the same procedure was carried out with soya milk. Group IV comparison with data with Volumen. CRITERIA FOR EVALUATION OF GUT DISTENSION ON CT IMAGES: (0) No distension, (1) 1 cm distension, (2) 1-2 cm distension, (3) >2 cm distension. For the study analysis, % of patients with criteria 2 and 3 were considered as good visualization. Stomach distension was16%, 47%, 88%, 75% in Gr1-4 respectively, Duodenum-11%, 27% 88%, 86%, Jejunum-33%, 49%, 89%, 76%(*) Ileum-40%, 77%, 82%, 80%(*) and Colon-55%, 58%, 7 4%. Visualization of bowel wall with enhancement of stomach, duodenum, jejunum, and ileum and proximal colon was significantly better with milk than with water or no intervention. Intensity of FDG uptake was mild to moderate with no overcorrection in normal bowel loops and in patients with GIT lesions. Gaseous distension was not increased with milk as an oral contrast agent. Images of patients with bowel tumor was well-delineated with milk administration as the FDG uptake ratio of tumor to gut was high. Distension and visualization of the stomach, duodenum, jejunum, and proximal bowel was significantly improved with milk as a low-attenuation contrast agent. Intensity of FDG uptake was not significantly increased in normal gut and delineation of tumor with increased FDG uptake was improved as overcorrection was minimal.


Life With Migraine: Effects on Relationships, Career, and Finances From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.
To assess the effects of migraine on important life domains and compare differences between respondents with episodic and chronic migraine and between sexes. Migraine is associated with a substantial personal and societal burden and can also affect the interpersonal dynamics, psychological health and well-being, and financial stability of the entire family of the person with migraine. The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a prospective, longitudinal, Web-based survey study undertaken between September 2012 and November 2013 in a systematic U.S. sample of people meeting modified International Classification of Headache Disorders, 3rd edition migraine criteria: 19,891 respondents were invited to complete the Family Burden Module, which assessed the perceived impact of migraine on family relationships and life, career and finances, and overall health. Respondents were stratified by episodic migraine (<15 headache days/month) and chronic migraine (≥15 headache days/month) and sex for comparisons. A total of 13,064 respondents (episodic migraine: 11,944 [91.4%]; chronic migraine: 1120 [8.6%]) provided valid data. Approximately 16.8% of respondents not currently in a romantic relationship (n = 536 of 3189) and 17.8% of those in a relationship but not living together (n = 236 of 1323) indicated that headaches had contributed to relationship problems. Of those in a relationship and living together (n = 8154), 3.2% reported that they chose not to have children, delayed having children or had fewer children because of migraine (n = 260; episodic migraine: n = 193 of 7446 [2.6%]; chronic migraine: n = 67 of 708 [9.5%]; P < .001). Of individuals responding to career/finance items (n = 13,061/13,036), 32.7% indicated that headaches negatively affected ≥1 career area (n = 4271; episodic migraine: n = 3617 of 11,942 [30.3%]; chronic migraine: n = 654 of 1119 [58.4%]), and 32.1% endorsed worry about long-term financial security due to migraine (n = 4180; episodic migraine: n = 3539 of 11,920 [29.7%]; chronic migraine: n = 641 of 1116 [57.4%]). Migraine can negatively affect many important aspects of life including marital, parenting, romantic and family relationships, career/financial achievement and stability, and overall health. Reported burden was consistently greater among those with chronic migraine than among people with episodic migraine; however, few differences were seen between the sexes.


Proteomic analysis of Flavobacterium psychrophilum cultured in vivo and in iron-limited media.
Flavobacterium psychrophilum is the etiologic agent of bacterial coldwater disease, but the pathogenic mechanisms of this important fish pathogen are not fully understood. Identifying bacterial genes of F. psychrophilum differentially expressed in vivo may lead to a better understanding of pathogenesis and provide targets for vaccine development. Therefore, the present study used a proteomic approach to identify and quantify proteins of F. psychrophilum following growth in vivo and under iron-limited growth conditions. As determined by 2D polyacrylamide gel electrophoresis (2D-PAGE), numerous proteins exhibited different spot intensities following culture of the bacterium in vivo, and of these, 20 were selected and identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis and Mascot searches of the F. psychrophilum genome. Eighteen proteins exhibited increased spot intensities in vivo, and these included: several chaperone and stress proteins, gliding motility protein GldN, outer membrane protein OmpH, 2 probable outer membrane proteins (OmpA family), probable aminopeptidase precursor, probable lipoprotein precursor, 3-oxoacyl-[acyl-carrier-protein]-reductase, and several proteins with unknown function. Two proteins exhibited decreased spot intensities in vivo and were identified as ferritin FtnA and outer membrane protein OmpA (P60). Culture of F. psychrophilum in iron-limited media resulted in similar protein spot intensity changes for 6 of the 20 proteins identified following growth in vivo. Results from the present study suggest a role of upregulated proteins in the pathogenesis of F. psychrophilum and these may represent potential vaccine candidate antigens.


Stimulated Brillouin scattering in highly birefringent microstructure fiber: experimental analysis.
We report on an experimental analysis of stimulated Brillouin scattering (SBS) in a 20-m-long highly birefringent microstructure fiber for sensing applications. In particular, an experimental setup based on Brillouin optical frequency-domain analysis, operating at a wavelength of 1550 nm, has been employed in order to analyze the distribution of Brillouin frequency shift along the fiber, as well as to study the dependence of Brillouin frequency shift on optical polarization, temperature, and strain. Our results indicate that, for any fixed polarization, the fiber has a dual-peaked Brillouin spectrum. A study about the origin of these two peaks is presented.