Lutein and zeaxanthin for macular degeneration.
The effects of increasing lutein and zeaxanthin dosages in people with age-related macular degeneration (AMD) are discussed. AMD is a disorder of the macula, the area associated with the sharpest visual acuity. AMD is classified as dry (nonneovascular) or wet (neovascular) and is associated with several risk factors, the biggest being age. The pathogenesis of AMD is unknown. Like many chronic illnesses, prevention is a key factor for managing AMD. Lutein and zeaxanthin, natural xanthophylls not synthesized by the human body, have been investigated for their use in promoting visual health. Lutein and zeaxanthin are dietary carotenoids that are components of a normal diet. The mechanism of protection that they confer is unknown, but two mechanisms have been hypothesized. Several studies have been conducted to assess the relationship between plasma levels of lutein and zeaxanthin and the risk of developing AMD and have yielded conflicting results. Increased dietary intake of or supplementation with lutein and zeaxanthin was found to result in increased plasma levels, which were positively and significantly associated with macular pigment optical density. Limited data have suggested that supplementation may also improve visual function. The optimal dose of lutein and zeaxanthin for the prevention or treatment of AMD has not yet been defined. A definite association between lutein and zeaxanthin supplementation and clinical benefit has yet to be shown; however, it may still be an appropriate cautionary measure for patients at high risk for developing AMD.


Taxonomy, chemodiversity, and chemoconsistency of Aspergillus, Penicillium, and Talaromyces species.
Aspergillus, Penicillium, and Talaromyces are among the most chemically inventive of all fungi, producing a wide array of secondary metabolites (exometabolites). The three genera are holophyletic in a cladistic sense and polythetic classes in an anagenetic or functional sense, and contain 344, 354, and 88 species, respectively. New developments in classification, cladification, and nomenclature have meant that the species, series, and sections suggested are natural groups that share many extrolites, including exometabolites, exoproteins, exocarbohydrates, and exolipids in addition to morphological features. The number of exometabolites reported from these species is very large, and genome sequencing projects have shown that a large number of additional exometabolites may be expressed, given the right conditions ("cryptic" gene clusters for exometabolites). The exometabolites are biosynthesized via shikimic acid, tricarboxylic acid cycle members, nucleotides, carbohydrates or as polyketides, non-ribosomal peptides, terpenes, or mixtures of those. The gene clusters coding for these compounds contain genes for the biosynthetic building blocks, the linking of these building blocks, tailoring enzymes, resistance for own products, and exporters. Species within a series or section in Aspergillus, Penicillium, and Talaromyces have many exometabolites in common, seemingly acquired by cladogenesis, but some the gene clusters for autapomorphic exometabolites may have been acquired by horizontal gene transfer. Despite genome sequencing efforts, and the many breakthroughs these will give, it is obvious that epigenetic factors play a large role in evolution and function of chemodiversity, and better methods for characterizing the epigenome are needed. Most of the individual species of the three genera produce a consistent and characteristic profile of exometabolites, but growth medium variations, stimulation by exometabolites from other species, and variations in abiotic intrinsic and extrinsic environmental factors such as pH, temperature, redox potential, and water activity will add significantly to the number of biosynthetic families expressed in anyone species. An example of the shared exometabolites in a natural group such as Aspergillus section Circumdati series Circumdati is that most, but not all species produce penicillic acids, aspyrones, neoaspergillic acids, xanthomegnins, melleins, aspergamides, circumdatins, and ochratoxins, in different combinations.


Optimization: Molecular Communication Networks for Viral Disease Analysis Using Deep Leaning Autoencoder.
Developing new treatments for emerging infectious diseases in infectious and noninfectious diseases has attracted a particular attention. The emergence of viral diseases is expected to accelerate; these data indicate the need for a proactive approach to develop widely active family specific and cross family therapies for future disease outbreaks. Viral disease such as pneumonia, severe acute respiratory syndrome type 2, HIV infection, and Hepatitis-C virus can cause directly and indirectly cardiovascular disease (CVD). Emphasis should be placed not only on the development of broad-spectrum molecules and antibodies but also on host factor therapy, including the reutilization of previously approved or developing drugs. Another new class of therapeutics with great antiviral therapeutic potential is molecular communication networks using deep learning autoencoder (DL-AEs). The use of DL-AEs for diagnosis and prognosis prediction of infectious and noninfectious diseases has attracted a particular attention. MCN is map to molecular signaling and communication that are found inside and outside the human body where the goal is to develop a new black box mechanism that can serve the future robust healthcare industry (HCI). MCN has the ability to characterize the signaling process between cells and infectious disease locations at various levels of the human body called point-to-point MCN through DL-AE and provide targeted drug delivery (TDD) environment. Through MCN, and DL-AE healthcare provider can remotely measure biological signals and control certain processes in the required organism for the maintenance of the patient's health state. We use biomicrodevices to promote the real-time monitoring of human health and storage of the gathered data in the cloud. In this paper, we use the DL-based AE approach to design and implement a new drug source and target for the MCN under white Gaussian noise. Simulation results show that transceiver executions for a given medium model that reduces the bit error rate which can be learned. Then, next development of molecular diagnosis such as heart sounds is classified. Furthermore, biohealth interface for the inside and outside human body mechanism is presented, comparative perspective with up-to-date current situation about MCN.


Risk of possible exposure to rabies among tourists and foreign residents in Nepal.
There is little data available on the actual risk to travelers of being possibly exposed to rabies. This data would be useful in advising travelers who are considering rabies pre-exposure immunization. In addition, it is not known how many travelers are already pre-immunized when they are bitten by a possibly rabid animal. The current study was performed to determine the rate at which travelers to Nepal are possibly exposed to rabies, and to determine risk factors for possible rabies exposure. A prospective 3-year study was carried out at the Canadian International Water and Energy Consultants (CIWEC) Clinic Travel Medicine Center in Kathmandu, Nepal, during the years 1996 through 1998. All non-Nepalese and non-Indian patients who presented with animal bites or scratches were eligible to be included in the study. Ninety-nine persons presented with possible rabies exposures to the CIWEC Clinic during the study period; 56 were tourists, and 43 were resident expatriates. The incidence of people presenting to the CIWEC clinic with possible rabies exposures was 1.9 per 1,000 persons/year for tourists, and 5.7 per 1,000 persons/year for resident expatriates (p <.0001). The incidence of possible exposure to rabies while trekking was 1.2 per 1,000 persons/year. Women were significantly more likely than men to present with a possible rabies exposure, accounting for 61% of patients (p =.0027). Younger people were more likely to have bite exposures to the face and head than older patients. The length of time between exposure and treatment averaged 1.6 to 5.0 days. Among patients presenting with animal bites, 56% of foreign residents, and 21% of tourists had been pre-immunized against rabies. Foreign residents of Nepal are significantly more likely to be exposed to rabies than tourists. Trekking does not increase the chances of being exposed to rabies. Children have a higher risk of being bitten on the face and head, and females are more likely than males to be bitten or scratched by a possibly rabid animal.


Pregnancy and the IUD.
Intrauterine devices are an effective method of birth control. Their use has resulted in pregnancy in a small number of women. If the device is left in situ after conception occurs, the pregnancy is often associated with infection and bleeding. The device apparently exerts its major effect on the uterus and offers little contraceptive protection to the fallopian tube and ovaries.


Methadyl acetate and methadone as maintenance treatments for heroin addicts. A veterans administration cooperative study.
This was a double-blind comparison of methadyl acetate and two dose levels of methadone hydrochloride in the maintenance of 430 street heroin addicts from 12 Veterans Administration hospitals. The starting sample consisted of 146 patients receiving low-dose methadone, 142 patients receiving methadyl acetate. Patients were first given 30 mg of both drugs, and doses were incremented by 10 mg/week until they stabilized at methadyl acetate, 80 mg three times a week, and methadone hydrochloride, 50 mg daily or 100 mg daily. Dosage was fixed for the balance of the 40-week treatment period. Safety was evaluated by clinical and laboratory observations conducted at frequent intervals throughout the study. Relative efficacy was evaluated by illicit drug use, program retention and attendance, and global staff judgments. It is concluded that methadyl acetate is as safe a drug as methadone and that it compares favorably with highdose methoadone in terms of efficacy. Both methyadyl acetate and high-dose methadone appear to be better maintenance regimens than low-dose methadone under the conditions of this study.


An exploration of quality of life and the experience of living with home parenteral nutrition.
The aim of this research was to achieve a deeper understanding of the experience of adults living with home parenteral nutrition (PN) and to define their quality of life (QOL). The research design was qualitative, using content and interpretative phenomenological analysis. The sample included adults with intestinal failure, stratified by length of home PN dependency. Sampling continued until data saturation was achieved. A second reviewer independently coded a subset of narratives (kappa = 0.684). Participants included 24 adults receiving home PN because of short bowel syndrome (95.8%) and pseudo-obstruction (4.2%). Twenty-five percent received PN for < 2 years, 20.8% for 2-5 years, 25% for 5-10 years, and 29.2% for > 10 years. Respondents viewed home PN as a "lifeline" and "nutritional safety net." QOL was defined as "enjoying life"; "being happy, satisfied, or content with life"; and "being able to do what you want to do, when you want to do it." Participants described their QOL as "good" to "wonderful." Lifestyle was affected by health, stamina, diarrhea, having an ostomy, and the amount of flexibility there was with the infusion schedule. There was a strong desire to achieve normalcy in life among all participants. Qualitative methodology provides new insights and richness of data regarding adults receiving home PN. The positive description of QOL in this study contrasts with the published nutrition literature. It is important for healthcare practitioners to understand and discuss the realities of home PN and lifestyle adaptation.


Simulating Energy Relaxation in Pump-Probe Vibrational Spectroscopy of Hydrogen-Bonded Liquids.
We introduce a nonequilibrium molecular dynamics simulation approach, based on the generalized Langevin equation, to study vibrational energy relaxation in pump-probe spectroscopy. A colored noise thermostat is used to selectively excite a set of vibrational modes, leaving the other modes nearly unperturbed, to mimic the effect of a monochromatic laser pump. Energy relaxation is probed by analyzing the evolution of the system after excitation in the microcanonical ensemble, thus providing direct information about the energy redistribution paths at the molecular level and their time scale. The method is applied to hydrogen-bonded molecular liquids, specifically deuterated methanol and water, providing a robust picture of energy relaxation at the molecular scale.


Facial asymmetry and the oral surgeon.
Facial asymmetry is often caused by deformities of the mandible or maxilla. Mandibular deformities are often pronounced, and various surgical procedures have been developed to treat such conditions. Deformities of the maxilla are similarly deviated from the normal. Although they are not always so noticeable as those of the mandible, they adversely affect function, esthetics and mental wellbeing. There are instances where both jaws are at fault and require treatment. More recently, osteotomies in the anterior of the maxilla or mandible have been performed with success. If the blood supply to the segment of bone and teeth is respected, a variety of procedures is possible in mandibular-maxillary surgery.


In vitro models to test orthopedic biomaterials in view of their clinical application in osteoporotic bone.
The development of in vitro cell cultures, in association with in vivo experimentation, greatly improved the characterization of biomaterials for orthopedic devices before their clinical use. In recent years an increasing interest has arisen in the use of both pathological osteoblast cultures and animal models to perform in vitro and in vivo tests on biomaterial behavior. A growing number of prostheses, in fact, are implanted in osteoporotic patients, due to the increasing age of the population. Moreover, the presence of osteoporosis may affect bone-biomaterial osteointegration in these patients. The present paper is a literature review and, after a short description of in vitro studies for characterization of osteoblasts derived from osteoporotic bone, the results of in vitro studies on biomaterial biocompatibility and osteointegration rate in the presence of osteoporotic bone derived osteoblast cultures are reported. Pathological cell culture models are able to demonstrate the different behavior of osteoblasts in response to biomaterials, when comparing normal and pathological conditions.


Mapping the genome of meta-generalized gradient approximation density functionals: the search for B97M-V.
A meta-generalized gradient approximation density functional paired with the VV10 nonlocal correlation functional is presented. The functional form is selected from more than 10(10) choices carved out of a functional space of almost 10(40) possibilities. Raw data come from training a vast number of candidate functional forms on a comprehensive training set of 1095 data points and testing the resulting fits on a comprehensive primary test set of 1153 data points. Functional forms are ranked based on their ability to reproduce the data in both the training and primary test sets with minimum empiricism, and filtered based on a set of physical constraints and an often-overlooked condition of satisfactory numerical precision with medium-sized integration grids. The resulting optimal functional form has 4 linear exchange parameters, 4 linear same-spin correlation parameters, and 4 linear opposite-spin correlation parameters, for a total of 12 fitted parameters. The final density functional, B97M-V, is further assessed on a secondary test set of 212 data points, applied to several large systems including the coronene dimer and water clusters, tested for the accurate prediction of intramolecular and intermolecular geometries, verified to have a readily attainable basis set limit, and checked for grid sensitivity. Compared to existing density functionals, B97M-V is remarkably accurate for non-bonded interactions and very satisfactory for thermochemical quantities such as atomization energies, but inherits the demonstrable limitations of existing local density functionals for barrier heights.


Growth Media Conditions Influence the Secretion Route and Release Levels of Engineered Extracellular Vesicles.
Extracellular vesicles (EVs) are nanosized cell-derived vesicles produced by all cells, which provide a route of intercellular communication by transmitting biological cargo. While EVs offer promise as therapeutic agents, the molecular mechanisms of EV biogenesis are not yet fully elucidated, in part due to the concurrence of numerous interwoven pathways which give rise to heterogenous EV populations in vitro. The equilibrium between the EV-producing pathways is heavily influenced by factors in the extracellular environment, in such a way that can be taken advantage of to boost production of engineered EVs. In this study, a quantifiable EV-engineering approach is used to investigate how different cell media conditions alter EV production. The presence of serum, exogenous EVs, and other signaling factors in cell media alters EV production at the physical, molecular, and transcriptional levels. Further, it is demonstrated that the ceramide-dependent EV biogenesis route is the major pathway to production of engineered EVs during optimized EV-production. These findings suggest a novel understanding to the mechanisms underlying EV production in cell culture which can be applied to develop advanced EV production methods.


Is Medicare contracting right for your managed care organization?
Americans older than 65 years represent the fastest-growing segment of the population. Today, the elderly comprise 12% of the population but account for one-third of health care spending. By the turn of the century, they will use half of these resources. Ironically, the elderly have been affected little by the managed care revolution; only 2.6 million have enrolled in HMOs that have contracts with the federal Medicare program to provide comprehensive health services to that population. In this article, the author explains the different types of Medicare managed care contracts, the advantages of these contracts, and how to succeed in this growing area of opportunity.


Molecular epidemiology of skin cancers: DNA repair and non-melanocytic skin cancer.
Exposure to sunlight has been clearly associated with non-melanocytic skin cancer, however individual susceptibility differs considerably. Ethnic origin and pigmentary characteristics are generally accepted as risk factors. Another important defense mechanism is the ability to repair DNA photoproducts. In the inherited disorder xeroderma pigmentosum the inability to repair such DNA damage, associated with a high incidence of skin cancers, suggests an important role for DNA repair capacity in the etiology of this cancer. The development of an in vitro repair assay based on human peripheral blood lymphocytes, has allowed the evaluation of DNA repair capacity as a risk factor in population based studies. This article reviews recent developments in this field.


System biology and bioinformatics pipeline to identify comorbidities risk association: Neurodegenerative disorder case study.
Alzheimer's disease (AD) is the commonest progressive neurodegenerative condition in humans, and is currently incurable. A wide spectrum of comorbidities, including other neurodegenerative diseases, are frequently associated with AD. How AD interacts with those comorbidities can be examined by analysing gene expression patterns in affected tissues using bioinformatics tools. We surveyed public data repositories for available gene expression data on tissue from AD subjects and from people affected by neurodegenerative diseases that are often found as comorbidities with AD. We then utilized large set of gene expression data, cell-related data and other public resources through an analytical process to identify functional disease links. This process incorporated gene set enrichment analysis and utilized semantic similarity to give proximity measures. We identified genes with abnormal expressions that were common to AD and its comorbidities, as well as shared gene ontology terms and molecular pathways. Our methodological pipeline was implemented in the R platform as an open-source package and available at the following link: https://github.com/unchowdhury/AD_comorbidity. The pipeline was thus able to identify factors and pathways that may constitute functional links between AD and these common comorbidities by which they affect each others development and progression. This pipeline can also be useful to identify key pathological factors and therapeutic targets for other diseases and disease interactions.


The effect of tobacco smoke and some of its constitutents on triglyceride secretion in the squirrel monkey.
The acute effects of tobacco smoke and some of its constituents on plasma free fatty acid levels and on triglyceride secretion were studied in anaesthetized squirrel monkeys given Triton WR-1339. All the treatments raised plasma free fatty acids in the order high tar smoke greater than medium tar vapour phase = air:CO greater than medium tar smoke. Plasma triglyceride secretion in animals inhaling high tar smoke did not differ from controls. There was a transient rise in triglyceride secretion in animals inhaling vapour phase but the largest increase (after a significant delay) was in monkeys breathing air:CO. Maximal concentrations of blood carboxyhaemoglobin did not differ between the experimental groups. It is suggested that, under these experimental conditions, there are present in the particulate phase of tobacco smoke factors which inhibit hepatic triglyceride secretion.


Risk factors for diabetic retinopathy in a rural Chinese population with type 2 diabetes: the Handan Eye Study.
To describe risk factors associated with diabetic retinopathy (DR) in a population-based sample of rural Chinese with type 2 diabetes. The Handan Eye Study is a population-based cross-sectional study surveyed 6830 Chinese people aged 30+ years from 13 randomly selected villages in 2006-2007. All participants underwent a standardized interview and extensive examinations including ophthalmologic and systemic conditions. Diabetic retinopathy was graded from fundus photographs according to the modified Early Treatment Diabetic Retinopathy Study classification system. Logistic regression models were used to assess risk factors associated with DR. Of 7577 eligible persons, 6830 (90.4%) participated, of which 5597 (81.9%) had fasting plasma glucose (FPG) data. There were 387 (6.9%) participants with diabetes, and 368 (95.1%) had gradable fundus photographs. The age-standardized prevalence of DR was 43.1%. In multivariable-adjusted logistic regression models for all diabetic participants, independent risk factors for DR were longer duration of diabetes (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.94, 4.85, per 5 years of duration), higher FPG levels (OR 1.17; 95% CI: 1.08, 1.27, per mmol/l increase) and higher systolic blood pressure (OR 1.22; 95% CI: 1.08, 1.37, per 10 mmHg increase). For newly diagnosed diabetes, the only significant factor of DR was higher FPG levels (OR 1.17; 95% CI: 1.05, 1.29, per mmol/l increase). In rural Chinese persons with diabetes, longer diabetes duration, hyperglycaemia and elevated blood pressure are risk factors for DR. These findings underscore the importance of controlling classic risk factors for DR in developing countries, where diabetes prevalence is increasing.


Surfactants modify the torsion properties of proteins: a single molecule study.
Surfactants are widely used in diagnostic assays to prevent protein aggregation and non-specific adsorption at surfaces. Here, a single molecule magnetic torque tweezers study is reported, aiming to quantify surfactant-induced changes in the torsional flexibility of a protein model system: protein-G-immunoglobulin G (IgG) attached to a glass surface. The influences of Sodium Dodecyl Sulphate (SDS) and Polysorbate 20 (Tween 20) on the protein pair have been investigated. The proteins were exposed to the surfactants at concentrations relative to the Critical Micelle Concentration (CMC), namely 0.1× CMC, 1× CMC and 10× CMC. Both surfactants increase the torsional flexibility of the protein-G-IgG complex. Tween 20 is most effective at increasing the torsional flexibility of the complex at the surface while SDS is more effective at dissociating the protein bonds. Tweezer data on the IgG-IgG protein pair show no influence of Tween 20 on the torsional flexibility. Furthermore, temperature dependent near-UV and far-UV Circular Dichroism (CD) data at 10× CMC show that Tween 20 does not significantly alter the secondary and tertiary structure of both protein-G and IgG while SDS does. These results provide evidence that both the mechanical properties of the protein structure and the interaction between proteins can alter the torsional rigidity measured with magnetic torque tweezers. This study shows for the first time the ability to use magnetic torque tweezers as a probe for surfactant-induced changes in proteins at a single molecule level.


Mechanism of idiosyncratic drug reactions: reactive metabolite formation, protein binding and the regulation of the immune system.
Drug-induced adverse reactions, especially type B reactions, represent a major clinical problem. They also impart a significant degree of uncertainty into drug development because they are often not detected until the drug has been released onto the market. Type B reactions are also termed idiosyncratic drug reactions by many investigators due to their unpredictable nature and our lack of understanding of the mechanisms involved. It is currently believed that the majority of these reactions are immune-mediated and are caused by immunogenic conjugates formed from the reaction of a reactive metabolite of a drug with cellular proteins. It has been shown that most drugs associated with idiosyncratic reactions form reactive metabolites to some degree. Covalent binding of reactive metabolites to cellular proteins has also been shown in many cases. However, studies to reveal the role of reactive metabolites and their protein-adducts in the mechanism of drug-induced idiosyncratic reactions are lacking. This review will focus on our current understanding and speculative views on how a reactive metabolite of a drug might ultimately lead to immune-mediated toxicity.


Opportunities for strengthening CTSA evaluation.
The purpose of the article is to describe the progress of the Clinical and Translational Science Award (CTSA) Program to address the evaluation-related recommendations made by the 2013 Institute of Medicine's review of the CTSA Program and guidelines published in CTS Journal the same year (Trochim et al., Clinical and Translational Science 2013; 6(4): 303-309). We utilize data from a 2018 national survey of evaluators administered to all 64 CTSA hubs and a content analysis of the role of evaluation in the CTSA Program Funding Opportunity Announcements to document progress. We present four new opportunities for further strengthening CTSA evaluation efforts: (1) continue to build the collaborative evaluation infrastructure at local and national levels; (2) make better use of existing data; (3) strengthen and augment the common metrics initiative; and (4) pursue internal and external opportunities to evaluate the CTSA program at the national level. This article will be of significant interest to the funders of the CTSA Program and the multiple stakeholders in the larger consortium and will promote dialog from the broad range of CTSA stakeholders about further strengthening the CTSA Program's evaluation.


Windows through the dusty disks surrounding the youngest low-mass protostellar objects.
The formation and evolution of young low-mass stars are characterized by important processes of mass loss and accretion occurring in the innermost regions of their placentary circumstellar disks. Because of the large obscuration of these disks at optical and infrared wavelengths in the early protostellar stages (class 0 sources), they were previously detected only at radio wavelengths using interferometric techniques. We have detected with the Infrared Space Observatory the mid-infrared (mid-IR) emission associated with the class 0 protostar VLA1 in the HH1-HH2 region located in the Orion nebula. The emission arises in three wavelength windows (at 5. 3, 6.6, and 7.5 micrometers) where the absorption due to ices and silicates has a local minimum that exposes the central part of the young protostellar system to mid-IR investigations. The mid-IR emission arises from a central source with a diameter of 4 astronomical units at an averaged temperature of approximately 700 K, deeply embedded in a dense region with a visual extinction of 80 to 100 magnitudes.


Retrospective study of mercury in raccoons (Procyon lotor) in south Florida.
Museum and recent collections of raccoon hair were used to assess whether temporal or spatial trends existed in MMHg distributions in south Florida. The hypothesis that MMHg in raccoon hair had remained the same since 1947 could not be rejected. Some sampling regions showed increases while others did not. However, large differences existed between sites, amounting to a factor of 20 for raccoons collected during 2000 and during the period prior to 1960 (museum samples). Raccoon feeding behavior and the production of MMHg most probably accounted for the spatial differences. Large differences in MMHg concentrations existed in different tissues ranging in order of hair, liver, kidney, muscle, heart, brain, and blood in their respective ratios to blood: 96:10:6:5:4:2.5:1. Liver Hg is 7% MMHg, while hair Hg is 99% MMHg. These associations appear largely regulated by metabolic processes. Speciation of Hg is very important for gaining an understanding of ecosystem and organism Hg dynamics. Further work is needed to establish whether Se plays a role in Hg sequestration and whether hair Hg is a good surrogate for estimating Hg concentrations in other tissues in south Florida raccoon populations.


Trends of Training Courses Conducted in the Human Resources Development Center of the National Institute for Quantum and Radiological Science and Technology After the Fukushima Dai-Ichi Nuclear Power Plant Accident.
Environmental contamination with radioactive materials caused by the Fukushima Dai-ichi Nuclear Power Plant (NPP) accident in 2011 raised a serious health concern among residents in Japan, and the demand for radiation experts who can handle the radiation-associated problems has increased. The Human Resources Development Center (HRDC) of the National Institute of for Quantum and Radiological Science and Technology in Japan has offered a variety of training programs covering a wide range of technologies associated with radiation since 1959. In this study, the time-course change in the number and age of the applicants for training programs regularly scheduled at HRDC were analyzed to characterize the demand after the NPP accident. The results suggested that the demand for the training of industrial radiation experts elevated sharply after the NPP accident followed by a prompt decrease, and that young people were likely stimulated to learn the basics of radiation. The demand for the training of medical radiation experts was kept high regardless of the NPP accident. The demand for the training of radiation emergency experts fluctuated apparently with three components: a terminating demand after the criticality accident that occurred in 1999, an urgent demand for handling of the NPP accident, and a sustained demand from local governments that undertook reinforcement of their nuclear disaster prevention program. The demand for the training of school students appeared to be increasing after the NPP accident. It could be foreseen that the demand for training programs targeting young people and medical radiation experts would be elevated in future.


Analysis of bronchoalveolar lavage fluid in patients with chronic hepatitis C before and after treatment with interferon alpha.
Previous studies have shown that patients with idiopathic pulmonary fibrosis (IPF) were more likely to be seropositive for hepatitis C virus (HCV) than normal controls, and that patients with chronic hepatitis C treated with interferon alpha (IFN-alpha) sometimes developed pulmonary fibrosis. The possibility that HCV infection and/or treatment with IFN-alpha are involved in the pathogenesis of pulmonary fibrosis or alveolitis was investigated. A prospective non-randomised study was performed in 13 healthy controls and in patients with chronic hepatitis C before (n = 13) and after (n = 10) treatment with IFN-alpha. Bronchoalveolar lavage (BAL) fluid cell counts, ratios and T cell subsets, and the concentrations of interleukin (IL)-1 beta, tumour necrosis factor(TNF)-alpha, and hepatocyte growth factor (HGF) were measured. Lymphocyte counts in the BAL fluid were significantly increased in both groups of patients (median (range) values: before treatment, 36.8 (1.5-226.0); after treatment, 16.2 (4.5-97.6)) compared with the normal controls (3.3 (0.5-32.3)). In the pretreatment group the activated T cell (HLA-Dr positive) count was also increased (51 (40-74)) compared with that in the normal controls (27 (4-52)), but after treatment it was decreased (40 (0-76)) compared with the pretreatment count. Administration of IFN-alpha did not affect these parameters. IL-1 beta, TNF-alpha, and HGF were not detected. These findings suggest that HCV infection is associated with increased counts of lymphocytes and neutrophils in BAL fluid and that treatment with IFN-alpha appears to alter lymphocyte surface markers.


Clinical course of chronic hepatitis C virus infection is not influenced by concurrent hepatitis G virus infection.
To determine the effects of hepatitis G virus (HGV) infection on chronic hepatitis C virus infection (HCV) and to evaluate HGV response to interferon, we investigated HGV RNA by polymerase chain reaction in 247 Japanese patients with chronic HCV infection (166 men and 81 women; 124 had chronic hepatitis and 26 cirrhosis, and 97 hepatocellular carcinoma). HGV RNA was detectable in 22 (8.9%) patients, among whom 21 were men: this male predominance was statistically significant (P < 0.01). There were no differences in age, aminotransferase level, stage of liver disease, HCV RNA level by competitive polymerase chain reaction, genotype, or interferon response to HCV RNA between patients with HCV infection alone or with HCV/HGV coinfection. Sustained elimination of HGV RNA was found in 28.6% of the 14 treated patients with HCV/HGV coinfection. In the 14 treated patients, sustained elimination of both viruses was seen in two, HCV alone was eliminated in two, and HGV alone was eliminated in two. Aminotransferase level improvement by interferon treatment was associated with clearance of HCV, but not of HGV. Thus, HGV infection had no apparent effects on HCV infection, and the sensitivity of HGV to interferon is comparable to but independent of HCV.


Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment.
We assesse the evolution and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (cTnT-HS) in transthyretin amyloid cardiomyopathy (ATTR-CA) before and after tafamidis treatment. 454 ATTR-CA patients without tafamidis (Cohort A) and 248 ATTR-CA with tafamidis (Cohort B) were enrolled. Event-free survival (EFS) events were death, heart transplant, or acute heart failure. In Cohort A, 27% of patients maintained NT-proBNP < 3000 ng/L and 14% cTnT-HS < 50 ng/L at 12 months relative to baseline levels. In Cohort B, the proportions were 49% and 29%, respectively. In Cohort A, among the 333 patients without an increased NT-proBNP > 50% relative to baseline EFS was extended compared to the 121 patients with an increased NT-proBNP > 50% (HR: 0.75 [0.57; 0.98]; p = 0.032). In Cohort A, baseline NT-proBNP > 3000 ng/L and cTnT-HS > 50 ng/L and a relative increase of NT-proBNP > 50% during follow-up were independent prognostic factors of EFS. The slopes of logs NT-proBNP and cTnT-HS increased with time before and stabilized after tafamidis. ATTR-CA patients with increasing NT-proBNP had an increased risk of EFS. Tafamidis stabilize NT-proBNP and cTnT-HS increasing, even if initial NT-proBNP levels were >3000 ng/L. Thus suggesting that all patients, irrespective of baseline NT-proBNP levels, may benefit from tafamidis.


Traumatic axonal injury: the prognostic value of lesion load in corpus callosum, brain stem, and thalamus in different magnetic resonance imaging sequences.
The aim of this study was to explore the prognostic value of visible traumatic axonal injury (TAI) loads in different MRI sequences from the early phase after adjusting for established prognostic factors. Likewise, we sought to explore the prognostic role of early apparent diffusion coefficient (ADC) values in normal-appearing corpus callosum. In this prospective study, 128 patients (mean age, 33.9 years; range, 11-69) with moderate (n = 64) and severe traumatic brain injury (TBI) were examined with MRI at a median of 8 days (range, 0-28) postinjury. TAI lesions in fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2*-weighted gradient echo (T2*GRE) sequences were counted and FLAIR lesion volumes estimated. In patients and 47 healthy controls, mean ADC values were computed in 10 regions of interests in the normal-appearing corpus callosum. Outcome measure was the Glasgow Outcome Scale-Extended (GOS-E) at 12 months. In patients with severe TBI, number of DWI lesions and volume of FLAIR lesions in the corpus callosum, brain stem, and thalamus predicted outcome in analyses with adjustment for age, Glasgow Coma Scale score, and pupillary dilation (odds ratio, 1.3-6.9; p = <0.001-0.017). The addition of Rotterdam CT score and DWI lesions in the corpus callosum yielded the highest R2 (0.24), compared to all other MRI variables, including brain stem lesions. For patients with moderate TBI only the number of cortical contusions (p = 0.089) and Rotterdam CT score (p = 0.065) tended to predict outcome. Numbers of T2*GRE lesions did not affect outcome. Mean ADC values in the normal-appearing corpus callosum did not differ from controls. In conclusion, the loads of visible TAI lesions in the corpus callosum, brain stem, and thalamus in DWI and FLAIR were independent prognostic factors in patients with severe TBI. DWI lesions in the corpus callosum were the most important predictive MRI variable. Interestingly, number of cortical contusions in MRI and CT findings seemed more important for patients with moderate TBI.


The impact of endovascular repair on management and outcome of ruptured thoracic aortic aneurysms.
Thoracic endovascular aortic repair (TEVAR) has become an alternative to open repair for the treatment of ruptured thoracic aortic aneurysms (rTAAs). The aim of this study was to assess national trends in the use of TEVAR for the treatment of rTAA and to determine its impact on perioperative outcomes. Patients admitted with an rTAA between 1993 and 2012 were identified from the National Inpatient Sample. Patients were grouped in accordance with their treatment: TEVAR, open repair, or nonoperative treatment. The primary outcomes were treatment trends over time and in-hospital death. Secondary outcomes included perioperative complications and length of stay. Trend analyses were performed using the Cochran-Armitage test for trend, and adjusted mortality risks were established using multivariable logistic regression analysis. A total of 12,399 patients were included, with 1622 (13%) undergoing TEVAR, 2808 (23%) undergoing open repair, and 7969 (64%) not undergoing surgical treatment. TEVAR has been increasingly used from 2% of total admissions in 2003-2004 to 43% in 2011-2012 (P < .001). Concurrently, there was a decline in the proportion of patients undergoing open repair (29% to 12%; P < .001) and nonoperative treatment (69% to 45%; P < .001). The proportion of patients undergoing surgical repair has increased for all age groups since 1993-1994 (P < .001 for all) but was most pronounced among those aged 80 years with a 7.5-fold increase. After TEVAR was introduced, procedural mortality decreased from 36% in 2003-2004 to 27% in 2011-2012 (P < .001); mortality among those undergoing nonoperative treatment remained stable between 63% and 60% (P = .167). Overall mortality after rTAA admission decreased from 55% to 42% (P < .001). Since 2005, mortality for open repair was 33% and 22% for TEVAR (P < .001). In adjusted analysis, open repair was associated with a twofold higher mortality than TEVAR (odds ratio, 2.0; 95% confidence interval, 1.7-2.5). TEVAR has replaced open repair as primary surgical treatment for rTAA. The introduction of endovascular treatment appears to have broadened the eligibility of patients for surgical treatment, particularly among the elderly. Mortality after rTAA admission has declined since the introduction of TEVAR, which is the result of improved operative mortality as well as the increased proportion of patients undergoing surgical repair.


The role of biliary calcium in gallstone pathogenesis.
Calcium is an element that is extremely important in the pathogenesis of gallstones. It is present in bile in large quantities since components of bile bind the calcium avidly. Precipitated calcium salts with the calcium sensitive ions, bilirubinate, carbonate and phosphate are major components of pigment gallstones and are present in high concentrations in the centers and rims of cholesterol gallstones. An understanding of the solubility of calcium in bile is thus essential if one is to understand the process that leads to gallstone formation. In addition, calcium also has a very important role in the function of the gallbladder epithelial cell. This manuscript discusses what is known about biliary calcium, the factors that regulate total and free calcium concentrations in bile, the solubility of calcium in both normal and lithogenic bile, and the role calcium plays in epithelial cell function during gallstone formation.


Iliac crest orientation and geometry in able-bodied and non-treated adolescent idiopathic scoliosis girls with moderate and severe spinal deformity.
To identify pelvic rotation and/or distortion in able-bodied and untreated AIS girls with moderate and severe scoliosis and verify association of pelvic morphological changes with Cobb angle increase. The 3D coordinates of nine anatomic bony landmarks were identified to estimate pelvic orientation using a Flock of Birds system. The distances between the first sacral vertebral body (S1) and each of the eight iliac spine landmarks in all three planes were calculated to identify pelvic distortion. Analysis of variance was used to assess pelvic orientation and determine pelvic distortion. Pearson coefficients of correlation were used to identify any relationships between Cobb angle and pelvic morphological parameters. Pelvic orientation was similar in able-bodied and scoliotic girls regardless of the severity of the spinal deformity. Significant differences were observed in pelvic morphology between AIS with severe untreated scoliosis and those with a moderate scoliosis for the right anterosuperior iliac spines (ASIS), the tip of the superior iliac crest (TSIC) and the widest tip of the iliac crest (WTIC) widths from S1. Statistically significant correlations were observed between the Cobb angles and the iliac crest distances measured from S1. Differences in iliac spine geometries occurred in the transverse plane correlating to Cobb angles which suggest altered bone growth in AIS girls. Such findings could indicate right thoracic spinal deformity as a result of pelvic torsion.


N-(2,3-Dichloro-phen-yl)-2-nitro-benzene-sulfonamide.
In the title compound, C12H8Cl2N2O4S, the N-C bond in the C-SO2-NH-C segment has gauche torsions with respect to the S=O bonds. Further, the N-H bond is syn to the ortho-nitro group in the sulfonyl benzene ring and also syn to both the ortho- and meta-Cl atoms in the aniline ring. The mol-ecule is twisted at the S-N bond with a torsion angle of 61.15 (18)°. The dihedral angle between the planes of the benzene rings is 68.00 (6)°. The amide H atom exhibits an intra-molecular bifurcated N-H⋯(O,O) hydrogen bond. In the crystal, pairs of N-H⋯O(S) hydrogen bonds link the mol-ecules into inversion dimers with R2(2)(8) motifs.


Prevalence of cardiovascular disease in Gabon: a population study.
Data supporting epidemiological transition from a predominant burden of infectious diseases to one of chronic diseases in Africa result mostly from hospital surveys. To estimate the cardiovascular disease (CVD) burden in Gabon. The study was conducted in Ntoum (8765 inhabitants). All subjects aged greater or equal to 40 years were invited to participate. Participants were interviewed about CVD history and risk factors; they responded to questionnaires on claudication and angina and had a clinical examination, including lower limb pulse palpation and bilateral brachial pressure measurement. Subjects were considered to have CVD in case of history of CVD (coronary artery, cerebrovascular and peripheral arterial diseases), a positive questionnaire or an abnormal finding during clinical examination. The study included 736 subjects (313 men; 423 women). Systolic hypertension was highly prevalent (up to 47.7% and 53.7% in men and women aged 50 to 60 years, respectively). Of the 382 patients with hypertension, 74 (19.4%) were treated and only 22 (5.8%) were considered to have controlled hypertension. Overall, CVD was identified in 98 (13.3%) cases. Overall and newly diagnosed CVD prevalence rates were 14.7% and 11.5% for men and 14.9% and 8.9% for women, respectively. The presence of CVD was associated with hypertension (hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.21-6.16; P<0.0001). Hypertension was predictive of stroke (HR 4.57, 95% CI 1.26-16.50; P<0.05), peripheral artery disease (HR 2.03, 95% CI 1.03-4.00; P<0.05) and subclavian artery stenosis (HR 5.79, 95% CI 2.21-15.2; P<0.05). Our findings provide strong evidence of ongoing epidemiological transition in Gabon, where CVD prevalence rates increase mainly with hypertension, affecting about one in six individuals aged over 40 years.


Anti-CD79 antibody induces B cell anergy that protects against autoimmunity.
B cells play a major role in the pathogenesis of many autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type I diabetes mellitus, as indicated by the efficacy of B cell-targeted therapies in these diseases. Therapeutic effects of the most commonly used B cell-targeted therapy, anti-CD20 mAb, are contingent upon long-term depletion of peripheral B cells. In this article, we describe an alternative approach involving the targeting of CD79, the transducer subunit of the B cell AgR. Unlike anti-CD20 mAbs, the protective effects of CD79-targeted mAbs do not require cell depletion; rather, they act by inducing an anergic-like state. Thus, we describe a novel B cell-targeted approach predicated on the induction of B cell anergy.


The development of depressogenic self-schemas: Associations with children's regional grey matter volume in ventrolateral prefrontal cortex.
Cognitive theories of depression contend that biased cognitive information processing plays a causal role in the development of depression. Extensive research shows that deeper processing of negative and/or shallower processing of positive self-descriptors (i.e., negative and positive self-schemas) predicts current and future depression in adults and children. However, the neural correlates of the development of self-referent encoding are poorly understood. We examined children's self-referential processing using the self-referent encoding task (SRET) collected from 74 children at ages 6, 9, and 12; around age 10, these children also contributed structural magnetic resonance imaging data. From age 6 to age 12, both positive and negative self-referential processing showed mean-level growth, with positive self-schemas increasing relatively faster than negative ones. Further, voxel-based morphometry showed that slower growth in positive self-schemas was associated with lower regional gray matter volume (GMV) in ventrolateral prefrontal cortex (vlPFC). Our results suggest that smaller regional GMV within vlPFC, a critical region for regulatory control in affective processing and emotion development, may have implications for the development of depressogenic self-referential processing in mid-to-late childhood.


[Obesity and hypertension: from physiopathology to treatment].
Obesity constitutes a problem of major concern in our industrialized countries. Overweight is frequently associated with hypertension (50% of hypertensive subjects are obese and the prevalence of hypertension in obese patients is twice that of the normal population). Both pathologies are major cardiovascular risk factors. This review aims at a better understanding of the relationship between hypertension and overweight and at giving to the clinicians simple and consistent guidelines to treat these two medical entities.


[Serum lactoferrin levels in children with viral hepatitis A].
Serum lactoferrin levels were studied in 79 healthy children and 80 children with viral hepatitis A in the Republic of Tyva. No statistically significant age- and gender-related differences were found in the healthy children. In viral hepatitis A, the level of the protein was shown to decrease with disease severity and to return to the normal values after 6 months.


Exposure to GSM 900 MHz electromagnetic fields affects cerebral cytochrome c oxidase activity.
The world-wide and rapidly growing use of mobile phones has raised serious concerns about the biological and health-related effects of radio frequency (RF) radiation, particularly concerns about the effects of RFs upon the nervous system. The goal of this study was conducted to measure cytochrome oxidase (CO) levels using histochemical methods in order to evaluate regional brain metabolic activity in rat brain after exposure to a GSM 900 MHz signal for 45 min/day at a brain-averaged specific absorption rate (SAR) of 1.5 W/Kg or for 15 min/day at a SAR of 6 W/Kg over seven days. Compared to the sham and control cage groups, rats exposed to a GSM signal at 6 W/Kg showed decreased CO activity in some areas of the prefrontal and frontal cortex (infralimbic cortex, prelimbic cortex, primary motor cortex, secondary motor cortex, anterior cingulate cortex areas 1 and 2 (Cg1 and Cg2)), the septum (dorsal and ventral parts of the lateral septal nucleus), the hippocampus (dorsal field CA1, CA2 and CA3 of the hippocampus and dental gyrus) and the posterior cortex (retrosplenial agranular cortex, primary and secondary visual cortex, perirhinal cortex and lateral entorhinal cortex). However, the exposure to GSM at 1.5 W/Kg did not affect brain activity. Our results indicate that 6 W/Kg GSM 900 MHz microwaves may affect brain metabolism and neuronal activity in rats.


Spontaneous carotid artery dissection.
Symptomatic spontaneous internal carotid artery dissection is responsible for up to 20% of strokes in patients under age 45 years. A carotid artery dissection occurs when arterial walls separate and create a false lumen. Risk factors include neck trauma, recent infection, family history, smoking, hypertension, oral contraceptives, migraine headaches, and connective tissue disease. Dissections can produce local pain, facial paralysis, and pupillary defects. Treatment includes anticoagulation and, in the event of pharmaceutical failure or recurrence, surgery.


Paranoid phenomena and pathological narcissism.
Paranoid phenomena can be seen to arise from pathological narcissism. As a result of certain kinds of trauma to the ego-ideal and/or losses of important self-object relationships, the self becomes dislodged from internal agencies and representations. Narcissistic cathexis of the self to these internal psychic structures loosens and hope, aspiration, affection and will become markedly diminished. Meaningful goals and choices become impossible to adopt and make. The paranoid patient is internally at "loose ends"; he is lost. Tragically, being gripped by the paranoid condition and its manifest delusional system is the only kind of security that the paranoid patient knows. No wonder it is so hard to give up. The vulnerability to paranoid phenomena may be seen to be a result of past experiences of subversion of "selfhood." In significant ways, the patient vulnerable to paranoid phenomena has not been adequately attended nor adequately "left alone." The self can be seen as arising out of crucial mother-infant exchanges that are paralleled by interactions between developing internal psychic structures. Out of these "reflections," the self is born. The narcisstic cathexis of self to the ego, superego and ego-ideal is the result of self-expression. If full self-ownership has not been possible then self-expression is vulnerable. Given these understandings of the relationship between paranoid phenomena and pathological narcissism, treatment will focus on reducing the threats to selfhood, refinding the self, and reestablishing ties to internal sources of affection, initiative and aspiration.


Efficacy and safety of herbal medicines for idiopathic Parkinson's disease: a systematic review.
The objective of this study is to assess the efficacy and safety of herbal medicines (HMs), as a monotherapy or adjunct therapy, compared to placebo or conventional approaches in the treatment of idiopathic Parkinson's disease (PD). We conducted a systematic review of randomized controlled trials from both conventional and alternative medicine sources. Outcome measures were overall improvement, quality of life, reduction of levodopa dose, and adverse events. Nine studies were included, each testing a different HM. Six of the trials had limited internal validity due to major flaws in design, including the lack of proper randomization; insufficient blinding; unclear inclusive criteria in terms of diagnostic criteria, baseline staging, and duration of disease; lack of proper sample size calculation; and insufficient data analysis. Imbalances in gender and ethnicity among the patients in the included trials were observed. No major adverse events emerged, and no specific pattern was detected from the trials describing such data. In addition to major methodological defects, heterogeneity in (1) HM tested, (2) control treatment, and (3) outcome measure hindered in-depth data analysis and synthesis. Current evidence is insufficient to evaluate the efficacy and safety of various HMs. Further studies with improved trial design and reporting, with assessment on cost-effectiveness, quality of life, and qualitative data are warranted.


Clonal evolution and hierarchy in myeloid malignancies.
Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the intricacies of clonal evolution in myeloid malignancies and its implications for the development of new diagnostic and therapeutic approaches.


Tongue suture placement after cleft palate repair.
Postoperative airway obstruction is a complication of cleft palate repair. A technique to control the airway is to place a suture through the tongue at the conclusion of the palate repair, but it is not uniformly adopted by surgeons. Although it has been frequently performed, the use and effectiveness of the tongue suture have not been studied. Our purpose was to determine the usefulness of tongue suture placement. We surveyed health care providers as to their frequency of use and the value of the tongue suture in postoperative airway management of the cleft palate patient. The survey was sent via e-mail to 2080 members of the American Cleft Palate-Craniofacial Association, with a total of 396 responders. Surgeons were nearly equally split on placing a tongue suture, with 41.1% responders reporting that they use a tongue suture all of the time and 41.1% of responders reporting that they never used a tongue suture. Some criterion used for placement was the complexity of the case, syndromic patients, and overseas cleft missions. Many cleft palate repairs are done annually without using tongue sutures, but it does not seem to affect the outcomes among surgeons, thus confounding the question of effectiveness. At this time, tongue suture placement after cleft palate repair is variable and subjective. Further studies need to be performed to assess outcomes after placing a tongue suture.


Traits of criticality in membrane potential fluctuations of pyramidal neurons in the CA1 region of rat hippocampus.
Evidence that neural circuits are operating near criticality has been provided at various levels of brain organisation with a presumed role in maximising information processing and multiscale activity association. Criticality has been linked to excitation at both the single-cell and network levels, as action potential generation marks an obvious phase transition from a resting to an excitable state. Using in vitro intracellular recordings, we examine irregular, small amplitude membrane potential fluctuations from CA1 pyramidal neurons of Wistar male rats. We show that these fluctuations, confounded with noise, carry information relevant to the neuronal state. The underlying dynamics exhibit intermittent characteristics shown to describe the temporal fluctuations of the order parameter of a macroscopic system at its critical point even in the absence of firing. An externally applied stimulus serves as the control parameter, driving the system in and out of its critical state. Based on our experimental observations we calculate the equivalent of the isothermal critical exponent δh finding a value which depends on the applied stimulus. For each neuron there is a stimulus amplitude for which the critical behaviour becomes most pronounced. The corresponding mean value of δh in the considered ensemble of neurons is δh ≈ 1.89, close to theoretical predictions for critical networks. Finally, we show that the firing rate of a neuron decreases exponentially with δh .


Effects of Supplementing Microbially-fermented Spent Mushroom Substrates on Growth Performance and Carcass Characteristics of Hanwoo Steers (a Field Study).
This study evaluated the effect of dietary supplementation of microbially-fermented spent mushroom substrates (MFSMS) on weight gain, carcass characteristics, and economic efficiency of Hanwoo steers. Highly cellulolytic bacteria (Enterobacter spp. and Bacillus spp.) isolated from spent mushroom substrates (SMS) stacks were inoculated (1% v/v) into the SMS, which was anaerobically fermented and fed to the steers for 12.6 months during the growing and fattening periods. Growing Hanwoo steers were assigned to the control group without supplementation of Microbially-fermented SMS (MFSMS), to a treatment group with 50% of MFSMS (1/2 of the ad libitum group), and to a treatment group with ad libitum access to SMS (the ad libitum group). All the groups were fed the formulated feed and rice straw. The voluntary intake (DM basis) of MFSMS was 1.6 kg/d during the growing period and 1.4 kg/d during the fattening period. The voluntary rice straw intake decreased by 6 to 11%, but the total voluntary DMI increased by 7 to 15% with MFSMS fed. The increased DMI with MFSMS supplementation resulted in a tendency of increased (p = 0.055) live weight gain by 8 to 12% compared with the control group. At slaughtering, the supplementation of MFSMS increased (p<0.05) the ribeye area by an average of 10 cm(2). In conclusion, feeding MFSMS improved growth performance and carcass traits of Hanwoo steers and could successfully replace a part of conventional roughage such as rice straw commonly used in Asian countries.


Developing measures of food and nutrition security within an Australian context.
To develop a measure of food and nutrition security for use among an Australian population that measures all pillars of food security and to establish its content validity. The study consisted of two phases. Phase 1 involved focus groups with experts working in the area of food security. Data were assessed using content analysis and results informed the development of a draft tool. Phase 2 consisted of a series of three online surveys using the Delphi technique. Findings from each survey were used to establish content validity and progressively modify the tool until consensus was reached for all items. Australia. Phase 1 focus groups involved twenty-five experts working in the field of food security, who were attending the Dietitians Association of Australia National Conference, 2013. Phase 2 included twenty-five experts working in food security, who were recruited via email. Findings from Phase 1 supported the need for an Australian-specific tool and highlighted the failure of current tools to measure across all pillars of food security. Participants encouraged the inclusion of items to measure barriers to food acquisition and the previous single item to enable comparisons with previous data. Phase 2 findings informed the selection and modification of items for inclusion in the final tool. The results led to the development of a draft tool to measure food and nutrition security, and supported its content validity. Further research is needed to validate the tool among the Australian population and to establish inter- and intra-rater reliability.


Vaginal douching among women of reproductive age in the United States: 1988.
Vaginal douching has been associated with pelvic inflammatory disease (PID) in several epidemiologic studies. To determine the extent to which douching is practiced and to describe the population subgroups in which it is most prevalent, we analyzed data from the 1988 National Survey of Family Growth, which is based on a nationally representative sample of 8450 United States women between the ages of 15 and 44 years. Thirty-seven percent of the sample reported douching; 18% douched at least once a week. The variable most strongly and consistently associated with douching was race: two thirds of Black women, but only one third of White women, reported douching. The practice was least frequent among 15- to 19-year-olds (31%) and most frequent among 20- to 24-year-olds (41%). Douching was more common among women who lived in poverty (50%) than among those who did not (28%). Seventy percent of Black women living in poverty reported douching. Women with less than a high school education were almost four times more likely to report douching as those with 16 or more years of schooling (56% vs 16%). Women with only 1 partner and those with 10 or more partners were less likely to douche than others. Sixteen percent of women who reported douching, compared with 10% of those who did not, also reported a history of PID. Douching may be a modifiable risk factor for PID, it should be a high priority for future etiologic research.


Immunohistological comparison of platelet factor 4 (PF4), fibronectin (Fn) and factor VIII related antigen (VIIIR:Ag) in human platelet granules.
Immunofluorescence microscopy was used to study the localization of platelet factor 4 (PF4), fibronectin (Fn) and factor VIII related antigen in washed normal platelets and those from patients with severe von Willebrand's disease (vWd). Platelets were prepared by an improved multi-unit modification of the Sayk chamber. This facilitated the preparation of samples with minimum disruption of platelets and readily permitted the demonstration of intact platelet granules by the immunological techniques used. The antigens were demonstrated by treating the same preparations sequentially with appropriate heterologous antisera and species specific fluorescein or rhodamine conjugated antisera. Comparison of the different antigens in identical platelets indicated that Fn and VIIIR:Ag were localized to the same granules as PF4 and the results were thus consistent with their presence in alpha granules. Fn and PF4, but not VIIIR:Ag, were present in platelet granules of patients with severe vWd. The antigens were always detected in the same granules, and major sub-populations of differently stained granules were not observed. The methods were applied to investigate normal platelets aggregated with collagen. Fn and VIIIR:Ag were detected in platelet granules after aggregation although the granules themselves were possibly differently distributed in these samples compared with the non-aggregated platelets. The localization of PF4 could not be reliably assessed in aggregated platelets by these methods. The techniques may be useful in localizing platelet antigens and studying release during aggregation.


Reformulation of pizza crust in restaurants may increase whole-grain intake among children.
Whole-grain intake among children is well below recommendations. The purpose of the present study was to test the acceptability and liking of pizza made with whole-grain crust compared with refined-grain crust among children in restaurant and school settings. Plate waste data were collected via observation from child restaurant patrons consuming pizza made with either whole-grain or refined-grain crust. Waste was estimated by trained observers over eight months (August 2012-March 2013). Percentage waste was calculated and compared by crust type. A taste test was conducted with school children who tasted pizza made with whole-grain crust alongside pizza made with refined-grain crust and rated their liking of each product. Liking ratings were compared by crust type. Five Green Mill restaurant (a Midwest US chain) locations and one elementary school in the Minneapolis/St. Paul metropolitan area, Minnesota, USA. Child restaurant patrons (n 394) and school children (n 120, grades 3-5). Children consumed as much of the pizza made with whole-grain crust (42·1 %) as the pizza made with refined-grain crust (44·6 %; P=0·55), based on an average serving size of 350-400 g. Liking ratings for both types of pizza were high (>4·5 of 5) and did not differ by crust type (P=0·47). These positive consumption and liking outcomes indicate that whole-grain pizza crust is well accepted among children in a restaurant setting. The impact on whole-grain intake could be substantial if large, national restaurant chains served pizza made with whole-grain crust.


Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.
Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets. We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates. Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births. Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies. Bill & Melinda Gates Foundation.


Differential PilA pilus assembly by a hospital-acquired and a community-derived Enterococcus faecium isolate.
Pili are hair-like structures protruding from the cell envelope of bacterial cells. Here, we describe the conditional and differential display of PilA-type pili, and PilE and PilF proteins, encoded from pilin gene cluster 1 at the surface of a hospital-acquired Enterococcus faecium bloodstream isolate (E1165) and a community-derived stool isolate (E1039), at two different temperatures. Both strains have virtually identical pilA gene clusters, as determined by sequencing. Western blotting and transmission immunoelectron microscopy revealed that PilA and PilF assembled into high-molecular-mass pilus-like structures at 37 degrees C in the E1165 strain, whereas PilE was not produced at either of the temperatures used; at 21 degrees C, PilA and PilF were cell-wall-anchored proteins. In contrast, in strain E1039, PilA, PilE and PilF pilin proteins were found to be displayed as cell-wall-anchored proteins at 37 degrees C only, and they were not associated with pilus-like structures. The discrepancy in pilus assembly between E1039 and E1165 cannot be explained by differences in expression of the genes encoding the predicted sortases in the pilA gene cluster, as these had similar expression levels in both strains at 21 and 37 degrees C. Double-labelling electron microscopy revealed that PilA formed the pilus backbone in E1165, and PilF the minor subunit which was distributed along the PilA pilus shaft and positioned at the tip; however, it was deposited as a cell-wall-anchored protein in a pilA isogenic mutant. The differential deposition of surface proteins from pilin gene cluster 1 and differences in pilus assembly in the two strains suggest a complex post-transcriptional regulatory mechanism of pilus biogenesis in E. faecium.


Sp1 Controls the Basal Level of Interleukin-34 Transcription.
Interleukin-34 (IL-34) is a cytokine that plays important roles at steady state and in diseases. The induced or inhibited expression of IL-34 by stimuli has been deeply investigated. However, the regulation of IL-34 basal expression is largely unknown. The aim of this study is to investigate whether IL-34 expression is regulated by a general transcription factor Specificity Protein 1 (Sp1) at transcription level. By using bioinformatic software, four putative Sp1-binding sites overlapping GC boxes were found in the core promoter region of IL-34. Alignment of the core promoter sequences of mammalian IL-34 showed GC box-C (-62/-57) and D (-11/-6) were conserved in some mammals. Luciferase assay results showed that only deletion of GC box-C (-62/-57) significantly reduced luciferase activities of IL-34 core promoter in SH-SY5Y cells. By using electrophoretic mobility shift assay (EMSA), it was found that Sp1 specifically interacted with GC box-C sequence CCCGCC (-62/-57) in the core promoter of IL-34. By using chromatin immunoprecipitation (ChIP), it was discovered that Sp1 bound to the core promoter of IL-34 in living cells. In addition, silencing of Sp1 expression by its specific siRNA reduced IL-34 mRNA and protein levels significantly in SH-SY5Y cells. Likewise, IL-34 expression was inhibited in a dose-dependent manner by a Sp1 inhibitor Plicamycin. Furthermore, silencing of Sp1 also downregulated mRNA and protein expression of IL-34 in GES-1 and 293T cell lines, suggesting that IL-34 transcription regulated by Sp1 was not cell-type specific. Taken together, these results indicate that Sp1 controls the basal level of IL-34 transcription.


[An asylum seeker with an abnormal chest X-ray].
A 29-year-old pregnant woman from Syria was screened for tuberculosis upon arrival in the Netherlands. The chest X-ray showed a smooth sharply demarcated mass in her left upper lobe. A low-dose CT showed that the mass was lobulated and surrounded by a hyperlucent pulmonary segment. To protect the foetus from further exposure to radiation, an MRI was performed, which confirmed bronchial atresia with a mucocele of the distal bronchus.


Spectrophotometric quantitative analysis of the main hemoglobin derivatives.
A spectrophotometric multiwavelength method for the simultaneous determination of the main hemoglobin derivatives including oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, and methemoglobin has been developed. The choice of analytical wavelengths was made by the methods of information factors and linear programming. The software for the quantitative analysis was developed considering the least square method, linear programming, algebraic background correction, and combined methods including linear programming and algebraic background correction.


Co-optimization of Heavy-Duty Fuels and Engines: Cost Benefit Analysis and Implications.
Heavy-duty vehicles require expensive aftertreatment systems for control of emissions such as particulate matter (PM) and nitrogen oxides (NOx) to comply with stringent emission standards. Reduced engine-out emissions could potentially alleviate the emission control burden, and thus bring about reductions in the cost associated with aftertreatment systems, which translates into savings in vehicle ownership. This study evaluates potential reductions in manufacturing and operating costs of redesigned emission aftertreatment systems of line-haul heavy-duty diesel vehicles (HDDVs) with reduced engine-out emissions brought about by co-optimized fuel and engine technologies. Three emissions reduction cases representing conservative, medium, and optimistic engine-out emission reduction benefits are analyzed, compared to a reference case: the total costs of aftertreatment systems (TCA) of the three cases are reduced to $11,400(1.63 ¢/km), $9,100 (1.30 ¢/km), and $8,800 (1.26 ¢/km), respectively, compared to $12,000 (1.71 ¢/km) for the reference case. The largest potential reductions result from reduced diesel exhaust fluid (DEF) usage due to lower NOx emissions. Downsizing aftertreatment devices is not likely, because the sizes of devices are dependent on not only engine-out emissions, but also other factors such as engine displacement. Sensitivity analysis indicates that the price and usage of DEF have the largest impacts on TCA reduction.


Ofloxacin otic solution for treatment of otitis externa in children and adults.
To compare the safety and efficacy of ofloxacin otic solution with those of Cortisporin otic solutions (neomycin sulfate, polymyxin B sulfate, and hydrocortisone) in otitis externa in adults and children. Two randomized, evaluator-blind, multicenter trials, 1 each in children and adults. Twenty-three primary care and referral ambulatory care sites per trial. A total of 314 adults (12 years and older) and 287 children (younger than 12 years). Of the total, data for 247 adults and 227 children were considered clinically evaluable (CE), and those for 98 children and 98 adults were microbiologically evaluable (ME). Ofloxacin (adults, 0.5 mL; children, 0.25 mL) twice daily or Cortisporin (adults, 0.2 mL; children, 0.15 mL) 4 times daily for 10 days. The CE subjects were cured if all signs and symptoms resolved at posttherapy (days 11-13) and test-of-cure (days 17-20) visits. The ME subjects had microbiological and clinical successes if they were cured and had microbiological eradication or presumed eradication. Cure was observed in 82% and 97% of CE adults and children treated with ofloxacin and 84% and 95% of CE adults and children treated with Cortisporin, respectively. The most common pathogens at the pretherapy visit were Pseudomonas aeruginosa, Staphylococcus aureus, and enteric bacilli. There were no statistically significant differences in clinical or microbiological and clinical cure or in the rates of adverse events between treatment groups. Ofloxacin given twice daily is as safe and effective as Cortisporin given 4 times daily for otitis externa. The bacteriological findings and treatment responses do not differ between adults and children.


Local adaptation and pronounced genetic differentiation in an extremophile fish, Poecilia mexicana, inhabiting a Mexican cave with toxic hydrogen sulphide.
We investigated genetic differentiation and migration patterns in a small livebearing fish, Poecilia mexicana, inhabiting a sulfidic Mexican limestone cave (Cueva del Azufre). We examined fish from three different cave chambers, the sulfidic surface creek draining the cave (El Azufre) and a nearby surface creek without the toxic hydrogen sulphide (Arroyo Cristal). Using microsatellite analysis of 10 unlinked loci, we found pronounced genetic differentiation among the three major habitats: Arroyo Cristal, El Azufre and the cave. Genetic differentiation was also found within the cave between different pools. An estimation of first-generation migrants suggests that (i) migration is unidirectional, out of the cave, and (ii) migration among different cave chambers occurs to some extent. We investigated if the pattern of genetic differentiation is also reflected in a morphological trait, eye size. Relatively large eyes were found in surface habitats, small eyes in the anterior cave chambers, and the smallest eyes were detected in the innermost cave chamber (XIII). This pattern shows some congruence with a previously proposed morphocline in eye size. However, our data do not support the proposed mechanism for this morphocline, namely that it would be maintained by migration from both directions into the middle cave chambers. This would have led to an increased variance in eye size in the middle cave chambers, which we did not find. Restricted gene flow between the cave and the surface can be explained by local adaptations to extreme environmental conditions, namely H2S and absence of light. Within the cave system, habitat properties are patchy, and genetic differentiation between cave chambers despite migration could indicate local adaptation at an even smaller scale.


Effect of long-term whole body vibration training on visceral adipose tissue: a preliminary report.
To determine the effect of whole body vibration (WBV), combined with caloric restriction, on weight, body composition and metabolic risk factors in overweight and obese adults. A randomized, controlled study with a 6-month intervention period and a 6-month 'no intervention' follow-up. 61 of the 79 participants completed the study. Data were collected at baseline and at 3, 6 and 12 months in the control group (CONTROL), the diet only group (DIET), the diet plus fitness group (FITNESS) and the diet plus WBV group (VIBRATION). Weight decreased significantly in all three intervention groups. Only FITNESS and VIBRATION managed to maintain a weight loss of 5% or more in the long term. Visceral adipose tissue (VAT) changed most in VIBRATION: -47.8 +/- 41.2 and -47.7 +/- 45.7 cm2 after 6 and 12 months respectively compared to CONTROL (-3.6 +/- 20.5 or +26.3 +/- 30.6 cm(2)), DIET (-24.3 +/- 29.8 or -7.5 +/- 28.3 cm(2)) and FITNESS (-17.6 +/- 36.6 or -1.6 +/- 33.3 cm(2)) (p < 0.001). Combining aerobic exercise or WBV training with caloric restriction can help to achieve a sustained long-term weight loss of 5-10%. These preliminary data show that WBV training may have the potential to reduce VAT more than aerobic exercise in obese adults, possibly making it a meaningful addition to future weight loss programs.


Thermoregulation of two sympatric species of horned lizards in the Chihuahuan Desert and their local extinction risk.
Thermoregulatory studies of ectothermic organisms are an important tool for ecological physiology, evolutionary ecology and behavior, and recently have become central for evaluating and predicting global climate change impacts. Here, we present a novel combination of field, laboratory, and modeling approaches to examine body temperature regulation, habitat thermal quality, and hours of thermal restriction on the activity of two sympatric, aridlands horned lizards (Phrynosoma cornutum and Phrynosoma modestum) at three contrasting Chihuahuan Desert sites in Mexico. Using these physiological data, we estimate local extinction risk under predicted climate change within their current geographical distribution. We followed the Hertz et al. (1993, Am. Nat., 142, 796-818) protocol for evaluating thermoregulation and the Sinervo et al. (2010, Science, 328, 894-899) eco-physiological model of extinction under climatic warming. Thermoregulatory indices suggest that both species thermoregulate effectively despite living in habitats of low thermal quality, although high environmental temperatures restrict the activity period of both species. Based on our measurements, if air temperature rises as predicted by climate models, the extinction model projects that P. cornutum will become locally extinct at 6% of sites by 2050 and 18% by 2080 and P. modestum will become extinct at 32% of sites by 2050 and 60% by 2080. The method we apply, using widely available or readily acquired thermal data, along with the modeling, appeared to identify several unique ecological traits that seemingly exacerbate climate sensitivity of P. modestum.


Space-for-time is not necessarily a substitution when monitoring the distribution of pelagic fishes in the San Francisco Bay-Delta.
Occupancy models are often used to analyze long-term monitoring data to better understand how and why species redistribute across dynamic landscapes while accounting for incomplete capture. However, this approach requires replicate detection/non-detection data at a sample unit and many long-term monitoring programs lack temporal replicate surveys. In such cases, it has been suggested that surveying subunits within a larger sample unit may be an efficient substitution (i.e., space-for-time substitution). Still, the efficacy of fitting occupancy models using a space-for-time substitution has not been fully explored and is likely context dependent. Herein, we fit occupancy models to Delta Smelt (Hypomesus transpacificus) and Longfin Smelt (Spirinchus thaleichthys) catch data collected by two different monitoring programs that use the same sampling gear in the San Francisco Bay-Delta, USA. We demonstrate how our inferences concerning the distribution of these species changes when using a space-for-time substitution. Specifically, we found the probability that a sample unit was occupied was much greater when using a space-for-time substitution, presumably due to the change in the spatial scale of our inferences. Furthermore, we observed that as the spatial scale of our inferences increased, our ability to detect environmental effects on system dynamics was obscured, which we suspect is related to the tradeoffs associated with spatial grain and extent. Overall, our findings highlight the importance of considering how the unique characteristics of monitoring programs influences inferences, which has broad implications for how to appropriately leverage existing long-term monitoring data to understand the distribution of species.


N-acetyl-beta-hexosaminidase: role in the degradation of glycosaminoglycans.
Extracts of cultured normal human skin fibroblasts released radioactivity from a (14)C-labeled heptasaccharide prepared by addition of [(14)C]N-acetylgalactosamine to the nonreducing terminus of a hexasaccharide derived from chondroitin 4-sulfate whereas fibroblast extracts from patients with Tay-Sachs and Sandhoff-Jatzkewitz diseases did not. The results suggest that N-acetyl-beta-hexosaminidase A is responsible for degradation of the oligosaccharide substrate.


The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: X. Results of ear examination.
In the five pocket mice flown on Apollo XVII, no evidence was found that the inner ear had been damaged, though poor fixation precluded detailed study. On the other hand, the middle ear cavity was involved in all the mice, hemorrhage having occurrred in response to excursions in pressure within the canister that housed the mice during their flight. The same occurred in flight control mice which had been subjected to pressure excursions of much the same magnitude. A greater degree of exudation into air cells and greater leukotaxis were noted in the flight animals than in the control animals. There was no increase in leukocyte population along the paths of the 23 cosmic ray particles registered in the subscalp dosimeters that traversed the middle ear cavities of the flight mice. The increased exudation and the greater response by leukocytes in the flight mice may have been causally related to the lesions found in their olfactory mucosa but there were no data in support of this possibility.


Li dopant induces moisture sensitive phase degradation of an all-inorganic CsPbI2Br perovskite.
All-inorganic halide perovskites without volatile components have great potential for long term thermal stability. However, the phase stability of all-inorganic perovskites is sensitive to moisture and has been seldom studied. In this work, the phase stability of α-CsPbI2Br was studied in different relative humidity conditions. The moisture resistance of α-CsPbI2Br can be significantly enhanced by using a polymer or organic molecule capping layer including Spiro-MeOTAD. Although an all-inorganic CsPbI2Br perovskite based device using the typical Li salt doped Spiro-MeOTAD layer could offer an efficiency up to 12.6%, it exhibited even worse moisture resistance than a bare perovskite film under the same ambient conditions. This unusual phenomenon is ascribed to the hygroscopic properties of Li-TFSI inducing moisture sensitive phase degradation. Therefore, it is desirable to decrease the amount of, or avoid the Li salt, as a dopant for stable all-inorganic perovskite solar cells with balanced stability and high performance.


Do women consult more than men? A review of gender and consultation for back pain and headache.
Because women consult their general practitioners more frequently on average than men, it is commonly assumed that they consult more for all symptoms and conditions. This assumption is reinforced by qualitative studies reporting a widespread reluctance to consult by men. However, few studies directly compare consultation in men and women experiencing similar symptoms or conditions. A systematic review of the evidence on gender and consultation for two common symptoms, back pain and headache. Extensive electronic searches identified 15 papers reporting the relationship between gender and help-seeking for back pain and 11 papers for headache. Two independent reviewers assessed articles for inclusion and extracted data from eligible studies. Few studies compared consultation patterns for these symptoms among men and women known to have experienced the symptom. The quality of the studies was variable. Overall, evidence for greater consultation by women with back pain was weak and inconsistent. Among those with back pain, the odds ratios for women seeking help, compared with men, ranged from 0.6 (95% confidence intervals 0.3, 1.2, adjusted only for age) to 2.17 (95% confidence intervals 1.35, 3.57, unadjusted), although none of the reported odds ratio, below 1.00 was statistically significant. The evidence for women being more likely to consult for headache was a little stronger. Five studies showed a statistically elevated odds ratio, and none suggested that men with headache symptoms were more likely to consult than women with headache symptoms. Limitations to the studies are discussed. Given the strength of assumptions that women consult more readily for common symptoms, the evidence for greater consultation amongst women for two common symptoms, headache and back pain, was surprisingly weak and inconsistent, especially with respect to back pain.


Application of bootstrap techniques to physical mapping.
Ordering genetic markers or clones from a genomic library into a physical map is a central problem in genetics. In the presence of errors, there is no efficient algorithm known that solves this problem. Based on a standard heuristic algorithm for it, we present a method to construct a confidence neighborhood for a computed solution. We compute a confidence value for putative local solutions derived from bootstrap replicates of the original solution. In the reliable parts, the confidence neighborhood and the computed solution tend to coincide. In regions that are ill-defined by the data, the neighborhood contains additional reasonable alternatives. This offers the possibility of designing further experiments for the badly defined regions to improve the quality of the physical map. We analyze our approach by a simulation study and by application to a dataset of the genome of the bacterium Xylella fastidiosa.


Sunitinib inhibits RNase L by destabilizing its active dimer conformation.
The pseudokinase (PK) RNase L is a functional ribonuclease and plays important roles in human innate immunity. The ribonuclease activity of RNase L can be regulated by the kinase inhibitor sunitinib. The combined use of oncolytic virus and sunitinib has been shown to exert synergistic effects in anticancer therapy. In this study, we aimed to uncover the mechanism of action through which sunitinib inhibits RNase L. We solved the crystal structures of RNase L in complex with sunitinib and its analogs toceranib and SU11652. Our results showed that sunitinib bound to the ATP-binding pocket of RNase L. Unexpectedly, the αA helix linking the ankyrin repeat-domain and the PK domain affected the binding mode of sunitinib and resulted in an unusual flipped orientation relative to other structures in PDB. Molecular dynamics simulations and dynamic light scattering results support that the binding of sunitinib in the PK domain destabilized the dimer conformation of RNase L and allosterically inhibited its ribonuclease activity. Our study suggested that dimer destabilization could be an effective strategy for the discovery of RNase L inhibitors and that targeting the ATP-binding pocket in the PK domain of RNase L was an efficient approach for modulating its ribonuclease activity.


Selective paired ion contrast analysis: a novel algorithm for analyzing postprocessed LC-MS metabolomics data possessing high experimental noise.
One of the consequences in analyzing biological data from noisy sources, such as human subjects, is the sheer variability of experimentally irrelevant factors that cannot be controlled for. This holds true especially in metabolomics, the global study of small molecules in a particular system. While metabolomics can offer deep quantitative insight into the metabolome via easy-to-acquire biofluid samples such as urine and blood, the aforementioned confounding factors can easily overwhelm attempts to extract relevant information. This can mar potentially crucial applications such as biomarker discovery. As such, a new algorithm, called Selective Paired Ion Contrast (SPICA), has been developed with the intent of extracting potentially biologically relevant information from the noisiest of metabolomic data sets. The basic idea of SPICA is built upon redefining the fundamental unit of statistical analysis. Whereas the vast majority of algorithms analyze metabolomics data on a single-ion basis, SPICA relies on analyzing ion-pairs. A standard metabolomic data set is reinterpreted by exhaustively considering all possible ion-pair combinations. Statistical comparisons between sample groups are made only by analyzing the differences in these pairs, which may be crucial in situations where no single metabolite can be used for normalization. With SPICA, human urine data sets from patients undergoing total body irradiation (TBI) and from a colorectal cancer (CRC) relapse study were analyzed in a statistically rigorous manner not possible with conventional methods. In the TBI study, 3530 statistically significant ion-pairs were identified, from which numerous putative radiation specific metabolite-pair biomarkers that mapped to potentially perturbed metabolic pathways were elucidated. In the CRC study, SPICA identified 6461 statistically significant ion-pairs, several of which putatively mapped to folic acid biosynthesis, a key pathway in colorectal cancer. Utilizing support vector machines (SVMs), SPICA was also able to unequivocally outperform binary classifiers built from classical single-ion feature based SVMs.


Medication adherence interventions for heart failure patients: A meta-analysis.
Adherence to medications is an essential part of heart failure self-care. Poor medication adherence leads to increased rates of exacerbation causing hospitalizations and increased morbidity and mortality. This meta-analysis aimed to quantify the effect of interventions to improve adherence to heart failure medications on adherence outcomes. Comprehensive search methods identified studies testing interventions designed to improve medication adherence among patients with heart failure. Data from eligible studies were independently coded by two coders and analyzed using random-effects meta-analysis methods. Moderator analyses to explain heterogeneity among the studies were conducted using meta-regression and ANOVA for moderators with sufficient numbers of comparisons. Searching yielded 6665 potential study reports. From these studies, we identified 29 eligible treatment versus control comparisons of heart failure medication adherence interventions (total n=4285). The mean effect size (d-index) for two-group comparisons was 0.29 (SE=0.09, p=0.004). Moderator analyses found effect sizes were larger as samples were older. Medication adherence effect sizes were larger for studies conducted in Europe or Asia versus North America, and for interventions focused on changing only medication adherence. Smaller effect sizes were seen for interventions with components directed at health care providers, and those including social support as an intervention component. While the medication adherence effect size across all studies was significant, the effect was modest. Approaches to improving heart failure medication adherence may be most effective when focused on medication adherence alone, and when seeking to change behavior of patients, rather than health care provider behavior.


Sleep bruxism and associated physiological events in children with obstructive sleep apnea: a polysomnographic study.
The aim of this study was to evaluate the physiological events associated with sleep bruxism (SB; presence of mandibular movement activity) and control window (4 minutes prior to SB event, where no mandibular movement activity was detected) in polysomnography study (PSG) in children with mild sleep apnea. PSG exams data from 4 to 9 years old children diagnosed with mild sleep apnea were analyzed by two trained examiners. The mandibular movement activity (bruxism event; SB) were classified into phasic and tonic. The control window was selected 4 minutes prior to the SB event. All physiological events were recorded in both bruxism and control windows, including sleep phase (N1, N2, N3 and REM), arousal, leg movements, tachycardia, bradycardia, oxygen desaturation and number of obstructive and central sleep apnea events. The moment in which those phenomena occurred when associated with SB was also analyzed (before/after). Data was analyzed using a 95% CI (α=5%). A total of 661 mandibular movements were analyzed and classified as tonic (n=372) or phasic (n=289). The mean apnea-hypopnea index (AHI) was 1.99 (SD=1.27). The frequency of leg movements, microarousal and tachycardia were increased in BS events when compared to the control window (p<0.05). There was an increase in bradycardia frequency in the control window when compared to BS (in both tonic and phasic events). The frequency of obstructive and central apnea and central apnea during SB were lower when compared to the other physiological phenomena. There is a difference in the physiological parameters evaluated in children with mild sleep apnea when comparing the two windows (SB and control). Sleep bruxism is associated with other physiological phenomena such as leg movements, tachycardia and microarousal. The use of a control window (where no mandibular activity was detected) was representative since it did not show activation of the sympathetic nervous system.