Patient Protection and Affordable Care Act; Market Stabilization. Final rule.
This rule finalizes changes that will help stabilize the individual and small group markets and affirm the traditional role of State regulators. This final rule amends standards relating to special enrollment periods, guaranteed availability, and the timing of the annual open enrollment period in the individual market for the 2018 plan year; standards related to network adequacy and essential community providers for qualified health plans; and the rules around actuarial value requirements.


Molecular motors for DNA translocation in prokaryotes.
DNA transport is an essential life process. From chromosome separation during cell division or sporulation, to DNA virus ejection or encapsidation, to horizontal gene transfer, it is ubiquitous in all living organisms. Directed DNA translocation is often energetically unfavorable and requires an active process that uses energy, namely the action of molecular motors. In this review we present recent advances in the understanding of three molecular motors involved in DNA transport in prokaryotes, paying special attention to recent studies using single-molecule techniques. We first discuss DNA transport during cell division, then packaging of DNA in phage capsids, and then DNA import during bacterial transformation.


Colony-Stimulating Factor 1 Receptor (CSF1R) Activates AKT/mTOR Signaling and Promotes T-Cell Lymphoma Viability.
Peripheral T-cell lymphomas are clinically aggressive and usually fatal, as few complete or durable remissions are achieved with currently available therapies. Recent evidence supports a critical role for lymphoma-associated macrophages during T-cell lymphoma progression, but the specific signals involved in the cross-talk between malignant T cells and their microenvironment are poorly understood. Colony-stimulator factor 1 receptor (CSF1R, CD115) is required for the homeostatic survival of tissue-resident macrophages. Interestingly, its aberrant expression has been reported in a subset of tumors. In this article, we evaluated its expression and oncogenic role in T-cell lymphomas. Loss-of-function studies, including pharmacologic inhibition with a clinically available tyrosine kinase inhibitor, pexidartinib, were performed in multiple in vitro and in vivo models. In addition, proteomic and genomic screenings were performed to discover signaling pathways that are activated downstream of CSF1R signaling. We observed that CSF1R is aberrantly expressed in many T-cell lymphomas, including a significant number of peripheral and cutaneous T-cell lymphomas. Colony-stimulating factor 1 (CSF1), in an autocrine or paracrine-dependent manner, leads to CSF1R autophosphorylation and activation in malignant T cells. Furthermore, CSF1R signaling was associated with significant changes in gene expression and in the phosphoproteome, implicating PI3K/AKT/mTOR in CSF1R-mediated T-cell lymphoma growth. We also demonstrated that inhibition of CSF1R in vivo and in vitro models is associated with decreased T-cell lymphoma growth. Collectively, these findings implicate CSF1R in T-cell lymphomagenesis and have significant therapeutic implications.


Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study.
The incidence of intrahepatic cholangiocarcinoma has been recently increasing in the United States. In this case-control study, we used the Surveillance, Epidemiology, and End Results-Medicare database to evaluate the prevalence of known risk factors for intrahepatic cholangiocarcinoma and explore other potential risk factors. We identified all patients with intrahepatic cholangiocarcinoma aged 65 years and older diagnosed between 1993 and 1999 in the population-based Surveillance, Epidemiology, and End Results registries (14% of the US population). Controls were randomly chosen from individuals without any cancer diagnosis in the underlying population of the Surveillance, Epidemiology, and End Results regions. We obtained information on risk factors from Medicare claims (parts A and B) for all cases and controls with at least 2 years of continuous Medicare enrollment. Unadjusted and adjusted odds ratios were calculated in logistic regression analysis. A total of 625 cases and 90,834 controls satisfied the inclusion and exclusion criteria. Cases were older than controls (78.7 vs. 76.5 years; P=.02) and were more likely to be male (48.3% vs. 36.8%; P <.0001). The racial composition was similar between cases and controls. Several risk factors were significantly more prevalent among cases. These included nonspecific cirrhosis (adjusted odds ratio, 27.2; P <.0001), alcoholic liver disease (adjusted odds ratio, 7.4; P <.0001), hepatitis C virus infection (adjusted odds ratio, 6.1; P <.0001), human immunodeficiency virus infection (adjusted odds ratio, 5.9; P=.003), diabetes (adjusted odds ratio, 2.0; P <.0001), and inflammatory bowel diseases (adjusted odds ratio, 2.3; P=.002). This population-based study shows that in addition to previously well described risk factors, several others could be associated with intrahepatic cholangiocarcinoma. These include hepatitis C virus, human immunodeficiency virus, liver cirrhosis, and diabetes.


Identification of a nonstructural DNA-binding protein (DBP) as an antigen with diagnostic potential for human adenovirus.
Human adenoviruses (HAdVs) have been implicated as important agents in a wide range of human illnesses. To date, 58 distinct HAdV serotypes have been identified and can be grouped into six species. For the immunological diagnosis of adenoviruses, the hexon protein, a structural protein, has been used. The potential of other HAdV proteins has not been fully addressed. In this study, a nonstructural antigenic protein, the DNA binding protein (DBP) of human adenovirus 5 and 35 (Ad5, Ad35) - was identified using immunoproteomic technology. The expression of Ad5 and Ad35 DBP in insect cells could be detected by rhesus monkey serum antibodies and healthy adult human serum positive for Ad5 and Ad35. Recombinant DBPs elicited high titer antibodies in mice. Their conserved domain displayed immunological cross-reactions with heterologous DBP antibodies in Western blot assays. DBP-IgM ELISA showed higher sensitivity adenovirus IgM detection than the commercial Adenovirus IgM Human ELISA Kit. A Western blot method developed based on Ad5 DBP was highly consistent with (χ(2) = 44.9, P<0.01) the Western blot assay for the hexon protein in the detection of IgG, but proved even more sensitive. The HAdV nonstructural protein DBP is an antigenic protein that could serve as an alternative common antigen for adenovirus diagnosis.


COVID-19 in South Korea.
A novel coronavirus (severe acute respiratory syndrome-CoV-2) that initially originated from Wuhan, China, in December 2019 has already caused a pandemic. While this novel coronavirus disease (COVID-19) frequently induces mild diseases, it has also generated severe diseases among certain populations, including older-aged individuals with underlying diseases, such as cardiovascular disease and diabetes. As of 31 March 2020, a total of 9786 confirmed cases with COVID-19 have been reported in South Korea. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. We are trying to reduce the reproduction number of COVID-19 to less than one and eventually succeed in controlling this outbreak using methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. This report aimed to describe the current situation of COVID-19 in South Korea and our response to this outbreak.


Maternal heavy alcohol use and toddler behavior problems: a fixed effects regression analysis.
Using data from the longitudinal Norwegian Mother and Child Cohort Study, the aims of the current study were to examine associations between postnatal maternal heavy alcohol use and toddler behavior problems, taking both observed and unobserved confounding factors into account by employing fixed effects regression models. Postnatal maternal heavy alcohol use (defined as drinking alcohol 4 or more times a week, or drinking 7 units or more per alcohol use episode) and toddler internalizing and externalizing behavior problems were assessed when the toddlers were aged 18 and 36 months. Maternal psychopathology, civil status and negative life events last year were included as time-variant covariates. Maternal heavy alcohol use was associated with toddler internalizing and externalizing behavior problems (p < 0.001) in the population when examined with generalized estimating equation models. The associations disappeared when observed and unobserved sources of confounding were taken into account in the fixed effects models [(p = 0.909 for externalizing behaviors (b = 0.002, SE = 0.021), p = 0.928 for internalizing behaviors (b = 0.002, SE = 0.023)], with an even further reduction of the estimates with the inclusion of time-variant confounders. No causal effect was found between postnatal maternal heavy alcohol use and toddler behavior problems. Increased levels of behavior problems among toddlers of heavy drinking mothers should therefore be attributed to other adverse characteristics associated with these mothers, toddlers and families. This should be taken into account when interventions aimed at at-risk families identified by maternal heavy alcohol use are planned and conducted.


Improving estimates of children living with HIV from the Spectrum AIDS Impact Model.
Estimated numbers of children living with HIV determine programmatic and treatment needs. We explain the changes made to the UNAIDS estimates between 2015 and 2016, and describe the challenges around these estimates. Estimates of children newly infected, living with HIV, and dying of AIDS are developed by country teams using Spectrum software. Spectrum files are available for 160 countries, which represent 98% of the global population. In 2016, the methods were updated to reflect the latest evidence on mother-to-child HIV transmission and improved assumptions on the age children initiate antiretroviral therapy. We report updated results using the 2016 model and validate these estimates against mother-to-child transmission rates and HIV prevalence from population-based surveys for the survey year. The revised 2016 model estimates 27% fewer children living with HIV in 2014 than the 2015 model, primarily due to changes in the probability of mother-to-child transmission among women with incident HIV during pregnancy. The revised estimates were consistent with population-based surveys of HIV transmission and HIV prevalence among children aged 5-9 years, but were lower than surveys among children aged 10-14 years. The revised 2016 model is an improvement on previous models. Paediatric HIV models will continue to evolve as further improvements are made to the assumptions. Commodities forecasting and programme planning rely on these estimates, and increasing accuracy will be critical to enable effective scale-up and optimal use of resources. Efforts are needed to improve empirical measures of HIV prevalence, incidence, and mortality among children.


Cell friction.
Cells sense and respond to their environment. Mechanotransduction is the process by which mechanical forces, stress, and strains are converted into biochemical signals that control cell behavior. In recent decades it has been shown that appropriate mechanical signals are essential to tissue health, but the role of friction and direct contact shearing across cell surfaces has been essentially unexplored. This, despite the obvious existence of numerous biological tissues whose express function depends on sliding contacts. In our studies on frictional interactions of corneal cells we find that the friction coefficients are on the order of mu = 0.03-0.06 for in vitro and in vivo experiments. Additionally, we observe cell death after single cycles of sliding at contact pressures estimated to be approximately 12 kPa. These experimental results suggest that frictional contact forces produce mechanical stresses and strains that are in the cellular mechanosensing ranges.


Emerging mechanisms of antimicrobial resistance in bacteria and fungi: advances in the era of genomics.
Bacteria and fungi continue to develop new ways to adapt and survive the lethal or biostatic effects of antimicrobials through myriad mechanisms. Novel antibiotic resistance genes such as lsa(C), erm(44), VCC-1, mcr-1, mcr-2, mcr-3, mcr-4, bla KLUC-3 and bla KLUC-4 were discovered through comparative genomics and further functional studies. As well, mutations in genes that hitherto were unknown to confer resistance to antimicrobials, such as trm, PP2C, rpsJ, HSC82, FKS2 and Rv2887, were shown by genomics and transcomplementation assays to mediate antimicrobial resistance in Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Saccharomyces cerevisae, Candida glabrata and Mycobacterium tuberculosis, respectively. Thus, genomics, transcriptomics and metagenomics, coupled with functional studies are the future of antimicrobial resistance research and novel drug discovery or design.


Beliefs and practices of First Nation women about weight gain during pregnancy and lactation: implications for women's health.
Many Cree women in northern Quebec experience excessive weight gain during pregnancy and retain the weight between pregnancies. This contributes to poor maternal-fetal outcomes and increased rates of obesity-related health problems. The purpose of this qualitative descriptive study was to explore (a) Cree women's perceptions of weight gain in pregnancy and weight loss following pregnancy, (b) the barriers that women face in maintaining a healthy body weight, and (c) the sociocultural context of health. Semi-structured interviews were conducted with 30 women who had given birth within the preceding 12 months. Many women spoke of the negative health consequences of excessive weight gain, yet they found it difficult to lose weight due to individual constraints such as lack of time, cultural beliefs about diet while breastfeeding, and community constraints including lack of child care and lack of community programs for mothers.


Rigid ring fixation of the mitral annulus does not impair left ventricular systolic function in the normal canine heart.
Previous studies suggest that rigid fixation of the mitral annulus with an annuloplasty ring may impair left ventricular (LV) systolic performance. We used load-insensitive indexes of global and regional LV contractile mechanics to test the hypothesis that rigid fixation of the mitral annulus alters LV systolic function. Global and regional LV systolic mechanics were compared in 10 dogs during two mitral annular conditions: rigidly fixed and freely mobile. Carpentier-Edwards annuloplasty rings (20-24 mm) were inserted using a special buttressing suture technique that permitted alternate cinching of the ring down onto the annulus and subsequent removal away from the annulus. Aortic flow was measured with an electromagnetic flow probe, LV pressure by a micromanometer, and LV wall thickness and three near-orthogonal LV endocardial chamber dimensions using piezoelectric crystals during four sequential ring conditions: 1) down, 2) away, 3) down, and 4) away. The following parameters were analyzed during each ring condition to assess global LV systolic function: end-systolic chamber elastance (end-systolic pressure-volume relation), fiber elastance (end-systolic stress-volume relation), preload recruitable stroke work, and myocardial stress-strain relation. Additionally, regional LV systolic performance was assessed using the end-systolic pressure-diameter relation and a regional analog of preload recruitable stroke work. No significant differences in any of these measurements of LV systolic mechanics were observed between the two mitral annular conditions. Rigid fixation of the mitral annulus alters neither global nor regional LV systolic function in anesthetized, open-chest dogs with normal ventricles.


Studies on mixed populations of human intestinal bacteria grown in single-stage and multistage continuous culture systems.
Mixed intestinal bacteria were grown for 336 h in two identical single-stage chemostats at low growth rates in a carbohydrate-limited medium. Complex bacterial populations were maintained and anaerobes always outnumbered aerobes. The predominant organisms belonged to the genera Bacteroides, Bifidobacterium, Lactobacillus, Clostridium, Eubacterium, Propionbacterium, Peptococcus, and Peptostreptococcus. Bacteroides species predominated in both fermentors, particularly B. ovatus and B. thetaiotaomicron. A high degree of reproducibility of bacteriological and fermentation product data was obtained in these experiments. When gut contents were inoculated into a five-stage continuous culture system (retention time of 79 or 38 h) containing soya bran, the medium flow rate had little quantitative effect on the formation of acidic fermentation products; however, more oxidized fermentation acids were produced at the higher retention time. Diverse bacterial populations were maintained in every vessel at each flow rate. Bacteroides fragilis group organisms, especially B. ovatus, were numerically the most important. The viability of bacteria decreased through the system, especially at a retention time of 79 h, when the bacteria were growing under severely nutrient-limited conditions.


External morphology and ultra-structure of eggs and first instar of Prepona laertes laertes (Hübner, [1811]), with notes on host plant use and taxonomy.
The external morphology and the tegument ultra-structure of Prepona laertes laertes (Hübner, [1811]) (Lepidoptera: Nymphalidae: Charaxinae) eggs and first instar larvae feeding on Inga spp. (Fabaceae) in a forest fragment in Joinville, Santa Catarina, Brazil, are described. Descriptions of the morphology with illustrations are presented, based upon observations through scanning electron microscopy and stereoscopic and optic microscopes attached to a camera lucida. Descriptions and illustrations of the head capsule, chaetotaxy, tegument, and setae are presented. The taxonomy, morphological characters, and host plant use of Prepona laertes immature stages are discussed.


IPCRG Consensus statement: tackling the smoking epidemic - practical guidance for primary care.
Tobacco use will become the world's foremost cause of premature death and disability within 20 years unless current trends are reversed. Many opportunities to reduce this epidemic are missed in primary care. This Discussion paper from the International Primary Care Respiratory Group (IPCRG) - which reflects the IPCRG's understanding of primary care practitioners' needs - summarises a new approach based on strong evidence for effective interventions. All primary care health professionals can increase smoking cessation rates among their patients, even when time and resources are limited. Medical and non-medical staff can support patients who choose to quit by providing information, referral to telephone counselling services, and behavioural counselling using motivational interviewing techniques, where resources permit. Drug therapy to manage nicotine dependence can significantly improve patients' chances of quitting successfully, and is recommended for people who smoke 10 or more cigarettes per day. All interventions should be tailored to the individual's circumstances and attitudes.


Persistent CD-19 depletion by rituximab is cost-effective in maintaining remission in calcineurin-inhibitor dependent podocytopathy.
A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent or steroid resistant, requiring long-term calcineurin inhibitors (CNI) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI-dependent patients. This was a prospective observational study conducted from July 2014 to February 2018. Steroid-dependent nephrotic syndrome or steroid-resistant nephrotic syndrome (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77 ± 7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD-19 levels were monitored monthly and patients having CD-19 levels >5/μL and/or > 1% received additional low-dose (100 mg) of rituximab. A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5% and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well-tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively. CD-19 targeted rituximab is a safe and cost-effective agent in remission maintenance in adults with CNI dependent. Over three-fourths of the patients with CNI-dependent podocytopathy maintain clinical remission with CD-19 targeted rituximab therapy.


Classification of current anticancer immunotherapies.
During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.


Alterations of carbohydrate and lipid intermediary metabolism during inhibition of glucose-6-phosphatase in rats.
S 4048 (1-[2-(4-Chloro-phenyl)-cyclopropylmethoxy]-3, 4-dihydroxy-5-(3-imidazo[4, 5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexanecarboxylic acid), a derivative of chlorogenic acid, specifically inhibits the glucose-6-phosphate translocating component T1 of the glucose-6-phosphatase system. Its pharmacological effect was studied on carbohydrate and lipid parameters in rats. In starved and fed rats, S 4048 caused a dose-dependent reduction of blood glucose levels with a corresponding increase in hepatic and renal glycogen and glucose-6-phosphate. The major quantitative route of carbon flux in the liver during S 4048-induced inhibition of the glucose-6-phosphatase activity seemed to be glycogenesis. Plasma free fatty acids were increased secondarily due to the S 4048-induced hypoglycemia. Hepatic triglycerides were increased possibly due to increased re-esterification of the readily available free fatty acids. Glucose-6-phosphate translocase inhibitors may be useful for experimentally studying aspects of type 1 glycogen storage disease in laboratory animals as well as for the therapeutic modulation of inappropriately high rates of hepatic glucose production in type 2 diabetes.


Inflammatory response and IgE sensitization at early age.
Microbial exposure may induce low-grade inflammation at an early age and decrease the risk of allergic diseases, as suggested by the hygiene hypothesis. We examined the associations between low-grade inflammation and the development of allergic sensitization, atopic dermatitis (AD), and asthma at the age of 4.5 yr. We studied 636 children participating in the PASTURE study in Finland, Germany, Austria, France, and Switzerland. Data of environmental factors, doctor-diagnosed AD, and asthma were collected by questionnaire. The serum high-sensitivity C-reactive protein (CRP) values were measured at the age of 1 yr, and serum-specific IgE concentrations (sIgE) at the age of one and 4.5 yr. Analyses were made by logistic regression analysis. The risk of allergic sensitization at the age of 4.5 yr was decreased in children who had increased CRP levels at the age of 1 yr (level in the highest vs. lowest quartile: aOR 0.48, 95% CI 0.24-0.95; p = 0.014). The risk of AD and asthma was not significantly related to CRP. The findings confirm that elevated levels of CRP at early age showed association with decreased allergic sensitization later in life. Our results suggest that poor inflammatory response could predispose for IgE sensitization.


High-gain holographic screens.
A high-gain screen can be made as a sandwich of a hologram and a retroreflective screen material. When a hologram is used in front of the screen instead of the screen material alone, the position of high-brightness viewing can be moved to any desired angle rather than being directed back along the projection beam.


Home is where their wheels are: experiences of women wheelchair users.
This paper examines the experiences of mothers who are wheelchair users in their roles of homemaking and parenting. A qualitative study using in-depth, focused interviews was conducted with a purposeful sample of 11 women with various physical disabilities. Three major themes were uncovered in the data: (a) lived space restricting personal autonomy, (b) advocacy strategies to secure appropriate housing, and (c) my wheelchair, my liberator, my sense of comfort. Findings from this study showed that women did not have the freedom or economic resources to seek out new living arrangements or make modifications to existing environments. Lack of space, stairs, difficult-to-reach spaces, poor transportation, and limited community access were barriers that women experienced. The study also points to the importance of recognizing that the women used many strategies to regain control over aspects of their environment to enable greater autonomy and participation for themselves. Sensitivity to the meaning of home and the relationship between the body and the environmental features that surround it may be a significant contribution of the clinician as he or she seeks to assist women wheelchair users.


Temperature during early development has long-term effects on microRNA expression in Atlantic cod.
Environmental temperature has serious implications in life cycle of aquatic ectotherms. Understanding the molecular mechanisms of temperature acclimation and adaptation of marine organisms is of the uttermost importance for ecology, fisheries, and aquaculture, as it allows modeling the effects of global warming on population dynamics. Regulatory molecules are major modulators of acclimation and adaptation; among them, microRNAs (miRNAs) are versatile and substantial contributors to regulatory networks of development and adaptive plasticity. However, their role in thermal plasticity is poorly known. We have asked whether the temperature and its shift during the early ontogeny (embryonic and larval development) affect the miRNA repertoire of Atlantic cod (Gadus morhua), and if thermal experience has long-term consequences in the miRNA profile. We characterized miRNA during different developmental stages and in juvenile tissues using next generation sequencing. We identified 389 putative miRNA precursor loci, 120 novel precursor miRNAs, and 281 mature miRNAs. Some miRNAs showed stage- or tissue-enriched expression and miRNAs, such as the miR-17 ~ 92 cluster, myomiRs (miR-206), neuromiRs (miR-9, miR-124), miR-130b, and miR-430 showed differential expression in different temperature regimes. Long-term effect of embryonic incubation temperature was revealed on expression of some miRNAs in juvenile pituitary (miR-449), gonad (miR-27c, miR-30c, and miR-200a), and liver (let-7 h, miR-7a, miR-22, miR-34c, miR-132a, miR-192, miR-221, miR-451, miR-2188, and miR-7550), but not in brain. Some of differentially expressed miRNAs in the liver were confirmed using LNA-based rt-qPCR. The effect of temperature on methylation status of selected miRNA promoter regions was mostly inconclusive. Temperature elevation by several degrees during embryonic and larval developmental stages significantly alters the miRNA profile, both short-term and long-term. Our results suggest that a further rise in seas temperature might affect life history of Atlantic cod.


Acceleration of sub-relativistic electrons with an evanescent optical wave at a planar interface.
We report on a theoretical and experimental study of the energy transfer between an optical evanescent wave, propagating in vacuum along the planar boundary of a dielectric material, and a beam of sub-relativistic electrons. The evanescent wave is excited via total internal reflection in the dielectric by an infrared (λ = 2 μm) femtosecond laser pulse. By matching the electron propagation velocity to the phase velocity of the evanescent wave, energy modulation of the electron beam is achieved. A maximum energy gain of 800 eV is observed, corresponding to the absorption of more than 1000 photons by one electron. The maximum observed acceleration gradient is 19 ± 2 MeV/m. The striking advantage of this scheme is that a structuring of the acceleration element's surface is not required, enabling the use of materials with high laser damage thresholds that are difficult to nano-structure, such as SiC, Al2O3 or CaF2.


Lifetime abstention of sexual intercourse and health in middle-aged and older adults: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.
This study aimed to examine the association of lifetime abstention of sexual intercourse with lifetime Axis I and II psychiatric disorders, attempted suicide, past-year Axis I psychiatric disorder, past-year medical condition, past-year obesity, health-related quality of life, and health service use in middle-aged and older adults in the United States. Face-to-face interviews were conducted in the 2004-2005 Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Analyses were performed for the subsample aged 40 years and older (males = 14,427; female = 19,860). Lifetime abstinence from sexual intercourse, sociodemographic variables, prevalence of lifetime Axis I and II DSM-IV psychiatric disorders, schizophrenia, and attempted suicide, past-year Axis I psychiatric disorders, 14 medical conditions, obesity, health-related quality of life, and health service use were obtained. The prevalence of lifetime abstinence from sexual intercourse was 0.90 % (0.88 % for males; 1.00 % for females). The adjusted risks of any lifetime and past-year Axis I disorder, any lifetime and past-year substance-use disorders, lifetime alcohol-use disorder, lifetime and past-year alcohol-abuse disorder, lifetime nicotine dependence, lifetime drug-use disorder, and lifetime drug-abuse disorder were significantly lower for who abstained from sexual intercourse than for those who did not. However, those who abstained from sexual intercourse were more likely to have a diagnosis of obesity and lifetime avoidant and dependent personality disorders. The unadjusted risk of dysthymic disorder was also significantly greater for those who abstained from sexual intercourse. Results indicate that the effect of lifetime absence of sexual intercourse on psychiatric disorders is mixed.


On the application of the tolerance factor to inorganic and hybrid halide perovskites: a revised system.
The tolerance factor is a widely used predictor of perovskite stability. The recent interest in hybrid perovskites for use as solar cell absorbers has lead to application of the tolerance factor to these materials as a way to explain and predict structure. Here we critically assess the suitability of the tolerance factor for halide perovskites. We show that the tolerance factor fails to accurately predict the stability of the 32 known inorganic iodide perovskites, and propose an alternative method. We introduce a revised set of ionic radii for cations that is anion dependent, this revision is necessary due to increased covalency in metal-halide bonds for heavier halides compared with the metal-oxide and fluoride bonds used to calculate Shannon radii. We also employ a 2D structural map to account for the size requirements of the halide anions. Together these measures yield a simple system which may assist in the search for new hybrid and inorganic perovskites.


Ambient-temperature isolation of a compound with a boron-boron triple bond.
Homoatomic triple bonds between main-group elements have been restricted to alkynes, dinitrogen, and a handful of reactive compounds featuring trans-bent heavier elements of groups 13 and 14. Previous attempts to prepare a compound with a boron-boron triple bond that is stable at ambient temperature have been unsuccessful, despite numerous computational studies predicting their viability. We found that reduction of a bis(N-heterocyclic carbene)-stabilized tetrabromodiborane with either two or four equivalents of sodium naphthalenide, a one-electron reducing agent, yields isolable diborene and diboryne compounds. Crystallographic and spectroscopic characterization confirm that the latter is a halide-free linear system containing a boron-boron triple bond.


Crowdsourcing, citizen sensing and sensor web technologies for public and environmental health surveillance and crisis management: trends, OGC standards and application examples.
'Wikification of GIS by the masses' is a phrase-term first coined by Kamel Boulos in 2005, two years earlier than Goodchild's term 'Volunteered Geographic Information'. Six years later (2005-2011), OpenStreetMap and Google Earth (GE) are now full-fledged, crowdsourced 'Wikipedias of the Earth' par excellence, with millions of users contributing their own layers to GE, attaching photos, videos, notes and even 3-D (three dimensional) models to locations in GE. From using Twitter in participatory sensing and bicycle-mounted sensors in pervasive environmental sensing, to creating a 100,000-sensor geo-mashup using Semantic Web technology, to the 3-D visualisation of indoor and outdoor surveillance data in real-time and the development of next-generation, collaborative natural user interfaces that will power the spatially-enabled public health and emergency situation rooms of the future, where sensor data and citizen reports can be triaged and acted upon in real-time by distributed teams of professionals, this paper offers a comprehensive state-of-the-art review of the overlapping domains of the Sensor Web, citizen sensing and 'human-in-the-loop sensing' in the era of the Mobile and Social Web, and the roles these domains can play in environmental and public health surveillance and crisis/disaster informatics. We provide an in-depth review of the key issues and trends in these areas, the challenges faced when reasoning and making decisions with real-time crowdsourced data (such as issues of information overload, "noise", misinformation, bias and trust), the core technologies and Open Geospatial Consortium (OGC) standards involved (Sensor Web Enablement and Open GeoSMS), as well as a few outstanding project implementation examples from around the world.


Effect of Dexamethasone on Room Temperature Three-Dimensional Printing, Rheology, and Degradation of a Low Modulus Polyester for Soft Tissue Engineering.
Three-dimensional (3D) printing has enabled benchtop fabrication of customized bioengineered constructs with intricate architectures. Various approaches are being explored to enable optimum integration of such constructs into the physiological environment including addition of bioactive fillers. In this work, we incorporated a corticosteroid drug, dexamethasone (Dex), in a low modulus polyester (SC5050) and examined the effect of Dex incorporation on solvent-, initiator-, and monomer-free pneumatic extrusion-based 3D printing of the polymer. Dex-SC5050 interactions were characterized by plotting thermodynamic binary phase diagrams based on the Flory-Huggins theory. The effect of Dex composition on the 3D printability of the SC5050 polyester was examined by rheological characterization and by image analysis of each layer of the 3D printed scaffolds. The drug release and the degradation of the polymer from the 3D printed scaffolds was used to analyze the effect of Dex composition on the performance of the 3D printed scaffolds. We found that Dex was insoluble in SC5050 polyester at relevant 3D printing temperatures and the insoluble drug particles physically reinforced the polymer, increasing the viscosity and the shear modulus of the base polymer. In addition, the reinforcing effect improved the shape fidelity of the printed filaments and the overall quality of the scaffolds. The Dex particles demonstrated a two-phase release, with an initial burst release and a slower sustained release of drug under in vitro conditions. To investigate preliminary host response of the 3D printed SC5050 scaffolds for tissue engineering applications, the printed scaffolds were implanted subcutaneously in Sprague-Dawley rats for 6 weeks and examined for fibrous tissue formation, infiltration of cells, and vascularization into the pores of the scaffolds.


Autonomously Moving Pine-Cone Robots: Using Pine Cones as Natural Hygromorphic Actuators and as Components of Mechanisms.
We have developed autonomously moving pine-cone robots, which are made of multiple joined pine-cone scales for outdoor natural environments. We achieved these natural robots by using pine cones as both natural hygromorphic actuators and components of the mechanisms. When they are put in outdoor places where moist periods (e.g., rain) and dry periods repeatedly occur, they can move up and down on the spot or move forward. This article describes the motivation behind our research, the design and implementation of three different hygromorphic actuators, and applications for autonomously moving robots in nature.


In situ gas sensing using a remotely detectable probe with replaceable insert.
We demonstrate a spectroscopic gas sensor using an optical fiber probe with a replaceable insert. The probe consists of a hollow-core photonic bandgap fiber (HC-PBGF) with a core diameter of 10.9 μm and a glass tube where a 2-μm hollow core fiber (HCF) with a gold coated end facet can be inserted. The HCF is designed to function as both a gate where gases can enter the HC-PBGF and a mirror reflecting the guided light back to the HC-PBGF. The opposite distal end of the probe is also designed to be able to regulate the gas pressure within the HC-PBGF for a high gas flow rate, while still transmitting the reflected light to the analysis instrument. The remote sensing probe, we believe, has much potential for detecting gases in hazardous environments.


5-Hydroxytryptophan Suppresses the Abdominal Fat Deposit and Is Beneficial to the Intestinal Immune Function in Broilers.
Serotonin (5-HT), a monoaminergic neurotransmitter, involves in the regulation of many physiological functions. In the present study, the effects of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, on lipid metabolism and intestinal immune function in broiler chickens were investigated in chickens. Two hundred broilers were divided randomly into two groups and fed separately with a corn-soybean basal diet (CD) or the basal diet supplemented with 0.2% 5-HTP. The results showed that 5-HTP reduced (P < 0.05) feed intake and the abdominal fat pad weight. 5-HTP treatment tended to upregulate the mRNA level of adiponectin receptor 1 (ADP1R) and ADP2R in abdominal fat but had no significant influence on their protein levels (P > 0.05). In 5-HTP-chickens, lipopolysaccharide exposure decreased secretory immunoglobulin A (sIgA) concentrations in serum and the duodenal contents. Expression of mRNA encoding interleukin (IL), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) decreased after 5-HTP treatment; however, LPS increased expression significantly in 5-HTP-treated chickens compared with CD chickens. In 5-HTP-chickens, the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) were reduced, but the phosphorylation of ribosomal p70S6 kinase (p70S6K) was increased in the duodenum. In summary, the result suggests that dietary 5-HTP supplementation reduces accumulation of abdominal fat and is beneficial to intestinal immune function.


Cranial suture biology: from pathways to patient care.
Craniosynostosis describes the premature pathologic partial or complete fusion of 1 or more of the cranial sutures. Over the past few decades, research on craniosynostosis has progressed from gross description of deformities to an understanding of some of the molecular etiologies behind premature suture fusion. Studies on patients with syndromic craniosynostosis have resulted in the identification of several genes, molecular events, and deformational forces involved in abnormal growth and development of the cranial vault. Conservation of craniofacial development and sequence homology between humans and other species have also led to insightful discoveries in cranial suture development. In this review, we discuss the development of the cranial vault and explain the basic science behind craniosynostosis in humans as well as in animal models and how these studies may lead to future advances in craniosynostosis treatments.


Antibody pressure by a human monoclonal antibody targeting the 2009 pandemic H1N1 virus hemagglutinin drives the emergence of a virus with increased virulence in mice.
In 2009, a novel H1N1 influenza A virus (2009 pH1N1) emerged and caused a pandemic. A human monoclonal antibody (hMAb; EM4C04), highly specific for the 2009 pH1N1 virus hemagglutinin (HA), was isolated from a severely ill 2009 pH1N1 virus-infected patient. We postulated that under immune pressure with EM4C04, the 2009 pH1N1 virus would undergo antigenic drift and mutate at sites that would identify the antibody binding site. To do so, we infected MDCK cells in the presence of EM4C04 and generated 11 escape mutants, displaying 7 distinct amino acid substitutions in the HA. Six substitutions greatly reduced MAb binding (K123N, D131E, K133T, G134S, K157N, and G158E). Residues 131, 133, and 134 are contiguous with residues 157 and 158 in the globular domain structure and contribute to a novel pH1N1 antibody epitope. One mutation near the receptor binding site, S186P, increased the binding affinity of the HA to the receptor. 186P and 131E are present in the highly virulent 1918 virus HA and were recently identified as virulence determinants in a mouse-passaged pH1N1 virus. We found that pH1N1 escape variants expressing these substitutions enhanced replication and lethality in mice compared to wild-type 2009 pH1N1 virus. The increased virulence of these viruses was associated with an increased affinity for α2,3 sialic acid receptors. Our study demonstrates that antibody pressure by an hMAb targeting a novel epitope in the Sa region of 2009 pH1N1 HA is able to inadvertently drive the development of a more virulent virus with altered receptor binding properties. This broadens our understanding of antigenic drift. Influenza viruses accumulate amino acid substitutions to evade the antibody response in a process known as antigenic drift, making it necessary to vaccinate against influenza annually. Mapping human monoclonal antibody (hMAb) epitopes is a necessary step towards understanding antigenic drift in humans. We defined the specificity of an hMAb that specifically targeted the 2009 pH1N1 virus and describe a novel epitope. In addition, we identified a previously unappreciated potential for antibody escape to enhance the pathogenicity of a virus. The escape mutation that we identified with in vitro immune pressure was independently reported by other investigators using in vivo selection in nonimmune mice. Although in vitro generation of escape mutants is unlikely to recapitulate antigenic drift in its entirety, the data demonstrate that pressure by a human monoclonal antibody targeting a novel epitope in the hemagglutinin of the 2009 pandemic H1N1 virus can inadvertently drive the development of escape mutants, of which a subset have increased virulence and altered receptor binding properties.


Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets.
Metabolic transformation of glucocorticoid hormones constitutes a determinant of their cell-specific effects. The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). In this study, we determined the role of glucocorticoid conversion by 11beta-HSD in pancreatic islets and its function in the regulation of insulin release. Pancreatic islets isolated from ob/ob mice display type 1 11beta-hydroxysteroid dehydrogenase activity, i.e. in intact cells the reductive reaction prevails, leading from dehydrocorticosterone to corticosterone. Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob/ob mice and also from human tissue. Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, indicating cellular activation of 11-dehydrocorticosterone to the receptor ligand, further confirmed by reporter gene assays. Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. The presence of 11beta-HSD in islets supports the concept that reactivation of inert circulating hormone precursors in a cell-specific manner plays a major role in glucocorticoid physiology in rodents and man.


Effectiveness of a novel ozone-based system for the rapid high-level disinfection of health care spaces and surfaces.
Vapor-based fumigant systems for disinfection of health care surfaces and spaces is an evolving technology. A new system (AsepticSure) uses an ozone-based process to create a highly reactive oxidative vapor with broad and high-level antimicrobial properties. Ozone gas at 50-500 ppm was combined with 3% hydrogen peroxide vapor in a test chamber and upscaled in rooms measuring 82 m3 and 90 m3 in area. Test organisms included methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, Escherichia coli, Pseudomonas aeruginosa, Clostridium difficile, and Bacillus subtilis spores dried onto steel discs or cotton gauze pads. The combination of 80-ppm ozone with 1% hydrogen peroxide vapor achieved a very high level of disinfection, with a ≥6 log10 reduction in the bacteria and spores tested on steel discs and MRSA tested on cotton gauze during a 30- to 90-minute exposure. The entire system was scalable such that it achieved the same high level of disinfection in both the 81-m3 and 90-m3 rooms in 60-90 minutes. The ozone hydrogen peroxide vapor system provides a very high level of disinfection of steel and gauze surfaces against health care-associated bacterial pathogens. The system is an advanced oxidative process providing a rapid and effective means of disinfecting health care surfaces and spaces.


Involvement of diamine oxidase and peroxidase in insolubilization of the extracellular matrix: implications for pea nodule initiation by Rhizobium leguminosarum.
Rhizobium leguminosarum colonizes host cells and tissues through infection threads, which are tubular in-growths of the plant cell wall. Monoclonal antibody MAC265 recognizes a plant matrix glycoprotein (MGP) associated with the lumen of these infection threads. This glycoprotein is also released in soluble form from the root tips of pea seedlings. In the presence of hydrogen peroxide, release of glycoprotein from root tips was not observed. Extractability from root tips was therefore used as the basis for investigating the peroxide-driven insolubilization of MGP and the possible involvement of two extracellular enzymes, peroxidase (POD) and diamine oxidase (DAO), was investigated. Release of MGP from root tips was enhanced by application of POD and DAO inhibitors (salicylhydroxamic acid and o-phenanthroline, respectively). Furthermore, release of MGP was inhibited by pretreatment of roots with putrescine (the substrate of DAO) and also by application of a partially purified extract of DAO from pea shoots. Following inoculation of pea roots with R. leguminosarum, elevated levels of DAO transcript were observed by reverse transcriptase-polymerase chain reaction (RT-PCR), but these then dropped to a low level from 4 to 10 days post inoculation, rising again in more mature nodules. In situ hybridization studies indicated that the bulk of the transcription was associated with the infected tissue in the center of the nodule. On the basis of these observations, we postulate that DAO may be involved in the peroxide-driven hardening of MGP in the lumen of infection threads and in the intercellular matrix.


Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory.
Gap junctions containing connexin 36 electrically couple interneurons in many brain regions and synchronize their activity. We used connexin-36 knock-out mice (Cx36(-/-)) to study the importance of electrical coupling between interneurons for spatial coding in the hippocampus and for different forms of hippocampus-dependent spatial memory. Recordings in behaving mice revealed that the spatial selectivity of hippocampal pyramidal neurons was reduced and less stable in Cx36(-/-) mice. Altered network activity was reflected in slower theta oscillations in the mutants. Temporal coding, assessed by determining the presence and characteristics of theta phase precession, had different dynamics in Cx36(-/-) mice compared with controls. At the behavioral level, Cx36(-/-) mice displayed impaired short-term spatial memory but normal spatial reference memory. These results highlight the functional role of electrically coupled interneurons for spatial coding and cognition. Moreover, they suggest that the precise spatial selectivity of place cells is not essential for normal performance on spatial tasks assessing associative long-term memory.


Looking beyond the issue of access to insulin: what is needed for proper diabetes care in resource poor settings.
Insulin's indispensible nature is recognised by its inclusion in the World Health Organization's Essential Medicines List. Despite this insulin is still not available on an uninterrupted basis in many parts of the developing world. The International Insulin Foundation has conducted in-country assessments and based on these findings, the barriers to access to insulin were more to do with problems linked distribution, tendering and government policies than purely accessibility and affordability issues. Lack of insulin leads to poor outcomes for people with diabetes, but access to medicines alone cannot improve levels of health in resource poor settings. Aspects such as strong political will and local champions, data, trained healthcare workers and diabetes associations are just as necessary. Strengthening health systems and developing sustainable and locally owned solutions are vital to improve health and health care for people with diabetes and other chronic conditions in resource poor settings.


European Union scientific production on alcohol and drug misuse (1976-2000).
Alcohol and drug misuse is a social and health phenomenon of great relevance in the European Union (EU). One indicator of scientific production in a given area is the analysis of publications included in bibliographic databases. Scientific production on alcohol and drug misuse was analysed in EU member countries, and comparisons were made between countries. Analysis of articles on alcohol and drug misuse published during the period 1976-2000 by institutions based in a country of the EU, indexed by PsycINFO. A total of 4825 citations was retrieved. Great Britain published 38.6%, while Sweden, Germany and Spain accounted for a further 30%. The articles dealt with drug and alcohol usage (12.8%), substance abuse (53.5%) and drug and alcohol rehabilitation (34.5%). The articles were published in 13 different languages, more than three-quarters being in English. Spanish was the second language, and was followed by French, German, Dutch and Italian. The articles were published in 521 different journals, and 62 of these published more than 10 articles. The journals publishing most were Addiction, Alcohol and Alcoholism and Drug and Alcohol Dependence. Sixty-eight per cent of the articles were signed by more than one author, and the index of collaboration, between 1996 and 2000, was 3.24. PsycINFO is useful for making comparisons between countries, because it includes the name and country of the institution. The number of publications in the EU on alcohol and drug misuse increased over the quarter-century analysed. The most used language was English, as it also is for PsycINFO as a whole, and a tendency towards its increased use was observed. Classification of the articles by subject by the Classification Code is too general, and makes it difficult to distinguish between the areas it proposes. Production tends to be concentrated in journals dealing specifically with drug dependence and psychiatry. The index of collaboration is similar to that found in other scientific areas.


Antimicrobial activity of Gentiana lutea L. extracts.
Methanolic extracts of flowers and leaves of Gentiana lutea L., together with the isolated compounds mangiferin, isogentisin and gentiopicrin, were used to investigate the antimicrobial activity of the plant. A variety of Gram-positive and Gram-negative bacteria as well as the yeast Candida albicans has been included in this study. Both extracts and isolated compounds showed antimicrobial activity with MIC values ranging from 0.12-0.31 mg/ml. Our study indicated that the synergistic activity of the pure compounds may be responsible for the good antimicrobial effect of the extracts. Quantification of the secondary metabolites was performed using HPLC.


Inducible covalent posttranslational modification of histone H3.
The physiological state of a eukaryotic cell is determined by endogenous and exogenous signals, and often the endpoint of the pathways that transmit these signals is DNA. DNA is organized into chromatin, a nucleoprotein complex, which not only facilitates the packaging of DNA within the nucleus but also serves as an important factor in the regulation of gene function. The nucleosome is the basic unit of chromatin and generally consists of approximately two turns of DNA wrapped around an octamer of core histone proteins. Each histone also contains an accessible N-terminal tail that extends outside the chromatin complex and is subject to posttranslational modifications that are crucial in the regulation of gene expression. Two distinct categories of histone posttranslational modification have been observed: (i) inducible or stimulation-dependent and (ii) mitosis-dependent. Stimulation by mitogens or stress leads to rapid transient posttranslational modifications of histones, in particular histone H3, which are mechanistically and temporarily distinct from modifications associated with mitosis. This Review focuses mainly on the inducible phosphorylation of histone H3 brought about by different stimuli, such as epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, arsenite, or ultraviolet radiation. We examine the most recent, and at times controversial, research data concerning the identity of the histone H3 kinases responsible for this phosphorylation. In addition, the interdependence of phosphorylation and acetylation will be discussed in light of data showing patterns of inducible modification at specific genes.


Vimentin filaments in fibroblasts are a reservoir for SNAP23, a component of the membrane fusion machinery.
Soluble N-ethyl maleimide-sensitive fusion protein attachment protein receptors (SNAREs) are core machinery for membrane fusion during intracellular vesicular transport. Synaptosome-associated protein of 23 kDa (SNAP23) is a target SNARE previously identified at the plasma membrane, where it is involved in exocytotic membrane fusion. Here we show that SNAP23 associates with vimentin filaments in a Triton X-100 insoluble fraction in fibroblasts in primary culture and HeLa cells. Upon treatment of human fibroblasts with N-ethyl-maleimide, SNAP23 dissociates from vimentin filaments and forms a protein complex with syntaxin 4, a plasma membrane SNARE. The vimentin-associated pool of SNAP23 can therefore be a reservoir, which would supply the plasma membrane fusion machinery, in fibroblasts. Our observation points to a yet unexplored role of intermediate filaments.


Cryoglobulinemia induced by monoclonal immunoglobulin G rheumatoid factors derived from autoimmune MRL/MpJ-lpr/lpr mice.
A MRL strain bearing the autosomal recessive mutant gene, lpr (lymphoproliferation), spontaneously develops, in addition to a lupus-like syndrome, unique serological and pathological manifestations. Production of high titers of IgG rheumatoid factors (RF) may be related to the formation of extremely large amounts of cryoglobulins and the development of tissue lesions such as necrotizing polyarteritis, arthritis, and glomerulonephritis. To analyze more directly the relationship of IgG RF to the development of cryoglobulins and tissue injuries, we have established four monoclonal IgG RF secreting hybridomas from unimmunized MRL-lpr/lpr mice and determined their pathogenic effects in normal strains of mice. All the monoclonal IgG RF obtained in this study were of the IgG3 subclass and generated cryoglobulins. However, the fact that not only IgG3 Rf monoclonals but also four of five non-RF IgG3 monoclonals were able to form cryoglobulins, which were composed exclusively of each IgG3 monoclonal, indicates that the IgG3 molecule has a unique physicochemical property to self-associate via nonimmunological interaction and the ability to form cryoglobulins. When the in vivo pathogenic activities of these IgG3 RF and non-RF monoclonals were examined, three of IgG3 RF monoclonals with the specificity to IgG2a were able to induce extensive pathologic manifestations including peripheral vasculitis and glomerulonephritis characteristic of patients with cryoglobulinemia. Our results indicate that the IgG3 itself, independently of its specificity, could be a potential source of cryoglobulins and IgG3 RF, combined with its activity of cryoglobulin formation, may play a significant role in the development of glomerulonephritis and cutaneous vascular lesions of ears and foot pads observed frequently in aged MRL-lpr/lpr mice.


Effects of including sprints during prolonged cycling on hormonal and muscular responses and recovery in elite cyclists.
This study investigated the acute effects of including 30-second sprints during prolonged low-intensity cycling on muscular and hormonal responses and recovery in elite cyclists. Twelve male cyclists (VO2max , 73.4 ± 4.0 mL/kg/min) completed a randomized crossover protocol, wherein 4 hours of cycling at 50% of VO2max were performed with and without inclusion of three sets of 3 × 30 seconds maximal sprints (E&S vs E, work-matched). Muscle biopsies (m. vastus lateralis) and blood were sampled at Pre, immediately after (Post) and 3 hours after (3 h) finalizing sessions. E&S led to greater increases in mRNA levels compared with E for markers of fat metabolism (PDK4, Δ-Log2 fold change between E&S and E ± 95%CI Post; 2.1 ± 0.9, Δ3h; 1.3 ± 0.7) and angiogenesis (VEGFA, Δ3h; 0.3 ± 0.3), and greater changes in markers of muscle protein turnover (myostatin, ΔPost; -1.4 ± 1.2, Δ3h; -1.3 ± 1.3; MuRF1, ΔPost; 1.5 ± 1.2, all P < .05). E&S showed decreased mRNA levels for markers of ion transport at 3h (Na+ -K+ α1; -0.6 ± 0.6, CLC1; -1.0 ± 0.8 and NHE1; -0.3 ± 0.2, all P < .05) and blunted responses for a marker of mitochondrial biogenesis (PGC-1α, Post; -0.3 ± 0.3, 3h; -0.4 ± 0.3, P < .05) compared with E E&S and E showed similar endocrine responses, with exceptions of GH and SHBG, where E&S displayed lower responses at Post (GH; -4.1 ± 3.2 μg/L, SHBG; -2.2 ± 1.9 nmol/L, P < .05). Both E&S and E demonstrated complete recovery in isokinetic knee extension torque 24 hours after exercise. In conclusion, we demonstrate E&S to be an effective exercise protocol for elite cyclists, which potentially leads to beneficial adaptations in skeletal muscle without impairing muscle recovery 24 hours after exercise.


Biotinidase deficiency: a survey of 10 cases.
Ten patients with biotinidase deficiency were studied. Clinical findings at presentation varied with dermatological signs (dermatitis and alopecia), neurological abnormalities (fits, hypotonia, and ataxia), and recurrent infections being the most common features, although none of these occurred in every case. Biochemically the disease is characterised by metabolic acidosis and organic aciduria. Treatment with biotin results in pronounced, rapid, clinical and biochemical improvement, but some patients have residual neurological damage comprising neurosensory hearing loss, visual pathway defects, ataxia, and mental retardation. The cause of this permanent damage remains obscure and it is not clear if the early introduction of treatment will prevent it.


Before-after field study of effects of wind turbine noise on polysomnographic sleep parameters.
Wind is considered one of the most advantageous alternatives to fossil energy because of its low operating cost and extensive availability. However, alleged health-related effects of exposure to wind turbine (WT) noise have attracted much public attention and various symptoms, such as sleep disturbance, have been reported by residents living close to wind developments. Prospective cohort study with synchronous measurement of noise and sleep physiologic signals was conducted to explore the possibility of sleep disturbance in people hosting new industrial WTs in Ontario, Canada, using a pre and post-exposure design. Objective and subjective sleep data were collected through polysomnography (PSG), the gold standard diagnostic test, and sleep diary. Sixteen participants were studied before and after WT installation during two consecutive nights in their own bedrooms. Both audible and infrasound noises were also concurrently measured inside the bedroom of each participant. Different noise exposure parameters were calculated (LAeq, LZeq) and analyzed in relation to whole-night sleep parameters. Results obtained from PSG show that sleep parameters were not significantly changed after exposure. However, reported sleep qualities were significantly (P = 0.008) worsened after exposure. Average noise levels during the exposure period were low to moderate and the mean of inside noise levels did not significantly change after exposure. The result of this study based on advanced sleep recording methodology together with extensive noise measurements in an ecologically valid setting cautiously suggests that there are no major changes in the sleep of participants who host new industrial WTs in their community. Further studies with a larger sample size and including comprehensive single-event analyses are warranted.


Adipocyte deficiency of ACE2 increases systolic blood pressures of obese female C57BL/6 mice.
Obesity increases the risk for hypertension in both sexes, but the prevalence of hypertension is lower in females than in males until menopause, despite a higher prevalence of obesity in females. We previously demonstrated that angiotensin-converting enzyme 2 (ACE2), which cleaves the vasoconstrictor, angiotensin II (AngII), to generate the vasodilator, angiotensin-(1-7) (Ang-(1-7)), contributes to sex differences in obesity-hypertension. ACE2 expression in adipose tissue was influenced by obesity in a sex-specific manner, with elevated ACE2 expression in obese female mice. Moreover, estrogen stimulated adipose ACE2 expression and reduced obesity-hypertension in females. In this study, we hypothesized that deficiency of adipocyte ACE2 contributes to obesity-hypertension of females. We generated a mouse model of adipocyte ACE2 deficiency. Male and female mice with adipocyte ACE2 deficiency or littermate controls were fed a low (LF) or a high fat (HF) diet for 16 weeks and blood pressure was quantified by radiotelemetry. HF-fed mice of each sex and genotype were challenged by an acute AngII injection, and blood pressure response was quantified. To translate these findings to humans, we performed a proof-of-principle study in obese transwomen in which systemic angiotensin peptides and blood pressure were quantified prior to and after 12 weeks of gender-affirming 17β-estradiol hormone therapy. Adipocyte ACE2 deficiency had no effect on the development of obesity in either sex. HF feeding increased systolic blood pressures (SBP) of wild-type male and female mice compared to LF-fed controls. Adipocyte ACE2 deficiency augmented obesity-induced elevations in SBP in females, but not in males. Obese female, but not obese male mice with adipocyte ACE2 deficiency, had an augmented SBP response to acute AngII challenge. In humans, plasma 17β-estradiol concentrations increased in obese transwomen administered 17β-estradiol and correlated positively with plasma Ang-(1-7)/AngII balance, and negatively to SBP after 12 weeks of 17β-estradiol administration. Adipocyte ACE2 protects female mice from obesity-hypertension, and reduces the blood pressure response to systemic AngII. In obese transwomen undergoing gender-affirming hormone therapy, 17β-estradiol administration may regulate blood pressure via the Ang-(1-7)/AngII balance.


Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites.
Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups.


TGF-β1 attenuates mitochondrial bioenergetics in pulmonary arterial endothelial cells via the disruption of carnitine homeostasis.
Transforming growth factor beta-1 (TGF-β1) signaling is increased and mitochondrial function is decreased in multiple models of pulmonary hypertension (PH) including lambs with increased pulmonary blood flow (PBF) and pressure (Shunt). However, the potential link between TGF-β1 and the loss of mitochondrial function has not been investigated and was the focus of our investigations. Our data indicate that exposure of pulmonary arterial endothelial cells (PAEC) to TGF-β1 disrupted mitochondrial function as determined by enhanced mitochondrial ROS generation, decreased mitochondrial membrane potential, and disrupted mitochondrial bioenergetics. These events resulted in a decrease in cellular ATP levels, decreased hsp90/eNOS interactions and attenuated shear-mediated NO release. TGF-β1 induced mitochondrial dysfunction was linked to a nitration-mediated activation of Akt1 and the subsequent mitochondrial translocation of endothelial NO synthase (eNOS) resulting in the nitration of carnitine acetyl transferase (CrAT) and the disruption of carnitine homeostasis. The increase in Akt1 nitration correlated with increased NADPH oxidase activity associated with increased levels of p47phox, p67phox, and Rac1. The increase in NADPH oxidase was associated with a decrease in peroxisome proliferator-activated receptor type gamma (PPARγ) and the PPARγ antagonist, GW9662, was able to mimic the disruptive effect of TGF-β1 on mitochondrial bioenergetics. Together, our studies reveal for the first time, that TGF-β1 can disrupt mitochondrial function through the disruption of cellular carnitine homeostasis and suggest that stimulating carinitine homeostasis may be an avenue to treat pulmonary vascular disease.


Effect of day of estrus cycle at time of transvaginal follicle aspiration for oocyte recovery on rates of in vitro maturation and blastocyst production after intracytoplasmic sperm injection.
To determine the effect of stage of estrus cycle (day after ovulation) at the time of transvaginal ultrasound-guided follicle aspiration (TVA) on parameters related to the success of in vitro equine embryo production. 14 healthy mares were used; 11 completed the study and were included for analysis. Mares underwent TVA of all follicles ≥ 5 mm diameter at each of 3 timepoints: 7 days after ovulation, 14 days after ovulation, and S-DSF (subordinate to a dominant stimulated follicle), during estrus at 24 hours after gonadotropin administration. The 3 treatments were assigned to each mare in random order; mares underwent follicle growth and ovulation between treatments. Recovered oocytes were matured in vitro, subjected to intracytoplasmic sperm injection (ICSI), and cultured to the blastocyst stage in vitro. Total follicle numbers differed significantly between individual mares but did not differ between treatments. The number of follicles of different sizes significantly (P < 0.05) differed between treatments, with mares in the Day 7 treatment having more follicles 5 to 9 mm in diameter and fewer follicles 20 to 24 mm in diameter than mares in the other 2 treatments. After in vitro maturation culture, there were significantly more mature oocytes in the S-DSF treatment than in the other 2 treatments. There were no differences in blastocyst rate after ICSI among treatment groups. Timing of TVA for aspiration of S-DSFs may increase the number of mature oocytes available for ICSI. Understanding of the effects of timing of TVA will help veterinarians to maximize the efficiency of this procedure.


Emergence of small-world anatomical networks in self-organizing clustered neuronal cultures.
In vitro primary cultures of dissociated invertebrate neurons from locust ganglia are used to experimentally investigate the morphological evolution of assemblies of living neurons, as they self-organize from collections of separated cells into elaborated, clustered, networks. At all the different stages of the culture's development, identification of neurons' and neurites' location by means of a dedicated software allows to ultimately extract an adjacency matrix from each image of the culture. In turn, a systematic statistical analysis of a group of topological observables grants us the possibility of quantifying and tracking the progression of the main network's characteristics during the self-organization process of the culture. Our results point to the existence of a particular state corresponding to a small-world network configuration, in which several relevant graph's micro- and meso-scale properties emerge. Finally, we identify the main physical processes ruling the culture's morphological transformations, and embed them into a simplified growth model qualitatively reproducing the overall set of experimental observations.


Can we predict amyloid deposition by objective cognition and regional cerebral blood flow in patients with subjective cognitive decline?
Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD. Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors. The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037). No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.


Description of case-mix adjusters by the Severity of Illness Working Group of the Society of Hospital Epidemiologists of America (SHEA).
Hospitals, insurance companies, and federal and state governments are increasingly concerned about reducing patient cost expenditures while maintaining high quality patient care. One method of reducing expenditures has been to tie hospital reimbursement with a prospective payment system based on diagnosis-related groups (DRGs). However, reimbursement under the DRG system is not acceptable for all patients in all hospitals because it is neither an accurate predictor of costs nor of clinical outcome. This deficiency poses significant problems for hospitals because DRGs are used nationwide as the prospective payment system for inpatients covered by Medicare. Several case-mix adjusters have been proposed to modify DRGs to improve their accuracy in predicting costs and outcome. We reviewed five of the most widely available indices: Acute Physiologic and Chronic Health Evaluation (APACHE II), Coded Disease Staging, Computerized Severity Index (CSI), Medical Illness Severity Group System (MEDISGROUPS), and Patient Management Categories (PMC). Recommendations for the use of a single case-mix adjuster cannot be made at this time because all indices have not been compared in sufficiently diverse settings and because some are better predictors of costs while others are better predictors of clinical outcome. Hospital epidemiologists and other infection control practitioners should be informed about these indices and their potential applications as they expand their role beyond infection control problems to issues concerning cost containment, quality assurance, and reimbursement.


High occurrence of head and spine injuries in the pediatric population following motocross accidents.
Off-road motorcycling is a very popular sport practiced by countless people worldwide. Despite its popularity, not much has been published on the severity and distribution of central nervous system-related injuries associated with this activity in the pediatric population. The purpose of this study was to confirm, characterize, and document the rate of head and spine injuries associated with off-road motorcycling in this population. All patients aged 18 years or less who were treated for a motorbike injury at the authors' institution (a Level 1 regional trauma center) between 2000 and 2007 were identified through in-house surgical and trauma registries. Type, mechanism, and severity of CNS-related injuries were assessed, including: incidence of traumatic brain injury (TBI), loss of consciousness (LOC), Glasgow Coma Scale (GCS) score, head CT findings, neurological deficits, spinal fractures, cervical strain, and use of protective gear, including helmets. During the 8-year period of study, 298 accidents were evaluated in 248 patients. The patients' mean age at the time of injury was 14.2 ± 2.7 years. Head injury or TBI was identified in 60 (20.1%) of 298 cases (involving 58 of 248 patients). Fifty-seven cases were associated with LOC, and abnormalities were identified on head CT in 10 patients; these abnormalities included skull fractures and epidural, subdural, subarachnoid, and intraparenchymal hemorrhages. The GCS score was abnormal in 11 cases and ranged from 3 to 15, with an overall mean of 14.5. No patients required cranial surgery. Helmet use was confirmed in 43 (71.6%) of the cases involving TBI. Spine fractures were identified in 13 patients (4.3%) and 5 required surgical fixation for their injury. The authors found a high occurrence of head injuries following pediatric off-road motorcycle riding or motocross accidents despite the use of helmets. Additionally, this study severely underestimates the rate of mild TBIs in this patient population. Our data indicate that motocross is a high-risk sport despite the use of protective gear. Riders and parents should be counseled accordingly about the risks prior to participation.


Imaging of adult brainstem gliomas.
Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as 18F-fluoro-ethyl-tyrosine positron emission tomography (18F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.


Luxury uptake of phosphorus by microalgae in full-scale waste stabilisation ponds.
Biological phosphorus removal was studied in two full-scale waste stabilisation ponds (WSP). Luxury uptake by microalgae was confirmed to occur and in one pond the biomass contained almost four times the phosphorus required by microalgae for normal metabolism. However, the phosphorus content within the biomass was variable. This finding means that assumptions made in prior publications on modelling of phosphorus removal in WSP are questionable. While fluctuations in microalgal growth causes variation in many water quality parameters, this further variation in luxury uptake explains the high degree of variability in phosphorus removal commonly reported in the literature. To achieve effective biological phosphorus removal high levels of both luxury uptake and microalgal concentration are needed. The findings of this work show that while high levels of these parameters did occur at times in the WSP monitored, they did not occur simultaneously. This is explained because accumulated phosphorus is subsequently consumed during rapid growth of biomass resulting in a high biomass concentration with a low phosphorus content. Previous laboratory research has allowed a number of key considerations to be proposed to optimise both luxury uptake and biomass concentration. Now that is has been shown that high levels of biomass concentration and luxury uptake can occur in the field it may be possible to redesign WSP to optimise these parameters.


Lateral ankle instability: MR imaging of associated injuries and surgical treatment procedures.
Chronic ankle instability has been defined as the development of recurrent ankle sprains and persistent symptoms after initial lateral ankle sprain. The diagnosis of ankle instability is usually established on the patient's history, physical examination, and radiographic assessment. Patients have signs of both functional and mechanical instability, and the repetitive, chronic nature of the injury may lead to intra-articular and periarticular pathologies. This article discusses the incidence, etiology, and magnetic resonance (MR) imaging of these pathologies, reviews the surgical treatment procedures for lateral ankle instability, and presents the postoperative MR imaging findings.


Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid-blood barrier.
The microenvironment of the cochlea is maintained by the barrier between the systemic circulation and the fluids inside the stria vascularis. However, the mechanisms that control the permeability of the intrastrial fluid-blood barrier remain largely unknown. The barrier comprises endothelial cells connected to each other by tight junctions and an underlying basement membrane. In a recent study, we found that the intrastrial fluid-blood barrier also includes a large number of perivascular cells with both macrophage and melanocyte characteristics. The perivascular-resident macrophage-like melanocytes (PVM/Ms) are in close contact with vessels through cytoplasmic processes. Here we demonstrate that PVM/Ms have an important role in maintaining the integrity of the intrastrial fluid-blood barrier and hearing function. Using a cell culture-based in vitro model and a genetically induced PVM/M-depleted animal model, we show that absence of PVM/Ms increases the permeability of the intrastrial fluid-blood barrier to both low- and high-molecular-weight tracers. The increased permeability is caused by decreased expression of pigment epithelial-derived factor, which regulates expression of several tight junction-associated proteins instrumental to barrier integrity. When tested for endocochlear potential and auditory brainstem response, PVM/M-depleted animals show substantial drop in endocochlear potential with accompanying hearing loss. Our results demonstrate a critical role for PVM/Ms in regulating the permeability of the intrastrial fluid-blood barrier for establishing a normal endocochlear potential hearing threshold.


Ehrlichia chaffeensis TRP120 interacts with a diverse array of eukaryotic proteins involved in transcription, signaling, and cytoskeleton organization.
Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes and survives by evading host cell defense mechanisms. Recently, molecular interactions between E. chaffeensis 47-kDa tandem repeat (TR) protein (TRP47) and the eukaryotic host cell have been described. In this investigation, yeast (Saccharomyces cerevisiae) two-hybrid analysis demonstrated that E. chaffeensis-secreted tandem repeat protein 120 (TRP120) interacts with a diverse group of host cell proteins associated with major biological processes, including transcription and regulation, cell signaling, protein trafficking, and actin cytoskeleton organization. Twelve target proteins with the highest frequency of interaction with TRP120 were confirmed by cotransformation in yeast. Host targets, including human immunoglobulin lambda locus (IGL), cytochrome c oxidase subunit II (COX2), Golgi-associated gamma adaptin ear-containing ARF binding protein 1 (GGA1), polycomb group ring finger 5 (PCGF5), actin gamma 1 (ACTG1), and unc-13 homolog D (UNC13D; Caenorhabditis elegans), colocalized strongly with TRP120 in HeLa cells and with E. chaffeensis dense-cored morulae and areas adjacent to morulae in the host cytoplasm. The TR domain of TRP120 interacted only with PCGF5, indicating that distinct TRP120 domains contribute to specific host target interactions and that multiple domains are required to reconstitute TRP120 interactions with other host targets. Three previously defined molecular interactions between TRP47 and host proteins, PCGF5, IGLL1, and CAP1, were also associated with TRP120, demonstrating that molecular cross talk occurs between Ehrlichia TRPs and host targets. These findings further support the role of TRPs as effectors that reprogram the host cell.


Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.
Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (Css ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.


Genomic minimalism in the early diverging intestinal parasite Giardia lamblia.
The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.


Comparative analysis of bioremediation potential of adapted and non-adapted fungi on azo dye containing textile effluent.
About 4 different predominant adapted fungal strains (screened from effluent sample) Aspergillus sp., Penicillium sp., Fusarium sp. and Mucor sp. and 4 predominant non-adapted strains (screened from soil, water and fungal fruiting bodies) Aspergillus sp., Penicillium sp., Fusarium sp. and Rhizopus sp., with potential dye decolorization ability on Reactive black 5, Amido black-10B, Red 5B, Reactive red 120 and Anthraquinone violet R were isolated. These organisms were used to develop a consortium which was used in analyzing the bioremediation efficiency on textile effluents containing a mixture of azo dyes. There was about 67% of reduction in color along with 34% of COD reduction by non-adapted fungal consortium while effective bioremediation efficiency was observed in adapted fungal consortium (Color 75% and COD 50%). The regression co-efficient for Langmuir and Freundlich adsorption isotherms were found to be higher for adapted fungal consortium (R2 = 0.97 and R2 = 0.92) than the non-adapted consortium (R2 = 0.97 and R2 = 0.85) proving that both monolayer and multilayer adsorption of dyes were observed on treating the samples with the adapted fungal consortium. On analyzing the results observed through chi-square test, the calculated value (28.712) was higher than the tabulated value (9.49) at a 4 degree freedom hence the hypothesis was rejected. So, there was an association between adapted fungal consortium and non-adapted fungal consortium and hence the adapted fungal consortium could be considered potentially useful for the bioremediation of textile effluent.


PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription.
Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and its co-factor CTCF. They not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina. Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity.


Curcumin, an antibiotic resistance breaker against a multiresistant clinical isolate of Mycobacterium abscessus.
Curcumin, a phenolic compound extracted from Curcuma longa, exerts multiple pharmacological effects, including an antimicrobial action. Mycobacterium abscessus, an environmental, nontuberculous, rapidly growing mycobacterium, is an emerging human pathogen causing serious lung infections and one of the most difficult to treat, due to its multidrug resistance and biofilm-forming ability. We wanted to evaluate the antimicrobial and antivirulence activity of curcumin and its ability to synergize with antibiotics against a clinical M. abscessus strain (29904), isolated from the bronchoaspirate of a 66-year-old woman admitted to hospital for suspected tuberculosis. Curcumin [minimum inhibitory concentrations (MIC) = 128 mg/L] was synergic (fractional inhibitory concentration index ≤0.5) with amikacin, clarithromycin, ciprofloxacin, and linezolid, to which strain 29904 showed resistance/intermediate susceptibility. Curcumin at 1/8 × MIC significantly reduced motility, whereas at 4 × MIC, it completely inhibited 4- and 8-day mature biofilms. Synergistic combinations of curcumin and amikacin induced a general reduction in microbial aggregates and substantial loss in cell viability. Disruption of 4- and 8-day biofilms was the main effect detected when curcumin was the predominant compound. The present findings support previous evidence that curcumin is a potential antibiotic resistance breaker. Curcumin, either alone or combined with antibiotics, could provide a novel strategy to combat antibiotic resistance and virulence of M. abscessus.


Teachers' conflicting cultural schemas of teaching comprehensive school-based sexuality education in Kampala, Uganda.
Teachers can feel uncomfortable teaching sexuality education when the content conflicts with their cultural values and beliefs. However, more research is required to understand how to resolve conflicts between teachers' values and beliefs and those implicit in comprehensive approaches to sexuality education. This study uses cultural schema theory to identify teachers' cultural schemas of teaching sexuality education and the internal conflicts arising between them. In-depth interviews were conducted with 40 secondary school teachers in Kampala, the capital city of Uganda. Embedded in a context of morality, conflicting cultural schemas of sexuality education and young people's sexual citizenship in traditional and present-day Ugandan society were found: young people are both innocent and sexually active; sexuality education both encourages and prevents sexual activity; and teachers need to teach sexuality education, but it is considered immoral for them to do so. In countries such as Uganda, supportive school regulations and a mandate from society could help teachers feel more comfortable adopting comprehensive approaches to sexuality education.


Cervical joint position sense in neck pain. Immediate effects of muscle vibration versus mental training interventions: a RCT.
Impaired cervical joint position sense is a feature of chronic neck pain and is commonly argued to rely on abnormal cervical input. If true, muscle vibration, altering afferent input, but not mental interventions, should have an effect on head repositioning acuity and neck pain perception. The aim of the present study was to determine the short-term effects of neck muscle vibration, motor imagery, and action observation on cervical joint position sense and pressure pain threshold in people with chronic neck pain. Forty-five blinded participants with neck pain received concealed allocation and were randomized in three treatment groups. A blinded assessor performed pre- and post-test measurement. Patients were recruited from secondary outpatient clinics in the southwest of Germany. Chronic, non specific neck pain patients without arm pain were recruited for this study. A single intervention session of 5 minutes was delivered to each blinded participant. Patients were either allocated to one of the following three interventions: (1) neck muscle vibration; (2) motor imagery; (3) action observation. Primary outcomes were cervical joint position sense acuity and pressure pain threshold. Repeated measures ANOVAs were used to evaluate differences between groups and subjects. Repositioning acuity displayed significant time effects for vibration, motor imagery, and action observation (all P<0.05), but revealed no time*group effect. Pressure pain threshold demonstrated a time*group effect (P=0.042) as only vibration significantly increased pressure pain threshold (P=0.01). Although motor imagery and action observation did not modulate proprioceptive, afferent input, they nevertheless improved cervical joint position sense acuity. This indicates that, against the common opinion, changes in proprioceptive input are not prerequisite to improve joint repositioning performance. However, the short-term applications of these cognitive treatments had no effect on pressure pain thresholds, whereas vibration reduced pressure pain thresholds. This implies different underlying mechanisms after vibration and mental training. Mental interventions were effective in improving cervical joint position sense and are easy to integrate in rehabilitation regimes. Neck muscle vibration is effective in improving cervical joint position sense and pressure pain thresholds within 5 minutes of application.