Isolation of virulent phages against multidrug-resistant Acinetobacter baumannii recovered from inanimate objects of Jimma Medical Center, Southwest Ethiopia.
Because of the multidrug resistance features of Acinetobacter baumannii, endurance to diverse conditions, and causing health fatalities in healthcare settings, the global health system is looking for the development of new antimicrobials for such bacteria. As the new antimicrobial drugs pipeline is running dry, it is imperative to look for eco-friendly bio-control strategies. In this regard, phages are one to combat the biofilm producer and MDR A. baumannii. Thus, the study aimed to isolate and examine the role of phages against biofilm producers and MDR A. baumannii from inanimate objects at Jimma Medical Center (JMC), Ethiopia. Institution-based cross-sectional study was conducted from June to November 2019. A total of 309 swab samples were collected from inanimate objects and the environment in JMC. Isolation of A. baumannii, antimicrobial susceptibility testing, and biofilm detection were carried out according to standard protocol. Kirby Bauer disk diffusion and microliter plate were methods for AST and biofilm detection, respectively. Specific phage was isolated and characterized from sewage at JMC compound. The data were analyzed by SPSS version 25.0, and chi-square (X2) cross-tabulation was used to determine the correlation of variables. A P-value of < 0.05 was considered a statistically significant association. A. baumannii from inanimate objects and surfaces of different environments at JMC was detected in 6.5% of the samples. From 20 of the isolates, 85% were biofilm producers, and 60% were MDR. The lytic phage isolated specifically against A. baumannii was found host specific, and thermally stable ranging from 10-50°C. The phage was active against 42% of MDR A. baumannii, 40% of both biofilm-producing and MDR A. baumannii (MDRAB), and 35.3% of the biofilm-producing isolates. The good activity of phages towards MDRAB isolates, its biofilm degradation capability, thermal stability, and host specificity in our study encourages viewing the potential use of phages as a bio-control agent besides the routine cleansing agents. Therefore, we recommend isolation of specific phages in the eradication of MDRAB from health facilities with additional efforts to characterize in detail and assess their efficacy in animal models.


Grazing high and low: Can we detect horse altitudinal mobility using high-resolution isotope (δ13 C and δ15 N values) time series in tail hair? A case study in the Mongolian Altai.
Carbon and nitrogen stable isotope time series performed in continuously growing tissues (hair, tooth enamel) are commonly used to reconstruct the dietary history of modern and ancient animals. Predicting the effects of altitudinal mobility on animal δ13 C and δ15 N values remains difficult as several variables such as temperature, water availability or soil type can contribute to the isotope composition. Modern references adapted to the region of interest are therefore essential. Between June 2015 and July 2018, six free-ranging domestic horses living in the Mongolian Altaï were fitted with GPS collars. Tail hairs were sampled each year, prepared for sequential C and N isotope analysis using EA-IRMS. Isotopic variations were compared with altitudinal mobility, and Generalized Additive Mixed (GAMMs) models were used to model the effect of geographic and environmental factors on δ13 C and δ15 N values. Less than half of the pasture changes were linked with a significant isotopic shift while numerous isotopic shifts did not correspond to any altitudinal mobility. Similar patterns of δ13 C and δ15 N variations were observed between the different horses, despite differences in mobility patterns. We propose that water availability as well as seasonal availability of N2 fixing type plants primarily controlled horse hair δ13 C and δ15 N values, overprinting the influence of altitude. Our study shows that altitudinal mobility is not the main factor that drives the variations in horse tail hair δ13 C and δ15 N values and that seasonal change in the animal dietary preference also plays an important role. It is therefore risky to interpret variations in δ13 C and δ15 N values of animal tissues in terms of altitudinal mobility alone, at least in C3 -dominated environments.


Nystagmus measured with video-oculography: methodological aspects and normative data.
Detailed analysis of eye movements is essential in order to understand the pathophysiology underlying vestibular disturbances. We applied a commercial video-oculography (VOG) to measure spontaneous and provoked nystagmus in 20 healthy subjects. The slow-phase velocity (SPV) of the nystagmus was calculated. We also simultaneously recorded the eye movements on a standard VHS videotape to be able to confirm the results derived from the VOG paper charts. The nystagmus results derived from the VOG charts and the simultaneous videotaping agreed well. Nystagmus was found in 17 subjects. Spontaneous nystagmus was seen in 20%, positional nystagmus in 55%, and head-shaking nystagmus in 35% of the participants. Although nystagmus was frequent (85%), the mean SPV for nystagmus was low (1.7 degrees /s). The VOG is a modern and sensitive method to record eye movements, but visual inspection of the videotape may be needed in selected cases to confirm occurrence of nystagmus.


The thermal C2-C6/[2 + 2] cyclisation of enyne-allenes: reversible diradical formation.
New enyne-allenes, structurally designed toward the thermal C(2)-C(6)/[2 + 2] cyclisation mode, were prepared and characterised, one of them even by X-ray crystallography. The mechanism of their transformation to formal [2 + 2] cycloadducts was interrogated by trapping experiments and DFT computations. The results support a stepwise mechanism that involves the reversible formation of the C(2)-C(6) diradical intermediate.


Evaluation of an oral subchronic exposure of deoxynivalenol on the composition of human gut microbiota in a model of human microbiota-associated rats.
Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is one of the most prevalent mycotoxins present in cereal crops worldwide. Due to its toxic properties, high stability and prevalence, the presence of DON in the food chain represents a health risk for both humans and animals. The gastrointestinal microbiota represents potentially the first target for these food contaminants. Thus, the effects of mycotoxins on the human gut microbiota is clearly an issue that needs to be addressed in further detail. Using a human microbiota-associated rat model, the aim of the present study was to evaluate the impact of a chronic exposure of DON on the composition of human gut microbiota. Four groups of 5 germ free male rats each, housed in 4 sterile isolators, were inoculated with a different fresh human fecal flora. Rats were then fed daily by gavage with a solution of DON at 100 µg/kg bw for 4 weeks. Fecal samples were collected at day 0 before the beginning of the treatment; days 7, 16, 21, and 27 during the treatment; and 10 days after the end of the treatment at day 37. DON effect was assessed by real-time PCR quantification of dominant and subdominant bacterial groups in feces. Despite a different intestinal microbiota in each isolator, similar trends were generally observed. During oral DON exposure, a significant increase of 0.5 log10 was observed for the Bacteroides/Prevotella group during the first 3 weeks of administration. Concentration levels for Escherichia coli decreased at day 27. This significant decrease (0.9 log10 CFU/g) remained stable until the end of the experiment. We have demonstrated an impact of oral DON exposure on the human gut microbiota composition. These findings can serve as a template for risk assessment studies of food contaminants on the human gut microbiota.


Incorporating community-level risk factors into traumatic stress research: Adopting a public health lens.
Infusing community-level risk factors into traumatic stress research can broaden intervention targets. The Neighborhood Deprivation Index (NDI) and the Index of Concentration at the Extremes (ICE) are two common community-level risk factors derived from U.S. census data. We provide R scripts facilitating the computation of these risk factors and demonstrate their relationship with PTSD symptomatology in 74 injury survivors assessed at 2-weeks, 6-weeks, and 3-months post-injury. The NDI and the ICE were computed using the Census Data Application Programming Interface, then matched to participants' census tracts using their residential addresses. Results indicated that after controlling for person-level characteristics, both risk factors were associated with PTSD symptom severity at follow up time points (Cohen's f2 =0.011,.14). This study provides an easy method for computing the NDI and ICE, demonstrates the increased mental health risk that they convey in the aftermath of injury, and highlights their value in intervention efforts.


[Oral health in the EpiFloripa: a prospective study of adult health in southern Brazil].
To describe methods and challenges of oral health studies nested in a prospective cohort study of adults. A sample of 2,016 adults was investigated in 2009. Household visits were performed in order to apply a questionnaire on socioeconomic, demographic, health related variables, medicine consumption, blood donation, domestic violence and a set of questions related to women's health. Oral health data included self-reported oral health, number of remaining teeth, dental services use, perception of dental treatment needs, occurrence, intensity and impact of dental pain on daily life, xerostomia and chewing impairment due to poor oral health. In addition, participants' blood pressure, weight, height and waist circumference were measured. The second wave of the study was carried out in 2012. A questionnaire on socioeconomic factors, quality of life, discriminatory experiences, 24-hour dietary recall and oral health aspects (the same used in 2009) was applied. In addition, blood pressure, weight, and waist circumference were measured and clinical oral health status was assessed (dental caries, tooth loss, and periodontal outcomes). Participation rate was 85.3% (n = 1,720) in 2009 and, among those, 1,222 (71.1%) were followed up in 2012. The follow-up of this population will contribute in the elucidation of the potentially causal associations between oral outcomes and general chronic diseases.


Early attenuation of autonomic nervous function in senescence accelerated mouse-prone 8 (SAMP8).
The senescence-accelerated mouse (SAM) strain has been established as an inbred strain with an accelerated aging phenotype. SAM prone-8 (SAMP8), one of the SAM strain, exhibits learning disability, immune deficiency, and circadian rhythm loss at a relatively young age. However, it has not been clarified whether aging affects the autonomic nervous activity in SAMP8. The aim of this study was to clarify the utility of SAMP8 in age-related studies of autonomic nervous function. Electrocardiogram (ECG), body temperature, and locomotor activity were recorded to evaluate bio-behavioral activities. Autonomic nervous activity was evaluated via power spectral analysis of heart rate variability from ECG recordings. SAMP8 significantly decreased both biological and autonomic nervous functions, and the animals exhibited circadian rhythm loss of locomotive activity at as early as 40 weeks of age compared with a control strain at the same age. We concluded that the SAMP8 strain can be used as an animal model for age-related studies of autonomic nervous function.


Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange.
Expression of experimental constructs in mammalian cells or transgenic animals is difficult to control because it is markedly influenced by position effects. This has limited both the analysis of cis -DNA regulatory elements for transcription and replication, and the physiological analysis of proteins expressed from transgenes. We report here two new methods based on the concept of recombinase-mediated cassette exchange (RMCE) to perform site-specific chromosomal integration. The first method permits the exchange of a negative selectable marker pre-localized on the chromosome with a transgene via a CRE-mediated double recombination between inverted Lox sites. Integration efficiency is close to 100 % of negatively selected mouse erythroleukemia cells and ranges from 10 to 50 % in embryonic stem cells. The second method allows RMCE with no selection at all except for cells that have taken up plasmid transiently. While less efficient, this technique permits novel experimental approaches. We find that integration of a transgene at a given genomic site leads to reproducible expression. RMCE should be useful to develop artificial genetic loci that impart specific and reproducible regulation of transgenes in higher eukaryotes. This should facilitate the analysis of cis -regulatory DNA elements governing expression and position effects, improve our control over the physiological effects of transgenes, and accelerate the development of animal models for complex human diseases.


Surface Measure to Depth (SMeTD): a new low-budget system for 3D water temperature measurements for combining with UAV-based thermal infrared imagery.
Characterising spatial patterns in water temperature is important for monitoring aquatic habitats and understanding physical and biogeochemical processes to support environmental management decisions. As freshwater bodies exhibit high spatial and temporal variability, high-resolution 3D temperature data are essential to understand local anomalies. The acquisition of simultaneously high spatial and temporal datasets in the field has so far been limited by costs and/or workload associated with commonly used monitoring systems.We present a new, low-cost, spatially and temporally flexible 3D water temperature monitoring system, Surface Measures to Depth (SMeTD). SMeTD can be used to provide information on the relation of water surface temperature to changes with depth, characterise water temperature in 3D and ground truth remotely sensed thermal infrared data. The systems performance was tested under laboratory conditions and under controlled conditions in the field. This revealed an accuracy comparable to established but more expensive monitoring systems. Field testing of SMeTD involved 1-min data collection of 3D water temperature for a full diurnal cycle in a lake. The 3D temperature patterns were supported by a thermal infrared image of the lakes surface. The field dataset demonstrated higher water temperatures and higher water temperature variation at the surface compared to deeper layers. SMeTD can be used to observe a broad range of hydrological processes in natural and artificial aquatic environments and help to understand processes involved with energy budgets, infiltration, limnology, or groundwater surface water exchange.


Impact of the visual environment on the execution of aimed movements.
The present study showed that movement execution depends on the direct visual environment. We replicated findings of an earlier study that showed a difference between real time information via a trace of the unfolding trajectory, and cursor feedback constituting real time information about the changing movement location. Detailed analyses involving subdividing a movement into four successive sections revealed that movements governed by trace feedback were typically slower and required more feedback guidance near the occurrence of peak velocity. The present study further showed that movement behavior under the two visual modes diverged even more due to the presence of a static object positioned within the action area of the movement. Movements in the trace feedback condition were affected by the presence of an object in the second half of the movement trajectory when the movement reached peak deceleration. Discussion focuses on the differences between the two modes of online visual information.


Machine Learning Models for Weight-Bearing Activity Type Recognition Based on Accelerometry in Postmenopausal Women.
Hip-worn triaxial accelerometers are widely used to assess physical activity in terms of energy expenditure. Methods for classification in terms of different types of activity of relevance to the skeleton in populations at risk of osteoporosis are not currently available. This publication aims to assess the accuracy of four machine learning models on binary (standing and walking) and tertiary (standing, walking, and jogging) classification tasks in postmenopausal women. Eighty women performed a shuttle test on an indoor track, of which thirty performed the same test on an indoor treadmill. The raw accelerometer data were pre-processed, converted into eighteen different features and then combined into nine unique feature sets. The four machine learning models were evaluated using three different validation methods. Using the leave-one-out validation method, the highest average accuracy for the binary classification model, 99.61%, was produced by a k-NN Manhattan classifier using a basic statistical feature set. For the tertiary classification model, the highest average accuracy, 94.04%, was produced by a k-NN Manhattan classifier using a feature set that included all 18 features. The methods and classifiers within this study can be applied to accelerometer data to more accurately characterize weight-bearing activity which are important to skeletal health.


Cutaneous infections in wrestlers.
Cutaneous infections are common in wrestlers. Although many are simply a nuisance in the everyday population, they can be problematic to wrestlers because such infections may result in disqualification from practice or competition. Prompt diagnosis and treatment are therefore important. Medline and PubMed databases, the Cochrane Database of Systematic Reviews, and UpToDate were searched through 2012 with the following keywords in various combinations: skin infections, cutaneous infections, wrestlers, athletes, methicillin-resistant Staphylococcus aureus, skin and soft tissue infections, tinea corporis, tinea capitis, herpes simplex, varicella zoster, molluscum contagiosum, verruca vulgaris, warts, scabies, and pediculosis. Relevant articles found in the primary search, and selected references from those articles were reviewed for pertinent clinical information. The most commonly reported cutaneous infections in wrestlers are herpes simplex virus infections (herpes gladiatorum), bacterial skin and soft tissue infections, and dermatophyte infections (tinea gladiatorum). The clinical appearance of these infections can be different in wrestlers than in the community at large. For most cutaneous infections, diagnosis and management options in wrestlers are similar to those in the community at large. With atypical presentations, testing methods are recommended to confirm the diagnosis of herpes gladiatorum and tinea gladiatorum. There is evidence to support the use of prophylactic medications to prevent recurrence of herpes simplex virus and reduce the incidence of dermatophyte infections in wrestlers.


Extracellular matrix in lung development, homeostasis and disease.
The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.


Superoxide generation by Kupffer cells and priming of neutrophils during reperfusion after hepatic ischemia.
The objective of this study was to identify the cellular source of the vascular oxidant stress in hepatic ischemia-reperfusion injury in male Fischer rats. Nonparenchymal cells (Kupffer cells, endothelial cells) and neutrophils were isolated from postischemic liver lobes by collagenase-pronase digestion followed by centrifugal elutriation. The spontaneous and stimulated generation of superoxide by these cells were subsequently quantified in vitro. Large Kupffer cells from the postischemic lobes spontaneously generated 300% more superoxide than similar cells from control animals. No difference in spontaneous superoxide formation was found when the small Kupffer cells were compared. No other cells isolated from the postischemic lobes or control liver including neutrophils released any detectable superoxide spontaneously. In contrast, small Kupffer cells and neutrophils from the postischemic liver generated significantly more superoxide after stimulation with phorbol ester or opsonized zymosan than the controls. The considerably higher response with zymosan stimulation compared to phorbol ester indicates a particular priming for a receptor-mediated signal transduction pathway during reperfusion. These studies demonstrate that Kupffer cells are the principal source of the oxidant stress during the initial reperfusion phase after hepatic ischemia. The priming of neutrophils during this time may be an important factor for the later neutrophil-induced injury phase.


Motivational Interviewing and Caregiver Engagement in the Family Check-Up 4 Health.
Motivational interviewing (MI) is a therapeutic style in which a provider elicits client motivation and helps strengthen commitment to change (Miller and Rollnick 2002). The original Family Check-Up (FCU; Dishion and Stormshak 2007)-and the adapted version for improving health behaviors in primary care, the Family Check-Up 4 Health (FCU4Health; Smith et al. 2018a)-are brief, assessment-driven, and family-centered preventive interventions that use MI to improve parent engagement in services to improve parenting and prevent negative child outcomes. This study examines the role of MI in the Raising Healthy Children project, a randomized trial to test the effectiveness of the FCU4Health for the prevention of obesity in pediatric primary care, with data from the 141 families assigned to receive the FCU4Health. Families were eligible for the study if the child was between 5.5 and 12 years of age at the time of identification and had a BMI ≥ 85th percentile for age and gender at the most recent visit to their primary care provider. MI skills at the first session predicted caregiver in-session active engagement, attendance at follow-up parenting sessions, and improvements in motivation to address child health and behavior goals. Baseline characteristics of the family (i.e., child health diagnosis, caregiver baseline depression, motivation, and Spanish language preference) had differential associations with responsiveness and MI skills. This study has implications for program development, provider training, and fidelity monitoring.


Impact of HMO market structure on physician-hospital strategic alliances.
To assess the impact of HMO market structure on the formation of physician-hospital strategic alliances from 1993 through 1995. The two trends, managed care and physician-hospital integration have been prominent in reshaping insurance and provider markets over the past decade. Pooled cross-sectional data from the InterStudy HMO Census and the Annual Survey conducted by the American Hospital Association (AHA) between 1993 and the end of 1995 to examine the effects of HMO penetration and HMO numbers in a market on the formation of hospital-sponsored alliances with physicians. Because prior research has found nonlinear effects of HMOs on a variety of dependent variables, we operationalized HMO market structure two ways: using a Taylor series expansion and cross-classifying quartile distributions of HMO penetration and numbers into 16 dummy indicators. Alliance formation was operationalized using the presence of any alliance model (IPA, PHO, MSO, and foundation) and the sum of the four models present in the hospital. Because managed care and physician-hospital integration are endogenous (e.g., some hospitals also sponsor HMOs), we used an instrumental variables approach to model the determinants of HMO penetration and HMO numbers. These instruments were then used with other predictors of alliance formation: physician supply characteristics, the extent of hospital competition, hospital-level descriptors, population size and demographic characteristics, and indicators for each year. All equations were estimated at the MSA level using mixed linear models and first-difference models. Contrary to conventional wisdom, alliance formation is shaped by the number of HMOs in the market rather than by HMO penetration. This confirms a growing perception that hospital-sponsored alliances with physicians are contracting vehicles for managed care: the greater the number of HMOs to contract with, the greater the development of alliances. The models also show that alliance formation is low in markets where a small number of HMOs have deeply penetrated the market. First-difference models further show that alliance formation is linked to HMO consolidation (drop in the number of HMOs in a market) and hospital downsizing. Alliance formation is not linked to changes in hospital costs, profitability, or market competition with other hospitals. Hospitals appear to form alliances with physicians for several reasons. Alliances serve to contract with the growing number of HMOs, to pose a countervailing bargaining force of providers in the face of HMO consolidation, and to accompany hospital downsizing and restructuring efforts. Physician-hospital integration is often mentioned as a provider response to increasing cost-containment pressures due to rising managed care penetration. Our findings do not support this view. Alliances appear to serve the hospital's interest in bargaining with managed care plans on a more even basis.


Gene Regulatory Network Rewiring in the Immune Cells Associated with Cancer.
The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i.e., B cell, CD4, CD8, CD8 naïve, CD8 Effector memory, CD8 Central Memory, regulatory T, Thelper1, Thelper2, Thelp17, and NK (Nature killer) and DC (Dendritic cell) cells associated with cancer immunologic therapies. We showed that most of the GRNs of these cells in blood share key important hub regulators, but their subnetworks for controlling cell type-specific receptors are different, suggesting that transformation between these immune cell subsets could be fast so that they can rapidly respond to environmental cues. To understand how cancer cells send molecular signals to immune cells to make them more cancer-cell friendly, we compared the GRNs of the tumor-infiltrating immune T cells and their corresponding immune cells in blood. We showed that the network size of the tumor-infiltrating immune T cells' GRNs was reduced when compared to the GRNs of their corresponding immune cells in blood. These results suggest that the shutting down certain cellular activities of the immune cells by cancer cells is one of the key molecular mechanisms for helping cancer cells to escape the defense of the host immune system. These results highlight the possibility of genetic engineering of T cells for turning on the identified subnetworks that have been shut down by cancer cells to combat tumors.


The Effect of Oral Montelukast in Controlling Asthma Attacks in Children: A Randomized Double-blind Placebo Control Study.
Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The present study was conducted to investigate the clinical efficacy of oral Montelukast for asthma attacks in children. This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission. In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge. The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit.


A European survey on biobanks: trends and issues.
Biobanks have recently gained great significance for research and personalised medicine, being recognised as a crucial infrastructure. At the same time, the widely varied practices in biobanking may also pose a barrier to cross-border research and collaboration by limiting access to samples and data. Nevertheless, the extent of the actual activities and the impact of the level of networking and harmonisation have not been fully assessed. To address these issues and to obtain missing knowledge on the extent of biobanking in Europe, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre, in collaboration with the European Science and Technology Observatory (ESTO), conducted a survey among European biobanks. In total, 126 biobanks from 23 countries responded to the survey. Most of them are small or medium-sized public collections set up either for population-based or disease-specific research purposes. The survey indicated a limited networking among the infrastructures. The large majority of them are stand-alone collections and only about half indicated to have a policy for cross-border sharing of samples. Yet, scientific collaborations based on the use of each biobank appear to be prominent. Significant variability was found in terms of consent requirements and related procedures as well as for privacy and data protection issues among the biobanks surveyed. To help promote networking of biobanks and thus maximise public health benefits, at least some degree of harmonisation should be achieved.


When Limb Surgery Has Become the Only Life-Saving Therapy in FOP: A Case Report and Systematic Review of the Literature.
Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [18F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described.


Influence of the protein structure surrounding the active site on the catalytic activity of [NiFeSe] hydrogenases.
A combined experimental and theoretical study of the catalytic activity of a [NiFeSe] hydrogenase has been performed by H/D exchange mass spectrometry and molecular dynamics simulations. Hydrogenases are enzymes that catalyze the heterolytic cleavage or production of H2. The [NiFeSe] hydrogenases belong to a subgroup of the [NiFe] enzymes in which a selenocysteine is a ligand of the nickel atom in the active site instead of cysteine. The aim of this research is to determine how much the specific catalytic properties of this hydrogenase are influenced by the replacement of a sulfur by selenium in the coordination of the bimetallic active site versus the changes in the protein structure surrounding the active site. The pH dependence of the D2/H(+) exchange activity and the high isotope effect observed in the Michaelis constant for the dihydrogen substrate and in the single exchange/double exchange ratio suggest that a "cage effect" due to the protein structure surrounding the active site is modulating the enzymatic catalysis. This "cage effect" is supported by molecular dynamics simulations of the diffusion of H2 and D2 from the outside to the inside of the protein, which show different accumulation of these substrates in a cavity next to the active site.


[Possibility of predicting the use of doxazosin in the treatment of arterial hypertension].
Fifteen patients with arterial hypertension (AH) were examined. Their peripheral venous hemodynamics, central circulation, systolic and diastolic functions were studied and a course therapy with doxazosin (cardura, Pfizer, USA) was performed for 30 days. Cardura (doxazosin) was found to be the drug of choice for antihypertensive therapy in patients with AH concurrent with baseline systemic venous normo- or hypertension. In patients with baseline venous hypervolemia in the presence of venous hypotension, cardura therapy resulted in deterioration of signs of venous insufficiency and promoted the development (in 38% of the cases) or progression (in 38%) of diastolic dysfunction of the left ventricle (LV). Thus, the venous circulation and LV myocardial function should be originally assessed in order to decide whether cardura (doxazosin) is used in antihypertensive therapy in patients with AH.


4D-DSA: Development and Current Neurovascular Applications.
Originally described by Davis et al in 2013, 4D-Digital Subtraction Angiography (4D-DSA) has developed into a commercially available application of DSA in the angiography suite. 4D-DSA provides the user with 3D time-resolved images, allowing observation of a contrast bolus at any desired viewing angle through the vasculature and at any time point during the acquisition (any view at any time). 4D-DSA mitigates some limitations that are intrinsic to both 2D- and 3D-DSA images. The clinical applications for 4D-DSA include evaluations of AVMs and AVFs, intracranial aneurysms, and atherosclerotic occlusive disease. Recent advances in blood flow quantification using 4D-DSA indicate that these data provide both the velocity and geometric information necessary for the quantification of blood flow. In this review, we will discuss the development, acquisition, reconstruction, and current neurovascular applications of 4D-DSA volumes.


Airway vascular endothelial function in healthy smokers without systemic endothelial dysfunction.
Cigarette smoking can lead to systemic endothelial dysfunction. Since the airway circulation is exposed to a high concentration of cigarette smoke constituents, we reasoned that airway vascular endothelial dysfunction could be present in healthy smokers without systemic endothelial dysfunction. The purpose of this study was to compare airway and systemic endothelial function and measure markers of systemic inflammation in lung-healthy current smokers. Since endothelial dysfunction in smokers has been related to systemic inflammation, we also investigated its response to an inhaled glucocorticosteroid (ICS). Fifteen healthy, current smokers and 17 healthy, lifetime nonsmokers were enrolled. Smokers were randomly assigned to 3-week treatments with inhaled fluticasone propionate or placebo in a crossover design. Vascular endothelial function was assessed in the airway by the airway blood-flow response to inhaled albuterol (ΔQaw) and in the extrapulmonary circulation by brachial arterial flow-mediated vasodilation (FMD). Venous blood was collected for C-reactive protein and IL-6. Baseline parameters did not differ between groups except for ΔQaw, which was greater in nonsmokers (45% ± 12%) than smokers (1% ± 12%) (P = .001). In the smokers, ICS treatment increased Qaw to 41% ± 7% (P < .001), but had no effect on FMD or inflammatory markers. There was an inverse relationship between baseline and ICS-induced changes in ΔQaw. Healthy smokers with no signs of systemic inflammation or endothelial dysfunction display impaired airway vascular endothelial function, possibly preceding systemic endothelial dysfunction. Airway endothelial function was restored with an ICS, and the response was directly related to the severity of endothelial dysfunction.


Honoring Lihong V. Wang, a pioneer in biomedical optics.
A pioneer in optics based on his development of novel optical imaging techniques and acknowledged by a long list of honors, Lihong V. Wang is a model for the aspiring young student or investigator pursuing a career in the rapidly expanding field of biomedical optics and biophotonics.


A comparative study of HO•- and SO4•--based AOPs for the degradation of non-ionic surfactant Brij30.
In the present study aqueous solutions of Brij30, an alcohol ethoxylate surfactant, were photocatalytically and photochemically treated by employing the TiO2/UV-A, H2O2/UV-C and persulfate (PS)/UV-C processes. During TiO2/UV-A treatment, even in short reaction periods (10 minutes), high rates of Brij30 removals were achieved; however, longer experiment periods (240-480 minutes) were needed in order to obtain notable total organic carbon (TOC) removals. Increasing the TiO2 dosage exhibited a positive effect on treatment efficiencies. For initial pH value of 3.0, increasing the TiO2 dosage from 1.0 to 1.5 g/L resulted in an improvement in Brij30 removal from 64% to 79% after 10 minutes whereas 68 and 88% TOC removals were observed after 480 minutes, respectively. Brij30 removal was very fast and complete via both H2O2/UV-C and PS/UV-C treatments, accompanied with significant mineralization rates ranging between 74 and 80%. Toxicity assessed by Vibrio fischeri, was found to be similar to that of the original Brij30 solution during H2O2/UV-C treatment, while in the PS/UV-C process, the relative inhibition of Brij30 towards V. fischeri fluctuated throughout the treatment and eventually non-toxic products were formed by the oxidation of SO4•- radicals.


Internet addiction, insomnia, and violence tendency in adolescents.
There is limited information on how the tendency to violence in adolescents is affected by internet addiction and insomnia. This study will contribute to the literature in revealing the effect of internet addiction on insomnia and violence tendency in adolescents. The data were collected between 26/May/2021 and 06/July/2021. A total of 2,502 adolescents studying in 9th and 12th grades were included in the study. Data were collected with the adolescent information form, Internet Addiction Scale-Short Form, Bergen Insomnia Scale, and Violence Tendency Scale. Descriptive statistics, independent samples t-test, one-way analysis of variance, correlation, and simple linear regression analyzes were used in the analysis of data. Participants were 15.92 ± 1.19 years old and 70.80% were women. While internet addiction do not change according to gender, and violence tendency mean scores do not change according to having a device to use the internet, the study variable mean score changes according to all the other socio-demographic variables included in our study. There is a positive relationship between internet addiction, violence tendency, and insomnia. Furthermore, while internet addiction explained 22.1% of insomnia scores, 18.8% of the variance changes in the violence tendency scores, insomnia explained 11.8% of violence tendency scores. Although the scale scores of the adolescents in our study were below the average, internet addiction is common problem necessitates working on the subject. In our study, there is a significant relationship between internet addiction, insomnia and tendency to violence, and internet addiction predicts other variables.


Poor immunogenicity of the H1N1 2009 vaccine in well controlled HIV-infected individuals.
To evaluate the safety and immunogenicity of the H1N1 2009 vaccine in HIV-positive individuals. A single-arm study. Clinic at the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. HIV-infected adults with an indication for H1N1 vaccination. Single intramuscular 15 microg dose of the monovalent, unadjuvanted, inactivated, split virus H1N1 vaccine. Immunogenicity, safety and tolerability. A total of 120 participants were enrolled, 71% men, 68% African-American, with median age of 46 years. All of them but one were on antiretroviral treatment, with a median current CD4 cell counts of 502 cells/microl, and a nadir CD4 cell counts of 132 cells/microl. The HIV RNA level was below 400 copies/ml in 92% of participants. All participants completed the 3 weeks of follow-up. Thirty of the 120 (25%) participants had antibody hemagglutination-inhibition assay titers equal or greater than 1: 40 at baseline. Among participants without evidence of previous exposure, only 61% develop protective titers by week 3 of the study. Nonresponders had lower current and nadir CD4 cell counts than responders. Only four of nine participants with detectable HIV viral load at baseline developed protective antibody titers. Age and race were not predictors of the response to the vaccine. The vaccine was well tolerated. These results suggest that only 60% of well controlled HIV-infected individuals without preexisting immunity to H1N1 develop protective antibody titers after immunization. Alternative vaccines, dosing, adjuvants or schedule strategies are needed to achieve effective immunization of this vulnerable population.


Measurements of Strontium Levels in Human Bone In Vivo Using Portable X-ray Fluorescence (XRF).
Measurement of bone strontium (Sr) is vital to determining the effectiveness of Sr supplementation, which is commonly used for the treatment of osteoporosis. Previous technology uses radioisotope sources and bulky equipment to measure bone Sr. This study demonstrates the effectiveness of portable X-ray fluorescence (XRF) for bone Sr measurement and validates it using data from a population of 238 children. We identified correlations between bone Sr and age in our participants.


Role of chromosome 9 in human bladder cancer.
The tumors of 20 patients with multifocal primary transitional cell carcinoma of the bladder or lymph node metastases were examined for molecular genetic defects which we have previously found to be present in > 50% of invasive tumors. These included loss of heterozygosity (LOH) of chromosome 9, which occurs in superficial as well as invasive bladder tumors, and LOH of chromosome 17p and p53 mutations, which are commonly found only in invasive tumors. Analysis of multiple or recurrent primary tumors in 7 patients for these markers was generally consistent with recently published data that the tumors are monoclonal in origin and that p53 mutations occur as a late event in the generation of invasive bladder cancers. Comparison of the primary tumors and metastases to regional lymph nodes in 14 patients demonstrated a complete concordance between the molecular genetic defects present, showing that LOH of chromosomes 9 and 17p and p53 mutations occurred in the primary tumors before metastasis. Because of the importance of chromosome 9 in bladder cancer, we mapped the location of a putative tumor suppressor gene by restriction fragment length polymorphism analysis of 123 cases obtained in this and earlier studies. Most of the tumors showed LOH for more than one marker on chromosome 9. Results of mapping of 4 tumors with partial deletion of chromosome 9 suggests that the tumor suppressor gene is located between 9p12 and 9q34.1.


Incidence of extended-spectrum beta-lactamases in clinical isolates of the family Enterobacteriaceae in a pediatric hospital.
The incidence of extended-spectrum beta-lactamases (ESBLs) was analyzed in Enterobacteriaceae population circulating in the Upper Silesian Child and Mother Health Center in Katowice (USC&MHC). Altogether 1164 clinical specimens, collected from children hospitalized in 8 different hospital units of USC&MHC were investigated. Five hundred and eighty-five clinical isolates of the family Enterobacteriaceae were identified in specimens collected from 403 patients. Two hundred and twenty-nine Enterobacteriaceae strains (39%) isolated from 162 patients were found to be putative ESBL producers as revealed by double-disc synergy (DDS) test. ESBL activity was the most prevalent in the population of Klebsiella pneumoniae (77%), followed by Klebsiella oxytoca (50%), Serratia marcescens (43%), Escherichia coli (30%), Enterobacter spp. (18%) and Proteus mirabilis (12%). ESBL producers demonstrated also wide resistance to the non-beta-lactam antimicrobial co-trimoxazole (93%) and the aminoglycosides netilmicin (88%), gentamicin (84%) and amikacin (79%).


Constructing a relevant decision aid for parents of children with bronchopulmonary dysplasia.
To develop and test a decision aid for counseling parents of children with bronchopulmonary dysplasia (BPD).Local problem:Parental education about complex conditions is not standardized and communication and understanding may not be adequate. Semi-structured interviews were conducted with 33 neonatal clinicians and 12 parents of children with BPD using a qualitative research design. The interviews were used to identify education topics that were felt to be important in BPD education. These topics were then used to create a visual decision aid to be used in counseling sessions with parents. The decision aid was then used in mock counseling sessions with 15 'experienced' participants and 7 'naïve' participants to assess its efficacy. The participants completed a pre and post test to assess change in knowledge as well as an 11-question Likert style acceptability survey. Implementation of a decision aid while educating parents about BPD. Topics identified during the interviews were used to create eight educational cards which included pictures, pictographs and statistics. Overall, participants thought the decision aid contained an appropriate amount of information, were easy to understand and improved their knowledge about BPD. Testing demonstrated a significant increase in knowledge in both the 'experienced' (P<0.0001) and 'naïve' group (P=0.0064). A decision aid for parents of children with BPD may improve understanding of the condition and help facilitate communication between parents and doctors.


Developments and Applications of Functional Protein Microarrays.
Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the technology has also been shown to be useful in profiling antibody specificity, as well as in the discovery of novel biomarkers, especially for autoimmune diseases and cancers. In this review, we will summarize the developments that have been made in protein microarray technology in both in basic and translational research over the past decade. We will also introduce a novel membrane protein array, the GPCR-VirD array, and discuss the future directions of functional protein microarrays.


The Translational Landscape of the Human Heart.
Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, suggesting inefficient translation termination. We identify hundreds of previously undetected microproteins, expressed from lncRNAs and circRNAs, for which we validate the protein products in vivo. The translation of microproteins is not restricted to the heart and prominent in the translatomes of human kidney and liver. We associate these microproteins with diverse cellular processes and compartments and find that many locate to the mitochondria. Importantly, dozens of microproteins are translated from lncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology.


Persistence, suppression and re-expression of pigment formation in somatic cell hybrids between mouse melanoma cells and non-melanoma cells.
Pigmented subtetraploid subhexaploid mouse melanoma cells were fused with a range of different cell types. Expression of pigment formation appeared to be dependent on the phenotype of the non-melanoma parent cell, so that hybrids with lymphoid cells or chick embryo erythrocytes produced pigment, but hybrids between fibroblasts or epithelial rat hepatoma cells did not. The results were independent of gene dosage of either parent cell. gamma-irradiation of suppressing partner cells prior to fusion caused progressive increase in pigmentation with increasing dose of radiation. Cybrids between cytoplasts of suppressing fibroblasts and melanoma cells were pigmented.


Potential of far-ultraviolet absorption spectroscopy as a highly sensitive quantitative and qualitative analysis method for aqueous solutions, part I: determination of hydrogen chloride in aqueous solutions.
This paper reports the usefulness of far-ultraviolet (FUV) absorption spectroscopy in highly sensitive quantitative and qualitative analysis of aqueous solutions. We propose a totally new idea for the utilization of FUV spectroscopy in pure water and aqueous solution analyses. We use an absorption band near 170 nm due to an n --> sigma* transition of water. The intensity of the foot of this band, which can be observed in the 190-210 nm region by use of an ordinary ultraviolet-visible (UV-Vis) spectrometer, is very sensitive to changes in hydration and hydrogen bonds of water. To demonstrate the potential of FUV spectroscopy in analytical chemistry, we undertook three kinds of experiments. The first one is concerned with the discrimination of eight kinds of commercial natural mineral water. The eight kinds of mineral water can be discriminated straightforwardly from the spectral patterns in the 190-250 nm region without any spectral pretreatment or spectral analysis such as multivariate analysis. The second experiment is the determination of hydrogen chloride (HCl) in aqueous solutions. FUV spectra of aqueous solutions of HCl over a concentration of 0-20 ppm were measured. A calibration model for predicting the concentration of HCl in the aqueous solutions was developed based on the absorbance at 193 nm. This method does not require any spectral pretreatment or multivariate analysis. The correlation coefficient and standard error of prediction of the calibration model developed are 0.9987 and 0.18 ppm, respectively. The detection limit of the proposal method for the determination of HCl in aqueous solutions was estimated to be 0.5 ppm (13.7 microM). The determination of HCl was also tried for natural mineral water to which HCl solutions with the concentrations of 2, 4, 6, 8, 12, 16, and 20 ppm were artificially added. The third study was the determination of ammonia (NH3) and hydrogen peroxide (H2O2) in aqueous solutions containing both NH3 and H2O2. It has been found that the present method is also useful for the determination of the two-component system.


Detailed Analysis of Insulin Absorption Variability and the Tissue Response to Continuous Subcutaneous Insulin Infusion Catheter Implantation in Swine.
Worldwide, ∼1 million people manage their type 1 diabetes with an insulin pump and a continuous subcutaneous insulin infusion (CSII) catheter. Patients routinely insert a new catheter every 2-3 days due to increasing variability of insulin absorption over time. Catheter insertion and maintenance damage capillaries, lymphatics, cells, and connective tissue leading to an acute inflammatory response. We compared an investigational CSII catheter (IC) and a commercial CSII catheter (CC) regarding insulin absorption pharmacokinetics (PK) and tissue inflammation. The two different catheter designs were implanted into the subcutaneous tissue of six swine for 5 days. Insulin boluses were given on days 1, 3, and 5 of wear-time to assess PK. Tissue around catheters was excised and stained to visualize inflammation and morphological changes of adjacent tissue. Insulin absorption was better when infused through a CC with highest Cmax and fastest tmax values on day 5 of catheter wear-time. Both catheter types produced high intra- and intersubject day-to-day insulin absorption variability. The IC caused significantly more tissue disruption and lead to irregular changes in tissue morphology. Both catheter types were surrounded by a layer of inflammatory tissue that varied in composition, thickness, and density over time. A catheter that was manually inserted by pushing a sharp tip through the skin caused more trauma and variability than a 90° Teflon cannula with automated insertion. Insulin absorption variability could be attributed to the layer of inflammatory tissue, which may function as a mechanical barrier to insulin flow into adjacent vascular tissue. The impact of the acute inflammatory tissue response on insulin absorption has to be considered in future catheter designs. A catheter that was manually inserted by pushing a sharp tip through the skin caused more trauma and variability than a 90° Teflon cannula with automated insertion.


Rapid and direct MALDI-MS identification of pathogenic bacteria from blood using ionic liquid-modified magnetic nanoparticles (Fe3O4@SiO2).
A novel method for pathogenic bacteria identification directly from blood samples using cationic ionic liquid-modified magnetic nanoparticles (CILMS) is reported. The magnetic nanoparticles were prepared by co-precipitation and the core-shell Fe3O4@SiO2 nanoparticles were prepared by the sol-gel process, followed by the grafting of 3-chloropropyltrimethoxysilane that was reacted further with N-methylimidazole to form cationic ionic liquid-modified Fe3O4@SiO2 magnetic nanoparticles (CILMS). The pathogenic bacteria were separated mainly based on the electrostatic interactions among the negative charges of the cell membranes and the positive charges of the CILMS particles. CILMS are used directly without the need for any further apparatus and auxiliary chemicals. The separated cells were detected using matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The lowest detectable number of bacteria was 3.4 × 103, 3.2 × 103, and 4.2 × 103 cfu mL-1 for Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, respectively. The bacterial affinity toward CILMS was investigated using transmission electron microscopy which revealed immobilization of the CILMS on the outer cell membranes. The present approach offers a highly sensitive, fast, and simple method for the cell capture of the pathogenic bacteria. The current approach could be adapted to separate and identify the pathogenic bacteria from septicemic patients or contaminated blood before blood transfusion.


Multienergetic verification of dynamic wedge angles in medical accelerators using multichannel linear array.
The aim of the modern radiotherapy is to get a homogenous dose distribution in PTV, which is obtained by using for example physical or dynamic wedges. The using of a physical wedge has provided such isodose distributions but their use resulted in detrimental dosimetric consequences, for example beam hardening effects and practical consequences of filter handling or possible misalignment. Linear accelerators are now equipped with collimator jaws systems and controlled by modern computers and it is possible to generate wedge shaped isodose distributions dynamically. Because of a more comfortable use of a dynamic wedge, there are alternatives to the standard physical wedge. During the treatment, different segments of the treatment field can be exposed to the primary beam at different intervals of time. This process of shrinking the field while modulating the collimator jaw velocity and dose rate creates the desired wedge-shaped isodose gradient across the treatment field. Dynamic wedges can replace physical wedges but they need more precise dosimetry and quality control procedures. The aim of this study was to perform a multienergetic verification of dynamic wedge angles using the multichannel detector PTW LA48 linear array. The measurements of angle value of dynamic wedges were performed for Clinac 2300 C/D accelerators (Varian). The accelerator was equipped with the EDW option for 6 MV and 15 MV photon beams. In this case, 7 wedge angle values were used: 10°, 15°, 20°, 25°, 30°, 45° and 60°. The dynamic wedges are realized by continuous movement of one collimator jaw. The field size is gradually reduced until the collimator is almost completely closed or the field increases, while the beam is on. The measurements were divided in two steps: in the first step, the dynamic wedges were verified with the recommended values and in the second step there the planned and measured angles of dynamic wedges were compared. Measurements were made by means of LA48 linear array of ionization chambers (PTW). The results of the measurements were compared with the reference profile produced by the treatment planning system ECLIPSE 8.5 (Varian). The results showed differences between measured and calculated angle of dynamic wedges. The differences were observed for both energies in the case of a small angle value. For energies 6 MV and 15 MV, almost all percentage difference between the measured and calculated profile was lower than 5%. The biggest difference was observed in the first step of measurements when the angle of Dynamic Wedge was verified. The comparison between the planned and measured angle value of Dynamic Wedge showed the difference between 0.1% and 4.5%. The difference for 6 MV for the angle value of 10° in orientation IN was 1.1% and for energy 15 MV in the same case the difference was 3.8%. Thinner wedges exhibit less difference. It is necessary to provide comprehensive quality control procedure for enhanced dynamic wedges. Verification measurements should be an obligatory procedure in the recommendation for the testing of medical accelerators. These results are the preliminary results to provide measurements in other Polish Cancer Centres.


Plant parasitic nematode effectors target host defense and nuclear functions to establish feeding cells.
Plant parasitic nematodes are microscopic worms, the most damaging species of which have adopted a sedentary lifestyle within their hosts. These obligate endoparasites have a biotrophic relationship with plants, in which they induce the differentiation of root cells into hypertrophied, multinucleate feeding cells (FCs). Effectors synthesized in the esophageal glands of the nematode are injected into the plant cells via the syringe-like stylet and play a key role in manipulating the host machinery. The establishment of specialized FCs requires these effectors to modulate many aspects of plant cell morphogenesis and physiology, including defense responses. This cell reprogramming requires changes to host nuclear processes. Some proteins encoded by parasitism genes target host nuclei. Several of these proteins were immunolocalized within FC nuclei or shown to interact with host nuclear proteins. Comparative genomics and functional analyses are gradually revealing the roles of nematode effectors. We describe here these effectors and their hypothesized roles in the unique feeding behavior of these pests.


Herpes zoster and small cell bronchogenic carcinoma.
In nine of 74 (12 per cent) consecutive, previously untreated patients with small cell bronchogenic carcinoma receiving combination chemotherapy herpes zoster developed. This is the highest frequenzy reported for this viral infection in patients with nonlymphoproliferative solid tumors. Cutaneous dissemination developed in six of the nine patients, but visceral involvement did not occur. The major difference between the patients with herpes zoster and those without was the superior duration of median survival for the infected patients. No relationship could be established between the development of herpes zoster and the extent of neoplastic disease, prior radiotherapy, treatment with specific chemotherapeutic agents or corticosteroids, cutaneous anergy or granulocytopenia. Serum specimens obtained from six of the nine patients prior to their infection demonstrated the preexistence of varicella zoster antibodies. As more effective and intensive chemotherapy prolongs the survival of patients with solid tumors, it is possible that the frequency of herpes zoster infection may approach that observed in patients with lymphoproliferative malignancies.


Role of Plasmodium falciparum Kelch 13 Protein Mutations in P. falciparum Populations from Northeastern Myanmar in Mediating Artemisinin Resistance.
Mutations in the Plasmodium falciparum Kelch 13 (PfK13) protein are associated with artemisinin resistance. PfK13 is essential for asexual erythrocytic development, but its function is not known. We tagged the PfK13 protein with green fluorescent protein in P. falciparum to study its expression and localization in asexual and sexual stages. We used a new antibody against PfK13 to show that the PfK13 protein is expressed ubiquitously in both asexual erythrocytic stages and gametocytes and is localized in punctate structures, partially overlapping an endoplasmic reticulum marker. We introduced into the 3D7 strain four PfK13 mutations (F446I, N458Y, C469Y, and F495L) identified in parasites from the China-Myanmar border area and characterized the in vitro artemisinin response phenotypes of the mutants. We found that all the parasites with the introduced PfK13 mutations showed higher survival rates in the ring-stage survival assay (RSA) than the wild-type (WT) control, but only parasites with N458Y displayed a significantly higher RSA value (26.3%) than the WT control. After these PfK13 mutations were reverted back to the WT in field parasite isolates, all revertant parasites except those with the C469Y mutation showed significantly lower RSA values than their respective parental isolates. Although the 3D7 parasites with introduced F446I, the predominant PfK13 mutation in northern Myanmar, did not show significantly higher RSA values than the WT, they had prolonged ring-stage development and showed very little fitness cost in in vitro culture competition assays. In comparison, parasites with the N458Y mutations also had a prolonged ring stage and showed upregulated resistance pathways in response to artemisinin, but this mutation produced a significant fitness cost, potentially leading to their lower prevalence in the Greater Mekong subregion.IMPORTANCE Artemisinin resistance has emerged in Southeast Asia, endangering the substantial progress in malaria elimination worldwide. It is associated with mutations in the PfK13 protein, but how PfK13 mediates artemisinin resistance is not completely understood. Here we used a new antibody against PfK13 to show that the PfK13 protein is expressed in all stages of the asexual intraerythrocytic cycle as well as in gametocytes and is partially localized in the endoplasmic reticulum. By introducing four PfK13 mutations into the 3D7 strain and reverting these mutations in field parasite isolates, we determined the impacts of these mutations identified in the parasite populations from northern Myanmar on the ring stage using the in vitro ring survival assay. The introduction of the N458Y mutation into the 3D7 background significantly increased the survival rates of the ring-stage parasites but at the cost of the reduced fitness of the parasites. Introduction of the F446I mutation, the most prevalent PfK13 mutation in northern Myanmar, did not result in a significant increase in ring-stage survival after exposure to dihydroartemisinin (DHA), but these parasites showed extended ring-stage development. Further, parasites with the F446I mutation showed only a marginal loss of fitness, partially explaining its high frequency in northern Myanmar. Conversely, reverting all these mutations, except for the C469Y mutation, back to their respective wild types reduced the ring-stage survival of these isolates in response to in vitro DHA treatment.


Doc2 Proteins Are Not Required for the Increased Spontaneous Release Rate in Synaptotagmin-1-Deficient Neurons.
Regulated secretion is controlled by Ca2+ sensors with different affinities and subcellular distributions. Inactivation of Syt1 (synaptotagmin-1), the main Ca2+ sensor for synchronous neurotransmission in many neurons, enhances asynchronous and spontaneous release rates, suggesting that Syt1 inhibits other sensors with higher Ca2+ affinities and/or lower cooperativities. Such sensors could include Doc2a and Doc2b, which have been implicated in spontaneous and asynchronous neurotransmitter release and compete with Syt1 for binding SNARE complexes. Here, we tested this hypothesis using triple-knock-out mice. Inactivation of Doc2a and Doc2b in Syt1-deficient neurons did not reduce the high spontaneous release rate. Overexpression of Doc2b variants in triple-knock-out neurons reduced spontaneous release but did not rescue synchronous release. A chimeric construct in which the C2AB domain of Syt1 was substituted by that of Doc2b did not support synchronous release either. Conversely, the soluble C2AB domain of Syt1 did not affect spontaneous release. We conclude that the high spontaneous release rate in synaptotagmin-deficient neurons does not involve the binding of Doc2 proteins to Syt1 binding sites in the SNARE complex. Instead, our results suggest that the C2AB domains of Syt1 and Doc2b specifically support synchronous and spontaneous release by separate mechanisms. (Both male and female neurons were studied without sex determination.)SIGNIFICANCE STATEMENT Neurotransmission in the brain is regulated by presynaptic Ca2+ concentrations. Multiple Ca2+ sensor proteins contribute to synchronous (Syt1, Syt2), asynchronous (Syt7), and spontaneous (Doc2a/Doc2b) phases of neurotransmitter release. Genetic ablation of synchronous release was previously shown to affect other release phases, suggesting that multiple sensors may compete for similar release sites, together encoding stimulus-secretion coupling over a large range of synaptic Ca2+ concentrations. Here, we investigated the extent of functional overlap between Syt1, Doc2a, and Doc2b by reintroducing wild-type and mutant proteins in triple-knock-out neurons, and conclude that the sensors are highly specialized for different phases of release.


Non-syndromic monogenic male infertility.
Infertility is a widespread clinical problem affecting 8-12% of couples worldwide. Of these, about 30% are diagnosed with idiopathic infertility since no causative factor is found. Overall 40-50% of cases are due to male reproductive defects. Numerical or structural chromosome abnormalities have long been associated with male infertility. Monogenic mutations have only recently been addressed in the pathogenesis of this condition. Mutations of specific genes involved in meiosis, mitosis or spermiohistogenesis result in spermatogenic failure, leading to the following anomalies: insufficient (oligozoospermia) or no (azoospermia) sperm production, limited progressive and/or total sperm motility (asthenozoospermia), altered sperm morphology (teratozoospermia), or combinations thereof. Androgen insensitivity, causing hormonal and sexual impairment in males with normal karyotype, also affects male fertility. The genetic causes of non-syndromic monogenic of male infertility are summarized in this article and a gene panel is proposed.


[Various indicators of cellular immunity in obesity. Effect of low-calorie diet].
The influence of obesity and a decrease of the body weight in the patients, treated with low-caloric diet, on several indices of cellular immunity has been studied. Absolute and relative T- and B-lymphocyte content, monocyte lysosome content and granulocyte phagocytic activity were examined in the peripheral blood of 27 obese patients and 30 normal subjects. Reversible inhibition of cellular immunity was revealed in the obese patients. The body weight lowering, which resulted from the treatment of obese patients with a low-caloric diet, promoted returning their immunity to normal.


Factors influencing family planning practice among reproductive age married women in Hlaing Township, Myanmar.
To study the factors that influence the family planning practice among married, reproductive age women in Hlaing Township, Myanmar. Cross-sectional survey research was conducted among 284 married, reproductive age women using stratified random sampling. The data were collected through questionnaire interviews during February and March 2012 and analyzed by frequency, percentage, Chi-square test, and multiple logistic regression. The proportion of families practicing family planning was 74.7%, contraceptive injection being the most commonly used method. The factors influencing family planning practice were attitude towards family planning, 24-hour availability of family planning services, health worker support, and partner and friends support. The women with a positive attitude toward family planning practiced family planning 3.7 times more than women who had a negative attitude. If family planning services were available for 24 hours, then women would practice 3.4 times more than if they were not available for 24 hours. When women got fair to good support from health workers, they practiced 15.0 times more on family planning and 4.3 times more who got fair to good support from partners and friends than women who got low support. The factors influencing family planning practice of married, reproductive age women were attitude toward family planning, 24-hour availability of family planning services, health worker support, and partner and friends support. The findings suggest that empowerment of health workers, training of volunteers, pharmacists and contraceptive drug providers, encouraging inter-spousal communication, and peer support, as well as an integrated approach to primary health care in order to target different populations to change women's attitudes on family planning, could increase family planning practice among Myanmar women.


Transcendental meditation and mental retardation.
A 26-year old moderately mentally retarded woman was taught the Transcendental Meditation technique. She experienced spontaneous improvements in her verbal and social behavior and physiological functioning over a period of three years while practicing the technique.


Application of the electron pencil beam redefinition algorithm to electron arc therapy.
This project investigated the potential of summing fixed-beam dose distributions calculated using the pencil-beam redefinition algorithm (PBRA) at small angular steps (1 degree) to model an electron arc therapy beam. The PRBA, previously modified to model skin collimation, was modified further by incorporating two correction factors. One correction factor that is energy, SSD (source-to-surface distance), and field-width dependent constrained the calculated dose output to be the same as the measured dose output for fixed-beam geometries within the range of field widths and SSDs encountered in arc therapy. Another correction factor (single field-width correction factor for each energy) compensated for large-angle scattering not being modeled, allowing a more accurate calculation of dose output at mid arc. The PBRA was commissioned to accurately calculate dose in a water phantom for fixed-beam geometries typical of electron arc therapy. Calculated central-axis depth doses agreed with measured doses to within 2% in the low-dose gradient regions and within 1-mm in the high-dose gradient regions. Off-axis doses agreed to within 2 mm in the high-dose gradient regions and within 3% in the low-dose gradient regions. Arced-beam calculations of dose output and depth dose at mid arc were evaluated by comparing to data measured using two cylindrical water phantoms with radii of 12 and 15 cm at 10 and 15 MeV. Dose output was measured for all combinations of phantom radii of curvature, collimator widths (4, 5, and 6 cm), and arc angles (0 degrees, 20 degrees, 40 degrees, 60 degrees, 80 degrees, and 90 degrees) for both beam energies. Results showed the calculated mid-arc dose output to agree within 2% of measurement for all combinations. For a 90 degree arc angle and 5 x 20 cm2 field size, the calculated mid-arc depth dose in the low-dose gradient region agreed to within 2% of measurement for all depths at 10 MeV and for depths greater than depth of dose maximum R100 at 15 MeV. For depths in the buildup region at 15 MeV the calculations overestimated the measured dose by as much as 3.4%. Mid-arc depth dose in the high-dose gradient region agreed to within 2.2 mm of measured dose. Calculated two-dimensional relative dose distributions in the plane of rotation were compared to dose measurements using film in a cylindrical polystyrene phantom for a 90 degree arc angle and field widths of 4, 5, and 6 cm at 10 and 15 MeV. Results showed that off-axis dose at the ends of arc (without skin collimation) agreed to within 2% in the low-dose gradient region and to within 1.2 mm in the high-dose gradient region. This work showed that the accuracy of the PBRA arced-beam dose model met the criteria specified by Van Dyk et al. [Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)] with the exception of the buildup region of the 15 MeV beam. Based on the present results, results of a previous study showing acceptable accuracy in the presence of skin collimation, and results of a previous study showing acceptable accuracy in the presence of internal heterogeneities, it is concluded that the PBRA arced-beam dose model should be adequate for planning electron arc therapy.


miRNA profiling of circulating EpCAM(+) extracellular vesicles: promising biomarkers of colorectal cancer.
Cancer cells secrete small membranous extracellular vesicles (EVs) into their microenvironment and circulation. These contain biomolecules, including proteins and microRNAs (miRNAs). Both circulating EVs and miRNAs have received much attention as biomarker candidates for non-invasive diagnostics. Here we describe a sensitive analytical method for isolation and subsequent miRNA profiling of epithelial-derived EVs from blood samples of patients with colorectal cancer (CRC). The epithelial-derived EVs were isolated by immunoaffinity-capture using the epithelial cell adhesion molecule (EpCAM) as marker. This approach mitigates some of the specificity issues observed in earlier studies of circulating miRNAs, in particular the negative influence of miRNAs released by erythrocytes, platelets and non-epithelial cells. By applying this method to 2 small-scale patient cohorts, we showed that blood plasma isolated from CRC patients prior to surgery contained elevated levels of 13 EpCAM(+)-EV miRNAs compared with healthy individuals. Upon surgical tumour removal, the plasma levels of 8 of these were reduced (miR-16-5p, miR-23a-3p, miR-23b-3p, miR-27a-3p, miR-27b-3p, miR-30b-5p, miR-30c-5p and miR-222-3p). These findings indicate that the miRNAs are of tumour origin and may have potential as non-invasive biomarkers for detection of CRC. This work describes a non-invasive blood-based method for sensitive detection of cancer with potential for clinical use in relation to diagnosis and screening. We used the method to study CRC; however, it is not restricted to this disease. It may in principle be used to study any cancer that release epithelial-derived EVs into circulation.


Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung.
Rhodococcus equi, and intracellular respiratory pathogen, causes sever e granulomatous pneumonia in humans with AIDS and in young horses. Pulmonary clearance of R. equi requires functional CD4+ T cells and gamma interferon (IFN-gamma) expression from bronchial lymph node cells. The purpose of this study was to investigate whether R. equi-specific CD4+ Th1 cells could effect clearance of R. equi from the lung. Adoptive transfer of a clearance of R. equi from the lungs. In contrast, mice transfused with a R. equi-specific CD4+ Th2 cell line expressed interleukin-4 but not IFN-gamma mRNA, failed to clear pulmonary infection, and developed granulomas in the lung. Control mice, which did not receive cells, did not produce IFN-gamma or interleukin-4 and developed small pulmonary granulomas. These results clearly show that a Th1 response is sufficient to effect pulmonary clearance of R. equi.


A case of acute exacerbation of idiopathic pulmonary fibrosis after proton beam therapy for non-small cell lung cancer.
There have been no reports describing acute exacerbations of idiopathic pulmonary fibrosis after particle radiotherapy for non-small cell lung cancer. The present study describes the case of a 76-year-old Japanese man with squamous cell carcinoma of the lung that relapsed in the left upper lobe 1 year after right upper lobectomy. He had been treated with oral prednisolone 20 mg/day every 2 days for idiopathic pulmonary fibrosis, and the relapsed lung cancer was treated by proton beam therapy, which was expected to cause the least adverse effects on the idiopathic pulmonary fibrosis. Fifteen days after the initiation of proton beam therapy, the idiopathic pulmonary fibrosis exacerbated, centered on the left upper lobe, for which intensive steroid therapy was given. About 3 months later, the acute exacerbation of idiopathic pulmonary fibrosis had improved, and the relapsed lung cancer became undetectable. Clinicians should be aware that an acute exacerbation of idiopathic pulmonary fibrosis may occur even in proton beam therapy, although proton beam therapy appears to be an effective treatment option for patients with idiopathic pulmonary fibrosis.


XAF1 expression and regulatory effects of somatostatin on XAF1 in prostate cancer cells.
Somatostatin prevents cell proliferation by inducing apoptosis. Downregulation of the XAF1 transcript may occur during the development of prostate cancer. It is interesting to evaluate the potential regulatory effects of somatostatin on XAF1 expression during the development of prostate cancer cells. XAF1 mRNA and protein expression in human prostate epithelial cells RWPE-1, androgen dependent prostate cancer LNCaP, and androgen independent DU145 and PC3 cells were evaluated using RT-PCR and Western blot. The regulation of XAF1 mRNA and protein expression by somatostatin and its analogue Octreotide was evaluated. Substantial levels of XAF1 mRNA and proteins were detected in RWPE-1 cells, whereas prostate cancer cells LNCaP, DU145 and PC3 exhibited lower XAF1 expression. Somatostatin and Octreotide up-regulated XAF1 mRNA and protein expression in all prostate cancer cell lines. XAF1 down-regulation may contribute to the prostate cancer development. The enhanced XAF1 expression by somatostatin indicates a promising strategy for prostate cancer therapy.


Viscosity and Self-Diffusion of Liquid Metals.
It is demonstrated that the empirical relationship between activation energy of viscosity and the melting point of a metal is also true for the energy of self-diffusion, in view of the Stokes-Einstein relation. The provision is that viscosity and self-diffusion be expressed in a self-consistent manner, as provided, for example, by the J. Frenkel's theory of liquids. Thus, one can now estimate either the viscosity or the self-diffusion of any metal over a substantial temperature range from its known melting point.


Joint position statement on the management of mesh-related complications for the FPMRS specialist.
The scientific approach to categorizing mesh complications and optimal methods to address them have been complicated by the rapid proliferation and evolution of materials and techniques that have been used over the past 20 years in surgical treatment of pelvic floor disorders. In addition, terminology used to diagnose and categorize mesh complications and the descriptions of surgical procedures to manage them have been adopted inconsistently, further hampering the development of a collective experience with a standardized lexicon. Finally, much of the high-quality data on management of mesh complications is based on materials that are rarely used or not commercially available today.Women experiencing mesh complications need to be heard and should have access to resources and providers who are most able to help. Many women require multiple procedures to address their mesh complications, and for some of these patients, relief is incomplete. We should strive to optimize the treatment at the initial diagnosis of a mesh-related complication.This Position Statement has 4 goals:1. Using the best and most relevant evidence available, provide guidance for the FPMRS subspecialist caring for patients who may be experiencing mesh complications2: Provide an algorithm outlining treatment choices for patients with mesh-related complications that can be used as a platform for shared decision making in the treatment of these complications3: Identify and prioritize gaps in evidence concerning specific mesh complications and their treatments4: Identify provider and health facility characteristics that may optimize the outcomes of treatments for these complications.


Mast cells are required for experimental oral allergen-induced diarrhea.
Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.


Transplacentally transferred maternal-infant antibodies to dengue virus.
Antibodies of all four dengue virus serotypes were detected by hemagglutination inhibition (HI) in 97% of 2,000 infants' cord sera at the time of delivery. In comparison with 250 mother-infant's paired sera, we found that 53% of the infants' serum HI titers were higher than those of the mother's. The mother/infant IgG subclasses 1, 2, 3, and 4 titers were 53.1/87.0, 8.4/11.7, 0.14/0.11, and 1.1/1.0 mg/dL, respectively. In 18 months of follow-up of 100 infants studied, we observed that antibody to dengue virus disappeared in 3% by two months of age, in 19% by four months of age, in 72% by six months of age, in 99% by nine months of age, and in 100% by 12 months of age, with a half-life of 41 days. We conclude that the antibodies to dengue virus disappeared in the first year of life. We suggest that the most appropriate age for vaccination with a live-attenuated dengue vaccine in an endemic area is one year of age.


Framing ecology as an urban concern has merit.
Margrit Hugentobler advocates a version of urban sustainable development which rests on an appeal to nature or "natural harmony." To do this, we have to have conceptions both of nature and of human society. These conceptions will determine, among other things, the extent to which human societies are to be regarded as part of the natural world. Then we have to have ethical or moral premises to argue that human societies and habitations should imitate or emulate nature. These moral premises are assumed rather than validated in Margrit Hugentobler's critique.


An essential function of ribosomal protein S1 in messenger ribonucleic acid translation.
A gentle and efficient method for selectively removing S1 from ribosomes was developed: the S1-free translation system prepared from such ribosomes is stimulated 10-20-fold (depending on the mRNA) by a stoichiometric amount of added purified S1. With this system, we examined the activity of mono- and di-N-ethylmaleimide derivatives of S1 in protein synthesis using synthetic and natural mRNAs and electrophoretic analysis of the translation products. The results show that ribosomes containing such modified S1's are functionally active although at a somewhat lower level (50-80% activity). Since treatment of S1 with N-ethylmaleimide abolishes the helix-destabilizing ability of S1, we conclude that this ability is not primarily responsible for S1's biological function. A new model for the role of S1 is proposed on the basis of the physical, structural, and RNA-binding properties of S1.


Impact of the Cancer Education Program on career paths of students.
A questionnaire sent to former University of North Carolina students who participated in the Cancer Education Program, a National Cancer Institute sponsored program designed to provide integrated educational opportunities in oncology for students in the health science schools, ascertained the career paths taken by students and elicited opinions regarding the impact of the program on those decisions. One hundred five surveys were returned. The opportunity to be involved in cancer research was the most common reason given for participation in the program (65 respondents). The opportunity to work with a specific faculty member (48) and improving academic credentials (44) were also important. Twenty-three individuals changed their career goals after participation in this program, 20 decided to pursue cancer-related careers, and 3 decided to avoid this field. One hundred three individuals were currently in health professions, 58 in academic, and 45 in community-based practice. Twenty-seven were not involved with cancer, while 56 spent up to 25% of their professional time, 8 spent 25%-50%, and 9 spent over 50% of their professional time in cancer-related activities.


Transcription Factors in Fungi: TFome Dynamics, Three Major Families, and Dual-Specificity TFs.
Transcription factors (TFs) are essential regulators of gene expression in a cell; the entire repertoire of TFs (TFome) of a species reflects its regulatory potential and the evolutionary history of the regulatory mechanisms. In this work, I give an overview of fungal TFs, analyze TFome dynamics, and discuss TF families and types of particular interest. Whole-genome annotation of TFs in more than 200 fungal species revealed ~80 families of TFs that are typically found in fungi. Almost half of the considered genomes belonged to basidiomycetes and zygomycetes, which have been underrepresented in earlier annotations due to dearth of sequenced genomes. The TFomes were analyzed in terms of expansion strategies genome- and lineage-wise. Generally, TFomes are known to correlate with genome size; but what happens to particular families when a TFome is expanding? By dissecting TFomes into single families and estimating the impact of each of them, I show that in fungi the TFome increment is largely limited to three families (C6 Zn clusters, C2H2-like Zn fingers, and homeodomain-like). To see whether this is a fungal peculiarity or a ubiquitous eukaryotic feature, I also analyzed metazoan TFomes, where I observed a similar trend (limited number of TFome-shaping families) but also some important differences connected mostly with the increased complexity in animals. The expansion strategies of TF families are lineage-specific; I demonstrate how the patterns of the TF families' distributions, designated as "TF signatures," can be used as a taxonomic feature, e.g., for allocation of uncertain phyla. In addition, both fungal and metazoan genomes contain an intriguing type of TFs. While usually TFs have a single DNA-binding domain, these TFs possess two (or more) different DNA-binding specificities. I demonstrate that dual-specific TFs comprising various combinations of all major TF families are a typical feature of fungal and animal genomes and have an interesting evolutionary history involving gene duplications and domain losses.


Physician practices, e-prescribing and accessing information to improve prescribing decisions.
Hoping to reduce medication errors and contain health care costs, policy makers are promoting electronic prescribing through Medicare and Medicaid financial incentives. Many e-prescribing systems provide electronic access to important information--for example, medications prescribed by physicians in other practices, patient formularies and generic alternatives--when physicians are deciding what medications to prescribe. However, physician practices with e-prescribing face challenges using these features effectively, according to a new qualitative study by the Center for Studying Health System Change (HSC) funded by the Agency for Healthcare Research and Quality (AHRQ). While most of the 24 practices studied reported that physicians had access to patient formulary information, only slightly more than half reported physician access to patient medication histories, and many physicians did not routinely review these sources of information when making prescribing decisions. Study respondents highlighted two barriers to use: (1) tools to view and import the data into patient records were cumbersome to use in some systems; and (2) the data were not always perceived as useful enough to warrant the additional time to access and review them, particularly during time-pressed patient visits. To support generic prescribing, practices typically set their system defaults to permit pharmacist substitution of generics; many practices also used other tools to more proactively identify and select generic alternatives at the point of prescribing. Overall, physicians who more strongly perceived the need for third-party data, those in practices with greater access to complete and accurate data, and those with easier-to-use e-prescribing systems were more likely to use these features consistently.


Electrosynthesis of Biobased Chemicals Using Carbohydrates as a Feedstock.
The current climate awareness coupled with increased focus on renewable energy and biobased chemicals have led to an increased demand for such biomass derived products. Electrosynthesis is a relatively new approach that allows a shift from conventional fossil-based chemistry towards a new model of a real sustainable chemistry that allows to use the excess renewable electricity to convert biobased feedstock into base and commodity chemicals. The electrosynthesis approach is expected to increase the production efficiency and minimize negative health for the workers and environmental impact all along the value chain. In this review, we discuss the various electrosynthesis approaches that have been applied on carbohydrate biomass specifically to produce valuable chemicals. The studies on the electro-oxidation of saccharides have mostly targeted the oxidation of the primary alcohol groups to form the corresponding uronic acids, with Au or TEMPO as the active electrocatalysts. The investigations on electroreduction of saccharides focused on the reduction of the aldehyde groups to the corresponding alcohols, using a variety of metal electrodes. Both oxidation and reduction pathways are elaborated here with most recent examples. Further recommendations have been made about the research needs, choice of electrocatalyst and electrolyte as well as upscaling the technology.


An isokinetic muscle strengthening program for adults with an acquired brain injury leads to meaningful improvements in physical function.
To investigate if an isokinetic strength training programme for leg muscles lead to personally meaningful changes in adults with an acquired brain injury (ABI). A qualitative exploratory design. Twelve people with ABI participated in pre- and post-intervention face-to-face interviews with open ended questions. Data were initially analysed using a case study research approach exploring individuals experiences and then cross case analysis to determine common themes for the group. Twelve-week isokinetic strength training programme for ankle and knee muscles. Participants perceived changes. Thematic analysis determined four main themes arising from the interviews; occupation, vitality, sense of self and personal interactions. Participants reported reductions in impairments as a response to the exercise programme and these changes led to increased function and participation in activities they valued. Also marked improvements in vitality were reported as well as increases in self-esteem and general well-being for many participants. An isokinetic strength training programme resulted in improvements in motor skills and functional abilities that were meaningful for the participants.


A classification scheme for aggregating U.S. census occupation and industry codes.
The use of occupation as a surrogate for workplace exposures when more specific information is unavailable is common yet is particularly challenging in studies involving many diverse occupations. A classification scheme that aggregates workers based on similar job tasks and potential exposures was developed for use in a Canadian study, and its adaptation for a similar U.S. study is described. The 56 occupational categories and 1980 U.S. census occupation and industry codes used to create each are presented. The scheme was developed using the distribution of occupations and industries in two limited study populations, and no exposure measurements were taken in its preparation. However, the aggregation of jobs with similar exposures has practical utility in the analysis of a large number of specific occupations, each with a small number of workers. As a result, the scheme presented can provide a starting point for researchers facing this task in the analysis of case-control occupational data.