A Quasi species of the pre-S/S gene and mutations of enhancer II/core promoter/pre-C in mothers and their children infected with hepatitis B virus via mother-to-infant transmission.
Hepatitis B virus (HBV) infection has a tendency to be chronic. The quasi species of HBV in the pre-S/S gene and mutations in enhancer II (EnhII)/core promoter (CP)/pre-C of HBV were studied in asymptomatic carrier (AsC) mothers and their children with different virus loads, to gain a better understanding of the pathogenic mechanisms of HBV. Quasi species were analyzed using an established phylogenetic tree based on the sequences of the pre-S/S gene from 3 mother-child pairs. The mutations of EnhII/CP/pre-C were studied in 15 mother-child pairs. Substitution was the main mutation model. The phylogenetic tree indicated that the pre-S/S gene in every mother-child pair had the same root. The sequences of the pre-S/S gene of each patient were somewhat different from one another, but there was limited evolutionary distance between them. The evolutionary distances between the pre-S/S gene and the base of the tree in patients with low virus loads were greater than those in patients with high virus loads. The mutations in patients with low virus loads were much more frequent than those in patients with high virus loads and were not related to age, irrespective of whether the pre-S/S gene or EnhII/CP/pre-C was considered. There are HBV quasi species in the sera of AsCs, and the mutations are related to virus load and hepatitis B e antigen seroconversion, irrespective of age.


Palladium-catalysed carbonylative α-arylation of acetone and acetophenones to 1,3-diketones.
Three COmponent -arylation: A carbonylative ketone -arylation process employing acetone for the first time, as well as acetophenones, is described (see scheme). The reaction tolerates a range of (hetero)aryl iodides and several functionalised aryl ketone coupling partners. Only low pressures of molecular CO are applied and no additional solvent is necessary.


Status and future developments in the physical aspects of hyperthermia.
The state of hyperthermia physics is reviewed. Major changes affecting the field are: (a) it is becoming far more sophisticated than just a few years ago, now that experts from many engineering and physical specialties are involved; (b) the ubiquitous computer is central to developments in data acquisition and analysis, treatment control, device comparison, treatment planning, and thermal dosimetry; and (c) entrepreneurial firms are arising to produce clinically engineered equipment. University and other research centers can concentrate their efforts on investigating new technologies up to the development of physical prototypes; they need no longer spend time on constructing complete clinical systems. At present, regional heating systems are unable to reliably induce therapeutic temperatures throughout the entire tumor volume. Interstitial techniques are able to accomplish this and so may make the greatest clinical impact in the near future. Invasive thermometry coupled with computerized data acquisition systems and numerical models appears to be a very promising approach to detailed thermal dosimetry. The tools for performing good clinical trials of hyperthermia are gradually becoming available.


Medical encounter characteristics of HIV seroconverters in the US Army and Air Force, 2000–2004.
Active duty US Army and Air Force military personnel undergo mandatory biennial HIV antibody screening. We compared pre- and post-HIV seroconversion health status by conducting a case-control study, which evaluated all medical encounters and sociodemographic factors among incident HIV seroconverters and HIV-negative controls from June 2000 through February 2004. A total of 274 HIV seroconverters and 6205 HIV-negative personnel were included. In multivariate analysis restricted to male personnel (cases = 261, controls = 5801), single marital status (adjusted odds ratio [AOR] = 14.37), clinical indicators or symptoms within four years of HIV diagnosis (AOR = 6.22), black race (AOR = 5.88), nonindicator clinical syndromes within 2 years of HIV diagnosis (AOR = 3.31), any mental disorder within 4 years of HIV diagnosis (AOR = 3.04), increasing service-connected time (AOR = 1.69), and older age (AOR = 1.12) were associated with HIV diagnosis among males. A prior history of a sexually transmitted infection (STI) was associated with post-HIV seroconversion STI (OR(M-H) = 4.10). Similarly, a prior history of mental disorder was associated with post-HIV seroconversion mental disorder (OR(M-H) = 4.98). Forty-seven (18%) male cases were hospitalized at least once after HIV diagnosis; infectious diseases, and mental disorders made up 53% of initial admissions. HIV seroconversion was associated with increased health care-seeking behavior, STIs, and mental disorders, some of which may be amenable to screening. The higher STI rate after HIV diagnosis may partially be a consequence of monitoring, but secondary transmission of STI and possibly HIV require further definition and subsequent tailored preventive interventions.


Evaluation of LDL subfractions in vascular complications of familial hypercholesterolemia.
The authors attempted to investigate the possibility of estimating modified LDL (acetylated LDL, oxidative LDL and glucosylated LDL) with peroxidized lipid in the native LDL from patients with familial hypercholesterolemia (FH). A group of 7 patients with FH were studied, with age ranging from 18 to 60 years. 10 ml of fasting blood were collected into siliconized syringes with 0.5 ml of 0.05 M ethylene diamine tetraacetic acid 2Na. LDL, LDL1 and LDL2 were separated by sequential ultracentrifugation. Total cholesterol (TC), triglycerides (TG) and phospholipids (PL) were estimated by enzymatic methods. Analyses of lipids in each LDL were done by thin layer chromatography (TCL). The modified LDL in native LDL of the FH patients was estimated by the authors' own method. The cholesterol concentration of LDL was 0.49 +/- 0.28 mmol/L in FH patients and 0.07 +/- 0.04 mmol/L in the healthy persons (P < 0.001). The LDL1 cholesterol concentrations in the patients with FH and the normal controls were similar while that of the LDL2 was of significant difference (P < 0.05). On the TLC plate, the detection of the spot X1 was considered an indicator of the existence of modified LDL. The percentages of spot X1 in LDL of FH patients were higher in all 3 fractions (LDL, LDL1, and LDL2), as compared to the corresponding percentages of spot X1 in the healthy controls. (P < 0.001). Using the authors' own method, the molecular size were found in the order of LDL > LDL1 > LDL2.


Outcome Of Use Of 1% Silver Nitrate In Patients With Low Lying Perianal Fistula.
Anorectal fistula is a common illness which is seen among the middle-aged male patients. Various surgical procedures have been proposed and are associated with the recurrence of the fistula, repeated surgery and in some cases incontinence which may reach up to 43% in complicated fistulas. The purpose of this study was to assess and formulate a non-surgical procedure for fistula in ano through irrigation of the fistula tract with 1% of silver nitrate solution in healing the low perianal fistula. Seventy-nine patients presenting to the outpatient department of Ward 3, Surgical unit 1 in Jinnah Postgraduate Medical Centre during a period of 8 months from April to November 2017 with complain of perianal pain and pussy discharge were included in the study. Three patients of the total 79 patients lost to follow up. Outcome measure were cessation of the symptoms for consecutive 10 weeks. Seventy-six patients were assessed and underwent irrigation using this 1% of silver nitrate solution. Out of 76 patients, 58 (76.3%) patients showed complete clinical healing while 18 (23.68%) of patients showed failure to clinical healing. Patients with continuous discharge had a significantly higher rate of complete clinical healing than those with intermittent discharge. From this study it can be concluded that cauterizing and corrosive properties of silver nitrate are effective in treating the patients with low lying perianal fistula. We suggest that this method should be used as a first line treatment option for all the patients presenting with low lying anal fistula since it is simple, can be easily performed on an OPD basis is minimally invasive and avoids any complication.


Re K.D. (a minor), 18 February 1988.
The British House of Lords held that, if a child's welfare so dictates, a parent's access can be terminated in wardship proceedings so as to permit a local authority to place the child for adoption. It rejected an argument that such termination of access was contrary to fundamental notions of family life and family ties as expressed in Article 8 of the European Convention for the Protection of Human Rights and Fundamental Freedoms. It ruled that the child's welfare principle and Article 8 both expressed the concept that the natural bond and relationship between a parent and child should be interfered with only if the child's welfare so dictates.


Outreach syphilis testing services by different health providers to female sex workers in southern China.
Health providers have played important roles on delivering prevention and care services to control syphilis in China. The current study was aimed to evaluate the performance of different health providers in providing outreach syphilis testing services to female sex workers (FSWs). The current study carried out during April to August 2009 in Liuzhou was aimed to investigate the services delivered by two different types of clinics in China. A total of 1,808 FSWs recruited from sex work venues were included in the study. Prevalence of positive syphilis test (6.4%) among FSWs accessed by the local center for disease control outreach teams (CDC teams) was significantly lower than that (9.3%) among FSWs accessed by the local reproductive health hospital outreach teams (RHH teams). As compared with CDC teams, RHH teams had more FSWs to be successfully referred to the designated STD clinics for further syphilis confirmation and intervention (85.7% vs. 26.7%, P<0.001). These findings indicate that RHH teams may be more efficient than CDC teams to provide outreach-based services to FSWs. Participation of the reproductive health providers or other medical facilities in outreach services to FSWs should be considered in developing intervention programs in China.


Is Instrumental Compression Equally Effective and Comfortable for Physiotherapists and Physiotherapy Students than Manual Compression? A Comparative Cross-Sectional Study.
The objective of this work is to compare the homogeneity of instrumental and manual compression during the simulation of a pressure release technique, measured with a dynamometer, as well as to evaluate the comparative degree of comfort by physiotherapists and physiotherapy students when performing this technique. A comparative cross-sectional study was carried out with physiotherapists (lecturers with clinical experience) and 4th year students of the Physiotherapy Degree at Universidad San Jorge. The amount of pressure performed and how it was maintained during 80 s with both techniques was analysed using a digital dynamometer. The degree of comfort was evaluated using a modified numeric rating scale, with higher values representing a higher degree of discomfort. A total of 30 subjects participated. Significant differences were found between the techniques in terms of maintaining a constant pressure level for 80 s (p = 0.043). A statistically significant difference was found between both techniques in the period from 45 to 80 s. Regarding the degree of discomfort, the value obtained from the students' responses was 4.67 (1.35) for the manual technique and 1.93 (0.88) for the instrumental technique. In the case of physiotherapists, the comfort was 4.87 (2.13) for the manual technique and 3.33 (1.54) for the instrumental technique. The sustained manual compression necessary in manual pressure release techniques in the treatment of myofascial trigger points can be performed with assistive tools that guarantee a uniform compression maintained throughout the development of the technique and are more comfortable for physiotherapists.


Design of a High-Performance Micro Integrated Surface Plasmon Resonance Sensor Based on Silicon-On-Insulator Rib Waveguide Array.
Based on silicon-on-insulator (SOI) rib waveguide with large cross-section, a micro integrated surface plasmon resonance (SPR) biochemical sensor platform is proposed. SPR is excited at the deeply etched facet of the bend waveguide by the guiding mode and a bimetallic configuration is employed. With the advantages of SOI rib waveguide and the silicon microfabrication technology, an array of the SPR sensors can be composed to implement wavelength interrogation of the sensors' output signal, so the spectrometer or other bulky and expensive equipment are not necessary, which enables the SPR sensor to realize the miniaturization and integration of the entire sensing system. The performances of the SPR sensor element are verified by using the two-dimensional finite-different time-domain method. The parameters of the sensor element and the array are optimized for the achievement of high performance for biochemical sensing application. As a typical example, a single bimetallic SPR sensor with 3 nm Au over 32 nm Al possesses a high sensitivity of 3.968 × 104 nm/RIU, a detection-accuracy of 14.7 μm(-1). For a uniparted SPR sensor, it can achieve a detection limit of 5.04 × 10(-7) RIU. With the relative power measurement accuracy of 0.01 dB, the refractive index variation of 1.14 × 10(-5) RIU can be detected by the SPR sensor array.


Blunt thoracic injury in older adults: application of Haddon's phase-factor matrix model.
Blunt thoracic injury (BTI) in older adults can lead to grave illness, permanent disability, and even death. Using Haddon's phase-factor matrix model, this article examines the phenomenon of BTI in older adults. Preventive, diagnostic, and treatment interventions are discussed from the perspective of the pre-event, event, and post-event phases. Relevant physiological and pathophysiological changes regarding senescence and injury are reviewed, as are the common mechanisms of blunt trauma and anatomic injury patterns seen in older adults. Considerations for clinical interventions and future research are also presented.


Food Animal Residue Avoidance Databank (FARAD): An Automated Pharmacologic Databank for Drug and Chemical Residue Avoidance.
The Food Animal Residue Avoidance Databank (FARAD) is a comprehensive computerized databank of regulatory and pharmacologic information useful for mitigation of drug and chemical residue problems in food-producing animals. For drugs, the databank contains information on proprietory products, labelled indications for use, and approved withdrawal and milk discard times. For drugs and chemicals, data are available on physiochemical properties of the chemical or generic drug, on tissue, egg and milk tolerances of these compounds, and on their pharmacokinetic behavior. This latter category is the most unique aspect of FARAD as it involves an extensive statistical analysis of published data, which results in estimates of the rates of depletion of these compounds in target animal species. These data have not been previously available. All data in FARAD are linked to specific sources which are listed in a citation file. Finally, resources produced as a result of USDA Residue Avoidance Program projects are listed in the database. Access to the databank is available at three regional access centers in California (916-752-7507), Illinois (217-333-3611) and Florida (904-392-4085), while the databank is maintained at a data analysis and support center in North Carolina. FARAD presently contains over 7,000 records with information on 250 compounds, and is supported by the USDA-Extension Service's Residue Avoidance Program.


Recurrent injection site reactions from interferon beta 1-b.
Recombinant human interferon beta-1b is an immune-modulatory drug used for a variety of conditions including multiple sclerosis (MS). Skin reactions to therapeutic use of injectable interferon beta-lb are relatively common, including injection site reactions and exacerbation of underlying skin disease. Injection site reactions are seen much more frequently in females. We discuss a case of prolonged susceptibility to injection site reaction with over a decade of use of interferon beta 1-b for MS. Given the prevalence of such reactions, the dermatologist should be aware of the phenomenon and that it frequently does not necessitate discontinuation of therapy.


Inflammation, antichymotrypsin, and lipid metabolism: autogenic etiology of Alzheimer's disease.
Alzheimer's disease is a multifactor pathology, some of whose causes have been inferred from genetic studies, primarily of associated early-onset cases. Much evidence implicates the A beta amyloid peptide as a neurotoxic agent, with chronic inflammation as an accompanying physiological contributor to the disease. The two central questions of how A beta kills neurons and of the autogenic basis of disease remain unanswered. We hypothesize that specific interactions of A beta with the inflammatory serpin, alpha 1-antichymotrypsin, abolish the serpin proteinase inhibitor activity and stimulate formation of the neurotoxic fibrillar form of A beta. Further, the fibrillar A beta interacts with specific cell surface receptors, prompting its own biosynthesis and disrupting cellular cholesterol metabolism. These molecular and cellular interactions autogenically sustain the processes of A beta formation, fibrillization, and receptor interaction, the last of which culminates in neuronal death through disruption of cholesterol metabolism.


Everyday moral decision-making after acute stress exposure: do social closeness and timing matter?
There is increasing empirical evidence that social distance and timing affect prosocial behavior after acute stress exposure. The present study focused on everyday moral decision-making after acute psychosocial stress and how it is influenced by effects of social closeness and timing. We exposed 40 young healthy men to the Trier Social Stress Test (TSST, n = 20) or its non-stressful placebo version (PTSST, n = 20). Moral decision-making was assessed early (+10 until +30 min) and late (+75 until +95 min) after (P)TSST exposure by the Everyday Moral Conflict Situations (EMCS) Scale. The EMCS Scale requests altruistic versus egoistic responses to everyday moral conflict situations with varying closeness of target persons. Results revealed significantly higher total percentages of altruistic decisions in the stress than in the control condition and for scenarios involving socially close (e.g., mother) versus socially distant (e.g., stranger) protagonists, while the main effect of timing was nonsignificant. Only secondary analyses showed increased altruistic decision-making after acute stress exposure toward socially close but not toward distant protagonists at the early but not at the late point of measurement. Moreover, psychological stress responses and personality traits were significantly associated with EMCS scores. Positive correlations between cortisol levels and altruistic decision-making were descriptively observable, but did not reach statistical significance. In sum, our findings suggest increased altruistic decision-making toward socially close compared to socially distant protagonists and provide further evidence that acute stress influences decision-making in everyday moral conflict scenarios in a prosocial manner.Lay summaryIn order to investigate the effects of acute stress on everyday moral decision-making, 40 young healthy men were exposed to moderate psychosocial stress by the use of the Trier Social Stress Test (TSST) or its non-stressful placebo version and then completed a hypothetical everyday moral decision-making paradigm. Our findings provide evidence that acute stress exposure influences decision-making in everyday moral conflict situations in a prosocial manner. Furthermore, participants decided more altruistically in scenarios involving socially close (e.g., mother) versus socially distant (e.g., stranger) protagonists.


Opportunities, challenges and trade-offs with decreasing avoidable food waste in the UK.
Around 6 million tonnes of edible food are being wasted (post-farm gate) in the UK each year. This fraction of edible wasted food is known as avoidable food waste. In a circular economy food is a valuable resource that must be captured at all stages of the food supply chain and, where possible, redistributed for consumption. This can prevent avoidable food waste generation, and dissipation of food's multidimensional value that spans environmental, economic, social, technical and political/organisational impacts. While the importance and benefits of surplus food redistribution have been well documented in the global literature, there are still barriers that prevent perfectly edible food from being wasted. This study looks at the main stages of the food supply chain, and amasses the opportunities, challenges and trade-offs associated with surplus food redistribution to the UK economy. It highlights points in the food system where interventions can be made, to improve food's circularity and sustainability potential. Stakeholder interrelations, regulatory and socio-economic aspects are discussed in relation to their influence on decreasing avoidable food waste. The main output from this work is a diagrammatic depiction of where challenges and trade-offs occur along the food supply chain, and how policy and socio-economic reforms are needed to maximise avoidable food waste prevention, and the surplus avoidable food redistribution in the food supply chain for social benefit.


Synthesis, structure, and physical properties of 5,7,14,16-tetraphenyl-8:9,12:13-bisbenzo-hexatwistacene.
A novel compound, 5,7,14,16-tetraphenyl-8:9,12:13-bisbenzo-hexatwistacene (TBH), has been successfully synthesized through a retro-Diels-Alder reaction. Single-crystal structure analysis indicated that TBH has a twisted configuration with a torsion angle of 27.34°. The HOMO-LUMO gap of TBH calculated from the difference between the half-wave redox potentials (E(1/2) (ox) =+0.40 eV and E(1/2)(red) =-1.78 eV) is 2.18 eV, which is in good agreement with the band gap (2.19 eV) derived from the UV/Vis absorption data. In addition, organic light-emitting devices using TBH as emitter have been fabricated. The results revealed that TBH is a promising red light-emitting candidate for applications in organic light-emitting diodes.


Near-ultraviolet lateral photovoltaic effect in Fe3O4/3C-SiC Schottky junctions.
In this paper, we report a sensitive lateral photovoltaic effect (LPE) in Fe3O4/3C-SiC Schottky junctions with a fast relaxation time at near-ultraviolet wavelengths. The rectifying behavior suggests that the large build-in electric field was formed in the Schottky junctions. This device has excellent position sensitivity as high as 67.8 mV mm-1 illuminated by a 405 nm laser. The optical relaxation time of the LPE is about 30 μs. The fast relaxation and high positional sensitivity of the LPE make the Fe3O4/3C-SiC junction a promising candidate for a wide range of ultraviolet/near-ultraviolet optoelectronic applications.


Differential scanning calorimetric studies of nickel-titanium rotary endodontic instruments after simulated clinical use.
Differential scanning calorimetric (DSC) analyses have been performed between -130 degrees and 100 degrees C on single-segment specimens obtained from ProFile and Lightspeed nickel-titanium rotary endodontic instruments in the as-received condition and after one, three, and six periods of simulated clinical use in extracted teeth. The DSC analyses showed that both brands of instruments were always in the superelastic condition, although the enthalpy values for the transformation from martensitic NiTi to austenitic NiTi were much smaller for the Lightspeed instruments. Simulated clinical use had no evident effect upon this transformation for both brands, which is attributed to insufficient mechanical deformation of the instruments. There were substantial differences in the enthalpy change associated with the transformation from martensitic NiTi to austenitic NiTi for test segments from different positions along the shafts of the instruments and for as-received instruments from two different batches that were analyzed in this study and a previous study. These differences are attributed to variations in work hardening along the shaft during instrument fabrication and to processing differences during production of the two batches of each instrument brand.


Online IMU Self-Calibration for Visual-Inertial Systems.
Low-cost microelectro mechanical systems (MEMS)-based inertial measurement unit (IMU) measurements are usually affected by inaccurate scale factors, axis misalignments, and g-sensitivity errors. These errors may significantly influence the performance of visual-inertial methods. In this paper, we propose an online IMU self-calibration method for visual-inertial systems equipped with a low-cost inertial sensor. The goal of our method is to concurrently perform 3D pose estimation and online IMU calibration based on optimization methods in unknown environments without any external equipment. To achieve this goal, we firstly develop a novel preintegration method that can handle the IMU intrinsic parameters error propagation. Then, we frame IMU calibration problem into general factors so that we can easily integrate the factors into the current graph-based visual-inertial frameworks and jointly optimize the IMU intrinsic parameters as well as the system states in a big bundle. We evaluate the proposed method with a publicly available dataset. Experimental results verify that the proposed approach is able to accurately calibrate all the considered parameters in real time, leading to significant improvement of estimation precision of visual-inertial system (VINS) compared with the estimation results with offline precalibrated IMU measurements.


How do yeast cells sense glucose?
A glucose-sensing mechanism has been described in Saccharomyces cerevisiae that regulates expression of glucose transporter genes. The sensor proteins Snf3 and Rgt2 are homologous to the transporters they regulate. Snf3 and Rgt2 are integral plasma membrane proteins with unique carboxy-terminal domains that are predicted to be localized in the cytoplasm. In a recent paper Ozcan and colleagues [Ozcan S, et al. EMBO J 1998; 17:2556-2773 (Ref. 1)] present evidence that the cytoplasmic domains of Snf3 and Rgt2 are required to transmit a glucose signal. They provide additional evidence to support their earlier assertion [Ozcan S, et al. Proc Natl Acad Sci USA 1996;93:12428-12432 (Ref. 2)] that glucose transport via Snf3 and Rgt2 is not involved in glucose sensing but, rather, that these proteins behave like glucose receptors. Other examples of transporter homologs with regulatory functions have recently been described in fungi as well [Madi L, et al. Genetics 1997; 146:499-508 (Ref. 3). and Didion T, et al. Mol Microbiol 1998;27:643-650 (Ref. 4)]. The identification of this class of nutrient sensors is an important step in elucidating the complex of regulatory mechanisms that leads to adaptation of fungi to different environments.


Correlations between terminal mitosis and differentiated fate of retinal precursor cells in vivo and in vitro: analysis with the "window-labeling" technique.
We have investigated with high resolution the timing of retinal precursor cell commitment to specific differentiated fates, using an in ovo modification of the in vitro "window-labeling" technique (A. M. Repka and R. Adler, J. Histochem. Cytochem. 40, 947-953, 1992a). The method involves an initial injection of tritiated thymidine into chick embryos, followed a specific number of hours later by an injection of bromodeoxyuridine (BrDU); cells born during this period are identified by being labeled with thymidine but not with BrDU. We used this method to determine, in a narrow region adjacent to the choroid fissure, the fate of cells born during defined 5-hr intervals between Embryonic Days (ED) 4-8. All the cohorts gave rise to heterogenous differentiated populations, indicating that time of cell birth is not a major cell fate determinant. A progressive restriction in the developmental potential of precursor cells, however, was suggested by the observed decrease in the number of different populations generated during each 5-hr period from ED 4 to 8, and supported also by dissociated cell culture experiments investigating the fate of cells born at different developmental stages. Microenvironmental influences were tested in vitro using cells windowed-labeled in ovo for 5 hr on ED 5. After spending at least 72 hr within the retina before their isolation for culture, these cells mimicked their in vivo fate, giving rise predominantly to nonphotoreceptor neurons; a completely different behavior was observed when the cells were isolated after shorter exposures to the retinal microenvironment, when they gave rise predominantly to photoreceptors. Together with data demonstrating that differential cell death cannot account for these results, our results are consistent with the hypothesis that cell fate determination occurs after the time of terminal mitosis.


Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature.
Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.


Proteomics and metabolomics analyses of camptothecin-producing Aspergillus terreus reveal the integration of PH domain-containing proteins and peptidylprolyl cis/trans isomerase in restoring the camptothecin biosynthesis.
Decreasing the camptothecin productivity by fungi with storage and subculturing is the challenge that halts their further implementation to be an industrial platform for camptothecin (CPT) production. The highest differentially abundant proteins were Pleckstrin homology (PH) domain-containing proteins and Peptidyl-prolyl cis/trans isomerase that fluctuated with the subculturing of A. terreus with a remarkable relation to CPT biosynthesis and restored with addition of F. elastica microbiome.


Application of Advanced Vibrational Spectroscopy in Revealing Critical Chemical Processes and Phenomena of Electrochemical Energy Storage and Conversion.
The future of the energy industry and green transportation critically relies on exploration of high-performance, reliable, low-cost, and environmentally friendly energy storage and conversion materials. Understanding the chemical processes and phenomena involved in electrochemical energy storage and conversion is the premise of a revolutionary materials discovery. In this article, we review the recent advancements of application of state-of-the-art vibrational spectroscopic techniques in unraveling the nature of electrochemical energy, including bulk energy storage, dynamics of liquid electrolytes, interfacial processes, etc. Technique-wise, the review covers a wide range of spectroscopic methods, including classic vibrational spectroscopy (direct infrared absorption and Raman scattering), external field enhanced spectroscopy (surface enhanced Raman and IR, tip enhanced Raman, and near-field IR), and two-photon techniques (2D infrared absorption, stimulated Raman, and vibrational sum frequency generation). Finally, we provide perspectives on future directions in refining vibrational spectroscopy to contribute to the research frontier of electrochemical energy storage and conversion.


Minimally Invasive Plate Osteosynthesis of Distal Tibia and Fibular Fractures Through a Single Distal Anterolateral Incision.
Treating distal tibia fractures is often challenging given the extent of soft tissue damage around the fracture and the risk of infection and other complications with internal fixation and the accompanying incisions. Minimally invasive plate osteosynthesis minimizes these complications and can be performed through a single incision. From April 2009 to January 2011, we treated 20 patients who had both tibial and fibular distal fractures through a distal anterolateral approach with this technique. The mean follow-up period was 15.5 (range 12 to 26) months. The mean interval to bony union was 21 (range 18 to 25) weeks. A 5° varus deformity was found in 1 patient. Another patient, who had a history of alcohol consumption and smoking, developed wound necrosis that was treated successfully with debridement and without skin grafting. The mean American Orthopaedic Foot and Ankle Society score for all patients was 91.8 (range 84 to 97). The anterolateral, minimally invasive plate osteosynthesis technique is a useful method for treating distal tibial and fibular fractures at the same level, with a low complication rate.


Heparin interactions with apoA1 and SAA in inflammation-associated HDL.
Apolipoprotein A1 (apoA1) is the main protein component responsible for transportation of cholesterol on high-density lipoprotein (HDL). Serum amyloid A (SAA) is an acute phase protein associated with HDL. Apart from their physiological functions, both apoA1 and SAA have been identified as 'amyloidogenic peptides'. We report herein that the polysaccharide heparin interacts with both apoA1 and SAA in HDL isolated from plasma of inflamed mice. The reaction is rapid, forming complex aggregates composed of heparin, apoA1 and SAA as revealed by gel electrophoresis. This interaction is dependent on the size and concentration of added heparin. Mass spectrometry analysis of peptides derived from chemically crosslinked HDL-SAA particles detected multiple crosslinks between apoA1 and SAA, indicating close proximity (within 25 Å) of these two proteins on the HDL surface, providing a molecular and structural mechanism for the simultaneous binding of heparin to apoA1 and SAA.


Temporal Variation of Chemical Persistence in a Swedish Lake Assessed by Benchmarking.
Chemical benchmarking was used to investigate the temporal variation of the persistence of chemical contaminants in a Swedish lake. The chemicals studied included 12 pharmaceuticals, an artificial sweetener, and an X-ray contrast agent. Measurements were conducted in late spring, late autumn, and winter. The transformation half-life in the lake could be quantified for 7 of the chemicals. It ranged from several days to hundreds of days. For 5 of the chemicals (bezafibrate, climbazole, diclofenac, furosemide, and hydrochlorothiazide), the measured persistence was lower in late spring than in late autumn. This may have been caused by lower temperatures and/or less irradiation during late autumn. The seasonality in chemical persistence contributed to changes in chemical concentrations in the lake during the year. The impact of seasonality of persistence was compared with the impact of other important variables determining concentrations in the lake: chemical inputs and water flow/dilution. The strongest seasonal variability in chemical concentration in lake water was observed for hydrochlorothiazide (over a factor of 10), and this was attributable to the seasonality in its persistence.


[Multiple schwannoma of the intrathoracic vagal nerve; report of a case].
A 67-year-old male referred to our hospital for the close examination of abnormal chest X-ray findings. Chest X-ray films showed abnormal shadows in the right lung field. Chest computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed the 3 tumors which located in superior, middle and posterior mediastinum. The operation underwent under the diagnosis of neurogenic tumors originating from the right intrathoracic vagal nerve. At the operation, the tumors existed the vagal nerve distal to the recurrent laryngeal nerve and they were resected with the transection of vagal nerve. The masses were histologically diagnosed as schwannoma. We reported a rare case of multiple schwannoma arising from the intrathoracic vagal nerve. He had no postoperative complications, and he has been free from recurrence for 4 years postoperatively.


Movement Is Life-Optimizing Patient Access to Total Joint Arthroplasty: Mental Health Disparities.
Mental illness affects 20.6% of American adults. The lifetime prevalence of depression and anxiety is 17% and 29%, respectively. In particular, women suffer more from mental illness than men. Racial and ethnic minorities experience disproportionate discrimination, which has been linked to depression, anxiety, and psychological distress. African Americans are more likely to be chronically depressed, have higher levels of impairment and more severe symptoms, and often have challenges accessing treatment. Poor mental health is associated with low socioeconomic status, prolonged hospital stays, psychosis, postoperative anemia, infection, and pulmonary embolism. For total hip and knee arthroplasty, mental health conditions have been linked to higher hospital charges, higher rates of nonroutine discharges, and an increased Charlson Comorbidity Index. Mechanisms to address mental health are varied and range from psychosocial to pharmacologic modalities. Optimization in these vulnerable patients includes appropriate preoperative screening, assessment of support systems, identifying resources, and providing a safe discharge plan.


Peptide-specific T cell clonal expansion in vivo following immunization in the eye, an immune-privileged site.
To visualize the primary antigen-specific T cell response to Ag introduced into the eye, we have used an adoptive transfer system in which a limiting number of OVA peptide (323-339)-specific T cells from a TCR-transgenic mouse were transferred into nonirradiated, syngeneic recipients and then tracked in vivo by staining for FACS analysis or immunohistochemistry with the clonotypic mAb KJ1-26. Following posterior chamber injection of Ag, KJ1-26+ cells accumulated primarily in the draining, submandibular lymph node (LN) within 3 days. Although reduced in number, by day 6 these cells were primarily in the paracortical regions and were able to proliferate and secrete IL-2 in response to Ag stimulation. In contrast, following i.v. injection of Ag, the KJ1-26+ cells accumulated in the paracortical regions of the LN to a comparable degree, but did not proliferate or secrete IL-2. The day 3 accumulation of KJ1-26+ cells in the submandibular LN was inhibited if the eye was removed within 5 h after injection of Ag. In the spleen, foci of KJ1-26+ cells were observed in the periarteriolar lymphoid sheaths at day 3; these were not observed to the same degree following other forms of immunization. These results demonstrate that the submandibular LN is the primary site for early clonal expansion of antigen-specific T cells following intraocular Ag administration and that these cells show changes consistent with immunity rather than tolerance.


Is dedifferentiated chondrosarcoma a 'de-differentiated' chondrosarcoma?
Since its first description 30 years ago, dedifferentiated chondrosarcoma has been the prototype of all dedifferentiated sarcomas. The presence of two tumour portions of different mesenchymal differentiation lineages in these neoplasms gives rise to three key questions, which are on the way to being resolved. Does it split up? And if so, how does it split up and when does it split up? Accumulating data provide evidence for a common monoclonal origin of both tumour portions and suggest that dedifferentiated chondrosarcoma is a paradigmatic neoplasm of mesenchymal transdifferentiaton in vivo. Two categories emerge of dedifferentiated chondrosarcomas with different cell biology: the classical one, with a low-grade chondroid component splitting up late, and a second type, with a high-grade chondroid component splitting up early in tumour development.


Sodium chloride stress induced morphological and ultrastructural changes in Aspergillus repens.
Halotolerant fungus, A. repens, showed a considerable difference in its growth rate, morphology, ultrastructural and molecular composition under NaCl stress as compared to control i.e. non-stressed condition. Light microscopic observations revealed significant differences in their mycelial thickness, their branching and septa. Transmission electron microscopic observations of both the conditions depicted significant differences in the qualitative and quantitative changes in mitochondria. Frequent pinocytotic vesiculation (vacuoles) of plasma membrane was observed in fungus under stress but no such vesiculation in control. The multivesiculate structures observed under stress with their origin from the cell membranes and subsequent release into vacuoles have not been reported in fungi under normal physiological conditions. The observations on pinocytosis are discussed in relation to ion compartmentation and salt tolerance in A. repens.


Regioselective Deaminative Allylation of Aliphatic Amines via Dual Cobalt and Organophotoredox Catalysis.
Despite the rapid progress in C-C bond-forming reactions using Katritzky salts, their deaminative allylation remains a challenge. Inspired by the metallaphotoredox-catalyzed allylic substitution regime, here, we report the deaminative allylation of Katritzky salts via cobalt/organophotoredox dual catalysis. This cross-electrophile coupling enables regioselective allylation using a variety of allylic esters, overcoming the substrate limitations of reported protocols. Mechanistic studies indicate the involvement of a π-allyl cobalt complex as a radicalophile that mediates C-C bond formation.


[Functions of human periodontal myofibroblast in vitro].
To investigate the functions of human periodontal myofibroblast (MFB) in vitro. Human periodontal fibroblast (hPDLFs) was cultured and induced to MFB by transforming growth factor-β1 (TGF-β1). MFB was denoted as the experimental group, whereas the hPDLFs was the control group. The groups were continuously cultured and harvested at 0, 12, 24, 48, and 72 h. The MFB marker α-smooth muscle actin (α-SMA) was examined by immunocytochemistry. The expression of fibronectin (FN) between MFB was examined by immunocytochemistry to detect the MFB contact relationship. The mRNA expression levels of α-SMA, collagen (Col) I, and Col III were measured by reverse transcription-polymerase chain reaction (RT-PCT) to analyze extracellular matrix secretion. The protein expression levels of α-SMA and Col I were also assessed by Western blot. The experimental group had significantly higher α-SMA expression than the control group at 0 h (P < 0.001). A positive expression of FN was found between MFB. The experimental group had significantly higher expression levels of Col I and Col III than the control group at 24 h (P < 0.001). Human periodontal MFB presents a continuous, high expression of α-SMA. MFB could interact through FN. MFB is significantly capable of extracellular matrix secretion.


Difficulties in managing the surgical patient who is morbidly obese.
Managing patients who are morbidly obese in the intensive care unit is associated with a variety of problems uncommonly experienced with the those who are not morbidly obese. Clinicians experience a myriad of unique problems and circumstances, from the need for special beds and lifts to unusual and unknown volumes of distribution resulting in unclear drug dosing. This review examines several issues including sedation, invasive monitoring, venous thromboembolism prophylaxis, surgical infections, nutritional support, and other complications that may be of particular importance to the critically ill patient who is morbidly obese. In many cases, care is altered based on the complicating issues surrounding morbid obesity. In other cases, the presence of obesity suggests no alterations in our routine critical care delivery. A comprehensive review of the literature is undertaken, data are critically considered, and overall opinion is rendered based on the available peer-reviewed literature. In many cases, data are not available that address the specific patient population in question, so related papers (like gastric bypass data) are considered. Many issues do not have definitive answers based on randomized controlled trials, and much is left to treating clinician opinion and local practice patterns. Where good data exist, however, one should consider carefully and individually deviation from the evidence-based approach.


The use of polymer heteronuclei for crystalline polymorph selection.
A method for the production of crystalline polymorphs from solution is described which utilizes a diverse set of polymer heteronuclei. Application to crystalline polymorph selection for the important pharmaceuticals acetaminophen and carbamazepine is demonstrated. This method provides a new paradigm for polymorph selection, where solvent and temperature conditions can be chosen on the basis of process considerations and the polymer heteronucleus can be varied for specific polymorph production.


cDNA libraries from human tissues and cell lines.
We report the construction of 34 cDNA libraries from human tissues and cell lines in lambda phage vectors (Charon BS, lambda gt11, lambda SHK, or lambda zapII). The cDNA was synthesized from poly A+ RNA, using oligo-dT as a primer, and size-selected before ligation to vector arms. High-complexity cDNA libraries from human tissues and cell lines should be a valuable resource for genome mapping studies and identification of disease genes.


Bayesian Assessment of Null Values Via Parameter Estimation and Model Comparison.
Psychologists have been trained to do data analysis by asking whether null values can be rejected. Is the difference between groups nonzero? Is choice accuracy not at chance level? These questions have been traditionally addressed by null hypothesis significance testing (NHST). NHST has deep problems that are solved by Bayesian data analysis. As psychologists transition to Bayesian data analysis, it is natural to ask how Bayesian analysis assesses null values. The article explains and evaluates two different Bayesian approaches. One method involves Bayesian model comparison (and uses Bayes factors). The second method involves Bayesian parameter estimation and assesses whether the null value falls among the most credible values. Which method to use depends on the specific question that the analyst wants to answer, but typically the estimation approach (not using Bayes factors) provides richer information than the model comparison approach.


[Pharmacological study on citrus fruits. II. Anti-allergic effect of fruit of Citrus unshiu MARKOVICH (2). On flavonoid components].
A study was carried out to clarify the active component of green fruit of Citrus unshiu MAKOVICH on the type I allergic reaction. The flavonoid component, isolated from its methanolic extract, hesperidin, was found to inhibit histamine release from peritoneal mast cells of rats induced by compound 48/80. Forty eight-hour homologous passive cutaneous anaphylaxis (PCA) in intact rats was significantly inhibited by the oral administration of hesperidin. However, the anti-allergic action on PCA was not observed in adrenalectomized rats. These results suggests that hesperidin is an effective component of the fruit of Citrus unshiu with the anti-allergic action against the type I reaction.


Primary breast sarcoma: A case series.
Primary Breast Sarcomas (PBS) are rare malignancies and seen in less than <1 % of all breast malignancies. PBS are non epithelial, composed of mesenchymal mammary tissue and are difficult to diagnose from other sarcomas arising in breast. A retrospective study was conducted in the Department of Pathology and slides of breast malignancies over a period of 5 years were reviewed. Out of total 1570 breast malignancies, 5 cases were reported as PBS. Diagnosis was made on the basis of Histopathology and IHC findings. Out of total 1570 cases, 5 cases were diagnosed as PBS (i.e. 0.32% of all cases). 3 out of 5 cases were males comprising of 60% of cases and 2 cases were females accounting for 40% of cases. The age group of presentation was 32-65 years with mean age being 48.5 years. A diagnosis of MPNST was rendered in two cases ( 1=M, 1=F), one each was diagnosed as DFSP ( with fibrosarcoma), Leiomyosarcoma and Fibrosarcoma. PBS is an extremely rare entity and locally aggressive. It requires diagnosis as its treatment protocol is different.


Effects of cyclophosphamide and rituximab in patients with connective tissue diseases with severe interstitial lung disease.
We aimed to analyse the effects of real-life immunomodulatory therapy with cyclophosphamide and rituximab for interstitial lung disease (ILD) in patients with systemic sclerosis (SSc-ILD), anti-synthetase syndrome (ASS-ILD), or Sjögren's syndrome (SjS-ILD), in a single academic centre. All inpatients with connective tissue diseases treated with intravenous bolus cyclophosphamide or rituximab were identified from the Medical Centre records. Information on patient characteristics, chest CT results, pulmonary function tests, therapies, and severe adverse events, were extracted from inpatient and outpatient records. Intravenous cyclophosphamide bolus therapy was used in 27 patients with SSc. Cyclophosphamide improved forced vital capacity (FVC) by more than 10% in 4 patients and stabilised it at -0.4% to +3.25% in 8. Rituximab constituted a rescue therapy in 14 SSc patients, and was used for treating 4 patients with ASS-ILD, 2 patients with SjS-ILD and one additional SSc-ILD patient. Rituximab led to FVC improvements of at least 5% in 8 patients and to stabilisation in another 6. 6 patients under cyclophosphamide and 8 patients under rituximab experienced severe adverse events. 8 of the 34 patients died, half of them from causes potentially related to therapy. In this subset of severely sick patients with connective tissue diseases, cyclophosphamide and/or rituximab led to improvement in 12 patients, and stabilisation was seen in 14. Despite the new options with nintedanib, immunomodulation remains a relevant therapeutic modality for ILD associated with connective tissue disease.


Experimental pathogenesis: drugs and chemical lesions in the gastric mucosa.
The goals of this article are to review the similarities and differences in the pathogenesis of acute gastric mucosal injury induced by alcohol, exemplified mostly by ethanol, and aspirin, as a representative of nonsteroidal anti-inflammatory drugs, and to deduce implications from pathogenetic studies for a better understanding of the concept of gastric cytoprotection. The main similarity between the hemorrhagic erosions caused by ethanol and aspirin is their localization in the acid-producing glandular stomach, the rate-limiting step in their pathogenesis being the extent of microvascular injury in the gastric mucosa. The major differences include the fast healing and low probability of transition into chronic gastritis after a single exposure to aspirin. On the other hand, perforated ulcer may develop, especially in the elderly, after chronic aspirin but not ethanol consumption. The main implications of pathogenetic investigations include the relative nature of gastroprotection: that is, initially, the superficial epithelial layer is not protected against concentrated luminal solutions, but it is rapidly replaced by migrating, adjacent, surviving cells if blood flow is maintained and the basement membrane is relatively intact. Vascular changes thus seem to be the rate-limiting step both in the pathogenesis and prevention of chemically induced acute gastric mucosal injury. The ultimate biochemical mechanisms of gastroprotection seem to include an effect on structural and enzymic proteins, and vascular mediators which influence vascular permeability and, indirectly, the extent of tissue injury.


Mode of action of an antibacterial peptide, KLKLLLLLKLK-NH2.
Previously, we reported that a synthetic undecapeptide, KLKLLLLLKLK-NH2, and its D-enantiomer have potent bactericidal activities against both Gram-positive and Gram-negative bacteria. Here we examined the mode of action of KLKLLLLLKLK-NH2 with special reference to its effect on bacterial membranes. We found that both the outer and inner membrane of Escherichia coli become permeable to low molecular mass substances when treated with this peptide. Under these conditions, the bacteria lost the ability to synthesize ATP and to transport proline, suggesting that their electrochemical membrane potential was disrupted. This peptide appears to form numerous channels in bacterial membranes that interfere with membrane functions, resulting in cell death.


Process validation: achieving the Operational Qualification phase.
The OQ phase of process validation is very important and is where the complete understanding of the process is determined by experimentation. This understanding is useful to: * establish optimal process parameters * understand variation that affect the process * aid in investigating process deviations. OQ is an important part of the entire process validation activity and essential to understanding a manufacturing process. The benefits of completing the OQ and overall process validation are the reasons that it makes business sense and receive the long-term benefits of producing high quality product and achieving customer satisfaction.


Potential benefits from cochlear implantation of children with unilateral hearing loss.
The aim of this discussion paper is to review several issues relevant to the viability of cochlear implantation of children with severe-profound unilateral hearing loss (UHL) and to discuss to what extent published findings on these issues can predict likely benefits from implantation in this population. Several key issues are apparent from the recent literature: (i) UHL results in significant educational and psycho-social difficulties, but these are not universal in pre-lingual cases and may not be apparent for several years after birth, (ii) conventional treatments (contralateral routing of signal aids or bone-anchored hearing aids) provide limited benefit in the majority of sensorineural cases, (iii) early published outcomes from implantation of a limited number of children with acquired UHL suggest benefits similar to those observed in postlingually deafened adults, (iv) unilateral auditory deprivation results in poorer outcomes from delayed implantation of children with congenital losses, and (v) a large proportion of cases of severe-profound sensorineural UHL are associated with structural abnormalities of the cochlea or VIII nerve, such that not all children with UHL may be suitable for cochlear implantation. Children with acquired UHL are likely to gain similar positive benefits from cochlear implantation as those recently reported in adults (improved localization and better speech understanding in specific noise conditions). However, implantation of children with prelingual UHL is currently problematic as the impact of UHL may not become apparent until the child enters full-time education, by which time outcomes from cochlear implantation may be sub-optimal due to auditory deprivation. Development of appropriate candidacy criteria is important but challenging as criteria may need to be based on real-world hearing difficulties as well as audiological measures.


Measurement properties of the Health Assessment Questionnaire Disability Index for generalized osteoarthritis.
Generalized OA (GOA) is highly prevalent in OA. Individuals with GOA typically suffer from limitations of both upper and lower extremity function, yet we lack a validated instrument to assess their activity limitations. An appropriate instrument might be the HAQ Disability Index (HAQ-DI). Therefore the aim of this study was to evaluate the measurement properties of the HAQ-DI in GOA. Data were used from a randomized controlled trial comparing the effectiveness of two multidisciplinary treatment programmes for patients with GOA. One hundred and thirty-seven of 147 included patients completed a standardized set of questionnaires before and after treatment. Interpretability, validity, reliability and responsiveness of the HAQ-DI were assessed using the Consensus-Based Standards for the Selection of Health Status Measurement Instruments checklist (COSMIN). Floor and ceiling effects were present. The content validity was questionable since the HAQ-DI encompasses activities that are either not relevant or too easy to perform as judged by patients and experts. Construct validity was good since 90% of the hypotheses were confirmed. Factor analysis confirmed the unidimensionality of the HAQ-DI (root mean square error of approximation = 0.057, χ(2)/df ratio = 1.48). Cronbach's α was 0.90, confirming internal consistency and the ICC was 0.81, reflecting good reliability. The minimal important change was 0.25 and the smallest detectable change was 0.60. We could not establish the responsiveness of the HAQ-DI. The HAQ-DI showed good construct validity, internal consistency and reliability, whereas its content validity and responsiveness were limited. We recommend updating the items of the HAQ-DI in future research focusing on functional limitations in GOA. Dutch Trial Register NTR2137, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2137.


The effect of chronic chromium exposure on the health of Chinook salmon (Oncorhynchus tshawytscha).
This study was designed to determine fish health impairment of Chinook salmon (Oncorhynchus tshawytscha) exposed to chromium. Juvenile Chinook salmon were exposed to aqueous chromium concentrations (0-266 microgl(-1)) that have been documented in porewater from bottom sediments and in well waters near salmon spawning areas in the Columbia River in the northwestern United States. After Chinook salmon parr were exposed to 24 and 54 microg Crl(-1) for 105 days, neither growth nor survival of parr was affected. On day 105, concentrations were increased from 24 to 120 microg Crl(-1) and from 54 to 266 microg Crl(-1) until the end of the experiment on day 134. Weight of parr was decreased in the 24/120 microg Crl(-1) treatment, and survival was decreased in the 54/266 microg Crl(-1) treatment. Fish health was significantly impaired in both the 24/120 and 54/266 microg Crl(-1) treatments. The kidney is the target organ during chromium exposures through the water column. The kidneys of fish exposed to the greatest concentrations of chromium had gross and microscopic lesions (e.g. necrosis of cells lining kidney tububules) and products of lipid peroxidation were elevated. These changes were associated with elevated concentrations of chromium in the kidney, and reduced growth and survival. Also, variations in DNA in the blood were associated with pathological changes in the kidney and spleen. These changes suggest that chromium accumulates and enters the lipid peroxidation pathway where fatty acid damage and DNA damage (expressed as chromosome changes) occur to cause cell death and tissue damage. While most of the physiological malfunctions occurred following parr exposures to concentrations > or =120 microg Crl(-1), nuclear DNA damage followed exposures to 24 microg Crl(-1), which was the smallest concentration tested. The abnormalities measured during this study are particularly important because they are associated with impaired growth and reduced survival at concentrations > or =120 microg Crl(-1). Therefore, these changes can be used to investigate the health of resident fish in natural waters with high chromium concentrations as well as provide insight into the mechanisms of chromium toxicity.


[The determination of free and bound oxyproline in urine].
A method of measuring urinary free, peptide- and protein-bound hydroxyproline is suggested. Adults were found to excrete 18 mumol of free, 155 mumol of peptide-bound, and 8 mumol of protein-bound hydroxyproline daily. In children daily urinary levels of free and peptide-bound hydroxyproline were higher. Data are presented on changes in various hydroxyproline forms in pneumonia, rheumatic fever, and hemorrhagic fever with the renal syndrome.


Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties.
Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole.


Short-term measurement of carbon isotope fractionation in plants.
Combustion-based studies of the carbon-13 content of plants give only an integrated, long-term value for the isotope fractionation associated with photosynthesis. A method is described here which permits determination of this isotope fractionation in 2 to 3 hours. To accomplish this, the plant is enclosed in a glass chamber, and the quantity and isotopic content of the CO(2) remaining in the atmosphere are monitored during photosynthesis. Isotope fractionation studies by this method give results consistent with what is expected from combustion studies of C(3), C(4), and Crassulacean acid metabolism plants. This method will make possible a variety of new studies of environmental and species effects in carbon isotope fractionation.


Dynamic motion analysis of dart throwers motion visualized through computerized tomography and calculation of the axis of rotation.
We used a dynamic three-dimensional (3D) mapping method to model the wrist in dynamic unrestricted dart throwers motion in three men and four women. With the aid of precision landmark identification, a 3D coordinate system was applied to the distal radius and the movement of the carpus was described. Subsequently, with dynamic 3D reconstructions and freedom to position the camera viewpoint anywhere in space, we observed the motion pathways of all carpal bones in dart throwers motion and calculated its axis of rotation. This was calculated to lie in 27° of anteversion from the coronal plane and 44° of varus angulation relative to the transverse plane. This technique is a safe and a feasible carpal imaging method to gain key information for decision making in future hand surgical and rehabilitative practices.


Long-term outcome in the repair of spinal cord perimedullary arteriovenous fistulas.
The natural history of PMAVFs, also known as type IV spinal cord AVFs, is incompletely understood. Both open surgical and endovascular approaches have been described as treatment modalities for this disease. The goal of this study was to evaluate the long-term outcome of patients with PMAVFs treated at a single tertiary care institution. We conducted a retrospective study of 32 patients with PMAVFs, evaluated between 1983 and 2009. Data were gathered by reviewing outpatient clinic notes, operative and radiologic reports, and spinal angiograms. The PMAVFs were categorized into 1 of 3 types based on the angiographic imaging criteria. Pretreatment and posttreatment ambulation and micturition symptoms were quantified by using the ALS. Thirty patients underwent corrective procedures, 4 by embolization alone, 11 by surgery alone, and 15 with a combination of the 2. Twenty-eight patients underwent follow-up spinal angiography, with residual shunt noted in 6 patients. The mean follow-up period was 54 months (range, 1-228 months). Analysis of the ALS scores revealed that treatment of PMAVFs, independent of technique, resulted in significant improvement in ambulation but inconsistent changes in micturition. In addition, residual fistula at the time of the follow-up angiogram was associated with worsened neurologic status or lack of improvement. Outcome analysis based on fistula type showed dramatic improvement in ALS ambulation scores (62%) for type 3 fistulas, compared with types 1 and 2 (26% and 27%, respectively). Significant improvement in ambulation but in not micturition was observed following treatment. Residual fistula on follow-up angiography was associated with progressive worsening or lack of improvement in neurologic function. Patients with type 3 fistulas were shown to benefit most from treatment, with marked improvement in posttreatment ambulation scores. As endovascular and surgical techniques continue to evolve, further studies are warranted.


A randomly stirred model for Bolgiano-Obukhov scaling in turbulence in a stably stratified fluid.
A randomly stirred model, akin to the one used by DeDominicis and Martin for homogeneous isotropic turbulence, is introduced to study Bolgiano-Obukhov scaling in fully developed turbulence in a stably stratified fluid. The energy spectrum E(k), where k is a wavevector in the inertial range, is expected to show the Bolgiano-Obukhov scaling at a large Richardson number Ri (a measure of the stratification). We find that the energy spectrum is anisotropic. Averaging over the directions of the wavevector, we find [Formula: see text], where εθ is the constant energy transfer rate across wavenumbers with very little contribution coming from the kinetic energy flux. The constant K0 is estimated to be of O(0.1) as opposed to the Kolmogorov constant, which is O(1). Further for a pure Bolgiano-Obukhov scaling, the model requires that the large distance 'stirring' effects dominate in the heat diffusion and be small in the velocity dynamics. These could be reasons why the Bolgiano-Obukhov scaling is difficult to observe both numerically and experimentally. This article is part of the theme issue 'Scaling the turbulence edifice (part 2)'.


Does the currently accepted RADS-2 factor structure apply to LGBTIQ youth?
First-stage measures of depressive symptoms need to demonstrate accuracy in capturing depression in diverse populations of youth. The research question in this study asked, 'How is the Reynolds Adolescent Depression Scale-2nd Edition (RADS-2) factor structure expressed in a sample of lesbian, gay, bisexual, transgender, intersex or queer adolescent students?' Reliability, validity and principal components with orthogonal rotation factor analysis testing were conducted on a sample of 265 school-based adolescents in grades 7-12, including 72 girls and 193 boys, who sought guidance for sexual orientation or gender identity issues in this secondary data analysis. Four factors were identified that each demonstrates adequate internal consistency reliability. The RADS-2 effectively captures the features of depressive symptoms in sexual minority adolescents.


The Validity of Disease-specific Quality of Life Attributions Among Adults with Multiple Chronic Conditions.
A crucial assumption underlying all disease-specific quality of life (QOL) measures, that patients can validly differentiate a specific disease in the presence of multiple chronic conditions, has not been tested using multiple methods. Our objective was to evaluate the convergent and discriminant validity of QOL attributions to specific diseases among adults with multiple chronic conditions (MCC). Adults age 18 and older (N=4,480) sampled from eight pre-identified condition groups (asthma, COPD, angina/MI with angina, congestive heart failure, diabetes, chronic kidney disease, osteoarthritis, rheumatoid arthritis) completed an Internet survey. Comorbid conditions were determined using a 35-condition checklist. Product-moment correlations were analyzed separately by pre-identified condition group using the multitrait-multimethod of construct validation, where traits were defined by 9-26 conditions and each condition was measured by two methods: disease severity rating and Disease-specific Quality of Life Impact Scale (QDIS) global rating. A third method (symptom or clinical marker) was available for the eight pre-identified conditions. Convergent validity was supported when correlations among different methods of measuring the same condition (trait) were substantial (r≥0.40). Discriminant validity was supported when correlations between the same and different methods of measuring different conditions were significantly lower than corresponding convergent correlations. In support of convergent validity, 22 of 24 convergent correlations were substantial (r=0.38-0.84, median=0.53). In support of discriminant validity, 833 of 924 tests (90.2%) yielded significantly higher convergent than discriminant correlations across the eight pre-identified conditions. Exceptions to this pattern of results were most often observed for comorbid conditions within the same clinical area. Collectively, convergent and discriminant test results support the construct validity of disease-specific QOL impact attributions across MCC within the eight pre-identified conditions. Noteworthy exceptions should be considered when interpreting some specific QOL impact attributions and warrant further study. Pursuit of a summary disease-specific QOL impact score standardized across MCC is recommended.


The primate pulvinar nuclei: vision and action.
The pulvinar nuclei of the thalamus are proportionately larger in higher mammals, particularly in primates, and account for a quarter of the total mass. Traditionally, these nuclei have been divided into oral (somatosensory), superior and inferior (both visual) and medial (visual, multi-sensory) divisions. With reciprocal connections to vast areas of cerebral cortex, and input from the colliculus and retina, they occupy an analogous position in the extra-striate visual system to the lateral geniculate nucleus in the primary visual pathway, but deal with higher-order visual and visuomotor transduction. With a renewed recent interest in this thalamic nuclear collection, and growth in our knowledge of the cortex with which it communicates, perhaps the time is right to look to new dimensions in the pulvinar code.


Preventing falls at home among people with intellectual disabilities: A scoping review.
Falls are common among people with intellectual disabilities. Many falls happen within the home. Our scoping review aimed to identify evidence for falls-risk factors and falls-prevention interventions for this population. We conducted a multi-database search to identify any type of published study that explored falls-risk factors or falls-prevention interventions for people with intellectual disabilities. Following a process of (i) title & abstract and (ii) full-text screening, data was extracted from the included studies and described narratively. Forty-one studies were included. Risks are multifactorial. There was limited evidence of medical, behavioural/psychological, or environmental interventions to address modifiable risk factors, and no evidence of the interventions' cost-effectiveness. Clinically and cost effective, acceptable and accessible falls-prevention pathways should be available for people with intellectual disabilities who are at risk of falls from an earlier age than the general population.


Midurethral slings: evidence-based medicine vs the medicolegal system.
Midurethral sling procedures are minimally invasive surgeries for stress urinary incontinence that use a trocar system to place a narrow ribbon of polypropylene mesh under the midurethra. The peer-reviewed scientific literature on these procedures is abundant and midurethral slings are the most well-studied incontinence procedure ever. Systematic reviews of the literature demonstrate that midurethral slings are safer and more (or equally) effective as traditional procedures. The midurethral sling is the worldwide standard for the treatment of female stress urinary incontinence and >3 million procedures have been performed. The Food and Drug Administration and international scientific review agencies have consistently differentiated transvaginal mesh for stress urinary incontinence from transvaginal mesh for prolapse. In the recruitment of patients to participate in transvaginal mesh litigation, plaintiff lawyers have not made the distinction between stress urinary incontinence and prolapse procedures because more women have received midurethral slings than transvaginal mesh for prolapse by an order of magnitude. The litigation costs of defending their products have forced several companies that manufactured midurethral slings to leave the marketplace. It is not inconceivable that midurethral slings could become absent from the US market. If that happens, then US women with stress urinary incontinence will be harmed because they will not have access in this country to the best and safest stress urinary incontinence surgical procedure ever developed. It may be time for the Institute of Medicine or another comparable national agency to provide evidence-based recommendations on the midurethral sling.


A Cellulose/Laponite Interpenetrated Polymer Network (IPN) Hydrogel: Controllable Double-Network Structure with High Modulus.
Laponite XLS™, which is a synthetic clay of nanometric dimensions containing a peptizing agent, has been associated with silanized hydroxypropylmethylcellulose (Si-HPMC) to form, after crosslinking, a novel composite hydrogel. Different protocols of sample preparation were used, leading to different morphologies. A key result was that the storage modulus of Si-HPMC/XLS composite hydrogel could be increased ten times when compared to that of pure Si-HPMC hydrogel using 2 wt % of Laponite. The viscoelastic properties of the composite formulations indicated that chemical and physical network structures co-existed in the Si-HPMC/XLS composite hydrogel. Images that were obtained from confocal laser scanning microscopy using labelled Laponite XLS in the composite hydrogels show two co-continuous areas: red light area and dark area. The tracking of fluorescent microspheres motions in the composite formulations revealed that the red-light area was a dense structure, whereas the dark area was rather loose without aggregated Laponite. This novel special double-network structure facilitates the composite hydrogel to be an adapted biomaterial for specific tissue engineering. Unfortunately, cytotoxicity's assays suggested that XLS Laponites are cytotoxic at low concentration. This study validates that the hybrid interpenetrated network IPN hydrogel has a high modulus that has adapted for tissue engineering, but the cell's internalization of Laponites has to be controlled.


Study of polyethyleneimine- and amidoxime-functionalized hybrid biomass of Spirulina (Arthrospira) platensis for adsorption of uranium (VI) ion.
This study investigates the potential application of the polyethyleneimine- (PEI) and amidoxime-modified Spirulina (Arthrospira) platensis biomasses for the removal of uranium ion in batch mode using the native biomass as a control system. The uranium ion adsorption was also characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectra, zeta potential analysis, and surface area measurement studies. The effects of pH, biomass amount, contact time, initial uranium ion concentration, and ionic strength were evaluated by using native and modified algal biomass preparations. The uranium ion removal was rapid, with more than 70% of total adsorption taking place in 40 min, and equilibrium was established within 60 min. From the experimental data, it was found that the amount of adsorption uranium ion on the algal preparations decreased in the following series: amidoxime-modified algal biomass > PEI-modified algal biomass > native algal biomass. Maximum adsorption capacities of amidoxime- and PEI-modified, and native algal biomasses were found to be 366.8, 279.5, and 194.6 mg/g, respectively, in batchwise studies. The adsorption rate of U(VI) ion by amidoxime-modified algal biomass was higher than those of the native and PEI-modified counterparts. The adsorption processes on all the algal biomass preparations followed by the Dubinin-Radushkevitch (D-R) and Temkin isotherms and pseudo-second-order kinetic models. The thermodynamic parameters were determined at four different temperatures (i.e., 15, 25, 35, and 45 °C) using the thermodynamics constant of the Temkin isotherm model. The ΔH° and ΔG° values of U(VI) ion adsorption on algal preparations show endothermic heat of adsorption; higher temperatures favor the process. The native and modified algal biomass preparations were regenerated using 10 mM HNO3. These results show that amidoxime-modified algal biomass can be a potential candidate for effective removal of U(VI) ion from aqueous solution.


Silencing of A-kinase anchor protein 4 inhibits the metastasis and growth of non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The treatment of advanced NSCLC can be challenging due to drug resistance. The discovery of novel cancer-testis antigens to develop new strategies for advanced metastatic NSCLC is required. AKAP4 is an oncogene discovered in some malignant tumors, and its molecular function of AKAP4 in NSCLC is unknown. This study aimed to explore the potential function of AKAP4 in the development and progression of NSCLC. AKAP-4 was found to be significantly upregulated in both clinical NSCLC tissues and NSCLC cell lines. Cell viability and migration were suppressed, apoptosis was induced, and tube formation was inhibited by the knockdown of AKAP-4, accompanied by the downregulation of VEGF, N-cadherin, EphA2, and MMP-2, and upregulation of c-AMP, PKA, and E-cadherin. In vivo xenograft experiments revealed that tumor growth was inhibited by the knockdown of AKAP4, accompanied by the activation of c-AMP/PKA signaling and inhibition of epithelial-mesenchymal transition progression. Our results show that AKAP4 might be an important target for treating NSCLC because of its function in promoting the migration and proliferation of NSCLC cells.


In planta transcriptomics reveals conflicts between pattern-triggered immunity and the AlgU sigma factor regulon.
In previous work, we determined the transcriptomic impacts of flg22 pre-induced Pattern Triggered Immunity (PTI) in Arabidopsis thaliana on the pathogen Pseudomonas syringae pv. tomato DC3000 (Pto). During PTI exposure we observed expression patterns in Pto reminiscent of those previously observed in a Pto algU mutant. AlgU is a conserved extracytoplasmic function sigma factor which has been observed to regulate over 950 genes in Pto in growth media. We sought to identify the AlgU regulon when the bacteria are inside the plant host and which PTI-regulated genes overlapped with AlgU-regulated genes. In this study, we analyzed transcriptomic data from RNA-sequencing to identify the AlgU regulon (while in the host) and its relationship with PTI. Our results showed that the upregulation of 224 genes while inside the plant host require AlgU, while another 154 genes are downregulated dependent on AlgU in Arabidopsis during early infection. Both stress response and virulence-associated genes were upregulated in a manner dependent on AlgU, while the flagellar motility genes are downregulated in a manner dependent on AlgU. Under the pre-induced PTI condition, more than half of these AlgU-regulated genes have lost induction/suppression in contrast to mock treated plants, and almost all function groups regulated by AlgU were affected by PTI.


[The helminth fauna of indigenous white storks (Ciconia ciconia)].
120 carcasses of white storks originating from the federal countries Saxonia-Anhalt and Brandenburg where examined between 1994 and 2000 for internal parasites. The established parasite spectrum consisted of 8 trematode (Tylodelphis excavata, Chaunocephalus ferox, Cathemasia hians, Echinostoma revolutum, Echinoparyphium sp., Monilifer spinulosus, Ignavia ciconiae and Brachylaimus sp.), 4 cestode (Anomotaenia discoidea and 3 Hymenolepidae species) and at least 3 nematode species (Capillaria spp., Syngamus palustris and Contracaecum microcephalum). 5 of the helminths are considered to be stork specific. Considering host age groups the highest percentage of infected birds was found in adults.


Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension.
To evaluate pulmonary vasoreactivity in children and young adults with primary pulmonary hypertension, we performed cardiac catheterizations on nine patients with primary pulmonary hypertension (nine months to 23 years old) and made hemodynamic measurements: before and after infusing prostacyclin, and before and after administering sublingual nifedipine. Based upon the response to prostacyclin, patients were divided into responders and nonresponders using the following criteria: 20 percent or greater decrease in mean pulmonary arterial pressure; an increase in cardiac index; and no change, or a decrease in the pulmonary vascular resistance to systemic vascular resistance ratio. By these criteria, five of the nine patients had a reactive pulmonary vascular bed and responded to prostacyclin administration. In addition, they all responded to nifedipine. The remaining four did not respond to either drug. There was a close correlation (r = 0.85, p less than 0.01) between the magnitude of the pulmonary vasodilator response to treatment with prostacyclin and nifedipine. There was also a significant inverse correlation between the age of the patient at the time of the study and the pulmonary vasodilator response to administration of prostacyclin (r = 0.91, p less than 0.01) and nifedipine (r = 0.82, p less than 0.01); ie, both drugs produced a greater fall in pulmonary arterial pressure in younger patients with primary pulmonary hypertension than in older ones.


Respiratory system involvement in Costello syndrome.
Costello syndrome (CS) is a multisystem disorder caused by heterozygous germline mutations in the HRAS proto-oncogene. Respiratory system complications have been reported in individuals with CS, but a comprehensive description of the full spectrum and incidence of respiratory symptoms in these patients is not available. Here, we report the clinical course of four CS patients with respiratory complications as a major cause of morbidity. Review of the literature identified 56 CS patients with descriptions of their neonatal course and 17 patients in childhood/adulthood. We found that in the neonatal period, respiratory complications are seen in approximately 78% of patients with transient respiratory distress reported in 45% of neonates. Other more specific respiratory diagnoses were reported in 62% of patients, the majority of which comprised disorders of the upper and lower respiratory tract. Symptoms of upper airway obstruction were reported in CS neonates but were more commonly diagnosed in childhood/adulthood (71%). Analysis of HRAS mutations and their respiratory phenotype revealed that the common p.Gly12Ser mutation is more often associated with transient respiratory distress and other respiratory diagnoses. Respiratory failure and dependence on mechanical ventilation occurs almost exclusively with rare mutations. In cases of prenatally diagnosed CS, the high incidence of respiratory complications in the neonatal period should prompt anticipatory guidance and development of a postnatal management plan. This may be important in cases involving rarer mutations. Furthermore, the high frequency of airway obstruction in CS patients suggests that otorhinolaryngological evaluation and sleep studies should be considered. © 2016 Wiley Periodicals, Inc.


The relationship of plumage colours with MC1R (Melanocortin 1 Receptor) and ASIP (Agouti Signaling Protein) in Japanese quail (Coturnix coturnix japonica).
1. The relationship of polymorphisms in the Melanocortin 1 Receptor (MC1R) and Agouti Signalling Protein (ASIP) genes with plumage colour in Japanese quail was investigated by cloning and sequencing the entire coding regions from black, white and maroon Japanese quail embryos at 12 d of incubation. 2. Three SNPs were identified in the MC1R coding region by multiple alignment of sequences from individuals with different plumage colours. A missense C/T mutation located at 169 bp within the Open Reading Frame caused a Ile57Val mutation in the amino acid sequence, and had a significant relationship with the black colour. 3. The expression of MC1R was higher in black plumage quails than that in maroon plumage quails, whereas the expression of ASIP was higher in maroon plumage quails than that in black plumage quails. 4. It is concluded that the black plumage colour in Japanese quails may be caused by either increased production of MC1R or decreased production of ASIP.


Addressing professionalism in both formative and summative simulated patient care activities - Experiences with a discretionary deduction approach.
Encouraging and assessing professionalism among pharmacy students can be challenging. While non-punitive approaches are preferred as part of professional socialization, our program found this insufficient to ensure professional behaviour, especially during ungraded simulation lab activities. In Winter 2015, we included a discretionary grade deduction within the assessments applied to a professional practice lab course in order to provide both intrinsic and extrinsic motivation to follow lab policies on professionalism. A professionalism code was developed and discussed with students, and was also used as a template to guide professional behaviour throughout the course. Students not exhibiting these behaviours in lab could be subject to up to a five percent deduction from their final course grade at the instructor's discretion. Instructors considering this strategy are encouraged to introduce it in the first year of the program to ensure consistent expectations throughout the duration of students' training, and to not determine the magnitude of deductions applied until the end of the semester to ensure consistency and consideration of ongoing behaviour. Documentation of actions leading to deductions should be kept to support the decision. A deduction-only approach to address unprofessional behaviours in addition to discussion offers additional motivation to students to exhibit professionalism across both graded and ungraded educational activities with minimal additional workload for instructors. The strategy has since been adopted across all lab courses in our program and has also been recommended in lecture-based courses.


Hair for brain trade-off, a metabolic bypass for encephalization.
Hair loss in humans is perplexing and raises many hypothetical explanations. This paper suggests that hair loss in humans is metabolically related to encephalization; and that hair covered hominids would have been unable to evolve large brains because of a dietary restriction of several amino acids which are essential for hair and brain development. We use simulations to imply that hair loss must have preceded increase in brain size & volume. In this respect we see hair loss as a major force in human evolution. We assume that hair reduction required favorable climatic conditions and must have been quick. Using evolutionary and ecological time scales, we pinpoint hair loss to a period around 2.2-2.4 million years ago. The dating is further supported by a rapid selection at that time of the sialic acid deletion mutation which may have protected growing human brains against calcium ion flux. In summary we view encephalization, in part, as a metabolic trade-off between hair and brain. Other biochemical changes may have intervened in the process too; and the deletion mutation of sialic acid hydroxylation may have been involved as well.


Identifying gross post-mortem organ images using a pre-trained convolutional neural network.
Identifying organs/tissue and pathology on radiological and microscopic images can be performed using convolutional neural networks (CNN). However, there are scant studies on applying CNN to post-mortem gross images of visceral organs. This proof-of-concept study used 537 gross post-mortem images of dissected brain, heart, lung, liver, spleen, and kidney, which were randomly divided into a training and teaching datasets for the pre-trained CNN Xception. The CNN was trained using the training dataset and subsequently tested on the testing dataset. The overall accuracies were >95% percent for both training and testing datasets and have an F1 score of >0.95 for all dissected organs. This study showed that small datasets of post-mortem images can be classified with a very high accuracy using a pre-trained CNN. This novel area has the potential for future application in data mining, education and teaching, case review, research, quality assurance, auditing purposes, and identifying pathology.


The Attributes of Physicians Assigned to Rural Clinics Designated for Areas without Physicians in Japan.
In Japan, there are rural clinics designated for areas without physicians to ensure the availability of medical care for rural area residents. The purpose of this study was to clarify the attributes of physicians working in the rural clinics. Using the 2018 Ministry of Health, Labour and Welfare data in Japan, we compared the attributes and board certifications of physicians in rural clinics with those of physicians in other clinics. The age group with the highest percentage of physicians was the over 70 group (16%) and the early 30s group (15%) at rural clinics; however, the highest percentage of physicians at other clinics was the 70 over group (20%) and the early 60s group (16%). The number of physicians working in the internal medicine field at rural clinics was 550 (89%). There were 147 (27%) board-certified physicians in that field. Among them, the number of board certifications in internal medicine, surgery, and other than internal medicine or surgery were 79 (54%), 17 (12%), and 51 (35%), respectively. The proportion of board-certified surgery physicians within the internal medicine field in rural clinics was significantly higher than in other clinics (5%). In rural clinics, the age distribution of physicians was different from that in other clinics, and many of the physicians worked in the internal medicine field, but some of them seemed to have a mismatch between their board-certifications and their fields of practice. Further studies are necessary to clarify what the mismatches mean in rural practice.


Propagation of plant viruses in hairy root cultures: a potential method for in vitro production of epitope vaccines and foreign proteins.
Hairy roots were used as an in vitro culture system for the propagation of wild-type and transgenic plant viruses. Tobacco mosaic virus (TMV) was added to the liquid culture medium at the same time as root inoculation. Hairy root growth was unaffected by viral infection. Maximum concentrations of TMV in Nicotiana benthamiana hairy roots were 1-2 orders of magnitude greater than in suspended N. benthamiana cells and reached levels of 1-2 mg g(-1) dry weight or 20-28% total soluble protein. Virus accumulated in the roots initially with a constant doubling time of about 1.0 day; subsequent reductions in viral growth rate were correlated with a significant decline in infectivity relative to the inoculum virus. The morphological integrity of the viral particles was maintained during propagation in hairy roots. The contribution to the overall viral titer of passive association of virus with the biomass, for example, by surface adsorption, was negligible compared with active viral replication. N. benthamiana hairy roots were also infected with a TMV-based viral vector developed to express green fluorescent protein (GFP). This vector was about 260-fold less infectious than wild-type TMV and accumulated much more slowly in the roots. Maximum levels of TMV-GFP in the biomass were about 65-fold lower than for TMV. This work demonstrates that hairy root cultures are a feasible means for in vitro propagation of wild-type and transgenic plant viruses under conditions that allow a high degree of environmental containment and control.


Primary structures of glucagon and glucagon-like peptide isolated from the intestine of the parasitic phase lamprey Petromyzon marinus.
Immunohistochemical studies have indicated that glucagon-containing cells are present in the intestinal mucosa of the agnathan Petromyzon marinus (sea lamprey) but are absent from the pancreas. Glucagon was isolated from an extract of intestinal tissue taken from specimens of sea lamprey during their parasitic phase. The primary structure of the peptide was established as: His-Ser-Glu-Gly-Thr5-Phe-Thr-Ser-Asp-Tyr10-Ser-Lys-Tyr-Leu- Glu15-Asn-Lys-Gln-Ala-Lys20-Asp-Phe-Val-Arg-Trp25-Leu- Met-Asn-Ala. This amino acid sequence shows 8 substitutions compared with that of mammalian glucagon but, with the exception of the COOH-terminal alanine residue, lamprey gut glucagon contains no structural features that have not been previously seen in glucagons isolated from the pancreata of gnathostomes. The amino acid sequence of lamprey glucagon-like peptide (GLP) demonstrates that the primary structure of this peptide has been less well conserved than that of glucagon. The sequence His-Ala-Asp-Gly-Thr5-Phe-Thr-Asn-Asp-Met10-Thr-Ser-Tyr- Leu-Asp15-Ala-Lys-Ala-Ala-Arg20-Asp-Phe-Val-Ser-Trp25- Leu-Ala-Arg-Ser-Asp30- Lys-Ser shows 16 amino acid substitutions compared with the corresponding region of mammalian GLP-1 and 15 substitutions compared with that of salmon GLP.


An Optimistic Vision of Future: Diagnosis of Bacterial Infections by Sensing Their Associated Volatile Organic Compounds.
Simple tests using sniff analysis that have the ability of diagnosing and rapidly distinguishing between infections due to different bacteria are urgently required by medical community worldwide. Professionals interested in this topic wish for these tests to be simultaneously cheap, fast, easily applicable, non-invasive, robust, reliable, and sensitive. Current analytical instrumentation has already the ability for performing real time (minutes or a few dozens of minutes) analysis of volatile bacterial biomarkers (the VOCs emitted by bacteria). Although many articles are available, a review displaying an objective evaluation of the current status in the field is still needed. This review tries to present an overview regarding the bacterial biomarkers released from in vitro cultivation of various bacterial strains and also from different biological matrices investigated, over the last 10 years. We have described results of relevant studies, which used modern analytical techniques to evaluate specific biomarker profiles associated with bacterial infections. Our purpose was to present a comprehensive view of available possibilities for detection of emitted bacterial VOCs from different matrices. We intend that this review to be of general interest for both medical doctors and for all researchers preoccupied with bacterial infectious diseases and their rapid diagnosis using analytical instrumentation.


[Results of ventral hernia repair: comparison of suture repair with mesh implantation (onlay vs sublay) using open and laparoscopic approach--prospective, randomized, multicenter study].
Incisional hernias is a frequent complication following abdominal surgery, it develops in 11-20% of patients who had laparotomies. Different operative techniques are used for repair but results are often poor. In the absence of valid scientific data, there is no general agreement on the best surgical treatment. To provide evidence based surgery a nation-wide multi-center, prospective, randomized study is set up. The present study compares suture and mesh repairs in different positions, using open and laparoscopic approach to define standard indication for the treatment of incisional hernias. The study was started in March, 2002, with 23 surgical departments participating. Each report about 100 patients with incisional hernia repair. The 2300 consecutive patients (who are 18 to 70 years old) with primary incisional hernia or first recurrent umbilical hernia are randomized. Patients are divided in two groups. If the hernia is between 5-25 cm2 (Group I) they are selected at random either for prosthetic (sublay) or suture repair. In patients with a hernia larger than 25 cm2 (Group II) mesh is implanted at random as either sublay or onlay position using a computer randomization program. After a short learning period, in Group II the laparoscopic approach will also be randomized. Postoperative outcome, complications and recurrence are recorded. The study will run for five years. All collected data are sent to the coordinating center via internet to be entered into database.