Class II major histocompatibility complex transactivator (CIITA) inhibits matrix metalloproteinase-9 gene expression.
Matrix metalloproteinases (MMPs) are a family of structurally related proteins with the collective capability to degrade all components of the extracellular matrix. Although MMP-mediated degradation of the extracellular matrix occurs physiologically, numerous pathological conditions exhibit increased MMP levels and excessive matrix degradation. Previous work from our laboratory has shown that interferon-gamma inhibits MMP-9 expression in a manner dependent upon STAT-1alpha. Here we extend our previous observations and show that the class II major histocompatibility complex transactivator (CIITA), a transcriptional target of STAT-1alpha, is also capable of inhibiting MMP-9 expression. By using stable cell lines that inducibly express CIITA or various mutant forms of CIITA, we show that CIITA requires the ability to bind the CREB-binding protein (CBP) to effectively inhibit MMP-9 expression. Furthermore, we show that CIITA-mediated inhibition of the MMP-9 gene does not rely on the transcriptional capability of CIITA. These findings support a model wherein CIITA inhibits MMP-9 expression by binding to and sequestering CBP, which reduces the levels of CBP at the MMP-9 promoter, inhibits levels of acetylated histone 3 at the MMP-9 promoter, and subsequently inhibits MMP-9 expression.


Closed-chest massage: an effective resuscitative procedure for the maintenance of the circulation during cardiac arrest.
Reports of clinical benefits of closed-chest cardiac resuscitation refute recently published studies contesting its effectiveness.Our experimental investigations demonstrate that closed-chest massage is able to achieve adequate cerebral circulation and oxygenation during cardiac arrest.Clinical studies indicate that a significant number of coronary patients can be saved if a monitor system is used to warn of the onset of ventricular fibrillation or arrest. To be successful, closed-chest resuscitation must be instituted within the four-minute limit after onset of cardiac arrest. When ventricular fibrillation occurs, electrical countershock is usually obligatory. Cardiac pacemaking is a specific necessity for patients with ventricular arrest.


Broad spectrum antibacterial activity of a mixture of isothiocyanates from nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix).
Isothiocyanates have been reported to exert antimicrobial activity. These compounds are found in a licensed native preparation of nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix) which is used for treatment of upper respiratory and urinary tract infections. The aim of our investigation was to assess the antimicrobial activity of a mixture of the contained benzyl-, allyl-, and phenylethyl- isothiocyanates against clinically important bacterial and fungal pathogens including antimicrobial resistant isolates. Susceptibility testing was performed by agar-dilution technique. Isothiocyanates were mixed in proportions identical to the licensed drug. Minimum inhibitory- and minimum bactericidal concentrations were assessed. The Minimum inhibitory concentration90 was defined as the concentration which inhibited 90% of the microbial species tested. H. influenzae, M. catarrhalis, S. marcescens, P. vulgaris, and Candida spp. were found to be highly susceptible, with minimum inhibitory concentration90 -values ranging between ≤0.0005% and 0.004% (v/v) of total ITC. Intermediate susceptibilities were observed for S. aureus, S. pyogenes, S. pneumoniae, K. pneumoniae, E. coli and P. aeruginosa, with Minimum inhibitory concentration90 -values ranging between 0.004% and 0.125% (v/v), but with elevated Minimum bactericidal concentrations90-values (2-7 dilution steps above Minimum inhibitory concentration90). Low susceptibilities were determined for viridans streptococci and enterococci. Interestingly, both resistant and non-resistant bacteria were similarly susceptible to the test preparation.


Staining of bone for aluminum: use of acid solochrome azurine.
Fourteen individuals on long term hemodialysis, with varying amounts of aluminum in bone from 11 to 296 mg/kg by flameless atomic absorption spectrophotometry, were examined to see whether the aluminon or acid solochrome azurine (ASA) staining reactions best approximated the chemical determination. Correlation coefficients were 0.78 for aluminon and 0.88 for ASA. Together with 11 additional patients morphometric parameters were compared with the two aluminum stains. The aluminon stain gave satisfactory results in the osteomalacic group but underestimated the amount of aluminum present in those with hyperparathyroid, mixed or aplastic disease. Some individuals showed a striking difference between the two techniques which could have led to an erroneous conclusion regarding the amount of aluminum present. The aluminon stain was pH dependent and together with ASA could be enhanced by prior heat treatment of the sections. It is recommended that ASA either replace aluminon for routine use or be used together with the aluminon stain, particularly for bones without osteomalacia or with mild to moderate aluminum storage.


Risk of mental disorders in children of parents with alcohol or heroin dependence: a controlled high-risk study.
To assess the specific effect of alcohol dependence (AD) or heroin dependence (HD) in patients and their spouses on the risk of psychopathology in their 276 6.0- to 17.9- year-old children (mean 11.3 years). The sample included 101 offspring of patients with AD, 23 of patients with HD, and 152 of medical controls, as well as their 2 parents. Participants were assessed using semistructured diagnostic interviews and family history reports by psychologists blind to patient diagnoses. Children of HD and AD patients had largely elevated rates of recurrent major depressive disorder. Children of HD patients were also at an increased risk for attention deficit hyperactivity disorder and substance use disorders (SUD). There were interactions between SUD in the 2 parents to increase the risk of SUD in offspring. These results emphasize the need for prompt identification and treatment of these children and highlight the need to pay clinical attention not only to the patient, but also to the co-parent in order to optimize prevention in offspring.


Impact of bariatric surgery--induced weight loss on heart rate variability.
Obesity is associated with an increased risk of sudden death that may be due to abnormal cardiac vagal modulation reflected by reduced heart rate variability (HRV). Few studies have been conducted analyzing the effect of bariatric surgery-induced weight loss on HRV assessed by 24-hour Holter monitoring. The aim of this study was to assess weight loss effect after bariatric surgery on HRV and ventricular size and function. Ten morbidly obese patients, 6 women and 4 men aged 24 to 47 years, underwent bariatric surgery. Seven morbidly obese patients without active obesity treatment were used as controls. Twenty-four-hour Holter monitoring and echocardiogram were obtained before and at 6 to 12 months after surgery or at follow-up in control patients. Changes in minimal, maximal, and mean heart rate along with HRV during daytime and nighttime were compared before and after surgery. Baseline characteristics in the control group did not differ significantly from the treatment group. Average weight in the treatment group was 141 +/- 31 kg (mean +/- SD) at baseline and decreased to 101 +/- 18 kg at follow-up, corresponding to a body mass index of 52.3 +/- 7.6 kg/m(2) at baseline and 37.7 +/- 5.3 kg/m(2) at follow-up. There was a decrease in minimal heart rate (48 +/- 10 vs 40 +/- 6 beats per minute, P = .021) and mean heart rate (82 +/- 7 vs 66 +/- 10 beats per minute, P < .001) during the Holter monitoring. Spectral analysis showed a significant enhancement in HRV parameters (high- and low-frequency power) because there was an increase in the standard deviation of normal to normal R-R intervals (116 +/- 25 vs 174 +/- 56 milliseconds, P < .001), the standard deviation of the mean R-R intervals calculated over a 5-minute period (104 +/- 25 vs 148 +/- 45 milliseconds, P < .001), the square root of the mean of the squared differences between adjacent normal R-R intervals (25 +/- 8 vs 50 +/- 20 milliseconds, P < .001), and the percentage of differences between adjacent normal R-R intervals exceeding 50 milliseconds (5% +/- 5% vs 22% +/- 13%, P < .001). Echocardiographic measures remained unchanged when comparing the groups. Weight loss after bariatric surgery enhances HRV and decreases mean and minimal heart rate during Holter monitoring through a better cardiac parasympathetic modulation.


Liquid Biopsies in the Screening of Oncogenic Mutations in NSCLC and its Application in Targeted Therapy.
Non-small cell lung cancer (NSCLC) still dominates cancer-related deaths in America. Despite this, new discoveries and advancements in technology are helping with the detection and treatment of NSCLC. The discovery of circulating tumor DNA in blood and other biofluids is essential for the creation of a DNA biomarker. Limitations in technology and sequencing have stunted assay development, but with recent advancements in the next-generation sequencing, droplet digital PCR, and EFIRM, the detection of mutations in biofluids has become possible with reasonable sensitivity and specificity. These methods have been applied to the detection of mutations in NSCLC by measuring the levels of circulating tumor DNA. ALK fusion genes along with mutations in EGFR and KRAS have been shown to correlate to tumor size and metastasis. These methods allow for noninvasive, affordable, and efficient diagnoses of oncogenic mutations that overcome the issues of traditional biopsies. These issues include tumor heterogeneity and early detection of cancers with asymptomatic early stages. Early detection and treatment remain the best way to ensure survival. This review aims to describe these new technologies along with their application in mutation detection in NSCLC in order to proactively utilize targeted anticancer therapy.


Are whale sharks exposed to persistent organic pollutants and plastic pollution in the Gulf of California (Mexico)? First ecotoxicological investigation using skin biopsies.
The whale shark (Rhincodon typus) is an endangered species that may be exposed to micro- and macro-plastic ingestion as a result of their filter-feeding activity, particularly on the sea surface. In this pilot project we perform the first ecotoxicological investigation on whale sharks sampled in the Gulf of California exploring the potential interaction of this species with plastic debris (macro-, micro-plastics and related sorbed contaminants). Due to the difficulty in obtaining stranded specimens of this endangered species, an indirect approach, by skin biopsies was used for the evaluation of the whale shark ecotoxicological status. The levels of organochlorine compounds (PCBs, DDTs), polybrominated diphenyl ethers (PBDEs) plastic additives, and related biomarkers responses (CYP1A) were investigated for the first time in the whale shark. Twelve whale shark skin biopsy samples were collected in January 2014 in La Paz Bay (BCS, Mexico) and a preliminary investigation on microplastic concentration and polymer composition was also carried out in seawater samples from the same area. The average abundance pattern for the target contaminants was PCBs>DDTs>PBDEs>HCB. Mean concentration values of 8.42ng/g w.w. were found for PCBs, 1.31ng/g w.w. for DDTs, 0.29ng/g w.w. for PBDEs and 0.19ng/g w.w. for HCB. CYP1A-like protein was detected, for the first time, in whale shark skin samples. First data on the average density of microplastics in the superficial zooplankton/microplastic samples showed values ranging from 0.00items/m3 to 0.14items/m3. A focused PCA analysis was performed to evaluate a possible correlation among the size of the whale sharks, contaminants and CYP1A reponses. Further ecotoxicological investigation on whale shark skin biopsies will be carried out for a worldwide ecotoxicological risk assessment of this endangerd species.


Absorption of ultrasound by mammalian ovaries.
The transient thermoelectric method was employed to determine the ultrasonic absorption coefficient of excised bovine, canine, feline, murine, ovine, and porcine ovaries at 1 MHz. The dynamics of the organ yields significant variations with physiological stage and structure. Values ranged from 0.017 cm-1 for the follicle to 0.050 cm-1 for the corpus luteum, largely reflecting macromolecular content. Little interspecies variation was observed.


Ranking cliques in higher-order complex networks.
Traditional network analysis focuses on the representation of complex systems with only pairwise interactions between nodes. However, the higher-order structure, which is beyond pairwise interactions, has a great influence on both network dynamics and function. Ranking cliques could help understand more emergent dynamical phenomena in large-scale complex networks with higher-order structures, regarding important issues, such as behavioral synchronization, dynamical evolution, and epidemic spreading. In this paper, motivated by multi-node interactions in a topological simplex, several higher-order centralities are proposed, namely, higher-order cycle (HOC) ratio, higher-order degree, higher-order H-index, and higher-order PageRank (HOP), to quantify and rank the importance of cliques. Experiments on both synthetic and real-world networks support that, compared with other traditional network metrics, the proposed higher-order centralities effectively reduce the dimension of a large-scale network and are more accurate in finding a set of vital nodes. Moreover, since the critical cliques ranked by the HOP and the HOC are scattered over a complex network, the HOP and the HOC outperform other metrics in ranking cliques that are vital in maintaining the network connectivity, thereby facilitating network dynamical synchronization and virus spread control in applications.


Mental Health of Asian American Caregivers of Family Members With Severe Mental Illness.
Within the general population, caregivers of individuals with severe mental illness experience considerable mental health burdens. Less is known about these burdens among Asian Americans, who frequently serve as primary caregivers of family members in accordance with cultural values of familism and interdependence. Asian American caregivers experience severe stigma regarding mental health issues as well as other barriers to care, often resulting in decreased help-seeking behaviors and poorer mental health. Given a paucity of research, the authors systematically reviewed the literature on mental health outcomes among Asian American caregivers. This column offers policy and practice suggestions for supporting the mental health of Asian American families affected by severe mental illness.


Fibrin sheath and its relation to subsequent events after tunneled dialysis catheter exchange.
The use of tunneled catheters (TDC) for chronic hemodialysis is frequent and often fails due to fibrin or thrombus and infection. We hypothesized that the presence of fibrin sheath in TDC increases the risk for subsequent catheter malfunction and infection. We did a retrospective review of TDC exchanges and de novo placements from January 2005 to September 2011. Demographic data, information about the catheter procedure, and radiological data were collected. Final outcome analysis included 168 procedure events. Three groups of catheter procedures were identified: catheter exchange without a fibrin sheath (CE), catheter exchange with a treated fibrin sheath (CEF), and de novo catheter placements (DCP). Fibrin sheath incidence was 47%. In the CEF group, there was no statistical difference in the incidence of subsequent infections or dysfunctions (7% and 60%, respectively), when compared with the CE group (9% and 43%, respectively), (p=0.3). Mean time to subsequent dysfunction or infection was similar for CEF and CE (135 vs. 136 days, p-value, 0.98). Fibrin sheaths are common and should be evaluated when performing TDC exchange. If the fibrin sheath is treated, there is no increased incidence in subsequent catheter dysfunction or infection compared with patients without a fibrin sheath.


[Isolation and purification of recombinant truncated (delta2-27) cytochrome P450 2B4 expressed in E. coli cells as a fusion protein with glutathione-S-transferase].
This paper describes the modification of the method by Coon and Pernecky (Meth. Enzymol. 1996, 272, 25-34) for purification of truncated (delta 2-27) recombinant form of cytochrome P450 2B4 expressed in E. coli as fusion protein with glutathione-S-transferase. The modifications included optimisation of conditions for proteolytic reaction of fusion protein with thrombine, removal of this protease from purified cytochrome P450 preparations using column chromatography on hydroxyapatite, introduction of the additional step for obtaining of spheroplasts using of lysozyme, and optimisation of conditions for enzyme stabilisation during of its purification and storage. The overall yield of purified cytochrome was 20% and the specific content of P450 was 14,5 nmol/mg protein was measured. This method is suitable for large-scale isolation of high purified cytochromes P450 which are necessary for study of structure-functional relationships of this hemoprotein with protein partners as well as for investigation of its structure and mechanism of action.


[Atherosclerotic calcification of coronary artery detected by electron beam CT: A new probation of calcific algorithm].
Electron beam computed tomography (EBCT) can detect the atherosclerotic calcification of coronary artery qualitatively and quantitatively. It was also verified that the atherosclerotic calcification was directly related to the atherosclerotic extent and had a limited relation to the occurrence of coronary heart disease (CHD). So EBCT is one of the good non-invasive methods for predicting the risk of CHD. However, there are some problems in the calcification parameters (calcification area, calcification score) adopted by EBCT which have high variability and low reproducibility. As a result, these parameters have imperfection and need to be improved further. This research provides a new calcification parameter (calcification volume) which makes the use of three dimensional information of all calcific pixels in EBCT scanning images of coronary artery. After experiment in 11 human coronary artery specimens, it was testified that calcification volume had a lower variability than calcification area and calcification score in 25% percentile, median, 75% percentile, Mean, respectively. P value of t test in Mean variability is 0.027, and 0.058. These results suggest that calcification volume may be a new calcification parameter.


Nasoantral window assessment by acoustic rhinometry.
Twenty-five patients who had each had inferior meatal antrostomies performed were endoscopically examined and assessed with acoustic rhinometry six weeks and six months after surgery. No significant increase in nasal cross-sectional area could be demonstrated at the site of the antrostomy in the post-operative cases, although the nasoantral window was found to be patent in 44 of the 50 nasal cavities.


Proton enhancement in an extended nanochannel.
Proton enhancement in an extended nanochannel is investigated by a continuum model consisting of three-dimensional Poisson-Nernst-Planck equations for the ionic mass transport of multiple ionic species with the consideration of surface chemistry on the nanochannel wall. The model is validated by the existing experimental data of the proton distribution inside an extended silica nanochannel. The proton enhancement behavior depends substantially on the background salt concentration, pH, and dimensions of the nanochannel. The proton enrichment at the center of the nanochannel is significant when the bulk pH is medium high (ca. 8) and the salt concentration is relatively low. The results gathered are informative for the development of biomimetic nanofluidic apparatuses and the interpretation of relevant experimental data.


Impact of collaborative nursing care on the recovery process of mental health day hospital users: a mixed-methods study protocol.
Very few collaborative nursing care interventions have been studied and shown to be effective in the context of the paradigm shift towards recovery in mental health nursing. Understanding the changes produced in the recovery process of people with mental health problems can contribute to the design and implementation of new methodologies to offer effective and person-centred care. This is a mixed-methods study, which is structured in three phases. In phase one (baseline) and phase three (follow-up), quantitative data will be collected from patients at a mental health day hospitals based on a two-armed, parallel-design, non-randomised trial. In phase two, two groups will be established: an intervention group in which the intervention based on collaborative nursing care will be carried out through the codesign and implementation of activities through Participatory Action Research, and a control group in which the usual care dynamics will be continued. All the users of three mental health day hospitals who agree to participate in the study will be studied consecutively until the necessary sample size is reached. The outcomes used to evaluate the impact of the intervention will be the stage of the recovery process, the quality of the therapeutic relationship and the patient's level of positive mental health. This study has been approved by the institutional review board of the reference hospital, FIDMAG Hermanas Hospitalarias (PR-2020-10) in July 2020. All participants will be able to voluntarily withdraw from the study at any time. For this reason, users will be given a sheet with all the precise information about the study to be carried out and written consent will be requested. Preliminary and final results will be published in peer-reviewed journals and presented at national and international congresses. NCT04814576.


Protein substitute for children and adults with phenylketonuria.
Phenylketonuria is an inherited disease characterised by an absence or deficiency of the enzyme phenylalanine hydroxylase. The aim of treatment is to lower blood phenylalanine concentrations to prevent developmental delay. Current treatment is based on a low phenylalanine diet in combination with a protein substitute (mixtures of amino acids free from or low in phenylalanine). Guidance regarding the dosage and distribution of this protein substitute, over a 24-hour period, is unclear and there is variation in recommendation between treatment centres. To assess in children and adults with phenylketonuria, who are adhering to a low phenylalanine diet, the benefits and adverse effects of protein substitute, its dosage and distribution of dose. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted manufacturers of the phenylalanine-free and low phenylalanine protein substitutes for any data from published and unpublished randomised controlled trials. Date of the most recent search of the Group's Trials Register: August 2005. All randomised or quasi-randomised controlled trials comparing: any dose of protein substitute with no protein substitute; an alternative dosage; or the same dose, but given as frequent small doses throughout the day compared with the same total daily dose given as larger boluses less frequently. Both authors independently extracted data and assessed trial quality. The searches identified 20 trials, of which one, including a total of 28 participants, was eligible for inclusion in the review. This was a two-phase trial, with only phase one being a randomised controlled trial. As data from both phases were combined in the analysis presented in the published paper, we are currently unable to include any data from the randomised controlled trial in the analysis of this review. No conclusions could be made about the short- or long-term use of protein substitute in phenylketonuria due to the lack of adequate trial data. A randomised controlled trial is needed to investigate the use of protein substitute in phenylketonuria. Until further evidence is available current practice in the use of protein substitute should continue to be observed and monitored with care.


Atom probe study of B2 order and A2 disorder of the FeCo matrix in an Fe-Co-Mo-alloy.
The physical and mechanical properties of intermetallic alloys can be tailored by controlling the degree of order of the solid solution by means of heat treatments. FeCo alloys with an appropriate composition exhibit an A2-disorder↔B2-order transition during continuous cooling from the disordered bcc region. The study of atomic order in intermetallic alloys by diffraction and its influence on the material properties is well established, however, investigating magnetic FeCo-based alloys by conventional methods such as X-ray diffraction is quite challenging. Thus, the imaging of ordered FeCo-nanostructures needs to be done with high resolution techniques. Transmission electron microscopy investigations of ordered FeCo domains are difficult, due to the chemical and physical similarity of Fe and Co atoms and the ferromagnetism of the samples. In this work it will be demonstrated, that the local atomic arrangement of ordered and disordered regions in an industrial Fe-Co-Mo alloy can be successfully imaged by atom probe measurements supported by field ion microscopy and transmission Kikuchi diffraction. Furthermore, a thorough atom probe parameter study will be presented and field evaporation artefacts as a function of crystallographic orientation in Fe-Co-samples will be discussed.


Responses of Membranes and the Photosynthetic Apparatus to Salt Stress in Cyanobacteria.
Cyanobacteria are autotrophs whose photosynthetic process is similar to that of higher plants, although the photosynthetic apparatus is slightly different. They have been widely used for decades as model systems for studying the principles of photosynthesis, especially the effects of environmental stress on photosynthetic activities. Salt stress, which is the most common abiotic stress in nature, combines ionic and osmotic stresses. High cellular ion concentrations and osmotic stress can alter normal metabolic processes and photosynthesis. Additionally, salt stress increases the intracellular reactive oxygen species (ROS) contents. Excessive amounts of ROS will damage the photosynthetic apparatus, inhibit the synthesis of photosystem-related proteins, including the D1 protein, and destroy the thylakoid membrane structure, leading to inhibited photosynthesis. In this review, we mainly introduce the effects of salt stress on the cyanobacterial membranes and photosynthetic apparatus. We also describe specific salt tolerance mechanisms. A thorough characterization of the responses of membranes and photosynthetic apparatus to salt stress may be relevant for increasing agricultural productivity.


Regulating synchronous states of complex networks by pinning interaction with an external node.
To shed light on how biological and technological systems can establish or maintain a synchronous functioning, we address the problem of how to engineer an external pinning action on a network of dynamical units. In particular, we study the regulation of a network toward a synchronized behavior by means of a bidirectional interaction with an external node that leaves unchanged its inner parameters and architecture. We demonstrate that there are two classes of networks susceptible of being regulated into a synchronous motion and provide a simple method, for each one of them, to properly design a pinning sequence to achieve regulation. We also discuss how the obtained sequence can be compared with a topological ranking of the network nodes.


Field location and player roles as constraints on emergent 1-vs-1 interpersonal patterns of play in football.
This study examined effects of player roles on interpersonal patterns of coordination that sustain decision-making in 1-vs-1 sub-phases of football in different field locations near the goal (left-, middle- and right zone). Participants were fifteen U-16yrs players from a local competitive amateur team. To measure interpersonal patterns of coordination in the 1-vs-1 dyads we recorded: (i) the relative distance value between each attacker and defender to the centre of the goal, and (ii), the relative angle between the centre of the goal, each defender and attacker. Results revealed how variations in field locations near the goal (left-, middle- and right-zones) constrained the relative distance and relative angle values that emerged between them and the goal. It reveals that relative position of the goal is a key informational variable that sustained participants' behaviours for dribbling and shooting. Higher values of relative distance and angle were observed in the middle zone, compared to other zones. Players' roles also constitute a constraint on the interpersonal coordination for dribbling and shooting. Additionally, it seems that players' foot preference constrains the dynamics of interpersonal patterns of coordination between participants, especially in left and right zones. The findings suggest that to increase participants' opportunities for action, coaches should account with field positions, players' roles and preference foot.


[Familial Mediterranean fever].
Familial Mediterranean Fever (FMF) is an hereditary disease that especially affects people living around the Mediterranean sea. It is characterized by recurring fever and abdominal pain, eventually associated with localised pleuritis, synovitis or skin inflammation. The most serious complication is amyloidosis, which can lead to terminal renal failure. The attacks and complications can be avoided by life long administration of colchicine. Two independent French and American teams discovered the gene responsible for the disease in 1997. It encodes for a protein named pyrin/marenostrin involved in the homeostasis the inflammatory mechanisms. The main mutations have been identified and are henceforth accessible for molecular screening.


Structure and physiological activity of the motoneurons of the nematode Ascaris.
The nervous system of the nematode worm Ascaris contains about 250 nerve cells; of these, the motoneurons consist of five segmental sets, each containing 11 cells. Morphologically, the motoneurons can be divided into seven different types. Their geometry is simple: some are unbranched, others have one branch point, and the most complex have two. There is no neuropil in the nerve cords; synapses are made by axo-axonal contact or onto short spines. These features enable us to study the anatomy and physiology of the system with a degree of completeness that would be difficult in other systems. The physiological activity of five of the motoneurons has been investigated, three being excitatory and two inhibitory. The excitatory motoneurons receive input from intersegmental interneurons. The inhibitory motoneurons do not receive input from the interneurons; instead they receive their input from the excitatory motoneurons in a circuit that can mediate reciprocal inhibition between the dorsal and the ventral musculature.


Percutaneous absorption of organophosphorus insecticides in pigs--the influence of different vehicles.
In 40 experiments on 20 pigs three different organophosphorus insecticides (OPs), parathion (n = 6), phoxim (n = 7) and phosmet (n = 7), were administered both intravenously (i.v.) and dermally (d.) as 'pour-ons' in a crossover design in order to determine the dermal bioavailability of the OPs. As percutaneous absorption of drugs may be affected by the vehicle used, three chemically different vehicles--DMSO, 1-octanol and macrogol 400-were used for the dermal administration of each of the OPs. The pharmacokinetic parameters measured showed that 15-30% of dermally applied parathion is absorbed when administered in DMSO or octanol, but only 4-5% when administered in macrogol. Absorption was fastest with DMSO and slowest with macrogol. For the two ectoparasiticides, phoxim and phosmet, only between 0.5 and 3% of the dermal dose was absorbed with little difference in the absorption rate between the three vehicles. On the basis of the very limited dermal bioavailability for these two OPs it seems doubtful whether sufficient concentrations can reach the ectoparasites through the systemic route.


From positive psychology to psychopathology: the continuum of attention-deficit hyperactivity disorder.
Integration of positive psychology into clinical research and treatment has been slow. This integration can be facilitated by the conceptualisation of mental disorders as the high, symptomatic extreme of continuous normal variation. This assumes that there is also a low, positive extreme, which is, however, unchartered territory. This study aims to examine how well current measures capture the low extreme of mental disorder continua, using attention-deficit hyperactivity disorder (ADHD) as an example. The ability of three validated scales to capture ADHD as a continuous trait was examined using Item Response Theory in a sample of 9,882 adolescents from the UK population-representative Twins Early Development Study. These scales were: the Strengths and Weakness of ADHD Symptoms and Normal behaviour scale (SWAN), Strength and Difficulties Questionnaire (SDQ - hyperactivity subscale), and Conners' Parent Rating Scale (Conners). Only the SWAN reliably differentiated interindividual differences between participants lying at any level of the continuous ADHD latent trait, including the extreme low, positive end (z-scores from -3 to +3). The SDQ showed low reliability across the ADHD latent trait. In contrast, the Conners performed best at differentiating individuals scoring at or above the mean to the high symptomatic range (z-scores from 0 to +3). The SWAN was the only measure to provide indicators of 'positive mental health', endorsed in the presence of particularly good attentive abilities. Scales such as the SWAN that reliably capture ADHD as a continuous trait, including the positive end, are important for not missing meaningful variation in population-based studies. Indicators of positive mental health may be helpful in clinical practice, as positive attributes have been shown to directly influence as well as buffer negative effects of psychiatric symptoms.


Is anti-Mullerian hormone an indicator of potential polycystic ovary syndrome in prepubertal girls with simple obesity?
The aim of this anti-Mullerian hormone (AMH) levels in prepubertal obese girls are a predictive marker for polycystic ovary syndrome (PCOS) and to investigate the relationship between insulin resistance and AMH. Sixty girls with premature pubarche or obesity and 20 healthy controls between the ages of 6-9 were enrolled. Of the patients, 22 (36.7%) were in the obese group (Group 1), 28 (46.7%) in the early pubarche group (Group 2) and 10 (16.6%) in the early pubarche + obese group (Group 3). Comparison of the subjects' fasting insulin and homeostatic model assessment insulin resistance (HOMA-IR) demonstrated significantly higher values for group 1 compared to group 2 (p=0.001 and 0.001) and, likewise, significantly higher values for group 3 compared to group 2. There was no significant differences between all groups for AMH levels. AMH levels were not significantly different in the obese girls compared to the other groups. There was also no relationship between AMH and insulin resistance in any of the groups. Further studies, however, are needed due the limited number of subjects in this study and in the absence of adequate relevant data.


Pathophysiology of plaque instability: insights at the genomic level.
Atherosclerosis and plaque rupture represent complex "traits" of unknown cause that involve multiple genes and their variants. Novel genomic technologies provide us with the tools that will allow for the identification of groupings of genes that determine either susceptibility or resistance relative to the development of atherosclerosis and its thromboembolic complications. This information may, in turn, lead to a clearer understanding of the cause and risk for atherosclerosis. Diagnostic tools, as well as preventive and therapeutic strategies, will be derived from such heightened understanding of the disease process. With this chapter, we have presented the current state of knowledge of atherosclerosis genomics.


Predictable preparation, staining, and cementation procedures for chairside CAD/CAM dentistry.
Although direct composite resin procedures yield acceptable results when used correctly, if a large quantity of resin is required, complications may arise. In such cases, an indirect protocol must be followed. Numerous CAD/CAM systems, both laboratory and chairside, are available for practitioner use. In a laboratory system, a traditional impression is made and sent to a dental laboratory, where the restoration is fabricated. A chairside system, however, utilizes a digital impression system, and the restoration can then be milled and cemented in a single visit.


Rice ASR1 and ASR5 are complementary transcription factors regulating aluminium responsive genes.
Rice is the most tolerant staple crop to aluminium (Al) toxicity, which is a limiting stress for grain production worldwide. This Al tolerance is the result of combined mechanisms that are triggered in part by the transcription factor ASR5. ASRs are dual target proteins that participate as chaperones in the cytoplasm and as transcription factors in the nucleus. Moreover, these proteins respond to biotic and abiotic stresses, including salt, drought and Al. Rice plants with silenced ASR genes are highly sensitive to Al. ASR5, a well-characterized protein, binds to specific cis elements in Al responsive genes and regulates their expression. Because the Al sensitive phenotype found in silenced rice plants could be due to the mutual silencing of ASR1 and ASR5, we investigated the effect of the specific silencing of ASR5. Plants with artificial microRNA silencing of ASR5 present a non-transformed phenotype in response to Al because of the induction of ASR1. ASR1 has the same subcellular localization as ASR5, binds to ASR5 cis-regulatory elements, regulates ASR5 regulated genes in a non-preferential manner and might replace ASR5 under certain conditions. Our results indicate that ASR1 and ASR5 act in concert and complementarily to regulate gene expression in response to Al.


Comparison of shear bond strength of amalgam bonded to primary and permanent dentin.
Amalgam's non-adhesive characteristics necessitate cavity preparations incorporating retentive features, which often require the removal of non-carious tooth structure. Use of adhesives beneath amalgam restorations, would be helpful to overcome this disadvantage. This study was undertaken to compare the mean shear bond strength of amalgam bonded to primary and permanent dentin, to evaluate the efficacy of amalgam adhesives in pediatric dentistry.27 primary and 28 permanent posterior teeth with intact buccal or lingual surfaces were grounded to expose dentin and wet-polished with 400-grit silicone carbide paper. Scotchbond Multi Purpose Plus adhesive system was applied to the dentin surfaces and light cured. Amalgam was condensed onto the treated dentin through a plastic mold.shear bond strength testing was done using an Instron Universal testing machine, at a crosshead speed of 0.5 mm/min.The data were analyzed by independent samples t-test The difference among the two groups was not statistically significant (p>0.05) Bonded amalgam showed the same level of bond strength to primary and permanent dentin; so, application of amalgam bonding agents in pediatric dentistry can be recommended.


Using Evidence To Inform Practice and Policy To Enhance the Quality of Care for Persons with Traumatic Spinal Cord Injury.
In today's economic climate, there is a need to demonstrate a return on investment for healthcare spending and for clinical practice and policy to be informed by evidence. Navigating this process is difficult for decision-makers, clinicians, and researchers alike. This article will describe how a knowledge translation framework and an evidence-based policy-making process were integrated to clarify the problem, frame options, and plan implementation, to impact clinical practice and policy in the area of traumatic spinal cord injury (tSCI). The Access to Care and Timing (ACT) project is focused on optimizing the access and timing of specialized healthcare delivery for persons sustaining a tSCI in Canada. A simulation model was developed that uses current patient data to address complex problems faced by the healthcare system. At a workshop, participants stressed the importance of linking interventions to short- and long-term outcomes to drive change. Presently, there are no national, system level indicators to monitor performance after tSCI. Although the ideal system of care after tSCI is unknown, indicator collection will establish a baseline to measure improvement. The workshop participants prioritized two indicators important from the clinician and patient perspective-timely admission to rehabilitation and meaningful community participation. The ACT simulation model for tSCI care will be used to promote the uptake of identified indicators and provide a predictive link between interventions on potential outcomes. The standardized collection of outcome-oriented indicators will help to evaluate the access and timing of care and to define the ideal system of care after SCI.


Ability of a Risk Prediction Tool to Stratify Quality and Cost for Older Patients With Operative Ankle Fractures.
To investigate the ability of a validated geriatric trauma risk prediction tool to stratify hospital quality metrics and inpatient cost for middle-aged and geriatric patients admitted from the emergency department for operative treatment of an ankle fracture. Prospective cohort study. Single Academic Medical Center. Patients 55 years of age and older who sustained a rotational ankle fracture and who were treated operatively during their index hospitalization. Calculation of validated trauma triage score, Score for Trauma Triage in Geriatric and Middle Aged (STTGMA), using patient demographics, injury severity, and functional status. Patients were stratified into groups based on scores to create a minimal-, low-, moderate-, and high-risk cohort. Length of stay, complications, need for intensive care unit-/step-down unit-level care, discharge location, and index admission costs. Fifty ankle fracture patients met inclusion criteria. The mean length of stay was 7.8 ± 5.2 days with a significant difference among the 4 risk groups (4.6-day difference between low and high risk). 73.1% of minimal-risk patients were discharged home compared with 0% of high-risk patients. There was no difference in complication rate or in need for intensive care unit-level care between groups. However, high-risk patients had a mean total inpatient cost 2 times greater than that of minimal-risk patients. The Score for Trauma Triage in Geriatric and Middle-Aged tool is able to meaningfully stratify older patients with ankle fracture who require operative fixation regarding hospital quality metrics and cost. This information may allow for efficient targeted reductions in costs while optimizing outcomes. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Generation of novel hybrid aptamer-molecularly imprinted polymeric nanoparticles.
A strategy to exploit aptamers as recognition elements of molecularly imprinted polymeric nanoparticles (AptaMIP NPs) is presented, via modification of the chemical structure of the DNA. It is demonstrated that the introduction of this modified "aptamer monomer" results in an increase of the affinity of the produced MIP NPs, without altering their physical properties such as size, shape, or dispersibility.


Different Continuous Training Intensities Improve Echocardiographic Parameters, Quality of Life, and Functional Capacity in Heart Failure Patients with Reduced Ejection Fraction.
Multiple comorbidities and physiological changes play a role in a range of heart failure conditions and influence the most effective approach to exercise-based rehabilitation. This research aimed to examine and compare the outcomes of continuous training at three different intensities, focusing on left ventricular (LV) remodeling, functional capacity, and quality of life among patients with heart failure with reduced ejection fraction (HFrEF). In this randomized control trial, a total of 60 male patients (average age: 54.33 ±2.35 years) with HFrEF were randomly allocated into three groups: 1) High-intensity continuous training group (HICT), 2) Moderate-intensity continuous training group (MICT), and 3) Low-intensity continuous training group (LICT). All the training was performed on a bicycle ergometer 3 times/week for 12 weeks. Echocardiographic parameters (left ventricular ejection fraction, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, N-terminal pro-B-type natriuretic peptide (NT-proBNP), quality of life (Minnesota Living with Heart Failure Questionnaire), and functional capacity (6-minute walking test) were assessed before and the end of the study. The HICT group demonstrated the greatest improvements in all measured variables when compared to the other two groups (P < 0.05). These findings were consistent across all measured outcomes. It was determined that HICT appears to yield the most favorable outcomes in enhancing echocardiographic measures, NT-proBNP levels, quality of life, and functional capacity among HFrEF patients.


Diagnostic problems of cervico-vaginal infections by HPV.
The diagnostic problems of cervico-vaginal infections by HPV have been considered. The colposcopic and cytological diagnoses have been compared with the histological one in order to evaluate the diagnostic reliability of the two methods of screening, and to seek evidence of those colposcopic and cytological aspects which, even if not pathognomic, are suggestive of HPV infection. The association between viral changes and CIN and the correlated problems have also been examined. The importance is underlined of screening and following up of HPV infections by the integrated use of colpocytology and colposcopy and of eventual aimed histologic checking as an improved prognostic evaluation, considering the potentiality of the evolutive risks of such infections.


The preprotein translocase of the mitochondrial outer membrane.
The translocase components of the mitochondrial outer membrane (Tom) are essential for the transfer of preproteins from the cytosol to the mitochondria. At least nine Tom components have now been identified and they fall into two categories; receptor components and components of the General Import Pore (GIP). The receptor components most likely diffuse laterally in the membrane and deposit preproteins atthe GIP where they are then inserted into the mitochondria. This review focuses on these components and their known interactions in the process of preprotein translocation.


Prevalence and Factors Associated with Fixed-Dose Combination Antiretroviral Drugs Adherence among HIV-Positive Pregnant Women on Option B Treatment in Mpumalanga Province, South Africa.
The possibility for all babies to be born and remain HIV-negative for the first year of life is achievable in South Africa. HIV-positive mothers' adherence to their antiretroviral medication is one of the crucial factors to achieve this target. Cross-sectional data were collected at 12 community health centres, over 12 months (2014-2015), from 673 HIV-positive women, less than 6 months pregnant, attending antenatal care, and on Option B treatment. Adherence measures included the Adults AIDS Clinical Trials Group (AACTG) four-day measure, as well as the Visual Analog Scale (VAS) seven-day measure. Bivariate analyses and multivariate logistic regressions are presented. 78.8% of respondents were adherent on AACTG, while 68.8% reported VAS adherence. Bivariate analyses for increased adherence show significant associations with older age, less/no alcohol usage, disclosure of HIV status, higher HIV knowledge, no desire to avoid ARV side effects, low stigma, and low depression. AACTG showed a negative association with intimate partner violence. Multivariable logistic regression on AACTG and VAS adherence rates resulted in unique contributions to increased adherence of older age, less/no alcohol usage, higher HIV knowledge, lack of depression, and non-disclosure. Programs targeting closer side effect monitoring, HIV disclosure, pre-natal depression, alcohol intake, and HIV knowledge need consideration.


Developmental barcoding of whole mouse via homing CRISPR.
In vivo barcoding using nuclease-induced mutations is a powerful approach for recording biological information, including developmental lineages; however, its application in mammalian systems has been limited. We present in vivo barcoding in the mouse with multiple homing guide RNAs that each generate hundreds of mutant alleles and combine to produce an exponential diversity of barcodes. Activation upon conception and continued mutagenesis through gestation resulted in developmentally barcoded mice wherein information is recorded in lineage-specific mutations. We used these recordings for reliable post hoc reconstruction of the earliest lineages and investigation of axis development in the brain. Our results provide an enabling and versatile platform for in vivo barcoding and lineage tracing in a mammalian model system.


Interleukin-6 is a potent thrombopoietic factor in vivo in mice.
To determine the biologic activity of interleukin-6 (IL-6) on megakaryocytopoiesis and thrombocytopoiesis in vivo, the cytokine was administered intraperitoneally to mice every 12 hours at varying doses for five days or for varying time intervals, based on the kinetic analysis of IL-6 serum levels indicating the peak of 40 minutes following injection, with no detection at 150 minutes. A dose-response experiment showed that IL-6 increased platelet counts in a dose-dependent fashion at a plateau stimulation level of 5 micrograms. Administration of 5 micrograms of IL-6 reproducibly elevated platelet counts at five days by approximately 50% to 60% of increase. Moreover, a striking increase in megakaryocytic size in response to IL-6 was elicited by the treatment, but no change in megakaryocyte numbers; whereas IL-6 administration did not expand CFU-MK numbers. The in vivo studies in this manner had negligible effects on other hematologic parameters, with the minor exception of monocyte levels. These data show that IL-6 acts on maturational stages in megakaryocytopoiesis and promotes platelet production in vivo in mice, suggesting that IL-6 functions as thrombopoietin.


Synthesis, Structure, and Properties of Monodispersed and Highly Luminescent Organoborane Oligomers.
Organoborane oligomers with well-defined molecular structures and high luminescence are scarce, among which those with boron not used as bridging atoms are even more so. Here, a series of well-defined ethynyl-linked or butadiynyl-linked conjugated organoborane oligomers with high fluorescence quantum yield and extinction coefficient (i.e., high brightness) were prepared by coupling different building blocks featuring dithienooxadiborepine moieties. Single crystal structures of hexyl modified dithienooxadiborepine (1a-hex) and hexyl-modified butadiynyl-linked conjugated dimer (D2-hex) not only verified the identity of the molecular structures but also revealed that the introduction of the hexyl chains distorted the molecular structures due to steric hindrance. Optical measurements showed that the absorption and emission maxima of the six oligomeric molecules bathochromic shifted with increasing numbers of repeating units. Molecules without hexyl chains emit efficient fluorescence upon photoexcitation, and the fluorescence quantum efficiency of the ethynyl-linked conjugated dimer (D1) is close to unity. Theoretical calculation results using density functional theory methods are consistent with the single crystal data, allowing a better understanding of the spectral properties. Such results indicate that the method is efficient for expanding small organoborane molecules into π-conjugated oligomers, which can be used to modulate to emit different colors with high efficiency.


Palmitic acid-induced apoptosis in pancreatic β-cells is increased by liver X receptor agonist and attenuated by eicosapentaenoate.
Saturated fatty acids are implicated in the development of diabetes via the impairment of pancreatic islet β-cell viability and function. Liver X receptors (LXRs) and eicosapentaenoate (EPA) are known regulators of fatty acid metabolism. However, their roles in the pathogenesis of diabetes remain incompletely understood. The aim of this study was to determine the effects of EPA and the LXR agonist T0901317 on saturated fatty acid (palmitic acid)-induced apoptosis in the insulinoma β-cell line INS-1, a model for insulin-secreting β-cells. T0901317 significantly promoted palmitic acid-induced apoptotic cell death in the INS-1 cells. Consistent with these results, caspase-3 activity and BAX and sterol regulatory element binding protein-1c (SREBP-1c) mRNA levels were markedly increased in INS-1 cells co-administered palmitic acid and T0901317. The production of reactive oxygen species was considerably higher in the cells cultured concurrently with T0901317 and palmitic acid than in the cells incubated with either agent alone. EPA treatment attenuated the cellular death promoted by palmitic acid and T0901317 in the INS-1 cells, disclosing a possible mediating mechanism involving the inhibition of SREBP-1c. Finally, T0901317 up-regulated the palmitic acid-induced expression of p27(KIP1), transforming growth factor beta 1, and SMAD3 proteins in INS-1 cells. These results demonstrate that palmitic acid-induced apoptosis in β-cells is enhanced by T0901317 via the activation of LXRs and is blocked by EPA via the inhibition of SREBP-1c, suggesting that the regulation of lipogenesis and lipotoxicity affecting pancreatic β-cell viability and insulin production may be a unique strategy for diabetes therapy.


Age-related changes in the morphology of tanycytes in the human female infundibular nucleus/median eminence.
Tanycytes are emerging as key players in the neuroendocrine control of gonadotrophin-releasing hormone (GnRH) release. Rodent studies have demonstrated that the structural relationship between tanycytes and GnRH terminals in the median eminence is highly dynamic, regulated by gonadal steroids and undergoes age-related changes. The present study aimed to determine whether the number and organisation of tanycytes changes throughout life in the female infundibular nucleus/median eminence (INF/ME) region. Post-mortem hypothalamic tissues were collected at the Netherlands Brain Bank and were stained for vimentin by immunohistochemistry. Hypothalami of 22 control female subjects were categorised into three periods: infant/prepubertal, adult and elderly. We measured the fractional area covered by vimentin immunoreactivity in the INF. Qualitative analysis demonstrated a remarkable parallel organisation of vimentin-immunoreactive processes during the infant/prepubertal and adult periods. During the elderly period, this organisation was largely lost. Semi-quantitatively, the fractional area covered in vimentin immunoreactivity was significantly higher at the infant/prepubertal compared to the adult period and almost reached statistical significance compared to the elderly period. By contrast, the number of tanycyte cell bodies did not appear to change throughout life. The results of the present study thus demonstrate that the number and structure of tanycytic processes are altered during ageing, suggesting that tanycytes might be involved in the age-related changes observed in GnRH release.


Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML.
Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2'3'-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2'3'-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML.


Direct conversion of human fibroblasts into neuronal restricted progenitors.
Neuronal restricted progenitors (NRPs) represent a type of transitional intermediate cells that lie between multipotent neural progenitors and terminal differentiated neurons during neurogenesis. These NRPs have the ability to self-renew and differentiate into neurons, but not into glial cells, which is considered an advantage for cellular therapy of human neurodegenerative diseases. However, difficulty in the extraction of highly purified NRPs from normal nervous tissue prevents further studies and applications. In this study, we report the conversion of human fetal fibroblasts into human induced NRPs (hiNRPs) in 11 days by using just three defined factors: Sox2, c-Myc, and either Brn2 or Brn4. The hiNRPs exhibited distinct neuronal characteristics, including cell morphology, multiple neuronal marker expression, self-renewal capacity, and a genome-wide transcriptional profile. Moreover, hiNRPs were able to differentiate into various terminal neurons with functional membrane properties but not glial cells. Direct generation of hiNRPs from somatic cells will provide a new source of cells for cellular replacement therapy of human neurodegenerative diseases.


Hyperbilirubinemia reduces the streptozotocin-induced pancreatic damage through attenuating the oxidative stress in the Gunn rat.
Oxidative stress is an important pathogenic factor in diabetes. Bilirubin may serve a cytoprotective function as an anti-oxidant. The Gunn rat lacks the enzyme uridine-diphosphate glucuronosyltransferase that is responsible for conjugation of bilirubin, exhibiting elevation of plasma bilirubin. We examined the effect of hyperbilirubinemia on the pancreatic damage caused by streptozotocin (STZ) in the Gunn rat. Male Wistar rats and male Gunn rats were treated with STZ (WS and GS groups, respectively) or vehicle (WC and GC groups, respectively). All 5 rats in the WS group developed diabetes, defined as fasting blood glucose 300 mg/dL or more, at 3 days, whereas only 2 of the 5 GS rats became diabetic at 7 days after STZ injection. Without insulin supplement at 7 days after STZ injection, the WS group displayed higher levels of fasting blood glucose (510.3 ± 50.3 vs. 236.4 ± 42.5 mg/dL, p = 0.003) and HbA1c (5.0 ± 0.1 vs. 3.9 ± 0.1, p = 0.001), compared to those of GS group. In Wistar rats, STZ induced apoptosis of the pancreatic islet cells, accompanied with activation of NADPH oxidase and increased production of reactive oxygen species and nitric oxide, but not in Gunn rats. Moreover, in a rat insulinoma cell line (RIN-m5F), pre-treatment with bilirubin (0.1 mg/dL) decreased cell death and apoptosis caused by STZ, and also reduced H₂O₂ production. Considering the protective effect of hyperbilirubinemia against STZ-induced injury, we postulate that bilirubin could be a potential therapeutic modality for oxidative stress of pancreas islets.


Comparison of the influence of nonpreserved oxybuprocaine and a preserved artificial tear (thera tears) on human corneal thickness measured by two pachymeters.
To compare the effect of nonpreserved oxybuprocaine and preserved artificial tears on central corneal thickness (CCT) obtained by 2 pachymeters. In this prospective, placebo-controlled study, involving a random sample of 100 eyes of 50 subjects, aged 24±2.3 years, CCT readings were obtained in 2 separate sessions with the Topcon SP-3000P and ultrasound pachymetry (USP), respectively, before, 5 and 10 min after instillation of a drop each of either oxybuprocaine hydrochloride (oxybuprocaine HCl) (group 1) or carboxymethylcellulose sodium, thera tears (group 2), and placebo. The baseline mean CCT for SP-3000P was 509±38 μm and 542±36 μm for USP. No statistical significant differences between baseline CCTs (P>0.05 for both devices) in both groups. In both group experimental eyes, neither SP-3000P nor USP-measured CCTs varied significantly from the control eyes at 5 (P>0.05) and 10 (P>0.05) mins postinstillation of drops in both sessions. In group one, the 95% confidence intervals (CIs) for the SP-3000P CCTs were similar at 5 (-16 to 17 μm) and 10 min (-16 to 17 μm), but in the USP-measured CCTs, it was wider at 10 min (-41 to 46 μm) than at 5 min (-30 to 41 μm) postinstillation. In group two, the 95% CIs at 5 and 10 mins postinstillation, respectively, ranged between -20 and 47 μm, -21 and 43 μm (SP-3000P) and -29 and 23 μm, -26 and 23 μm (USP). Within groups and between groups, variations in CCT were similar at both times intervals in all comparisons. Although oxybuprocaine HCl and thera tears consistently did not affect the mean CCT obtained by both devices at both time intervals, variation in SP-3000P measured CCT was more consistent in both sessions and narrower in relation to USP-measured CCT. It may be reasonable to suggest that measurements of CCT in normal patients be taken before examinations requiring instillation of anesthetics or such measurements when obtained postinstillation of either oxybuprocaine or preserved artificial tears be interpreted with caution.


[Analysis of hidden blood loss after percutaneous kyphoplasty for osteoporotic vertebral compression fracture and its influencing factors].
To investigate the hidden blood loss and related risk factors of osteoporotic vertebral compression fractures after percutaneous kyphoplasty. The clinical data of 153 patients with osteoporotic vertebral compression fractures who underwent percutaneous kyphoplasty from March 2015 to December 2017 were retrospectively analyzed, including 55 males and 98 females, aged 68 to 87(78.6±11.4) years old. Erythrocyte specific volume was collected before and after operation to calculate the hidden blood loss. The influence of sex, age, body mass index, bone mineral density, diabetes mellitus and hypertension, operation mode (unilateral or bilateral), operation time, operative segment and number, loss height of vertebral body and recovery height ratio on hidden blood loss was analyzed by multiple linear regression model. Postoperative hidden blood loss was (287.7±68.5) ml. Multivariate linear regression analysis showed that the history of diabetes mellitus (β=2.405, P=0.012), the mode of operation(β=3.042, P<0.001), the time of operation (β=2.043, P=0.038), the operative segment (β=1.993, P=0.043), the number (β=0.374, P<0.001), the loss of vertebral height (β=2.785, P=0.003) and the recovery ratio(β=7.301, P<0.001) were correlated with occult hemorrhage. There is a certain degree of occult hemorrhage in kyphoplasty for osteoporotic vertebral compression fractures. The risk factors of hidden hemorrhage are diabetes history, operation method, operation time, operative segment and number, loss of vertebral height and recovery ratio.


Similar trends of pyrimethamine resistance-associated mutations in Plasmodium vivax and P. falciparum.
The antifolate drugs sulfadoxine and pyrimethamine are commonly used to treat Plasmodium falciparum malaria. However, they can also affect the Plasmodium vivax parasite if it coexists with P. falciparum, as both species have common drug targets. Resistance to the antifolate drugs arises due to point mutations in the target enzymes of the respective parasite. To assess the cross-species impact of antifolate drug treatment, we describe here the dihydrofolate reductase (DHFR) mutations among field isolates of P. vivax and P. falciparum. The overall DHFR mutation rate for P. vivax was lower than that for P. falciparum. However, both species of Plasmodium followed similar trends of DHFR mutations. Similar to P. falciparum, the DHFR mutation rate of P. vivax also varied from region to region. It was lower in P. vivax-dominant regions but higher in the P. falciparum-dominated areas and highest where antifolates are used as the first line of antimalarial treatment. In conclusion, the antifolate treatment of falciparum malaria is proportionately affecting the DHFR mutations of P. vivax, suggesting that the drug should be used with caution to minimize the development of cross-species resistance in the field.


Complete quantum control of the population transfer branching ratio between two degenerate target states.
A five-level four-pulse phase-sensitive extended stimulated Raman adiabatic passage scheme is proposed to realize complete control of the population transfer branching ratio between two degenerate target states. The control is achieved via a three-node null eigenstate that can be correlated with an arbitrary superposition of the target states. Our results suggest that complete suppression of the yield of one of two degenerate product states, and therefore absolute selectivity in photochemistry, is achievable and predictable, even without studying the properties of the unwanted product state beforehand.


Pain management mini-series. Part I. A review of management of acute pain.
Acute pain is a complex process involving activation of nociceptors, chemical mediators and inflammation. Medications can be used to target each of the key elements within the pain pathway and eliminate or reduce the sensation of pain. Pain management begins, when possible, prior to the tissue trauma and continues throughout the perioperative period. When acute pain is appropriately managed, patient's clinical outcomes and satisfaction are improved.


High Quality of Care Persists With Shifting Depression Services From VA Specialty to Integrated Primary Care.
Offering depression collaborative care services in primary care (PC) settings can reduce use of nonintegrated mental health care resources and improve mental health care access, particularly for vulnerable PC patients. Tests of effects on depression care quality, however, are needed. We examined overall quality of depression care and tested whether increasing clinic engagement in Veterans Affairs (VA)'s Primary Care-Mental Health Integration (PC-MHI) services was associated with differences in depression care quality over time. We conducted a retrospective longitudinal cohort study of 80,136 Veterans seen in 26 Southern California VA PC clinics (October 1, 2008-September 30, 2013). Using multilevel regression models adjusting for year, clinic, and patient characteristics, we predicted effects of clinic PC-MHI engagement (ie, percent of PC patients receiving PC-MHI services) on 3 VA-developed longitudinal electronic population-based depression quality measures among Veterans newly diagnosed with depression (n=12,533). Clinic PC-MHI engagement rates were not associated with significant depression care quality differences. Across all clinics, average rates of follow-up within 84 or 180 days were, 66.4% and 74.5%, respectively. Receipt of minimally appropriate treatment was 80.5%. Treatment probabilities were significantly higher for vulnerable PC patients (homeless: 4.5%, P=0.03; serious mental illness: 15.2%, P<0.001), than for otherwise similar patients without these characteristics. Study patients treated in PC clinics with greater PC-MHI engagement received similarly high quality depression care, and even higher quality for vulnerable patients. Findings support increasing use of PC-MHI models to the extent that they confer some advantage over existing services (eg, access, patient satisfaction) other than quality of care.


Modelling toxoplasma incidence from longitudinal seroprevalence in Stockholm, Sweden.
Age-stratified data on toxoplasma seroprevalence in pregnant women in Stockholm, Sweden for the years 1969, 1979 and 1987 provide the basis for an analysis of temporal patterns of Toxoplasma gondii infection, and estimation of the risk of maternal toxoplasmosis, in this population. A catalytic infection model, in which the rate or force of infection is assumed to be a function of time (and not, as is more usual, age), was employed to describe the observed changes in levels of toxoplasma seropositivity. A range of simple incidence functions (up to 3 parameters) were fitted using a method of maximum likelihood. The data were significantly better described by a linear or an exponential decay in the rate of infection through time compared with a constant level. More complex incidence functions gave no better data description. Thus, whilst there is strong evidence for declining incidence in Stockholm over the past 4-5 decades, the data do not allow discrimination between different possibilities for the nature of this decline. Based on these modelling results, best estimates of the force of infection in 1987 acting on susceptible women are within the range 0 to 0.0045/susceptible/year (95% confidence limits), yielding a possible risk of maternal toxoplasmosis of between 0 and 2.7 cases/1000 pregnancies. These values are shown to be significantly lower than estimates based upon an assumption of temporal stability in toxoplasma incidence, which may be of practical significance to public health policy.


Healthcare managers in negative media focus: a qualitative study of personification processes and their personal consequences.
Over the last decade healthcare management and managers have increasingly been in focus in public debate. The purpose of the present study was to gain a deeper understanding of how prolonged, unfavorable media focus can influence both the individual as a person and his or her managerial practice in the healthcare organization. In-depth interviews (n = 49) with 24 managers and their superiors, or subordinate human resources/information professionals, and partners were analyzed using a grounded theory approach. The conceptual model explains how perceived uncertainties related to the managerial role influence personification and its negative consequences. The role ambiguities comprised challenges regarding the separation of individual identity from the professional function, the interaction with intra-organizational support and political play, and the understanding and acceptance of roles in society. A higher degree of uncertainty in role ambiguity increased both personification and the personal reaction to intense media pressure. Three types of reactions were related to the feeling of being infringed: avoidance and narrow-mindedness; being hard on self, on subordinates, and/or family members; and resignation and dejection. The results are discussed so as to elucidate the importance of support from others within the organization when under media scrutiny. The degree of personification seems to determine the personal consequences as well as the consequences for their managerial practice. Organizational support for managers appearing in the media would probably be beneficial for both the manager and the organization.


[Evaluation of GP specialty training in Bavaria - An online survey among postgraduate trainees].
Statistical projections suggest that by 2020 the number of general practitioners (GPs) in Germany will have decreased by about 13 %, which will lead to a risk of medical undersupply, especially in rural areas. This study was conducted on behalf of the Bavarian Ministry of Environment and Health in order to answer the following questions: How satisfied are young Bavarian physicians in GP specialty training with their training situation? To what extent are they willing to start a private practice, in general and, in particular, in rural areas? The study's online questionnaire contained items concerning the context of GP specialty training and the willingness to set up a private practice. In addition, the "Heidelberger Niederlassungsbarometer", a structured questionnaire illustrating self-assessment of competencies of GPs in training, was included in the survey. We asked GP specialty trainees to participate by e-maiI, directly or via their GP trainers. In total, 99 questionnaires were returned, whereof 95 fulfilled the criteria for analysis. In 76 % of the cases participants were female, 63 % working in practice and 37 % in a structured training programme. The majority of participants (58 %) preferred to work in a practice with more than one GP, followed by those preferring to work as a salaried GP (26 %). Their disposition to work in rural areas after having passed their specialty certificate examination was high or very high (59 %). Feedback on a regular basis was given to 29 % of the study participants. Almost every second participant received a structured initial training programme. Most of the participating GP trainees (59%) were satisfied or very satisfied with their training. In general, there is a high level of motivation among study participants to become an independent and self-employed GP, also in rural areas. Despite the fact that not even every second received central training elements like individual feedback and structured initial training, the participants were mostly satisfied with their GP specialty training.


Dielectric relaxation and anhydrous proton conduction in [C2H5NH3][Na0.5Fe0.5(HCOO)3] metal-organic frameworks.
Metal-organic frameworks (MOFs), in which metal clusters are coupled by organic moieties, exhibit inherent porosity and crystallinity. Although these systems have been examined for vast potential applications, the elementary proton conduction in anhydrous MOFs still remains elusive. One of the approaches to deal with this problem is the utilization of protic organic molecules, to be accommodated in the porous framework. In this work we report the temperature-dependent crystal structure and proton conduction in [C2H5NH3][Na0.5Fe0.5(HCOO)3] metal-organic frameworks using X-ray diffraction and broadband dielectric spectroscopic techniques. The detailed analysis of the crystal structure reveals disorder of the terminal ethylene groups in the polar phase (space group Pn). The structural phase transition from Pn to P21/n at T ≈ 363 K involves the distortion of the metal formate framework and ordering of EtA+ cations due to the reduction of the cell volume. The dielectric data have been presented in the dynamic window of permittivity formalism to understand the ferroelectric phase transition. The relaxation times have been estimated from the Kramers-Kronig transformation of the dielectric permittivity. A Grotthuss type mechanism of the proton conduction is possible at low temperatures with the activation energy of 0.23 eV. This type of experimental observation is expected to provide new prospective on the fundamental aspect of elementary proton transfer in anhydrous MOFs.


Purification of biologically active SPARC expressed in Saccharomyces cerevisiae.
SPARC (secreted protein, acidic and rich in cysteine) is a secreted, Ca+2-binding glycoprotein that modulates interactions between cells and their immediate extracellular matrix. Traditional sources of SPARC have been mammalian bone, platelets, a basement membrane tumor, and cultured cells; most if not all preparations, however, contain platelet-derived growth factor and one or more serum proteins that bind specifically to purified SPARC. To avoid these contaminants, as well as the toxic lipid moiety associated with endotoxin, we expressed recombinant wild-type and a mutated murine SPARC in two strains of Saccharomyces cerevisiae: one strain was transfected with an expression vector encoding a proprietory signal peptide that directed the secretion of the recombinant protein. Recombinant SPARC was also purified from cell lysates of a different, nonreverting strain of S. cerevisiae that was optimized for large-scale fermentation runs. A mutant murine SPARC lacking the single glycosylation site was also expressed following substitution of Asn98 with Asp98 in the wild-type sequence. Purification of SPARC was achieved by copper-affinity and hydrophobic-interaction chromatography. Both the wild-type and the glycosylation-defective recombinant proteins exhibited high levels of activity in two bioassays with endothelial cells: inhibition of cell spreading/disruption of actin microfilaments and competition for the binding of nonrecombinant 125I-labeled SPARC to the cell surface. The availability of biologically active, recombinant SPARC will facilitate investigation of the structural and functional properties of this protein, which is expressed at high levels in healing wounds, atherosclerotic plaque, and several cancers and diseases of connective tissue.


Determination of aflatoxins B1, B2, G1, and G2 in olive oil, peanut oil, and sesame oil using immunoaffinity column cleanup, postcolumn derivatization, and liquid chromatography/fluorescence detection: collaborative study.
The accuracy, repeatability, and reproducibility characteristics of a method using immunoaffinity column (IAC) cleanup with postcolumn derivatization and LC with a fluorescence detector (FLD) for determination of aflatoxins (AFs; sum of AFs B1, B2, G1, and G2) in olive oil, peanut oil, and sesame oil have been established in a collaborative study involving 15 laboratories from six countries. Blind duplicate samples of blank, spiked at levels ranging from 0.25 to 20.0 microg/kg for AF, were analyzed. A naturally contaminated peanut oil sample was also included. Test samples were extracted with methanol-water (55 + 45, v/v). After shaking and centrifuging, the lower layer was filtered, diluted with water, and filtered through glass microfiber filter paper. The filtrate was then passed through an IAC, and the toxins were eluted with methanol. The toxins were then subjected to RPLC-FLD analysis after postcolumn derivatization. Average recoveries of AFs from olive oil, peanut oil, and sesame oil ranged from 84 to 92% (at spiking levels ranging from 2.0 to 20.0 microg/kg); of AFB1 from 86 to 93% (at spiking levels ranging from 1.0 to 10.0 microg/kg); of AFB2 from 89 to 95% (at spiking levels ranging from 0.25 to 2.5 microg/kg); of AFG1 from 85 to 97% (at spiking levels ranging from 0.5 to 5.0 microg/kg); and of AFG2 from 76 to 85% (at spiking levels ranging from 0.25 to 2.5 microg/kg). RSDs for within-laboratory repeatability (RSD(r)) ranged from 3.4 to 10.2% for AF, from 3.5 to 10.9% for AFB1, from 3.2 to 9.5% for AFB2, from 6.5 to 14.9% for AFG1, and from 4.8 to 14.2% for AFG2. RSDs for between-laboratory reproducibility (RSDR) ranged from 6.1 to 14.5% for AF, from 7.5 to 15.4% for AFB1, from 7.1 to 14.6% for AFB2, from 10.8 to 18.1% for AFG1, and from 7.6 to 23.7% for AFG2. Horwitz ratio values were < or = 2 for the analytes in the three matrixes.


Abolition of methacholine induced bronchoconstriction by the hyperventilation of exercise or volition.
Total pulmonary resistance was measured from continuous records of flow and oesophageal pressure in five normal subjects on three separate days before and after inhalation of methacholine. The dose of methacholine produced, on average, a fivefold increase in airway resistance. Immediately after methacholine inhalation the subjects underwent a progressive exercise test on a cycle ergometer (day 1) or voluntary hyperventilation (day 2) or remained resting (day 3). On the first day during exercise pulmonary resistance fell rapidly to baseline levels within two to three minutes and remained there for the 10 minute duration of the exercise. On day 2 voluntary reproduction of the same level and pattern of ventilation as during exercise resulted in a similar fall of resistance. On the third day, when the subjects remained at rest, pulmonary resistance remained raised for 10 minutes. It is concluded that the bronchodilator effects of exercise can be explained by the increased ventilation rather than the exercise itself, but with much smaller tidal volumes than have previously been thought necessary to reduce drug induced bronchoconstriction.


[Effect of feedback and self-evaluation on the prescription of addictive drugs].
Prescribing of anti-anxiety benzodiazepines was registered in five one month periods in 1989 and 1990 in Moss, a medium-sized Norwegian town. The general practitioners received feed-back on their own prescribing habits and were offered an opportunity to meet colleagues in a self-evaluation group. The results indicate that GPs are influenced by such feed-back, since a reduction in the amount of defined daily doses prescribed was registered. The reduction was mainly a consequence of a change to prescribing a smaller number of pills on each occasion. The authors anticipated a potential reduction in prescribing to elderly persons, but in fact found a substantial reduction in the prescribing of anti-anxiety drugs to young men (with a potential problem of misuse).


Novel hairpin-shaped primer assay to study the association of the -44 single-nucleotide polymorphism of the DEFB1 gene with early-onset periodontal disease.
A powerful, cost-effective new method for studying single-nucleotide polymorphisms (SNPs) is described. This method is based on the use of hairpin-shaped primers (HP), which give a sensitive and specific PCR amplification of each specific allele, without the use of costly fluorophore-labeled probes and any post-PCR manipulation. The amplification is monitored in real-time using SYBR Green I dye and takes only 2 h to yield results. The HP assay has a simple design and utilizes a conventional real-time PCR apparatus. The -44 C-->G transversion in the DEFB1 gene (which encodes human beta-defensin 1) has been previously associated with Candida carriage in oral epithelia. In this study, we analyzed the association between early-onset periodontal disease (EOP) and the -44 SNP. We used an HP assay to study the distribution of the -44 SNP in 264 human DNAs obtained from two cohorts of EOP patients and healthy controls from different ethnic backgrounds. The results indicate that the -44 SNP has a similar distribution between EOP and healthy patients, suggesting that it is not associated with the disease.


Molecularly imprinted polymers (MIPs): sensing, an explosive new opportunity?
Our group is currently developing in-field detection systems alongside the Australian Federal Police Forensic Services utilising molecularly imprinted polymers as the recognition elements. This review looks at MIP synthesis and our perceptions of future directions from an Australian and forensic perspective.


Role of nitric oxide in tumor progression: lessons from experimental tumors.
Nitric oxide (NO), a potent biological mediator, plays a key role in physiological as well as pathological processes, including inflammation and cancer. The role of NO in tumor biology remains incompletely understood. While a few reports indicate that the presence of NO in tumor cells or their microenvironment is detrimental to tumor cell survival and consequently their metastatic ability, a large body of clinical and experimental data suggest a promoting role of NO in tumor progression and metastasis. We suggest that tumor cells capable of very high levels of NO production die in vivo, and those producing or exposed to lower levels of NO, or capable of resisting NO-mediated injury undergo a clonal selection because of their survival advantage; they also utilize certain NO-mediated mechanisms for promotion of growth, invasion and metastasis. The possible mechanism(s) are: (a) a stimulatory effect on tumor cell invasiveness, (b) a promotion of tumor angiogenesis and blood flow in the tumor neovasculature, and (c) a suppression of host anti-tumor defense. In this review, we discuss these mechanisms on the basis of data derived from experimental models, in particular, a mouse mammary tumor model in which the expression of eNOS by tumor cells is positively correlated with invasive and metastatic abilities. Tumor-derived NO was shown to promote tumor cell invasiveness and angiogenesis. The invasion-stimulating effects of NO were due to an upregulation of matrix metalloproteases and a downregulation of their natural inhibitors. Treatment of tumor-bearing mice with NO-blocking agents reduced the growth and vascularity of primary tumors and their spontaneous metastases. We propose that selected NO-blocking drugs may be useful in treating certain human cancers either as single agents or as a part of combination therapies.


Exploring the effect of sialic acid orientation on ligand-receptor interactions.
Here, we present the synthesis of two sialo-micelles to validate the significance of sialic acid orientation during specific carbohydrate-protein and carbohydrate-carbohydrate interactions. Our data clearly suggest that orientation of carboxylic acid and glycerol side chains of sialic acid moieties exert fine tuning of ligand-receptor interactions.


Allergic Stomatitis From Orthodontic Adhesives.
We report a case of a type IV hypersensitivity reaction causing oral stomatitis, presumed to be the result of common dental adhesives. The case was diagnosed using patch testing to the dental adhesives that were used in the patient. Both of the adhesives tested contained a form of acrylate that is being seen more frequently in the literature as a cause of type IV hypersensitivity reactions. Metals can cause allergic reactions; however, other contact items need to be considered as a cause of oral allergic reactions. Cases of allergic stomatitis are rising and there is question if all-in-one adhesives may be contributing to this rise.


The taxonomy statistic uncovers novel clinical patterns in a population of ischemic stroke patients.
In this paper, we describe a simple taxonomic approach for clinical data mining elaborated by Marczewski and Steinhaus (M-S), whose performance equals the advanced statistical methodology known as the expectation-maximization (E-M) algorithm. We tested these two methods on a cohort of ischemic stroke patients. The comparison of both methods revealed strong agreement. Direct agreement between M-S and E-M classifications reached 83%, while Cohen's coefficient of agreement was κ = 0.766(P < 0.0001). The statistical analysis conducted and the outcomes obtained in this paper revealed novel clinical patterns in ischemic stroke patients. The aim of the study was to evaluate the clinical usefulness of Marczewski-Steinhaus' taxonomic approach as a tool for the detection of novel patterns of data in ischemic stroke patients and the prediction of disease outcome. In terms of the identification of fairly frequent types of stroke patients using their age, National Institutes of Health Stroke Scale (NIHSS), and diabetes mellitus (DM) status, when dealing with rough characteristics of patients, four particular types of patients are recognized, which cannot be identified by means of routine clinical methods. Following the obtained taxonomical outcomes, the strong correlation between the health status at moment of admission to emergency department (ED) and the subsequent recovery of patients is established. Moreover, popularization and simplification of the ideas of advanced mathematicians may provide an unconventional explorative platform for clinical problems.


The impact of the viscosity and osmolality of iodine contrast agents on renal elimination.
The iodinated contrast agents (CAs) that are currently used in radiographic procedures possess special physicochemical properties and a high safety profile; however, according to a large retrospective study (Swedish registry), the viscosity of CAs may have an underestimated impact on renal failure. The aim of our study was to investigate the possible consequences of CA viscosity differences, such as CA retention in the kidney. Five Göttingen minipigs were each intravenously injected in a crossover setting at intervals of at least 7 days with monomeric (Iopromide) and dimeric (Iodixanol) CAs at 2 doses (1 and 2 g iodine/kg bodyweight), and the retention of the CA in the kidneys was determined during the first 6 hours postinjection using a 64-slice computed tomography scanner. Additionally we performed in vitro dialysis of the monomeric and dimeric CAs across the various physiological osmolalities of the renal tubulus (300, 600, 800, and 1200 mOsm/kg H(2)O) to estimate CA viscosity in vivo. Following the dialyzes, iodine concentrations and CA viscosities were determined. A different exposure of the kidneys to iodine and a different elimination kinetics from the kidneys was observed after the administration of monomeric and dimeric CAs. The monomeric agent was observed to clear from the kidney immediately after administration. In contrast, after administration of the dimeric CA an increase in iodine concentration in the kidney was observed up to 180 minutes postinjection, before the CA was observed to begin clearing; however, no difference was observed between the plasma half-lives of the 2 investigated CAs. In vitro dialysis of the dimeric CA increased iodine concentrations and strongly increased viscosity at all of the tested osmolalities. In contrast, the monomeric agent only demonstrated increases in iodine concentration and viscosity at 800 and 1200 mOsm/kg, and these changes were smaller than those observed for the dimeric CA. In summary, dialysis strongly enhanced the viscosity differences between the 2 investigated CAs. The viscosity differences between the investigated monomeric and dimeric CAs are strongly enhanced by concentration processes, such as the process taking place in the tubular system. These viscosity differences may be the cause of the prolonged retention and the different elimination kinetics from the kidney observed after application of the dimeric CA relative to the monomeric CA.


Connectivity distribution of spatial networks.
We study spatial networks constructed by randomly placing nodes on a manifold and joining two nodes with an edge whenever their distance is less than a certain cutoff. We derive the general expression for the connectivity distribution of such networks as a functional of the distribution of the nodes. We show that for regular spatial densities, the corresponding spatial network has a connectivity distribution decreasing faster than an exponential. In contrast, we also show that scale-free networks with a power law decreasing connectivity distribution are obtained when a certain information measure of the node distribution (integral of higher powers of the distribution) diverges. We illustrate our results on a simple example for which we present simulation results. Finally, we speculate on the role played by the limiting case P(k) proportional, variant k(-1) which appears empirically to be relevant to spatial networks of biological origin such as the ones constructed from gene expression data.


Myofibrillar incorporation of 3H (G) L-leucine in pgrogressive muscular dystrophy and motor neuron disease.
A study of the incorporation of hydrogen 3 (3H) leucine into skeletal muscle in patients with human muscular dystrophy and motor neuron disease showed uptake in cytoplasm and myofibrils. The techniques used were light and electron microscopy and autoradiography before and after glycerination (Szent-Gyorgyi). The results indicated an increase of 3H leucine uptake into cytoplasm of the dystrophic muscle and a marked drop in incorporation into structural protein. In the patients with motor neuron disease, the normal incorporation into cytoplasm was seen, with reduced uptake into structural protein. These results showed a different protein synthesis pattern in dystrophic and denervated muscle.


In vivo effects of nifedipine and BAY 1 8201 on ceruletide induced gallbladder contraction.
Studies in animals suggest that calcium channel blockers may influence gallbladder contraction. In order to study possible actions in man we examined by ultrasonography the effects of two dihydropyridine derivatives, i.e. nifedipine (20 mg p. o.) and BAY 1 8201 (100 mg p.o.) on ceruletide induced human gallbladder contraction in 9 healthy male volunteers in a randomized, double-blind, three fold crossover study (latin square design). Blood samples for the measurement of plasma drug concentrations were drawn before and at regular intervals up to 8 h after drug ingestion. Ceruletide decreased gallbladder volumes by 52.1 +/- 8.2% (mean +/- 1 SEM) after nifedipine, 53.1 +/- 8.1% after BAY 1 8201 and by 59.3 +/- 10.1% after placebo (NS). Peak plasma concentrations of 53.7 x/: 2.3 ng/ml (geometric mean x/: geometric standard deviation) and of 35.5 x/: 1.5 ng/ml were reached after oral application of nifedipine and BAY 1 8201, respectively. We conclude that human gallbladder contraction in response to ceruletide is not markedly influenced by dihydropyridine derivates in the dosages used in this study. The results reported here stress the importance of calcium released from intracellular stores for the contractility of smooth muscle in the human gallbladder.


Distribution of myelin basic protein and P2 mRNAs in rabbit spinal cord oligodendrocytes.
Myelin basic protein (MBP) and P2 protein are small positively charged proteins found in oligodendrocytes of rabbit spinal cord. Both proteins become incorporated into compact myelin. We have begun investigations into the mechanisms by which MBP and P2 become incorporated into the myelin membrane. We find that P2, like the MBPs, is synthesized on free polysomes in rabbit spinal cord. Cell fractionation experiments reveal that rabbit MBP mRNAs are preferentially segregated to the peripheral myelinating regions whereas P2 mRNAs are predominantly localized within the perikaryon of the cell. In vitro synthesized rabbit MBP readily associates with membranes added to translation mixtures, whereas P2 protein does not. It is possible that P2 requires a "receptor" molecule, perhaps a membrane-anchored protein, for association with the cytoplasmic face of the myelin membrane.


Decision making in bone conduction and active middle ear implants - hearing outcomes and experiences over a 10-year period.
To review the decision-making paradigm in the recommendations of BCI and aMEI overlapping candidacy for patients with conductive or mixed HL, and to determine if there are differences in hearing and quality of life outcomes between these implantable hearing devices. Retrospective data from patients receiving BCI or aMEI in the past decade were analysed. Patients were grouped into: 1. BCI candidates, 2. BCI or aMEI candidates, and 3. aMEI candidates. We compared outcomes and examined the impact of BC threshold, age at implantation, and duration of hearing loss on candidacy. 89 participants were included: 30 BCI, 37 aMEI, and 22 BCI or aMEI candidates. All groups performed similarly in aided sound field threshold testing. BCI group had lower speech scores in quiet compared to 'BCI or aMEI.' No significant differences were found in APHAB global scores. BC threshold, duration of hearing loss, and age at implantation had no significant effects. Outcomes were generally similar across groups, except for higher effective gain in the aMEI group. Our proposed patient pathway and decision-making approach facilitate candidate selection for aMEI and BCI, aiming to optimise outcomes.


Lung cancer in the very elderly: incidence, presentation, and diagnostic decision-making. A retrospective analysis at a teaching community hospital.
Lung cancer presentation and decision-making in the very elderly patient population, 80 years of age and older, was studied given the projected increase in cancer incidence in the very elderly and yet only limited management guidelines. A 10-year experience at the Unity Health System of Rochester, NY, was reviewed using tumor registry data for the entire lung cancer population plus focused medical record review of very elderly patients. A questionnaire survey on the clinical approach to lung cancer in the elderly was distributed to medical staff involved in their care. Of 997 patients, approximately 100 cases each year, the very elderly comprised 18% of patients from year 1998 through 2002, and 23% from year 2003 through 2007. One-third of the very elderly were diagnosed with lung cancer on clinical grounds without tissue confirmation. The majority of this group had cardio-pulmonary symptoms and an advanced clinical stage. The very elderly had no tissue sampling as per their own decision in 12 of 44 of cases, per family decision in 28 of 44, and per physician and other input in 4 of 44. Physicians stated that patient wishes and health-related factors, more so than socio-economic factors, were primary concerns for management decision-making. The number of very elderly lung cancer patients in this community setting has been significant and appears to be increasing. These patients were more likely to have an incomplete diagnostic work-up, with patient and family wishes being the major factor in medical decision-making. The physician approach to these patients emphasized patient autonomy and medical factors.